Pharmacotherapy of heart failure is likely to be most efficacious when individually tailored to the prevailing pathophysiological derangements. Their diagnostic definition and understanding of the mechanisms involved affords the greatest opportunity for their correction and retardation of further progression of the syndrome, together with related improvements in quality of life, reduction of morbid cardiovascular events and improvement in prognosis. Four approaches may be identified, each of which allows rational therapeutic intervention. The disordered contractile geometry of the failing ventricle gives rise to increased ventricular wall tension and myocardial hypertrophy. The phenotype change largely responsible for this progression may be retarded, halted, or even reversed by a reduction of the elevated ventricular pressure and volume induced by diuresis and/or systemic vasodilatation. Knowledge of the subcellular changes responsible for electromechanical coupling and subsequent myocardial cell contraction in the various stages of heart failure is still incomplete. Pharmacotherapeutic interventions with positive inotropic agents have not been universally clinically efficacious,
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