Changing Composition of the Hypertrophied Heart
The complexity of cardiac hypertrophy was recognized almost a century ago by Osier, who observed that the heart’s first response to sudden hemodynamic overload, such as that caused by aortic-valve rupture, is a phase of “development” in which the myocardium begins to hypertrophy. The resulting augmentation of muscle mass, by distributing the excess load among an increased number of sarcomeres, alleviates the acute heart failure and so is clearly beneficial. Although the initial hypertrophic response leads to Osler’s second phase, compensation, and is thus adaptive, the hypertrophy that initially helped the heart to meet the overload does not end well. Instead, the chronically overloaded heart degenerates and weakens, leading to a final stage that Osier called broken compensation. Thus, like salt and water retention and vasoconstriction, myocardial hypertrophy provides effective compensation for only a limited time. Following a pattern similar to that of the circulatory adjustments to low cardiac output, cardiac hypertrophy appears to become deleterious when it becomes chronic. Unfortunately, in most patients who seek medical care for heart failure, the myocardium has probably already entered Osier’s final phase of broken compensation, the cardiomyopathy of overload.
Changing Composition of the Hypertrophied Heart
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Central to an understanding of the cardiomyopathy of overload is a knowledge of the structural and functional abnormalities that initiate and perpetuate the deterioration of the hypertrophied, failing myocardium (Osler’s broken compensation). These abnormalities have been studied in depth from a morphologic standpoint and are now beginning to be understood at a molecular level in the light of the growing knowledge of changes in gene expression by the cells of the overloaded myocardium.
Morphologic Changes
Using traditional morphologic techniques, Linzbach noted that after initially thickening in response to overload, the walls of the heart become thinned in end-stage heart failure. Myocyte necrosis stimulates the proliferation of fibroblasts, replacing myocardial cells with connective tissue, and causes the late dilatation that increases the tension that must be developed by the muscular walls of the failing heart. The resulting progressive overload on the surviving cells of the hypertrophied heart, together with the relative decrease in capillary density and the number of mitochondria discussed earlier, probably contributes to a chronic energy deficit that sets up a vicious circle in the failing heart. Thus, although hypertrophy increases the number of sarcomeres and so is beneficial at first, this response represents an imperfect compensation because, when overloading is sustained, the hypertrophied myocardial cells ultimately deteriorate and die.