INTRODUCTION — Peripartum cardiomyopathy (PPCM, also called pregnancy-associated cardiomyopathy) is a rare cause of heart failure (HF) that affects women late in pregnancy or in the early puerperium [1]. Although initially described in 1849 [2], it was not recognized as a distinct clinical entity until the 1930s [3]. Earlier terms for this condition include toxic postpartum HF, Meadows syndrome, Zaria syndrome, and postpartum myocardiosis.

This topic will discuss the etiology, clinical manifestations, and diagnosis of PPCM. Treatment and prognosis of PPCM, critical illness during pregnancy and the peripartum period, HF during pregnancy, and issues related to pregnancy in women with acquired or congenital heart disease are discussed separately. (See "Peripartum cardiomyopathy: Treatment and prognosis" and "Critical illness during pregnancy and the peripartum period" and "Management of heart failure during pregnancy" and "Acquired heart disease and pregnancy" and "Pregnancy in women with congenital heart disease: General principles".)

DEFINITION — A variety of definitions have been used to identify PPCM [1,4-7]. The definition developed by the 2010 European Society of Cardiology (ESC) Working Group on Peripartum Cardiology is the most widely used and has been included in the 2018 ESC guidelines on management of cardiovascular diseases during pregnancy and in the position statement from the Heart Failure Association of the European Society of Cardiology Study Group on PPCM [1,7,8]. The definition is broad, as the Working Group sought to avoid underdiagnosis of PPCM [8].

The 2010 ESC Working Group defined PPCM as an idiopathic cardiomyopathy with the following characteristics:

●Development of heart failure (HF) toward the end of pregnancy or within five months following delivery.

●Absence of another identifiable cause for the HF.

●Left ventricular (LV) systolic dysfunction with an LV ejection fraction (LVEF) of less than 45 percent. The LV may or may not be dilated.

Additionally, some patients with LVEF between 45 and 50 percent may be diagnosed with PPCM if they have typical clinical features [8]. Prior definitions excluded cardiomyopathy that presented as HF before the last month of pregnancy [4-6], although the disease process is likely the same. The term pregnancy-associated cardiomyopathy (also known as early pregnancy-associated cardiomyopathy) has been used to describe this condition. The characteristics of early-onset disease were evaluated in a review of 123 women with a history of cardiomyopathy diagnosed during pregnancy [9]. One hundred women met the traditional criteria for PPCM, presenting at a mean of 38 weeks, and 23 presented earlier at a mean of 32 weeks. There were no differences between the two groups in terms of age, race, associated conditions, LVEF (29 versus 27 percent), the rate and time of recovery, and maternal outcomes. These observations suggest that patients with an early presentation are likely part of the spectrum of PPCM.

EPIDEMIOLOGY — A large prospective international registry of 411 women from 43 countries has demonstrated that PPCM occurs globally, affecting women from all ethnicities on all continents [10]. However, incidence rates vary widely depending on geographical location. Published incidences of PPCM range widely (figure 1) [1,5,11-23]:

●1:20,000 live births in Japan

●1:10,149 in Denmark

●1: 5719 in Sweden

●1:968 to 1:4000 in the United States

●1:2400 in Canada

●1:1000 in South Africa

●1:300 in Haiti

●1:100 in Zaria, Nigeria

It must be noted that this information is incomplete as incidence data are not available for many countries such as those in the Middle East, Asia, South America, and Australia. Also, the incidence of PPCM may be higher as milder forms may be missed.

The wide range in reported incidence may reflect an overestimation in studies that rely solely on clinical criteria to make the diagnosis (see 'Diagnosis' below). There may also be differences in search criteria and a lack of chart review when large national registries are used. The high incidence in Nigeria may be related to a local Hausa custom of eating kanwa, a dry lake salt for forty days after delivery. It has been suggested that the development of PPCM in these patients may be related in part to hypervolemia and possibly hypertension [15,24,25]. However, a genetic predisposition may also contribute to geographical variability.

The incidence of PPCM is also increasing [19]. This may be due to improved diagnosis and recognition but also increasing maternal age, preeclampsia, multiple gestations, and maternal cardiovascular risk factors.

ETIOLOGY — Despite many attempts to uncover a distinct etiology of PPCM, the cause remains unknown and may be multifactorial. While a number of potential factors have been evaluated and may contribute, experimental research suggests that these multiple factors result in a common final pathway with enhanced oxidative stress, cleavage of prolactin to an angiostatic N-terminal 16 kDA prolactin fragment, and impaired vascular endothelial growth factor (VEGF) signaling because of upregulated soluble fms-like tyrosine kinase (sFLT1) [1,16,26,27].

Angiogenic imbalance — Data from studies in mice and humans suggest that PPCM may be caused by systemic angiogenic imbalance [26,28-30]. Mice that lack cardiac PGC-1α, a regulator of pro-angiogenic factors such as VEGF, develop severe PPCM. The PPCM is rescued by dual pro-angiogenic therapy (VEGF plus bromocriptine).

These data may also explain why preeclampsia and multiple gestations are risk factors for PPCM [30-32]. During late gestation, the human placenta secretes VEGF inhibitors such as soluble fms-like tyrosine kinase (sFLt1), which also damages the vasculature, with higher levels seen with multiple gestation or preeclampsia [26]. Among women with preeclampsia, subclinical cardiac dysfunction (as detected by the myocardial performance index) correlates with sFlt1 levels.

Role of prolactin — Altered prolactin processing is believed to be involved in the pathogenesis of PPCM. Mice with a knockout in the cardiac tissue-specific signal transduction and activator of transcription 3 (STAT3) develop PPCM [33]. Reduction in STAT3 leads to increased cleavage of prolactin into an antiangiogenic and proapoptotic 16kDa isoform by cathepsin D. Thus, alterations in prolactin processing may contribute to the angiogenic imbalance described above. (See 'Angiogenic imbalance' above.)

The 16 kDa prolactin fragment (16K PRL) also causes endothelial damage and myocardial dysfunction [27]. 16K PRL induces microRNA-146a expression in endothelial cells, which leads to most of the anti-angiogenic effects of 16K PRL. Women with PPCM have elevated levels of microRNA-146a compared with healthy postpartum women or women with other cardiomyopathies [27].

Treatment with bromocriptine, an inhibitor of prolactin secretion, prevents the development of PPCM in these mice. Also, pharmacological inhibition of microRNA 146a attenuated PPCM in STAT3 knock-out mice without disturbing their nursing ability.

Reduced cardiac STAT3 levels have also been observed in terminally failing hearts from PPCM patients [33], but this is a nonspecific finding generally seen in end-stage dilated cardiomyopathy (DCM) [34]. It is unknown whether STAT3 levels are reduced in PPCM at an earlier stage of disease.

PI3K/Akt signaling postpartum results in more oxidative stress and subsequent generation of 16K PRL, which impairs the cardiac vasculature and leads to PPCM [35].

The potential role of prolactin as a target in the treatment of PPCM is discussed separately. (See "Peripartum cardiomyopathy: Treatment and prognosis", section on 'Bromocriptine'.)

Inflammatory cytokines — Inflammatory cytokines may play a role in the pathogenesis and progression of cardiomyopathy and heart failure (HF). The cytokines that are elevated in PPCM compared with controls include tumor necrosis factor (TNF)-alpha and interleukin-6 [36,37]. In addition, Fas/Apo-1, an apoptosis signaling receptor, and C-reactive protein are associated with more severe disease [37]. (See "Pathophysiology of heart failure with reduced ejection fraction: Hemodynamic alterations and remodeling", section on 'Other factors'.)

Myocarditis — Though some investigators have suggested myocarditis as a possible cause of PPCM [38-42], the role of myocarditis in PPCM is uncertain [43]. The following observations illustrate the range of findings:

●One study evaluated 11 African women in Nairobi who presented with the clinical features of PPCM [39]. Endomyocardial biopsies in five patients were consistent with a "healing" myocarditis. Of the nine patients with at least six months follow-up, three of four with myocarditis had persistent HF, while four of five with no or sparse evidence of myocarditis had improvement in HF symptoms and/or left ventricular (LV) size and function.

●In two other series, myocarditis was present in 4 of 14 and 14 of 18 patients with PPCM, respectively [40,41]. In comparison, myocarditis was present in only 5 of 55 patients (9 percent) in a comparator group with an idiopathic cardiomyopathy [40].

●Among 26 patients with PPCM who had evidence of interstitial inflammation, viral genomes were noted in eight (31 percent). Viral genomes have also been noted in other forms of myocarditis. (See "Myocarditis: Causes and pathogenesis", section on 'Viral or "idiopathic" myocarditis'.)

●In a nonrandomized study, three patients with PPCM and myocarditis were treated with prednisone and azathioprine and showed clinical improvement with no inflammatory infiltrate on repeat biopsy [38].

By contrast, a retrospective review of endomyocardial biopsy specimens from 34 patients fulfilling the clinical criteria for a diagnosis of PPCM found a lower incidence of myocarditis (9 percent) than that reported in other studies [43]. This incidence was comparable to that found in an age- and sex-matched control population undergoing transplantation for idiopathic DCM (9.1 percent).

The reason for the discrepancy among the various studies is unclear. In addition to small sample size, the timing of biopsy in relation to the onset of symptoms may also be important, since the incidence of inflammation is greater in patients who are biopsied soon after presentation [41,43]. Other potential reasons for the variability of the prevalence of myocarditis include: the inclusion of patients outside the accepted time frame of PPCM, variability among patient populations, and limitations of endomyocardial biopsy as a means of diagnosis of myocarditis. These limitations include sampling error (since myocardial involvement may be patchy) and variability in histologic criteria for myocarditis (ie, whether patients with borderline myocarditis were included together with those with active myocarditis as defined by the Dallas criteria) [5].

Abnormal immune response — It has been suggested that a maternal immunologic response to a fetal antigen can lead to PPCM. Fetal cells may escape into the maternal circulation and remain there without being rejected due to weak immunogenicity of the paternal haplotype of the chimeric cells [44]. If these cells lodge in the cardiac tissue, they can trigger a pathologic autoimmune response [5].

High titers of autoantibodies compared with controls have been described against normal human cardiac tissue proteins (including myosin), adenine nucleotide translocator, and branched chain alpha ketoacid dehydrogenase [5,45]. In addition, the immunoglobulins in patients with PPCM may be significantly different in frequency and reactivity to those in DCM cohorts and healthy donors [42]. In contrast to these findings, a study of humoral immunity in 39 Nigerian women with PPCM found no difference compared with controls in the levels of serum immunoglobulins, circulating immune complexes, or cardiac muscle antibodies between subjects and controls [46].

Overall, the available data are insufficient to establish whether abnormal maternal immunological response is the cause of PPCM. The observed autoantibodies may be secondary epiphenomena or contribute directly to myocyte injury.

Genetic predisposition — Evidence from several studies supports the hypothesis that PPCM may develop as a result of interaction between pregnancy-related factors (eg, late pregnancy oxidative stress) and a susceptible genetic background. Familial clustering of PPCM together with DCM has been observed and DCM-associated mutations have been identified in some patients with PPCM [47-49]. A study examined sequences of 43 genes with variants associated with DCM in each of 172 women with PPCM [50]. Twenty-six distinct truncating variants were identified in eight genes. The prevalence of truncating variants (26 of 172 or 15 percent) was similar to that seen in a cohort of patients with DCM (17 percent) but significantly higher than that seen in a reference population (4.7 percent). Two-thirds of identified truncating variants were in TTN, which encodes the sarcomere protein titin. Seven of the TTN-truncating variants were known to be associated with DCM. In a subgroup of 83 patients, the presence of a TTN-truncating variant was significantly correlated with lower LV ejection fraction (LVEF) at one-year follow-up. In fact, some patients with PPCM and these TTN-truncating variants may be presenting with an initial manifestation of familial DCM. Studies have reported that women with a family history of DCM have poorer recovery rates than those without a family history [47,49].

African genomic ancestry may be a risk factor for the development of PPCM and explain the high prevalence of PPCM in Haiti, Africa, and in Americans. It may also explain why Black patients have a delay in recovery of LVEF, and a higher proportion do not recover to an LVEF greater than 50 percent [51,52]. It has been demonstrated that the guanine nucleotide-binding proteins beta-3 subunit (GNB3) has a polymorphism called C825T [53]. This polymorphism is associated with an increased risk of hypertension, low plasma renin, and cardiac remodeling. It has a prevalence of 50 percent in Black individuals compared with 10 percent in White individuals. In a study of 97 women, the GNB3 TT genotype was associated with lower LVEF at 6 and 12 months in women with PPCM [53]. Given the higher frequency of this genotype in Black individuals, it is felt that it likely contributes to the lower LVEF recovery noted in Black women with PPCM.

PPCM may also develop in female carriers of X-linked forms of cardiomyopathies such as Duchenne or Becker muscular dystrophy and Danon disease [50,54,55].

Hemodynamic factors — During pregnancy, there is a 40 to 50 percent increase in blood volume and cardiac output, which results in transient LV remodeling and hypertrophy. It is possible that there is an exaggerated remodeling response with decrease in LV systolic function in women who develop PPCM. The hemodynamic stress of gestational hypertension, which is more common in women with PPCM, may contribute to the development of HF, though an angiogenic imbalance may better explain the association between preeclampsia and PPCM. (See 'Angiogenic imbalance' above.)

Risk factors — Although the etiology of PPCM remains unclear, the following are among the factors associated with increased risk of PPCM:

●Age greater than 30 years [3,4,9,11]

●African descent [56]

●Pregnancy with multiple fetuses [9,57]

●A history of preeclampsia, eclampsia, or postpartum hypertension [28]

●Maternal cocaine abuse [58]

●Long-term (>4 weeks) oral tocolytic therapy with beta adrenergic agonists such as terbutaline [59]

However, some of the above risk factors (preeclampsia, pregnancy-induced hypertension, and cocaine cardiomyopathy/hypertension disorder) are themselves etiologies of HF in late pregnancy. Studies of patients with PPCM have often excluded women with preeclampsia to avoid misclassification of patients. However, high incidences of preeclampsia are seen in patients with PPCM, suggesting that preeclampsia is associated with predisposition to PPCM through a shared pathophysiologic mechanism [10,28].

Diabetes has been reported as a risk factor for PPCM, but this relationship may be confounded by other risk factors such as hypertensive disorders during pregnancy [22].

There are conflicting data as to whether selenium deficiency is [60,61] or is not [62] a risk factor for PPCM.

Although multiparity has been traditionally considered a risk factor for PPCM, studies have shown that the majority of patients who develop PPCM do so during the first or second pregnancy [9,63,64].

In the United States, African Americans have a higher prevalence of PPCM compared with White Americans and may also have more severe disease. In a series comparing 52 African American and 104 White Americans with PPCM, African American patients were younger, had a higher prevalence of gestational hypertension, and had a lower rate of recovery of ventricular function, which resulted in a higher rate of the combined end point of mortality and cardiac transplantation [52,65]. Differences within countries may also exist in other populations. A retrospective study found that Aboriginal Canadian women with PPCM presented with lower LVEFs and larger LVs than other Canadian women with PPCM [66]. While there are differences in incidence and severity among ethnic groups, a prospective worldwide registry found that mode of presentation and mean age were similar across ethnic, socioeconomic, and geographic backgrounds [10]. The mean age at presentation was 31 years and then mean parity was 3.  

CLINICAL MANIFESTATIONS

Timing of presentation — PPCM is rarely seen before 36 weeks of gestation, and affected patients usually present during the first month postpartum [9,24,67].

In a report from the worldwide registry on PPCM that included 411 women, one-third of women presented prepartum [10]. Among women who presented prepartum, 21 percent have had a diagnosis of cardiomyopathy in a previous pregnancy. However, this rate is 10 percent in those from European Society of Cardiology countries versus 28 percent in those from non-European Society of Cardiology countries. While details are unavailable, it is likely that these previous episodes were PPCM.

Pregnant women with other types of cardiac disease (eg, ischemic, valvular, or myopathic) may present earlier in the antepartum period, coincident with increases in the hemodynamic burden imposed by the gravid state during the second trimester, though they may also present during the third trimester or postpartum [68]. Thus, although late presentation during pregnancy can be helpful to identify women with PPCM, the entire clinical picture should be considered. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes" and "Acquired heart disease and pregnancy".)

The majority of women with PPCM are diagnosed early after delivery during readmission after discharge [8]. No significant differences in demographics, presentation, or hospital outcomes are noted between those who present during pregnancy of after delivery.

Symptoms and signs — Presentation of PPCM is variable and similar to that in other forms of systolic HF due to cardiomyopathy [1]. Patients most commonly complain of dyspnea; other frequent symptoms include cough, orthopnea, paroxysmal nocturnal dyspnea, pedal edema, and hemoptysis. Initial diagnosis may be delayed since symptoms such as nonspecific fatigue, shortness of breath, and pedal edema are similar to those observed in normal pregnancy [4]. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

Physical signs may include an elevated jugular venous pressure, a displaced apical impulse, a third heart sound, and a murmur of mitral regurgitation [69]. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Physical examination'.)

Signs and symptoms of systemic or pulmonary thromboembolism may be present. Case series have reported varying rates of thromboembolism [16,70-72] and further data are needed to quantify the risk of this complication [1]. Patients with PPCM and left ventricular ejection fraction (LVEF) <35 percent are at risk for developing LV thrombus. As an example, LV thrombus was identified by echocardiography in 16 of 100 patients with PPCM (with mean LVEF of 26 percent) in one series [37]. (See "Overview of acute pulmonary embolism in adults" and "Overview of the evaluation of stroke".)

DIAGNOSIS

Overview — As noted above, the diagnosis of PPCM is based upon three clinical criteria [4-6]: development of heart failure (HF) toward the end of pregnancy or in the months following delivery, absence of another identifiable cause of HF, and left ventricular (LV) systolic dysfunction with an LV ejection fraction (LVEF) generally <45 percent [1]. The last criterion was added to prevent the inclusion of patients with disorders that mimic systolic HF [6,16]. Such disorders include accelerated hypertension, diastolic dysfunction, systemic infection, pulmonary embolism, or complications of late pregnancy (eg, preeclampsia or amniotic fluid embolus). Investigations should be directed to timely diagnosis and treatment.

An electrocardiogram (ECG) and echocardiogram should be performed in patients who are clinically suspected of having PPCM.

Other studies such as brain natriuretic peptide (BNP) levels, chest x-ray, cardiac magnetic resonance (CMR) imaging, cardiac catheterization, and endomyocardial biopsy (EMB) may be helpful in selected cases. One study has examined the use of invasive cardiac investigations in PPCM [73]. Using the national inpatient database in Japan, the authors identified 283 PPCM patients from 177 hospital from 2007 to 2014. They reported that invasive cardiac examinations such as coronary angiography and EMB are performed in less than one-quarter of patients.

Viral and bacterial cultures, as well as viral titers (eg, Coxsackie B), are generally not indicated. The results of these tests are nonspecific and thus without proven value in patients with myocarditis. (See "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Identifying the cause of myocarditis'.)

While novel markers, such as plasma concentrations of proangiogenic and antiangiogenic factors, including placenta growth factor, fms-like-tyrosine-kinase 1 receptor, and their ratios, have been proposed to be used to distinguish patients with PPCM, these studies are still very preliminary [74].

Electrocardiogram — ECG abnormalities may be found in up to 50 percent of PPCM patients, but a normal ECG does not exclude PPCM [75]. ECG findings in patients with PPCM are nonspecific and include sinus tachycardia (or rarely, atrial fibrillation) and nonspecific ST and T wave abnormalities. Q waves are occasionally present in the anterior precordium. PR and QRS intervals may be prolonged [4,12]. An ECG is helpful in identifying conditions in the differential diagnosis such as myocardial infarction and pulmonary embolism. (See 'Differential diagnosis' below.)

BNP — Measurement of plasma BNP or N-terminal pro-BNP (NT-proBNP) is suggested in the evaluation of patients with suspected HF when the diagnosis is uncertain. Women presenting with PPCM typically have elevated BNP and NT-proBNP levels that are higher than seen in healthy women during pregnancy or postpartum [76]. Measurement of BNP levels during pregnancy is discussed further separately. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Acquired heart disease and pregnancy", section on 'Brain natriuretic peptide' and "Natriuretic peptide measurement in heart failure".)

Chest radiograph — The chest radiograph typically shows enlargement of the cardiac silhouette with evidence of pulmonary venous congestion and/or interstitial edema, and, on occasion, pleural effusions. However, a chest radiograph is not necessary to make a diagnosis of HF or PPCM, and exposes the patient to ionizing radiation (table 1). (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Chest radiograph'.)

If, despite a thorough physical examination, the diagnosis of pulmonary edema is uncertain and a chest radiograph is deemed necessary to make that diagnosis, it can be considered and discussed with the pregnant patient. If a chest x-ray is performed during pregnancy, fetal shielding should be used. (See "Diagnostic imaging in pregnant and nursing patients".)

Echocardiography — The echocardiogram generally reveals a global reduction in LV systolic function with LVEF nearly always <45 percent [1]. The LV is frequently but not always dilated (image 1 and image 2) [1]. Doppler assessment of right ventricular systolic pressures can usually also be performed, making right heart catheterization unnecessary in most patients.

Other possible echocardiographic findings include left atrial enlargement, LV or left atrial thrombus, dilated right ventricle, right ventricular hypokinesis, mitral and tricuspid regurgitation, and rarely small pericardial effusion [77].

Cardiac magnetic resonance imaging — CMR is not generally required to make the diagnosis of PPCM but it can be helpful to assess LV systolic function and LV volumes, particularly if echocardiography is technically suboptimal. Experience with CMR in PPCM is limited and its role is still being evaluated [78-85].

Case reports and small series have noted variable presence of late gadolinium enhancement (LGE) in patients with PPCM [80-85]. This variability likely reflects the diverse processes that lead to PPCM. The presence and persistence of LGE may be associated with poor recovery of cardiac function [84]; improving LGE may be associated with cardiac recovery [81], while lack of LGE may be associated with presence or absence of cardiac recovery [83]. However, a later paper did not find a relationship between LGE and LVEF as only 2 of 40 women had LGE [86]. This suggests factors other than focal myocardial damage detectable by LGE may explain the transient LVEF depression in PPCM. However, in the two women with focal myocardial damage detected by LGE, persistent myocardial dysfunction and a lack of recovery were observed. Overall though, the prognostic value of CMR in PPCM has not been established. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Late gadolinium enhancement'.)

Magnetic resonance imaging and gadolinium administration during pregnancy are discussed separately. (See "Diagnostic imaging in pregnant and nursing patients", section on 'Fetal risks from magnetic resonance imaging' and "Diagnostic imaging in pregnant and nursing patients", section on 'Use of gadolinium'.)

Cardiac catheterization — Right heart catheterization is rarely needed because assessment of cardiac pressures can usually be made with physical examination and Doppler echocardiography. It may be helpful in critically ill patients who need more complete assessment or ongoing evaluation of their hemodynamic state.

Left heart catheterization with coronary angiography is only indicated in selected patients in whom it is deemed necessary to evaluate coronary artery disease as a potential cause for the cardiomyopathy (see "Non-ST-elevation acute coronary syndromes: Revascularization", section on 'Immediate angiography'). Diagnostic coronary angiography exposes the patient to ionizing radiation (equivalent to approximately 100 or more chest radiographs) (table 1), and therefore it is important to carefully consider the appropriate timing of testing, to discuss the risks of fluoroscopy with the patient, and to employ fetal shielding if the procedure must be performed during pregnancy. (See "Diagnostic imaging in pregnant and nursing patients".)

Endomyocardial biopsy — EMB is generally not required in patients with suspected PPCM. EMB is recommended in clinical scenarios in which a biopsy is anticipated to yield a diagnosis of a specific condition with treatment implications. These scenarios include heart failure with hemodynamic compromise of less than two weeks duration or heart failure of less than three months duration if associated with heart block, new ventricular arrhythmias, or refractory heart failure. EMB is not recommended for the routine evaluation of heart failure. (See "Endomyocardial biopsy".)

There are no pathognomonic findings in PPCM. As noted above, a variable proportion of patients have evidence of myocarditis. Other histologic findings in PPCM can include myofiber hypertrophy and/or degeneration, fibrosis, and interstitial edema [4,11]. The risk of a serious acute complication is <1 percent using flexible bioptomes. The decision whether or not to perform an EMB should be left to the discretion of the physician and patient.

DIFFERENTIAL DIAGNOSIS — PPCM is a diagnosis of exclusion. Some pre-existing cardiac lesions may become manifest during pregnancy due to pregnancy-associated hemodynamic changes (see "Acquired heart disease and pregnancy", section on 'Physiology of normal pregnancy'). As noted in the 2010 European Society of Cardiology working group statement on PPCM, the following conditions should be considered in the differential diagnosis [1,87]:

●Pre-existing cardiomyopathy: Types of cardiomyopathy that may be unmasked during pregnancy include idiopathic dilated cardiomyopathy, familial dilated cardiomyopathy, or HIV/AIDS cardiomyopathy (which often presents without ventricular dilatation). In patients with a pre-existing cardiomyopathy, heart failure is more likely to manifest antepartum in contrast to PPCM, which most commonly presents postpartum, though there is overlap in the timing of presentation of these conditions. (See "Acquired heart disease and pregnancy", section on 'Cardiomyopathy'.)

●Pre-existing acquired or congenital valvular heart disease unmasked by pregnancy may present in the antenatal period in contrast to PPCM, which generally presents postpartum, though there is overlap in the timing of presentation of these conditions. Mitral stenosis, most commonly from rheumatic heart disease, is seen in women from endemic regions. Aortic stenosis, aortic regurgitation, and mitral regurgitation are other valve lesions that cause heart failure during pregnancy. Valvular heart disease is diagnosed by physical examination and echocardiography. (See "Pregnancy and valve disease".)

Some patients with PPCM also have significant valvular disease, particularly mitral regurgitation.

●Pre-existing undetected congenital heart disease. Aside from bicuspid valve disease, the most common congenital lesions that may be first diagnosed during pregnancy are atrial septal defects, ventricular septal defects, and patent ductus arteriosus. The clinical presentation and echocardiography are helpful in distinguishing these lesions. (See "Pregnancy in women with congenital heart disease: Specific lesions".)

●Diastolic heart failure due to hypertensive heart disease. This diagnosis is suggested by a prior history of severe hypertension and consistent findings on echocardiography. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

●Myocardial infarction. Although myocardial infarction is rare in women of childbearing age, some studies have suggested an increased risk during pregnancy and during the early postpartum period. Causes of myocardial infarction during pregnancy include coronary artery dissection, coronary artery disease, coronary embolus/thrombosis (in a normal coronary artery), and coronary artery spasm. Risk factors include older maternal age, hypertension, diabetes mellitus, and obesity. Clinical manifestations include anginal chest pain, electrocardiogram changes, elevations in cardiac biomarkers, and regional wall motion abnormalities on echocardiography. (See "Acute myocardial infarction and pregnancy".)

●Pulmonary embolus. Pregnancy and the early postpartum period are associated with increased risk of venous thrombosis and pulmonary embolism but diagnosis of pulmonary embolus can be challenging. The presence of dyspnea without evidence of heart failure favors the diagnosis of pulmonary embolus over PPCM. Pulmonary embolus can be diagnosed by lung scintigraphy or computed tomographic pulmonary angiography, as discussed separately. (See "Diagnosis of pulmonary embolism in pregnancy", section on 'Differential diagnosis of PE'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults" and "Society guideline links: Cardiomyopathy" and "Society guideline links: Management of cardiovascular diseases during pregnancy".)

SUMMARY AND RECOMMENDATIONS

●Peripartum cardiomyopathy (PPCM) is defined as the development of systolic heart failure towards the end of pregnancy or in the months following pregnancy with left ventricular ejection fraction (LVEF) generally less than 45 percent in the absence of another identifiable cause of heart failure. (See 'Definition' above and 'Differential diagnosis' above.)

●The etiology of PPCM is unknown, with possible causes including angiogenic imbalance, altered prolactin processing, genetic, inflammatory, hormonal, hemodynamic, and autoimmune factors. (See 'Etiology' above.)

●A number of risk factors for PPCM have been identified, including greater age, multiple gestation, African descent, and a history of preeclampsia, eclampsia, or postpartum hypertension. (See 'Risk factors' above.)

●The clinical presentation of PPCM is variable and similar to that in other forms of systolic heart failure due to cardiomyopathy. (See 'Clinical manifestations' above.)

●The echocardiogram generally reveals global reduction in LV systolic function with LVEF nearly always <45 percent. The LV is frequently but not always dilated. (See 'Echocardiography' above.)