Abstract 18476: Myocardial Recovery in Peripartum Cardiomyopathy: Effect of the GNB3 C825T Polymorphism in the Multicenter IPAC study

Abstract

Background: Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. Black race is a risk factor for the disorder and although most women recover myocardial function, previous studies suggest less recovery in black women than in whites. The genetic basis of this racial difference in risk and recovery remains unknown. A polymorphism of a G protein beta subunit (GNB3 C825T) in exon 10 has been studied extensively for a potential role in increased risk of hypertension in blacks. We investigated the impact of the GNB3 C825T polymorphism on myocardial recovery in PPCM in the multicenter IPAC study (Investigation of Pregnancy Associated Cardiomyopathy). Method: 97 women with new onset of PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Myocardial function was assessed by echocardiography at study entry, 2, 6 and 12 months postpartum and LVEF calculated at a core lab. Myocardial recovery in subjects with the GNB3TT genotype was compared to subjects with the GNB3 C allele (CC and CT combined) first for the overall cohort then separately in black and white subsets. Results: Overall the cohort was 30% black, mean age 30 + 6, and LVEF 0.35 + 0.10 at study entry 31 + 25days post-partum. For the overall cohort, the % GNB3 genotype TT/CT/CC =23/41/36 and differed markedly by Race (Black= 52/38/10 versus Whites=10/43/47, p<0.001). In subjects with the GNB3TT genotype, LVEF was similar early postpartum (TT= 0.35 + 0.07; CT+CC= 0.35 + 0.09, p=0.98) but significantly lower at 2 month (TT=0.38 + 0.15; CT+CC= 0.44 + 0.10, p=0.02), 6 months (TT=0.45 + 0.15; CT+CC= 0.53 + 0.08, p=0.002), and 12 months (TT=0.45 + 0.15; CT+CC= 0.56 + 0.07, p<0.001.). The difference in recovery for GNB3 TT subjects was most pronounced in black women (12 months LVEF for GNB3 TT=0.39 + 0.16; versus CT+CC= 0.53 + 0.09, p=0.02) but was still evident in whites ((TT=0.50 + 0.11; CT+CC= 0.56 + 0.06, p=0.04). Conclusion: In IPAC, Women with the GNB3 TT genotype had significantly less myocardial recovery over the first year post-partum, and its impact was particularly evident in black women. The increase prevalence of the GNB3 TT genotype in blacks may contribute to racial differences in myocardial recovery in women with PPCM