Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation.

ABSTRACT:

Background

Maximal exercise capacity after heart transplantion (HTx) is reduced to the 50-70% level of healthy controls when assessed by cardiopulmonary exercise testing (CPET) despite of normal left ventricular function of the donor heart. This study investigates the role of donor heart ?1 and ?2- adrenergic receptor (AR) polymorphisms for maximal exercise capacity after orthotopic HTx.

Methods

CPET measured peak VO2 as outcome parameter for maximal exercise in HTx recipients ?9 months and ?4 years post-transplant (n = 41; mean peak VO2: 57±15% of predicted value). Donor hearts were genotyped for polymorphisms of the ?1-AR (Ser49Gly, Arg389Gly) and the ?2-AR (Arg16Gly, Gln27Glu). Circumferential shortening of the left ventricle was measured using magnetic resonance based CSPAMM tagging.

Results

Peak VO2 was higher in donor hearts expressing the ?1-Ser49Ser alleles when compared with ?1-Gly49 carriers (60±15% vs. 47±10% of the predicted value; p = 0.015), and by trend in cardiac allografts with the ?1-AR Gly389Gly vs. ?1-Arg389 (61±15% vs. 54±14%, p = 0.093). Peak VO2 was highest for the haplotype Ser49Ser-Gly389, and decreased progressively for Ser49Ser-Arg389Arg > 49Gly-389Gly > 49Gly-Arg389Arg (adjusted R2 = 0.56, p = 0.003). Peak VO2 was not different for the tested ?2-AR polymorphisms. Independent predictors of peak VO2 (adjusted R2 = 0.55) were ?1-AR Ser49Gly SNP (p = 0.005), heart rate increase (p = 0.016), and peak systolic blood pressure (p = 0.031). Left ventricular (LV) motion kinetics as measured by cardiac MRI CSPAMM tagging at rest was not different between carriers and non-carriers of the ?1-AR Gly49allele.

Conclusion

Similar LV cardiac motion kinetics at rest in donor hearts carrying either ?1-AR Gly49 or ?1-Ser49Ser variant suggests exercise-induced desensitization and down-regulation of the ?1-AR Gly49 variant as relevant pathomechanism for reduced peak VO2 in ?1-AR Gly49 carriers.

SUBMITTER: Metrich M 

PROVIDER: S-EPMC5036840 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature