[Show abstract][Hide abstract] ABSTRACT: 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 non-ischemic cardiomyopathy.
First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with non-ischemic cardiomyopathy. Patients with ischemic and non-ischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and non-ischemic cardiomyopathy (HR range 0.11-0.34, P < 0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and non-ischemic cardiomyopathy patients.
High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and non-ischemic cardiomyopathy. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of Cardiovascular Electrophysiology 12/2014; · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is unknown whether circadian variation of ventricular tachyarrhythmias (VTA) affects clinical outcome in heart failure patients.
A total of 1790 patients (males 75%) with heart failure, NYHA class I and II and implantable cardioverter defibrillators (ICD) or cardiac resynchronization (CRT-D) enrolled in the MADIT-CRT study were included. Time of first and all VTAs as detected and treated by the device with appropriate ICD therapy (ATP or shock) was evaluated by hours of the day and weekdays and related to all-cause mortality using Cox regression analyses.
During a mean follow-up period of 40 months, a total of 3300 VTA episodes were registered. Of all VTAs recorded, most of them (n = 2977, 90%) occurred in males. Recurrent as well as first VTA episodes were more common in the morning and evening with bimodal peaks from 7:00-10:59 (21%) and 18:00-21:59 (23%). VTAs that occurred during morning hours were associated with higher mortality when compared to VTA episodes occurring at other hours (HR = 2.07, CI: 1.135-3.77, p = 0.018) with a significant gender interaction placing females at significantly higher risk of death (HR 6.78, CI 1.55-29.860 p = 0.011) than males (HR 1.79, CI 0.92-3.46, p = 0.086) (interaction p = 0.041) despite an overall lower probability for morning VTA among females (HR 0.32, CI 0.16-0.68 p = 0.003) CONCLUSIONS: The occurrence of VTAs in heart failure patients shows a circadian variation with highest incidence during morning hours that translates into a significant higher risk of all-cause mortality, with significantly higher risk among females than males. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of Cardiovascular Electrophysiology 11/2014; · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Long QT syndrome type 3 (LQT3) is caused by mutations in the SCN5A-encoded Nav1.5 channel. LQT3 patients exhibit time of day associated abnormal increases in their heart rate corrected QT (QTc) intervals and risk for life-threatening episodes. This study determines the effects of uncoupling environmental time cues that entrain circadian rhythms (time of light and time of feeding) on heart rate and ventricular repolarization in wild type (WT) or transgenic LQT3 mice (Scn5a(+/ΔKPQ)). We used an established light-phase restricted feeding paradigm that disrupts the alignment among the circadian rhythms in the central pacemaker of the suprachiasmatic nucleus and peripheral tissues including heart. Circadian analysis of the RR and QT intervals showed the Scn5a(+/ΔKPQ) mice had QT rhythms with larger amplitudes and 24-hr midline means and a more pronounced slowing of the heart rate. For both WT and Scn5a(+/ΔKPQ) mice, light-phase restricted feeding shifted the RR and QT rhythms ~12 hrs, increased their amplitudes >2-fold, and raised the 24-hr midline mean by ~10%. In contrast to WT mice, the corrected QT (QTc) interval in Scn5a(+/ΔKPQ) mice exhibited time-of-day prolongation that was flipped after light-phase restricted feeding. The time-of-day changes in the QTc intervals of Scn5a(+/ΔKPQ) mice were secondary to a steeper power relation between their QT and RR intervals. We conclude that uncoupling time of feeding from normal light cues can dramatically slow heart rate to unmask genotype-specific differences in the QT intervals and aggravate the LQT3-related phenotype.
AJP Heart and Circulatory Physiology 10/2014; · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -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.
[Show abstract][Hide abstract] ABSTRACT: Low pulse pressure (PP) is associated with poor outcome among 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 pre-implantation PP and echocardiographic response to CRT-D and subsequent clinical outcome after 1-year. The relationship between pre-implantation PP and echocardiographic response to CRT-D (defined as >15% reduction in left ventricular end systolic volume [LVESV] at 1 year) was evaluated among 754 CRT-D patients with left bundle branch block (LBBB) enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Cardioverter Defibrillator Implantation Trial-Cardiac Resynchronization Therapy). The association between PP at 1 year and the risk for subsequent heart failure (HF) or death was evaluated using multivariate Cox model. Patients with high vs. low PP (>40 vs. ≤ 40 mmHG [lower quartile]) had a significantly greater reduction in LVESV, 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 mmHG, >lower quartile) one 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 to patients with low PP. In conclusion, high baseline PP is an independent predictor of echocardiographic response to CRT-D and high PP following device implantation is associated with improved subsequent clinical outcome.
The American Journal of Cardiology 10/2014; · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
In LQTS, β-blocker therapy is effective in reducing the risk of cardiac events (syncope, aborted cardiac arrest, sudden cardiac death). Limited studies have compared the efficacy of different β-blockers.
The goal of this study was to compare the efficacy of different β-blockers in long QT syndrome (LQTS) and in genotype-positive patients with LQT1 and LQT2.
The study included 1,530 patients from the Rochester, New York–based LQTS Registry who were prescribed common β-blockers (atenolol, metoprolol, propranolol, or nadolol). Time-dependent Cox regression analyses were used to compare the efficacy of different β-blockers with the risk of cardiac events in LQTS.
Relative to being off β-blockers, the hazard ratios and 95% confidence intervals (CIs) for first cardiac events for atenolol, metoprolol, propranolol, and nadolol were 0.71 (0.50 to 1.01), 0.70 (0.43 to 1.15) 0.65 (0.46 to 0.90), and 0.51 (0.35 to 0.74), respectively. In LQT1, the risk reduction for first cardiac events was similar among the 4 β-blockers, but in LQT2, nadolol provided the only significant risk reduction (hazard ratio: 0.40 [0.16 to 0.98]). Among patients who had a prior cardiac event while taking β-blockers, efficacy for recurrent events differed by drug (p = 0.004), and propranolol was the least effective compared with the other β-blockers.
Although the 4 β-blockers are equally effective in reducing the risk of a first cardiac event in LQTS, their efficacy differed by genotype; nadolol was the only β-blocker associated with a significant risk reduction in patients with LQT2. Patients experiencing cardiac events during β-blocker therapy are at high risk for subsequent cardiac events, and propranolol is the least effective drug in this high-risk group.
Journal of the American College of Cardiology 09/2014; 64(13):1352–1358. · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of the American College of Cardiology 09/2014; 64(10):971-81. · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -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.
Circulation Arrhythmia and Electrophysiology 08/2014; · 5.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
European Heart Journal 08/2014; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Unaffected long-QT syndrome family members (FMs) frequently experience syncope. The aims of this study were to test the hypothesis that syncope events in FMs are benign events and to compare clinical characteristics, triggers eliciting the syncope events, and long-term outcomes between FMs and those with LQT1 or LQT2 mutations from the international Long QT Syndrome Registry. A total of 679 FMs, 864 LQT1 patients, and 782 LQT2 patients were included. Seventy-eight FMs (11%) experienced cardiovascular events. Almost all cardiovascular events were nonfatal syncope; only 1 FM, with an additional mitral valve prolapse, experienced aborted cardiac arrest during exercise. The mean age at first syncope in FMs was 17 years, and female FMs experienced syncope more frequently than male FMs (14% vs 9%, p = 0.027). Syncope was more frequently triggered by exercise in LQT1 patients (43% in LQT1 patients vs 5% in FMs, p <0.001), while syncope triggered by a variety of other triggers was more frequent in FMs (54% in FMs vs 22% in LQT1 patients and 30% in LQT2 patients, p <0.001 for both). None of the FMs experienced aborted cardiac arrest or sudden cardiac death after the first syncopal episode. In conclusion, syncope is frequently present in FMs, and these syncopal events occurred more frequently in female than in male FMs, with an increased incidence in midadolescence. Triggers eliciting the syncopal events were different between FMs and patients with long-QT syndrome mutations. Hence, the type of trigger is useful in distinguishing between high- and low-risk syncope. These data indicate that FMs from families with LQTS have a benign form of syncope, most likely related to vasovagal syncope and not ventricular tachyarrhythmic syncope.
The American Journal of Cardiology 07/2014; · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The benefit of a primary prevention implantable cardioverter-defibrillator (ICD) among patients with chronic kidney disease is uncertain.
Meta-analysis of patient-level data from randomized controlled trials.
Setting & Population
Patients with symptomatic heart failure and left ventricular ejection fraction < 35%.
Selection Criteria for Studies
From 7 available randomized controlled studies with patient-level data, we selected studies with available data for important covariates. Studies without patient-level data for baseline estimated glomerular filtration rate (eGFR) were excluded.
Primary prevention ICD versus usual care effect modification by eGFR.
Mortality, rehospitalizations, and effect modification by eGFR.
We included data from the Multicenter Automatic Defibrillator Implantation Trial I (MADIT-I), MADIT-II, and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). 2,867 patients were included; 36.3% had eGFR < 60 mL/min/1.73 m2. Kaplan-Meier estimate of the probability of death during follow-up was 43.3% for 1,334 patients receiving usual care and 35.8% for 1,533 ICD recipients. After adjustment for baseline differences, there was evidence that the survival benefit of ICDs in comparison to usual care depends on eGFR (posterior probability for null interaction P < 0.001). The ICD was associated with survival benefit for patients with eGFR ≥ 60 mL/min/1.73 m2 (adjusted HR, 0.49; 95% posterior credible interval, 0.24-0.95), but not for patients with eGFR < 60 mL/min/1.73 m2 (adjusted HR, 0.80; 95% posterior credible interval, 0.40-1.53). eGFR did not modify the association between the ICD and rehospitalizations.
Few patients with eGFR < 30 mL/min/1.73 m2 were available. Differences in trial-to-trial measurement techniques may lead to residual confounding.
Reductions in baseline eGFR decrease the survival benefit associated with the ICD. These findings should be confirmed by additional studies specifically targeting patients with varying eGFRs.
American Journal of Kidney Diseases 07/2014; · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -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.
Circulation Arrhythmia and Electrophysiology 06/2014; · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the clinical benefit of implantable cardioverter defibrillator (ICD), there is a high frequency of inappropriate ICD therapy associated with impaired quality of life, unwanted health care resource utilization, and adverse clinical outcome. Alternative strategies of ICD programming are needed to reduce the risk of inappropriate and "unnecessary" ICD therapies and to improve patient outcome. In this review, we provide an overview of the rate of inappropriate and appropriate ICD therapies in clinical trials and large registries as well as a review of current trials evaluating novel ICD programming to reduce inappropriate ICD therapy to avoid unnecessary ICD therapy. Based on recent studies including a large randomized trial, we recommend a simple programming approach involving high-rate device therapy beginning at 200 bpm with a 2.5 sec delay for it reduces inappropriate therapy, unnecessary therapy, and all-cause mortality in patients receiving ICD or CRT-D devices for primary prevention indications.
[Show abstract][Hide abstract] ABSTRACT: Background
There are no prior studies assessing the relationship between left atrial volume and inappropriate ICD therapy following treatment with cardiac resynchronization therapy.
We hypothesized that patients randomized to CRT-D in the MADIT-CRT trial who had significant left atrial volume (LAV) reductions would have reduced risks of inappropriate ICD therapy.
Cardiac resynchronization remodeling was assessed by measuring LAV change between baseline and 12-month echocardiograms in 751 CRT-D treated patients. Patients were stratified into quartiles based on percent reduction of LAV change: High LAV responders were those in the highest three quartiles of LAV reduction (LAV reduction >21%) and low LAV responders were those in the lowest quartile of LAV reduction (LAV reduction <21%). Clinical factors associated with >21% reduction in LAV were evaluated by linear regression analysis.
In Cox proportional-hazards regression analyses, high LAV responders had a 39% reduction in the risk of inappropriate therapy (hazard ratio 0.61, p=0.04) and LBBB patients exhibited an even greater risk reduction in inappropriate therapy (hazard ratio 0.51, p=0.02) compared to low LAV responders during follow-up extending up to 3 years after the 12-month echocardiogram. High LAV responders also had a significantly lower risk of heart failure or death during follow-up than low LAV responders.
A ≥21% reduction in LAV with cardiac resynchronization therapy is associated with significant reductions in inappropriate ICD therapy and in heart failure or death during a 3-year follow-up.
Heart rhythm: the official journal of the Heart Rhythm Society 06/2014; · 4.56 Impact Factor