Cardiac Reserve in the Transplanted Heart: Effect of a Graft Polymorphism in the β1-adrenoceptor

Background Polymorphism of the β 1 -adrenoceptor (β1-AR) affects outcome and β-blocker efficacy in patients with heart failure. We studied the influence of the β1-AR Ser49Gly polymorphism on cardiac reserve in transplanted hearts. Methods β1-AR polymorphism was determined by allelic discrimination analysis. Patients were divided into two groups: either homozygous for Ser49 ( n = 15) or with Gly49 in one or both alleles (Gly49; n = 5). Patients underwent a maximal bicycle exercise test and echocardiographic evaluation at rest and during low-dose dobutamine stress. Results Patients with Gly49 grafts had better physical endurance (144 ± 26 vs 112 ± 31 W, p = 0.03), a trend toward better chronotropic reserve (ΔHR 64 ± 13 vs 47 ± 16 bpm, p = 0.056) during exercise, and lower resting heart rate (82 ± 7 vs 90 ± 7 bpm, p = 0.04) than those homozygous for Ser49. There were no significant differences in left ventricular ejection fraction (LVEF), with the exception of a decrease in cardiac reserve in patients with the Gly49 variants at the lowest dose of dobutamine (ΔLVEF −4.4 ± 1.5 vs 2.2 ± 5.8%, p = 0.04). Doppler myocardial tissue velocities of early relaxation were increased in patients with the Gly49 variants compared with patients homozygous for Ser49, both at rest (14.5 ± 3.2 vs 10.4 ± 2.0 cm/s, p = 0.03) and during the lowest dose of dobutamine (15.0 ± 3.7 vs 10.9 ± 2.5 cm/s, p = 0.04). Conclusions Heart transplant patients with the β1-AR Gly49 variants had a lower heart rate, and better stress endurance and diastolic function compared with patients homozygous for Ser49. They also showed a trend toward better chronotropic reserve. These results provide a possible explanation for differences in cardiac reserve among patients with heart transplants.