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guidelines that do exist acknowledge the lack of high-quality pediatric studies.309 Medical therapy is based on extrapolated data from adult DCM, and whether this is applicable remains unclear.275,310 Diuretics and Mineralocorticoid Antagonists Loop diuretics are typically the initial therapy for symptomatic treatment Thiazide diuretics may also be used as monotherapy or in addition to loop diuretics The mineralocorticoid antagonists spironolactone and eplerenone have been shown to improve outcomes in adults with symptomatic heart failure and reduced ejection fraction (HFrEF).311,312 There are few data assessing the effect of mineralocorticoid antagonists in children outside of patients with muscular dystrophy Early studies have suggested that eplerenone may have a therapeutic benefit in patients with Duchenne muscular dystrophy.313 Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Multiple large multicenter, placebo-controlled trials have shown that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve cardiovascular outcomes in adults with HFrEF.314–317 Retrospective, single-center and multicenter studies in children have reported a more mixed effect.274,275,318,319 However, these studies are limited by their retrospective nature, inconsistent dosing strategies, and patient selection bias Early initiation of angiotensin-converting enzyme inhibitors in patients with dystrophinopathy may delay the onset of cardiac dysfunction and slow the progression of myocardial fibrosis.320,321 β-Blockers Multiple large, multicenter, placebo-controlled trials have shown that β-blockers improve outcomes in adults with HFrEF.322,323 Studies examining the effects of β-blockers in children are limited.324,325 The largest study to date showed no difference in outcome among children who received carvedilol.326 However, this included a heterogeneous population (including patients with congenital heart disease and across a range of ages) Recent data suggest that age- and genotype- dependent β-adrenergic signaling and pharmacokinetics may drive outcome and therapeutic response and thus may obscure the potential treatment effect.310,327–329 Anticoagulation The risk of thromboembolism in pediatric DCM is not well defined Studies in adults have suggested that warfarin does not provide a therapeutic benefit among most patients in sinus rhythm; however, improved outcomes may be seen in patients with greater time in the therapeutic range.330,331 Other Therapies Digoxin improves symptom severity but not outcome in adults with heart failure.332,333 Routine monitoring of digoxin concentration is recommended, given the association between higher digoxin (>1 to 1.1 ng/mL) levels and mortality in adults with heart failure.334,335 Data in pediatric patients are again limited Cardiac Resynchronization Therapy Cardiac resynchronization therapy reduces symptoms and improves left ventricular function in subgroups of adults with HFrEF and cardiac dyssynchrony.336–338 Cardiac resynchronization therapy appears to confer some benefits in pediatric patients with electromechanical dyssynchrony; however, the studies to date have largely focused on the use of short-term cardiac resynchronization therapy in patients with repaired congenital heart disease.339,340 It remains unclear whether the long-term use of cardiac resynchronization therapy is beneficial in pediatric patients with DCM and the patient population (including QRS duration) that may benefit most from therapy Therapy With Ventricular Assist Devices Ventricular assist devices have been shown to improve outcomes among children with end-stage heart failure due to DCM.341–343 The use of ventricular assist devices and heart transplantation are discussed in detail in other chapters Restrictive Cardiomyopathy Definition RCM is characterized by normal or decreased ventricular volumes, normal left ventricular wall thickness, normal or near-normal systolic function, and diastolic dysfunction with biatrial enlargement Epidemiology RCM is the least common of the cardiomyopathies and accounts for approximately 3% of cardiomyopathy cases in children.267,268 There is no gender predominance in RCM The majority of patients present between 1 year of age and the teenage years.267–269 Clinical Outcomes Historically the outcomes have been quite poor Patients are at risk of sudden death as well as progressive heart failure, with reported actuarial survival of approximately 50% at 2 years after diagnosis; in some patients there is rapid, fulminant disease progression.344–346 However, the outcomes were not uniformly poor, with 30% to 50% of patients surviving for more than 5 years from the time of diagnosis.345,347,348 Given that the optimal timing for listing was unclear, early listing for transplantation has been common The waitlist outcomes from the Pediatric Heart Transplant Study reflect the competing risks.349 There is an early hazard for death, especially in status 1 patients and those below 1 year of age, whereas older patients have a better prognosis In fact, 40% of the waitlist mortality occurred in infants, in spite of the fact that they accounted for only 10% of the listed patients Analysis of data from the PCMR showed similar results There was an early significant risk for death, as the median time from diagnosis to death was 0.3 months in the patients who did not survive.350 Progressive heart failure was the most common cause of death, followed by sudden death, whereas stroke was rare and occurred in only 1 patient Symptomatic heart failure and lower fractional shortening were associated adverse outcomes in this cohort The risk of sudden death was significantly lower in the data from the National Australian Childhood Cardiomyopathy ... therapeutic response and thus may obscure the potential treatment effect.310,327–329 Anticoagulation The risk of thromboembolism in pediatric DCM is not well defined Studies in adults have suggested that warfarin does not provide a therapeutic benefit among... given the association between higher digoxin (>1 to 1.1 ng/mL) levels and mortality in adults with heart failure.334,335 Data in pediatric patients are again limited Cardiac Resynchronization Therapy Cardiac resynchronization therapy reduces symptoms and improves left... ventricular function in subgroups of adults with HFrEF and cardiac dyssynchrony.336–338 Cardiac resynchronization therapy appears to confer some benefits in pediatric patients with electromechanical dyssynchrony; however, the studies to date have largely focused on the use of short-term cardiac