Endomyocardial Fibrosis

Restrictive cardiomyopathy in which fibrous thickening of the endocardium of the inflow and apex of one or both ventricles obliterates the cavity, tethers the atrioventricular valves, and often contains thrombus. It is common in tropical and subtropical regions (West and East Africa, India especially Kerala, Brazil, Colombia) and mainly affects children and young adults (age 10 to 30), often in rural poverty near the equator.

• Prevalence is substantial where it occurs: in endemic parts of Africa it accounts for up to about 20% of heart failure admissions, and echocardiographic screening finds signs in a few percent of rural residents. The cause is unknown. Proposed factors: eosinophilia from helminth infection, malnutrition, magnesium deficiency, cerium and thorium exposure, cassava consumption, and genetic or autoimmune susceptibility.
• Forms: right ventricular (about a quarter), left ventricular (about 40%), and biventricular (about a third). Right sided disease gives apical obliteration, tricuspid regurgitation, massive right atrial dilatation and ascites; left sided disease gives mitral regurgitation, pulmonary hypertension and breathlessness.
• Prognosis is poor: mortality is about 30 to 50% within 2 years of symptoms in older series, and surgery improves survival in selected patients.

• Dyspnoea, fatigue, abdominal swelling from ascites (often out of proportion to leg oedema), facial puffiness, weight loss, jaundice from hepatic congestion.
• Signs: raised jugular venous pressure with a prominent y descent and Kussmaul sign, hepatomegaly, ascites, pleural effusion, tricuspid and mitral regurgitation murmurs, S3, atrial fibrillation, and embolic events.
• Differential diagnosis: constrictive pericarditis (including tuberculous), restrictive cardiomyopathy from amyloid or sarcoid, hypereosinophilic syndrome with Loeffler endocarditis, rheumatic valve disease, Budd-Chiari syndrome and cirrhosis, carcinoid heart disease, radiation heart disease, Chagas cardiomyopathy, Ebstein anomaly, Uhl anomaly, and pulmonary hypertension.
• Complications: refractory ascites, protein losing enteropathy, cardiac cachexia, atrial fibrillation, intracardiac thrombus with stroke or pulmonary embolism, pericardial effusion, conduction disease, hepatic fibrosis, and sudden death.

• ECG: low voltage, atrial fibrillation, right atrial enlargement, T wave inversion. Chest X-ray: cardiomegaly, pleural effusion, occasional apical calcification.
• Echocardiography: obliterated ventricular apex with bright, thickened endocardium, thrombus, enlarged atria with small ventricles, tethered posterior mitral leaflet or tricuspid leaflets with regurgitation, restrictive filling (E to A ratio greater than 2, deceleration time less than 150 ms), pericardial effusion in 30 to 40%, and raised pulmonary pressure.
• Cardiac MRI is the best test: subendocardial late gadolinium enhancement with a characteristic apical "V" sign, thrombus, and a three layer appearance.
• Cardiac catheterisation when constriction cannot be excluded: dip-and-plateau pressure trace.
• Blood tests: full blood count with eosinophil count (raised in early disease), stool and urine for parasites, serology for schistosomiasis and filariasis, HIV test, liver function, albumin, INR, urinalysis.
• Pericardial fluid analysis (cells, protein, adenosine deaminase, Xpert MTB/RIF, culture, cytology) when an effusion is present. Endomyocardial biopsy is seldom needed.

• No drug reverses the fibrosis; treatment is for heart failure, thrombosis and rhythm, and surgery is the main disease modifying option for advanced disease.
• Heart failure and congestion (the ventricle is preload dependent, so avoid over diuresis):
  • Furosemide 40 to 160 mg daily with spironolactone 25 to 100 mg daily; sodium restriction to less than 2 g/day.
  • Ramipril 1.25 to 10 mg daily where left ventricular systolic dysfunction exists (evidence is limited).
  • Digoxin 0.125 to 0.25 mg daily for atrial fibrillation (reduce in renal impairment); bisoprolol 1.25 to 5 mg daily only when tolerated and heart rate remains rapid.
  • Refractory ascites: paracentesis of 2 to 5 L at a time, with albumin 6 to 8 g per litre removed when more than 5 L is taken.
• Anticoagulation:
  • Warfarin to INR 2.0 to 3.0 for atrial fibrillation, intracardiac thrombus, or prior embolism. Evidence for direct oral anticoagulants is limited, so use warfarin for thrombus.
• Early inflammatory (eosinophilic) phase, with eosinophil count greater than 1500 per microlitre:
  • Prednisolone 1 mg/kg/day for 4 to 12 weeks, then taper (possible benefit; evidence limited).
  • Treat identified parasites: albendazole 400 mg single dose for soil transmitted helminths, ivermectin 200 micrograms/kg daily for 2 days for strongyloidiasis, praziquantel 40 mg/kg single dose for schistosomiasis. A causal role for helminths is unproven.
  • Hypereosinophilic syndrome with the FIP1L1-PDGFRA fusion: imatinib 100 to 400 mg daily under specialist care.
• Rhythm: amiodarone 200 mg daily after a loading period for atrial or ventricular arrhythmia; pacemaker for symptomatic bradycardia or high grade block.
• Surgery: endocardial resection (decortication) with mitral or tricuspid valve repair or replacement, indicated for functional class III or IV symptoms despite medical therapy, severe atrioventricular valve regurgitation, or refractory ascites. Operative mortality is about 10 to 25% (higher in biventricular disease); survivors improve symptomatically and 5-year survival is about 60 to 70%, against 30 to 50% with medical therapy alone. Fibrosis recurs in about 10 to 20%. After mechanical valve replacement give warfarin to INR 2.5 to 3.5 (mitral) or 2.5 to 3.5 (mechanical tricuspid valve); after a bioprosthesis, warfarin to INR 2.0 to 3.0 for 3 months.
• Nutrition: high protein, adequate calorie diet; treat anaemia and micronutrient deficiency; vaccinate against influenza and pneumococcus.
• Special groups:
  • Children: growth monitoring and nutritional support, with albendazole 400 mg single dose if helminths are found.
  • Pregnancy: high risk; advise against it; if it occurs, use furosemide, enoxaparin 1 mg/kg SC twice daily rather than warfarin in the first trimester, and avoid ACE inhibitors and spironolactone.
  • HIV: start antiretroviral therapy and screen for tuberculosis.
• Red flags: syncope, stroke, rapidly increasing ascites, massive oedema, haemoptysis, fever, new arrhythmia.
• Follow up: every 3 months initially, with echocardiography and natriuretic peptide every 6 months; monthly INR on warfarin; renal function and electrolytes with diuretics; early surgical referral when symptoms progress.