L eft ventricular remodeling is the process by which ventricular size, shape, and function are regulated by mechanical, neurohormonal, and genetic factors. 1,2 Remodeling may be physiological and adaptive during normal growth or pathological due to myocardial infarction, cardiomyopathy, hypertension, or valvular heart disease ( Figure 1). This article will review postinfarction remodeling, pathophysiological mechanisms, and therapeutic intervention. Pathophysiology Postinfarction Left Ventricular RemodelingThe acute loss of myocardium results in an abrupt increase in loading conditions that induces a unique pattern of remodeling involving the infarcted border zone and remote noninfarcted myocardium. Myocyte necrosis and the resultant increase in load trigger a cascade of biochemical intracellular signaling processes that initiates and subsequently modulates reparative changes, which include dilatation, hypertrophy, and the formation of a discrete collagen scar. Ventricular remodeling may continue for weeks or months until the distending forces are counterbalanced by the tensile strength of the collagen scar. This balance is determined by the size, location, and transmurality of the infarct, the extent of myocardial stunning, the patency of the infarct-related artery, and local tropic factors. 1,3 The myocardium consists of 3 integrated components: myocytes, extracellular matrix, and the capillary microcirculation that services the contractile unit assembly. Consideration of all 3 components provides important insights into the remodeling process and a rationale for future therapeutic strategies. The cardiomyocyte is terminally differentiated and develops tension by shortening. The extracellular matrix provides a stress-tolerant, viscoelastic scaffold consisting of type I and type III collagen that couples myocytes and maintains the spatial relations between the myofilaments and their capillary microcirculation. 4,5 The collagen framework couples adjacent myocytes by intercellular struts that align myofilaments to optimize force development, distribute force evenly to the ventricular walls, and prevent sarcomeric deformation. 5 Myocardial infarction results in the migration of macrophages, monocytes, and neutrophils into the infarct zone; this initiates intracellular signaling and neurohormonal activation, which localizes the inflammatory response. Changes in circulatory hemodynamics are determined primarily by the magnitude of myocyte loss, the stimulation of the sympathetic nervous system and renin-angiotensin-aldosterone system, and the release of natriuretic peptides.Postinfarction remodeling has been arbitrarily divided into an early phase (within 72 hours) and a late phase (beyond 72 hours). The early phase involves expansion of the infarct zone, 5 which may result in early ventricular rupture or aneurysm formation. Late remodeling involves the left ventricle globally and is associated with time-dependent dilatation, the distortion of ventricular shape, and mural hypertrophy. The failure to normalize increa...

for the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) Study GroupBackground-Cardiac resynchronization therapy (CRT) has recently emerged as an effective treatment for patients with moderate to severe systolic heart failure and ventricular dyssynchrony. The purpose of the present study was to determine whether improvements in left ventricular (LV) size and function were associated with CRT. Methods and Results-Doppler echocardiograms were obtained at baseline and at 3 and 6 months after therapy in 323 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Of these, 172 patients were randomized to CRT on and 151 patients to CRT off. Measurements were made of LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E-wave) and late (A-wave) diastolic filling, and the myocardial performance index. At 6 months, CRT was associated with reduced end-diastolic and end-systolic volumes (both PϽ0.001), reduced LV mass (PϽ0.01), increased ejection fraction (PϽ0.001), reduced MR (PϽ0.001), and improved myocardial performance index (PϽ0.001) compared with control. ␤-Blocker treatment status did not influence the effect of CRT. Improvements with CRT were greater in patients with a nonischemic versus ischemic cause of heart failure. Conclusions-CRT in patients with moderate-to-severe heart failure who were treated with optimal medical therapy is associated with reverse LV remodeling, improved systolic and diastolic function, and decreased MR. LV remodeling likely contributes to the symptomatic benefits of CRT and may herald improved longer-term survival. (Circulation.

Background-Leaflet curvature is known to reduce mechanical stress. There are 2 major components that contribute to this curvature. Leaflet billowing introduces the most obvious form of leaflet curvature. The saddle shape of the mitral annulus imparts a more subtle form of leaflet curvature. This study explores the relative contributions of leaflet billowing and annular shape on leaflet curvature and stress distribution. Methods and Results-Both numerical simulation and experimental data were used. The simulation consisted of an array of numerically generated mitral annular phantoms encompassing flat to markedly saddle-shaped annular heights. Highest peak leaflet stresses occurred for the flat annulus. As saddle height increased, peak stresses decreased. The minimum peak leaflet stress occurred at an annular height to commissural width ratio of 15% to 25%. The second phase involved data acquisition for the annulus from 3 humans by 3D echocardiography, 3 sheep by sonomicrometry array localization, 2 sheep by 3D echocardiography, and 2 baboons by 3D echocardiography. All 3 species imaged had annuli of a similar shape, with an annular height to commissural width ratio of 10% to 15%. Conclusion-The saddle shape of the mitral annulus confers a mechanical advantage to the leaflets by adding curvature.This may be valuable when leaflet curvature becomes reduced due to diminished leaflet billowing caused by annular dilatation. The fact that the saddle shape is conserved across mammalian species provides indirect evidence of the advantages it confers. This analysis of mitral annular contour may prove applicable in developing the next generation of mitral annular prostheses.