Maladaptive growth in the failing heart: The cardiomyopathy of overload

The hypertrophic response to overload plays an important role in the progressive deterioration of the failing heart - the "Cardiomyopathy of Overload" - and so contributes to the poor prognosis in patients with heart failure. Although increased myocyte size reduces the load on individual sarcomeres, hypertrophy also has maladaptive features. The latter include molecular changes that weaken and impair relaxation in the overloaded heart, and accelerate cardiac myocyte death. Different types of overload lead to concentric and eccentric hypertrophy; as the latter tends to progress ("remodeling"), dilatation is associated with an especially poor prognosis. Concentric hypertrophy is due largely to cardiac myocyte thickening, while eccentric hypertrophy is caused by cell elongation. These differences, along with evidence that concentric hypertrophy is initiated by increased diastolic stretch while eccentric hypertrophy results from increased systolic stress, indicate that these growth responses are mediated by different signal transudation pathways. The beneficial effects of neurohumoral blockers in patients with heart failure are due partly to their ability to inhibit maladaptive features of overload-induced proliferative signaling. The molecular complexity of the hypertrophic response now being uncovered offers opportunities for the development of new therapy to inhibit remodeling and cell death in the failing heart.