Polymorphisms of the β2-Adrenergic Receptor Determine Exercise Capacity in Patients With Heart Failure

Abstract—The β2-adrenergic receptor (β2AR) exists in multiple polymorphic forms with different characteristics. Their relevance to heart failure (HF) physiology is unknown. Cardiopulmonary exercise testing was performed on 232 compensated HF patients with a defined β2AR genotype. Patients with the uncommon Ile164 polymorphism had a lower peak Vo2 (15.0±0.9 mL · kg−1 · min−1) than did patients with Thr164 (17.9±0.9 mL · kg−1 · min−1, P<0.0001). The percentage achieved of predicted peak Vo2 was also lower in patients with Ile164 (62.3±4.5% versus 71.5±5.1%, P=0.045). The relative risk of a patient having a Vo2 ≤14 mL · kg−1 · min−1 who had Ile164 was 8.0 (P=0.009). Catheterization-based invasive exercise testing revealed depressed changes in the exercise-induced cardiac index, systemic vascular resistance, stroke volume, and Vo2 in patients with Ile164. The polymorphisms at position 16 also impacted exercise capacity: peak Vo2 for Arg16 versus Gly16 was 17.0±0.8 versus 15.6±0.5 mL · kg−1 · min−1, respe...