Impact of Left Atrial Posterior Wall Ablation During Pulsed-Field Ablation for Persistent Atrial Fibrillation.

BACKGROUND: Pulmonary vein isolation (PVI) alone is insufficient to treat many patients with persistent atrial fibrillation (PersAF). Adjunctive left atrial posterior wall (LAPW) ablation with thermal technologies has revealed lack of efficacy, perhaps limited by the difficulty in achieving lesion durability amid concerns of esophageal injury. OBJECTIVES: This study aims to compare the safety and effectiveness of PVI + LAPW ablation vs PVI in patients with PersAF using pulsed-field ablation (PFA). METHODS: In a retrospective analysis of the MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-approval Clinical Use of Pulsed Field Ablation) registry, we studied consecutive PersAF patients undergoing post-approval treatment with a pentaspline PFA catheter. The primary effectiveness outcome was freedom from any atrial arrhythmia of ≥30 seconds. Safety outcomes included the composite of acute and chronic major adverse events. RESULTS: Of the 547 patients with PersAF who underwent PFA, 131 (24%) received adjunctive LAPW ablation. Compared to PVI-alone, patients receiving adjunctive LAPW ablation were younger (65 vs 67 years of age, P = 0.08), had a lower CHA2DS2-VASc score (2.3 ± 1.6 vs 2.6 ± 1.6, P = 0.08), and were more likely to receive electroanatomical mapping (48.1% vs 39.0%, P = 0.07) and intracardiac echocardiography imaging (46.1% vs 17.1%, P < 0.001). The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmias was not statistically different between groups in the full (PVI + LAPW: 66.4%; 95% CI: 57.6%-74.4% vs PVI: 73.1%; 95% CI: 68.5%-77.2%; P = 0.68) and propensity-matched cohorts (PVI + LAPW: 71.7% vs PVI: 68.5%; P = 0.34). There was also no significant difference in major adverse events between the groups (2.2% vs 1.4%, respectively, P = 0.51). CONCLUSIONS: In patients with PersAF undergoing PFA, as compared to PVI-alone, adjunctive LAPW ablation did not improve freedom from atrial arrhythmia at 12 months.

Prospective 1-year results of atrial fibrillation ablation using the pentaspline pulsed field ablation catheter: The initial French experience.

BACKGROUND: Pulsed field ablation has recently emerged as an interesting non-thermal energy for atrial fibrillation ablation. At a time of rapid spread of this technology, there is still a lack of prospective real-life data. AIM: To describe multicentre prospective safety and 1-year efficacy data in three of the first French centres to use pulsed field ablation. METHODS: All consecutive patients undergoing a first pulsed field ablation were included prospectively. The primary outcome was freedom from documented atrial arrhythmia. The safety endpoint was a composite of major adverse events. Univariate and multivariable analyses, including patient and procedural characteristics, were performed to identify factors predictive of recurrence. RESULTS: Between May 2021 and June 2022, 311 patients were included (paroxysmal atrial fibrillation in 53%, persistent atrial fibrillation in 35% and long-standing persistent atrial fibrillation in 11%). Additional non-pulmonary vein pulsed field ablation applications were performed in 104/311 patients. One-year freedom from arrhythmia recurrence was 77.6% in the overall population and was significantly higher in patients with paroxysmal atrial fibrillation (88.4%) compared with patients with persistent atrial fibrillation (69.7%; P<0.001) and those with long-standing persistent atrial fibrillation (49.0%; P<0.001). The major complication rate was 2.6% (tamponade in four patients, stroke in two patients and coronary spasm in one patient). Besides the usual predictors of recurrences (left atrium size, CHA2DS2-VASc score, type of atrial fibrillation), the presence of atrial fibrillation at procedure start was independently associated with arrhythmia recurrence (hazard ratio: 2.04, 95% confidence interval: 1.10-3.77). CONCLUSION: In this prospective multicentre real-world study, pulsed field ablation for atrial fibrillation ablation seems to be associated with a good safety profile and rather favourable acute and 1-year success rates.

Pentaspline Pulsed Field Ablation Catheter Versus Cryoballoon for Atrial Fibrillation Ablation: Results From a Prospective Comparative Study.

BACKGROUND: Cryoballoon ablation is currently the gold standard technique for single-shot pulmonary vein isolation (PVI). Pulsed field ablation (PFA) has recently emerged as an interesting nonthermal alternative energy for PVI. The purpose of our study was to evaluate the safety and long-term efficacy of PVI using the pentaspline PFA catheter in comparison to cryoballoon ablation. METHODS AND RESULTS: Between January 2021 and December 2022, we included all consecutive patients of our center in whom a first PVI-only procedure was performed using PFA or cryoballoon. The choice of the energy was based on patients' preference between general anesthesia (PFA) and local anesthesia (cryoballoon). The primary end point was freedom from documented atrial arrhythmia recurrence after a 3-month blanking period. A total of 301 patients (paroxysmal atrial fibrillation in 220 patients) underwent a first PVI procedure performed using PFA (n=151) or cryoballoon (n=150). Complete short-term PVI was obtained in 144 of 150 patients (96%) in the cryoballoon group and in all patients of the PFA group (P=0.01). Procedure duration was significantly longer in the cryoballoon group. Transient and persistent phrenic nerve injuries were observed in the cryoballoon group only (13/150 and 2/150, respectively). One-year freedom from atrial arrhythmia was significantly higher in the PFA group compared with the cryoballoon group (87.9% versus 77.7%; adjusted hazard ratio, 0.53 [95% CI, 0.30-0.96]; P=0.037). CONCLUSIONS: This prospective, comparative, real-life study suggested that PFA could overcome safety limitations of cryoballoon with optimal effectiveness. Randomized controlled studies are required to further investigate the potential superiority of PFA over cryoballoon.

Predictors of nonpulmonary vein triggers for atrial fibrillation: A clinical risk score.

BACKGROUND: Targeting non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation may reduce atrial fibrillation (AF) recurrence. Isoproterenol infusion and cardioversion of spontaneous or induced AF can provoke NPVTs but typically require vasopressor support and increased procedural time. OBJECTIVE: The purpose of this study was to identify risk factors for the presence of NPVTs and create a risk score to identify higher-risk subgroups. METHODS: Using the AF ablation registry at the Hospital of the University of Pennsylvania, we included consecutive patients who underwent AF ablation between January 2021 and December 2022. We excluded patients who did not receive NPVT provocation testing after failing to demonstrate spontaneous NPVTs. NPVTs were defined as non-pulmonary vein ectopic beats triggering AF or focal atrial tachycardia. We used risk factors associated with NPVTs with P <.1 in multivariable logistic regression model to create a risk score in a randomly split derivation set (80%) and tested its predictive accuracy in the validation set (20%). RESULTS: In 1530 AF ablations included, NPVTs were observed in 235 (15.4%). In the derivation set, female sex (odds ratio [OR] 1.40; 95% confidence interval [CI] 0.96-2.03; P = .080), sinus node dysfunction (OR 1.67; 95% CI 0.98-2.87; P = .060), previous AF ablation (OR 2.50; 95% CI 1.70-3.65; P <.001), and left atrial scar (OR 2.90; 95% CI 1.94-4.36; P <.001) were risk factors associated with NPVTs. The risk score created from these risk factors (PRE2SSS2 score; [PRE]vious ablation: 2 points, female [S]ex: 1 point, [S]inus node dysfunction: 1 point, left atrial [S]car: 2 points) had good predictive accuracy in the validation cohort (area under the receiver operating characteristic curve 0.728; 95% CI 0.648-0.807). CONCLUSION: A risk score incorporating predictors for NPVTs may allow provocation of triggers to be performed in patients with greatest expected yield.

Clinical Outcomes by Sex After Pulsed Field Ablation of Atrial Fibrillation.

Importance: Previous studies evaluating the association of patient sex with clinical outcomes using conventional thermal ablative modalities for atrial fibrillation (AF) such as radiofrequency or cryoablation are controversial due to mixed results. Pulsed field ablation (PFA) is a novel AF ablation energy modality that has demonstrated preferential myocardial tissue ablation with a unique safety profile. Objective: To compare sex differences in patients undergoing PFA for AF in the Multinational Survey on the Methods, Efficacy, and Safety on the Postapproval Clinical Use of Pulsed Field Ablation (MANIFEST-PF) registry. Design, Setting, and Participants: This was a retrospective cohort study of MANIFEST-PF registry data, which included consecutive patients undergoing postregulatory approval treatment with PFA to treat AF between March 2021 and May 2022 with a median follow-up of 1 year. MANIFEST-PF is a multinational, retrospectively analyzed, prospectively enrolled patient-level registry including 24 European centers. The study included all consecutive registry patients (age ≥18 years) who underwent first-ever PFA for paroxysmal or persistent AF. Exposure: PFA was performed on patients with AF. All patients underwent pulmonary vein isolation and additional ablation, which was performed at the discretion of the operator. Main Outcomes and Measures: The primary effectiveness outcome was freedom from clinically documented atrial arrhythmia for 30 seconds or longer after a 3-month blanking period. The primary safety outcome was the composite of acute (<7 days postprocedure) and chronic (>7 days) major adverse events (MAEs). Results: Of 1568 patients (mean [SD] age, 64.5 [11.5] years; 1015 male [64.7%]) with AF who underwent PFA, female patients, as compared with male patients, were older (mean [SD] age, 68 [10] years vs 62 [12] years; P < .001), had more paroxysmal AF (70.2% [388 of 553] vs 62.4% [633 of 1015]; P = .002) but had fewer comorbidities such as coronary disease (9% [38 of 553] vs 15.9% [129 of 1015]; P < .001), heart failure (10.5% [58 of 553] vs 16.6% [168 of 1015]; P = .001), and sleep apnea (4.7% [18 of 553] vs 11.7% [84 of 1015]; P < .001). Pulmonary vein isolation was performed in 99.8% of female (552 of 553) and 98.9% of male (1004 of 1015; P = .90) patients. Additional ablation was performed in 22.4% of female (124 of 553) and 23.1% of male (235 of 1015; P = .79) patients. The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was similar in male and female patients (79.0%; 95% CI, 76.3%-81.5% vs 76.3%; 95% CI, 72.5%-79.8%; P = .28). There was also no significant difference in acute major AEs between groups (male, 1.5% [16 of 1015] vs female, 2.5% [14 of 553]; P = .19). Conclusion and Relevance: Results of this cohort study suggest that after PFA for AF, there were no significant sex differences in clinical effectiveness or safety events.

Heart transplantation as a rescue strategy for patients with refractory electrical storm.

AIMS: Heart transplantation (HT) can be proposed as a therapeutic strategy for patients with severe refractory electrical storm (ES). Data in the literature are scarce and based on case reports. We aimed at determining the characteristics and survival of patients transplanted for refractory ES. METHODS AND RESULTS: Patients registered on HT waiting list during the following days after ES and eventually transplanted, from 2010 to 2021, were retrospectively included in 11 French centres. The primary endpoint was in-hospital mortality. Forty-five patients were included [82% men; 55.0 (47.8-59.3) years old; 42.2% and 26.7% non-ischaemic dilated or ischaemic cardiomyopathies, respectively]. Among them, 42 (93.3%) received amiodarone, 29 received (64.4%) beta blockers, 19 (42.2%) required deep sedation, 22 had (48.9%) mechanical circulatory support, and 9 (20.0%) had radiofrequency catheter ablation. Twenty-two patients (62%) were in cardiogenic shock. Inscription on wait list and transplantation occurred 3.0 (1.0-5.0) days and 9.0 (4.0-14.0) days after ES onset, respectively. After transplantation, 20 patients (44.4%) needed immediate haemodynamic support by extracorporeal membrane oxygenation (ECMO). In-hospital mortality rate was 28.9%. Predictors of in-hospital mortality were serum creatinine/urea levels, need for immediate post-operative ECMO support, post-operative complications, and surgical re-interventions. One-year survival was 68.9%. CONCLUSION: Electrical storm is a rare indication of HT but may be lifesaving in those patients presenting intractable arrhythmias despite usual care. Most patients can be safely discharged from hospital, although post-operative mortality remains substantial in this context of emergency transplantation. Larger studies are warranted to precisely determine those patients at higher risk of in-hospital mortality.

Safety and Effectiveness of Pulsed Field Ablation to Treat Atrial Fibrillation: One-Year Outcomes From the MANIFEST-PF Registry.

BACKGROUND: Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care. METHODS: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events. RESULTS: At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA2DS2-VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289-421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%-80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P=0.001). Acute major adverse events occurred in 1.9% of patients. CONCLUSIONS: In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.

Conduction system pacing in France in 2022: A snapshot survey from the Working Group of Pacing and Electrophysiology of the French Society of Cardiology.

BACKGROUND: Conduction system pacing (CSP) is an emerging and promising approach for physiological ventricular pacing. While data from randomized controlled trials are scarce, use of His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP) has increased in France. AIM: To perform a national snapshot survey for cardiac electrophysiologists to evaluate adoption of CSP in France. METHODS: An online survey, distributed to every senior cardiac electrophysiologist in France, was conducted in November 2022. RESULTS: A total of 120 electrophysiologists completed the survey. Eighty-three (69%) respondents reported experience in undertaking CSP procedures and 27 (23%) were planning to start performing CSP in the coming 2 years. The implantation techniques and criteria used for successful implantation differed significantly among operators. The most frequent indications for HBP and LBBAP were high-degree atrioventricular block with left ventricular ejection fraction (LVEF) < 40% (24 and 82%, respectively) or with LVEF ≥ 40% (27 and 74%, respectively), and after failure of a coronary sinus left ventricular lead (27 and 71%, respectively). The limitations respondents most frequently perceived when performing HBP were bad sensing/pacing parameters (45%), increased procedure duration (41%) and risk of lead dislodgement (30%). The most frequently perceived limitations to performing LBBAP were absence of guidelines or consensus (31%), lack of medical training (23%) and increased procedure duration (23%). CONCLUSIONS: Our national survey-based study supports wide adoption of CSP in France. CSP is currently used as a second-line approach for both antibradycardia and resynchronization indications, with important variations regarding implantation techniques and criteria for measuring success.

Is excessive ventricular irregularity predictive of rehospitalization in patients with permanent AF and HFpEF?

AIMS: There are currently limited therapeutic approaches for patients with heart failure with preserved ejection fraction (HFpEF) who have developed permanent atrial fibrillation (AF). We aimed to analyse the impact of ventricular irregularity on heart failure rehospitalization in patients with permanent AF and HFpEF. METHODS AND RESULTS: All 24 h ambulatory Holter monitoring performed in our centre within a month after a first heart failure hospitalization were screened. Patients with HFpEF and permanent AF were included in the retrospective analysis. The following parameters of ventricular irregularity were calculated over the 24 h recording period: standard deviation of all RR intervals (SDNN), coefficient of variation of SDNN (CV-SDNN = SDNN/mean RR), root of the mean squared differences of successive RR intervals (RMSSD), and percentage of consecutive RR intervals with difference over 50 ms (pNN50). The primary endpoint was rehospitalization for acute heart failure (HFrH). From 2010 to 2021, 51/216 screened patients were included. During a median follow-up of 3.13 years, 29/51 patients reached the primary endpoint. HFrH patients had higher SDNN (205 ± 65 vs. 154 ± 46 ms; P < 0.01), CV-SDNN (26 ± 8% vs. 19 ± 5%, P < 0.01), RMSSD (182 ± 47 vs. 138 ± 65 ms, P = 0.013), and pNN50 (76 ± 9 vs. 58 ± 26, P < 0.001) when compared with patients with no HFrH. In multivariate analysis, all those parameters remained significantly associated with HFrH. CONCLUSIONS: In this pilot study, we found some evidences for a deleterious impact of excessive ventricular irregularity on HFrH in AF patients with HFpEF. Those new findings could pave the way for new prognosis and therapeutic approaches in this patients' population.

RVOT premature ventricular contractions induce significant anatomical displacement during 3D mapping: A cause of mid-term ablation failure?

BACKGROUND: Catheter ablation is a first-line treatment for symptomatic right ventricular outflow tract (RVOT) premature ventricular complexes (PVCs). There is evidence of displacement of the ablation target site during PVCs relative to the location in sinus rhythm (SR). AIM: To analyse the extent of displacement induced by RVOT PVCs and its effect on the ablation sites and the mid-term efficacy of ablation. METHODS: In this multicentre French study, we retrospectively included 18 consecutive adults referred for ablation of RVOT PVCs using a three-dimensional (3D) mapping system. PVC activation maps were performed conventionally (initial map), then each PVC activation point was manually reannotated considering the 3D location on a previous SR beat (corrected map). The ablation-site locations on the initial or the corrected area, including the 10 best activation points, were analysed. Mid-term efficacy was evaluated. RESULTS: The direction of map shift during PVCs relative to the map in SR occurred along a vertical axis in 16 of 18 patients. The mean activation-point displacement for each of the 18 mapped chambers was 5.6±2.2mm. Mid-term recurrence of RVOT PVCs occurred in 5 (28%) patients. In all patients with recurrences, no significant ablation lesion was located on the corrected (true) site of origin. CONCLUSIONS: RVOT PVCs induce a vertical anatomical shift that can mislead physicians about the true location of the arrhythmia's site of origin. Our study highlights the association between mid-term PVC recurrence and the absence of spatial overlap between ablation points and the corrected site of origin.

His-bundle pacing and atrioventricular nodal ablation for noncontrolled atrial arrhythmia: A technical challenge with major clinical benefits.

BACKGROUND: His-bundle pacing (HBP) is an appealing alternative to right ventricular pacing in patients referred for permanent ventricular pacing and atrioventricular nodal ablation (AVNA) because it preserves physiological ventricular activation. Only limited data regarding HBP combined with AVNA are available in the literature. OBJECTIVE: The purpose of this study was to provide further evidence on the feasibility and efficacy of this therapeutic approach in patients with uncontrolled atrial arrhythmia. METHODS: We prospectively included all patients who had undergone AVNA after HBP in 3 different hospitals between 2017 and 2022. RESULTS: AVNA following HBP lead implantation was performed in 75 patients. Complete atrioventricular (AV) block was obtained in 58 patients (77%), and significant modulation of AV nodal conduction (heart rate <60 bpm) was obtained in 12 patients (16%). AVNA failure was observed in 5 patients (7%). Recording of an atrial signal by the HBP lead was more frequently observed in patients with AVNA modulation/failure than in patients with complete AV block (11/17 vs 5/58; P <.001). No lead dislodgment occurred during the AVNA procedures. Acute His-bundle (HB) capture threshold increase >1 V occurred in 11 patients (15%), with return to baseline value on day 1 in 9 patients. New York Heart Association functional class and left ventricular ejection fraction significantly improved from baseline to last follow-up (3.0 ± 0.7 vs 1.6 ± 0.5; P <.001; and 47% ± 14% vs 60% ± 9%; P <.0001, respectively). CONCLUSION: AVNA combined with HBP for noncontrolled atrial arrhythmia was feasible and clinically efficient. Implanting the HB lead on the ventricular aspect of the tricuspid annulus avoiding atrial signal recording can facilitate AVNA.

Left bundle branch area pacing in patients with baseline narrow, left, or right bundle branch block QRS patterns: insights into electrocardiographic and echocardiographic features.

AIMS: Left bundle branch area pacing (LBBAP) is a recent technique aiming at preservation of physiological ventricular electrical activation. Our goal was to assess mechanical synchrony parameters in relation to electrocardiographic features during LBBAP performed in routine practice. METHODS AND RESULTS: From June 2020 to August 2021, all patients of our institution with permanent pacemaker implantation indication were eligible for LBBAP. A 'qR' pattern in V1 and a delay from pacing spike to the peak of the R-wave in V6 < 80 ms defined a successful LBBAP. Electrocardiogram and echocardiography were performed during spontaneous rhythm and LBBAP: left ventricular mechanical synchrony (LVMS) parameters using 2D Speckle tracking and interventricular mechanical delay (IVMD) were collected. LBBAP was attempted with success in 134/163 patients (82.2%). During LBBAP, the mean QRS width was 104 ± 12 ms. In patients with left bundle branch block (n = 47), LBBAP provided a significant decrease of QRS width from 139 ± 16 to 105 ± 12 ms (P < 0.001) with reduction of LVMS (53 ± 21 vs. 90 ± 46 ms, P = 0.009), and IVMD (14 ± 13 vs. 49 ± 18 ms, P < 0.001). In patients with right bundle branch block (n = 38), LBBAP led to a significant decrease of QRS width from 134 ± 14 to 106 ± 13 ms (P < 0.001) with no effect on LVMS and a reduction of IVMD (17 ± 14 vs. 50 ± 16 ms, P < 0.001). CONCLUSION: LBBAP in routine practice preserved intra-ventricular mechanical synchrony in patients with narrow and RBBB QRS and improved asynchrony parameters in patients with LBBB.

Machine learning-based scoring system to predict in-hospital outcomes in patients hospitalized with COVID-19.

BACKGROUND: The evolution of patients hospitalized with coronavirus disease 2019 (COVID-19) is still hard to predict, even after several months of dealing with the pandemic. AIMS: To develop and validate a score to predict outcomes in patients hospitalized with COVID-19. METHODS: All consecutive adults hospitalized for COVID-19 from February to April 2020 were included in a nationwide observational study. Primary composite outcome was transfer to an intensive care unit from an emergency department or conventional ward, or in-hospital death. A score that estimates the risk of experiencing the primary outcome was constructed from a derivation cohort using stacked LASSO (Least Absolute Shrinkage and Selection Operator), and was tested in a validation cohort. RESULTS: Among 2873 patients analysed (57.9% men; 66.6±17.0 years), the primary outcome occurred in 838 (29.2%) patients: 551 (19.2%) were transferred to an intensive care unit; and 287 (10.0%) died in-hospital without transfer to an intensive care unit. Using stacked LASSO, we identified 11 variables independently associated with the primary outcome in multivariable analysis in the derivation cohort (n=2313), including demographics (sex), triage vitals (body temperature, dyspnoea, respiratory rate, fraction of inspired oxygen, blood oxygen saturation) and biological variables (pH, platelets, C-reactive protein, aspartate aminotransferase, estimated glomerular filtration rate). The Critical COVID-19 France (CCF) risk score was then developed, and displayed accurate calibration and discrimination in the derivation cohort, with C-statistics of 0.78 (95% confidence interval 0.75-0.80). The CCF risk score performed significantly better (i.e. higher C-statistics) than the usual critical care risk scores. CONCLUSIONS: The CCF risk score was built using data collected routinely at hospital admission to predict outcomes in patients with COVID-19. This score holds promise to improve early triage of patients and allocation of healthcare resources.

Epicardial origin of cardiac arrhythmias: clinical evidences and pathophysiology.

Recent developments in imaging, mapping, and ablation techniques have shown that the epicardial region of the heart is a key player in the occurrence of ventricular arrhythmic events in several cardiac diseases, such as Brugada syndrome, arrhythmogenic cardiomyopathy, or dilated cardiomyopathy. At the atrial level as well, the epicardial region has emerged as an important determinant of the substrate of atrial fibrillation, pointing to common underlying pathophysiological mechanisms. Alteration in the gradient of repolarization between myocardial layers favouring the occurrence of re-entry circuits has largely been described. The fibro-fatty infiltration of the subepicardium is another shared substrate between ventricular and atrial arrhythmias. Recent data have emphasized the role of the epicardial reactivation in the formation of this arrhythmogenic substrate. There are new evidences supporting this structural remodelling process to be regulated by the recruitment of epicardial progenitor cells that can differentiate into adipocytes or fibroblasts under various stimuli. In addition, immune-inflammatory processes can also contribute to fibrosis of the subepicardial layer. A better understanding of such 'electrical fragility' of the epicardial area will open perspectives for novel biomarkers and therapeutic strategies. In this review article, a pathophysiological scheme of epicardial-driven arrhythmias will be proposed.

Prognostic value of right ventricular dilatation in patients with COVID-19: a multicentre study.

AIMS: Although cardiac involvement has prognostic significance in coronavirus disease 2019 (COVID-19) and is associated with severe forms, few studies have explored the prognostic role of transthoracic echocardiography (TTE). We investigated the link between TTE parameters and prognosis in COVID-19. METHODS AND RESULTS: Consecutive patients with COVID-19 admitted to 24 French hospitals were retrospectively included. Comprehensive data, including clinical and biological parameters, were recorded at admission. Focused TTE was performed during hospitalization, according to clinical indication. Patients were followed for a primary composite outcome of death or transfer to intensive care unit (ICU) during hospitalization. Among 2878 patients, 445 (15%) underwent TTE. Most of these had cardiovascular risk factors, a history of cardiovascular disease, and were on cardiovascular treatments. Dilatation and dysfunction were observed in, respectively, 12% (48/412) and 23% (102/442) of patients for the left ventricle, and in 12% (47/407) and 16% (65/402) for the right ventricle (RV). Primary composite outcome occurred in 44% (n = 196) of patients [9% (n = 42) for death without ICU transfer and 35% (n = 154) for admission to ICU]. RV dilatation was the only TTE parameter associated with the primary outcome. After adjustment, male sex [hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.09 - 2.25; P = 0.02], higher body mass index (HR 1.10, 95% CI 1.02 - 1.18; P = 0.01), anticoagulation (HR 0.53, 95% CI 0.33 - 0.86; P = 0.01), and RV dilatation (HR 1.66, 95% CI 1.05 - 2.64; P = 0.03) remained independently associated with the primary outcome. CONCLUSION: Echocardiographic evaluation of RV dilatation could be useful for assessing risk of severe COVID-19 developing in hospitalized patients.

Cardiovascular Characteristics and Outcomes of Young Patients with COVID-19.

Although 18-45-year-old (y-o) patients represent a significant proportion of patients hospitalized for COVID-19, data concerning the young population remain scarce. The Critical COVID France (CCF) study was an observational study including consecutive patients hospitalized for COVID-19 in 24 centers between 26 February and 20 April 2020. The primary composite outcome included transfer to the intensive care unit (ICU) or in-hospital death. Secondary outcomes were cardiovascular (CV) complications. Among 2868 patients, 321 (11.2%) patients were in the 18-45-y-o range. In comparison with older patients, young patients were more likely to have class 2 obesity and less likely to have hypertension, diabetes and dyslipidemia. The primary outcome occurred less frequently in 18-45-y-o patients in comparison with patients > 45 years old (y/o) (16.8% vs. 30.7%, p < 0.001). The 18-45-y-o patients presented with pericarditis (2.2% vs. 0.5%, p = 0.003) and myocarditis (2.5% vs. 0.6%, p = 0.002) more frequently than patients >45 y/o. Acute heart failure occurred less frequently in 18-45-y-o patients (0.9% vs. 7.2%, p < 0.001), while thrombotic complications were similar in young and older patients. Whereas both transfer to the ICU and in-hospital death occurred less frequently in young patients, COVID-19 seemed to have a particular CV impact in this population.

Characteristics and outcomes of patients hospitalized for COVID-19 in France: The Critical COVID-19 France (CCF) study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis. Only limited data are available on the characteristics and outcomes of patients hospitalized for COVID-19 in France. AIMS: To investigate the characteristics, cardiovascular complications and outcomes of patients hospitalized for COVID-19 in France. METHODS: The Critical COVID-19 France (CCF) study is a French nationwide study including all consecutive adults with a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection hospitalized in 24 centres between 26 February and 20 April 2020. Patients admitted directly to intensive care were excluded. Clinical, biological and imaging parameters were systematically collected at hospital admission. The primary outcome was in-hospital death. RESULTS: Of 2878 patients included (mean±SD age 66.6±17.0 years, 57.8% men), 360 (12.5%) died in the hospital setting, of which 7 (20.7%) were transferred to intensive care before death. The majority of patients had at least one (72.6%) or two (41.6%) cardiovascular risk factors, mostly hypertension (50.8%), obesity (30.3%), dyslipidaemia (28.0%) and diabetes (23.7%). In multivariable analysis, older age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P<0.001), male sex (HR 1.69, 95% CI 1.11-2.57; P=0.01), diabetes (HR 1.72, 95% CI 1.12-2.63; P=0.01), chronic kidney failure (HR 1.57, 95% CI 1.02-2.41; P=0.04), elevated troponin (HR 1.66, 95% CI 1.11-2.49; P=0.01), elevated B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide (HR 1.69, 95% CI 1.0004-2.86; P=0.049) and quick Sequential Organ Failure Assessment score ≥2 (HR 1.71, 95% CI 1.12-2.60; P=0.01) were independently associated with in-hospital death. CONCLUSIONS: In this large nationwide cohort of patients hospitalized for COVID-19 in France, cardiovascular comorbidities and risk factors were associated with a substantial morbi-mortality burden.

Characteristics and impact of cardiovascular comorbidities on coronavirus disease 2019 in women: A multicentre cohort study.

BACKGROUND: Although women account for up to half of patients hospitalized for coronavirus disease 2019 (COVID-19), no specific data have been reported in this population. AIMS: To assess the burden and impact of cardiovascular comorbidities in women with COVID-19. METHODS: All consecutive patients hospitalized for COVID-19 across 24 hospitals from 26 February to 20 April 2020 were included. The primary composite outcome was transfer to an intensive care unit or in-hospital death. RESULTS: Among 2878 patients, 1212 (42.1%) were women. Women were older (68.3±18.0 vs. 65.4±16.0 years; P<0.001), but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8%) experienced the primary outcome, including 161 (13.3%) transfers to an intensive care unit and 115 (9.5%) deaths without transfer to intensive care unit. The rate of in-hospital death or transfer to an intensive care unit was lower in women versus men (crude hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.53-0.72). Age (adjusted HR: 1.05 per 5-year increase, 95% CI: 1.01-1.10), body mass index (adjusted HR: 1.06 per 2-unit increase, 95% CI: 1.02-1.10), chronic kidney disease (adjusted HR: 1.57, 95% CI: 1.11-2.22) and heart failure (adjusted HR: 1.52, 95% CI: 1.04-2.22) were independently associated with the primary outcome in women. Elevated B-type natriuretic peptide/N-terminal prohormone of B-type natriuretic peptide (adjusted HR: 2.41, 95% CI: 1.70-3.44) and troponin (adjusted HR: 2.00, 95% CI: 1.39-2.88) concentrations at admission were also associated with the primary outcome, even in women free of previous coronary artery disease or heart failure. CONCLUSIONS: Although female sex was associated with a lower risk of transfer to an intensive care unit or in-hospital death, COVID-19 remained associated with considerable morbimortality in women, especially in those with cardiovascular diseases.