Prevalence of pre-eclampsia and adverse pregnancy outcomes in women with pre-existing cardiomyopathy: a multi-centre retrospective cohort study.

Pre-eclampsia is associated with postnatal cardiac dysfunction; however, the nature of this relationship remains uncertain. This multicentre retrospective cohort study aimed to determine the prevalence of pre-eclampsia in women with pre-existing cardiac dysfunction (left ventricular ejection fraction < 55%) and explore the relationship between pregnancy outcome and pre-pregnancy cardiac phenotype. In this cohort of 282 pregnancies, pre-eclampsia prevalence was not significantly increased (4.6% [95% C.I 2.2-7.0%] vs. population prevalence of 4.6% [95% C.I. 2.7-8.2], p = 0.99); 12/13 women had concurrent obstetric/medical risk factors for pre-eclampsia. The prevalence of preterm pre-eclampsia (< 37 weeks) and fetal growth restriction (FGR) was increased (1.8% vs. 0.7%, p = 0.03; 15.2% vs. 5.5%, p < 0.001, respectively). Neither systolic nor diastolic function correlated with pregnancy outcome. Antenatal ß blockers (n = 116) were associated with lower birthweight Z score (adjusted difference - 0.31 [95% C.I. - 0.61 to - 0.01], p = 0.04). To conclude, this study demonstrated a modest increase in preterm pre-eclampsia and significant increase in FGR in women with pre-existing cardiac dysfunction. Our results do not necessarily support a causal relationship between cardiac dysfunction and pre-eclampsia, especially given the population's background risk status. The mechanism underpinning the relationship between cardiac dysfunction and FGR merits further research but could be influenced by concomitant ß blocker use.

Postnatal cardiovascular morbidity following preterm pre-eclampsia: An observational study.

OBJECTIVE: To explore the nature of postnatal cardiovascular morbidity following pregnancies complicated by preterm pre-eclampsia and investigate associations between pregnancy characteristics and maternal postnatal cardiovascular function. STUDY DESIGN: This was an observational sub-study of a single-centre feasibility randomised double-blind placebo-controlled trial (https://www. CLINICALTRIALS: gov; NCT03466333), involving women with preterm pre-eclampsia, delivering before 37 weeks. Eligible women underwent echocardiography, arteriography and blood pressure monitoring within three days of birth, six weeks and six months postpartum. Correlations between pregnancy and cardiovascular characteristics were assessed using Spearman's correlation. MAIN OUTCOME MEASURES: The prevalence of cardiovascular dysfunction and remodelling six months following preterm pre-eclampsia. RESULTS: Forty-four women completed the study. At six months, 27 (61 %) had diastolic dysfunction, 33 (75 %) had raised total vascular resistance (TVR) and 18 (41 %) had left ventricular remodelling. Sixteen (46 %) women had de novo hypertension by six months and only two (5 %) women had a completely normal echocardiogram. Echocardiography did not change significantly from six weeks to six months. Earlier gestation at delivery and lower birthweight centile were associated with worse six-month diastolic dysfunction (E/E': rho = -0.39, p = 0.001 & rho = -0.42, p = 0.005) and TVR (rho = -0.34, p = 0.02 & rho = -0.37, p = 0.01). CONCLUSIONS: Preterm pre-eclampsia is associated with persistent cardiovascular morbidity-six months postpartum in the majority of women. These cardiovascular changes have significant implications for long-term cardiovascular health. The graded severity of diastolic dysfunction and TVR with worsening pre-eclampsia phenotype suggests a dose-effect. However, the mechanistic link remains uncertain.

Postnatal Enalapril to Improve Cardiovascular Function Following Preterm Preeclampsia (PICk-UP):: A Randomized Double-Blind Placebo-Controlled Feasibility Trial.

Hypertensive disease in pregnancy is associated with future cardiovascular disease and, therefore, provides an opportunity to identify women who could benefit from targeted interventions aimed at reducing cardiovascular morbidity. This study focused on the highest-risk group, women with preterm preeclampsia, who have an 8-fold risk of death from future cardiovascular disease. We performed a single-center feasibility randomized controlled trial of 6 months' treatment with enalapril to improve postnatal cardiovascular function. Echocardiography and hemodynamic measurements were performed at baseline (<3 days), 6 weeks, and 6 months postdelivery on 60 women. At randomization, 88% of women had diastolic dysfunction, and 68% had concentric remodeling/hypertrophy. No difference was seen in total vascular resistance (P=0.59) or systolic function (global longitudinal strain: P=0.14) between groups at 6 months. However, women treated with enalapril had echocardiographic measurements consistent with improved diastolic function (E/E'[the ratio of early mitral inflow velocity and early mitral annular diastolic velocity]: P=0.04) and left ventricular remodeling (relative wall thickness: P=0.01; left ventricular mass index: P=0.03) at 6 months, compared with placebo. Urinary enalapril was detectable in 85% and 63% of women in the enalapril arm at 6 weeks and 6 months, respectively. All women responded positively to taking enalapril in the future. Our study confirmed acceptability and feasibility of the study protocol with a recruitment to completion rate of 2.2 women per month. Importantly, postnatal enalapril treatment was associated with improved echocardiographic measurements; these early improvements have the potential to reduce long-term cardiovascular disease risk. A definitive, multicenter randomized controlled trial is now required to confirm these findings. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT03466333.