Peripartum cardiomyopathy: current management and future perspectives

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Pregnancy is associated with marked physiological changes challenging the cardiovascular system. Among the more severe pregnancy associated cardiovascular complications, peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease emerging towards the end of pregnancy or in the first postpartal months in previously healthy women. A major challenge is to distinguish the peripartum discomforts in healthy women (fatigue, shortness of breath, and oedema) from the pathological symptoms of PPCM. Moreover, pregnancy-related pathologies such as preeclampsia, myocarditis, or underlying genetic disease show overlapping symptoms with PPCM. Difficulties in diagnosis and the discrimination from other pathological conditions in pregnancy may explain why PPCM is still underestimated. Additionally, underlying pathophysiologies are poorly understood, biomarkers are scarce and treatment options in general limited. Experience in long-term prognosis and management including subsequent pregnancies is just beginning to emerge. This review focuses on novel aspects of physiological and pathophysiological changes of the maternal cardiovascular system by comparing normal conditions, hypertensive complications, genetic aspects, and infectious disease in PPCM-pregnancies. It also presents clinical and basic science data on the current state of knowledge on PPCM and brings them in context thereby highlighting promising new insights in diagnostic tools and therapeutic approaches and management.

Related collections

Most cited references 37

Record: found
Abstract: found
Article: not found

MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy.

Ngoc-Quynh-Nhu Nguyen, Sebastien P Tabruyn, Marc Thiry … (2013)

Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment (16K PRL), the underlying molecular mechanisms are poorly understood. We found that 16K PRL induced microRNA-146a (miR-146a) expression in ECs, which attenuated angiogenesis through downregulation of NRAS. 16K PRL stimulated the release of miR-146a-loaded exosomes from ECs. The exosomes were absorbed by cardiomyocytes, increasing miR-146a levels, which resulted in a subsequent decrease in metabolic activity and decreased expression of Erbb4, Notch1, and Irak1. Mice with cardiomyocyte-restricted Stat3 knockout (CKO mice) exhibited a PPCM-like phenotype and displayed increased cardiac miR-146a expression with coincident downregulation of Erbb4, Nras, Notch1, and Irak1. Blocking miR-146a with locked nucleic acids or antago-miRs attenuated PPCM in CKO mice without interrupting full-length prolactin signaling, as indicated by normal nursing activities. Finally, miR-146a was elevated in the plasma and hearts of PPCM patients, but not in patients with dilated cardiomyopathy. These results demonstrate that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM.

0 comments Cited 177 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy

Ian Patten, Sarosh Rana, Sajid Shahul … (2012)

Peri-partum cardiomyopathy (PPCM) is a frequently fatal disease that affects women near delivery, and occurs more frequently in women with pre-eclampsia and/or multiple gestation. The etiology of PPCM, or why it associates with pre-eclampsia, remains unknown. We show here that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble Flt1 (sFlt1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by sub-clinical cardiac dysfunction, the extent of which correlates with circulating levels of sFlt1. Exogenous sFlt1 alone caused diastolic dysfunction in wildtype mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFlt1. These data strongly suggest that PPCM is in large part a vascular disease, caused by excess anti-angiogenic signaling in the peri-partum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.

0 comments Cited 157 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review.

Anees Ansari, S Rahimtoola, J Veille … (2000)

Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women. In April 1997, the National Heart, Lung, and Blood Institute (NHLBI) and the Office of Rare Diseases of the National Institutes of Health (NIH) convened a Workshop on Peripartum Cardiomyopathy to foster a systematic review of information and to develop recommendations for research and education. Fourteen workshop participants were selected by NHLBI staff and represented cardiovascular medicine, obstetrics, immunology, and pathology. A representative subgroup of 8 participants and NHLBI staff formed the writing group for this article and updated the literature on which the conclusions were based. The workshop was an open meeting, consistent with NIH policy. Data presented at the workshop were augmented by a MEDLINE search for English-language articles published from 1966 to July 1999, using the terms peripartum cardiomyopathy, cardiomyopathy, and pregnancy. Articles on the epidemiology, pathogenesis, pathophysiology, diagnosis, treatment, and prognosis of PPCM were included. RECOMMENDATION PROCESS: After discussion of data presented, workshop participants agreed on a standardized definition of PPCM, a general clinical approach, and the need for a registry to provide an infrastructure for future research. Peripartum cardiomyopathy is a rare lethal disease about which little is known. Diagnosis is confined to a narrow period and requires echocardiographic evidence of left ventricular systolic dysfunction. Symptomatic patients should receive standard therapy for heart failure, managed by a multidisciplinary team. If subsequent pregnancies occur, they should be managed in collaboration with a high-risk perinatal center. Systematic data collection is required to answer important questions about incidence, treatment, and prognosis.

0 comments Cited 115 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Eur Heart J

Journal ID (iso-abbrev): Eur. Heart J

Journal ID (publisher-id): eurheartj

Journal ID (hwp): ehj

Title: European Heart Journal

Publisher: Oxford University Press

ISSN (Print): 0195-668X

ISSN (Electronic): 1522-9645

Publication date (Print): 07 May 2015

Publication date (Electronic): 30 January 2015

Publication date PMC-release: 30 January 2015

Volume: 36

Issue: 18 , Focus issue on Pregnancy and Peripartum

Pages: 1090-1097

Affiliations

Department of Cardiology and Angiology, Medical School Hannover , Carl-Neuberg-Str. 1, 30625 Hannover, Germany

Author notes

[* ]Corresponding author: Tel: +49 511 532 2531, Fax: +49 511 532 3263, Email: hilfiker.denise@ 123456mh-hannover.de

Article

Publisher ID: ehv009

DOI: 10.1093/eurheartj/ehv009

PMC ID: 4422973

PubMed ID: 25636745

SO-VID: f0cad880-7972-4347-a98d-090096c0e930

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

History

Date received : 28 October 2014

Date revision received : 8 December 2014

Date accepted : 8 January 2015

Comments

Comment on this article

scite_

Cited by 70

See all cited by

Most referenced authors 634

See all reference authors

- Version 1

Peripartum cardiomyopathy: current management and future perspectives

Read this article at

Abstract

Related collections

Cardiovascular Innovations and Applications

Most cited references 37

MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy.

Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy

Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 501

Cited by 70

Most referenced authors 634