Andersons pediatric cardiology 1659

Arrhythmogenic Right Ventricular Cardiomyopathy Definition Arrhythmogenic right ventricular cardiomyopathy is characterized by fibrofatty replacement of cardiomyocytes with associated cardiac dysfunction and ventricular arrhythmias In spite of its name, fibrofatty replacement may occur in either the right or left ventricle (~50% of adult cases have left-sided involvement) and left-dominant forms are described.368 Fatty replacement of the ventricle is typically followed by ventricular dysfunction, dilation, and arrhythmia Epidemiology The prevalence of ARVC has been estimated to range from 1 : 1000 to 1 : 5000, but ascertaining the true prevalence has been limited by changing diagnostic criteria, age- and gender-dependent penetrance, as well as tertiary referral bias.369–371 The disease affects men more frequently than women The diagnosis is a rare cause of cardiomyopathy in children, although it is an important cause of sudden death in teenage and young adult athletes.372,373 Clinical Outcomes Arrhythmogenic right ventricular cardiomyopathy has an age- and activitydependent phenotype.374,375 Fibrofatty replacement of the myocardium typically begins in the epicardial or midmyocardial tissue Patients are typically asymptomatic in the initial phase, although they are at risk of sudden death Symptoms and clinically significant events very rarely appear before age 13.376 The second phase of disease is characterized by an elevated risk of lifethreatening arrhythmias The highest risk for life-threatening arrhythmias occurs between ages 20 and 40, although sudden death may occur in the teenage years as well.377 Approximately 10% of patients will have sudden death or aborted sudden death (~5% of patients each) as their first manifestation of disease.376–378 The late stage of disease (in adulthood) is characterized by continued risk for arrhythmias as well as the onset of ventricular dysfunction (right, left, or both depending on the phenotype).376,378 In spite of the risks, the overall mortality rate is below 1% among nontertiary referral center populations.379 Etiology Thirty to 50% of patients with ARVC will have a family history of disease and approximately 40% to 50% of patients will have a disease-causing mutation identified, although not all patients with a mutation will develop phenotypic disease.371,376 The disease is typically inherited in autosomal dominant fashion, and a number of desmosomal proteins have been associated with it (see Table 61.1) Desmosomal proteins and other components of intercalated disks have been implicated in disease development These proteins modulate cell-cell adhesion and electromechanical coupling, and their roles in each has been used to explain the relationship between disease severity and exercise.374,375,377 A few extradesmosomal genes have also been implicated in ARVC (e.g., ryanodine receptor).380 As in the other cardiomyopathies, widespread exome data are modifying our understanding of the pathogenicity of mutations.381 Pathology The pathologic findings of disease vary based on patient age and stage of disease Early autopsy- and catheterization-based studies have identified pathology primarily in the apical, inflow, and infundibular segments of the right ventricle, subsequently called the “triangle of dysplasia.”382 More recently, widespread patient screening and the use of CMRI data have suggested that apical involvement may in fact be a late manifestation of disease.383 Left ventricular disease is common in the late stages of disease but may be the predominant manifestation of disease in a minority of patients.384 Clinical Features The diagnostic criteria for ARVC were revised in 2010 and rely on multimodality diagnostic evaluation in addition to family history.385 Based on the current task force criteria, patients are categorized as “definite, borderline or possible” ARVC Symptoms The majority of patients are asymptomatic through their early teens Symptoms typically begin in the second decade of life, at which point there is increasing risk of cardiovascular events due to sudden death and eventually heart failure.369–371,376,377 Arrhythmic symptoms predominate in children (e.g., palpitations, syncope), as the risk of heart failure is low until adulthood The risk of cardiovascular events appears to be lifelong, even for patients who present late with disease.386 Physical Examination The physical exam findings are generally relatively unremarkable during childhood The apical impulse is typically unremarkable until the onset of ventricular dilation and dysfunction There may be a murmur of atrioventricular valve regurgitation if dilation and dysfunction are present A prominently split S2 may be present in the setting of right bundle branch block Dermatologic manifestations of disease may be present in patients with cardiocutaneous disease (Naxos disease and Carvajal syndrome) Electrocardiography The ECG typically shows inverted T waves (in the absence or right bundle branch block) and may show presence of an epsilon wave in the anterior precordial leads (V1 to V3) However, T-wave inversion in leads V1 and V2 is a normal finding in 3% to 5% of late teens and early adults, so it can pose a diagnostic conundrum, especially in young athletes.387–389 T-wave inversion beyond V2 is less common in this population and should raise greater suspicion for ARVC T-wave inversion in the inferior or lateral leads is suggestive of left ventricular disease Ventricular ectopy may be present on a resting ECG For patients with classic, right-dominant disease, a left bundle branch block pattern is typical, given that the right ventricle is the origin of ectopy The axis may be superior or inferior depending on the exact location of the ectopic focus.390,391 Patients with left-sided or biventricular disease may show alternate morphologies