The term peripartum cardiomyopathy (PPCM) was first introduced in 1971 by Demakis et al. and Demakis and Rahimtoola in their influential publications.1,2 Although heart failure associated with pregnancy and/or the peripartum period had been identified much earlier by Virchow and others in the 1800s,3,4 the dawn of echocardiography permitted the development of diagnostic criteria for PPCM in 1999.5

Traditionally, PPCM was defined as the development of heart failure in the last month of pregnancy or within five months postpartum in the absence of prior heart disease or an identifiable cause of heart failure, with left ventricular ejection fraction (LVEF) <45%, fractional shortening <30%, or both, with or without a left ventricular (LV) end-diastolic dimension (LVEDD) >2.7 cm/m2 body surface area.5 This definition was first approved by a workshop held by the US National Heart, Lung, and Blood Institute (NHLBI) and the Office of Rare Diseases. However, in 2010 it was updated and simplified by the Heart Failure Association of the European Society of Cardiology (ESC) Working Group on peripartum cardiomyopathy. Many patients present with PPCM before the 36th week of gestation, giving rise to widespread concerns that the NHLBI definition could lead to underdiagnosis.6 The ESC therefore proposed a simpler definition: “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%.”7

Irrespective of the diagnostic criteria, PPCM remains an overlooked or misdiagnosed condition. It is rare and is therefore not widely recognized among physicians, leading to delayed diagnosis and treatment. Counseling of women with a history of PPCM regarding risk of relapse in subsequent pregnancies is a challenge in the absence of definitive knowledge in this field. In this review we have attempted to summarize the current literature on the pathogenesis, presentation, and management of PPCM.

Few countries worldwide have definitive data on the incidence of PPCM. The reported incidence in a single center in South India was one case per 1541 live births,8 while in the US it ranges from ≈1 in 1000 to 1 in 4000 live births.9,10 Analysis of data from the US Nationwide Inpatient Sample database of 64 million hospital records identified 34219 cases of PPCM, with an incidence of 1 in 968 births. A worldwide registry on PPCM revealed 500 cases up to April 30, 2016, the incidence varying according to ethnicity, i.e. Caucasian (34%), Black African (25.8%), Asian (21.8%), and Middle Eastern backgrounds (16.4%).11 A literature search revealed the highest incidence in Haiti and Nigeria, with reported incidences of 1 in 300 and 1 in 100 live births, respectively,12,13 and the lowest in Japan, with an incidence of 1 in 15000 births.14 This wide range of incidence reflects different population demographics and uncertainty over definition, resulting in under-reporting and lack of awareness or misdiagnosis.

Isogai and Kamiya investigated the worldwide incidence of PPCM in 2019, highlighting various difficulties in determining its incidence accurately.14 Their search revealed only four prospective studies, all the others being retrospective. Lack of clarity on the pathogenesis and diagnostic criteria for PPCM means a large-scale prospective cohort study is required to determine an accurate incidence; however, the rarity of PPCM makes conducting such a study difficult.

Age over 30 years is associated with PPCM in more than 50% of cases.6 In a 2011 study, women's race and ethnicity was found to be associated with the occurrence of PPCM, with higher rates observed among non-Hispanic African American and Filipino groups and lower rates in Chinese and Hispanic women.10 The study showed that PPCM was more likely to occur in older women with four or more total births. Independent predictors of PPCM included severe anemia, multiple gestation, pre-existing and pregnancy-related hypertension, pre-eclampsia or eclampsia, and hemolysis, elevated liver enzymes and low platelets syndrome.10

Pre-eclampsia is a rare but important cause of peripartum cardiomyopathy.14 A meta-analysis of 22 studies including 979 cases revealed a 22% prevalence of pre-eclampsia in women with PPCM, four times the 3–5% population prevalence, and a hypertensive disorder was present in 37% of cases.15 The ESC's EURObservational Research Programme PPCM registry revealed that women with pre-eclampsia had more severe symptoms, more frequent signs of heart failure and a smaller LVEDD than women with no hypertensive disorder. However, they were likely to have better recovery.16

A higher incidence of peripartum cardiomyopathy among Nigerian women and the results of the PEACE registry may indicate that poor nutrition plays a role.17 Selenium deficiency among Nigerian women is reported to be a risk factor for PPCM,13,18 and selenium supplementation in patients with heart failure leads to improved outcomes.18

There is evidence that various mechanisms may be responsible for PPCM, including hemodynamic stresses of pregnancy, vasculo-hormonal factors, inflammation, immunology and genetics.18–28 These remain plausible etiologies, but none of them is definitive since PPCM is primarily considered an idiopathic myocardial disease of pregnancy.

Women with PPCM most commonly present in the last month of pregnancy or in the first five months postpartum with symptoms of dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, edema of the lower extremities, fatigue, chest pain and cough.17,21,36 A few patients may also present in cardiogenic shock, in which case a diagnosis of myocardial infarction (MI), pulmonary embolism (PE) or amniotic fluid embolism (AFE) should also be considered. A minority of patients present with severe arrhythmias.37 Physical examination may reveal pulmonary rales, raised jugular venous pressure, peripheral edema, tachypnea, and tachycardia with irregular peripheral pulses, displaced apical impulse, or murmurs of mitral and tricuspid regurgitation.

Associated conditions such as hypertensive disorders of pregnancy, pre-eclampsia, advanced maternal age, multifetal pregnancy and multiparity are risk factors for PPCM and should be suspected in women presenting with symptoms and signs of cardiac failure.20,33 Women with pre-eclampsia present with peripheral edema and pulmonary rales, increased serum creatinine levels, prolonged QRS duration and left bundle branch block.16

An initial 12-lead electrocardiogram will help in identifying associated arrhythmia and differentiating PPCM form certain other cardiac causes. No specific electrocardiographic (ECG) pattern is associated with PPCM, therefore conditions with specific ECG findings such as acute MI and right heart causes of heart failure including PE and AFE can be ruled out.

In the epidemiological setting of COVID-19, viral myocarditis may also be ruled out.38 In the presence of raised cardiac biomarkers and viral symptoms, viral panels should be performed or the presence of virus in the endocardium can be demonstrated with an endomyocardial biopsy, to rule out viral myocarditis. Natriuretic peptides, with a threshold of <100 pg/ml for B-type natriuretic peptide (BNP) and <300 pg/ml for N-terminal proBNP, play an important role in ruling out heart failure,21,39 since levels remain normal or are only slightly elevated during pregnancy and postpartum and are markedly elevated in PPCM.

Echocardiography should be used early in all cases of suspected PPCM to confirm the diagnosis, to assess associated cardiac conditions and their severity, and to exclude complications of PPCM such as thromboembolism. Prognostic information can also be obtained at the same time. Echocardiography will typically reveal LV dilatation, depressed systolic function, impaired diastolic function, reduced LVEF (<45%), biatrial dilatation, and increased pulmonary pressure resulting in moderate to severe tricuspid and mitral regurgitation.4,40 Annular dilatation secondary to marked LV enlargement leads to mitral regurgitation. The echocardiographic features are generally indistinguishable from those of primary idiopathic DCM and can be differentiated based on the onset of presenting symptoms. Idiopathic DCM generally presents during the second trimester and PPCM has a rapidly worsening clinical course with poor outcome.

Women with PPCM appear to have a more favorable outcome than those with other forms of cardiomyopathy. Mortality at six months ranged from 2% in Germany to 12.6% in South Africa, while mortality at 12 months was 4–14% and 7% at a mean follow-up of 19 months. Much of this information is from small studies of selected geographical populations.16,53,54

Women are recommended to undergo six-monthly echocardiography until LVEF recovers to >50% and annual visits for 10 years for women who remain stable after tapering of drug therapy for heart failure.21 Echocardiographic findings of persistent LV dilatation or reduced myocardial strain may be present in some patients despite normal LV function. In such patients life-long heart failure therapy should be continued.

Few studies have reported subsequent pregnancies in women with PPCM. Heart failure symptoms are more frequent in women whose LVEF had not normalized before a subsequent pregnancy. Therefore, all patients with persistent LV dysfunction should be advised against future pregnancies. All patients with previously diagnosed PPCM and their partners should receive careful counseling (class I recommendation) concerning the longer-term prognosis and undergo a risk stratification if further pregnancies are considered.54 Based on a recent publication reporting on the outcome of women with PPCM and subsequent pregnancy in cohorts from Germany, Scotland and South Africa, women with impaired systolic function are at substantial risk of relapse and death and should therefore be strongly advised against pregnancy. As any subsequent pregnancy in a woman with PPCM entails a substantial risk, those women should be monitored by an experienced multidisciplinary team throughout pregnancy and for at least one year postpartum.

PPCM remains an underdiagnosed peripartum disease due to its rarity. Women with symptoms consistent with heart failure should undergo clinical examination and cardiac biomarker testing, and echocardiography should be considered if these are abnormal. Tests of miR-146a and Fas/APO-1 may be useful bedside diagnostic modalities in the future. Heart failure should be managed according to current guidelines, respecting the safety limitations during pregnancy and breastfeeding. There is some evidence that bromocriptine might be helpful; a definitive trial is currently underway in the USA. Supportive therapy for heart failure should be initiated promptly and patient monitoring should be continued even after recovery of LV function. Women with PPCM or who experienced PPCM in a previous pregnancy should be managed by an experienced multidisciplinary pregnancy heart team. This should include careful pre-pregnancy reassessment and counseling.

Rajni Bala and Dr. Sakshi Mehta are employees of Adduct Healthcare Pvt. Ltd., Mohali, India. Vikas C. Roy, Geetika Kaur and Antonio de Marvao have no conflicts of interest to declare.