LAUSR

Heart failure is invariably associated with cardiac hypertrophy and impaired cardiac performance. Although several drugs have been developed to delay the progression of heart failure, none of the existing interventions have shown beneficial effects in reducing morbidity and mortality. In order to determine specific targets for future drug development, we have discussed different mechanisms involving both cardiomyocytes and non-myocyte (extracellular matrix) alterations for the transition of cardiac hypertrophy to heart failure as well as for the progression of heart failure. We have emphasized the role of oxidative stress, inflammatory cytokines, metabolic alterations and Ca2+-handling defects in adverse cardiac remodeling and heart dysfunction in hypertrophied myocardium. Alterations in the regulatory process due to several protein kinases as well as participation of mitochondrial Ca2+-overload, activation of proteases and phospholipases and changes in gene expression for subcellular remodeling have also been described for the occurrence of cardiac dysfunction. Association of cardiac arrhythmia with heart failure has been explained as a consequence of catecholamine oxidation products. Since these multifactorial defects in extracellular matrix and cardiomyocytes are evident in the failing heart, it is a challenge for experimental cardiologists to develop appropriate combination drug therapy for improving cardiac function in heart failure.