High prevalence of familial and genetic disease in children with cardiomyopathies: baseline paediatric data from the ESC EORP Cardiomyopathy and Myocarditis registry

Background Previous studies on paediatric cardiomyopathies have provided useful information on their epidemiology and clinical presentation but have been limited by a lack of detailed data on genetic testing and aetiology. Purpose The purpose of this study was to examine the frequency of familial and genetic disease among children with cardiomyopathy enrolled in the European Society of Cardiology (ESC) Cardiomyopathy and Myocarditis EORP Long-Term Registry (CMY-LT). Methods 633 individuals aged <18 years with hypertrophic cardiomyopathy [HCM; n=387 (61%)], dilated cardiomyopathy (DCM; n=205 (33%)], restrictive cardiomyopathy [RCM; n=28 (4%)] and arrhythmogenic right ventricular cardiomyopathy [ARVC; n=11 (2%)] were enrolled by 26 centres from 14 countries. Mean age at diagnosis was 5.2 (±5.4) years and there was a male predominance [n=372 (59%)] across all cardiomyopathy subtypes, with the exception of DCM in those diagnosed <10 years of age (p=0.005). 541 (87%) were probands compared to 83 (13%) first-degree relatives. Results Overall, 253 patients (47% of those reported) had familial disease; in those diagnosed between 10 and 18 years of age, familial disease was most frequent in HCM and least frequent in DCM [57 (55%) vs 12 (32%); p=0.046]. Genetic testing was performed in 414 (68%) patients. In those diagnosed <10 years, genetic testing was more frequently performed in HCM [128 (67%) vs 33 (37%) in DCM, 10 (56%) in RCM and 1 (50%) in ARVC; p=0.008]; in those aged 10–18, genetic testing was most frequent in ARVC [n=8 (89%)] followed by HCM [n=81 (69%)], RCM [n=1 (50%)] and DCM [n=22 (46%); p=0.007]. A causative mutation was reported in 250 patients (60%), with a higher yield in those aged 10–18 vs <10 years [77 (69%) vs 172 (57%), p=0.032]. In those <10 years, the prevalence of reported causative mutations was highest in HCM [128 (67%) vs 10 (56%) in RCM, 1 (50%) in ARVC and 33 (37%) in DCM; p<0.001]; in those 10–18 years, there was no significant difference in prevalence of reported causative variants between cardiomyopathy subtypes. Rare disease phenocopies were reported in 171 patients (27%): malformation syndromes [n=75 (12%)]; neuromuscular disorders [n=49 (8%)]; inborn errors of metabolism [n=20 (3%)]; mitochondrial [n=18 (3%)]; and chromosomal [n=15 (2%)]. Phenocopies were reported most frequently in patients <10 years [135 (30%) vs 35 (20%) in those aged 10–18 years; p=0.008], particularly in HCM in those <10 years [n=110 (41%); p<0.001 vs other subtypes] and DCM in those aged 10–18 years [n=18 (38%); p=0.03 vs other subtypes]. Conclusion This study confirms the heterogeneous aetiology of childhood cardiomyopathies and demonstrate a higher prevalence of familial disease than previously reported in paediatric populations. Genetic testing is performed in a high proportion of patients, with a high yield of reported causative variants. Funding Acknowledgement Type of funding source: None

1055 Cardiometabolic Disease Risk And Sleep Difficulty: Associations With Diet, Physician Support, Proactive Health Behaviors, And Family Risk Knowledge

Introduction Research relating sleep impairment and cardiometabolic disease supports exercise and diet in improving both conditions. The role of self- and other-informed knowledge on self-care behaviors is unknown. This study investigated how proactive health behaviors, physician support, and familial disease awareness are related in this comorbid population. Methods National Health and Nutrition Examination Survey (NHANES) data from 2015-2016 was used. For this study, U.S. adults (N=9,971;49.3% female) with dietary, sleep, cardiometabolic disease risk, proactive health behavior, physician-informed, and familial knowledge of cardiometabolic disease data were selected. Self-reported sleep difficulty was defined as ever telling a doctor/health professional of trouble sleeping. Kendall’s tau-b correlations and multinomial regression were performed. Covariates included race, gender, weight control, dietary efforts, and exercise. Results Statistically significant associations between comorbid cardiometabolic disease/sleep difficulty (CMD/SD) and efforts to control/lose weight(X2(6)=63.956,p>0.0001), reduce dietary salt(X2(6)=69.702,p>0.0001), and reduce dietary fat(X2(6)=70.666,p>0.0001) were found. Despite having comorbid CMD/SD, most participants (51%) reported no history of receiving physician-informed health improvement methods. However, statistically significant associations between comorbid CMD/SD and physician-informed methods and weight loss efforts(X2(4)=76.873,p>0.0001), increased exercise(X2(4)=72.713,p>0.0001), reduced dietary salt(X2(4)=96.892,p>0.0001), and reduced dietary fat(X2(4)=104.231,p>0.0001) were found. Statistically significant associations between comorbid CMD/SD and knowledge of close relative with heart attack(X2(9)=23.905,p=0.004) or diabetes(X2(9)=129.705,p>0.0001) were found. Participants with comorbid CMD/SD were more likely to reduce dietary fat(X2(1)=4.575,p< 0.032) than participants with comorbid sleep difficulty/cardiovascular disease or comorbid sleep difficulty/metabolic disease. Although no association between age of cardiometabolic diagnosis onset and proactive health behaviors was found, the regression model showed that male gender(p=0.008) and reducing dietary fat was predictive of comorbid CMD/SD(p=0.032). Conclusion Participants with comorbid CMD/SD directed proactive health efforts towards eating behavior (less food/decreasing salt and fat). With physician-informed support, participants additionally increased exercise level. Further exploring the role of familial disease knowledge, gender-specific support, and innovative efforts by health professionals in treating/preventing comorbid CMD/SD is warranted. Support None

Left ventricular non-compaction: diagnosis and clinical management

Left ventricular non-compaction (LVNC) is characterized by a specific morphological appearance of the myocardium with an inner non-compacted hypertrabeculated layer and deep recesses communicating with the left ventricular cavity, and an outer compacted myocardium. LVNC is a specific morphological finding and may be present in healthy individuals with apparently normal hearts and in patients with various cardiac and systemic conditions including X-linked Barth syndrome, cardiomyopathies, congenital heart diseases, and non-cardiac systemic diseases. Recent investigations have revealed that LVNC may appear as the sole manifestation of disease in carriers of genetic mutations associated with dilated and hypertrophic cardiomyopathies. Therefore, it is important to consider the possibility of familial disease when diagnosing LVNC and explore the family history of the patient. Clinical screening of relatives should be offered when familial disease is suspected or when LVNC remains unexplained. Anticoagulation should be considered when LVNC appears in patients with impaired systolic function of the left ventricle to avoid formation of thrombi and cardiac embolization following an assessment of the entire risk profile of the individual patient.

Left ventricular non-compaction: diagnosis and clinical management

Left ventricular non-compaction (LVNC) is characterized by a specific morphological appearance of the myocardium with an inner non-compacted hypertrabeculated layer and deep recesses communicating with the left ventricular cavity, and an outer compacted myocardium. LVNC is a specific morphological finding and may be present in healthy individuals with apparently normal hearts and in patients with various cardiac and systemic conditions including X-linked Barth syndrome, cardiomyopathies, congenital heart diseases, and non-cardiac systemic diseases. Recent investigations have revealed that LVNC may appear as the sole manifestation of disease in carriers of genetic mutations associated with dilated and hypertrophic cardiomyopathies. Therefore, it is important to consider the possibility of familial disease when diagnosing LVNC and explore the family history of the patient. Clinical screening of relatives should be offered when familial disease is suspected or when LVNC remains unexplained. Anticoagulation should be considered when LVNC appears in patients with impaired systolic function of the left ventricle to avoid formation of thrombi and cardiac embolization following an assessment of the entire risk profile of the individual patient.