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IMPACT OF THE BETA-1 ADRENERGIC RECEPTOR POLYMORPHISM ON EFFICACY AND TOLERABILITY OF BETA BLOCKER THERAPY IN HEART FAILURE PATIENTS
A760 JACC April 1, 2014 Volume 63, Issue 12
Heart Failure and Cardiomyopathies Impact of the Beta-1 Adrenergic Receptor Polymorphism on Efficacy and Tolerability of Beta Blocker Therapy in Heart Failure Patients Poster Contributions Hall C Saturday, March 29, 2014, 10:00 a.m.-10:45 a.m.
Session Title: Heart Failure and Cardiomyopathies: Therapy I Abstract Category: 14. Heart Failure and Cardiomyopathies: Therapy Presentation Number: 1113-164 Authors: Hae-Young Lee, Wook-Jin Chung, Hee-Kyung Jeon, Hong-Seog Seo, Dong-Ju Choi, Eun-Seok Jeon, Jae-Joong Kim, Joon Han Shin, SeokMin Kang, Sang Hong Baek, Catholic University Seoul St. Mary’s Hospital, Seoul, South Korea, Seoul National University Hospital, Seoul, South Korea Background: The response to beta blockers in chronic heart failure (CHF) patients is heterogeneous according to genetic variations in the adrenergic signaling genes. This study investigated the association between the coding region variations of adrenergic receptor genes and therapeutic effect of beta blocker. Methods: Association between Beta adrenergic receptor polymorphism and Bisoprolol therapy in heArt failure (ABBA) study enrolled 100 CHF patients (NYHA class II-III) with reduced left ventricular ejection fraction < 45%. Enrolled patients started bisoprolol 1.25mg once daily, and the dose was up-titrated to the maximally tolerable dose. Patients were genotyped for ADRB1 Arg389Gly (rs1801253). Genotypic results were doubleblinded to the patients as well as investigators throughout the study period. Results: 1) At position 389 of the beta-1 adrenergic receptor (ADRB1), 53 patients were homozygous for the Arg genotype, 5 patients were homozygous for the Gly genotype and 25 patients were heterozygous. The observed minor Gly allele frequency was 21% and no deviation from Hardy-Weinberg equilibrium was seen in the genotype distribution of Arg389Gly (p=0.75). 2) ABRB1 Arg389Arg genotype group showed better tolerability to bisoprolol compared with Gly389X (Gly389Arg+Gly389Gly) group with significantly larger dose (5.19±2.66mg vs 3.95±2.19mg, p=0.046). 3) Following 12 weeks’ bisoprolol therapy, LVEF was significantly improved from 32.6±7.8% to 41.3±10.4% in overall (p<0.0001). Left ventricular volume was significantly reduced by 18% in Arg389Arg group (p<0.0001) compared with insignificant 7% reduction in Gly389X group (111.5±42.9ml), and there was significant difference in left ventricular volume reduction between two groups (p=0.03). 4) Exercise capacity increased with marginal significance in Arg389Arg group (+21±90 m, p=0.09), whereas there was essentially no change in Gly389X group (-1±93 m, p=0.96). Conclusion: In heart failure patients, ABRB1 Arg389Arg genotype showed better tolerability and reverse remodeling effect to bisoprolol. The findings of this study implicate the potential of individually tailoring of beta blocker therapy according to genotypes.
Heart Failure and Cardiomyopathies Impact of the Beta-1 Adrenergic Receptor Polymorphism on Efficacy and Tolerability of Beta Blocker Therapy in Heart Failure Patients Poster Contributions Hall C Saturday, March 29, 2014, 10:00 a.m.-10:45 a.m.
Session Title: Heart Failure and Cardiomyopathies: Therapy I Abstract Category: 14. Heart Failure and Cardiomyopathies: Therapy Presentation Number: 1113-164 Authors: Hae-Young Lee, Wook-Jin Chung, Hee-Kyung Jeon, Hong-Seog Seo, Dong-Ju Choi, Eun-Seok Jeon, Jae-Joong Kim, Joon Han Shin, SeokMin Kang, Sang Hong Baek, Catholic University Seoul St. Mary’s Hospital, Seoul, South Korea, Seoul National University Hospital, Seoul, South Korea Background: The response to beta blockers in chronic heart failure (CHF) patients is heterogeneous according to genetic variations in the adrenergic signaling genes. This study investigated the association between the coding region variations of adrenergic receptor genes and therapeutic effect of beta blocker. Methods: Association between Beta adrenergic receptor polymorphism and Bisoprolol therapy in heArt failure (ABBA) study enrolled 100 CHF patients (NYHA class II-III) with reduced left ventricular ejection fraction < 45%. Enrolled patients started bisoprolol 1.25mg once daily, and the dose was up-titrated to the maximally tolerable dose. Patients were genotyped for ADRB1 Arg389Gly (rs1801253). Genotypic results were doubleblinded to the patients as well as investigators throughout the study period. Results: 1) At position 389 of the beta-1 adrenergic receptor (ADRB1), 53 patients were homozygous for the Arg genotype, 5 patients were homozygous for the Gly genotype and 25 patients were heterozygous. The observed minor Gly allele frequency was 21% and no deviation from Hardy-Weinberg equilibrium was seen in the genotype distribution of Arg389Gly (p=0.75). 2) ABRB1 Arg389Arg genotype group showed better tolerability to bisoprolol compared with Gly389X (Gly389Arg+Gly389Gly) group with significantly larger dose (5.19±2.66mg vs 3.95±2.19mg, p=0.046). 3) Following 12 weeks’ bisoprolol therapy, LVEF was significantly improved from 32.6±7.8% to 41.3±10.4% in overall (p<0.0001). Left ventricular volume was significantly reduced by 18% in Arg389Arg group (p<0.0001) compared with insignificant 7% reduction in Gly389X group (111.5±42.9ml), and there was significant difference in left ventricular volume reduction between two groups (p=0.03). 4) Exercise capacity increased with marginal significance in Arg389Arg group (+21±90 m, p=0.09), whereas there was essentially no change in Gly389X group (-1±93 m, p=0.96). Conclusion: In heart failure patients, ABRB1 Arg389Arg genotype showed better tolerability and reverse remodeling effect to bisoprolol. The findings of this study implicate the potential of individually tailoring of beta blocker therapy according to genotypes.