Structural basis for heart failure. Ventricular remodeling and its pharmacological inhibition.

The syndrome of heart failure has traditionally been viewed as a functional disorder precipitated by impaired left ventricular pump performance. The classification into systolic and diastolic dysfunction has emphasized the functional distinction between abnormalities in contraction and relaxation. Recently, however, attention has been directed toward the possibility that the systolic dysfunction, which has been thought to be related to contractile failure, could be a consequence of a structural increase in ventricular chamber volume. This construct would revise the conventional view—contractile failure leads to chamber dilatation—with a more anatomic basis for heart failure: Chamber dilatation occurs as an early response that results in the reduced wall motion that is mandated to generate a normal stroke volume from a large ventricular end-diastolic volume. This structural alteration is not necessarily related to the underlying etiological cardiac pathology but rather represents an intrinsic morphological change that progresses over time in response to an initiating event. The term “remodeling” often is used to address these structural changes and may be best defined as a change in chamber volume and shape not related to a preload-mediated increase in sarcomere length. In this issue of Circulation , Greenberg and his SOLVD colleagues1 revisit the remodeling issue in chronic heart failure with echocardiographic data collected in the long-term trial of enalapril versus placebo in both symptomatic and asymptomatic patients with left ventricular remodeling. Patients were selected for this study on the basis of an ejection fraction of ≤35%. At the time the study was designed, this low ejection fraction was defined as systolic dysfunction. The implication of that designation is that an impairment of myocardial shortening was the primary abnormality. A more contemporary hypothesis, based on the concept of left ventricular remodeling, is that the low ejection fraction reflects in part a primary increase in chamber volume …