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Beta‐adrenergic receptor blockade and the angiotensin‐converting enzyme deletion polymorphism in patients with chronic heart failure
Author(s) -
Groote Pascal,
Helbecque Nicole,
Lamblin Nicolas,
Hermant Xavier,
Amouyel Philippe,
Bauters Christophe,
Dallongeville Jean
Publication year - 2004
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2003.09.006
Subject(s) - medicine , ejection fraction , heart failure , angiotensin converting enzyme , blockade , genotype , cardiology , bisoprolol , radionuclide angiography , pharmacogenetics , cardiac function curve , endocrinology , receptor , blood pressure , biochemistry , chemistry , gene
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 V o 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.