title: Adrenergic receptor gene polymorphism and left ventricular reverse remodelling after cardiac resynchronization therapy: preliminary results.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Civil Hospital of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pezzali
authors.forename: Antonio
authors.initials: A
authors.lastname: Curnis
authors.forename: Claudia
authors.initials: C
authors.lastname: Specchia
authors.forename: Valentina
authors.initials: V
authors.lastname: Carubelli
authors.forename: Loredana
authors.initials: L
authors.lastname: Covolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Donato
authors.forename: Angelo
authors.initials: A
authors.lastname: Auricchio
authors.forename: François
authors.initials: F
authors.lastname: Regoli
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
mesh_terms: D000368:Aged; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D058406:Cardiac Resynchronization Therapy / Q000009:adverse effects / Q000401:mortality; D002311:Cardiomyopathy, Dilated / Q000453:epidemiology; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D006720:Homozygote; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D020127:Recovery of Function; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2
keywords: Beta-adrenergic receptors gene polymorphism; Cardiac resynchronization therapy (CRT); ICD shocks; Left ventricular reverse remodelling