Mechanisms of Altered Ca2+ Handling in Heart Failure

Among the many causes of myocardial injury that can lead to congestive heart failure (CHF), myocardial infarction (MI) is the most common in the developed world. The hallmark features of heart failure include reduced contractile function manifested as blunted, slowed, dysynchronous contraction and impaired relaxation. The physiological positive force–frequency relationship and increased myocardial contractile response to increased preload are compromised in heart failure. The failing heart attempts to compensate for injury by various mechanisms, such as myocardial hypertrophy, increasing filling pressure, and enhanced neurohumoral signals, which together drive a feed-forward pathophysiological spiral leading to adverse ventricular remodeling and electric instability. Each of these maladaptive events is associated with loss of myocardial Ca homeostasis.