Abstract and Introduction
Abstract
The insight that decreases in left ventricular (LV) volume and mass occur secondary to the recovery of the myocardium at the cellular and molecular level has engendered a wider appreciation of the importance of LV remodelling as a mechanism for worsening heart failure. Despite these recent insights into the recognition of the importance of LV reverse remodelling in heart failure, many clinicians do not consider simple measurements of LV structure (i.e. LV volume) in their routine clinical decision-making process, preferring instead to rely on measurements of LV function [e.g. ejection fraction (EF)] when making decisions about medical and surgical treatment options. Although there are probably multiple reasons of why the use of LV volumes has not gained wider acceptance in day-to-day clinical management of heart failure patients, the most likely reason is that clinicians remain extremely comfortable using the LVEF to assess their heart failure patients. Importantly, LV volumes predict outcome more reliably than does the EF. Moreover, knowledge regarding LV volumes is extremely useful in optimizing patient selection for surgical and device therapies. Based on the foregoing arguments, we suggest that it is time to begin developing individualized clinical strategies based upon a consideration of the important role that LV remodelling plays in the pathogenesis of heart failure, and that we begin to incorporate measurements of LV volume and mass into the clinical decision-making process.
Introduction
Clinical studies have shown that medical, surgical and device therapies that reduce heart failure morbidity and mortality in dilated cardiomyopathy, also result in reversal of the characteristic anatomical features of the failing heart, namely increased left ventricular (LV) dimension and LV mass. Such structural measurements differ from reliance upon on measurements of ejection fraction (EF) in determining whether myocardial recovery has occurred. Indeed, myocardial recovery has a specific 'molecular signature' that is characterized by reversal of many of the abnormal changes in gene expression that occur in the failing heart, as well as decreased size (hypertrophy) of the failing cardiac myocyte (reviewed in Mann and Bristow). The capacity to temporarily decompress the heart by mechanical devices has allowed for evaluation of how reducing stretch has improved function, and focuses upon clarifying the roles of sarcomeric, calcium-handling and fibroblast genes signal transduction, transcriptional regulation, apoptosis, stress proteins, matrix remodelling and neurohormonal signalling in the failing human heart before and after mechanical circulatory support. A keynote factor in device support is mechanical reduction of cardiac load, but the master molecular switches orchestrating the process of 'reverse remodelling' are still unknown because variability of responses exist, despite identification of several highly involved dynamic molecular changes.
Thus, the changes in LV volume that occur secondary to myocardial recovery have a different molecular signature that distinguishes reverse remodelling from changes that occur secondary to changes in loading conditions of the heart. The insight that decreases in LV volume and mass, occur secondary to the myocardial recovery, which occurs at the cellular and molecular level has engendered a wider appreciation of the importance of LV remodelling as a mechanism for worsening heart failure. In this regard, one of the first observations regarding the pathophysiological significance of LV remodelling was that the remodelled heart was not only larger, but was also more spherical in shape. The change in shape of the LV from a prolate ellipse to a more spherical shape results in an increase in meridional wall stress of the LV, thereby creating a de novo energetic burden for the failing heart. Inasmuch as the load on the ventricle at end-diastole contributes importantly to the afterload that the ventricle faces at the onset of systole, it follows that LV dilation itself will increase mechanical energy expenditure of the ventricle, which exacerbates the underlying problems with energy utilization in the failing ventricle. In addition to the increase in LV end-diastolic volume, LV wall thinning also occurs as the ventricle begins to remodel.