Outcome in German and South African peripartum cardiomyopathy cohorts associates with medical therapy and fibrosis markers.

AIMS: This study aims to compare the clinical course of peripartum cardiomyopathy (PPCM) cohorts from Germany (G-PPCM) and South Africa (SA-PPCM) with fibrosis-related markers to get insights into novel pathomechanisms of PPCM. METHODS AND RESULTS: G-PPCM (n = 79) and SA-PPCM (n = 72) patients and healthy pregnancy-matched women from Germany (n = 56) and South Africa (n = 40) were enrolled. Circulating levels of procollagen type-I (PINP) and type-III (PIIINP) N-terminal propeptides, soluble ST2, galectin-3, and full-length and cleaved osteopontin (OPN) were measured at diagnosis (baseline) and 6 months of follow-up. Both cohorts received standard heart failure therapy while anticoagulation therapy was applied in 100% of G-PPCM but only in 7% of SA-PPCM patients. In G-PPCM patients, baseline left ventricular ejection fraction (LVEF) was lower, and outcome was better (baseline LVEF, 24 ± 8%, full recovery: 52%, mortality: 0%) compared with SA-PPCM patients (baseline LVEF: 30 ± 9%, full recovery: 32%, mortality: 11%; P < 0.05). At baseline, PINP/PIIINP ratio was lower in SA-PPCM and higher in G-PPCM compared with respective controls, whereas total OPN was elevated in both collectives. Cleaved OPN, which increases PIIINP levels, is generated by thrombin and was reduced in patients receiving anticoagulation therapy. High baseline galectin-3, soluble ST2, and OPN levels were associated with poor outcome in all PPCM patients. CONCLUSIONS: SA-PPCM patients displayed a more profibrotic biomarker profile, which was associated with a less favourable outcome despite better cardiac function at baseline, compared with G-PPCM patients. Use of bromocriptine and anticoagulation therapy in G-PPCM may counteract fibrosis and may in part be responsible for their better outcome.

Effectiveness of Implanted Cardiac Rhythm Recorders With Electrocardiographic Monitoring for Detecting Arrhythmias in Pregnant Women With Symptomatic Arrhythmia and/or Structural Heart Disease: A Randomized Clinical Trial.

Importance: Arrhythmias are an important cause of maternal morbidity and mortality but remain difficult to diagnose. Objective: To compare implantable loop recorder (ILR) plus 24-hour Holter electrocardiographic (ECG) monitoring with standard 24-hour Holter ECG monitoring alone in terms of acceptability, ability to identify significant arrythmias, and effect on management and pregnancy outcome in women who were symptomatic or at high risk of arrythmia because of underlying structural heart disease. Design, Setting, and Participants: This single-center, prospective randomized clinical trial recruited 40 consecutive patients from the Cardiac Disease and Maternity Clinic at Groote Schuur Hospital in Cape Town, South Africa. Pregnant patients with symptoms of arrhythmia and/or structural heart disease at risk of arrhythmia were included. Intervention: Patients were randomized to standard care (SC; 24-hour Holter ECG monitoring [n = 20]) or standard care plus ILR (SC-ILR; 24-hour Holter ECG monitoring plus ILR [n = 20]). Only 17 consented to ILR insertion, and the 3 who declined ILR were allocated to the SC group. Main Outcomes and Measures: Arrhythmias considered included atrial fibrillation, atrial flutter, premature ventricular complexes, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation. Results: Among the 40 women in this trial, the mean (SD) age was 28.4 (5.5) years. Holter monitoring detected arrhythmias in 3 of 23 patients (13%) in the SC group and 4 of 17 patients (24%) in the SC-ILR group compared with 9 of 17 patients (53%) patients who had arrhythmias detected by ILR. Seven patients (4 with supraventricular tachycardia, 1 with premature ventricular complexes, and 2 with paroxysmal atrial fibrillation recorded by ILR) did not have arrhythmias detected by 24-hour Holter monitoring. Three of these 7 patients (43%) had a change in management as a result of their ILR recordings. There were no maternal deaths. However, the SC group had a significantly lower mean (SD) gestational stage at delivery (35 [5] weeks vs 38 [2], P = .04). Conclusions and Relevance: The ILR was better than 24-hour Holter monitoring in detecting arrhythmias, which led to a change in management for a significant proportion of patients. Our findings suggest that ILR may be beneficial for pregnant women at risk of arrhythmia. Trial Registration: ClinicalTrials.gov Identifier: NCT02249195.

The effect of beta-blockers on foetal birth weight in pregnancies in women with structural heart disease: a prospective cohort study.

OBJECTIVE: To examine whether treatment with beta-blockers (BBs) in pregnant women with structural heart disease (SHD) resulted in a decrease in foetal birth weight (FBW) in a South African cohort. METHODS: This was a prospective cohort study conducted in a tertiary-level hospital in Cape Town from 2010 to 2016. Of the 178 pregnant women with SHD, 24.2% received BBs for a minimum of two weeks. Adverse foetal outcomes and mean FBW were compared between the BB groups and subgroups (congenital, valvular, cardiomyopathy and other). Adverse foetal outcome was defined as: low birth weight (LBW) < 2 500 g, Apgar score < 7, premature birth (< 37 weeks) and small for gestational age (SGA). RESULTS: BB exposure during pregnancy was found to be associated with a non-significant increased FBW (2 912 vs 2 807 g, p = 0.347). A significant decrease (p = 0.009) was noted in FBW for valvular SHD pregnancies using BBs, while a significant increase (p = 0.049) was observed for the same outcome in the cardiomyopathy subgroup using BBs. A significant increase was observed for SGA (p = 0.010) and LBW (p = 0.003) pregnancies within the valvular subgroup when exposed to BBs. CONCLUSIONS: BB use in pregnant women with SHD in a South African cohort showed no association with a decrease in FBW or an increase in adverse foetal outcomes when compared to non-BB usage.

Reducing late maternal death due to cardiovascular disease - A pragmatic pilot study.

BACKGROUND: Late maternal mortality (up-to 1-year postpartum) is poorly reported globally and is commonly due to cardiovascular disease (CVD). We investigated targeted interventions aiming at reducing peripartum heart failure admission and late maternal death. METHODS AND RESULTS: Prospective single-centre study of 269 peripartum women presenting with CVD in pregnancy, or within 6-months postpartum. Both cardiac disease maternity (CDM) Group-I and Group-II were treated by a dedicated cardiac-obstetric team. CDM Group-II received additional interventions: 1. Early (2-6 weeks) postpartum follow-up at the CDM clinic and immediate referral to dedicated CVD specialist clinics. 2. Beta-blocker therapy was continued in women with LVEF<45% while pregnant, or immediately started postpartum. Of 269 consecutive women (mean age 28.6 ±â€¯5.9), 213 presented prepartum, 22% in NYHA groups III-IV and 79% in modified WHO groups III-IV. Patients were diagnosed with congenital heart disease (30%), valvular heart disease (25%) and cardiomyopathy (31%). The groups were similar in age, diagnosis, NYHA, modified WHO, BP and HIV, but Group-II had a higher rate of previously known CVD (p < 0.001) and a lower rate of being nulliparous (p < 0.0005). Of Group-I patients 9 died within the 12-month follow-up period versus one death in Group-II (p = 0.047). Heart failure leading to admission was 32% in Group-I versus 14% in Group-II (p = 0.0008), with Group-II having a higher beta-blocker use peripartum (p = 0.009). Perinatal mortality rate was 22/1000 live births with no differences between groups. CONCLUSION: Early follow-up in a dedicated CDM clinic with targeted pharmacological interventions led to a significant reduction in peripartum heart failure admission and mortality.