Response to catecholamine stimulation of polymorphisms of the beta-1 and beta-2 adrenergic receptors

Previous studies have demonstrated that β-adrenergic receptor polymorphisms affect outcomes in patients with heart failure or after an acute coronary syndrome. Whether β-adrenergic polymorphisms influence catecholamine responses in patients with cardiovascular disease is not known. Cardiovascular responses to the β1-receptor agonist dobutamine and the β2-receptor agonist terbutaline were studied using gated blood pool scintigraphy in 21 patients on long-term β-blocker therapy. Heart rate (HR), stroke volume (SV), and cardiac output (CO) increased, and end-systolic volume decreased with dobutamine and terbutaline. Changes in HR and CO with dobutamine were higher for those with ≥1 β1 Arg389 allele than those homozygous for the Gly389 allele (change in HR 15 vs 1 beat/min, p = 0.02; change in CO 2.4 vs 1.0 L/min, p = 0.02). Increases in HR, CO, and SV with terbutaline were greater for those homozygous for the β2 Glu27 allele than those with ≥1 Gln27 allele (change in HR 13.7 vs 4.8 beats/min, p = 0.048; change in CO 3.1 vs 1.6 L/min, p = 0.034; change in SV 28.3 vs 14.8 ml, p = 0.045). Changes in CO and volume with terbutaline were greater in those with an ejection fraction <40% than in those with an ejection fraction ≥40%. In conclusion, β-receptor gene variants significantly influence inotropic and chronotropic responses to β-agonist exposure in patients on β-blocker therapy.