Distinct Substrates of Idiopathic Ventricular Fibrillation Revealed by Arrhythmia Characteristics on Implantable Cardioverter-Defibrillator.

BACKGROUND: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts. OBJECTIVE: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates. METHODS: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates. RESULTS: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF. CONCLUSIONS: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications.

Type 3 long QT syndrome: Is the effectiveness of treatment with beta-blockers population-specific?

BACKGROUND: The efficacy of beta-blocker treatment in type 3 long QT syndrome (LQT3) remains debated. OBJECTIVES: The purpose of this study was to test the hypothesis that beta-blocker use is associated with cardiac events (CEs) in a French cohort of LQT3 patients. METHODS: All patients with a likely pathogenic/pathogenic variant in the SCN5A gene (linked to LQT3) were included and followed-up. Documented ventricular tachycardia/ventricular fibrillation, torsades de pointes, aborted cardiac arrest, sudden death, and appropriate shocks were considered as severe cardiac events (SCEs). CEs also included syncope. RESULTS: We included 147 patients from 54 families carrying 23 variants. Six of the patients developed symptoms before the age of 1 year and were analyzed separately. The 141 remaining patients (52.5% male; median age at diagnosis 24.0 years) were followed-up for a median of 11 years. The probabilities of a CE and an SCE from birth to the age of 40 were 20.5% and 9.9%, respectively. QTc prolongation (hazard ratio [HR] 1.12 [1.0-1.2]; P = .005]) and proband status (HR 4.07 [1.9-8.9]; P <.001) were independently associated with the occurrence of CEs. Proband status (HR 8.13 [1.7-38.8]; P = .009) was found to be independently associated with SCEs, whereas QTc prolongation (HR 1.11 [1.0-1.3]; P = .108) did not reach statistical significance. The cumulative probability of the age at first CE/SCE was not lower in patients treated with a beta-blocker. CONCLUSION: In agreement with the literature, proband status and lengthened QTc were associated with a higher risk of CEs. Our data do not show a protective effect of beta-blocker treatment.

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.).

Economic evaluation of remote monitoring of patients with an implantable cardiac defibrillator (REMOTE-CIED study).

INTRODUCTION: Remote patient monitoring (RPM) of heart failure patients has the potential to reduce healthcare resource use and costs, but current evidence has been inconclusive. This study aims assess the impact of RPM of heart failure patients with an implantable cardioverter defibrillator on medical resource use, direct medical costs, quality-adjusted life years (QALYs), and travel time of patients, and to estimate its commercial headroom in the Netherlands and Germany. METHODS: Data from the REMOTE-CIED randomized controlled trial were used to calculate differences in length of hospital stay, outpatient clinic visits, telephone consults, emergency room visits, and travel time between patients on in-clinic follow-up and RPM in the Netherlands, Germany, and France. Incremental cardiac-related healthcare costs and QALYs were calculated and used to calculate the commercial headroom of RPM in the Netherlands and Germany. The impact of imputation, parameter, and case-mix uncertainty on these outcomes was explored using probabilistic analysis. RESULTS: Length of hospitalization, number of unscheduled admissions, and number of outpatient visits were lower in the remote monitoring group in all three countries. Number of hospital admissions was higher, and number of calls was lower in the Netherlands and Germany but not in France. Costs were lower in both the Netherlands (-€1041, 95% confidence interval (CI): -€3308, €1005) and Germany (-€2865, 95% CI: -€7619, €1105), while incremental effectiveness differed: -0.003 (95% CI: -0.114, 0.107) QALY in the Netherlands and +0.086 (95% CI: -0.083, 0.256) in Germany. Commercial headroom was estimated at €881 (95% CI: -€5430, €7208) in the Netherlands and €5005 (95% CI: -€1339, €11,960) in Germany. DISCUSSION: RPM was found to result in reduced medical resource use and travel time. Whether it is cost saving or cost effective strongly depends on the costs of remote monitoring. TRIAL REGISTRATION NUMBER AND TRIAL REGISTER: ClinicalTrials.gov: NCT01691586.

Ablation of multifocal premature ventricular contractions using automated pace-mapping software.

INTRODUCTION AND OBJECTIVES: Ablation of multifocal premature ventricular complexes (PVCs) is challenging. Activation mapping can be performed for the predominant morphology, but may be useless for other less prevalent ones. We aimed to describe the efficacy of an automated pace-mapping software-based ablation strategy for ablating the site of origin of multiple PVC locations. METHODS: Consecutive patients referred for ablation of multifocal PVCs were prospectively enrolled. Spontaneous PVC templates were recorded and a detailed pace-mapping map was generated to spot the site of origin of PVCs. RESULTS: A total of 47 PVCs were targeted in 21 patients (five and 16 patients with three or two PVCs morphologies each, respectively). Detailed pace-mapping comprising 73.5±41.6 different pacing locations was performed (best matching 97.2% [IQR 95.9-98.3%] similar to the clinical PVC). Activation points were acquired if possible, although ablation was only based on pace-mapping in 13 (27.6%) foci. Complete acute procedural success was obtained in 14 (66.7%) patients, while one PVC morphology was deliberately not ablated in five patients (23.8%). After 12.3±9.4 months of follow-up, PVC burden decreased from 24.4±10.4% to 5.6±5.0% (p<0.001). Interestingly, patients with acute procedural failures or with some PVCs deliberately not targeted during the procedure also experienced a significant decrease in PVC burden (30.0±8.9% to 11.9±3.5%, p=0.002). CONCLUSION: Quantitative morphology-matching software can be used to obtain a detailed map identifying the site of origin of each single PVC, and successful ablation can be performed at these sites, even if activation points cannot be obtained due to the paucity of ectopic beats.

Outcome of patients with early repolarization pattern and syncope.

BACKGROUND: Syncope in patients with an early repolarization (ER) pattern presents a challenge for clinicians as it has been identified as an indicator of a higher risk of life-threatening ventricular arrhythmias (VAs). OBJECTIVES: This study aimed to analyze the outcome of patients with an ER pattern and syncope and to evaluate the factors predictive of VAs. METHODS: Over a period of 5 years, we enrolled 143 patients with an ER pattern and syncope in a multicenter prospective registry. RESULTS: After the initial examinations, 97 patients (67.8%) were implanted with a device allowing electrocardiogram monitoring, including 84 (58.7%) with an implantable loop recorder. During a mean follow-up period of 68 ± 34 months, we documented 16 arrhythmias presumably responsible for syncope (5 VAs, 10 bradycardias, and 1 supraventricular tachycardia). Additionally, recurrent syncope not associated with electrocardiogram documentation occurred in 16 patients (11.2%). The cause of syncope was identified in 23 of 97 patients with a monitoring device (23.8%). The 5-year incidence of VAs and arrhythmic events presumably responsible for syncope was 4.9% and 11.0%, respectively. Patients who developed VAs showed no prodromes or specific triggers at the time of syncope. Neither the presence of a family history of sudden cardiac death nor the previously reported high-risk electrocardiographic parameters differed between patients with and without VAs. CONCLUSION: VAs occurred in 4.9% of patients with an ER pattern and syncope. Device implantation based on detailed history taking seems to be a reasonable strategy. Previously reported high-risk electrocardiographic patterns did not identify patients with VAs.

Prognostic impact of permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Conduction disturbances requiring permanent pacemaker implantation (PPI) remain a common complication of transcatheter aortic valve replacement (TAVR). OBJECTIVE: The purpose of this study was to determine the prognostic impact of PPI after TAVR according to the timing of implantation relative to TAVR. METHODS: A total of 1199 patients (median age 83 years; interquartile range 78-86 years; 549 [45.8%] female) were included in the analysis, of whom 894 (70.8%) had not undergone PPI, 130 (10.8%) had undergone previous PPI, 116 (9.7%) had undergone in-hospital PPI, and 59 (4.9%) had undergone PPI during follow-up. Median follow-up was 2.94 years (1.42-4.32 years). The primary outcome was the composite of all-cause mortality and hospitalization for heart failure. RESULTS: PPI during follow-up was associated with a higher occurrence of the primary outcome (hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.39-3.20) whereas previous PPI and in-hospital PPI were not (HR 0.96; 95% CI 0.71-1.29 and HR 1.26; 95% CI 0.88-1.81, respectively). PPI during follow-up was associated with a higher risk of hospitalization for heart failure (sub-HR 3.21; 95% CI 2.02-5.11), while this relationship was only borderline significant for previous PPI (sub-HR 1.51; 95% CI 0.99-2.29). In contrast, there was no relationship between in-hospital PPI and the subsequent risk of hospitalization for heart failure. CONCLUSION: Previous PPI and in-hospital PPI had no long-term prognostic impact on the risk of all-cause mortality and hospitalization for heart failure, whereas PPI during follow-up was associated with a higher risk of hospitalization for heart failure. The present study questions the deleterious influence of periprocedural post-TAVR PPI, which has previously been suggested by certain studies.

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.

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.

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.

Cryoballoon ablation of atrial fibrillation in patients with atypical right pulmonary vein anatomy.

BACKGROUND: Cryoballoon ablation is widely used for pulmonary vein isolation in patients with atrial fibrillation. There are no data regarding the clinical efficacy of cryoballoon ablation in patients with atypical right pulmonary vein anatomy. AIM: We aimed to evaluate the impact of right pulmonary vein anatomy on the safety and efficacy of cryoballoon ablation. METHODS: Patients referred for cryoballoon ablation of paroxysmal atrial fibrillation were enrolled prospectively. Left atrial computed tomography was performed before cryoballoon ablation to determine whether the right pulmonary vein anatomy was "normal" or "atypical". For patients with atypical anatomy, cryoballoon ablation was only performed for right superior and right inferior pulmonary veins, neglecting accessory pulmonary veins. RESULTS: Overall, 303 patients were included: 254 (83.8%) with normal and 49 (16.2%) with atypical right pulmonary vein anatomy. First-freeze isolation for right superior and right inferior pulmonary veins occurred in 44 (89.8%) and 37 (75.5%) patients with atypical pulmonary vein anatomy, and in 218 (85.8%) and 217 (85.4%) patients with typical pulmonary vein anatomy, respectively (P not significant). Phrenic nerve palsies were only observed in patients with normal anatomy (0 vs. 26 [8.6%]; P=0.039). Mid-term survival free from atrial arrhythmia was similar, regardless of right pulmonary vein anatomy. CONCLUSIONS: A significant proportion of patients have atypical right pulmonary vein anatomy. Procedural characteristics, acute pulmonary vein isolation success and mid-term procedural efficacy were similar, regardless of right pulmonary vein anatomy. In addition to left-side pulmonary vein isolation, cryoballoon ablation of right superior and right inferior pulmonary veins only, neglecting accessory pulmonary veins, is sufficient to obtain acute right-side pulmonary vein isolation and mid-term sinus rhythm maintenance in patients with atypical anatomy.

Rate, Time Course, and Predictors of Implantable Cardioverter Defibrillator Infections: An Analysis From the SIMPLE Trial.

BACKGROUND: The number of implantable cardioverter defibrillator (ICD) infections is increasing due to an increased number of ICD implants, higher-risk patients, and more frequent replacement procedures, which carry a higher risk of infection. Reducing the morbidity, mortality, and cost of ICD-related infections requires an understanding of the current rate of this complication and its predictors. METHODS: The Shock Implant Evaluation Trial (SIMPLE) trial randomized 2500 ICD recipients to defibrillation testing or not. Over an average of 3.1 years, patients were seen every 6 months and examined for evidence of ICD infection, which was defined as requiring device removal and/or intravenous antibiotics. RESULTS: Within 24 months, 21 patients (0.8%) developed infection. Fourteen patients (67%) with infection presented within 30 days, 20 patients by 12 months, and only 1 patient beyond 12 months. Univariate analysis demonstrated that patients with primary electrical disorders (3 patients, P = 0.009) and those with a secondary prevention indication (13 patients, P = 0.0009) were more likely to develop infection. Among the 2.2% of patients who developed an ICD wound hematoma, 10.4% developed an infection. Among the 8.3% of patients requiring an ICD reintervention, 1.9% developed an infection. CONCLUSIONS: This cohort of ICD recipients at high-volume centres have a low risk of device-related infection. However; strategies to reduce wound hematoma and the need for ICD reintervention could further reduce the rate of infection.

CONTEXTE: L'incidence des cas d'infection du défibrillateur cardioverteur implantable (DCI) augmente en raison du nombre accru d'implantations, de l'emploi de ces dispositifs chez des patients exposés à un risque très élevé et de l'augmentation de la fréquence des interventions de remplacement, qui sont associées à un plus grand risque d'infections. Pour parvenir à réduire la morbidité, la mortalité et les coûts associés aux infections liées à un DCI, il faut connaître la fréquence de cette complication et les facteurs qui permettent de la prédire. MÉTHODOLOGIE: Lors de l'essai S hock Impl ant E valuation Trial (SIMPLE), 2 500 patients ayant reçu un DCI ont été répartis aléatoirement en deux groupes, l'un subissant des tests de défibrillation et l'autre, non. Sur une période de 3,1 ans en moyenne, les patients ont été vus en consultation tous les 6 mois et examinés à la recherche de signes d'infection du DCI, définie comme étant une infection exigeant le retrait du dispositif et/ou l'administration d'antibiotiques par voie intraveineuse. RÉSULTATS: Au total, 21 patients (0,8 %) ont présenté une infection dans les 24 mois suivant l'implantation. Quatorze patients (67 %) ont présenté une infection dans les 30 jours suivant l'intervention; à 12 mois, 20 patients avaient présenté une infection. Un seul patient a présenté une infection plus de 12 mois après l'intervention. Les résultats d'une analyse univariée ont démontré qu'une infection était plus probable chez les patients qui présentaient un trouble électrique primaire (3 patients, p = 0,009) et chez ceux qui avaient reçu un dispositif en prévention secondaire (13 patients, p = 0,0009). Parmi les patients qui présentaient un hématome après l'implantation du DCI (2,2 %), 10,4 % ont présenté une infection. Parmi les patients qui ont eu besoin d'une nouvelle intervention relative au DCI (8,3 %), 1,9 % ont présenté une infection. CONCLUSIONS: Les patients de cette cohorte ayant reçu un DCI dans des établissements à haut volume étaient exposés à un faible risque d'infection du défibrillateur. Des stratégies visant à réduire les hématomes et la nécessité d'une nouvelle intervention sur les DCI pourraient toutefois contribuer à réduire encore plus la fréquence des infections.

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.

Dynamic changes in ventricular depolarization during exercise in patients with Brugada syndrome.

Brugada syndrome (BS) is a genetic pathological condition associated with a high risk for sudden cardiac death (SCD). Ventricular depolarization disorders have been suggested as a potential electrophysiological mechanism associated with high SCD risk on patients with BS. This paper aims to characterize the dynamic changes of ventricular depolarization observed during physical exercise in symptomatic and asymptomatic BS patients. To this end, cardiac ventricular depolarization features were automatically extracted from 12-lead ECG recordings acquired during standardized exercise stress test in 110 BS patients, of whom 25 were symptomatic. Conventional parameters were evaluated, including QRS duration, R and S wave amplitudes ([Formula: see text], [Formula: see text]), as well as QRS morphological features, such as up-stroke and down-stroke slopes of the R and S waves ([Formula: see text], [Formula: see text] and [Formula: see text]). The effects of physical exercise and recovery on the dynamics of these markers were assessed in both BS populations. Features showing significantly different dynamics between the studied groups were used alone and in combination with the clinical characteristics of the patients in a logistic regression analysis. Results show larger changes in the second half of the QRS complex through [Formula: see text] and [Formula: see text] measured in the right precordial leads for asymptomatic patients, especially during recovery, when the vagal tone is more pronounced. Multivariate analysis involving both types of features resulted in a reduced model of three relevant features ([Formula: see text] in lead V2, Sex and heart rate recovery, HRR), which achieved a suitable discrimination performance between groups; sensitivity = 80% and specificity = 75% (AUC = 83%). However, after controlling the model for possible confounding factors, only one feature ([Formula: see text]) remained meaningful. This adjusted model significantly improved the overall discrimination performance by up to: sensitivity = 84% and specificity = 100% (AUC = 94%). The study highlights the importance of physical exercise test to unmask differentiated behaviors between symptomatic and asymptomatic BS patients through depolarization dynamic analysis. This analysis together with the obtained model may help to identify asymptomatic patients at low or high risk of future cardiac events, but it should be confirmed by further prospective studies.

Association of estimated plasma volume status with hemodynamic and echocardiographic parameters.

BACKGROUND: Estimated plasma volume status (ePVS) has diagnostic and prognostic value in patients with heart failure (HF). However, it remains unclear which congestion markers (i.e., biological, imaging, and hemodynamic markers) are preferentially associated with ePVS. In addition, there is evidence of sex differences in both the hematopoietic process and myocardial structure/function. METHOD AND RESULTS: Patients with significant dyspnea (NYHA ≥ 2) underwent echocardiography and lung ultrasound within 4 h prior to cardiac catheterization. Patients were divided according to tertiles based on sex-specific ePVS thresholds calculated from hemoglobin and hematocrit measurements using Duarte's formula. Among the 78 included patients (median age 74.5 years; males 69.2%; HF 48.7%), median ePVS was 4.1 (percentile25-75 = 3.7-4.9) mL/g in males (N = 54) and 4.8 (4.4-5.3) mL/g in females (N = 24). Patients with the highest ePVS had more frequently HF, higher NT-proBNP, larger left atrial volume, and higher E/e' (all p values < 0.05), but no difference in inferior vena cava diameter or pulmonary congestion assessed by lung ultrasound (all p values > 0.10). In multivariable analysis, higher E/e' and lower diastolic blood pressure were significantly associated with increased ePVS. The association between ePVS and congestion variables was not sex-dependent except for left-ventricular end-diastolic pressure, which was only correlated with ePVS in females (Spearman Rho = 0.53, p < 0.01 in females and Spearman Rho = - 0.04, p = 0.76 in males; pinteraction = 0.08). CONCLUSION: ePVS is associated with E/e' regardless of sex, while only associated with invasively measured left-ventricular end-diastolic pressure in females. These results suggest that ePVS is preferably associated with left-sided hemodynamic markers of congestion.

Age at diagnosis of Brugada syndrome: Influence on clinical characteristics and risk of arrhythmia.

BACKGROUND: Despite a strong genetic background, Brugada syndrome (BrS) mainly affects middle-age patients. Data are scarce in the youngest and oldest age groups. OBJECTIVE: The purpose of this study was to describe the clinical characteristics and variations in rhythmic risk in BrS patients according to age. METHODS: Consecutive BrS patients diagnosed in 15 French tertiary centers in France were enrolled from 1993 to 2016 and followed up prospectively. All of the clinical and ECG data were double reviewed. RESULTS: Among the 1613 patients enrolled (age 45 ± 15 years; 69% male), 3 groups were defined according to age (52 patients <17 years; 1285 between 17 and 59 years; and 276 >60 years). In the youngest patients, we identified more female gender (42%), diagnosis by familial screening (63%), previous sudden cardiac death (15%), SCN5A mutation (62%) sinus dysfunction (8%) and aVR sign (37%) (P <.001). The oldest patients had the same clinical characteristics except for gender (40% women; P <.001). During median follow-up of 5.5 [2.1, 10.0] years, 91 patients experienced an arrhythmic event, including 7 (13%) in the youngest patients, 80 (6%) in middle-age patients, and 4 (1%) in the oldest patients. Annual event rates were 2.1%, 1%, and 0.3%, respectively (P <.01). CONCLUSION: Age on diagnosis changes the clinical presentation of BrS. Although children are identified more during familial screening, they present the highest risk of sudden cardiac death, which is an argument for early and extensive familial screening. The oldest patients present the lowest risk of SCD.

Number of electrocardiogram leads in the diagnosis of spontaneous Brugada syndrome.

BACKGROUND: The recently recommended single lead-based criterion for the diagnosis of Brugada syndrome may lead to overdiagnosis of this disorder and overestimation of the risk of sudden cardiac death. AIM: To investigate the value of a single-lead diagnosis in patients with Brugada syndrome and a spontaneous type 1 electrocardiogram. METHODS: Consecutive patients with Brugada syndrome were included in a multicentre prospective registry; only those with a spontaneous type 1 electrocardiogram were enrolled. Clinical and electrocardiogram data were reviewed by two physicians blinded to the patients' clinical and genetic status. RESULTS: Among 1613 patients, 505 (31%) were enrolled (79% male; mean age 46±15 years). A spontaneous type 1 electrocardiogram pattern was found in one lead in 250 patients (group 1), in two leads in 227 patients (group 2) and in three leads in 27 patients (group 3). Groups were similar except for individuals in group 3, who presented more frequently a fragmented QRS complex, an early repolarization pattern and a prolonged Tpeak-Tend interval. After a mean follow-up of 6.4±4.7 years, ventricular arrhythmia, sudden cardiac death or implantable cardiac defibrillator shock occurred in 46 (9%) patients, without differences between groups. CONCLUSION: The prognosis of Brugada syndrome with a spontaneous type 1 electrocardiogram pattern does not appear to be affected by the number of leads required for the diagnosis.