Effects of ACE-inhibitors and beta-blockers on left ventricular remodeling in chronic heart failure.

In recent years, it has become increasingly recognised that a central feature of the disease progression associated with heart failure is the process of left ventricular remodeling. The remodeling process manifests as an increase in left ventricular volumes, leading to a rise in wall stress and a compensatory increase in myocardial mass. The left ventricle also gradually assumes a more spherical shape, resulting in functional mitral regurgitation leading to further haemodynamic overload, worsening myocardial function and an unfavourable clinical course. Accumulating clinical data support the hypothesis that the benefits in clinical outcome with ACE-inhibitors and beta-blockers may relate to modification of the remodeling process resulting in slowing of disease progression and preservation of contractile function. The general trend from a number of clinical studies indicates that whereas ACE-inhibitors seem to prevent progressive left ventricular dilatation, the third generation beta-blocker, carvedilol, may actually reverse the remodelling process by reducing left ventricular volumes and improving systolic function. Direct comparisons indicate that carvedilol has a similar safety and tolerability profile to ACE-inhibitors and thereby support the feasibility of administering this drug as first-line therapy in selected patients with mild to moderate chronic heart failure. Therefore, the decision to initiate treatment with carvedilol or an ACE-inhibitor might in future be tailored on an individual basis and followed thereafter by combination therapy at the earliest and safest opportunity. Finally, the possible development of treatment strategies addressing the cellular and molecular mechanisms responsible for the remodeling process and the recently published benefits of device therapies herald a combined, synergistic approach to the future management of heart failure.