Peripartum cardiomyopathy

Contents

Overview

Peripartum cardiomyopathy (PPCM) is a dilated cardiomyopathy with left ventricular ejection fraction (LVEF) <45%, arising in the last month of pregnancy or within five months of delivery, with no other identifiable cause. Incidence ranges from 1 in 300 to 1 in 4,000 deliveries. Risk factors include Black African ethnicity (3–4× higher incidence and worse outcomes), advanced maternal age, multiparity, twin pregnancy, pre-eclampsia, prolonged tocolytic therapy, and malnutrition. It accounts for a significant proportion of maternal ICU admissions.

Pathophysiology

The precise mechanism is incompletely understood. Current evidence supports a multi-hit model:

Prolactin cleavage: Under oxidative stress, cathepsin D cleaves the 23 kDa prolactin molecule to a 16 kDa fragment. This fragment is antiangiogenic, pro-apoptotic, and toxic to cardiomyocytes — forming the rationale for bromocriptine therapy.

Fetal microchimerism: Fetal cells migrate into maternal myocardium and may trigger an autoimmune response.

Viral myocarditis: Subclinical viral myocarditis may precipitate PPCM in susceptible individuals.

Haemodynamic stress: The normal peripartum increase in cardiac output, afterload changes around delivery, and fluid shifts all stress a vulnerable myocardium.

Clinical Presentation

PPCM mimics other causes of acute heart failure. Presenting features include:

  • Dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea
  • Peripheral oedema
  • Fatigue, reduced exercise tolerance
  • Palpitations (arrhythmias are common)

Presentations range from subacute decompensated heart failure to fulminant cardiogenic shock. Thromboembolic events (stroke, PE) occur from LV thrombus, AF, or the hypercoagulable state of late pregnancy.

Diagnosis

Echocardiography: Diagnostic. LVEF <45%, dilated LV, global hypokinesia. May identify LV thrombus, pericardial effusion, or pulmonary hypertension.

BNP/NT-proBNP: Markedly elevated. Useful for monitoring response to treatment.

ECG: Non-specific — sinus tachycardia, left bundle branch block, AF, ST/T wave changes.

CXR: Cardiomegaly, pulmonary oedema, pleural effusions.

MRI: Not routinely required; useful if echo windows are poor or if myocarditis is suspected (late gadolinium enhancement).

Differential diagnoses include pre-existing dilated cardiomyopathy first diagnosed in pregnancy, hypertensive heart disease, and valvular disease — all must be excluded.

Management

Management differs between the antenatal and postpartum periods due to the teratogenicity of standard heart failure medications.

Antenatal Management

Diuretics: Furosemide for pulmonary oedema. Use cautiously — excessive diuresis reduces placental perfusion.

Vasodilators: ACE inhibitors and ARBs are contraindicated (teratogenic, causing renal dysgenesis). Use hydralazine and nitrates as the vasodilator combination instead.

Beta-blockers: Carvedilol and bisoprolol are used for neurohormonal blockade (preferred over metoprolol in cardiomyopathy). Monitor fetal heart rate.

Digoxin: Safe in pregnancy; useful for rate control in AF and as positive inotrope.

Anticoagulation: LMWH is recommended throughout pregnancy. LV thrombus, AF, and LVEF <35% all increase thromboembolic risk significantly.

Postpartum Management

Full standard heart failure therapy can now be started:

  • ACE inhibitor (enalapril, ramipril): cornerstone — start after delivery; contraindicated in breastfeeding if using agents that transfer to breast milk (enalapril and captopril considered safer)
  • Beta-blocker: carvedilol or bisoprolol
  • Aldosterone antagonist (spironolactone): add if LVEF remains <35%
  • SGLT2 inhibitors: emerging evidence in HFrEF; not yet established in PPCM specifically

Acute decompensation/cardiogenic shock: IV diuretics, vasodilators (IV nitrates), inotropes (dobutamine, levosimendan). Mechanical circulatory support (IABP, Impella, VA-ECMO) for refractory cardiogenic shock.

Bromocriptine

Bromocriptine is a dopamine agonist that suppresses prolactin secretion, thereby reducing the toxic 16 kDa prolactin fragment. Small RCTs — including the REBIRTH trial — have shown that bromocriptine added to standard care improves LV recovery and reduces adverse events in PPCM.

  • Dose: 2.5 mg BD for 2 weeks, then 2.5 mg daily for a further 6 weeks (short course protocol); longer courses in severe PPCM
  • Suppresses lactation — this must be discussed with the patient
  • Anticoagulation with LMWH is required during bromocriptine use (increased thrombotic risk)

Bromocriptine is now recommended by the ESC Heart Failure guidelines as a treatment option in PPCM in addition to standard therapy.

Delivery and Obstetric Considerations

  • If PPCM is diagnosed antenatally and the fetus is viable, delivery should be expedited once the mother is haemodynamically stable
  • Mode of delivery: vaginal delivery is preferred if haemodynamically stable (less blood loss, lower anaesthetic risk). Caesarean section is reserved for obstetric indications or haemodynamic instability
  • Cardiac output rises further with delivery (autotransfusion at placental expulsion); careful fluid management is essential
  • Epidural analgesia reduces the haemodynamic stress of labour
  • Multidisciplinary team (obstetrics, cardiology, ICU, anaesthesia) should be involved from diagnosis

Prognosis and Recurrence

  • Approximately 50–70% of patients recover LVEF to ≥50% within 6–12 months
  • Recovery is more likely if LVEF at diagnosis is >30% and BNP is not severely elevated
  • Mortality is 2–10% in high-income settings; higher in sub-Saharan Africa
  • Black ethnicity is associated with more severe disease, lower recovery rates, and higher mortality
  • Recurrence risk: PPCM recurs in subsequent pregnancies in approximately 30–50% of cases. If LVEF has not recovered to >50%, subsequent pregnancy carries a very high risk of deterioration and death. Pregnancy is strongly discouraged if LVEF remains <50%; it is absolutely contraindicated if LVEF <25% at the time of diagnosis.

Viva Questions

How does the management of peripartum cardiomyopathy differ between the antenatal and postpartum periods?

The key difference is that ACE inhibitors and ARBs — the cornerstone of standard heart failure with reduced ejection fraction (HFrEF) treatment — are teratogenic and absolutely contraindicated during pregnancy. They cause fetal renal tubular dysgenesis, oligohydramnios, and fetal death. In the antenatal period, the vasodilator combination used instead is hydralazine plus nitrates, which is safe in pregnancy. Diuretics (furosemide) can be used cautiously for pulmonary oedema, bearing in mind that excessive diuresis reduces placental perfusion. Beta-blockers — carvedilol or bisoprolol — are used in pregnancy as they are in standard HFrEF. Digoxin is also safe and may be used for rate control and as a positive inotrope. Anticoagulation with LMWH is recommended throughout. After delivery, the full standard HFrEF regimen can be started: ACE inhibitor, beta-blocker, aldosterone antagonist. In addition, bromocriptine — a prolactin inhibitor — should be considered based on trial evidence, as it reduces the toxic 16 kDa prolactin fragment implicated in PPCM pathogenesis. Bromocriptine requires concurrent anticoagulation and suppresses lactation, which requires patient counselling.

What is the role of bromocriptine in peripartum cardiomyopathy and what is the evidence?

Bromocriptine suppresses prolactin secretion by acting on dopamine D2 receptors in the anterior pituitary. In the oxidative stress environment of peripartum illness, the normal 23 kDa prolactin molecule is cleaved by cathepsin D into a 16 kDa fragment that is directly cardiotoxic — antiangiogenic and pro-apoptotic to cardiomyocytes. Blocking prolactin production removes this mechanism of cardiac injury. The evidence comes from small randomised trials, most notably the South African REBIRTH trial, which showed that bromocriptine added to standard heart failure therapy significantly improved LV recovery rates and reduced major adverse cardiac events. The ESC Heart Failure Guidelines now recommend considering bromocriptine in PPCM in addition to standard care. The usual regimen is 2.5 mg twice daily for two weeks, followed by 2.5 mg daily for six weeks. Key practical considerations are that it suppresses lactation (requiring a sensitive conversation with the patient about breastfeeding) and it increases the risk of thromboembolism, so concurrent LMWH anticoagulation is required. Longer courses are used in severe PPCM with significant haemodynamic compromise.

What advice would you give a woman with peripartum cardiomyopathy about future pregnancies?

The key determinant is whether LVEF has fully recovered. In women whose LVEF has normalised to ≥50% by 12 months, subsequent pregnancy carries an elevated but potentially acceptable risk — approximately 20–30% will experience deterioration in LV function during a subsequent pregnancy, though outcomes are generally better than the index pregnancy if recovery was complete. Preconception counselling, early echocardiographic monitoring in any future pregnancy, and a dedicated multidisciplinary team are essential. If LVEF has not recovered to ≥50%, subsequent pregnancy should be strongly discouraged — the risk of further deterioration, heart failure, and maternal death is substantially higher. If LVEF at the time of diagnosis was below 25%, subsequent pregnancy is absolutely contraindicated. Women should understand that even in those with apparent full recovery, subclinical myocardial dysfunction may be present and the myocardium may not tolerate the haemodynamic demands of pregnancy. Contraception should be discussed actively, and reliable long-acting contraception offered. This counselling requires sensitivity — it touches on reproductive autonomy as well as clinical risk — and should involve both cardiology and obstetric specialists.