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061 Borderzone Myocardial Dyssynchrony Following Anteroapical Myocardial Infarction: A Real-Time Three-Dimensional Echocardiographic Study Liam P. Ryan 1 , Benjamin M. Jackson 1 , Landi M. Parish 1 , Martin G. St. John Sutton 2 , Theodore Plappert 2 , Joseph H. Gorman III 1 , Robert C. Gorman 1 ; 1 Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA; 2 Department of Medicine, Division of Cardiology, University of Pennsylvania School of Medicine, Philadelphia, PA Introduction: The hypocontractile but normally perfused borderzone myocardium (BZM) has been implicated in the pathogenesis of congestive heart failure following myocardial infarction (MI). Hypothesis: We used real-time three-dimensional echo- cardiography (rt-3DE) to test the hypothesis that BZM dysfunction is associated with delayed systolic activation of this region. Methods: Rt-3DE was performed in 9 Dorsett hybrid sheep at baseline, immediately following a moderately sized anteroap- ical myocardial infarction (MI) and at 10 weeks following MI. Manual endocardial tracing was performed using Tomtec software. The BZM was defined by the 6 segments adjacent to the dyskinetic infarcted myocardium. BZM end systolic delay (ESD) was defined as the average delay with respect to the first segment to reach its minimum seg- mental volume. BZM systolic dyssynchrony index (SDI) was defined as the standard deviation of ESDs for a given data set. In order to normalize the data for different heart rates, phase shift was expressed as a percentage of the cardiac cycle duration. Results: QRS widening did not occur in any experimental subject. A statistically significant (p ! 0.05) decrement in EF occurred between all measured time points. A statistically significant (p ! 0.001) increase in ESD occurred both immediately following infarc- tion and at 10 weeks. A statistically significant (p ! 0.05) increase in SDI occurred at 10 weeks when compared to both baseline and post-infarction values. The magnitude of change was greatest during the interval between infarction and 10 weeks follow-up in all cases. Conclusions: Longitudinal increases in BZM hypokinesis and dyssynchrony were observed in the absence of QRS widening using rt-3DE during a 10 week interval in an ovine model of apical myocardial infarction. Rt-3DE may allow for echocardio- graphically guided BZM resynchronization in the future. 062 Real-Time Three-Dimensional Echocardiography To Quantify Remodeling after Infarction in Ovine Heart Failure Models Liam P. Ryan 1 , Hirotsugu Hamamoto 1 , Benjamin M. Jackson 1 , Landi M. Parish 1 , Martin G. St. John Sutton 2 , Theodore Plappert 2 , Joseph H. Gorman III 1 , Robert C. Gorman 1 ; 1 Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA; 2 Department of Medicine, Division of Cardiology, University of Pennsylvania School of Medicine, Philadelphia, PA Introduction: Magnetic resonance imaging (MRI) has been the gold-standard for the assessment of ventricular size and geometry. However, MRI is expensive, time and labor intensive, not universally available and often requires transport of human and animal subjects to remote areas of the hospital. In addition, MRI currently does not allow assessment of valvular structure and function. Hypothesis: Real-time three-dimensional echocardiography (rt-3DE) overcomes many of the limitations as- sociated with MRI. While rt-3DE volumetric analysis has been validated in human subjects, cardiac geometry differs in many experimental animal species raising con- cern regarding the adequacy of volume averaging algorithms incorporated into both the two-dimensional echocardiography (2DE) and rt-3DE analysis software. Methods: Rt-3DE, 2DE and MRI were performed in 9 Dorsett hybrid sheep at base- line and at 10 weeks following apical MI. End-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were calculated independently at each time point by means of rt-3DE, 2DE and MRI. Results: Statistically significant (p ! 0.01) increases in both EDV and ESV and decreased in EF occurred as determined by all three modalities. Correlation between EDV, ESV and EF as determined by rt-3DE and MRI was excellent with R equal to 0.99. 0.99 and 0.98 respectively. Correlation between EDV, ESV and EF as determined by means of 2DE and MRI was also ac- ceptable with R equal to 0.83, 0.87 and 0.84 respectively. Conclusions: Left ventric- ular volumes as determined by rt-3DE are nearly identical to those determined by MRI. Those determined by 2DE are also very similar. Both echocardiographic tech- niques are accurate in a well-established ovine model of CHF which has become an increasingly prominent platform for heart failure research. Left Ventricular Volumes and EF Before and After Apical MI Basline 10 Weeks Post-MI EDV (mm 3 ) 3DE 53.0 149.6 MRI 55.3 149.0 2DE 69.0 156.1 ESV (mm 3 ) 3DE 22.1 123.1 MRI 24.3 122.0 2DE 37.3 126.9 EF (%) 3DE 58.5 18.8 MRI 56.1 18.9 2DE 46.0 19.1 063 Aldosterone Agonist Enhances Ventricular but Not Vascular Stiffness in an Aged Canine Model of Hypertensive Heart Disease Brian Shapiro 1 , Theophilus E. Owan 1 , Margaret M. Redfield 1 ; 1 Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN In aged canines, induction of hypertension by renal wrapping (rwHTN) is associated with hypertrophy, LV fibrosis and increased systolic and diastolic LVand effective arterial stiffness (elastance). Deoxycorticosterone acetate (DOCA), an aldosterone analog, promotes LV fibrosis. We hypothesized that administration of DOCA to aged dogs with rwHTN would accelerate increases in LV diastolic and systolic stiff- ness. Methods: Old dogs (n 5 22, age 8 to 12 years) underwent renal wrapping and were followed for 8 weeks. Dogs were randomized to receive DOCA (1 mg/kg IM) during weeks 6e8 (rwHTNþDOCA, n 5 11) or not (rwHTN). Dogs were anesthe- tized and instrumented for pressure volume analysis during preload reduction to char- acterize end systolic (ESPVR; ESP 5 slope * ESVþV 0 ) and end diastolic (EDPVR; EDP 5 ae b*EDV ) pressure volume relationships and effective arterial elastance (Ea). Aortic pressure, dimension and flow were also measured to characterize the aor- tic elastic modulus (EM), a measure of aortic stiffness. Results: See table. The rwHTNþDOCA dogs had increased diastolic (higher EDPVR-b and smaller EDV at a common EDP of 30 mmHg (EDV 30 )) and systolic (higher ESPVR-slope (Ees)) stiffness. Contractility was unchanged (similar preload recruitable stroke work (PRSW)). Aortic stiffness was not increased (similar aortic EM). While arterial pressures were higher in conscious rwHTNþDOCA vs rwHTN dogs (p 5 0.01), after the preload reducing effects of anesthesia and instrumentation, rwHTNþDOCA dogs had lower LV systolic pressure (p 5 0.02), a finding consistent with their higher Ees. Increased Ees without increases in vascular stiffness led to impaired ventricular vas- cular coupling (decrease in Ea/Ees ratio) in rwHTNþDOCA dogs. The LV mass/ EDV ratio was greater in rwHTNþDOCA dogs. Conclusions: DOCA administration in hypertensive heart disease worsens LV systolic and diastolic stiffening without changing arterial stiffness. We speculate this is due to increased LV fibrosis. rwHTN rwHTNþDOCA p EM (dyne/cm 2 ) 0.71 6 0.05 0.69 6 0.14 0.91 EDPVR-b 0.053 6 0.009 0.105 6 0.018 0.02 EDPVR-a 1.31 6 0.42 0.70 6 0.32 0.27 EDV at EDP 5 30 (ml) 79 6 6 56 6 5 0.007 ESPVR-slope (Ees, mmHg/ml) 4.83 6 0.81 13.19 6 5.93 0.047 PRSW (erg*cm -3* 10 3 ) 79 6 4 79 6 6 0.97 Ea/Ees 1.81 6 0.35 0.76 6 0.15 0.01 LV mass/BW (g/Kg) 5.6 6 0.3 5.8 6 0.3 0.66 LV mass/EDV (g/ml) 2.9 6 0.3 4.2 6 0.6 0.048 064 ECG-Gated Multislice Computed Tomography To Assess Right Ventricular Function Marc A. Simon 1 , Christopher Deible 2 , Navin Rajagopalan 1 , Shobhit Madan 2 , Orly Goitein 2 , Angel Lopez-Candales 1 , Michael Mathier 1 , Joan Lacomis 2 ; 1 Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA; 2 Department of Radiology, University of Pittsburgh, Pittsburgh, PA Background: Assessment of right ventricular (RV) function is essential for manage- ment of heart failure (HF) and pulmonary hypertension (PH). Standard methods to evaluate RV function are limited to 2D echocardiography (echo) and right heart cath- eterization (RHC). Objective: To develop an ECG-gated CT protocol to provide 3D anatomical and functional data of the RV. Methods: A total of 17 pts (age 51 6 11, 7 males, mean PA pressure range 17e79 mmHg) underwent RHC, 2D echo with RV fractional area change (FAC) calculated from the apical 4-chamber view and ECG- gated multislice CTof the chest with IV contrast timed to opacify the RV. RV CT protocol obtained on GE Lightspeed 16 (n 5 13) or VCT 64 slice (n 5 4) scanners: initial test bolus of IV contrast to time for peak pulmonary artery (PA), pulmonary vein (PV) and ascending aortic (AA) enhancement; then, after injection of scanning bolus, ECG-gated, single breath hold, helical acquisition with 0.63 mm (64-slice) or 1.25 mm (16-slice) collimation through the chest. Scans were reconstructed in 20 phases (5e95% R-R q 5%). RV EDV, ESV, EF were obtained utilizing GE ADW 5.2 software after manual endocardial tracings. Results: RV CT protocol was suc- cessful in all pts, regardless of heart rate. RV EF calculated by CT correlated well with RV FAC calculated by 2D echo (figure,R 2 5 0.589, p 5 0.0003) and with car- diac index from RHC (R 2 5 0.612, p 5 0.0002). RV FAC by echo was O0.35 in 7 pts and !0.35 in 10 (mean 0.51 6 0.12 vs. 0.20 6 0.05, p ! 0.0005). Transit time of IV contrast to PA, to PV, and from PAto PV was significantly shorter in RVFAC O0.35 pts (13 6 2 sec vs. 17 6 3 sec, p 5 0.02; 17 6 3 sec vs. 26 6 3 sec, p ! 0.0005; 9 6 3 sec vs. 4 6 1 sec, p 5 0.001). Conclusions: ECG-gated multislice CT is The 10 th Annual Scientific Meeting HFSA S19

Aldosterone Agonist Enhances Ventricular but Not Vascular Stiffness in an Aged Canine Model of Hypertensive Heart Disease

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061Borderzone Myocardial Dyssynchrony Following Anteroapical MyocardialInfarction: A Real-Time Three-Dimensional Echocardiographic StudyLiam P. Ryan1, Benjamin M. Jackson1, Landi M. Parish1, Martin G. St. John Sutton2,Theodore Plappert2, Joseph H. Gorman III1, Robert C. Gorman1; 1HarrisonDepartment of Surgical Research, University of Pennsylvania School of Medicine,Philadelphia, PA; 2Department of Medicine, Division of Cardiology, University ofPennsylvania School of Medicine, Philadelphia, PA

Introduction: The hypocontractile but normally perfused borderzone myocardium(BZM) has been implicated in the pathogenesis of congestive heart failure followingmyocardial infarction (MI). Hypothesis: We used real-time three-dimensional echo-cardiography (rt-3DE) to test the hypothesis that BZM dysfunction is associatedwith delayed systolic activation of this region. Methods: Rt-3DE was performed in9 Dorsett hybrid sheep at baseline, immediately following a moderately sized anteroap-ical myocardial infarction (MI) and at 10 weeks following MI. Manual endocardialtracing was performed using Tomtec software. The BZM was defined by the 6 segmentsadjacent to the dyskinetic infarcted myocardium. BZM end systolic delay (ESD) wasdefined as the average delay with respect to the first segment to reach its minimum seg-mental volume. BZM systolic dyssynchrony index (SDI) was defined as the standarddeviation of ESDs for a given data set. In order to normalize the data for different heartrates, phase shift was expressed as a percentage of the cardiac cycle duration. Results:QRS widening did not occur in any experimental subject. A statistically significant(p ! 0.05) decrement in EF occurred between all measured time points. A statisticallysignificant (p ! 0.001) increase in ESD occurred both immediately following infarc-tion and at 10 weeks. A statistically significant (p ! 0.05) increase in SDI occurred at10 weeks when compared to both baseline and post-infarction values. The magnitude ofchange was greatest during the interval between infarction and 10 weeks follow-up inall cases. Conclusions: Longitudinal increases in BZM hypokinesis and dyssynchronywere observed in the absence of QRS widening using rt-3DE during a 10 week intervalin an ovine model of apical myocardial infarction. Rt-3DE may allow for echocardio-graphically guided BZM resynchronization in the future.

062Real-Time Three-Dimensional Echocardiography To Quantify Remodeling afterInfarction in Ovine Heart Failure ModelsLiam P. Ryan1, Hirotsugu Hamamoto1, Benjamin M. Jackson1, Landi M. Parish1,Martin G. St. John Sutton2, Theodore Plappert2, Joseph H. Gorman III1, Robert C.Gorman1; 1Harrison Department of Surgical Research, University of PennsylvaniaSchool of Medicine, Philadelphia, PA; 2Department of Medicine, Division ofCardiology, University of Pennsylvania School of Medicine, Philadelphia, PA

Introduction: Magnetic resonance imaging (MRI) has been the gold-standard for theassessment of ventricular size and geometry. However, MRI is expensive, time andlabor intensive, not universally available and often requires transport of human andanimal subjects to remote areas of the hospital. In addition, MRI currently doesnot allow assessment of valvular structure and function. Hypothesis: Real-timethree-dimensional echocardiography (rt-3DE) overcomes many of the limitations as-sociated with MRI. While rt-3DE volumetric analysis has been validated in humansubjects, cardiac geometry differs in many experimental animal species raising con-cern regarding the adequacy of volume averaging algorithms incorporated into boththe two-dimensional echocardiography (2DE) and rt-3DE analysis software.Methods: Rt-3DE, 2DE and MRI were performed in 9 Dorsett hybrid sheep at base-line and at 10 weeks following apical MI. End-diastolic volume (EDV), end-systolicvolume (ESV) and ejection fraction (EF) were calculated independently at each timepoint by means of rt-3DE, 2DE and MRI. Results: Statistically significant (p ! 0.01)increases in both EDV and ESV and decreased in EF occurred as determined by allthree modalities. Correlation between EDV, ESV and EF as determined by rt-3DEand MRI was excellent with R equal to 0.99. 0.99 and 0.98 respectively. Correlationbetween EDV, ESV and EF as determined by means of 2DE and MRI was also ac-ceptable with R equal to 0.83, 0.87 and 0.84 respectively. Conclusions: Left ventric-ular volumes as determined by rt-3DE are nearly identical to those determined byMRI. Those determined by 2DE are also very similar. Both echocardiographic tech-niques are accurate in a well-established ovine model of CHF which has become anincreasingly prominent platform for heart failure research.

Left Ventricular Volumes and EF Before and After Apical MI

Basline 10 Weeks Post-MI

EDV (mm3)3DE 53.0 149.6MRI 55.3 149.02DE 69.0 156.1

ESV (mm3)3DE 22.1 123.1MRI 24.3 122.02DE 37.3 126.9

EF (%)3DE 58.5 18.8MRI 56.1 18.92DE 46.0 19.1

063Aldosterone Agonist Enhances Ventricular but Not Vascular Stiffness in an AgedCanine Model of Hypertensive Heart DiseaseBrian Shapiro1, Theophilus E. Owan1, Margaret M. Redfield1; 1Cardiorenal ResearchLaboratory, Mayo Clinic and Foundation, Rochester, MN

In aged canines, induction of hypertension by renal wrapping (rwHTN) is associatedwith hypertrophy, LV fibrosis and increased systolic and diastolic LV and effectivearterial stiffness (elastance). Deoxycorticosterone acetate (DOCA), an aldosteroneanalog, promotes LV fibrosis. We hypothesized that administration of DOCA toaged dogs with rwHTN would accelerate increases in LV diastolic and systolic stiff-ness. Methods: Old dogs (n 5 22, age 8 to 12 years) underwent renal wrapping andwere followed for 8 weeks. Dogs were randomized to receive DOCA (1 mg/kg IM)during weeks 6e8 (rwHTNþDOCA, n 5 11) or not (rwHTN). Dogs were anesthe-tized and instrumented for pressure volume analysis during preload reduction to char-acterize end systolic (ESPVR; ESP 5 slope*ESVþV0) and end diastolic (EDPVR;EDP 5 aeb*EDV) pressure volume relationships and effective arterial elastance(Ea). Aortic pressure, dimension and flow were also measured to characterize the aor-tic elastic modulus (EM), a measure of aortic stiffness. Results: See table. TherwHTNþDOCA dogs had increased diastolic (higher EDPVR-b and smaller EDVat a common EDP of 30 mmHg (EDV30)) and systolic (higher ESPVR-slope(Ees)) stiffness. Contractility was unchanged (similar preload recruitable strokework (PRSW)). Aortic stiffness was not increased (similar aortic EM). While arterialpressures were higher in conscious rwHTNþDOCA vs rwHTN dogs (p 5 0.01), afterthe preload reducing effects of anesthesia and instrumentation, rwHTNþDOCA dogshad lower LV systolic pressure (p 5 0.02), a finding consistent with their higher Ees.Increased Ees without increases in vascular stiffness led to impaired ventricular vas-cular coupling (decrease in Ea/Ees ratio) in rwHTNþDOCA dogs. The LV mass/EDV ratio was greater in rwHTNþDOCA dogs. Conclusions: DOCA administrationin hypertensive heart disease worsens LV systolic and diastolic stiffening withoutchanging arterial stiffness. We speculate this is due to increased LV fibrosis.

rwHTN rwHTNþDOCA p

EM (dyne/cm2) 0.71 6 0.05 0.69 6 0.14 0.91EDPVR-b 0.053 6 0.009 0.105 6 0.018 0.02EDPVR-a 1.31 6 0.42 0.70 6 0.32 0.27EDV at EDP 5 30 (ml) 79 6 6 56 6 5 0.007ESPVR-slope (Ees, mmHg/ml) 4.83 6 0.81 13.19 6 5.93 0.047PRSW (erg*cm-3*103) 79 6 4 79 6 6 0.97Ea/Ees 1.81 6 0.35 0.76 6 0.15 0.01LV mass/BW (g/Kg) 5.6 6 0.3 5.8 6 0.3 0.66LV mass/EDV (g/ml) 2.9 6 0.3 4.2 6 0.6 0.048

064ECG-Gated Multislice Computed Tomography To Assess Right VentricularFunctionMarc A. Simon1, Christopher Deible2, Navin Rajagopalan1, Shobhit Madan2,Orly Goitein2, Angel Lopez-Candales1, Michael Mathier1, Joan Lacomis2;1Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA; 2Department ofRadiology, University of Pittsburgh, Pittsburgh, PA

Background: Assessment of right ventricular (RV) function is essential for manage-ment of heart failure (HF) and pulmonary hypertension (PH). Standard methods toevaluate RV function are limited to 2D echocardiography (echo) and right heart cath-eterization (RHC). Objective: To develop an ECG-gated CT protocol to provide 3Danatomical and functional data of the RV. Methods: A total of 17 pts (age 51 6 11, 7males, mean PA pressure range 17e79 mmHg) underwent RHC, 2D echo with RVfractional area change (FAC) calculated from the apical 4-chamber view and ECG-gated multislice CT of the chest with IV contrast timed to opacify the RV. RV CTprotocol obtained on GE Lightspeed 16 (n 5 13) or VCT 64 slice (n 5 4) scanners:initial test bolus of IV contrast to time for peak pulmonary artery (PA), pulmonaryvein (PV) and ascending aortic (AA) enhancement; then, after injection of scanningbolus, ECG-gated, single breath hold, helical acquisition with 0.63 mm (64-slice) or1.25 mm (16-slice) collimation through the chest. Scans were reconstructed in 20phases (5e95% R-R q 5%). RV EDV, ESV, EF were obtained utilizing GE ADW5.2 software after manual endocardial tracings. Results: RV CT protocol was suc-cessful in all pts, regardless of heart rate. RV EF calculated by CT correlated wellwith RV FAC calculated by 2D echo (figure, R2 5 0.589, p 5 0.0003) and with car-diac index from RHC (R2 5 0.612, p 5 0.0002). RV FAC by echo was O0.35 in 7 ptsand !0.35 in 10 (mean 0.51 6 0.12 vs. 0.20 6 0.05, p ! 0.0005). Transit time of IVcontrast to PA, to PV, and from PA to PV was significantly shorter in RV FAC O0.35pts (13 6 2 sec vs. 17 6 3 sec, p 5 0.02; 17 6 3 sec vs. 26 6 3 sec, p ! 0.0005; 9 6

3 sec vs. 4 6 1 sec, p 5 0.001). Conclusions: ECG-gated multislice CT is

The 10th Annual Scientific Meeting � HFSA S19