Cardiac reserve in the transplanted heart: effect of a graft polymorphism in the beta1-adrenoceptor.
BACKGROUND
Polymorphism of the beta1-adrenoceptor (beta1-AR) affects outcome and beta-blocker efficacy in patients with heart failure. We studied the influence of the beta1-AR Ser49Gly polymorphism on cardiac reserve in transplanted hearts.


METHODS
Beta1-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 (deltaHR 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 (deltaLVEF -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 beta1-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.
Scharin Täng
Margareta
M
Department of Molecular and Clinical Medicine/Cardiology, Wallenberg Laboratory, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. meta@wlab.gu.se
Lindberg
Erika
E
Grüner Sveälv
Bente
B
Magnusson
Yvonne
Y
Andersson
Bert
B
D000328:Adult; D004280:Dobutamine; D004452:Echocardiography; D025401:Echocardiography, Stress; D005080:Exercise Test; D005260:Female; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D010807:Physical Endurance; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D013318:Stroke Volume; D014019:Tissue Donors
D018342:Receptors, Adrenergic, beta-1; D004280:Dobutamine