Speckle tracking echocardiography in the assessment of mouse models of cardiac dysfunction.

Two-dimensional (2-D) speckle tracking echocardiography (STE) accurately quantifies circumferential strain (S(circ)) and radial strain (S(rad)) in humans and in large and small animals. This study was performed to assess sensitivity of S(circ) and S(rad) to left ventricular (LV) dysfunction in mouse models. We performed 2-D and M-mode echocardiography 1) in 6 mice during superficial and profound isoflurane anesthesia, 2) serially in 12 mice to monitor the development of heart failure induced by transverse aortic constriction (TAC) and in 8 corresponding control mice, and 3) in 26 mice with varying degrees of TAC-induced heart failure and 12 corresponding control mice immediately before euthanasia. Fractional shortening (FS) and LV mass were measured from standard M-mode tracings, whereas S(circ) and S(rad) were derived by STE. Percent fibrosis and myocyte diameters were assessed from whole heart cross-sectional specimens stained by Masson trichrome. Profound isoflurane anesthesia decreased S(circ) (P = 0.027) but not S(rad) (P > 0.05). Mice subjected to TAC showed an immediate and sustained decrease in FS (P = 0.035), S(circ) (P = 0.016), and S(rad) (P = 0.012). S(circ) showed better correlation with FS (r = 0.56 and P < 0.0001) and LV mass (r = 0.42 and P = 0.0003) than S(rad) (r = 0.54 and P < 0.0001 for FS and r = 0.37 and P = 0.014 for LV mass, respectively). Percent fibrosis correlated better with S(circ) (r = 0.46 and P = 0.004) than with S(rad) (r = -0.32 and P = 0.05), whereas myocyte diameter showed similar correlation with both strains (r = 0.45 and r = -0.44, respectively, and P = 0.006 for both). STE correctly identifies LV dysfunction and histological changes in mice and can be used for the serial assessment of cardiac remodeling in murine models.

Speckle-tracking echocardiography correctly identifies segmental left ventricular dysfunction induced by scarring in a rat model of myocardial infarction.

Speckle-tracking echocardiography (STE) uses a two-dimensional echocardiographic image to estimate two orthogonal strain components. The aim of this study was to assess sensitivity of circumferential (S(circ)) and radial (S(rad)) strains to infarct-induced left ventricular (LV) remodeling and scarring of the LV in a rat. To assess the relationship among S(circ), S(rad), and scar size, two-dimensional echocardiographic LV short-axis images (12 MHz transducer, Vivid 7 echo machine) were collected in 34 Lewis rats 4 to 10 wk after ligation of the left anterior descending artery. Percent segmental fibrosis was assessed from histological LV cross sections stained by Masson trichrome. Ten normal rats served as echocardiographic controls. S(circ) and S(rad) were assessed by STE. Histological data showed consistent scarring of anterior and lateral segments with variable extension to posterior and inferior segments. Both S(circ) and S(rad) significantly decreased after myocardial infarction (P<0.0001 for both). As anticipated, S(circ) and S(rad) were lowest in the infarcted segments. Multiple linear regression showed that segmental S(circ) were similarly dependent on segmental fibrosis and end-systolic diameter (P<0.0001 for both), whereas segmental S(rad) measurements were more dependent on end-systolic diameter (P<0.0001) than on percent fibrosis (P<0.002). STE correctly identifies segmental LV dysfunction induced by scarring that follows myocardial infarction in rats.

Scaling of diastolic intraventricular pressure gradients is related to filling time duration.

In early diastole, pressure is lower in the apex than in the base of the left ventricle (LV). This early intraventricular pressure difference (IVPD) facilitates LV filling. We assessed how LV diastolic IVPD and intraventricular pressure gradient (IVPG), defined as IVPD divided by length, scale to the heart size and other physiological variables. We studied 10 mice, 10 rats, 5 rabbits, 12 dogs, and 21 humans by echocardiography. Color Doppler M-mode data were postprocessed to reconstruct IVPD and IVPG. Normalized LV filling time was calculated by dividing filling time by RR interval. The relationship between IVPD, IVPG, normalized LV filling time, and LV end-diastolic volume (or mass) as fit to the general scaling equation Y = kM beta, where M is LV heart size parameter, Y is a dependent variable, k is a constant, and beta is the power of the scaling exponent. LV mass varied from 0.049 to 194 g, whereas end-diastolic volume varied from 0.011 to 149 ml. The beta values relating normalized LV filling time with LV mass and end-diastolic volume were 0.091 (SD 0.011) and 0.083 (SD 0.009), respectively (P < 0.0001 vs. 0 for both). The beta values relating IVPD with LV mass and end-diastolic volume were similarly significant at 0.271 (SD 0.039) and 0.243 (SD 0.0361), respectively (P < 0.0001 vs. 0 for both). Finally, beta values relating IVPG with LV mass and end-diastolic volume were -0.118 (SD 0.013) and -0.104 (SD 0.011), respectively (P < 0.0001 vs. 0 for both). As a result, there was an inverse relationship between IVPG and normalized LV filling time (r = -0.65, P < 0.001). We conclude that IVPD decrease, while IVPG increase with decreasing animal size. High IVPG in small mammals may be an adaptive mechanism to short filling times.

Evaluation of left ventricular outflow tract area after septal reduction in obstructive hypertrophic cardiomyopathy: a real-time 3-dimensional echocardiographic study.

BACKGROUND: The comparative impact of percutaneous alcohol septal reduction (ASR) and surgical myectomy on the left ventricular outflow tract (LVOT) area in patients with obstructive hypertrophic cardiomyopathy (HC) is not well defined. Real-time 3-dimensional echocardiography (RT3DE) provides accurate information about the LVOT geometry and shape. We aimed to analyze the change in LVOT area after septal reduction interventions in patients with obstructive HC using RT3DE. METHODS: Thirty-one HC patients (mean age 53 +/- 17 years) undergoing ASR (n = 14) or myectomy (n = 17) were studied at baseline and during follow-up with RT3DE. LVOT area was measured after observing the LVOT in the 3D space as the smallest area during midsystole. LVOT pressure gradients were determined by conventional continuous wave Doppler. RESULTS: Overall, LVOT area increased from 0.86 +/- 0.20 to 2.50 +/- 0.88 cm2 (P < .01), and the resting LVOT pressure gradient decreased from 64 +/- 41 to 16 +/- 10 mm Hg (P < .01) after a median follow-up of 3 months after intervention (range 1-24 months). A similar significant decrease in LVOT pressure gradients was seen in myectomy and ASR groups (from 62 +/- 39 to 12 +/- 5 mm Hg and from 67 +/- 43 to 21 +/- 14 mm Hg, respectively, P < .01 in between each group, and P = NS between both groups). However, the increase in LVOT area was greater in myectomy than in ASR group (from 0.81 +/- 0.22 to 2.90 +/- 0.64 cm2 and 0.93 +/- to 0.16 to 2.02 +/- 0.92 cm2, respectively, P < .01 between both groups). CONCLUSION: RT3DE demonstrated an effective increase in LVOT area after both ASR and myectomy. This technique may be useful for assessing the results of septal reduction in patients with obstructive HC.

Differences in left ventricular long-axis function from mice to humans follow allometric scaling to ventricular size.

While the heart size maintains a constant proportion to body size, heart function parameters, such as heart rate and cardiac output, show a more complex scaling pattern. How these phenomena affect the long-axis left ventricular (LV) function is unknown. We studied 10 mice, 15 rats, 6 rabbits, 8 mongrel dogs and 38 human volunteers. Doppler tissue echocardiography data were postprocessed to reconstruct mitral annulus (MA) peak systolic velocity and displacement. The relationship between MA peak velocity, MA displacement and LV ejection time, and LV end-diastolic volume (and mass) were fit to an allometric (power-law) equation Y=kMbeta. LV mass varied from 0.062 to 255 g, while end-diastolic volume varied from 0.014 to 205 ml. beta values of the relation between LV ejection time and LV end-diastolic volume and mass were 0.247+/-0.017 and 0.267+/-0.018, respectively. beta values of the relationship between MA displacement and LV end-diastolic volume and mass were 0.358+/-0.047 and 0.390+/-0.051 (P<0.023 versus beta of LV ejection time). beta values of the relationship between MA peak systolic velocity and LV end-diastolic volume and mass were 0.096+/-0.012 and 0.100+/-0.013, respectively (P<0.0001 versus 0). Finally, beta values of the relationship between the long-to-short axis displacement ratio and LV end-diastolic volume and mass were 0.077+/-0.017 and 0.086+/-0.019 (P<0.0001 versus 0). We conclude that MA velocity, displacement, and long-to-short axis displacement ratio scale allometrically to heart size. This reduces the relative long-axis contribution to heart function in small mammals.

Determinant of left atrial dilation in patients with hypertrophic cardiomyopathy: a real-time 3-dimensional echocardiographic study.

To identify the determinants of left atrial (LA) dilation for patients with hypertrophic obstructive cardiomyopathy (HOCM), first we validated LA volume determination by real-time 3-dimensional echocardiography using magnetic resonance imaging in patients. Subsequently, real-time 3-dimensional echocardiography and 2-dimensional Doppler echocardiography were performed in 60 patients with HOCM and in 17 age-matched control subjects. LA volumes and left ventricular (LV) filling pressures were higher for patients with HOCM than in control subjects. By stepwise multilinear regression analysis, LV end-diastolic pressure, resting LV outflow tract pressure gradient, and LV wall thickness were significant determinants of LA dilation. However, tau, -dP/dt, LV stiffness, provokable pressure gradient, and mitral regurgitation did not have any independent relationship with LA volumes. Therefore, it is concluded that LA volume can be accurately determined by real-time 3-dimensional echocardiography; and LA dilation in patients with HOCM is related to LV filling pressure, LV outflow tract pressure gradient, and LV wall thickness.

Comparison of left ventricular diastolic function in obstructive hypertrophic cardiomyopathy in patients undergoing percutaneous septal alcohol ablation versus surgical myotomy/myectomy.

Both percutaneous transcoronary alcohol septal reduction (ASR) and surgical myectomy are effective treatments to relieve left ventricular (LV) outflow tract obstruction in obstructive hypertrophic cardiomyopathy (HC). LV diastolic function was assessed by echocardiography in 57 patients with obstructive HC at baseline and 5 +/- 4 months after ASR (n = 37) or surgical myectomy (n = 20). LV outflow tract pressure gradient decreased from 65 +/- 40 to 23 +/- 21 mm Hg (p <0.01) after treatment. The ratio of the early-to-late peak diastolic LV inflow velocities, and the ratio of the early peak diastolic LV inflow velocity to the lateral mitral annulus early diastolic velocity determined by tissue Doppler imaging significantly decreased after the procedures (1.6 +/- 1.7 vs 1.0 +/- 0.7 and 15 +/- 8 vs 11 +/- 5, respectively), whereas LV inflow propagation velocity significantly increased (60 +/- 24 vs 71 +/- 36 cm/s). Left atrial size decreased from 29 +/- 7 to 25 +/- 6 cm(2) (p <0.05). Patients had a significant improvement in New York Heart Association functional class and in exercise performance. When comparing ASR with myectomy, no difference was found in the degree of change in any parameter of diastolic function. Thus, diastolic function indexes obtained by echocardiography changed after septal reduction interventions in patients with obstructive HC; this change was similar to that after surgical myectomy and ASR.