Background
Endocardial fibroelastosis (EFE) refers to a pronounced, diffuse thickening of the ventricular endocardium and presents as unexplained heart failure in infants and children. The term endocardial fibroelastosis was introduced by Weinberg and Himmelfarb in 1943. [1, 2]
The disease can be primary or secondary to various congenital heart diseases, most notably hypoplastic left heart syndrome, [2] aortic stenosis, or atresia.The two pathologic forms of primary endocardial fibroelastosis are dilated, which is most common, and contracted. Primary endocardial fibroelastosis is not associated with any significant structural anomaly of the heart. Secondary endocardial fibroelastosis is associated with other congenital heart diseases.
Once regarded as a common cause of unexplained heart failure, endocardial fibroelastosis is now considered rare. However, a study has highlighted that 25% of children who were transplanted for dilated cardiomyopathy demonstrated significant endocardial fibroelastosis on histopathology of the explanted hearts. [3]
Note the following:
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Symptoms of endocardial fibroelastosis include feeding difficulty, excessive sweating, breathlessness, failure to thrive, and wheezing.
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Onset may acute enough to produce cardiogenic shock or sudden death; it is a recognized cause of sudden death in infancy.
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Approximately 20% of patients have a history of frequent or recent respiratory tract infections.
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Echocardiography forms the mainstay to the diagnosis. Careful assessment of the heart for any associated congenital heart disease including coronary artery anomalies is essential before making a diagnosis of primary endocardial fibroelastosis.
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The treatment of endocardial fibroelastosis is essentially the same as that for chronic cardiac failure; its acute exacerbations are often precipitated by respiratory infections.
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Primary endocardial fibroelastosis prognosis is relatively poor, although the condition is not universally fatal.
Pathophysiology
The underlying pathophysiology of endocardial fibroelastosis (EFE) is believed to be deposition of acellular fibrocartilagenous tissue in the subendothelial layer of the endocardium predominantly involving the inflow tracts, apices of either left or both ventricles. [2] Endocardial fibroelastosis is characterized by diffuse endocardial thickening and myocardial dysfunction. The endocardial thickening is believed to be caused by persistent and increased wall tension in the ventricles, possibly secondary to damaged myocardium, mitral regurgitation, or both. However, endocardial fibroelastosis changes are progressive with age. The disease is usually sporadic, but familial cases have been reported (10%). Observations that favor a viral etiology include a clinical presentation similar to that of chronic myocarditis, findings of myocarditis or myocardial fibrosis in affected patients, a higher incidence following epidemics of coxsackievirus B infection, demonstration of persistent viral infection with molecular studies, and experimental production of the disease in animal models by viral infections of the myocardium. A phenotypic resemblance to dilated cardiomyopathy has also been noted. A report suggests that the epicardium-derived mesenchymal cells could be the origin of the endocardial fibroelastosis fibroblasts. [4]
Dilated endocardial fibroelastosis is characterized by a markedly enlarged globular heart, mainly involving the left ventricle (LV) and left atrium (LA). The LV endocardium is opaque, glistening, milky white, and diffusely thickened to about 1-2 mm. The thickening is most marked in the outflow tract.
Papillary muscles arise more superiorly on the ventricular wall with thickened and shortened chordae tendineae, the characteristic rolled-free edge of mitral leaflets. Papillary muscles and trabeculae carneae are flattened and partially incorporated in the fibrotic process, giving a smooth appearance to the lining of the cavity; thus, the papillary muscles exert an undesirable lateral traction on the chordae tendineae and mitral cusps, leading to faulty leaflet opposition.
Although the endocardium is thickened, the ventricular wall (myocardium) thickness is within the reference range. Endocardial thickening extends to the LA, right ventricle, and right atrium. Microthrombi may adhere to the endocardium. The right ventricle is anteriorly displaced to the right, and its cavity is usually flattened. The pulmonary artery may be enlarged, but the aorta and coronary arteries appear normal in caliber. In approximately 50% of patients, the mitral and aortic valves are involved, often producing marked deformity and either valvar regurgitation or stenosis.
The less common contracted type of primary endocardial fibroelastosis is associated with a relatively hypoplastic or normal LV size. The right and left atria and the right ventricle are markedly enlarged and hypertrophied, with minimal or no endocardial sclerosis. An early event in fetal life is believed to result in dilated endocardial fibroelastosis, which later morphoses into a contracted type. This suggests that the dilated type could appear as two different diseases while remaining a single disease. Secondary endocardial fibroelastosis, associated with cardiac malformations, is attributed to the cardiac hypertrophy and consequent imbalance in the myocardial oxygen supply-demand relationship. Resultant fibroelastotic thickening is often focal and less severe. However, the endocardial fibroelastosis may independently affect the ventricular function as shown in a study from Germany. [5]
Acute congestive heart failure (CHF) becomes progressive CHF that results in death within weeks, usually within the first 6 months of life. In a subgroup of individuals who survive from a few months to several years, a more chronic course is common. Such patients respond to medications used to treat CHF. A variable cyclical clinical course ensues, with CHF recurrences related to respiratory or other intercurrent infections or to progression of disease. Remissions can occur with intensification of medical therapy. Occasionally, cardiac arrhythmias can be the main presenting problem. [6]
Etiology
Possible causative factors include intrauterine viral infection (mumps, coxsackievirus B), subendocardial ischemia, impaired lymphatic drainage of the heart, and systemic carnitine deficiency. Using polymerase chain reaction (PCR) analysis, Ni et al reported that the mumps viral genome persisted in the myocardium of children with endocardial fibroelastosis; however, this requires further study. [7] The authors suggested cause and effect and speculated that the disease disappeared after the initiation of the measles-mumps-rubella (MMR) vaccination.
Nine patients with familial endocardial fibroelastosis were reported in 4 families, and inheritance patterns included X-linked recessive, autosomal dominant, and autosomal recessive. [8] Relatively recently, mutation of the gene G4.5 (tafazzin) has been associated with familial X-linked endocardial fibroelastosis and Barth syndrome and has been reported to result in morphologic changes in the fetal heart as early as 18 weeks' gestation.
Dilated (primary) endocardial fibroelastosis occurs when the heart is otherwise normal and no other cause of unexplained heart failure, including systemic carnitine deficiency, is demonstrable. Dilated endocardial fibroelastosis (secondary) is associated with aortic stenosis or atresia and includes coarctation of the aorta, ventricular septal defect, anomalous origin of left coronary artery from the pulmonary artery, myocardial injury from any cause, and metabolic or carnitine deficiency. Contracted endocardial fibroelastosis (secondary) is associated with hypoplastic left heart syndrome.
Epidemiology
United States data
The exact incidence and prevalence of endocardial fibroelastosis (EFE) is unknown owing to the relative scarcity of this condition. [2] A 1964 study demonstrated an incidence rate of 1 per 5,000 live births. [9] The incidence over subsequent years has been markedly reduced for unknown reasons, with almost no new cases in the current era. The disappearance of this condition is believed to be related to the declining prevalence of mumps.
International data
A 1978 study reported that endocardial fibroelastosis comprised 1-2% of all congenital heart diseases. [10] Currently, the number of endocardial fibroelastosis cases has dramatically fallen to almost zero. The idiopathic form of the disease is sporadic, but familial cases are also reported (10%).
Sex- and age-related demographics
Endocardial fibroelastosis equally affects both sexes.
Endocardial fibroelastosis presents during the first 3-6 months of life in 80% of cases. The typical age at diagnosis is 2-12 months. Endocardial fibroelastosis is rarely reported in adolescents and adults and is an important cause of nonimmune hydrops fetalis.
Prognosis
Primary endocardial fibroelastosis (EFE) has a relatively poor prognosis, although the condition is not universally fatal. The prognosis is worse if early onset of heart failure occurs.
Congestive heart failure (CHF) may be present. Note the following:
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Acute CHF becomes progressive CHF and terminates in death within weeks, usually within the first 6 months of life.
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In patients who survive from a few months to several years, a more chronic course is common. Such patients respond to medications for CHF. A variable cyclical clinical course ensues, with CHF recurrence related to respiratory or other intercurrent infections or to progression of disease. Remissions can occur through intensification of medical therapy.
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Poor prognostic signs of CHF include (1) presentation in the newborn period and (2) recurrent episodes of CHF despite adequate therapy, especially if episodes recur more than 6 months after initial onset of symptoms.
Morbidity/mortality
Progressive CHF causes deteriorating conditions that lead to death in one third of patients. One third of the patients survive and may experience persistent symptoms or have residual ECG abnormalities or evidence of cardiomegaly. Although some authorities are skeptical, some believe that approximately one third of the patients completely recover.
Early diagnosis and prompt persistent administration of digitalis may result in clinical improvement and reversion of the electrocardiogram (ECG) and cardiac enlargement (CE) to normal.
Morbidity varies depending on presentation. Infants who present with acute failure almost always die from the acute episode unless they receive a transplant. Patients with a chronic presentation have a 30-40% mortality due to resistant heart failure. Contracted endocardial fibroelastosis has a grave prognosis and is generally fatal.
Complications
Complications of endocardial fibroelastosis include the following:
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Resistant cardiac failure
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Recurrent chest infections
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Severe failure to thrive
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Cardiac cirrhosis
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Cerebral, coronary, and pulmonary thromboembolism
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Persistent collapse of left lower lobe or entire left lung
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Endocardial Fibroelastosis. Chest radiograph, anteroposterior view, showing cardiomegaly and pulmonary venous congestion in a 6-month-old infant with endocardial fibroelastosis (EFE).
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Endocardial Fibroelastosis. Chest radiograph, left lateral view, showing an enlarged heart in 6-month-old infant.
