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Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease. ACM is caused by genetic defects of parts of the cardiac muscle known as desmosomes, areas on the surface of muscle cells which link them together. The desmosomes are composed of several proteins, and many of those proteins can have harmful mutations. ARVC can also develop in intense endurance athletes in the absence of desmosomal abnormalities. Exercise-induced ARVC cause possibly is a result of excessive right ventricular wall stress during high intensity exercise. The disease is a type of non-ischemic cardiomyopathy that primarily involves the right ventricle, though cases of exclusive left ventricular disease have been reported. It is characterized by hypokinetic areas involving the free wall of the ventricle, with fibrofatty replacement of the myocardium, with associated arrhythmias often originating in the right ventricle. The nomenclature ARVD is currently thought to be inappropriate and misleading as ACM does not involve dysplasia of the ventricular wall. Cases of ACM originating from the left ventricle led to the abandonment of the name ARVC. ACM can be found in association with diffuse palmoplantar keratoderma, and woolly hair, in an autosomal recessive condition called Naxos disease, because this genetic abnormality can also affect the integrity of the superficial layers of the skin most exposed to pressure stress.: 513  ACM is an important cause of ventricular arrhythmias in children and young adults. It is seen predominantly in males, and 30–50% of cases have a familial distribution. Signs and symptoms Those affected by arrhythmogenic cardiomyopathy may not have any symptoms at all despite having significant abnormalities in the structure of their hearts. If symptoms do occur, the initial presentation is often due to abnormal heart rhythms (arrhythmias) which in arrhythmogenic cardiomyopathy may take the form of palpitations, or blackouts. Sudden death may be the first presentation of ACM without any preceding symptoms. These symptoms often occur during adolescence and early adulthood, but signs of ACM may rarely be seen in infants. As ACM progresses, the muscle tissue within the ventricles may dilate and weaken. The right ventricle typically weakens first, leading to fatigue and ankle swelling. In the later stages of the disease in which both ventricles are involved shortness of breath may develop, especially when lying flat. Causes Genetics ACM is usually inherited in an autosomal dominant pattern, with variable expression. Only 30% to 50% of individuals affected by ACM will test positive to one of the known genetic mutations in chromosomal loci associated with the disease. Novel studies showed that mutations (point mutations) in genes encoding for desmosomal proteins (see intercalated disc) are the main causatives for the development of this disease. Recently it has been shown, that mutations in the desmin DES gene could cause ACM. Desmin is an intermediate filament protein, which is linked to the desmosomes. Different DES mutations cause an abnormal aggregation of desmin and associated proteins. The penetrance is 20–35% in general, but significantly higher in Italy. Seven gene loci have been implicated in ACM. It is unclear whether the pathogenesis varies with the different loci involved. Standard genetic screening test are currently tested and evaluated in different state of the art cardiovascular research centres and hospitals. Types include: Exercise-induced ARVC In recent years, several studies have found that excessive long-term sports activity can cause exercise-induced arrhythmogenic right ventricular cardiomyopathy (EIARVC). For some athletes ARVC might develop due to high-endurance exercise and it most often develops without an underlying desmosomal abnormalities. This could possibly be a result of excessive right ventricular (RV) wall stress during very high volumes of training, which is known to be causing a disproportionate remodeling of RV. In a 2003 study, 46 endurance athletes, mostly cyclists, presented with various symptoms suggestive of arrhythmia of RV origin. 59% of participants tested met the criteria for ARVC, and another 30% for possible ARVC. Only 1 athlete of the group had a family history of hereditary ARVC. Exercise-induced ARVC and athlete's heart have overlapping features. Pathogenesis The pathogenesis of ACM is largely unknown. Apoptosis (programmed cell death) appears to play a large role. It was previously thought that only the right ventricle is involved, but recent cohorts have shown many cases of left ventricular disease and biventricular disease. The disease process starts in the subepicardial region and works its way towards the endocardial surface, leading to transmural involvement (possibly accounting for the aneurysmal dilatation of the ventricles). Residual myocardium is confined to the subendocardial region and the trabeculae of the ventricles. These trabeculae may become hypertrophied. Aneurysmal dilatation is seen in 50% of cases at autopsy. It usually occurs in the diaphragmatic, apical, and infundibular regions (known as the triangle of dysplasia). The left ventricle is involved in 50–67% of individuals. If the left ventricle is involved, it is usually late in the course of disease, and confers a poor prognosis. There are two pathological patterns seen in ACM, Fatty infiltration and fibro-fatty infiltration. Fatty infiltration At first, fatty infiltration, is confined to the right ventricle. This involves a partial or near-complete substitution of myocardium with fatty tissue without wall thinning. It involves predominantly the apical and infundibular regions of the RV. The left ventricle and ventricular septum are usually spared. No inflammatory infiltrates are seen in fatty infiltration. There is evidence of myocyte (myocardial cell) degeneration and death seen in 50% of cases of fatty infiltration. Fibro-fatty infiltration The second, fibro-fatty infiltration, involves replacement of myocytes with fibrofatty tissue. A patchy myocarditis is involved in up to 2/3 of cases, with inflammatory infiltrates (mostly T cells) seen on microscopy. Myocardial atrophy is due to injury and apoptosis. This leads to thinning of the RV free wall (to < 3 mm thickness) Myocytes are replaced with fibrofatty tissue. The regions preferentially involved include the RV inflow tract, the RV outflow tract, and the RV apex. However, the LV free wall may be involved in some cases. Involvement of the ventricular septum is rare. The areas involved are prone to aneurysm formation. The Role of Exercise Recently, some studies have identified strenuous exercise as a novel risk for accelerated progression of the disease. One retrospective study on 301 patients conclusively demonstrated that the subpopulations participating in strenuous physical activity (professional athletes for example) had an earlier onset of symptoms and earlier mortality compared to othe.... Discover the Simone Malacrida popular books. Find the top 100 most popular Simone Malacrida books.