Adherence to heart failure treatment in patients with peripartum cardiomyopathy.

AIMS: Peripartum cardiomyopathy (PPCM) is characterized by left ventricular (LV) dysfunction developing towards the end of pregnancy or in the first months postpartum. Although about 60% of women with PPCM (the majority of which are prescribed evidence based heart failure [HF] medications) show LV recovery within 6 to 12 months, others remain with persistently impaired LV function. Poor adherence to medical therapy represents a major cause of avoidable hospitalizations, disability, and death in other cardiovascular conditions. In this study, we aimed to determine drug adherence to HF therapy among women with PPCM and to identify possible associations between drug adherence and LV recovery, functional status and psychological well-being. METHODS AND RESULTS: In this single-centre, prospective, observational study, we included 36 consecutive women with PPCM. Adherence to HF treatment was assessed by (i) verifying the collection of pharmacy refills and (ii) using liquid chromatography high-resolution mass spectrometry (LC-HRMS). Participants were thereby classified as 'adherent' (i.e. all prescribed HF drugs were detectable by LC-HRMS), 'partially adherent' (i.e. at least one prescribed drug detectable) or 'non-adherent' (i.e. none of the prescribed drugs detectable). Health state index scores were assessed by EQ-5D-5L and HADS-A/D (for anxiety/depression). Patients' median age was 32.4 years (IQR 27.6-36.1). At the adherence visit (which occurred at a median of 16 months [IQR 5-45] after PPCM diagnosis), prescription included beta-blockers (77.8%), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (75%), mineralocorticoid receptor antagonists (47.2%) and loop diuretics (95.2%). Less than two thirds of patients (63.9%) collected all their pharmacy refills in the 6 months prior to adherence visit. According to LC-HRMS, 23.5% participants were classified as adherent, 53.0% as partially adherent, and 23.5% as non-adherent. Adherence was associated with significantly lower LVEDD at follow-up (47 mm [IQR 46-52), vs. 56 mm [IQR 49-64] with partial adherence, and 62 mm [IQR 55-64] with non-adherence, P = 0.022), and higher LVEF at follow-up (60% [IQR 41-65]), vs. partially adherence (46% [IQR 34-50]) and non-adherence (41.0% [IQR 29-47], P = 014). Adherent patients had a lower overall EQ- 5D score (5.5 [IQR 5-7.5], vs. 6 [IQR 5-7] in partially adherent, and 10 [IQR 8-15] in non-adherent patients, P = 0.032) suggestive of a better self-rated health status. CONCLUSIONS: Adherence to HF therapy was associated with favourable LV reverse remodelling in PPCM and better self-rated health status. Our study highlights the importance of drug adherence for functional recovery. Drug adherence should be an important component of patient communication and specific interventions in PPCM.

Outcomes at one year in women with peripartum cardiomyopathy: Findings from the ESC EORP PPCM Registry.

AIMS: There are few prospective reports of 1-year outcomes for women with peripartum cardiomyopathy (PPCM). We report findings from the European Society of Cardiology EURObservational Research Programme PPCM Registry. METHODS AND RESULTS: The registry enrolled women from 51 countries from 2012 to 2018. Eligibility included: (i) a peripartum state, (ii) signs or symptoms of heart failure, (iii) left ventricular (LV) ejection fraction ≤45%, (iv) exclusion of alternative causes of heart failure. We report mortality, thromboembolism, stroke, rehospitalization, LV recovery and remodelling at 1 year. Differences between regions were compared. One-year mortality data were available in 535 (71%) women and follow-up differed across regions. At 1 year, death from any cause occurred in 8.4% of women, with regional variation (Europe 4.9%, Africa 6.5%, Asia-Pacific 9.2%, Middle East 18.9%; p < 0.001). The frequencies of thromboembolism and stroke were 6.3% and 2.5%, respectively, and were similar across regions. A total of 14.0% of women had at least one rehospitalization and 3.5% had recurrent rehospitalizations (i.e. two or more). Overall, 66.1% of women had recovery of LV function (22% between 6 months and 1 year), with a mean LV ejection fraction increase from baseline of 21.2% (±13.6). Recovery occurred most frequently in Asia-Pacific (77.5%) and least frequently in the Middle East (32.7%). There were significant regional differences in the use of heart failure pharmacotherapies. CONCLUSIONS: Approximately 1 in 12 women with PPCM had died by 1 year and thromboembolism and stroke occurred in 6.3% and 2.5%, respectively. Around 1 in 7 women had been rehospitalized and, in 1 in 3, LV recovery had not occurred. PPCM is associated with substantial mortality and morbidity globally.

Effectiveness of implantable loop recorder and Holter electrocardiographic monitoring for the detection of arrhythmias in patients with peripartum cardiomyopathy.

BACKGROUND: Patients with peripartum cardiomyopathy (PPCM) are at increased risk of sudden cardiac death (SCD). However, the exact underlying mechanisms of SCD in PPCM remain unknown. By means of extended electrocardiographic monitoring, we aimed to systematically characterize the burden of arrhythmias occurring in patients with newly diagnosed PPCM. METHODS AND RESULTS: Twenty-five consecutive women with PPCM were included in this single-centre, prospective clinical trial and randomised to receiving either 24 h-Holter ECG monitoring followed by implantable loop recorder implantation (ILR; REVEAL XT, Medtronic®) or 24 h-Holter ECG monitoring alone. ILR + 24 h-Holter monitoring had a higher yield of arrhythmic events compared to 24 h-Holter monitoring alone (40% vs 6.7%, p = 0.041). Non-sustained ventricular tachycardia (NSVT) occurred in four patients (16%, in three patients detected by 24 h-Holter, and multiple episodes detected by ILR in one patient). One patient deceased from third-degree AV block with an escape rhythm that failed. All arrhythmic events occurred in patients with a severely impaired LV systolic function. CONCLUSIONS: We found a high prevalence of potentially life-threatening arrhythmic events in patients with newly diagnosed PPCM. These included both brady- and tachyarrhythmias. Our results highlight the importance of extended electrocardiographic monitoring, especially in those with severely impaired LV systolic function. In this regard, ILR in addition to 24 h-Holter monitoring had a higher yield of VAs as compared to 24 h-Holter monitoring alone. In settings where WCDs are not readily available, ILR monitoring should be considered in patients with severely impaired LV systolic dysfunction, especially after uneventful 24 h-Holter monitoring. TRIAL REGISTRATION: Pan African Clinical Trials Registry: PACTR202104866174807. Extended electrocardiographic monitoring for the detection of arrhythmias in PPCM. (CHB, complete heart block/third degree AV block; ECG, electrocardiogram; ILR, implantable loop recorder; NSVT, non-sustained ventricular tachycardia; PPCM, peripartum cardiomyopathy).

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.

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.