Study of heart function in PRE-Eclampsia during and after PreGnancy (SHePREG): The pilot cohort

Abstract

Background: Pre-eclampsia with severe features (severe PreE) is associated with heart dysfunction, yet the impact beyond pregnancy, including its association with cardiomyopathic genetic polymorphisms, remains poorly understood.

Objective: We aimed to characterize the temporal impact of severe PreE on heart function through the 4th trimester in women with and without deleterious cardiomyopathic genetic variants.

Methods: Pregnant women were enrolled to undergo transthoracic echocardiography (TTE) in late pregnancy and 3 months postpartum. In women with severe PreE a targeted approach to identify pathogenic cardiomyopathic genetic polymorphisms was undertaken, and heart function was compared in carriers and noncarriers.

Results: Pregnant women (32 ± 4 years old, severe PreE = 14, control = 8) were enrolled between 2019 - 2021. Women with severe PreE displayed attenuated myocardial relaxation (mitral e' = 11.0 ± 2.2 vs 13.2 ± 2.3 cm/sec, P < .05) in late pregnancy, and on in-silico analysis, deleterious cardiomyopathic variants were found in 58%. At 103 ± 33 days postpartum, control women showed stability in myocardial relaxation (Mitral e' Entry: 13.2 ± 2.3 vs Postpartum: 13.9 ± 1.7cm/sec, P = .464), and genetic negative severe PreE women (G-) demonstrated recovery of diastolic function to control level (Mitral e' Entry: 11.0 ± 3.0 vs Postpartum 13.7 ± 2.8cm/sec, P < .001), unlike their genetic positive (G+) counterparts (Mitral e' Entry: 10.5 ± 1.7 vs Postpartum 10.8 ± 2.4cm/sec, P = .853).

Conclusions: Postpartum recovery of heart function after severe PreE is attenuated in women with deleterious cardiomyopathic genetic polymorphisms.

Figure 1.

Deleterious Cardiomyopathic Genetic Polymorphisms in Women with Severe Pre-Eclampsia In-silico analyses (Polyphen2 data shown) of variant pathogenicity in severe pre-eclamptic patients is shown ranging from benign to damaging, with actual score represented by the black X (A). Sequence conservation across species is shown for each of the likely pathogenic variants (B).

Figure 2.

Heart Function in Severe Pre-Eclampsia Select measures of cardiovascular function in women (control = 8 (blue), Severe PreE/+DCGP = 7 (dark pink), Severe PreE/-DCGP = 5 (light pink)) at the time of delivery and 3 months postpartum are shown. All women with severe PreE demonstrated attenuated mitral annular velocity (e’) during pregnancy, with persistence of attenuated e’ 3-months postpartum in those that were G+, unlike their G− counterparts, who recovered function. * p< 0.05, † < 0.01. DCGP = deleterious cardiomyopathic genetic polymorphism, PreE: pre-eclampsia.