Predictors of risk for sudden death in childhood hypertrophic cardiomyopathy: the importance of the ECG risk score

Abstract

ObjectiveTo establish which risk factors are predictive for sudden death in hypertrophic cardiomyopathy (HCM) diagnosed in childhood.MethodsA Swedish national cohort of patients with HCM diagnosed <19 years of age was collected between 1972 and 2014, consisting of 155 patients with available ECGs, with average follow-up of 10.9±(SD 9.0) years, out of whom 32 had suffered sudden death or cardiac arrest (SD/CA group). Previously proposed risk factors and clinical features, ECG and ultrasound measures were compared between SD/CA group and patients surviving >2 years (n=100), and features significantly more common in SD/CA group were further analysed with univariate and multivariate Cox hazard regression in the total cohort.ResultsRanked according to relative risk (RR) the ECG risk score >5 points had an RR of 46.5 (95% CI 6.6 to 331), sensitivity of 97% (83% to 100%) and specificity of 80% (71% to 88%) (p<0.0001), and was the best ECG predictor, predicting a 5-year risk of SD/CA of 30.6%. The following are other features with importantly raised RR: Detroit wall thickness Z-score >4.5: 9.9 (3.1 to 31.2); septal thickness ≥190% of upper limit of normal for age (septum in % of 95th centile for age (SEPPER) ≥190%): 7.9 (3.2 to 19.4); ventricular tachycardia: 9.1 (3.6 to 22.8); ventricular ectopics on exercise testing: 7.4 (2.7 to 20.2); and left ventricular outflow gradient (left ventricular outflow tract obstruction (LVOTO)) >50 mm Hg: 6.6 (4.0 to 11.0). Family history was non-significant. Multivariate Cox hazard analysis gives the following as early predictors: limb-lead QRS amplitude sum (p=0.020), SEPPER ≥190% (p<0.001) and LVOTO at rest (p=0.054); and for late predictors: last ECG risk score (p=0.002) and last Detroit Z-score (p=0.001). Both early (p=0.028) and late (p=0.037) beta-blocker doses reduced risk in the models.ConclusionsECG phenotype as assessed by ECG risk score is important for risk of sudden death and should be considered for inclusion in risk stratification of paediatric patients with HCM.

TNNI3 and KCNQ1 co-inherited variants in a family with hypertrophic cardiomyopathy and long QT phenotypes: A case report

“…The presence of long QTc is found in about 12% of HCM patients [ 17 ] and it is considered a predictor for the need of ICD (Implantable Cardioverter-Defibrillator) implantation. The QTc length risk in HCM was also a feature noted by other groups [ 18 , 19 ]. Concerning the cause of QTc abnormalities in HCM, either a structural or a genetic origin could be hypothesized.…”

Factors influencing long-term heart failure mortality in patients with obstructive hypertrophic cardiomyopathy in Western Sweden: probable dose-related protection from beta-blocker therapy

“…Beta-blocker therapy reduces LVOT gradient in HOCM, both at rest and during exercise, and improves symptoms, diastolic function and exercise capacity 16–21. In childhood HCM, it is also associated with improved survival22 in a dose-related manner,23 24 and reduces risk of SCD 25. It has been claimed that beta-blocker therapy does not affect survival in adult HCM,26 although Frank et al 27 reported particularly low SCD mortality (0.3%) in patients treated with relatively high doses of propranolol, aiming for ≥320 mg/day.…”

“…A prospective randomised trial in non-obstructive HCM has not been performed. The observation that it takes around 5 years for survival curves to diverge significantly (figure 1A) indicates that the effect may be particularly on myocardial preservation perhaps affecting progress of fibrosis, rather than reducing SCD mortality as reported with higher paediatric dosages 25. Lacking controlled trials, it would be desirable that large international registries for HCM should collect and publish data on mortality related to pharmacotherapy, both type and dose.…”

Cardiomyopathy in children – clinical, genetic and morphological aspects

“…Результаты крупного научного исследования, проведенного швейцарскими учеными, позволили установить, что смертность от ГКМП у детей в возрасте от 8 до 16 лет сопоставима с таковой у взрослых и составила 0,112 на 100000. Смертность у детей до 8 лет ми-нимальна и составляет 1,6%, затем увеличивается, достигая максимума к 10 годам -9,7% [15]. В структуре непосредственных причин смерти до 18% приходится на долю внезапной остановки сердца, которая может стать первым и единственным проявлением заболевания [15].…”

“…Смертность у детей до 8 лет ми-нимальна и составляет 1,6%, затем увеличивается, достигая максимума к 10 годам -9,7% [15]. В структуре непосредственных причин смерти до 18% приходится на долю внезапной остановки сердца, которая может стать первым и единственным проявлением заболевания [15].…”