Mechanisms of Ventricular Reserve Limitation in Cardiac Hypertrophy

Summary

Ventricular hypertrophy is usually characterized by resting abnormalities of diastolic function with preserved systolic performance. However, there are often profound limitations of both diastolic and systolic functional reserve to physiologic stress. One of the most well studied reserve limitations is to chronotropic stress. Rapid atrial pacing can result in marked elevation of diastolic pressure and stiffness in animal hypertrophy models and in humans with idiopathic asymmetric hypertrophy presenting with chest pain syndrome. In other patients with severe hypertrophy and congestive failure symptoms, diastolic function does not deteriorate with rapid pacing, suggesting that underlying etiology and severity of disease are important factors to this response. Systolic reserve limitations to pacing stress are also found in both animal and human hypertrophy. Raising heart rate from 80 to 160 min—1 increases endsystolic elastance by nearly 100% in normal humans, while it is virtually unchanged in hypertrophied hearts. Mechanisms that may underlie the loss of contractile reserve to chronotropic challenge are abnormal subendocardial perfusion, altered calcium cycling, and changes in myofilament proteins. Each mechanism is reviewed. In addition to chronotropic reserve limitations, the hypertrophied heart has limited preload and inotropic reserve due to increased end-systolic chamber stiffness. A high end-systolic stiffness results in minimal augmentation of pump function (i. e., cardiac output) when contractility is increased. Furthermore, such a heart is highly sensitive to preload change, with marked alterations in systolic pressure generation and thus wall stress resulting from relatively small changes in chamber diastolic filling. Current and future therapeutic approaches to this disorder need to consider all of these reserve limitation mechanisms.