Impaired IKs channel activation by Ca(2+)-dependent PKC shows correlation with emotion/arousal-triggered events in LQT1.

Background: The most common inherited cardiac arrhythmia, LQT1, is due to IKs potassium channel mutations and is linked to high risk of adrenergic-triggered cardiac events. We recently showed that although exercise-triggered events are very well treated by ß-blockers for these patients, acute arousal-triggered event rate were not significantly reduced after beta-blocker treatment, suggesting that the mechanisms underlying arousal-triggered arrhythmias may be different from those during exercise. IKs is strongly regulated by β-adrenergic receptor (β-AR) signaling, but little is known about the role of α1-AR-mediated regulation.

Comparison of age (<75 Years versus ≥75 Years) to risk of ventricular tachyarrhythmias and implantable cardioverter defibrillator shocks (from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).

There are limited data regarding the effect of age on the risk of ventricular tachyarrhythmias (VTAs). The present study was designed to compare the risk for VTAs in young and older patients with left bundle branch block (LBBB) and mildly symptomatic heart failure who receive device therapy. The risk of the first ventricular tachycardia (VT) or ventricular fibrillation (VF) event and the risk of first appropriate implantable cardioverter defibrillator (ICD) shock was compared between young (<75 years, n = 1,037) and older (≥75 years, n = 227) patients with LBBB enrolled in Multicenter Automatic Implantation Trial with Cardiac Resynchronization Therapy.

Circadian distribution of ventricular tachyarrhythmias and association with mortality in the MADIT-CRT trial.

Background: It is unknown whether circadian variation of ventricular tachyarrhythmias (VTA) affects clinical outcome in heart failure patients. 

Methods: A total of 1,790 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 (antitachycardia pacing or shock) was evaluated by hours of the day and weekdays and related to all-cause mortality using Cox regression analyses.

Acute Changes in Ambient Temperature Are Associated With Adverse Changes in Cardiac Rhythm.

Background: Both increases and decreases in ambient temperature have been associated with increased cardiovascular mortality and morbidity. However, the mechanism(s) remain unclear.

Objectives: We examined associations between biomarkers of pathways thought to, in part, explain these associations and changes in ambient temperature in a panel of predominantly post-myocardial infarction or post-stent patients.

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.

Negative T wave in ischemic heart disease: a consensus article.

Background: For many years was considered that negative T wave in ischemic heart disease represents ischemia and for many authors located in subepicardial area.

Methods: We performed a review based in the literature and in the experience of the authors commenting the real significance of the presence of negative T wave in patients with ischemic heart disease.

Results: The negative T wave may be of primary or secondary type.

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.

Assessing the interaction of respiration and heart rate in heart failure and controls using ambulatory Holter recordings.

Breathing is a critical component of cardiopulmonary function, but few tools exist to evaluate respiration in ambulatory patients. Holter monitoring allows accurate diagnosis of a host of cardiac issues, and several investigators have demonstrated the ability to detect respiratory effort on the electrocardiogram. In this study we introduce a myogram signal derived from 12-lead, high frequency Holter as a means of detecting respiratory effort.

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 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.

Comparison of low versus high (>40 mm Hg) pulse pressure to predict the benefit of cardiac resynchronization therapy for heart failure (from the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy Trial).

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 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.

Inhalation of ultrafine carbon particles alters heart rate and heart rate variability in people with type 2 diabetes.

Background: Diabetes may confer an increased risk for the cardiovascular health effects of particulate air pollution, but few human clinical studies of air pollution have included people with diabetes. Ultrafine particles (UFP, ≤100 nm in diameter) have been hypothesized to be an important component of particulate air pollution with regard to cardiovascular health effects.

Methods: 17 never-smoker subjects 30-60 years of age, with stable type 2 diabetes but otherwise healthy, inhaled either filtered air (0-10 particles/cm3) or elemental carbon UFP (~107 particles/cm3, ~50 ug/m3, count median diameter 32 nm) by mouthpiece, for 2 hours at rest, in a double-blind, randomized, crossover study design.

Ventricular arrhythmias in the North American multidisciplinary study of ARVC: predictors, characteristics, and treatment.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with sudden cardiac death. However, the selection of patients for implanted cardioverter-defibrillators (ICDs), as well as programming of the ICD, is unclear.

Objectives: The objective of this study was to identify predictors, characteristics, and treatment of ventricular arrhythmias in patients with ARVC.

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 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 impact of nonsustained ventricular tachycardia on reverse remodeling, heart failure, and treated ventricular tachyarrhythmias 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.

ICD programming to reduce shocks and improve outcomes.

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.

Left ventricular pacing threshold and outcome in MADIT-CRT.

Introduction: High left ventricular (LV) pacing threshold (PT) may in some cases indicate the presence of scarred myocardium, a predictor of poor outcome in cardiac resynchronization therapy (CRT) treated patients. We hypothesized that intraoperative LVPT can be used to determine echocardiographic and clinical responses to CRT.

Methods And Results: The study comprised 975 patients enrolled in the CRT-D arm of the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT).

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.

Early procedure-related adverse events by gender in MADIT-CRT.

Background: Whether gender differences exist in procedure-related adverse events following cardiac resynchronization therapy (CRT-D) implantation is unknown. We investigated the type and frequency of procedure-related adverse events among those enrolled in MADIT-CRT and identified clinical predictors for gender-specific events.

Methods: We compared differences in the rate of procedure-related adverse events by gender (444 females and 1,346 males) that occurred ≤30 days after the index procedure in the implantable cardioverter defibrillator (ICD) and CRT-D groups.

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.

A metric for evaluating the cardiac response to resynchronization therapy.

We hypothesized that the response to cardiac resynchronization therapy with a defibrillator (CRT-D) in patients with mildly symptomatic heart failure (HF) is more favorable than the commonly referenced figure of 70%. This study involves the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study population in which paired echocardiograms from baseline and 1-year follow-up were available in 621 implantable cardioverter-defibrillator-treated patients and 749 patients treated with CRT-D. We prespecified CRT-D responders as the patients who at 1-year follow-up had a reduction in left ventricular end-systolic volume (LVESV) that corresponded to the top (best) quintile of LVESV reduction in the implantable cardioverter-defibrillator-treated patients, that is, a ≥17% reduction in LVESV.

Smoking is associated with an increased risk of first and recurrent ventricular tachyarrhythmias in ischemic and nonischemic patients with mild heart failure: a MADIT-CRT substudy.

Background: Limited data exist regarding the proarrhythmic effects of smoking.

Objective: To evaluate the relationship between smoking and the risk of first and recurrent ventricular tachyarrhythmias (VTAs) in patients with mild heart failure.

Methods: The risk of a first and recurrent appropriate implantable cardioverter-defibrillator therapy for VTAs or death was compared between nonsmokers (n = 465), past smokers (n = 780), and current smokers (n = 197) in patients with ischemic and nonischemic cardiomyopathy who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy study.

Cardiac resynchronization therapy is associated with reductions in left atrial volume and inappropriate implantable cardioverter-defibrillator therapy in MADIT-CRT.

Background: There are no prior studies assessing the relationship between left atrial volume (LAV) and inappropriate implantable cardioverter-defibrillator (ICD) therapy following treatment with cardiac resynchronization therapy.

Objective: The purpose of this study was to investigate the hypothesis that patients randomized to cardiac resynchronization therapy with defibrillator (CRT-D) in the Multicenter Automatic Defibrillator Trial-Cardiac Resynchronization Therapy (MADIT-CRT) who had significant LAV reductions would have reduced risks of inappropriate ICD therapy.

Methods: Cardiac resynchronization remodeling was assessed by measuring LAV change between baseline and 12-month echocardiograms in 751 CRT-D treated patients.