Healthcare utilization and quality of life for atrial fibrillation burden: the CIRCA-DOSE study.

AIMS: Atrial tachyarrhythmia recurrence ≥30 s remains the primary endpoint of clinical trials; however, this definition has not been correlated with clinical outcomes or pathophysiological processes. This study sought to determine the atrial tachyarrhythmia duration and burden associated with meaningful clinical outcomes. METHODS AND RESULTS: The time and duration of every atrial tachyarrhythmia episode recorded on implantable cardiac monitor were evaluated. Healthcare utilization and quality of life in the year following ablation were prospectively collected. Three hundred and forty-six patients provided 126 110 monitoring days. One-year freedom from recurrence increased with arrhythmia duration thresholds, from 52.6 (182/346) to 93.3% (323/346; P < 0.0001). Patients with atrial fibrillation (AF) recurrence limited to durations ≤1 h had rates of healthcare utilization comparable with patients free of recurrence, while patients with AF recurrences lasting >1 h had a relative risk for emergency department consultation of 3.2 [95% confidence interval (CI) 2.0-5.3], hospitalization of 5.3 (95% CI 2.9-9.6), and repeat ablation of 27.1 (95% CI 10.5-71.0). Patients with AF burden of ≤0.1% had rates of healthcare utilization comparable with patients free of recurrence, while patients with AF burden of >0.1% had a relative risk for emergency department consultation of 2.4 (95% CI 1.9-3.9), hospitalization of 6.8 (95% CI 3.6-13.0), cardioversion of 9.1 (95% CI 3.3-25.6), and repeat ablation of 21.8 (95% CI 9.2-52.2). Compared with patients free of recurrence, the disease-specific quality of life was significantly impaired with AF episode durations >24 h, or AF burdens >0.1%. CONCLUSION: AF recurrence, as defined by 30 s of arrhythmia, lacks clinical relevance. AF episode durations >1 h or burdens >0.1% were associated with increased rates of healthcare utilization.

Feasibility of concomitant left atrial appendage closure and percutaneous coronary intervention in patients with acute coronary syndrome and atrial fibrillation: a randomized pilot study.

The optimal approach for prevention of cardiovascular events and reduction of bleeding in patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) is still controversial. The aim of our study is to asses our single-center experience with concomitant left atrial appendage occlusion (LAAO) and percutaneous coronary intervention (PCI). 50 patients with ACS without ST elevation and history of AF were randomized after successful PCI to LAAO or conventional medical therapy. The primary endpoints were safety and length of hospitalization. The follow-up period was 30 days. The mean procedural times were 113 ± 23 min PCI + LAAO implantation and 39 ± 19 min of PCI only (p < 0.001), while mean fluoroscopy times were 18 ± 8 min and 12 ± 8 min (p < 0.001), respectively. No procedure-related complications were observed. There was no difference observed for length of hospitalization between two groups. LAAO in patients with ACS and AF undergoing PCI appears safe.

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study.

BACKGROUND: Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations. METHODS: The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. CONCLUSIONS: The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

2021 ISHNE/ HRS/ EHRA/ APHRS collaborative statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society.

This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/ Heart Rhythm Society/ European Heart Rhythm Association/ Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.

Renal Denervation for Patients With Atrial Fibrillation.

PURPOSE OF REVIEW: During the last decade, several case series and small reports have indicated that pulmonary vein isolation (PVI) in combination with renal denervation (RDN) may increase the rate of atrial fibrillation (AF) freedom in patients with hypertension. We aimed to provide a contemporary systematic overview on the techniques, and the efficacy/safety of RDN on AF recurrence, and the current landscape of ongoing investigation. RECENT FINDINGS: The recent Evaluate Renal Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation (ERADICATE-AF) trial has demonstrated convincingly that among patients with paroxysmal AF and poorly controlled (but not "resistant") hypertension, RDN added to catheter ablation, compared with catheter ablation alone, significantly increased the likelihood of freedom from AF at 12 months. RDN has proven to be a unique, effective and safe interventional therapy for the management of AF. Future investigation will likely focus on confirming current findings; expanding the population of eligible patients (eg., non-hypertensives, well controlled hypertensives); determining long-term maintenance of effect and therapeutics.

Effect of Renal Denervation and Catheter Ablation vs Catheter Ablation Alone on Atrial Fibrillation Recurrence Among Patients With Paroxysmal Atrial Fibrillation and Hypertension: The ERADICATE-AF Randomized Clinical Trial.

Importance: Renal denervation can reduce cardiac sympathetic activity that may result in an antiarrhythmic effect on atrial fibrillation. Objective: To determine whether renal denervation when added to pulmonary vein isolation enhances long-term antiarrhythmic efficacy. Design, Setting, and Participants: The Evaluate Renal Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation (ERADICATE-AF) trial was an investigator-initiated, multicenter, single-blind, randomized clinical trial conducted at 5 referral centers for catheter ablation of atrial fibrillation in the Russian Federation, Poland, and Germany. A total of 302 patients with hypertension despite taking at least 1 antihypertensive medication, paroxysmal atrial fibrillation, and plans for ablation were enrolled from April 2013 to March 2018. Follow-up concluded in March 2019. Interventions: Patients were randomized to either pulmonary vein isolation alone (n = 148) or pulmonary vein isolation plus renal denervation (n = 154). Complete pulmonary vein isolation to v an end point of elimination of all pulmonary vein potentials; renal denervation using an irrigated-tip ablation catheter delivering radiofrequency energy to discrete sites in a spiral pattern from distal to proximal in both renal arteries. Main Outcomes and Measures: The primary end point was freedom from atrial fibrillation, atrial flutter, or atrial tachycardia at 12 months. Secondary end points included procedural complications within 30 days and blood pressure control at 6 and 12 months. Results: Of the 302 randomized patients (median age, 60 years [interquartile range, 55-65 years]; 182 men [60.3%]), 283 (93.7%) completed the trial. All successfully underwent their assigned procedures. Freedom from atrial fibrillation, flutter, or tachycardia at 12 months was observed in 84 of 148 (56.5%) of those undergoing pulmonary vein isolation alone and in 111 of 154 (72.1%) of those undergoing pulmonary vein isolation plus renal denervation (hazard ratio, 0.57; 95% CI, 0.38 to 0.85; P = .006). Of 5 prespecified secondary end points, 4 are reported and 3 differed between groups. Mean systolic blood pressure from baseline to 12 months decreased from 151 mm Hg to 147 mm Hg in the isolation-only group and from 150 mm Hg to 135 mm Hg in the renal denervation group (between-group difference, -13 mm Hg; 95% CI, -15 to -11 mm Hg; P < .001). Procedural complications occurred in 7 patients (4.7%) in the isolation-only group and 7 (4.5%) of the renal denervation group. Conclusions and Relevance: Among patients with paroxysmal atrial fibrillation and hypertension, renal denervation added to catheter ablation, compared with catheter ablation alone, significantly increased the likelihood of freedom from atrial fibrillation at 12 months. The lack of a formal sham-control renal denervation procedure should be considered in interpreting the results of this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT01873352.

Prophylactic pulmonary vein isolation during isthmus ablation for atrial flutter: Three-year outcomes of the PREVENT AF I study.

INTRODUCTION: The PREVENT AF I study demonstrated that prophylactic pulmonary vein isolation (PVI) in patients with pure typical atrial flutter (AFL) resulted in substantial reduction of new-onset atrial fibrillation (AF) during 1-year follow-up as assessed by continuous implantable cardiac monitor (ICM). The objective of this study was to assess 3-year outcomes. METHODS AND RESULTS: Fifty patients with documented AFL were randomized to either cavotricuspid isthmus (CTI) ablation alone (n = 25) or CTI with concomitant PVI (n = 25). The primary endpoint of the study was the occurrence of any atrial tachyarrhythmia with the monthly burden exceeding 0.5% on the ICM. At the end of 3 years, freedom from any atrial tachyarrhythmia was 48% (95% confidence interval [CI]: 32-72%) in the CTI plus PVI group as compared to 20% (95% CI: 9-44%) in the CTI-only group (P = 0.01). Freedom from redo procedures was also higher: 92% (95% CI: 82-100%) versus 68% (95% CI: 52-89%), respectively (P = 0.027). The 3-year AF burden favored the combined ablation group: 6.2% versus 16.8% (P = 0.03). In the CTI-only group, 12 (48%) patients were hospitalized compared to 4 (16%) in the PVI + CTI group (P = 0.03). Two patients in the CTI-only group developed stroke with no serious adverse events in the PVI + CTI group. CONCLUSION: Prophylactic PVI in patients with only typical AFL resulted in a significant reduction of new-onset AF and burden during long-term follow-up as assessed by ICM, with consequent reduction in hospitalizations and need to perform repeat ablation for AF.

Postimplantation ventricular ectopic burden and clinical outcomes in cardiac resynchronization therapy-defibrillator patients: a MADIT-CRT substudy.

BACKGROUND: Frequent ventricular ectopy on preimplantation Holter has been associated with attenuated benefit from cardiac resynchronization therapy (CRT). However, it is unclear whether ectopic burden measured post-CRT implantation can be utilized to evaluate long-term prognosis. We aimed to describe the association between post-CRT implantation ectopic burden and subsequent risk of clinical outcomes. METHODS: At the 12-month follow-up visit, 24-hour Holter recordings were performed in 698 CRT-D patients from the MADIT-CRT study. The mean number of ventricular premature complexes (VPCs/hour) was calculated. High ectopic burden was defined as >10 VPCs/hour and low burden as ≤10 VPCs/hour. Multivariate Cox proportional hazards models were utilized to assess the association between 12-month ectopic burden and the risk of the end points of heart failure (HF) or death and ventricular tachyarrhythmias (VT/VF). RESULTS: At 12 months, 282 (40%) patients presented with low ectopic burden and 416 (60%) patients presented with high ectopic burden. The 3-year risk of HF/death and VT/VF was lower in patients with a low burden (7% and 8%) and significantly higher (25% and 24%) in patients with high burden. In multivariate analyses, patients with a high ectopic burden had approximately threefold increased risk of both HF/death (HR=2.76 [1.62-4.70], p < .001) and VT/VF (HR=2.79 [1.69-4.58], p < .001). CONCLUSION: In CRT-D patients with mild heart failure, high ectopic burden at 12-month follow-up was associated with a high 3-year risk of HF/death and VT/VF and threefold increased risk as compared to patients with low burden. Ectopic burden at 12 months may be a valuable approach for evaluating long-term prognosis.

Pharmacologic Conversion during Dofetilide Treatment for Persistent Atrial Fibrillation.

BACKGROUND: Dofetilide is a pure IKr blocker and is one of the few drugs specifically studied and approved in the United States for the management of persistent atrial fibrillation (AF). Dofetilide has been noted to have a high rate of pharmacologic conversion during initial dosing in prior smaller studies. The intent of the study was to examine the safety of an inpatient loading strategy, and the incidence and patterns of pharmacologic conversion by dofetilide during the treatment of persistent AF in a large consecutive cohort. METHODS AND RESULTS: This is a retrospective analysis of 308 consecutive patients with persistent AF electively admitted for inpatient dofetilide loading. The initiation dose of dofetilide was determined by the creatinine clearance. Overall, 88% (n = 271) successfully completed initiation of dofetilide and were discharged in sinus rhythm. The most common reason for failure to complete initiation of dofetilide loading was QTc prolongation in 24 patients (7.8%), and torsade de pointes occurred in three patients (1%). Pharmacologic conversion was observed in 56% (n = 151) after a median of two doses. The rate of pharmacologic conversion based on the final dose was 75%, 9%, and 0% for 500 mcg, 250 mcg, and 125 mcg, respectively (P < 0.05). CONCLUSIONS: Dofetilide is a well-tolerated antiarrhythmic drug with a low incidence of proarrhythmia and an especially high rate of pharmacologic conversion in patients with persistent AF.

2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry.

Ambulatory ECG (AECG) is very commonly employed in a variety of clinical contexts to detect cardiac arrhythmias and/or arrhythmia patterns which are not readily obtained from the standard ECG. Accurate and timely characterization of arrhythmias is crucial to direct therapies that can have an important impact on diagnosis, prognosis or patient symptom status. The rhythm information derived from the large variety of AECG recording systems can often lead to appropriate and patient-specific medical and interventional management. The details in this document provide background and framework from which to apply AECG techniques in clinical practice, as well as clinical research.

Robotic-Assisted Left Ventricular Lead Placement.

Robot-assisted left ventricular lead implantation for cardiac resynchronization therapy is a feasible and safe technique with superior visualization, dexterity, and precision to target the optimal pacing site. The technique has been associated with clinical response and beneficial reverse remodeling comparable with the conventional approach via the coronary sinus. The lack of clinical superiority and a residual high nonresponder rate suggest that the appropriate clinical role for the technique remains as rescue therapy.

Renal denervation for treatment of cardiac arrhythmias: state of the art and future directions.

It has now been more than a quarter of a century since modulation of the sympathetic nervous system was proposed for the treatment of cardiac arrhythmias of different origins. But it has also been some time since some of the early surgical attempts have been abandoned. With the development of ablation techniques, however, new approaches and targets have been recently introduced that have revolutionized our way of thinking about sympathetic modulation. Renal nerve ablation technology is now being successfully used for the treatment of resistant hypertension, but the indication spectrum might broaden and new therapeutic options might arise in the near future. This review focuses on the possible impact of renal sympathetic system modulation on cardiac arrhythmias, the current evidence supporting this approach, and the ongoing trials of this method in electrophysiological laboratories. We will discuss the potential roles that sympathetic modulation may play in the future.

Absolute survival after cardiac resynchronization therapy according to baseline QRS duration: a multinational 10-year experience: data from the Multicenter International CRT Study.

BACKGROUND: In the major trials of cardiac resynchronization therapy (CRT), the survival benefit of the therapy, relative to control subjects, increases with QRS duration. In the non-CRT heart failure population, however, a wide QRS duration is associated with a shorter survival. Relative survival benefit from a therapy, however, is not synonymous with a longer absolute survival. We sought to determine whether baseline QRS duration relates to the absolute survival after CRT. METHODS AND RESULTS: In this prospective, longitudinal, observational study, 3,319 consecutive patients undergoing CRT (QRS 120-149 ms 26%, QRS 150-199 ms 58%, and QRS ≥200 ms 16%) were assessed in relation to mortality over 10 years. Overall mortality rates (per 100 patient-years) were 9.2%, 9.3%, and 13.3% in the 3 groups, respectively (all P < .001). Cardiac mortality rates were 6.2, 6.0, and 9.9 per 100 patient-years, respectively (all P < .001). Compared with the QRS 120-149 ms group, cardiac mortality was highest in the QRS ≥200 ms group (hazard ratio [HR] 1.72 [95% CI 1.35-2.19], P < .001), independent of age, gender, New York Heart Association class, presence of atrial fibrillation, heart failure etiology, and left ventricular ejection fraction. Median survival after CRT was longest in patients with a width of QRS 120-149 ms and shortest in patients with a QRS ≥200 ms (P < .001). In multivariable analyses, a QRS ≥200 ms emerged as a powerful independent predictor of both overall (HR 1.44 [95% CI 1.07-1.94], P = .017) and cardiac mortality (HR 1.59 [95% CI 1.14-2.24], P = .007). CONCLUSIONS: At long-term follow-up, absolute overall and cardiac survival after CRT is similar in patients with a preimplant QRS duration of 120 to 149 ms and 150 to 199 ms but markedly shorter in patients with a QRS ≥200 ms.

The impact of nonsustained ventricular tachycardia on reverse remodeling, heart failure, and treated ventricular tachyarrhythmias in MADIT-CRT.

INTRODUCTION: This study determined whether the presence of nonsustained ventricular tachycardia (NSVT) was predictive of clinical events in MADIT-CRT (multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy) patients treated with CRT-defibrillator. METHODS AND RESULTS: We analyzed 24-hour Holters for the presence of NSVT. Patients were then stratified by the etiology (ischemic or nonischemic) of cardiomyopathy. The impact of NSVT on heart failure events (HF), implantable cardioverter-defibrillator (ICD) therapy for rapid ventricular tachycardia (VT) or fibrillation (VF), and reverse remodeling was determined. At least a single episode of NSVT was recorded in 483 (49%) patients. These patients had a higher burden of premature ventricular contractions, lower percentage of biventricular (BiV) pacing, and significantly less reduction in left ventricular end-diastolic and end-systolic volumes. The risk of HF was significantly greater in patients with nonischemic cardiomyopathy and NSVT (hazard ratio [HR] 2.89; 95% confidence interval [CI]: 1.49-5.61; P = 0.002). The risk of rapid VT/VF was significantly greater (in both ischemic and nonischemic patients) when NSVT was observed (HR 2.06; 95% CI: 1.30-3.26; P = 0.002 in ischemic patients; HR 3.09; 95% CI: 1.80-5.28; P < 0.001 in nonischemic patients). CONCLUSIONS: MADIT-CRT patients with NSVT had a high burden of ventricular ectopy, lower percentage of BiV pacing, and less reverse remodeling. These patients had an increase in HF (in nonischemic cardiomyopathy patients) and rapid VT/VF ICD therapies (in ischemic and nonischemic patients). These findings may have implications for the management of nonsustained ventricular ectopy in CRT patients.

Initial independent outcomes from focal impulse and rotor modulation ablation for atrial fibrillation: multicenter FIRM registry.

INTRODUCTION: The success of pulmonary vein isolation (PVI) for atrial fibrillation (AF) may be improved if stable AF sources identified by Focal Impulse and Rotor Mapping (FIRM) are also eliminated. The long-term results of this approach are unclear outside the centers where FIRM was developed; thus, we assessed outcomes of FIRM-guided AF ablation in the first cases at 10 experienced centers. METHODS: We prospectively enrolled n = 78 consecutive patients (61 ± 10 years) undergoing FIRM guided ablation for persistent (n = 48), longstanding persistent (n = 7), or paroxysmal (n = 23) AF. AF recordings from both atria with a 64-pole basket catheter were analyzed using a novel mapping system (Rhythm View(TM) ; Topera Inc., CA, USA). Identified rotors/focal sources were ablated, followed by PVI. RESULTS: Each institution recruited a median of 6 patients, each of whom showed 2.3 ± 0.9 AF rotors/focal sources in diverse locations. 25.3% of all sources were right atrial (RA), and 50.0% of patients had ≥1 RA source. Ablation of all sources required a total of 16.6 ± 11.7 minutes, followed by PVI. On >1 year follow-up with a 3-month blanking period, 1 patient lost to follow-up (median time to 1st recurrence: 245 days, IQR 145-354), single-procedure freedom from AF was 87.5% (patients without prior ablation; 35/40) and 80.5% (all patients; 62/77) and similar for persistent and paroxysmal AF (P = 0.89). CONCLUSIONS: Elimination of patient-specific AF rotors/focal sources produced freedom-from-AF of ≈80% at 1 year at centers new to FIRM. FIRM-guided ablation has a rapid learning curve, yielding similar results to original FIRM reports in each center's first cases.

Comparative safety of periablation anticoagulation strategies for atrial fibrillation: data from a large multicenter study.

BACKGROUND: There are a variety of periprocedural anticoagulation strategies for atrial fibrillation (AF) ablation, including the use of dabigatran. It is unclear which strategy is superior. OBJECTIVE: To compare the safety and efficacy of anticoagulation with uninterrupted warfarin, dabigatran, and warfarin with heparin bridging in patients undergoing ablation of AF at four experienced centers. METHODS AND RESULTS: In this retrospective analysis, 882 patients (mean age: 61 ± 11 years) underwent ablation of AF using uninterrupted warfarin (n = 276), dabigatran (n = 374), or warfarin with heparin bridging (n = 232) for periprocedural anticoagulation. The rate of total complications was 23/276 (8.3%) in the uninterrupted warfarin group, 30/374 (8.0%) in the dabigatran group, and 29/232 (12.5%) in the bridged group (P = 0.15). Major complications were more frequent in the uninterrupted warfarin group 12/276 (4.3%) compared with 3/374 (0.8%) in dabigatran and 6/232 (2.6%) in the bridged group (P = 0.01). The most common major complication was the need for transfusion or occurrence of major bleeding. Minor complications did not differ among the three groups. On multivariate analysis, female gender (odds ratio [OR] 1.93, confidence interval [CI] 1.16-3.19, P = 0.011), bridging heparin (OR 2.13, CI 1.100-3.941, P = 0.016), use of triple antithrombotic therapy (OR 1.77, CI 1.05-2.98, P = 0.033), and prior myocardial infarction (OR 2.40, CI 1.01-5.67, P = 0.046) independently predicted total complications. CONCLUSIONS: When comparing the use of uninterrupted warfarin, dabigatran, and warfarin with heparin bridging in patients undergoing catheter ablation of AF, dabigatran was not associated with increased risk, major complications were more common in the uninterrupted warfarin group, and after adjustment, warfarin with bridging increased total complications.

QRS Morphology and the Risk of Ventricular Tachyarrhythmia in Cardiac Resynchronization Therapy Recipients.

BACKGROUND: There are conflicting data on the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risk of life-threatening ventricular tachyarrhythmia in heart failure patients. OBJECTIVES: The authors aimed to assess whether QRS morphology is associated with risk of ventricular arrhythmias in CRT recipients. METHODS: The study population comprised 2,862 patients implanted with implantable cardioverter defibrillator (ICD)/CRT-D for primary prevention who were enrolled in 5 landmark primary prevention ICD trials (MADIT-II [Multicenter Automated Defibrillator Implantation Trial], MADIT-CRT [Multicenter Automated Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], MADIT-RIT [Multicenter Automated Defibrillator Implantation Trial-Reduction in Inappropriate Therapy], MADIT-RISK [Multicenter Automated Defibrillator Implantation Trial-RISK], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter Defibrillators]). Patients with QRS duration ≥130 ms were divided into 2 groups: those implanted with an ICD only vs CRT-D. The primary endpoint was fast ventricular tachycardia (VT)/ventricular fibrillation (VF) (defined as VT ≥200 beats/min or VF), accounting for the competing risk of death. Secondary endpoints included appropriate shocks, any sustained VT or VF, and the burden of fast VT/VF, assessed in a recurrent event analysis. RESULTS: Among patients with left bundle branch block (n = 1,792), those with CRT-D (n = 1,112) experienced a significant 44% (P < 0.001) reduction in the risk of fast VT/VF compared with ICD-only patients (n = 680), a significantly lower burden of fast VT/VF (HR: 0.55; P = 0.001), with a reduced burden of appropriate shocks (HR: 0.44; P < 0.001). In contrast, among patients with non-left bundle branch block (NLBBB) (N = 1,070), CRT-D was not associated with reduction in fast VT/VF (HR: 1.33; P = 0.195). Furthermore, NLBBB patients with CRT-D experienced a statistically significant increase in the burden of fast VT/VF events compared with ICD-only patients (HR: 1.90; P = 0.013). CONCLUSIONS: Our data suggest a potential proarrhythmic effect of CRT among patients with NLBBB. These data should be considered in patient selection for treatment with CRT.