Andersons pediatric cardiology 1657

Study; however, there were only eight patients with RCM in this cohort, making it difficult to extrapolate the data on a larger scale.232 Etiology Sarcomeric Mutations Mutations in a number of sarcomeric, cytoskeletal, and Z-band proteins have been associated with RCM (see Table 61.1) As in the case of HCM and DCM, the advent of low-cost genetic screening has revealed that what was previously called idiopathic RCM is in fact genetically driven Mutations in desmin are associated with RCM, atrioventricular block, and skeletal myopathy.351 This is typically inherited in an autosomal dominant pattern; however, recessive inheritance has also been described.352 Mutations in myosin-binding protein C, β-myosin heavy chain, troponin I, troponin T, filamin C, myopalladin, and cardiac α-actin have also been linked to RCM.70,353–355 Given the affected genes, it is no surprise that there is often an overlapping spectrum of disease with HCM Next-generation sequencing has also identified a number of mutations in numerous sarcomeric, cytoskeletal, and Z-band proteins that are possibly pathogenic; however, further phenotypic evaluations are needed to confirm the early findings.356 Endomyocardial Fibrosis and Eosinophilic Cardiomyopathy (Loeffler Syndrome) Endomyocardial fibrosis is a disease of tropical Africa, Asia, and South America that may lead to restrictive physiology It has a bimodal distribution with a notable peak in the teenage years and again around age 30 years.357 The outcome is typically very poor and management relies on symptomatic relief and anticoagulation owing to the risk of thromboembolic disease.358 The cause remains unclear but—given the individual factors do not adequately explain the geographic and clinical characteristics of disease—likely involves a combination of environmental, infectious, and genetic risk factors.359 Restrictive physiology may also develop in the chronic phase of hypereosinophilic disease (Loeffler syndrome or endocarditis).360 Infiltrative Disease Cardiac sarcoidosis is a rare cause of RCM in children The disease typically manifests as systolic dysfunction with or without heart block in young and middle-aged adults.361,362 Clinical studies using a broader screening protocol suggest that subclinical cardiac manifestations of disease may be evident by CMR.362,363 Mutations in transthyretin lead to inherited amyloidosis, which may manifest as RCM; however, this is again a more notable cause of disease in adults than in children.364 Restrictive physiology may also be seen in the spectrum of disease in patients with lysosomal storage disease, although these diseases are typically associated with an HCM phenotype Pathology Macroscopically, RCM is characterized by biatrial dilation with a small or normal-sized left ventricular cavity without the presence of ventricular hypertrophy There is a spectrum of disease that extends into HCM, so-called HCM with restrictive physiology.350 The atrial enlargement may predispose patients to the development of atrial thrombus Microscopically, RCM is characterized patchy atrial and ventricular fibrosis with variable myocyte hypertrophy.344 Fibrosis may be present in the sinuatrial and atrioventricular nodes and contributes to the risk of bradyarrhythmic death.365,366 Pathophysiology RCM is characterized by reduced ventricular compliance, leading to elevated ventricular filling pressures and impaired cardiac output Chronically elevated left atrial pressures may lead to the rapid and unpredictable development of pulmonary vascular disease.346 Arrhythmias—including high-grade heart block, atrial tachycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation—have all been reported and contribute to the risk of death, both sudden and due to thromboembolic disease.346,350,366 Clinical Features Symptoms Infants and toddlers may present with respiratory distress, tachypnea, and failure to thrive Older children and adolescents present with similar symptoms as well as chest pain, near syncope, syncope, or palpitations The venous congestion associated with RCM may also produce significant edema and ascites Physical Examination The physical exam findings are consistent with those expected for elevated right and left ventricular filling pressures Jugular venous distention, hepatomegaly, ascites, and peripheral edema may be present The apical impulse is typically unremarkable The pulmonary component of the second heart sound is often accentuated, given the elevated pulmonary artery pressures A gallop is frequently heard Electrocardiography and Ambulatory Electrocardiographic Monitoring The ECG findings of RCM are often pathognomonic, with giant significant biatrial enlargement (Fig 61.11) Sinus node bradycardia, atrial arrhythmias, varying grades of atrioventricular block, and QRS prolongation may be present.366 Nonspecific ST- and T-wave abnormalities are also commonly present