title: Critical review of heart failure: the role of left ventricular remodeling in the therapeutic response.
abstract: Recent clinical investigations have provided new insights into physiologic alterations taking place as heart failure progresses. As a result, new end points may be more relevant to monitor in patients, rather than the classical assessment of severity based on subjective evaluation of functional capacity. Structural changes of the myocardium, referred to as remodeling, have profound effects on the performance of the left ventricle and on long-term prognosis. Left ventricular ejection fraction may serve as a clinical marker for remodeling changes. Remodeling changes involve hypertrophy of the muscle mass, dilation of the left ventricle, and a change in the shape of the ventricle. Histologically, these changes are produced by myocyte lengthening, interstitial growth, and myocyte slippage. The consequences of remodeling include an abnormal bio-energetic state because of the augmented wall stress and accentuated myocardial oxygen consumption. The elevated wall stress promotes further hypertrophy. Superimposed on the remodeling changes is neurohormonal activation. Both remodeling and neurohormonal activation are directly related to mortality. An experimental canine model has been used successfully to investigate the potential impact of pharmacologic intervention on remodeling. Angiotensin-converting enzyme inhibitors and the combination of hydralazine and isosorbide dinitrate have been shown in clinical trials to reduce long-term mortality and increase ejection fraction. The effects of these drugs appear to be mediated in part by alterations in remodeling and neurohormonal activation. Thus, left ventricular ejection fraction can be used as a clinical marker for remodeling processes, and plasma norepinephrine levels can be used as a marker for neurohormonal activation.
mesh_terms: D000818:Animals; D018450:Disease Progression; D004285:Dogs; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*