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IMPORTANCE: Patients with hypertrophic cardiomyopathy (HCM) are prone to body weight increase and obesity. Whether this predisposes these individuals to long-term adverse outcomes is still unresolved. OBJECTIVE: To describe the association of body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) with long-term outcomes in patients with HCM in terms of overall disease progression, heart failure symptoms, and arrhythmias. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, retrospective data were analyzed from the ongoing prospective Sarcomeric Human Cardiomyopathy Registry, an international database created by 8 high-volume HCM centers that includes more than 6000 patients who have been observed longitudinally for decades. Records from database inception up to the first quarter of 2018 were analyzed. Patients were divided into 3 groups according to BMI class (normal weight group, 30). Patients with 1 or more follow-up visits were included in the analysis. Data were analyzed from April to October 2018. EXPOSURES: Association of baseline BMI with outcome was assessed. MAIN OUTCOME AND MEASURES: Outcome was measured against overall and cardiovascular mortality, a heart failure outcome (ejection fraction less than 35%, New York Heart Association class III/IV symptoms, cardiac transplant, or assist device implantation), a ventricular arrhythmic outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter-defibrillator therapy), and an overall composite outcome (first occurrence of any component of the ventricular arrhythmic or heart failure composite end point, all-cause mortality, atrial fibrillation, or stroke). RESULTS: Of the 3282 included patients, 2019 (61.5%) were male, and the mean (SD) age at diagnosis was 47 (15) years. These patients were observed for a median (interquartile range) of 6.8 (3.3-13.3) years. There were 962 patients in the normal weight group (29.3%), 1280 patients in the preobesity group (39.0%), and 1040 patients in the obesity group (31.7%). Patients with obesity were more symptomatic (New York Heart Association class of III/IV: normal weight, 87 [9.0%]; preobesity, 138 [10.8%]; obesity, 215 [20.7%]; P

Supplemental Digital Content is available in the text., Background: Genetic testing for families with hypertrophic cardiomyopathy (HCM) provides a significant opportunity to improve care. Recent trends to increase gene panel sizes often mean variants in genes with questionable association are reported to patients. Classification of HCM genes and variants is critical, as misclassification can lead to genetic misdiagnosis. We show the validity of previously reported HCM genes using an established method for evaluating gene-disease associations. Methods: A systematic approach was used to assess the validity of reported gene-disease associations, including associations with isolated HCM and syndromes including left ventricular hypertrophy. Genes were categorized as having definitive, strong, moderate, limited, or no evidence of disease causation. We also reviewed current variant classifications for HCM in ClinVar, a publicly available variant resource. Results: Fifty-seven genes were selected for curation based on their frequent inclusion in HCM testing and prior association reports. Of 33 HCM genes, only 8 (24%) were categorized as definitive (MYBPC3, MYH7, TNNT2, TNNI3, TPM1, ACTC1, MYL2, and MYL3); 3 had moderate evidence (CSRP3, TNNC1, and JPH2; 33%); and 22 (66%) had limited (n=16) or no evidence (n=6). There were 12 of 24 syndromic genes definitively associated with isolated left ventricular hypertrophy. Of 4191 HCM variants in ClinVar, 31% were in genes with limited or no evidence of disease association. Conclusions: The majority of genes previously reported as causative of HCM and commonly included in diagnostic tests have limited or no evidence of disease association. Systematically curated HCM genes are essential to guide appropriate reporting of variants and ensure the best possible outcomes for HCM families.