Anne-Christine Ruwald

Left Ventricular Ejection Fraction Normalization in Cardiac Resynchronization Therapy and Risk of Ventricular Arrhythmias and Clinical Outcomes Results From the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT–CRT) Trial

Background— Appropriate guideline criteria for use of implantable cardioverter-defibrillators (ICDs) do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-defibrillator. Methods and Results— Patients randomized to CRT-defibrillator from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial who survived and had paired echocardiograms at enrollment and at 12 months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF ⩽35% [reference], 36%–50%, and >50%) on outcomes of ventricular tachyarrhythmias (VTAs), VTA ≥200 bpm, ICD shock, heart failure or death, and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization (>50%). The average follow-up was 2.2±0.8 years. The risk of VTA was reduced in patients with LVEF >50% (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.07–0.82; P=0.023) and LVEF of 36% to 50% (HR, 0.44; 95% CI, 0.28–0.68; P<0.001). Among patients with LVEF >50%, only 1 patient had VTA ≥200 bpm (HR, 0.16; 95% CI, 0.02–1.51), none were shocked by the ICD, and 2 died of nonarrhythmic causes. The risk of HF or death was reduced with improvements in LVEF (LVEF >50%: HR, 0.29; 95% CI, 0.09–0.97; P=0.045; and LVEF of 36%–50%: HR, 0.44; 95% CI, 0.28–0.69; P<0.001). For inappropriate ICD therapy, no additional risk reduction for LVEF>50% was seen compared with an LVEF of 36% to 50%. A total of 6 factors were associated with LVEF normalization, and patients with all factors present (n=42) did not experience VTAs (positive predictive value, 100%). Conclusions— Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present, and these patients could be considered for downgrade from CRT-defibrillator to CRT-pacemaker at the time of battery depletion if no VTAs have occurred. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.Background —Appropriate guideline criteria for use of ICDs do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-D. Methods and Results —Patients randomized to CRT-D from the MADIT-CRT trial, who survived and had paired echocardiograms at enrollment and at 12-months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF≤35% (reference), LVEF:36-50%, and LVEF>50%) on outcomes of ventricular tachyarrhythmias (VTA), VTA≥200 bpm, ICD-shock, heart failure or death and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization>50%. Average follow-up hereafter was 2.2±0.8 years. The risk of VTA was reduced in LVEF>50% (HR:0.24, CI:0.07-0.82, p=0.023) and LVEF:36-50% (HR:0.44, CI:0.28-0.68 p 50% only 1 had VTA≥200 bpm (HR:0.16, CI:0.02-1.51), none were shocked by the ICD and 2 died of non-arrhythmic causes. The risk of HF/death was reduced with improvements in LVEF (>50%: HR:0.29, CI:0.09-0.97 p=0.045 and LVEF:36-50%: HR:0.44, CI:0.28-0.69 p 50% was seen when compared to LVEF:36-50%. A total of 6 factors were associated with LVEF normalization and patients with all factors present (n=42) did not experience VTAs (PPV=100%). Conclusions —Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present and these patients could be considered for downgrade from CRT-D to CRT-P at time of battery-depletion if no VTAs have occurred. Clinical Trial Registration Information —www.clinicaltrials.org. Identifier: [NCT00180271][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00180271&atom=%2Fcirculationaha%2Fearly%2F2014%2F10%2F09%2FCIRCULATIONAHA.114.011283.atom

Left Ventricular Ejection Fraction Normalization in Cardiac Resynchronization Therapy and Risk of Ventricular Arrhythmias and Clinical Outcomes: Results from the MADIT-CRT Trial

Background— Appropriate guideline criteria for use of implantable cardioverter-defibrillators (ICDs) do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-defibrillator. Methods and Results— Patients randomized to CRT-defibrillator from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial who survived and had paired echocardiograms at enrollment and at 12 months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF ⩽35% [reference], 36%–50%, and >50%) on outcomes of ventricular tachyarrhythmias (VTAs), VTA ≥200 bpm, ICD shock, heart failure or death, and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization (>50%). The average follow-up was 2.2±0.8 years. The risk of VTA was reduced in patients with LVEF >50% (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.07–0.82; P=0.023) and LVEF of 36% to 50% (HR, 0.44; 95% CI, 0.28–0.68; P<0.001). Among patients with LVEF >50%, only 1 patient had VTA ≥200 bpm (HR, 0.16; 95% CI, 0.02–1.51), none were shocked by the ICD, and 2 died of nonarrhythmic causes. The risk of HF or death was reduced with improvements in LVEF (LVEF >50%: HR, 0.29; 95% CI, 0.09–0.97; P=0.045; and LVEF of 36%–50%: HR, 0.44; 95% CI, 0.28–0.69; P<0.001). For inappropriate ICD therapy, no additional risk reduction for LVEF>50% was seen compared with an LVEF of 36% to 50%. A total of 6 factors were associated with LVEF normalization, and patients with all factors present (n=42) did not experience VTAs (positive predictive value, 100%). Conclusions— Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present, and these patients could be considered for downgrade from CRT-defibrillator to CRT-pacemaker at the time of battery depletion if no VTAs have occurred. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.Background —Appropriate guideline criteria for use of ICDs do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-D. Methods and Results —Patients randomized to CRT-D from the MADIT-CRT trial, who survived and had paired echocardiograms at enrollment and at 12-months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF≤35% (reference), LVEF:36-50%, and LVEF>50%) on outcomes of ventricular tachyarrhythmias (VTA), VTA≥200 bpm, ICD-shock, heart failure or death and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization>50%. Average follow-up hereafter was 2.2±0.8 years. The risk of VTA was reduced in LVEF>50% (HR:0.24, CI:0.07-0.82, p=0.023) and LVEF:36-50% (HR:0.44, CI:0.28-0.68 p 50% only 1 had VTA≥200 bpm (HR:0.16, CI:0.02-1.51), none were shocked by the ICD and 2 died of non-arrhythmic causes. The risk of HF/death was reduced with improvements in LVEF (>50%: HR:0.29, CI:0.09-0.97 p=0.045 and LVEF:36-50%: HR:0.44, CI:0.28-0.69 p 50% was seen when compared to LVEF:36-50%. A total of 6 factors were associated with LVEF normalization and patients with all factors present (n=42) did not experience VTAs (PPV=100%). Conclusions —Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present and these patients could be considered for downgrade from CRT-D to CRT-P at time of battery-depletion if no VTAs have occurred. Clinical Trial Registration Information —www.clinicaltrials.org. Identifier: [NCT00180271][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00180271&atom=%2Fcirculationaha%2Fearly%2F2014%2F10%2F09%2FCIRCULATIONAHA.114.011283.atom

Mortality Reduction In Relation To ICD Programming In MADIT-RIT

Background —The benefit of novel ICD programming in reducing inappropriate ICD therapy and mortality was demonstrated in MADIT-RIT. However, the cause of the mortality reduction remains incompletely evaluated. We aimed to identify factors associated with mortality, with focus on ICD therapy and programming in the MADIT-RIT population. Methods and Results —In MADIT-RIT, 1500 patients with a primary prophylactic indication for ICD or CRT-D were randomized to one of three different ICD programming arms: conventional programming (VT-zone ≥170 bpm); high-rate programming (VT-zone ≥200 bpm); and delayed programming (60 sec. delay before therapy≥170 bpm). Multivariate Cox models were used to assess the influence of time-dependent appropriate and inappropriate ICD therapy (shock and/or antitachycardia pacing [ATP]) and randomized programming arm on all-cause mortality. During an average follow-up of 1.4±0.6 years, 71 of 1500 (5%) patients died: cardiac in 40 patients (56.3 %), non-cardiac in 23 patients (32.4%), and unknown in 8 patients (11.3%). Appropriate shocks (Hazard Ratio [HR] = 6.32 [95% CI: 3.13-12.75], p<0.001) and inappropriate therapy (HR=2.61 [1.28-5.31], p=0.01) were significantly associated with an increased mortality risk. There was no evidence of increased mortality risk in patients who experienced appropriate ATP only (HR=1.02 [0.36-2.88], p=0.98). Randomization to conventional programming was identified as an independent predictor of death when compared to patients randomized to high-rate programming (HR=2.0 [1.06-3.71], p=0.03). Conclusions —In the MADIT-RIT trial, appropriate shocks, inappropriate ICD therapy, and randomization to conventional ICD programming were independently associated with an increased mortality risk. Appropriate ATP was not related to an adverse outcome. Clinical Trial Registration —clinicaltrials.gov; Unique Identifier: [NCT00947310][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00947310&atom=%2Fcircae%2Fearly%2F2014%2F08%2F17%2FCIRCEP.114.001623.atomBackground—The benefit of novel implantable cardioverter defibrillator (ICD) programming in reducing inappropriate ICD therapy and mortality was demonstrated in Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). However, the cause of mortality reduction remains incompletely evaluated. We aimed to identify factors associated with mortality, with focus on ICD therapy and programming in the MADIT-RIT population. Methods and Results—In MADIT-RIT, 1500 patients with a primary prophylactic indication for ICD or cardiac resynchronization therapy with defibrillator were randomized to 1 of 3 different ICD programming arms: conventional programming (ventricular tachycardia zone ≥170 beats per minute), high-rate programming (ventricular tachycardia zone ≥200 beats per minute), and delayed programming (60-second delay before therapy ≥170 beats per minute). Multivariate Cox models were used to assess the influence of time-dependent appropriate and inappropriate ICD therapy (shock and antitachycardia pacing) and randomized programming arm on all-cause mortality. During an average follow-up of 1.4±0.6 years, 71 of 1500 (5%) patients died: cardiac in 40 patients (56.3%), noncardiac in 23 patients (32.4%), and unknown in 8 patients (11.3%). Appropriate shocks (hazard ratio, 6.32; 95% confidence interval, 3.13–12.75; P<0.001) and inappropriate therapy (hazard ratio, 2.61; 95% confidence interval, 1.28–5.31; P=0.01) were significantly associated with an increased mortality risk. There was no evidence of increased mortality risk in patients who experienced appropriate antitachycardia pacing only (hazard ratio, 1.02; 95% confidence interval, 0.36–2.88; P=0.98). Randomization to conventional programming was identified as an independent predictor of death when compared with patients randomized to high-rate programming (hazard ratio, 2.0; 95% confidence interval, 1.06–3.71; P=0.03). Conclusions—In MADIT-RIT, appropriate shocks, inappropriate ICD therapy, and randomization to conventional ICD programming were independently associated with an increased mortality risk. Appropriate antitachycardia pacing was not related to an adverse outcome. Clinical Trial Registration—URL: clinicaltrials.gov Unique identifier: NCT00947310.

The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling

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.

Association between myocardial substrate, implantable cardioverter defibrillator shocks and mortality in MADIT-CRT

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.

Effect of metoprolol versus carvedilol on outcomes in MADIT-CRT (multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy).

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.

Impact of carvedilol and metoprolol on inappropriate implantable cardioverter-defibrillator therapy: the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy).

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).

Association Between Frequency of Atrial and Ventricular Ectopic Beats and Biventricular Pacing Percentage and Outcomes in Patients With Cardiac Resynchronization Therapy

BACKGROUND A high percentage of biventricular pacing is required for optimal outcome in patients treated with cardiac resynchronization therapy (CRT), but the influence of ectopic beats on the success of biventricular pacing has not been well established. OBJECTIVES This study sought to determine if increased ectopic beats reduce the chance of high biventricular pacing percentage and are associated with subsequent adverse outcomes. METHODS From the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy), 801 patients with an implanted CRT-defibrillator device with data available on biventricular pacing percentage and pre-implantation 24-h Holter recordings were included. Using logistic regression, we estimated the influence of ectopic beats on the percentage of biventricular pacing. Reverse remodeling was measured as reductions in atrial and left ventricular end-systolic volumes (LVESV) at 1 year. Cox models were used to assess the influence of ectopic beats on the outcomes of heart failure (HF) or death, ventricular tachyarrhythmias (VTAs), and death. RESULTS In the pre-implantation Holter recording, ectopic beats accounted for a mean 3.2 ± 5.5% of all beats. The probability of subsequent low biventricular pacing percentage (<97%) was increased 3-fold (odds ratio: 3.37; 95% confidence interval: 1.74 to 6.50; p < 0.001) in patients with 0.1% to 1.5% ectopic beats and 13-fold (odds ratio: 13.42; 95% confidence interval: 7.02 to 25.66; p < 0.001) in patients with >1.5% ectopic beats compared with those with <0.1% ectopic beats. Patients with ≥0.1% ectopic beats had significantly less reverse remodeling (percent reduction in LVESV 31 ± 15%) than patients with <0.1% ectopic beats (percent reduction in LVESV 39 ± 14%; p < 0.001). The risk of HF/death and VTA was increased significantly in those with 0.1% to 1.5% ectopic beats (hazard ratio: 3.13 and 1.84, respectively) and for >1.5% ectopic beats (hazard ratio: 2.38 and 2.74, respectively). CONCLUSIONS Relatively low frequencies of ectopic beats (≥0.1%) dramatically increase the probability of low biventricular pacing (<97%), with reduced CRT efficacy by less reverse remodeling and higher risk of HF/death and VTA. This supports pre-implantation Holter monitoring of patients selected for CRT for optimal outcome. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271).

Predictors of Spontaneous Reverse Remodeling in Mild Heart Failure Patients With Left Ventricular Dysfunction

Background—There are limited data regarding factors associated with spontaneous left ventricular reverse remodeling (S-LVRR) among mildly symptomatic heart failure (HF) patients and its prognostic implications on clinical outcomes. Methods and Results—Best subsets logistic regression analysis was used to identify factors associated with S-LVRR (defined as ≥15% reduction in left ventricular end-systolic volume at 1-year of follow-up) among 612 patients treated with internal cardioverter defibrillator–only therapy in Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) and to create a score for the prediction of S-LVRR. Cox proportional hazards regression modeling was used to assess the clinical outcome of all internal cardioverter defibrillator–only patients (n=714) with a high S-LVRR score. S-LVRR occurred in 25% of internal cardioverter defibrillator–only patients. Predictors of S-LVRR included systolic blood pressure≥140 mm Hg, serum creatinine<1.0 mg/dL, QRS 130 to 160 ms, and nonischemic cardiomyopathy. Multivariate analysis showed that each 1-point increment in S-LVRR score (range, 0–7) was associated with an 11% (P=0.019) reduction in the risk of HF or death. Treatment with cardiac resynchronization therapy was associated with a significant reduction in the risk of HF or death only among internal cardioverter defibrillator–treated patients with a low (Q1–3) S-LVRR score (hazard ratio=0.55; P<0.001), but not among those with a higher (Q4) score (hazard ratio=1.06; P=0.72). Conclusions—Our data suggest that approximately one quarter of mild HF patients eligible for biventricular pacing experience S-LVRR. Combined assessment of clinical factors associated with S-LVRR can be used to identify mild HF patients with a low risk for clinical events without cardiac resynchronization therapy intervention. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

The Effect of Intermittent Atrial Tachyarrhythmia on Heart Failure or Death in Cardiac Resynchronization Therapy With Defibrillator Versus Implantable Cardioverter-Defibrillator Patients: A MADIT-CRT Substudy (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy)

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).