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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., (© 2017 Wiley Periodicals, Inc.)

Aims: Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group., Methods and Results: Using Kaplan-Meier plots, we estimated the threshold of BIV pacing percentage needed for CRT-D to be superior to ICD on the end-point of heart failure (HF) or death in 1219 left bundle branch block (LBBB) patients in the MADIT-CRT trial. Patients were censored at the time of crossover. In multivariable Cox analyses, no difference was seen in the risk of HF/death between ICD and CRT-D patients with BIV pacing ≤90% [HR = 0.78 (0.47-1.30), P = 0.344], and with increasing BIV pacing the risk of HF/death was decreased [CRT-D BIV 91-96% vs. ICD: HR = 0.63 (0.42-0.94), P = 0.024 and CRT-D BIV ≥97% vs. ICD: HR = 0.32 (0.23-0.44), P < 0.001]. The risk of death alone was reduced by 52% in CRT-D patients with BIV ≥97% (HR = 0.48, P < 0.016), when compared with ICD patients. Within the CRT-D group, for every 1 percentage point increase in BIV pacing, the risk of HF/death and death alone significantly decreased by 6 and 10%, respectively. Increasing BIV pacing percentage was associated with significant reductions in left ventricular volume., Conclusion: In patients with LBBB, who were in sinus rhythm at enrolment, BIV pacing exceeding 90% was associated with a benefit of CRT-D in HF/death when compared with ICD patients. Furthermore, BIV pacing ≥97% was associated with an even further reduction in HF/death, a significant 52% reduction in death alone, and increased reverse remodelling. Clinical trials.gov identifier: NCT00180271., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Objective: The aim of the present study was to assess a possible association between myocardial substrate, implantable cardioverter defibrillator (ICD) shocks, and subsequent mortality., Methods: Within the multicentre automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) population (n = 1790), we investigated the association between myocardial substrate, ICD shocks and subsequent mortality using multivariate Cox regression analyses and landmark analyses at 1-year follow-up., Results: The 4-year cumulative probability of ICD shocks was 13% for appropriate shock and 6% for inappropriate shock. Compared with patients who never received ICD therapy, patients who received appropriate shock had an increased risk of mortality [HR = 2.3 (1.47-3.54), P < 0.001], which remained increased after adjusting for echocardiographic remodelling at 1 year (HR = 2.8, P = 0.001). Appropriate anti-tachycardia pacing (ATP) only was not associated with increased mortality (P = 0.42). We were not able to show an association between inappropriate shocks (P = 0.53), or inappropriate ATP (P = 0.10) and increased mortality. Advanced myocardial structural disease, i.e. higher baseline echocardiographic volumes and lack of remodelling at 1 year, was present in patients who received appropriate shocks but not in patients who received inappropriate shocks or no shocks., Conclusion: In the MADIT-CRT study, receiving appropriate ICD shocks was associated with an increased risk of subsequent mortality. This association was not evident for appropriate ATP only. These findings, along with advanced cardiac structural disease in the patients who received appropriate shocks, suggest that the compromised myocardium is a contributing factor to the increased mortality associated with appropriate ICD shock therapy. Clinical trials.gov identifier: NCT00180271.

Background: Optimization of the interventricular delay (VV-optimization) in cardiac resynchronization therapy (CRT) patients can be performed by evaluation of mechanical dyssynchrony. However, there is no consensus on which method to use. In this study, three conceptually different methods were evaluated., Methods: Thirty consecutive CRT patients were included. At day 1, patients were atrioventricular and VV optimized by left ventricular outflow tract (LVOT) velocity time integral (VTI). At 6 months, 2D strain (2DS) echocardiography and tissue Doppler imaging (TDI) was performed at six different VV-programming delay in steps of 20 ms. LVOT and three indices of dyssynchrony were evaluated at each setting: standard deviation (SD) of time-to-peak strain in 12 segments (2DS-SD), SD of time-to-peak velocities in 12 segments (TDI-SD), and maximal activation delay (AD-max) by cross-correlation analysis (XCA) of TDI-derived myocardial acceleration curves., Results: Feasibility was 90% for 2DS-SD and TDI-SD and 97% for AD-max. Coefficients of variation for intraobserver variability were 13% for 2DS-SD, 11% for TDI-SD, and 6% for AD-max. A relative increase in LVOT VTI > 10% was observed in 5/12 (42%) nonresponders and 7/18 (39%) responders to CRT. Optimization by all three dyssynchrony indices significantly increased LVOT VTI compared to simultaneous pacing and optimal setting at day 1 (P < 0.05, all). LVOT VTI was highest when using AD-max, and AD-max showed the best agreement (k = 0.71)., Conclusion: VV optimization at 6 months acutely benefits both responders and nonresponders; however, dyssynchrony indices do not perform equally well. XCA has a high feasibility and reproducibility and appears to be superior to time-to-peak techniques., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Objectives: The goal of this study was to evaluate the effects of carvedilol and metoprolol on the endpoint of inappropriate implantable cardioverter-defibrillator therapy in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy) study., Background: The impact of carvedilol and metoprolol on inappropriate therapy in heart failure patients with devices has not yet been investigated., Methods: All patients in the MADIT-CRT study who received a device (N = 1,790) were identified. Using time-dependent Cox regression analysis, we compared patients treated with different types of beta-blockers or no beta-blockers on the primary endpoint of inappropriate therapy, delivered as antitachycardia pacing (ATP) or shock therapy. Secondary endpoints were inappropriate therapy due to atrial fibrillation and atrial tachyarrhythmias, also evaluated as ATP or shock therapy., Results: Inappropriate therapy occurred in 253 (14%) of 1,790 patients during a follow-up period of 3.4 ± 1.1 years. Treatment with carvedilol was associated with a significantly decreased risk of inappropriate therapy compared with metoprolol (hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.48 to 0.85]; p = 0.002). The reduction in risk was consistent for inappropriate ATP (HR: 0.66 [95% CI: 0.48 to 0.90]; p = 0.009) and inappropriate shock therapy (HR: 0.54 [95% CI: 0.36 to 0.80]; p = 0.002). The risk of inappropriate therapy caused by atrial fibrillation was also reduced in patients receiving carvedilol compared with metoprolol (HR: 0.50 [95% CI: 0.32 to 0.81]; p = 0.004). General use of beta-blockers (93%) and adherence in this study was high., Conclusions: In heart failure patients undergoing either cardiac resynchronization therapy with a defibrillator or with an implantable cardioverter-defibrillator device, carvedilol was associated with a 36% lower rate of inappropriate ATP and shock therapy compared with metoprolol. Inappropriate therapy due to atrial fibrillation was associated with a 50% lower rate in patients receiving carvedilol compared with those receiving metoprolol. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The majority of implantable cardioverter defibrillators (ICDs) are dual-chamber devices, but studies on the frequency of inappropriate therapy in dual- versus single-chamber devices have shown conflicting results. The aim of this study is to determine whether implantation of dual-chamber ICD devices decrease the incidence of inappropriate therapy without an unacceptable increase in complications., Methods: In the ICD arm of the MADIT-CRT study (N = 704), comparisons of single- versus dual-chamber ICD devices were investigated on the endpoints of inappropriate therapy (antitachycardia pacing [ATP] and shocks) and device- and procedure-related complications by use of multivariate Cox proportional hazard regression analysis (hazard ratio dual:single chamber) adjusting for relevant covariates., Results: The frequency of inappropriate therapies in single- and dual-chamber recipients was 41/294 (14%) and 50/410 (12%), respectively. There was no significant difference in overall inappropriate therapy (hazard ratio [HR] = 0.95 [CI: 0.63-1.45], P = 0.95) or inappropriate ATP (HR = 0.98 [CI: 0.61-1.58], P = 0.94), between single- and dual-chamber devices, using single-chamber as a reference (Dual:Single). However, there was a trend toward a decrease in inappropriate shocks (HR = 0.60 [CI: 0.34-1.08], P = 0.09) in the dual-chamber group. The same was evident when only analyzing inappropriate therapy for atrial tachyarrhythmias (HR = 0.88 [CI: 0.56-1.38], P = 0.58). There was no significant difference between the groups in device- or procedure-related complications (HR = 1.54 [CI: 0.82-2.90], P = 0.18)., Conclusion: No significant difference was found in inappropriate therapy or complications in patients treated with single- versus dual-chamber ICD devices., (© 2013 Wiley Periodicals, Inc.)

Objectives: This study sought to compare the effects of metoprolol and carvedilol in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study., Background: The impact of beta-blockers in heart failure (HF) patients with devices is uninvestigated., Methods: All patients receiving either metoprolol or carvedilol in the MADIT-CRT study were identified and compared. Time-dependent Cox proportional hazard regression analyses were performed to assess differences in hospitalization for HF or death and ventricular arrhythmias., Results: Hospitalization for HF or death occurred in 30% of the patients on metoprolol and in 23% on carvedilol. Treatment with carvedilol was associated with a significantly decreased risk of hospitalization for HF or death when compared with metoprolol (hazard ratio [HR]: 0.70, [95% confidence interval (CI): 0.57 to 0.87], p = 0.001). This reduction in risk was further attenuated in the subgroup of cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) patients (HR: 0.61 [95% CI: 0.46 to 0.82], p = 0.001) and CRT-D patients with left bundle branch block (LBBB) (HR: 0.51 [95% CI: 0.35 to 0.76], p < 0.001). Ventricular arrhythmias occurred in 26% and in 22%, respectively, of the patients receiving metoprolol or carvedilol (HR: 0.80 [95% CI: 0.63 to 1.00], p = 0.050). General use of beta-blockers and adherence in this study was high, and a clear dose-dependent relationship was found in carvedilol, but not in metoprolol., Conclusions: In HF patients in New York Heart Association functional class I and II and with wide QRS complexes, carvedilol was associated with a 30% reduction in hospitalizations for HF or death when compared with metoprolol. A novel beneficial and synergistic effect of carvedilol was seen in patients with CRT-D and LBBB. Furthermore, we found a pronounced dose-dependent relationship in carvedilol, but not in metoprolol., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Patients with cancer are insufficiently represented in randomized clinical trials investigating efficacy of implantable cardioverter-defibrillators (ICDs). We aimed to describe outcomes in patients with a pre-existing diagnosis of cancer at time of ICD implantation.Methods and Results: We utilized Danish nationwide registries to identify primary and secondary prevention ICD implantations from 2007 to 2012. Multivariable Cox models were used to assess the risk of appropriate ICD therapy and mortality in patients with and without cancer at time of implantation. During a median follow-up of 2.1 years, 2935 primary prevention ICD and 2730 secondary prevention ICD implantations were identified. Out of these [289 (5.1%)] had pre-existing cancer [primary 140 (4.8%), secondary 149 (5.5%)]. No differential risk for appropriate ICD therapy was found between patients with or without cancer, [primary cancer: 19/140, no cancer: 380/2795, hazard ratio (HR) = 1.07 (0.67-1.69)] and [secondary cancer: 42/149, no cancer: 699/2581, HR = 1.28 (0.93-1.75)]. In primary patients, cancer was not associated with higher risk of 1-year [cancer: 10/140, no cancer: 133/2795, HR = 1.20 (0.84-2.28)] or all-time mortality [cancer: 22/140, no cancer: 339/2795, HR = 1.13 (0.74-1.75)]. In secondary patients, cancer was associated with a higher 1-year [cancer: 19/149, no cancer: 108/2581, HR = 2.62 (1.60-4.29)] and all-time mortality [cancer: 44/149, no cancer: 315/2581, HR = 2.36 (1.71-3.24)].Conclusion: Implantable cardioverter-defibrillators were implanted in a minority of cancer patients. No difference in risk of appropriate therapy was observed between cancer and non-cancer patients, regardless of implant indication. Cancer was associated with increased mortality in secondary prevention ICD patients, but not in primary prevention ICD patients. In secondary prevention ICD patients, the majority of deaths were attributable to cancer. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to test myocardial deformation imaging using speckle-tracking echocardiography for predicting outcomes in chronic aortic regurgitation. Background: In chronic aortic regurgitation, left ventricular (LV) dysfunction must be detected early to allow timely surgery. Speckle-tracking echocardiography has been proposed for this purpose, but the clinical value of this method in aortic regurgitation has not been established. Methods: A longitudinal study was performed in 64 patients with moderate to severe aortic regurgitation. Thirty-five patients were managed conservatively with frequent clinical visits and sequential echocardiography and followed for an average of 19 ± 8 months, while 29 patients underwent surgery for the valve lesion and were followed for 6 months post-operatively. Baseline LV function by speckle-tracking and conventional echocardiography was compared with impaired outcome after surgery (defined as persisting symptoms or persisting LV dilation [LV end-diastolic volume index ≥87 ml/m2] or dysfunction [LV ejection fraction <50%]) and with disease progression during conservative management (defined as development of symptoms, increase in LV volume >15%, or decrease in LV ejection fraction >10%). Results: Reduced myocardial systolic strain, systolic strain rate, and early diastolic strain rate by speckle-tracking echocardiography was associated with disease progression during conservative management (−16.3% vs. −19.0%, p = 0.02; −1.04 vs. −1.19 s−1, p = 0.02; and 1.20 vs. 1.60 s−1, p = 0.002, respectively) and with impaired outcome after surgery (−11.5% vs. −15.6%, p = 0.01; −0.88 vs. −1.01 s−1, p = 0.04; and 0.98 vs. 1.33 s−1, p = 0.01, respectively). Conventional parameters of LV function and size (LV ejection fraction and LV end-diastolic volume index) were associated with outcome after surgery (p = 0.04 and p = 0.01, respectively) but not with outcome during conservative management (p = 0.57 and p = 0.39, respectively). Conclusions: Speckle-tracking echocardiography is useful for the early detection of LV systolic and diastolic dysfunction in chronic aortic regurgitation. [Copyright &y& Elsevier]

Background: The incidence and risk associated with new-onset atrial fibrillation (AF) occurring after discharge in patients with acute myocardial infarction (MI) remains unknown. Objective: This study sought to describe the incidence and clinical risk associated with postdischarge new-onset AF in post-MI patients with left ventricular systolic dysfunction. Methods: The population included 271 post-MI patients with left ventricular ejection fraction ≤40% and no history of previous AF from the Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction (CARISMA) study. All patients were implanted with an implantable cardiac monitor and followed up every 3 months for 2 years. Major cardiovascular events were defined as reinfarction, stroke, hospitalization for heart failure, or death. Results: The risk of new-onset AF is highest during the first 2 months after the acute MI (16% event rate) and decreases until month 12 post-MI, after which the risk for new-onset AF is stable. The risk of major cardiovascular events was increased in patients with AF events ≥30 seconds (hazard ratio [95% CI] = 2.73 [1.35 to 5.50], P = .005), but not in patients with AF events lasting <30 seconds (hazard ratio [95% CI] = 1.17 [0.35 to 3.92], P = .80). More than 90% of all recorded AF events were asymptomatic. Conclusion: Using an implantable cardiac monitor, the incidence of new-onset AF was found to be 4-fold higher than earlier reported. In the study population, in which treatment with beta-blockers was optimized, the vast majority of AF events were asymptomatic, emphasizing the importance of using continuous monitoring for studies concerning AF in heart failure patients. A duration of 30 seconds or more identified clinically important AF episodes documented by an implantable cardiac monitor. [ABSTRACT FROM AUTHOR]

Background: Limited data regarding the effect of right ventricular pacing (RVP) on long-term survival following implantable cardioverter-defibrillator (ICD) implantation are available. Objective: The purpose of this study was to evaluate the effect of RVP on the long-term survival benefit of primary ICD therapy. Methods: Mortality data were obtained for all patients enrolled in the Multicenter Automatic Defibrillator Trial-II (MADIT-II) during an extended follow-up period of 8 years. The cumulative percent RVP during the trial was categorized as low (≤50% [n = 369]) and high (>50% [n = 198]). The benefit of ICD versus non-ICD therapy (n = 490) was evaluated in the two pacing categories during the early (0–3 years) and late (4–8 years) phases of the extended follow-up period. Results: During the early phase of the extended follow-up period, ICD therapy was associated with similar benefits in the low-RVP and high-RVP subgroups (hazard ratio [HR] = 0.35 and 0.38, respectively, P <.001 for both). In contrast, during the late phase, the long-term survival benefit of the ICD was maintained among patients with low RVP (HR = 0.60, P <.001) and attenuated among those with the high RVP (HR = 0.89, P = .45). An increased risk for late mortality associated with high versus low RVP was evident only among patients without left bundle branch [LBBB] at enrollment (HR = 1.63, P = .002). Conclusion: Among ICD recipients, high RVP is associated with a significant increase in the risk of long-term mortality and with attenuated device efficacy. The deleterious effects of RVP are pronounced mainly in non-LBBB patients, suggesting a possible role for combined cardiac resynchronization–defibrillator therapy in this population. [ABSTRACT FROM AUTHOR]

Predicting New-Onset AF. Background: Atrial fibrillation (AF) increases morbidity and mortality in patients with previous myocardial infarction and left ventricular systolic dysfunction. The purpose of this study was to identify patients with a high risk for new-onset AF in this population using invasive and noninvasive electrophysiological tests. Methods: The study included 271 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with an acute myocardial infarction (AMI) and left ventricular ejection fraction ≤40% without previous AF at enrollment. Within 21 days after the AMI, an implantable loop recorder was inserted and used to diagnose AF over the 2-year study duration. The following tests were performed: heart rate variability (HRV) and turbulence (HRT) analyses from repeated 24-hour Holter recordings, 2-dimensional (2D)-echocardiograms, exercise test, and programmed electrophysiologic stimulation. Results: A total of 101 patients (37%) developed AF during the study. Predictive measures included several indexes of HRV including reduced low-frequency (LF) power from spectral HRV analysis (adjusted HR = 1.6, P = 0.034), HRT slope ≤2.5 (HR = 1.6, P = 0.032) and Detrended Fluctuation Analysis (DFA1) from HRV analysis (HR = 1.8, P = 0.011); all are measures of cardiac autonomic nervous system dysfunction. Combined with age >60 years, low values for LF, HRT slope, and DFA1 provided a powerful risk score for prediction of new-onset AF (1–2 points: HR = 4.3, P = 0.001, 3–4 points: HR = 7.0, P < 0.001). Conclusion: Abnormal HRV and HRT parameters, which are associated with disturbances in the cardiac autonomic regulation, are associated with increased risk of new-onset AF independently of conventional clinical risk variables. (J Cardiovasc Electrophysiol, Vol. 21, pp. 983-990, September 2010) [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the association between diastolic dysfunction and long-term occurrence of new-onset atrial fibrillation (AF) and cardiac events in patients with acute myocardial infarction (AMI) and left ventricular (LV) systolic dysfunction. [ABSTRACT FROM AUTHOR]

Background--The relationship between diabetes mellitus and risk of inappropriate or appropriate therapy in patients receiving an implantable cardioverter-defibrillator (ICD) and resynchronization therapy has not been investigated thoroughly. The effect of innovative ICD programming on therapy delivery in these patients is unknown. Methods and Results--The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) randomized patients with a primary prophylactic ICD indication to 3 different types of ICD programming: conventional programming with a ventricular tachycardia zone of 170 to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone ≥200 bpm (arm B), or 60-second-delayed therapy (arm C). The end points of inappropriate therapy, appropriate therapy, and death were assessed among 485 patients with and 998 without diabetes mellitus. Innovative ICD programming reduced the risk of inappropriate therapy regardless of diabetes mellitus, although a trend toward a more pronounced effect of high-rate cutoff programming was seen in patients without diabetes mellitus (P for interaction=0.06). Diabetes mellitus was associated with a decreased risk of inappropriate therapy (hazard ratio, 0.54; 95% confidence interval, 0.36-0.80; P=0.002) and increased risk of appropriate therapy (hazard ratio,l.58; 95% confidence interval, 1.17-2.14; P=0.003). In diabetic patients, there was significantly increased risk of death in those who had inappropriate therapy (hazard ratio, 4.17; 95% confidence interval, 1.52-11.40; P=0.005) and appropriate therapy (hazard ratio, 2.49; 95% confidence interval, 1.06-5.87; P=0.037) compared with those who did not. Conelusions--Innovative high-rate cutoff or delayed ICD programming was associated with a reduction in inappropriate therapy in patients with and without diabetes mellitus. Diabetes mellitus was associated with lower risk of inappropriate therapy but higher risk of appropriate therapy. Appropriate and inappropriate ICD therapy was associated with increased mortality in diabetic patients. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the effect of both history of intermittent atrial tachyarrhythmias (IAT) and in-trial IAT on the risk of heart failure (HF) or death comparing cardiac resynchronization therapy with defibrillator (CRT-D) to implantable cardioverter-defibrillator (ICD) treatment in mildly symptomatic HF patients with left bundle branch block (LBBB). Background: Limited data exist regarding the benefit of CRT-D in patients with IAT. Methods: The benefit of CRT-D in reducing the risk of HF/death was evaluated using multivariate Cox models incorporating the presence of, respectively, a history of IAT at baseline and time-dependent development of in-trial IAT during follow-up in 1,264 patients with LBBB enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study. Results: The overall beneficial effect of CRT-D versus ICD on the risk of HF/death was not significantly different between LBBB patients with or without history of IAT (HR: 0.50, p = 0.028, and HR: 0.46, p < 0.001, respectively; p for interaction = 0.79). Among patients who had in-trial IAT, CRT-D was associated with a significant 57% reduction in the risk of HF/death compared with ICD-only therapy (HR: 0.43, p = 0.047), similar to the effect of the device among patients who did not have IAT (HR: 0.47, p < 0.001; p for interaction = 0.85). The percentage of patients with biventricular pacing ≥92% was similar in both groups (p = 0.43). Consistent results were shown for the benefit of CRT-D among patients who had in-trial atrial fibrillation/flutter (HR: 0.30, p = 0.027; p for interaction = 0.41). Conclusions: In the MADIT-CRT study, the clinical benefit of CRT-D in LBBB patients was not attenuated by prior history of IAT or by the development of in-trial atrial tachyarrhythmias. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy; NCT00180271) [Copyright &y& Elsevier]