8
Pre-ejection mitral annular motion velocity responses to dobutamine infusion: A quantitative approach for assessment of myocardial viability Khaled Darahim a,, Ihab Attia a , Nabil Farag a , Walid El-Hammady a , Ahmed Onsy a a Department of Cardiovascular Medicine, Faculty of Medicine, Ain Shams University, Cairo a Egypt Background: Dobutamine stress echocardiography (DSE) is widely used for detection of myocardial viability. The main limitation of DSE is its subjective interpretation. Assessment of mitral annular motion velocities with tissue Doppler imaging is a simple and quantitative measurement. Objective: To determine the relationship between myocardial viability and regional systolic mitral annular motion tissue Doppler velocities responses to dobutamine stress. Methods: Our study group included 42 patients with previous myocardial infarction referred for coronary angiography and revascularization. We did dobutamine stress tissue Doppler echocardiography (DSTDE) measur- ing velocities of pre-ejection wave (pre-Ej) and peak ejection wave (Ej) at rest and during low-dose dobutamine infusion. We did follow up echocardiography after 1 month. Results: After exclusion of the normokinetic walls, we analyzed 196 walls. Using receiver operator characteristic ROC curves, the optimal cut-off value for viability assessment was an increase of 1.75 cm/s in pre-ejection velocity during DSTDE (area under the curve 0.70, p < 0.001). On the other hand, the optimal cut-off value for viability assess- ment was an increase of 1.75 cm/s in ejection velocity during DSTDE (area under the curve 0.613, p = 0.01). The sensitivity, specificity, and total accuracy of the DSTSE (pre-Ej) versus the gold standard for detection of myocardial viability were 66.15%, 67.94%, and 67.35%, respectively. The sensitivity, specificity, and total accuracy of the DTSE (Ej) were 56.92%, 64.12%, and 61.43%, respectively. There was a good correlation between the pre-Ej at 5 ug/kg/min dobutamine infusion and the pre-Ej after revascularization (r = 0.64, p = 0.01) while the correlation with the Ej was moderate (r = 0.50, p = 0.01). Conclusion: Viable left ventricular myocardium could be identified easily and quantitatively with pre-ejection mitral annular velocity during dobutamine infusion. The pre-ejection wave during DSTDE showed greater sensitiv- ity and specificity for the prediction of myocardial viability than the ejection wave. Ó 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University. Keywords: Dobutamine stress echocardiography, Tissue Doppler imaging, Myocardial viability P.O. Box 2925 Riyadh – 11461KSA Tel: +966 1 2520088 ext 40151 Fax: +966 1 2520718 Email: [email protected] URL: www.sha.org.sa FULL LENGTH ARTICLE Disclosure: Authors have nothing to disclose with regard to commercial support. Funding of this study was supported by our institution. Received 1 June 2013; revised 29 July 2013; accepted 2 August 2013. Available online 13 August 2013 Corresponding author. Address: Department of Cardiovascular Medicine, Ain Shams University Hospital, Abbasia, ZIP 11381, Cairo, Egypt. Tel.: +20 1061777957; fax: +20 222608283. E-mail address: [email protected] (K. Darahim). 1016–7315 Ó 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University. Peer review under responsibility of King Saud University. URL: www.ksu.edu.sa http://dx.doi.org/10.1016/j.jsha.2013.08.002 Production and hosting by Elsevier

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P.O. Box 2925 Riyadh – 11461KSATel: +966 1 2520088 ext 40151Fax: +966 1 2520718Email: [email protected]: www.sha.org.sa

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Disclosure: Authors have nothing to disclose with regard to commercialsupport.

Funding of this study was supported by our institution.

Received 1 June 2013; revised 29 July 2013; accepted 2 August 2013.Available online 13 August 2013

⇑ Corresponding author. Address: Department of CardiovascularMedicine, Ain Shams University Hospital, Abbasia, ZIP 11381, Cairo,Egypt. Tel.: +20 1061777957; fax: +20 222608283.

E-mail address: [email protected] (K. Darahim).

Pre-ejection mitral annular motion velocityresponses to dobutamine infusion:A quantitative approach for assessmentof myocardial viability

1016–7315 � 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

Peer review under responsibility of King Saud University.

URL: www.ksu.edu.sa

http://dx.doi.org/10.1016/j.jsha.2013.08.002 Production and hosting by Elsevier

Khaled Darahim a,⇑, Ihab Attia a, Nabil Farag a, Walid El-Hammady a, Ahmed Onsy a

a Department of Cardiovascular Medicine, Faculty of Medicine, Ain Shams University, Cairoa Egypt

Background: Dobutamine stress echocardiography (DSE) is widely used for detection of myocardial viability. Themain limitation of DSE is its subjective interpretation. Assessment of mitral annular motion velocities with tissueDoppler imaging is a simple and quantitative measurement.

Objective: To determine the relationship between myocardial viability and regional systolic mitral annularmotion tissue Doppler velocities responses to dobutamine stress.

Methods: Our study group included 42 patients with previous myocardial infarction referred for coronaryangiography and revascularization. We did dobutamine stress tissue Doppler echocardiography (DSTDE) measur-ing velocities of pre-ejection wave (pre-Ej) and peak ejection wave (Ej) at rest and during low-dose dobutamineinfusion. We did follow up echocardiography after 1 month.

Results: After exclusion of the normokinetic walls, we analyzed 196 walls. Using receiver operator characteristicROC curves, the optimal cut-off value for viability assessment was an increase of 1.75 cm/s in pre-ejection velocityduring DSTDE (area under the curve 0.70, p < 0.001). On the other hand, the optimal cut-off value for viability assess-ment was an increase of 1.75 cm/s in ejection velocity during DSTDE (area under the curve 0.613, p = 0.01). Thesensitivity, specificity, and total accuracy of the DSTSE (pre-Ej) versus the gold standard for detection of myocardialviability were 66.15%, 67.94%, and 67.35%, respectively. The sensitivity, specificity, and total accuracy of the DTSE(Ej) were 56.92%, 64.12%, and 61.43%, respectively. There was a good correlation between the pre-Ej at 5 ug/kg/mindobutamine infusion and the pre-Ej after revascularization (r = 0.64, p = 0.01) while the correlation with the Ej wasmoderate (r = 0.50, p = 0.01).

Conclusion: Viable left ventricular myocardium could be identified easily and quantitatively with pre-ejectionmitral annular velocity during dobutamine infusion. The pre-ejection wave during DSTDE showed greater sensitiv-ity and specificity for the prediction of myocardial viability than the ejection wave.

� 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

Keywords: Dobutamine stress echocardiography, Tissue Doppler imaging, Myocardial viability

Abbreviations

+Vic myocardial positive pre-ejection velocityCABG Gcoronary artery bypass graftingCI 95% confidence intervalDSE Dobutamine stress echocardiographyDSTDE dobutamine stress tissue Doppler echocardio-

graphyEF ejection fractionEj ejection waveIVS interventricular septal thickeningLA left atrial diameterLAD left anterior descendingLCX left circumflexLDDSE low dose dobutamine stress echocardiographyLV left ventricularLVEDD left ventricular end diastolic diameterLVEF left ventricular ejection fractionLVESD left ventricular end systolic diameterMI myocardial infarctionMRI magnetic resonance imagingPCI percutaneous coronary interventionPET positron emission tomographypre-Ej pre-ejection wavePW posterior wall thickeningRCA right coronary arteryROC receiver operator characteristicTDI tissue Doppler imaging

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16 DARAHIM ET ALPRE-EJECTION MITRAL ANNULAR MOTION VELOCITY RESPONSES TO DOBUTAMINE INFUSION:A QUANTITATIVE APPROACH FOR ASSESSMENTOF MYOCARDIAL VIABILITY

J Saudi Heart Assoc2014;26:15–22

Introduction

Assessment of myocardial viability in patientswith myocardial infarction is important.

Myocardial scintigraphy [1], dobutamine stressechocardiography, [2] and contrast echocardiogra-phy [3] are used in the determination of viability.Among these procedures, dobutamine stressechocardiography is widely used in the clinicalsetting because it is a safe and accurate methodfor detection of myocardial viability. The mainlimitation of dobutamine echocardiography is itssubjective interpretation [4].

Because the mitral annulus shifts towards thecardiac apex during systole [5], the mitral annularmotion recorded with M-mode echocardiographycorrelates with the left ventricular ejection fraction[6,7] and myocardial viability [8]. One studyshowed that changes in the amplitude of the AVplane displacement during low-dose dobutaminestress echocardiography can easily be used todetect myocardial viability at an early stage withlate potential for spontaneous recovery [9].

Tissue Doppler imaging facilitates the directmeasurement of the left ventricular wall and mi-tral annular motion velocities [10,11]. This methodcan therefore be used for quantitation of regionalleft ventricular wall motion [12]. Thus, the param-eters obtained from mitral annular systolic motionvelocities with pulsed tissue Doppler imagingreflect left ventricular (LV) asynergy correspond-ing to the infarct regions in patients with myocar-dial infarction, and global LV systolic functionmay be evaluated with these parameters [13].Assessment of mitral annular motion velocitiesalong the long axis with tissue Doppler imaginghas several advantages over other methods, suchas the simplicity of measurement, superior timeresolution, and preload independence [13–15].

However, there have been no many studiescorrelating myocardial viability and regionalsystolic mitral annular motion velocity responseto dobutamine stress, particularly during earlysystole. It has been found that the pre-systolicannular motion towards the cardiac apexaccurately predicts regional left ventricular myo-cardial viability [12].

Objective

The objective of this study is to determinethe accuracy of regional systolic mitral annularmotion tissue Doppler velocities responses todobutamine stress in the detection of myocardialviability in patients with previous myocardialinfarction.

Methodology

We enrolled consecutive patients with previousmyocardial infarction who were referred to AinShams University Hospitals for coronary angiog-raphy and revascularization.

Inclusion criteria were: (1) Significant (>50%)reduction in the luminal diameter of a majorcoronary artery corresponding to the infarctedarea on the basis of recent coronary angiographicresults; (2) previous Q-wave myocardial infarctionof more than one-week duration; and (3) regionalleft ventricular wall motion abnormality corre-sponding to the infracted region on the basis oftwo-dimensional echocardiography. The infract-related coronary artery stenosis was revascular-ized by either coronary artery bypass grafting(CABG) or percutaneous coronary intervention(PCI).

Exclusion criteria were: (1) Postinfarction unsta-ble angina or infarction complicated by severehemodynamic instability; (2) decompensated con-gestive heart failure; (3) protruding thrombus inthe left ventricular cavity with fresh mobile edges;(4) significant valvular or congenital heart disease;(5) any myocardial disease apart from ischemia;(6) coexistent relevant liver or renal disease; (7) acontraindication to dobutamine administrationparticularly; (8) moderate or severe mitral regurgi-

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tation; and (9) technically inadequate echocardio-graphic imaging.

The study was approved by the medical ethicscommittee of our institution. The study protocolwas designed in accordance with The Code ofEthics of the World Medical Association (Declara-tion of Helsinki) for experiments involvinghumans. All patients gave informed consent be-fore the procedure.

Baseline transthoracic echocardiographic exam-ination: Images were acquired with the patientin the left lateral decubitus position using a multi-frequency phased array transducer of 2.5–3.5 MHzattached to Vivid V echocardiography machine(General Electric medical systems, manufacturedin Horten, Norway) equipped with Doppler tissueimaging (DTI) technology. We measured the leftventricular end diastolic diameter (LVEDD), leftventricular end systolic diameter (LVESD), left at-rial diameter (LA), Ejection fraction (EF), restingsegmental wall motion. The left ventricle wasdivided into the standard 16-segment model rec-ommended by the American Society of Echocardi-ography [16]

We graded each myocardial segment using thefollowing semi-quantitative scoring system: Nor-mal contraction was defined as 5 mm endocardialexcursion, 25% systolic thickening, and assigned ascore of 1. Hypokinesia was defined as <5 mmendocardial excursion, <25% systolic thickening,and assigned a score of 2. Akinesia was definedas virtual absence of systolic myocardial thicken-ing, even if slight inward motion was present dur-ing systole, and assigned a score of 3. Dyskinesiawas defined as paradoxical endocardial excursionaway from the left ventricular lumen in systole,and assigned a score of 4.

Aneurysm was defined as continuous distortionof the wall both in systole and diastole, andassigned a score of 5. Aneurysm with scar wasdefined as score 5 + scar of previous MI. It was as-signed a score of 6.

Dobutamine stress tissue Dopplerechocardiography (DSTDE)

We infused dobutamine in a stepwise manner(0, 5 and 10 ug/kg/min) during 3 min intervals.At each dose, heart rate and blood pressure weremeasured. We calculated left ventricular ejection(LVEF) fraction at rest and at the end of eachinfusion stage of the pharmacologic stressprotocol.

DSTDE was done for studying the systolic mitralannular motion velocities at six mitral annularsites that reflect the asynergy at these sites corre-

sponding to the infarct regions in patients withmyocardial infarction: (anteroseptal and posteriorwalls in the apical long axis view, posteroseptaland lateral walls in the apical 4-chamber view,and anterior and inferior walls in the apical 2-chamber view). The acoustic power and filter fre-quencies of the ultrasound scan system were setto the lowest values possible, and the sample col-umns (width of approximately 8 mm) were set atthe mitral annulus. The peak velocity was deter-mined as the average peak velocity from threeconsecutive beats, both in the pre-ejection phaseand during left ventricular contraction in the ejec-tion period. Briefly, to define the pre-ejection per-iod, aortic flow was recorded by pulsed-waveDoppler at the level of LV outflow tract at thebeginning and at the end of each examination.Pre-ejection was defined as a time interval be-tween the onset of QRS complex and the onsetof aortic flow. Cardiac cycles with extrasystolic,post-extrasystolic beats, or any rhythm distur-bance were excluded. Recording was repeatedduring dobutamine infusion at 0, 5 and 10 ug/kg/min. Analysis was performed by one observer(AO). Measurements of theses parameters werehighly reproducible by the same observer for eachpatient. Reproducibility (intra-observer variabil-ity) was assessed by coefficient of variation for re-peated measures in the first 10 patients.

End points for interrupting any of the abovementioned infusion protocols were: (1) intolerablesymptoms such as severe headache, severe nau-sea and vomiting; (2) severe chest pain and/ordyspnea with evidence of clinical ischemiadefined as P2.0 mm of additional ST segmentdepression or elevation in at least two contiguousleads compared with rest ± new remote wallmotion abnormality or worsening contractility inpreviously asynergic segments; (3) limitingasymptomatic side effects including hypertension(systolic blood pressure > 220 mmHg and/or dia-stolic blood pressure > 120 mmHg), hypotension(relative or absolute i.e. >30 mmHg decrease inblood pressure), sustained supraventriculartachyarrhythmia particularly atrial fibrillation,ventricular arrhythmias (frequent, polymorphouspremature ventricular beats or ventricular tachy-cardia) and bradyarrhythmias. In the event ofdemonstrable ischemia, intravenous beta blockersand/or nitroglycerin were administered.

Follow upWe performed transthoracic two-dimensional

echocardiography at 1 month after revasculariza-tion to detect improvement in regional wall mo-

Table 1. Baseline clinical and angiographic characteristics ofthe study group.

Patients (n = 42)

Age in years 53.5 ± 8.7Sex

Male 38 (90.5%)Female 4 (9.5%)

Risk factors

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tion and left ventricular function. Also, anotherTDI study was conducted during follow-up todetect improvement in the value of the pre-ejec-tion wave or ejection waves. Improvement afterrevascularization (the gold standard of viability)was considered if there was any improvement byone or more grades of at least one myocardial seg-ment of the affected wall.

Smoking 33 (78.6%)Diabetes 15 (35.7%)Hypertension 16 (38.1%)Dyslipidemia 15 (35.7%)Family history 9(21.4%)

Previous MIAnterior 24 (57.1%)Inferior 5 (11.9Anterior and inferior 13 (31%)

Duration of MI in months 7.3 ± 11.3

Coronary artery affectionLAD 38 (90.5%)LCX 31 (73.8%)RCA 26 (21.9%)

Coronary artery affectionSingle vessel 9 (21.4%)Double vessel 13 (31%)Three vessel 20 (47.6%)

Baseline echocardiographyLVEDD in mm 59.8 ± 9.2LVESD in mm 45.4 ± 9.7IVS in mm 9.7 ± 1.6PW in mm 1.3 ± 1.3

Statistical analysis

The data were statistically analyzed using theStatistical Package for Social Sciences (SPSS) soft-ware version 14. Categorical variables were com-pared by Chi square test. Continuous normallydistributed variables were compared by Paired-sample t-test. Pearson correlation was done forcontinuous variables. Specificity and sensitivityof dobutamine mitral annular TDI echo were cal-culated against the gold standard of viability(improvement with revascularization). The opti-mal pre-ejection and ejection velocity changesfor the prediction of myocardial viability(improvement with revascularization) were deter-mined by a receiver operator characteristic (ROC)curve constructed for the pre-ejection and ejectionvelocity values. A p value 60.05 (2-tailed) was con-sidered significant and a p value 60.01 was con-sidered highly significant.

LVEF 38.2 ± 9.5LAD in mm 39.4 ± 7.1

MI = myocardial infarction, LAD = left anterior descending, LCX = leftcircumflex, RCA = right coronary artery, LVEDD = left ventricular enddiastolic diameter, LVESD = left ventricular end systolic diameter,IVS = interventricular septal thickening, PW = posterior wall thicken-ing, LVEF = left ventricular ejection fraction, LAD = left atrial diameter.Data are expressed as a mean ± standard deviation or a number(percent).

Table 2. Mitral annular tissue Doppler pre-ejection andejection velocities during DSTDE.

Velocities(cm/s)

Rest Dobutamine(5 ug/kg/min)

p Values

Pre-ejection wave 5.86 ± 1.69 7.59 ± 2.32 0.001Ejection wave 7.47 ± 1.59 9.23 ± 2.01 0.001

Data expressed as mean ± standard deviation.

Results

The study included 42 consecutive patients withrecent or old myocardial infarction with docu-mented significant coronary artery disease bycoronary angiography and submitted to electivepercutaneous coronary intervention (18 patients)or coronary artery bypass grafting surgery withtwo or three grafts (24 patients). They allunderwent complete successful revascularizationthat included the infarct-related arteries. Thebaseline characteristics are detailed in Table 1.

The LVEF at rest was 38.2 ± 9.5% while at 5 ug/kg/min infusion rate of dobutamine during thestudy was 43.2 ± 9.7%. The ejection fractionimproved at one-month follow up after revascu-larization (38.2 ± 9.5% vs. 44.1 ± 10.3%, p = 0.0001).There was an excellent correlation between LVEFduring 5 ug/kg/min dobutamine infusion andLVEF after revascularization (r = 0.93, p < 0.0001).

Detection of myocardial viability

Low dose dobutamine echocardiography fordetection of viability was performed on the 42 pa-

tients by using TDI. Among the 42 patients, 252walls were studied. The normokinetic walls at restdetected by 2D conventional echocardiographywere excluded from the study, so the remainingdiseased walls were 196. Table 2 presents the val-ues of the pre-ejection and the ejection waves dur-

Figure 2. ROC curve: THE best cut-off value for the change of theejection wave at 5 ug/kg/min dobutamine infusion to predictimprovement after revascularization is 1.75 cm/s. AUC = 0.615,CI = 0.533–0.693, p = 0.01.

Table 3. The diagnostic accuracy of the DSTDE.

DSTDE (pre-ejection wave)

DSTDE (ejectionwave)

Sensitivity 66.15% CI: 53.35–77.43%

56.92%CI: 44.04–69.15%

Specificity 67.94% CI: 59.22–75.82%

64.12% CI:55.28–72.31%

Positive 50.59% CI: 39.52– 44.05% CI:

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DARAHIM ET AL 19PRE-EJECTION MITRAL ANNULAR MOTION VELOCITY RESPONSES TO DOBUTAMINE INFUSION:

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ing DSTDE. Both waves increased significantlyduring dobutamine infusion (5 ug/kg/min).

Another two-dimensional and TDI study wasconducted after revascularization at one-monthfollow up. Improvement was detected at one-month post-revascularization in 65 walls out ofthe 196 walls (33.16%).

There was good correlation between the pre-ejection wave at 5 ug/kg/min dobutamine infusionand the pre-ejection wave after revascularization(r = 0.64, p = 0.01). There was moderate correlationbetween the ejection wave at 5 ug/kg/min dobuta-mine infusion and the ejection wave after revascu-larization (r = 0.50, p = 0.01).

Using ROC curves, the optimal cut-off value forviability assessment was an increase of 1.75 cm/sin pre-ejection velocity during DSTDE (65% sensi-tivity, 67% specificity, area under the curve 0.70,p < 0.001, Fig. 1). On the other hand, the optimalcut-off value for viability assessment was an in-crease of 1.75 cm/s in ejection velocity duringDSTDE (58% sensitivity, 63% specificity, area un-der the curve 0.613, p = 0. 01, Fig. 2).

The diagnostic accuracy of the DSTDE was cal-culated against the gold standard of viability(improvement after revascularization). DSTDE(pre-ejection wave) correctly identified 43 wallsas viable and 89 walls as non-viable. Twenty-twowalls were erroneously classified as non-viableand 42 walls as viable. Thus, the sensitivity, spec-ificity, and total accuracy of the DSTDE (pre-ejec-tion wave) were 66.15%, 67.94%, and 67.35%,respectively.

Figure 1. ROC curve: the best cut-off value for the change of the pre-ejection wave at 5 ug/kg/min dobutamine infusion to predictimprovement after revascularization is 1.75 cm/s. AUC = 0.700,CI = 0.627–0.773, p = 0.001.

predictivevalue

61.61% 33.22–55.30%

Negativepredictivevalue

80.18% CI: 71.54–87.14%

75.00% CI:65.93–82.70%

DTSE = dobutamine stress tissue Doppler echocardiography, CI = 95%confidence interval.

DSTDE (ejection wave) correctly identified 37walls as viable and 84 walls as non-viable.Twenty-eight walls were erroneously classifiedas non-viable and 47 walls as viable. Thus, thesensitivity, specificity, and total accuracy of theDSTDE (ejection wave) were 56.92%, 64.12%, and61.43%, respectively (Table 3).

Discussion

Assessment of myocardial viability in patientswith myocardial infarction is important. Dobuta-mine stress echocardiography is widely used inthe clinical setting because it is a safe and accuratemethod for detection of myocardial viability. The

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main limitation of dobutamine echocardiographyis its subjective interpretation [4]. TDI, as aquantitative technique for the assessment ofmyocardial velocities, is at least as accurate inidentifying viable myocardium as are traditionalqualitative methods. However, the recording ofmyocardial velocities during the dobutaminestress echo is a time consuming technique [17–18]. The need to acquire all values on-line withina limited time margin at peak stress is a limitationof this modality [18].

Assessment of mitral annular motion velocitiesalong the long axis with tissue Doppler imaginghas several advantages over regional left ventricu-lar wall motion velocities, such as the simplicity ofmeasurement, superior time resolution, and pre-load independence [13–15]. Various studies havefocused on the relationship between mitral annu-lar motion and LV systolic function. Specifically, ithas been reported that mitral annular motiondetermined with M-mode or two-dimensionalechocardiography correlates with the LVEF inhealthy individuals or in patients with heartdiseases [6,7]. Alam found that the amplitude ofmitral annular motion decreases in infracted re-gions [7]. In addition, another study reported thatsystolic mitral annular motion toward the cardiacapex measured with M-mode echocardiographycould have a high degree of sensitivity and speci-ficity for detection of myocardial viability [8]. Itwas also found that the correlation between ejec-tion fraction (EF) and the systolic mitral annularvelocity is relatively good irrespective of the pres-ence or absence of significant mitral regurgitation.Measurements of annular velocities constitute asimple and useful method for evaluating patientswith heart failure [19]. In another study, it wasfound that M-mode echocardiography andpulsed-wave DTI used for assessment of mitralannular motion are useful methods for evaluationof LV function. However, parameters measuredby pulsed-wave DTI correlate more strongly withplasma brain natriuretic peptide levels thanthose measured by M-mode echocardiographyand provide a simple, sensitive, accurate andreproducible tool for early diagnosis of LV dys-function [20].

Therefore, the main point of this study was thatTDI of the mitral annular motion, as a quantitativeand easy technique for the assessment of myocar-dial viability, is accurate in identifying viable myo-cardium in patients with previous myocardialinfarction.

These results coincide with those of an earlierreport which also studied the response of systolic

mitral annular motion velocities to dobutamineinfusions and its relation to prediction of myocar-dial viability. The study included 45 patients withprevious myocardial infarction. A 99mTc-meth-oxyisobutylisonitrile scintigraphy was performedto detect viability. This study showed that whenthe cut-off value for an increase in pre-systolicwave was set at 2 cm/s, myocardial viability waspredicted with a sensitivity of 92% and specificityof 90% [12]. When the cut-off value for an increasein systolic wave was set at 2 cm/s, myocardialviability was predicted with a sensitivity of 67%and specificity of 58% [12].

Another report investigated low dose dobuta-mine stress echocardiography (LDDSE) combinedwith tissue Doppler imaging (TDI) of the myocar-dial segments for the quantitative assessment ofthe content of viable myocardium (definedaccording to postoperative recovery) [18]. Conven-tional qualitative LDDSE showed a sensitivity of78% and specificity of 85% in predicting myocar-dial recovery. The optimal cut-off value for viabil-ity assessment was an increase of 0.5 cm/s inejection velocity during LDDSE (80% sensitivityand 88% specificity, area under the curve 0.801),0.6 cm/s in pre-ejection velocity (91% sensitivityand 90% specificity, area under the curve 0.890)[18].

Penicka et al. [21] assessed the accuracy of tissueDoppler imaging-derived myocardial positivepre-ejection velocity (+Vic) in detecting myocar-dial viability defined by dobutamine stressechocardiography (DSE), fluorine-18 fluorodeo-xyglucose positron emission tomography (PET),contrast-enhanced magnetic resonance imaging(MRI), and recovery of left ventricular (LV) func-tion after coronary artery bypass grafting inpatients with chronic ischemic LV dysfunction. Agood agreement was observed between +Vic anddetection of viable myocardium at DSE, PET,and MRI (kappa = 0.76). The presence of +Vic ingreater than or equal to five dysfunctional seg-ments had the highest sensitivity (93%) and spec-ificity (60%) to identify patients (n = 28) with > or=10% increase in LVEF between baseline andsix-month echocardiogram [21].

Another study tested the ability of pre-ejectionvelocity to predict recovery of myocardial contrac-tile function after coronary revascularization inacute myocardial infarction. Longitudinal myocar-dial velocities were recorded at rest by pulsed-wave TDI echocardiography 6 +/� 2 h after revas-cularization. They showed a positive pre-ejectionvelocity after revascularization predicted recoveryof contractile function in the reperfused area [22].

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Thus, several studies found that when myocar-dial viability was evaluated by TDI, the pre-ejec-tion wave during early systole showed greatersensitivity and specificity for the prediction ofmyocardial viability than the ejection wave. Ithas been reported that endocardial dysfunctiongenerally occurs during the early stages of ische-mia, resulting in a predominant impairment oflongitudinal fiber contraction during early systole[23,24]. Residual viability of longitudinal fibers inthe infarcted region is closely associated with anincrease in pre-ejection wave velocity after dobu-tamine administration [12]. Moreover, segmentswith extensive scar tissue may show an increasein ejection velocity during dobutamine infusiondue to the tethering effect of adjacent viable myo-cardium. A possible way to avoid this effect couldbe the evaluation of pre-ejection velocity changes.During that period, the left ventricle does notchange its shape, and the tethering effect is thusminimized. Furthermore, the effect of cardiacrotation is lower during the pre-systolic periodthan during the ejection period.

The increase in wall thickness that occurs in nor-mal myocardium after ventricular activation andbefore aortic opening corresponds to the briefpre-ejection velocity. In our study, the pre-ejec-tion velocity increased during low dose dobuta-mine infusion. There was good correlationbetween the pre-ejection wave at 5ug/kg/mindobutamine infusion and the pre-ejection waveafter revascularization (r = 0.64, p = 0.01). Thismeans that viable hibernating myocardium maycontract at rest when both left ventricular pressureand wall stress are low (e.g. during pre-ejectionphase); however, it cannot sustain the higher loadduring ejection. This is consistent with findingsthat positive pre-ejection velocity wave is a signof non-transmural necrosis [25] and that increasedsegmental systolic velocity during low dose DSE isassociated with viability of these segments [26].

Therefore, the pre-ejection wave more sensi-tively reflects myocardial viability than theejection wave and gives important informationfor the detection of reversible myocardial dysfunc-tion (hibernation) with low dose dobutaminestress. Furthermore, because pulsed TDI facili-tates the evaluation of myocardial viability alongthe long axis, measurements are relatively easierto evaluate than measurements along the shortaxis, and are minimally influenced by whole heartmotion. To the best of our knowledge, our study isthe first study to predict myocardial viability,defined by improvement after revascularization,with pre-ejection mitral annular velocity during

dobutamine stress tissue Doppler echocardiog-raphy.

Currently, the most cost-effective imaging tech-niques to detect reversible contractile function arestress echocardiography and nuclear perfusionimaging [1,2]. Echocardiography has the advan-tage of widespread availability, but subjectiveevaluation remains its main limitation [4]. TDIprovides quantitative data; however, the record-ing of myocardial velocities during dobutaminestress echo is a time consuming technique [18].Therefore, recording of mitral annular TDI veloci-ties is relatively simple and should be technicallyfeasible for evaluation of regional myocardial via-bility in patients with myocardial infarction.

Limitations of the study

We arbitrarily timed the outcome of dysfunc-tional segment 1 month after revascularization toavoid the interaction of possible restenosis onfunctional recovery. However, potential functionalimprovement after this time cannot be ruled out.Accurate definition of culprit artery restenosiscould have been done with another follow-upangiography, but that would have increased thecost of the study. Pulsed TDI was performed atthe level of the mitral annulus, but the regionalmyocardium itself was not evaluated. Therefore,measured values might be influenced by the in-farcted area or wall motion in the non-infarctedregions. Moreover, left atrial hemodynamicsmight influence mitral annular motion in patientswith markedly elevated LV end diastolic pressureor left atrial dilatation. It was not possible to assessthe ability of TDI to optimize prediction of death-free outcome in long-term follow-up.

Conclusion and recommendations

Viable left ventricular myocardium could beidentified quantitatively and easily with peakpre-ejection mitral annular velocity during dobu-tamine stress tissue Doppler echocardiography.The pre-ejection wave during early systoleshowed greater sensitivity and specificity for theprediction of myocardial viability than the ejectionwave. In view of the small sample size included inthis report, larger clinical studies are needed toconfirm these observations.

Appendix A. Supplementary data

Supplementary data associated with this articlecan be found, in the online version, at http://dx.doi.org/10.1016/j.jsha.2013.08.002.

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22 DARAHIM ET ALPRE-EJECTION MITRAL ANNULAR MOTION VELOCITY RESPONSES TO DOBUTAMINE INFUSION:A QUANTITATIVE APPROACH FOR ASSESSMENTOF MYOCARDIAL VIABILITY

J Saudi Heart Assoc2014;26:15–22

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