Browsing by Author "Hilfiker-Kleiner, Denise (6602676885)"

Background and Aims Peripartum cardiomyopathy (PPCM) remains a serious threat to maternal health around the world. While bromocriptine, in addition to standard treatment for heart failure, presents a promising pathophysiology-based disease-specific treatment option in PPCM, the evidence regarding its efficacy remains limited. This study aimed to determine whether bromocriptine treatment is associated with improved maternal outcomes in PPCM. Methods Peripartum cardiomyopathy patients from the EORP PPCM registry with available follow-up were included. The main exposure of this exploratory non-randomized analysis was bromocriptine treatment, and the main outcome was a composite endpoint of maternal outcome [death or hospital readmission within the first 6 months after diagnosis, or persistent severe left ventricular dysfunction (left ventricular ejection fraction < 35%) at 6-month follow-up]. Inverse probability weighting was used to minimize the effects of confounding by indication. Multiple imputation was used to account for the missing data. Results Among the 552 patients with PPCM, 85 were treated with bromocriptine (15%). The primary endpoint was available in 491 patients (89%) and occurred in 18 out of 82 patients treated with bromocriptine in addition to standard of care (22%) and in 136 out of 409 patients treated with standard of care (33%) (P = .044). In complete case analysis, bromocriptine treatment was associated with reduced adverse maternal outcome [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.10–0.83, P = .021]. This association remained after applying multiple imputation and methods to correct for confounding by indication (inverse probability weighted model on imputed data: OR 0.47, 95% CI 0.31-0.70, P < 0.001). Thromboembolic events were observed in 6.0% of the patients in the bromocriptine group vs. 5.6% in the standard of care group (P = .900). Conclusions Among women with PPCM, bromocriptine treatment in addition to standard of care was associated with better maternal outcomes after 6 months. © The European Society of Cardiology 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.

We sought to describe the clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy (PPCM) globally. Methods and results: In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global registry on PPCM, under the auspices of the ESC EURObservational Research Programme. These societies were tasked with identifying centres who could participate in this registry. In low-income countries, e.g. Mozambique or Burkina Faso, where there are no national societies due to a shortage of cardiologists, we identified potential participants through abstracts and publications and encouraged participation into the study. Seven hundred and thirty-nine women were enrolled in 49 countries in Europe (33%), Africa (29%), Asia-Pacific (15%), and the Middle East (22%). Mean age was 31 ± 6 years, mean left ventricular ejection fraction (LVEF) was 31 ± 10%, and 10% had a previous pregnancy complicated by PPCM. Symptom-onset occurred most often within 1 month of delivery (44%). At diagnosis, 67% of patients had severe (NYHA III/IV) symptoms and 67% had a LVEF ≤35%. Fifteen percent received bromocriptine with significant regional variation (Europe 15%, Africa 26%, Asia-Pacific 8%, the Middle East 4%, P < 0.001). Follow-up was available for 598 (81%) women. Six-month mortality was 6% overall, lowest in Europe (4%), and highest in the Middle East (10%). Most deaths were due to heart failure (42%) or sudden (30%). Re-admission for any reason occurred in 10% (with just over half of these for heart failure) and thromboembolic events in 7%. Myocardial recovery (LVEF > 50%) occurred only in 46%, most commonly in Asia-Pacific (62%), and least commonly in the Middle East (25%). Neonatal death occurred in 5% with marked regional variation (Europe 2%, the Middle East 9%). Conclusion: Peripartum cardiomyopathy is a global disease, but clinical presentation and outcomes vary by region. Just under half of women experience myocardial recovery. Peripartum cardiomyopathy is a disease with substantial maternal and neonatal morbidity and mortality. © 2020 Published on behalf of the European Society of Cardiology. All rights reserved.

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition typically presenting as heart failure with reduced ejection fraction (HFrEF) in the last month of pregnancy or in the months following delivery in women without another known cause of heart failure. This updated position statement summarizes the knowledge about pathophysiological mechanisms, risk factors, clinical presentation, diagnosis and management of PPCM. As shortness of breath, fatigue and leg oedema are common in the peripartum period, a high index of suspicion is required to not miss the diagnosis. Measurement of natriuretic peptides, electrocardiography and echocardiography are recommended to promptly diagnose or exclude heart failure/PPCM. Important differential diagnoses include pulmonary embolism, myocardial infarction, hypertensive heart disease during pregnancy, and pre-existing heart disease. A genetic contribution is present in up to 20% of PPCM, in particular titin truncating variant. PPCM is associated with high morbidity and mortality, but also with a high probability of partial and often full recovery. Use of guideline-directed pharmacological therapy for HFrEF is recommended in all patients respecting contraindications during pregnancy/lactation. The oxidative stress-mediated cleavage of the hormone prolactin into a cardiotoxic fragment has been identified as a driver of PPCM pathophysiology. Pharmacological blockade of prolactin release using bromocriptine as a disease-specific therapy in addition to standard therapy for heart failure treatment has shown promising results in two clinical trials. Thresholds for devices (implantable cardioverter-defibrillators, cardiac resynchronization therapy and implanted long-term ventricular assist devices) are higher in PPCM than in other conditions because of the high rate of recovery. The important role of education and counselling around contraception and future pregnancies is emphasised. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology

This position paper focusses on the pathophysiology, diagnosis and management of women diagnosed with a cardiomyopathy, or at risk of heart failure (HF), who are planning to conceive or present with (de novo or previously unknown) HF during or after pregnancy. This includes the heterogeneous group of heart muscle diseases such as hypertrophic, dilated, arrhythmogenic right ventricular and non-classified cardiomyopathies, left ventricular non-compaction, peripartum cardiomyopathy, Takotsubo syndrome, adult congenital heart disease with HF, and patients with right HF. Also, patients with a history of chemo-/radiotherapy for cancer or haematological malignancies need specific pre-, during and post-pregnancy assessment and counselling. We summarize the current knowledge about pathophysiological mechanisms, including gene mutations, clinical presentation, diagnosis, and medical and device management, as well as risk stratification. Women with a known diagnosis of a cardiomyopathy will often require continuation of drug therapy, which has the potential to exert negative effects on the foetus. This position paper assists in balancing benefits and detrimental effects. © 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesteraseinhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2þ. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term. © 2018 The Author(s).