Diastolic function as a target of therapeutic interventions in chronic heart failure

Although conventional wisdom holds that pharmacological interventions improve the haemodynamic and clinical status of patients with chronic heart failure by enhancing systolic performance, this hypothesis fails to explain many of the responses seen following the administration of these drugs. The observation that abnormalities of diastolic function are an earlier and more sensitive marker of heart failure than abnormalities of systolic function suggests that vasodilator and inotropic drugs may act primarily by improving diastolic function. This belief is supported by the following findings: (1) exercise capacity in chronic heart failure is more closely related to left ventricular filling pressure than to cardiac output or limb blood flow; (2) only drugs that lower left ventricular filling pressure have been shown to improve exercise capacity, whereas drugs that primarily increase cardiac output or left ventricular ejection fraction do not enhance effort tolerance; (3) the primary mechanism by which vasodilator and inotropic drugs lower left ventricular filling pressure is by exerting a favourable effect on left ventricular diastolic function rather than on left ventricular volume; (4) drugs that improve diastolic function tend to affect favourably the clinical status of patients with chronic heart failure, whereas drugs that adversely alter ventricular relaxation produce deleterious haemodynamic and clinical effects. These observations suggest that the diastolic abnormalities of heart failure may be an ideal target for the development of new therapeutic interventions.