Bromocriptine for the Treatment of Peripartum Cardiomyopathy Tobias Koenig, Johann Bauersachs and Denise Hilfiker-Kleiner Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
Abstract Peripartum cardiomyopathy (PPCM) is a life-threatening, pregnancy-associated heart disease that develops towards the end of pregnancy or in the first months following delivery in previously healthy women. Understanding of the pathophysiology has progressed in recent years, highlighting an oxidative-stress mediated cleavage of the nursing hormone prolactin into a toxic 16-kDa prolactin fragment as a major factor driving the disease. The 16-kDa prolactin fragment induces detrimental but potentially reversible effects on heart function. Bromocriptine, a clinically-approved drug to block prolactin release, was initially tested in a PPCM mouse model where it efficiently prevented the onset of PPCM. Consequently, this treatment concept was transferred to and successfully used in humans as a bench-tobedside approach. Encouraging proof-of-concept studies led to a randomised trial that further strengthens the role of bromocriptine in addition to standard heart failure therapy in clinical practice. The aim of this article is to summarise this novel and disease-specific medical treatment, along with current knowledge on the epidemiology and pathophysiology of PPCM.
Keywords Peripartum cardiomyopathy, bromocriptine, prolactin, heart failure, pregnancy Disclosure: The authors have no conflicts of interest to declare. Received: 11 January 2018 Accepted: 14 February 2018 Citation: Cardiac Failure Review 2018;4(1):46–9. DOI: https://doi.org/10.15420/cfr.2018:2:2 Correspondence: Denise Hilfiker-Kleiner, Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. E: firstname.lastname@example.org
Cardiovascular diseases (CVD) are a major cause of complications in pregnancies worldwide, and can be largely attributed to increased cardiovascular risk factors, such as obesity and hypertensive disorders.1 Today, up to 4 % of all pregnancies are complicated by CVD, with increasing frequency.2 Cardiomyopathies – whether inherited or acquired – represent the leading cause of maternal morbidity and mortality in Western industrialised countries.2 Among these, peripartum cardiomyopathy (PPCM) is particularly important because of notable foetal and maternal morbidity and a significant contribution to maternal deaths in previously healthy women.3–5 Early diagnosis and immediate initiation of an appropriate therapy are crucial in improving the prognosis of this life-threatening disease in young women.3,6–11
Definition, Epidemiology and Risk Factors of Peripartum Cardiomyopathy The Study Group on PPCM of the Heart Failure Association (HFA) of the European Society of Cardiology defines PPCM as follows: “Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found. It is a diagnosis of exclusion. The left ventricle may not be dilated but the ejection fraction is nearly always reduced below 45 %.”10 Other causes of heart failure, such as pre-existing cardiomyopathy, pulmonary embolism, amniotic fluid embolism, and myocardial infarction should be ruled out by thorough evaluation of the patient’s history, physical examination and by means of electrocardiography and/or cardiovascular imaging (such as echocardiography or cardiac magnetic resonance imaging).6,8 The course of the disease can range from mild forms with unspecific symptoms, such as exercise intolerance, general discomfort and peripheral oedema, to severe forms with cardiogenic shock, including
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agitation, orthopnoea and lung oedema.8 Increasing awareness and better diagnostic and therapeutic insights have contributed to improved outcomes in PPCM patients over recent years.11–15 If treated according to published recommendations, approximately 50 % of all women recover fully (defined as left-ventricular ejection fraction [LVEF] ≥50 % and New York Heart Association [NYHA] functional class I) whereas an additional 35–40 % recover at least partially (defined as improvement of LVEF ≥10 % and at least one NYHA functional class).12 Delayed diagnosis can negatively influence prognosis in these previously healthy women. The incidence of PPCM differs widely depending on the ethnic and regional background of women. Interestingly, Africans and African Americans are at a higher risk for developing PPCM, with an estimated incidence of 1:100 in Nigeria, 1:299 in Haiti and 1:1,000 pregnancies in South Africa. Estimated incidences in Caucasian populations range from 1:1,500 in Germany to 1:10,149 in Denmark.4,10,12,16 An increase in incidence rates has been observed in the US in recent years. While the incidence was formerly reported to be one in 3,250 pregnancies, current data estimate an incidence of one in 1,150 pregnancies.15,17 This trend is also observed in Germany. This may be explained by rising maternal age, a higher number of fertility-assisted treatments and the higher incidence of hypertensive disorders of pregnancy. Higher awareness may also contribute to the detection of more cases with mild-to-moderate LV dysfunction. An ongoing, worldwide, multicentre, observational registry as part of the EURObservational Research Program (EORP) was initiated by the Study Group on PPCM of the HFA.18 The aim of the registry (https://www.escardio.org/Research/Registries‑&‑surveys/ Observational‑registry‑programme/PeriPartum‑CardioMyopathy‑ PPCM‑Registry) is to further investigate epidemiological data, patient characteristics and disease-specific outcomes.
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Cardiac Failure Review Volume 4 Issue 1 Spring 2018