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Background: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. Methods: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. Results: Two hundred eighty-eight patients (41.0 +/- 14.5 years, 55.9% male, right ventricular ejection fraction 42.5 +/- 11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (PFunding Agencies|Leonie-Wild Foundation; Leyla Erkan Family Fund for ARVD Research; Hugh Calkins, Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center; Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center; Dr. Francis P. Chiramonte Private Foundation; Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins; Bogle Foundation; Healing Hearts Foundation; Campanella Family; Patrick J. Harrison Family; Peter French Memorial Foundation; Wilmerding Endowments; Fondation Leducq; National Center for Advancing Translational Sciences [UL1TR001079]; Philippa and Marvin Carsley cardiology research chair; Montreal Heart Institute Foundation; Georg und Bertha Schwyzer-Winiker Foundation; Baugarten Foundation; Swiss Heart Foundation [FF17019, FF21073]; Swiss National Science Foundation [160327]; Swedish Heart Lung Foundation [20200674]; Swedish state under the Avtal om lakarutbildning och forsknin (ALF)-agreement; Netherlands Cardiovascular Research Initiative; Dutch Heart Foundation [CVON201512/2018-30]

INTRODUCTION We sought to explore the relationship between ventricular tachycardia (VT) and premature ventricular complex (PVC) burden (from implantable cardioverter-defibrillator diagnostics), before and during corticosteroid use in patients with newly diagnosed clinically manifest cardiac sarcoidosis (CS). METHODS A single-centre, prospective cohort study was performed in consecutive patients who met all of the following criteria: (1) presentation with clinically manifest CS, (2) abnormal myocardial fluoro-deoxyglucose (FDG) uptake on positron emission tomography scan, (3) plan for implantation with implantable cardioverter-defibrillator device that reports accurate PVC count, (4) plan to initiate corticosteroids after the device healing period. Data were collected during each device interrogation visit for all patients in the study. For each inter-visit period the total number of episodes of VT-sustained and nonsustained, and the number of PVCs was obtained. Each inter-visit period was classified into one of the following three periods: (1) New diagnosis of treatment-naive active disease without corticosteroids during the period. (2) Known treatment-naive active disease with corticosteroids initiated during the inter-visit period. (3) On corticosteroid therapy during the entire period. RESULTS A total of 20 patients with a mean age of 59.7 ± 7.7 years were recruited and 82 inter-visit periods were analyzed. All patients were corticosteroid responders based on FDG uptake. The maximum left ventricular standardized uptake value was 11.14 ± 5.19 before corticosteroid initiation and 4.07 ± 0.88 after (p

This Canadian Cardiovascular Society position statement is focused on the management of sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) that occurs in patients with structural heart disease (SHD), including previous myocardial infarction, dilated cardiomyopathy, and other forms of nonischemic cardiomyopathy. This patient population is rapidly increasing because of advances in care and improved overall survival of patients with all forms of SHD. In this position statement, the acute and long-term management of VT/VF are outlined, and the many unique aspects of care in this population are emphasized. The initial evaluation, acute therapy, indications for chronic suppressive therapy, choices of chronic suppressive therapy, implantable cardioverter-defibrillator programming, alternative therapies, and psychosocial care are reviewed and recommendations for optimal care are provided. The target audience for this statement includes all health professionals involved in the continuum of care of patients with SHD and VT/VF.

Background Access to pacemakers and defibrillators is problematic in places with limited resources. Resterilization and reuse of implantable cardiac devices obtained post mortem from patie...

Background: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and can be challenging to treat. Pharmacologically based rhythm control of AF has not proven to be superior to rate control. Ablation-based rhythm control was compared with rate control to evaluate if clinical outcomes in patients with HF and AF could be improved. Methods: This was a multicenter, open-label trial with blinded outcome evaluation using a central adjudication committee. Patients with high-burden paroxysmal (>4 episodes in 6 months) or persistent (duration Results: From December 1, 2011, to January 20, 2018, 411 patients were randomly assigned to ablation-based rhythm control (n=214) or rate control (n=197). The primary outcome occurred in 50 (23.4%) patients in the ablation-based rhythm-control group and 64 (32.5%) patients in the rate-control group (hazard ratio, 0.71 [95% CI, 0.49–1.03]; P =0.066). Left ventricular ejection fraction increased in the ablation-based group (10.1±1.2% versus 3.8±1.2%, P =0.017), 6-minute walk distance improved (44.9±9.1 m versus 27.5±9.7 m, P =0.025), and NT-proBNP demonstrated a decrease (mean change –77.1% versus –39.2%, P P =0.0036), as did the AF Effect on Quality of Life score (least-squares mean difference of 6.2 [95% CI, 1.7–10.7]; P =0.0005). Serious adverse events were observed in 50% of patients in both treatment groups. Conclusions: In patients with high-burden AF and HF, there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control versus rate control; however, there was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01420393.

Endocardial catheter ablation for ventricular tachycardia (VT) may fail owing to the inability to deliver transmural lesions. Saline-enhanced radiofrequency (SERF) ablation uses a needle-tip catheter that is placed at varying depths into the myocardial tissue and heated saline solution is injected along with radiofrequency power (RF), creating fully transmural lesions. We report the first in-human SERF ablation for VT in Canada.Twenty-five patients with ischemic and nonischemic cardiomyopathy, with recurrent monomorphic drug-refractory VT who had failed a prior catheter ablation underwent SERF ablation in 3 different centres in Canada. After a voltage map, the mapping catheter was replaced with the needle-tipped ablation catheter, which was located perpendicular to the myocardium and extended either 6 or 8 mm into the tissue. Sterile saline solution was infused at a flow rate of 10 mL/min and at 60 °C, and 20-50 W RF was used.Baseline left ventricular ejection fraction was 33.3 ± 8.6%, mean age was 69.5 ± 6.4 years; 92% were male. From 43 clinical VTs induced, 42 were ablated and 266 SERF lesions were delivered (10.6 ± 4.9 per patient). Of the 42 treated clinical VTs, 41 VTs (98%) were noninducible and 24 patients (96%) had their VT eliminated. At 6 months' follow-up, 42% of patients were free from VT and there was a 73% reduction in shocks.SERF ablation is feasible and permits control of symptomatic monomorphic VT in drug-refractory patients with a prior failed ablation.

Europace : the European journal of pacing, arrhythmias and cardiac electrophysiology euac062 (2022). doi:10.1093/europace/euac062, Published by Oxford Univ. Press, Oxford

Aims Genetic testing is recommended in specific inherited heart diseases but its role remains unclear and it is not currently recommended in unexplained cardiac arrest (UCA). We sought to assess the yield and clinical utility of genetic testing in UCA using whole-exome sequencing (WES). Methods and results Survivors of UCA requiring external defibrillation were included from the Cardiac Arrest Survivor with Preserved Ejection fraction Registry. Whole-exome sequencing was performed, followed by assessment of rare variants in previously reported cardiovascular disease genes. A total of 228 UCA survivors (mean age at arrest 39 ± 13 years) were included. The majority were males (66%) and of European ancestry (81%). Following advanced clinical testing at baseline, the likely aetiology of cardiac arrest was determined in 21/228 (9%) cases. Whole-exome sequencing identified a pathogenic or likely pathogenic (P/LP) variant in 23/228 (10%) of UCA survivors overall, increasing the proportion of ‘explained’ cases from 9% only following phenotyping to 18% when combining phenotyping with WES. Notably, 13 (57%) of the 23 P/LP variants identified were located in genes associated with cardiomyopathy, in the absence of a diagnosis of cardiomyopathy at the time of arrest. Conclusions Genetic testing identifies a disease-causing variant in 10% of apparent UCA survivors. The majority of disease-causing variants was located in cardiomyopathy-associated genes, highlighting the arrhythmogenic potential of such variants in the absence of an overt cardiomyopathy diagnosis. The present study supports the use of genetic testing including assessment of arrhythmia and cardiomyopathy genes in survivors of UCA.

Background Approximately 5% of patients with sarcoidosis have clinically manifest cardiac involvement. Clinical features of Cardiac Sarcoidosis are dependent on the location, extent, and activity of the disease. First line therapy is usually with prednisone and this is recommended based on clinician experience, expert opinion and small observational cohorts. There are no published clinical trials in cardiac sarcoidosis and multiple experts in the field have called for randomized clinical trials to answer important patient care questions. Corticosteroid are associated with multiple adverse effects including hypertension, diabetes, weight gain, osteoporosis, and increased risk of infections. In contrast Methotrexate is generally well tolerated and is increasingly used in other forms of sarcoidosis. Objectives The Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial (CHASM CS-RCT; NCT03593759 ) is a multicenter randomized controlled trial designed to evaluate the optimal initial treatment strategy for patients with active cardiac sarcoidosis. We hypothesize that (1) a low dose prednisone/methotrexate combination will have non-inferior efficacy to standard dose prednisone and that (2) the low dose prednisone/ methotrexate combination will result in significantly better quality of life than standard dose prednisone, as a result of reduced burden of side effects. Methods/design Eligible study subjects will have active clinically manifest cardiac sarcoidosis presenting with one or more of the following clinical findings: advanced conduction system disease, significant sinus node dysfunction, non-sustained or sustained ventricular arrhythmia, left ventricular dysfunction or right ventricular dysfunction. Subjects will be randomized in a 1:1 ratio to prednisone 0.5 mg/kg/day for 6 months (maximum dose 30 mg daily) OR to prednisone 20 mg daily for 1 month, then 10 mg daily for 1 month, then 5 mg daily for one month then stop AND methotrexate 15–20 mg once weekly for 6 months. The primary endpoint is summed perfusion rest score on 6-month PET (blinded core-lab review). The summed perfusion rest score is measure of myocardial fibrosis/scar. The design is non-inferiority with a sample size of 97 per group. Discussion Given the multiorgan system potential adverse side effects of prednisone, proving noninferiority of an alternate regimen would be sufficient to make the alternative compare favorably to standard dose steroids. This is the first ever clinical trial in cardiac sarcoidosis and thus in addition to the listed goals of the trial, we will also establish a multi-center, multinational cardiac sarcoidosis clinical trials network. Such a collaborative infrastructure will enable a new era of high quality data to guide physicians when treating cardiac sarcoidosis patients.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P

Aims Complexity of the ventricular tachycardia (VT) substrate and the size and thickness of infarction area border zones differ based on location of myocardial infarctions (MIs). These differences may translate into heterogeneity in the effectiveness of treatments. This study aims to examine the influence of infarct location on the effectiveness of VT ablation in comparison with escalated pharmacological therapy in patients with prior MI and antiarrhythmic drug (AAD)-refractory VT. Methods and results VANISH trial participants were categorized based on the presence or absence of an inferior MI scar. Inverse probability of treatment weighted Cox models were calculated for each subgroup. Of 259 randomized patients (median age 69.8 years, 7.0% women), 135 had an inferior MI and 124 had a non-inferior MI. Among patients with an inferior MI, no statistically significant difference in the composite primary outcome of all-cause mortality, appropriate implantable cardioverter-defibrillator (ICD) shock, and VT storm was detected between treatment arms [adjusted hazard ratio (aHR) 0.80, 95% confidence interval (CI) 0.51–1.20]. In contrast, patients with non-inferior MIs had a statistically significant reduction in the incidence of the primary outcome with ablation (aHR 0.48, 95% CI 0.27–0.86). In a sensitivity analysis of anterior MI patients (n = 83), a trend towards a reduction in the primary outcome with ablation was detected (aHR 0.50, 95% CI 0.23–1.09). Conclusion The effectiveness of VT ablation versus escalated AADs varies based on the location of the MI. Patients with MI scars located only in non-inferior regions of the ventricles derive greater benefit from VT ablation in comparison to escalation of AADs in reducing VT-related events.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Fonds de recherché du Québec-Santé (FRQS) [post doctoral award for Dr. Samuel) BACKGROUND Complexity of ventricular tachycardia (VT) substrate, efficiency of lesion formation, and the size and thickness of infarction area border zones differ based on location of myocardial infarctions (MI). These differences may translate into heterogeneity in risk of events and effectiveness of treatments for VT. Small observational studies suggest that VT from inferior infarctions have higher risk of early recurrence despite smaller infarct areas. However, differential effectiveness of VT treatments based on location of MI not been definitively established. PURPOSE The objective of this sub-study of the Ventricular tachycardia AblatioN versus escalated antiarrhythmic drug therapy in ISchemic Heart disease (VANISH) randomized trial was to compare the effectiveness of VT ablation by location of MI in reducing the composite endpoint of all-cause mortality, VT storm, or appropriate ICD therapy when compared to escalated pharmacological therapy in VT patients with a prior MI. METHODS VANISH participants were categorized into 3 subgroups based on MI location: 1. Inferior (may also have MI in other locations); 2. Non-inferior (no inferior MI, all patients not in group 1); and 3. Anterior (may also have MI in other locations). Inverse probability of treatment weighting was used to balance baseline characteristics (ie. age, sex, comorbidities, medications, and the location of additional infarctions) between patients randomized to ablation or escalated therapy within each subgroup. Weighted Cox proportional hazards models were calculated separately for each subgroup. RESULTS Of 259 patients enrolled in the VANISH trial [median age 69.8 (IQR 63.0-74.2) years, 7.0% women], 135 had an inferior MI, 124 a non-inferior MI, and 83 an anterior MI. Among patients with an inferior MI, no statistically significant difference in the primary outcome was detected between patients randomized to ablation or escalated therapy [aHR 0.78 (95% CI 0.51-1.20)]. In contrast, patients with non-inferior MIs had a statistically significant reduction in the incidence of the primary outcome with ablation [aHR 0.48 (95% CI 0.27-0.86)]; which was of greater magnitude than the reduction observed in the overall results of the VANISH trial [HR 0.72 (95% CI 0.53-0.98)]. In addition, a trend towards a reduction in the primary outcome with ablation was detected in patients with anterior MIs [aHR 0.50 (95% CI 0.23-1.09)]. CONCLUSION The effectiveness of VT ablation versus escalated pharmacological therapy varies based on the location of the MI. Patients with MI scars located only in non-inferior regions of the ventricles derive greater benefit from VT ablation in reducing VT-related events. Further studies are required to explore reasons for this finding and to assess the impact of VT treatment strategies based on MI location in optimizing outcomes.

Supplemental Digital Content is available in the text., Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77–10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69–0.80) and calibration slope of 0.95 (95% CI, 0.94–0.98) indicating minimal over-optimism. Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.

BACKGROUND: Pulmonary vein (PV) stenosis is a complication of atrial fibrillation (AF) ablation. The incidence of PV stenosis after routine post-ablation imaging remains unclear and is limited to single-centre studies. Our objective was to determine the incidence and predictors of PV stenosis following circumferential radiofrequency ablation in the multicentre Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination (ADVICE) trial. METHODS: Patients with symptomatic AF underwent circumferential radiofrequency ablation in one of 13 trial centres. Computed tomographic (CTA) or magnetic resonance (MRA) angiography was performed before ablation and 90 days after ablation. Two blinded reviewers measured PV diameters and areas. PVs with stenosis were classified as severe (> 70%), moderate (50%-70%), or mild (< 50%). Predictors of PV stenosis were identified by means of multivariable logistic regression. RESULTS: A total of 197 patients (median age 59.5 years, 29.4% women) were included in this substudy. PV stenosis was identified in 41 patients (20.8%) and 47 (8.2%) of 573 ablated PVs. PV stenosis was classified as mild in 42 PVs (7.3%) and moderate in 5 PVs (0.9%). No PVs had severe stenosis. Both cross-sectional area and diameter yielded similar classifications for severity of PV stenosis. Diabetes was associated with a statistically significant increased risk of PV stenosis (OR 4.91, 95% CI 1.45-16.66). CONCLUSIONS: In the first systematic multicentre evaluation of post-ablation PV stenosis, no patient acquired severe PV stenosis. Although the results are encouraging for the safety of AF ablation, 20.8% of patients had mild or moderate PV stenosis, in which the long-term effects are unknown.

Introduction Left ventricle (LV) substrate can be characterized by imaging modalities providing physiological variables (tissue perfusion, ischemia, etc.) grouped in a complex dataset. Principal Component Analysis (PCA) can identify the dataset variables that best explain its variance. Variables linked to substrate arrhythmogenicity will lead PCA to identify LV regions most influenced by the variables on a LV 3D geometry. Purpose To evaluate whether regions identified by PCA correspond to regions targeted by physicians in a ventricular tachycardia (VT) ablation procedure. Methods Ischemic VT subjects underwent SPECT/CT perfusion imaging (rest and stress) prior to LV voltage mapping with the cardiac mapping system. Co-registration allowed projection of ablation sites onto SPECT/CT geometries. PCA retrospectively analyzed the following dataset: tissue perfusion (rest and stress), tissue ischemia and the local (1cm2 sub-regions) stress-rest difference for: 1) standard deviation (STD) and 2) skewness (Skew). PCA components (PCAc) explaining ≥85% of the total variance were plotted on the LV 3D geometry to display regions highly influenced by the dataset variables (see figure below). Results Ten subjects (9 males, 66 ± 8 years old, LVEF 37 ± 11%) underwent co-registration. In 7/10 subjects, tissue perfusion (in PCAc#1) and ischemia (in PCAc#2) were most influential on LV regions variance. Ischemia and low perfusion (≤40%) areas equaled 32 ± 19 % of the LV with 21 ± 23% of these areas highly involved in the arrhythmogenic substrate (≥75% of explained LV variance). The location of 63 ± 18% of ablation sites were Conclusion Preliminary results showed that PCA can synthesize the influence of different perfusion derived variables, like tissue perfusion and ischemia, used in SPECT/CT imaging of the LV. Further analysis is needed to confirm whether this could be used to select VT ablation targets. Abstract Figure.

Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular cardiomyopathies. We present a family with arrhythmogenic cardiomyopathy associated with a novel missense variant in DSP (NM_004415.4): c.877G>A, p.(Glu293Lys). The phenotype is characterized by predominant involvement of the left ventricle with systolic dysfunction, fibrosis, and life-threatening arrhythmias. We performed a systematic review of literature collecting all cardiomyopathy cases with rare missense variants in DSP. We demonstrate that the distribution of missense variants across the protein domains in cardiomyopathy cases differs from that in gnomAD (p = .04), with a case enrichment of rare missense variants in the spectrin repeat domain (36/78 [46%] in cases vs. 449/1495 [30%] in gnomAD; p = .004). Our findings highlight the predominance of cardiac arrhythmia and left ventricular involvement in desmoplakin cardiomyopathy and pinpoint to a potential mutation hotspot in DSP thereby facilitating missense variant interpretation in the diagnostic setting.

Objectives This study sought to evaluate the predictive value of noninducibility on long-term outcomes. Background The traditional endpoint for catheter ablation of ventricular tachycardia (VT) is noninducibility of VT by programmed stimulation; however, the definition of inducibility remains variable and its prognostic value limited by nonstandardized periprocedural antiarrhythmic drug therapy and implantable cardioverter-defibrillator programming in prior observational studies. The VANISH trial randomized patients with prior myocardial infarction and VT to ablation (with an endpoint of noninducibility of VT ≥300 ms after ablation) versus antiarrhythmic drug escalation. Methods Patients enrolled in the VANISH study randomized to catheter ablation were included. The relationship between post-ablation inducibility and the primary composite endpoint (death, VT storm >30 days, or appropriate implantable cardioverter-defibrillator shock >30 days) was assessed using a time-to-event analysis, adjusting for other clinical and procedural characteristics. Results A total of 129 patients from the ablation arm were included in the primary analysis, of which 51 were noninducible post-ablation compared with 78 who had inducible VT or in whom inducibility testing was not performed. There were no significant baseline characteristic or procedural differences except for increased implantable cardioverter-defibrillator shocks before randomization in the noninducible group. In multivariate analysis, inducibility significantly increased the risk of death, appropriate shock, or VT storm after 30 days (HR: 1.87; p = 0.017). Conclusions Inducibility of any VT post-ablation was associated with an increased risk of the composite endpoint in the VANISH trial. A randomized trial is required to confirm whether more aggressive ablation targeting faster induced VTs (

Keywords: European Heart Rhythm Association, Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society, Cognitive, Arrythmias, Dementia Table of Contents Introduction 1400 Evidence review 1400 Relationships with industry and other conflicts 1400a Decline of cognitive function: terminology and epidemiology 1400a Terminology: cognitive decline, mild cognitive impairment, and dementia 1400a Epidemiology of dementia 1400a Methods for assessment of cognitive function 1400b Role of imaging 1400c Atrial fibrillation and cognitive function 1400c Atrial fibrillation, overt stroke, and cognitive function 1400c Atrial fibrillation, silent stroke, and cognitive function 1400e Atrial fibrillation and cognitive function in the absence of stroke 1400g Assessment of cognitive function in atrial fibrillation patients in clinical practice 1400g Prevention of cognitive dysfunction in atrial fibrillation patients 1400h Other arrhythmias and cognitive dysfunction 1400j Cognitive dysfunction in patients with regular supraventricular tachycardias 1400j Cognitive impairment after cardiac arrest 1400j Cardiac implantable electronic devices and cognitive dysfunction 1400k Catheter ablation 1400k Implications for electrophysiological procedures and cognitive function 1400l Current knowledge gaps, future directions, and areas for research 1400m Recommendations 1400m Introduction This expert consensus statement of the European Heart Rhythm Association (EHRA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS) summarizes the consensus of the international writing group and is based on a thorough review of the medical literature regarding cognitive function in arrhythmias. The document is intended to describe the impact of different types of arrhythmias on cognitive function, to highlight possible risk markers for cognitive decline and to formulate implications for clinical practice regarding follow-up methods, prevention and treatment strategies. Our objective is to raise awareness of cognitive function among physicians treating patients with arrhythmias and to provide them with practical proposals that may lead to improvement of patient care in this regard. This document reviews terminology and the epidemiology of cognitive dysfunction, methods for assessment of cognitive function and the role of imaging. Recent studies have suggested possible associations between cognitive decline and atrial fibrillation (AF). We review the reported literature on AF and cognitive function, including the scenarios of AF with overt stroke, silent stroke, or no stroke, and then make recommendations for assessment of cognitive function and prevention of cognitive decline in patients with AF in clinical practice. The document also reviews the association of other arrhythmias and cognitive dysfunction, including settings such as post-cardiac arrest, cardiac implantable devices, such as implantable cardioverter-defibrillators (ICDs) and pacemakers, or ablation procedures. Implications for electrophysiological procedures and cognitive function are discussed. Long QT syndrome and cognitive function is not addressed in the document. For quick reference, sub-chapters are followed by a short section on consensus recommendations. The document concludes with a summary of consensus statements, current knowledge gaps, and future directions of research. Evidence review Members of the Task Force were asked to perform a detailed literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes for which data exist. Patient-specific modifiers, co-morbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered, as are frequency of follow-up and cost-effectiveness. In controversial areas, or with regard to issues without evidence other than usual clinical practice, a consensus was achieved by agreement of the expert panel after thorough deliberations. This document was prepared by the Task Force with representation from EHRA, HRS, APHRS, and LAHRS. The document was peer-reviewed by official external reviewers representing EHRA, HRS, APHRS, and LAHRS. Consensus statements are evidence-based and derived primarily from published data or determined through consensus opinion if data are not available. Current systems of ranking level of evidence are becoming complicated in a way that their practical utility might be compromised.1 In contrast to guidelines, we opted for an easier and user-friendly system of ranking using ‘coloured hearts’ that should allow physicians to easily assess the current status of the evidence and consequent guidance (Table ​Table11). This EHRA grading of consensus statements does not have separate definitions of the level of evidence. This categorization, used for consensus statements, must not be considered as directly similar to that used for official society guideline recommendations, which apply a classification (Class I–III) and level of evidence (A, B, and C) to recommendations used in official guidelines. Table 1 Scientific rationale of recommendations*

Introduction In patients with ischemic heart disease and ventricular tachycardia (VT) refractory to high dose amiodarone, the two most common therapeutic options are adjunctive mexiletine therapy or catheter ablation. There are little existing data on the efficacy of these strategies. We examined the relative efficacy of adjunctive mexiletine and catheter ablation among patients enrolled in the VANISH trial. Methods All subjects enrolled in the VANISH trial who had VT refractory to high dose (≥ 300 mg daily) amiodarone at baseline were included. Per protocol, subjects randomized to escalated drug therapy received adjunctive mexiletine. Results Nineteen of the 259 patients were receiving high-dose amiodarone at baseline and 11 were randomized to escalated therapy with mexiletine and 8 to ablation. The adjunctive mexiletine group had a higher rate of the primary composite outcome (death, VT storm, or appropriate shock) in comparison to catheter ablation (HR 6.87 [2.08-22.8]). Over 90% of the patients in the adjunctive mexiletine/group experienced a primary endpoint during a median 9.2 months' follow-up. There was no difference in the rate of adverse events between the two groups. Conclusions Mexiletine has limited efficacy in the treatment of recurrent VT despite high-dose amiodarone therapy, in patients with ischemic heart disease. Catheter ablation is a superior strategy in this population.

Atrial fibrillation (AF) and dementia are major health issues, with growing evidence suggesting a consistent association between AF and all forms of dementia. Although dementia and AF share several risk factors, the association appears to be independent of a history of clinical stroke and other comorbidities such as hypertension, heart failure, and diabetes. Proposed mechanisms linking AF to cognitive decline include altered hemodynamics resulting in cerebral hypoperfusion, inflammation, genetic factors, and silent cerebral ischemia due to subclinical microemboli. Evidence in support of the microembolization hypothesis includes the much higher incidence of silent cerebral ischemia detected in imaging studies in patients with AF, the association between presence of silent cerebral ischemia and cognitive dysfunction, and a "dose response" relationship between extent of silent cerebral ischemia and degree of cognitive impairment. Preventive therapies are currently being investigated and include anticoagulation, antiplatelet therapy, statins, pharmacological rhythm and rate control treatment strategies for AF, and catheter ablation procedures. Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) trial is currently assessing whether oral anticoagulation can prevent cognitive decline in patients at low risk of overt stroke. Considering the strong and independent association between AF and neurocognitive outcomes and the major clinical implications, evidence-based preventive approaches are critically required to diminish the health burden from the scourge of dementia and related conditions.

Background Atrial arrhythmias are the most common complication encountered in the growing and aging population with congenital heart disease. Objectives This study sought to assess the types and patterns of atrial arrhythmias, associated factors, and age-related trends. Methods A multicenter cohort study enrolled 482 patients with congenital heart disease and atrial arrhythmias, age 32.0 ± 18.0 years, 45.2% female, from 12 North American centers. Qualifying arrhythmias were classified by a blinded adjudicating committee. Results The most common presenting arrhythmia was intra-atrial re-entrant tachycardia (IART) (61.6%), followed by atrial fibrillation (28.8%), and focal atrial tachycardia (9.5%). The proportion of arrhythmias due to IART increased with congenital heart disease complexity from 47.2% to 62.1% to 67.0% in patients with simple, moderate, and complex defects, respectively (p = 0.0013). Atrial fibrillation increased with age to surpass IART as the most common arrhythmia in those ≥50 years of age (51.2% vs. 44.2%; p Conclusions IART is the most common presenting atrial arrhythmia in patients with congenital heart disease, with a predominantly paroxysmal pattern. However, atrial fibrillation increases in prevalence and atrial arrhythmias progressively become permanent as the population ages.

Introduction The standard 4-minute application time for transcatheter cryoablation was determined in the 1990s when the system employed less potent chlorofluorocarbon refrigerants. The current refrigerant, nitrous oxide, generates substantially colder temperatures, with a faster cooling rate. Methods and results We conducted a preclinical study on 32 mongrel dogs with stratified randomization of right atrial, right ventricular, and left ventricular chambers to 2-minute versus 4-minute application times using 8-mm electrode tip cryocatheters (Freezor Max, Medtronic CryoCath LP, Montreal, Canada). Animals were sacrificed one month after the procedure. Three-dimensional morphometric analyses were conducted in a blinded fashion. A total of 193 identified ablation lesions were processed for histological analyses, 102 with 2-minute applications and 91 with 4-minute applications. Ablation lesion surface area (167.8 ± 21.6 mm2 vs. 194.3 ± 22.6 mm2 , P = 0.40), maximum depth (4.4 ± 0.2 mm vs. 4.5 ± 0.2 mm, P = 0.71), and volume (125.7 ± 69.5 mm3 vs. 141.0 ± 83.5 mm3 , P = 0.25) were similar between groups. Overall, 90.2% of ablation lesions in the right atrium were transmural, 45.6% in the right ventricle, and 2.4% in the left ventricle, with no differences between 2-minute and 4-minute application times (P = 0.55). Thrombus was detected on the endocardial surface of 0.0% and 3.3% of ablation lesions created with 2-minute and 4-minute application times, respectively (P = 0.10). Conclusion Single 2-minute and 4-minute application times result in catheter ablation lesions of similar size using the modern cryoablation system with nitrous oxide as a refrigerant. While these findings suggest the potential to reduce the standard 4-minute application time, further studies are required to compare clinical efficacy.

Introduction: Ventricular arrhythmias are often seen in association with structural heart disease. However, approximately a tenth of affected patients have apparently normal hearts, where such arrhythmias typically occur in young patients, are sometimes inherited and can occasionally lead to sudden cardiac death (SCD). Over the past two decades, increased understanding of the underlying pathophysiology resulted in improved targeted pharmacological therapy.Areas covered: This article reviews current knowledge regarding drug therapy for inherited arrhythmia syndromes (Brugada, early repolarization, long QT and short QT syndromes, and catecholaminergic polymorphic ventricular tachycardia), and acquired arrhythmias (idiopathic ventricular fibrillation, short-coupled torsade de pointes, outflow tract ventricular tachycardia, idiopathic left, papillary muscle and annular ventricular tachycardias).Expert opinion: In inherited arrhythmia syndromes, appropriate clinical and genetic diagnoses followed by proper selection and dosing of antiarrhythmic drugs are of utmost importance to prevent SCD, most often without the need of implantable cardioverter-defibrillators. In acquired arrhythmias, appropriate pharmacotherapy in selected patients can also provide symptomatic relief and avoid the need for invasive therapy. Further research is needed to develop novel antiarrhythmic drugs or targeted therapy to increase efficacy and limit side effects.

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined disease associated with a significant risk of ventricular arrhythmias and sudden cardiac death (SCD)...

Aims Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods and results Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 +/- 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). Conclusion Using the Largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com). Funding Agencies|Canadian Heart Rhythm Society George Mines Traveling Fellowship; Montreal Heart Institute Foundation; Fondation LeducqLeducq Foundation [16 CVD 02]; Dutch Heart FoundationNetherlands Heart Foundation [2015T058, CVON2015-12 eDETECT, 2012-10 PREDICT]; Netherlands Organisation for Scientific ResearchNetherlands Organization for Scientific Research (NWO) [040.11.586]; Netherlands Heart Institute [06901]; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [320030_160327]; UMC Utrecht 2017 Alexandre Suerman Stipend; UMC Utrecht Fellowship Clinical Research Talent; European Unions Horizon 2020 research and innovation program under the ERA-NET Co-fund action [680969]; Dr Francis P. Chiaramonte Private Foundation; Leyla Erkan Family Fund for ARVD Research; Dr Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins; Bogle Foundation; Healing Hearts Foundation; Campanella family; Patrick J. Harrison Family; Peter French Memorial Foundation; Wilmerding Endowments; Georg und Bertha Schwyzer-Winiker Foundation; Baugarten Foundation; Swiss Heart Foundation; Leonie-Wild Foundation; Marvin and Philippa Carsley Chair of Medicine; UCL Hospitals NIHR Biomedical Research Centre

Objectives The impact of beta-blockers on mortality and hospitalizations was assessed in the largest randomized trial of patients with both atrial fibrillation (AF) and heart failure with a reduced ejection fraction (HFrEF): the Atrial Fibrillation-Congestive Heart Failure trial. Background Although beta-blockers are the cornerstone of therapy for HFrEF, a recent patient-level meta-analysis cast doubt on their efficacy in patients with coexisting AF. Methods From a total of 1,376 subjects randomized in the AF-CHF trial, those without beta-blockers at baseline were propensity matched to a maximum of 2 exposed patients. All absolute standardized differences after matching were ≤10%. Primary analyses respected the intention-to-treat principle. In on-treatment sensitivity analyses, beta-blocker status was modeled as a time-dependent covariate. Results Baseline characteristics were comparable among the matched cohorts (mean age 70 ± 11 years, 81% male, and mean left ventricular ejection fraction 27 ± 6%). During a median follow-up of 37 months, beta-blockers were associated with significantly lower all-cause mortality (hazard ratio [HR]: 0.721, 95% confidence interval [CI]: 0.549 to 0.945; p = 0.0180) but not hospitalizations (HR: 0.886; 95% CI: 0.715 to 1.100; p = 0.2232). Similar results were obtained in sensitivity analyses that modeled beta-blockers as a time-dependent variable (HR: 0.668 for all-cause mortality; 95% CI: 0.511 to 0.874; p = 0.0032; HR: 0.814 for hospitalizations; 95% CI: 0.653 to 1.014; p = 0.0658). There were no significant interactions between beta-blockers and patterns (i.e., persistent vs. paroxysmal) or burden of AF with respect to mortality or hospitalizations. Conclusions In propensity-matched analyses, beta-blockers were associated with significantly lower mortality but not hospitalizations in patients with HFrEF and AF, irrespective of the pattern or burden of AF. These results support current evidence-based recommendations for beta-blockers in patients with HFrEF, whether or not they have associated AF.

Arrhythmic or electrical storm (AES) is a clinical condition characterized by 3 or more sustained ventricular arrhythmia episodes leading to appropriate device therapy in a 24-hour period and is associated with very high mortality. The clinical presentation is dramatic, and the management remains challenging. Although pharmacologic treatment and sedation are still part of the initial treatment, newer approaches that include ablation (endocardial, epicardial, or alternative procedures), sympathetic blockade (pharmacologic or by interventional sympathetic denervation), and mechanical hemodynamic support are used increasingly in this setting. In this article we review the current technologies at our disposal clinically to treat AES.

Background There is a paucity of data to guide decisions regarding thromboprophylaxis for atrial arrhythmias in congenital heart disease. Methods A retrospective multicenter cohort study enrolled patients with documented sustained atrial arrhythmias and congenital heart disease from 12 North American centers to quantify thromboembolic and bleeding rates associated with antiplatelet and anticoagulation therapy, and explore associated factors. A blinded committee adjudicated all qualifying arrhythmias and outcomes. Results A total of 482 patients, 45.2% female, age 32.0±18.0years, were followed for 11.3±9.4years since the qualifying arrhythmia. Antiplatelet therapy was administered to 37.8%, anticoagulation to 54.4%, and neither to 7.9%. Congenital heart disease complexity was simple, moderate, and severe in 18.5%, 34.4%, and 47.1%, respectively. Freedom from thromboembolic events was 84.7±2.7% at 15years, with no difference between anticoagulation versus antiplatelet therapy (P=0.97). Congenital heart disease complexity was independently associated with thromboembolic events, with rates of 0.00%, 0.93%, and 1.95%/year in those with simple, moderate, and severe forms (P 2 and CHA 2 DS 2 -VASc scores were not predictive of thromboembolic risk. Annualized bleeding rates with antiplatelet and anticoagulation therapy were 0.66% and 1.82% (P=0.039). In multivariable analyses, anticoagulation [hazard ratio (HR) 4.76, 95% CI (1.05–21.58), P=0.043] and HAS-BLED score [HR 3.15, 95% CI (1.02, 9.78), P=0.047] were independently associated with major bleeds. Conclusion Current management of atrial arrhythmias in congenital heart disease is associated with a modest rate of thromboembolic events, which is predicted by disease complexity but not CHADS 2 /CHA 2 DS 2 -VASc scores. HAS-BLED score is applicable to the congenital population in predicting major bleeds.

Sensor-Based Navigation and CRT ImplantationIntroduction Cardiac resynchronization therapy (CRT) implant procedures are often complex and prolonged, resulting in substantial ionizing radiation (IR) exposure to the patient and operator. We assessed the impact of lower-dose fluoroscopy settings and a sensor-based electromagnetic tracking system (MediGuide™, MDG) on reducing IR exposure during CRT implantation. Methods A single-center 2-group cohort study was conducted on 348 consecutive patients, age 66.4 ± 11.0 years, 80.4% male, with CRT implant procedures from 2013 to 2015. Patients were arbitrarily assigned to MDG (N = 239) versus no MDG (N = 109) guidance. Lower-dose fluoroscopy settings were adopted in January 2015 (3 instead of 6 fps; 23 instead of 40 nGy/pulse; N = 101). Results Overall, MDG was associated with an 82.1% reduction in IR exposure (393 μGray·m2 vs. 2191 μGray·m2, P < 0.001). Lower-dose fluoroscopy resulted in a 59.5% reduction in IR-exposure without MDG (1055 μGray·m2 vs. 2608 μGray·m2, P < 0.001) and 81.8% reduction with MDG (108 μGray·m2 vs. 595 μGray·m2, P < 0.001). Low-dose fluoroscopy combined with MDG was associated with a 95.9% lower exposure to IR when compared to standard fluoroscopy without MDG (108 μGray·m2 vs. 2608 μGray·m2, P < 0.001). Procedures with MDG were shorter (96 minutes vs. 123 minutes, P < 0.001) and associated with a trend towards a higher success rate (94.6% vs. 89.0%, P = 0.062), with fewer coronary sinus cannulation failures (2.1% vs. 6.4%, P = 0.040). Conclusion Low-dose fluoroscopy settings are highly effective (>50%) in reducing IR exposure during CRT implant procedures. When combined with MDG, >95% reduction in IR exposure is achieved. Moreover, MDG shortens procedural duration and may improve acute procedural outcomes.

Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain.We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock.Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group.In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).

Dynamic right ventricular outflow tract obstruction is rare in the cardiac surgical population. Significant obstruction developing in the perioperative period can contribute to systemic hemodynamic instability. We describe 2 cases of dynamic right ventricular outflow tract obstruction that developed immediately after separation from cardiopulmonary bypass, due to temporary right ventricular epicardial pacing. Both patients had systemic hypotension which improved once ventricular pacing was discontinued. We discuss the recognition of right ventricular outflow tract obstruction as a contributing factor to hemodynamic instability, as well as the importance of identifying the underlying cause such as to institute appropriate management in these patients.

Background Compelling evidence showing a link between atrial fibrillation (AF) and cognitive decline and dementia is accumulating. Methods Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) is a prospective, multicentric, double-blind, randomized-controlled trial, recruiting patients with nonvalvular AF and a low risk of stroke. Patients with a high risk of bleeding will be excluded from the study. Participants will be randomized to receive either rivaroxaban (15 mg daily) or standard of care (placebo in patients without vascular disease or acetylsalicylic acid 100 mg daily in patients with vascular disease). Results The primary outcome is the composite of stroke, transient ischemic attack, and cognitive decline (defined by a decrease in the Montreal Cognitive Assessment score ≥ 3 at any follow-up visit after baseline). Approximately 3250 patients will be enrolled in approximately 130 clinical sites until 609 adjudicated primary outcome events have occurred. Conclusions BRAIN-AF determines whether oral anticoagulation therapy with rivaroxaban compared with standard of care reduces the risk of stroke, transient ischemic attack, or cognitive decline in patients with nonvalvular AF and a low risk of stroke.

Atrial fibrillation (AF) is the most frequent arrhythmia worldwide. While mostly seen in elderly, it can also affect young adults (≤ 45 years of age), older adolescent, and children. Areas covered: The aim of this review is to provide an overview of the current management of AF in young patients. Specific issues arise over diagnostic workup as well as antiarrhythmic and anticoagulation therapies. The future management and diagnostic strategies are also discussed. Expert commentary: Management of AF in the young adult is largely extrapolated from adult studies and guidelines. In this population, AF could reveal a genetic pathology (e.g. Brugada, Long QT or Short QT syndromes) or be the initial presentation of a cardiomyopathy. Therefore, thorough workup in the young population to eliminate potential malignant pathology.

ECG and Cardiovascular Outcomes in AFBackground The association between standard parameters from a simple 12-lead ECG (i.e., QRS duration and PR, JT, and QT intervals) and adverse cardiovascular outcomes (cardiovascular mortality, all-cause mortality, arrhythmic mortality, and hospitalizations) in patients with a history of atrial fibrillation (AF) has not been previously studied. Methods and Results A pooled analysis of patient-level data was conducted on 5,436 patients, age 68.2 ± 8.3 years, 34.8% female, with a history of non-permanent AF randomized in AFFIRM and AF-CHF trials. The predictive value of ECG parameters was assessed in AF and sinus rhythm in multivariate Cox regression models. During a follow-up of 40.8 ± 16.3 months, QRS duration >120 milliseconds was independently associated with all-cause mortality (hazard ratio [HR] 1.46, 95% confidence interval [CI; 1.21–1.76] in AF, P 200 milliseconds) was independently associated with cardiovascular (HR 1.56, 95% CI [1.11–2.21], P = 0.010) and arrhythmic (HR 1.91, 95% CI [1.14–3.18], P = 0.004) mortality. The JT and QTc intervals were not predictive of mortality. Conclusions Simple parameters from standard ECGs are significantly and independently associated with adverse cardiovascular outcomes in patients with a history of AF.