Chronic heart failure

In chronic heart failure, myocardial cells die from energy starvation, from cytotoxic mechanisms leading
to necrosis, or from the acceleration of apoptosis or programmed cell death. Necrosis stimulates
fibroblast proliferation, which results in the replacement of myocardial cells with collagen. The loss of
myocytes leads to cardiac dilation and an increased afterload and wall tension, which results in further
systolic dysfunction. In addition, the loss of mitochondrial mass leads to increased energy starvation.

Acute heart failure

During acute congestive heart failure, the sympathetic nervous system and renin-angiotensin system act
to maintain blood flow and pressure to the vital organs. Increased neurohormonal activity results in
increased myocardial contractility, selective peripheral vasoconstriction, salt and fluid retention, and
blood pressure maintenance. As a chronic state of failure ensues, these same mechanisms cause
adverse effects.

The myocardial oxygen demand, which exceeds the supply, increases because of an increase in the heart
rate, in contractility, and in wall stress. Alterations in calcium homeostasis and changes in contractile
proteins occur, resulting in a hypertrophic response of the myocytes. Neurohormonal factors may lead
to direct cardiotoxicity and necrosis.