Rivaroxaban vs Vitamin K Antagonist in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease.

Background: Treatment with vitamin K antagonists (VKAs) has been linked to worsening of kidney function in patients with atrial fibrillation (AF). Objectives: XARENO (Factor XA-inhibition in RENal patients with non-valvular atrial fibrillation Observational registry; NCT02663076) is a prospective observational study comparing adverse kidney outcomes in patients with AF and advanced chronic kidney disease receiving rivaroxaban or VKA. Methods: Patients with AF and an estimated glomerular filtration rate (eGFR) of 15 to 49 mL/min/1.73 m2 were included. Blinded adjudicated outcome analysis evaluated adverse kidney outcomes (a composite of eGFR decline to <15 mL/min/1.73 m2, need for chronic kidney replacement therapy, or development of acute kidney injury). A composite net clinical benefit outcome (stroke or systemic embolism, major bleeding, myocardial infarction, acute coronary syndrome, or cardiovascular death) was also analyzed. HRs with 95% CIs were calculated using propensity score overlap weighting Cox regression. Results: There were 1,455 patients (764 rivaroxaban; 691 VKA; mean age 78 years; 44% females). The mean eGFR was 37.1 ± 9.0 in those receiving rivaroxaban and 36.4 ± 10.1 mL/min/1.73 m2 in those receiving VKA. After a median follow-up of 2.1 years, rivaroxaban was associated with less adverse kidney outcomes (HR: 0.62; 95% CI: 0.43-0.88) and all-cause death (HR: 0.76, 95% CI: 0.59-0.98). No significant differences were observed in net clinical benefit. Conclusions: In patients with AF and advanced chronic kidney disease, those receiving rivaroxaban had less adverse kidney events and lower all-cause mortality compared to those receiving VKA, supporting the use of rivaroxaban in this high-risk group of patients.

Setting the optimal threshold of NT-proBNP and BNP for the diagnosis of heart failure in patients over 75 years.

AIMS: Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this context. This study aims to establish the diagnostic thresholds of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for AHF in patients aged over 75 years, both with and without co-morbidities. METHODS AND RESULTS: In this retrospective longitudinal multicentre cohort study, data were gathered from 12 071 hospitalized patients aged 75 years or older, presenting with acute dyspnoea and undergoing BNP or NT-proBNP measurement within 48 h of admission across 10 Assistance Publique-Hôpitaux de Paris facilities between 2011 and 2022, encompassing geriatrics, cardiology, and pulmonology departments. Final diagnoses were categorized using ICD-10 criteria as either AHF or other acute respiratory conditions such as COPD exacerbation, pulmonary embolism, and pneumonia. The mean (SD) age of the population was 84.0 (80.0, 89.0) years, with 52.7% being female. Out of these, 7946 (65.8%) were diagnosed with AHF upon discharge. For NT-proBNP, the identified 'optimal' threshold for diagnosing AHF was 1748 ng/L, with a positive predictive value (PPV) of 84%. Among patients aged over 85 years, a threshold of 2235 pg/mL for NT-proBNP was associated with an 84% PPV. In patients with atrial fibrillation (AF), a threshold of 2332 pg/mL for NT-proBNP demonstrated a PPV of 90% for AHF diagnosis. Additionally, in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min, a threshold of 3474 pg/mL for NT-proBNP yielded a 90% PPV for AHF diagnosis. In male patients, a threshold of 1800 pg/mL showed an 85% PPV for AHF diagnosis, while in patients with obesity, a threshold of 1375 pg/mL demonstrated an 85% PPV for AHF diagnosis. CONCLUSIONS: In older patients, we found significant effects of co-morbidities on natriuretic peptides results, particularly in patients over 85 years old, older patients with abnormal renal function, obesity, and atrial fibrillation. Despite the consideration of those co-morbid conditions, NT-proBNP and BNP level continue to demonstrate utility in the diagnosis of AHF in older patients.

Personalized screening before subcutaneous cardioverter-defibrillator implantation: Usefulness and outcomes in clinical practice-the S-ICD screening SIS prospective study.

BACKGROUND: Electrocardiographic screening before subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is unsuccessful in around 10% of cases. A personalized screening method, by slightly moving the electrodes, to obtain a better R/T ratio has been described to overcome traditional screening failure. OBJECTIVE: The objectives of the SIS study were to assess to what extent a personalized screening method improves eligibility for S-ICD implantation and to evaluate the inappropriate shock rate after such screening success. METHODS: All consecutive patients eligible for an S-ICD implantation were prospectively recruited across 20 French centers between December 2019 and January 2022. In case of traditional screening failure, patients received a second personalized screening. If at least 1 vector was positive, the personalized screening was considered successful, and the patient was eligible for implantation. RESULTS: The study included 474 patients (mean age, 50.4 ± 14.1 years; 77.4% men). Traditional screening was successful in 456 (96.2%) cases. This figure rose to 98.3% (n = 466; P = .002) when personalized screening was performed. All patients implanted after successful personalized screening had correct signal detection on initial device interrogation. Nevertheless, after 1-year follow-up, 3 of the 7 patients (43%) implanted with personalized screening experienced inappropriate shock vs 18 of the 427 patients (4.2%) with traditional screening and S-ICD implantation (P = .003). CONCLUSION: Traditional S-ICD screening was successful in our study in a high proportion of patients. Considering the small improvement in success of screening and a higher rate of inappropriate shock, a strategy of personalized screening cannot be routinely recommended. CLINICALTRIALS: gov identifier: NCT04101253.

Catheter ablation of atrial arrhythmias in cardiac amyloidosis: Impact on heart failure and mortality.

BACKGROUND: Atrial arrhythmias (AA) commonly affect patients with cardiac amyloidosis (CA) and are a contributing risk factor for the development of heart failure (HF). This study sought to investigate the long-term efficacy and impact of catheter ablation on HF progression in patients with CA and AA. METHODS: Thirty-one patients with CA and AA undergoing catheter ablation were retrospectively included (transthyretin-ATTR CA 61% and light chain-AL CA 39%). AA subtypes included atrial fibrillation (AFib) in 22 (paroxysmal in 10 and persistent in 12), atrial flutter (AFl) in 17 and atrial tachycardia (AT) in 11 patients. Long-term AA recurrence rates were evaluated along with the impact of sinus rhythm (SR) maintenance on HF and mortality. RESULTS: AA recurrence was observed in 14 patients (45%) at a median of 3.5 months (AFib n = 8, AT n = 6, AFl = 0). Post-cardioversion, medical therapy or catheter ablation, 10 patients (32%) remained in permanent AA. Over a median follow-up of 19 months, all-cause mortality was 39% (n = 12): 3 with end-stage HF, 5 due to late complications of CA, 1 sudden cardiac death, 1 stroke, 1 COVID 19 (and one unknown). With maintenance of SR following catheter ablation, significant reductions in serum creatinine and natriuretic peptide levels were observed with improvements in NYHA class. Two patients required hospitalization for HF in the SR maintenance cohort compared to 5 patients in the AA recurrence cohort (p = 0.1). All 3 patients with deaths secondary to HF had AA recurrence compared to 11 out of the 28 patients whom were long-term survivors or deaths not related to HF (p = 0.04). All-cause mortality was not associated with AA recurrence. CONCLUSION: This study demonstrates moderate long-term efficacy of SR maintenance with catheter ablation for AA in patients with CA. Improvements in clinical and biological status with positive trends in HF mortality are observed if SR can be maintained.

Risk Profiles and Treatment Patterns in Atrial Fibrillation Patients with Chronic Kidney Disease Receiving or not Receiving Anticoagulation Therapy.

Background Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are at high risk for both thromboembolism and bleeding events. The latter induces a potential reason for withholding oral anticoagulation (OAC) despite an indication for prophylaxis of thromboembolic events. Methods AF patients with CKD (estimated glomerular filtration [eGFR] rate between 15 and 49 mL/min per 1.73 m 2 ) were included in a prospective international registry in Europe between 2016 and 2020, that is, XARENO (factor XA inhibition in renal patients with nonvalvular atrial fibrillation observational registry). The study enrolled adult patients treated at the discretion of physicians with rivaroxaban, vitamin K antagonists (VKA), or without OAC (w/oOAC). Here, we report a prespecified explorative baseline comparison between patients receiving OAC or no OAC within XARENO. Results In total, 1,544 patients (mean age: 78.2 years, mean eGFR: 36.2 mL/min) were studied (rivaroxaban n = 764, VKA n = 691, w/oOAC n = 89). Patients in the w/oOAC group were older and had a similar stroke (mean CHA 2 DS 2 -VASc score 4.0) but higher bleeding risk (mean modified Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score 2.5 vs. 1.8) compared with the OAC groups. The distribution of comorbidities including hypertension, diabetes, and heart failure was similar. Treatment with antiplatelet drugs was fivefold more frequent in the w/oOAC group. Conclusion Only 5.8% of the overall population of AF patients with advanced CKD received no OAC. These patients were older and had a higher bleeding risk, which might explain this decision, but which contrasts with the more frequent use of antiplatelet drugs in this vulnerable group of patients.

Position paper on sustainability in cardiac pacing and electrophysiology from the Working Group of Cardiac Pacing and Electrophysiology of the French Society of Cardiology.

Sustainability in healthcare, particularly within the domain of cardiac electrophysiology, assumes paramount importance for the near future. The escalating environmental constraints encountered necessitate a proactive approach. This position paper aims to raise awareness among physicians, spark critical inquiry and identify potential solutions to enhance the sustainability of our practice. Reprocessing of single-use medical devices has emerged as a potential solution to mitigate the environmental impact of electrophysiology procedures, while also offering economic advantages. However, reprocessing remains unauthorized in certain countries. In regions where it is possible, stringent regulatory standards must be adhered to, to ensure patient safety. It is essential that healthcare professionals, policymakers and manufacturers collaborate to drive innovation, explore sustainable practices and ensure that patient care remains uncompromised in the face of environmental challenges. Ambitious national/international programmes of disease prevention should be the cornerstone of the strategy. It is equally vital to implement immediate actions, as delineated in this position paper, to bring about tangible change quickly.

Acute mitral isthmus block during catheter ablation with vein of Marshall ethanol infusion: Angiographic considerations.

BACKGROUND: Achieving bidirectional mitral isthmus block is still challenging. Conventional ablation methods involve radiofrequency applications on the endocardial aspect of the lateral mitral isthmus, and often epicardial applications inside the coronary sinus. AIM: To evaluate the impact of the systematic use of ethanol infusion in the vein of Marshall on the achievement of acute mitral isthmus block of additional epicardial component lesion. METHODS: We evaluated patients referred to two centres for long-standing persistent atrial fibrillation ablation or recurrent peri-mitral flutter. All patients had pulmonary vein isolation and mitral isthmus line using ethanol infusion in the vein of Marshall for the first procedure and additional radiofrequency ablation lesion if necessary. For redo procedures, additional ablations (atrial lines and complex fractionated atrial electrogram ablations, if needed) were also performed. RESULTS: We included 149 patients, and ethanol infusion in the vein of Marshall was not performed in 27 patients (18%). Among 122 patients, 115 had long-standing persistent atrial fibrillation (94.2%) and seven had peri-mitral flutter (5.8%). The mean duration of continuous atrial fibrillation was 53 months before ablation. Acute bidirectional mitral isthmus block was obtained in 115 (94.2%) of the 122 patients who received ethanol infusion in the vein of Marshall (77% when considering the total population). The mean radiofrequency delivery time to obtain mitral isthmus block was 2.6minutes for the endocardial mitral isthmus radiofrequency ablation and 2.6minutes for the epicardial mitral isthmus radiofrequency ablation. Failure to obtain mitral isthmus block was associated with increased mitral isthmus length and left atrial dilation. No major complications related to ethanol infusion in the vein of Marshall were observed. CONCLUSION: Ethanol infusion in the vein of Marshall, when feasible (82%), was a safe approach to obtaining a high success rate (94%) of acute bidirectional endocardial and epicardial mitral isthmus block.

Eligibility for icosapent ethyl in a French population of coronary outpatients with type 2 diabetes.

Introduction: We determined eligibility for icosapent ethyl (EPA) treatment in coronary artery disease (CAD). Methods: Consecutive patients with type 2 diabetes and CAD were prospectively included from 03/2019 to 12/2020. Results: 574 patients were included; mean age 71 years, 81% males, with a high prevalence of other risk factors (81% hypertension). Mean lipid-density lipoprotein cholesterol was 85 mg/dl, mean glycated hemoglobin HbA1c 7.1%, mean triglycerides 148 mg/dl; 82% received statins. Based on National Lipid Association criteria, 31% would be eligible for EPA. Conclusions: In this contemporary survey in consecutive, unselected CAD patients in daily practice, almost a third would be potentially eligible for EPA.

Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF.

AIMS: Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs. METHODS AND RESULTS: Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF). We evaluated 1890 patients with AF receiving DOACs (apixaban 55%, dabigatran 7%, and rivaroxaban 38%). Inappropriate dosing was noted in 18% of the population. Patients with appropriate dosing had less comorbidities: younger age (75 ± 10 vs. 82 ± 8 years old, P < 0.0001), reduced chronic renal failure (26 vs. 61%, P < 0.0001), and lower CHA2DS2VASc and HASBLED scores (3 ± 2 vs. 4 ± 3, P < 0.0001; 2 ±1 vs. 2 ± 2, P < 0.0001), respectively. In multivariate analysis, older age (P < 0.0001) and a higher CHA2DS2VASc score (P = 0.0056) were independently associated with inappropriate DOAC dosing. Among 472 patients (27%) treated with low-dose rivaroxaban or apixaban, 46% were inappropriately underdosed. Patients inappropriately underdosed were younger (82.3 ± 8.4 vs. 85.9 ± 5.9 years, P < 0.0001) with less chronic renal disease (47 vs. 98%, P < 0.0001). However, these patients had higher rates of prior haemorrhagic events (18 vs. 10%, P = 0.01), clopidogrel use (11 vs. 3%, P = 0.0002), and apixaban prescription (74 vs. 50%, P < 0.0001). CONCLUSION: Within this large registry, DOACs were associated with inappropriate dosing in 18% of cases. Independent predictors of inappropriate dosing were high CHA2DS2VASc scores and older age. Moreover, 46% of patients treated with low-dose DOACs were inappropriately underdosed and more frequently in patients treated with apixaban.

Determinants of ventricular arrhythmias in sickle cell anemia: toward better prevention of sudden cardiac death.

Sudden death is 1 of the leading causes of death in adults with sickle cell anemia (SCA) but its etiology remains mostly unknown. Ventricular arrhythmia (VA) carries an increased risk of sudden death; however, its prevalence and determinants in SCA are poorly studied. This study aimed to identify the prevalence and predictors of VA in patients with SCA. From 2019 to 2022, 100 patients with SCA were referred to the physiology department to specifically analyze cardiac function and prospectively included in the DREPACOEUR registry. They underwent a 24-hour electrocardiogram monitoring (24h-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary end point was the occurrence of VA, defined as sustained or nonsustained ventricular tachycardia (VT), >500 premature ventricular contractions (PVCs) on 24h-Holter, or a recent history of VT ablation. The mean patient age was 46 ± 13 years, and 48% of the patients were male. Overall, VA was observed in 22 (22%) patients. Male sex (81% vs 34%; P = .02), impaired global longitudinal strain (GLS): -16% ± 1.9% vs -18.3% ± 2.7%; P = .02), and decreased platelet count (226 ± 96 giga per liter [G/L] vs 316 ± 130 G/L) were independently associated with VA. GLS correlated with PVC load every 24 hours (r = 0.39; P < .001) and a cutoff of -17.5% could predict VA with a sensitivity of 82% and a specificity of 63%. VAs are common in patients with SCA, especially in men. This pilot study uncovered GLS as a valuable parameter for improving rhythmic risk stratification.

Atrial Septal Defect Associated With Right Bundle Branch Block Masking Brugada Syndrome.

A type 1 Brugada electrocardiogram pattern may be masked by typical right bundle branch block aspect. We present 2 cases (male patients, aged 18 and 22 years) of associated ostium secundum atrial septal defect with a right bundle branch block aspect and symptomatic confirmed Brugada syndrome. Both patients underwent cardiac defibrillator implantation. (Level of Difficulty: Advanced.).

Impact of peri-procedural management of direct oral anticoagulants on pocket haematoma after cardiac electronic device implantation: the StimAOD multicentre prospective study.

AIMS: The study aims to investigate the impact of direct oral anticoagulant (DOAC) management on the incidence of pocket haematoma in patients undergoing pacemaker or implantable cardioverter-defibrillator implantation. METHODS AND RESULTS: All consecutive patients receiving DOAC and undergoing cardiac electronic device implantation were included in a large multicentre prospective observational study (NCT03879473). The primary endpoint was clinically relevant haematoma within 30 days after implantation. Overall, 789 patients were enrolled [median age 80 (IQR 72-85) years old, 36.4% women, median CHA2DS2-VASc score 4 (IQR 0-8)], of which 632 (80.1%) received a pacemaker implantation. Antiplatelet therapy was combined with DOAC in 146 patients (18.5%). Direct oral anticoagulants (DOACs) were interrupted 52 (IQR 37-62) h before the procedure and resumed 31 (IQR 21-47) h later. Ninety-six percent of the patients had at least 12 h DOAC interruption before the procedure, and 78% had at least 12 h DOAC interruption after the procedure. Overall, anticoagulation was interrupted for 72 (IQR 48-96) h. Pre- or post-procedural heparin bridging was used in 8.2% and 3.9%, respectively. Timing of DOAC interruption of resumption was not associated with clinically relevant haematoma. Clinically relevant haematoma occurred in 26 patients (3.3%), and thromboembolic events occurred in 5 patients (0.6%). CONCLUSION: In this large real-life registry where most patients had DOAC interruption, clinically relevant haematoma was rare. Despite DOAC interruption and high CHA2DS2-VASc score, thromboembolic events occurred seldomly, highlighting that bleeding exceeds thromboembolic risk in this peri-procedural period. Future research is needed to identify risk factors for clinically relevant haematoma and meaningfully guide clinicians in optimizing DOAC management.

Initial experience of temperature-controlled irrigated radiofrequency ablation for ischaemic cardiomyopathy ventricular tachycardia ablation.

BACKGROUND: The DiamondTemp ablation (DTA) catheter system delivers high power, open-irrigated, temperature-controlled radiofrequency (RF) ablation. This novel ablation system has not been previously used for ventricular tachycardia (VT) ablation. OBJECTIVE: Feasibility of using the DTA catheter system for VT ablation in ischaemic cardiomyopathy (ICM) patients. METHOD: Ten ICM patients with optimal anti-arrhythmic drug therapy and implantable cardiac defibrillators (ICD) were recruited. VT inducibility testing was performed at the end of the procedure. ICD data for device detected VT episodes and device treated VT episodes were collected for 6-months pre- and post-ablation. RESULTS: Substrate analysis demonstrated reductions in the borderzone area of 4.4 cm2 (p = 0.026) and late potential area of 3.5 cm2 (p = 0.0449) post-ablation, with reductions in the mean bipolar and unipolar voltages of the ablation target areas (0.14 mV (p = 0.0007); 0.59 mV (p = 0.0072) respectively). Complete procedural success was achieved in 9 procedures. Post-ablation VT inducibility testing was not performed in 1 procedure due to a steam pop complication resulting in pericardial tamponade requiring drainage. Mean follow-up of 214 ± 33 days revealed an 88% reduction in total VT episodes (n = 266 median 16 [IQR 3-57] to n = 33 median 0; p = 0.0164) and 77% reduction in ICD therapies (n = 128 median 5 [IQR 2-15] to n = 30 median 0; p = 0.0181). CONCLUSION: The DTA system resulted in adequate lesion characteristics with effective substrate modification, acute procedural success and improved outcomes at intermediate-term follow-up. Randomised controlled trials are required to compare the performance of the DTA system against conventional ablation catheters.

Atrial fibrillation detection with long-term continuous Holter ECG recording in patients with high cardiovascular risk and clinical palpitations: the prospective after study.

AIM: New technologic tools for continuous ECG monitoring have been developed to detect and treat atrial fibrillation (AF) in specific populations with high cardiovascular risk. We evaluated the prevalence and the management of AF diagnosed in patients with high cardiovascular risk and non-documented clinical palpitation undergoing systematic 14-day continuous ECG-Holter monitoring. METHODS: Patients were prospectively enrolled from December 2019 to December 2021 in this multicentre study, sponsored by the French National College of Cardiology. Patients met the following criteria: CHA2DS2VASc score ≥ 2 in males and ≥ 3 in females and clinical palpitations without previously documented arrhythmia. Enrolled patients underwent a continuous 14-day Holter-ECG monitoring for arrhythmia detection. RESULTS: Among the 336 included patients, 39% were male, 75% were greater than 65 years of age and 46.5% had suffered a prior stroke. AF was detected in 14% of patients, among which 23.4% were detected in the first 24 h of monitoring. Finally, age ≥ 65 years (p = 0.037) was significantly associated with AF, as well as male gender (p = 0.023) and a lower rate of antiplatelet therapy (p = 0.018). Patients with diagnosed AF had a prescription of anticoagulation therapy in 90%. Antiarrhythmic drugs were administered in 90% of AF patients and 13% underwent AF ablation. CONCLUSIONS: The systematic AF screening of patients with palpitations and high cardiovascular risk resulted in a diagnostic yield of AF in 14% of the population with a 14-day continuous ECG-Holter monitor. This strategy resulted in the prescription of anticoagulation and antiarrhythmic therapy in 90% of the AF detected population.

Rapid ventricular tachycardia in patients with tetralogy of Fallot and implantable cardioverter-defibrillator: Insights from the DAI-T4F nationwide registry.

BACKGROUND: In repaired tetralogy of Fallot (TOF), little is known about characteristics of patients with rapid ventricular tachycardia (VT). Also, whether patients with a first episode of nonrapid VT may subsequently develop rapid VT or ventricular fibrillation (VF) has not been addressed. OBJECTIVES: The objectives of this study were to compare patients with rapid VT/VF with those with nonrapid VT and to assess the evolution of VT cycle lengths (VTCLs) overtime. METHODS: Data were analyzed from a nationwide registry including all patients with TOF and implantable cardioverter-defibrillator (ICD) since 2000. Patients with ≥1 VT episode with VTCL ≤250 ms (240 beats/min) formed the rapid VT/VF group. RESULTS: Of 144 patients (mean age 42.0 ± 12.7 years; 104 [72%] men), 61 (42%) had at least 1 VT/VF episode, including 28 patients with rapid VT/VF (46%), during a median follow-up of 6.3 years (interquartile range 2.2-10.3 years). Compared with patients in the nonrapid VT group, those in the rapid VT/VF group were significantly younger at ICD implantation (35.2 ± 12.6 years vs 41.5 ± 11.2 years; P = .04), had more frequently a history of cardiac arrest (8 [29%] vs 2 [6%]; P = .02), less frequently a history of atrial arrhythmia (11 [42%] vs 22 [69%]; P = .004), and higher right ventricular ejection fraction (43.3% ± 10.3% vs 36.6% ± 11.2%; P = .04). The median VTCL of VT/VF episodes was 325 ms (interquartile range 235-429 ms). None of the patients with a first documented nonrapid VT episode had rapid VT/VF during follow-up. CONCLUSION: Patients with TOF and rapid VT/VF had distinct clinical characteristics. The relatively low variation of VTCL over time suggests a room for catheter ablation without a backup ICD in selected patients with well-tolerated VT.

Lack of early etiologic investigations in young sudden cardiac death.

BACKGROUND: Since majority of sudden cardiac arrest (SCA) victims die in the intensive care unit (ICU), early etiologic investigations may improve understanding of SCA and targeted prevention. METHODS: In this prospective, population-based registry all SCA admitted alive across the 48 hospitals of the Paris area were enrolled. We investigated the extent of early etiologic work-up among young SCD cases (<45 years) eventually dying within the ICU. RESULTS: From May 2011 to May 2018, 4,314 SCA patients were admitted alive. Among them, 3,044 died in ICU, including 484 (15.9%) young patients. SCA etiology was established in 233 (48.1%) and remained unexplained in 251 (51.9%). Among unexplained (compared to explained) cases, coronary angiography (17.9 vs. 49.4%, P < 0.001), computed tomography scan (24.7 vs. 46.8%, P < 0.001) and trans-thoracic echocardiography (31.1 vs. 56.7%, P < 0.001) were less frequently performed. Only 22 (8.8%) patients with unexplained SCD underwent all three investigations. SCDs with unexplained status decreased significantly over the 7 years of the study period (from 62.9 to 35.2%, P = 0.005). While specialized TTE and CT scan performances have increased significantly, performance of early coronary angiography did not change. Autopsy, genetic analysis and family screening were performed in only 48 (9.9%), 5 (1.0%) and 14 cases (2.9%) respectively. CONCLUSIONS: More than half of young SCD dying in ICU remained etiologically unexplained; this was associated with a lack of early investigations. Improving early diagnosis may enhance both SCA understanding and prevention, including for relatives. Failure to identify familial conditions may result in other preventable deaths within these families.