Abstract 2855: Transforming Growth Factor-β Polymorphisms and Prediction of Clinical Outcome With Prophylactic Defibrillator Implantation in Chronic Heart Failure
Transforming growth factor-β (TGF-β) is linked to favorable myocardial remodeling during ischemic damage. Gene polymorphisms of TGF-β codon 10 and 25 correlate with magnitude of protein expression allowing separation into high, intermediate and low producer genotypes. We evaluated TGF- β polymorphisms and clinical outcomes in heart failure patients with ICD’s implanted for primary prophylaxis. DNA was isolated from 83 patients with LVEF≤ 0.35 (NYHA I-III, age 62±13 years, 85% men, 50% African American, 70% CAD, 52% prior MI, LVEF 23±6.5%) who received an ICD for primary prevention of sudden death. Patients were followed for at least 1 year (median 655;range 183–933 days) for death or ventricular arrhythmias requiring ICD therapy. TGF-β polymorphisms were analyzed using a PCR-based kit from One lambda (CA, USA). In all,14 deaths occurred (11 cardiac) and 32 patients suffered new ventricular arrhythmias or cardiac death. 36 (43%) exhibited high producer genotype, 8 (10%) were low producers and the remainder intermediate (n=39) for either TGF-β codon 10 or 25 (combined). No effect of age, sex, race, LVEF, co-morbidities, atrial fibrillation/flutter or CAD (with or without MI) was discernable on death or ventricular arrhythmias. None expressing TGF-β codon 10 high producer genotype died while those with either codon 10 or 25 high producer genotypes had lower incidence of death and ventricular arrhythmias (all p<0.05). (Figure⇓).
Inferences: The high producer genotype for TGF-β is protective in chronic heart failure patients undergoing prophylactic ICD implantation. If validated, these findings could assist in the refinement of cost-effectiveness of this therapeutic approach.