Abstract 20666: Renin-Angiotensin System Genetic Polymorphisms Associate with Left Ventricular Remodeling and Clinical Outcome in Patients with Severe Pressure Overload Cardiomyopathy
Objectives: To investigate the impact of renin-angiotensin system polymorphisms on left ventricular (LV) geometry, mortality and morbidity in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR).
Methods: Two hundred ninety nine patients with severe AS (area≤0.8 cm2) were prospectively enrolled. Concentric remodeling was defined as relative wall thickness>0.42 and LV mass index>115 for men or >95 gr/m2 for women. Peripheral blood was analyzed for ACE levels, ACE II, ID and DD polymorphisms, 1166 AGTR1 AA, AC and CC and B2BKR −9/−9, −9/+9 and +9/+9 variants. The primary end-points were short- (30-day) and long-term (2 years) survival. The secondary end-points were long-term event-free (stroke, myocardial infarction, revascularization) survival and long-term hospitalization-free survival.
Results: In DD genotype, higher ACE levels (39±1 vs 31±15 vs 23±12 U/L for DD, ID and II respectively, p=0.0004) and a higher incidence of LV concentric remodeling (16% vs 13% vs 5% for DD, ID and II respectively, p=0.04) were observed. After AVR, a better short-term survival in DD genotype but similar long-term survival rates among the ACE genotypes were observed (figure). The 2-year event-free survival was comparable in ACE polymorphisms (68 vs 65 vs 58% for DD, ID and II, p=0.4 respectively). There was a trend towards a worse hospitalization-free survival in II genotype (85 vs 77 vs 75 for DD, ID and II, p=0.16). The AGRT1 AC/ACEII genotype was associated with a worse long-term survival rate (53 vs 81 vs 81% for AGRT1/ACEII, ID and DD respectively, p=0.013) as well as the B2BKR +9/+9/AGRT1 AA genotype (56 vs 78 vs 100% for B2BKR +9/+9/AGRT1 AA, AC and CC respectively, p=0.017).
Conclusions: ACE DD genotype associates with a specific pattern of LV geometry and better perioperative clinical outcomes in patients with severe AS submitted to valve replacement. AGRT1 and B2BKR polymorphisms may impact on long-term survival in special subgroups of patients with AS.
- © 2010 by American Heart Association, Inc.