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Cardiac Disease & Maternity Research Group

Over the last decade a steady increase in institutional maternal mortality rate for cardiac disease in South Africa has been reported. We have found that after non-pregnancy related infections, cardiac disease is the second most common cause of indirect maternal death, with Peripartum cardiomyopathy and complications due to rheumatic heart disease contributing to more than 50% of the cases.  The objective of this research group is to investigate cardiac disease interlinked with pregnancy or the postpartum period.

RESEARCH COLLABORATORS: Prof. Karen Sliwa ( HICRA); Prof. John Anthony (Dept Obstetrics & Gynaecology, UCT); Dr. Tony Lachmann ( UCT); Dr. Liesl Zϋhlke ( UCT); Prof. Ana Mocumbi (Mavelane Hospital, Mozambique); Prof. Albertino Damasceno (Eduardo Mondlane University, Maputo, Mozambique); Dr. Feriel Azibani ( HICRA);  Prof. Kamilu Karaye and Prof. Mahmoud Sani (Kano University, Nigeria);  Prof. Abel Makubi (Muhimbili National Hospital, Dar Es Salaam, Tanzania);  Mrs Olivia Briton ( HICRA);  Prof. Sandrine Lecour ( HICRA);  Prof. Denise Hilfiker-Kleiner (Hannover University, GE);  Prof. Michael Böhm ( University of Saarland, Homburg, GE) and Dr. Kemi Tibazarwa ( Muhimbili Hospital, Tanzania); Prof. Jolien Roos - Hesselink (Erasmus Medical Centre,Rotterdam, Netherlands); Mark Johnson (Imperial College, London, UK); Prof.  Alexandre Mebazaa (Hôpitaux Universitaires Saint-Louis-Lariboisière University Paris Diderot); Dr Naisa Manafe (Maputo Mozambique); Dr. Mark Petrie (University of Glasgow); Dr. ​​​​​​​Johann Bauersachs (Medizinische Hochschule Hannover)

SELECTED PROJECTS:

Peripartum Cardiomyopathy – Current Research

The team has for many years investigated the pathogenesis, etiology, epidemiology and management of a condition, peripartum cardiomyopathy (PPCM), common in African women. PPCM is a disease which develops in previously healthy women, before delivery or in the postpartum period, with a reported mortality of about 25%.

This research has resulted in numerous publications in prestigious journals such as the European Heart Journal (2006, 2014, 2016), Journal of the American College of Cardiology, The Lancet (2006), Cell ( 2007) and Circulation (2011, 2012, 2013).  Research into subsequent pregnancy in women who had a PPCM resulted in a practical guidance paper:  Sliwa K, Petrie MC, Hilfiker-Kleiner D, et al. Long-term prognosis, subsequent pregnancy, contraception and overall management of peripartum cardiomyopathy: practical guidance paper from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy. Eur J Heart Fail. 2018 20(6):951-962.

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The positive results of the proof-of-concept pilot was published in Circulation March 2010 and confirmed in a multi-centre study performed in Germany. Hilfiker-Kleiner, Haghikia A, Berliner D, … Sliwa K, Bauersachs J.  Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study.  European Heart Journal. 2017; 0: 1-9. 

The use of bromocriptine 2.5 mg daily for 7 days post diagnosis of PPCM has also been included in the 2018 ESC guidelines on cardiac disease in pregnancy.

The importance of PPCM contributing to later maternal death has been recently highlighted by us in The Lancet ( 2016). Some aspects of the research forms part of collaborative projects with the University of Hannover, Germany (Prof. Hilfiker-Kleiner) and the University of Saarland, Homburg, Germany (Prof. Böhm).

 

Our team reported that a ‘broken’ Prolactin (16kd) causes activation of pro-apoptotic signalling pathways in the heart, leading to left ventricular dilatation and a failing heart.We have investigated the effect of a medication (Bromocryptine) inhibiting prolactin in a randomized study of newly diagnosed patients with PPCM.  Further research has shown that endothelial microparticles (EMPs), vesicles released from endothelial cellular membranes during cell activation/apoptosis, could directly demonstrate endothelial damage in PPCM (Walenta K, Sliwa K, et al. Circulating microparticles as indicators of peripartum cardiomyopathy. Eur Heart J. 2012). It is still unclear whether hypertension in pregnancy-induced heart failure (PIH-HF) and peripartum cardiomyopathy (PPCM) are disparate clinical entities with different underlying pathogenetic mechanisms, natural histories and disease outcomes, which may sometimes overlap.

PPCM Working Group of Heart Failure Association of European Society of Cardiology

Prof Sliwa’s research translated into the establishment, in 2009, of the Peripartum Cardiomyopathy Working Group, Heart Failure Association of the European Cardiac Society (ESC), chaired by Prof Karen Sliwa and Prof. Johann Bauersachs ( Hannover University). The study group aims:

  • To establish a platform where current knowledge on peripartum cardiomyopathy based on experimental and clinical studies is summarized and regularly up-dated.
  • To raise awareness of this uncommon but devastating problem by promoting sessions at congresses and publishing articles
  • To coordinate the collection and analysis of data internationally for better understanding of the condition. • To meet regularly to discuss and update management strategies with a focus on novel diagnostic and therapeutic approaches.
  • To provide information and contact addresses on our webpage for physicians and patients concerned about PPCM.
  • To initiate and be advocates for the PPCM Registry

 A number of position papers have been published as Sliwa et al. Eur J Heart Failure 2010 and 2014, Bauersachs et al. Eur J Heart Failure 2016 and 2019:  Bauersachs J, König T, van der Meer P, Petrie MC, … . Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy.  Eur J Heart Fail. 2019

PPCM EuroObservational Research Program

The PPCM HFA Study group has subsequently leveraged funding for a Global registry on PPCM. Prof. K. Sliwa and Prof. Johann Bauersachs are the chairs of EORP Program on PPCM.  The study design has been published:

Sliwa K, Mebazaa A, Hilfiker-Kleiner D, et al. Clinical characteristics of patients from the worldwide registry on peripartum cardiomyopathy (PPCM): EURObservational Research Programme in conjunction with the Heart Failure Association of the European Society of Cardiology Study Group on PPCM. Eur J Heart Fail.  Eur J Heart Fail. 2017 Sep;19(9):1131-1141

The results of the 6 months outcome of more than 700 patients were presented as a Late Breaking Trial session at the ESC Heart Failure Congress, Athens, May 2019. Figure 1 Shows Global recruitment.

Groote Schuur Hospital Cardiac Disease in Maternity Cohort Study

The rationale for this cohort study is that the incidence of cardiovascular disease during pregnancy is increasing across the world, resulting in significant morbidity and mortality. Etiology and outcome varies between developing and developed countries. In developing countries, women may have pre-existing disease unmasked by pregnancy (e.g. mitral stenosis due to rheumatic heart disease), a superimposed condition unique to pregnancy (e.g. peripartum cardiomyopathy), or a complication of pregnancy itself (e.g. pregnancy-induced hypertension). There is, however, a lack of data from Africa on this important topic.

This cohort study was initiated by Professor Karen Sliwa at the Cardiac Clinic, Department of Medicine, Groote Schuur Hospital, in conjunction with Professor John Anthony, Department of Obstetrics and Gynaecology, Groote Schuur Hospital, in July 2011.

The objective is to study the natural history of these pregnant women with cardiovascular disease, pre- and postpartum, as well as to identify risk factors and clinical predictors of outcome.

Clinicians are invited to refer patients with a known cardiac condition (e.g. operated congenital heart disease, operated valvular disease) or patients with a suspected cardiac condition, during or post pregnancy, to the Cardiac Disease and Maternity Clinic. More than 500 patients from Cape Town have been entered into the cohort so far.

Serum and plasma are stored at the Hatter Institute. Detailed information on clinical presentation, socio-economic factors, laboratory markers, ECG and echocardiography is collected via a web-based data entry platform. A number of papers have been reported from this cohort. Other sub-studies as e.g. studying the use of loop recorders in pregnant women with arrhythmia ( CDM-REVEAL), funded by Medtronic CRE are under way.

Educating Health Care Workers and Patients in Cardiovascular Disease in Maternity – A multi-media approach implementing cutting edge technology into a culture-sensitive and education and preventative health programme (part of the HEDU-Africa Scheme)

The HEDUAfrica website has become part of the social media community with many Facebook likes (https://www.facebook.com/HeduAfrica) and followers on Twitter (https://twitter.com/HEDUAfrica) at present.

We have developed a multi-media resource that we envision will become a widely available tool for preventing and managing the causes and consequences of cardiovascular diseases in pregnancy and postpartum in Africa. We propose to distribute this resource widely to healthcare providers who manage pregnant women.

This project was initiated by Prof Karen Sliwa, together with the collective expertise of Prof John Anthony (Department of Obstetrics and Gynaecology, Groote Schuur Hospital), Dr Friedrich Thienemann (University of Cape Town) and Christian Diederichs (Integerafrica). This project received funding from the Medtronic Foundation USA (2011-2015)

 

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