Long-term Outcomes of Pediatric-Onset Hypertrophic Cardiomyopathy and Age-Specific Risk Factors for Lethal Arrhythmic Events

Abstract

<div class="section"> <a class="named-anchor" id="ab-hbr180004-1"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e514">Question</h5> <p id="d5525218e516">What is the long-term outcome of pediatric-onset hypertrophic cardiomyopathy, and are there age-specific risk factors for lethal arrhythmic events? </p> </div><div class="section"> <a class="named-anchor" id="ab-hbr180004-2"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e519">Findings</h5> <p id="d5525218e521">In this cohort study, 24 of 100 patients with hypertrophic cardiomyopathy diagnosed between age 1 and 16 years had major events in 9.2 years (mean rate, 1.9% per year), including 19 lethal arrhythmic events (at a mean [SD] age of 23.1 [11.5] years and up to 33 years after diagnosis) and 5 heart failure–related events. Risk was predicted by limiting symptoms at initial evaluation and Troponin I or T gene mutations. </p> </div><div class="section"> <a class="named-anchor" id="ab-hbr180004-3"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e524">Meaning</h5> <p id="d5525218e526">Pediatric-onset hypertrophic cardiomyopathy is characterized by adverse outcomes driven mainly by arrhythmic events; risk extends well beyond adolescence, requiring unchanged levels of surveillance into adulthood, and predictors of risk in this age group differ from those of adult populations. </p> </div><p class="first" id="d5525218e529">This study describes the long-term outcome of pediatric-onset hypertrophic cardiomyopathy and identifies age-specific arrhythmic risk factors. </p><div class="section"> <a class="named-anchor" id="ab-hbr180004-4"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e533">Importance</h5> <p id="d5525218e535">Predictors of lethal arrhythmic events (LAEs) after a pediatric diagnosis of hypertrophic cardiomyopathy (HCM) are unresolved. Existing algorithms for risk stratification are limited to patients older than 16 years because of a lack of data on younger individuals. </p> </div><div class="section"> <a class="named-anchor" id="ab-hbr180004-5"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e538">Objective</h5> <p id="d5525218e540">To describe the long-term outcome of pediatric-onset HCM and identify age-specific arrhythmic risk factors. </p> </div><div class="section"> <a class="named-anchor" id="ab-hbr180004-6"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e543">Design, Setting, and Participants</h5> <p id="d5525218e545">This study assessed patients with pediatric-onset hypertrophic cardiomyopathy diagnosed from 1974 to 2016 in 2 national referral centers for cardiomyopathies in Florence, Italy. Patients with metabolic and syndromic disease were excluded. </p> </div><div class="section"> <a class="named-anchor" id="ab-hbr180004-7"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e548">Exposures</h5> <p id="d5525218e550">Patients were assessed at 1-year intervals, or more often, if their clinical condition required. </p> </div><div class="section"> <a class="named-anchor" id="ab-hbr180004-8"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e553">Main Outcomes and Measures</h5> <p id="d5525218e555">Lethal arrhythmic events (LAEs) and death related to heart failure.</p> </div><div class="section"> <a class="named-anchor" id="ab-hbr180004-9"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e558">Results</h5> <p id="d5525218e560">Of 1644 patients with HCM, 100 (6.1%) were 1 to 16 years old at diagnosis (median [interquartile range], 12.2 [7.3-14.1] years). Of these, 63 (63.0%) were boys. Forty-two of the 100 patients (42.0%) were symptomatic (defined as an New York Heart Association classification higher than 1 or a Ross score greater than 2). The yield of sarcomere gene testing was 55 of 70 patients (79%). During a median of 9.2 years during which a mean of 1229 patients were treated per year, 24 of 100 patients (24.0%) experienced cardiac events (1.9% per year), including 19 LAEs and 5 heart failure–related events (3 deaths and 2 heart transplants). Lethal arrhythmic events occurred at a mean (SD) age of 23.1 (11.5) years. Two survivors of LAEs with symptoms of heart failure experienced recurrent cardiac arrest despite an implantable cardioverter defibrillator. Risk of LAE was associated with symptoms at onset (hazard ratio [HR], 8.2; 95% CI, 1.5-68.4; <i>P</i> = .02) and Troponin I or Troponin T gene mutations (HR, 4.1; 95% CI, 0.9-36.5; <i>P</i> = .06). Adult HCM risk predictors performed poorly in this population. Data analysis occurred from December 2016 to October 2017. </p> </div><div class="section"> <a class="named-anchor" id="ab-hbr180004-10"> <!-- named anchor --> </a> <h5 class="section-title" id="d5525218e569">Conclusions and Relevance</h5> <p id="d5525218e571">Pediatric-onset HCM is rare and associated with adverse outcomes driven mainly by arrhythmic events. Risk extends well beyond adolescence, which calls for unchanged clinical surveillance into adulthood. In this study, predictors of adverse outcomes differ from those of adult populations with HCM. In secondary prevention, the implantable cardioverter defibrillator did not confer absolute protection in the presence of limiting symptoms of heart failure. </p> </div>