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.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to reduce complications associated with transvenous leads while preserving efficacy in terminating malignant ventricular arrhythmias. However, current evidence supporting the S-ICD is primarily derived from industry-sponsored studies and highly specialized centers. This study aims to offer a comprehensive, nationwide, real-world assessment of all patients who underwent S-ICD implantation in France. The HONEST (coHOrte fraNcaise des dEfibrillateurs Sous cuTanés) cohort is a French nationwide, single-arm, observational ongoing study that enrolled all patients who underwent implantation of an S-ICD (EMBLEM, Boston Scientific) between October 2012 (the first implantation in France) and December 2019. Clinical endpoints are centrally adjudicated. Overall, 4,924 (77% males; 49.9 years) patients, representing 98.2% of all S-ICD implantations during the study period in France, were included. The HONEST study represents the first nationwide cohort evaluating S-ICD recipients to provide contemporary, real-world data. Its goal is to identify areas for improvement and refine strategies to prevent sudden cardiac death. (S-ICD French Cohort Study [HONEST]; NCT05302115)

AIMS:Continuous cardiac monitoring with implantable loop recorders (ILRs) is recommended after cryptogenic stroke to detect occult atrial fibrillation (AF). We aimed to develop and validate a dedicated risk score for AF detection in patients undergoing ILR monitoring after cryptogenic stroke. METHODS AND RESULTS:This multicentre study enrolled 1002 consecutive patients (mean age 66.0 ± 12.3 years, 57.9% male) who received an ILR after cryptogenic stroke. The primary outcome was a first episode of AF or atrial tachycardia (AT). A score was developed in a randomly split development cohort and validated internally, accounting for competing risks, missing data imputation, and hazard ratio-based weighting. Among the 668 patients in the development cohort, cumulative incidences of AF/AT at 1, 2, and 3 years were 20.3%, 28.9%, and 33.0%, respectively. Four independent predictors were identified: premature atrial contractions > 200/24 h on Holter-ECG (2 points), age >58-78 years (3 points) or > 78 years (4 points), significant valvular heart disease (1 point), and left atrial dilatation (2 points), forming the PAVA (premature atrial contractions, age, significant valvular heart disease, and left atrial dilatation) score. Discrimination was good in both the development and validation cohorts (c-index 0.73 and 0.79, respectively). The 3-year areas under the curve were 0.800 and 0.905, respectively. A PAVA score ≤ 2, observed in 23.6% of patients, yielded negative predictive values of 89.2% and 100% in the development and validation cohorts. ROC-curve analysis confirmed superior clinical utility over existing scores (Brown ESUS-AF [Brown embolic stroke of undetermined source-atrial fibrillation], HAVOC). CONCLUSION:A PAVA score ≤ 2 demonstrates a high negative predictive value for AF/AT on ILR after cryptogenic stroke, offering a practical tool to optimize patient prioritization for ILR implantation.

BACKGROUND AND AIMS:Stroke and systemic embolism are recognized but poorly characterized complications of atrial fibrillation (AF) and left atrial flutter (AFL) catheter ablation. Their incidence, outcomes, and procedural associations remain insufficiently defined. METHODS:Retrospective global registry was initiated by the European Heart Rhythm Association Scientific Committee. A secure database captured data from ablation centres worldwide on general AF and left AFL ablation activity, as well as detailed information on patients with symptomatic embolic events between 2017 and 2024. RESULTS:Overall, 204 centres reported 335 743 ablation procedures and 550 embolic events (incidence 0.16%). Centre-level rate ranged from 0% to 3.1%. Most events were cerebral (94%), followed by peripheral (5%), and combined (1%). Coronary air embolism accounted for 62% of all peripheral events. Intraprocedural events occurred in 93 patients (17%), within 72 h in 357 (78%) and beyond 72 h in 100 (22%); 128 cases (23%) were diagnosed after hospital discharge. Nonparoxysmal AF (0.23% vs 0.15%; P < .001), centre experience, and ablation energy source (radiofrequency, 0.16%; cryoballoon, 0.16%; pulsed field ablation, 0.25%; laserballoon, 0.88%; P < .001) were associated with embolic risk. Median NIHSS score after stroke was 4 (interquartile range, 2-9). Three-month follow-up was available for 518 patients with embolism (95%): 181 (35%) had sequelae and 16 (3%) died. CONCLUSIONS:Symptomatic embolic events are infrequent but associated with significant morbidity and mortality. Most events occur early, though a substantial proportion arise later. Higher event rates were observed with laser and possibly with pulsed field ablation. A greater centre experience was associated with a lower embolism incidence.

BACKGROUND:Optimisation of medical therapy is recommended for patients with newly diagnosed non-ischaemic cardiomyopathies (NICM) before consideration of a primary preventive implantable cardioverter-defibrillator (ICD). During this optimisation period, patients face a potentially elevated risk for sudden cardiac death (SCD) that can be countered with a wearable cardioverter-defibrillator (WCD). This systematic review aims to assess the risk for SCD in patients with newly diagnosed NICM. METHODS:A systematic review was performed in Medline, Embase and Cochrane Library last updated on March 2025. Studies with patients aged ≥18 years with newly diagnosed NICM (≤90 days) who were recipients of WCD were included. Study selection, study quality assessment and data extraction were performed by two reviewers independently. Data on percentage of patients with appropriate WCD shocks (as proxy for sustained ventricular arrhythmia, potentially leading to SCD), inappropriate WCD shocks and device implantation were pooled by random-effects model. RESULTS:50 non-controlled observational studies were included, comprising a total of 10 066 patients with NICM. The percentage of appropriate shocks was 1% (87/7708; 95% CI 1% to 2%) in patients with NICM, 2% (16/1049; 95% CI 1% to 2%) in patients with myocarditis, 3% (7/183; 95% CI 0% to 20%) in peripartum cardiomyopathy, 2% (2/102; 95% CI 0% to 7%) in Takotsubo syndrome and 1% (8/594; 95% CI 1% to 3%) for congenital/inherited or genetic cardiomyopathy. Inappropriate shocks ranged from 0% to 1%. At the end of follow-up, between 6% (Takotsubo syndrome) and 43% (congenital/inherited or genetic cardiomyopathy) of patients received an ICD. CONCLUSION:Patients with NICM face a significant risk of SCD during the drug optimisation period before deciding if they qualify for ICD implantation. Results of this meta-analysis are based on non-comparative studies; however, the assessment of an appropriate shock delivered and recorded by the WCD is highly reliable. PROSPERO REGISTRATION NUMBER:CRD42024555879.

Background Despite accounting for a substantial proportion of the global population and disease burden, African countries are underrepresented in randomized controlled trials (RCTs), including those informing cardiovascular (CV) care. Objectives In this study, we sought to quantify African representation in RCTs published from 2019 to 2024 in: 1) 5 leading general medical journals; and 2) 3 leading CV journals. Methods We conducted a systematic review of RCTs published from 2019 to 2024 in the British Medical Journal, the Journal of the American Medical Association, The Lancet, Nature Medicine, and the New England Journal of Medicine, and in Circulation, the European Heart Journal, and the Journal of the American College of Cardiology. Eligible studies included traditional, pragmatic, cluster, and stepped-wedge RCTs. African representation was assessed by trial scope (Africa-only vs multicontinental), country and regional participation, disease category, and African authorship. Results Among 2,138 RCTs published in leading general medical journals, only 83 (3.9%) were conducted exclusively in Africa, and 195 (9.1%) were multicontinental studies including at least 1 African site. In the CV journals, 2 out of 334 RCTs (0.6%) were conducted exclusively in Africa, and African sites were included in only 9 multicontinental trials (2.7%). South Africa accounted for the majority of Africa-based RCTs across both journal categories. Regionally, southern Africa predominated and central Africa was minimally represented. Trials published in general medical journals and conducted exclusively in Africa largely focused on infectious diseases (n = 63; 75.9%), with only 3 addressing cardiovascular disease (CVD). In contrast, Africa-including multicontinental trials more frequently investigated noncommunicable diseases, including CVD. African leadership was common in Africa-only trials but rare in multicontinental studies. Conclusions African countries are profoundly underrepresented in RCTs published in the world’s most influential medical and CV journals. Addressing this imbalance requires expanding African participation in global trials, investing in local research capacity, and promoting equitable leadership to strengthen the relevance and validity of clinical evidence. (Underrepresentation of African Countries in Randomized Controlled Trials: A Systematic Review of Leading General Medical and Cardiovascular Journals; CRD42024603157)

BACKGROUND AND AIMS:Although use of the subcutaneous implantable cardioverter defibrillator (S-ICD) is increasing, evidence from industry-independent and unselected populations remains limited. METHODS:HONEST is a ongoing nationwide academic observational study enrolling 98.2% of patients implanted with an S-ICD across France (2012-2019). Five-year clinical endpoints were centrally adjudicated. RESULTS:Overall, 4924 patients were enrolled (mean age 49.9 ± 15 years, 76.7% male, 63.0% for primary prevention). Implants used general anaesthesia (78.9%), and defibrillation testing (82.6%). Perioperative complications (within 30 days) occurred in 4.4%. At 5 years, cumulative incidence rates were 13.8% for inappropriate shocks, 10.8% for early battery depletion, 2.4% for infections, 1.5% for lead dysfunction, and 1.4% for chronic discomfort. Reoperation was required in 16.9%, need for cardiac pacing in 3.1%, and definite S-ICD extraction in 8.4%. Inappropriate shocks were independently associated with male sex (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.14-1.46, P < .001), obesity (HR 1.35, 95% CI 1.02-1.79, P = .032), arrhythmogenic right ventricular cardiomyopathy (HR 1.70, 95% CI 1.03-2.81, P = .036), and the presence of a pacemaker (HR 2.20, 95% CI 1.16-4.17, P = .016). SMART Pass filtering significantly reduced inappropriate shocks (HR 0.67, 95% CI 0.50-0.89, P = .007). Among patients with inappropriate shocks, ∼1% developed induced ventricular fibrillation (one fatality), and 10% underwent device extraction. Ineffective shocks or undetected arrhythmias occurred in only 0.2%. Among 547 deaths (11.1%), 53.9% were cardiovascular, including 26 sudden deaths, and 8 were S-ICD/procedure-related, with none related to S-ICD extraction. CONCLUSIONS:This nationwide study refines the long-term event profile of S-ICD therapy and may inform clinical practice and device selection.

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:The aim of the DESAC study (Devenir des Survivants d'Arrets Cardiaques) was to describe the survival rate and neurological status of out-of-hospital (out-of-hospital cardiac arrest) survivors, and to assess the influence of prehospital and intrahospital factors. METHODS:Between July 2015 and October 2018, consecutive nontraumatic out-of-hospital cardiac arrest patients aged over 18 years discharged alive from 33 intensive care units in Paris and the suburbs (France) were included. Their neurological status was assessed every 6 months using the Cerebral Performance Category (CPC) scale. Prognostic factors associated with a favorable neurological outcome at 24 months (CPC category of 1 or 2) were assessed by covariate-adjusted logistic regression. Trajectories of CPC level over time were derived using a linear mixed model in survivors with at least 3 repeated assessments. RESULTS:Out of 593 survivors, 525 were followed up for 24 months (mean age, 58.1±15.3 years, 79% males), and 449 of 525 (86%) had a favorable neurological outcome. Initial shockable rhythm (adjusted odds ratio, 3.33 [95% CI, 1.57-7.07]) and previous practice of sport (adjusted odds ratio, 3.13 [95% CI, 1.21-8.12]) were associated with favorable outcome, whereas factors with reduced odds ratio were older age (adjusted odds ratio per 10 years, 0.53 [95% CI, 0.41-0.69]) and prior percutaneous coronary intervention (adjusted odds ratio, 0.38 [95% CI, 0.17-0.85]). Therapeutic hypothermia or acute coronary interventions were not related to prognosis (P>0.05). Overall, among the 514 patients with at least 3 repeated assessments, 5 distinct CPC trajectories (2 reflecting early death were combined) were derived: 64% remained in CPC1, 13.4% in CPC2, 11% improved from CPC2 to CPC1, and 11.6% died either early or lately (>3 months) during follow-up. CONCLUSIONS:This multicentric prospective study indicates that 86% of out-of-hospital cardiac arrest survivors had a favorable neurological outcome at 24 months. Pre-event and intraevent factors (including previous practice of sport and shockable rhythm), but not in-hospital management (therapeutic hypothermia or acute coronary interventions), were associated with a favorable outcome. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02494414.

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.

BACKGROUND:Evidence supporting the Micra AV leadless pacing system has largely derived from highly experienced centers, potentially limiting generalizability to routine clinical practice. METHODS:The AV-CESAR study (French Cohort Evaluating the Effectiveness of Atrioventricular Synchrony by the micRa AV) is a nationwide retrospective cohort, including the first 1000 patients implanted with a Medtronic Micra AV leadless pacemaker in France (2020-2024). Mean follow-up was 13.4±10.6 months. Primary end points were early (in-hospital) and late (postdischarge) device-related major complications; pacemaker syndrome and need for implantation of a new pacing system were centrally adjudicated. RESULTS:Among 1003 patients, device implantation was successful in 1000 (99.7%). Mean age was 72.0±15 years; 62.8% were men, 44.0% had ≥2 comorbidities, and 62.4% were unsuitable for transvenous pacemakers. The primary indication was permanent complete atrioventricular block with preserved sinus rhythm (78.0%). Early major complications occurred in 2.4%, including pericardial effusion (0.8%; 3 requiring surgery), access-site complications (0.8%), and thromboembolism (0.3%). Late major complications included pacemaker syndrome (2.5%), pacing-induced cardiomyopathy (1.2%), high thresholds (>4 V/0.24ms, 0.3%), and premature battery depletion (0.2%). No device infections or dislodgements were observed. Overall, 2.5% of patients required implantation of a new pacing system (pacing-induced cardiomyopathy n=11; pacemaker syndrome n=7; high threshold n=3; battery/software failure n=3; tricuspid regurgitation n=1) and 12.7% were permanently reprogrammed to ventricular paced/sensed, inhibited (VVI) mode. In pacing-dependent patients with ambulatory Holter monitoring (>3.4 million paced cycles), mean atrioventricular synchrony was 67.6±17.3% and correlated with device-reported AM-VP (74.8±17.1%; R2=0.92; P<0.001). Atrioventricular synchrony declined at heart rates >90 beats per minute (5.6% of monitored time). All-cause mortality was 13.8%, with 0.2% directly device-related; 41.7% of deaths were cardiovascular. CONCLUSIONS:The Micra AV system is primarily used as an alternative when dual-chamber conventional pacemakers are not feasible. It demonstrated acceptable safety and clinical performance in a high-risk population. The marked reduction in atrioventricular synchrony at higher heart rates may suggest limited clinical benefit in patients with higher exertional heart rates. REGISTRATION:URL: https://clinicaltrials.gov/study/NCT05953558; Unique identifier: NCT05953558.