Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy.

AIMS: In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. METHODS AND RESULTS: Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients' clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P < 0.001). Mutations in PKP2 predominated in the LBBB-VT (65.2%) and the LBBB + RBBB-VT (41.7%) groups while DSP mutations predominated in the RBBB-VT group (45.5%). By multivariable analysis, female sex was associated with LBBB + RBBB-VT (P = 0.011) while DSP mutations were associated with RBBB-VT (P < 0.001). After a median follow-up of 103 (51-185) months, death occurred in 106 (11.1%) patients with no intergroup difference (P = 0.176). CONCLUSION: RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

Initial rhythm control with cryoballoon ablation vs drug therapy: Impact on quality of life and symptoms.

BACKGROUND: Cryoballoon ablation (CBA) as a first-line rhythm control strategy is superior to antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrence; the impact of first-line CBA on quality of life (QoL) and symptoms has not been well characterized. METHODS: Patients aged 18 to 75 with symptomatic paroxysmal AF naïve to rhythm control therapy were randomized (1:1) to CBA (Arctic Front Advance, Medtronic) or AAD (Class I or III). Symptoms and QoL were assessed at baseline, 1, 3, 6, 9, and 12 months using the EHRA classification and Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and SF-36v2 questionnaires. Symptomatic palpitations were evaluated via patient diary. RESULTS: Overall, 107 patients were randomized to CBA and 111 to AAD; crossovers occurred in 9%. Larger improvements in the AFEQT summary, subscale and treatment satisfaction scores were observed at 12 months with CBA vs AAD (all P <0.05). At 12 months, the mean adjusted difference in the AFEQT summary score was 9.9 points higher in the CBA group (95% CI: 5.5 -14.2, P <0.001). Clinically important improvements in the SF-36 physical and mental component scores were observed at 12 months in both groups, with no significant between group differences at this timepoint. In the CBA vs AAD group, larger improvements in EHRA class were observed at 6, 9 and 12 months (P <0.05) and the incidence rate of symptomatic palpitations was lower (4.6 vs 15.2 days/year post-blanking; IRR: 0.30, P <0.001). CONCLUSIONS: In patients with symptomatic AF, first-line CBA was superior to AAD for improving AF-specific QoL and symptoms. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01803438.

Left atrial appendage closure for stroke prevention in atrial fibrillation: Final report from the French left atrial appendage closure registry.

OBJECTIVES: The French left atrial appendage (LAA) closure registry (FLAAC) aimed to assess the safety and efficacy of LAA closure in daily practice. BACKGROUND: LAA closure has emerged as an alternative for preventing thromboembolic events (TE) in patients with non-valvular atrial fibrillation (NVAF). Clinical data in this field remains limited and few investigator-initiated, real-world registries have been reported. METHODS: This nationwide, prospective study was performed in 36 French centers. The primary endpoint was the TE rate after successful LAA closure. RESULTS: The FLAAC registry included 816 patients with a mean age of 75.5 ± 0.3 years, mean follow-up of 16.0 ± 0.3 months, high TE (CHA2 DS2 -VASc score: 4.6 ± 0.1) and bleeding risks (HAS-BLED score: 3.2 ± 0.05) and common contraindications to long-term anticoagulation (95.7%). Procedure or device-related serious adverse events occurred in 49 (6.0%) patients. The annual rate of ischemic stroke/systemic embolism was 3.3% (2.4-4.6). This suggests a relative 57% reduction compared to the risk of stroke in historical NVAF populations without antithrombotic therapy. By multivariate analysis, history of TE was the only factor associated with stroke/systemic embolism during follow-up (HR, 3.3 [1.58-6.89], p = 0.001). The annual mortality rate was 10.2% (8.4-12.3). Most of the deaths were due to comorbidities or underlying cardiovascular diseases and unrelated to the device or to TE. CONCLUSIONS: Our study suggests that LAA closure can be an option in patients with NVAF. Long-term follow-up mortality was high, mostly due to comorbidities and underlying cardiovascular diseases, highlighting the importance of multidisciplinary management after LAA closure. REGISTRATION: NCT02252861.

Cryoballoon ablation vs. antiarrhythmic drugs: first-line therapy for patients with paroxysmal atrial fibrillation.

AIMS: Treatment guidelines for patients with atrial fibrillation (AF) suggest that patients should be managed with an antiarrhythmic drug (AAD) before undergoing catheter ablation (CA). This study evaluated whether pulmonary vein isolation employing cryoballoon CA is superior to AAD therapy for the prevention of atrial arrhythmia (AA) recurrence in rhythm control naive patients with paroxysmal AF (PAF). METHODS AND RESULTS: A total of 218 treatment naive patients with symptomatic PAF were randomized (1 : 1) to cryoballoon CA (Arctic Front Advance, Medtronic) or AAD (Class I or III) and followed for 12 months. The primary endpoint was ≥1 episode of recurrent AA (AF, atrial flutter, or atrial tachycardia) >30 s after a prespecified 90-day blanking period. Secondary endpoints included the rate of serious adverse events (SAEs) and recurrence of symptomatic palpitations (evaluated via patient diaries). Freedom from AA was achieved in 82.2% of subjects in the cryoballoon arm and 67.6% of subjects in the AAD arm (HR = 0.48, P = 0.01). There were no group differences in the time-to-first (HR = 0.76, P = 0.28) or overall incidence [incidence rate ratio (IRR)=0.79, P = 0.28] of SAEs. The incidence rate of symptomatic palpitations was lower in the cryoballoon (7.61 days/year) compared with the AAD arm (18.96 days/year; IRR = 0.40, P < 0.001). CONCLUSIONS: Cryoballoon CA was superior to AAD therapy, significantly reducing AA recurrence in treatment naive patients with PAF. Additionally, cryoballoon CA was associated with lower symptom recurrence and a similar rate of SAEs compared with AAD therapy.

Wearable cardioverter-defibrillator in patients with a transient risk of sudden cardiac death: the WEARIT-France cohort study.

AIMS: We aimed to provide contemporary real-world data on wearable cardioverter-defibrillator (WCD) use, not only in terms of effectiveness and safety but also compliance and acceptability. METHODS AND RESULTS: Across 88 French centres, the WEARIT-France study enrolled retrospectively patients who used the WCD between May 2014 and December 2016, and prospectively all patients equipped for WCD therapy between January 2017 and March 2018. All patients received systematic education session through a standardized programme across France at the time of initiation of WCD therapy and were systematically enrolled in the LifeVest Network remote services. Overall, 1157 patients were included (mean age 60 ± 12 years, 16% women; 46% prospectively): 82.1% with ischaemic cardiomyopathy, 10.3% after implantable cardioverter-defibrillator explant, and 7.6% before heart transplantation. Median WCD usage period was 62 (37-97) days. Median daily wear time of WCD was 23.4 (22.2-23.8) h. In multivariate analysis, younger age was associated with lower compliance [adjusted odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95-0.99, P < 0.01]. A total of 18 participants (1.6%) received at least one appropriate shock, giving an incidence of appropriate therapy of 7.2 per 100 patient-years. Patient-response button allowed the shock to be aborted in 35.7% of well-tolerated sustained ventricular arrhythmias and in 95.4% of inappropriate ventricular arrhythmia detection, finally resulting in an inappropriate therapy in eight patients (0.7%). CONCLUSION: Our real-life findings reinforce previous studies on the efficacy and safety of the WCD in the setting of transient high-risk group in selected patients. Moreover, they emphasize the fact that when prescribed appropriately, in concert with adequate patient education and dedicated follow-up using specific remote monitoring system, compliance with WCD is high and the device well-tolerated by the patient.

Atrial fibrillation evolution and rhythm control strategy following left appendage closure: new insights from the prospective FLAAC registry.

BACKGROUND: Percutaneous left atrial appendage (LAA) closure is an alternative to oral anticoagulation (OAC) for atrial fibrillation (AF) patients with high thromboembolism risk, particularly with contraindications to OAC. The LAA itself could possess proarrhythmogenic properties. As patients undergoing LAA closure could be candidates for cardioversion or ablation, we aimed to evaluate AF disease progression following LAA closure and the outcome of patients undergoing a rhythm control strategy after the procedure. METHODS: The prospective multicenter French Nationwide Observational LAA Closure Registry (FLAAC) comprises 33 French interventional cardiology departments. Patients were included if they fulfilled the following criteria: history of non-valvular AF, successful LAA closure and long-term ECG follow-up. RESULTS: A total of 331 patients with successful LAA closure were enrolled in the study. Patients mean age was 75.4 ± 0.5 years. The study population was characterized by a high thromboembolic risk (CHA2DS2-VASc score: 4.5 ± 0.1) and frequent comorbidities. The median follow-up was 11.9 months. One hundred and nineteen (36.0%) patients were in sinus rhythm (SR) at baseline. Among SR patients, documented AF was observed in 16 (13.4%) patients whereas 15 (7.1%) patients in AF at baseline restored SR, at the end of follow up. Finally, only 13 patients (4%) underwent procedures to restore SR without complications during the follow-up. CONCLUSIONS: The vast majority of patients undergoing LAA closure have the same AF status at baseline and one year after the index procedure. During the follow-up, a very small proportion (4%) of our population underwent procedures to restore SR without complications whatever the post-procedural antithrombotic strategy was.

Cryoballoon catheter ablation versus antiarrhythmic drugs as a first-line therapy for patients with paroxysmal atrial fibrillation: Rationale and design of the international Cryo-FIRST study.

BACKGROUND: Radiofrequency current (RFC) catheter ablation for patients with paroxysmal atrial fibrillation (AF) has been shown to be safe and effective in first-line therapy. Recent data demonstrates that RFC ablation provides better clinical outcomes compared to antiarrhythmic drug (AAD) in the treatment of early AF disease. Furthermore, studies comparing RFC and cryoballoon have established comparable efficacy and safety of pulmonary vein isolation (PVI) for patients with symptomatic paroxysmal AF. OBJECTIVES: The Cryo-FIRST trial was designed to compare AAD treatment against cryoballoon PVI as a first-line therapy in treatment naïve patients with AF. Efficacy and safety will be compared between the two cohorts and amongst subgroups. METHODS: The primary hypothesis is that cryoablation is superior to AAD therapy. To test this hypothesis, patients will be randomized in a 1:1 design. Using a 90-day blanking period, primary efficacy endpoint failure is defined as (at least) one episode of atrial arrhythmia with a duration >30 sec (documented by 7-day Holter or 12-lead ECG). Secondary endpoints (Quality-of-Life, rehospitalization, arrhythmia recurrence rate, healthcare utilization, and left atrial function) and adverse events will also be evaluated. Study enrollment will include 218 patients in up to 16 centers. CONCLUSIONS: This study will be a multi-national randomized controlled trial comparing cryoablation against AAD as a first-line treatment in patients with paroxysmal AF. The results may help guide the selection of patients for early AF disease therapy via cryoballoon ablation.

Management of acute cardiac tamponade by direct autologous blood transfusion in interventional electrophysiology.

AIMS: Acute cardiac tamponade (ACT) is the most common life-threatening complication of interventional electrophysiology. Urgent drainage by percutaneous pericardiocentesis and anticoagulation reversal are required. Immediate direct transfusion of the blood volume aspirated from the pericardial space to the patient has been rarely described. This study was designed to assess the efficacy and safety of immediate direct autologous blood transfusion (AutoBT). METHODS: A retrospective case series of direct AutoBT performed for ACT was collected. Urgent drainage by percutaneous pericardiocentesis and immediate direct AutoBT were performed to achieve hemodynamic stabilization without a cell-saver system. RESULTS: Twenty-two electrophysiology centers were contacted to participate in the case series. Fourteen centers reported not to use direct AutoBT. Three centers reported using direct AutoBT with the cell-saver system. Fourteen cases of immediate direct AutoBT without cell-saver system were included from the five remaining centers. Electrophysiological procedures were performed for ventricular tachycardia (n = 5), atrial fibrillation (n = 5), atrial tachycardia (n = 2), left accessory pathway (n = 1), and premature ventricular contraction (n = 1) with transseptal (n = 9), retroaortic (n = 4), and/or epicardial access (n = 4). Pericardial drainage was performed by percutaneous pericardiocentesis for 13 patients and via the transseptal sheath for one patient. Surgical hemostasis was required for seven patients. The mean volume of autologous blood directly transfused was 1207 ± 963 mL. Direct AutoBT permitted to resume the procedure in four patients. No major complication related to the use of AutoBT occurred. CONCLUSION: Direct AutoBT without a cell-saver system is a feasible, safe, and useful technique for salvage therapy in ACT in interventional electrophysiology.

Effect of lead design and pacing vector on electrical parameters of quadripolar coronary sinus leads: The RALLY-X4 study.

BACKGROUND: Various lead designs have been developed to accommodate different coronary sinus anatomies. Our objectives were to compare electrical parameters of straight and spiral left ventricular leads, to evaluate capture thresholds and impedances using different pacing vectors, and to study evolution of thresholds over time. METHODS: The RALLY-X4 study enrolled patients implanted with a lead from the Acuity X4 family (straight, spiral short, or spiral long). Electrical parameters (including capture thresholds from all 17 vectors) were measured at baseline and follow-up. RESULTS: Data from 795 patients who were successfully implanted were analyzed. Straight and spiral leads had similar proportions of patients with thresholds <2.5 V/0.4 ms using the distal electrode (61-65% of patients) or from at least one of the proximal (E2-E4) electrodes (81-83% of patients). Unipolar vectors had significantly lower thresholds and impedances than bipolar vectors, with similar measurements compared to extended bipolar configurations. Capture thresholds increased with more proximal electrodes for all leads. Over a mean follow-up of 1 year, a slight decrease in capture thresholds was observed. CONCLUSION: Straight and spiral quadripolar leads allow to obtain clinically acceptable capture thresholds from at least one of the proximal electrodes in >80% of patients. Pacing vectors significantly affect electrical parameters, with higher thresholds in more proximal electrodes and lower thresholds with unipolar and extended bipolar configurations. Capture thresholds slightly decreased over a mean follow-up of 1 year.

Prevalence and predictive factors of left atrial tachycardia occurring after second-generation cryoballoon ablation of atrial fibrillation.

INTRODUCTION: Assess the prevalence and predictors of left atrial tachycardia (LAT) after cryoballoon ablation of pulmonary veins. METHODS AND RESULTS: Patients who underwent catheter ablation of pulmonary veins with a second-generation cryoballoon for symptomatic paroxysmal (151 of 270, 56%) or persistent (119 of 270, 44%) atrial fibrillation were entered in a single-center prospective registry. Patients who experienced postcryoballoon LAT (pcryo-LAT) were selected on the basis of 12-lead ECG characteristics. Left atrial origin was confirmed during conventional EP study and electroanatomical activation mapping, and patients were treated by RF catheter ablation. Pcryo-LAT was observed in 15 (5.6%) of 270 patients and was attributed to a reentrant mechanism in 11 patients (73%). The other four cases of pcryo-LAT were due to focal atrial tachycardia associated with reconnection of one pulmonary vein. In comparison with patients who remained in sinus rhythm, LA area (HR = 1.09; CI 1.01, 1.2; P = 0.02), LVEF (HR = 0.94; CI 0.90, 0.97; P < 0.001), and LVEF <50% (HR = 8.5; CI 3.1, 23.6; P < 0.001) were predictors of pcryo-LAT. After multivariate Cox analysis, only left ventricular ejection fraction < 50% remained predictive of pcryo-LAT, (HR = 7.8, CI 2.3 26.7, P = 0.002). With a mean survival of 23 months, 73% of patients who experienced pcryo-LAT were in sinus rhythm versus 78% of patients without pcryo-LAT (log rank P = 0.85). CONCLUSION: The prevalence of pcryo-LAT in patients with atrial fibrillation is low. Left ventricular ejection fraction < 50% is associated with an increased risk of pcryo-LAT. When treated by RF catheter ablation, the presence of pcryo-LAT is not a predictive factor of subsequent recurrence of atrial fibrillation during follow-up.

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.

Feasibility and safety of temporary subcutaneous venous figure-of-eight suture to achieve haemostasis after ablation of atrial fibrillation.

AIMS: This prospective study was carried out to assess the feasibility and safety of venous figure-of-eight suture to achieve haemostasis after atrial fibrillation (AF) ablation. METHODS AND RESULTS: Consecutive patients who underwent catheter ablation of AF were prospectively enrolled from February 2012 to September 2013. At the end of the procedure, a temporary subcutaneous 'Figure-of-eight' suture technique was used to achieve haemostasis. Anticoagulation strategy evolved during the study. Initially, vitamin K antagonists (VKAs) were stopped and replaced by administration of low-molecular-weight heparin. It was subsequently decided to perform these procedures without stopping VKA. With the arrival of direct oral anticoagulants (DOACs), it was decided to miss the evening dose before the procedure. One hundred and twenty-four patients were included. Seventy-three per cent of patients were male, and the mean age was 58 ± 10 years old. One hundred and twelve patients (90%) experienced paroxysmal AF and were treated by cryotherapy with the use of a 15 Fr outer diameter Flexcath Advance sheath. The 'Figure-of-eight' suture technique was able to be performed in all patients and was sufficient in 114 patients. Mechanical external compression was required for 10 patients. Three patients developed a haematoma. The overall incidence of haematoma was therefore 2.4%. CONCLUSION: Figure-of-eight suture is a fast closure technique that can be used as an efficient alternative to usual compression methods to prevent bleeding during high-intensity anticoagulation and the use of large-diameter venous sheaths and multiple femoral venous accesses.

Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study.

AIMS: The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice. METHODS AND RESULTS: A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P < 0.0001), less often male (P < 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P < 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41-94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56-2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07-2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death. CONCLUSION: When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator.

Long-term follow-up of asymptomatic Brugada patients with inducible ventricular fibrillation under hydroquinidine.

AIMS: To evaluate the long-term efficacy and safety of an electrophysiologically guided therapy, based on a strategy of treatment using hydroquinidine (HQ) among asymptomatic Brugada patients with inducible ventricular fibrillation (VF). METHODS AND RESULTS: In two French reference centres, consecutive asymptomatic type 1 Brugada patients with inducible VF were treated with HQ (600 mg/day, targeting a therapeutic range between 3 and 6 µmol/L) and enroled in a specific follow-up (mean 6.6 ± 3 years), including a second programmed ventricular stimulation (PVS) under HQ. An implantable cardioverter defibrillator (ICD) was eventually implanted in patients inducible under HQ, or during follow-up in case of HQ intolerance, as well as occurrence of arrhythmic events. From a total of 397 Brugada patients, 44 were enroled (47 ± 10 years, 95% male). Of these, 34 (77%) were no more inducible (Group PVS-), and were maintained under HQ alone during a mean follow-up of 6.2 ± 3 years. In this group, an ICD was eventually implanted in four patients (12%), with occurrence of appropriate ICD therapies in one. Among the 10 other patients (22%), who remained inducible and received ICD (Group PVS+), none of them received appropriate therapy during a mean follow-up of 7.7 ± 2 years. The overall annual rate of arrhythmic events was 1.04% (95% confidence interval 0.00-2.21), without any significant difference according to the result of PVS under HQ. One-third of patients experienced device-related complications. CONCLUSION: Our long-term follow-up results emphasize that the rate of arrhythmic events among asymptomatic Brugada patients with inducible VF remains low over time. Our results also suggest that residual inducibility under HQ is of limited value to predict events during follow-up.

Costs of remote monitoring vs. ambulatory follow-ups of implanted cardioverter defibrillators in the randomized ECOST study.

AIMS: The Effectiveness and Cost of ICD follow-up Schedule with Telecardiology (ECOST) trial evaluated prospectively the economic impact of long-term remote monitoring (RM) of implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: The analysis included 310 patients randomly assigned to RM (active group) vs. ambulatory follow-ups (control group). Patients in the active group were seen once a year unless the system reported an event mandating an ambulatory visit, while patients in the control group were seen in the ambulatory department every 6 months. The costs of each follow-up strategy were compared, using the actual billing documents issued by the French health insurance system, including costs of (i) (a) ICD-related ambulatory visits and transportation, (b) other ambulatory visits, (c) cardiovascular treatments and procedures, and (ii) hospitalizations for the management of cardiovascular events. The ICD and RM system costs were calculated on the basis of the device remaining longevity at the end of the study. The characteristics of the study groups were similar. Over a follow-up of 27 months, the mean non-hospital costs per patient-year were €1695 ± 1131 in the active, vs. €1952 ± 1023 in the control group (P = 0.04), a €257 difference mainly due to device management. The hospitalization costs per patient-year were €2829 ± 6382 and €3549 ± 9714 in the active and control groups, respectively (P = 0.46). Adding the ICD to the non-hospital costs, the savings were €494 (P = 0.005) or, when the monitoring system was included, €315 (P = 0.05) per patient-year. CONCLUSION: From the French health insurance perspective, the remote management of ICD patients is cost saving. CLINICAL TRIALS REGISTRATION: NCT00989417, www.clinicaltrials.gov.

A randomized study of remote follow-up of implantable cardioverter defibrillators: safety and efficacy report of the ECOST trial.

AIMS: The ECOST trial examined prospectively the long-term safety and effectiveness of home monitoring (HM) of implantable cardioverter defibrillators (ICD). METHODS AND RESULTS: The trial's primary objective was to randomly compare the proportions of patients experiencing ≥ 1 major adverse event (MAE), including deaths from all causes, and cardiovascular, procedure-related, and device-related MAE associated with HM (active group) vs. ambulatory follow-ups (control group) in a sample of 433 patients. The 221 patients assigned to the active group were seen once a year, unless HM reported an ICD dysfunction or a clinical event requiring an ambulatory visit, while the 212 patients in the control group underwent ambulatory visits every 6 months. The characteristics of the study groups were similar. Over a follow-up of 24.2 months, 38.5% of patients in the active and 41.5% in the control group experienced ≥ 1 MAE (P < 0.05 for non-inferiority). The overall number of shocks delivered was significantly lower in the active (n = 193) than in the control (n = 657) group (P < 0.05) and the proportion of patients who received inappropriate shocks was 52% lower in the active (n = 11) than in the control (n = 22) group (P < 0.05). At the end of the follow-up, the battery longevity was longer in the active group because of a lower number of capacitor charges (499 vs. 2081). CONCLUSION: Our observations indicate that long-term HM of ICD is at least as safe as standard ambulatory follow-ups with respect to a broad spectrum of MAE. It also lowered significantly the number of appropriate and inappropriate shocks delivered, and spared the device battery. Clinical trials registration NCT00989417.

Systematic analysis of SCN5A variants associated with inherited cardiac diseases.

BACKGROUND: SCN5A variants are associated with a spectrum of cardiac electrical disorders with clear phenotypes. However, they may also be associated with complex phenotypic traits like overlap syndromes, or pleiotropy, which have not been systematically described. Additionally, the involvement of SCN5A in dilated cardiomyopathies (DCM) remains controversial. OBJECTIVE: We aimed to (1) evaluate the different phenotypes associated with pathogenic (P)/likely pathogenic (LP) SCN5A variants and (2) determine the prevalence of pleiotropy in a large multicentric cohort of P/LP SCN5A variant carriers. METHODS: The DNA of 13,510 consecutive probands (9960 with cardiomyopathies) was sequenced using a custom panel of genes. Individuals carrying a heterozygous single P/LP SCN5A variant were selected and phenotyped. RESULTS: The study included 170 P/LP variants found in 495 patients. Among them, 119 (70%) were exclusively associated with a single well-established phenotype: 91 with Brugada syndrome, 15 with type 3 long QT syndrome, six with progressive cardiac conduction disease, four with multifocal ectopic Purkinje-related premature contraction, and three with sick sinus syndrome. Thirty-two variants (19%) were associated with overlap syndromes and/or pleiotropy. The 19 remaining variants (11%) were associated with atypical or unclear phenotypes. Among those, eight were carried by eight patients presenting with DCM with a debatable causative genotype/phenotype link. CONCLUSION: Most P/LP SCN5A variants were found in patients with primary electrical disorders, mainly Brugada syndrome. Nearly 20% were associated with overlap syndromes or pleiotropy, underscoring the need for comprehensive phenotypic evaluation. The concept of SCN5A variants causing DCM is extremely rare (8/9960), if not questionable.

Progressive decrease in amplitude of intracardiac ventricular electrogram and higher left ventricular ejection fraction are associated with conductors' externalization in Riata leads.

AIMS: Increased rates of structural abnormalities including externalized conductors have been reported in the Riata family of implantable cardioverter-defibrillator leads (St Jude Medical). Little is known about their reliability and the time lag for emergence of functional or structural abnormalities. METHODS AND RESULTS: Thirty-six patients who received small-caliber leads of the Riata family and who completed face-profile flouroscopies, repeated at every 6 months were included. We assessed the prevalence of conductors' externalization and its relation to abnormal electrical parameters or adverse events. Thirty-six patients, mean age = 64 ± 10 years, with at least 7-month completed fluoroscopy follow-up were included in the analysis. Externalized conductors were identified in 12 (33%) patients after a 53-month (13-114) mean delay. A higher left ventricular ejection fraction (LVEF): 47 ± 13 vs. 33 ± 12%, P = 0.04, and a progressive decrease (≥30% of the initial value) in amplitude of ventricular electrogram 9/12 (75%) vs. 4/24 (17%), P = 0.03 were independently associated with the fluoroscopic failures. Detection of the conductors' externalization was preceded by an electrical lead abnormality in 10 (83%) patients. CONCLUSION: Repeated face-profile fluoroscopies allowed detection of conductors' externalization in 33% of patients implanted with Riata leads. Better LVEF and a progressive decrease in amplitude of intracardiac ventricular electrogram were independently associated with externalized conductors. The structural abnormality was preceded by an electrical lead dysfunction 83% of patients.

Use of implantable loop recorders in patients with Brugada syndrome and suspected risk of ventricular arrhythmia.

AIMS: Implantable cardioverter defibrillator (ICD) therapy is recommended in patients with Brugada syndrome (BS) who experienced aborted sudden cardiac death (SCD) or syncope while the risk stratification of ventricular arrhythmias is a difficult step in patients with atypical symptoms. Implantable loop recorder (ILR) use has been proposed to study patients with unexplained recurrent syncopal events, but its usefulness remains to be defined in patients with BS. In this retrospective study we aimed to investigate the effectiveness of ILR as a diagnostic tool in BS patients suspected of low or moderate risk of SCD. METHODS AND RESULTS: We gathered data from 11 ILR recipients with supposed risk of ventricular arrhythmia, issue of Amiens registry of 204 patients with BS. We reported clinical events before and after implant, electrocardiogram (ECG) characteristics, ILR findings, and its limitations as well as tried to specify ILR utility in diagnosis approach and its consequent contribution to guide the optimal therapy. Within the 11 patients (8 men, 3 women), 9 were symptomatic, and 5 had a spontaneous Type 1 ECG pattern. During mean follow-up period of 33 months, 8 patients had a recurrence of symptoms with a mean delay of 9 months after implant. Bradycardia (two atrioventricular blocks and two sinus bradycardia) was detected in four out of eight patients (50%), and there was no ventricular arrhythmia in any patient during symptomatic events which included six vasovagal syncopes and two epileptic seizures. Two initially asymptomatic patients did not experience any symptoms after ILR implant and their ILR recordings did not reveal any arrhythmias. CONCLUSION: The ILR contributed to the exclusion of a ventricular arrhythmia as a mechanism of an atypical syncope in patients with electrocardiographic BS and the suspension of the ICD implant. Episodes of transient symptomatic bradycardia were the most common findings suggesting the vagal mechanism of symptoms. The use of ILR should be considered in selected patients with atypical syncope and spontaneous or transient Type 1 ECG pattern.