Huang, David T.

Background Sex‐specific risk management may improve outcomes in congenital long QT syndrome (LQTS). We recently developed a prediction score for cardiac events (CEs) and life‐threatening events (LTEs) in postadolescent women with LQTS. In the present study, we aimed to develop personalized risk estimates for the burden of CEs and LTEs in male adolescents with potassium channel‐mediated LQTS. Methods and Results The prognostic model was derived from the LQTS Registry headquartered in Rochester, NY, comprising 611 LQT1 or LQT2 male adolescents from age 10 through 20 years, using the following variables: genotype/mutation location, QTc‐specific thresholds, history of syncope, and β‐blocker therapy. Anderson‐Gill modeling was performed for the end point of CE burden (total number of syncope, aborted cardiac arrest, and appropriate defibrillator shocks). The applicability of the CE prediction model was tested for the end point of the first LTE (excluding syncope and adding sudden cardiac death) using Cox modeling. A total of 270 CEs occurred during follow‐up. The genotype–phenotype risk prediction model identified low‐, intermediate‐, and high‐risk groups, comprising 74%, 14%, and 12% of the study population, respectively. Compared with the low‐risk group, high‐risk male subjects experienced a pronounced 5.2‐fold increased risk of recurrent CEs ( P <0.001), whereas intermediate‐risk patients had a 2.1‐fold ( P =0.004) increased risk . At age 20 years, the low‐, intermediate‐, and high‐risk adolescent male patients had on average 0.3, 0.6, and 1.4 CEs per person, respectively. Corresponding 10‐year adjusted probabilities for a first LTE were 2%, 6%, and 8%. Conclusions Personalized genotype–phenotype risk estimates can be used to guide sex‐specific management in male adolescents with potassium channel‐mediated LQTS.

Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.

Abstract Background The aim of the Subcutaneous ICD Combined with Ventricular Tachycardia Ablation (SICD-VTAbl) Study is to provide preliminary data on the safety and efficacy of a management strategy that incorporates S-ICD implantation and VT ablation among patients with a secondary prevention indication for an ICD. We hypothesize that VT ablation for the prevention of monomorphic VT recurrence combined with S-ICD implantation for termination of life-threatening VT/VF is safe, while reducing the need for device interventions and systemic complications associated with conventional transvenous ICD implantation for secondary prevention. Methods SICD-VTAbl is an uncontrolled, prospective, multinational observational study, conducted in France, Germany, US (Rochester NY, and Rochester MN) and coordinated in Israel. We aim to prospectively enroll 30 patients presenting with scar-related VT/VF who will undergo VT ablation/substrate modification followed by S-ICD implantation. The primary endpoint is the first occurrence of S-ICD therapy (appropriate and inappropriate). Secondary endpoints include separate occurrence of appropriate and inappropriate ICD therapies, peri-procedural complications, and adverse clinical outcomes. Results We provide clinical, arrhythmia, and outcome data on the first 15 patients enrolled in the SICD-VTAbl Study through February 2021. Mean age was 59±12 years, 78% were males, 60% had New York Heart Association (NYHA) Class ≥II symptoms, 20% had renal insufficiency, and 33% were treated with an antiarrhythmic medication (all amiodarone). Periprocedural, arrhythmia, and long-term outcome data are provided in Table 1. There were no major complications associated with the VT ablation and the S-ICD implantation procedures. During a median follow-up of 6 months (interquartile range: 2–12 months), 2 patients (13%) received S-ICD therapy: one patient (7%) experienced VF terminated by the S-ICD and one patient experienced a single episode of inappropriate S-ICD therapy. Adverse events during follow-up, unrelated to study procedures, occurred in 3 patients (20%): hospitalization for heart failure exacerbation (N=1) and non-cardiovascular hospitalizations (N=2). None of the patients died during follow-up (Table 1). Conclusions Our preliminary data from the SICD-VTAbl Study suggest that a management approach that incorporates VT ablation followed by S-ICD implantation is safe and may lead to improved arrhythmia and clinical outcomes in patients presenting with a secondary prevention indication for an ICD. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Research grant to Sheba Medical Center from Boston Scientific

Background We aimed to provide personalized risk estimates for cardiac events (CEs) and life‐threatening events in women with either type 1 or type 2 long QT. Methods and Results The prognostic model was derived from the Rochester Long QT Syndrome Registry, comprising 767 women with type 1 long QT (n=404) and type 2 long QT (n=363) from age 15 through 60 years. The risk prediction model included the following variables: genotype/mutation location, QTc‐specific thresholds, history of syncope, and β‐blocker therapy. A model was developed with the end point of CEs (syncope, aborted cardiac arrest, or long QT syndrome–related sudden cardiac death), and was applied with the end point of life‐threatening events (aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shocks). External validation was performed with data from the Mayo Clinic Genetic Heart Rhythm Clinic (N=467; type 1 long QT [n=286] and type 2 long QT [n=181]). The cumulative follow‐up duration among the 767 enrolled women was 22 243 patient‐years, during which 323 patients (42%) experienced ≥1 CE. Based on genotype‐phenotype data, we identified 3 risk groups with 10‐year projected rates of CEs ranging from 15%, 29%, to 51%. The corresponding 10‐year projected rates of life‐threatening events were 2%, 5%, and 14%. C statistics for the prediction model for the 2 respective end points were 0.68 (95% CI 0.65–0.71) and 0.71 (95% CI 0.66–0.76). Corresponding C statistics for the model in the external validation Mayo Clinic cohort were 0.65 (95% CI 0.60–0.70) and 0.77 (95% CI 0.70–0.84). Conclusions This is the first risk prediction model that provides absolute risk estimates for CEs and life‐threatening events in women with type 1 or type 2 long QT based on personalized genotype‐phenotype data. The projected risk estimates can be used to guide female‐specific management in long QT syndrome.