202410270926

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Tags: Obstetrics, Cardiology

Peripartum cardiomyopathy

Background

Peripartum cardiomyopathy is a form of acute and sometimes severe cardiac degeneration that leads to clinical heart failure during pregnancy or in the early postpartum period

Approximately 60% of cases of cardiogenic shock during pregnancy or in the early postpartum period are caused by peripartum cardiomyopathy

Sixty to ninety percent of cases of peripartum cardiomyopathy occur after delivery, with the highest incidence in the first postpartum week

Although cardiac function typically recovers in more than 50% of affected patients, morbidity and mortality are nevertheless high, with some patients requiring a left ventricular assist device (LVAD) or cardiac transplantation

Definition

Classical definition

• maternal heart failure
  • systolic dysfunction
    • LVEF <45%
• develops in the last month of pregnancy or in the first 5 months after delivery
• in the absence of known preexisting cardiac dysfunction
• Dx of exclusion

The 2010 Heart Failure Association of the European Society of Cardiology Working Group revised the definition of PPCM to “an idiopathic cardiomyopathy presenting with HF secondary to LV systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found”

Risk factors

• hypertensive diseases of pregnancy
  • including Preeclampsia
• multiple gestations
• advanced maternal age
• anaemia
• ethnicity: black > white
  MOD (e.g. CS) not a risk factor

Diagnosis

The majority of women with PPCM are diagnosed after delivery, typically in the first month postpartum

Presentation: heart failure, cardiogenic shock

Infrequently, affected persons present with a complication of the disease, such as an arrhythmia or a thromboembolic event

Although there is no specific ECG pattern for PPCM, at initial evaluation, the ECG is rarely normal and repolarization abnormalities are common

Genetic testing is increasingly offered to patients with peripartum cardiomyopathy, and it should be considered in most cases

Differential Diagnosis	Differentiating Markers
Preexisting Cardiomyopathy	History, family history, prior echocardiography
Preeclampsia-induced pulmonary edema in the absence of systolic dysfunction	History, preserved ejection fraction on echocardiography, sFlt-1 and PLGF levels
Pulmonary or amniotic embolism	History, chest CT
Valvular heart disease, including rheumatic disease	History, echocardiography
Congenital heart disease that has resulted in surgical correction	History, echocardiography
Chemotherapy-induced cardiomyopathy	History, especially of treatment with doxorubicin or other anthracyclines, trastuzumab, or sorafenib
Spontaneous coronary-artery dissection	History, echocardiography, elevated troponin levels
Other causes of myocardial infarction, including MINOCA	History, echocardiography, elevated troponin levels
Myocarditis, including giant-cell myocarditis	History, endomyocardial biopsy
Takotsubo cardiomyopathy	History, apical ballooning on echocardiography
Tachycardia-induced cardiomyopathy	History, especially atrial fibrillation
Pulmonary edema resulting from prolonged tocolysis	History, preserved ejection fraction on echocardiography
Sepsis, thyrotoxicosis, and other high-output causes of heart failure	History, high output on echocardiography
Aortic dissection	History, findings on CT angiogram

Pathogenesis

Peripartum cardiomyopathy has often been proposed to represent a failed hemodynamic stress test. However, the disorder typically develops after delivery, and systolic function appears to be preserved earlier during gestation

the maximal cardiovascular changes occur in the second trimester, when most women with pre-existing cardiac disease develop symptomatic HF
cf PPCM: late pregnancy

Myocarditis has also been suggested to cause peripartum cardiomyopathy, but endomyocardial biopsy specimens from patients with peripartum cardiomyopathy do not appear to contain any more viral genomes that have been implicated in myocarditis than do control specimens, and cardiovascular MRI studies with late gadolinium enhancement in women with peripartum cardiomyopathy of recent onset rarely reveal evidence of myocarditis

Studies have suggested that the disorder is triggered by hormones that emanate from the pituitary and placenta during the peripartum period, synergizing, in ways still poorly understood, with intrinsic cardiac factors that render some women susceptible to these hormonal imbalances.

Hormones produced by the pituitary and the placenta normally modulate maternal physiology to support fetal and newborn growth and development. Under certain circumstances, however, some of these processes can lead to cardiac dysfunction

2 vascular-hormonal animal models: 16-kD prolactin

prolactin, secreted from the pituitary in late gestation and after delivery in lactating persons, was shown in mouse models of peripartum cardiomyopathy to be cleaved to a breakdown product that damages the cardiac vasculature. The damaged vessels, in turn, trigger ventricular systolic dysfunction through a combination of cardiac ischemia and paracrine signaling, including the secretion by endothelial cells of exosomes containing microRNAs (miRNAs) that, when taken up by cardiomyocytes, promote cardiomyocyte apoptosis

suppression of prolactin secretion, either by pharmacologic means or by cessation of breast-feeding, may be beneficial in patients with peripartum cardiomyopathy

Of note, human prolactin has been shown to be more resistant to cleavage than prolactin in rats, and extrapolations from rodent models may be limited

Oxytocin, which is secreted by the pituitary to promote lactation, can also have vasculotoxic effects, promoting postpartum aortic dissection in models of Marfan’s syndrome, but a definitive role in peripartum cardiomyopathy has not been directly established.

Soluble fms-like tyrosine kinase 1 (sFlt-1), a soluble decoy receptor for VEGF that is abundantly secreted by the placenta in late gestation, has been shown to trigger cardiovascular rarefaction, leading to peripartum cardiomyopathy in mice. The latter observation may explain the strong epidemiologic associations of preeclampsia and multiple gestations with peripartum cardiomyopathy, because large increases in placental secretion of sFlt-1 are seen in both contexts

The late-gestation placenta is also abundantly steroidogenic. Progesterone, highly secreted by the placenta, suppresses the burning of carbohydrates by the heart, promotes cardiac hypertrophy, and may have direct negative-inotropic effects, all of which probably sensitize the heart to further insults

Approximately 15% of women with peripartum cardiomyopathy have heterozygous loss-of-function genetic variants in one of several genes known to be associated with nonischemic dilated cardiomyopathy, a disease that in part resembles peripartum cardiomyopathy

The frequencies of identified variants in dilated cardiomyopathy and in peripartum cardiomyopathy are nearly identical, suggesting that these two diseases may lie on a spectrum, reflecting different environmental insults superimposed on the background of a similar genetic predisposition to disease

Selenium deficiency appears to contribute to peripartum cardiomyopathy in some parts of Nigeria, through unknown mechanisms

Management

Current management is thus largely extrapolated from guideline-directed medical treatment for nonischemic dilated cardiomyopathy and other forms of heart failure with a reduced ejection fraction

Neurohormonal blockade with angiotensin-converting–enzyme inhibitors, angiotensin II receptor blockers, and aldosterone receptor antagonists can be administered after delivery but are contraindicated before delivery

Hydralazine plus isosorbide dinitrate is an alternative regimen for afterload reduction during pregnancy

Beta-blockers are routinely indicated and are safe during pregnancy

No data on entresto & SGLT2i but often used post-partum

SCD / arrhythmia

Ventricular arrhythmias are common in patients with peripartum cardiomyopathy

Given the high rate of improvement of LV function during optimal heart failure drug therapy, early implantation of an implantable cardioverter-defibrillator (ICD) in patients with newly diagnosed PPCM is generally not advisable

Wearable cardioverter-defibrillators (WCDs) have been proposed as a mechanism to prevent sudden cardiac death during the first 3–6 months after diagnosis until a definitive decision about ICD implantation can be made

Anticoagulation

The hypercoagulable state of pregnancy, especially the peripartum period, increases the risk of thrombotic complications, including left ventricular thrombus and thromboembolic events, which occur in 5 to 20% of cases

anticoagulation should be considered in the setting of severely decreased LVEF during late pregnancy and 6 to 8 weeks postpartum

Heart transplant

Patients with PPCM appear to have higher rates of graft failure and death after heart transplantation, which may be partly explained by higher allosensitization, higher pre-transplant acuity, and increased rejection

As late recovery beyond 6–12 months is possible and outcomes with heart transplantation in PPCM are worse than in other causes of heart failure, delaying heart transplantation as long as possible is desirable.

Delivery

Patients who are hemodynamically stable can deliver vaginally

Epidural analgesia is preferred

Following delivery, removal of caval compression by the fetus, autotransfusion due to uterine contractions, and fluid mobilization and resorption contribute to an increase in venous return. The post-partum risk of fluid overload and pulmonary edema must be anticipated.

Lactation / Bromocriptine

Lactation is generally not contraindicated

There are no proven disease-specific therapies for peripartum cardiomyopathy, but the use of Bromocriptine to suppress the release of prolactin from the pituitary is currently under investigation and may be considered in patients with a left ventricular ejection fraction of less than 35%.

A bromocriptine treatment scheme has been suggested:
bromocriptine (2.5 mg once daily) for at least 1 week may be considered in uncomplicated cases

prolonged treatment (2.5 mg twice daily for 2 weeks, then 2.5 mg once daily for another 6 weeks) may be applied in patients with EF < 25%, right ventricular involvement, intensive care treatment, and/or cardiogenic shock

Outcome

In most women, the LVEF increases to more than 50% within 6 months after diagnosis

Implantation of an LVAD or heart transplantation is required in up to 10% of cases

mortality among patients with peripartum cardiomyopathy can be as high as 20%, and it is higher in low-income countries than in high-income countries, despite a generally lower incidence of known risk factors in low-income countries

The occurrence of preeclampsia with peripartum cardiomyopathy has been associated with better left ventricular recovery and with a higher incidence of adverse cardiovascular outcomes

Contraception & future pregnancy

In the early postpartum setting with severe LV dysfunction, the increased risk of thromboembolism should dissuade the use of estrogen-containing contraceptives

Progesterone-releasing subcutaneous implants or the Mirena intrauterine device are safe and effective choices

In a woman with persistent LV dysfunction, the risk of a subsequent pregnancy likely outweighs any risk associated with contraception

Women who recover LVEF >50% have lower risk of complications during a subsequent pregnancy, but there is still increased risk of recurrent HF

Subsequent pregnancy

The risks associated with a subsequent pregnancy depend primarily upon whether the myocardial function has fully recovered, and the pre-pregnancy LVEF is the strongest predictor of outcomes

2023 ESC guideline:

References

Peripartum Cardiomyopathy - NEJM

2023 ESC Guidelines for the management of cardiomyopathies | European Heart Journal | Oxford Academic (oup.com)

Pathophysiology, Diagnosis and Management of Peripartum Cardiomyopathy A Position Statement From the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy
Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy - Bauersachs - 2019 - European Journal of Heart Failure - Wiley Online Library

Peripartum Cardiomyopathy JACC State-of-the-Art Review
Peripartum Cardiomyopathy: JACC State-of-the-Art Review | Journal of the American College of Cardiology