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Aims: Patients with impaired renal function were shown to have an attenuated benefit from implantable cardioverter-defibrillator. However, there are limited data on the competing risk of ventricular arrhythmia events and death by renal function in patients without severe disease. Therefore, we aimed to assess the competing risk of ventricular arrhythmia events and death by renal function.Methods and Results: We analysed 1782 patients (99%) enrolled in Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) with glomerular filtration rate (GFR) data available. Cumulative incidence function curves were used to display the rate of ventricular tachycardia (VT), ventricular fibrillation (VF), and the competing risk of death without experiencing VT/VF. Multivariable Fine and Gray regression models and recurrent event analysis were performed. There were 355 (20%) patients with GFR < 52 and 1427 with GFR ≥ 52 (lowest quintile). The incidence of non-fatal VT/VF at 4 years was higher in patients with high GFR (26%) as compared to low GFR (16%), whereas rates of death without non-fatal VT/VF were 5% and 20% (P < 0.001). In Fine and Gray models, the low GFR group was 35% less likely to experience VT/VF compared to the high GFR [95% confidence interval (CI) 0.48-0.88, P = 0.005]. In contrast,death without experiencing VT/VF was 3.5-fold higher in the low GFR group (95% CI 2.38-5.12, P-value < 0.001). Recurrent event analysis consistently showed a lower risk of recurrent VT/VF, recurrent anti-tachycardia pacing only, and shock in the low GFR group.Conclusions: We show, in a competing risk model, a lower risk of VT/VF events and a higher risk of mortality without an arrhythmic event in patients with moderate renal dysfunction in MADIT-CRT. These findings can be used for improved selection of patients for defibrillator therapy among CRT candidates.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00180271. [ABSTRACT FROM AUTHOR]

Aims: To explore the association between resting heart rate (RHR) and ventricular tachyarrhythmias (VTA) events among patients who were enrolled in MADIT-RIT.Methods and Results: Multivariate Cox proportional hazards regression modelling was employed to evaluate the association between baseline RHR [dichotomized at the lower quartile (≤63 b.p.m.) and further assessed as a continuous measure] and the risk for any VTA, fast VTA (>200 b.p.m.), and appropriate implantable cardioverter-defibrillator (ICD) therapy, among 1500 patients who were enrolled in MADIT-RIT. Kaplan-Meier survival analysis showed that at 2 years of follow-up the rate of any VTA was significantly lower among patients with low baseline RHR (≤63 b.p.m.) as compared with faster RHR (11% vs. 19%, respectively; P = 0.001 for the overall difference during follow-up). Similar results were shown for the association with the rate of fast VTA (8% vs. 14%, respectively; P = 0.016), and appropriate ICD therapy (10% vs. 18%, respectively; P = 0.004). Multivariate analysis, after adjustment for medical therapy, showed that low baseline RHR was associated with a significant 45% (P = 0.002) reduction in the VTA risk as compared with faster baseline RHRs. When assessed as a continuous measure, each 10 b.p.m. decrement in RHR was associated with a corresponding 13% (P = 0.014) reduction in the VTA risk.Conclusion: In MADIT-RIT, low RHR was independently associated with a lower risk for life-threatening arrhythmic events. These findings suggest a possible role for RHR for improved selection of candidates for ICD therapy. [ABSTRACT FROM AUTHOR]

Background Weight loss has been associated with adverse outcomes among heart failure (HF) patients, including those receiving cardiac resynchronization therapy with defibrillator (CRT-D). The effect of significant weight change on inappropriate implantable cardioverter-defibrillator (ICD) therapy among CRT-D patients is not well understood. Methods We evaluated the impact of significant weight change at 1 year on subsequent inappropriate ICD therapy during follow-up among 993 CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. Patients were divided into three subgroups based on weight change at 1 year after enrollment: weight loss (weight loss ≥ 5%), weight gain (weight gain ≥ 5%), and stable weight (weight loss and weight gain < 5%). The primary end point was inappropriate ICD therapy. Secondary end point included inappropriate ICD therapy related to supraventricular arrhythmias (SVAs). Results There were 102 (10.3%) patients who experienced weight loss, 689 (69.4%) whose weight was stable, and 202 (20.3%) who gained weight at 1 year. Patients with weight loss had increased risk of subsequent inappropriate ICD therapy relative to patients with stable weight (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.39-3.98, P = 0.001) or weight gain (HR = 2.27, 95% CI: 1.18-4.38, P = 0.014). Furthermore, patients losing weight were at greater risk of subsequent inappropriate ICD therapy related to SVAs when compared to patients with stable weight (HR = 2.16, 95% CI: 1.18-3.95, P = 0.013) or weight gain (HR = 2.02, 95% CI: 0.95-4.29, P = 0.068). Conclusion In mild HF patients receiving CRT-D, significant weight loss at 1 year is associated with increased risk of subsequent inappropriate ICD therapy, including risk related to SVAs. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with multiple adverse cardiovascular conditions and may increase the risk of ventricular tachyarrhythmias (VT/VF). There is limited data on the association between obesity and risk of VT/VF requiring appropriate implantable cardioverter-defibrillator (ICD) therapies and the effectiveness of cardiac resynchronization therapy (CRT) to reduce risk for VT/VF. The multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT) was design to investigate effectiveness of CRT therapy to reduce cardiovascular outcome for patients with heart failure (HF) and reduced ejection fraction. Methods and results: We identified patients enrolled in the MADIT CRT trial as obese (n = 433) and non-obese (n = 845) and analyzed their risk for appropriate device therapy for VT/VF, repeated VT/VF events, fast VT/VF, as well as events after first VT/VF episodes. Obesity was defined as body mass index (BMI) ≥30 kg/m2. Among ICD patients, the risk of first appropriate ICD therapy for VT/VF at 3 years was similar between obese and non-obese patients (23 vs. 21 %, p = 0.76). CRT-D treatment reduced the risk of first appropriate ICD therapy both in non-obese ([HR]; 0.58 [CI]: 0.42-0.79; p < 0.001) and obese patients (HR 0.75, 95 % CI 0.5-1.38; p = 0.179) (interaction p value 0.323). Similarly, a significant reduction in the risk of fast VT/VF was observed in non-obese patients ([HR]; 0.49 [CI]: 0.33-0.73; p < 0.001) and obese ([HR]; 0.49 [CI]: 0.29-0.81; p < 0.01), (interaction p value 0.984). Conclusion: Obese and non-obese patients with mild heart failure have a similar risk of ventricular tachyarrhythmias. Obesity in mild heart failure did not diminish the clinical benefit of cardiac resynchronization therapy to reduce risk for appropriate ICD therapy. Clinical trial registration http://clinicaltrials.gov/ct2/show/NCT00180271. [ABSTRACT FROM AUTHOR]

Aims: We hypothesized that the relationship between LVEF and the risk of life-threatening ventricular tachyarrhythmias (VTAs) may modify the effect of a CRT device with a defibrillator (CRT-D) on VTA risk.Methods and Results: The risk of fast (≥200 b.p.m.) ventricular tachycardia/ventricular fibrillation (VT/VF) and the benefit of CRT-D in reducing VT/VF were assessed by baseline LVEF (categorized as ≤30% or 30% and assessed as a continuous measurement) in 1783 patients with mild heart failure (HF) implanted with an implantable cardioverter defibrillator (ICD) or CRT-D, enrolled in MADIT-CRT. Higher LVEF (>30%) at baseline was associated with a significantly lower risk of fast VT/VF [hazard ratio (HR) 0.54, P = 0.006], VT/VF (HR 0.62, P = 0.005), and VT/VF/death (HR 0.64, P = 0.003). Treatment with CRT-D was shown to reduce the risk of fast VT/VF in patients with LVEF ≤ 30% (n = 1100) [HR 0.64, 95% confidence interval (CI) 0.48-0.85, P = 0.002], but not among those with LVEF > 30% (n = 683) (HR 1.19, 95% CI 0.73-1.91, P = 0.502, interaction P-value = 0.03). When LVEF was assessed as a continuous measure, each 5% increment was shown to be associated with a significant 30% (P < 0.001) reduction in the risk for fast VT/VF, and with a corresponding linear reduction in the benefit of CRT-D in reducing fast VTA risk (P -value for treatment by LVEF interaction = 0.003).Conclusions: Our data suggest that in mild HF patients with cardiomyopathy there is an inverse correlation between LVEF and the risk of life-threatening VTAs, possibly contributing to the attenuation in the antiarrhythmic properties of CRT with increasing left ventricular function.Trial Registration: NCT00180271. [ABSTRACT FROM AUTHOR]

Aims There are limited and contradictory data on the effects of CRT with implantable cardioverter defibrillator ( CRT-D) on mortality as compared with CRT with pacemaker ( CRT-P). Methods and results We evaluated the long-term outcome of patients implanted with a CRT-D or CRT-P device in our high-volume single-centre experience. Data on all-cause mortality were derived from clinic visits and the Hungarian National Healthcare Fund Death Registry. Kaplan-Meier survival analyses and multivariate Cox regression models were used to evaluate all-cause mortality in patients with CRT-D vs. CRT-P, stratified by the aetiology of cardiomyopathy. From 2000 to 2011, 1122 CRT devices, 693 CRT-P ( LVEF 28.2 ± 7.4%) and 429 CRT-D ( LVEF 27.6 ± 6.4%), were implanted at our centre. During the median follow-up of 28 months, 379 patients died from any cause, 250 patients (36%) with an implanted CRT-P and 129 patients (30%) with an implanted CRT-D. There was no evidence of mortality benefit in patients implanted with a CRT-D compared with a CRT-P in the total cohort [hazard ratio ( HR) 0.98, 95% confidence interval ( CI) 0.73-1.32, P = 0.884]. In patients with ischaemic cardiomyopathy, CRT-D treatment was associated with a significant 30% risk reduction in all-cause mortality compared with an implanted CRT-P ( HR 0.70, 95% CI 0.51-0.97, P = 0.03). In non-ischaemic patients, there was no mortality benefit of CRT-D over CRT-P ( HR 0.98, 95% CI 0.73-1.32, P = 0.894, interaction P-value = 0.15). Conclusions In heart failure patients with ischaemic cardiomyopathy, CRT-D was associated with a mortality benefit compared with CRT-P, but no benefit of CRT-D over CRT-P in mortality was observed in non-ischaemic cardiomyopathy. [ABSTRACT FROM AUTHOR]

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

Loss of biventricular (BiV) pacing occurs during ventricular sensed events such as frequent ventricular ectopy, nonsustained ventricular tachycardia, and intrinsic atrioventricular nodal conduction, such as in atrial fibrillation. Ventricular sense response (VSR) pacing, a novel cardiac resynchronization therapy pacing strategy, maintains BiV pacing during these sensed ventricular events. Patients who underwent echocardiographic optimization after BiV pacemaker implantation were enrolled, and aortic velocity-time integrals (VTIs) were recorded and compared during intrinsic conduction without pacing, optimized BiV pacing, and intrinsic conduction with VSR pacing alone. Thirty-two patients were enrolled (mean age 68 ± 11 years, 78% men), with a mean baseline QRS duration of 164 ± 24 ms and a mean left ventricular ejection fraction of 23 ± 10%. The mean aortic VTI during intrinsic conduction with VSR pacing was 16.5 ± 3.6 cm, compared with 15.3 ± 3.4 cm during intrinsic conduction without pacing (p <0.001). The mean aortic VTI with optimized BiV pacing was 17.3 ± 3.6 cm, significantly better (p <0.001) compared with intrinsic conduction without pacing. Improvements in aortic VTI were higher with optimized BiV pacing compared with VSR pacing alone (p = 0.02). In the subgroup of patients with left bundle branch block–type activation, the hemodynamic improvements realized with VSR pacing were similar to optimized BiV pacing. Mean aortic VTI improvements with VSR were similar in patients with ischemic and nonischemic cardiomyopathy. In conclusion, a cardiac resynchronization therapy algorithm that maintains BiV pacing during a ventricular sensed event appears to have an aortic VTI response that is significantly better compared with intrinsic conduction without pacing. [Copyright &y& Elsevier]

Abstract: During cardiac surgery temporary epicardial atrial and ventricular leads are placed in case cardiac pacing is required postoperatively. We present the first reported series of patients with reversal of atrioventricular electrodes in the temporary pacemaker without any consequent deleterious hemodynamic effect. We review the electrocardiographic findings and discuss the findings that lead to the discovery of atrioventricular lead reversal. [Copyright &y& Elsevier]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Low pulse pressure (PP) is associated with poor outcome in hospitalized patients with systolic heart failure (HF). However, the relation between PP and response to cardiac resynchronization therapy with defibrillator (CRT-D) is unknown. We aimed to evaluate the relation between preimplantation PP and echocardiographic response to CRT-D and subsequent clinical outcome after 1 year. The relation between preimplantation PP and echocardiographic response to CRT-D (defined as >15% reduction in left ventricular (LV) end-systolic volume at 1 year) was evaluated in 754 patients with CRT-D with left bundle branch block enrolled in Multicenter Automatic Defibrillator Cardioverter Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. The association between PP at 1 year and the risk for subsequent HF or death was evaluated using multivariate Cox model. Patients with high versus low PP (>40 vs ⩽40 mm Hg [lower quartile]) had a significantly greater reduction in LV end-systolic volume, LV end-diastolic volume, and LV dyssynchrony (p <0.01 for all comparisons). In multivariate analysis, the presence of high PP was associated with a 3.5-fold (p <0.001) increase in the likelihood of a positive echocardiographic response to CRT-D. Patients with high PP (>40 mm Hg, >lower quartile) 1 year after CRT-D implantation experienced a 50% reduction in the risk of subsequent HF or death (p = 0.001) and 63% reduction in death only (p =0.001), compared with patients with low PP. In conclusion, high baseline PP is an independent predictor of echocardiographic response to CRT-D, and high PP after device implantation is associated with improved subsequent clinical outcome. [ABSTRACT FROM AUTHOR]

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 ) [ABSTRACT FROM AUTHOR]