Relation between left ventricular remodeling and clinical outcomes in heart failure patients with left ventricular systolic dysfunction

Background: A major advance in understanding the pathophysiology of the heart failure syndrome has been an understanding of the process of left ventricular (LV) remodeling. After any insult to the left ventricle resulting in diminished systolic performance and stroke volume, a series of histopathologic changes in the myocardium and structural changes in the LV chamber occurs over time. Methods and Results: Early work on understanding this process of LV remodeling emerged from the studies of Pfeffer and colleagues, who used a rat model of myocardial infarction (MI). Compared to those with smaller MIs, rats with larger induced MIs underwent a substantially greater degree of chamber remodeling over time, and importantly, these structural changes were associated with significantly higher morality. These studies established for the first time the relation between the structural changes now widely known as LV remodeling and a natural history outcome in the setting of LV systolic dysfunction. Subsequently, these investigators demonstrated that angiotensin-converting enzyme (ACE) inhibition with captopril, when initiated soon after the induced MI, attenuated the remodeling process. Also observed was an improvement in survival among rats in whom the remodeling process has been attenuated. These important data paved the way for human studies that have subsequently provided substantial evidence to support two important concepts: (1) that LV remodeling is related to clinical outcomes that represent the natural history of the heart failure syndrome such as mortality and surrogate markers of the progression of heart failure, and (2) that therapeutic interventions in humans that slow or reverse the process of LV remodeling, such as ACE inhibitors and beta-blockers, appear to have a favorable effect on that natural history. Conclusions: This review will examine the issue of the relation between LV remodeling and clinical outcomes in the human heart failure syndrome from several interrelated aspects: (1) the relation between LV volume at one time point and subsequent oucome, (2) the relation between changes in LV volumes over time (LV remodeling) and clinical outcomes, and (3) the relation between the effect of medical therapeutic interventions on the LV remodeling process and the effect of those same medical interventions on natural history outcomes in human heart failure.