??1-Adrenergic receptor polymorphisms and left ventricular remodeling changes in response to ??-blocker therapy

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Abstract
Objective Large variability exists in the improvement in eft ventricular (LV) function from β-blocker treatment. We hypothesized that polymorphisms at codon 389 (Arg389Gly) and 49 (Ser49Gly) in the β1-adrenergic receptor (AR) gene were associated with LV reverse remodeling changes in response to β-blocker therapy among heart failure patients. Methods We prospectively enrolled 61 β-blocker naïve patients with systolic heart failure. Patients underwent baseline echocardiography followed by metoprolol CR/XL. The dose was doubled on a biweekly basis up to 200 mg/day or attainment of maximum tolerated dose. Echocardiography was repeated after the patient received the target or highest tolerated dose for 3 months. Results Among patients with the Arg389Arg genotype, ejection fraction (EF) increased from 23±5 to 29±10 (P=0.008). Gly389 carriers did not demonstrate any significant change in EF (22±9 to 23±11; P=0.45). There was a significant between-group difference in EF by genotype (P=0.04). The Arg389Arg genotype was also associated with significantly greater reductions in LV end-diastolic and end-systolic diameters compared to Gly389 carriers. Patients with the Gly49 variant also had a significantly greater reduction in LV end-diastolic diameter compared to Ser49 homozygotes. Multiple regression analysis modeling revealed that the codon 389 polymorphism was a significant predictor of an improvement in EF and both codon 49 and 389 polymorphisms were significant predictors of final LV end-diastolic diameter. Conclusions Heart failure patients with the Arg389Arg genotype and Gly49 carriers had greater improvements in LV remodeling from β-blocker treatment.