Endocardial Fibroelastosis (EFE)

Endocardial Fibroelastosis (EFE)

Background

The term endocardial fibroelastosis (EFE) was introduced by Weinberg and Himmelfarb in 1943.1 Endocardial fibroelastosis refers to a pronounced, diffuse thickening of the ventricular endocardium and presents as unexplained heart failure in infants and children. The disease can be primary or secondary to various congenital heart diseases, most notably hypoplastic left heart syndrome, aortic stenosis, or atresia. The 2 pathologic forms of primary endocardial fibroelastosis include 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.

Pathophysiology

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 been noted.

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 2 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.

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.

Frequency

United States
A 1964 study demonstrated an incidence rate of 1 per 5,000 live births.2 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
A 1978 study reported that endocardial fibroelastosis comprised 1-2% of all congenital heart diseases.3 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%).

Mortality/Morbidity
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 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 rate due to resistant heart failure. Contracted endocardial fibroelastosis has a grave prognosis and is generally fatal.

Sex
Endocardial fibroelastosis equally affects both sexes.

Age
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.

Clinical

History

o Symptoms of endocardial fibroelastosis (EFE) include feeding difficulty, excessive sweating, breathlessness, failure to thrive, and wheezing.
o Onset may acute enough to produce cardiogenic shock or sudden death; it is a recognized cause of sudden death in infancy.
o Approximately 20% of patients have a history of frequent or recent respiratory tract infections.
o Episodes of severe sudden abdominal pain may indicate coronary insufficiency.
o The contracted form of endocardial fibroelastosis presents with features of left-sided obstructive disease and acute left ventricular failure.
o Endocardial fibroelastosis is one of the recognized causes of nonimmune hydrops fetalis.

Physical

o Endocardial fibroelastosis manifests as the classic features of heart failure.
o Tachypnea during feeding and grunting respirations with subcostal or intercostal retractions have been reported. Fine expiratory wheezes or rales in the lung bases are common.
o The following may be present upon admission:
oPallor
oPeripheral cyanosis
oFever
oLeukocytosis
oAnemia
oRash
o Thromboembolic episodes may lead to sudden death, myocardial infarction, cerebrovascular events, or even pulmonary embolism.
o The usual physical findings are as follows:
oCardiomegaly with normal-to-faint first and second heart sounds, a gallop rhythm with an audible third heart sound, apical pansystolic murmur of mitral regurgitation, and hepatosplenomegaly
oClinically detectable pleural or pericardial effusions (rare)

Causes

o Possible causative factors include intrauterine viral infection (mumps, coxsackievirus B), subendocardial ischemia, impaired lymphatic drainage of the heart, and systemic carnitine deficiency.

o 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.