Abstract 3579: ACE D/I and Beta 1 Arg389Gly Polymorphisms and Left Ventricular Recovery in Recent Onset Cardiomyopathy
Introduction: Left ventricular (LV) remodeling and recovery in acute cardiomyopathy is markedly heterogeneous, and much of the variability may be genetically based. The ACE D allele and the β1 Arg389 receptor adversely affect outcomes in chronic heart failure, and may influence the effectiveness of beta blockers (BB). We investigated the impact of ACE D and Arg389 on left ventricular recovery in recent onset cardiomyopathy for subjects in the IMAC 2 trial.
Method: IMAC 2 is an NHLBI funded genetic outcomes registry investigating left ventricular recovery in subjects with recent onset cardiomyopathy. Subjects, all with LVEF <0.40, less than 6 months of symptoms, and an evaluation consistent with primary cardiomyopathy or myocarditis were enrolled at 16 centers. DNA was obtained from peripheral blood at entry and genotyped for ACE D/I and β1Arg389Gly polymorphisms. LVEF was assessed at baseline and 6 months (6M) after entry by transthoracic echocardiography. LVEF at baseline, 6M and the change was compared by genotype.
Results: The overall cohort of 359 subjects was 39% female, 21% black, with a mean age 45±14. 81% of subjects were on BB at entry, which increased to 95 % at 6 months. ACE D/I genotype did not differ by race, however the Arg389 receptor was less prevalent among blacks (p=0.025) as previously reported. The ACE D allele was associated with more severe LV dysfunction at baseline (LVEF II/ID/DD= 0.24/0.25/0.20, p=0.01), but with a trend toward greater recovery (change in LVEF 0.15/0.16/0.18, p=0.12) which eliminated any difference at 6M (0.39/0.41/0.0.39, p=0.77). In contrast β1 Arg389Arg was associated with trend toward higher LVEF at entry (ArgAgr/ArgGly/GlyGly=0.25/0.23/23, p=0.06), no difference in recovery (0.16/0.16/0.14, p=0.46) and a significantly higher LVEF at 6M (0.41/0.39/0.37, p=0.03).
Conclusion: For subjects with recent onset cardiomyopathy, the ACE D allele and Arg389 receptor both appear to affect the LVEF at presentation. At follow up the effect of the ACE D allele was no longer evident while the impact of the Arg389 was still present. The genetics of LV recovery and BB response requires further investigation.