| disease | Endocardial Fibroelastosis |
| alias | Endocardial Sclerosis, EFE, Primary Endocardial Fibroelastosis |
Endocardial fibroelastosis (EFE), also known as endocardial sclerosis, is a disease with an unclear etiology. It is one of the more common types of primary cardiomyopathy in children and is also referred to as primary endocardial fibroelastosis. Congenital heart diseases such as aortic coarctation, aortic valve stenosis, and aortic valve atresia complicated by endocardial fibroelastosis are termed secondary endocardial fibroelastosis. The clinical significance of this condition depends on the primary cardiac malformation and is not covered in this section.
bubble_chart Etiology
As early as 1816, it was proposed that this disease might be caused by intrauterine infection leading to fetal endocarditis. To this day, the etiology remains unclear, but several hypotheses have been suggested: 1. **Viral infection**: Inflammation caused by viral infections during fetal development or after birth. Coxsackie B virus, mumps virus, and infectious mononucleosis virus have been implicated. Coxsackie B virus has been isolated from the myocardium of children who died from endocardial fibroelastosis, with histological evidence of myocarditis. Inoculating mumps virus in chicken embryos and maternal mumps infection during early pregnancy have been linked to the disease in newborns. Some reports also suggest that diffuse myocarditis caused by infectious mononucleosis can progress to endocardial fibroelastosis. Additionally, pathological examinations of interstitial myocarditis and endocardial fibroelastosis cases often reveal coexisting lesions. In acute cases, myocarditis is prominent, while endocardial fibroelastosis is less pronounced. In chronic cases (lasting over four months until death), myocarditis is mild, but endocardial fibroelastosis is severe, suggesting that myocarditis may precede endocardial fibroelastosis as different stages of the same disease. Among 102 pathological cases at Beijing Children’s Hospital, 65 showed myocarditis, including four neonatal cases. 2. **Intrauterine hypoxia** leading to impaired endocardial development. 3. **Genetic factors**: Familial occurrence in 9% of cases, suggesting autosomal inheritance. 4. **Inborn errors of metabolism**: Cases of endocardial fibroelastosis have been reported in children with glycogen storage disease type II (Pompe disease), mucopolysaccharidosis, and carnitine deficiency. 5. **Secondary to hemodynamic changes**: Severe ventricular dilation increases wall tension, promoting endocardial fibroelastosis as a nonspecific response to hemodynamic stress.
The heart is enlarged, with thickened endocardium appearing milky-white or gray-white, smooth and glossy. In most cases, the entire heart is involved, predominantly the left ventricle, followed by the left atrium and right ventricle. The papillary muscles, chordae tendineae, mitral valve, and aortic valve may also be affected. Mural thrombi may form in the ventricular walls. Microscopically, enlargement is observed, and sometimes mononuclear proliferation in the interstitium and myocardial fibrosis are seen. Based on left ventricular size, it can be classified into two types: ① Dilated type, with left ventricular grade I hypertrophy. This type is the most common, accounting for about 95%. ② Constrictive type: the left ventricular cavity is small and underdeveloped, with enlargement of the right atrium and ventricle, thickened myocardium, and thickened endocardium in both ventricles. This type is rare and mainly seen in newborns.
bubble_chart Clinical Manifestations
Two-thirds of the affected children develop the disease within the first year of life. The primary clinical manifestation is congestive heart failure, often occurring after respiratory infections.
1. General Symptoms Based on the severity and progression of symptoms, the condition can be classified into three types:
(1) Fulminant Type: Sudden onset with acute symptoms such as dyspnea, vomiting, refusal to eat, perioral cyanosis, pallor, restlessness, and tachycardia. Scattered wheezing or dry rales may be heard in the lungs, along with hepatomegaly and edema—all signs of congestive heart failure. A few infants may exhibit cardiogenic shock, presenting with restlessness, ashen complexion, cold and clammy extremities, and a rapid yet weak pulse. This type predominantly affects infants under six months and may lead to sudden death.
(2) Acute Type: The onset is also rapid, but the progression of congestive heart failure is less abrupt than in the fulminant type. It is often complicated by pneumonia, accompanied by fever and moist rales in the lungs. Some children may develop cerebral embolism due to dislodged mural thrombi. Most cases succumb to heart failure, though a few may improve with treatment.(3) Chronic Type: The onset is slower, typically affecting infants over six months of age. Symptoms resemble the acute type but progress gradually, sometimes impairing growth and development. Treatment may lead to remission, allowing survival into adulthood, though recurrent heart failure can still be fatal.
Most cases are of the acute type, while the chronic type accounts for about one-third. Neonatal cases are rare and often present as a constrictive form, with symptoms of left ventricular obstruction. Occasionally, heart failure may develop in utero, leading to death within hours after birth.
2. Signs The heart is enlarged to grade II or higher, with a bulging precordium observed in chronic cases. The apical impulse is weakened, heart sounds are muffled, and tachycardia is present, sometimes with a gallop rhythm. Murmurs are usually absent or limited to a grade I systolic murmur. In some cases, mitral regurgitation or relative mitral insufficiency due to cardiac dilation may result in a grade II–III systolic murmur at the apex.
3. X-ray Examination Left ventricular enlargement is prominent, with generalized cardiomegaly resembling a "stirred pulse" silhouette. The left heart border shows weakened pulsations, especially under fluoroscopy in the left anterior oblique view, where left ventricular pulsations disappear while right ventricular pulsations remain normal—a diagnostically significant finding. Left atrial enlargement is common, along with increased pulmonary vascular markings and evident pulmonary static blood.
4. Electrocardiogram (ECG) Most cases show left ventricular hypertrophy with ST-segment and T-wave abnormalities. Prolonged heart failure leading to elevated pulmonary stirred pulse pressure may result in right ventricular hypertrophy or biventricular hypertrophy. Occasionally, premature beats or atrioventricular block are observed. The constrictive type exhibits right ventricular hypertrophy and right axis deviation.
5. Echocardiography Findings include left ventricular cavity dilation, reduced motion amplitude of the left ventricular posterior wall, and enhanced echoes from the left ventricular endocardial membrane.
Left ventricular systolic function is impaired, with decreased fractional shortening and ejection blood aspect.
6. Cardiac Catheterization Elevated mean left atrial, pulmonary stirred pulse, and left ventricular end-diastolic pressures are observed. Selective left ventriculography reveals left ventricular enlargement and delayed contrast clearance. Mitral and aortic regurgitation are common.
The characteristics of this disease are: ① Most infants under 1 year of age suddenly develop heart failure at 2-6 months; ② Chest X-ray shows cardiac enlargement, predominantly in the left ventricle, with weakened heartbeats; ③ No significant heart murmurs are present; ④ The electrocardiogram shows left ventricular hypertrophy or inverted T waves in V5 and 6 leads. ⑤ Echocardiography reveals left ventricular enlargement, thickened endocardial echoes, and reduced systolic function. Histological confirmation requires endocardial myocardial biopsy.
bubble_chart Treatment Measures
The main treatment is to control heart failure. For acute heart failure, intravenous injection of digoxin or cedilanid is required for rapid digitalization, and long-term maintenance doses of digoxin should be taken, which may last for 2 to 3 years or even longer, until the heart returns to normal size. Premature discontinuation of medication may lead to worsening of the condition. In recent years, the addition of long-term oral captopril has shown some effectiveness in improving cardiac function. For critical cases, dopamine, dobutamine, furosemide, and corticosteroids may be added (refer to the sections on congestive heart failure and cardiogenic shock). Antibiotics should be used to control pulmonary infections. Patients with concomitant mitral regurgitation should undergo valve replacement surgery, after which cardiac function may improve. For patients with grade III cardiac enlargement, severely reduced ejection fraction, and poor response to drug therapy, heart transplantation should be considered.
The pathogenesis of this disease may be related to immune dysfunction. In recent years, immunosuppressive therapy has been applied, primarily using prednisone at 1.5 mg/(kg·day). After 8 weeks, the dosage should be gradually reduced, decreasing by 2.5 to 1.25 mg every 2 weeks until a maintenance dose of 0.25 to 5 mg per day is reached. The medication should be discontinued gradually once the electrocardiogram normalizes and the cardiac size on chest X-ray approaches normal. The treatment course lasts 1 to 1.5 years.
The disease has a severe prognosis, with a mortality rate of approximately 20-25%. Patients with older age of onset who respond well to Rehmannia treatment have a better prognosis and may achieve clinical recovery. A long-term follow-up study of 52 confirmed cases showed an average follow-up period of 47 months (1-228 months), with survival rates of 93% at six months, 83% at one year, and 77% at four years. It is also noted that patients with significantly decreased cardiac index and ejection fraction have a poor prognosis and often die in the early stages of the disease.
This disease must be differentiated from other cardiac conditions presenting with heart failure in infancy, absence of significant murmurs, and predominant left ventricular enlargement: (1) Acute viral myocarditis: There is a history of viral infection, and the electrocardiogram primarily shows low QRS voltage, prolonged Q-T interval, and ST-T changes; whereas endocardial fibroelastosis manifests as left ventricular hypertrophy, high RV5,6 voltage, and inverted RV5,6. Sometimes, endocardial myocardial biopsy is required for differentiation. (2) Anomalous origin of the left coronary artery from the pulmonary artery: Due to myocardial ischemia, the infant exhibits extreme dysphoria, restlessness, crying, and colicky heart pain. The electrocardiogram often shows patterns of anterior wall myocardial infarction, with ST-segment elevation or depression and QS waves in leads I, aVL, and RV5,6. (3) Glycogen storage disease of the heart: The infant displays muscle weakness and macroglossia, with a shortened P-R interval on the electrocardiogram. Skeletal muscle biopsy can aid in differentiation. (4) Coarctation of the aorta: Weakened or absent pulses in the lower limbs, elevated blood pressure in the upper limbs, and bounding pulses can help differentiate. (5) Dilated cardiomyopathy: More common in children over 2 years old. Additionally, it must be distinguished from pneumonia, bronchiolitis, pericarditis, and pericardial effusion. Special attention should be paid to the fact that this condition is clinically prone to misdiagnosis as pneumonia. Cardiac examination must be emphasized to facilitate early diagnosis and treatment. Chest X-ray and echocardiography are crucial for diagnosis. Due to the proximity of the enlarged heart's left border to the chest wall, misdiagnosis as pleural effusion or mediastinal tumor should be guarded against.
