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Pathophysiology and risk factors of peripartum cardiomyopathy

Nature Reviews Cardiology volume 19, pages 555–565 (2022)Cite this article

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Abstract

Peripartum cardiomyopathy (PPCM) is a potentially fatal form of idiopathic heart failure with variable prevalence across different countries and ethnic groups. The cause of PPCM is unclear, but environmental and genetic factors and pregnancy-associated conditions such as pre-eclampsia can contribute to the development of PPCM. Furthermore, animal studies have shown that impaired vascular and metabolic function might be central to the development of PPCM. A better understanding of the pathogenic mechanisms involved in the development of PPCM is necessary to establish new therapies that can improve the outcomes of patients with PPCM. Pregnancy hormones tightly regulate a plethora of maternal adaptive responses, including haemodynamic, structural and metabolic changes in the cardiovascular system. In patients with PPCM, the peripartum period is associated with profound and rapid hormonal fluctuations that result in a brief period of disrupted cardiovascular (metabolic) homeostasis prone to secondary perturbations. In this Review, we discuss the latest studies on the potential pathophysiological mechanisms of and risk factors for PPCM, with a focus on maternal cardiovascular changes associated with pregnancy. We provide an updated framework to further our understanding of PPCM pathogenesis, which might lead to an improvement in disease definition.

Key points

  • Physiological cardiovascular changes during pregnancy mediate the development of peripartum cardiomyopathy (PPCM) in women who are predisposed to the disease.

  • Risk factors for PPCM include the presence of genetic variants that are common in other types of cardiomyopathy as well as low socioeconomic status, pre-eclampsia and a history of cancer.

  • PPCM onset typically overlaps with the most extreme fluctuations in hormone levels during pregnancy that occur during the third trimester and at birth.

  • Studies involving mouse models of PPCM demonstrate that the disease results from dysregulated metabolic pathways and angiogenic imbalance, possibly owing to aberrant hormonal signalling.

  • Our understanding of the pathophysiology underlying PPCM is mainly derived from studies on animal models, which require confirmation in patient studies, but these preclinical data form the basis of current clinical guidelines and future experiments.

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Fig. 1: Pregnancy hormone levels correlate with cardiac bioenergetic profile.
Fig. 2: Pregnancy hormones elicit cardiovascular-specific effects.
Fig. 3: Proposed pathogenic pathways in peripartum cardiomyopathy.

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Acknowledgements

M.F.H. was supported by the Dutch Heart Foundation (2021T017). Z.A. is supported by the Department of Defense (grant W81XWH18-1-0503). D.H.-K. is supported by Fondation Leducq and the German Research Foundation (grants HI 842/4-3). M.C.P. is supported by the British Heart Foundation Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217+). K.S. is supported by Hippocrate Foundation Servier. P.v.d.M. is supported by the European Research Council (715732, ERC-2016-STG).

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Authors and Affiliations

  1. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

    Martijn F. Hoes & Peter van der Meer

  2. Department of Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Zoltan Arany

  3. Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany

    Johann Bauersachs

  4. Department of Cardiovascular Complications in Pregnancy and in Oncologic Therapies, Comprehensive Cancer Center, Philipps University Marburg, Marburg, Germany

    Denise Hilfiker-Kleiner

  5. Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK

    Mark C. Petrie

  6. Department of Medicine & Cardiology, Cape Heart Institute, Faculty of Heath Sciences, University of Cape Town, Cape Town, South Africa

    Karen Sliwa

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M.F.H. wrote the article. All the authors researched data for the article, contributed to discussion of content, and reviewed and edited the manuscript before submission.

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J.B. has received consulting fees and honoraria for lectures from Abiomed, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cardior, Corvia, CVRx, Daichii Sankyo, MSD, Novartis, Pfizer, Servier and Vifor, and departmental research support from Abiomed, CVRx, Vifor and Zoll. M.C.P. has received honoraria from AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Corvia, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Roche, Siemens and Takeda, and research funding from 3R LifeSciences, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Roche and SQ Innovations. P.v.d.M. has received consultancy fees and/or grants from AstraZeneca, Corvidia, Ionis, Novartis, Pfizer, Pharmacosmos, PharmaNord Servier, Singulex and Vifor Pharma.

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Hoes, M.F., Arany, Z., Bauersachs, J. et al. Pathophysiology and risk factors of peripartum cardiomyopathy. Nat Rev Cardiol 19, 555–565 (2022). https://doi.org/10.1038/s41569-021-00664-8

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