Beta-adrenergic receptor blockade and the angiotensin-converting enzyme deletion polymorphism in patients with chronic heart failure

Abstract

Background: Beta-adrenergic receptor blockade is an established treatment of chronic heart failure (HF). Previous studies have suggested a potential pharmacogenetic interaction between beta-blocker therapy and the angiotensin-converting enzyme (ACE) I/D polymorphism in patients with HF.

Aims: We designed this study to analyze changes in myocardial function of HF patients in response to beta-blocker therapy as a function of the ACE I/D polymorphism.

Methods and results: We studied 199 consecutive patients with chronic HF not treated with beta-blockers. Before initiation of beta-blockers and 3 months after the maximal tolerated dose was reached, patients underwent echocardiography, radionuclide angiography, and a cardiopulmonary exercise test. We extracted genomic DNA from white blood cells and determined the ACE I/D polymorphism. Thirty-five (18%) patients had the II genotype, 86 (43%) the ID genotype and 78 (39%) the DD genotype. A significant and similar improvement in left ventricular ejection fraction (LVEF) was observed in II (from 0.30+/-0.10 to 0.41+/-0.13; P<0.0001), ID (from 0.29+/-0.11 to 0.39+/-0.13; P<0.0001) and DD patients (from 0.31+/-0.11 to 0.40+/-0.13; P<0.0001). Peak Vo(2) before and after beta-blockade was similar among the three groups. The proportion of responders to beta-blockers (patients without cardiac events during titration who had an increase in LVEF >5% after beta-blockers) was similar among the three groups (II: 65.9%%, ID: 60.6%%, DD: 65.9%; P=NS). During a median follow-up of 933 days, there was no evidence for any effect of ACE I/D polymorphism on cardiac survival.

Conclusions: We observed no evidence of pharmacogenetic interaction between the ACE I/D polymorphism and the effects of beta-blockade on LVEF and other prognostic parameters in patients with chronic HF. Our results support the initiation of beta-blockers in HF patients with the II or the ID genotype as well as in those with the DD genotype.