Impact of myocardial structure and function postinfarction on diastolic strain measurements: implications for assessment of myocardial viability.

We sought to assess the role of regional diastolic function by Doppler echocardiography in predicting myocardial viability. Sixteen dogs underwent left anterior descending coronary artery (n = 8) or circumflex (n = 8) occlusion. All animals were imaged at baseline and 1-8 wk postinfarction (post-MI). In 10 dogs, invasive hemodynamic monitoring with a conductance catheter placed in the left ventricle (LV) was performed at the above time points. Dobutamine was infused at 1-8 wk post-MI to determine LV contractile reserve. Histomorphological analysis was performed to determine the presence of viable myocardium and changes in interstitial matrix. Post-MI, diastolic strain rate measurements (in radial and longitudinal planes) decreased significantly in the distribution of the diseased artery (P < 0.01) and on multiple regression analysis were determined by time constant of LV relaxation, end-diastolic pressure, regional stiffness, and the ratio of cellular infiltration to collagen deposition in the interstitial matrix. Among several indexes, diastolic strain rate during dobutamine infusion readily identified segments with >20% transmural infarction and related best to the extent of interstitial fibrosis (r = -0.86, P < 0.01). In an animal model of healing canine infarcts, diastolic strain rate by Doppler echocardiography appears to be a promising novel index of myocardial viability.

Evolution of expression of cardiac phenotypes over a 4-year period in the beta-myosin heavy chain-Q403 transgenic rabbit model of human hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young, is characterized by a diverse array of cardiac phenotypes evolving over several decades. We have developed transgenic rabbits that fully recapitulate the phenotype of human HCM and provide for the opportunity to delineate the sequence of evolution of cardiac phenotypes, and thus, the pathogenesis of HCM. We determined evolution of biochemical, molecular, histological, structural and functional phenotypes at 4 age-periods in 47 beta-myosin heavy chain-glutamine (MyHC-Q)-403 transgenic rabbits. Ca(+2) sensitivity of myofibrillar ATPase activity was reduced very early and in the absence of other discernible phenotypes. Myocyte disarray also occurred early, prior to, and independent of hypertrophy and fibrosis. The latter phenotypes evolved predominantly during puberty in conjunction with activation of stress-related signaling kinases. Myocardial contraction and relaxation velocities were decreased early despite normal global cardiac function and in the absence of histological phenotype. Global cardiac function declined with aging, while left atrial size was increased along with Doppler indices of left ventricular filling pressure. Thus, Ca(+2) sensitivity of myofibrillar ATPase activity is a primary phenotype expressed early and independent of the ensuing phenotypes. Pathogenesis of myocyte disarray, which exhibits age-independent penetrance, differs from those of hypertrophy and fibrosis, which show age-dependent expression. Myocardial dysfunction is an early marker that predicts subsequent development of hypertrophy. These findings in an animal model that recapitulates the phenotype of human HCM, implicate involvement of multiple independent mechanisms in the pathogenesis of cardiac phenotypes in HCM.

Time interval between onset of mitral inflow and onset of early diastolic velocity by tissue Doppler: a novel index of left ventricular relaxation: experimental studies and clinical application.

OBJECTIVES: The goal of this study was to examine the diagnostic utility of the time to onset of early (Ea) diastolic velocity of the mitral annulus by tissue Doppler (TD) in comparison with the time to onset of mitral inflow (T(Ea-E)) for the assessment of left ventricular (LV) relaxation. BACKGROUND: Tissue Doppler imaging of the mitral annulus provides useful information about myocardial function. So far, studies have focused on the measurement of peak Ea, but have not evaluated the diagnostic utility of the time to onset of Ea. METHODS: Simultaneous left heart catheterization and Doppler echocardiography (DE) were performed in 10 dogs. Left atrial pressures and LV volumes and pressures were measured before and after constriction of the circumflex (cx) coronary artery. The delay in Ea was next examined in 60 consecutive patients, undergoing simultaneous right heart catheterization and DE. Furthermore, (T(Ea-E)) was used to predict filling pressures in a prospective group of 33 patients. RESULTS: In canine studies, significant prolongation in the time interval (T(Ea-E)) was noted after cx constriction, which had a significant relation with tau (tau) (r = 0.93, p < 0.01). In human studies, Ea was significantly delayed in patients with impaired relaxation and pseudonormal LV filling in comparison with age-matched controls. In the prospective group, pulmonary capillary wedge pressure (PCWP) derived as: PCWP(Doppler) = LV(end-systolic pressure) x e(-IVRT/(T(Ea-E))), where IVRT is isovolumetric relaxation time; PCWP(Doppler) related well to PCWP(catheter) (r = 0.84, p < 0.001). CONCLUSIONS: T(Ea-E) is a useful novel index of LV relaxation. It can be used to identify patients with diastolic dysfunction and predict PCWP.

Diagnostic accuracy and cost-effectiveness of contrast echocardiography on evaluation of cardiac function in technically very difficult patients in the intensive care unit.

Echocardiographic assessment of cardiac function can be quite difficult in the intensive care unit and may require transesophageal echocardiography (TEE). We therefore compared harmonic imaging alone or in combination with contrast to TEE in 32 consecutive patients in the intensive care units who were considered technically very difficult (> or =50% of the 16 segments not visualized from any view). Excellent or adequate endocardial visualization was achieved in 13% of segments with fundamental imaging, 34% with harmonic imaging, and 87% with contrast (p < 0.0001); the latter success rate was similar to TEE (87% vs 90%; p = NS). When TEE was used as the standard, agreement in exact interpretation of wall motion increased from 48% for fundamental imaging to 58% with harmonic imaging, and reached 70% with contrast (p <0.0001). Contrast had the best sensitivity (89%) for detecting wall motion abnormalities. Estimation of ejection fraction was possible in 31% with fundamental imaging, 50% with harmonic imaging, and in 97% with contrast. Ejection fraction quantitated by contrast enhancement correlated best with TEE (r = 0.91). Cost-effectiveness analysis revealed that contrast echo was cost-effective compared with TEE in determining regional and global ventricular function, with a cost saving of 3% and 17%, respectively. Thus, contrast echocardiography provides an accurate, safe, and cost-effective alternative to TEE for evaluating ventricular function in technically very difficult studies.