ASE Young Investigator’s Award FinalistsMonday, June 5, 2006 - 8:00 am – 9:30 am

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Tissue Doppler and Strain Echocardiography in Arrhythmogenic Right Ventricular Dysplasia

Kalpana R Prakasa, Jianwen Wang, Crystal Tichnell, Cynthia James, Darshan Dalal, David Bluemke, Mary Corretti, Daniel Judge, Hugh Calkins, Theodore P Abraham Johns Hopkins University School of Medicine, Baltimore, MD

Background: Arrhythmogenic Right Ventricular Dysplasia (ARVD) is a heritable cardiomyopathy characterized by fibro-fatty replacement of right ventricular (RV) myocardium leading to RV failure and sudden death. A recently reported plakophilin-2 (PKP2) mutation has emerged as the most common mutation in ARVD patients. We examined the functional implications of the PKP2 mutation in ARVD using tissue Doppler strain echocardiography (TDSE).Methods and Results: We prospectively imaged 60 subjects using conventional and TDSE. Of these, 30 had ARVD by the Task Force criteria and 30 were healthy controls. PKP2 mutation was noted in 12 ARVD and no control subjects. We determined RV peak systolic (RVS) and early diastolic tissue velocities (RVE), displacement (RVD), strain, strain rate, outflow tract diameter (RVOT) and fractional area change (FAC). Peak RVS (6.4±2.2 versus 9±1.6cm/s, p<0.0001), RVE (-6.7±2.7 versus -9.4±2cm/s, p<0.0001), RVD (13.7±5.8 versus 18.7±3.5mm, p<0.0003), peak systolic RV strain (-10%±6 vs.-28%±11, p=0.001), RV strain rate (-1s-1±0.7 vs. -2s-1±1, p=0.002) were significantly lower in ARVD compared to controls, respectively. Sensitivity and specificity was 67% and 89% for RVS, 77% and 71% for RVD, 73% and 87% for RV strain, 50% and 96% for RV strain rate, 53% and 93% for RVOT and 47% and 83% for FAC. Receiver Operating Characteristic analysis was as follows: RVS (AUC=0.83, p<0.0001), RVD (AUC=0.77, p=0.002), RV strain (AUC=0.82, p=0.004), RV strain rate (AUC=0.76, p=0.01), RVOT (AUC=0.73, p=0.01) and FAC (AUC= 0.61, p=0.26). Inter and intra observer agreement for TDE/SE parameters was high. PKP2 mutation was found in 43% of ARVD patients and the mean age was lower in PKP(+) patients. Abnormal RV function was detected in a larger number of PKP2 (-) vs. PKP2 (+) patients (43% vs. 14%, p= 0.09).Conclusion: TDE/SE is superior to conventional echocardiography in diagnosing ARVD and has potential clinical value in assessment of patients with suspected ARVD. PKP2 mutation is relatively common in the United States ARVD population and its presence appears to be associated with a milder RV dysfunction.

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Physiology of the Third Heart Sound: Novel Insights from Tissue Doppler Imaging and Invasive Left Ventricular Hemodynamics

Sanjiv J Shah, Gregory M Marcus, Ivor L Gerber, Barry H McKeown, Joshua C Vessey, Mark V Jordan, Michele Huddleston, Elyse Foster, Kanu Chatterjee, Andrew D Michaels University of California, San Francisco, San Francisco, CA

Background: The third heart sound (S3) is thought to be due to 1) abrupt deceleration of left ventricular (LV) inflow during early diastole, 2) increased LV filling pressures, and 3) decreased LV compliance. We sought to determine whether measurement of the ratio of mitral inflow velocity to diastolic velocity of the mitral annulus (E/E’) with echocardiographic tissue Doppler imaging (TDI) could confirm this proposed mechanism of the S3.Methods: Within a 4-hour period, 90 subjects underwent computerized heart sound analysis, echocardiography, left heart catheterization, and B-type natriuretic peptide (BNP) testing.Results:The mean age was 62±14 years and 32 patients (36%) had heart failure. Phonocardiography detected an S3 in 21 patients (23%). Subjects with an S3 had a higher incidence of heart failure (p<0.0001), lower mean LVEF (p=0.0006), higher LV mid- and end-diastolic pressure (p<0.0001), higher BNP (p=0.0008), higher E/E’ (p<0.0001), and increased early diastolic mitral inflow velocity deceleration rate (E height/E deceleration time; p<0.0001). The phonocardiographic confidence score of the S3 also correlated with E/E’ (r=0.46; p<0.0001) and E deceleration rate (r=0.43; p=0.0001). After controlling for age, sex, and deceleration time, E/E‘ remained independently associated with the S3 confidence score (p = 0.003).Conclusions: Phonocardiographic S3 is independently associated with an elevated E/E’ on TDI. The most important determinants of the S3 are an increased deceleration rate of early mitral inflow, elevated LV filling pressures, and abnormal relaxation of the ventricular wall as measured by TDI. Therefore, the true physiology of the S3 may be an abrupt deceleration of high-pressure mitral inflow acting in concert with decreased velocity of the mitral annulus.

BNP and Echocardiographic Characteristics by Presence of S3Characteristic No S3 (N=69) S3 (N=21) P-valueBNP - pg/mL [median (IQR)] 101 (49-256) 568 (211-1280) 0.0008Ejection fraction (%) 61.3 +/- 16.8 45.0 +/- 19.2 0.0006LV end-diastolic volume (ml) 56 +/- 28 75 +/- 34 0.02LV end-systolic volume (ml) 25 +/- 26 47 +/- 30 0.002LV mass index (g/m2) 114 +/- 38 126 +/- 36 0.30Mitral E velocity (m/s) 0.78 +/- 0.20 0.97 +/- 0.25 0.0017Mitral A velocity (m/s) 0.79 +/- 0.22 0.74 +/- 0.30 0.48Mitral E deceleration rate (m/s2) 4.1 +/- 1.7 6.8 +/- 3.1 <0.0001E’ velocity (m/s) 0.14 +/- 0.05 0.11 +/- 0.05 0.01E/E’ ratio 6.2 +/- 3.4 11.4 +/- 6.4 <0.0001

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Dynamics of Mitral Complex Geometry and Functional Mitral Regurgitation During Heart Failure Treatment: Real-Time Three-Dimensional Echocardiographic Study

Nozomi Watanabe, Yasuo Ogasawara, Yasuko Yamaura, Katsunori Yamamoto, Nozomi Wada, Noriko Okahashi, Takahiro Kawamoto, Eiji Toyota, Kiyoshi Yoshida Kawasaki Medical School, Kurashiki, Japan

Objective. We sought to investigate the contributions of dynamic changes in the mitral complex geometry, to the reduction of functional mitral regurgitation (MR) after intensive treatment for heart failure.Methods. 2D/3D echocardiography was performed in 10 patients with decompensated heart failure and functional MR before and after intensive therapy. We used novel software to analyze the 3D volumetric images. Reconstructed 3D images show leaflets and annulus configuration with papillary muscle (PM) position. We measured maximum and mean tenting length (max-Tent-L, mean-Tent-L), tenting volume (Tent-V), distances from anterior annulus to anterolateral PM (A-tethering length) and posteromedial PM (P-tethering length), distance between two PMs (intrapapillary distance).Results. MR reduced after the intensive treatment in all patients (p<0.0001). Leaflet tenting decreased significantly after the therapy (max-Tent-L, 16.8±2.5 vs. 13.3±2.0mm, p=0.0002; mean-Tent-L, 9.5±2.1 vs. 7.3±1.3mm, p=0.0013; Tent-V, 10.3±2.8 vs. 6.2±1.6ml, p=0.0002). P-tethering length shortened (46.9±5.1 vs. 38.6±4.9mm, p=0.0004). Intrapapillary distance (25.8±5.6 vs. 17.2±4.0mm, p=0.0001) decreased after treatment.Conclusions. Dynamic changes of PM position during heart failure treatment resulted in the reduction of mitral valve tenting, which caused the improvement of functional MR.

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Serial Changes in Segmental Strain Estimate Depleted Energy Reserves During Acute Ischemia

Josef Korinek, Bijoy K Khadheria, Partho P Sengupta, Anna E Boukatina, Petras Dzeja, Jianwen Wang, Eileen McMahon, Abel Romero-Corral, Andre Terzic, Marek BelohlavekMayo Clinic College of Medicine, Rochester, MN

Background: Presence of regional postsystolic shortening as opposed to dyskinesis has been suggested to differentiate viable from necrotic myocardium. Energetic mechanisms that are linked with the deformational changes seen during acute ischemia, however, remain inadequately characterized. We hypothesized that characteristic patterns of segmental deformation curves quantified by strain echocardiography would predict the serial changes in high energy phosphate metabolism seen during progressive ischemia and also estimates the energy reserves.Methods: 20 open-chest pigs were randomized into 5 groups of 4 animals each. In the first 4 groups we occluded the left anterior descending coronary artery successively for increasing time intervals (10, 30, 90 and 180 min.), while the remaining group was used for baseline measurements. Longitudinal strains (in %) were measured in control (mid posterior) and ischemic (apical anterior) regions. Myocardial biopsies were obtained at the end of each interval from control and ischemic regions for measuring the ratio of adenosine tri- and di-phosphate (ATP/ADP ratio). Dyskinesis (DK) strain, peak negative strains (PkS), and postsystolic shortening strain were measured at the same time periods. A mathematical model based on DK and PSS obtained from the first set of 20 animals was prospectively evaluated in another set of 8 animals for testing the utility of the model in predicting the ATP/ADP ratio in the ischemic myocardium.Results: The ATP/ADP ratio decreased significantly in the ischemic region (from 4.1±0.5 at baseline to 2.7±0.4 at 10 min, 1.5±0.6 at 30 min, 0.7±0.3 at 90 min, and 0.5±0.1 at 180 min; respectively, P<0.05 ). Similarly, PkS changed significantly in the ischemic region (from -11.1±1.9 to -6.9±1.2, -4.1±1.8, -1.6±1.0 and -1.4±0.7; for respective time intervals, P<0.05). The ATP/ADP ratio correlated closely with PkS (r=0.81, P<0.001), DK (r=0.73, P<0.001) and PSS (r=0.86, P<0.0001). The mathematical model (ATP/ADP ratio = -0.97+0.2*DK+0.25*PSS) accurately predicted the ATP/ADP ratio in acute persisting ischemia (3.0±0.6 vs. 2.7±0.4, 1.7±1.1 vs. 1.5±0.6, 0.8±0.7 vs. 0.7±0.3 and 0.4±0.5 vs. 0.5±0.1, respectively). Conclusions:Quantitative measurements with strain echocardiography closely reflect the serial changes in high energy phosphate metabolism seen during acute myocardial ischemia. This study provides for the first time a mathematical method for accurate noninvasive estimation of energy reserves of ischemic myocardium that may be useful for optimizing the therapeutic interventions used during acute coronary syndromes.

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