Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry.

AIMS: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. METHODS AND RESULTS: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. CONCLUSION: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator

Impact of pediatric cardiac surgery regionalization on health care utilization and mortality

ObjectiveRegionalization directs patients to high-volume hospitals for specialized care. We investigated regionalization trends and outcomes in pediatric cardiac surgery.Data sources/study settingStatewide inpatient data from eleven states between 2000 and 2012.Study designMortality, length of stay (LOS), and cost were assessed using multivariable hierarchical regression with state and year fixed effects. Primary predictor was hospital case-volume, categorized into low-, medium-, and high-volume tertiles.Data collection/extraction methodsWe used Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) to select pediatric cardiac surgery discharges.Principal findingsIn total, 2841 (8.5 percent), 8348 (25.1 percent), and 22 099 (66.4 percent) patients underwent heart surgeries in low-, medium-, and high-volume hospitals. Mortality decreased over time, but remained higher in low- and medium-volume hospitals. High-volume hospitals had lower odds of mortality and cost than low-volume hospitals (odds ratio [OR] 0.59, P < 0.01, and relative risk [RR] 0.91, P < 0.01, respectively). LOS was longer for high- and medium-volume hospitals, compared to low-volume hospitals (high-volume: RR 1.18, P < 0.01; medium-volume: RR 1.05, P < 0.01).ConclusionsRegionalization reduced mortality and cost, indicating fewer complications, but paradoxically increased LOS. Further research is needed to explore the full impact on health care utilization