Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).

Effect of remote monitoring on clinical outcomes in European heart failure patients with an implantable cardioverter-defibrillator: secondary results of the REMOTE-CIED randomized trial.

AIMS: Remote patient monitoring (RPM) systems offer a promising alternative to conventional In-Clinic check-ups, hereby reducing unnecessary clinic visits. Especially with the rise of the COVID-19 pandemic, this reduction is of paramount importance. Regarding the association between RPM and clinical outcomes, findings of previous studies have been inconsistent. The aim of this study is to elucidate the effect of partly substituting In-Clinic visits by RPM on clinical outcomes in implantable cardioverter-defibrillator (ICD) patients. METHODS AND RESULTS: The study included 595 heart failure patients (LVEF ≤35%; NYHA Class II/III) implanted with an ICD compatible with the Boston Scientific LATITUDE™ system. Participants were randomized to RPM plus an annual In-Clinic visit or 3-6 months In-Clinic check-ups alone. The investigated endpoints after 2 years of follow-up included a composite of all-cause mortality and cardiac hospitalization, mortality and cardiac hospitalization as independent endpoints and ICD therapy. The incidence of mortality and hospitalization did not differ significantly as independent, nor as composite endpoint between the RPM and In-Clinic group (all Ps <0.05). The results were similar regarding ICD therapy, except for appropriate ICD therapy (odds ratio 0.50; 95% confidence interval 0.26-0.98; P = 0.04). Exploratory subgroup analyses indicated that the effect of RPM differs between patients with specific characteristics, i.e. ≥60 years and permanent atrial fibrillation (all Ps < 0.05). CONCLUSION: RPM is non-inferior to conventional In-Clinic visits regarding clinical outcomes. Routine In-Clinic follow-up may partly be substituted by RPM without jeopardizing safety and efficiency, and thus reducing unnecessary In-Clinic visits. CLINICALTRIALS.GOV IDENTIFIER: NCT01691586.

Robustness and relevance of predictive score in sudden cardiac death for patients with Brugada syndrome.

AIMS: Risk stratification of sudden cardiac arrest (SCA) in Brugada syndrome (Brs) remains the main challenge for physicians. Several scores have been suggested to improve risk stratification but never replicated. We aim to investigate the accuracy of the Brs risk scores. METHODS AND RESULTS: A total of 1613 patients [mean age 45 ± 15 years, 69% male, 323 (20%) symptomatic] were prospectively enrolled from 1993 to 2016 in a multicentric database. All data described in the risk score were double reviewed for the study. Among them, all patients were evaluated with Shanghai score and 461 (29%) with Sieira score. After a mean follow-up of 6.5 ± 4.7 years, an arrhythmic event occurred in 75 (5%) patients including 16 SCA, 11 symptomatic ventricular arrhythmia, and 48 appropriate therapies. Predictive capacity of the Shanghai score (n = 1613) and the Sieira (n = 461) score was, respectively, estimated by an area under the curve of 0.73 (0.67-0.79) and 0.71 (0.61-0.81). Considering Sieira score, the event rate at 10 years was significantly higher with a score of 5 (26.4%) than with a score of 0 (0.9%) or 1 (1.1%) (P < 0.01). No statistical difference was found in intermediate-risk patients (score 2-4). The Shanghai score does not allow to better stratify the risk of SCA. CONCLUSIONS: In the largest cohort of Brs patient ever described, risk scores do not allow stratifying the risk of arrhythmic event in intermediate-risk patient.

The emergence of Staphylococcus aureus as the primary cause of cardiac device-related infective endocarditis.

BACKGROUND: Increasing use of cardiovascular implantable electronic devices (CIED), as permanent pacemakers (PPM), implantable cardioverter defibrillators (ICD), or cardiac resynchronization therapy (CRT), is associated with the emergence of CIED-related infective endocarditis (CIED-IE). We aimed to characterize CIED-IE profile, temporal trends, and prognostic factors. METHODS: CIED-IE diagnosed at Rennes University Hospital during years 1992-2017 were identified through computerized database, and included if they presented all of the following: (1) clinical signs of infection; (2) microbiological documentation through blood and/or CIED lead cultures; (3) lead or valve vegetation, or definite IE according to Duke criteria. Data were retrospectively extracted from medical charts. The cohort was categorized in three periods: 1992-1999, 2000-2008, and 2009-2017. RESULTS: We included 199 patients (51 women, 148 men, median age 73 years [interquartile range, 64-79]), with CIED-IE: 158 PPMs (79%), 24 ICD (12%), and 17 CRT (9%). Main pathogens were coagulase-negative staphylococci (CoNS: n = 86, 43%), Staphylococcus aureus (n = 60, 30%), and other Gram-positive cocci (n = 28, 14%). Temporal trends were remarkable for the decline in CoNS (P = 0.002), and the emergence of S. aureus as the primary cause of CIED-IE (24/63 in 2009-2017, 38%). Factors independently associated with one-year mortality were chronic obstructive pulmonary disease (COPD: hazard ratio 3.84 [1.03-6.02], P = 0.03), left-sided endocarditis (HR 2.25 [1.09-4.65], P = 0.03), pathogens other than CoNS (HR 3.16 [1.19-8.39], P = 0.02), and CIED removal/reimplantation (HR 0.41 [0.20-0.83], P = 0.01). CONCLUSIONS: S. aureus has emerged as the primary cause of CIED-IE. Left-sided endocarditis, COPD, pathogens other than CoNS, and no CIED removal/reimplantation are independent risk factors for one-year mortality.

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies.

BACKGROUND: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. METHODS: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. RESULTS: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. CONCLUSIONS: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.

Prognostic value of the 12-lead surface electrocardiogram in sarcomeric hypertrophic cardiomyopathy: data from the REMY French register.

AIMS: To identify independent electrocardiogram (ECG) predictors of long-term clinical outcome based on standardized analysis of the surface ECG in a large multicentre cohort of patients with sarcomeric hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Retrospective observational study from the REMY French HCM clinical research observatory. Primary endpoint was a composite of all-cause mortality, major non-fatal arrhythmic events, hospitalization for heart failure (HF), and stroke. Secondary endpoints were components of the primary endpoint. Uni- and multivariable Cox proportional hazard regression analysis was performed to identify independent predictors. Among 994 patients with HCM, only 1.8% had a strictly normal baseline ECG. The most prevalent abnormalities were inverted T waves (63.7%), P-wave abnormalities (30.4%), and abnormal Q waves (25.5%). During a mean follow-up of 4.0 ± 2.0 years, a total of 272 major cardiovascular events occurred in 217 patients (21.8%): death or heart transplant in 98 (9.8%), major arrhythmic events in 40 (4.0%), HF hospitalization in 115 (11.6%), and stroke in 23 (2.3%). At multivariable analysis using ECG covariates, prolonged QTc interval, low QRS voltage, and PVCs of right bundle branch block pattern predicted worse outcome, but none remained independently associated with the primary endpoint after adjustment on main demographic and clinical variables. For secondary endpoints, abnormal Q waves independently predicted all-cause death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.23-4.47; P = 0.009] and prolonged QTc the risk of HF hospitalization (HR 1.006, 95% CI 1.001-1.011; P = 0.024). CONCLUSION: The 12-lead surface ECG has no independent value to predict the primary outcome measure in patients with HCM. The 12-lead surface ECG has been widely used as a screening tool in HCM but its prognostic value remains poorly known. The value of baseline surface ECG to predict long-term clinical outcomes was studied in a cohort of 994 patients with sarcomeric HCM. The surface ECG has no significant additional value to predict outcome in this patient population.

CRT-Pacemaker Versus CRT-Defibrillator Who Needs Sudden Cardiac Death Protection?

PURPOSE OF THE REVIEW: Patients with cardiomyopathy and impaired left ventricular (LV) ejection fraction are at risk of sudden cardiac death (SCD). In selected heart failure patients, cardiac resynchronization therapy (CRT) provides LV reverse remodeling and improves the cellular and molecular function leading to a reduced risk of ventricular arrhythmia and SCD. Consequently, some CRT candidates may not need concomitant ICD therapy. This review aimed at focusing on the residual risk of SCD in patients receiving CRT and discussing the requirement of a concomitant ICD therapy in CRT candidates. RECENT FINDINGS: New imaging diagnostic tools may be helpful to accurately predict patient with a residual risk of SCD and who required a CRT-D implantation. Recent data highlighted that cardiac computed tomography (CT) or myocardial scar tissue analysis using contrast-enhanced cardiac magnetic resonance (CMR) was able to predict the occurrence of VA in patients with bi-ventricular pacing. Cardiac imaging and specifically myocardial scar analysis seem promising to evaluate the risk of SCD following bi-ventricular pacing and will probably be of great help in the future to accurately identify those who needs concomitant defibrillator's protection.

Myocardial constructive work and cardiac mortality in resynchronization therapy candidates.

BACKGROUND: Recent studies have shown that myocardial constructive work (CW) assessed by pressure-strain loops (PSLs) is an independent predictor of a volumetric response to cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the role of CW in predicting the cardiac outcome of heart failure patients undergoing CRT. METHODS: This is a retrospective study including 166 CRT candidates (ejection fraction [EF] ≤35%, QRS duration ≥120 milliseconds). Two-dimensional standard echocardiography and speckle-tracking echocardiography were performed before CRT and at 6-month follow-up. PSLs were used to assess myocardial CW. RESULTS: After a median follow-up of 4 years (range 1.3-5 years), cardiac death occurred in 14 patients (8%). A multivariable Cox regression analysis including age, coronary artery disease, and septal flash showed that CW≤888 mm Hg% was the only independent predictor of cardiac mortality (hazard ratio 4.23, 95% CI 1.08-16.5, P = .03). After 6 months of CRT, a 15% reduction in left ventricular end-systolic volume was observed in 118 (71%) patients, and a CRT volumetric response was identified. Among CRT responders, the concomitant presence of CW ≤888 mm Hg% identified a subgroup of patients at high risk of cardiac death (P = .04 in the log-rank test). The addition of CW ≤888 mm Hg% to a model including age, coronary artery disease, septal flash, and CRT response caused a significant increase in model power for the prediction of cardiac death (χ2: 12.6 vs 25.7, P = .02). CONCLUSIONS: The estimation of left ventricular CW by PSLs is a relatively novel tool that allows for the prediction of cardiac outcome in CRT candidates.

Effectiveness of single- vs dual-coil implantable defibrillator leads: An observational analysis from the SIMPLE study.

INTRODUCTION: Dual-coil leads (DC-leads) were the standard of choice since the first nonthoracotomy implantable cardioverter/defibrillator (ICD). We used contemporary data to determine if DC-leads offer any advantage over single-coil leads (SC-leads), in terms of defibrillation efficacy, safety, clinical outcome, and complication rates. METHODS AND RESULTS: In the Shockless IMPLant Evaluation study, 2500 patients received a first implanted ICD and were randomized to implantation with or without defibrillation testing. Two thousand and four hundred seventy-five patients received SC-coil or DC-coil leads (SC-leads in 1025/2475 patients; 41.4%). In patients who underwent defibrillation testing (n = 1204), patients with both lead types were equally likely to achieve an adequate defibrillation safety margin (88.8% vs 91.2%; P = 0.16). There was no overall effect of lead type on the primary study endpoint of "failed appropriate shock or arrhythmic death" (adjusted HR 1.18; 95% CI, 0.86-1.62; P = 0.300), and on all-cause mortality (SC-leads: 5.34%/year; DC-leads: 5.48%/year; adjusted HR 1.16; 95% CI, 0.94-1.43; P = 0.168). However, among patients without prior heart failure (HF), and SC-leads had a significantly higher risk of failed appropriate shock or arrhythmic death (adjusted HR 7.02; 95% CI, 2.41-20.5). There were no differences in complication rates. CONCLUSION: In this nonrandomized evaluation, there was no overall difference in defibrillation efficacy, safety, outcome, and complication rates between SC-leads and DC-leads. However, DC-leads were associated with a reduction in the composite of failed appropriate shock or arrhythmic death in the subgroup of non-HF patients. Considering riskier future lead extraction with DC-leads, SC-leads appears to be preferable in the majority of patients.

Radiofrequency ablation of right ventricular tachycardia in patients with no femoral access: safety and efficacy of a superior approach.

AIMS: Ventricular tachycardia (VT) ablation has been proven to be effective and safe to avoid arrhythmia recurrences in patients with repaired congenital heart disease (CHD). However, some of these patients may present right ventricular (RV) access issues [agenesia or thrombosis of inferior vena cava (IVC)], making impossible to access the right ventricle through an inferior approach. In such patients, only a superior approach would theoretically be feasible. METHODS AND RESULTS: All VT ablations performed through a jugular or subclavian approach in CHD patients between 2012 and 2017 were included. Among 247 patients scheduled for VT ablation, two patients underwent three VT ablation procedures via a superior approach for due to the inability to access the right ventricle through a conventional IVC access (IVC interruption with azygos continuation in one patient and IVC thrombosis in the other). Ablation was performed using a three-dimensional system through a superior approach, using a subclavian access in both cases. A redo ablation had to be performed in the first patient using a jugular approach. Large curve catheters were used to facilitate RV outflow tract access. Supposed critical isthmuses could be localized and ablated. Patients remained free from arrhythmias during follow-up. CONCLUSION: In patients with repaired CHD and 'no femoral access', ablation of RV tachycardia can be performed using a subclavian or a jugular approach. Mapping may be challenging, requiring large curve catheters. Conventional isthmuses can be mapped and ablated successfully, and such patients should not be denied radiofrequency ablation.

Effect of remote monitoring on patient-reported outcomes in European heart failure patients with an implantable cardioverter-defibrillator: primary results of the REMOTE-CIED randomized trial.

AIMS: The European REMOTE-CIED study is the first randomized trial primarily designed to evaluate the effect of remote patient monitoring (RPM) on patient-reported outcomes in the first 2 years after implantation of an implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: The sample consisted of 595 European heart failure patients implanted with an ICD compatible with the Boston Scientific LATITUDE® RPM system. Patients were randomized to RPM plus a yearly in-clinic ICD check-up vs. 3-6-month in-clinic check-ups alone. At five points during the 2-year follow-up, patients completed questionnaires including the Kansas City Cardiomyopathy Questionnaire and Florida Patient Acceptance Survey (FPAS) to assess their heart failure-specific health status and ICD acceptance, respectively. Information on clinical status was obtained from patients' medical records. Linear regression models were used to compare scores between groups over time. Intention-to-treat and per-protocol analyses showed no significant group differences in patients' health status and ICD acceptance (subscale) scores (all Ps > 0.05). Exploratory subgroup analyses indicated a temporary improvement in device acceptance (FPAS total score) at 6-month follow-up for secondary prophylactic in-clinic patients only (P < 0.001). No other significant subgroup differences were observed. CONCLUSION: Large clinical trials have indicated that RPM can safely and effectively replace most in-clinic check-ups of ICD patients. The REMOTE-CIED trial results show that patient-reported health status and ICD acceptance do not differ between patients on RPM and patients receiving in-clinic check-ups alone in the first 2 years after ICD implantation.ClinicalTrials.gov Identifier: NCT01691586.

Time-to-first appropriate shock in patients implanted prophylactically with an implantable cardioverter-defibrillator: data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS).

AIMS: Data on predictors of time-to-first appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with Brugada Syndrome (BrS) and prophylactically implanted ICD's are scarce. METHODS AND RESULTS: SABRUS (Survey on Arrhythmic Events in BRUgada Syndrome) is an international survey on 678 BrS patients who experienced arrhythmic event (AE) including 252 patients in whom AE occurred after prophylactic ICD implantation. Analysis was performed on time-to-first appropriate ICD discharge regarding patients' characteristics. Multivariate logistic regression models were utilized to identify which parameters predicted time to arrhythmia ≤5 years. The median time-to-first appropriate ICD therapy was 24.8 ± 2.8 months. A shorter time was observed in patients from Asian ethnicity (P < 0.05), those with syncope (P = 0.001), and those with Class IIa indication for ICD (P = 0.001). A longer time was associated with a positive family history of sudden cardiac death (P < 0.05). Multivariate Cox regression revealed shorter time-to-ICD therapy in patients with syncope [odds ratio (OR) 1.65, P = 0.001]. In 193 patients (76.6%), therapy was delivered during the first 5 years. Factors associated with this time were syncope (OR 0.36, P = 0.001), spontaneous Type 1 Brugada electrocardiogram (ECG) (OR 0.5, P < 0.05), and Class IIa indication (OR 0.38, P < 0.01) as opposed to Class IIb (OR 2.41, P < 0.01). A near-significant trend for female gender was also noted (OR 0.13, P = 0.052). Two score models for prediction of <5 years to shock were built. CONCLUSION: First appropriate therapy in BrS patients with prophylactic ICD's occurred during the first 5 years in 76.6% of patients. Syncope and spontaneous Type 1 Brugada ECG correlated with a shorter time to ICD therapy.

Remote monitoring of implantable cardioverter defibrillators: Patient experiences and preferences for follow-up.

BACKGROUND: Patient satisfaction with remote patient monitoring (RPM) of implantable cardioverter defibrillators (ICDs) seems to be high, yet knowledge on long-term patient experiences is limited. The European REMOTE-CIED study explored patients' experiences with RPM, examined patient's preferences for ICD follow-up, and identified determinants of patient's preferences in the first 2 years postimplantation. METHODS: European heart failure patients (N = 300; median age = 66 years [interquartile range (IQR) = 59-73], and 22% female) with a first-time ICD received a Boston Scientific LATITUDE RPM system (Marlborough, MA, USA) and had scheduled in-clinic follow-ups once a year. Patients completed questionnaires at 1-2 weeks and also at 3, 6, 12, and 24 months postimplantation and clinical data were obtained from their medical records. Patient evaluation data were analyzed descriptively, and Student's t-tests/Man-Whitney U tests or Chi-square tests/Fisher's exact tests were performed to examine determinants of patient preferences. RESULTS: At 2 years postimplantation, the median patient satisfaction score with the RPM system was 9 out of 10 (IQR = 8-10), despite 53% of the patients experiencing issues (eg, failure to transmit data). Of the 221 patients who reported their follow-up preferences, 43% preferred RPM and 19% preferred in-clinic follow-up. Patients with a preference for RPM were more likely to be higher educated (P = 0.04), employed (P = 0.04), and equipped with a new LATITUDE model (P = 0.04), but less likely to suffer from chronic obstructive pulmonary disease (P = 0.009). CONCLUSION: In general, patients were highly satisfied with RPM, but a subgroup preferred in-clinic follow-up. Therefore, physicians should include patients' concerns and preferences in the decision-making process, to tailor device follow-up to individual patients' needs and preferences.

Pacing for hypertrophic obstructive cardiomyopathy: an update and future directions.

In hypertrophic cardiomyopathy (HCM) patients with symptoms caused by left ventricular outflow tract obstruction (LVOTO), treatment options include negative inotropic drugs, myectomy, septal alcohol ablation and AV sequential pacing with or without an implantable cardioverter defibrillator (ICD). Pacing is rarely used in spite of its relative simplicity and promising results. In this review the current evidence of AV sequential pacing from observational, randomised studies and long and very long-term follow-up studies is given and put in the context of present guidelines recommendations. These studies indicate that AV sequential pacing improves symptoms and quality of life through decreases in LVOTO, systolic anterior movement and mitral regurgitation. Effects on morbidity and mortality are lacking. We describe the mechanisms of action, the prerequisites for successful pacing and provide practical advice on how to optimise therapy. Moreover, the role of the ICD for primary and secondary prevention is discussed with reference to the ESC HCM guidelines. In summary, AV sequential pacing for HOCM is underused in clinical practise despite evidence from two randomised controlled studies. This concept is currently the focus of two randomised studies: a planned randomised controlled study that will compare AV sequential pacing to TASH and an ongoing study that compares CRT to AAI pacing in HOCM patients. In this review we highlight the current evidence and the new interest for this therapy.

The second generation cryoballoon has improved durable isolation of left but not right pulmonary veins: new insights from a multicentre study.

Aims: Pulmonary vein isolation (PVI) using second-generation cryoballoon (CB2) is associated with improved outcomes compared with first generation (CB1). We aimed at investigating the characteristics of left and right PV reconnections after CB1 and CB2 ablations in patients with clinical recurrences requiring redo ablation. Methods and results: From 2010 to 2016, 776 patients underwent 28-mm cryoballoon PVI for symptomatic paroxysmal atrial fibrillation (AF) in 3 centres, 279 with CB1 and 497 with CB2. Among them, 94 patients (12.1%) had symptomatic AF recurrences requiring a redo ablation [43 (15.4%) CB1 and 51 (10.3%) CB2]. The benefit of CB2 over CB1 was compared for each PV. Durable PVI was confirmed in 7 CB1 (16.3%) and 14 CB2 (27.4%) patients, and 2.7 ± 2.1 and 1.4 ± 1.4 gaps per patient were found, respectively (P = 0.002). Significantly more left superior and left inferior PVs were found to be isolated in CB2 compared with CB1 group (78.4% vs. 48.8%, P = 0.005 and 78.4% vs. 46.5%, P = 0.003, respectively) while the rate of durable right superior and right inferior PVs isolation were similar (68.6% vs. 60.5%, P = 0.542 and 66.7% vs. 55.8%, P = 0.387, respectively). Significantly fewer gaps were found in left PVs in CB2 patients, while there was no significant difference for right PVs. Gaps localization was similar in both groups. Conclusion: Fewer reconnection gaps are observed during redo ablations of paroxysmal AF in patients primarily ablated with CB2. This difference is driven by less reconnection gaps observed in both left PVs, while no difference was observed for right PVs.

Catheter ablation reduces ventricular tachycardia burden in patients with arrhythmogenic right ventricular cardiomyopathy: insights from a north-western French multicentre registry.

Aims: Studies assessing radiofrequency ablation (RFA) of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy (ARVC) report VT recurrences, but have not evaluated the impact of RFA on relevant clinical events during follow-up. We aimed to investigate relevant RFA outcomes in a multicentric registry. Methods and results: This study included 49 patients with ARVC (46 with definite diagnosis, 3 with borderline diagnosis according to revised Task Force Criteria) who underwent 92 RFA procedures (83 endocardial, 9 combined endo-epicardial) between 1999-2015. Ventricular tachycardia recurrences and VT burden were assessed after each procedure or after the last RFA. Over a mean follow-up of 64 ± 51 months, VT-free survival was 37% at 1 year, 19% at 5 years, and 14% at 10 years. Ventricular tachycardia burden was significantly reduced after one procedure (23 vs. 11 VT episodes/year, P < 0.01) and after the last RFA (14 vs. 2 VT episodes/year, P < 0.01). Over a mean follow-up of 49 ± 52 months, clinical response after the last RFA (freedom from sudden cardiac death, VT requiring hospitalization, or heart transplantation) was 86% at 1 year, 69% at 5 years, and 60% at 10 years. Clinical response was associated with right ventricular dysfunction (RVD) and low numbers of mappable VT before the first RFA. Conclusion: RFA was predominantly targeted at the endocardial surface. Ventricular tachycardia recurrences were common, but few ARVC patients experienced major clinical events during follow-up. Further studies should investigate the benefit of extensive substrate ablation combined with endo-epicardial strategies.

Sex Differences in Autonomic Response to Exercise Testing in Patients with Brugada Syndrome.

INTRODUCTION: Cardiac events in patients with Brugada syndrome (BS) typically occur at rest and mainly during sleep, suggesting that changes in autonomic modulation play an important role in the arrhythmogenesis of the disease. Moreover, sex differences in clinical manifestations of BS have been reported, identifying male patients with worse prognosis. The aim of our work was to assess and compare, according to sex, autonomic response to exercise in a clinical series including 105 BS patients. METHOD: Standard 12-lead electrocardiogram recordings were collected during a physical stress test divided into four phases: warm-up, incremental exercise, active recovery, and passive recovery. Spectral non-stationary heart rate variability indicators were extracted by means of a smoothed pseudo Wigner-Ville distribution approach that adapts frequency bands to respiratory information. These indicators were then averaged in non-overlapped windows of 1 min for each patient to compare groups at each minute of the physical stress test. RESULTS: From the last minute of warm-up and until the third minute of incremental exercise, asymptomatic male patients presented significantly greater low-frequency (LF) values ([Formula: see text]: p = 0.015;[Formula: see text]: p = 0.024; [Formula: see text]: p = 0.011; [Formula: see text]: p = 0.002) than asymptomatic females. Conversely, asymptomatic women showed increased vagal modulation during the first minutes of incremental exercise ([Formula: see text]: p = 0.031; [Formula: see text]: p = 0.001). However, no significant differences were observed between symptomatic male and female patients. CONCLUSION: As previously reported in healthy subjects, enhanced parasympathetic and decreased sympathetic tones appear to be not only greater in women but also defensive during cardiac stress. Based on the results, asymptomatic patients presented same-sex tendencies. However, we observed that symptomatic males developed a more female-like autonomic modulation, probably related to a more protective autonomic response to exercise. These results could be a step forward toward the understanding of the autonomic function in BS along with a potential impact on risk stratification.

Avoiding non-responders to cardiac resynchronization therapy: a practical guide.

Over two decades after the introduction of cardiac resynchronization therapy (CRT) into clinical practice, ∼30% of candidates continue to fail to respond to this highly effective treatment of drug-refractory heart failure (HF). Since the causes of this non-response (NR) are multifactorial, it will require multidisciplinary efforts to overcome. Progress has, thus far, been slowed by several factors, ranging from a lack of consensus regarding the definition of NR and technological limitations to the delivery of therapy. We critically review the various endpoints that have been used in landmark clinical trials of CRT, and the variability in response rates that has been observed as a result of these different investigational designs, different sample populations enrolled and different means of therapy delivered, including new means of multisite and left ventricular endocardial simulation. Precise recommendations are offered regarding the optimal device programming, use of telemonitoring and optimization of management of HF. Potentially reversible causes of NR to CRT are reviewed, with emphasis on loss of biventricular stimulation due to competing arrhythmias. The prevention of NR to CRT is essential to improve the overall performance of this treatment and lower its risk-benefit ratio. These objectives require collaborative efforts by the HF team, the electrophysiologists and the cardiac imaging experts.

Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome.

The Brugada syndrome (BrS) is a rare heritable cardiac arrhythmia disorder associated with ventricular fibrillation and sudden cardiac death. Mutations in the SCN5A gene have been causally related to BrS in 20-30% of cases. Twenty other genes have been described as involved in BrS, but their overall contribution to disease prevalence is still unclear. This study aims to estimate the burden of rare coding variation in arrhythmia-susceptibility genes among a large group of patients with BrS. We have developed a custom kit to capture and sequence the coding regions of 45 previously reported arrhythmia-susceptibility genes and applied this kit to 167 index cases presenting with a Brugada pattern on the electrocardiogram as well as 167 individuals aged over 65-year old and showing no history of cardiac arrhythmia. By applying burden tests, a significant enrichment in rare coding variation (with a minor allele frequency below 0.1%) was observed only for SCN5A, with rare coding variants carried by 20.4% of cases with BrS versus 2.4% of control individuals (P = 1.4 × 10(-7)). No significant enrichment was observed for any other arrhythmia-susceptibility gene, including SCN10A and CACNA1C. These results indicate that, except for SCN5A, rare coding variation in previously reported arrhythmia-susceptibility genes do not contribute significantly to the occurrence of BrS in a population with European ancestry. Extreme caution should thus be taken when interpreting genetic variation in molecular diagnostic setting, since rare coding variants were observed in a similar extent among cases versus controls, for most previously reported BrS-susceptibility genes.

Rationale and design of the Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA) trial.

BACKGROUND: Device-detected subclinical atrial fibrillation (AF) refers to infrequent, short-lasting, asymptomatic AF that is detected only with long-term continuous monitoring. Subclinical AF is common and associated with an increased risk of stroke; however, the risk of stroke with subclinical AF is lower than for clinical AF, and very few patients with subclinical AF alone have been included in large AF anticoagulation trials. The net benefit of anticoagulation in patients with subclinical AF is unknown. DESIGN: ARTESiA is a prospective, multicenter, double-blind, randomized controlled trial, recruiting patients with subclinical AF detected by an implanted pacemaker, defibrillator, or cardiac monitor, and who have additional risk factors for stroke. Patients with clinical AF documented by surface electrocardiogram will be excluded from the study. Participants will be randomized to receive either apixaban (according to standard AF dosing) or aspirin 81mg daily. The primary outcome is the composite of stroke, transient ischemic attack with diffusion-weighted magnetic resonance imaging evidence of cerebral infarction, and systemic embolism. Approximately 4,000 patients will be enrolled from around 230 clinical sites, with an anticipated mean follow-up of 36months until 248 adjudicated primary outcome events have occurred. SUMMARY: ARTESiA will determine whether oral anticoagulation therapy with apixaban compared with aspirin reduces the risk of stroke or systemic embolism in patients with subclinical AF and additional risk factors.