Hypertrophic cardiomyopathy (HCM) is rare among children, and predictors of death and adverse events are largely distinct from classic risk factors seen in adult patients with the disorder.
Death and other adverse outcomes in pediatric HCM are mainly driven by arrhythmic events, and risk extends well beyond adolescence, according to findings from a newly published retrospective review based on more than 4 decades of observation.
HCM refers to the condition in which the heart muscle becomes abnormally thick, with clinical manifestations ranging from asymptomatic left ventricle hypertrophy to exercise intolerance, heart failure, and heart transplant.
The study, published online in JAMA Cardiology, included 1,644 consecutive patients with HCM diagnosed from 1974 to 2016 at two referral centers in Florence, Italy, including 100 pediatric patients (6.1%) diagnosed between the ages of 1 and 16.
Highly symptomatic pediatric HCM patients with mutations in the gene encoding for the thin filament proteins troponin I had the highest lethal arrhythmia event (LAE) rates.
LAEs were defined as sudden cardiac death or aborted cardiac arrest in patients who were successfully resuscitated or who received implantable cardioverter-defibrillator (ICD) shocks. Heart transplant was considered a surrogate for heart failure-related death.
"In severely symptomatic children with a prior lethal arrhythmia event, the implantable cardioverter defibrillator did not confer absolute protection, which warrants early consideration for heart transplant," wrote Niccolo Maurizi, MD, of Careggi University Hospital in Florence, Italy, and colleagues.
The researchers noted that prior studies of HCM in children and adolescents have been limited to registry population studies and small studies with short follow-up.
"Thus, critical issues such as long-term prognosis and predictors of LAEs after a pediatric diagnosis of HCM are unresolved," Maurizi et al wrote.
Existing algorithms for HCM risk-stratification do not include patients who are 16 and younger due to the lack of outcome data on these patients.
The new study excluded HCM patients with metabolic and syndromic disease. The median age of the 100 pediatric HCM patients at diagnosis was 12.2 (range of 7.3 to 14.1), and 63 (63%) were boys.
Forty-two of the 100 patients (42.0%) were symptomatic at diagnosis. The yield of sarcomere gene testing was 55 of 70 patients (79%).
"During a median of 9.2 years during which a mean of 1,229 patients were treated per year, 24 of 100 patients (24.0%) experienced cardiac events (1.9% per year), including 19 lethal arrhythmic events [LAEs] and five heart failure–related events (three deaths and two heart transplants)."
LAEs occurred at a mean (SD) age of 23.1 (11.5), and two survivors of LAEs with symptoms of heart failure had recurrent cardiac arrest despite an ICD.
The risk of LAE was associated with symptoms at onset (hazard ratio [HR], 8.2; 95% CI, 1.5 to 68.4; P=0.02) and Troponin I or Troponin T gene mutations (HR, 4.1; 95% CI, 0.9 to 36.5; P=0.06).
"The likelihood of arrhythmic events was poorly related to the classic risk factors introduced for adult patients with HCM, including extreme left ventricle hypertrophy and syncope," the researchers wrote. "This is somewhat expected, given that all known risk factors also have low positive predictive accuracy in adults. However, an impressive 79.0% of the patients in this study who experienced an LAE would not have been considered high risk under adult recommendations."
The researchers did identify limiting symptoms at diagnosis and disease-causing mutations in Troponin I and T genes as age-specific risk factors, carrying eight- and four-fold increases in the risk of an LAE, respectively.
"Therefore, risk stratification in patients with pediatric-onset HCM may improve with detailed assessment of functional status as well as genotype."
One of the 58 children in the study (2%) who were asymptomatic at initial clinical evaluation later had an LAE, while LAEs occurred in 18 of the 42 patients with symptoms identified at diagnosis (43%).
"This difference was likely associated with the severe structural substrate underlying heart failure in pediatric HCM," the researchers wrote. "Despite the unquestionable value of the ICD, we also observed two instances in which a device implanted for secondary prevention failed to prevent cardiac arrest in severely symptomatic children."
In an accompanying editorial, Elizabeth McNally, MD, PhD, of Northwestern University Feinberg School of Medicine in Chicago, wrote that findings from the study, and another recently published report from Australia, "underscore that pediatric HCM cannot be considered the same as adult-onset HCM, necessitating specific management strategies."
In the Italian cohort, 21% of pediatric HCM patients either died or required a heart transplant. This risk was highest in the first year after presentation (14%) and much lower in later years (0.4%).
"We know hypertrophic cardiomyopathy is remarkably variable and includes those without any symptoms at all to those with profound heart failure," McNally wrote in an email message to MedPage Today. "In general, it has been difficult to decipher what features modify the outcomes in HCM, and factors in the environment as well as additional genetic variants likely explain why some individuals are more severely affected in HCM."
Funding for the research was provided by the Italian Ministry of Health, the Luisa Fanti Melloni Foundation, the University of Bologna, and others.
The researchers reported having no relevant relationships with industry related to the study.
- Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner