Peripartum cardiomyopathy ; SUMMARY TOG

 

Key Points on Peripartum Cardiomyopathy (PPCM)

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Introduction

• 💔 Leading maternal killer in the UK: Cardiovascular diseases, with PPCM as a significant contributor.
• 📋 Definition (ESC, 2010):
  • Idiopathic heart muscle disease.
  • Onset: End of pregnancy or within 6 months postpartum.
  • Heart failure due to left ventricular dysfunction (ejection fraction <45%).
  • Diagnosis of exclusion: No other heart failure causes found.

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Epidemiology and Risk Factors

• 🌍 Incidence:

  • Western countries: 1 in 1000–4000 pregnancies.
  • High-risk regions:
    • Nigeria: 1 in 100 live births.
    • Haiti: 1 in 300 live births.

• 👩🏾‍🦱 High-risk populations:

  • Afro-Caribbean lineage (worse outcomes).
  • Advanced maternal age (>30 years).
  • Multiparity, multiple pregnancies, obesity.
  • Chronic hypertension, preeclampsia (22% of PPCM cases).

• 🤰 Preeclampsia link:

  • Occurs 4 times more in PPCM patients than the general population.

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Pathogenesis

Two-Hit Hypothesis for Pathogenesis of Peripartum Cardiomyopathy (PPCM)

Overview

• 🔬 The pathogenesis of PPCM is now understood to be multifactorial.
• 🧩 A single theory cannot explain it fully; instead, the "two-hit hypothesis" is widely accepted.

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Two-Hit Hypothesis

1. Genetic Predisposition:

   • 🧬 Regional and familial patterns highlight a strong genetic basis.
   • Key genetic mutations linked to PPCM:
     • TTN, TTNCI, BAG3, PTHLH, and PGC-1a.
   • These genes regulate myocyte function, and mutations predispose women to PPCM.

2. Vascular Hormonal Insult:

• Secretion of prolactin by the anterior pituitary, enhanced production of endothelial microRNA-146a (miRNA-146a) and placental secretion of soluble fms-like tyrosine kinase receptor 1 (sFlt-1) on a background of genetic susceptibility ultimately leads to endothelial dysfunction and cardiomyocyte apoptosis
  
  
  

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Clinical Relevance

• 🧪 Highlights the genetic and vascular hormonal interplay in PPCM development.
• 💊 Forms the basis for treatments like bromocriptine (prolactin antagonist) and strategies to manage endothelial damage.

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Clinical Presentation of PPCM

Symptoms

• Heart failure-like symptoms:
  • 😮‍💨 Dyspnea (shortness of breath).
  • 😴 Orthopnea (difficulty breathing when lying flat).
  • 🌙 Paroxysmal nocturnal dyspnea (PND).
  • 🤧 Unexplained cough, especially when lying down or producing frothy pink sputum.
  • ❤️‍🔥 Palpitations (irregular or fast heartbeats).
  • 🌀 Dizziness and fatigue.
  • 🦶 Pedal edema (swelling in legs).
  • 💢 Chest pain and abdominal discomfort (due to hepatic congestion).

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Timing of Presentation

• 🗓️ Postpartum cases:
  • 78% develop symptoms within 4 months postpartum.
  • 9% present during the last month of pregnancy.
  • 13% present earlier or later than the above timeframe.

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Examination Findings

• Common signs:
  • 💓 Sinus tachycardia (fast heart rate).
  • 💦 Raised jugular venous pressure (JVP).
  • 🫁 Lung crepitations (crackling sounds).
• Uncommon findings:
  • 🎵 Third heart sound (S3).
  • ✋ Displaced apex beat.

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Red Flag Signs (MBRRACE 2019)

• ⚡ Persistent tachycardia.
• 🫢 Tachypnea (rapid breathing).
• 🔥 Chest pain.
• 😴 Orthopnea.

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Diagnostic Approach

• Initial Evaluation:

  • 📜 History of congenital/acquired heart disease or family history of heart failure.
  • 🩺 Physical examination: Tachypnea, tachycardia, JVP, peripheral edema.

• Investigations:

1. 📈 Electrocardiogram (ECG):
   • Sinus tachycardia, nonspecific ST-T wave changes.
   • Rules out ischemia or thromboembolism.
2. 🩸 Blood tests:
   • Elevated BNP/NT-proBNP (heart failure marker).
   • C-reactive protein, white cell count (elevated but nonspecific).
   • Normal or mildly elevated troponin T (no significant myocyte injury).
3. 🫀 Echocardiography (Key diagnostic tool):
   • EF <45%; ventricles may or may not be dilated.
   • Provides prognostic information (e.g., poor outcomes if EF <30%).
4. 🩻 Chest X-ray:
   • Signs of cardiac strain: Cardiomegaly, pulmonary edema, pleural effusion.
5. 📷 Cardiac MRI:
   • Useful for detailed imaging and detecting intracardiac thrombus.
   • Not routinely used due to gadolinium risks in pregnancy.
6. 🔬 Endomyocardial biopsy (EMB):
• Rarely performed to exclude other causes of heart failure.
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Management of Peripartum Cardiomyopathy (PPCM)

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Principles of Management 🩺

• 🏥 Interdisciplinary, patient-centered approach.
• 💊 Optimal medical therapy for heart failure.
• 🛠️ Rarely, mechanical augmentation of circulation and ventilation.

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Pharmacotherapy 💊

• Management aligns with heart failure with reduced ejection fraction (HFrEF).
• Includes:
  • 🌡️ ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB).
  • ⚙️ Mineralocorticoid receptor antagonists (MRA) (e.g., spironolactone, eplerenone).
  • 💓 Beta-blockers (e.g., metoprolol).
  • 🧬 Angiotensin receptor neprilysin inhibitors (ARNI) (superior to ACEi/ARB).
  • 🩸 Sodium-glucose co-transporter-2 (SGLT2) inhibitors: Originally for type 2 diabetes, beneficial in HFrEF.
• ⏳ Therapy duration: Continue at least until ejection fraction recovery; no evidence supports treatment continuation beyond this.
• 🔄 Anticoagulation: Continue for 6–8 months postpartum unless otherwise indicated.

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Treatment Groups

1. Pregnant and Hemodynamically Stable 🤰
   • 🧂 Salt restriction: First-line measure for volume control.
   • 💧 Loop diuretics: Furosemide or bumetanide to manage breathlessness and edema (caution: avoid overdiuresis).
   • 💓 Beta-blockers: Prefer selective β-1 antagonists like metoprolol.
   • 🚫 Contraindicated: ACEi, ARB, MRA.
   • 🔄 Alternative: Hydralazine + nitrates for vasodilation to reduce afterload.
   • 🩺 Anticoagulation: Use low-molecular-weight heparin (LMWH) (warfarin contraindicated).
   • ⚡ Antiarrhythmics: Adenosine, verapamil, flecainide, and procainamide can be used (limited safety evidence).

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2. Postpartum, Breastfeeding, and Hemodynamically Stable 🤱
   • 🌡️ ACEi/ARBs: Compatible with breastfeeding.
   • ✅ Continue:
     • 💓 Beta-blockers.
     • ⚙️ MRA therapy.
     • Hydralazine and nitrates (may stop to initiate ACEi/ARB).
   • 🩸 Anticoagulation: LMWH or warfarin (compatible with breastfeeding).

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3. Postpartum and Not Breastfeeding 🚼
   • 🌐 All pharmacological options available, including:
     • 🧬 ARNI.
     • 🩸 SGLT2 inhibitors.
     • ⚖️ Direct oral anticoagulants (DOAC).
   • 📊 Use based on general HFrEF management data.

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Management of Peripartum Cardiomyopathy (PPCM)

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4. Haemodynamically Unstable 🚑

• Intensive care admission required: Rapid and aggressive therapy is necessary.

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Initial Therapy Principles

1. Optimisation of Preload 💧

   • Use intravenous diuretics (e.g., furosemide) to manage congestion like pulmonary edema.
   • Start intravenous vasodilators (e.g., nitrates) if systolic BP >110 mmHg.

2. Adequate Oxygenation 🫁

   • Maintain SpO2 >95% with the patient upright.
   • Use CPAP for noninvasive ventilation to decrease intubation rates.
   • Consider intubation and ventilation in refractory hypoxia.

3. Circulatory Support with Inotropes/Vasopressors 🩺

   • For cardiogenic shock, ensure circulatory stability to prevent organ damage.
   • Avoid catecholamines (e.g., adrenaline, dobutamine) due to increased myocardial oxygen demand.
   • Levosimendan (calcium-sensitizing agent) preferred for inotropic support.

4. Urgent Delivery During Pregnancy 🤰

   • Prioritize maternal safety over fetal interest.
   • Urgent delivery, regardless of gestational age, requires a multidisciplinary approach.

5. Mechanical Circulatory Support 🛠️

   • Use short-term options like intra-aortic balloon pump (IABP) or Impella for ventricular support.
   • For pulmonary dysfunction, consider ECMO (extracorporeal membrane oxygenation).
   • Long-term options: LVAD or BiVAD as a bridge to recovery or transplant.

6. Bromocriptine for Endocrine Modulation 💊

   • Dose:
     • 2.5 mg once daily for uncomplicated cases.
     • 2.5 mg twice daily for 2 weeks, then once daily for 6 weeks if EF <25%.
   • Start anticoagulation (e.g., LMWH) with bromocriptine due to thrombosis risk.

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Pregnancy-Specific Considerations 👶

1. Timing of Delivery:

   • Urgent delivery for worsening maternal condition.
   • Vaginal delivery preferred unless caesarean is obstetrically indicated.

2. Intrapartum Management:

   • Monitor continuously:
     • CTG for fetal heart.
     • Blood pressure, oxygen, and fluid balance for the mother.
   • Use low-dose regional analgesia to minimize stress.
   • Avoid long-acting oxytocin and ergometrine (risk of hypertension and heart failure).

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Breastfeeding 🤱

• Breastfeeding discouraged if:
  • LVEF <45%.
  • Symptoms of heart failure persist.
• Compatible medications during breastfeeding:
  • ACEi (e.g., enalapril, captopril).
  • Beta-blockers (e.g., metoprolol).
• Contraindicated medications: Spironolactone, long-acting carvedilol.

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Prognosis 📈

• Recovery:
  • 50–80% recover LVEF ≥50% within 6 months.
  • Afro-Caribbean women have lower recovery rates.
• Mortality rate: Improved to 10% compared to 30–50% in the 1970s

Contraception ⚠️

1. Recommended Methods:

   • Intrauterine devices (IUDs): Copper or progestogen-releasing .Women with PPCMhave a high risk of cardiac arrhythmias.
   •  Arrhythmias tend to cause vasovagal collapse because the heart rate is too fast-paced to allow satisfactory filling, or too slow to enable adequate outflow.
   • For this reason, hospitalisasafer place for IUD fitting.
   • Long-acting reversible contraceptives (LARC): Subcutaneous or subdermal progesterone-based options.

2. Avoid:

   • Combined hormonal contraceptives (estrogen increases thromboembolism risk).
   • Barrier methods (e.g., condoms) due to high failure rates.

3. Sterilization:

   • Options include vasectomy or tubal ligation.
   • Requires thorough counseling due to psychological and anesthetic risks.

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Subsequent Pregnancy 🤰 

Persistent LVEF dysfunction: 50% risk of deterioration and 20% mortality 

Full recovery: 20% risk of recurrence.

• Avoid pregnancy if:
  • Initial LVEF <25%.
  • Persistent LVEF dysfunction post-treatment.

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Management in Subsequent Pregnancy 🤰💉

Pre-conceptional Counselling 🩺💬

• Multidisciplinary Team Approach: Pre-conceptional counselling should involve a team of experts, including a cardiologist, obstetric physicians, obstetricians with expertise in maternal-fetal medicine, anaesthetists, neonatologists, and other allied specialties.
• Tertiary Care Centre: Ideally, these consultations should take place in a tertiary care centre to ensure comprehensive care.
• Medication Review: Medications should be thoroughly reviewed.
  • Stop ACE inhibitors (ACEi), ARB blockers, and MRA during the pre-pregnancy period.
  • Switch to hydralazine-nitrate combination therapy as an alternative.

Early Pregnancy Management 🍼👶

• Early Booking & Consultant-Led Care: Once pregnancy is confirmed, arrange early booking and frequent antenatal visits under a consultant-led team.
• Continued Treatment:
  • Beta-blockers should be continued.
  • Monitor closely using echocardiography and brain natriuretic peptide (BNP) levels.
  • Timing of echocardiograms is detailed in Figure 4 (not shown here).
• Anticoagulation Consideration: In women with peripartum cardiomyopathy (PPCM), particularly those with left ventricular (LV) dysfunction, anticoagulation with low molecular weight heparin (LMWH) should be considered.

Monitoring During Pregnancy 📈🩺

• Serial Scans: Begin serial scans to monitor fetal growth from 24 weeks of gestation.
• Delivery Planning: Timing of delivery is guided by:
  • Obstetric indications (e.g., fetal growth restriction, pre-eclampsia).
  • Cardiac reasons (e.g., worsening cardiac function).
  • Goal: Aim for 37 weeks of gestation for optimal maternal and fetal outcomes.

Delivery Mode 🤱

• Vaginal Birth Preferred: Recommended unless a caesarean section is required for:
  • Obstetric indications.
  • Acute haemodynamic compromise.

Postpartum Care 👩‍⚕️💊

• Anticoagulation: Consider anticoagulation with LMWH for 6 weeks postpartum due to increased thrombotic risk during this period.