Dataset Information

Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy.

ABSTRACT:

Aims

Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM.

Methods and results

We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [<1 year (infancy), 1-18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade. Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36-4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16-2.41), P = 0.006]. When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03-1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23-3.23)].

Conclusion

Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into the natural history of disease and can help inform clinical risk stratification.

SUBMITTER: Marston NA

PROVIDER: S-EPMC8139852 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy.

Marston Nicholas A NA Han Larry L Olivotto Iacopo I Day Sharlene M SM Ashley Euan A EA Michels Michelle M Pereira Alexandre C AC Ingles Jodie J Semsarian Christopher C Jacoby Daniel D Colan Steven D SD Rossano Joseph W JW Wittekind Samuel G SG Ware James S JS Saberi Sara S Helms Adam S AS Ho Carolyn Y CY

European heart journal 20210501 20

<h4>Aims</h4>Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM.<h4>Methods and results</h4>We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [<1 year (infancy), 1-18 years (childhood), > ...[more]

PMID: 33769460

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Project description:BackgroundMaximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort.MethodsThe study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids).ResultsMLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk.ConclusionsIn children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Project description:AimsRecognition of transthyretin amyloid cardiomyopathy is increasing due to advances in cardiac imaging and diagnostic strategies, but questions remain regarding disease frequency and characteristics. We examined the prevalence and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy of unascertained aetiology.Methods and resultsTTRACK was a multicentre, non-interventional, cross-sectional epidemiologic study funded by Pfizer and conducted in 20 hospitals and medical centres in 11 countries (NCT03842163). Eligible patients were aged ≥50 years, had hypertrophic cardiomyopathy (maximal end-diastolic left ventricular wall thickness ≥15 mm on echocardiogram) without an identified genetic or alternative origin at study enrolment, and underwent 99mTechnetium bone scintigraphy, with or without single photon emission computed tomography (SPECT). Cardiac-versus-bone uptake on scans was visually scored from 0 to 3 (Perugini scoring). Patients with grades 1-3 underwent monoclonal protein and laboratory testing and transthyretin (TTR) gene sequencing. Of 766 eligible patients, 691 (90.2%) had scintigraphy alone and 75 (9.8%) scintigraphy plus SPECT. Two hundred and eight patients (27.2%) had grade 2 or 3 cardiac uptake on scintigraphy; 144 (18.8%) had grade 2 or 3 cardiac uptake and no evidence of plasma cell dyscrasia and were diagnosed with transthyretin amyloid cardiomyopathy. Of patients with transthyretin amyloid cardiomyopathy, 11 (7.6%) had a pathogenic TTR gene variant and 34 (23.8%), 74 (51.7%), and 35 (24.5%) had New York Heart Association class I, II, and III/IV heart failure (HF) symptoms, respectively. Clinical and laboratory diagnostic characteristics were observed in ≥90% of patients with transthyretin amyloid cardiomyopathy. The characteristics most strongly associated with transthyretin amyloid cardiomyopathy on multivariable analysis were carpal tunnel syndrome (odds ratio [OR] 54.3; P < 0.0001) and male sex (OR 7.9; P < 0.0001).ConclusionsIn the TTRACK study, almost one in five patients ≥50 years of age with hypertrophic cardiomyopathy had transthyretin amyloid cardiomyopathy. Greater awareness of the frequency and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy are needed to help improve early detection of this debilitating but treatable disease.

Dataset Information

Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy.

Aims

Methods and results

Conclusion

Publications

Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy.

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