Effects of calcium-channel blocking agents on left ventricular diastolic function in hypertrophic cardiomyopathy and in coronary artery disease

Abnormal left ventricular (LV) diastolic performance is a characteristic feature of hypertrophic cardiomyopathy (HC) and an important contributor to the development of symptoms. Impaired diastolic filling of the hypertrophied left ventricle results from both diminished distensibility and prolonged or incomplete relaxation. LV distensibility is not only influenced by fixed anatomic abnormalities (such as fibrosis or hypertrophy) that determine the passive elastic properties of the left ventricle, but also is modulated by the dynamics of myocardial relaxation: prolonged or incomplete LV relaxation may restrict the rate and extent of LV filling and result in altered pressure-volume relations throughout diastole. Several studies indicate that impaired LV relaxation and filling in HC may be modified favorably by verapamil or nifedipine administered on a short-term basis in the catheterization laboratory, associated with improved diastolic pressure-volume relations. Verapamil also improves LV filling during oral therapy. Improved indexes of LV filling correlate with symptomatic improvement, both short-term and long-term: Approximately 80% of patients having a persistent increase in peak LV filling rate have persistent improvement in objective exercise tolerance compared with preverapamil values. Altered LV relaxation and filling are also often observed in patients with coronary artery disease (CAD) after myocardial infarction or during acute ischemia. Moreover, impaired filling occurs under resting conditions in many patients who have normal systolic function and no evidence of previous infarction. Nifedipine improves indexes of LV relaxation and distensibility during pacing-induced ischemia and verapamil improves indexes of LV filling at rest and during exercise-induced ischemia. In both HC and CAD, improved LV diastolic function by nifedipine or verapamil may reflect reduced ischemia, improved coronary flow, alterations in LV loading conditions or primary myocardial effects. These changes may contribute to the improvement in symptoms in many patients during treatment with these drugs.