Valentina Kutyifa

Survival with Cardiac-Resynchronization Therapy in Mild Heart Failure

BACKGROUND The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed that early intervention with cardiac-resynchronization therapy with a defibrillator (CRT-D) in patients with an electrocardiographic pattern showing left bundle-branch block was associated with a significant reduction in heart-failure events over a median follow-up of 2.4 years, as compared with defibrillator therapy alone. METHODS We evaluated the effect of CRT-D on long-term survival in the MADIT-CRT population. Post-trial follow-up over a median period of 5.6 years was assessed among all 1691 surviving patients (phase 1) and subsequently among 854 patients who were enrolled in post-trial registries (phase 2). All reported analyses were performed on an intention-to-treat basis. RESULTS At 7 years of follow-up after initial enrollment, the cumulative rate of death from any cause among patients with left bundle-branch block was 18% among patients randomly assigned to CRT-D, as compared with 29% among those randomly assigned to defibrillator therapy alone (adjusted hazard ratio in the CRT-D group, 0.59; 95% confidence interval [CI], 0.43 to 0.80; P<0.001). The long-term survival benefit of CRT-D in patients with left bundle-branch block did not differ significantly according to sex, cause of cardiomyopathy, or QRS duration. In contrast, CRT-D was not associated with any clinical benefit and possibly with harm in patients without left bundle-branch block (adjusted hazard ratio for death from any cause, 1.57; 95% CI, 1.03 to 2.39; P=0.04; P<0.001 for interaction of treatment with QRS morphologic findings). CONCLUSIONS Our findings indicate that in patients with mild heart-failure symptoms, left ventricular dysfunction, and left bundle-branch block, early intervention with CRT-D was associated with a significant long-term survival benefit. (Funded by Boston Scientific; ClinicalTrials.gov numbers, NCT00180271, NCT01294449, and NCT02060110.).

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

Use of the Wearable Cardioverter Defibrillator in High-Risk Cardiac Patients: Data from the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II Registry)

Background— Prospective data on the safety and efficacy of the wearable cardioverter defibrillator (WCD) in a real-world setting are lacking. The Prospective Registry of Patients Using the Wearable Defibrillator (WEARIT-II) Registry was designed to provide real-world data on the WCD as a strategy during a period of risk stratification. Methods and Results— The WEARIT-II Registry enrolled 2000 patients with ischemic (n=805, 40%), or nonischemic cardiomyopathy (n=927, 46%), or congenital/inherited heart disease (n=268) prescribed WCD between August 2011 and February 2014. Clinical data, arrhythmia events, implantable cardioverter defibrillator implantation, and improvement in ejection fraction were captured. The median age was 62 years; the median ejection fraction was 25%. The median WCD wear time was 90 days, with median daily use of 22.5 hours. There was a total of 120 sustained ventricular tachyarrhythmias in 41 patients, of whom 54% received appropriate WCD shock. Only 10 patients (0.5%) received inappropriate WCD therapy. The rate of sustained ventricular tachyarrhythmias by 3 months was 3% among patients with ischemic cardiomyopathy and congenital/inherited heart disease, and 1% among nonischemic patients (P=0.02). At the end of WCD use, 840 patients (42%) were implanted with an implantable cardioverter defibrillator. The most frequent reason not to implant an implantable cardioverter defibrillator following WCD use was improvement in ejection fraction. Conclusions— The WEARIT-II Registry demonstrates a high rate of sustained ventricular tachyarrhythmias at 3 months in at-risk patients who are not eligible for an implantable cardioverter defibrillator, and suggests that the WCD can be safely used to protect patients during this period of risk assessment.

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 Implantable Cardioverter Defibrillator Programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (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 Influence of Left Ventricular Ejection Fraction on the Effectiveness of Cardiac Resynchronization Therapy MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy)

OBJECTIVES The aim of this study was to evaluate the relationship between left ventricular (LV) ejection fraction and clinical outcome to cardiac resynchronization therapy (CRT) in mild heart failure patients enrolled in MADIT-CRT [corrected]. BACKGROUND Left ventricular ejection fraction (LVEF) is a surrogate marker of heart failure (HF) status and associated risk. Data on the effectiveness of cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild HF and better LVEF are limited. METHODS In the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study, the echocardiography core laboratory assessed baseline LVEF independent of the enrolling centers and identified a range of LVEFs, including those >30% (i.e., beyond the eligibility criteria). Echocardiographic response with CRT, defined as percent change in left ventricular end-diastolic volume (LVEDV), was analyzed in 3 prespecified LVEF groups: >30%, 26% to 30%, and ≤25%. The primary endpoint was HF or death. Secondary endpoint included all-cause mortality. RESULTS LVEF was evaluated in 1,809 study patients. There were 696 (38%) patients with LVEF >30% (in the range of 30.1% to 45.3%); 914 patients (50.5%) with LVEF 26% to 30%; and 199 patients with LVEF ≤25% (11%). The mean reduction in LVEDV with CRT-D therapy at the 1-year follow-up was directly related to increasing LVEF (LVEF >30%: 22.3%; LVEF 26% to 30%: 20.1%; and LVEF ≤25%: 18.7% reduction, respectively [p = 0.001]). CRT-D treatment similarly reduced the risk of HF/death in patients with LVEF >30% (hazard ratio [HR]: = 0.56 [95% confidence interval (CI): 0.39 to 0.82], p = 0.003), LVEF 26% to 30% (HR: 0.67: [95% CI: 0.50 to 0.90], p = 0.007), and LVEF ≤25% (HR: 0.57 [95% CI: 0.35 to 0.95], p = 0.03; all p values for LVEF-by-treatment interactions >0.1). CONCLUSIONS In MADIT-CRT, the clinical benefit of CRT was evident regardless of baseline LVEF, including those with LVEF >30%, whereas the echocardiographic response was increased with increasing LVEF, indicating that CRT might benefit patients with better LVEF. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

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.

Dyssynchrony and the Risk of Ventricular Arrhythmias

OBJECTIVES The aim of our study was to evaluate the relationship between left ventricular (LV) dyssynchrony and the risk of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) trial. BACKGROUND Intraventricular mechanical dyssynchrony might be an important factor in ventricular arrhythmogenesis by enhancing electrical heterogeneity in heart failure patients. The effects of dyssynchrony have not yet been evaluated in a large cohort of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy with defibrillator (CRT-D) patients. METHODS LV dyssynchrony was measured at baseline and at 12-months by speckle-tracking echocardiography, defined as the standard deviation of time to peak systolic strain in 12 LV myocardial segments. The endpoint was the first VT/VF/death or VT/VF. LV dyssynchrony was evaluated in 764 left bundle branch block (LBBB) patients and in 312 non-LBBB patients. RESULTS Baseline LV dyssynchrony was not predictive of VT/VF/death or VT/VF in LBBB or non-LBBB patients in either treatment arm. In CRT-D patients with LBBB, improvement in LV dyssynchrony over a year was associated with significantly lower incidence of VT/VF/death (p < 0.001) and VT/VF (p < 0.001) compared to ICD patients and to CRT-D patients with unchanged or worsening dyssynchrony. Among LBBB patients, 15% decrease in LV dyssynchrony was associated with lower risk of VT/VF/death (hazard ratio: 0.49, 95% confidence interval: 0.24 to 0.99, p = 0.049) and VT/VF (hazard ratio: 0.30, 95% confidence interval: 0.12 to 0.77, p = 0.009) as compared to ICD patients. Patients without LBBB receiving CRT-D did not show reduction in VT/VF/death or in VT/VF in relation to improving dyssynchrony when evaluating cumulative event rates or risk of events. CONCLUSIONS Baseline LV dyssynchrony did not predict VT/VF/death or VT/VF in mild heart failure patients with or without LBBB. CRT-induced improvement of LV dyssynchrony was associated with significant reduction of ventricular arrhythmias in patients with LBBB.

PR Interval Identifies Clinical Response in Patients With Non–Left Bundle Branch Block A Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy Substudy

Background —In MADIT-CRT, patients with non-LBBB (including RBBB, IVCD) did not have clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D). We hypothesized that baseline PR-interval modulates clinical response to CRT-D therapy in patients with non-LBBB. Methods and Results —Non-LBBB patients (n=537, 30%) were divided in two groups based on their baseline PR-interval as normal (including minimally prolonged) PR (PR < 230 ms), and prolonged PR (PR ≥ 230 ms). The primary end point was heart failure (HF) or death. Separate secondary end points included HF events and all-cause mortality. Cox proportional hazards regression models were used to compare risk of end point events by CRT-D to ICD therapy in the PR subgroups. There were 96 patients (22%) with a prolonged PR and 438 patients (78%) with a normal PR interval. In non-LBBB patients with a prolonged PR-interval, CRT-D treatment was associated with a 73% reduction in the risk of HF/Death (HR=0.27, 95% CI: 0.13-0.57, p<0.001) and 81% decrease in the risk of all-cause mortality (HR=0.19, 95% CI: 0.13-0.57, p<0.001) compared to ICD therapy. In non-LBBB patients with normal PR, CRT-D therapy was associated with a trend towards an increased risk of HF/Death (HR=1.45, 95% CI: 0.96-2.19, p=0.078, interaction p-value<0.001) and more than a 2-fold higher mortality (HR=2.14, 95% CI: 1.12-4.09, p=0.022, interaction p-value<0.001) compared to ICD therapy. Conclusions —The data support the use of CRT-D in MADIT-CRT, non-LBBB patients with a prolonged PR-interval. In non-LBBB patients with a normal PR-interval, implantation of a CRT-D may be deleterious. Clinical Trial Registration —http://clinicaltrials.gov; Unique Identifier: [NCT00180271][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00180271&atom=%2Fcircae%2Fearly%2F2014%2F06%2F24%2FCIRCEP.113.001299.atomBackground—In Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT), patients with non–left bundle branch block (LBBB; including right bundle branch block, intraventricular conduction delay) did not have clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D). We hypothesized that baseline PR interval modulates clinical response to CRT-D therapy in patients with non-LBBB. Methods and Results—Non-LBBB patients (n=537; 30%) were divided into 2 groups based on their baseline PR interval as normal (including minimally prolonged) PR (PR <230 ms) and prolonged PR (PR ≥230 ms). The primary end point was heart failure or death. Separate secondary end points included heart failure events and all-cause mortality. Cox proportional hazards regression models were used to compare risk of end point events by CRT-D to implantable cardioverter defibrillator therapy in the PR subgroups. There were 96 patients (22%) with a prolonged PR and 438 patients (78%) with a normal PR interval. In non-LBBB patients with a prolonged PR interval, CRT-D treatment was associated with a 73% reduction in the risk of heart failure/death (hazard ratio, 0.27; 95% confidence interval, 0.13–0.57; P<0.001) and 81% decrease in the risk of all-cause mortality (hazard ratio, 0.19; 95% confidence interval, 0.13–0.57; P<0.001) compared with implantable cardioverter defibrillator therapy. In non-LBBB patients with normal PR, CRT-D therapy was associated with a trend toward an increased risk of heart failure/death (hazard ratio, 1.45; 95% confidence interval, 0.96–2.19; P=0.078; interaction P<0.001) and a more than 2-fold higher mortality (hazard ratio, 2.14; 95% confidence interval, 1.12–4.09; P=0.022; interaction P<0.001) compared with implantable cardioverter defibrillator therapy. Conclusions—The data support the use of CRT-D in MADIT-CRT non-LBBB patients with a prolonged PR interval. In non-LBBB patients with a normal PR interval, implantation of a CRT-D may be deleterious. Clinical Trial Registration—http://clinicaltrials.gov; Unique Identifier: NCT00180271.

Stabilization of the coronary sinus electrode position with coronary stent implantation to prevent and treat dislocation.

Introduction: Coronary sinus (CS) leads used for cardiac resynchronization have undergone development in the last years. However, dislocation rate remained high (5–9%). The aim of this study was to investigate the effectiveness and safety of stent implantation in a CS side vein to stabilize the left ventricular lead position after postoperative or intraoperative dislocation of the electrode.