Endocardial Fibroelastosis

Endocardial fibroelastosis is diffuse thickening of the endocardium, most often of the left ventricle, by collagen and elastic fibres. It presents mainly in infants with heart failure and ventricular dysfunction.

Dilated and contracted (restrictive) forms exist. The dilated form is more common and mimics dilated cardiomyopathy. Incidence fell sharply once mumps vaccination became widespread, and it is now rare.

It is primary (idiopathic) or secondary. Secondary causes are left ventricular outflow obstruction (critical aortic stenosis, hypoplastic left heart syndrome, coarctation), anomalous origin of the left coronary artery from the pulmonary artery, viral myocarditis (enterovirus, parvovirus B19, mumps, adenovirus), maternal anti-Ro and anti-La antibodies, and metabolic or genetic disease (Barth syndrome from TAZ variants, carnitine deficiency, lysosomal and glycogen storage diseases).

Pathophysiology.

Raised wall stress, ischaemia, inflammation and endothelial injury drive endothelial-to-mesenchymal transition. Fibroblast activation lays down collagen and elastin on the endocardium.

Stiffened endocardium impairs diastolic filling and systolic function. Papillary muscle tethering and annular dilatation cause mitral regurgitation, and subendocardial ischaemia adds to dysfunction and arrhythmia.

In utero, critical aortic stenosis can produce a dilated, fibroelastotic, failing left ventricle that may recover after relief of obstruction in selected foetuses.

Outcome varies. Some infants recover function with sustained treatment, while others progress to transplantation.

Infants have tachypnoea, poor feeding, sweating on feeds, failure to thrive, irritability, pallor, hepatomegaly, a gallop rhythm and a mitral regurgitation murmur. Recurrent chest infections are common. Presentation may be with cardiogenic shock, arrhythmia or sudden death. Older children present with heart failure.

• Echocardiography: an echo bright, thickened endocardium, a dilated globular left ventricle with reduced ejection fraction (or a small contracted ventricle), a dilated left atrium, mitral regurgitation, and thrombus. Examine the aortic valve, aortic arch, and the origin of the left coronary artery, and exclude other structural causes.
• ECG: left ventricular hypertrophy, ST and T changes; anterolateral Q waves with inferior or lateral T inversion suggest anomalous left coronary artery.
• NT-proBNP and troponin.
• Metabolic and genetic workup: lactate, ammonia, carnitine and acylcarnitine profile, urine organic acids (3-methylglutaconic acid in Barth syndrome), neutrophil count, creatine kinase, and gene panel for cardiomyopathy.
• Infection workup: PCR for enterovirus, parvovirus B19 and adenovirus (blood, nasopharynx, tissue); maternal anti-Ro and anti-La antibodies.
• Cardiac MRI in older children (diffuse subendocardial late gadolinium enhancement). Endomyocardial biopsy shows endocardial thickening with elastic fibres and helps exclude myocarditis.

Differential diagnosis.

• Idiopathic dilated cardiomyopathy and acute myocarditis.
• Anomalous left coronary artery from the pulmonary artery.
• Critical aortic stenosis, coarctation and hypoplastic left heart syndrome.
• Left ventricular non-compaction, Pompe disease and other metabolic cardiomyopathy.

Treat the cause first. Surgical reimplantation for anomalous left coronary artery (urgent). Balloon valvuloplasty for critical aortic stenosis. Repair coarctation. Treat infection and correct metabolic defects (carnitine 50 to 100 mg/kg daily orally in 2 to 3 doses for carnitine deficiency).

Heart failure therapy (dosing in infants and children).

• Furosemide 0.5 to 1 mg/kg intravenously every 6 to 12 hours, or 1 to 2 mg/kg orally every 6 to 12 hours (maximum 6 mg/kg daily); monitor electrolytes, creatinine and urine output; reduce frequency in renal impairment.
• Spironolactone 1 to 3 mg/kg orally daily in 1 to 2 doses; check potassium at 1 week and 4 weeks.
• Enalapril 0.05 to 0.1 mg/kg orally daily in 1 to 2 doses, increased gradually to a maximum of 0.5 mg/kg daily; monitor blood pressure, potassium and creatinine at 1 to 2 weeks; avoid in renal artery stenosis and avoid in the first weeks of life unless essential. Captopril is an alternative in neonates at 0.01 to 0.05 mg/kg every 8 to 12 hours.
• Carvedilol 0.05 mg/kg twice daily, doubled every 2 weeks to 0.4 to 0.5 mg/kg twice daily (maximum 25 mg twice daily) once stable and not congested; monitor heart rate and blood pressure; reduce in hepatic impairment.
• Decompensation: milrinone 0.25 to 0.75 microgram/kg/min intravenously (reduce in renal impairment), or dobutamine 5 to 10 microgram/kg/min; avoid hypovolaemia.
• Anticoagulation for thrombus or severe dysfunction: enoxaparin 1.5 mg/kg subcutaneously every 12 hours under 2 months of age and 1 mg/kg every 12 hours thereafter (anti-Xa 0.5 to 1.0 units/mL at 4 hours), then warfarin to INR 2.0 to 3.0 or aspirin 3 to 5 mg/kg daily in lower risk disease.
• Avoid digoxin when conduction disease or arrhythmia is present; if used, give 5 to 10 microgram/kg daily in 2 doses with serum levels and electrolytes.

Advanced disease. Extracorporeal membrane oxygenation for refractory shock, ventricular assist device (paracorporeal in infants) as a bridge to transplantation, and cardiac transplantation. Endocardial resection with mitral repair in selected children.

Monitoring. Weight, feeding and oxygen saturation at each visit; echocardiography every 1 to 3 months in the first year; NT-proBNP; electrolytes and creatinine with each drug change; ambulatory ECG every 6 to 12 months.

Referral and escalation. Refer every infant with suspected endocardial fibroelastosis to a tertiary paediatric cardiology centre the same day. Admit for shock, arrhythmia, thrombus or failure to respond to oral therapy.

Special groups.

• Pregnancy: with anti-Ro or anti-La antibodies, hydroxychloroquine 200 to 400 mg daily reduces the risk of foetal disease. Dexamethasone 4 mg daily to the mother is used for foetal myocarditis or incomplete block, with limited evidence. Monitor the foetal PR interval from 16 to 26 weeks.
• Relatives: echocardiography and genetic counselling when a genetic cause is found.
• Region specific: vaccination against mumps and measles prevents secondary disease; maternal and neonatal viral infection should be explored.