Peripartum cardiomyopathy: Treatment and prognosis

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, Meadow syndrome, Zaria syndrome, and postpartum myocardiosis.

Treatment of PPCM is similar to the treatment of other types of HF with left ventricular (LV) systolic dysfunction. However, modifications to standard therapy are often necessary to ensure the safety of the mother and the unborn or breastfeeding child. (See "Management of heart failure during pregnancy", section on 'Management goals'.)

Etiology, clinical manifestations, and diagnosis 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: Etiology, clinical manifestations, and diagnosis".)

●(See "Critical illness during pregnancy and the peripartum period".)

●(See "Management of heart failure during pregnancy".)

●(See "Acquired heart disease and pregnancy".)

●(See "Pregnancy in women with congenital heart disease: General principles".)

COMPONENTS OF THERAPY — In women with PPCM and HF, many of the treatment goals of are similar to those in patients with acute and chronic HF with reduced ejection fraction due to other causes. However, additional considerations of fetal and neonatal risks of medications and/or treatments, labor and delivery plans (timing of delivery, mode of delivery, cardiac monitoring during delivery), postpartum care, and counseling about future pregnancy risks need to be included in management planning. Medication choices may vary according to the timing of presentation (antenatal versus postpartum) and whether patients are breastfeeding.

General goals of care include:

●Heart failure (HF) goal-directed medical therapy

•Symptom relief

•Decrease pulmonary congestion

•Preload and afterload optimization, including afterload reduction when appropriate

●Hemodynamic support with inotropes and vasopressors if required

●If PPCM is diagnosed intrapartum, patients should be medically optimized prior to delivery when possible

●Multidisciplinary team planning of labor, delivery, and postpartum care

●When possible, institute chronic therapies that improve long-term outcomes

●Shared decision-making about contraception

●Education about future pregnancy risks

ACUTE MANAGEMENT — Treatment of PPCM is generally similar to treatment for other types of heart failure (HF) with reduced ejection fraction. However, several medications used in nonpregnant patients are not safe or do not have sufficient safety data in pregnancy to support their use. Additional therapeutic issues for this population may include arrhythmia management, anticoagulation therapy, mechanical support, and therapies such as bromocriptine (algorithm 1) [4].

For women with PPCM who have delivered and are not breastfeeding, acute and chronic HF are managed using standard therapy. (See "Treatment of acute decompensated heart failure: Specific therapies" and "Overview of the management of heart failure with reduced ejection fraction in adults".)

Initial management — We use supplemental oxygen and assisted ventilation as needed. If the patient presents during pregnancy, referral to a cardio-obstetrics team and careful labor and delivery planning may be required; patients may require transfer to hospitals with advanced HF capabilities. (See 'Delivery' below.)

Excluding other causes of HF may be necessary, especially if the diagnosis of PPCM is not certain. This may include tests such as computed tomography angiography, coronary angiography, or cardiac magnetic resonance imaging.

Due to the unique issues related to pregnancy and the peripartum period, each therapeutic decision has additional implications. The treatment of HF in pregnant and breastfeeding patients is discussed in detail separately. (See "Management of heart failure during pregnancy", section on 'Treatment regimens'.)

During the antenatal period, we avoid the use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin receptor-neprilysin inhibitors, sodium-glucose luminal cotransporter-2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists, as they are contraindicated in pregnancy. Diuretics, beta blockers, hydralazine/nitrates, digoxin, and inotropes can be used for the treatment of PPCM during the antenatal period. There are many nuances to the care of pregnant patients, and treatment decisions should take into account clinical status, left ventricular ejection fraction (LVEF), presence of arrhythmia, recovery trajectory, pregnancy status, and whether patients are breastfeeding:

●Betablockers. (See "Management of heart failure during pregnancy", section on 'Beta blockers'.)

●Isosorbide. (See "Management of heart failure during pregnancy", section on 'Vasodilators'.)

●Hydralazine. (See "Management of heart failure during pregnancy", section on 'Hydralazine plus nitrate'.)

●Loop or thiazide diuretics. (See "Management of heart failure during pregnancy", section on 'Diuretics'.)

●Digoxin. (See "Management of heart failure during pregnancy", section on 'Digoxin'.)

●Dopamine or dobutamine. (See 'Ionotropes' below.)

Antithrombotic therapy — Our approach to antithrombotic therapy in patients with PPCM is the same as our approach to antithrombotic therapy for any patients with LV systolic dysfunction (with or without HF). Therefore, for patients with LV systolic dysfunction (with or without HF) without LV thrombus or other indications for antithrombotic therapy, we do not use antiplatelet or anticoagulant therapy (see "Antithrombotic therapy in patients with heart failure", section on 'Our approach').

However, experts differ in their approach to anticoagulation, and some routinely give anticoagulation to patients with PPCM with severe LV systolic dysfunction [5,6]. This is because patients with PPCM are at high risk for thrombus formation and thromboembolism due to both the hypercoagulable state of pregnancy and stasis of blood due to severe LV dysfunction [7,8]. Approximately 7 percent will have a peripheral arterial or venous thromboembolism within the first 30 days after delivery [9]. However, data are inconclusive on the utility of antithrombotic therapy (antiplatelet therapy or anticoagulation) to reduce thromboembolic events or mortality in patients with systolic HF who are in sinus rhythm. (See "Antithrombotic therapy in patients with heart failure", section on 'Role of antithrombotic therapy'.)

Among patients with PPCM, we consider anticoagulation with antithrombotic therapy in the following settings:

●Definite thrombus – We suggest anticoagulation for patients with PPCM who have acute intracardiac thrombus or evidence of systemic embolism. This recommendation is consistent with recommendations for management of acute ventricular thrombus or thromboembolism in patients with HF generally. (See "Antithrombotic therapy in patients with heart failure", section on 'Role of antithrombotic therapy'.)

●Atrial fibrillation – Standard guidelines for antithrombotic therapy for atrial fibrillation should be followed in patients with PPCM and atrial fibrillation, including recommending anticoagulation for patients with PPCM with HF and atrial fibrillation. (See "Atrial fibrillation in adults: Use of oral anticoagulants".)

●Concomitant bromocriptine – We suggest anticoagulation in patients with PPCM treated with bromocriptine; anticoagulation in this setting has not been investigated in controlled trials [10]. Thromboembolic events (including stroke and myocardial infarction) have been reported as a complication of bromocriptine use in patients with PPCM [11]. In a clinical trial of two different dosing regimens of bromocriptine, two patients had a venous thromboembolism, and one had a peripheral arterial occlusion [12]. (See 'Bromocriptine or antiprolactin therapy' below.)

For pregnant women who require anticoagulation, choosing a specific anticoagulation regimen is challenging due to differing risks during each stage of pregnancy. These include the potential teratogenic effects of warfarin in the first trimester, dosing complexities of the various agents, management during labor and delivery, and the risk of postpartum hemorrhage. These issues are discussed in detail separately. (See "Use of anticoagulants during pregnancy and postpartum".)

Bromocriptine or antiprolactin therapy — Bromocriptine acts by blocking the release of prolactin from the pituitary, which is theorized to potentiate PPCM. While preliminary data have suggested a benefit from bromocriptine in patients with PPCM, further trials are needed to establish safety and efficacy. Until additional data are available, we suggest against routinely using bromocriptine for patients with PPCM. Some other experts advocate using bromocriptine routinely for patients with PPCM [5].

If bromocriptine is used, anticoagulation should also be started to prevent thromboembolic events. Bromocriptine stops the production of breast milk, precluding breastfeeding.

The dose for bromocriptine is 2.5 mg once daily for at least one week in uncomplicated cases. In those with LVEF <25 percent and/or shock, the dose is 2.5 mg twice daily for two weeks, then 2.5 mg once daily for six weeks [13].

●Evidence of efficacy – Use of bromocriptine for PPCM is based upon an experimental observation of prevention of PPCM in mice via prolactin blockade with bromocriptine [14]. Small randomized studies and several observational reports have suggested beneficial responses to bromocriptine therapy in patients with PPCM, including enhanced recovery of left and right ventricular function [4,12,15-20].

In a randomized open-label study performed in South Africa, 20 women with newly diagnosed PPCM were randomly assigned to receive either standard care plus bromocriptine (2.5 mg twice daily for two weeks followed by 2.5 mg daily for six weeks) or standard care alone [4]. The following findings were noted in those assigned bromocriptine compared with usual care:

•Greater improvement in LVEF (27 to 58 percent versus 27 to 36 percent).

•Fewer numeric deaths (1 versus 4; no statistical test was performed for this comparison).

•Fewer patients had the composite end point of death, New York Heart Association functional class III or IV HF (table 1), or LVEF <35 percent at six months (1 versus 8; p = 0.006).

The generalizability of these results is unclear given the small sample size, the higher-than-expected mortality rate in the standard-care group, and differences in characteristics of PPCM in patients in Africa as compared with those elsewhere [21].

A trial from Germany enrolled 63 women with PPCM and LVEF ≤35 percent and randomly assigned short-term bromocriptine (one week of 2.5 mg daily) or long-term bromocriptine (eight weeks: 5 mg for two weeks, followed by 2.5 mg for six weeks) [12]. The following findings were noted:

•Improvement in LVEF at six months was similar in the two groups (28 to 49 percent in the one-week group and 27 to 51 percent in the eight-week group).

•The frequency of full recovery (LVEF ≥50 percent) was numerically but not statistically higher in the eight-week group compared with the one-week group (68 versus 52 percent; odds ratio 0.51; 95% CI 0.17-1.49).

•None of the patients required heart transplantation, LV assist devices, or died during the study period.

Notably, a placebo control group was not included in the study; investigators indicated that it was not considered ethical to include such a group based on prior evidence of potential efficacy.

Large ongoing multicenter trials assessing the role of bromocriptine for PPCM are ongoing.

Globally, there are differences in bromocriptine use for PPCM. In North America, use of bromocriptine in this setting continues to be viewed as experimental, as noted in a 2020 review by North American PPCM experts [6]. In the North American IPAC study, only 1 of 100 patients was treated with bromocriptine [22]. In contrast, some European experts suggest bromocriptine use, as reflected by the 2018 European Society of Cardiology guidelines for management of cardiovascular diseases during pregnancy, which included a weak recommendation for bromocriptine use for PPCM [13]. The 2019 position statement from the Heart Failure Association of the European Society of Cardiology Study Group on PPCM also included a weak recommendation for bromocriptine use [5]. A meta-analysis found that 87.5 percent of European PPCM patients in literature are treated with bromocriptine or cabergoline, and such treatments were associated with improved outcomes (improved LVEF and less death) [23].

As noted above, we suggest anticoagulation in patients with PPCM treated with bromocriptine (when this investigational therapy is used) given the risk of thromboembolic complications [13]. (See 'Antithrombotic therapy' above.)

The 2019 position statement from the Heart Failure Association of the European Society of Cardiology Study Group on PPCM suggested that cabergoline be used as an alternative to bromocriptine if bromocriptine is not available [5]. We do not use cabergoline in this setting since supportive data are limited to observational studies and case reports [24,25].

Management of sequelae

Cardiogenic shock — Patients with acute decompensated HF and systolic dysfunction who are hypotensive or who remain in pulmonary edema despite oxygen, diuresis, and, if tolerated, vasodilators, may benefit from intravenous inotropic support.

Ionotropes — Norepinephrine, milrinone, and levosimendan can be used for ionotropic support in pregnant patients. These agents are discussed in detail separately. (See "Management of heart failure during pregnancy", section on 'Inotropes'.)

Mechanical circulatory support — In unstable patients with PPCM, temporary short- and intermediate-term mechanical circulatory support (MCS) devices may be used as an escalation strategy to manage cardiogenic shock or cardiorespiratory failure refractory to optimal medical therapy. Patients with PPCM should be seen in centers with advanced HF services. Short-term MCS should be considered early in patients who are hemodynamically unstable and unresponsive to medical therapy with maximal inotropic support. (See "Short-term mechanical circulatory assist devices".)

●Types of devices – When MCS is indicated, devices that can be used include intraaortic balloon counter pulsation, venoarterial extracorporeal membrane oxygenation (ECMO), and LV assist device [10]. The choice of which initial device to implant will depend on patient hemodynamics and local availability and expertise.

Venoarterial ECMO has been associated with an increase in prolactin levels, which may be detrimental in patients with PPCM [26]. However, we do not use bromocriptine to suppress prolactin levels in patients receiving venoarterial ECMO, as there is little evidence to support this treatment [27]. Some experts have suggested administration of bromocriptine doses up to 10 mg twice daily to suppress prolactin levels in patients receiving venoarterial ECMO with significantly elevated prolactin levels [5].

●Efficacy – Outcomes were reported for 99 women with PPCM, who had received durable MCS [28]. Those who received durable MCS had a two-year survival of 83 percent. However, rates of recovery of myocardial function were poor at 6 percent.

Indications and use of MCS are discussed separately. (See "Short-term mechanical circulatory assist devices" and "Treatment of advanced heart failure with a durable mechanical circulatory support device" and "Management of long-term mechanical circulatory support devices".)

Arrhythmia — Arrhythmias are common among patients hospitalized for PPCM [29].

●Ventricular arrythmia and cardiac arrest – The reported incidence of ventricular arrhythmias has been variable. A large inpatient database study reported that of 9841 hospitalizations for PPCM, 18.7 percent had an arrhythmia, with ventricular tachycardia occurring in 4.2 percent and cardiac arrest in 2.2 percent. Much smaller series have reported cardiac arrest rates between 20 and 25 percent [30,31].

Management is discussed separately. (See "Ventricular arrhythmias during pregnancy".)

●Atrial fibrillation – Atrial fibrillation also occurs commonly and was observed in 3 to 12 percent of patients with PPCM in various studies [30,32,33]. Management is discussed separately. (See "Supraventricular arrhythmias during pregnancy".)

Delivery — Limited data are available to guide the timing and mode of delivery in PPCM. Timing and mode of delivery plan depend on the clinical status of the patient and the degree of fetal maturity. The risks and benefits of early delivery should be considered and discussed with the patient in a shared decision-making discussion. Decisions regarding timing and mode of delivery should be based on combined input from the cardio-obstetric team including cardiology, obstetrics, anesthesiology, and neonatology services [1]. In this regard, multidisciplinary conferences are necessary.

Unstable patients — We stabilize the mother prior to delivery if possible. In women with PPCM with advanced HF and hemodynamic instability despite medical therapy, we suggest prompt delivery for maternal cardiovascular indications. Urgent delivery may be required in women with advanced HF with hemodynamic instability [5]. For patients with advanced HF requiring inotropic therapy or MCS, we prefer planned cesarean delivery with central neuraxial anesthesia [1,5,34]. (See "Cesarean birth: Preoperative planning and patient preparation" and "Anesthesia for cesarean delivery".)

Stable patients — In hemodynamically stable women with no absolute indication for cesarean delivery, we advise vaginal delivery with close hemodynamic monitoring and epidural analgesia [5]. (See "Neuraxial analgesia for labor and delivery (including instrumental delivery)".)

The 2010 European Society of Cardiology working group statement advised that early delivery is not required if the maternal and fetal conditions are stable [1]. However, patient-specific issues, including gestational age, cervical status, fetal status, and the potential cardiovascular impact of continuing pregnancy should be considered in timing of delivery. As for women with other types of cardiac conditions, cesarean delivery in patients with stable cardiovascular status is generally reserved for obstetrical indications (eg, failure of progression of labor, placenta previa, fetal intolerance of labor). (See "Acquired heart disease and pregnancy", section on 'Mode and timing of delivery'.)

Breastfeeding — Whereas some experts discourage breastfeeding, others advise that clinically stable patients continue breastfeeding as long as it is compatible with their cardiovascular medications. Differing views are summarized as follows:

●The 2018 European Society of Cardiology guidelines for the management of cardiovascular diseases during pregnancy suggest that prevention of lactation be considered in patients with severe HF because of the potential effects of prolactin subfragments and the high metabolic demands of lactation and breastfeeding [13]. (See "Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis", section on 'Role of prolactin'.)

●In one registry study, 37 of 55 patients chose to breastfeed; none had adverse maternal effects, and rate of recovery of LV function was higher in lactating versus non-lactating women (39.5 versus 8.3 percent) [35]. A limitation of this analysis was the lack of adjusting for any confounders.

If a decision is made to proceed with breastfeeding, we suggest avoiding angiotensin II receptor blockers due to lack of safety data. (See "Management of heart failure during pregnancy", section on 'Avoid angiotensin inhibition'.)

Investigational therapy — We do not use the following investigational therapies for PPCM since the efficacy and safety of these approaches have not been established.

●Immunosuppressive agents – Immunosuppressive therapy is not recommended for PPCM [1]. Although immunosuppressive therapy has been reported in patients with PPCM and biopsy-proven myocarditis in an observational study [36], its efficacy is unclear. Therefore empiric immunosuppression, in the absence of evidence of a responsive form of myocarditis (eg, giant cell myocarditis), is not recommended [37]. These drugs often have significant side effects, and studies in other forms of myocarditis have not shown clear benefit from immunosuppressive therapy [38]. (See "Treatment and prognosis of myocarditis in adults", section on 'Immunosuppressive therapy'.)

●Intravenous immune globulin – Intravenous immune globulin (IVIG) has no clear clinical benefit for patients with myocarditis or recent-onset dilated cardiomyopathy. A retrospective study of six women with PPCM treated with IVIG and 11 historical controls found a greater increase in LVEF at six months in patients treated with IVIG compared with controls (26 versus 13 percent) [39]. However, the efficacy of this approach has not been confirmed in clinical trials for PPCM or myocarditis. (See "Treatment and prognosis of myocarditis in adults", section on 'Intravenous immune globulin'.)

●Other investigational therapies – Administration of antisense therapy against microRNA-146a is an attractive potential option, as it would allow lactation. It has been tested in mouse models and was found to be effective in lessening the development of systolic dysfunction but did not fully reverse PPCM [40]. Treatment in humans has not been tried to date.

A case report described use of apheresis to remove circulating soluble fms-like tyrosine kinase-1 (sFlt-1) in a woman with severe PPCM requiring prolonged biventricular assist device support [29]. The safety and efficacy of apheresis in this setting has not been determined.

LONG-TERM MANAGEMENT — The management of PPCM is summarized in an algorithm (algorithm 1).

Patients with recovery of left ventricular function — With appropriate therapy, nearly 60 percent of patients with PPCM will achieve full recovery of left ventricular (LV) function (LV ejection fraction [LVEF] >50 percent). (See 'Recovery of left ventricular function' below.)

Although there are no studies examining long-term medical therapy in this population, in those patients with normal LV function (LVEF >50 percent) for a period of at least six months, we suggest stepwise weaning of the HF regimen with close clinical follow-up (eg, every three to four months) and with echocardiographic monitoring (eg, every six months) to ensure stability of LV function during and for at least one to two years after weaning of HF medications to ensure stability.

●Weaning protocol example – An example of such a protocol from 2015 is described in a review by PPCM experts, as follows [41]:

•If LV structure and function have recovered and remain normal for six months, mineralocorticoid receptor antagonist (eg, spironolactone) is withdrawn with continuation of beta blockade and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers.

•If six months after stopping the mineralocorticoid receptor antagonist, LV function remains normal and the patient remains free of clinical heart failure (HF) symptoms, withdrawal of the angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker is suggested. The patient then continues on beta blockade alone.

•If there is no decline in LV function, the patient is then weaned from beta blocker therapy, preferably over a period of two to four weeks to avoid rebound phenomena, and again with close clinical monitoring and echocardiographic follow-up.

•If the patient is free of congestive symptoms, loop diuretics or thiazides may be discontinued at any time (even before full recovery of LV function); recurrence of congestive symptoms would prompt reintroduction of these medications.

●Reinstitution of HF therapy – A decline in LV systolic function as documented by echocardiographic assessment, or the recurrence of HF symptoms at any point in the process of weaning HF medications, would dictate a reinstitution of standard HF therapy.

These recommendations are based on expert opinion only; there is a paucity of data in this area to guide clinicians. Therefore, it is imperative that if HF therapies are withdrawn, the patient should be followed clinically and by echocardiography to ensure stability, as described above.

Patients with recurrent left ventricular dysfunction — LV dysfunction can reoccur despite initial full recovery, and this recurrence risk is not limited to subsequent pregnancies. For patients with recovery of LV function, there are limited studies examining the relationship between medication withdrawal and clinical outcomes, and there are no major societal guidelines regarding this management pathway. Clinical markers (ie, contractile reserve on stress echocardiography) or biomarkers that may predict outcomes in this group are under study.

Durable mechanical circulatory support — In patients with PPCM who have advanced HF refractory to optimal medical and device-based therapies, long-term mechanical circulatory support (MCS) with a ventricular assist device or artificial heart may be an option. These devices can reduce the risk of death and improve quality of life. Durable MCS can be offered to in patients as a bridge to transplant, a bridge to evaluation for transplant, or as destination therapy. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".)

In patients with PPCM, a severely depressed baseline LVEF alone should not be considered an indication for use of aggressive therapies such as MCS and cardiac transplantation. In PPCM, lower baseline LVEF is associated with lower likelihood of recovery of LVEF with medical management as discussed below. However, the baseline LVEF does not adequately predict the probability of recovery in individual patients. (See 'Maternal outcome' below.)

Cardiac transplantation — Cardiac transplantation is reserved for patients who have refractory severe HF symptoms despite maximal therapy.

●Prevalence of cardiac transplantation – Older studies found that transplantation was performed in up to one-third of women with PPCM [36,42,43]. Contemporary reports demonstrate that transplantation rates vary from 4 to 23 percent of patients [44-48]. Thus, women with PPCM and significant LV systolic dysfunction should be managed at a center with transplant capabilities. (See "Heart transplantation in adults: Indications and contraindications".)

●Outcomes in patients with PPCM – In addition to the potential maternal and fetal risks related to pregnancy after heart transplantation for any reason, women who have been transplanted for PPCM have worse outcomes compared with other cardiac transplant recipients. Women with PPCM who received a cardiac transplant had higher mortality, higher incidence of rejection, poorer graft survival, and higher retransplantation rates. The factors underlying these poorer outcomes include younger patient age, higher allosensitization, higher pretransplant acuity, and increased rejection rates. The largest series of cardiac transplantation for PPCM included 809 PPCM patients derived from 20,352 females from the United Network for Organ Sharing database. This study found that transplant recipients with PPCM had a higher risk of one-year mortality compared with nonischemic cardiomyopathy patients (hazard ratio 1.38; 95% CI 1.11-1.69) [49]. The 5-, 10-, and 15-year survivals in patients with PPCM were 66.5, 49, and 40.2 percent compared with 74.3, 56, and 37.5 percent in female heart transplant recipients with other HF diagnoses.

Device therapy — When considering the use of device therapies, we use similar indications for patients with PPCM compared with other forms of cardiomyopathy. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Our approach for patients with nonischemic dilated cardiomyopathy' and "Cardiac resynchronization therapy in heart failure: Indications and choice of system".)

Specific indications for use of implantable cardioverter-defibrillator (ICD) therapy have not been established for PPCM [1], since scant evidence on use of these devices is available in this patient population [50]. When considering device therapy, we take into account the natural history of PPCM, including the potential of recovery of ventricular function [1]. Up to 20 to 70 percent of women with PPCM have complete recovery of LVEF to normal by 3 to 12 months [22]. (See 'Recovery of left ventricular function' below.)

Potential device therapies for patients with PPCM who have advanced HF are presented in the following sections.

Implantable cardioverter-defibrillator for prevention of sudden cardiac — death — In patients with PPCM who do not have significant ventricular arrhythmias, ICD placement should generally be deferred for at least six months following presentation, with the patient receiving optimum medical therapy to determine whether criteria for placement are present.

Whether a wearable defibrillator would prevent sudden cardiac death in those being monitored for LVEF improvement is unclear [31,51]. A registry study has demonstrated that wearable defibrillators do deliver appropriate shocks for ventricular fibrillation within the first months after diagnosis [31]. However, a wearable defibrillator is not without its risks and concerns. The role of implantable loop recorders in detecting arrhythmias in this population is also unclear.

Cardiac resynchronization therapy — This is used as an advanced HF therapy that can improve LV systolic function, symptoms of HF, survival for selected patients with LV systolic dysfunction, and electrocardiographic evidence of ventricular dyssynchrony. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".)

Information on the use of cardiac resynchronization therapy in PPCM is limited. One observational case series of eight patients with PPCM suggests that resynchronization in medically optimized patients resulted in improved systolic function and cardiac remodeling [52].

Cardiac resynchronization therapy should generally be deferred until at least six months following presentation, with the patient receiving optimum medical therapy to determine whether criteria for placement are present.

FUTURE PREGNANCY

Risks and contraception advice — Women with PPCM should receive counseling regarding the risk of recurrence with subsequent pregnancies [1].

Recovery of left ventricular function — Although the risk of recurrence appears to be lower in women with PPCM with recovered left ventricular (LV) function, such patients should receive counseling, including the option of avoidance of subsequent pregnancy, due to the risk of relapse of PPCM.

Among women in whom LV function returns to normal, the risk of LV dysfunction during subsequent pregnancy appears lower than for those with persistent LV dysfunction, but elevated compared with the general population [53-55].

In a series of 28 women who recovered to an LV ejection fraction (LVEF) ≥50 percent after the initial episode, the following results in subsequent pregnancies were noted [53]:

●There were no deaths

●There was a reduction in the mean LVEF (56 to 49 percent), and the LVEF fell by more than 20 percent in six women (21 percent)

●Six of 28 patients developed HF symptoms

The persistent risk in such women may be related to subclinical residual dysfunction that is not detected on resting evaluations. In a report of seven women with a history of PPCM who regained normal resting LV size and performance [56], contractile reserve, assessed by dobutamine challenge, was significantly impaired compared with matched controls. Other small preliminary studies of the value of dobutamine stress echocardiography to predict recovery of LV function have yielded mixed results [57,58].

Persistent left ventricular dysfunction — Although limited data are available, we suggest that patients with PPCM with persistent LV dysfunction (LVEF <50 percent) or LVEF ≤25 percent at diagnosis should be advised to avoid a subsequent pregnancy due to the risk of HF progression and death [1]. The available data on risk of recurrence of PPCM come from several small studies, which suggest that the risk of complications is high, particularly among women who do not have full recovery of LV function. Also, a small study suggested that women with PPCM may have reduced fertility [59].

In subsequent pregnancies, patients with persistent LV systolic dysfunction from PPCM are at risk of adverse outcomes, including mortality. This has been quantified in small case series [53,60-62]. In one series of 16 such pregnancies, seven developed heart failure (HF) symptoms, four developed a >20 percent reduction in LVEF, and three patients died [53]. In another series of 14 such pregnancies, eight patients experienced worsened HF and one patient died [61].

However, these series also demonstrate that not all patients experience adverse outcomes. In the latter series, 7 of the 14 patients did not experience worsening HF during pregnancy but rather had continued improvement and ultimately normalization of LVEF within 30 months of the subsequent pregnancy [61]. Some evidence suggests that bromocriptine may help LV function recover. (See 'Therapy to improve left ventricular function' below.)

Management and monitoring of subsequent pregnancies — We follow all pregnant patients with a history of PPCM in a multidisciplinary cardio-obstetrics program. It is reasonable to follow the patient for development of HF signs and symptoms and for any decline in LV function with an echocardiogram during each trimester of pregnancy and early postpartum. For those women with baseline LV systolic dysfunction, closer monitoring during pregnancy is necessary. This approach allows for early diagnosis, treatment, and planning for labor and delivery.

OUTCOMES — The prognosis of PPCM includes maternal, obstetric, and neonatal outcomes

Maternal outcome — Several studies have evaluated the outcome for women with PPCM [22,44-46,50,56,63-66]. (See "Acquired heart disease and pregnancy", section on 'Cardiomyopathy'.)

Mortality and morbidity — The mortality rate for PPCM varies with region [67,68]. Mortality rates range from 1.4 to 3.4 percent within 30 days of diagnosis [69]. A systematic review reporting an all-cause mortality rate of 8 percent at six months reported the following regional rates [23]:

●11.5 percent in Asia/Pacific

●10.9 percent in Africa

●6.6 percent in the Middle East

●2.9 percent in North America

●0.7 percent in Europe

Twelve-month mortality in this meta-analysis was 9.8 percent, with a range from 2.3 percent in Europe to 15.2 percent in Africa. Mortality was 10 percent in two years [44], 6 percent in five years (figure 1) [64], and 11 percent in three years [50].

A study on the long-term survival of 45 women with PPCM (30 with recovered left ventricular ejection fraction [LVEF] >50 percent and 15 with persistently reduced LVEF <50 percent) who had subsequent pregnancies found that women with persistently reduced LVEF <50 percent who had subsequent pregnancies had higher rates of recurrent PPCM (53.3 versus 20 percent); mortality at five years was numerically but not statistically higher (13.3 versus 3.3 percent) [70]. However, at a median follow-up of eight years, mortality was equivalent between women with recovered and persistently reduced LVEF (20 percent in each group).

Death due to PPCM is usually caused by ventricular arrhythmias, progressive pump failure, sudden death, or thromboembolic events. The following adverse prognostic factors have been identified in various studies:

●Worse New York Heart Association functional class (table 1) [71]

●LVEF ≤25 percent [17]

●Being from a Black population [34,63]

●Indigent status [72]

●Multiparity (ie, having given birth two or more times) [34]

●Age greater than 30 to 35 years [73,74]

PPCM is associated with significant extracardiac morbidity, including brain injury. In a study of 182 women with PPCM, 46 had major adverse events (MAEs) including death, cardiac transplantation, mechanical circulatory support (MCS), cardiopulmonary arrest, fulminant pulmonary edema, thromboembolic complications, and defibrillator or pacemaker implantation [75]. In half of the patients with an MAE, the MAE preceded diagnosis of PPCM. One-third of patients who had an MAE other than death or cardiac transplantation had residual brain damage from a cerebrovascular accident or cardiopulmonary arrest.

Recovery of left ventricular function — Partial or complete recovery of LV function is common among patients with PPCM [76]. In a systematic review, complete recovery of LV systolic function (LVEF >50 percent) was 44 percent within six months overall, with a lower rate of 13.6 percent in the Middle East and a higher rate of 56.8 percent in Europe [23]. At one year, 58.7 percent had recovered their LV function. In the North American IPAC Study, 72 percent had recovery of LV systolic function (LVEF ≥50 percent) at one year [22].

Although recovery of LV systolic function often occurs within six months of diagnosis [44,63,77], delayed recovery of LV function is also reported [33,50,72,78]. In one series of 100 patients, 42 women showed partial or complete improvement in LVEF occurring over months to five years [50]. In this series, only 4 of 23 women who eventually had complete recovery achieved this within six months.

It has been observed that women with recovered LVEF may have subtle systolic and diastolic dysfunction and reduced maximal exercise capacity [75,79].

Various studies have identified the following predictors of persistent LV dysfunction at follow-up:

●LVEF ≤30 percent [44]

●Fractional shortening less than 20 percent and an LV end-diastolic dimension ≥6 cm [80]

●Elevated cardiac troponin T [81]

●Low blood pressure [82]

●Being from a Black population [50,76]

●Diagnosis during pregnancy [50]

●Reduced right ventricular function measured using fractional area change on echocardiography [83] or volumes on cardiac magnetic resonance imaging [84]

While recovery of LV function in patients with PPCM is related to the degree of dysfunction at the time of diagnosis, baseline LVEF has limited sensitivity for prediction of improvement in individual patients [85].

Obstetric and neonatal outcomes — Data are more limited on obstetric and fetal outcomes. In a report of 100 patients with PPCM or pregnancy-related cardiomyopathy, cesarean delivery was performed in 40 percent of patients, largely for obstetric indications [44]. Preterm birth (<37 weeks) occurred in 25 percent, the mean birth weight was 3.1 kg (range 1.4 to 5 kg), and 5.9 percent of infants were small for date. There were two stillbirths, one neonatal death, and four newborns had congenital anomalies.

Therapy to improve left ventricular function — Bromocriptine may be effective; however, further studies are needed to determine the safety and efficacy of this approach. A study of 34 patients with PPCM with a subsequent pregnancy found that patients treated immediately after delivery with at least four weeks of bromocriptine therapy in addition to standard therapy for HF had higher rates of recovery and higher LVEFs compared with those who were treated with standard HF therapy alone [62]. However, further studies are needed to determine the efficacy and safety of this approach. (See 'Bromocriptine or antiprolactin therapy' above.)

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

●Components of therapy – In women with peripartum cardiomyopathy (PPCM) and heart failure (HF), many goals of medical therapy are similar to those in patients with acute and chronic HF with reduced ejection fraction (EF) due to other causes. Additional goals include fetal risks and planning around labor and delivery and for future pregnancies. (See 'Components of therapy' above.)

●Acute management – The management of HF due to PPCM is like that of HF due to other causes that occur during pregnancy with special attention to particular risks during pregnancy, including fetal risks (algorithm 1). (See 'Components of therapy' above and "Management of heart failure during pregnancy", section on 'Management goals'.)

•General measures – We use supplemental oxygen and assisted ventilation as needed. If the patient presents during pregnancy, referral to a cardio-obstetrics team and careful labor and delivery planning may be required. (See 'Initial management' above.)

•Initial therapy – Many therapies are similar to those for nonpregnant patients with HF. However, we avoid the use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin receptor-neprilysin inhibitor, sodium-glucose luminal cotransporter-2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists, as they are contraindicated in pregnancy. (See 'Initial management' above.)

•Bromocriptine – We suggest against the routine use of bromocriptine in patients with PPCM (Grade 2C); however, other experts advocate for the use of bromocriptine in this setting as preliminary data suggest a possible benefit. Shared decision-making discussions with patients should emphasize uncertain benefits and harms of treatment as well as the impact of therapy in regard to breastfeeding. If bromocriptine is used, anticoagulation should also be started to prevent thromboembolic events. (See 'Bromocriptine or antiprolactin therapy' above.)

•Management of sequelae – Some patients with acute decompensated HF may benefit from intravenous inotropic support. Mechanical circulatory support (MCS) should be considered early in patients who are hemodynamically unstable and unresponsive; MCS includes intraaortic balloon counter pulsation, venoarterial extracorporeal membrane oxygenation, and left ventricular (LV) assist device. (See 'Management of sequelae' above.)

●Long-term management – In those patients who demonstrate persistent normal LV function (LVEF >50 percent) for a period of at least six months, we suggest stepwise weaning of the HF regimen with close clinical follow-up and with echocardiographic monitoring to ensure stability of LV function during and for at least one to two years after weaning of HF medications to ensure stability (algorithm 1). Cardiac transplantation is reserved for patients who have refractory severe HF symptoms despite maximal therapy.

●Delivery – Decisions regarding the timing and mode of delivery in PPCM should be made based upon combined input from cardiology, obstetrics, anesthesiology, and neonatology services. Prompt delivery is suggested in women with advanced HF and hemodynamic instability despite medical therapy.

●Risk of recurrence – The risk of recurrence with subsequent pregnancy is highest among women with persistent LV systolic dysfunction (LVEF <50), although women with recovered LV systolic function are also at risk for recurrence.

All women with PPCM should receive counseling on the potential risk of recurrence with future pregnancies. We suggest that women with a history of PPCM who have persistent LV dysfunction (LVEF <50 percent) avoid future pregnancy due to the risk of HF progression and death (Grade 2C); we advise such patients to use reliable contraception or undergo sterilization. (See 'Patients with recurrent left ventricular dysfunction' above and 'Risks and contraception advice' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Amy Bales, MD, who contributed to earlier versions of this topic review.