The heart wall comprises three distinct layers: the epicardium, myocardium, and endocardium. The outermost layer, the epicardium, is the visceral layer of the serous pericardium, featuring a thin, transparent mesothelial surface and an inner layer of areolar connective tissue with fat deposits that increase with age.

The myocardium, the thickest layer, consists of cardiac muscle cells interconnected by intercalated discs and crisscrossing connective tissue fibers. These muscle fibers contract to facilitate the heart's pumping action. The innermost layer, the endocardium, features a thin endothelial lining over connective tissue, providing a smooth surface for the heart's chambers and valves, thereby reducing blood flow friction.

In addition to these layers, the heart includes four connective tissue rings that surround the heart valves and merge with the interventricular septum. This dense network, referred to as the fibrous or cardiac skeleton, offers structural support and inhibits the overstretching of valves.

Two conditions can affect these layers: myocarditis and endocarditis. Myocarditis is an inflammation of the myocardium often caused by viral infections, rheumatic fever, radiation exposure, or certain chemicals or medications. Myocarditis is usually mild, with recovery typically occurring within two weeks. More severe cases can lead to cardiac failure and death, with treatment focusing on rest, a low-salt diet, electrocardiographic monitoring, and addressing cardiac failure.

Endocarditis refers to inflammation of the endocardium, typically involving the heart valves. Most cases result from bacterial infections. Treatment for endocarditis generally involves intravenous antibiotics.