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

Abstract

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.

Altered Ca2+ and Na+ Homeostasis in Human Hypertrophic Cardiomyopathy: Implications for Arrhythmogenesis

“…However, a clear relationship between fibrosis (measured with LGE), microvascular dysfunction (measured by PET) and arrhythmic risk is observed only in the minority of patients (10–15%) that experience a slow progression toward end-stage HCM, an highly arrhythmogenic condition not unlike terminal ischemic heart failure, thus requiring aggressive preventive strategies ( Priori et al, 2015 ). On the contrary, the majority of sudden cardiac death events due to lethal ventricular arrhythmias occur in patients at earlier stages of disease progression, often in the absence of marked structural abnormalities besides left-ventricular (LV) hypertrophy, also in very young patients ( Maurizi et al, 2018 ). In early stages of hypertrophic cardiomyopathies, replacement scars are absent and only microscopic intramyocardial fibrosis is present, and its extent can be assessed by CMR using T1-mapping ( Dass et al, 2012 ) or extracellular volume (ECV) measurements with gadolinium contrast, both altered even before the onset of hypertrophy in HCM-mutation carriers ( Ho et al, 2013 ).…”

Sudden Cardiac Death in Children Affected by Cardiomyopathies: An Update on Risk Factors and Indications at Transvenous or Subcutaneous Implantable Defibrillators

“…More recently, Norrish et al (45) developed a novel risk prediction model for sudden cardiac death in HCM children through a retrospective, multicenter, longitudinal cohort study on 1,024 patients below 16 years and the most predictive variables included in the model were unexplained syncope, degree of hypertrophy, LA diameter and NSVT, while the maximal LVOT gradient appeared to be inversely related with SCD risk, a data that clearly needs further investigation. Finally, Maurizi et al (29) described the long-term outcome of 100 pediatric patients with HCM, with a 40-year follow-up. Interestingly, genetic data emerged as major predictors of SCD at multivariate analysis.…”

Can positron emission tomography help stratify the risk of sudden cardiac death in patients with hypertrophic cardiomyopathy?

“…[1][2][3][4] The clinical consequences of these mutations are widely variable, ranging from patients remaining totally asymptomatic to the most dreaded outcome, sudden cardiac death (SCD) which accounts for over 50% of deaths in this population. 4 Despite considerable advances in our understanding of the genetic basis for this disease and its relation to the clinical course of patients with these mutations, 5 there remains considerable heterogeneity in the risk of adverse outcomes. This is especially relevant as a clinician tries to prevent sudden cardiac death for an individual patient while minimizing the burden of therapy.…”

“…[7][8][9] The generally accepted indications for prevention of SCD with an ICD in HCM are based on recognized risk factors, including a prior history of ventricular fibrillation or sustained ventricular tachycardia, maximum LV wall thickness C 30 mm, 10 SCD in a first degree relative with HCM, 11 unexplained syncope within the past 6 months, 12 nonsustained VT (especially if [ 150 bpm), 13 or an abnormal blood pressure response to exercise (failure to increase systolic pressure [ 20 mm Hg). 1,2,6,7,9,11,14 The risk of lethal arrhythmic events is higher for patients presenting with HCM in childhood, 5 those having Troponin I or T mutations, 5 and those with higher serum BNP concentrations. 15 The positive and negative predictive values of any one of these clinical risk factors to predict SCD have been relatively poor.…”

“…15 The positive and negative predictive values of any one of these clinical risk factors to predict SCD have been relatively poor. 5,6 In addition, for continuous variables such as LV wall thickness, the risk of SCD increases in a curvilinear manner, making a clear cut-off value that is ''safe'' all but impossible to establish. 16 Potential clinical features that increase the risk of SCD include younger age (\ 30 years), LV outflow tract obstruction, 17 a remote history of syncope, the presence of epicardial coronary artery disease, end-diastolic LV cavity dimension, 1 left atrial diameter, 12 and the presence of an LV aneurysm.…”