Compared with the mechanisms of adaptive responses of the heart, the mechanisms of maladaptation have been less elucidated. However, the followings are probably responsible for the progression of heart failure: 1) progressive loss of cardiac myocytes (quantity change); 2) progression of systolic dysfunction of individual myocytes(quality change); or 3) both. Apoptosis may be responsible for the myocyte death although controversial. Myocytes of failing hearts shows dramatic phenotype alterations in the structure, function, and biochemical events such as fetal type gene induction. Hypertrophy and degeneration of myocytes are the common, but not specific, features in failing hearts. Meanwhile, not only myocyte phenotype alterations but also myocardial interstitial changes such as extracellular matrix deposition, activation of fibroblasts, and narrowing of vessel lumens play important roles for the progression of heart failure.