| Endocardial Fibroelastosis | |
|---|---|
| Other names | EFE |
| Specialty | Cardiology  |
Endocardial fibroelastosis (EFE) is a rare heart disorder usually occurring in children two years old and younger. [1] It may also be considered a reaction to stress, not necessarily a specific disease. [2]
It should not be confused with endomyocardial fibrosis.[ citation needed ]
EFE is characterized by a thickening of the innermost lining of the heart chambers (the endocardium) due to an increase in the amount of supporting connective tissue and elastic fibres. It is an uncommon cause of unexplained heart failure in infants and children, and is one component of HEC syndrome. Fibroelastosis is strongly seen as a primary cause of restrictive cardiomyopathy in children, along with cardiac amyloidosis, which is more commonly seen in progressive multiple myeloma patients and the elderly.[ citation needed ]
A review cites references to 31 different diseases and other stresses associated with the EFE reaction. [2] These include infections, cardiomyopathies, immunologic diseases, congenital malformations, even electrocution by lightning strike. EFE has two distinct genetic forms, each having a different mode of inheritance. An X-linked recessive form, [3] and an autosomal recessive form [4] have both been observed.
A Cardiac MRI can show eccentric patchy thickening of endocardium which is a non-specific finding. Myocardial biopsy is a definitive test.[ citation needed ]
The cause should be identified and, where possible, the treatment should be directed to that cause. A last resort form of treatment is heart transplant. [5]
An infant with dilated, failing heart was no rarity on the pediatric wards of hospitals in the mid-twentieth century. On autopsy, most of these patients' hearts showed the thickened endocardial layer noted above. This was thought to be a disease affecting both the heart muscle and the endocardium and it was given various names such as: idiopathic hypertrophy of the heart, endocardial sclerosis, cardiac enlargement of unknown cause, etc. Some of these hearts also had overt congenital anomalies, especially aortic stenosis and coarctation of the aorta.[ citation needed ]
The term "endocardial fibroelastosis" was introduced by Weinberg and Himmelfarb in 1943. [6] In their pathology laboratory they noted that usually the endocardium was pearly white or opaque instead of normally thin and transparent and microscopically showed a systematic layering of collagenous and elastic fibers. They felt their new term was more adequately descriptive, and, indeed it was quickly and widely adopted. Clinicians began applying it to any infant with a dilated, failing heart, in spite of the fact that the only way to definitively establish the presence of EFE was to see it at autopsy. EFE had quickly become the name of a disease, and it continues to be used by many physicians in this way, though many patients with identical symptoms do not have the endocardial reaction of EFE.[ citation needed ]
In the latter decades of the twentieth century, new discoveries and new thinking about heart muscle disease gave rise to the term "cardiomyopathy". Many of the cases of infantile cardiac failure were accordingly called "primary cardiomyopathy" as well as "primary EFE", while those with identifiable congenital anomalies stressing the heart were called "secondary EFE". In 1957 Black-Schaffer proposed a unitary explanation that stress on the ventricle, of any kind, may trigger the endocardial reaction, so that all EFE could be thought of as secondary. [7]
Evidence gradually accumulated as to the role of infection as one such type of stress. The studies of Fruhling and colleagues in 1962 were critical. [8] They followed a series of epidemics of Coxsackie virus infection in their part of France. After each epidemic there were increased numbers of cases with EFE coming to autopsy. On closer study there were cases of pure acute myocarditis, cases of mixed myocarditis and EFE, and cases where myocarditis had healed, leaving just EFE. They were able to culture Coxsackie virus from the tissues of many of the cases at all stages of this apparent progression. A similar progression from myocarditis to EFE was later observed at Johns Hopkins but no virology was done. [9]
Noren and colleagues at the University of Minnesota, acting on an idea floated at a pediatric meeting, were able to show a relation between exposure to maternal mumps in fetal life, EFE, and a positive skin test for mumps in infants. [10] This brought on a large ongoing controversy and finally prompted a virologist colleague of theirs to inject embryonated eggs with mumps virus. [11] The chicks at first showed the changes of myocarditis, about a year later, typical EFE, and transitional changes in between. Despite this, the controversy about the role of mumps continued as the actual incidence of EFE plummeted. The proponents of mumps as a cause pointed to this as the effect of the recent implementation of widespread mumps immunization.[ citation needed ]
Evidence that viral infection may play a role as a cause or trigger of EFE was greatly reinforced by the study directed by Towbin in the virus laboratory of Texas Children's Hospital. [12] They applied the methods of today's genetics to old preserved specimens from autopsies of patients with EFE done well before mumps immunization began and found mumps genome in the tissues of over 80% of these patients. It seems undeniable that transplacental mumps infection had been in the past the major cause of EFE, and that immunization was indeed the cause of EFE having become rare.[ citation needed ]
Non-infectious causes of EFE have also been studied, spurred by the opening of new avenues of genetics research. Now there are specific named genes associated with certain cardiomyopathies, some of which show the characteristic reaction of EFE. A typical example is Barth syndrome and the responsible gene, tafazzin. [13]
Developments in echocardiography, both the technology of the machines and the skill of the operators, have made it no longer necessary to see the endocardium at autopsy. EFE can now be found non-invasively by the recording of increased endocardial echos. Fetal echocardiography has shown that EFE can begin to accumulate as early as 14 weeks of gestation, and increase with incredible rapidity [14] and even that it can be reversed if the stress can be removed early in fetal life. [15]
The North American Pediatric Cardiomyopathy Registry was founded in 2000 and has been supported since by the National Heart, Lung and Blood Institute. Because of the logic of the diagnostic tree, where EFE applies to many branches of the tree and thus cannot occupy a branch, it is not listed by the Registry as a cause but rather, "with EFE" is a modifier that can be applied to any cause. [16]
Thus, the past half-century has seen EFE evolve from a mysterious but frequently observed disease to a rare but much better understood reaction to many diseases and other stresses.[ citation needed ]
Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. An irregular heart beat and fainting may occur. Those affected are at an increased risk of sudden cardiac death.
Mumps is a highly contagious viral disease caused by the mumps virus. Initial symptoms of mumps are non-specific and include fever, headache, malaise, muscle pain, and loss of appetite. These symptoms are usually followed by painful swelling around the side of the face, which is the most common symptom of a mumps infection. Symptoms typically occur 16 to 18 days after exposure to the virus. About one third of people with a mumps infection do not have any symptoms (asymptomatic).
Congenital rubella syndrome (CRS) occurs when a human fetus is infected with the rubella virus via maternal-fetal transmission and develops birth defects. The most common congenital defects affect the ophthalmologic, cardiac, auditory, and neurologic systems.
Barth syndrome (BTHS) is a rare but serious X-linked genetic disorder, caused by changes in phospholipid structure and metabolism. It may affect multiple body systems, and is potentially fatal. The syndrome is diagnosed almost exclusively in males.
Coxsackie B is a group of six serotypes of coxsackievirus (CVB1-CVB6), a pathogenic enterovirus, that trigger illness ranging from gastrointestinal distress to full-fledged pericarditis and myocarditis.
Myocarditis is defined as inflammation of the myocardium. Myocarditis can progress to inflammatory cardiomyopathy when there are associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure due to dilated cardiomyopathy or cardiac arrest.
Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease.
Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Complications can include heart failure, heart valve disease, or an irregular heartbeat.
Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when sitting up and more severe when lying down or breathing deeply. Other symptoms of pericarditis can include fever, weakness, palpitations, and shortness of breath. The onset of symptoms can occasionally be gradual rather than sudden.
Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy that is defined as a deterioration in cardiac function presenting typically between the last month of pregnancy and up to six months postpartum. As with other forms of dilated cardiomyopathy, PPCM involves systolic dysfunction of the heart with a decrease of the left ventricular ejection fraction (EF) with associated congestive heart failure and an increased risk of atrial and ventricular arrhythmias, thromboembolism (blockage of a blood vessel by a blood clot), and even sudden cardiac death. In essence, the heart muscle cannot contract forcefully enough to pump adequate amounts of blood for the needs of the body's vital organs.
Enterovirus is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine.
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. Myopathy means muscle disease. This meaning implies that the primary defect is within the muscle, as opposed to the nerves or elsewhere.
Cardiomegaly is a medical condition in which the heart becomes enlarged. It is more commonly referred to simply as "having an enlarged heart". It is usually the result of underlying conditions that make the heart work harder, such as obesity, heart valve disease, high blood pressure (hypertension), and coronary artery disease. Cardiomyopathy is also associated with cardiomegaly.
Loeffler endocarditis is a form of heart disease characterized by a stiffened, poorly-functioning heart caused by infiltration of the heart by white blood cells known as eosinophils. Restrictive cardiomyopathy is a disease of the heart muscle which results in impaired diastolic filling of the heart ventricles, i.e. the large heart chambers which pump blood into the pulmonary or systemic circulation. Diastole is the part of the cardiac contraction-relaxation cycle in which the heart fills with venous blood after the emptying done during its previous systole.
Neonatal lupuserythematosus is an autoimmune disease in an infant born to a mother with anti-Ro/SSA and with or without anti-La/SSB antibodies. The disease most commonly presents with a rash resembling subacute cutaneous lupus erythematosus and can have systemic abnormalities such as complete heart block or hepatosplenomegaly. Neonatal lupus is usually benign and self-limited. Many of the clinical manifestations are transient, but certain heart problems can be permanent. Diagnosis is based on maternal antibodies and clinical manifestations. Treatment and management is mainly supportive and focused on preventing complete heart block if possible.
sCAR-Fc is an experimental prophylactic treatment against coxsackievirus B3 (CVB) infections. Coxsackievirus B3 can cause cardiac damage, eventually resulting in a weakened and enlarged heart that is termed dilated cardiomyopathy. While many other treatments inhibit viral proliferation in myocytes, sCAR-Fc prevents the virus entering the cell by competitively binding to coxsackie virus and adenovirus receptors (CAR) on the membrane of myocytes.
Coxsackieviruses-induced cardiomyopathy are positive-stranded RNA viruses in picornavirus family and the genus enterovirus, acute enterovirus infections such as Coxsackievirus B3 have been identified as the cause of virally induced acute myocarditis, resulting in dilated cardiomyopathy. Dilated cardiomyopathy in humans can be caused by multiple factors including hereditary defects in the cytoskeletal protein dystrophin in Duchenne muscular dystrophy (DMD) patients). A heart that undergoes dilated cardiomyopathy shows unique enlargement of ventricles, and thinning of the ventricular wall that may lead to heart failure. In addition to the genetic defects in dystrophin or other cytoskeletal proteins, a subset of dilated cardiomyopathy is linked to enteroviral infection in the heart, especially coxsackievirus B. Enterovirus infections are responsible for about 30% of the cases of acquired dilated cardiomyopathy in humans.
Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1N1, Epstein–Barr virus, rubella, varicella, mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies and the viruses that cause hepatitis A and C, as well as COVID-19, which has been seen to cause this in persons otherwise thought to have a "low risk" of the virus's effects.
Heart problems are more common in people with HIV/AIDS. Those with left ventricular dysfunction have a median survival of 101 days as compared to 472 days in people with AIDS with healthy hearts. HIV is a major cause of cardiomyopathy. The most common type of HIV induced cardiomyopathy is dilated cardiomyopathy also known as eccentric ventricular hypertrophy which leads to impaired contraction of the ventricles due to volume overload. The annual incidence of HIV associated dilated cardiomyopathy was 15.9/1000 before the introduction of highly active antiretroviral therapy (HAART). However, in 2014, a study found that 17.6% of HIV patients have dilated cardiomyopathy (176/1000) meaning the incidence has greatly increased.
Eosinophilic myocarditis is inflammation in the heart muscle that is caused by the infiltration and destructive activity of a type of white blood cell, the eosinophil. Typically, the disorder is associated with hypereosinophilia, i.e. an eosinophil blood cell count greater than 1,500 per microliter. It is distinguished from non-eosinophilic myocarditis, which is heart inflammation caused by other types of white blood cells, i.e. lymphocytes and monocytes, as well as the respective descendants of these cells, NK cells and macrophages. This distinction is important because the eosinophil-based disorder is due to a particular set of underlying diseases and its preferred treatments differ from those for non-eosinophilic myocarditis.