Aims: Several factors can influence the extent of left ventricular (LV) reverse remodelling after cardiac resynchronization therapy (CRT) in patients with heart failure (HF). Polymorphism in genes involved in cardiac remodelling, namely beta-adrenergic receptors (ARs), may have a role. We studied the influence of beta-1 Arg389Gly, beta-2 Arg16Gly, and beta-2 Gln27Glu ARs gene polymorphisms on the magnitude of reverse remodelling response to CRT and its possible correlations with the incidence of appropriate implantable cardioverter-defibrillator (ICD) shocks.
Methods and results: Beta-ARs were assessed in 101 patients with HF due to idiopathic (50.5%) or ischaemic (49.5%) dilated cardiomyopathy, undergoing CRT for standard indications [left ventricular ejection fraction (LVEF) 23.5 ± 7.5%, QRS ≥ 120 ms]. Left ventricular ejection fraction was measured by echocardiography at baseline, 6 months after CRT, and periodically afterwards. The LVEF change from baseline was of 3.1 ± 11 units among Gln27Gln, 8.3 ± 10.4 units among Gln27Glu, 11 ± 6.4 units among Glu27Glu carriers (P = 0.018 for Gln27Gln vs. Glu27Glu carriers), and 8.8 ± 9.8 units among Gln27Glu + Glu27Glu carriers (P = 0.006 vs. Gln27Gln). Gln27 homozygotes had a higher incidence of appropriate ICD shocks for fast ventricular tachycardia/ventricular fibrillation.
Conclusion: Beta-2 Gln27Glu ARs gene polymorphism may influence LV reverse remodelling after CRT with Glu27Glu carriers showing the greatest improvement. It may also influence the incidence of malignant ventricular tachyarrhythmias.
Keywords: Beta-adrenergic receptors gene polymorphism; Cardiac resynchronization therapy (CRT); ICD shocks; Left ventricular reverse remodelling.