BACKGROUND AND AIMS:Patients with LMNA gene variants are at high risk for dilated cardiomyopathy and heart failure (HF), but no prediction model for severe HF events exists. This study aimed to describe the incidence of severe HF events and develop a prediction model in a large cohort of patients with adult-onset laminopathies. METHODS:From a population of 660 patients enrolled in the French LMNA nationwide registry, 470 adults were included in the derivation cohort. An independent international validation cohort included 245 additional patients. Baseline characteristics at genetic testing were assessed and the cumulative incidence of the primary endpoint HF-major adverse cardiac events (HF-MACE) was calculated, defined as HF hospitalization, HF-related death, mechanical circulatory support, or heart transplantation. Predictors of HF-MACE were studied after excluding patients with left ventricular ejection fraction (LVEF) <30% at baseline using a Fine-Gray competing risk model, adjusted hazard ratio (aHR) with 95% confidence interval (CI), and Harrell's concordance (C-) index. A secondary composite endpoint, without hospitalization, was also studied. RESULTS:Among 470 patients of the derivation cohort, HF-MACE occurred in 65 over a median follow-up of 7.1 years (interquartile range: 3.4-12.1). Four independent predictors of HF-MACE were identified: male sex (aHR 1.86; 95% CI 1.060-3.290), LVEF <50% (aHR 2.18; 95% CI 1.080-4.400), missense variants in head and rod domains (aHR 2.91; 95% CI 1.110-7.630), and complete left bundle branch block (aHR 2.99; 95% CI 1.400-6.400). The C-index of the model was 0.750 (95% CI 0.720-0.780) in the derivation cohort and 0.758 (95% CI 0.720-0.800) in the validation cohort. The 5-year cumulative incidence of HF-MACE was 1.5% (95% CI 0.6-3.6), 5.0% (95% CI 1.8-8.2), and 22.0% (95% CI 15.6-28.4) among patients with 0, 1, and ≥2 risk factors, respectively. In patients with LVEF <30% at baseline, the 1-year incidence of HF-MACE was 50%, and those patients were excluded from the risk score. CONCLUSIONS:The first prediction model for severe HF events in adult laminopathies was developed, which may facilitate early and optimal preventive management. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov Unique identifier: NCT03058185.

BACKGROUND:Cardiac stereotactic arrhythmia radioablation (STAR) has emerged as a promising alternative for patients with refractory ventricular arrhythmias (VAs). However, the absence of recommendations for margin selection may lead to considerable differences in the treatment plan generation between teams. OBJECTIVES:This systematic review and pooled analysis aimed at determining the inter-study variability in target volumes as well as the main drivers of the final treated volume during STAR for refractory VAs. METHODS:MEDLINE and EMBASE databases were searched until January 31, 2025, to identify all studies describing the use of STAR for treating refractory VAs. Treatment volumes were extracted including clinical target volume (CTV), internal target volume (ITV), and planning target volume (PTV). Volume expansion was assessed using PTV/CTV, ITV/CTV and PTV/ITV ratios. RESULTS:A total of 1020 references were retrieved, of which 13 studies met the inclusion criteria, representing 126 patients treated with STAR for VAs. In aggregates, the pooled total volume expansion (PTV/CTV ratio) was 2.8 (95% CI: 2.0-3.6, I2 = 73%), the pooled volume expansion related to treatment delivery uncertainties (PTV/ITV ratio) was 1.9 (95% CI: 1.7-2.2, I2 = 12%) and the pooled volume expansion related to cardiorespiratory margins (ITV/CTV ratio) was 1.9 (95% CI: 1.4-2.3, I2 = 36.5%). CONCLUSION:Generation of the treatment volume in STAR for refractory VA is subject to high variability even among expert teams, with a ninefold difference observed between the smallest and largest reported average PTV. Margins related to uncertainties in treatment delivery seem to contribute as much as margins related to cardiorespiratory movement in determining the final treatment volume. PROSPERO registration: CRD42024580242.

Ventricular tachycardia (VT) refractory to conventional therapies can be treated with stereotactic arrhythmia radioablation (STAR), yet its biological mechanisms remain unclear. To locally analyze the myocardial response to irradiation, we propose an full workflow integrating in-vivo treatment planning, ex-vivo imaging, and histopathology from an explanted human heart post-STAR. The method establishes a landmarkbased registration framework aligning ex-vivo and in-vivo data within a common coordinate system using anatomical landmarks (base, apex, and a rotation point). Twenty-one anatomical landmarks enabled consistent registration of CT, radiation dose maps and histopathology descriptors. By quantifying the fibrosis fraction in each histological sample, the framework expanded the dataset from 21 to 210 localized measurements. Correlation analysis revealed heterogeneous dose-effect relationships, with higher fibrosis density in regions exposed to 27-31 Gy and minimal changes in apical areas (< 2 Gy). This framework demonstrates the feasibility of direct dose-histopathology correlation in human cardiac tissue and provides a reproducible approach bridging radiotherapy, cardiology, and pathology for STAR evaluation.

AIMS:Loss-of-function (LOF) variants in SCN5A are associated with Brugada syndrome (BrS), progressive conduction slowing, and other arrhythmias. While the prognosis of SCN5A carriers with a positive sodium channel blocker challenge (SCBC) is established, data on those with negative SCBC are limited. OBJECTIVE:To assess the clinical presentation and prognosis of SCN5A variant carriers with negative SCBC, and compare them to relatives with positive SCBC. METHODS AND RESULTS:We retrospectively included patients from five university hospitals (2000-2024) carrying a pathogenic or likely pathogenic SCN5A variant and negative SCBC. Relatives with the same variant and positive SCBC were also analysed. Patients with spontaneous type 1 ECG, gain-of-function variants, double variants, or ACMG class 1-3 variants were excluded. Clinical, ECG, genetic, and follow-up data were collected. Conduction slowing was evaluated using the PR interval and QRS duration. The cohort included 162 patients from 43 families (median age 37 ± 19 years, 46% male), of whom 69 (43%) had negative SCBC. Among these 69 patients, 25 (36%) had baseline intraventricular conduction defects, and 19 (28%) had first-degree AV block. After a median follow-up of 75 [40-168] months, 52% of patients developed progressive conduction slowing. Negative SCBC patients had fewer conduction defects (36% vs. 70%, p = 0.002) and ICD implantations (1% vs. 23%, P < 0.001). Non-missense variants were associated with more conduction slowing (71% vs. 42%, P = 0.04). CONCLUSION:This multicentre study provides the largest analysis of SCN5A carriers with negative SCBC, showing excellent arrhythmic prognosis despite frequent progressive conduction slowing.

BACKGROUND AND AIMS:Current evidence on catheter ablation for patients with congenital heart disease (CHD) is derived from small, retrospective studies. This study aims to provide insights from a nationwide contemporary registry. METHODS:This prospective study included all CHD patients referred for catheter ablation from 2020 to July 2024 across 28 French centres. The primary outcome was the rate of per-procedural acute success. Secondary outcomes included complications as well as freedom from arrhythmia recurrence. RESULTS:A total of 1135 consecutive catheter ablation procedures were performed in 998 patients (mean age 46.1 ± 16 years, 55.5% male). The main primary clinical arrhythmias targeted were atrial flutter/tachycardia in 677 (59.6%), atrial fibrillation in 195 (17.2%), ventricular arrhythmia in 188 (16.6%), and atrioventricular reentrant tachycardia in 38 (3.3%), with significant variations in patterns observed based on the underlying substrate. Clinical arrhythmia was successfully ablated in 1071 patients (94.4%). The mean number of arrhythmias targeted per procedure was 1.5 ± 0.7, with overall acute success rates exceeding 90% for all arrhythmias except for ventricular arrhythmias (86.7%). Acute complication occurred in 43 procedures (3.8%), including 1 (0.1%) death. The overall 1- and 2-year recurrence-free rates were 77.3% (95% confidence interval 74.2%-80.4%) and 68.4% (95% confidence interval 64.7%-72.3%), respectively. Significant variations in recurrence rates were noted based on the type of arrhythmia and the underlying CHD. CONCLUSIONS:Catheter ablation in patients with CHD demonstrates highly favourable acute outcomes and a low complication rate. Recurrence rates during follow-up vary depending on the targeted arrhythmia and the underlying CHD. These findings should be considered in the benefit-risk assessment.

Background Recurrence rates of atrial arrhythmias after catheter ablation in patients with congenital heart disease (CHD) remain substantial. Given the high prevalence of peritricuspid flutter, systematic cavotricuspid isthmus (CTI) ablation may represent a rational preventive strategy. Objectives The objective of this study was to assess the impact of empirical CTI ablation in CHD patients. Methods This prospective nationwide study included all CHD patients referred for a first catheter ablation of an atrial arrhythmia between 2020 and 2024. Empirical ablation comprised probabilistic (noninducible arrhythmia with prior documentation) and prophylactic (no prior documentation) ablation. The primary endpoint was freedom from any atrial arrhythmia recurrence. Secondary endpoints included arrhythmia-related hospitalizations, redo ablations, and complications. Results Among 575 patients undergoing a first catheter ablation for atrial arrhythmia, 345 (60.0%) had CTI-dependent flutter. The remaining 230 patients formed the study population (mean age: 48.2 ± 16.4 years; 50.9% male). CHD complexity was predominantly moderate (57.4%). Targeted arrhythmias were atrial macro-re-entry (53.0%), atrial fibrillation (47.0%), and focal atrial tachycardia (17.4%), with multiple arrhythmias in 16.5%. Empirical CTI ablation was performed in 71 patients (30.9%) and was associated with significantly higher freedom from any atrial arrhythmia at 1 year (78.1% vs 65.6%, P = 0.010) and 2 years (71.2% vs 56.1%, P = 0.025), remaining independently associated with lower risk of recurrence after multivariable adjustment (HR: 0.47, 95% CI: 0.24-0.92, P = 0.027). This benefit was primarily observed in patients without atrial fibrillation history (interaction P = 0.005). Arrhythmia-related hospitalization was also significantly reduced (14.1% vs 25.8%, P = 0.048). Conclusions Empirical CTI ablation is associated with improved freedom from atrial arrhythmia and reduced rehospitalization in CHD patients.

Aims Electrical storm (ES) is a highly heterogeneous condition with wide-ranging clinical presentations. The absence of standardized classification hampers risk stratification and limits effective multidisciplinary coordination. Objective The aim of this study was to develop a classification system based on simple clinical characteristics and stratify 30-day mortality in patients with ES. Methods and results Patients admitted to intensive care units for ES between 2010 and 2023 across four tertiary centres were retrospectively included. The five-stage STORM severity-response classification, based on treatment intensity during hospitalization, incorporated four clinically relevant parameters: signs of acute heart failure or haemodynamic instability, need for inotropes or vasopressors, use of advanced supportive therapies (including deep sedation) and renal replacement therapy, and implementation of mechanical circulatory support. The primary outcome was all-cause mortality at 30 days. A total of 788 patients were included. The cohort was predominantly male (84.3%), with a median age of 66.0 years (57.0-74.0). The majority had ischaemic cardiomyopathy (65.6%), with a median LVEF of 30.0% (20.0-45.0). According to the STORM classification, 421 patients (53.4%) were categorized as STORM-1, 45 (5.7%) as STORM-2, 86 (10.9%) as STORM-3, 220 (27.9%) as STORM-4 and 16 (2.0%) as STORM-5. Overall, 117 patients (14.8%) died within 30 days. A stepwise increase in 30-day mortality was observed across STORM stages - 5.0%, 6.7%, 20.9%, 30.5% and 50.0% for stages 1 through 5, respectively (P < 0.01). Conclusion The STORM classification may facilitate standardized multidisciplinary management strategies and effectively stratifies 30-day mortality risk in patients with ES, ranging from 5% in stage 1% to 50% in stage 5. Further prospective studies are warranted to validate our findings.

While heart failure (HF) duration before left ventricular assist device (LVAD) implantation may influence postoperative outcomes, data evaluating this relationship remains limited. This study investigated the association between HF duration and outcomes following LVAD implantation. This international retrospective multicenter study included 1,071 patients who underwent LVAD implantation between 2006—2019. Patients were stratified into quartiles by HF duration before implantation: Q1 ≤ 3.9 months, Q2 > 3.9 months-4 years, Q3 > 4—10.7 years, and Q4 ≥ 10.7 years. Primary outcome was 3-year all-cause mortality. Secondary outcomes included cardiac death, early (≤ 30 days) and late ventricular arrhythmias (VAs), and left ventricular ejection fraction (LVEF) recovery. Multivariable Cox regression and restricted cubic spline analyses were performed. After 3-year follow-up, 426 patients died (31.1

BACKGROUND:Although ventricular arrhythmias (VAs) are common after left ventricular assist device (LVAD) implantation, the features of early electrical storm (ES) remain poorly characterized. OBJECTIVES:This study aimed to evaluate the incidence and clinical impact of early ES in LVAD recipients. METHODS:This international, multicenter, retrospective study included 1,309 recipients of LVADs implanted between 2006 and 2019. Early ES was defined as ≥3 sustained VA episodes within 24 hours during the first 30 days' postimplantation. The primary outcome was 3-month all-cause mortality. Secondary endpoints included 3-month cardiac mortality and early (≤30 days) right ventricular (RV) failure. RESULTS:Early ES occurred in 56 patients (4.3%), with a median onset at 5 days' postimplantation. Patients with early ES experienced higher 3-month all-cause mortality (adjusted HR [aHR]: 3.09; 95% CI: 1.91-5.01; P < 0.01) and increased early RV failure (aHR: 2.05; 95% CI: 1.10-3.92; P = 0.03). Notably, early VA without ES showed no prognostic impact. Multivariable analysis identified 4 independent predictors of early ES: pre-LVAD RV S' wave ≤9.5 cm/s (aHR: 2.25; 95% CI: 1.23-4.14), heart failure duration of ≥5 years (aHR: 2.41; 95% CI: 1.10-5.28), history of VAs (aHR: 4.43; 95% CI: 2.21-8.87), and prior mechanical circulatory support (aHR: 6.40; 95% CI: 2.12-19.33). The EarlyES-LVAD score, based on these variables, showed good discrimination (C-statistic 0.75) and stratified patients into low-risk (score 0-1), intermediate-risk (score 2-3), and high-risk (score 4-6) groups, with corresponding early ES rates of 1.1%, 3.9%, and 12.4%. CONCLUSIONS:Early ES, but not isolated early VAs, is associated with substantially worse outcomes in LVAD recipients. The EarlyES-LVAD score enables practical risk stratification, facilitating targeted therapeutic interventions in high-risk patients.

Stereotactic Arrhythmia Radioablation (STAR) is a promising treatment for refractory ventricular tachycardia. However, its precision may be hampered by cardiac and respiratory motions. Multiple techniques exist to mitigate the effects of these displacements. The purpose of this work was, based on cardiac and respiratory dynamic CT scans, to generate a patient-specific dynamic model of the structures of interest, that enables simulation of treatments for evaluation of motion management methods. Deep learning-based segmentation was used to extract the geometry of the cardiac structures, whose deformations and displacements were assessed using deformable and rigid image registrations. The combination of the model with dose maps enabled to evaluate the dose locally accumulated during the treatment. The reproducibility of each step was evaluated considering expert references, and treatment simulations were evaluated using data of a physical phantom. The exploitation of the model was illustrated on the data of nine patients, demonstrating that the impact of cardiorespiratory dynamics is potentially important and highly patient-specific, and allowing for future evaluations of motion management methods.

Magnetic resonance imaging (MRI) of patients with cardiac implantable electronic devices (CIEDs) is challenged by susceptibility artifacts. We propose a simulation-to-learning framework for artifact suppression in cine MRI. Subjectspecific digital phantoms were derived from the ACDC dataset by encoding proton density (PD), longitudinal relaxation (T1), transverse relaxation (T2), effective transverse relaxation (T2*), and off-resonance ($\Delta \omega$). Susceptibility effects were modeled as randomized dipole perturbations applied to the off-resonance map, yielding perfectly paired-MRI images artifact-free and artifact-present. MRI reconstruction was conducted with KomaMRI. In order to remove artifacts effects, approximately 32,500 paired images were generated to train a Residual U-Net. It resulted in a improved SSIM from 0.63 (artifacted) to 0.71 (denoised). After transfer learning on a small real coronal cine cohort, high-frequency energy decreased by ~ 52% and edge-aware sharpness showed a reduction (-23%, $\sigma=1$), indicating substantial noise suppression with preserved edges. These results demonstrate that digital phantoms and paired simulations enable artifact correction and provide a scalable pathway toward artifactresilient cine MRI in patients with CIEDs.

BACKGROUND:While guideline-directed medical therapy (GDMT) is recommended for left ventricular assist device (LVAD) recipients, real-world evidence supporting its clinical impact remains limited. This study evaluated the association between GDMT prescription and clinical outcomes in LVAD patients. METHODS:This international retrospective multicentre study included 875 LVAD patients from 22 centres. Patients were categorized based on the number of GDMT (ACE-I/ARBs, beta-blockers, MRAs) prescribed. Primary outcome was 6-month all-cause mortality. Secondary outcome was late ventricular arrhythmias (VAs) (>30 days post-implant). Multivariable Cox regression and ordinal logistic regression analyses were performed. RESULTS:Overall, only 261 patients (29.8%) received triple GDMT, while 97 (11.1%) received no GDMT. After multivariable adjustment, the number of prescribed GDMTs was independently associated with improved survival, with aHRs for all-cause mortality of 0.51 (0.33-0.75, P < .01) for triple therapy, 0.39 (0.26-0.59, P < .01) for dual therapy, and 0.45 (0.30-0.67, P < .01) for single therapy, all compared with no GDMT. Similarly, ACE-I/ARB were associated with a lower risk of late VAs (aHR 0.65 [0.50-0.84], P < .01). Female sex, diabetes, early VAs, and higher bilirubin levels were associated with lower GDMT prescription rates. Major LVEDD improvement (≥10 mm reduction) increased progressively from 51.5% without GDMT to 66.1% with triple therapy. CONCLUSION:In this large international study, the use of GDMT in LVAD patients was associated with improved survival, with benefits observed even with single-agent therapy. Despite these benefits, only 30% of patients received optimal triple therapy, highlighting the need for improved implementation strategies and standardized protocols in this population.

BACKGROUND:Although ventricular arrhythmias (VAs) are frequent after left ventricular assist device (LVAD) implantation, the characteristics and prognostic significance of late electrical storm (ES) remain incompletely understood. OBJECTIVE:This study aimed to assess the incidence and clinical impact of late ES in LVAD recipients. METHODS:This international, multicenter, retrospective study included 1151 LVAD recipients implanted between 2006 and 2019. Late ES was defined as ≥ 3 sustained VA episodes within 24 hours occurring beyond 30 days after implantation. The primary outcome was 5-year all-cause mortality. The secondary endpoint was 5-year cardiac mortality. RESULTS:Late ES occurred in 49 patients (4.3%), with a median onset at 9.2 months after implantation. Patients with late ES experienced significantly higher 5-year all-cause mortality (adjusted hazard ratio [aHR] 2.87 [1.81-4.54]; P < .01) and cardiac mortality (aHR 3.47 [2.14-5.62]; P < .01). Notably, late VA without ES showed no prognostic impact. Multivariable analysis identified 4 independent predictors of late ES: left ventricular end-diastolic diameter of ≥80 mm before LVAD implantation (aHR 2.47 [1.29-4.87]), nonischemic cardiomyopathy (aHR 2.20 [1.10-4.40]), history of VAs (aHR 2.35 [1.27-4.32]), and implantable cardioverter-defibrillator before LVAD implantation (aHR 4.80 [1.12-20.85]). The late ES-LVAD score, based on these variables, demonstrated good discrimination (C-statistic 0.76) and stratified patients into low- (score 0-1), intermediate- (score 2-3), and high-risk groups (score 4-5), with corresponding late ES rates of 1.0%, 3.9%, and 7.8%. CONCLUSION:Late ES, but not isolated late VAs, is independently associated with substantially worse long-term outcomes in LVAD recipients. The late ES-LVAD score enables practical risk stratification, facilitating targeted therapeutic interventions in high-risk patients.

Electrical storm (ES) with refractory cardiogenic shock carries high mortality. While veno-arterial extracorporeal membrane oxygenation (V-A ECMO) may stabilize circulation, the role and timing of ventricular arrhythmia (VA) ablation under ECMO remain unclear. To assess the impact and optimal timing of VA ablation on ECMO weaning success in patients supported with V-A ECMO for ES-related refractory cardiogenic shock. We conducted a French multicenter retrospective cohort study including 218 patients treated between 2015 and 2023 in 9 tertiary centers. Patients requiring V-A ECMO for ES-related cardiogenic shock were included; 115 underwent VA ablation, and 103 did not. The primary endpoint was successful ECMO weaning, defined as liberation from ECMO alive without transition to durable mechanical circulatory support or heart transplantation 28 days after ECMO liberation. Analyses combined propensity-score matching, time-dependent Cox models, spline-based analysis, and landmark Fine Gray competing-risk analyses to account for immortal time and competing events. VA ablation was associated with higher ECMO weaning success (cs-HR 1.72, 95

INTRODUCTION:Radiofrequency ablation is a cornerstone therapy for patients with ischemic cardiomyopathy (ICM) presenting with ventricular tachycardia (VT). In this context, ablation is typically performed endocardially as a first-line approach. However, despite acute procedural success, the risk of recurrence remains high, potentially due to the presence of epicardial substrate. Several observational studies have suggested the potential benefits of a first-line endo-epicardial approach in decreasing recurrence. In this context, the EPIC-VT trial was designed to compare endocardial-only ablation versus combined endo-epicardial ablation as a first-line approach in ICM patients with VT. METHODS:The EPIC-VT trial is a prospective, multicenter, controlled, randomized, open-label superiority trial with two parallel groups (endocardial-only approach vs. combined endo-epicardial approach) in a 1:1 ratio. The primary objective of this study is to demonstrate that a combined endo-epicardial approach reduces the risk of VT recurrence compared to an endocardial approach alone in patients with ICM. Patients will be followed for 2 years after the procedure. RESULTS AND CONCLUSION:To date, only retrospective studies have compared VA recurrences in patients with ICM, depending on whether ablation was performed using an endocardial or an endo-epicardial approach, with conflicting results. A meta-analysis suggested an advantage of the endo-epicardial approach over the endocardial approach (odds ratio = 0.39 [95% CI: 0.18-0.83]). However, the level of evidence remains low, and no controlled randomized study has confirmed this hypothesis. If the EPIC-VT study confirms the superiority of a first-line endo-epicardial approach, such strategy could become the preferred option for VT ablation in ICM, thereby reducing the risk of VA recurrence.