Martin Stockburger

Preventing ventricular dysfunction in pacemaker patients without advanced heart failure: results from a multicentre international randomized trial (PREVENT-HF)

Previous experimental and clinical studies have consistently suggested that right ventricular (RV) apical pacing has important adverse effects. Ventricular pacing (VP), however, is required, and cannot be reduced in many patients with atrioventricular (AV) block. The PREVENT‐HF study was an international randomized trial that explored differences in left ventricular (LV) remodelling during RV apical vs. biventricular (BIV) pacing in patients with AV block.

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.

PR-Interval Identifies Clinical Response in Patients with Non-LBBB: A MADIT-CRT Sub-Study

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.

The impact of impaired renal function on mortality in patients with acutely decompensated chronic heart failure

Acute heart failure syndromes, commonly recognized as de novo heart failure or acute decompensated chronic heart failure (ADHF), are characterized by a rapid onset or change in signs and symptoms of heart failure requiring urgent treatment. Coexisting renal dysfunction is associated with poor prognosis in these patients. We sought to determine whether renal impairment in particular and other admission factors in general predict long‐term mortality after hospitalization for ADHF.

Long-term clinical effects of ventricular pacing reduction with a changeover mode to minimize ventricular pacing in a general pacemaker population

Abstract Aim Right ventricular pacing (VP) has been hypothesized to increase the risk in heart failure (HF) and atrial fibrillation (AF). The ANSWER study evaluated, whether an AAI-DDD changeover mode to minimize VP (SafeR) improves outcome compared with DDD in a general dual-chamber pacemaker population. Methods and results ANSWER was a randomized controlled multicentre trial assessing SafeR vs. standard DDD in sinus node disease (SND) or AV block (AVB) patients. After a 1-month run-in period, they were randomized (1 : 1) and followed for 3 years. Pre-specified co-primary end-points were VP and the composite of hospitalization for HF, AF, or cardioversion. Pre-specified secondary end-points were cardiac death or HF hospitalizations and cardiovascular hospitalizations. ANSWER enrolled 650 patients (52.0% SND, 48% AVB) at 43 European centres and randomized in SafeR (n = 314) or DDD (n = 318). The SafeR mode showed a significant decrease in VP compared with DDD (11.5 vs. 93.6%, P < 0.0001 at 3 years). Deaths and syncope did not differ between randomization arms. No significant difference between groups [HR = 0.78; 95% CI (0.48–1.25); P = 0.30] was found in the time to event of the co-primary composite of hospitalization for HF, AF, or cardioversion, nor in the individual components. SafeR showed a 51% risk reduction (RR) in experiencing cardiac death or HF hospitalization [HR = 0.49; 95% CI (0.27–0.90); P = 0.02] and 30% RR in experiencing cardiovascular hospitalizations [HR = 0.70; 95% CI (0.49–1.00); P = 0.05]. Conclusion SafeR safely and significantly reduced VP in a general pacemaker population though had no effect on hospitalization for HF, AF, or cardioversion, when compared with DDD.

Survival and Appropriate Device Interventions in Recipients of Cardioverter Defibrillators Implanted for the Primary Versus Secondary Prevention of Sudden Cardiac Death

Background: Implantable cardioverter‐defibrillators (ICD) implanted after an episode of ventricular tachyarrhythmia (VTA) or in patients at high risk of VTA lower the long‐term mortality. Comparisons of the clinical outcomes of the two indications are scarce.

Electrical Remodeling and Cardiac Dimensions in Patients Treated by Cardiac Resynchronization and Heart Failure Controls

Background: Cardiac resynchronization therapy (CRT) reduces the left ventricular diameter (LVEDD) in heart failure (HF) patients with left bundle branch block (LBBB). The study compares structural and electrical remodeling in HF patients on CRT and matched HF controls without LBBB.

The effect of ICD programming on inappropriate and appropriate ICD therapies in ischemic and nonischemic cardiomyopathy: The MADIT-RIT trial

The MADIT‐RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high‐rate cut‐off and 60‐second‐delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT‐RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy.

Extraordinarily favorable left ventricular reverse remodeling through long-term cardiac resynchronization: super-response to cardiac resynchronization.

Background: Some chronic heart failure (CHF) patients show remarkable improvement in left ventricular (LV) remodeling after cardiac resynchronization therapy (CRT), for unclear reasons. This study aimed at identifying predictors of an extraordinarily favorable response to CRT.

The Effect of Weight Loss on Clinical Outcomes in Patients Implanted With a Cardiac Resynchronization Therapy Device—A MADIT-CRT Substudy

BACKGROUND There are no data regarding the effect of weight loss on clinical outcomes in patients undergoing cardiac resynchronization therapy. This study was designed to evaluate the effect of weight loss on clinical outcomes in patients implanted with a cardiac resynchronization therapy with defibrillator (CRT-D). METHODS AND RESULTS The risk of heart failure (HF) or death, and of death alone, was compared between patients with and without weight loss of ≥2 kg or more at 1 year in the CRT-D arm of the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT). Weight loss was observed in 170 of 994 patients (17%) implanted with a CRT-D. Multivariate analysis showed a significant increase in the risk of HF or death among patients with weight loss compared with those without weight loss (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.26-2.63; P = .001). Weight loss was associated with a 79% increase in the risk of all-cause mortality (HR 1.79, 95% CI 1.16-3.34; P = .01). When analyzed in a continuous fashion, each kg of weight loss was associated with a 4% increase in the risk of HF or death (P = .03). In left bundle branch block (LBBB) patients with a CRT-D, weight loss was associated with an especially high risk of HF or death (HR 2.23, 95% CI 1.36-3.65; P = .002) and of death alone (HR 2.33, 95% CI 1.07-5.06; P = .03; interaction P = .26). CONCLUSIONS In patients with mild symptoms of HF receiving CRT-D, weight loss observed at 1 year is associated with adverse clinical outcomes, especially in those with a LBBB electrocardiographic pattern.