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Echocardiographic measurements of the heart

To my family Hubert, Lovisa and Natasha

Örebro Studies in Medicine 52

KARIN LOISKE

Echocardiographic measurements of the heart With focus on the right ventricle

To my family Hubert, Lovisa and Natasha

Örebro Studies in Medicine 52

KARIN LOISKE

Echocardiographic measurements of the heart With focus on the right ventricle

© Karin Loiske, 2011

Title: Echocardiographic measurements of the heart. With focus on the right ventricle.

Publisher: Örebro University 2011

www.publications.oru.se [email protected]

Print: Intellecta Infolog, Kållered 02/2011

ISSN 1652-4063 ISBN 978-91-7668-783-3

Abstract Karin Loiske (2011): Echocardiographic measurements of the heart. With focus on the right ventricle. Örebro Studies in Medicine 52, 63 pp. Echocardiography is a well established technique when evaluating the size and function of the heart. One of the most common ways to measure the size of the right ventricle (RV) is to measure the RV outflow tract 1 (RVOT1). Several ways to measure RVOT1 are described in the literature. These ways were compared with echocardiography on 27 healthy subjects. The result showed significant differences in RVOT1, depending on the way it was measured, concluding that the same site, method and body position should be used when comparing RVOT1 in the same subject over time.

One parameter to evaluate the RV diastolic function (RVDF) is to meas-ure the RV isovolumetric relaxation time (RV-IVRT), a sensitive marker of RV dysfunction. There are different ways to measure this. In this thesis two ways of measuring RV-IVRT and their time intervals were compared in 20 patients examined with echocardiography. There was a significant differ-ence between the two methods indicating that they are not measuring the same interval.

Another way to assess the RVDF is to measure the maximal early dia-stolic velocity (MDV) in the long-axis direction. MDV can be measured by different methods, hence 29 patients were examined and MDV was meas-ured according to two methods. There was a good correlation but a poor agreement between the two methods meaning that reference values cannot be used interchangeably.

Takotsubo cardiomyopathy is characterized by apical wall motion ab-normalities without coronary stenosis. The pathology of this condition remains unclear. To evaluate biventricular changes in systolic long-axis function and diastolic parameters in the acute phase and after recovery, 13 patients were included and examined with echocardiography at admission and after recovery. The results showed significant biventricular improve-ment of systolic long-axis function while most diastolic parameters re-mained unchanged.

Keywords: Echocardiography, heart, right ventricle, right ventricular out-flow tract 1, isovolumetric relaxation time, maximal early diastolic relaxa-tion velocity, takotsubo cardiomyopathy, long-axis function Karin Loiske, School of Health and Medical Sciences/Clinical Medicin Örebro University, SE-701 82 Örebro, Sweden, [email protected]

© Karin Loiske, 2011

Title: Echocardiographic measurements of the heart. With focus on the right ventricle.

Publisher: Örebro University 2011

www.publications.oru.se [email protected]

Print: Intellecta Infolog, Kållered 02/2011

ISSN 1652-4063 ISBN 978-91-7668-783-3

Abstract Karin Loiske (2011): Echocardiographic measurements of the heart. With focus on the right ventricle. Örebro Studies in Medicine 52, 63 pp. Echocardiography is a well established technique when evaluating the size and function of the heart. One of the most common ways to measure the size of the right ventricle (RV) is to measure the RV outflow tract 1 (RVOT1). Several ways to measure RVOT1 are described in the literature. These ways were compared with echocardiography on 27 healthy subjects. The result showed significant differences in RVOT1, depending on the way it was measured, concluding that the same site, method and body position should be used when comparing RVOT1 in the same subject over time.

One parameter to evaluate the RV diastolic function (RVDF) is to meas-ure the RV isovolumetric relaxation time (RV-IVRT), a sensitive marker of RV dysfunction. There are different ways to measure this. In this thesis two ways of measuring RV-IVRT and their time intervals were compared in 20 patients examined with echocardiography. There was a significant differ-ence between the two methods indicating that they are not measuring the same interval.

Another way to assess the RVDF is to measure the maximal early dia-stolic velocity (MDV) in the long-axis direction. MDV can be measured by different methods, hence 29 patients were examined and MDV was meas-ured according to two methods. There was a good correlation but a poor agreement between the two methods meaning that reference values cannot be used interchangeably.

Takotsubo cardiomyopathy is characterized by apical wall motion ab-normalities without coronary stenosis. The pathology of this condition remains unclear. To evaluate biventricular changes in systolic long-axis function and diastolic parameters in the acute phase and after recovery, 13 patients were included and examined with echocardiography at admission and after recovery. The results showed significant biventricular improve-ment of systolic long-axis function while most diastolic parameters re-mained unchanged.

Keywords: Echocardiography, heart, right ventricle, right ventricular out-flow tract 1, isovolumetric relaxation time, maximal early diastolic relaxa-tion velocity, takotsubo cardiomyopathy, long-axis function Karin Loiske, School of Health and Medical Sciences/Clinical Medicin Örebro University, SE-701 82 Örebro, Sweden, [email protected]

Table of contents

LIST OF PAPERS ....................................................................................... 9

ABBREVIATIONS ................................................................................... 11

INTRODUCTION ................................................................................... 13 Echocardiography and right ventricular size ............................................ 14 Right ventricular function ........................................................................ 15

Right ventricular isovolumetric relaxation time ........................................... 16 Maximal early diastolic velocity in right ventricular long-axis direction .... 17

Takotsubo cardiomyopathy ..................................................................... 17 AIMS OF THE THESIS ........................................................................... 21

SUBJECTS AND METHODS .................................................................. 23 Subjects .................................................................................................... 23 Methods ................................................................................................... 25

Echocardiographic examination ................................................................... 25 2D/M-mode echocardiography..................................................................... 26 Doppler echocardiography ........................................................................... 29 Doppler tissue imaging .................................................................................. 30 Reproducibility of the measurements ........................................................... 32 Statistics ......................................................................................................... 32 Ethics ............................................................................................................. 33

RESULTS ................................................................................................. 35 Echocardiographic measurements of the right ventricle: RVOT1 ............. 35 Two parameters to evaluate right ventricular diastolic function .............. 37

Right ventricular isovolumetric relaxation time ........................................... 37 Maximal early diastolic velocity in right ventricular long-axis direction .... 38 Reproducibility studies .................................................................................. 39

Takotsubo cardiomyopathy ..................................................................... 41 DISCUSSION ........................................................................................... 45 Methodological considerations ................................................................ 45 Theoretical implications ........................................................................... 47 Practical implications ............................................................................... 50 CONCLUSIONS ...................................................................................... 53

ACKNOWLEDGEMENTS ...................................................................... 55

REFERENCES ......................................................................................... 57

Table of contents

LIST OF PAPERS ....................................................................................... 9

ABBREVIATIONS ................................................................................... 11

INTRODUCTION ................................................................................... 13 Echocardiography and right ventricular size ............................................ 14 Right ventricular function ........................................................................ 15

Right ventricular isovolumetric relaxation time ........................................... 16 Maximal early diastolic velocity in right ventricular long-axis direction .... 17

Takotsubo cardiomyopathy ..................................................................... 17 AIMS OF THE THESIS ........................................................................... 21

SUBJECTS AND METHODS .................................................................. 23 Subjects .................................................................................................... 23 Methods ................................................................................................... 25

Echocardiographic examination ................................................................... 25 2D/M-mode echocardiography..................................................................... 26 Doppler echocardiography ........................................................................... 29 Doppler tissue imaging .................................................................................. 30 Reproducibility of the measurements ........................................................... 32 Statistics ......................................................................................................... 32 Ethics ............................................................................................................. 33

RESULTS ................................................................................................. 35 Echocardiographic measurements of the right ventricle: RVOT1 ............. 35 Two parameters to evaluate right ventricular diastolic function .............. 37

Right ventricular isovolumetric relaxation time ........................................... 37 Maximal early diastolic velocity in right ventricular long-axis direction .... 38 Reproducibility studies .................................................................................. 39

Takotsubo cardiomyopathy ..................................................................... 41 DISCUSSION ........................................................................................... 45 Methodological considerations ................................................................ 45 Theoretical implications ........................................................................... 47 Practical implications ............................................................................... 50 CONCLUSIONS ...................................................................................... 53

ACKNOWLEDGEMENTS ...................................................................... 55

REFERENCES ......................................................................................... 57

KARIN LOISKE Echocardiographic measurements of the heart 9

LIST OF PAPERS

This thesis is based on the following original papers and will be referred in the text by their Roman numerals.

I. Loiske K, Hammar S, Emilsson K. Echocardiographic

measurements of the right ventricle: right ventricular out-flow tract 1. Clin Res Cardiol. 2010;99(7):429-435.

II. Emilsson K, Loiske K. Isovolumetric relaxation time of the

right ventricle assessed by tissue Doppler imaging. Scand Cardiovasc J. 2004;38(5):278-282.

III. Emilsson K, Loiske K. Comparison between maximal early

diastolic velocity in long-axis direction obtained by M-mode echocardiography and by tissue Doppler in the as-sessment of right ventricular diastolic function. Clin Physiol Funct Imaging. 2005;25(3):178-182.

IV. Loiske K, Waldenborg M, Fröbert O, Rask P, Emilsson K.

Left and right ventricular systolic long-axis function and diastolic function in patients with takotsubo cardiomyopa-thy. Accepted for publication in Clin Physiol Funct Imaging 2010.

The articles are reprinted with permission from the publishers, which are gratefully acknowledged.


LIST OF PAPERS

This thesis is based on the following original papers and will be referred in the text by their Roman numerals.

I. Loiske K, Hammar S, Emilsson K. Echocardiographic

measurements of the right ventricle: right ventricular out-flow tract 1. Clin Res Cardiol. 2010;99(7):429-435.

II. Emilsson K, Loiske K. Isovolumetric relaxation time of the

right ventricle assessed by tissue Doppler imaging. Scand Cardiovasc J. 2004;38(5):278-282.

III. Emilsson K, Loiske K. Comparison between maximal early

diastolic velocity in long-axis direction obtained by M-mode echocardiography and by tissue Doppler in the as-sessment of right ventricular diastolic function. Clin Physiol Funct Imaging. 2005;25(3):178-182.

IV. Loiske K, Waldenborg M, Fröbert O, Rask P, Emilsson K.

Left and right ventricular systolic long-axis function and diastolic function in patients with takotsubo cardiomyopa-thy. Accepted for publication in Clin Physiol Funct Imaging 2010.

The articles are reprinted with permission from the publishers, which are gratefully acknowledged.


ABBREVIATIONS RV Right ventricle LV Left ventricle EF Ejection fraction DF Diastolic function IVRT Isovolumetric relaxation time PW Pulsed wave DTI Doppler tissue imaging TDI Tissue Doppler imaging 2D color DTI Two-dimensional color Doppler tissue imaging MAM Mitral annulus motion TAM Tricuspid annulus motion MDV Maximal early diastolic velocity S Peak systolic velocity E Peak velocity during early diastole A Peak velocity during atrial systole (late diastole) E/A Ratio of the E and A velocity é Myocardial peak velocity during early diastole á Myocardial peak velocity during atrial systole (late diastole) RVOT1 Right ventricular outflow tract 1 RVIT3 Right ventricular inflow tract 3


ABBREVIATIONS RV Right ventricle LV Left ventricle EF Ejection fraction DF Diastolic function IVRT Isovolumetric relaxation time PW Pulsed wave DTI Doppler tissue imaging TDI Tissue Doppler imaging 2D color DTI Two-dimensional color Doppler tissue imaging MAM Mitral annulus motion TAM Tricuspid annulus motion MDV Maximal early diastolic velocity S Peak systolic velocity E Peak velocity during early diastole A Peak velocity during atrial systole (late diastole) E/A Ratio of the E and A velocity é Myocardial peak velocity during early diastole á Myocardial peak velocity during atrial systole (late diastole) RVOT1 Right ventricular outflow tract 1 RVIT3 Right ventricular inflow tract 3


INTRODUCTION The heart is an amazing muscle. The heart muscle cell is striated and shares the same contractile unit as the skeletal muscle, the sarcomere. The sar-comere contains myosin thick filaments and thin filaments of actin, tro-ponin and tropomyosin. In the presence of calcium the myosin interacts with actin, which produces a cross-bridge between the filaments enabling contraction (systole) to occur. The relaxed state (diastole) is brought about by a decrease in intracellular calcium and the tropomyosin inhibitory sub-unit prevents myosin from interacting with actin (1). What makes the heart muscle cells unique are the intercalated discs that connects the cells to-gether at specialized junctional sites. The intercalated discs serve at least three important functions:

1. They bind the heart muscle cells together with desmosomes, which helps to stabilize and maintain the structure of the tissue.

2. They connect the actin filament of the myofibrils in two interlock-ing heart cells so the two cells can “pull” together with maximum efficiency.

3. They contain gap junctions, which allows a direct electrical con-nection between two cells, an action potential can spread rapidly from one heart muscle cell to another.

This means the heart muscle cells are unique in their kind since they are mechanically, chemically and electrically linked together. The heart tissue functions like a single, enormous muscle cell and the contraction of one cell will trigger the contraction of several others making the contraction spread throughout the myocardium (2,3).

The heart is located slightly left of the midline of the thorax in the body. The base is at the level of the third costal cartilage, posterior to the ster-num. The inferior, pointed tip, called the apex, reaches the fifth intercostal space about 7.5 cm to the left of the midline. A normal adult heart meas-ures approximately 12.5 cm from base to apex. The anatomical differences between left and right ventricles are quite substantial. The right ventricle (RV) wall is thin and it resembles a crescent shaped moon attached to a full moon, the massive wall of the left ventricle (LV). The ventricles share the inter-ventricular septum, which separates the RV from the LV. The RV contraction resembles a bellows pump, squeezing the blood against the mass of the LV, an efficient way to move blood with minimal effort. This develops a relatively low pressure, approximately 1/6 of the pressure of the


INTRODUCTION The heart is an amazing muscle. The heart muscle cell is striated and shares the same contractile unit as the skeletal muscle, the sarcomere. The sar-comere contains myosin thick filaments and thin filaments of actin, tro-ponin and tropomyosin. In the presence of calcium the myosin interacts with actin, which produces a cross-bridge between the filaments enabling contraction (systole) to occur. The relaxed state (diastole) is brought about by a decrease in intracellular calcium and the tropomyosin inhibitory sub-unit prevents myosin from interacting with actin (1). What makes the heart muscle cells unique are the intercalated discs that connects the cells to-gether at specialized junctional sites. The intercalated discs serve at least three important functions:

1. They bind the heart muscle cells together with desmosomes, which helps to stabilize and maintain the structure of the tissue.

2. They connect the actin filament of the myofibrils in two interlock-ing heart cells so the two cells can “pull” together with maximum efficiency.

3. They contain gap junctions, which allows a direct electrical con-nection between two cells, an action potential can spread rapidly from one heart muscle cell to another.

This means the heart muscle cells are unique in their kind since they are mechanically, chemically and electrically linked together. The heart tissue functions like a single, enormous muscle cell and the contraction of one cell will trigger the contraction of several others making the contraction spread throughout the myocardium (2,3).

The heart is located slightly left of the midline of the thorax in the body. The base is at the level of the third costal cartilage, posterior to the ster-num. The inferior, pointed tip, called the apex, reaches the fifth intercostal space about 7.5 cm to the left of the midline. A normal adult heart meas-ures approximately 12.5 cm from base to apex. The anatomical differences between left and right ventricles are quite substantial. The right ventricle (RV) wall is thin and it resembles a crescent shaped moon attached to a full moon, the massive wall of the left ventricle (LV). The ventricles share the inter-ventricular septum, which separates the RV from the LV. The RV contraction resembles a bellows pump, squeezing the blood against the mass of the LV, an efficient way to move blood with minimal effort. This develops a relatively low pressure, approximately 1/6 of the pressure of the

14 KARIN LOISKE Echocardiographic measurements of the heart

LV, which is important to protect the delicate pulmonary vessels. The LV has a thick wall and it is almost round in cross section. When the LV con-tracts, two things happen; the long-axis distance between the base and the apex decreases and the short-axis diameter of the ventricular chambers decreases, making the pressure high enough to push the blood around the systemic circuit. When the LV contraction occurs, the inter-ventricular septum bulges into the RV cavity (2).

Echocardiography and right ventricular size Echocardiography is a well established technique used worldwide. The size of the heart, especially its ventricles, is important to establish during the clinical echocardiographic examination, since larger ventricles often indi-cate an underlying disease such as dilated cardiomyopathy, valvular disor-der or shunt.

The size of the LV is associated with the prognosis of the patient. It has important therapeutic implications and can provide data that is necessary to determine the optimal time for cardiac surgery, for instance, in patients with aortic- or mitral regurgitation (4). A large RV may be seen in patients with different kinds of conditions such as arrhythmogenic right ventricular dysplasia (ARVD) (5) and primary pulmonary disease, but it could also be a result of elevated LV filling pressure through the pulmonary circulation, thus augmenting RV afterload (6). Large ventricles and ventricular hyper-trophy, however, is not always an indication of pathology but could also be seen in apparently healthy individuals such as athletes (7).

The RV has a complex anatomy. It has a separate outflow and inflow portion and a main body, which is crescent shaped and truncated. The RV free wall consists of a variable trabecular pattern. These factors make evaluation of the structure of the RV including the measurement of cavity size and wall thickness difficult. The position of the RV, close to the ster-num and an anterior relation to the left heart, also complicates the accessi-bility (8). Several ways to measure the RV have been suggested in the lit-erature (8-18). To measure the RV inflow tract 3 (RVIT3) and RV outflow tract 1 (RVOT1) are the most commonly used ways, probably due to the high reproducibility (8). RVIT3 is measured in the apical four-chamber view 1/3 from the base of the RV (14), but when it comes to the RVOT1, different ways to measure it are described (8,9,13,14,16-18).

Anatomically the RVOT extends cephalic and in a leftward direction from the anteromedial portion of the tricuspid valve annulus to the pulmo-nary annulus. The anterior border is the anterior RV free wall. The poste-rior border is the anteromedial portion of the aortic root. In normal hearts,


the crista supraventricularis is an anatomically identifiable structure to RVOT (18).

The myocardial fiber architecture of the RV is fundamentally different from the fiber architecture of the LV. The dominant muscle layer of the LV is circumferential fibers. In the RV the inflow tract mainly consists of circumferential fibers in the subepicardium and partially longitudinal fibers in the subendocardium. At the outflow tract the fibers run longitudinally overlain by fibers running at right angles to the outflow long-axis, which can be traced to the crista supraventricularis and to the anterior sulcus. Some of these fibers continue across the sulcus, crossing the infundibulum, serving to bind the two ventricles together. Because the inflow and outflow long-axis are approximately at right angels to each other, the fibers per-pendicular to the inflow long-axis are running parallel to the outflow long-axis with little change in orientation (19).

Since several ways have been described to measure RVOT1, both at dif-ferent locations and with different methods, echocardiographers do not use a uniform way to implement the measurement.

When performing an echocardiographic examination the patient is usu-ally lying in the left lateral decubitus position simply because the quality of images improves. However, seriously ill patients or patients that for other reasons are unable to lie in the left position, have to be examined in the supine decubitus position. This does not only impair the quality of image but there are indications that the RV dimension increases when the patient move from supine to left lateral decubitus position (9).

Right ventricular function The LV function has earned a lot of interest in the past; whereas the RV function has played a more inconspicuous part. More focus has recently been dedicated, however, to the RV function since it plays a very important role as it has shown to be a sensitive predictor in a number of cardiac syn-dromes. The RV, for example, is involved in approximately 40-50% of patients with acute inferior infarction and may result in a hemodynamic compromised situation with a poor clinical outcome. Pulmonary diseases affect the RV function as a result of pulmonary hypertension and of course a lot of LV pathology such as severe aortic or mitral valve disease give pulmonary hypertension and commonly affects the RV function. The con-sequence of this is that early detection of RV dysfunction is important to optimize patient management (15,20,21).

For early diagnosis of RV dysfunction the commonly used technique has been two-dimensional echocardiography. This is not ideal because of the complex anatomy of the RV and its position close to the sternum. Meth-


LV, which is important to protect the delicate pulmonary vessels. The LV has a thick wall and it is almost round in cross section. When the LV con-tracts, two things happen; the long-axis distance between the base and the apex decreases and the short-axis diameter of the ventricular chambers decreases, making the pressure high enough to push the blood around the systemic circuit. When the LV contraction occurs, the inter-ventricular septum bulges into the RV cavity (2).

Echocardiography and right ventricular size Echocardiography is a well established technique used worldwide. The size of the heart, especially its ventricles, is important to establish during the clinical echocardiographic examination, since larger ventricles often indi-cate an underlying disease such as dilated cardiomyopathy, valvular disor-der or shunt.

The size of the LV is associated with the prognosis of the patient. It has important therapeutic implications and can provide data that is necessary to determine the optimal time for cardiac surgery, for instance, in patients with aortic- or mitral regurgitation (4). A large RV may be seen in patients with different kinds of conditions such as arrhythmogenic right ventricular dysplasia (ARVD) (5) and primary pulmonary disease, but it could also be a result of elevated LV filling pressure through the pulmonary circulation, thus augmenting RV afterload (6). Large ventricles and ventricular hyper-trophy, however, is not always an indication of pathology but could also be seen in apparently healthy individuals such as athletes (7).

The RV has a complex anatomy. It has a separate outflow and inflow portion and a main body, which is crescent shaped and truncated. The RV free wall consists of a variable trabecular pattern. These factors make evaluation of the structure of the RV including the measurement of cavity size and wall thickness difficult. The position of the RV, close to the ster-num and an anterior relation to the left heart, also complicates the accessi-bility (8). Several ways to measure the RV have been suggested in the lit-erature (8-18). To measure the RV inflow tract 3 (RVIT3) and RV outflow tract 1 (RVOT1) are the most commonly used ways, probably due to the high reproducibility (8). RVIT3 is measured in the apical four-chamber view 1/3 from the base of the RV (14), but when it comes to the RVOT1, different ways to measure it are described (8,9,13,14,16-18).

Anatomically the RVOT extends cephalic and in a leftward direction from the anteromedial portion of the tricuspid valve annulus to the pulmo-nary annulus. The anterior border is the anterior RV free wall. The poste-rior border is the anteromedial portion of the aortic root. In normal hearts,


the crista supraventricularis is an anatomically identifiable structure to RVOT (18).

The myocardial fiber architecture of the RV is fundamentally different from the fiber architecture of the LV. The dominant muscle layer of the LV is circumferential fibers. In the RV the inflow tract mainly consists of circumferential fibers in the subepicardium and partially longitudinal fibers in the subendocardium. At the outflow tract the fibers run longitudinally overlain by fibers running at right angles to the outflow long-axis, which can be traced to the crista supraventricularis and to the anterior sulcus. Some of these fibers continue across the sulcus, crossing the infundibulum, serving to bind the two ventricles together. Because the inflow and outflow long-axis are approximately at right angels to each other, the fibers per-pendicular to the inflow long-axis are running parallel to the outflow long-axis with little change in orientation (19).

Since several ways have been described to measure RVOT1, both at dif-ferent locations and with different methods, echocardiographers do not use a uniform way to implement the measurement.

When performing an echocardiographic examination the patient is usu-ally lying in the left lateral decubitus position simply because the quality of images improves. However, seriously ill patients or patients that for other reasons are unable to lie in the left position, have to be examined in the supine decubitus position. This does not only impair the quality of image but there are indications that the RV dimension increases when the patient move from supine to left lateral decubitus position (9).

Right ventricular function The LV function has earned a lot of interest in the past; whereas the RV function has played a more inconspicuous part. More focus has recently been dedicated, however, to the RV function since it plays a very important role as it has shown to be a sensitive predictor in a number of cardiac syn-dromes. The RV, for example, is involved in approximately 40-50% of patients with acute inferior infarction and may result in a hemodynamic compromised situation with a poor clinical outcome. Pulmonary diseases affect the RV function as a result of pulmonary hypertension and of course a lot of LV pathology such as severe aortic or mitral valve disease give pulmonary hypertension and commonly affects the RV function. The con-sequence of this is that early detection of RV dysfunction is important to optimize patient management (15,20,21).

For early diagnosis of RV dysfunction the commonly used technique has been two-dimensional echocardiography. This is not ideal because of the complex anatomy of the RV and its position close to the sternum. Meth-


ods, such as Simpson’s formula, are based on mathematical assumptions of RV anatomy, which result in inaccuracies and are not useful in clinical practice (15,22). Several authors instead recommend M-mode and Doppler tissue imaging (DTI, in the text also referred to as tissue Doppler imaging (TDI)), as useful methods in clinical practice (15,20,21,23). M-mode meas-urement of the systolic long-axis motion of the RV free wall, also called tricuspid annulus motion (TAM), is a popular method, simple to imple-ment and it has shown a good correlation with the RV ejection fraction (EF) obtained by radionuclide angiography (24). Using TAM, however, in assessing the RV function only gives an estimate over the function of the inflow free wall segments, thus missing the function of the outflow tract and the septal segments. A method, measuring the RVOT fractional short-ening, adds great value (11). Conventional Doppler can be used to estimate pulmonary artery systolic and mean diastolic pressure. Tei index, is used to assess the overall RV function and is calculated as the ratio between several RV Doppler parameters (15).

DTI is a relatively new echocardiographic technique, available in most modern ultrasound systems, and it allows characterisation of myocardial movement and time intervals throughout the cardiac cycle. Pulsed wave (PW) Doppler detects high velocity with low amplitudes while DTI detects low velocity with high amplitudes. Pulsed DTI is simple to use, has a high temporal resolution but a poor spatial resolution (because of movements of the heart since the sample volume is fixed). Two-dimensional color DTI (2D color DTI) is another way to measure myocardial movement and can be used off-line, giving the echocardiographer multiple choice for simulta-neous wall motion analysis, although it provides mean values compared to pulsed DTI that provides peak velocities (15).

Other ways to assess the right heart function are radionuclide tech-niques, computed tomography (CT), cardiac catheterisation and magnetic resonance imaging. These methods give accurate and good evaluation of the RV function although availability, cost and sometimes a risk of side effects makes echocardiography an attractive alternative due to its simplic-ity.

Right ventricular isovolumetric relaxation time For the early detection of an incipient RV dysfunction, the RV diastolic function (RVDF) has to be evaluated since a decrease in RVDF precedes a RV systolic dysfunction. One of the most sensitive functional markers of RV dysfunction is to measure the RV isovolumetric relaxation time (RV-IVRT) (23). The RV-IVRT is a parameter of RVDF and has been shown to correlate well to elevated pulmonary artery pressure where RV-IVRT is


prolonged (23,25). RV-IVRT is defined as the interval from the pulmonic valve closure to the start of the tricuspid valve opening (26). Since there is no good echocardiographic view from which both the pulmonic valve and the tricuspid inflow can be measured simultaneously a method based on ECG and PW Doppler can be used (27), however using this method is somewhat time consuming.

During recent years some authors have used PW-DTI when measuring RV-IVRT (20,21,23,25), a method that is easier and faster than the method based on ECG and PW Doppler. It has not been sufficiently inves-tigated, however, in patients whether the interval measured with the both methods are in fact the same.

Maximal early diastolic velocity in right ventricular long-axis direction During recent years recordings of the maximal early diastolic relaxation velocity in the LV long-axis direction obtained by echocardiographic M-mode (MDV MAM) (28-30) or tissue Doppler imaging (31-33) have been used in the assessment of LVDF. At the right side of the heart the maximal early diastolic relaxation velocity in the RV long-axis direction obtained by tissue Doppler imaging (MDV TDI) has been found to have a fairly good correlation with other diastolic parameters of the RV such as transtricuspid E wave and transtricuspid E/A waves ratios (34). In accordance with the findings on the left side of the heart MDV TDI has been found to decrease with age and it has been suggested that this is due to deterioration in the diastolic properties of the myocardium of the ventricles with age (34,35).

As mentioned earlier it is of great importance to have simple tools to evaluate RVDF. In the same way as MDV MAM has been used in the as-sessment of LVDF, it has been suggested that the maximal early diastolic relaxation velocity in the long-axis direction of the RV obtained by M-mode echocardiography (MDV TAM) can be an index of RVDF (36). This method is based on M-mode, which is one of the oldest echocardiographic techniques and is available on all ultrasound systems while TDI is a rela-tively new technique that might not be available on older echocardio-graphs. Since both indices are measuring the MDV there are reasons to believe that there could be a good correlation and a good agreement be-tween them. If that is the case, either technique could be used in clinical evaluation of the RVDF.

Takotsubo cardiomyopathy Takotsubo cardiomyopathy is a clinical syndrome, typically characterized by acute reversible apical LV dysfunction with acute reduced EF that suc-


ods, such as Simpson’s formula, are based on mathematical assumptions of RV anatomy, which result in inaccuracies and are not useful in clinical practice (15,22). Several authors instead recommend M-mode and Doppler tissue imaging (DTI, in the text also referred to as tissue Doppler imaging (TDI)), as useful methods in clinical practice (15,20,21,23). M-mode meas-urement of the systolic long-axis motion of the RV free wall, also called tricuspid annulus motion (TAM), is a popular method, simple to imple-ment and it has shown a good correlation with the RV ejection fraction (EF) obtained by radionuclide angiography (24). Using TAM, however, in assessing the RV function only gives an estimate over the function of the inflow free wall segments, thus missing the function of the outflow tract and the septal segments. A method, measuring the RVOT fractional short-ening, adds great value (11). Conventional Doppler can be used to estimate pulmonary artery systolic and mean diastolic pressure. Tei index, is used to assess the overall RV function and is calculated as the ratio between several RV Doppler parameters (15).

DTI is a relatively new echocardiographic technique, available in most modern ultrasound systems, and it allows characterisation of myocardial movement and time intervals throughout the cardiac cycle. Pulsed wave (PW) Doppler detects high velocity with low amplitudes while DTI detects low velocity with high amplitudes. Pulsed DTI is simple to use, has a high temporal resolution but a poor spatial resolution (because of movements of the heart since the sample volume is fixed). Two-dimensional color DTI (2D color DTI) is another way to measure myocardial movement and can be used off-line, giving the echocardiographer multiple choice for simulta-neous wall motion analysis, although it provides mean values compared to pulsed DTI that provides peak velocities (15).

Other ways to assess the right heart function are radionuclide tech-niques, computed tomography (CT), cardiac catheterisation and magnetic resonance imaging. These methods give accurate and good evaluation of the RV function although availability, cost and sometimes a risk of side effects makes echocardiography an attractive alternative due to its simplic-ity.

Right ventricular isovolumetric relaxation time For the early detection of an incipient RV dysfunction, the RV diastolic function (RVDF) has to be evaluated since a decrease in RVDF precedes a RV systolic dysfunction. One of the most sensitive functional markers of RV dysfunction is to measure the RV isovolumetric relaxation time (RV-IVRT) (23). The RV-IVRT is a parameter of RVDF and has been shown to correlate well to elevated pulmonary artery pressure where RV-IVRT is


prolonged (23,25). RV-IVRT is defined as the interval from the pulmonic valve closure to the start of the tricuspid valve opening (26). Since there is no good echocardiographic view from which both the pulmonic valve and the tricuspid inflow can be measured simultaneously a method based on ECG and PW Doppler can be used (27), however using this method is somewhat time consuming.

During recent years some authors have used PW-DTI when measuring RV-IVRT (20,21,23,25), a method that is easier and faster than the method based on ECG and PW Doppler. It has not been sufficiently inves-tigated, however, in patients whether the interval measured with the both methods are in fact the same.

Maximal early diastolic velocity in right ventricular long-axis direction During recent years recordings of the maximal early diastolic relaxation velocity in the LV long-axis direction obtained by echocardiographic M-mode (MDV MAM) (28-30) or tissue Doppler imaging (31-33) have been used in the assessment of LVDF. At the right side of the heart the maximal early diastolic relaxation velocity in the RV long-axis direction obtained by tissue Doppler imaging (MDV TDI) has been found to have a fairly good correlation with other diastolic parameters of the RV such as transtricuspid E wave and transtricuspid E/A waves ratios (34). In accordance with the findings on the left side of the heart MDV TDI has been found to decrease with age and it has been suggested that this is due to deterioration in the diastolic properties of the myocardium of the ventricles with age (34,35).

As mentioned earlier it is of great importance to have simple tools to evaluate RVDF. In the same way as MDV MAM has been used in the as-sessment of LVDF, it has been suggested that the maximal early diastolic relaxation velocity in the long-axis direction of the RV obtained by M-mode echocardiography (MDV TAM) can be an index of RVDF (36). This method is based on M-mode, which is one of the oldest echocardiographic techniques and is available on all ultrasound systems while TDI is a rela-tively new technique that might not be available on older echocardio-graphs. Since both indices are measuring the MDV there are reasons to believe that there could be a good correlation and a good agreement be-tween them. If that is the case, either technique could be used in clinical evaluation of the RVDF.

Takotsubo cardiomyopathy Takotsubo cardiomyopathy is a clinical syndrome, typically characterized by acute reversible apical LV dysfunction with acute reduced EF that suc-

cessively normalises (Fig. 1) (37,38). There are reports of atypical ta-kotsubo cardiomyopathy, for instance with inferior wall akinesia, although it is not common. The name takotsubo cardiomyopathy has its origin in Japan, where the first cases were described in the early 1990. Takotsubo means octopus trap. It was given this name because of the typical shape of the LV during ventriculogram, with a round bottom and a thin neck, re-sembling the trap in which Japanese fisherman catch octopuses (Fig. 2).

Figure 1. Echocardiographic apical four-chamber view in end-systole in a 77 year-old woman during the acute phase of takotsubo cardiomyopathy. Note the apical ballooning of the left ventricle (LV).

A typical characteristic for this syndrome is that the area of myocardium involved does not correspond to any specific coronary artery territory. Clinically at the onset of the disease the symptom is acute chest pain with ECG changes. The characteristic ECG changes associated with takotsubo cardiomyopathy are transient Q-waves, ST-segment elevation during the acute phase, which evolves into deep negative T-waves and QT interval prolongation. Cardiac enzymes are often slightly elevated. The onset of this cardiomyopathy is therefore very similar to acute myocardial infarction with the significant difference that coronary angiography shows no signifi-


cant coronary artery stenosis (39). Postmenopausal women are predomi-nated to suffer from takotsubo cardiomyopathy and the onset of the dis-ease is typically triggered by acute emotional or physiological stress event (39,40). The treatment is usually conventional medication for LV dysfunc-tion, such as angiotensin converting enzyme inhibitors and β-blockers. The prognosis seems to be good even though occasional deaths do occur. This disorder is rare with an estimated annual population incidence from 0.00006% to 0.05%. The apical ballooning usually resolves spontaneously within an average of 18 days (range 9 to 53 days) and myocardial perfu-sion studies shows that the reduced apical uptake normalises in 25 to 90 days (38-40). The main hypotheses regarding the cause of takotsubo car-diomyopathy are catecholamine cardiotoxicity and neurogenic stunned myocardium but the underlying pathophysiology remains unclear (39). Figure 2. Left ventriculogram in 30 degrees right ante-

rior oblique view of the same patient as in figure 1.

Earlier echocardiographic studies have mainly focused on the LV func-

tion, although RV apical involvement can also occur (39,41). There are very few reports of systolic long-axis function of the LV and

the RV, to our knowledge there is only one study dealing with takotsubo cardiomyopathy and mitral annulus motion (MAM) (38) and no study dealing with TAM.

1KARIN LOISKE Echocardio 9graphic measurements of the heart

cessively normalises (Fig. 1) (37,38). There are reports of atypical ta-kotsubo cardiomyopathy, for instance with inferior wall akinesia, although it is not common. The name takotsubo cardiomyopathy has its origin in Japan, where the first cases were described in the early 1990. Takotsubo means octopus trap. It was given this name because of the typical shape of the LV during ventriculogram, with a round bottom and a thin neck, re-sembling the trap in which Japanese fisherman catch octopuses (Fig. 2).

Figure 1. Echocardiographic apical four-chamber view in end-systole in a 77 year-old woman during the acute phase of takotsubo cardiomyopathy. Note the apical ballooning of the left ventricle (LV).

A typical characteristic for this syndrome is that the area of myocardium involved does not correspond to any specific coronary artery territory. Clinically at the onset of the disease the symptom is acute chest pain with ECG changes. The characteristic ECG changes associated with takotsubo cardiomyopathy are transient Q-waves, ST-segment elevation during the acute phase, which evolves into deep negative T-waves and QT interval prolongation. Cardiac enzymes are often slightly elevated. The onset of this cardiomyopathy is therefore very similar to acute myocardial infarction with the significant difference that coronary angiography shows no signifi-


cant coronary artery stenosis (39). Postmenopausal women are predomi-nated to suffer from takotsubo cardiomyopathy and the onset of the dis-ease is typically triggered by acute emotional or physiological stress event (39,40). The treatment is usually conventional medication for LV dysfunc-tion, such as angiotensin converting enzyme inhibitors and β-blockers. The prognosis seems to be good even though occasional deaths do occur. This disorder is rare with an estimated annual population incidence from 0.00006% to 0.05%. The apical ballooning usually resolves spontaneously within an average of 18 days (range 9 to 53 days) and myocardial perfu-sion studies shows that the reduced apical uptake normalises in 25 to 90 days (38-40). The main hypotheses regarding the cause of takotsubo car-diomyopathy are catecholamine cardiotoxicity and neurogenic stunned myocardium but the underlying pathophysiology remains unclear (39). Figure 2. Left ventriculogram in 30 degrees right ante-

rior oblique view of the same patient as in figure 1.

Earlier echocardiographic studies have mainly focused on the LV func-

tion, although RV apical involvement can also occur (39,41). There are very few reports of systolic long-axis function of the LV and

the RV, to our knowledge there is only one study dealing with takotsubo cardiomyopathy and mitral annulus motion (MAM) (38) and no study dealing with TAM.



AIMS OF THE THESIS

To investigate if there is a significant difference in size of RVOT1 using different methods, described in literature, to measure it. A sec-ond objective is to evaluate if there actually is a significant differ-ence in size of RVOT1 due to body position.

To compare RV-IVRT measured with the method based on ECG and PW Doppler with RV-IVRT measured with PW-DTI and to try to explain any eventual difference.

To compare RV MDV TDI with MDV TAM.

To investigate biventricular changes in systolic long-axis and dia-stolic function between the acute phase and the recovery phase of a specific disease, takotsubo cardiomyopathy.


AIMS OF THE THESIS

To investigate if there is a significant difference in size of RVOT1 using different methods, described in literature, to measure it. A sec-ond objective is to evaluate if there actually is a significant differ-ence in size of RVOT1 due to body position.

To compare RV-IVRT measured with the method based on ECG and PW Doppler with RV-IVRT measured with PW-DTI and to try to explain any eventual difference.

To compare RV MDV TDI with MDV TAM.

To investigate biventricular changes in systolic long-axis and dia-stolic function between the acute phase and the recovery phase of a specific disease, takotsubo cardiomyopathy.


SUBJECTS AND METHODS

SUBJECTS Study I 27 healthy subjects, mean age 25±4 years, were included. They had a nor-mal ECG and no history of cardiac disease.

Studies II and III In study II, 20 consecutive patients, mean age 63±13 years, referred to echocardiography, were included. Since earlier studies have shown pro-longed RV-IVRT in patients with hypertrophic cardiomyopathy (42), pa-tients with LV wall thickness >14 mm were not included nor patients with atrial fibrillation, bundle branch block, pacemaker treatment or a history of cardiac surgery since the effect of RV-IVRT has not been sufficiently investigated in these cases.

In study III, 29 consecutive patients, mean age 56±15 years, referred to echocardiography, were included. Patients with atrial fibrillation, bundle branch block, pacemaker treatment or a history of cardiac surgery were not included. The number of patients, in studies II and III, with diseases that might influence the heart, is presented in Table 1.

Study IV In this prospective study all consecutive patients between January 2008 and March 2010 admitted to acute coronary angiography, suspected of having ST-elevation myocardial infarction, were screened for takotsubo cardiomyopathy if no angiographically significant stenosis was seen in the coronary angiogram. The definition of takotsubo cardiomyopathy was chest pain discomfort, ECG changes (ST-elevation, ST-depression, negative T-waves or Q-waves), no significant angiographic stenosis (≥50% visual estimate) on coronary angiogram and apical dysfunction on contrast left ventriculogram in 30 degrees right anterior oblique view. In the screening period 16 patients fulfilled inclusion criteria and 13 patients (all women), mean age 68±10 years, were willing to participate in the study. Echocardi-ography was performed within 24 hours after admission (acute phase) and repeated after about three months (recovery phase).

No patient had a history of cardiac disease except for one who had pre-viously suffered from arrhythmia and had received a pacemaker.


SUBJECTS AND METHODS

SUBJECTS Study I 27 healthy subjects, mean age 25±4 years, were included. They had a nor-mal ECG and no history of cardiac disease.

Studies II and III In study II, 20 consecutive patients, mean age 63±13 years, referred to echocardiography, were included. Since earlier studies have shown pro-longed RV-IVRT in patients with hypertrophic cardiomyopathy (42), pa-tients with LV wall thickness >14 mm were not included nor patients with atrial fibrillation, bundle branch block, pacemaker treatment or a history of cardiac surgery since the effect of RV-IVRT has not been sufficiently investigated in these cases.

In study III, 29 consecutive patients, mean age 56±15 years, referred to echocardiography, were included. Patients with atrial fibrillation, bundle branch block, pacemaker treatment or a history of cardiac surgery were not included. The number of patients, in studies II and III, with diseases that might influence the heart, is presented in Table 1.

Study IV In this prospective study all consecutive patients between January 2008 and March 2010 admitted to acute coronary angiography, suspected of having ST-elevation myocardial infarction, were screened for takotsubo cardiomyopathy if no angiographically significant stenosis was seen in the coronary angiogram. The definition of takotsubo cardiomyopathy was chest pain discomfort, ECG changes (ST-elevation, ST-depression, negative T-waves or Q-waves), no significant angiographic stenosis (≥50% visual estimate) on coronary angiogram and apical dysfunction on contrast left ventriculogram in 30 degrees right anterior oblique view. In the screening period 16 patients fulfilled inclusion criteria and 13 patients (all women), mean age 68±10 years, were willing to participate in the study. Echocardi-ography was performed within 24 hours after admission (acute phase) and repeated after about three months (recovery phase).

No patient had a history of cardiac disease except for one who had pre-viously suffered from arrhythmia and had received a pacemaker.

Table 1. Number of patients with diseases, in studies II (n=20) and III (n=29), which might influence the heart.

Disease Number of patients study II

Number of patients study III

No disease 7 13 Solely hypertension 7 5 Solely myocardial infarction 1 3 Solely diabetes mellitus 0 1 Solely angina pectoris 0 1 History of pulmonary embolism 0 1 Hypertension and history of pulmonary embolism

1 0

Hypertension and diabetes mellitus

1 0

Angina pectoris and myocardial infarction

1 2

Angina pectoris and diabetes mellitus

0 1

Angina pectoris and hypertension

0 1

Angina pectoris, hypertension and myocardial infarction

0 1

Angina pectoris, myocardial infarction and diabetes mellitus

1 0

Angina pectoris, hypertension, myocardial infarction and diabetes mellitus

1 0



METHODS

ECHOCARDIOGRAPHIC EXAMINATION Study I. Echocardiography was performed using a Vivid 7 system (GE Vingmed Ultrasound A/S Horten, Norway) equipped with a multifre-quency phased array transducer (M3S, 1.5-4.0 MHz). Measurements were made after the examination using stored images in an Echopac (GE Ving-med Ultrasound A/S) Compaq DeskPro Workstation 300 (Compac Com-puter Corporation, Houston, Tx, USA).

Studies II and III. Echocardiography was performed using an Acuson As-pen system (Siemens-Acuson Co., Mountain View, CA, USA) equipped with PW-DTI technology and variable frequency phased array transducers (4V2c and 3V2c). All measurements were made on screen during the ex-amination. Study IV. Echocardiography was performed using a Vivid 7 system (GE Vingmed Ultrasound A/S, Horten, Norway) equipped with a multifre-quency phased array transducer (M3S 1.5-4.0 MHz) and PW-DTI technol-ogy. Measurements were made after the examination using stored images in an Echopac (GE Vingmed Ultrasound A/S) Compaq DeskPro Work-station 300 (Compac Computer Corporation, Houston, Tx, USA). The average time between the echocardiographic examination at the acute and recovery phase was 12.9±1.0 weeks. In all the studies the measurements were made at the end of expiration in the left lateral decubitus position except for study I in which, in addition, measurements were also performed in the supine decubitus position. All patients or subjects were in sinus rhythm.

Table 1. Number of patients with diseases, in studies II (n=20) and III (n=29), which might influence the heart.

Disease Number of patients study II

Number of patients study III

No disease 7 13 Solely hypertension 7 5 Solely myocardial infarction 1 3 Solely diabetes mellitus 0 1 Solely angina pectoris 0 1 History of pulmonary embolism 0 1 Hypertension and history of pulmonary embolism

1 0

Hypertension and diabetes mellitus

1 0

Angina pectoris and myocardial infarction

1 2

Angina pectoris and diabetes mellitus

0 1

Angina pectoris and hypertension

0 1

Angina pectoris, hypertension and myocardial infarction

0 1

Angina pectoris, myocardial infarction and diabetes mellitus

1 0

Angina pectoris, hypertension, myocardial infarction and diabetes mellitus

1 0



METHODS

ECHOCARDIOGRAPHIC EXAMINATION Study I. Echocardiography was performed using a Vivid 7 system (GE Vingmed Ultrasound A/S Horten, Norway) equipped with a multifre-quency phased array transducer (M3S, 1.5-4.0 MHz). Measurements were made after the examination using stored images in an Echopac (GE Ving-med Ultrasound A/S) Compaq DeskPro Workstation 300 (Compac Com-puter Corporation, Houston, Tx, USA).

Studies II and III. Echocardiography was performed using an Acuson As-pen system (Siemens-Acuson Co., Mountain View, CA, USA) equipped with PW-DTI technology and variable frequency phased array transducers (4V2c and 3V2c). All measurements were made on screen during the ex-amination. Study IV. Echocardiography was performed using a Vivid 7 system (GE Vingmed Ultrasound A/S, Horten, Norway) equipped with a multifre-quency phased array transducer (M3S 1.5-4.0 MHz) and PW-DTI technol-ogy. Measurements were made after the examination using stored images in an Echopac (GE Vingmed Ultrasound A/S) Compaq DeskPro Work-station 300 (Compac Computer Corporation, Houston, Tx, USA). The average time between the echocardiographic examination at the acute and recovery phase was 12.9±1.0 weeks. In all the studies the measurements were made at the end of expiration in the left lateral decubitus position except for study I in which, in addition, measurements were also performed in the supine decubitus position. All patients or subjects were in sinus rhythm.


2D/M-mode echocardiography Echocardiographic techniques and calculations of different cardiac dimen-sions in study I-IV were performed in accordance with the recommenda-tions of The American Society of Echocardiography Committee (16,43,44).

LV EF was measured using the Teichholz method (study I) and the bi-plane Simpson’s method (45) (study II-IV).

As a measure of RV systolic function TAM was measured from the RV atrioventricular plane at the basal lateral site in the apical four-chamber view from M-mode recordings (46,47) (study I-IV). The size of the RV was measured one-third from the base of the RV, RVIT3 (14,47) (study II-IV). In study IV RVOT1 was measured according to Foale et al. (8).

In study I the measurements of RVOT1 were performed from the parasternal long-axis view. The different ways of measuring RVOT1 from this view were at site “b” from the 2D-image (Fig 3.) and from the M-mode image (8,9) (Fig. 4), at site “a” from the 2D-image (13,18) (Fig. 5) and from the M-mode image (16,17) (Fig. 6). RVOT1 in the short-axis projection has in earlier studies, to the best of our knowledge, been meas-ured only by using 2D-images, except for Lindqvist et al. (11), who focused on the RV function (RVOT fractional shortening) and not the size of the RV, which is why it was only measured with this method in the present study (14) (Fig. 7).


Figure 4. RVOT1 measured in the paraster-nal long-axis view in the M-mode image according to site b (8,9).

Figure 3. RVOT1 measured in the paraster-nal long-axis view from the 2D-image ac-cording to site b (8,9).

Figure 6. RVOT1 measured in the paraster-nal long-axis view from the M-mode image according to site a (16,17).

Figure 5. RVOT1 measured in the paraster-nal long-axis view from the 2D-image ac-cording to site a (13,18).

Figure 7. RVOT1 measured in the parasternal short-axis view from the 2D-image (14).


2D/M-mode echocardiography Echocardiographic techniques and calculations of different cardiac dimen-sions in study I-IV were performed in accordance with the recommenda-tions of The American Society of Echocardiography Committee (16,43,44).

LV EF was measured using the Teichholz method (study I) and the bi-plane Simpson’s method (45) (study II-IV).

As a measure of RV systolic function TAM was measured from the RV atrioventricular plane at the basal lateral site in the apical four-chamber view from M-mode recordings (46,47) (study I-IV). The size of the RV was measured one-third from the base of the RV, RVIT3 (14,47) (study II-IV). In study IV RVOT1 was measured according to Foale et al. (8).

In study I the measurements of RVOT1 were performed from the parasternal long-axis view. The different ways of measuring RVOT1 from this view were at site “b” from the 2D-image (Fig 3.) and from the M-mode image (8,9) (Fig. 4), at site “a” from the 2D-image (13,18) (Fig. 5) and from the M-mode image (16,17) (Fig. 6). RVOT1 in the short-axis projection has in earlier studies, to the best of our knowledge, been meas-ured only by using 2D-images, except for Lindqvist et al. (11), who focused on the RV function (RVOT fractional shortening) and not the size of the RV, which is why it was only measured with this method in the present study (14) (Fig. 7).


Figure 4. RVOT1 measured in the paraster-nal long-axis view in the M-mode image according to site b (8,9).

Figure 3. RVOT1 measured in the paraster-nal long-axis view from the 2D-image ac-cording to site b (8,9).

Figure 6. RVOT1 measured in the paraster-nal long-axis view from the M-mode image according to site a (16,17).

Figure 5. RVOT1 measured in the paraster-nal long-axis view from the 2D-image ac-cording to site a (13,18).

Figure 7. RVOT1 measured in the parasternal short-axis view from the 2D-image (14).

In studies III and IV MDV TAM was measured from the basal lateral cor-ner of the RV in the apical four-chamber view. The steepest portion of the M-mode curve in early diastole was identified and measured. The inclina-tion of the dotted line represents MDV TAM (mm s-1) (36) (Fig. 8). In study IV MDV MAM was measured in the same way but from the lateral corner of the LV (29).


Figure 8. The maximal early diastolic velocity in the long-axis direction of the right ventricle (RV) obtained by M-mode echo-cardiography (MDV TAM) was measured from the basal lateral corner of the RV in the apical four-chamber view. The steepest portion of the M-mode curve in early diastole was identified and measured. The inclination of the dotted line represents MDV TAM (mm s-1).

In study IV M-mode measurements of the amplitude of MAM were per-

formed from four sites situated about 90 degrees apart according to Höglund et al. (48). Recordings from the septal and lateral part of the mi-tral annulus were obtained from the apical four-chamber view (Fig. 1) and recordings from the inferior and anterior parts from the apical two-chamber view. MAM was calculated as the average of four sites. The lead-ing edge technique was used.

In the same study the length of the LV was measured in end-diastole from the epicardial apex to the septal and lateral site of the mitral annulus. The end-diastolic and end-systolic diameter of the LV basal part was measured. The widest part of the LV in end-diastole was also measured.

The length of the RV was measured in end-diastole from the epicardial apex to the septal and lateral site of the tricuspid annulus.

Doppler echocardiography The PW-Doppler examinations were performed at a transducer frequency of 2 MHz and the PW gate was set at 3 mm. PW-Doppler mitral and tri-cuspid diastolic flow velocities were recorded from the apical four-chamber view by placing the sample volume between the leaflet tips in the center of the flow stream. The transmitral and transtricuspid peak rapid filling ve-locity (E), peak atrial filling velocity (A), E-wave deceleration time and E/A ratio were measured (study IV).

The LV-IVRT using PW-Doppler was recorded from the apical four-chamber view by simultaneous recording of the aortic and mitral flows (study IV).

The RV-IVRT using PW-Doppler was measured as described by Lar-razet et al. (27) (Figs. 9 and 10): the time from the R wave on the ECG to the end of the pulmonic flow (R-P) was measured from the parasternal short-axis view at the level of the aortic orifice for pulmonic flow velocity recording. The apical four-chamber view was used for measuring the time from the R wave on the ECG to the onset of tricuspid flow (R-T). The sample volume was located at the central part of the tricuspid annulus at the tips of the tricuspid leaflets. RV-IVRT was calculated as [(R-T)-(R-P)]. The measurements were performed almost at the same heart rate (R-R-interval) for each patient (study II and IV).


Figure 9. PW-Doppler was used to measure the time (R-P) from the R wave on the ECG to the end of the pulmonic flow (PV) from the parasternal short-axis view.

Figure 10. PW-Doppler was used to measure the time (R-T) from the R wave on the ECG to the onset of the early diastolic wave (E) of the tricuspid flow from an apical four-chamber view. A=atrial contraction.

In studies III and IV MDV TAM was measured from the basal lateral cor-ner of the RV in the apical four-chamber view. The steepest portion of the M-mode curve in early diastole was identified and measured. The inclina-tion of the dotted line represents MDV TAM (mm s-1) (36) (Fig. 8). In study IV MDV MAM was measured in the same way but from the lateral corner of the LV (29).


Figure 8. The maximal early diastolic velocity in the long-axis direction of the right ventricle (RV) obtained by M-mode echo-cardiography (MDV TAM) was measured from the basal lateral corner of the RV in the apical four-chamber view. The steepest portion of the M-mode curve in early diastole was identified and measured. The inclination of the dotted line represents MDV TAM (mm s-1).

In study IV M-mode measurements of the amplitude of MAM were per-

formed from four sites situated about 90 degrees apart according to Höglund et al. (48). Recordings from the septal and lateral part of the mi-tral annulus were obtained from the apical four-chamber view (Fig. 1) and recordings from the inferior and anterior parts from the apical two-chamber view. MAM was calculated as the average of four sites. The lead-ing edge technique was used.

In the same study the length of the LV was measured in end-diastole from the epicardial apex to the septal and lateral site of the mitral annulus. The end-diastolic and end-systolic diameter of the LV basal part was measured. The widest part of the LV in end-diastole was also measured.


Doppler echocardiography The PW-Doppler examinations were performed at a transducer frequency of 2 MHz and the PW gate was set at 3 mm. PW-Doppler mitral and tri-cuspid diastolic flow velocities were recorded from the apical four-chamber view by placing the sample volume between the leaflet tips in the center of the flow stream. The transmitral and transtricuspid peak rapid filling ve-locity (E), peak atrial filling velocity (A), E-wave deceleration time and E/A ratio were measured (study IV).

The LV-IVRT using PW-Doppler was recorded from the apical four-chamber view by simultaneous recording of the aortic and mitral flows (study IV).

The RV-IVRT using PW-Doppler was measured as described by Lar-razet et al. (27) (Figs. 9 and 10): the time from the R wave on the ECG to the end of the pulmonic flow (R-P) was measured from the parasternal short-axis view at the level of the aortic orifice for pulmonic flow velocity recording. The apical four-chamber view was used for measuring the time from the R wave on the ECG to the onset of tricuspid flow (R-T). The sample volume was located at the central part of the tricuspid annulus at the tips of the tricuspid leaflets. RV-IVRT was calculated as [(R-T)-(R-P)]. The measurements were performed almost at the same heart rate (R-R-interval) for each patient (study II and IV).


Figure 9. PW-Doppler was used to measure the time (R-P) from the R wave on the ECG to the end of the pulmonic flow (PV) from the parasternal short-axis view.

Figure 10. PW-Doppler was used to measure the time (R-T) from the R wave on the ECG to the onset of the early diastolic wave (E) of the tricuspid flow from an apical four-chamber view. A=atrial contraction.


Doppler tissue imaging The PW-DTI examinations were performed at a transducer frequency of 2 MHz and the PW gate was set at 3 mm.

In study IV the velocities at the mitral annulus were measured using PW-DTI from four sites about 90 degrees apart. Recordings from the septal and lateral part of the mitral annulus were obtained from the four-chamber view (Fig. 1) and the recordings from the inferior and anterior parts from the apical two-chamber view. The parameters measured were the velocities of the myocardial systolic wave (S), the early diastolic wave (é), the atrial wave (á), the é/á ratio and the ratio between E by PW-Doppler and é by PW-DTI (E/é). The velocities were calculated as the average of the values at the four sites. Velocities at the tricuspid annulus were measured at the basal lateral part of the RV in the apical four-chamber view, the same pa-rameters measured as from the mitral annulus, except for E/é. The PW-DTI measurements of both the mitral and the tricuspid annuli were made ac-cording to Alam et al. (34). The different components of the PW DTI pat-tern are shown in Fig. 11.

The MDV TDI in study III was measured from the outer edge of the dense part of the spectral curve in accordance with the recommendations of the American Society of Echocardiography Committee (49) (Fig. 11).

The IVRT at the both annuli was also measured using PW-DTI as de-scribed by Caso et al. (23) (study II and IV). The different components of the PW-DTI pattern from the RV are shown in Fig. 12, RV-IVRT (PWDTI) was measured as the duration in milliseconds (ms) between the end of the systolic wave and the onset of the early diastolic wave. In study II the time from the R wave on the ECG to the end of the S wave (R-S) was also measured. The time from the R wave on the ECG to the onset of the early diastolic wave (R-E) was calculated as [(R-S)+(RV-IVRT(PWDTI))]. The angle to the beam was kept as small as possible because the measured ve-locities in the tissue depend on the angle between the Doppler beam and the measured tissue.


Figure 11. The maximal early diastolic velocity in long-axis direction of the right ventricle obtained by tissue Doppler imag-ing (MDV TDI) was measured from the apical four-chamber view at the basal lateral corner of the tricuspid annulus. The com-ponents of the DTI patterns are: S=myocardial systolic wave, E=early diastolic wave and A=atrial wave. MDV TDI was measured from the outer edge of the dense part of the early dia-stolic wave (horizontal white line).

Figure 12. The pattern obtained using pulsed wave Doppler tissue imaging (PW-DTI) at the basal lateral corner of the tricuspid annulus in the apical four-chamber view. S corresponds to the systolic myocardial wave, E is the early diastolic wave and A is the atrial contraction. R-S is the time in milliseconds from the R wave on the ECG to the end of the S wave and R-E is the time from the R wave on the ECG to the onset of the E wave. The interval between the two vertical lines, marked with an x repre-sents the isovolumetric relaxation time of the right ventricle (RV-IVRT(PWDTI)) measured with PW-DTI.


Doppler tissue imaging The PW-DTI examinations were performed at a transducer frequency of 2 MHz and the PW gate was set at 3 mm.

In study IV the velocities at the mitral annulus were measured using PW-DTI from four sites about 90 degrees apart. Recordings from the septal and lateral part of the mitral annulus were obtained from the four-chamber view (Fig. 1) and the recordings from the inferior and anterior parts from the apical two-chamber view. The parameters measured were the velocities of the myocardial systolic wave (S), the early diastolic wave (é), the atrial wave (á), the é/á ratio and the ratio between E by PW-Doppler and é by PW-DTI (E/é). The velocities were calculated as the average of the values at the four sites. Velocities at the tricuspid annulus were measured at the basal lateral part of the RV in the apical four-chamber view, the same pa-rameters measured as from the mitral annulus, except for E/é. The PW-DTI measurements of both the mitral and the tricuspid annuli were made ac-cording to Alam et al. (34). The different components of the PW DTI pat-tern are shown in Fig. 11.

The MDV TDI in study III was measured from the outer edge of the dense part of the spectral curve in accordance with the recommendations of the American Society of Echocardiography Committee (49) (Fig. 11).

The IVRT at the both annuli was also measured using PW-DTI as de-scribed by Caso et al. (23) (study II and IV). The different components of the PW-DTI pattern from the RV are shown in Fig. 12, RV-IVRT (PWDTI) was measured as the duration in milliseconds (ms) between the end of the systolic wave and the onset of the early diastolic wave. In study II the time from the R wave on the ECG to the end of the S wave (R-S) was also measured. The time from the R wave on the ECG to the onset of the early diastolic wave (R-E) was calculated as [(R-S)+(RV-IVRT(PWDTI))]. The angle to the beam was kept as small as possible because the measured ve-locities in the tissue depend on the angle between the Doppler beam and the measured tissue.


Figure 11. The maximal early diastolic velocity in long-axis direction of the right ventricle obtained by tissue Doppler imag-ing (MDV TDI) was measured from the apical four-chamber view at the basal lateral corner of the tricuspid annulus. The com-ponents of the DTI patterns are: S=myocardial systolic wave, E=early diastolic wave and A=atrial wave. MDV TDI was measured from the outer edge of the dense part of the early dia-stolic wave (horizontal white line).

Figure 12. The pattern obtained using pulsed wave Doppler tissue imaging (PW-DTI) at the basal lateral corner of the tricuspid annulus in the apical four-chamber view. S corresponds to the systolic myocardial wave, E is the early diastolic wave and A is the atrial contraction. R-S is the time in milliseconds from the R wave on the ECG to the end of the S wave and R-E is the time from the R wave on the ECG to the onset of the E wave. The interval between the two vertical lines, marked with an x repre-sents the isovolumetric relaxation time of the right ventricle (RV-IVRT(PWDTI)) measured with PW-DTI.


In study IV the velocities at the mitral and tricuspid annuli were also meas-ured with 2D color TDI in the same way as described with PW-DTI. The measurements were made from the peak point of the systolic curve and from the lowest point of the early diastolic and late diastolic curves, respec-tively, in accordance with Nikitin et al. (35). When measuring the peak systolic velocities, the initial peak, which is observed during the isometric ventricular contraction, was ignored. The IVRT at the both annuli was also measured using 2D color TDI as described by Lind et al. (50).

Reproducibility of the measurements Reproducibility of measurements was investigated by repeating measure-ments by the same investigator (A), intraobserver, and independently by a second investigator (B), interobserver. Investigator A first implemented the measurements on screen during the examination and then investigator B (blinded from the measurements of investigator A) measured the same parameters in the same way. Investigator A then performed the same pro-cedure again. The intra- and interobserver reproducibilities were examined in:

10 of the subjects in study I in which RVOT1 according to Figs. 3-7 were measured with the subject in the left lateral decubitus posi-tion and in the supine decubitus position.

12 new subjects in study II in which R-T and R-P (R-T–R-P=RV-IVRT) and RV-IVRT(PWDTI) were measured.

11 of the patients in study III in which MDVTAM and MDVTDI were measured.

Statistics All data was analyzed using SPSS statistical software (versions 10.0, 12.0.1, 16.0 and 17.0 respectively, SPSS Inc., Chicago, IL, USA). All values are given as mean ± SD. A difference at the 5% level was regarded as sig-nificant.

The paired sampled t-test was used to compare the difference between the parameters in papers II-III. This test was also used to compare the dif-ference between body positions in paper I.

Bland-Altman diagrams were used in papers II and III to evaluate the agreement (51).

The Pearson’s correlation coefficient was used for analyses of linear cor-relation between different variables in study III. The two-tailed t-test was used to determine whether correlations were statistically significant.


ANOVA for repeated measurements, General Linear Model (GLM), was used to compare the difference between several groups in study I. Post hoc test was performed using the Bonferroni correction.

The Wilcoxon signed-rank test was used to test for differences between the acute and recovery phases in study IV as some of the parameters were found not to be normally distributed.

The reproducibility of measurements, an estimate of agreement, was ob-tained by using Pearson’s intraclass correlation coefficient, r (52), in studies I-III. The coefficient has a range from -1.0 to +1.0 with high positive values indicating high agreement, negative values indicating disagreement.

Ethics All studies were approved by the regional ethical committee. Informed consent was obtained from each participant. In study IV the patients also gave written consent.


In study IV the velocities at the mitral and tricuspid annuli were also meas-ured with 2D color TDI in the same way as described with PW-DTI. The measurements were made from the peak point of the systolic curve and from the lowest point of the early diastolic and late diastolic curves, respec-tively, in accordance with Nikitin et al. (35). When measuring the peak systolic velocities, the initial peak, which is observed during the isometric ventricular contraction, was ignored. The IVRT at the both annuli was also measured using 2D color TDI as described by Lind et al. (50).

Reproducibility of the measurements Reproducibility of measurements was investigated by repeating measure-ments by the same investigator (A), intraobserver, and independently by a second investigator (B), interobserver. Investigator A first implemented the measurements on screen during the examination and then investigator B (blinded from the measurements of investigator A) measured the same parameters in the same way. Investigator A then performed the same pro-cedure again. The intra- and interobserver reproducibilities were examined in:

10 of the subjects in study I in which RVOT1 according to Figs. 3-7 were measured with the subject in the left lateral decubitus posi-tion and in the supine decubitus position.

12 new subjects in study II in which R-T and R-P (R-T–R-P=RV-IVRT) and RV-IVRT(PWDTI) were measured.

11 of the patients in study III in which MDVTAM and MDVTDI were measured.

Statistics All data was analyzed using SPSS statistical software (versions 10.0, 12.0.1, 16.0 and 17.0 respectively, SPSS Inc., Chicago, IL, USA). All values are given as mean ± SD. A difference at the 5% level was regarded as sig-nificant.

The paired sampled t-test was used to compare the difference between the parameters in papers II-III. This test was also used to compare the dif-ference between body positions in paper I.

Bland-Altman diagrams were used in papers II and III to evaluate the agreement (51).

The Pearson’s correlation coefficient was used for analyses of linear cor-relation between different variables in study III. The two-tailed t-test was used to determine whether correlations were statistically significant.


ANOVA for repeated measurements, General Linear Model (GLM), was used to compare the difference between several groups in study I. Post hoc test was performed using the Bonferroni correction.

The Wilcoxon signed-rank test was used to test for differences between the acute and recovery phases in study IV as some of the parameters were found not to be normally distributed.

The reproducibility of measurements, an estimate of agreement, was ob-tained by using Pearson’s intraclass correlation coefficient, r (52), in studies I-III. The coefficient has a range from -1.0 to +1.0 with high positive values indicating high agreement, negative values indicating disagreement.

Ethics All studies were approved by the regional ethical committee. Informed consent was obtained from each participant. In study IV the patients also gave written consent.

RESULTS

Echocardiographic measurements of the right ventricle: RVOT1 The diameters of RVOT1 measured at site a and b were compared with each other, both from 2D-images, when using M-mode and from the two body positions. There was found to be an overall significant difference (p<0.001) between the diameters of RVOT1 measured at site a and b, with the diameters measured at site b being higher than those measured at site a (30.9±5.7 mm vs. 24.2±5.4 mm).

A comparing of the diameters of RVOT1 at sites a and b measured with 2D and M-mode, respectively, also shows an overall significant difference (p<0.001) between both methods (Table 2). There was also an overall sig-nificant difference when comparing the different body positions, (p=0.001) (Table 2).

The two-way interaction between the different sites and methods was also statistically significant (p<0.001), as was the interaction between the sites and body positions (p=0.022). There was no significant difference between the methods and body positions (p=0.290). Three-way interaction between the different sites, methods and body positions did not show any significant difference (p=0.270) (Table 2).

Table 2. ANOVA for repeated measurements of RVOT1 at two different sites, a and b, measured with different methods, 2D and M-mode, in different body positions. Left=left lateral decubitus position, supine=supine decubitus position.

1. Main effects Site (a/b) p<0.001 Method (2D/M-mode) p<0.001 Body position (left/supine) p=0.001 2. Two-way interaction Site/method p<0.001 Site/position p=0.022 Method/position p=0.290 3. Three way interaction Site/method/position p=0.270


RESULTS

Echocardiographic measurements of the right ventricle: RVOT1 The diameters of RVOT1 measured at site a and b were compared with each other, both from 2D-images, when using M-mode and from the two body positions. There was found to be an overall significant difference (p<0.001) between the diameters of RVOT1 measured at site a and b, with the diameters measured at site b being higher than those measured at site a (30.9±5.7 mm vs. 24.2±5.4 mm).

A comparing of the diameters of RVOT1 at sites a and b measured with 2D and M-mode, respectively, also shows an overall significant difference (p<0.001) between both methods (Table 2). There was also an overall sig-nificant difference when comparing the different body positions, (p=0.001) (Table 2).

The two-way interaction between the different sites and methods was also statistically significant (p<0.001), as was the interaction between the sites and body positions (p=0.022). There was no significant difference between the methods and body positions (p=0.290). Three-way interaction between the different sites, methods and body positions did not show any significant difference (p=0.270) (Table 2).

Table 2. ANOVA for repeated measurements of RVOT1 at two different sites, a and b, measured with different methods, 2D and M-mode, in different body positions. Left=left lateral decubitus position, supine=supine decubitus position.

1. Main effects Site (a/b) p<0.001 Method (2D/M-mode) p<0.001 Body position (left/supine) p=0.001 2. Two-way interaction Site/method p<0.001 Site/position p=0.022 Method/position p=0.290 3. Three way interaction Site/method/position p=0.270


Comparing RVOT1 measured in the parasternal long-axis view at site a, site b and short-axis using 2D-images shows an overall significant differ-ence (p<0.001) with the highest mean at site b (31.4±5.8 mm vs. short-axis 29.5±5.6 mm and site a 27.4±4.6 mm) (Table 3). There was also an overall significant difference (p=0.013) between RVOT1 measured using 2D at the three different sites and the body positions (Table 3).

The two-way interaction between the sites and the body positions was also shown to be statistically significant (p=0.042) (Table 3).

Table 3. ANOVA for repeated measurements of RVOT1, using 2D at three dif-ferent sites (a, b and short-axis) and in different body positions. Left=left lateral decubitus position, supine=supine decubitus position.

1. Main effects Site (a, b and short-axis) p<0.001 Position (left versus supine) p=0.013 2. Two-way interaction Site/position p=0.042

Pair wise comparisons using post hoc test (Bonferroni correction) of ANOVA between the three different sites also showed significant differ-ences (a vs. b p<0.001, a vs. short-axis p=0.009 and b vs. short-axis p<0.001).

Comparing RVOT1 at the three different sites with the two body positions There was no significant difference in RVOT1 measured from the parast-ernal long-axis view from 2D-image or with M-mode according to site b in the left lateral decubitus position versus the supine decubitus position (p=0.28 and p=0.27). Nor was there any significant difference in RVOT1 measured from the parasternal short-axis view from the 2D-image in the left lateral decubitus position versus the supine decubitus position (p=0.43).

There was, however, a significant difference between the left lateral decubitus position and the supine decubitus position in RVOT1 measured from the parasternal long-axis view according to site a, from the 2D-image (p=0.01) and with M-mode (p=0.01).


Two parameters to evaluate right ventricular diastolic function

Right ventricular isovolumetric relaxation time There was a significant difference (p<0.001) between RV-IVRT (measured with the method based on ECG and PW-Doppler) and RV-IVRT(PWDTI) (15.0±10.1 ms vs. 48.5±30.2 ms). The agreement between RV-IVRT and RV-IVRT(PWDTI) is shown in Fig. 13.

A significant difference (p<0.001) was found between the time from the R wave to the end of the pulmonic flow (R-P) with PW-Doppler (387.3±40.7 ms) and the time from the R wave on the ECG to the end of the S wave (R-S) with PW-DTI (348.0±41.0 ms). There was no significant difference between the time from the R wave on the ECG to the onset of the tricuspid flow (R-T) with PW-Doppler (402.3±37.1 ms) and the time from the R wave on the ECG to the onset of the early diastolic wave (R-E) with PW-DTI (396.5±44.9 ms).

Figure 13. Bland-Altman diagram showing the agreement, or rather disagreement, between the right ventricular isovolu-metric relaxation time (IVRT) measured in milliseconds (ms) obtained by the method based on ECG and pulsed wave Doppler (PW) and the method based on pulsed wave Dop-pler tissue imaging (PWDTI) (n=20).


Comparing RVOT1 measured in the parasternal long-axis view at site a, site b and short-axis using 2D-images shows an overall significant differ-ence (p<0.001) with the highest mean at site b (31.4±5.8 mm vs. short-axis 29.5±5.6 mm and site a 27.4±4.6 mm) (Table 3). There was also an overall significant difference (p=0.013) between RVOT1 measured using 2D at the three different sites and the body positions (Table 3).

The two-way interaction between the sites and the body positions was also shown to be statistically significant (p=0.042) (Table 3).

Table 3. ANOVA for repeated measurements of RVOT1, using 2D at three dif-ferent sites (a, b and short-axis) and in different body positions. Left=left lateral decubitus position, supine=supine decubitus position.

1. Main effects Site (a, b and short-axis) p<0.001 Position (left versus supine) p=0.013 2. Two-way interaction Site/position p=0.042

Pair wise comparisons using post hoc test (Bonferroni correction) of ANOVA between the three different sites also showed significant differ-ences (a vs. b p<0.001, a vs. short-axis p=0.009 and b vs. short-axis p<0.001).

Comparing RVOT1 at the three different sites with the two body positions There was no significant difference in RVOT1 measured from the parast-ernal long-axis view from 2D-image or with M-mode according to site b in the left lateral decubitus position versus the supine decubitus position (p=0.28 and p=0.27). Nor was there any significant difference in RVOT1 measured from the parasternal short-axis view from the 2D-image in the left lateral decubitus position versus the supine decubitus position (p=0.43).

There was, however, a significant difference between the left lateral decubitus position and the supine decubitus position in RVOT1 measured from the parasternal long-axis view according to site a, from the 2D-image (p=0.01) and with M-mode (p=0.01).


Two parameters to evaluate right ventricular diastolic function

Right ventricular isovolumetric relaxation time There was a significant difference (p<0.001) between RV-IVRT (measured with the method based on ECG and PW-Doppler) and RV-IVRT(PWDTI) (15.0±10.1 ms vs. 48.5±30.2 ms). The agreement between RV-IVRT and RV-IVRT(PWDTI) is shown in Fig. 13.

A significant difference (p<0.001) was found between the time from the R wave to the end of the pulmonic flow (R-P) with PW-Doppler (387.3±40.7 ms) and the time from the R wave on the ECG to the end of the S wave (R-S) with PW-DTI (348.0±41.0 ms). There was no significant difference between the time from the R wave on the ECG to the onset of the tricuspid flow (R-T) with PW-Doppler (402.3±37.1 ms) and the time from the R wave on the ECG to the onset of the early diastolic wave (R-E) with PW-DTI (396.5±44.9 ms).

Figure 13. Bland-Altman diagram showing the agreement, or rather disagreement, between the right ventricular isovolu-metric relaxation time (IVRT) measured in milliseconds (ms) obtained by the method based on ECG and pulsed wave Doppler (PW) and the method based on pulsed wave Dop-pler tissue imaging (PWDTI) (n=20).


Maximal early diastolic velocity in right ventricular long-axis direction There was a good correlation (r=0.76; p<0.001) between MDV TAM and MDV TDI (Fig. 14).

The agreement between MDV TDI and MDV TAM is shown in Fig. 15. MDV TDI (126.7±38.9 mm s-1) was significantly (p<0.001) higher than MDV TAM (78.3±27.8 mm s-1).

Figure 14. Correlation between the maximal early diastolic velocity in the long-axis direction of the right ventricle obtained by M-mode echocardiography (MDV TAM) and tissue Doppler imaging (MDV TDI).

Figure 15. Bland-Altman diagram showing the agreement between the maximal early diastolic velocity in the long-axis direction of the right ventricle obtained by M-mode echocardiography (MDV TAM) and tissue Doppler imaging (MDV TDI) (n=29).


Reproducibility studies The intra- and interobserver reproducibilities were measured using Pear-son’s intraclass correlation coefficient and the results are presented in Ta-ble 4 for study I and Table 5 for study II and III respectively.

Table 4. The intra- and interobserver reproducibility of measuring RVOT1 from the 2D-image and M-mode according to site a and b from the parasternal long-axis view and from the 2D-image in short-axis, with the subject in the left lateral decubitus position (left) and the supine decubitus position (supine) in ten of the subjects. The agreement was measured using Pearsons’s intraclass correlation coefficient (which has a range -1.0 to +1.0, high positive values indicating high agreement, negative values indicating dis-agreement).

Agreement, single

measuments, investigator

A and B

Agreement, double

measurements, investigator A

RVOT1 measured from 2D-image, site b, left 0.94 0.95 RVOT1 measured from 2D-image, site b, supine 0.94 0.92 RVOT1 measured from M-mode, site b, left 0.91 0.90 RVOT1 measured from M-mode, site b, supine 0.92 0.94 RVOT1 measured from 2D-image, site a, left 0.88 0.95 RVOT1 measured from 2D-image, site a, supine 0.84 0.98 RVOT1 measured from M-mode, site a, left 0.35 0.79 RVOT1 measured from M-mode, site a, supine 0.48 0.86 RVOT1 measured from 2D-image, short-axis, left 0.95 0.87 RVOT1 measured from 2D-image, short-axis, supine 0.78 0.95


Maximal early diastolic velocity in right ventricular long-axis direction There was a good correlation (r=0.76; p<0.001) between MDV TAM and MDV TDI (Fig. 14).

The agreement between MDV TDI and MDV TAM is shown in Fig. 15. MDV TDI (126.7±38.9 mm s-1) was significantly (p<0.001) higher than MDV TAM (78.3±27.8 mm s-1).

Figure 14. Correlation between the maximal early diastolic velocity in the long-axis direction of the right ventricle obtained by M-mode echocardiography (MDV TAM) and tissue Doppler imaging (MDV TDI).

Figure 15. Bland-Altman diagram showing the agreement between the maximal early diastolic velocity in the long-axis direction of the right ventricle obtained by M-mode echocardiography (MDV TAM) and tissue Doppler imaging (MDV TDI) (n=29).


Reproducibility studies The intra- and interobserver reproducibilities were measured using Pear-son’s intraclass correlation coefficient and the results are presented in Ta-ble 4 for study I and Table 5 for study II and III respectively.

Table 4. The intra- and interobserver reproducibility of measuring RVOT1 from the 2D-image and M-mode according to site a and b from the parasternal long-axis view and from the 2D-image in short-axis, with the subject in the left lateral decubitus position (left) and the supine decubitus position (supine) in ten of the subjects. The agreement was measured using Pearsons’s intraclass correlation coefficient (which has a range -1.0 to +1.0, high positive values indicating high agreement, negative values indicating dis-agreement).

Agreement, single

measuments, investigator

A and B

Agreement, double

measurements, investigator A

RVOT1 measured from 2D-image, site b, left 0.94 0.95 RVOT1 measured from 2D-image, site b, supine 0.94 0.92 RVOT1 measured from M-mode, site b, left 0.91 0.90 RVOT1 measured from M-mode, site b, supine 0.92 0.94 RVOT1 measured from 2D-image, site a, left 0.88 0.95 RVOT1 measured from 2D-image, site a, supine 0.84 0.98 RVOT1 measured from M-mode, site a, left 0.35 0.79 RVOT1 measured from M-mode, site a, supine 0.48 0.86 RVOT1 measured from 2D-image, short-axis, left 0.95 0.87 RVOT1 measured from 2D-image, short-axis, supine 0.78 0.95


Table 5. The intra- and interobserver reproducibility of measuring: 1. the iso-volumetric relaxation time of the right ventricle using a method based on ECG and pulsed wave Doppler (RV-IVRT) and a method using pulsed wave Doppler tissue imaging (RV-IVRT(PWDTI)) (n=12). 2. The maximal early diastolic veloc-ity in right ventricular long-axis direction obtained by M-mode echocardiography (MDV TAM) and the maximal early diastolic velocity obtained by tissue Doppler imaging (MDV TDI) (n=11). The agreement was measured using Pearsons’s intra-class correlation coefficient (which has a range -1.0 to +1.0, high positive values indicating high agreement, negative values indicating disagreement).

Agreement, single

measurements, investigators A and B

Agreement, double measurements, investigator A

RV-IVRT 0.77 0.83 RV-IVRT(PWDTI) 0.88 0.84 MDV TAM 0.60 0.96 MDV TDI 0.80 0.94



Takotsubo cardiomyopathy

Left ventricle There was a significant difference between the amplitudes of MAM (the total of four sites) between the acute (9.6±1.0 mm) and recovery phase (11.2±1.9 mm) (p=0.02) (Table 6). There was a significant difference be-tween the different sites except for the septal site (Table 6). There was a significant difference (p<0.01) between LVEF obtained by the biplane Simpson’s method in the acute phase (53.4±9.5%) compared to the recov-ery phase (63.3±4.4%).

Both the é and á diastolic velocities as well as the S velocity measured by PW-DTI increased significantly from the acute to the recovery phase but there were no significant differences when they were measured using 2D color DTI. The S, é and á diastolic velocities were all significantly higher when measured at the acute and recovery phase using PW-DTI compared to using 2D color DTI. There was no statistically significant difference between the other measured diastolic parameters (Table 6).

There was no significant difference in the length of the LV in end-diastole from the epicardial apex to the septal or lateral sites of the mitral annulus between the acute and the recovery phase. There was also no sig-nificant difference in end-diastolic diameter, not even at the widest part of the LV, or end-systolic diameter between the two phases.

Table 5. The intra- and interobserver reproducibility of measuring: 1. the iso-volumetric relaxation time of the right ventricle using a method based on ECG and pulsed wave Doppler (RV-IVRT) and a method using pulsed wave Doppler tissue imaging (RV-IVRT(PWDTI)) (n=12). 2. The maximal early diastolic veloc-ity in right ventricular long-axis direction obtained by M-mode echocardiography (MDV TAM) and the maximal early diastolic velocity obtained by tissue Doppler imaging (MDV TDI) (n=11). The agreement was measured using Pearsons’s intra-class correlation coefficient (which has a range -1.0 to +1.0, high positive values indicating high agreement, negative values indicating disagreement).

Agreement, single

measurements, investigators A and B

Agreement, double measurements, investigator A

RV-IVRT 0.77 0.83 RV-IVRT(PWDTI) 0.88 0.84 MDV TAM 0.60 0.96 MDV TDI 0.80 0.94



Takotsubo cardiomyopathy

Left ventricle There was a significant difference between the amplitudes of MAM (the total of four sites) between the acute (9.6±1.0 mm) and recovery phase (11.2±1.9 mm) (p=0.02) (Table 6). There was a significant difference be-tween the different sites except for the septal site (Table 6). There was a significant difference (p<0.01) between LVEF obtained by the biplane Simpson’s method in the acute phase (53.4±9.5%) compared to the recov-ery phase (63.3±4.4%).

Both the é and á diastolic velocities as well as the S velocity measured by PW-DTI increased significantly from the acute to the recovery phase but there were no significant differences when they were measured using 2D color DTI. The S, é and á diastolic velocities were all significantly higher when measured at the acute and recovery phase using PW-DTI compared to using 2D color DTI. There was no statistically significant difference between the other measured diastolic parameters (Table 6).

There was no significant difference in the length of the LV in end-diastole from the epicardial apex to the septal or lateral sites of the mitral annulus between the acute and the recovery phase. There was also no sig-nificant difference in end-diastolic diameter, not even at the widest part of the LV, or end-systolic diameter between the two phases.

Table 6. Significance of difference between the acute and recovery phase of some left ven-

tricular variables (EF=ejection fraction, MAM=mitral annulus motion, PW=pulsed wave,

PW DTI=pulsed wave Doppler tissue imaging, 2D color DTI=two-dimensional color Dop-

pler tissue imaging, IVRT=isovolumetric relaxation time, S=systolic velocity, E=early dia-

stolic velocity by PW, A=late diastolic velocity by PW, é=early diastolic velocity by PW

DTI, á=late diastolic velocity by PW DTI) (n=13).

Variable Acute phase

Recovery

phase

Significance of

difference

EF (biplane Simpson’s method, %) 53.4±9.5 63.3±4.4 p<0.01

MAM, septal site (mm) 9.4±2.1 10.1±2.3 n.s.

MAM, lateral site (mm) 10.1±2.3 12.1±2.6 p<0.02

MAM, inferior site (mm) 9.9±2.8 11.6±2.0 p=0.03

MAM, anterior site (mm) 9.0±2.6 10.8±1.9 p<0.02

Total MAM (all sites, mm) 9.6±2.2 11.2±1.9 p<0.02

E/A 1.2±0.7 0.9±0.3 n.s.

Deceleration time (ms) 206.2±91.5 249.6±69.4 n.s.

IVRT by PW (ms) 91.5±19.3 90.6±17.3 n.s.

IVRT by PW-DTI (ms)* 89.4±20.0 87.1±23.0 n.s.

IVRT by 2D color DTI (ms) 65.2±17.9 66.3±16.9 n.s.

S by PW-DTI (cm/s) 5.9±1.5 7.2±1.9 p=0.02

é (cm/s) 6.5±2.6 8.2±3.3 p=0.04

á (cm/s) 7.0±2.0 8.6±2.9 p=0.04

é/á 1.1±0.8 1.1±0.7 n.s.

S by 2D color DTI (cm/s) 5.3±3.2 5.3±1.9 n.s.

é by 2D color DTI (cm/s) 4.4±2.1 6.1±3.2 n.s

á by 2D color DTI (cm/s) 5.4±1.8 6.2±2.3 n.s.

é/á by 2D color DTI 0.9±0.6 1.2±1.1 n.s.

Relaxation velocity (cm/s) 51.0±32.7 52.9±28.7 n.s.

Length in end-diastole (apex-septal site, mm) 82.2±8.5 79.1±7.7 n.s.

Length in end-diastole (apex-lateral site, mm) 86.7±8.8 83.7±8.1 n.s.

End-diastolic diameter (basal, mm) 43.7±4.6 43.1±3.2 n.s.

End-diastolic diameter (widest place, mm) 47.8±5.0 46.4±4.1 n.s

End-systolic diameter (basal, mm) 27.9±6.1 26.9±3.0 n.s.

E/é 12.6±6.5 11.9±9.6 n.s.

*one missing patient due to difficulties measuring IVRT by PW-DTI


Right ventricle There was a statistically significant difference (p=0.02) between the total amplitude of TAM in the acute phase (21.3±3.6mm) and the recovery phase (24.1±2.8mm) but no significant differences were found between the size or the length of the RV. Nor were there any significant differences of the diastolic parameters between the two phases (table 7).

Table 7. Significance of difference between the acute phase and the recovery phase of some right ventricular variables (TAM=tricuspid annulus motion, PW=pulsed wave, PW DTI=pulsed wave Doppler tissue imaging, 2D color DTI=two-dimensional color Doppler tissue imaging, IVRT=isovolumetric relaxation time; S=systolic velocity, E=early diastolic velocity by PW, A=late diastolic velocity by PW, é=early diastolic velocity by PW-DTI, á=late diastolic velocity by PW-DTI, RVOT1=right ventricular outflow tract 1, RVIT3=right ventricular inflow tract 3) (n=13).

Variable Acute phase Recovery

phase

Significance

of

difference

TAM (mm) 21.3±3.6 24.1±2.8 p=0.02

E/A 1.3±0.5 1.1±0.4 n.s.


IVRT by PW (ms) 84.8±27.5 63.4±25.6 n.s.

IVRT by PW-DTI (ms) 70.4±21.9 60.6±23.5 n.s.


S by PW-DTI (cm/s) 12.2±2.2 12.5±2.3 n.s.

é (cm/s) 11.3±3.6 11.8±2.8 n.s.

á (cm/s) 16.2±3.9 15.7±3.0 n.s.

é/á 0.7±0.2 0.8±0.4 n.s.


é by 2D color DTI (cm/s) 9.5±3.6 8.6±2.7 n.s.






RVOT1 (mm) 27.0±4.2 28.0±4.2 n.s.

RVIT3 (mm) 29.7±5.2 30.0±2.9 n.s.


Table 6. Significance of difference between the acute and recovery phase of some left ven-

tricular variables (EF=ejection fraction, MAM=mitral annulus motion, PW=pulsed wave,

PW DTI=pulsed wave Doppler tissue imaging, 2D color DTI=two-dimensional color Dop-

pler tissue imaging, IVRT=isovolumetric relaxation time, S=systolic velocity, E=early dia-

stolic velocity by PW, A=late diastolic velocity by PW, é=early diastolic velocity by PW

DTI, á=late diastolic velocity by PW DTI) (n=13).

Variable Acute phase

Recovery

phase

Significance of

difference

EF (biplane Simpson’s method, %) 53.4±9.5 63.3±4.4 p<0.01

MAM, septal site (mm) 9.4±2.1 10.1±2.3 n.s.

MAM, lateral site (mm) 10.1±2.3 12.1±2.6 p<0.02

MAM, inferior site (mm) 9.9±2.8 11.6±2.0 p=0.03

MAM, anterior site (mm) 9.0±2.6 10.8±1.9 p<0.02

Total MAM (all sites, mm) 9.6±2.2 11.2±1.9 p<0.02

E/A 1.2±0.7 0.9±0.3 n.s.


IVRT by PW (ms) 91.5±19.3 90.6±17.3 n.s.



S by PW-DTI (cm/s) 5.9±1.5 7.2±1.9 p=0.02

é (cm/s) 6.5±2.6 8.2±3.3 p=0.04

á (cm/s) 7.0±2.0 8.6±2.9 p=0.04

é/á 1.1±0.8 1.1±0.7 n.s.


é by 2D color DTI (cm/s) 4.4±2.1 6.1±3.2 n.s









E/é 12.6±6.5 11.9±9.6 n.s.

*one missing patient due to difficulties measuring IVRT by PW-DTI


Right ventricle There was a statistically significant difference (p=0.02) between the total amplitude of TAM in the acute phase (21.3±3.6mm) and the recovery phase (24.1±2.8mm) but no significant differences were found between the size or the length of the RV. Nor were there any significant differences of the diastolic parameters between the two phases (table 7).

Table 7. Significance of difference between the acute phase and the recovery phase of some right ventricular variables (TAM=tricuspid annulus motion, PW=pulsed wave, PW DTI=pulsed wave Doppler tissue imaging, 2D color DTI=two-dimensional color Doppler tissue imaging, IVRT=isovolumetric relaxation time; S=systolic velocity, E=early diastolic velocity by PW, A=late diastolic velocity by PW, é=early diastolic velocity by PW-DTI, á=late diastolic velocity by PW-DTI, RVOT1=right ventricular outflow tract 1, RVIT3=right ventricular inflow tract 3) (n=13).

Variable Acute phase Recovery

phase

Significance

of

difference

TAM (mm) 21.3±3.6 24.1±2.8 p=0.02

E/A 1.3±0.5 1.1±0.4 n.s.


IVRT by PW (ms) 84.8±27.5 63.4±25.6 n.s.



S by PW-DTI (cm/s) 12.2±2.2 12.5±2.3 n.s.

é (cm/s) 11.3±3.6 11.8±2.8 n.s.

á (cm/s) 16.2±3.9 15.7±3.0 n.s.

é/á 0.7±0.2 0.8±0.4 n.s.


é by 2D color DTI (cm/s) 9.5±3.6 8.6±2.7 n.s.






RVOT1 (mm) 27.0±4.2 28.0±4.2 n.s.

RVIT3 (mm) 29.7±5.2 30.0±2.9 n.s.



DISCUSSION

Methodological considerations Reproducibility of RVOT1 There was a good intraindividual reproducibility for most of the investi-gated parameters (table 4) except when measuring RVOT1 at site a with M-mode, which was somewhat lower. Even interindividual reproducibility was good for most of the measured parameters. The lowest interindividual reproducibility was found when measuring RVOT1 at site a with M-mode. This indicates that site a should be avoided.

One cause of the lower reproducibility at this site compared to the other sites is probably due to the absence of a reference point from which to measure. At site b, the aortic root can be used as a reference point and at the short-axis it is easier to find a reference point at the aortic root level than when measuring from site a. When RVOT1 is measured according to site a, using M-mode, there is also a risk that the M-mode line cuts the RV more apically than at the RVOT1 region. It may also be difficult to deter-mine the septal wall contour, especially in the M-mode image but also in the 2D-image, since the chordae tendinae and papillary muscles sometimes make it hard to determine the septal wall border which therefore makes it difficult to asses the border of the RV lumen.

In some cases, however, the lower interindividual reproducibility was probably due to investigator B being less experienced in measuring RVOT1 compared to investigator A.

Reproducibility of RV-IVRT and RV-IVRT(PWDTI) The reproducibility study (table 5), concerning RV-IVRT and RV-IVRT(PWDTI) indicate good intra- and interobserver reproducibility of the measurements.

Reproducibility of MDV TAM and MDV TDI The reproducibility study (table 5) indicate good intraobserver reproduci-bility in the measurement of MDV TAM and MDV TDI. There was also good interobserver reproducibility in the measurement of MDV TDI. The interobserver reproducibility in the measurement of MDV TAM was somewhat poorer. This was probably due to investigator B being less ex-perienced in measuring MDV TAM compared to investigator A. When measuring MDV TAM it is important to measure during the end of expira-


DISCUSSION

Methodological considerations Reproducibility of RVOT1 There was a good intraindividual reproducibility for most of the investi-gated parameters (table 4) except when measuring RVOT1 at site a with M-mode, which was somewhat lower. Even interindividual reproducibility was good for most of the measured parameters. The lowest interindividual reproducibility was found when measuring RVOT1 at site a with M-mode. This indicates that site a should be avoided.

One cause of the lower reproducibility at this site compared to the other sites is probably due to the absence of a reference point from which to measure. At site b, the aortic root can be used as a reference point and at the short-axis it is easier to find a reference point at the aortic root level than when measuring from site a. When RVOT1 is measured according to site a, using M-mode, there is also a risk that the M-mode line cuts the RV more apically than at the RVOT1 region. It may also be difficult to deter-mine the septal wall contour, especially in the M-mode image but also in the 2D-image, since the chordae tendinae and papillary muscles sometimes make it hard to determine the septal wall border which therefore makes it difficult to asses the border of the RV lumen.

In some cases, however, the lower interindividual reproducibility was probably due to investigator B being less experienced in measuring RVOT1 compared to investigator A.

Reproducibility of RV-IVRT and RV-IVRT(PWDTI) The reproducibility study (table 5), concerning RV-IVRT and RV-IVRT(PWDTI) indicate good intra- and interobserver reproducibility of the measurements.

Reproducibility of MDV TAM and MDV TDI The reproducibility study (table 5) indicate good intraobserver reproduci-bility in the measurement of MDV TAM and MDV TDI. There was also good interobserver reproducibility in the measurement of MDV TDI. The interobserver reproducibility in the measurement of MDV TAM was somewhat poorer. This was probably due to investigator B being less ex-perienced in measuring MDV TAM compared to investigator A. When measuring MDV TAM it is important to measure during the end of expira-


tion and to search for the steepest portion of the M-mode curve in early-diastole.

Correlation and agreement between MDV TDI and MDV TAM There was a good correlation between MDV TAM and MDV TDI (Fig. 14) indicating that MDV TAM might be used in the same way as MDV TDI in the assessment of RVDF. The agreement, however, was rather poor (Fig. 15), with MDV TDI (126.7±38.9 mm s-1) being about 60% higher (p<0.001) than MDV TAM (78.3±27.8 mm s-1). This finding is somewhat surprising as both MDV TAM and MDV TDI measure the maximal early diastolic relaxation velocity in the long-axis direction of the RV.

One reason for the difference between the MDV TDI and MDV TAM could be that the TDI technique reports instantaneous velocities, whereas the M-mode procedure implies some degree of averaging around the maximal value as a finite-length segment in the maximal slope tract must be chosen for practical reasons.

Another reason for the difference could have been that MDV TAM is measured endocardially whilst MDV TDI is measured in the myocardium more epicardially. As the spatial resolution when using MDV TDI is poor (15,53), however, the placement of the sample volume seems to be of mi-nor importance. In addition, another study (54) has shown no significant difference between the diastolic velocities of TAM measured endocardially and the diastolic velocities at two sites of the right coronary artery, which is situated epicardially.

In a study by Fornander et al. (30) it was discussed whether the differ-ence between the maximal diastolic velocities of the LV measured by M-mode echocardiography and TDI could be due to the point of the spectral curve from which the MDV TDI is measured. In accordance with guide-lines (49) it was measured by Fornander et al. as well as in study III from the outer edge of the dense part of the spectral curve. As the cells in the myocardium move together and not separately from each other (in contrast to blood velocity measurements) there is seldom a scatter of velocities and the spectral curve is often very easy to define so it is not probable that this could explain the difference found. Furthermore, a phantom study has shown overestimation of velocities by PW-DTI (55). Limitations of the studies Study I was performed on healthy subjects aged 25-35 years, with generally good quality of image and examination technique. It would be of interest to perform a similar study on patients, in which the quality of the images and examination technique are not always optimal. Patients with different


heart conditions also sometimes present anatomically deviant ventricles, which could make it more challenging to implement the measurement of RVOT1 than on healthy subjects.

In study IV there were surprisingly few diastolic parameters that im-proved between the acute phase and the recovery phase of takotsubo car-diomyopathy. Considering that both the LV and RV functions improved significantly (Tables 6 and 7) we expected an increase in the diastolic pa-rameters as well. In the LV there was only a significant difference for the early and late diastolic velocities measured by PW-DTI, both increasing from the acute to the recovery phase (Table 6). In the RV none of the dia-stolic parameters showed a significant difference (Table 7). Perhaps some of the diastolic measurements, that didn’t differ between the acute and recovery phase, would have become significant with a larger sample.

Theoretical implications RVOT1

The size of RVOT1 was measured significantly higher from site a, with the subjects in the left lateral decubitus position compared to when the subjects were in the supine decubitus position (both 2D and M-mode indi-cate this). If this difference was not due to the measuring technique, one could wonder if there is a difference in RV volume depending on body position. This would also, however, have affected RVOT1 measured from site b and short-axis, so this theory seems less probable.

There is also a risk that the RV may appear abnormal, especially from the parasternal view, in some individuals due to the position of the RV relative to the image plane and where the RV may be imaged in an oblique orientation (56). It is therefore important that the size of the RV, in addi-tion to measuring from the parasternal view, is also measured from other echocardiographic windows, such as apical four-chamber view or subcostal view.

Isovolumetric relaxation time IVRT of the RV is usually defined as the time from the closure of the pul-monic valve to the opening of the tricuspid valve (26) that is, to the onset of the tricuspid flow. The time from the R wave on the ECG to the closure of the pulmonic valve (R-P) was found to be significantly longer than the time from the R wave on the ECG to the end of the S wave (R-S), meaning that the method using PW-DTI does not measure the time from the closure of the pulmonic valve.


tion and to search for the steepest portion of the M-mode curve in early-diastole.

Correlation and agreement between MDV TDI and MDV TAM There was a good correlation between MDV TAM and MDV TDI (Fig. 14) indicating that MDV TAM might be used in the same way as MDV TDI in the assessment of RVDF. The agreement, however, was rather poor (Fig. 15), with MDV TDI (126.7±38.9 mm s-1) being about 60% higher (p<0.001) than MDV TAM (78.3±27.8 mm s-1). This finding is somewhat surprising as both MDV TAM and MDV TDI measure the maximal early diastolic relaxation velocity in the long-axis direction of the RV.

One reason for the difference between the MDV TDI and MDV TAM could be that the TDI technique reports instantaneous velocities, whereas the M-mode procedure implies some degree of averaging around the maximal value as a finite-length segment in the maximal slope tract must be chosen for practical reasons.

Another reason for the difference could have been that MDV TAM is measured endocardially whilst MDV TDI is measured in the myocardium more epicardially. As the spatial resolution when using MDV TDI is poor (15,53), however, the placement of the sample volume seems to be of mi-nor importance. In addition, another study (54) has shown no significant difference between the diastolic velocities of TAM measured endocardially and the diastolic velocities at two sites of the right coronary artery, which is situated epicardially.

In a study by Fornander et al. (30) it was discussed whether the differ-ence between the maximal diastolic velocities of the LV measured by M-mode echocardiography and TDI could be due to the point of the spectral curve from which the MDV TDI is measured. In accordance with guide-lines (49) it was measured by Fornander et al. as well as in study III from the outer edge of the dense part of the spectral curve. As the cells in the myocardium move together and not separately from each other (in contrast to blood velocity measurements) there is seldom a scatter of velocities and the spectral curve is often very easy to define so it is not probable that this could explain the difference found. Furthermore, a phantom study has shown overestimation of velocities by PW-DTI (55). Limitations of the studies Study I was performed on healthy subjects aged 25-35 years, with generally good quality of image and examination technique. It would be of interest to perform a similar study on patients, in which the quality of the images and examination technique are not always optimal. Patients with different


heart conditions also sometimes present anatomically deviant ventricles, which could make it more challenging to implement the measurement of RVOT1 than on healthy subjects.

In study IV there were surprisingly few diastolic parameters that im-proved between the acute phase and the recovery phase of takotsubo car-diomyopathy. Considering that both the LV and RV functions improved significantly (Tables 6 and 7) we expected an increase in the diastolic pa-rameters as well. In the LV there was only a significant difference for the early and late diastolic velocities measured by PW-DTI, both increasing from the acute to the recovery phase (Table 6). In the RV none of the dia-stolic parameters showed a significant difference (Table 7). Perhaps some of the diastolic measurements, that didn’t differ between the acute and recovery phase, would have become significant with a larger sample.

Theoretical implications RVOT1

The size of RVOT1 was measured significantly higher from site a, with the subjects in the left lateral decubitus position compared to when the subjects were in the supine decubitus position (both 2D and M-mode indi-cate this). If this difference was not due to the measuring technique, one could wonder if there is a difference in RV volume depending on body position. This would also, however, have affected RVOT1 measured from site b and short-axis, so this theory seems less probable.

There is also a risk that the RV may appear abnormal, especially from the parasternal view, in some individuals due to the position of the RV relative to the image plane and where the RV may be imaged in an oblique orientation (56). It is therefore important that the size of the RV, in addi-tion to measuring from the parasternal view, is also measured from other echocardiographic windows, such as apical four-chamber view or subcostal view.

Isovolumetric relaxation time IVRT of the RV is usually defined as the time from the closure of the pul-monic valve to the opening of the tricuspid valve (26) that is, to the onset of the tricuspid flow. The time from the R wave on the ECG to the closure of the pulmonic valve (R-P) was found to be significantly longer than the time from the R wave on the ECG to the end of the S wave (R-S), meaning that the method using PW-DTI does not measure the time from the closure of the pulmonic valve.


That the myocardium stops its systolic movement, which is the end of the S-wave with PW-DTI, just before the closure of the pulmonic valve is not surprising. During systole the myocardium of the RV contracts causing the pressure in the RV to rise. When the pressure in the pulmonary artery is exceeded the pulmonic valve opens and blood can flow into the pulmo-nary artery. As the myocardium starts to relax the pressure in the RV falls and at the end of systole, that is, at the end of the S wave, when the pres-sure in the pulmonary artery exceeds that in the RV (57), the pulmonic valve closes, which explains why R-P has a longer duration than R-S.

The somewhat, but not significantly, shorter duration from the R wave on the ECG to the onset of the E wave (R-E), (that is, to the onset of the myocardium moving), compared to the duration to the onset of the tricus-pid flow (R-T), may as has been suggested on the left side of the heart (31), be due to elastic recoil of the RV during diastole promoting the flow across the tricuspid orifice into the RV (58). Takotsubo cardiomyopathy and its effect on LV function The improvement of LV systolic long-axis shortening is in line with the improvement of LVEF obtained by the biplane Simpson’s method (table 6). The lower amplitudes of MAM in the acute phase indicate that the longi-tudinal fibers are affected in takotsubo cardiomyopathy. These fibers are mostly located subendocardially and this part of the myocardium has the highest risk of ischaemia (19,59). From this it’s easy to make the conclu-sion that atherosclerotic coronary disease-mediated myocardial ischemia could be a cause of the decrease in systolic long-axis shortening. This the-ory is not, however, supported by findings during, for instance, magnetic resonance imaging studies since there is no evidence of focal perfusion abnormalities corresponding to a specific coronary vessel territory (60). Also, the fact that all the patients had no significant coronary artery steno-sis makes this theory less probable.

The non-significant difference of the amplitude of MAM at the septal site between the two phases could be explained by fewer longitudinal fibers at septum than at the other anatomical locations. Septum is composed of subendocardial fibers from the RV and LV together with at middle layer composed of circumferential fibers in continuity with those from the corre-sponding layer of LV free wall. Circumferential septal fibers are lacking towards the apex (19).

One conjecture of the pathogenesis of takotsubo is elevated catechola-mine levels causing epicardial coronary arterial spasm, but multivessel epicardial spasms seem unlikely (61). Other studies have been unable to


confirm spasms as a cause of takotsubo, which is why it seems unlikely to be the cause of this disease (39).

Another theory is catecholamine mediated myocardial stunning caused by direct myocyte injury. Elevated catecholamine levels decrease the viabil-ity of myocytes through cyclic AMP-mediated calcium overload (62). In-teraction of the endocardial endothelium with circulating substances in the blood such as catecholamine may modify myocardial performance (39). The catecholamine hypothesis, which seems like the most plausible theory which could explain the findings in study IV, is supported by apical bal-looning in some case reports with dobutamine stress echocardiography (41), in reports of patients with phaeochromocytoma (63,64) and in pa-tients with subarachnoid haemorrhage (65). In the latter case a catechola-mine surge has been proposed as the explanation for the cardiomyopathy.

When looking at the LVDF there were, as mentioned earlier, only two parameters that significantly improved from the acute to the recovery phase, namely the early and the late diastolic velocities measured by PW-DTI. This is not an unexpected improvement since the velocities are meas-ured at the basal parts of the LV as are the amplitudes of MAM. The in-crease in the systolic long-axis shortening may therefore also explain the increase in those parameters. What is surprising, however, is that the same parameters measured by 2D color DTI did not change significantly al-though these velocities are also measured at the basal part of the LV. These velocities were significantly lower than the velocities measured by PW-DTI. One explanation for this could be that the velocities obtained with 2D color DTI are peak-mean velocities due to autocorrelation methodology, while PW-DTI measures peak velocities with a fast Fourier transformation technique (66). Where the sample volume is placed in the myocardium at the basal part of the LV may also cause the differences as well as the angle of the transducer.

Another reason for the lack of the expected increase of diastolic parame-ters could be that few patients had severely reduced LVEF and total ampli-tude of MAM during the acute phase. In another study (38), however, LVEF in the acute phase was lower than in the present study and higher in the recovery phase and despite this the authors found no significant changes in diastolic parameters.

There were no significant differences found in LV length or diameter be-tween the two phases (Table 6), which also is somewhat surprising since it could have been expected that the apical ballooning contributes to a longer/wider LV in the acute phase. The angle of the transducer, however, might have influenced this result.


That the myocardium stops its systolic movement, which is the end of the S-wave with PW-DTI, just before the closure of the pulmonic valve is not surprising. During systole the myocardium of the RV contracts causing the pressure in the RV to rise. When the pressure in the pulmonary artery is exceeded the pulmonic valve opens and blood can flow into the pulmo-nary artery. As the myocardium starts to relax the pressure in the RV falls and at the end of systole, that is, at the end of the S wave, when the pres-sure in the pulmonary artery exceeds that in the RV (57), the pulmonic valve closes, which explains why R-P has a longer duration than R-S.

The somewhat, but not significantly, shorter duration from the R wave on the ECG to the onset of the E wave (R-E), (that is, to the onset of the myocardium moving), compared to the duration to the onset of the tricus-pid flow (R-T), may as has been suggested on the left side of the heart (31), be due to elastic recoil of the RV during diastole promoting the flow across the tricuspid orifice into the RV (58). Takotsubo cardiomyopathy and its effect on LV function The improvement of LV systolic long-axis shortening is in line with the improvement of LVEF obtained by the biplane Simpson’s method (table 6). The lower amplitudes of MAM in the acute phase indicate that the longi-tudinal fibers are affected in takotsubo cardiomyopathy. These fibers are mostly located subendocardially and this part of the myocardium has the highest risk of ischaemia (19,59). From this it’s easy to make the conclu-sion that atherosclerotic coronary disease-mediated myocardial ischemia could be a cause of the decrease in systolic long-axis shortening. This the-ory is not, however, supported by findings during, for instance, magnetic resonance imaging studies since there is no evidence of focal perfusion abnormalities corresponding to a specific coronary vessel territory (60). Also, the fact that all the patients had no significant coronary artery steno-sis makes this theory less probable.

The non-significant difference of the amplitude of MAM at the septal site between the two phases could be explained by fewer longitudinal fibers at septum than at the other anatomical locations. Septum is composed of subendocardial fibers from the RV and LV together with at middle layer composed of circumferential fibers in continuity with those from the corre-sponding layer of LV free wall. Circumferential septal fibers are lacking towards the apex (19).

One conjecture of the pathogenesis of takotsubo is elevated catechola-mine levels causing epicardial coronary arterial spasm, but multivessel epicardial spasms seem unlikely (61). Other studies have been unable to


confirm spasms as a cause of takotsubo, which is why it seems unlikely to be the cause of this disease (39).

Another theory is catecholamine mediated myocardial stunning caused by direct myocyte injury. Elevated catecholamine levels decrease the viabil-ity of myocytes through cyclic AMP-mediated calcium overload (62). In-teraction of the endocardial endothelium with circulating substances in the blood such as catecholamine may modify myocardial performance (39). The catecholamine hypothesis, which seems like the most plausible theory which could explain the findings in study IV, is supported by apical bal-looning in some case reports with dobutamine stress echocardiography (41), in reports of patients with phaeochromocytoma (63,64) and in pa-tients with subarachnoid haemorrhage (65). In the latter case a catechola-mine surge has been proposed as the explanation for the cardiomyopathy.

When looking at the LVDF there were, as mentioned earlier, only two parameters that significantly improved from the acute to the recovery phase, namely the early and the late diastolic velocities measured by PW-DTI. This is not an unexpected improvement since the velocities are meas-ured at the basal parts of the LV as are the amplitudes of MAM. The in-crease in the systolic long-axis shortening may therefore also explain the increase in those parameters. What is surprising, however, is that the same parameters measured by 2D color DTI did not change significantly al-though these velocities are also measured at the basal part of the LV. These velocities were significantly lower than the velocities measured by PW-DTI. One explanation for this could be that the velocities obtained with 2D color DTI are peak-mean velocities due to autocorrelation methodology, while PW-DTI measures peak velocities with a fast Fourier transformation technique (66). Where the sample volume is placed in the myocardium at the basal part of the LV may also cause the differences as well as the angle of the transducer.

Another reason for the lack of the expected increase of diastolic parame-ters could be that few patients had severely reduced LVEF and total ampli-tude of MAM during the acute phase. In another study (38), however, LVEF in the acute phase was lower than in the present study and higher in the recovery phase and despite this the authors found no significant changes in diastolic parameters.

There were no significant differences found in LV length or diameter be-tween the two phases (Table 6), which also is somewhat surprising since it could have been expected that the apical ballooning contributes to a longer/wider LV in the acute phase. The angle of the transducer, however, might have influenced this result.


Takotsubo cardiomyopathy and it’s effect on RV function There was, as with the total amplitude of MAM, a significant difference between the acute and recovery phase concerning the amplitude of TAM (table 7). The improvement of this systolic long-axis shortening of the RV at the lateral site indicates that also the longitudinal fibers of the RV are affected in this disease, probably most in the apical regions.

This suggests that the RV is involved in takotsubo cardiomyopathy, something that only has been shown in a few studies (37,67). When RV involvement occurs it follows a similar pattern of regional wall motion abnormalities as the LV, but RV involvement portends a longer and more critical hospitalization course compared to patients with isolated LV in-volvement (67). The mechanisms explaining the involvement of the RV in takotsubo are unclear but argue against LV outflow tract obstruction as a cause of takotsubo (37).

There were no significant differences found in the RV length between the two phases (table 7). The angle of the transducer, however, might have influenced this result.

Practical implications RVOT1 From this thesis it seems obvious that echocardiographers should use the same site, method and body position when measuring RVOT1 in a single patient/subject that is followed over time. RVOT1 should preferably be measured from site b (Figs. 3 and 4) or short-axis (Fig. 7) since these sites showed good intra- and interindividual reproducibility and also did not show a significant difference when the subject was examined in the left lateral decubitus position or the supine decubitus position.

Isovolumetric relaxation time of the right ventricle The RV-IVRT is one of the most sensitive markers on RV dysfunction (23). In study II two different methods for measuring the IVRT of the RV were compared, one method based on ECG and PW-Doppler (27), RV-IVRT, and the other based on PW-DTI (20,21,23), RV-IVRT(PWDTI). A signifi-cant difference was found between IVRT obtained by the two methods, RV-IVRT being shorter than RV-IVRT(PWDTI).

Since the two methods, RV-IVRT and RV-IVRT(PWDTI), have been shown not to measure the same time interval in patients it seems obvious that different reference values have to be used when using the method based on PW-DTI than when using the method based on ECG and PW-


Doppler. Since the method based on ECG and PW-Doppler is more time consuming to perform than the method based on PW-DTI this latter method seems to be the first choice to use if PW-DTI is available on the echocardiograph.

Maximal early diastolic velocity of the right ventricle MDV TDI and MDV TAM showed a good correlation but a rather poor agreement indicating that reference values cannot be used interchangeably. Since there already are established reference values for MDV TDI it seems preferable to use this technique as most ultrasound systems today are equipped with PW-DTI technology. Furthermore, MDV TAM showed a somewhat poorer interindividual reproducibility.

Takotsubo cardiomyopathy The significant improvement in RV systolic long-axis function between the acute and recovery phase in takotsubo cardiomyopathy indicates that ta-kotsubo is not an isolated LV disorder. As earlier studies have shown a longer and more critical hospitalization for patients with RV dysfunction (67) it is important to, in addition to the LV function, also examine the RV function among patients with takotsubo cardiomyopathy. However, to fully understand the underlying pathophysiology behind this rare disease more large-scale studies need to be performed.


Takotsubo cardiomyopathy and it’s effect on RV function There was, as with the total amplitude of MAM, a significant difference between the acute and recovery phase concerning the amplitude of TAM (table 7). The improvement of this systolic long-axis shortening of the RV at the lateral site indicates that also the longitudinal fibers of the RV are affected in this disease, probably most in the apical regions.

This suggests that the RV is involved in takotsubo cardiomyopathy, something that only has been shown in a few studies (37,67). When RV involvement occurs it follows a similar pattern of regional wall motion abnormalities as the LV, but RV involvement portends a longer and more critical hospitalization course compared to patients with isolated LV in-volvement (67). The mechanisms explaining the involvement of the RV in takotsubo are unclear but argue against LV outflow tract obstruction as a cause of takotsubo (37).

There were no significant differences found in the RV length between the two phases (table 7). The angle of the transducer, however, might have influenced this result.

Practical implications RVOT1 From this thesis it seems obvious that echocardiographers should use the same site, method and body position when measuring RVOT1 in a single patient/subject that is followed over time. RVOT1 should preferably be measured from site b (Figs. 3 and 4) or short-axis (Fig. 7) since these sites showed good intra- and interindividual reproducibility and also did not show a significant difference when the subject was examined in the left lateral decubitus position or the supine decubitus position.

Isovolumetric relaxation time of the right ventricle The RV-IVRT is one of the most sensitive markers on RV dysfunction (23). In study II two different methods for measuring the IVRT of the RV were compared, one method based on ECG and PW-Doppler (27), RV-IVRT, and the other based on PW-DTI (20,21,23), RV-IVRT(PWDTI). A signifi-cant difference was found between IVRT obtained by the two methods, RV-IVRT being shorter than RV-IVRT(PWDTI).

Since the two methods, RV-IVRT and RV-IVRT(PWDTI), have been shown not to measure the same time interval in patients it seems obvious that different reference values have to be used when using the method based on PW-DTI than when using the method based on ECG and PW-


Doppler. Since the method based on ECG and PW-Doppler is more time consuming to perform than the method based on PW-DTI this latter method seems to be the first choice to use if PW-DTI is available on the echocardiograph.

Maximal early diastolic velocity of the right ventricle MDV TDI and MDV TAM showed a good correlation but a rather poor agreement indicating that reference values cannot be used interchangeably. Since there already are established reference values for MDV TDI it seems preferable to use this technique as most ultrasound systems today are equipped with PW-DTI technology. Furthermore, MDV TAM showed a somewhat poorer interindividual reproducibility.

Takotsubo cardiomyopathy The significant improvement in RV systolic long-axis function between the acute and recovery phase in takotsubo cardiomyopathy indicates that ta-kotsubo is not an isolated LV disorder. As earlier studies have shown a longer and more critical hospitalization for patients with RV dysfunction (67) it is important to, in addition to the LV function, also examine the RV function among patients with takotsubo cardiomyopathy. However, to fully understand the underlying pathophysiology behind this rare disease more large-scale studies need to be performed.


CONCLUSIONS

There is an overall significant difference of the diameters of RVOT1 at different sites, when using different methods and in dif-ferent body positions. Thus, the same site, method and body posi-tion should preferably be used when comparing RVOT1 over time in the same patient or subject. Site b or short-axis should prefera-bly be used since there was a good reproducibility and no signifi-cant difference between body positions when RVOT1 is measured from these sites. Site a should be avoided due to the lower repro-ducibility and the significant difference of RVOT1 between the two body positions when using this site.

The two methods measuring RV-IVRT are not measuring the same

time interval. With PW-DTI the time interval measured is the time from the end of the systolic motion of the tissue at the tricuspid annulus to the onset of the diastolic motion of the tissue at the same annulus. This interval has a longer duration than the time in-terval measured with ECG and PW-Doppler, which measures the time from the closure of the pulmonic valve to the onset of the tri-cuspid flow, which is the usual definition of RV-IVRT. Thus, dif-ferent reference values have to be used when measuring RV-IVRT with the two different methods.

The RV MDV can be measured using two different methods, one

based on M-mode and one based on PW-DTI. The methods showed a good correlation but a poor agreement. This means that reference values cannot be used interchangeably between the two methods. As most new ultrasound systems are equipped with PW-DTI technology it seems preferable to use this method, which al-ready has established reference values (34).

The systolic long-axis shortening of the LV and the RV improved

significantly between the acute phase and the recovery phase in ta-kotsubo cardiomyopathy. There were also improvements in LV early and late diastolic velocities measured by PW-DTI while other diastolic parameters of the LV and the diastolic parameters of the RV remained unchanged.


CONCLUSIONS

There is an overall significant difference of the diameters of RVOT1 at different sites, when using different methods and in dif-ferent body positions. Thus, the same site, method and body posi-tion should preferably be used when comparing RVOT1 over time in the same patient or subject. Site b or short-axis should prefera-bly be used since there was a good reproducibility and no signifi-cant difference between body positions when RVOT1 is measured from these sites. Site a should be avoided due to the lower repro-ducibility and the significant difference of RVOT1 between the two body positions when using this site.

The two methods measuring RV-IVRT are not measuring the same

time interval. With PW-DTI the time interval measured is the time from the end of the systolic motion of the tissue at the tricuspid annulus to the onset of the diastolic motion of the tissue at the same annulus. This interval has a longer duration than the time in-terval measured with ECG and PW-Doppler, which measures the time from the closure of the pulmonic valve to the onset of the tri-cuspid flow, which is the usual definition of RV-IVRT. Thus, dif-ferent reference values have to be used when measuring RV-IVRT with the two different methods.

The RV MDV can be measured using two different methods, one

based on M-mode and one based on PW-DTI. The methods showed a good correlation but a poor agreement. This means that reference values cannot be used interchangeably between the two methods. As most new ultrasound systems are equipped with PW-DTI technology it seems preferable to use this method, which al-ready has established reference values (34).

The systolic long-axis shortening of the LV and the RV improved

significantly between the acute phase and the recovery phase in ta-kotsubo cardiomyopathy. There were also improvements in LV early and late diastolic velocities measured by PW-DTI while other diastolic parameters of the LV and the diastolic parameters of the RV remained unchanged.


ACKNOWLEDGEMENTS I wish to express my sincere gratitude to all my friends and colleagues who have supported me to complete this thesis, and in particular:

All patients and healthy volunteers who participated in the studies, without you this thesis would never have been accomplished.

Kent Emilsson, my supervisor. Thanks for introducing me to research and to this project in particular, for excellent tutorship and last but not least for your never ending enthusiastic engagement.

Allan Sirsjö, my co-supervisor.

Olle Fröbert , Sofia Hammar, Peter Rask, Mikael Waldenborg and Birgitta Öhlin for being my co-authors in papers I, III and IV.

Anders Magnusson for your statistical advice.

Terence Kearey for correcting my English.

Leif Bojö my “sparring partner”, for your involvement and constructive critics.

To all my former colleagues at the Department of Clinical Physiology, Karlskoga hospital, a special thanks to Bo Engström for having taught me the fundamentals in echocardiography and to Charlotta Håkansson for your excellent leadership and friendship. To all my former colleagues at the Department of Clinical Physiology, Örebro University Hospital, a special thanks to Ann-Louise Ståhl, head biomedical scientist, for believing in me. To all my colleagues at the Department of Clinical Physiology, Karolinska University Hospital, Solna, a special thanks to Ann-Louise Launila, head biomedical scientist, for all your support and help.

The staff at the Medical Library at Örebro University Hospital for your help in searching for and finding the literature I wanted.


ACKNOWLEDGEMENTS I wish to express my sincere gratitude to all my friends and colleagues who have supported me to complete this thesis, and in particular:

All patients and healthy volunteers who participated in the studies, without you this thesis would never have been accomplished.

Kent Emilsson, my supervisor. Thanks for introducing me to research and to this project in particular, for excellent tutorship and last but not least for your never ending enthusiastic engagement.

Allan Sirsjö, my co-supervisor.

Olle Fröbert , Sofia Hammar, Peter Rask, Mikael Waldenborg and Birgitta Öhlin for being my co-authors in papers I, III and IV.

Anders Magnusson for your statistical advice.

Terence Kearey for correcting my English.

Leif Bojö my “sparring partner”, for your involvement and constructive critics.

To all my former colleagues at the Department of Clinical Physiology, Karlskoga hospital, a special thanks to Bo Engström for having taught me the fundamentals in echocardiography and to Charlotta Håkansson for your excellent leadership and friendship. To all my former colleagues at the Department of Clinical Physiology, Örebro University Hospital, a special thanks to Ann-Louise Ståhl, head biomedical scientist, for believing in me. To all my colleagues at the Department of Clinical Physiology, Karolinska University Hospital, Solna, a special thanks to Ann-Louise Launila, head biomedical scientist, for all your support and help.

The staff at the Medical Library at Örebro University Hospital for your help in searching for and finding the literature I wanted.


Relatives and friends for your invaluable support and friendship. Last but not least, my beloved family:

Mother, father and Lena, my sister and Mats, grandmother and Natasha: for your endless love, support and caring for Lovisa. Hubert, for your love that knows no boundary. My daughter Lovisa (1 year), for teaching me what it’s all about. To my unborn child for your encouraging kicks.

Financial support was received from: The Örebro County Council Research Committee.


REFERENCES 1. Souhami RL, Moxham J. Textbook of medicin. 3rd ed. London:

Churchill Livingstone; 1997. Chapter 14, Cardiovascular disease; p.382.

2. Martini FH, Timmons MJ. Human anatomy. 2nd ed. New Jersey: Prentice Hall; 1997. Chapter 21, The Cardiovascular System: The Heart; p.523-528.

3. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecu-lar biology of the cell. 3rd ed. New York: Garland Publishing; 1994. Chapter 16, The Cytoskeleton; p.856.

4. Aurigemma GP, Douglas PS, Gaasch WH. The practice of clinical echocardiography. 2nd ed. Philadelphia: Saunders company; 2002. Quantitative evaluation of the left ventricular structure, wall stress and systolic function; p.65.

5. Francés RJ. Arrhythmogenic right ventricular dyspla-sia/cardiomyopathy. A review and update. Int J Cardiol. 2006;110:279-287.

6. Wong SP, Otto CM. The practice of clinical echocardiography. 2nd ed. Philadelphia: Saunders company; 2002. Echocardiographic find-ings in acute and chronic pulmonary disease; p.741.

7. Lauschke J, Maisch B. Athlete’s heart or hypertrofic cardiomyopa-thy? Clin Res Cardiol. 2009;98(2):80-88.

8. Foale R, Nihoyannopoulos P, Mckenna W, Klienebenne A, Nadaz-din A, Rowland E, Smith G. Echocardiographic measurement of the normal adult right ventricle. Br Heart J. 1986;56:33-44.

9. Norgård G, Vik-Mo H. Effects of respiration on right ventricular size and function: an echocardiographic study. Pediatr Cardiol. 1992;13:136-140.

10. Henriksen E, Landelius J, Kangro T, Jonason T, Hedberg P, Wesslén L, Rosander CN, Rolf C, Ringqvist I, Friman G. An echocardio-graphic study of the right and left ventricular adaptation to physical exercise in elite female orienteers. Eur Heart J. 1999;20:309-316.


Relatives and friends for your invaluable support and friendship. Last but not least, my beloved family:

Mother, father and Lena, my sister and Mats, grandmother and Natasha: for your endless love, support and caring for Lovisa. Hubert, for your love that knows no boundary. My daughter Lovisa (1 year), for teaching me what it’s all about. To my unborn child for your encouraging kicks.

Financial support was received from: The Örebro County Council Research Committee.


REFERENCES 1. Souhami RL, Moxham J. Textbook of medicin. 3rd ed. London:

Churchill Livingstone; 1997. Chapter 14, Cardiovascular disease; p.382.

2. Martini FH, Timmons MJ. Human anatomy. 2nd ed. New Jersey: Prentice Hall; 1997. Chapter 21, The Cardiovascular System: The Heart; p.523-528.

3. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecu-lar biology of the cell. 3rd ed. New York: Garland Publishing; 1994. Chapter 16, The Cytoskeleton; p.856.

4. Aurigemma GP, Douglas PS, Gaasch WH. The practice of clinical echocardiography. 2nd ed. Philadelphia: Saunders company; 2002. Quantitative evaluation of the left ventricular structure, wall stress and systolic function; p.65.

5. Francés RJ. Arrhythmogenic right ventricular dyspla-sia/cardiomyopathy. A review and update. Int J Cardiol. 2006;110:279-287.

6. Wong SP, Otto CM. The practice of clinical echocardiography. 2nd ed. Philadelphia: Saunders company; 2002. Echocardiographic find-ings in acute and chronic pulmonary disease; p.741.

7. Lauschke J, Maisch B. Athlete’s heart or hypertrofic cardiomyopa-thy? Clin Res Cardiol. 2009;98(2):80-88.

8. Foale R, Nihoyannopoulos P, Mckenna W, Klienebenne A, Nadaz-din A, Rowland E, Smith G. Echocardiographic measurement of the normal adult right ventricle. Br Heart J. 1986;56:33-44.

9. Norgård G, Vik-Mo H. Effects of respiration on right ventricular size and function: an echocardiographic study. Pediatr Cardiol. 1992;13:136-140.

10. Henriksen E, Landelius J, Kangro T, Jonason T, Hedberg P, Wesslén L, Rosander CN, Rolf C, Ringqvist I, Friman G. An echocardio-graphic study of the right and left ventricular adaptation to physical exercise in elite female orienteers. Eur Heart J. 1999;20:309-316.


11. Lindqvist P, Henein M, Kazzam E. Right ventricular outflow-tract fractional shortening: an applicable measure of right ventricular sys-tolic function. Eur J Echocardiogr. 2003;4:29-35.

12. Otto C. Textbook of clinical echocardiography. 3rd ed. Philadelphia, Elsevier; 2004. Left and right ventricular systolic function; p.151-152.

13. Feigenbaum H, Armstrong W, Ryan T. Echocardiography. 6th ed. Philadelphia, Williams & Wilkins; 2005. Left atrium, right atrium and right ventricle; p.202-204.

14. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pel-likka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MSJ, Stewart WJ. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standard Committee and the Chamber Quantification Writing Group, developed with the Euro-pean Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440-1463.

15. Lindqvist P, Calcutteea A, Henein M. Echocardiography in the as-sessment of right heart function. Eur J Echocardiogr. 2008;9:225-234.

16. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations re-garding quantitation in M-mode echocardiography: results of a sur-vey of echocardiographic measurements. Circulation. 1978;58(6):1072-1083.

17. Baker BJ, Scovil JA, Kane JJ, Murphy ML. Echocardiographic detec-tion of right ventricular hypertrophy. Am Heart J. 1983;105:611-614.

18. Feigenbaum H. Echocardiography. 5th ed. Philadelphia: Williams & Wilkins; 1994. Chapter 2, The Echocardiographic Examination; p. 88.

19. Greenbaum RA, Ho SY, Gibson DG, Becker AE, Anderson RH. Left ventricular fibre architecture in man. Br Heart J. 1981;45:248-263.

20. Özdemir K, Altunkeser BB, Icli A, Özdil H, Gök H. New parameters in identification of right ventricular myocardial infarction and proximal right coronary artery lesion. Chest. 2003;124:219-226.


21. Severino S, Caso P, Cicala S, Galderisi M, De Simone L, D’Andrea A, D’Errico A, Mininni N. Involvement of right ventricle in left ven-tricular hypertrofic cardiomyopathy: analysis by pulsed doppler tis-sue imaging. Eur J Echocardiogr. 2000;1(4):281-288.

22. Loiske K, Emilsson K. A comparison of right ventricular volume change during systole obtained using the monoplane Simpson’s method in two-dimensional echocardiographic apical four-chamber view with right ventricular volume change obtained using a prisma model reflecting the systolic long-axis shortening of the right ventri-cle of the heart: A pilot study. Exp Clin Cardiol. 2008;13(2):75-78.

23. Caso P, Galderisi M, Cicala S, Cioppa C, D’Andrea A, Lagioia G, Liccardo B, Martiniello AR, Mininni N. Association between myo-cardial right ventricular relaxation time and pulmonary arterial pressure in chronic obstructive lung disease: analysis by pulsed Dop-pler tissue imaging. J Am Soc Echocardiogr. 2001;14(10):970-977.

24. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricu-lar function using two-dimensional echocardiography. Am Heart J. 1984;107(3):526-531.

25. Lindqvist P, Waldenström A, Wikström G, Kazzam E. Right ven-tricular isovolumetric relaxation time and pulmonary pressure. Clin Physiol Funct Imaging. 2006;26(1):1-8.

26. Otto C. Textbook of clinical echocardiography. 2nd ed. Philadelphia, WB Saunders; 2000. Chapter 5, Echocardiographic evaluation of left and right ventricular systolic function; p.127.

27. Larrazet F, Pellerin D, Fournier C, Witchitz S, Veyrat C. Right and left isovolumic ventricular relaxation time intervals compared in pa-tients by means of a single-pulsed Doppler method. J Am Soc Echo-cardiogr. 1997;10(7):699-706.

28. Bojö L, Wandt B, Ahlin NG. Reduced left ventricular relaxation velocity after acute myocardial infarction. Clin Physiol. 1998;18(3):195-201.

29. Nilsson B, Bojö L, Wandt B. Influence of body size and age on maximal diastolic velocity of mitral annulus motion. J Am Soc Echocardiogr. 2002;15(1):29-35.

30. Fornander Y, Nilsson B, Egerlid R, Wandt B. Left ventricular longi-tudinal relaxation velocity: a sensitive index of diastolic function. Scand Cardiovasc J. 2004;38:33-38.


11. Lindqvist P, Henein M, Kazzam E. Right ventricular outflow-tract fractional shortening: an applicable measure of right ventricular sys-tolic function. Eur J Echocardiogr. 2003;4:29-35.

12. Otto C. Textbook of clinical echocardiography. 3rd ed. Philadelphia, Elsevier; 2004. Left and right ventricular systolic function; p.151-152.

13. Feigenbaum H, Armstrong W, Ryan T. Echocardiography. 6th ed. Philadelphia, Williams & Wilkins; 2005. Left atrium, right atrium and right ventricle; p.202-204.

14. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pel-likka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MSJ, Stewart WJ. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standard Committee and the Chamber Quantification Writing Group, developed with the Euro-pean Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440-1463.

15. Lindqvist P, Calcutteea A, Henein M. Echocardiography in the as-sessment of right heart function. Eur J Echocardiogr. 2008;9:225-234.

16. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations re-garding quantitation in M-mode echocardiography: results of a sur-vey of echocardiographic measurements. Circulation. 1978;58(6):1072-1083.

17. Baker BJ, Scovil JA, Kane JJ, Murphy ML. Echocardiographic detec-tion of right ventricular hypertrophy. Am Heart J. 1983;105:611-614.

18. Feigenbaum H. Echocardiography. 5th ed. Philadelphia: Williams & Wilkins; 1994. Chapter 2, The Echocardiographic Examination; p. 88.

19. Greenbaum RA, Ho SY, Gibson DG, Becker AE, Anderson RH. Left ventricular fibre architecture in man. Br Heart J. 1981;45:248-263.

20. Özdemir K, Altunkeser BB, Icli A, Özdil H, Gök H. New parameters in identification of right ventricular myocardial infarction and proximal right coronary artery lesion. Chest. 2003;124:219-226.


21. Severino S, Caso P, Cicala S, Galderisi M, De Simone L, D’Andrea A, D’Errico A, Mininni N. Involvement of right ventricle in left ven-tricular hypertrofic cardiomyopathy: analysis by pulsed doppler tis-sue imaging. Eur J Echocardiogr. 2000;1(4):281-288.

22. Loiske K, Emilsson K. A comparison of right ventricular volume change during systole obtained using the monoplane Simpson’s method in two-dimensional echocardiographic apical four-chamber view with right ventricular volume change obtained using a prisma model reflecting the systolic long-axis shortening of the right ventri-cle of the heart: A pilot study. Exp Clin Cardiol. 2008;13(2):75-78.

23. Caso P, Galderisi M, Cicala S, Cioppa C, D’Andrea A, Lagioia G, Liccardo B, Martiniello AR, Mininni N. Association between myo-cardial right ventricular relaxation time and pulmonary arterial pressure in chronic obstructive lung disease: analysis by pulsed Dop-pler tissue imaging. J Am Soc Echocardiogr. 2001;14(10):970-977.

24. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricu-lar function using two-dimensional echocardiography. Am Heart J. 1984;107(3):526-531.

25. Lindqvist P, Waldenström A, Wikström G, Kazzam E. Right ven-tricular isovolumetric relaxation time and pulmonary pressure. Clin Physiol Funct Imaging. 2006;26(1):1-8.

26. Otto C. Textbook of clinical echocardiography. 2nd ed. Philadelphia, WB Saunders; 2000. Chapter 5, Echocardiographic evaluation of left and right ventricular systolic function; p.127.

27. Larrazet F, Pellerin D, Fournier C, Witchitz S, Veyrat C. Right and left isovolumic ventricular relaxation time intervals compared in pa-tients by means of a single-pulsed Doppler method. J Am Soc Echo-cardiogr. 1997;10(7):699-706.

28. Bojö L, Wandt B, Ahlin NG. Reduced left ventricular relaxation velocity after acute myocardial infarction. Clin Physiol. 1998;18(3):195-201.

29. Nilsson B, Bojö L, Wandt B. Influence of body size and age on maximal diastolic velocity of mitral annulus motion. J Am Soc Echocardiogr. 2002;15(1):29-35.

30. Fornander Y, Nilsson B, Egerlid R, Wandt B. Left ventricular longi-tudinal relaxation velocity: a sensitive index of diastolic function. Scand Cardiovasc J. 2004;38:33-38.


31. Garcia MJ, Rodriguez L, Ares M, Griffin BP, Thomas JD, Klein AL. Differentiation of constrictive pericarditis from restrictive cardio-myopathy: assessment of left ventricular diastolic velocities in longi-tudinal axis by Doppler tissue imaging. J Am Coll Cardiol. 1996;27(1):108-114.

32. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30(6):1527-1533.

33. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricu-lar diastolic function. J Am Coll Cardiol. 1997;30(2):474-480.

34. Alam M, Wardell J, Andersson E, Samad BA, Nordlander R. Char-acteristics of mitral and tricuspid annular velocities determined by pulsed wave Doppler tissue imaging in healthy subjects. J Am Soc Echocardiogr. 1999;12(8):618-628.

35. Nikitin NP, Witte KK, Thackray SD, de Silva R, Clark AL, Cleland JG. Longitudinal ventricular function: normal values of atrioven-tricular annular and myocardial velocities measured with quantita-tive two-dimensional color Doppler tissue imaging. J Am Soc Echo-cardiogr. 2003;16(9):906-921.

36. Emilsson K. Right ventricular long-axis function in relation to left ventricular systolic function. Clin Physiol Funct Imaging. 2004;24(4):212-215.

37. Haghi D, Fluechter S, Suselbeck T, Kaden JJ, Borggrefe M, Papavas-siliu T. Cardiovascular magnetic resonance findings in typical versus atypical forms of the acute apical ballooning syndrome (Takotsubo cardiomyopathy). Int J Cardiol. 2007;120:205-211.

38. Memoin P, Malaquin D, Benali T, Boulanger J, Zemir H, Tribouil-loy C. Transient impairment of coronary flow reserve in tako-tsubo cardiomyopathy is related to left ventricular systolic parameters. Eur J Echocardiogr. 2009;10:265-270.

39. Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, Rysz J, Michalska M, Akashi YJ, Banach M. Takotsubo cardiomyopathy – The current state of knowledge. Int J Cardiol. 2010; 142:120-125.


40. Tsuchihashi K, Ueshima K, Ushida T, Oh-mura N, Kimura K, Owa M, Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I. Transient left ventricular apical ballooning with-out coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris Myocardial Infarction Investigastions in Japan. J Am Coll Cardiol. 2001;38(1):11-18.

41. Margey R, Diamond P, McCann H, Sugrue D. Dobutamine stress echo-induced apical ballooning (Takotsubo) syndrome. Eur J Echo-cardiogr. 2009;10:395-399.

42. Efthimiadis GK, Parharidis GE, Karvounis HI, Gemitzis KD, Styliadis IH, Louridas GE. Doppler echocardiographic evaluation of right ventricular diastolic function in hypertrophic cardiomyopathy. Eur J Echocardiogr. 2002;3(2):143-148.

43. Henry WL, DeMaria A, Gramiak R, King DL, Kisslo JA, Popp R, Sahn DJ, Schiller NB, Tajik A, Teichholz LE, Wyeman AE. Report of the American Society of Echocardiography Committee on nomen-clature and standards in two-dimensional echocardiography. Circu-lation. 1980;62(2):212-215.

44. Shiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Fei-genbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik JA. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Soci-ety of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2(5):358-367.

45. Feigenbaum H. Feigenbaums echocardiography. Philadelphia, Lip-pincott Williams & Wilkins; 2010. Evaluation of systolic function of the left ventricle; p.126-127.

46. Feigenbaum H. Feigenbaums echocardiography. Philadelphia, Lip-pincott Williams & Wilkins; 2010. Left and right atrium, and right ventricle; p.209.

47. Feigenbaum H. Echocardiography. 5th ed. Philadelphia, Lea & Fe-biger; 1994. Echocardiographic evaluation of cardiac chambers; p.160-161.

48. Höglund C, Alam M, Thorstrand C. Atrioventricular valve plane displacement in healthy persons. An echocardiographic study. Acta Med Scand. 1988;224:557-562.


31. Garcia MJ, Rodriguez L, Ares M, Griffin BP, Thomas JD, Klein AL. Differentiation of constrictive pericarditis from restrictive cardio-myopathy: assessment of left ventricular diastolic velocities in longi-tudinal axis by Doppler tissue imaging. J Am Coll Cardiol. 1996;27(1):108-114.

32. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30(6):1527-1533.

33. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricu-lar diastolic function. J Am Coll Cardiol. 1997;30(2):474-480.

34. Alam M, Wardell J, Andersson E, Samad BA, Nordlander R. Char-acteristics of mitral and tricuspid annular velocities determined by pulsed wave Doppler tissue imaging in healthy subjects. J Am Soc Echocardiogr. 1999;12(8):618-628.

35. Nikitin NP, Witte KK, Thackray SD, de Silva R, Clark AL, Cleland JG. Longitudinal ventricular function: normal values of atrioven-tricular annular and myocardial velocities measured with quantita-tive two-dimensional color Doppler tissue imaging. J Am Soc Echo-cardiogr. 2003;16(9):906-921.

36. Emilsson K. Right ventricular long-axis function in relation to left ventricular systolic function. Clin Physiol Funct Imaging. 2004;24(4):212-215.

37. Haghi D, Fluechter S, Suselbeck T, Kaden JJ, Borggrefe M, Papavas-siliu T. Cardiovascular magnetic resonance findings in typical versus atypical forms of the acute apical ballooning syndrome (Takotsubo cardiomyopathy). Int J Cardiol. 2007;120:205-211.

38. Memoin P, Malaquin D, Benali T, Boulanger J, Zemir H, Tribouil-loy C. Transient impairment of coronary flow reserve in tako-tsubo cardiomyopathy is related to left ventricular systolic parameters. Eur J Echocardiogr. 2009;10:265-270.

39. Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, Rysz J, Michalska M, Akashi YJ, Banach M. Takotsubo cardiomyopathy – The current state of knowledge. Int J Cardiol. 2010; 142:120-125.


40. Tsuchihashi K, Ueshima K, Ushida T, Oh-mura N, Kimura K, Owa M, Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I. Transient left ventricular apical ballooning with-out coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris Myocardial Infarction Investigastions in Japan. J Am Coll Cardiol. 2001;38(1):11-18.

41. Margey R, Diamond P, McCann H, Sugrue D. Dobutamine stress echo-induced apical ballooning (Takotsubo) syndrome. Eur J Echo-cardiogr. 2009;10:395-399.

42. Efthimiadis GK, Parharidis GE, Karvounis HI, Gemitzis KD, Styliadis IH, Louridas GE. Doppler echocardiographic evaluation of right ventricular diastolic function in hypertrophic cardiomyopathy. Eur J Echocardiogr. 2002;3(2):143-148.

43. Henry WL, DeMaria A, Gramiak R, King DL, Kisslo JA, Popp R, Sahn DJ, Schiller NB, Tajik A, Teichholz LE, Wyeman AE. Report of the American Society of Echocardiography Committee on nomen-clature and standards in two-dimensional echocardiography. Circu-lation. 1980;62(2):212-215.

44. Shiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Fei-genbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik JA. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Soci-ety of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2(5):358-367.

45. Feigenbaum H. Feigenbaums echocardiography. Philadelphia, Lip-pincott Williams & Wilkins; 2010. Evaluation of systolic function of the left ventricle; p.126-127.

46. Feigenbaum H. Feigenbaums echocardiography. Philadelphia, Lip-pincott Williams & Wilkins; 2010. Left and right atrium, and right ventricle; p.209.

47. Feigenbaum H. Echocardiography. 5th ed. Philadelphia, Lea & Fe-biger; 1994. Echocardiographic evaluation of cardiac chambers; p.160-161.

48. Höglund C, Alam M, Thorstrand C. Atrioventricular valve plane displacement in healthy persons. An echocardiographic study. Acta Med Scand. 1988;224:557-562.


49. Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomen-clature and Standard Committee of the American Society of Echo-cardiography. J Am Soc Echocardiogr. 2002;15(2):167-184.

50. Lind B, Nowak J, Cain P, Quintana M, Brodin LÅ. Left ventricular isovolumic velocity and duration variables calculated from color- coded myocardial velocity images in normal individuals. Eur J Echo-cardiogr. 2004;5:284-293.

51. Bland J, Altman D. Statistical methods for assessing agreements between two methods of clinical measurements. Lancet. 1986;1:307-310.

52. Dunn G. Design and analysis of reliability studies. New York: Ox-ford University Press. 1989:34.

53. Rambaldi R, Poldermans D, Vletter WB, ten Cate FJ, Roelandt JR, Fioretti PM. Doppler tissue imaging in the new era of digital echo-cardiography. G Ital Cardiol. 1997;27:827-839.

54. Emilsson K, Kähäri A, Bodin L. Comparison between right coronary artery motion and echocardiographic tricuspid annulus motion. Scand Cardiovasc J. 2004;38(2):85-92.

55. Kukulski T, Voigt JU, Wilkenshoff UM, Strotmann JM, Wranne B, Hatle L, Sutherland GR. A comparison of regional myocardial ve-locity information derived by pulsed and color Doppler techniques: an in vitro and in vivo study. Echocardiography. 2000;17(7):639-651.

56. Otto C. Textbook of clinical echocardiography. 2nd ed. Philadelphia, W.B Saunders Company; 2000. Chapter 5, Echocardiographic evaluation of left end right ventricular systolic function; p.120.

57. Braunwald E. Heart disease – a textbook of cardiovascular medi-cine. 5th ed. Philadelphia, W.B Saunders; 1997. Mechanism of car-diac contraction and relaxation; p.377.

58. Robinson TF, Factor SM, Sonnenblick EH. The heart as a suction pump. Sci Am. 1986;254:84-91.

59. Henein MY, Priestly K, Davarashvili T, Buller N, Gibson DG. Early changes in subendocardial function after successful coronary angio-plasty. Br Heart J. 1993;69:501-506.


60. Gerbaud E, Montaudon M, Leroux L, Corneloup O, Dos Santos P, Jais C, Coste P, Laurent F. MRI for the diagnosis of left ventricular apical ballooning syndrome (LVABS). Eur Radiol. 2008;18:847-954.

61. Wittstein IS, Thiemann DR, Lima JA, Baughmann KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emo-tional stress. N Eng J Med. 2005;352(6):539-548.

62. Mann DL, Kent RL, Parsons B, Cooper G. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation. 1992;85(2):790-804.

63. Takizawa M, Kobayakawa N, Uozumi H, Yonemura S, Kodama T, Fukusima K, Takeuchi H, Kaneko Y, Kaneko T, Fujita K, Honma Y, Aoyagi T. A case of transient left ventricular ballooning with pheochromocytoma, supporting pathogenetic role of cathechola-mines in stress induced cardiomyopathy of takotsubo cardiomyopa-thy. Int J Cardiol. 2007;114:e14-e17.

64. Lassnig E, Weber T, Auer J, Nömeyer R, Eber B. Pheochromocy-toma crisis presenting with shock and tako-tsubo-like cardiomyopa-thy. Int J Cardiol. 2009;134:e138-e140.

65. Trio O, de Gregorio C, Andó G. Myocardial dysfunction after su-barachnoid haemorrhage and tako-tsubo cardiomyopathy : a differ-ential diagnosis? Ther Adv Cardiovasc Dis. 2010;4(2):105-107.

66. Hummel YM, Klip IJ, de Jong RM, Pieper PG, van Veldhuisen DJ, Voors AA. Diastolic function measurements and diagnostic conse-quences: a comparison of pulsed wave- and color-coded tissue Dop-pler imaging. Clin Res Cardiol. 2010;99:453-458.

67. Elesber AA, Prasad A, Bybee KA, Valeti U, Motiei A, Lerman A, Chandrasekaran K, Rihal CS. Transient cardiac apical ballooning syndrome: prevalence and clinical implications of right ventricular involvement. J Am Coll Cardiol. 2006;47(5):1082-1083.


49. Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomen-clature and Standard Committee of the American Society of Echo-cardiography. J Am Soc Echocardiogr. 2002;15(2):167-184.

50. Lind B, Nowak J, Cain P, Quintana M, Brodin LÅ. Left ventricular isovolumic velocity and duration variables calculated from color- coded myocardial velocity images in normal individuals. Eur J Echo-cardiogr. 2004;5:284-293.

51. Bland J, Altman D. Statistical methods for assessing agreements between two methods of clinical measurements. Lancet. 1986;1:307-310.

52. Dunn G. Design and analysis of reliability studies. New York: Ox-ford University Press. 1989:34.

53. Rambaldi R, Poldermans D, Vletter WB, ten Cate FJ, Roelandt JR, Fioretti PM. Doppler tissue imaging in the new era of digital echo-cardiography. G Ital Cardiol. 1997;27:827-839.

54. Emilsson K, Kähäri A, Bodin L. Comparison between right coronary artery motion and echocardiographic tricuspid annulus motion. Scand Cardiovasc J. 2004;38(2):85-92.

55. Kukulski T, Voigt JU, Wilkenshoff UM, Strotmann JM, Wranne B, Hatle L, Sutherland GR. A comparison of regional myocardial ve-locity information derived by pulsed and color Doppler techniques: an in vitro and in vivo study. Echocardiography. 2000;17(7):639-651.

56. Otto C. Textbook of clinical echocardiography. 2nd ed. Philadelphia, W.B Saunders Company; 2000. Chapter 5, Echocardiographic evaluation of left end right ventricular systolic function; p.120.

57. Braunwald E. Heart disease – a textbook of cardiovascular medi-cine. 5th ed. Philadelphia, W.B Saunders; 1997. Mechanism of car-diac contraction and relaxation; p.377.

58. Robinson TF, Factor SM, Sonnenblick EH. The heart as a suction pump. Sci Am. 1986;254:84-91.

59. Henein MY, Priestly K, Davarashvili T, Buller N, Gibson DG. Early changes in subendocardial function after successful coronary angio-plasty. Br Heart J. 1993;69:501-506.


60. Gerbaud E, Montaudon M, Leroux L, Corneloup O, Dos Santos P, Jais C, Coste P, Laurent F. MRI for the diagnosis of left ventricular apical ballooning syndrome (LVABS). Eur Radiol. 2008;18:847-954.

61. Wittstein IS, Thiemann DR, Lima JA, Baughmann KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emo-tional stress. N Eng J Med. 2005;352(6):539-548.

62. Mann DL, Kent RL, Parsons B, Cooper G. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation. 1992;85(2):790-804.

63. Takizawa M, Kobayakawa N, Uozumi H, Yonemura S, Kodama T, Fukusima K, Takeuchi H, Kaneko Y, Kaneko T, Fujita K, Honma Y, Aoyagi T. A case of transient left ventricular ballooning with pheochromocytoma, supporting pathogenetic role of cathechola-mines in stress induced cardiomyopathy of takotsubo cardiomyopa-thy. Int J Cardiol. 2007;114:e14-e17.

64. Lassnig E, Weber T, Auer J, Nömeyer R, Eber B. Pheochromocy-toma crisis presenting with shock and tako-tsubo-like cardiomyopa-thy. Int J Cardiol. 2009;134:e138-e140.

65. Trio O, de Gregorio C, Andó G. Myocardial dysfunction after su-barachnoid haemorrhage and tako-tsubo cardiomyopathy : a differ-ential diagnosis? Ther Adv Cardiovasc Dis. 2010;4(2):105-107.

66. Hummel YM, Klip IJ, de Jong RM, Pieper PG, van Veldhuisen DJ, Voors AA. Diastolic function measurements and diagnostic conse-quences: a comparison of pulsed wave- and color-coded tissue Dop-pler imaging. Clin Res Cardiol. 2010;99:453-458.

67. Elesber AA, Prasad A, Bybee KA, Valeti U, Motiei A, Lerman A, Chandrasekaran K, Rihal CS. Transient cardiac apical ballooning syndrome: prevalence and clinical implications of right ventricular involvement. J Am Coll Cardiol. 2006;47(5):1082-1083.

STUDY I

STUDY I

ORIGINAL PAPER

Echocardiographic measurements of the right ventricle:right ventricular outflow tract 1

K. Loiske • S. Hammar • K. Emilsson

Received: 14 December 2009 / Accepted: 15 February 2010

� Springer-Verlag 2010

Abstract

Purpose The size of the ventricles of the heart is

important to establish during the clinical echocardiographic

examination. Due to the complex anatomy of the right

ventricle, it is difficult to measure its size at times. One of

the most frequently used ways is to measure the right

ventricular outflow tract (RVOT1), probably due to its

good reproducibility. However, in the literature different

ways are described to measure RVOT1, both at different

sites and using different methods such as M-mode and 2D.

The first aim of the present study was to exam if there is a

significant difference in the outcome of RVOT1 using

different sites and methods to measure it. The second aim

was to study if there is a significant difference between the

usually preferred left lateral decubitus position during the

echocardiographic examination and the supine decubitus

position, which the echocardiographer sometimes can be

compelled to use if the patient is unable to lie in the left

lateral decubitus position.

Methods Twenty-seven healthy subjects were included

and examined by echocardiography. RVOT1 was measured

at different sites using different methods; first with the

subject in the left lateral decubitus position and then

repeating the same measurements with the subject in the

supine decubitus position.

Results Comparing the RVOT1 measured at different

sites and with different methods showed an overall

significant difference (p\ 0.001). Also when comparing

the different body positions, there was an overall signifi-

cant difference (p = 0.001).

Conclusions When comparing RVOT1 of the same

patient or subject over time, the results from the present

study indicate that the same site, method and body position

should be used.

Keywords Heart � Right ventricular size �Echocardiography � Body position

Introduction

The size of the heart, especially its ventricles, is important

to establish during the clinical echocardiographic exami-

nation, since larger ventricles often indicates an underlying

disease such as dilated cardiomyopathy, valvular disorder

or shunt.

The size of the left ventricle (LV) is associated with the

prognosis of the patient. It has important therapeutic

implications and can provide data that are necessary to

define the optimal time for cardiac surgery, for instance, in

patients with aortic- or mitral regurgitation [1]. A large

right ventricle (RV) may be seen in patients with different

kinds of heart diseases such as arrhytmogenic right ven-

tricular dysplasia (ARVD) [2], primary pulmonary disease,

but often it is a result of backward transmission of elevated

LV filling pressure through the pulmonary circulation, thus

augmenting RV afterload [3]. Large ventricles and ven-

tricular hypertrophy could, however, also be seen in

apparently healthy individuals such as athletes [4].

Different techniques such as two dimensional (2D)- or

three dimensional (3D) echocardiography and magnetic

resonance imaging, can be used to measure the size of the

K. Loiske � K. Emilsson (&)

Department of Clinical Physiology, Orebro University Hospital,

701 85 Orebro, Sweden

e-mail: [email protected]

S. Hammar

School of Health and Medical Sciences/Clinical Medicine,

Orebro University, Orebro, Sweden

123

Clin Res Cardiol

DOI 10.1007/s00392-010-0137-7

ORIGINAL PAPER

Echocardiographic measurements of the right ventricle:right ventricular outflow tract 1

K. Loiske • S. Hammar • K. Emilsson

Received: 14 December 2009 / Accepted: 15 February 2010

� Springer-Verlag 2010

Abstract

Purpose The size of the ventricles of the heart is

important to establish during the clinical echocardiographic

examination. Due to the complex anatomy of the right

ventricle, it is difficult to measure its size at times. One of

the most frequently used ways is to measure the right

ventricular outflow tract (RVOT1), probably due to its

good reproducibility. However, in the literature different

ways are described to measure RVOT1, both at different

sites and using different methods such as M-mode and 2D.

The first aim of the present study was to exam if there is a

significant difference in the outcome of RVOT1 using

different sites and methods to measure it. The second aim

was to study if there is a significant difference between the

usually preferred left lateral decubitus position during the

echocardiographic examination and the supine decubitus

position, which the echocardiographer sometimes can be

compelled to use if the patient is unable to lie in the left

lateral decubitus position.

Methods Twenty-seven healthy subjects were included

and examined by echocardiography. RVOT1 was measured

at different sites using different methods; first with the

subject in the left lateral decubitus position and then

repeating the same measurements with the subject in the

supine decubitus position.

Results Comparing the RVOT1 measured at different

sites and with different methods showed an overall

significant difference (p\ 0.001). Also when comparing

the different body positions, there was an overall signifi-

cant difference (p = 0.001).

Conclusions When comparing RVOT1 of the same

patient or subject over time, the results from the present

study indicate that the same site, method and body position

should be used.

Keywords Heart � Right ventricular size �Echocardiography � Body position

Introduction

The size of the heart, especially its ventricles, is important

to establish during the clinical echocardiographic exami-

nation, since larger ventricles often indicates an underlying

disease such as dilated cardiomyopathy, valvular disorder

or shunt.

The size of the left ventricle (LV) is associated with the

prognosis of the patient. It has important therapeutic

implications and can provide data that are necessary to

define the optimal time for cardiac surgery, for instance, in

patients with aortic- or mitral regurgitation [1]. A large

right ventricle (RV) may be seen in patients with different

kinds of heart diseases such as arrhytmogenic right ven-

tricular dysplasia (ARVD) [2], primary pulmonary disease,

but often it is a result of backward transmission of elevated

LV filling pressure through the pulmonary circulation, thus

augmenting RV afterload [3]. Large ventricles and ven-

tricular hypertrophy could, however, also be seen in

apparently healthy individuals such as athletes [4].

Different techniques such as two dimensional (2D)- or

three dimensional (3D) echocardiography and magnetic

resonance imaging, can be used to measure the size of the

K. Loiske � K. Emilsson (&)

Department of Clinical Physiology, Orebro University Hospital,

701 85 Orebro, Sweden

e-mail: [email protected]

S. Hammar

School of Health and Medical Sciences/Clinical Medicine,

Orebro University, Orebro, Sweden

123

Clin Res Cardiol

DOI 10.1007/s00392-010-0137-7

STUDY I

ventricles. Even though 3D echocardiography nowadays

has increased popularity, most echocardiographic examin-

ations still are performed using 2D echocardiography.

Due to the complex anatomy of RV, it is at times

difficult to measure its size. Several ways to measure the

RV have been suggested in the literature [5–15]. However,

probably because earlier studies [14] have shown the best

reproducibility measuring the RV inflow tract (RVIT3) and

RV outflow tract (RVOT1), those are the most frequently

used parameters.

RVIT3 is measured in the apical four chamber view one-

third from the base of the RV [10] but when it comes to

RVOT1, different ways are described in the literature on

how to measure it [5, 9, 10, 12–15].

Anatomically the RVOT extends cephalic and in a

leftward direction from the anteromedial portion of the

tricuspid valve annulus to the pulmonary annulus. The

anterior border is the anterior RV free wall. The posterior

boundary is the anteromedial portions of the aortic root. In

normal hearts, the crista supraventricularis is an anatomi-

cally identifiable structure to RVOT [15].

Considering that in the literature different ways have

been described to measure RVOT1 at different sites and

using different methods such as M-mode and 2D, the main

aim of the present study was to exam if there is a signifi-

cant difference in outcome of RVOT1 using the different

ways to measure it.

The left lateral decubitus position is often preferred to

obtain the best quality of images during the echocardio-

graphic examination. However, when echocardiography is

performed on seriously ill patients, for instance, patients

admitted to the intensive care unit or patients, for other

reasons, unable to lie in the left lateral decubitus position,

echocardiographers are sometimes compelled to examine

patients in a supine decubitus position. Earlier studies have

shown an increase in RV dimensions from supine to left

lateral decubitus position [5], why our second aim with this

study was to exam if there actually is a significant differ-

ence in RVOT1 due to the body position. If this is the case,

this should be taken into account when RVOT1 is mea-

sured in the supine decubitus position.

Patients and methods

Patients

Twenty-seven healthy subjects, 15 men and 12 women aged

21–35 years with average age 25.5 years, were included and

examined by echocardiography at the Department of Clini-

cal Physiology, Orebro University Hospital. They had a

normal ECG and no history of cardiac diseases. The inves-

tigations on the subjects were approved by the regional

ethical committee and informed consent was obtained from

each subject. Some basic characteristics and measured and

calculated variables are shown in Table 1.

Echocardiographic examination

A Vivid 7 echocardiograph (GE Vingmed Ultrasound A/S,

Horten, Norway) equipped with a multifrequency phased

array transducer (M35, 1.5–4.0 MHz) was used for the

echocardiographic examinations and measurements were

made after the examination using stored images in an

Echopac (GE Vingmed Ultrasound A/S) Compaq DeskPro

Workstation 300 (Compaq Computer Corporation, Hous-

ton, TX, USA).

The measurements of RVOT1 were performed from the

parasternal long-axis view, first with the subject in the left

lateral decubitus position and then in the supine decubitus

position. The different ways of measuring RVOT1 from

this view was at site ‘‘b’’ from the 2D-image (Fig. 1) [5,

14] and from the M-mode image (Fig. 2) [5, 14], at site ‘‘a’’

from the 2D-image (Fig. 3) [9, 15] and from the M-mode

image (Fig. 4) [12, 13].

As in the literature, RVOT1 in the short-axis projection

has been measured only using 2D-images, except for

Lindqvist et al. [7] who focused on the RV function (RVOT

fractional shortening) and not on the size of the RV, it was

only measured with this method in the present study, first

with the subject in the left lateral decubitus position and then

in the supine decubitus position (Fig. 5) [10].

To minimize the influence of respiration on RVOT1, the

measurements were done at the end of expiration and the

measurements and results were calculated as the average of

three beats. All subjects were in sinus rhythm.

Reproducibility of the measurements

The intra- and interindividual reproducibility (reproduc-

ibility study) was examined in ten of the subjects.

Table 1 Some basic characteristics and measured and calculated

variables (n = 27)

Variable Mean ± SD

Age (years) 25.5 ± 3.5

Height (m) 1.7 ± 0.1

Weight (kg) 70.2 ± 11.6

Left ventricular end-diastolic diameter (mm) 50.1 ± 5.8

Left ventricular end-systolic diameter (mm) 33.5 ± 5.1

Left ventricular septal wall thickness (mm) 8.2 ± 1.8

Left ventricular posterior wall thickness (mm) 8.7 ± 2.0

Tricuspid annulus motion (mm) 24.7 ± 4.2

Left ventricular ejection fraction (Teichholz) (%) 60.3 ± 6.4

Clin Res Cardiol

123

Investigator A (Karin Loiske) first measured RVOT1

according to Figs. 1, 2, 3, 4 and 5 in the left lateral decu-

bitus position and in the supine decubitus position.

Thereafter investigator B (Sofia Hammar) (blinded from

the measurements of investigator A) measured the same

parameters in the same way. Investigator A then again

performed the same procedure.

Statistics

ANOVA for repeated measurements, General Linear

Model (GLM), was used to exam if the overall obtained

differences and interactions of RVOT1 at the different

sites, different body positions and with different methods

were statistically significant. Post hoc test was done using

Bonferroni correction. The paired sampled t test was used

to compare the difference between body positions (left

lateral decubitus position versus supine decubitus position)

at each site.

In the intra- and interindividual reproducibility study, an

estimate of agreement was obtained by using Pearson’s

intraclass correlation coefficient, r [16]. The coefficient has

a range -1.0 to ?1.0 with high positive values indicating

high agreement, negative values indicating disagreement.

A difference at the 5% level was regarded as significant.

Data were analysed using the SPSS 16.0 statistical software

(SPSS, Chicago, IL, USA).

Results

First, the diameters of RVOT1 measured at site ‘‘a’’ and

‘‘b’’ in the parasternal long- axis view were compared with

each other, both from 2D-images and when using M-mode,

and from the two different body positions. There was found

to be an overall significant difference (p\ 0.001) between

the diameters of RVOT1 measured at sites ‘‘a’’ and ‘‘b’’,

with the diameters measured at ‘‘b’’ being higher than that

Fig. 1 RVOT1 measured in the parasternal long-axis view from the

2D-image according to site b [5, 14]

Fig. 2 RVOT1 measured in the

parasternal long-axis view in the

M-mode image according to site

b [5, 14]


2D-image according to site a [9, 15]

Clin Res Cardiol

123

ventricles. Even though 3D echocardiography nowadays

has increased popularity, most echocardiographic examin-

ations still are performed using 2D echocardiography.

Due to the complex anatomy of RV, it is at times

difficult to measure its size. Several ways to measure the

RV have been suggested in the literature [5–15]. However,

probably because earlier studies [14] have shown the best

reproducibility measuring the RV inflow tract (RVIT3) and

RV outflow tract (RVOT1), those are the most frequently

used parameters.

RVIT3 is measured in the apical four chamber view one-

third from the base of the RV [10] but when it comes to

RVOT1, different ways are described in the literature on

how to measure it [5, 9, 10, 12–15].

Anatomically the RVOT extends cephalic and in a

leftward direction from the anteromedial portion of the

tricuspid valve annulus to the pulmonary annulus. The

anterior border is the anterior RV free wall. The posterior

boundary is the anteromedial portions of the aortic root. In

normal hearts, the crista supraventricularis is an anatomi-

cally identifiable structure to RVOT [15].

Considering that in the literature different ways have

been described to measure RVOT1 at different sites and

using different methods such as M-mode and 2D, the main

aim of the present study was to exam if there is a signifi-

cant difference in outcome of RVOT1 using the different

ways to measure it.

The left lateral decubitus position is often preferred to

obtain the best quality of images during the echocardio-

graphic examination. However, when echocardiography is

performed on seriously ill patients, for instance, patients

admitted to the intensive care unit or patients, for other

reasons, unable to lie in the left lateral decubitus position,

echocardiographers are sometimes compelled to examine

patients in a supine decubitus position. Earlier studies have

shown an increase in RV dimensions from supine to left

lateral decubitus position [5], why our second aim with this

study was to exam if there actually is a significant differ-

ence in RVOT1 due to the body position. If this is the case,

this should be taken into account when RVOT1 is mea-

sured in the supine decubitus position.


Patients

Twenty-seven healthy subjects, 15 men and 12 women aged

21–35 years with average age 25.5 years, were included and

examined by echocardiography at the Department of Clini-

cal Physiology, Orebro University Hospital. They had a

normal ECG and no history of cardiac diseases. The inves-

tigations on the subjects were approved by the regional

ethical committee and informed consent was obtained from

each subject. Some basic characteristics and measured and

calculated variables are shown in Table 1.


A Vivid 7 echocardiograph (GE Vingmed Ultrasound A/S,

Horten, Norway) equipped with a multifrequency phased

array transducer (M35, 1.5–4.0 MHz) was used for the

echocardiographic examinations and measurements were

made after the examination using stored images in an

Echopac (GE Vingmed Ultrasound A/S) Compaq DeskPro

Workstation 300 (Compaq Computer Corporation, Hous-

ton, TX, USA).

The measurements of RVOT1 were performed from the

parasternal long-axis view, first with the subject in the left

lateral decubitus position and then in the supine decubitus

position. The different ways of measuring RVOT1 from

this view was at site ‘‘b’’ from the 2D-image (Fig. 1) [5,

14] and from the M-mode image (Fig. 2) [5, 14], at site ‘‘a’’

from the 2D-image (Fig. 3) [9, 15] and from the M-mode

image (Fig. 4) [12, 13].

As in the literature, RVOT1 in the short-axis projection

has been measured only using 2D-images, except for

Lindqvist et al. [7] who focused on the RV function (RVOT

fractional shortening) and not on the size of the RV, it was

only measured with this method in the present study, first

with the subject in the left lateral decubitus position and then

in the supine decubitus position (Fig. 5) [10].

To minimize the influence of respiration on RVOT1, the

measurements were done at the end of expiration and the

measurements and results were calculated as the average of

three beats. All subjects were in sinus rhythm.


The intra- and interindividual reproducibility (reproduc-

ibility study) was examined in ten of the subjects.

Table 1 Some basic characteristics and measured and calculated

variables (n = 27)

Variable Mean ± SD

Age (years) 25.5 ± 3.5

Height (m) 1.7 ± 0.1

Weight (kg) 70.2 ± 11.6

Left ventricular end-diastolic diameter (mm) 50.1 ± 5.8

Left ventricular end-systolic diameter (mm) 33.5 ± 5.1

Left ventricular septal wall thickness (mm) 8.2 ± 1.8

Left ventricular posterior wall thickness (mm) 8.7 ± 2.0

Tricuspid annulus motion (mm) 24.7 ± 4.2

Left ventricular ejection fraction (Teichholz) (%) 60.3 ± 6.4

Clin Res Cardiol

123

Investigator A (Karin Loiske) first measured RVOT1

according to Figs. 1, 2, 3, 4 and 5 in the left lateral decu-

bitus position and in the supine decubitus position.

Thereafter investigator B (Sofia Hammar) (blinded from

the measurements of investigator A) measured the same

parameters in the same way. Investigator A then again


Statistics

ANOVA for repeated measurements, General Linear

Model (GLM), was used to exam if the overall obtained

differences and interactions of RVOT1 at the different

sites, different body positions and with different methods

were statistically significant. Post hoc test was done using

Bonferroni correction. The paired sampled t test was used

to compare the difference between body positions (left

lateral decubitus position versus supine decubitus position)

at each site.

In the intra- and interindividual reproducibility study, an

estimate of agreement was obtained by using Pearson’s

intraclass correlation coefficient, r [16]. The coefficient has

a range -1.0 to ?1.0 with high positive values indicating

high agreement, negative values indicating disagreement.

A difference at the 5% level was regarded as significant.

Data were analysed using the SPSS 16.0 statistical software

(SPSS, Chicago, IL, USA).

Results

First, the diameters of RVOT1 measured at site ‘‘a’’ and

‘‘b’’ in the parasternal long- axis view were compared with

each other, both from 2D-images and when using M-mode,

and from the two different body positions. There was found

to be an overall significant difference (p\ 0.001) between

the diameters of RVOT1 measured at sites ‘‘a’’ and ‘‘b’’,

with the diameters measured at ‘‘b’’ being higher than that


2D-image according to site b [5, 14]

Fig. 2 RVOT1 measured in the

parasternal long-axis view in the

M-mode image according to site

b [5, 14]


2D-image according to site a [9, 15]

Clin Res Cardiol

123

STUDY I

measured at ‘‘a’’ (mean 30.9 ± 5.7 mm vs.

24.2 ± 5.4 mm) (Fig. 6).

Comparing the diameters of RVOT1 at ‘‘a’’ and ‘‘b’’

measured with 2D and M-mode, respectively, also shows

an overall significant difference (p\ 0.001) between the

both methods (Table 2). Also when comparing the differ-

ent body positions there were an overall significant dif-

ference (p = 0.001) (Table 2).

The two-way interaction between the different sites and

methods was also statistically significant (p\ 0.001), as

were the interaction between the sites and body positions

(p = 0.022). There was no significant difference between

the methods and body positions (p = 0.290). Three-way

interaction between the different sites, methods and body

positions did not show any significant difference

(p = 0.270) (Table 2).

Comparing RVOT1 measured in the parasternal long-

axis view at sites ‘‘a’’ and ‘‘b’’ and short-axis using

2D-images shows an overall significant difference

(p\ 0.001) with the highest mean at site ‘‘b’’ (31.4 ±

5.8 mm vs. short-axis 29.5 ± 5.6 mm and site ‘‘a’’

27.4 ± 4.6 mm) (Fig. 7). There was also an overall sig-

nificant difference (p = 0.013) between RVOT1 measured

using 2D at the three different sites and the body positions.

The two-way interaction between the sites and the body

positions was also shown to be statistically significant

(p = 0.042) (Table 3). Pair wise comparisons using post

hoc test (Bonferroni correction) of ANOVA between the

three different sites also showed significant differences:

‘‘a’’ versus ‘‘b’’ p\ 0.001; ‘‘a’’ versus ‘‘short-axis’’

p = 0.009; ‘‘b’’ versus ‘‘short-axis’’ p\ 0.001.

Using paired sampled t test comparing RVOT1 at the

three different sites and the two body positions there was

found to be no significant difference in RVOT1 measured

from the parasternal long-axis view from 2D-image

according to site ‘‘b’’ in the left lateral decubitus position

versus the supine decubitus position (p = 0.28). Nor was it

found to be any significant difference between RVOT1

measured from the parasternal long-axis view with M-

mode according to site ‘‘b’’ in the left lateral decubitus

position versus the supine decubitus position (p = 0.27).

RVOT1 measured from the parasternal short-axis view

from the 2D-image did not show any significant difference

in the left lateral decubitus position versus the supine

decubitus position either (p = 0.43). There was, however,

a significant difference between the left lateral decubitus

position and the supine decubitus position in RVOT1

measured from the parasternal long-axis view from the 2D-

image according to site ‘‘a’’ (p = 0.01) and from the par-

asternal long-axis view with M-mode according to site ‘‘a’’

(p = 0.01). The intra- and interindividual reproducibility

using the intraclass correlation coefficient is presented in

Table 4.

Fig. 5 RVOT1 measured from the parasternal short-axis view from

the 2D-image [10]

Fig. 4 RVOT1 measured from

the parasternal long-axis view in

the M-mode image according to

site a [12, 13]

Clin Res Cardiol

123

Discussion

In the present study, a significant difference between

RVOT1 has been shown when it is measured at the dif-

ferent proposed sites and also considering sites ‘‘a’’ and

‘‘b’’ there is a significant difference between when RVOT1

is measured using M-mode or from 2D-images. An overall

significant difference between RVOT1 at the different sites

and the body positions has also been shown.

How should then RVOT1 be measured? First of all it

seems obvious that one should use the same site, method

and body position when a single patient/subject is followed

over time. However, due to the low interindividual repro-

ducibility, especially using M-mode, and also rather low

intraindividual reproducibility (Table 4), site ‘‘a’’ should

be avoided.

The cause of the lower reproducibility at this site

compared to the other sites is probably due to the absence

of a reference point to measure from. When measuring at

site ‘‘b’’ the aortic root can be used as a reference point

giving higher inter- and intraindividual reproducibility.

Also when measuring in short-axis it is easier to find a

reference point at the aortic root level than when mea-

suring according to site ‘‘a’’. When RVOT1 is measured

using M-mode according to site ‘‘a’’ it is also a risk that

the M-mode line cuts the RV more apical than at the

RVOT1 region.

The subjects RV are configured differently, some are

more round in their shape while others are long. This could

contribute to the significant differences between methods

and body positions when using site ‘‘a’’ since it can make it

difficult to exam the RV with a good image quality. It may,

as was noted in some of the subjects, be difficult to

determine the septal wall contour, especially in the M-

mode image but also in the 2D image, due to that the

chordae tendinae and papillary muscles sometimes disturb

the determination of the septal wall border, and therefore

making it difficult to assess the borders of the RV lumen.

When measuring at the different sites, thus preferably

site ‘‘b’’ and short-axis, one should use the same method,

M-mode or 2D, at different occasions if one should be able

to compare if the diameter of RVOT1 has changed over

time in the same patient or subject.

When it comes to the body position, this also preferably

should be the same between different occasions of inves-

tigations. However, sometimes there are reasons to why the

patient not can be in the same position as at the last

examination, for instance unconscious patients at the

intensive care unit that not can be laid in the left lateral

decubitus position. In such cases, one should use site ‘‘b’’

or short-axis, since the present study have not shown

27 subjects n=216

measurements

Site ”a” 24.2 (5.4)

n=108

Site ”b” 30.9 (5.7)

n=108

Method 2D 27.4 (4.6)

n=54

Method MM 21.1 (4.3)

n=54

Method 2D 31.4 (5.8)

n=54


n=54

Left28.6 (4.6)

n=27

Supine26.2 (4.3)

n=27

Left22.8 (4.4)

n=27

Supine19.3 (3.5)

n=27

Left31.8 (5.9)

n=27

Supine31.0 (5.9)

n=27

Left30.8 (5.3)

n=27

Supine30.0 (5.9)

n=27

Fig. 6 RVOT1, in mm, measured at site ‘‘a’’ and ‘‘b’’ in the parasternal long-axis view, from 2D-images and when using M-mode, and from the

two different body positions (left lateral decubitus position and supine decubitus position)

Table 2 ANOVA for repeated measurements of RVOT1 at two

different sites, ‘‘a’’ and ‘‘b’’, measured with different methods, 2D and

M-mode, in different body positions

1. Main effects

Site (‘‘a’’/’’b’’) p\ 0.001

Method (2D/M-mode) p\ 0.001

Body position (left/supine) p = 0.001

2. Two-way interaction

Site/method p\ 0.001

Site/position p = 0.022

Method/position p = 0.290

3. Three-way interaction

Site/method/position p = 0.270

Left left lateral decubitus position, supine supine decubitus position

Clin Res Cardiol

123

measured at ‘‘a’’ (mean 30.9 ± 5.7 mm vs.

24.2 ± 5.4 mm) (Fig. 6).

Comparing the diameters of RVOT1 at ‘‘a’’ and ‘‘b’’

measured with 2D and M-mode, respectively, also shows

an overall significant difference (p\ 0.001) between the

both methods (Table 2). Also when comparing the differ-

ent body positions there were an overall significant dif-

ference (p = 0.001) (Table 2).

The two-way interaction between the different sites and

methods was also statistically significant (p\ 0.001), as

were the interaction between the sites and body positions

(p = 0.022). There was no significant difference between

the methods and body positions (p = 0.290). Three-way

interaction between the different sites, methods and body

positions did not show any significant difference

(p = 0.270) (Table 2).

Comparing RVOT1 measured in the parasternal long-

axis view at sites ‘‘a’’ and ‘‘b’’ and short-axis using

2D-images shows an overall significant difference

(p\ 0.001) with the highest mean at site ‘‘b’’ (31.4 ±

5.8 mm vs. short-axis 29.5 ± 5.6 mm and site ‘‘a’’

27.4 ± 4.6 mm) (Fig. 7). There was also an overall sig-

nificant difference (p = 0.013) between RVOT1 measured

using 2D at the three different sites and the body positions.

The two-way interaction between the sites and the body

positions was also shown to be statistically significant

(p = 0.042) (Table 3). Pair wise comparisons using post

hoc test (Bonferroni correction) of ANOVA between the

three different sites also showed significant differences:

‘‘a’’ versus ‘‘b’’ p\ 0.001; ‘‘a’’ versus ‘‘short-axis’’

p = 0.009; ‘‘b’’ versus ‘‘short-axis’’ p\ 0.001.

Using paired sampled t test comparing RVOT1 at the

three different sites and the two body positions there was

found to be no significant difference in RVOT1 measured

from the parasternal long-axis view from 2D-image

according to site ‘‘b’’ in the left lateral decubitus position

versus the supine decubitus position (p = 0.28). Nor was it

found to be any significant difference between RVOT1

measured from the parasternal long-axis view with M-

mode according to site ‘‘b’’ in the left lateral decubitus

position versus the supine decubitus position (p = 0.27).

RVOT1 measured from the parasternal short-axis view

from the 2D-image did not show any significant difference

in the left lateral decubitus position versus the supine

decubitus position either (p = 0.43). There was, however,

a significant difference between the left lateral decubitus

position and the supine decubitus position in RVOT1

measured from the parasternal long-axis view from the 2D-

image according to site ‘‘a’’ (p = 0.01) and from the par-

asternal long-axis view with M-mode according to site ‘‘a’’

(p = 0.01). The intra- and interindividual reproducibility

using the intraclass correlation coefficient is presented in

Table 4.

Fig. 5 RVOT1 measured from the parasternal short-axis view from

the 2D-image [10]

Fig. 4 RVOT1 measured from

the parasternal long-axis view in

the M-mode image according to

site a [12, 13]

Clin Res Cardiol

123

Discussion

In the present study, a significant difference between

RVOT1 has been shown when it is measured at the dif-

ferent proposed sites and also considering sites ‘‘a’’ and

‘‘b’’ there is a significant difference between when RVOT1

is measured using M-mode or from 2D-images. An overall

significant difference between RVOT1 at the different sites

and the body positions has also been shown.

How should then RVOT1 be measured? First of all it

seems obvious that one should use the same site, method

and body position when a single patient/subject is followed

over time. However, due to the low interindividual repro-

ducibility, especially using M-mode, and also rather low

intraindividual reproducibility (Table 4), site ‘‘a’’ should

be avoided.

The cause of the lower reproducibility at this site

compared to the other sites is probably due to the absence

of a reference point to measure from. When measuring at

site ‘‘b’’ the aortic root can be used as a reference point

giving higher inter- and intraindividual reproducibility.

Also when measuring in short-axis it is easier to find a

reference point at the aortic root level than when mea-

suring according to site ‘‘a’’. When RVOT1 is measured

using M-mode according to site ‘‘a’’ it is also a risk that

the M-mode line cuts the RV more apical than at the

RVOT1 region.

The subjects RV are configured differently, some are

more round in their shape while others are long. This could

contribute to the significant differences between methods

and body positions when using site ‘‘a’’ since it can make it

difficult to exam the RV with a good image quality. It may,

as was noted in some of the subjects, be difficult to

determine the septal wall contour, especially in the M-

mode image but also in the 2D image, due to that the

chordae tendinae and papillary muscles sometimes disturb

the determination of the septal wall border, and therefore

making it difficult to assess the borders of the RV lumen.

When measuring at the different sites, thus preferably

site ‘‘b’’ and short-axis, one should use the same method,

M-mode or 2D, at different occasions if one should be able

to compare if the diameter of RVOT1 has changed over

time in the same patient or subject.

When it comes to the body position, this also preferably

should be the same between different occasions of inves-

tigations. However, sometimes there are reasons to why the

patient not can be in the same position as at the last

examination, for instance unconscious patients at the

intensive care unit that not can be laid in the left lateral

decubitus position. In such cases, one should use site ‘‘b’’

or short-axis, since the present study have not shown

27 subjects n=216

measurements

Site ”a” 24.2 (5.4)

n=108

Site ”b” 30.9 (5.7)

n=108

Method 2D 27.4 (4.6)

n=54


n=54

Method 2D 31.4 (5.8)

n=54


n=54

Left28.6 (4.6)

n=27

Supine26.2 (4.3)

n=27

Left22.8 (4.4)

n=27

Supine19.3 (3.5)

n=27

Left31.8 (5.9)

n=27

Supine31.0 (5.9)

n=27

Left30.8 (5.3)

n=27

Supine30.0 (5.9)

n=27

Fig. 6 RVOT1, in mm, measured at site ‘‘a’’ and ‘‘b’’ in the parasternal long-axis view, from 2D-images and when using M-mode, and from the

two different body positions (left lateral decubitus position and supine decubitus position)

Table 2 ANOVA for repeated measurements of RVOT1 at two

different sites, ‘‘a’’ and ‘‘b’’, measured with different methods, 2D and

M-mode, in different body positions

1. Main effects

Site (‘‘a’’/’’b’’) p\ 0.001

Method (2D/M-mode) p\ 0.001

Body position (left/supine) p = 0.001


Site/method p\ 0.001


Method/position p = 0.290

3. Three-way interaction

Site/method/position p = 0.270


Clin Res Cardiol

123

STUDY I

significant difference in RVOT1 measured at those sites at

different body positions. Site ‘‘a’’ should be avoided since

there was found to be a significant difference at this site

between RVOT1 measured in supine versus left lateral

decubitus position.

The size of RVOT1 was significantly measured higher

from site ‘‘a’’ with the subjects in the left lateral decubitus

position compared when subjects were in the supine

decubitus position (both 2D and M-mode indicated this). If

this difference was not due to the measuring technique, one

could wonder if there is a difference in the RV volume

depending on body position. This would, however, also

have affected RVOT1 measured from site ‘‘b’’ and from

short-axis, why this theory seems less probable.

This study was performed on healthy subjects, aged 21–

35 years, with generally good quality of image and

examination technique. It would be of interest to perform a

similar study on patients, in which the quality of images

and examination technique are not always optimal.

Reproducibility study

There was a good intraindividual reproducibility for most

of the investigated parameters except when measuring

RVOT1 at site ‘‘a’’ with M-mode, which was somewhat

lower. Even the interindividual reproducibility was good

for most of the measured parameters. However, in some

cases lower intraindividual reproducibility was probably

because investigator B was not an experienced echocardi-

ographer as investigator A.

The lowest interindividual reproducibility was found for

measuring RVOT1 at site ‘‘a’’ with M-mode, which to

some extent may be due to investigator B not being an

experienced echocardiographer as investigator A. Also

probably due to the absence of reference point when

measuring at site ‘‘a’’ compared to measuring at site ‘‘b’’

and at short-axis as has been mentioned earlier.

Conclusions

The RV has a complex anatomy and therefore it is often

difficult to measure its size. A parameter that many times

has been used to measure its size, probably due to that it

has been found to have good reproducibility, is RVOT1.

However, as has been shown in the present study, the

diameters of RVOT1 are different at different sites, when

using different methods and in different body positions.

When comparing RVOT1 over time in the same patient

or subject the results from the present study therefore

indicate that the same site, method and body position

should be used. Due to the lower reproducibility at site ‘‘a’’

than at site ‘‘b’’ and short-axis, probably due to the absence

of reference point when measuring at site ‘‘a’’, the two

latter sites should be preferred before site ‘‘a’’ when mea-

suring RVOT1.

Limitations of the study

It would have been of interest to compare the obtained

values of RVOT1 in the present study with measurements

of the same parameters with 3D echocardiography and to

compare the obtained values with a reference method such

as real-time 3D echo or magnetic resonance imaging to

establish which of the measurements is the best estimate

for true RV size. However, there was no equipment

27 subjects 2-D

n=162 measurements

Site ”b” 31.4 (5.8)

n=54

Site ”a” 27.4 (4.6)

n=54

Short axis 29.5 (5.6)

n=54

Left28.6 (4.6)

n=27

Supine 26.2 (4.3)

n=27

Left31.8 (5.9)

n=27

Supine 31.0 (5.9)

n=27

Left29.7 (5.5)

n=27

Supine 29.2 (5.8)

n=27

Fig. 7 RVOT1, in mm,

measured in the parasternal

long-axis view at site ‘‘a’’ and

‘‘b’’ and short axis using 2D-

images and in left lateral and

supine decubitus position

Table 3 ANOVA for repeated measurements of RVOT1, using 2D at

three different sites (‘‘a’’, ‘‘b’’ and short-axis) and in different body

positions

1. Main effects

Site (‘‘a’’, ‘‘b’’ and short axis) p\ 0.001

Position (left versus supine) p = 0.013




Clin Res Cardiol

123

available to do 3D echocardiography at our laboratory

when the study was performed and a magnetic resonance

imaging study in close connection to the echocardiographic

examination could not be arranged.

Acknowledgments We gratefully thank statistician Anders Mag-

nuson, Units of Statistics and Epidemiology, Centre for Clinical

Research, Orebro University Hospital, for his statistical advice and

Hubert Bouma, Canada, for correcting the English language in the

text.

References

1. Aurigemma GP, Douglas PS, Gaasch WH (2002) Quantitative

evaluation of left ventricular structure, wall stress and systolic

function. In: Otto C (ed) The practice of clinical echocardiogra-

phy, 2nd edn. W.B. Saunders company, Philadelphia, p 65

2. Frances RJ (2006) Arrhythmogenic right ventricular dysplasia/

cardiomyopathy. A review and update. Int J Cardiol 110:279–287

3. Wong SP, Otto CM (2002) Echocardiographic findings in acute

and chronic pulmonary disease. In: Otto C (ed) The practice of

clinical echocardiography, 2nd edn. W.B. Saunders company,

Philadelphia, p 741

4. Lauschke J, Maisch B (2009) Athlete0s heart or hypertrophic

cardiomyopathy? Clin Res Cardiol 98:80–88

5. Norgard G, Vik-Mo H (1992) Effects of respiration on right

ventricular size and function: an echocardiographic study. Pediatr

Cardiol 13:136–140

6. Henriksen E, Landelius J, Kangro T, Jonason T, Hedberg P,

Wesslen L, Rosander CN, Rolf C, Ringqvist I, Friman G (1999)

An echocardiographic study of the right and left ventricular

adaptation to physical exercise in elite female orienteers. Eur

Heart J 20:309–316

7. Lindqvist P, Henein M, Kazzam E (2003) Right ventricular

outflow-tract fractional shortening: an applicable measure of right

ventricular systolic function. Eur J Echocardiogr 4:29–35

8. Otto C (2004) Left and right ventricular systolic function. In: Otto

C (ed) Textbook of clinical echocardiography, 3rd edn. Elsevier,

Philadelphia, pp 151–152

9. Feigenbaum H, Armstrong W, Ryan T (2005) Left atrium, right

atrium and right ventricle. In: Feigenbaum H (ed) Echocardiog-

raphy, 6th edn. Williams & Wilkins, Philadelphia, pp 202–204

10. Lang RM, Bierig M et al (2005) Recommendations of chamber

quantification: a report from the American society of echocardi-

ography’s guidelines and standards committee and the chamber

quantification group, developed in conjunction with the European

association of echocardiography, a branch of the European

society of cardiology. J Am Soc Echocardiogr 18:1440–1463

11. Lindqvist P, Calcutteea A, Henein M (2008) Echocardiography

on the assessment of right heart function. Eur J Echocardiogr

9:225–234

12. Sahn DJ, DeMaria A, Kisslo J, Weyman A (1978) Recommen-

dations regarding quantitation in m-mode echocardiography:

results of a survey of echocardiographic measurements. Circu-

lation 6:1072–1083

13. Baker BJ, Scovil JA, Kane JJ, Murphy ML (1983) Echocardio-

graphic detection of right ventricular hypertrophy. Am Heart J

105:611–614

14. Foale R, Nihoyannopoulos P, McKenna W, Klienebenne A,

Nadazdin A, Rowland E, Smith G (1986) Echocardiographic

measurement of the normal adult right ventricle. Br Heart J

56:33–44

15. Feigenbaum H (ed) (1994) Echocardiography, 5th edn. Williams

& Wilkins, Philadelphia, p 88

16. Dunn G (1989) Design and analysis of reliability studies. Oxford

University Press, New York

Table 4 The intra- and interobserver reproducibility of measuring

RVOT1 from the 2D-image and in M-mode according to site ‘‘a’’ and

‘‘b’’ from the parasternal long-axis view and from the 2D-image in

short-axis, with the subject in the left lateral decubitus position and

the supine decubitus position measured in ten of the subjects

Agreement, single

measurements,

investigator A and B

Agreement, double

measurements,

investigator A

RVOT1 measured from 2D-image, site ‘‘b’’, left lateral decubitus position 0.94 0.95

RVOT1 measured from 2D-image, site ‘‘b’’, supine decubitus position 0.94 0.92

RVOT1 measured from M-mode, site ‘‘b’’, left lateral decubitus position 0.91 0.90

RVOT1 measured from M-mode, site ‘‘b’’, supine decubitus position 0.92 0.94

RVOT1 measured from 2D-image, site ‘‘a’’, left lateral decubitus position 0.88 0.95

RVOT1 measured from 2D-image, site ‘‘a’’, supine decubitus position 0.84 0.98

RVOT1 measured from M-mode, site ‘‘a’’, left lateral decubitus position 0.35 0.79

RVOT1 measured from M-mode, site ‘‘a’’, supine decubitus position 0.48 0.86

RVOT1 measured from 2D-image, short axis, left lateral decubitus position 0.95 0.87

RVOT1 measured from 2D-image, short axis, supine decubitus position 0.78 0.95

The agreement was measured by Pearson’s intraclass correlation coefficient (the coefficient has a range -1.0 to ?1.0 with high positive values

indicating high agreement, negative values indicating disagreement)

Clin Res Cardiol

123

significant difference in RVOT1 measured at those sites at

different body positions. Site ‘‘a’’ should be avoided since

there was found to be a significant difference at this site

between RVOT1 measured in supine versus left lateral

decubitus position.

The size of RVOT1 was significantly measured higher

from site ‘‘a’’ with the subjects in the left lateral decubitus

position compared when subjects were in the supine

decubitus position (both 2D and M-mode indicated this). If

this difference was not due to the measuring technique, one

could wonder if there is a difference in the RV volume

depending on body position. This would, however, also

have affected RVOT1 measured from site ‘‘b’’ and from

short-axis, why this theory seems less probable.

This study was performed on healthy subjects, aged 21–

35 years, with generally good quality of image and

examination technique. It would be of interest to perform a

similar study on patients, in which the quality of images

and examination technique are not always optimal.


There was a good intraindividual reproducibility for most

of the investigated parameters except when measuring

RVOT1 at site ‘‘a’’ with M-mode, which was somewhat

lower. Even the interindividual reproducibility was good

for most of the measured parameters. However, in some

cases lower intraindividual reproducibility was probably

because investigator B was not an experienced echocardi-

ographer as investigator A.

The lowest interindividual reproducibility was found for

measuring RVOT1 at site ‘‘a’’ with M-mode, which to

some extent may be due to investigator B not being an

experienced echocardiographer as investigator A. Also

probably due to the absence of reference point when

measuring at site ‘‘a’’ compared to measuring at site ‘‘b’’

and at short-axis as has been mentioned earlier.

Conclusions

The RV has a complex anatomy and therefore it is often

difficult to measure its size. A parameter that many times

has been used to measure its size, probably due to that it

has been found to have good reproducibility, is RVOT1.

However, as has been shown in the present study, the

diameters of RVOT1 are different at different sites, when

using different methods and in different body positions.

When comparing RVOT1 over time in the same patient

or subject the results from the present study therefore

indicate that the same site, method and body position

should be used. Due to the lower reproducibility at site ‘‘a’’

than at site ‘‘b’’ and short-axis, probably due to the absence

of reference point when measuring at site ‘‘a’’, the two

latter sites should be preferred before site ‘‘a’’ when mea-

suring RVOT1.

Limitations of the study

It would have been of interest to compare the obtained

values of RVOT1 in the present study with measurements

of the same parameters with 3D echocardiography and to

compare the obtained values with a reference method such

as real-time 3D echo or magnetic resonance imaging to

establish which of the measurements is the best estimate

for true RV size. However, there was no equipment

27 subjects 2-D

n=162 measurements

Site ”b” 31.4 (5.8)

n=54

Site ”a” 27.4 (4.6)

n=54

Short axis 29.5 (5.6)

n=54

Left28.6 (4.6)

n=27

Supine 26.2 (4.3)

n=27

Left31.8 (5.9)

n=27

Supine 31.0 (5.9)

n=27

Left29.7 (5.5)

n=27

Supine 29.2 (5.8)

n=27

Fig. 7 RVOT1, in mm,

measured in the parasternal

long-axis view at site ‘‘a’’ and

‘‘b’’ and short axis using 2D-

images and in left lateral and

supine decubitus position

Table 3 ANOVA for repeated measurements of RVOT1, using 2D at

three different sites (‘‘a’’, ‘‘b’’ and short-axis) and in different body

positions

1. Main effects

Site (‘‘a’’, ‘‘b’’ and short axis) p\ 0.001

Position (left versus supine) p = 0.013




Clin Res Cardiol

123

available to do 3D echocardiography at our laboratory

when the study was performed and a magnetic resonance

imaging study in close connection to the echocardiographic

examination could not be arranged.

Acknowledgments We gratefully thank statistician Anders Mag-

nuson, Units of Statistics and Epidemiology, Centre for Clinical

Research, Orebro University Hospital, for his statistical advice and

Hubert Bouma, Canada, for correcting the English language in the

text.

References

1. Aurigemma GP, Douglas PS, Gaasch WH (2002) Quantitative

evaluation of left ventricular structure, wall stress and systolic

function. In: Otto C (ed) The practice of clinical echocardiogra-

phy, 2nd edn. W.B. Saunders company, Philadelphia, p 65

2. Frances RJ (2006) Arrhythmogenic right ventricular dysplasia/

cardiomyopathy. A review and update. Int J Cardiol 110:279–287

3. Wong SP, Otto CM (2002) Echocardiographic findings in acute

and chronic pulmonary disease. In: Otto C (ed) The practice of

clinical echocardiography, 2nd edn. W.B. Saunders company,

Philadelphia, p 741

4. Lauschke J, Maisch B (2009) Athlete0s heart or hypertrophic

cardiomyopathy? Clin Res Cardiol 98:80–88

5. Norgard G, Vik-Mo H (1992) Effects of respiration on right

ventricular size and function: an echocardiographic study. Pediatr

Cardiol 13:136–140

6. Henriksen E, Landelius J, Kangro T, Jonason T, Hedberg P,

Wesslen L, Rosander CN, Rolf C, Ringqvist I, Friman G (1999)

An echocardiographic study of the right and left ventricular

adaptation to physical exercise in elite female orienteers. Eur

Heart J 20:309–316

7. Lindqvist P, Henein M, Kazzam E (2003) Right ventricular

outflow-tract fractional shortening: an applicable measure of right

ventricular systolic function. Eur J Echocardiogr 4:29–35

8. Otto C (2004) Left and right ventricular systolic function. In: Otto

C (ed) Textbook of clinical echocardiography, 3rd edn. Elsevier,

Philadelphia, pp 151–152

9. Feigenbaum H, Armstrong W, Ryan T (2005) Left atrium, right

atrium and right ventricle. In: Feigenbaum H (ed) Echocardiog-

raphy, 6th edn. Williams & Wilkins, Philadelphia, pp 202–204

10. Lang RM, Bierig M et al (2005) Recommendations of chamber

quantification: a report from the American society of echocardi-

ography’s guidelines and standards committee and the chamber

quantification group, developed in conjunction with the European

association of echocardiography, a branch of the European

society of cardiology. J Am Soc Echocardiogr 18:1440–1463

11. Lindqvist P, Calcutteea A, Henein M (2008) Echocardiography

on the assessment of right heart function. Eur J Echocardiogr

9:225–234

12. Sahn DJ, DeMaria A, Kisslo J, Weyman A (1978) Recommen-

dations regarding quantitation in m-mode echocardiography:

results of a survey of echocardiographic measurements. Circu-

lation 6:1072–1083

13. Baker BJ, Scovil JA, Kane JJ, Murphy ML (1983) Echocardio-

graphic detection of right ventricular hypertrophy. Am Heart J

105:611–614

14. Foale R, Nihoyannopoulos P, McKenna W, Klienebenne A,

Nadazdin A, Rowland E, Smith G (1986) Echocardiographic

measurement of the normal adult right ventricle. Br Heart J

56:33–44

15. Feigenbaum H (ed) (1994) Echocardiography, 5th edn. Williams

& Wilkins, Philadelphia, p 88

16. Dunn G (1989) Design and analysis of reliability studies. Oxford

University Press, New York

Table 4 The intra- and interobserver reproducibility of measuring

RVOT1 from the 2D-image and in M-mode according to site ‘‘a’’ and

‘‘b’’ from the parasternal long-axis view and from the 2D-image in

short-axis, with the subject in the left lateral decubitus position and

the supine decubitus position measured in ten of the subjects

Agreement, single

measurements,


Agreement, double

measurements,

investigator A

RVOT1 measured from 2D-image, site ‘‘b’’, left lateral decubitus position 0.94 0.95

RVOT1 measured from 2D-image, site ‘‘b’’, supine decubitus position 0.94 0.92

RVOT1 measured from M-mode, site ‘‘b’’, left lateral decubitus position 0.91 0.90

RVOT1 measured from M-mode, site ‘‘b’’, supine decubitus position 0.92 0.94

RVOT1 measured from 2D-image, site ‘‘a’’, left lateral decubitus position 0.88 0.95

RVOT1 measured from 2D-image, site ‘‘a’’, supine decubitus position 0.84 0.98

RVOT1 measured from M-mode, site ‘‘a’’, left lateral decubitus position 0.35 0.79

RVOT1 measured from M-mode, site ‘‘a’’, supine decubitus position 0.48 0.86

RVOT1 measured from 2D-image, short axis, left lateral decubitus position 0.95 0.87

RVOT1 measured from 2D-image, short axis, supine decubitus position 0.78 0.95

The agreement was measured by Pearson’s intraclass correlation coefficient (the coefficient has a range -1.0 to ?1.0 with high positive values

indicating high agreement, negative values indicating disagreement)

Clin Res Cardiol

123

STUDY I

STUDY II

STUDY II

��

��

Objectives—The isovolumetric relaxation time of theright ventricle (RV-IVRT) can be assessed using amethod based on ECG and pulsed wave Doppler (PW).Recently pulsed wave Doppler tissue imaging (PW-DTI) has been introduced in the assessment.Design—RV-IVRT obtained by the two methods wascompared in 20 consecutive patients as was the timefrom the R wave on the ECG to the onset of tricuspidflow (R-T), to the closure of the pulmonic valve (R-P),to the onset of early diastolic motion of the tricuspidannulus tissue (R-E) and to the end of the systolicmotion (R-S).Results—RV-IVRT obtained by the PW method wassignificantly (p � 0.001) shorter than RV-IVRT ob-tained by PW-DTI. R-S had significantly (p � 0.001)shorter duration than R-P, while there was nosignificant difference between R-E and R-T.Conclusions—The methods are not measuring thesame interval. Only the PW method measures RV-IVRT according to the usual definition. Differentreference values have to be used if the methods areused in the assessment of RV diastolic function.

��

Left ventricular relaxation time (LV-IVRT), defined asthe time from aortic valve closure to the start of mitralflow (1), is used in the assessment of LV diastolicfunction and is relatively easy to measure by echocardio-graphy from an apical transducer position using thepulsed wave (PW) or continuous wave (CW) Dopplertechnique as described by Appleton et al. (1) or withECG and PW Doppler as described by Larrazet et al. (2).

The right ventricular isovolumetric relaxation time(RV-IVRT), that is the interval from pulmonic valveclosure to the start of tricuspid valve opening (3), mayin the same way as the LV-IVRT is used as an index ofLV diastolic function, be used as an index of RVdiastolic function (4). RV-IVRT has been shown tohave a shorter duration than LV-IVRT (2).

The RV-IVRT is more difficult to obtain than LV-IVRT since there is no good echocardiographic viewfrom which both the pulmonic valve and the tricuspidinflow can be measured simultaneously. However, evenin this case the method described by Larrazet et al. (2)can be used.

During recent years some authors, for instanceSeverino et al. (5), Caso et al. (6) and Ozdemir et al.(7), have used pulsed wave Doppler tissue imaging(PW-DTI) when measuring RV-IVRT, from now oncalled RV-IVRT(PWDTI). However, it has not beensufficiently investigated in patients whether the durationof the interval measured with PW-DTI is the sameas the duration of the interval measured with themethod based on ECG and PW Doppler. The aim ofthe present study was therefore to compare RV-IVRTand RV-IVRT(PWDTI) and to try to explain aneventual difference.

��

��Twenty consecutive patients referred to echocardiography were included.Since earlier studies have shown prolonged RV-IVRT in patients withhypertrophic cardiomyopathy (8), patients with LV wall thickness�14 mm were not included as were not patients with atrial fibrillation,left and right bundle branch block, pacemaker treatment or a history ofcardiac surgery since the effect on RV-IVRT has not been sufficientlyinvestigated in those cases.

The investigations on the patients were approved by the local ethicalcommittee and informed consent was obtained from each patient.

Some basic characteristics and measurements are shown in Tables Iand II.

��

�� Acuson Aspen or Sequioa echocardiographs equipped with PW-DTItechnology and variable frequency phased-array transducers (4V2c and3V2c, respectively) (Siemens-Acuson Co., Mountainview, CA, USA)were used for the echocardiographic examinations. The patients werestudied in the lateral recumbent position. Echocardiographic techniquesand calculations of different cardiac dimensions were performed inaccordance with the recommendations of the American Society of

2004 Taylor & Francis. ISSN 1401–7431DOI 10.1080/14017430410022849 Scand Cardiovasc J 38

Received May 22, 2004; accepted July 14, 2004.Department of Clinical Physiology, Karlskoga Hospital, Sweden.Correspondence to Kent Emilsson, MD, PhD, Department of Clinical Physiology/Fysiologiska avdelningen, Karlskoga Hospital/Karlskoga Lasarett, SE-691 81 Karlskoga,Sweden. Tel: �46 058666430. Fax: �46 058666433. E-mail: [email protected] Cardiovasc J 38; 278–282, 2004

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Objectives—The isovolumetric relaxation time of theright ventricle (RV-IVRT) can be assessed using amethod based on ECG and pulsed wave Doppler (PW).Recently pulsed wave Doppler tissue imaging (PW-DTI) has been introduced in the assessment.Design—RV-IVRT obtained by the two methods wascompared in 20 consecutive patients as was the timefrom the R wave on the ECG to the onset of tricuspidflow (R-T), to the closure of the pulmonic valve (R-P),to the onset of early diastolic motion of the tricuspidannulus tissue (R-E) and to the end of the systolicmotion (R-S).Results—RV-IVRT obtained by the PW method wassignificantly (p � 0.001) shorter than RV-IVRT ob-tained by PW-DTI. R-S had significantly (p � 0.001)shorter duration than R-P, while there was nosignificant difference between R-E and R-T.Conclusions—The methods are not measuring thesame interval. Only the PW method measures RV-IVRT according to the usual definition. Differentreference values have to be used if the methods areused in the assessment of RV diastolic function.

��

Left ventricular relaxation time (LV-IVRT), defined asthe time from aortic valve closure to the start of mitralflow (1), is used in the assessment of LV diastolicfunction and is relatively easy to measure by echocardio-graphy from an apical transducer position using thepulsed wave (PW) or continuous wave (CW) Dopplertechnique as described by Appleton et al. (1) or withECG and PW Doppler as described by Larrazet et al. (2).

The right ventricular isovolumetric relaxation time(RV-IVRT), that is the interval from pulmonic valveclosure to the start of tricuspid valve opening (3), mayin the same way as the LV-IVRT is used as an index ofLV diastolic function, be used as an index of RVdiastolic function (4). RV-IVRT has been shown tohave a shorter duration than LV-IVRT (2).

The RV-IVRT is more difficult to obtain than LV-IVRT since there is no good echocardiographic viewfrom which both the pulmonic valve and the tricuspidinflow can be measured simultaneously. However, evenin this case the method described by Larrazet et al. (2)can be used.

During recent years some authors, for instanceSeverino et al. (5), Caso et al. (6) and Ozdemir et al.(7), have used pulsed wave Doppler tissue imaging(PW-DTI) when measuring RV-IVRT, from now oncalled RV-IVRT(PWDTI). However, it has not beensufficiently investigated in patients whether the durationof the interval measured with PW-DTI is the sameas the duration of the interval measured with themethod based on ECG and PW Doppler. The aim ofthe present study was therefore to compare RV-IVRTand RV-IVRT(PWDTI) and to try to explain aneventual difference.

��

��Twenty consecutive patients referred to echocardiography were included.Since earlier studies have shown prolonged RV-IVRT in patients withhypertrophic cardiomyopathy (8), patients with LV wall thickness�14 mm were not included as were not patients with atrial fibrillation,left and right bundle branch block, pacemaker treatment or a history ofcardiac surgery since the effect on RV-IVRT has not been sufficientlyinvestigated in those cases.

The investigations on the patients were approved by the local ethicalcommittee and informed consent was obtained from each patient.

Some basic characteristics and measurements are shown in Tables Iand II.

��

�� Acuson Aspen or Sequioa echocardiographs equipped with PW-DTItechnology and variable frequency phased-array transducers (4V2c and3V2c, respectively) (Siemens-Acuson Co., Mountainview, CA, USA)were used for the echocardiographic examinations. The patients werestudied in the lateral recumbent position. Echocardiographic techniquesand calculations of different cardiac dimensions were performed inaccordance with the recommendations of the American Society of

2004 Taylor & Francis. ISSN 1401–7431DOI 10.1080/14017430410022849 Scand Cardiovasc J 38

Received May 22, 2004; accepted July 14, 2004.Department of Clinical Physiology, Karlskoga Hospital, Sweden.Correspondence to Kent Emilsson, MD, PhD, Department of Clinical Physiology/Fysiologiska avdelningen, Karlskoga Hospital/Karlskoga Lasarett, SE-691 81 Karlskoga,Sweden. Tel: �46 058666430. Fax: �46 058666433. E-mail: [email protected] Cardiovasc J 38; 278–282, 2004

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Echocardiography Committee (9–11). As a measure of RV systolicfunction (12) the amplitude of tricuspid annulus motion (TAM) wasmeasured from the RV atrioventricular plane at the basal lateral site in theapical four-chamber view (13) from M-mode recordings. The size of theRV was measured in the apical four-chamber view one-third from thebase of the RV (RVIT3) (13).

Both the PW Doppler and PW-DTI examinations were performed at atransducer frequency of 2 MHz and the PW gate was set at 3 mm. Foroptimal definition of the onset and of the end of the Doppler recordings,filter 1 (about 100 Hz) was used, which, according to the user manuals ofthe echocardiographs, allows the display of all velocities. The minimaloptimal gain setting was used. A Doppler velocity range of �20 to20 cm/s was used during the PW-DTI measurements. The examinationswere recorded on magneto-optical disks and high-fidelity paper strips(velocity 50 mm/s). All measurements were made on screen duringthe examinations.

RV-IVRT was measured as described by Larrazet et al. (2) (Figs 1and 2): the time from the R wave on the ECG to the end of the pulmonicflow (R-P) was measured from the parasternal short-axis view at the levelof the aortic orifice for pulmonic flow velocity recording. The apical four-chamber view was used for measuring the time from the R wave on theECG to the onset of tricuspid flow (R-T). The 3-mm sample volume waslocated at the central part of the tricuspid annulus at the tips of thetricuspid leaflets. RV-IVRT was calculated as [(R-T) � (R-P)].

RV-IVRT(PWDTI), that is RV-IVRT obtained by PW-DTI, wasmeasured as has been described by for instance Caso et al. (6) (Fig. 3): theapical view was chosen to obtain quantitative assessment of regionalmyocardial wall motion almost simultaneously with Doppler RV inflowand to minimize the angle between the Doppler beam and the RVlongitudinal motion. The 3-mm sample volume was placed at the basallateral corner of the tricuspid annulus. The different components of the

PW-DTI pattern are shown in Fig. 3, S being the myocardial systolicwave, E the early diastolic wave and A the atrial wave. RV-IVRT(PWDTI) was measured as the duration in milliseconds (ms)between the end of the systolic wave and the onset of the early diastolicwave. The time from the R wave on the ECG to the end of the S wave(R-S) was also measured. The time from the R wave on the ECG to theonset of the early diastolic wave (R-E) was calculated as [(R-S)�(RV-IVRT(PWDTI))].

Although Larrazet et al. (2) did not find any correlation between RV-IVRT and heart rate the measurements with the two methods were done atalmost the same heart rate (R-R interval) for each patient.

��

Table I. Some basic characteristics and measured and calculatedvariables (n = 20)

Variable Mean � SD

Age (years) 63 � 13Height (cm) 170.0 � 7.6Weight (kg) 79.2 � 15.5Left ventricular end-diastolic

diameter (mm)49.2 � 6.6

Left ventricular wall thickness(mean of septal and posteriorwall thickness) (mm)

10.2 � 1.2

Left ventricular ejection fractionobtained by biplane Simpson’srule (%)

63.1 � 13.9

Tricuspid annulus motion (mm) 22.6 � 3.7Right ventricular inflow tract 1

(RVIT3) in end-diastole (mm)29.1 � 4.3

Table II. Number of patients with diseases, which might influencethe heart (n = 20)

DiseaseNo. ofpatients

No disease 7Solely hypertension 7Solely myocardial infarction 1Hypertension and history of pulmonary

embolism1

Hypertension and diabetes mellitus 1Angina pectoris and myocardial infarction 1Angina pectoris, myocardial infarction

and diabetes mellitus1

Angina pectoris, hypertension, myocardialinfarction and diabetes mellitus

1

��

Scand Cardiovasc J 38

Isovolumetric relaxation time 279

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DY II

To minimize the influence of respiration on RV-IVRT and RV-IVRT(PWDTI) the measurements were done at the end of expiration andthe measurements and calculations were calculated as the average of fourbeats. All patients were in sinus rhythm. The modified biplane Simpson’srule was used for calculation of LV ejection fraction.

�� The intra- and interobserver reproducibility (reproducibility study) wasexamined in 12 new subjects (9 consecutive patients and 3 healthyvolunteers), mean age 55 � 19.7 years. Investigator A (Karin Loiske) firstmeasured R-T and R-P (R-T � R-P = RV-IVRT) and RV-IVRT(PWDTI)on screen during the examination and thereafter investigator B (KentEmilsson) (blinded from the measurements of investigator A) measuredthe same parameters in the same way. Investigator A then againperformed the same procedure.

��The paired samples t-test was used for comparison between RV-IVRTand RV-IVRT(PWDTI) and between R-T and R-E and R-P and R-S,respectively.

The Bland–Altman method (14) was used for a graphical assessment ofagreement between IVRT of the RV measured by the ECG and PWDoppler method and the PW-DTI method, respectively.

In the intra- and interobserver reproducibility study an estimate ofagreement was obtained by using Pearson’s intraclass correlationcoefficient, ri (15). The coefficient has a range from �1.0 to �1.0 withhigh positive values indicating high agreement, negative values indicat-ing disagreement.

The 5% level was used for statistical significance. Data were analysedusing the SPSS (Base 10.0) statistical software (SPSS, Chicago, IL,USA).

��

There was a significant difference (p � 0.001) betweenRV-IVRT (15.0 � 20.1 ms) and RV-IVRT(PWDTI)(48.5 � 30.2 ms). The agreement between RV-IVRTand RV-IVRT(PWDTI) is shown in Fig. 4.

A significant difference (p � 0.001) was foundbetween the time from the R wave on the ECG to theend of the pulmonic flow velocity recording (R-P) withPW Doppler (387.3 � 40.7 ms) and the time from the Rwave on the ECG to the end of the S wave from thebasal lateral site of the tricuspid annulus (R-S) with PW-DTI (348.0 � 41.0 ms).

There was no significant difference between the timefrom the R wave on the ECG to the onset of tricuspidflow (R-T) with PW Doppler (402.3 � 37.1 ms) and thetime from the R wave on the ECG to the onset of theearly diastolic velocity (E) of the tricuspid annulustissue (R-E) with PW-DTI (396.5 � 44.9 ms).

The intra- and interobserver reproducibility wasmeasured using Pearson’s intraclass correlation coeffi-cient and the results are presented in Table III.

��

�� The main aim of the present study was to compare twodifferent methods to calculate the IVRT of the RV, onemethod based on ECG and PW Doppler (2), RV-IVRT,and the other based on PW-DTI (5–7), RV-IVRT(PWDTI). A significant difference was found betweenIVRT obtained by both methods, RV-IVRT beingshorter than RV-IVRT(PWDTI).

��

��


280 K. Emilsson and K. Loiske

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To minimize the influence of respiration on RV-IVRT and RV-IVRT(PWDTI) the measurements were done at the end of expiration andthe measurements and calculations were calculated as the average of fourbeats. All patients were in sinus rhythm. The modified biplane Simpson’srule was used for calculation of LV ejection fraction.

�� The intra- and interobserver reproducibility (reproducibility study) wasexamined in 12 new subjects (9 consecutive patients and 3 healthyvolunteers), mean age 55 � 19.7 years. Investigator A (Karin Loiske) firstmeasured R-T and R-P (R-T � R-P = RV-IVRT) and RV-IVRT(PWDTI)on screen during the examination and thereafter investigator B (KentEmilsson) (blinded from the measurements of investigator A) measuredthe same parameters in the same way. Investigator A then againperformed the same procedure.

��The paired samples t-test was used for comparison between RV-IVRTand RV-IVRT(PWDTI) and between R-T and R-E and R-P and R-S,respectively.

The Bland–Altman method (14) was used for a graphical assessment ofagreement between IVRT of the RV measured by the ECG and PWDoppler method and the PW-DTI method, respectively.

In the intra- and interobserver reproducibility study an estimate ofagreement was obtained by using Pearson’s intraclass correlationcoefficient, ri (15). The coefficient has a range from �1.0 to �1.0 withhigh positive values indicating high agreement, negative values indicat-ing disagreement.

The 5% level was used for statistical significance. Data were analysedusing the SPSS (Base 10.0) statistical software (SPSS, Chicago, IL,USA).

��

There was a significant difference (p � 0.001) betweenRV-IVRT (15.0 � 20.1 ms) and RV-IVRT(PWDTI)(48.5 � 30.2 ms). The agreement between RV-IVRTand RV-IVRT(PWDTI) is shown in Fig. 4.

A significant difference (p � 0.001) was foundbetween the time from the R wave on the ECG to theend of the pulmonic flow velocity recording (R-P) withPW Doppler (387.3 � 40.7 ms) and the time from the Rwave on the ECG to the end of the S wave from thebasal lateral site of the tricuspid annulus (R-S) with PW-DTI (348.0 � 41.0 ms).

There was no significant difference between the timefrom the R wave on the ECG to the onset of tricuspidflow (R-T) with PW Doppler (402.3 � 37.1 ms) and thetime from the R wave on the ECG to the onset of theearly diastolic velocity (E) of the tricuspid annulustissue (R-E) with PW-DTI (396.5 � 44.9 ms).

The intra- and interobserver reproducibility wasmeasured using Pearson’s intraclass correlation coeffi-cient and the results are presented in Table III.

��

�� The main aim of the present study was to compare twodifferent methods to calculate the IVRT of the RV, onemethod based on ECG and PW Doppler (2), RV-IVRT,and the other based on PW-DTI (5–7), RV-IVRT(PWDTI). A significant difference was found betweenIVRT obtained by both methods, RV-IVRT beingshorter than RV-IVRT(PWDTI).

��

��



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IVRT of the RV is usually defined as the time fromthe closure of the pulmonic valve to the tricuspid valveopening (3) that is, to the onset of tricuspid flow. Thetime to the closure of the pulmonic valve (R-P) was inthe present study found to be significantly longer thanthe time to the end of the S wave, meaning that themethod using PW-DTI doesn’t measure the time fromthe closure of the pulmonic valve.

The time to the onset of tricuspid flow (R-T) wassomewhat, but not significantly, longer than the time tothe onset of the early diastolic velocity (E) of thetricuspid annulus tissue (R-E).

From these findings it is obvious that PW-DTI is notmeasuring RV-IVRT according to the usual definition.

The found end of the tissue (myocardium) to move,that is the end of the S wave with PW-DTI, just beforethe closure of the pulmonic valve is not surprising:during systole the myocardium of the RV contractscausing the pressure in the RV to rise and whenthe pressure in the pulmonary artery is exceeded thepulmonic valve opens and blood can flow into thepulmonary artery. As the myocardium starts to relaxthe pressure in the RV falls and at the end of systole,that is, at the end of the S wave, when the pressure in thepulmonary artery exceeds that in the right ventricle (16)the pulmonic valve closes, which explains why R-P hasa longer duration than R-S.

The somewhat, but not significantly, shorter durationfrom the R wave on the ECG to the onset of the earlydiastolic velocity (E) that is, to the onset of the tissue(myocardium) to move, than to the onset of tricuspidflow, may as has been suggested on the left side of theheart (17), be due to elastic recoil of the RV duringdiastole promoting the flow across the tricuspid orificeinto the RV (18).

�� The findings concerning reproducibility of measuringRV-IVRT and RV-IVRT(PWDTI), which has been

presented under “Results”, indicate good intra- andinterobserver reproducibility of the measurements.

�� As both methods in the present study have been shownto not measure the same interval it seems obvious thatdifferent reference values have to be used when usingthe method based on PW-DTI than when using themethod based on ECG and PW Doppler in theassessment of RV diastolic function.

��

PW-DTI measures the interval from the end of thesystolic wave, that is, the end of the systolic motion ofthe tissue at the tricuspid annulus, to the onset of theearly diastolic wave, that is, to the onset of the diastolicmotion of the tissue at the tricuspid annulus. Thisinterval is different from the interval measured with themethod based on PW Doppler and ECG, whichmeasures the time from the closure of the pulmonicwave to the onset of tricuspid flow, that is, the intervalthat usually is the definition of RV-IVRT. This meansthat different reference values have to be used whenusing the method based on PW-DTI than when using themethod based on ECG and PW Doppler in theassessment of RV diastolic function.

��

1. Appleton CP, Jensen JL, Hatle LK, Oh JK. Doppler evaluation of left and rightventricular diastolic function: A technical guide for obtaining optimal flowvelocity recordings. J Am Soc Echocardiogr 1997; 10: 271–292.

2. Larrazet F, Pellerin D, Fournier C, Witchitz S, Veyrat C. Right and leftisovolumic ventricular relaxation time intervals compared in patients by meansof a single-pulsed Doppler method. J Am Soc Echocardiogr 1997; 10: 699–706.

3. Otto C. Echocardiographic evaluation of left and right ventricular systolicfunction. In: Otto C. Textbook of clinical echocardiography. 2nd ed.Philadelphia: W.B. Saunders, 2000: 127.

4. Otto C. Echocardiographic evaluation of ventricular diastolic filling andfunction. In: Otto C. Textbook of clinical echocardiography. 2nd ed.Philadelphia: W.B. Saunders, 2000: 144.

5. Severino S, Caso P, Cicala S, et al. Involvement of right ventricle in leftventricular hypertrophic cardiomyopathy: Analysis by pulsed Doppler tissueimaging. Eur J Echocardiogr 2000; 1: 281–288.

6. Caso P, Galderisi M, Cicala S, et al. Association between myocardial rightventricular relaxation time and pulmonic arterial pressure in chronic obstructivelung disease: Analysis by pulsed Doppler tissue imaging. J Am SocEchocardiogr 2001; 14: 970–977.

7. Ozdemir K, Altunkeser BB, Icli A, Ozdil H, Gok H. New parameters inidentification of right ventricular myocardial infarction and proximal rightcoronary artery lesion. Chest 2003; 124: 219–226.

8. Efthimiadis GK, Parharidis GE, Karvounis HI, Gemitzis KD, Styliadis IH,Louridas GE. Doppler echocardiographic evaluation of right ventriculardiastolic function in hypertrophic cardiomyopathy. Eur J Echocardiogr 2002;3: 143–148.

9. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regardingquantitation in M-mode echocardiography: Results of a survey of echocardio-graphic measurements. Circulation 1978; 58: 1072–1083.

10. Henry WL, De Maria A, Gramiak R, et al. Report of the American Society ofEchocardiography Committee on nomenclature and standards in two-dimen-sional echocardiography. Circulation 1980; 62: 212–215.

Table III. The intra- and interobserver reproducibility of measuringthe isovolumetric relaxation time of the right ventricle using amethod based on ECG and pulsed wave Doppler (RV-IVRT) and amethod using pulsed wave Doppler tissue imaging (RV-IVRT(PWDTI)). The agreement was measured by Pearson’s intraclasscorrelation coefficient. (The coefficient has a range from � 1.0 to�1.0 with high positive values indicating high agreement, negativevalues indicating disagreement)

Variable

Agreement,a doublemeasurements,investigator A

Agreement,a singlemeasurements,investigators A and B

RV-IVRT 0.83 0.77RV-IVRT(PWDTI) 0.84 0.88

a Agreement measured by Pearson’s intraclass correlationcoefficient.


Isovolumetric relaxation time 281

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11. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation ofthe left ventricle by two-dimensional echocardiography. American Society ofEchocardiography Committee on Standards, Subcommittee on Quantitation ofTwo-dimensional Echocardiograms. J Am Soc Echocardiogr 1989; 5: 358–367.

12. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular functionusing two-dimensional echocardiography. Am Heart J 1984; 107: 526–531.

13. Feigenbaum H. Echocardiographic evaluation of cardiac chambers. In:Feigenbaum H, editor. Echocardiography. 5th ed. Philadelphia: Lea & Febiger,1994: 160–161.

14. Bland J, Altman D. Statistical methods for assessing agreement between twomethods of clinical measurement. Lancet 1986; 1: 307–310.

15. Dunn G. Design and analysis of reliability studies. New York: OxfordUniversity Press, 1989: 34.

16. Braunwald E. Mechanisms of cardiac contraction and relaxation. In: BraunwaldE, editor. Heart disease – a textbook of cardiovascular medicine. 5th ed.Philadelphia: W.B. Saunders, 1997: 377.

17. Garcia MJ, Rodriguez L, Ares M, Griffin BP, Thomas JD, Klein AL.Differentiation of constrictive pericarditis from restrictive cardiomyopathy:Assessment of left ventricular diastolic velocities in longitudinal axis byDoppler tissue imaging. J Am Coll Cardiol 1996; 27: 108–114.

18. Robinson TF, Factor SM, Sonnenblick EH. The heart as a suction pump. Sci Am1986; 254: 84–91.



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STUDY III

11. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation ofthe left ventricle by two-dimensional echocardiography. American Society ofEchocardiography Committee on Standards, Subcommittee on Quantitation ofTwo-dimensional Echocardiograms. J Am Soc Echocardiogr 1989; 5: 358–367.

12. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular functionusing two-dimensional echocardiography. Am Heart J 1984; 107: 526–531.

13. Feigenbaum H. Echocardiographic evaluation of cardiac chambers. In:Feigenbaum H, editor. Echocardiography. 5th ed. Philadelphia: Lea & Febiger,1994: 160–161.

14. Bland J, Altman D. Statistical methods for assessing agreement between twomethods of clinical measurement. Lancet 1986; 1: 307–310.

15. Dunn G. Design and analysis of reliability studies. New York: OxfordUniversity Press, 1989: 34.

16. Braunwald E. Mechanisms of cardiac contraction and relaxation. In: BraunwaldE, editor. Heart disease – a textbook of cardiovascular medicine. 5th ed.Philadelphia: W.B. Saunders, 1997: 377.

17. Garcia MJ, Rodriguez L, Ares M, Griffin BP, Thomas JD, Klein AL.Differentiation of constrictive pericarditis from restrictive cardiomyopathy:Assessment of left ventricular diastolic velocities in longitudinal axis byDoppler tissue imaging. J Am Coll Cardiol 1996; 27: 108–114.

18. Robinson TF, Factor SM, Sonnenblick EH. The heart as a suction pump. Sci Am1986; 254: 84–91.



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STUDY III

Comparison between maximal early diastolic velocity inlong-axis direction obtained by M-mode echocardiographyand by tissue Doppler in the assessment of right ventriculardiastolic functionK. Emilsson, K. Loiske and B. Ohlin

Department of Clinical Physiology, Karlskoga Hospital, Karlskoga, Sweden

CorrespondenceKent Emilsson, Department of Clinical Physiology,

Karlskoga Hospital, SE-691 81 Karlskoga, Sweden

E-mail: [email protected]

Accepted for publicationReceived 20 November 2004;

accepted 7 March 2005

Key wordsheart; tissue Doppler imaging; tricuspid annulus

Summary

Recently the maximal early diastolic velocity in long-axis direction of the rightventricle (RV) obtained by tissue Doppler imaging (MDV TDI) has been introducedin the assessment of RV diastolic function (RVDF). There are reasons to think thatalso the maximal early diastolic velocity in long-axis direction of the RV obtainedusing M-mode echocardiography (MDV TAM) could be used to assess RVDF.Therefore, 29 patients were examined with echocardiography and MDV TAM andMDV TDI were measured and compared. A good correlation (r ¼ 0Æ76, P<0Æ001)was found between MDV TAM and MDV TDI indicating that MDV TAM might beused in the assessment of RVDF. However, the velocities obtained by MDV TDI(126Æ7 ± 38Æ9 mm s)1) were significantly (P<0Æ001) higher than the velocitiesobtained by MDV TAM (78Æ3 ± 27Æ8 mm s)1) and the agreement between MDVTAM and MDV TDI was rather poor probably mainly due to differences in themeasuring technique. This means that reference values cannot be used interchange-ably between MDV TAM and MDV TDI. If MDV TAM is going to be used in theassessment of RVDF new reference values have to be produced if today’s techniqueand recommendations to measure MDV TAM and MDV TDI are used. However, asmost new echocardiographs are equipped with PW-TDI technology it seemspreferable to use this technique and compare obtained values with alreadyestablished reference values.

Introduction

During recent years recording of the maximal early diastolic

relaxation velocity in the left ventricular (LV) long-axis direction

obtained by echocardiographic M-mode (MDV MAM) (Bojo

et al., 1998, 2000; Nilsson et al., 2002; Fornander et al., 2004)

or tissue Doppler imaging (TDI) (Garcia et al., 1996; Nagueh

et al., 1997; Sohn et al., 1997) have been used in the assessment

of LV diastolic function.

At the right side of the heart the maximal early diastolic

relaxation velocity in the right ventricular (RV) long-axis

direction obtained by tissue Doppler imaging (MDV TDI) has

been found to be significantly lower in older healthy subjects

than in younger subjects (Alam et al., 1999; Nikitin et al., 2003)

and MDV TDI has been found to have a rather good correlation

with other diastolic parameters of the RV such as transtricuspid E

wave and transtricuspid E/A-waves ratio (Alam et al., 1999).

The decrease in MDV TDI with age is in accordance with the

findings on the left side of the heart (Alam et al., 1999) and has

been suggested to be due to deterioration in the diastolic

properties of the myocardium of the ventricles with age (Nikitin

et al., 2003).

In the same way as MDV MAM has been used in the

assessment of LV diastolic function, Emilsson (2004a) has

suggested the maximal early diastolic relaxation velocity in the

long-axis direction of the RV obtained by M-mode echocardio-

graphy (MDV TAM) to be an index of RV diastolic function

(RVDF).

In the present study the main aim was to compare MDV TAM

with MDV TDI. As both indices are measuring the maximal early

diastolic relaxation velocity in the RV long-axis direction there

are reasons to think that there should be a good correlation and

also a good agreement between them but is the agreement good

and if not, why is it poor?

Clin Physiol Funct Imaging (2005) 25, pp178–182

� 2005 Blackwell Publishing Ltd • Clinical Physiology and Functional Imaging 25, 3, 178–182178

If the correlation between MDV TAM and MDV TDI is good

MDV TAM might be used in the assessment of RVDF in the same

way as MDV TDI.

Methods

Patients

Twenty-nine consecutive patients (18 women, 11 men) referred

to echocardiography at the Department of Clinical Physiology at

Karlskoga Hospital were included in the study.

Patients with atrial fibrillation, bundle branch block, pace-

maker-treatment or an history of cardiac surgery were not

included. The investigations on the patients were approved by

the local ethical committee and informed consent was obtained

from each patient.

Some basic characteristics and measurements are shown in

Tables 1 and 2.


Acuson Aspen echocardiographs equipped with pulsed wave

(PW) TDI technology and variable frequency phased-array

transducers (4V2c) (Siemens-Acuson Co., Mountain View, CA,

USA) were used for the echocardiographic examinations. The

patients were studied in the left lateral recumbent position.

Echocardiographic techniques and calculations of different

cardiac dimensions were performed in accordance with the

recommendations of The American Society of Echocardiography

Committee (Sahn et al., 1978; Henry et al., 1980; Schiller et al.,

1989). As a measure of RV systolic function (Kaul et al., 1984)

the amplitude of tricuspid annulus motion (TAM) was measured

from the RV atrioventricular plane at the basal lateral site in the

apical four-chamber view from M-mode recordings (Feigen-

baum, 1994). The size of the RV was measured in the apical

four-chamber view one-third from the base of the RV (RVIT3)

(Feigenbaum, 1994).

The PW TDI examinations were performed at a transducer

frequency of 2 MHz and the PW gate was set at 3 mm. The

minimal optimal gain setting was used. A Doppler velocity range

of )20 to 20 cm s)1 was used during the PW TDI measure-

ments. The examinations were recorded on magneto-optical

discs and printed on high-fidelity paper strips (velocity

50 mm s)1). All measurements were made on screen during

the examinations at the end of expiration.

MDV TAM was measured during the end of expiration from

the basal lateral corner of the RV in the apical four-chamber

view. The steepest portion of the M-mode curve in early diastole

was identified and measured on screen during the examination.

The inclination of the dotted line represents MDV TAM

(mm s)1) (Fig. 1).

When measuring MDV TDI the apical four-chamber view was

chosen to minimize the angle between the Doppler beam and

the RV longitudinal motion. The 3 mm sample volume was

placed at the basal lateral corner of the tricuspid annulus. The

different components of the PW TDI pattern are shown in

Fig. 2, S being the myocardial systolic wave, E the early diastolic

wave and A the atrial wave. MDV TDI was measured from the

outer edge of the dense part of the spectral curve in accordance

with the recommendations of the American Society of Echo-

cardiography Committee (Quinones et al., 2002). All patients

were in sinus rhythm. The modified biplane Simpson’s rule was

used for calculation of LV ejection fraction.


The intra- and interobserver reproducibility (reproducibility

study) was examined in 11 consecutive patients, four women,

seven men (mean age 55 ± 16 years). Investigator A (Karin

Loiske) first measured MDVTAM and MDVTDI on screen during

the examination and thereafter investigator B (Birgitta Ohlin)

(blinded from the measurements of investigator A) measured

the same parameters in the same way. Investigator A then again


Statistics

The Pearson’s correlation coefficient was used for analyses of

linear correlation between different variables. The two-tailed

Table 1 Some basic characteristics and measured and calculatedvariables (n ¼ 29).

Variable Mean ± SD

Age (years) 56 ± 15Height (cm) 170Æ3 ± 8Æ1Weight (kg) 72Æ1 ± 11Æ8Left ventricular end-diastolic diameter (mm) 45Æ5 ± 5Æ5Left ventricular wall thickness(mean of septal and posterior wall thickness) (mm)

11Æ0 ± 1Æ6

Left ventricular ejection fractionobtained by biplane Simpson’s rule (%)

58Æ8 ± 9Æ1

Tricuspid annulus motion (mm) 21Æ3 ± 6Æ2Right ventricular inflowtract 3 (RVIT3) in end-diastole (mm)

32Æ5 ± 5Æ1

Table 2 Number of patients with diseases, which might influencethe action of the heart (n ¼ 29).

Disease Number of patients

No disease 13Solely hypertension 5Solely diabetes mellitus 1Solely angina pectoris 1Solely myocardial infarction 3History of pulmonary embolism 1Angina pectoris and myocardial infarction 2Angina pectoris and diabetes mellitus 1Angina pectoris and hypertension 1Angina pectoris, hypertensionand myocardial infarction

1

Maximal early diastolic velocity, K. Emilsson et al.


179

Comparison between maximal early diastolic velocity inlong-axis direction obtained by M-mode echocardiographyand by tissue Doppler in the assessment of right ventriculardiastolic functionK. Emilsson, K. Loiske and B. Ohlin

Department of Clinical Physiology, Karlskoga Hospital, Karlskoga, Sweden

CorrespondenceKent Emilsson, Department of Clinical Physiology,

Karlskoga Hospital, SE-691 81 Karlskoga, Sweden

E-mail: [email protected]

Accepted for publicationReceived 20 November 2004;

accepted 7 March 2005

Key wordsheart; tissue Doppler imaging; tricuspid annulus

Summary

Recently the maximal early diastolic velocity in long-axis direction of the rightventricle (RV) obtained by tissue Doppler imaging (MDV TDI) has been introducedin the assessment of RV diastolic function (RVDF). There are reasons to think thatalso the maximal early diastolic velocity in long-axis direction of the RV obtainedusing M-mode echocardiography (MDV TAM) could be used to assess RVDF.Therefore, 29 patients were examined with echocardiography and MDV TAM andMDV TDI were measured and compared. A good correlation (r ¼ 0Æ76, P<0Æ001)was found between MDV TAM and MDV TDI indicating that MDV TAM might beused in the assessment of RVDF. However, the velocities obtained by MDV TDI(126Æ7 ± 38Æ9 mm s)1) were significantly (P<0Æ001) higher than the velocitiesobtained by MDV TAM (78Æ3 ± 27Æ8 mm s)1) and the agreement between MDVTAM and MDV TDI was rather poor probably mainly due to differences in themeasuring technique. This means that reference values cannot be used interchange-ably between MDV TAM and MDV TDI. If MDV TAM is going to be used in theassessment of RVDF new reference values have to be produced if today’s techniqueand recommendations to measure MDV TAM and MDV TDI are used. However, asmost new echocardiographs are equipped with PW-TDI technology it seemspreferable to use this technique and compare obtained values with alreadyestablished reference values.

Introduction

During recent years recording of the maximal early diastolic

relaxation velocity in the left ventricular (LV) long-axis direction

obtained by echocardiographic M-mode (MDV MAM) (Bojo

et al., 1998, 2000; Nilsson et al., 2002; Fornander et al., 2004)

or tissue Doppler imaging (TDI) (Garcia et al., 1996; Nagueh

et al., 1997; Sohn et al., 1997) have been used in the assessment

of LV diastolic function.

At the right side of the heart the maximal early diastolic

relaxation velocity in the right ventricular (RV) long-axis

direction obtained by tissue Doppler imaging (MDV TDI) has

been found to be significantly lower in older healthy subjects

than in younger subjects (Alam et al., 1999; Nikitin et al., 2003)

and MDV TDI has been found to have a rather good correlation

with other diastolic parameters of the RV such as transtricuspid E

wave and transtricuspid E/A-waves ratio (Alam et al., 1999).

The decrease in MDV TDI with age is in accordance with the

findings on the left side of the heart (Alam et al., 1999) and has

been suggested to be due to deterioration in the diastolic

properties of the myocardium of the ventricles with age (Nikitin

et al., 2003).

In the same way as MDV MAM has been used in the

assessment of LV diastolic function, Emilsson (2004a) has

suggested the maximal early diastolic relaxation velocity in the

long-axis direction of the RV obtained by M-mode echocardio-

graphy (MDV TAM) to be an index of RV diastolic function

(RVDF).

In the present study the main aim was to compare MDV TAM

with MDV TDI. As both indices are measuring the maximal early

diastolic relaxation velocity in the RV long-axis direction there

are reasons to think that there should be a good correlation and

also a good agreement between them but is the agreement good

and if not, why is it poor?

Clin Physiol Funct Imaging (2005) 25, pp178–182


If the correlation between MDV TAM and MDV TDI is good

MDV TAM might be used in the assessment of RVDF in the same

way as MDV TDI.

Methods

Patients

Twenty-nine consecutive patients (18 women, 11 men) referred

to echocardiography at the Department of Clinical Physiology at

Karlskoga Hospital were included in the study.

Patients with atrial fibrillation, bundle branch block, pace-

maker-treatment or an history of cardiac surgery were not

included. The investigations on the patients were approved by

the local ethical committee and informed consent was obtained

from each patient.

Some basic characteristics and measurements are shown in

Tables 1 and 2.


Acuson Aspen echocardiographs equipped with pulsed wave

(PW) TDI technology and variable frequency phased-array

transducers (4V2c) (Siemens-Acuson Co., Mountain View, CA,

USA) were used for the echocardiographic examinations. The

patients were studied in the left lateral recumbent position.

Echocardiographic techniques and calculations of different

cardiac dimensions were performed in accordance with the

recommendations of The American Society of Echocardiography

Committee (Sahn et al., 1978; Henry et al., 1980; Schiller et al.,

1989). As a measure of RV systolic function (Kaul et al., 1984)

the amplitude of tricuspid annulus motion (TAM) was measured

from the RV atrioventricular plane at the basal lateral site in the

apical four-chamber view from M-mode recordings (Feigen-

baum, 1994). The size of the RV was measured in the apical

four-chamber view one-third from the base of the RV (RVIT3)

(Feigenbaum, 1994).

The PW TDI examinations were performed at a transducer

frequency of 2 MHz and the PW gate was set at 3 mm. The

minimal optimal gain setting was used. A Doppler velocity range

of )20 to 20 cm s)1 was used during the PW TDI measure-

ments. The examinations were recorded on magneto-optical

discs and printed on high-fidelity paper strips (velocity

50 mm s)1). All measurements were made on screen during

the examinations at the end of expiration.

MDV TAM was measured during the end of expiration from

the basal lateral corner of the RV in the apical four-chamber

view. The steepest portion of the M-mode curve in early diastole

was identified and measured on screen during the examination.

The inclination of the dotted line represents MDV TAM

(mm s)1) (Fig. 1).

When measuring MDV TDI the apical four-chamber view was

chosen to minimize the angle between the Doppler beam and

the RV longitudinal motion. The 3 mm sample volume was

placed at the basal lateral corner of the tricuspid annulus. The

different components of the PW TDI pattern are shown in

Fig. 2, S being the myocardial systolic wave, E the early diastolic

wave and A the atrial wave. MDV TDI was measured from the

outer edge of the dense part of the spectral curve in accordance

with the recommendations of the American Society of Echo-

cardiography Committee (Quinones et al., 2002). All patients

were in sinus rhythm. The modified biplane Simpson’s rule was

used for calculation of LV ejection fraction.


The intra- and interobserver reproducibility (reproducibility

study) was examined in 11 consecutive patients, four women,

seven men (mean age 55 ± 16 years). Investigator A (Karin

Loiske) first measured MDVTAM and MDVTDI on screen during

the examination and thereafter investigator B (Birgitta Ohlin)

(blinded from the measurements of investigator A) measured

the same parameters in the same way. Investigator A then again


Statistics

The Pearson’s correlation coefficient was used for analyses of

linear correlation between different variables. The two-tailed

Table 1 Some basic characteristics and measured and calculatedvariables (n ¼ 29).

Variable Mean ± SD

Age (years) 56 ± 15Height (cm) 170Æ3 ± 8Æ1Weight (kg) 72Æ1 ± 11Æ8Left ventricular end-diastolic diameter (mm) 45Æ5 ± 5Æ5Left ventricular wall thickness(mean of septal and posterior wall thickness) (mm)

11Æ0 ± 1Æ6

Left ventricular ejection fractionobtained by biplane Simpson’s rule (%)

58Æ8 ± 9Æ1

Tricuspid annulus motion (mm) 21Æ3 ± 6Æ2Right ventricular inflowtract 3 (RVIT3) in end-diastole (mm)

32Æ5 ± 5Æ1

Table 2 Number of patients with diseases, which might influencethe action of the heart (n ¼ 29).

Disease Number of patients

No disease 13Solely hypertension 5Solely diabetes mellitus 1Solely angina pectoris 1Solely myocardial infarction 3History of pulmonary embolism 1Angina pectoris and myocardial infarction 2Angina pectoris and diabetes mellitus 1Angina pectoris and hypertension 1Angina pectoris, hypertensionand myocardial infarction

1



179

STUDY III

t-test was used to determine whether correlations were statistical

significant.

The paired samples t-test was used to compare the difference

between MDV TAM and MDV TDI.

The Bland–Altman method (Bland & Altman, 1986) was used

for a graphical assessment of agreement between MDV TAM and

MDV TDI, respectively.

Figure 1 The maximal early diastolic velocity in the long-axis direction of the right ventricle (RV) obtained by M-mode echocardiography (MDV TAM)was measured from the basal lateral corner of the RV in the apical four-chamber view. The steepest portion of the M-mode curve in early diastole wasidentified and measured on screen during the examination at the end of expiration. The inclination of the dotted line represents MDV TAM (mm s)1).

Figure 2 The maximal early diastolic velocity in long-axis direction of the right ventricle obtained by tissue Doppler imaging (MDV TDI) wasmeasured at the end of expiration using the echocardiographic apical four-chamber view with the 3 mm sample volume placed at the basal lateralcorner of the tricuspid annulus. The different components of the PW TDI pattern are: S being the myocardial systolic wave, E the early diastolic waveand A the atrial wave. MDV TDI was measured from the outer edge of the dense part of the early diastolic wave (horizontal white line).



180

In the intra- and interobserver reproducibility study an

estimate of agreement was obtained by using Pearson’s intraclass

correlation coefficient, ri (Dunn, 1989). The coefficient has a

range )1Æ0 to +1Æ0 with high positive values indicating high

agreement, negative values indicating disagreement.

A difference at the 5% level was regarded as significant. Data

were analysed using the SPSS 12.0.1 statistical software (SPSS,

Chicago, IL, USA).

Results

There was a good correlation (r ¼ 0Æ76; P<0Æ001) between

MDV TAM and MDV TDI (Fig. 3).

The agreement between MDV TDI and MDV TAM is shown in

Fig. 4.

MDV TDI (126Æ7 ± 38Æ9 mm s)1) was significantly

(P<0Æ001) higher than MDV TAM (78Æ3 ± 27Æ8 mm s)1).

The intra- and interobserver reproducibility was measured

using Pearson’s intraclass correlation coefficient and the results

are presented in Table 3.

Discussion

As has been shown there was a good correlation between MDV

TAM and MDV TDI (Fig. 3) indicating that MDV TAM in the

same way as MDV TDI (Alam et al., 1999; Kukulski et al., 2000a;

Nikitin et al., 2003) might be used in the assessment of RVDF.

However, the agreement was rather poor (Fig. 4), the

maximal early diastolic velocities obtained by TDI being about

60% higher than MDV TAM. This finding is somewhat

surprising as both MDV TAM and MDV TDI are measuring the

maximal early diastolic relaxation velocity in the long-axis

direction of the RV.

One reason to the difference between the maximal early

diastolic velocities could be that the TDI technique reports instantaneous velocities, whereas the M-mode procedure

implies some degree of averaging around the maximal value

as a finite-length segment in the maximal slope tract must be

chosen for practical reasons.

Another reason to the difference could have been that MDV

TAM is measured endocardially whilst MDV TDI is measured in

the myocardium more epicardially. However, as the spatial

resolution when using MDV TDI is poor (Rambaldi et al., 1997)

the placement of the sample volume is therefore of minor

importance. In addition, a recent study (Emilsson et al., 2004b)

has showed no significant differences between the diastolic

velocities of TAM measured endocardially and the diastolic

velocities at two sites of the right coronary artery,which is situated

epicardially.

In a study by Fornander et al. (2004) it was discussed if the

difference between the maximal diastolic velocities of the left

ventricle measured by M-mode echocardiography and tissue

Doppler imaging could be due to the point of the spectral

curve from which the MDV TDI is measured: in accordance

with recent guidelines (Quinones et al., 2002) it was

measured by Fornander et al. (2004) as well as in the present

Figure 3 Correlation between the maximal early diastolic velocity inlong-axis direction of the right ventricle obtained by M-modeechocardiography (MDV TAM) and tissue Doppler imaging (MDV TDI).

Figure 4 Bland–Altman diagram showing the agreement between themaximal early diastolic velocity in long-axis direction of the rightventricle obtained by M-mode echocardiography (MDV TAM) and tissueDoppler imaging (MDV TDI) (n ¼ 29).

Table 3 The intra- and interobserver reproducibility of measuring themaximal early diastolic relaxation velocity in the long-axis direction ofthe right ventricle (RV) obtained by M-mode echocardiography (MDVTAM) and the maximal early diastolic relaxation velocity in the RV long-axis direction obtained by tissue Doppler imaging (MDV TDI) measuredin 11 consecutive patients. The agreement was measured by Pearson’sintraclass correlation coefficient. (The coefficient has a range )1Æ0 to+1Æ0 with high positive values indicating high agreement, negativevalues indicating disagreement.)

Agreement,double measurements,

investigator A

Agreement,single measurements,


MDV TAM 0Æ96 0Æ60MDV TDI 0Æ94 0Æ80



181

t-test was used to determine whether correlations were statistical

significant.

The paired samples t-test was used to compare the difference

between MDV TAM and MDV TDI.

The Bland–Altman method (Bland & Altman, 1986) was used

for a graphical assessment of agreement between MDV TAM and

MDV TDI, respectively.

Figure 1 The maximal early diastolic velocity in the long-axis direction of the right ventricle (RV) obtained by M-mode echocardiography (MDV TAM)was measured from the basal lateral corner of the RV in the apical four-chamber view. The steepest portion of the M-mode curve in early diastole wasidentified and measured on screen during the examination at the end of expiration. The inclination of the dotted line represents MDV TAM (mm s)1).

Figure 2 The maximal early diastolic velocity in long-axis direction of the right ventricle obtained by tissue Doppler imaging (MDV TDI) wasmeasured at the end of expiration using the echocardiographic apical four-chamber view with the 3 mm sample volume placed at the basal lateralcorner of the tricuspid annulus. The different components of the PW TDI pattern are: S being the myocardial systolic wave, E the early diastolic waveand A the atrial wave. MDV TDI was measured from the outer edge of the dense part of the early diastolic wave (horizontal white line).



180

In the intra- and interobserver reproducibility study an

estimate of agreement was obtained by using Pearson’s intraclass

correlation coefficient, ri (Dunn, 1989). The coefficient has a

range )1Æ0 to +1Æ0 with high positive values indicating high

agreement, negative values indicating disagreement.

A difference at the 5% level was regarded as significant. Data

were analysed using the SPSS 12.0.1 statistical software (SPSS,

Chicago, IL, USA).

Results

There was a good correlation (r ¼ 0Æ76; P<0Æ001) between

MDV TAM and MDV TDI (Fig. 3).

The agreement between MDV TDI and MDV TAM is shown in

Fig. 4.

MDV TDI (126Æ7 ± 38Æ9 mm s)1) was significantly

(P<0Æ001) higher than MDV TAM (78Æ3 ± 27Æ8 mm s)1).

The intra- and interobserver reproducibility was measured

using Pearson’s intraclass correlation coefficient and the results

are presented in Table 3.

Discussion

As has been shown there was a good correlation between MDV

TAM and MDV TDI (Fig. 3) indicating that MDV TAM in the

same way as MDV TDI (Alam et al., 1999; Kukulski et al., 2000a;

Nikitin et al., 2003) might be used in the assessment of RVDF.

However, the agreement was rather poor (Fig. 4), the

maximal early diastolic velocities obtained by TDI being about

60% higher than MDV TAM. This finding is somewhat

surprising as both MDV TAM and MDV TDI are measuring the

maximal early diastolic relaxation velocity in the long-axis

direction of the RV.

One reason to the difference between the maximal early

diastolic velocities could be that the TDI technique reports instantaneous velocities, whereas the M-mode procedure

implies some degree of averaging around the maximal value

as a finite-length segment in the maximal slope tract must be

chosen for practical reasons.

Another reason to the difference could have been that MDV

TAM is measured endocardially whilst MDV TDI is measured in

the myocardium more epicardially. However, as the spatial

resolution when using MDV TDI is poor (Rambaldi et al., 1997)

the placement of the sample volume is therefore of minor

importance. In addition, a recent study (Emilsson et al., 2004b)

has showed no significant differences between the diastolic

velocities of TAM measured endocardially and the diastolic

velocities at two sites of the right coronary artery,which is situated

epicardially.

In a study by Fornander et al. (2004) it was discussed if the

difference between the maximal diastolic velocities of the left

ventricle measured by M-mode echocardiography and tissue

Doppler imaging could be due to the point of the spectral

curve from which the MDV TDI is measured: in accordance

with recent guidelines (Quinones et al., 2002) it was

measured by Fornander et al. (2004) as well as in the present

Figure 3 Correlation between the maximal early diastolic velocity inlong-axis direction of the right ventricle obtained by M-modeechocardiography (MDV TAM) and tissue Doppler imaging (MDV TDI).

Figure 4 Bland–Altman diagram showing the agreement between themaximal early diastolic velocity in long-axis direction of the rightventricle obtained by M-mode echocardiography (MDV TAM) and tissueDoppler imaging (MDV TDI) (n ¼ 29).

Table 3 The intra- and interobserver reproducibility of measuring themaximal early diastolic relaxation velocity in the long-axis direction ofthe right ventricle (RV) obtained by M-mode echocardiography (MDVTAM) and the maximal early diastolic relaxation velocity in the RV long-axis direction obtained by tissue Doppler imaging (MDV TDI) measuredin 11 consecutive patients. The agreement was measured by Pearson’sintraclass correlation coefficient. (The coefficient has a range )1Æ0 to+1Æ0 with high positive values indicating high agreement, negativevalues indicating disagreement.)

Agreement,double measurements,

investigator A

Agreement,single measurements,


MDV TAM 0Æ96 0Æ60MDV TDI 0Æ94 0Æ80



181

STUDY III

study from the outer edge of the dense part of the spectral

curve. As the cells in the myocardium move together and not

separately from each other (in contrast to blood velocity

measurements) there is seldom a scatter of velocities and the

spectral curve is often very easy to define so it seems obvious

that this not explains the found difference.

A phantom study has shown overestimation of velocities by

PW Doppler (Kukulski et al., 2000b).


The findings concerning reproducibility of measuring MDV

TAM and MDV TDI, which has been presented under Results,

indicate good intraobserver reproducibility of measuring the

both parameters and also good interobserver reproducibility of

measuring MDV TDI. The interobserver reproducibility of

measuring MDV TAM was somewhat poorer, probably mainly

due to that investigator B was not so experienced of measuring

MDV TAM as was investigator A. When measuring MDV TAM it

is important to do the measurements during the end of

expiration and to search for the steepest portion of the M-mode

curve in early diastole.

Conclusions

In the present study it has been shown that MDV TAM has a good

correlation with MDV TDI and might as MDV TDI be used in the

assessment of RVDF.However, the agreement betweenMDVTAM

andMDV TDI was found to be rather poor probably mainly due to

differences in the technique to measure the two indices.

This means that reference values cannot be used interchange-

ably between MDV TAM and MDV TDI.

If MDV TAM is going to be used in the assessment of RVDF

new reference values have to be produced if today’s technique

and recommendations to measure MDV TAM and MDV TDI are

used. However, as most new echocardiographs are equipped

with PW-TDI technology it seems preferable to use this

technique and compare the obtained values with already

established reference values (Alam et al., 1999).

References

Alam M, Wardell J, Andersson E, Samad BA, Nordlander R. Character-

istics of mitral and tricuspid annular velocities determined by pulsedwave Doppler tissue imaging in healthy subjects. J Am Soc Echocardiogr

(1999); 12: 618–628.Bland J, Altman D. Statistical methods for assessing agreement between

two methods of clinical measurement. Lancet (1986); 1: 307–310.Bojo L, Wandt B, Ahlin NG. Reduced left ventricular relaxation velocity

after acute myocardial infarction. Clin Physiol (1998); 18: 195–201.Bojo L, Wandt B, Haaga S. How should we assess diastolic function in

hypertension? Scand Cardiovasc J (2000); 34: 377–383.Dunn G. Design and Analysis of Reliability Studies (1989). Oxford University

Press, New York.Emilsson K. Right ventricular long-axis function in relation to left ven-

tricular systolic function. Clin Physiol Funct Imaging (2004a); 24: 212–215.

Emilsson K, Kahari A, Bodin L, Thunberg P. Comparison between right

coronary artery motion and echocardiographic tricuspid annulusmotion. Scand Cardiovasc J (2004b); 38: 85–92.

Feigenbaum H. Echocardiographic evaluation of cardiac chambers. In:Echocardiography, 5th edn (ed. Feigenbaum, H) (1994), pp. 160–161.

Lea & Febiger, Philadelphia.Fornander Y, Nilsson B, Egerlid R, Wandt B. Left ventricular longitudinal

relaxation velocity: a sensitive index of diastolic function. ScandCardiovasc J (2004); 38: 33–38.

Garcia MJ, Rodriguez L, Ares M, Griffin BP, Thomas JD, Klein AL. Dif-

ferentiation of constrictive pericarditis from restrictive cardiomyopa-thy: assessment of left ventricular diastolic velocities in longitudinal

axis by Doppler tissue imaging. J Am Coll Cardiol (1996); 27: 108–114.Henry WL, De Maria A, Gramiak R, King DL, Kisslo JA, Popp R, Sahn DJ,

Schiller NB, Tajik A, Teichholz LE, Weyman AE. Report of theAmerican Society of Echocardiography Committee on nomenclature

and standards in two-dimensional echocardiography. Circulation(1980); 62: 212–215.

Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricularfunction using two-dimensional echocardiography. Am Heart J (1984);

107: 526–531.Kukulski T, Hubbert L, Arnold M, Wranne B, Hatle L, Sutherland GR.

Normal regional right ventricular function and its change with age: aDoppler myocardial imaging study. J Am Soc Echocardiogr (2000a); 13:

194–204.Kukulski T, Voigt JU, Wilkenshoff UM, Strotmann JM, Wranne B, Hatle

L, Sutherland GR. A comparison of regional myocardial velocityinformation derived by pulsed and color Doppler techniques: an in

vitro and in vivo study. Echocardiography (2000b); 17: 639–651.Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA.

Doppler tissue imaging: a noninvasive technique for evaluation of leftventricular relaxation and estimation of filling pressures. J Am Coll

Cardiol (1997); 30: 1527–1533.Nikitin NP, Witte KK, Thackray SD, de Silva R, Clark AL, Cleland JG.

Longitudinal ventricular function: normal values of atrioventricularannular and myocardial velocities measured with quantitative two-

dimensional color Doppler tissue imaging. J Am Soc Echocardiogr (2003);16: 906–921.

Nilsson B, Bojo L, Wandt B. Influence of body size and age on maximaldiastolic velocity of mitral annulus motion. J Am Soc Echocardiogr (2002);

15: 29–35.Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA. Rec-

ommendations for quantification of Doppler echocardiography: a

report from the Doppler Quantification Task Force of the Nomen-clature and Standards Committee of the American Society of Echo-

cardiography. J Am Soc Echocardiogr (2002); 15: 167–184.Rambaldi R, Poldermans D, Vletter WB, ten Cate FJ, Roelandt JR, Fioretti

PM. Doppler tissue imaging in the new era of digital echocardio-graphy. G Ital Cardiol (1997); 27: 827–839.

Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regardingquantitation in M-mode echocardiography: results of a survey of

echocardiographic measurements. Circulation (1978); 58: 1072–1083.Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum

H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendationsfor quantitation of the left ventricle by two-dimensional echocardio-

graphy. American Society of Echocardiography Committee onStandards, Subcommittee on Quantitation of Two-Dimensional

Echocardiograms. J Am Soc Echocardiogr (1989); 5: 358–367.Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB,

Choi YS, Seo JD, Lee YW. Assessment of mitral annulus velocity byDoppler tissue imaging in the evaluation of left ventricular diastolic

function. J Am Coll Cardiol (1997); 30: 474–480.



182

STUDY IV

study from the outer edge of the dense part of the spectral

curve. As the cells in the myocardium move together and not

separately from each other (in contrast to blood velocity

measurements) there is seldom a scatter of velocities and the

spectral curve is often very easy to define so it seems obvious

that this not explains the found difference.

A phantom study has shown overestimation of velocities by

PW Doppler (Kukulski et al., 2000b).


The findings concerning reproducibility of measuring MDV

TAM and MDV TDI, which has been presented under Results,

indicate good intraobserver reproducibility of measuring the

both parameters and also good interobserver reproducibility of

measuring MDV TDI. The interobserver reproducibility of

measuring MDV TAM was somewhat poorer, probably mainly

due to that investigator B was not so experienced of measuring

MDV TAM as was investigator A. When measuring MDV TAM it

is important to do the measurements during the end of

expiration and to search for the steepest portion of the M-mode

curve in early diastole.

Conclusions

In the present study it has been shown that MDV TAM has a good

correlation with MDV TDI and might as MDV TDI be used in the

assessment of RVDF.However, the agreement betweenMDVTAM

andMDV TDI was found to be rather poor probably mainly due to

differences in the technique to measure the two indices.

This means that reference values cannot be used interchange-

ably between MDV TAM and MDV TDI.

If MDV TAM is going to be used in the assessment of RVDF

new reference values have to be produced if today’s technique

and recommendations to measure MDV TAM and MDV TDI are

used. However, as most new echocardiographs are equipped

with PW-TDI technology it seems preferable to use this

technique and compare the obtained values with already

established reference values (Alam et al., 1999).

References

Alam M, Wardell J, Andersson E, Samad BA, Nordlander R. Character-

istics of mitral and tricuspid annular velocities determined by pulsedwave Doppler tissue imaging in healthy subjects. J Am Soc Echocardiogr

(1999); 12: 618–628.Bland J, Altman D. Statistical methods for assessing agreement between

two methods of clinical measurement. Lancet (1986); 1: 307–310.Bojo L, Wandt B, Ahlin NG. Reduced left ventricular relaxation velocity

after acute myocardial infarction. Clin Physiol (1998); 18: 195–201.Bojo L, Wandt B, Haaga S. How should we assess diastolic function in

hypertension? Scand Cardiovasc J (2000); 34: 377–383.Dunn G. Design and Analysis of Reliability Studies (1989). Oxford University

Press, New York.Emilsson K. Right ventricular long-axis function in relation to left ven-

tricular systolic function. Clin Physiol Funct Imaging (2004a); 24: 212–215.

Emilsson K, Kahari A, Bodin L, Thunberg P. Comparison between right

coronary artery motion and echocardiographic tricuspid annulusmotion. Scand Cardiovasc J (2004b); 38: 85–92.

Feigenbaum H. Echocardiographic evaluation of cardiac chambers. In:Echocardiography, 5th edn (ed. Feigenbaum, H) (1994), pp. 160–161.

Lea & Febiger, Philadelphia.Fornander Y, Nilsson B, Egerlid R, Wandt B. Left ventricular longitudinal

relaxation velocity: a sensitive index of diastolic function. ScandCardiovasc J (2004); 38: 33–38.

Garcia MJ, Rodriguez L, Ares M, Griffin BP, Thomas JD, Klein AL. Dif-

ferentiation of constrictive pericarditis from restrictive cardiomyopa-thy: assessment of left ventricular diastolic velocities in longitudinal

axis by Doppler tissue imaging. J Am Coll Cardiol (1996); 27: 108–114.Henry WL, De Maria A, Gramiak R, King DL, Kisslo JA, Popp R, Sahn DJ,

Schiller NB, Tajik A, Teichholz LE, Weyman AE. Report of theAmerican Society of Echocardiography Committee on nomenclature

and standards in two-dimensional echocardiography. Circulation(1980); 62: 212–215.

Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricularfunction using two-dimensional echocardiography. Am Heart J (1984);

107: 526–531.Kukulski T, Hubbert L, Arnold M, Wranne B, Hatle L, Sutherland GR.

Normal regional right ventricular function and its change with age: aDoppler myocardial imaging study. J Am Soc Echocardiogr (2000a); 13:

194–204.Kukulski T, Voigt JU, Wilkenshoff UM, Strotmann JM, Wranne B, Hatle

L, Sutherland GR. A comparison of regional myocardial velocityinformation derived by pulsed and color Doppler techniques: an in

vitro and in vivo study. Echocardiography (2000b); 17: 639–651.Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA.

Doppler tissue imaging: a noninvasive technique for evaluation of leftventricular relaxation and estimation of filling pressures. J Am Coll

Cardiol (1997); 30: 1527–1533.Nikitin NP, Witte KK, Thackray SD, de Silva R, Clark AL, Cleland JG.

Longitudinal ventricular function: normal values of atrioventricularannular and myocardial velocities measured with quantitative two-

dimensional color Doppler tissue imaging. J Am Soc Echocardiogr (2003);16: 906–921.

Nilsson B, Bojo L, Wandt B. Influence of body size and age on maximaldiastolic velocity of mitral annulus motion. J Am Soc Echocardiogr (2002);

15: 29–35.Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA. Rec-

ommendations for quantification of Doppler echocardiography: a

report from the Doppler Quantification Task Force of the Nomen-clature and Standards Committee of the American Society of Echo-

cardiography. J Am Soc Echocardiogr (2002); 15: 167–184.Rambaldi R, Poldermans D, Vletter WB, ten Cate FJ, Roelandt JR, Fioretti

PM. Doppler tissue imaging in the new era of digital echocardio-graphy. G Ital Cardiol (1997); 27: 827–839.

Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regardingquantitation in M-mode echocardiography: results of a survey of

echocardiographic measurements. Circulation (1978); 58: 1072–1083.Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum

H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendationsfor quantitation of the left ventricle by two-dimensional echocardio-

graphy. American Society of Echocardiography Committee onStandards, Subcommittee on Quantitation of Two-Dimensional

Echocardiograms. J Am Soc Echocardiogr (1989); 5: 358–367.Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB,

Choi YS, Seo JD, Lee YW. Assessment of mitral annulus velocity byDoppler tissue imaging in the evaluation of left ventricular diastolic

function. J Am Coll Cardiol (1997); 30: 474–480.



182

STUDY IV

1

Left and right ventricular systolic long-axis function and diastolic function in patients with takotsubo cardiomyopathy

1Loiske K, Msc, 1Waldenborg M, Msc, 2Fröbert O, MD, PhD, 1Rask P, MD, PhD, 1Emilsson K, MD, PhD

1Department of Clinical Physiology, Örebro University Hospital, Sweden 2Department of Cardiology, Örebro University Hospital, Sweden

Short title: Takotsubo cardiomyopathy and long-axis function

Corresponding author: Kent Emilsson, MD, PhD Department of Clinical Physiology Örebro University Hospital SE-701 85 ÖREBRO SWEDEN E-mail: [email protected] Phone: +46 19 602 5978

1

Left and right ventricular systolic long-axis function and diastolic function in patients with takotsubo cardiomyopathy

1Loiske K, Msc, 1Waldenborg M, Msc, 2Fröbert O, MD, PhD, 1Rask P, MD, PhD, 1Emilsson K, MD, PhD

1Department of Clinical Physiology, Örebro University Hospital, Sweden 2Department of Cardiology, Örebro University Hospital, Sweden

Short title: Takotsubo cardiomyopathy and long-axis function

Corresponding author: Kent Emilsson, MD, PhD Department of Clinical Physiology Örebro University Hospital SE-701 85 ÖREBRO SWEDEN E-mail: [email protected] Phone: +46 19 602 5978

STUDY IV

2

Summary Aims: Takotsubo cardiomyopathy is characterized by apical wall motion abnormalities without coronary stenosis. Limited information is available on the genesis of the underlying reversible contractile disorder.

Our objective in this prospective study was to investigate biventricular changes in systolic long-axis function and diastolic parameters in the acute phase and after recovery. Methods and results: Thirteen consecutive patients were examined by echocardiography and coronary angiography at admission and again by echocardiography after three months. Amplitudes, systolic and diastolic velocities of the mitral and tricuspid annuli and conventional diastolic pa-rameters were measured.

Systolic long-axis shortening of the left ventricle (LV) and right ventricle (RV) improved from 9.6±2.2 mm to 11.2±1.9 mm (p=0.02) and from 21.3±3.6 mm to 24.1±2.8 mm (p=0.02) respectively.

LV systolic, early and late diastolic velocities measured by pulsed wave tissue Doppler also improved while additional conventional diastolic pa-rameters of the LV and RV diastolic function were unchanged. Conclusions: Takotsubo cardiomyopathy temporarily affects systolic LV and RV function while most diastolic parameters remain unchanged.

Key words: Heart, Echocardiography, Annulus motion, Atrioventricular displacement, Doppler

3

Introduction Takotsubo cardiomyopathy is a clinical syndrome characterized by acute reversible apical ventricular dysfunction. Patients typically complain of chest pain and experience of acute emotional stress in the days preceding their illness is common. The ECG is often abnormal showing ST segment changes or Q-waves, cardiac enzymes and troponins are elevated mimick-ing acute myocardial infarction and patients have no angiographic stenosis corresponding to the contractile dysfunction (Tsuchihashi et al., 2001). The main hypotheses regarding the cause of takotsubo cardiomyopathy are cate-cholamine cardiotoxicity and neurogenic stunned myocardium but the un-derlying pathophysiology remains unclear (Bielecka-Dabrowa et al., 2010).

To our knowledge, mitral annulus motion (MAM), has only been investi-gated in one previous study on takotsubo cardiomyopathy (Meimoun et al., 2009) and tricuspid annulus motion (TAM) has not been studied previously.

Our objective in this study was to investigate biventricular changes in systolic long-axis and diastolic function between the acute and the recovery phase in takotsubo cardiomyopathy.


Patients In this prospective study all consecutive patients between January 2008 and March 2010 admitted to acute coronary angiography in the depart-ment of Cardiology, Örebro University Hospital, suspected of having ST-elevation myocardial infarction were screened for takotsubo cardiomyopa-thy if no angiographically significant stenosis was seen in the coronary angiogram.

We defined takotsubo cardiomyopathy as chest pain discomfort, ECG changes (ST elevation, ST depression, negative T waves or Q waves), no significant angiographic stenosis (≥ 50%, visual estimate) on coronary angiogram and apical dysfunction on contrast left ventriculogram in 30 degrees right anterior oblique view. In the screening period, 16 patients fulfilled inclusion criteria and 13 patients (all women) with a mean age of 68.1±10.4 years were willing to participate in the study.

Echocardiography was performed within 24 hours after admission (acute phase) and repeated after about three months (recovery phase).

The study was approved by the regional ethical committee and all pa-tients gave written informed consent to participate.

2

Summary Aims: Takotsubo cardiomyopathy is characterized by apical wall motion abnormalities without coronary stenosis. Limited information is available on the genesis of the underlying reversible contractile disorder.

Our objective in this prospective study was to investigate biventricular changes in systolic long-axis function and diastolic parameters in the acute phase and after recovery. Methods and results: Thirteen consecutive patients were examined by echocardiography and coronary angiography at admission and again by echocardiography after three months. Amplitudes, systolic and diastolic velocities of the mitral and tricuspid annuli and conventional diastolic pa-rameters were measured.

Systolic long-axis shortening of the left ventricle (LV) and right ventricle (RV) improved from 9.6±2.2 mm to 11.2±1.9 mm (p=0.02) and from 21.3±3.6 mm to 24.1±2.8 mm (p=0.02) respectively.

LV systolic, early and late diastolic velocities measured by pulsed wave tissue Doppler also improved while additional conventional diastolic pa-rameters of the LV and RV diastolic function were unchanged. Conclusions: Takotsubo cardiomyopathy temporarily affects systolic LV and RV function while most diastolic parameters remain unchanged.

Key words: Heart, Echocardiography, Annulus motion, Atrioventricular displacement, Doppler

3

Introduction Takotsubo cardiomyopathy is a clinical syndrome characterized by acute reversible apical ventricular dysfunction. Patients typically complain of chest pain and experience of acute emotional stress in the days preceding their illness is common. The ECG is often abnormal showing ST segment changes or Q-waves, cardiac enzymes and troponins are elevated mimick-ing acute myocardial infarction and patients have no angiographic stenosis corresponding to the contractile dysfunction (Tsuchihashi et al., 2001). The main hypotheses regarding the cause of takotsubo cardiomyopathy are cate-cholamine cardiotoxicity and neurogenic stunned myocardium but the un-derlying pathophysiology remains unclear (Bielecka-Dabrowa et al., 2010).

To our knowledge, mitral annulus motion (MAM), has only been investi-gated in one previous study on takotsubo cardiomyopathy (Meimoun et al., 2009) and tricuspid annulus motion (TAM) has not been studied previously.

Our objective in this study was to investigate biventricular changes in systolic long-axis and diastolic function between the acute and the recovery phase in takotsubo cardiomyopathy.


Patients In this prospective study all consecutive patients between January 2008 and March 2010 admitted to acute coronary angiography in the depart-ment of Cardiology, Örebro University Hospital, suspected of having ST-elevation myocardial infarction were screened for takotsubo cardiomyopa-thy if no angiographically significant stenosis was seen in the coronary angiogram.

We defined takotsubo cardiomyopathy as chest pain discomfort, ECG changes (ST elevation, ST depression, negative T waves or Q waves), no significant angiographic stenosis (≥ 50%, visual estimate) on coronary angiogram and apical dysfunction on contrast left ventriculogram in 30 degrees right anterior oblique view. In the screening period, 16 patients fulfilled inclusion criteria and 13 patients (all women) with a mean age of 68.1±10.4 years were willing to participate in the study.

Echocardiography was performed within 24 hours after admission (acute phase) and repeated after about three months (recovery phase).

The study was approved by the regional ethical committee and all pa-tients gave written informed consent to participate.

STUDY IV

4

Echocardiographic examination A Vivid 7 ultrasound machine (GE Vingmed Ultrasound A/S, Horten, Norway) equipped with a multi-frequency phased array transducer (M3S, 1.5-4.0 MHz) was used for the echocardiographic examinations and meas-urements were made after the examination using stored images on an EchoPac workstation (GE Vingmed). The subjects were examined in the left lateral recumbent position. Echocardiographic techniques and calcula-tions of different cardiac dimensions were performed in accordance with the recommendations of The American Society of Echocardiography (Sahn et al., 1978; Henry et al., 1980; Schiller et al., 1989). The size of the RV was measured as right ventricular inflow tract 3 (RVIT3), which is meas-ured in the apical four chamber view one third from the base of the RV (Lang et al., 2005) and as right ventricular outflow tract 1 (RVOT1) as described by Foale et al., (1986) from the parasternal long-axis view.

The amplitudes and velocities at the mitral annulus were measured using M-mode, pulsed wave tissue Doppler imaging (PW-DTI) and 2D color DTI (two-dimensional color Doppler tissue Imaging) from four sites about 90° apart. Recordings from the septal and lateral part of the mitral annulus were obtained from the apical four-chamber view and recordings from the inferior and anterior parts from the apical two-chamber view. Average amplitudes and velocities were calculated as the average of the values at the four sites.

The amplitudes and velocities at the tricuspid annulus were measured at the basal lateral part of the RV in the apical four-chamber view. Because the measured velocities of the tissues depend on the angle between the Doppler beam and the measured tissue, the angle to the beam was kept as small as possible.

M-mode measurements of the amplitudes of MAM were performed as described by Höglund et al., (1988) and the M-mode measurements of the amplitude of TAM as described by Feigenbaum, (2010a). The measure-ments of velocities using 2D color DTI from all the above mentioned sites were done from the peak point of the systolic curve and from the lowest point of the early diastolic and late diastolic curves, respectively, in accor-dance with Nikitin et al., (2003). When measuring the peak systolic veloci-ties the initial peak that is observed during isometric ventricular contrac-tion was ignored.

PW-DTI measurements of both the mitral and tricuspid annuli were done as described by Alam et al., (1999).

The maximal relaxation velocity of the mitral annulus was measured as the steepest part of the curve in early diastole (Nilsson et al, 2002) at the

5

lateral site. The maximal relaxation velocity of the tricuspid annulus was measured in the same way (Emilsson, 2004).

PW-Doppler mitral and tricuspid diastolic flow velocities were recorded from the apical 4-chamber view by placing the sample volume between the leaflet tips in the center of the flow stream. The transmitral and transtri-cuspid peak rapid filling velocity (E), peak atrial filling velocity (A), E-wave deceleration time, and E/A ratio were measured.

The LV isovolumetric relaxation time (IVRT) using PW-Doppler was re-corded from the apical 4-chamber view by simultaneous recording of the aortic and mitral flows. The IVRT of the RV by PW-Doppler was meas-ured as described by Larrazet et al., (1997): the time from the R wave on ECG to the end of the pulmonic flow (R-P) was measured from the parast-ernal short-axis view at the level of the aortic orifice for pulmonic flow velocity recording. The apical four-chamber view was used for measuring the time from the R wave on ECG to the onset of tricuspid flow (R-T). The sample volume was located at the central part of the tricuspid annulus at the tips of the tricuspid leaflets. IVRT was calculated as [(R-T) - (R-P)]. Although Larrazet et al. did not find any correlation between IVRT and heart rate the measurements were done at almost the same heart rate (R-R-interval) for each patient.

The IVRT at the both annuli was also measured using PW-DTI as de-scribed by Caso et al., (2001) and by using 2D color DTI as described by Lind et al., (2004).

LV ejection fraction (LVEF) was measured using the biplane Simpson´s method (Feigenbaum, 2010b).

The length of the LV was measured in end-diastole from the epicardial apex to the septal and lateral site of the mitral annulus.


All measurements were done at the end of expiration. The average of three beats was calculated for each cardiac measurement.

Statistics As some of the parameters were found not to be normally distributed Wil-coxon signed-rank test was used to test differences between acute and re-covery phase parameters.

p<0.05 was considered statistically significant. Data were analyzed using SPSS version 17 statistical software (SPSS Inc.,

Chicago, IL, USA).

4

Echocardiographic examination A Vivid 7 ultrasound machine (GE Vingmed Ultrasound A/S, Horten, Norway) equipped with a multi-frequency phased array transducer (M3S, 1.5-4.0 MHz) was used for the echocardiographic examinations and meas-urements were made after the examination using stored images on an EchoPac workstation (GE Vingmed). The subjects were examined in the left lateral recumbent position. Echocardiographic techniques and calcula-tions of different cardiac dimensions were performed in accordance with the recommendations of The American Society of Echocardiography (Sahn et al., 1978; Henry et al., 1980; Schiller et al., 1989). The size of the RV was measured as right ventricular inflow tract 3 (RVIT3), which is meas-ured in the apical four chamber view one third from the base of the RV (Lang et al., 2005) and as right ventricular outflow tract 1 (RVOT1) as described by Foale et al., (1986) from the parasternal long-axis view.

The amplitudes and velocities at the mitral annulus were measured using M-mode, pulsed wave tissue Doppler imaging (PW-DTI) and 2D color DTI (two-dimensional color Doppler tissue Imaging) from four sites about 90° apart. Recordings from the septal and lateral part of the mitral annulus were obtained from the apical four-chamber view and recordings from the inferior and anterior parts from the apical two-chamber view. Average amplitudes and velocities were calculated as the average of the values at the four sites.

The amplitudes and velocities at the tricuspid annulus were measured at the basal lateral part of the RV in the apical four-chamber view. Because the measured velocities of the tissues depend on the angle between the Doppler beam and the measured tissue, the angle to the beam was kept as small as possible.

M-mode measurements of the amplitudes of MAM were performed as described by Höglund et al., (1988) and the M-mode measurements of the amplitude of TAM as described by Feigenbaum, (2010a). The measure-ments of velocities using 2D color DTI from all the above mentioned sites were done from the peak point of the systolic curve and from the lowest point of the early diastolic and late diastolic curves, respectively, in accor-dance with Nikitin et al., (2003). When measuring the peak systolic veloci-ties the initial peak that is observed during isometric ventricular contrac-tion was ignored.

PW-DTI measurements of both the mitral and tricuspid annuli were done as described by Alam et al., (1999).

The maximal relaxation velocity of the mitral annulus was measured as the steepest part of the curve in early diastole (Nilsson et al, 2002) at the

5

lateral site. The maximal relaxation velocity of the tricuspid annulus was measured in the same way (Emilsson, 2004).

PW-Doppler mitral and tricuspid diastolic flow velocities were recorded from the apical 4-chamber view by placing the sample volume between the leaflet tips in the center of the flow stream. The transmitral and transtri-cuspid peak rapid filling velocity (E), peak atrial filling velocity (A), E-wave deceleration time, and E/A ratio were measured.

The LV isovolumetric relaxation time (IVRT) using PW-Doppler was re-corded from the apical 4-chamber view by simultaneous recording of the aortic and mitral flows. The IVRT of the RV by PW-Doppler was meas-ured as described by Larrazet et al., (1997): the time from the R wave on ECG to the end of the pulmonic flow (R-P) was measured from the parast-ernal short-axis view at the level of the aortic orifice for pulmonic flow velocity recording. The apical four-chamber view was used for measuring the time from the R wave on ECG to the onset of tricuspid flow (R-T). The sample volume was located at the central part of the tricuspid annulus at the tips of the tricuspid leaflets. IVRT was calculated as [(R-T) - (R-P)]. Although Larrazet et al. did not find any correlation between IVRT and heart rate the measurements were done at almost the same heart rate (R-R-interval) for each patient.

The IVRT at the both annuli was also measured using PW-DTI as de-scribed by Caso et al., (2001) and by using 2D color DTI as described by Lind et al., (2004).

LV ejection fraction (LVEF) was measured using the biplane Simpson´s method (Feigenbaum, 2010b).

The length of the LV was measured in end-diastole from the epicardial apex to the septal and lateral site of the mitral annulus.


All measurements were done at the end of expiration. The average of three beats was calculated for each cardiac measurement.

Statistics As some of the parameters were found not to be normally distributed Wil-coxon signed-rank test was used to test differences between acute and re-covery phase parameters.

p<0.05 was considered statistically significant. Data were analyzed using SPSS version 17 statistical software (SPSS Inc.,

Chicago, IL, USA).

STUDY IV

6

Results Baseline patient characteristics are shown in Table 1. No patient had a history of cardiac disease except for one who previously suffered from arrhythmia and had received a pacemaker.

The average time between the echocardiographic examination at the acute and recovery phase was 12.9±1.0 weeks (range 12-15 weeks).

Left ventricle There was a significant difference between the amplitudes of MAM (the total of the four sites) between the acute (9.6±2.2 mm) and recovery phase (11.2±1.9 mm) (p=0.02) (Table 2). Regarding the different sites of measur-ing MAM there was a significant difference between the different sites (Table 2) except for the septal site.

There was a significant difference (p<0.01) between LVEF obtained by the biplane Simpson´s method in the acute (53.4±9.5%) compared with the recovery phase (63.3±4.4%).

There was no significant difference in length of the LV in end-diastole from the epicardial apex to the septal or lateral sites of the mitral annulus between the acute and the recovery phase.

There was also no significant difference in end-diastolic diameter, not even at the widest part of the LV, or end-systolic diameter between the two phases.

The area of the left atrium was significantly smaller (p=0.01) in the re-covery phase (16.2±3.7 cm2) than in the acute phase (18.1±3.6 cm2).

Both the early and late diastolic velocities as well as the systolic velocity measured by PW-DTI increased significantly from the acute to the recovery phase but there was no significant differences when they were measured using 2D color DTI. The systolic, early and late diastolic velocities were all significantly higher when measured at the acute and recovery phase using PW-DTI than when using 2D color DTI. There was no statistically signifi-cant difference between the other measured diastolic parameters (Table 2).

Right ventricle There was a statistically significant difference (p=0.02) between the total amplitude of TAM in the acute (21.3±3.6 mm) and the recovery phase (24.1±2.8 mm) but no significant differences were found between the size or the length of the RV or the diastolic parameters of the RV between the two phases (Table 3).

7

Discussion The main findings of the present study of consecutive patients with ta-kotsubo cardiomyopathy are that the systolic long axis shortening of both the LV and RV as well as the LV systolic, early and late diastolic velocities measured by PW-DTI improved from the acute to the recovery phase while conventional diastolic parameters of the LV and the diastolic parameters of the RV and the length of the ventricles remained unchanged between the two phases.

Left ventricle

Systolic function The improvement in LV systolic long axis shortening is in line with the improvement of LVEF obtained by the biplane Simpson´s method.

Our findings of lower amplitudes of MAM in the acute phase indicate that the longitudinal fibers are affected in takotsubo. These fibers are mostly located subendocardially and this part of the myocardium has the highest risk of ischaemia (Greenbaum et al., 1981; Henein et al., 1993). One might therefore think that atherosclerotic coronary disease-mediated myocardial ischemia could be a cause to the decrease in systolic long-axis shortening. However, that theory is not supported by findings during for instance magnetic resonance imaging studies, since there is no evidence of focal perfusion abnormalities corresponding to a specific coronary vessel territory (Gerbaud et al., 2008).

One conjecture of the pathogenesis of takotsubo is rising catecholamine levels causing epicardial coronary arterial spasm, but multivessel epicardial spasm seems unlikely (Wittstein et al., 2005).

Another theory is catecholamine mediated myocardial stunning caused by direct myocyte injury. Elevated catecholamine levels decrease the viabil-ity of myocytes through cyclic AMP-mediated calcium overload (Mann et al., 1992). Interaction of the endocardial endothelium with circulating substances in the blood such as catecholamine may modify myocardial performance (Bielecka-Dabrowa et al., 2010).

The catecholamine hypothesis, which we think is the most plausible hy-pothesis and could explain our findings in the present study, is supported by findings of apical ballooning in some case reports with dobutamine stress-echocardiography (Margey et al., 2009), in reports of patients with phaeochromocytoma (Takizawa et al., 2007; Lassnig et al., 2009) and in patients with subarachnoid haemorrhage (Trio et al., 2010). In the latter case a catecholamine surge has been proposed as explanation to the car-diomyopathy.

6

Results Baseline patient characteristics are shown in Table 1. No patient had a history of cardiac disease except for one who previously suffered from arrhythmia and had received a pacemaker.

The average time between the echocardiographic examination at the acute and recovery phase was 12.9±1.0 weeks (range 12-15 weeks).

Left ventricle There was a significant difference between the amplitudes of MAM (the total of the four sites) between the acute (9.6±2.2 mm) and recovery phase (11.2±1.9 mm) (p=0.02) (Table 2). Regarding the different sites of measur-ing MAM there was a significant difference between the different sites (Table 2) except for the septal site.

There was a significant difference (p<0.01) between LVEF obtained by the biplane Simpson´s method in the acute (53.4±9.5%) compared with the recovery phase (63.3±4.4%).

There was no significant difference in length of the LV in end-diastole from the epicardial apex to the septal or lateral sites of the mitral annulus between the acute and the recovery phase.

There was also no significant difference in end-diastolic diameter, not even at the widest part of the LV, or end-systolic diameter between the two phases.

The area of the left atrium was significantly smaller (p=0.01) in the re-covery phase (16.2±3.7 cm2) than in the acute phase (18.1±3.6 cm2).

Both the early and late diastolic velocities as well as the systolic velocity measured by PW-DTI increased significantly from the acute to the recovery phase but there was no significant differences when they were measured using 2D color DTI. The systolic, early and late diastolic velocities were all significantly higher when measured at the acute and recovery phase using PW-DTI than when using 2D color DTI. There was no statistically signifi-cant difference between the other measured diastolic parameters (Table 2).

Right ventricle There was a statistically significant difference (p=0.02) between the total amplitude of TAM in the acute (21.3±3.6 mm) and the recovery phase (24.1±2.8 mm) but no significant differences were found between the size or the length of the RV or the diastolic parameters of the RV between the two phases (Table 3).

7

Discussion The main findings of the present study of consecutive patients with ta-kotsubo cardiomyopathy are that the systolic long axis shortening of both the LV and RV as well as the LV systolic, early and late diastolic velocities measured by PW-DTI improved from the acute to the recovery phase while conventional diastolic parameters of the LV and the diastolic parameters of the RV and the length of the ventricles remained unchanged between the two phases.

Left ventricle

Systolic function The improvement in LV systolic long axis shortening is in line with the improvement of LVEF obtained by the biplane Simpson´s method.

Our findings of lower amplitudes of MAM in the acute phase indicate that the longitudinal fibers are affected in takotsubo. These fibers are mostly located subendocardially and this part of the myocardium has the highest risk of ischaemia (Greenbaum et al., 1981; Henein et al., 1993). One might therefore think that atherosclerotic coronary disease-mediated myocardial ischemia could be a cause to the decrease in systolic long-axis shortening. However, that theory is not supported by findings during for instance magnetic resonance imaging studies, since there is no evidence of focal perfusion abnormalities corresponding to a specific coronary vessel territory (Gerbaud et al., 2008).

One conjecture of the pathogenesis of takotsubo is rising catecholamine levels causing epicardial coronary arterial spasm, but multivessel epicardial spasm seems unlikely (Wittstein et al., 2005).

Another theory is catecholamine mediated myocardial stunning caused by direct myocyte injury. Elevated catecholamine levels decrease the viabil-ity of myocytes through cyclic AMP-mediated calcium overload (Mann et al., 1992). Interaction of the endocardial endothelium with circulating substances in the blood such as catecholamine may modify myocardial performance (Bielecka-Dabrowa et al., 2010).

The catecholamine hypothesis, which we think is the most plausible hy-pothesis and could explain our findings in the present study, is supported by findings of apical ballooning in some case reports with dobutamine stress-echocardiography (Margey et al., 2009), in reports of patients with phaeochromocytoma (Takizawa et al., 2007; Lassnig et al., 2009) and in patients with subarachnoid haemorrhage (Trio et al., 2010). In the latter case a catecholamine surge has been proposed as explanation to the car-diomyopathy.

STUDY IV

8

The non-significant difference of the amplitude of MAM at the septal site between the two phases could perhaps be explained by fewer longitu-dinal fibers at septum than at the other anatomical locations. The septum is formed by subendocardial fibers from the RV and LV together with a middle layer composed of circumferential fibers in continuity with those from the corresponding layer of the LV free wall. Circumferential septal fibers are lacking towards the apex (Greenbaum et al., 1981).

Diastolic function We found no significant change in any of the conventionally measured diastolic parameters between the acute and the recovery phase except for the early and late diastolic velocities measured by PW-DTI, both increasing from the acute to the recovery phase.

When using PW-DTI the velocities are measured at the basal parts of the LV as are the amplitudes of MAM. The increase in the systolic long-axis shortening may therefore also explain the increase in those parameters. However, the same velocities measured by 2D color DTI did not change significantly although these velocities are also measured at the basal parts of the LV. These velocities were significantly lower than the velocities ob-tained by PW-DTI. The lower velocities using 2D color DTI might be ex-plained by autocorrelation methodology resulting in peak-mean velocity, while PW-DTI is computed with a fast Fourier transformation technique resulting in measured peak velocities (Hummel et al., 2010). Where the sample volume is placed in the myocardium at the basal part of the LV may also cause the differences as well as the transducer angulation.

Because of the increase in LVEF using the biplane Simpson´s method and in the total amplitude of MAM, we expected an increase in all the other conventional parameters of measuring diastolic function as well. One rea-son to the lack of increase could be that few patients had severely reduced LVEF and total amplitude of MAM during the acute phase. However, in a study by Meimoun (Meimoun et al., 2009) LVEF in the acute phase (43±7%) was lower than in the present study and recovery phase LVEF was higher (69±5%) and despite this, the authors found no significant changes in diastolic parameters.

We cannot exclude the possibility that statistical significance could have been reached in some of the diastolic measurements with a larger sample.

LV length It could be expected that the apical ballooning often seen in takotsubo cardiomyopathy would contribute to a longer LV in the acute phase than

9

in the recovery phase, however, in the present study there was no signifi-cant difference in length in end-diastole from the epicardial apex to the septal and lateral sites of the LV. However, the transducer angulation might have influenced this result.

Right ventricle

Systolic function There was also, as with the total amplitude of MAM, a significant differ-ence between the acute and recovery phase concerning the total amplitude of TAM, that is, in the systolic shortening of the RV in long-axis direction measured at the lateral site. This means that also the RV is affected in ta-kotsubo, something that has been shown in a few studies only (Elesber et al., 2006; Haghi et al., 2007). In the study by Elesber it was found that RV involvement, when present, follows a similar pattern of regional wall mo-tion abnormalities, as does the LV in this syndrome and that RV involve-ment portends a longer and more critical hospitalization course as com-pared with patients with isolated LV involvement. The mechanisms ex-plaining the involvement of RV in takotsubo are unclear and the involve-ment argues against LV outflow tract obstruction causing takotsubo (Haghi et al., 2007).

The improvement of systolic long axis shortening of the RV at the lat-eral site indicates that also the longitudinal fibers of the RV, are affected in this disease, probably most in the apical regions.

RV diastolic function and length There was no significant change in RV diastolic parameters from the acute to the recovery phase, but trends in RV parameters might have been statis-tically significant with a larger sample. We have not been able to find pre-vious accounts on RV diastolic function in takotsubo.

As with the LV there was no significant change in RV end-diastolic length between the two phases, but also in this case the transducer angula-tion might have influenced the result.

8

The non-significant difference of the amplitude of MAM at the septal site between the two phases could perhaps be explained by fewer longitu-dinal fibers at septum than at the other anatomical locations. The septum is formed by subendocardial fibers from the RV and LV together with a middle layer composed of circumferential fibers in continuity with those from the corresponding layer of the LV free wall. Circumferential septal fibers are lacking towards the apex (Greenbaum et al., 1981).

Diastolic function We found no significant change in any of the conventionally measured diastolic parameters between the acute and the recovery phase except for the early and late diastolic velocities measured by PW-DTI, both increasing from the acute to the recovery phase.

When using PW-DTI the velocities are measured at the basal parts of the LV as are the amplitudes of MAM. The increase in the systolic long-axis shortening may therefore also explain the increase in those parameters. However, the same velocities measured by 2D color DTI did not change significantly although these velocities are also measured at the basal parts of the LV. These velocities were significantly lower than the velocities ob-tained by PW-DTI. The lower velocities using 2D color DTI might be ex-plained by autocorrelation methodology resulting in peak-mean velocity, while PW-DTI is computed with a fast Fourier transformation technique resulting in measured peak velocities (Hummel et al., 2010). Where the sample volume is placed in the myocardium at the basal part of the LV may also cause the differences as well as the transducer angulation.

Because of the increase in LVEF using the biplane Simpson´s method and in the total amplitude of MAM, we expected an increase in all the other conventional parameters of measuring diastolic function as well. One rea-son to the lack of increase could be that few patients had severely reduced LVEF and total amplitude of MAM during the acute phase. However, in a study by Meimoun (Meimoun et al., 2009) LVEF in the acute phase (43±7%) was lower than in the present study and recovery phase LVEF was higher (69±5%) and despite this, the authors found no significant changes in diastolic parameters.

We cannot exclude the possibility that statistical significance could have been reached in some of the diastolic measurements with a larger sample.

LV length It could be expected that the apical ballooning often seen in takotsubo cardiomyopathy would contribute to a longer LV in the acute phase than

9

in the recovery phase, however, in the present study there was no signifi-cant difference in length in end-diastole from the epicardial apex to the septal and lateral sites of the LV. However, the transducer angulation might have influenced this result.

Right ventricle

Systolic function There was also, as with the total amplitude of MAM, a significant differ-ence between the acute and recovery phase concerning the total amplitude of TAM, that is, in the systolic shortening of the RV in long-axis direction measured at the lateral site. This means that also the RV is affected in ta-kotsubo, something that has been shown in a few studies only (Elesber et al., 2006; Haghi et al., 2007). In the study by Elesber it was found that RV involvement, when present, follows a similar pattern of regional wall mo-tion abnormalities, as does the LV in this syndrome and that RV involve-ment portends a longer and more critical hospitalization course as com-pared with patients with isolated LV involvement. The mechanisms ex-plaining the involvement of RV in takotsubo are unclear and the involve-ment argues against LV outflow tract obstruction causing takotsubo (Haghi et al., 2007).

The improvement of systolic long axis shortening of the RV at the lat-eral site indicates that also the longitudinal fibers of the RV, are affected in this disease, probably most in the apical regions.

RV diastolic function and length There was no significant change in RV diastolic parameters from the acute to the recovery phase, but trends in RV parameters might have been statis-tically significant with a larger sample. We have not been able to find pre-vious accounts on RV diastolic function in takotsubo.

As with the LV there was no significant change in RV end-diastolic length between the two phases, but also in this case the transducer angula-tion might have influenced the result.

STUDY IV

10

Conclusions From the acute phase to the recovery phase in takotsubo cardiomyopathy we found not only a significant increase in LVEF obtained by the biplane Simpson´s method but also a significant increase in systolic long-axis short-ening of both the LV and RV indicating that the longitudinal fibers are affected.

There was also an improvement in LV early and late diastolic velocities measured by PW-DTI while the other measured conventional diastolic parameters of the LV and the diastolic parameters of the RV as well as the length of the ventricles remained unchanged between the two phases.

11

References Alam M, Wardell J, Andersson E, Samad BA, Nordlander R. Character-

istics of mitral and tricuspid annular velocities determined by pulsed wave Doppler tissue imaging in healthy subjects. J Am Soc Echocardiogr (1999);12:618-628.

Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, Rysz J, Michalska M, Akashi Y J, Banach M. Takotsubo cardiomyopathy — The current state of knowledge. Int J Cardiol (2010);142:120-125.

Caso P, Galderisi M, Cicala S, Cioppa C, D'Andrea A, Lagioia G, Lic-cardo B, Martiniello AR, Mininni N. Association between myocardial right ventricular relaxation time and pulmonic arterial pressure in chronic ob-structive lung disease: Analysis by pulsed Doppler tissue imaging. J Am Soc Echocardiogr (2001);14:970–977.

Elesber AA, Prasad A, Bybee KA, Valeti U, Motiei A, Lerman A, Chandrasekaran K, Rihal CS. Transient cardiac apical ballooning syn-drome: prevalence and clinical implications of right ventricular involve-ment. J Am Coll Cardiol (2006);47:1082-1083.

Emilsson K. Right ventricular long-axis function in relation to left ven-tricular systolic function. Clin Physiol Funct Imaging (2004);24:212-215.

Feigenbaum H. Left and right atrium, and right ventricle. In: Fei-genbaum´s echocardiography (ed. Armstrong WF, Ryan T) (2010a); p.209. Lippincott Williams & Wilkins, Philadelphia.

Feigenbaum H. Evaluation of systolic function of the left ventricle. In: Feigenbaum´s echocardiography (ed. Armstrong WF, Ryan T) (2010b); pp. 126-127. Lippincott Williams & Wilkins, Philadelphia.

Foale R, Nihoyannopoulos P, McKenna W, Klienebenne A, Nadazdin A, Rowland E, Smith G. Echocardiographic measurement of the normal adult right ventricle. Br Heart J (1986);56:33-44.

Gerbaud E, Montaudon M, Leroux L, Corneloup O, Dos Santos P, Jais C, Coste P, Laurent F. MRI for the diagnosis of left ventricular apical bal-looning syndrome (LVABS). Eur Radiol (2008);18:947-954.

Greenbaum RA, Ho SY, Gibson DG, Becker AE, Anderson RH. Left ventricular fibre architecture in man. Br Heart J (1981);45:248-263.

Haghi D, Fluechter S, Suselbeck T, Kaden JJ, Borggrefe M, Papavassiliu T. Cardiovascular magnetic resonance findings in typical versus atypical forms of the acute apical ballooning syndrome (Takotsubo cardiomyopa-thy). Int J Cardiol (2007);120:205-211.

Henein MY, Priestley K, Davarashvili T, Buller N, Gibson DG. Early changes in left ventricular subendocardial function after successful coro-nary angioplasty. Br Heart J (1993);69:501-506.

10

Conclusions From the acute phase to the recovery phase in takotsubo cardiomyopathy we found not only a significant increase in LVEF obtained by the biplane Simpson´s method but also a significant increase in systolic long-axis short-ening of both the LV and RV indicating that the longitudinal fibers are affected.

There was also an improvement in LV early and late diastolic velocities measured by PW-DTI while the other measured conventional diastolic parameters of the LV and the diastolic parameters of the RV as well as the length of the ventricles remained unchanged between the two phases.

11

References Alam M, Wardell J, Andersson E, Samad BA, Nordlander R. Character-

istics of mitral and tricuspid annular velocities determined by pulsed wave Doppler tissue imaging in healthy subjects. J Am Soc Echocardiogr (1999);12:618-628.

Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, Rysz J, Michalska M, Akashi Y J, Banach M. Takotsubo cardiomyopathy — The current state of knowledge. Int J Cardiol (2010);142:120-125.

Caso P, Galderisi M, Cicala S, Cioppa C, D'Andrea A, Lagioia G, Lic-cardo B, Martiniello AR, Mininni N. Association between myocardial right ventricular relaxation time and pulmonic arterial pressure in chronic ob-structive lung disease: Analysis by pulsed Doppler tissue imaging. J Am Soc Echocardiogr (2001);14:970–977.

Elesber AA, Prasad A, Bybee KA, Valeti U, Motiei A, Lerman A, Chandrasekaran K, Rihal CS. Transient cardiac apical ballooning syn-drome: prevalence and clinical implications of right ventricular involve-ment. J Am Coll Cardiol (2006);47:1082-1083.

Emilsson K. Right ventricular long-axis function in relation to left ven-tricular systolic function. Clin Physiol Funct Imaging (2004);24:212-215.

Feigenbaum H. Left and right atrium, and right ventricle. In: Fei-genbaum´s echocardiography (ed. Armstrong WF, Ryan T) (2010a); p.209. Lippincott Williams & Wilkins, Philadelphia.

Feigenbaum H. Evaluation of systolic function of the left ventricle. In: Feigenbaum´s echocardiography (ed. Armstrong WF, Ryan T) (2010b); pp. 126-127. Lippincott Williams & Wilkins, Philadelphia.

Foale R, Nihoyannopoulos P, McKenna W, Klienebenne A, Nadazdin A, Rowland E, Smith G. Echocardiographic measurement of the normal adult right ventricle. Br Heart J (1986);56:33-44.

Gerbaud E, Montaudon M, Leroux L, Corneloup O, Dos Santos P, Jais C, Coste P, Laurent F. MRI for the diagnosis of left ventricular apical bal-looning syndrome (LVABS). Eur Radiol (2008);18:947-954.

Greenbaum RA, Ho SY, Gibson DG, Becker AE, Anderson RH. Left ventricular fibre architecture in man. Br Heart J (1981);45:248-263.

Haghi D, Fluechter S, Suselbeck T, Kaden JJ, Borggrefe M, Papavassiliu T. Cardiovascular magnetic resonance findings in typical versus atypical forms of the acute apical ballooning syndrome (Takotsubo cardiomyopa-thy). Int J Cardiol (2007);120:205-211.

Henein MY, Priestley K, Davarashvili T, Buller N, Gibson DG. Early changes in left ventricular subendocardial function after successful coro-nary angioplasty. Br Heart J (1993);69:501-506.

STUDY IV

12

Henry WL, DeMaria A, Gramiak R, King DL, Kisslo JA, Popp RL, Sahn DJ, Schiller NB, Tajik A, Teichholz LE, Weyman AE. Report of the Ameri-can Society of Echocardiography Committee on nomenclature and stan-dards in two-dimensional echocardiography. Circulation (1980);62:212-215.

Hummel YM, Klip IJ, de Jong RM, Pieper PG, van Veldhuisen DJ, Voors AA. Diastolic function measurements and diagnostic consequences: a comparison of pulsed wave-and color-coded tissue Doppler imaging. Clin Res Cardiol 2010;99:453-458.

Höglund C, Alam M, Thorstrand C. Atrioventricular valve plane dis-placement in healthy persons. An echocardiographic study. Acta Med Scand (1988);224: 557-562.

Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ. Recommendations of chamber quantification: A report from the American society of echocardiography’s guidelines and standards committee and the chamber quantification group, developed in conjunction with the European association of echocardiography, a branch of the European society of cardiology. J Am Soc Echocardiogr (2005);18:1440-1463.

Larrazet F, Pellerin D, Fournier C, Witchitz S, Veyrat C. Right and left isovolumic ventricular relaxation time intervals compared in patients by means of a single-pulsed Doppler method. J Am Soc Echocardiogr (1997);10:699-706.

Lassnig E, Weber T, Auer J, Nömeyer R, Eber B. Pheochromocytoma crisis presenting with shock and tako-tsubo-like cardiomyopathy. Int J Cardiol (2009);134:e138-140.

Lind B, Nowak J, Cain P, Quintana M, Brodin LÅ. Left ventricular iso-volumic velocity and duration variables calculated from colour-coded myocardial velocity images in normal individuals. Eur J Echocardiogr (2004);5:284-293.

Mann DL, Kent RL, Parsons B, Cooper G. Adrenergic effects on the bi-ology of the adult mammalian cardiocyte. Circulation (1992);85:790-804.

Margey R, Diamond P, Mc Cann H, Sugrue D. Dobutamine stress echo-induced apical ballooning (Takotsubo) syndrome. Eur J Echocardiogr (2009); 10:395-399.

Meimoun P, Malaquin D, Benali T, Boulanger J, Zemir H, Tribouilloy C. Transient impairment of coronary flow reserve in tako-tsubo cardio-myopathy is related to left ventricular systolic parameters. Eur J Echocar-diogr (2009);10: 265-270.

13

Nikitin NP, Witte, KK, Thackray DR, de Silva R, Clark AL, Cleland JG. Longitudinal ventricular function: normal values of atrioventricular annu-lar and myocardial velocities measured with quantitative two-dimensional color Doppler tissue imaging. J Am Soc Echocardiogr (2003);16:906-921.

Nilsson B, Bojö L, Wandt B. Influence of body size and age on maximal diastolic velocity of mitral annulus motion. J Am Soc Echocardiogr (2002);15: 29-35.

Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocar-diographic measurements. Circulation (1978);58:1072-1083.

Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Fei-genbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik J. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr (1989);2:358-367.

Takizawa M, Kobayakawa N, Uozumi H, Yonemura S, Kodama T, Fu-kusima K, Takeuchi H, Kaneko Y, Kaneko T, Fujita K, Honma Y, Aoyagi T. A case of transient left ventricular ballooning with pheochromocytoma, supporting pathogenetic role of catecholamines in stress induced cardio-myopathy or takotsubo cardiomyopathy. Int J Cardiol (2007);114:e15-e17.

Trio O, de Gregorio C, Andó G. Myocardial dysfunction after su-barachnoid haemorrhage and tako-tsubo cardiomyopathy : a differential diagnosis? Ther Adv Cardiovasc Dis (2010);4:105-107.

Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I. Transient left ventricular apical ballooning without coronary ar-tery stenosis: a novel heart syndrome mimicking acute myocardial infarc-tion. Angina Pectoris-Myocardial Infarction Investigations in Japan. J Am Coll Cardiol (2001);38:11-18.

Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Ger-stenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohu-moral features of myocardial stunning due to sudden emotional stress. N Eng J Med (2005):352:539-548.

12

Henry WL, DeMaria A, Gramiak R, King DL, Kisslo JA, Popp RL, Sahn DJ, Schiller NB, Tajik A, Teichholz LE, Weyman AE. Report of the Ameri-can Society of Echocardiography Committee on nomenclature and stan-dards in two-dimensional echocardiography. Circulation (1980);62:212-215.

Hummel YM, Klip IJ, de Jong RM, Pieper PG, van Veldhuisen DJ, Voors AA. Diastolic function measurements and diagnostic consequences: a comparison of pulsed wave-and color-coded tissue Doppler imaging. Clin Res Cardiol 2010;99:453-458.

Höglund C, Alam M, Thorstrand C. Atrioventricular valve plane dis-placement in healthy persons. An echocardiographic study. Acta Med Scand (1988);224: 557-562.

Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ. Recommendations of chamber quantification: A report from the American society of echocardiography’s guidelines and standards committee and the chamber quantification group, developed in conjunction with the European association of echocardiography, a branch of the European society of cardiology. J Am Soc Echocardiogr (2005);18:1440-1463.

Larrazet F, Pellerin D, Fournier C, Witchitz S, Veyrat C. Right and left isovolumic ventricular relaxation time intervals compared in patients by means of a single-pulsed Doppler method. J Am Soc Echocardiogr (1997);10:699-706.

Lassnig E, Weber T, Auer J, Nömeyer R, Eber B. Pheochromocytoma crisis presenting with shock and tako-tsubo-like cardiomyopathy. Int J Cardiol (2009);134:e138-140.

Lind B, Nowak J, Cain P, Quintana M, Brodin LÅ. Left ventricular iso-volumic velocity and duration variables calculated from colour-coded myocardial velocity images in normal individuals. Eur J Echocardiogr (2004);5:284-293.

Mann DL, Kent RL, Parsons B, Cooper G. Adrenergic effects on the bi-ology of the adult mammalian cardiocyte. Circulation (1992);85:790-804.

Margey R, Diamond P, Mc Cann H, Sugrue D. Dobutamine stress echo-induced apical ballooning (Takotsubo) syndrome. Eur J Echocardiogr (2009); 10:395-399.

Meimoun P, Malaquin D, Benali T, Boulanger J, Zemir H, Tribouilloy C. Transient impairment of coronary flow reserve in tako-tsubo cardio-myopathy is related to left ventricular systolic parameters. Eur J Echocar-diogr (2009);10: 265-270.

13

Nikitin NP, Witte, KK, Thackray DR, de Silva R, Clark AL, Cleland JG. Longitudinal ventricular function: normal values of atrioventricular annu-lar and myocardial velocities measured with quantitative two-dimensional color Doppler tissue imaging. J Am Soc Echocardiogr (2003);16:906-921.

Nilsson B, Bojö L, Wandt B. Influence of body size and age on maximal diastolic velocity of mitral annulus motion. J Am Soc Echocardiogr (2002);15: 29-35.

Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocar-diographic measurements. Circulation (1978);58:1072-1083.

Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Fei-genbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik J. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr (1989);2:358-367.

Takizawa M, Kobayakawa N, Uozumi H, Yonemura S, Kodama T, Fu-kusima K, Takeuchi H, Kaneko Y, Kaneko T, Fujita K, Honma Y, Aoyagi T. A case of transient left ventricular ballooning with pheochromocytoma, supporting pathogenetic role of catecholamines in stress induced cardio-myopathy or takotsubo cardiomyopathy. Int J Cardiol (2007);114:e15-e17.

Trio O, de Gregorio C, Andó G. Myocardial dysfunction after su-barachnoid haemorrhage and tako-tsubo cardiomyopathy : a differential diagnosis? Ther Adv Cardiovasc Dis (2010);4:105-107.

Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I. Transient left ventricular apical ballooning without coronary ar-tery stenosis: a novel heart syndrome mimicking acute myocardial infarc-tion. Angina Pectoris-Myocardial Infarction Investigations in Japan. J Am Coll Cardiol (2001);38:11-18.

Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Ger-stenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohu-moral features of myocardial stunning due to sudden emotional stress. N Eng J Med (2005):352:539-548.

STUDY IV

Table 1. Some basic characteristics of the patients and some measured and calcu-lated variables at inclusion (n=13).

Variable Mean±SD Age (years) 68.1±10.4 Height (m) 1.58±0.09 Weight (kg) 70.4±19.5 Left ventricular end-diastolic diameter (mm) 43.7±4.6 Left ventricular end-systolic diameter (mm) 27.9±6.1 Septal wall (mm) 10.7±2.5 Posterior wall (mm) 9.1±1.1 Right ventricular outflow tract 1 (mm) 27.0±4.2 Right ventricular inflow tract 3 (mm) 29.7±5.2

14

Table 2. Significance of difference between the acute and recovery phase of some left ventricular variables (EF=ejection fraction; MAM=amplitude of mitral annulus motion; PW=pulsed wave; PW DTI=pulsed wave Doppler tissue imaging; IVRT=isovolumetric relaxation time; DT=deceleration time; S=systolic velocity; E=early diastolic velocity by PW; A=late diastolic velocity by PW; é=early diastolic velocity by PW-DTI; á=late dia-stolic velocity by PW-DTI; 2D color DTI=two-dimensional color Doppler tissue imag-ing; color coded é=early diastolic velocity by 2D color DTI; color coded á=late diastolic velocity by 2D color DTI) (n=13).

Variable Acute

phase

Recovery

phase

Significance of

difference

EF obtained by biplane Simpson’s method (%) 53.4±9.5 63.3±4.4 p<0.01

MAM at the septal site (mm) 9.4±2.1 10.1±2.3 n.s.

MAM at the lateral site (mm) 10.1±2.3 12.1±2.6 p<0.02

MAM at the inferior site (mm) 9.9±2.8 11.6±2.0 p=0.03

MAM at the anterior site (mm) 9.0±2.6 10.8±1.9 p<0.02

Total MAM (all four sites, mm) 9.6±2.2 11.2±1.9 p<0.02

E/A 1.2±0.7 0.9±0.3 n.s.

DT (ms) 206.2±91.5 249.6±69.4 n.s.

IVRT by PW (ms) 91.5±19.3 90.6±17.3 n.s.



S by PW-DTI (cm/s) 5.9±1.5 7.2±1.9 p=0.02

é (cm/s) 6.5±2.6 8.2±3.3 p=0.04

á (cm/s) 7.0±2.0 8.6±2.9 p=0.04

é/á 1.1±0.8 1.1±0.7 n.s.


Color coded é (cm/s) 4.4±2.1 6.1±3.2 n.s

Color coded á by (cm/s) 5.4±1.8 6.2±2.3 n.s.

Color coded é/á 0.9±0.6 1.2±1.1 n.s.







E/é 12.6±6.5 11.9±9.6 n.s.

*one missing patient due to difficulties to measure IVRT by PW-DTI

15

Table 1. Some basic characteristics of the patients and some measured and calcu-lated variables at inclusion (n=13).

Variable Mean±SD Age (years) 68.1±10.4 Height (m) 1.58±0.09 Weight (kg) 70.4±19.5 Left ventricular end-diastolic diameter (mm) 43.7±4.6 Left ventricular end-systolic diameter (mm) 27.9±6.1 Septal wall (mm) 10.7±2.5 Posterior wall (mm) 9.1±1.1 Right ventricular outflow tract 1 (mm) 27.0±4.2 Right ventricular inflow tract 3 (mm) 29.7±5.2

14

Table 2. Significance of difference between the acute and recovery phase of some left ventricular variables (EF=ejection fraction; MAM=amplitude of mitral annulus motion; PW=pulsed wave; PW DTI=pulsed wave Doppler tissue imaging; IVRT=isovolumetric relaxation time; DT=deceleration time; S=systolic velocity; E=early diastolic velocity by PW; A=late diastolic velocity by PW; é=early diastolic velocity by PW-DTI; á=late dia-stolic velocity by PW-DTI; 2D color DTI=two-dimensional color Doppler tissue imag-ing; color coded é=early diastolic velocity by 2D color DTI; color coded á=late diastolic velocity by 2D color DTI) (n=13).

Variable Acute

phase

Recovery

phase

Significance of

difference

EF obtained by biplane Simpson’s method (%) 53.4±9.5 63.3±4.4 p<0.01

MAM at the septal site (mm) 9.4±2.1 10.1±2.3 n.s.

MAM at the lateral site (mm) 10.1±2.3 12.1±2.6 p<0.02

MAM at the inferior site (mm) 9.9±2.8 11.6±2.0 p=0.03

MAM at the anterior site (mm) 9.0±2.6 10.8±1.9 p<0.02

Total MAM (all four sites, mm) 9.6±2.2 11.2±1.9 p<0.02

E/A 1.2±0.7 0.9±0.3 n.s.

DT (ms) 206.2±91.5 249.6±69.4 n.s.

IVRT by PW (ms) 91.5±19.3 90.6±17.3 n.s.



S by PW-DTI (cm/s) 5.9±1.5 7.2±1.9 p=0.02

é (cm/s) 6.5±2.6 8.2±3.3 p=0.04

á (cm/s) 7.0±2.0 8.6±2.9 p=0.04

é/á 1.1±0.8 1.1±0.7 n.s.


Color coded é (cm/s) 4.4±2.1 6.1±3.2 n.s

Color coded á by (cm/s) 5.4±1.8 6.2±2.3 n.s.

Color coded é/á 0.9±0.6 1.2±1.1 n.s.







E/é 12.6±6.5 11.9±9.6 n.s.

*one missing patient due to difficulties to measure IVRT by PW-DTI

15

STUDY IV

Table 3. Significance of difference between the acute and recovery phase of some right ventricular variables (TAM=amplitude of tricuspid annulus motion; PW=pulsed wave; PW-DTI=pulsed wave Doppler tissue imaging; IVRT=isovolumetric relaxation time; DT=deceleration time; S=systolic velocity; E=early diastolic velocity by PW; A=late diastolic velocity by PW; é=early diastolic velocity by PW-DTI; á=late diastolic velocity by PW-DTI; 2D color DTI=two-dimensional color Doppler tissue imaging; color coded é=early dia-stolic velocity by 2D color DTI; á=late diastolic velocity by 2D color DTI; RVOT1=right ventricular outflow tract 1; RVIT3=right ventricular inflow tract 3) (n=13).

Variable Acute

phase Recovery

phase Significance

of difference

TAM (mm) 21.3±3.6 24.1±2.8 p=0.02

E/A 1.3±0.5 1.1±0.4 n.s.

DT (ms) 195.0±58.7 201.3±42.1 n.s.

IVRT by PW (ms) 84.8±27.5 63.4±25.6 n.s.



S by PW-DTI (cm/s) 12.2±2.2 12.5±2.3 n.s.

é (cm/s) 11.3±3.6 11.8±2.8 n.s.

á (cm/s) 16.2±3.9 15.7±3.0 n.s.

é/á 0.7±0.2 0.8±0.4 n.s.


Color coded é (cm/s) 9.5±3.6 8.6±2.7 n.s.

Color coded á (cm/s) 11.7±3.1 12.3±2.7 n.s.

Color coded é/á 0.9±0.4 0.8±0.5 n.s.


Length in end-diastole (apex-septal site, mm)

72.3±11.6 71.7±8.5 n.s.

Length in end-diastole (apex-lateral site, mm)

83.9±14.4 82.4±9.2 n.s.

RVOT1 (mm) 27.0±4.2 28.0±4.2 n.s.

RVIT3 (mm) 29.7±5.2 30.0±2.9 n.s.

16

Publications in the series

Örebro Studies in Medicine

1. Bergemalm, Per-Olof (2004). Audiologic and cognitive long-term sequelae from closed head injury.

2. Jansson, Kjell (2004). Intraperitoneal Microdialysis.Technique and Results.

3. Windahl, Torgny (2004). Clinical aspects of laser treatment of lichen sclerosus and squamous cell carcinoma of the penis.

4. Carlsson, Per-Inge (2004). Hearing impairment and deafness.Genetic and environmental factors – interactions – consequences. A clinical audiological approach.

5. Wågsäter, Dick (2005). CXCL16 and CD137 in Atherosclerosis.

6. Jatta, Ken (2006). Inflammation in Atherosclerosis.

7. Dreifaldt, Ann Charlotte (2006). Epidemiological Aspects onMalignant Diseases in Childhood.

8. Jurstrand, Margaretha (2006). Detection of Chlamydia trachomatis and Mycoplasma genitalium by genetic and serological methods.

9. Norén, Torbjörn (2006). Clostridium difficile, epidemiology and antibiotic resistance.

10. Anderzén Carlsson, Agneta (2007). Children with Cancer – Focusing on their Fear and on how their Fear is Handled.

11. Ocaya, Pauline (2007). Retinoid metabolism and signalling invascular smooth muscle cells.

12. Nilsson, Andreas (2008). Physical activity assessed by accelerometry in children.

13. Eliasson, Henrik (2008). Tularemia – epidemiological, clinical and diagnostic aspects.

14. Walldén, Jakob (2008). The influence of opioids on gastric function: experimental and clinical studies.

15. Andrén, Ove (2008). Natural history and prognostic factors inlocalized prostate cancer.

16. Svantesson, Mia (2008). Postpone death? Nurse-physicianperspectives and ethics rounds.

Table 3. Significance of difference between the acute and recovery phase of some right ventricular variables (TAM=amplitude of tricuspid annulus motion; PW=pulsed wave; PW-DTI=pulsed wave Doppler tissue imaging; IVRT=isovolumetric relaxation time; DT=deceleration time; S=systolic velocity; E=early diastolic velocity by PW; A=late diastolic velocity by PW; é=early diastolic velocity by PW-DTI; á=late diastolic velocity by PW-DTI; 2D color DTI=two-dimensional color Doppler tissue imaging; color coded é=early dia-stolic velocity by 2D color DTI; á=late diastolic velocity by 2D color DTI; RVOT1=right ventricular outflow tract 1; RVIT3=right ventricular inflow tract 3) (n=13).

Variable Acute

phase Recovery

phase Significance

of difference

TAM (mm) 21.3±3.6 24.1±2.8 p=0.02

E/A 1.3±0.5 1.1±0.4 n.s.

DT (ms) 195.0±58.7 201.3±42.1 n.s.

IVRT by PW (ms) 84.8±27.5 63.4±25.6 n.s.



S by PW-DTI (cm/s) 12.2±2.2 12.5±2.3 n.s.

é (cm/s) 11.3±3.6 11.8±2.8 n.s.

á (cm/s) 16.2±3.9 15.7±3.0 n.s.

é/á 0.7±0.2 0.8±0.4 n.s.


Color coded é (cm/s) 9.5±3.6 8.6±2.7 n.s.

Color coded á (cm/s) 11.7±3.1 12.3±2.7 n.s.

Color coded é/á 0.9±0.4 0.8±0.5 n.s.


Length in end-diastole (apex-septal site, mm)

72.3±11.6 71.7±8.5 n.s.

Length in end-diastole (apex-lateral site, mm)

83.9±14.4 82.4±9.2 n.s.

RVOT1 (mm) 27.0±4.2 28.0±4.2 n.s.

RVIT3 (mm) 29.7±5.2 30.0±2.9 n.s.

16

Publications in the series

Örebro Studies in Medicine

1. Bergemalm, Per-Olof (2004). Audiologic and cognitive long-term sequelae from closed head injury.

2. Jansson, Kjell (2004). Intraperitoneal Microdialysis.Technique and Results.

3. Windahl, Torgny (2004). Clinical aspects of laser treatment of lichen sclerosus and squamous cell carcinoma of the penis.

4. Carlsson, Per-Inge (2004). Hearing impairment and deafness.Genetic and environmental factors – interactions – consequences. A clinical audiological approach.

5. Wågsäter, Dick (2005). CXCL16 and CD137 in Atherosclerosis.

6. Jatta, Ken (2006). Inflammation in Atherosclerosis.

7. Dreifaldt, Ann Charlotte (2006). Epidemiological Aspects onMalignant Diseases in Childhood.

8. Jurstrand, Margaretha (2006). Detection of Chlamydia trachomatis and Mycoplasma genitalium by genetic and serological methods.

9. Norén, Torbjörn (2006). Clostridium difficile, epidemiology and antibiotic resistance.

10. Anderzén Carlsson, Agneta (2007). Children with Cancer – Focusing on their Fear and on how their Fear is Handled.

11. Ocaya, Pauline (2007). Retinoid metabolism and signalling invascular smooth muscle cells.

12. Nilsson, Andreas (2008). Physical activity assessed by accelerometry in children.

13. Eliasson, Henrik (2008). Tularemia – epidemiological, clinical and diagnostic aspects.

14. Walldén, Jakob (2008). The influence of opioids on gastric function: experimental and clinical studies.

15. Andrén, Ove (2008). Natural history and prognostic factors inlocalized prostate cancer.

16. Svantesson, Mia (2008). Postpone death? Nurse-physicianperspectives and ethics rounds.

17. Björk, Tabita (2008). Measuring Eating Disorder Outcome – Definitions, dropouts and patients’ perspectives.

18. Ahlsson, Anders (2008). Atrial Fibrillation in Cardiac Surgery.

19. Parihar, Vishal Singh (2008). Human Listeriosis – Sources and Routes.

20. Berglund, Carolina (2008). Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus. Epidemiological aspects of MRSA and the dissemination in the community and in hospitals.

21. Nilsagård, Ylva (2008). Walking ability, balance and accidental falls in persons with Multiple Sclerosis.

22. Johansson, Ann-Christin (2008). Psychosocial factors in patientswith lumbar disc herniation: Enhancing postoperative outcome by the identification of predictive factors and optimised physiotherapy.

23. Larsson, Matz (2008). Secondary exposure to inhaled tobacco products.

24. Hahn-Strömberg, Victoria (2008). Cell adhesion proteins in different invasive patterns of colon carcinoma: A morphometric and molecular genetic study.

25. Böttiger, Anna (2008). Genetic Variation in the Folate Receptor-α and Methylenetetrahydrofolate Reductase Genes as Determinants of Plasma Homocysteine Concentrations.

26. Andersson, Gunnel (2009). Urinary incontinence. Prevalence, treatment seeking behaviour, experiences and perceptions among persons with and without urinary leakage.

27. Elfström, Peter (2009). Associated disorders in celiac disease.

28. Skårberg, Kurt (2009). Anabolic-androgenic steroid users in treatment: Social background, drug use patterns and criminality.

29. de Man Lapidoth, Joakim (2009). Binge Eating and Obesity Treatment – Prevalence, Measurement and Long-term Outcome.

30. Vumma, Ravi (2009). Functional Characterization of Tyrosineand Tryptophan Transport in Fibroblasts from Healthy Controls, Patients with Schizophrenia and Bipolar Disorder.

31. Jacobsson, Susanne (2009). Characterisation of Neisseria meningitidis from a virulence and immunogenic perspective that includes variations in novel vaccine antigens.

32. Allvin, Renée (2009). Postoperative Recovery. Development of a Multi-Dimensional Questionnaire for Assessment of Recovery.

33. Hagnelius, Nils-Olof (2009). Vascular Mechanisms in Dementia with Special Reference to Folate and Fibrinolysis.

34. Duberg, Ann-Sofi (2009). Hepatitis C virus infection. A nationwide study of assiciated morbidity and mortality.

35. Söderqvist, Fredrik (2009). Health symptoms and potential effects on the blood-brain and blood-cerebrospinal fluid barriers associated with use of wireless telephones.

36. Neander, Kerstin (2009). Indispensable Interaction. Parents’ perspectives on parent–child interaction interventions and beneficial meetings.

37. Ekwall, Eva (2009). Women’s Experiences of Gynecological Cancer and Interaction with the Health Care System through Different Phases of the Disease.

38. Thulin Hedberg, Sara (2009). Antibiotic susceptibility and resistancein Neisseria meningitidis – phenotypic and genotypic characteristics.

39. Hammer, Ann (2010). Forced use on arm function after stroke. Clinically rated and self-reported outcome and measurement during the sub-acute phase.

40. Westman, Anders (2010). Musculoskeletal pain in primary health care: A biopsychosocial perspective for assessment and treatment.

41. Gustafsson, Sanna Aila (2010). The importance of being thin – Perceived expectations from self and others and the effect on self-evaluation in girls with disordered eating.

42. Johansson, Bengt (2010). Long-term outcome research on PDR brachytherapy with focus on breast, base of tongue and lip cancer.

43. Tina, Elisabet (2010). Biological markers in breast cancer and acute leukaemia with focus on drug resistance.

44. Overmeer, Thomas (2010). Implementing psychosocial factors in physical therapy treatment for patients with musculoskeletal pain in primary care.

45. Prenkert, Malin (2010). On mechanisms of drug resistance in acute myloid leukemia.

46. de Leon, Alex (2010). Effects of Anesthesia on Esophageal Sphincters in Obese Patients.

17. Björk, Tabita (2008). Measuring Eating Disorder Outcome – Definitions, dropouts and patients’ perspectives.

18. Ahlsson, Anders (2008). Atrial Fibrillation in Cardiac Surgery.

19. Parihar, Vishal Singh (2008). Human Listeriosis – Sources and Routes.

20. Berglund, Carolina (2008). Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus. Epidemiological aspects of MRSA and the dissemination in the community and in hospitals.

21. Nilsagård, Ylva (2008). Walking ability, balance and accidental falls in persons with Multiple Sclerosis.

22. Johansson, Ann-Christin (2008). Psychosocial factors in patientswith lumbar disc herniation: Enhancing postoperative outcome by the identification of predictive factors and optimised physiotherapy.

23. Larsson, Matz (2008). Secondary exposure to inhaled tobacco products.

24. Hahn-Strömberg, Victoria (2008). Cell adhesion proteins in different invasive patterns of colon carcinoma: A morphometric and molecular genetic study.

25. Böttiger, Anna (2008). Genetic Variation in the Folate Receptor-α and Methylenetetrahydrofolate Reductase Genes as Determinants of Plasma Homocysteine Concentrations.

26. Andersson, Gunnel (2009). Urinary incontinence. Prevalence, treatment seeking behaviour, experiences and perceptions among persons with and without urinary leakage.

27. Elfström, Peter (2009). Associated disorders in celiac disease.

28. Skårberg, Kurt (2009). Anabolic-androgenic steroid users in treatment: Social background, drug use patterns and criminality.

29. de Man Lapidoth, Joakim (2009). Binge Eating and Obesity Treatment – Prevalence, Measurement and Long-term Outcome.

30. Vumma, Ravi (2009). Functional Characterization of Tyrosineand Tryptophan Transport in Fibroblasts from Healthy Controls, Patients with Schizophrenia and Bipolar Disorder.

31. Jacobsson, Susanne (2009). Characterisation of Neisseria meningitidis from a virulence and immunogenic perspective that includes variations in novel vaccine antigens.

32. Allvin, Renée (2009). Postoperative Recovery. Development of a Multi-Dimensional Questionnaire for Assessment of Recovery.

33. Hagnelius, Nils-Olof (2009). Vascular Mechanisms in Dementia with Special Reference to Folate and Fibrinolysis.

34. Duberg, Ann-Sofi (2009). Hepatitis C virus infection. A nationwide study of assiciated morbidity and mortality.

35. Söderqvist, Fredrik (2009). Health symptoms and potential effects on the blood-brain and blood-cerebrospinal fluid barriers associated with use of wireless telephones.

36. Neander, Kerstin (2009). Indispensable Interaction. Parents’ perspectives on parent–child interaction interventions and beneficial meetings.

37. Ekwall, Eva (2009). Women’s Experiences of Gynecological Cancer and Interaction with the Health Care System through Different Phases of the Disease.

38. Thulin Hedberg, Sara (2009). Antibiotic susceptibility and resistancein Neisseria meningitidis – phenotypic and genotypic characteristics.

39. Hammer, Ann (2010). Forced use on arm function after stroke. Clinically rated and self-reported outcome and measurement during the sub-acute phase.

40. Westman, Anders (2010). Musculoskeletal pain in primary health care: A biopsychosocial perspective for assessment and treatment.

41. Gustafsson, Sanna Aila (2010). The importance of being thin – Perceived expectations from self and others and the effect on self-evaluation in girls with disordered eating.

42. Johansson, Bengt (2010). Long-term outcome research on PDR brachytherapy with focus on breast, base of tongue and lip cancer.

43. Tina, Elisabet (2010). Biological markers in breast cancer and acute leukaemia with focus on drug resistance.

44. Overmeer, Thomas (2010). Implementing psychosocial factors in physical therapy treatment for patients with musculoskeletal pain in primary care.

45. Prenkert, Malin (2010). On mechanisms of drug resistance in acute myloid leukemia.

46. de Leon, Alex (2010). Effects of Anesthesia on Esophageal Sphincters in Obese Patients.

47. Josefson, Anna (2010). Nickel allergy and hand eczema – epidemiological aspects.

48. Almon, Ricardo (2010). Lactase Persistence and Lactase Non-Persistence. Prevalence, influence on body fat, body height, and relation to the metabolic syndrome.

49. Ohlin, Andreas (2010). Aspects on early diagnosis of neonatal sepsis.

50. Oliynyk, Igor (2010). Advances in Pharmacological Treatment of Cystic Fibrosis.

51. Franzén, Karin (2011). Interventions for Urinary Incontinence in Women. Survey and effects on population and patient level.

52. Loiske, Karin (2011). Echocardiographic measurements of the heart. With focus on the right ventricle.

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