AnaLysIs of Both sex and device specific factoRs on outcomes in pAtients with non-ischemic cardiomyopathy (BIO-LIBRA): Design and clinical protocol.

Background: Outcomes of patients with nonischemic cardiomyopathy and low ejection fraction implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D), especially in contemporary, real-life cohorts, are not fully understood.

Objective: We aimed to better characterize outcomes of death and ventricular tachyarrhythmias in patients with nonischemic cardiomyopathy, implanted with an ICD or CRT-D, and specifically assess differences by sex.

Methods: The AnaLysIs of Both Sex and Device Specific FactoRs on Outcomes in PAtients with Non-Ischemic Cardiomyopathy (BIO-LIBRA) study was designed to prospectively assess outcomes of device-treated ventricular tachyarrhythmias and all-cause mortality events in nonischemic cardiomyopathy patients, indicated for an ICD or CRT-D implantation for the primary prevention of sudden cardiac death (SCD), with a specific focus on sex differences.

Need for pacing in patients who qualify for an implantable cardioverter-defibrillator: Clinical implications for the subcutaneous ICD.

Background: Implantation of the subcutaneous implantable cardioverter-defibrillator (S-ICD) is spreading and has been shown to be safe and effective; however, it does not provide brady-pacing. Currently, data on the need for brady-pacing and cardiac resynchronization therapy (CRT) implantation in patients with ICD indication are limited.

Methods: The Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II enrolled post-MI patients with reduced ejection fraction (EF ≤ 35%), randomized to either an implantable cardioverter-defibrillator (ICD) or conventional medical therapy.

Association of Cardiac Resynchronization Therapy With Change in Left Ventricular Ejection Fraction in Patients With Chemotherapy-Induced Cardiomyopathy.

Importance: The incidence of chemotherapy-induced cardiomyopathy is increasing and is associated with poor clinical outcomes.

Objective: To assess the association of cardiac resynchronization therapy (CRT) with improvement in cardiac function, as well as clinical improvement in patients with chemotherapy-induced cardiomyopathy.

Design, Setting, And Participants: The Multicenter Automatic Defibrillator Implantation Trial-Chemotherapy-Induced Cardiomyopathy was an uncontrolled, prospective, cohort study conducted between November 21, 2014, and June 21, 2018, at 12 tertiary centers with cardio-oncology programs in the United States.

Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial.

Background: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs).

Objectives: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD.

Methods: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo.

A checklist for clinical trials in rare disease: obstacles and anticipatory actions-lessons learned from the FOR-DMD trial.

Background: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) for 5 years (July 2010 to June 2015), anticipating that all sites (40 across the USA, Canada, the UK, Germany and Italy) would be open to recruitment from July 2011.

Multicenter Automatic Defibrillator Implantation Trial-Subcutaneous Implantable Cardioverter Defibrillator (MADIT S-ICD): Design and clinical protocol.

Patients with diabetes mellitus, prior myocardial infarction, older age, and a relatively preserved left ventricular ejection fraction remain at risk for sudden cardiac death that is potentially amenable by the subcutaneous implantable cardioverter defibrillator with a good risk-benefit profile. The launched MADIT S-ICD study is designed to test the hypothesis that post-myocardial infarction diabetes patients with relatively preserved ejection fraction of 36%-50% will have a survival benefit from a subcutaneous implantable cardioverter defibrillator.

Inverse Relationship of Blood Pressure to Long-Term Outcomes and Benefit of Cardiac Resynchronization Therapy in Patients With Mild Heart Failure: A Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Long-Term Follow-Up Substudy.

Background: Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with left ventricular dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase systolic blood pressure (SBP). Therefore, we hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values.

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.

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.

Right ventricular function, pulmonary pressure estimation, and clinical outcomes in cardiac resynchronization therapy.

Background: Right ventricular function (RVF) is an important determinant of outcome in patients with heart failure, and those with severe RV dysfunction have worse outcome after cardiac resynchronization therapy (CRT). We used data from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) Trial to determine whether therapy with CRT is influenced by or affects RV function and to define the relationship between RV function and outcomes.

Methods And Results: A total of 1820 patients were randomly assigned to CRT plus implantable cardioverter defibrillator or implantable cardioverter defibrillator-only in a 3:2 ratio.

Acute effects of withdrawal of cardiac resynchronization therapy on left and right ventricular function, dyssynchrony, and contractile function in patients with New York Heart Association functional class I/II heart failure: MADIT-CRT.

Background: Cardiac resynchronization therapy (CRT) improves left ventricular (LV) function, size, mitral regurgitation, and clinical outcomes. Whether these improvements are due to the short-term effects of improvement in synchrony or contractile performance, or to long-term improvement in ventricular structure and function remains insufficiently elucidated.

Methods And Results: We used echocardiographic data from 63 patients enrolled in the MADIT-CRT trial who, after 1 year of CRT therapy, underwent echocardiographic evaluation with CRT turned both on and off within minutes.

Reduction in inappropriate therapy and mortality through ICD programming.

Background: The implantable cardioverter-defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential adverse effects.

Methods: We randomly assigned 1500 patients with a primary-prevention indication to receive an ICD with one of three programming configurations. The primary objective was to determine whether programmed high-rate therapy (with a 2.

Multicenter automatic defibrillator implantation trial: reduce inappropriate therapy (MADIT-RIT): background, rationale, and clinical protocol.

The implantable cardioverter defibrillator (ICD) is highly effective in reducing mortality due to cardiac arrhythmias in high-risk cardiac patients. However, inappropriate therapies caused predominantly by supraventricular tachyarrhythmias (SVTs) remain a significant side effect of ICD therapy despite medical treatment, affecting 8-40% of patients. The MADIT-RIT is a global, prospective, randomized, nonblinded, three-arm, multicenter clinical investigation to be performed in the Unites States, Europe, Canada, Israel and Japan, and will utilize approximately 90 centers with plan to enroll 1500 patients programmed to three treatment arms.

Reduction of the risk of recurring heart failure events with cardiac resynchronization therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).

Objectives: The evaluation of the risk of recurring heart failure events (HFEs) was a pre-specified substudy of MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).

Background: There are limited data regarding the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the occurrence of recurring heart failure episodes after a first post-implantation HFE.

Methods: Data with regard to recurring HFEs were prospectively collected for all 1,820 MADIT-CRT participants.

Clinical course and outcome of patients enrolled in US and non-US centres in MADIT-CRT.

Aims: We aimed to evaluate within the MADIT-CRT database whether different enrollment characteristics between US and non-US centres affected the clinical course of study patients.

Methods And Results: We evaluated differences in baseline characteristics, procedure-associated complications, clinical as well as echocardiographic response to cardiac resynchronization therapy with a defibrillator (CRT-D), between patients enrolled in 87 US centres (n = 1271) and 23 non-US centres (n = 549) in MADIT-CRT. Non-US patients displayed significant differences in baseline characteristics from US patients, including a higher frequency of left bundle branch block, a more advanced heart failure (HF) functional class >3 months prior to enrollment, and larger baseline cardiac volumes.

Response to preventive cardiac resynchronization therapy in patients with ischaemic and nonischaemic cardiomyopathy in MADIT-CRT.

Aims: There are no data regarding the differential response to cardiac resynchronization therapy with defibrillator (CRT-D) by the aetiology of cardiomyopathy in mildly symptomatic patients. We evaluated the outcome of patients enrolled in MADIT-CRT by ischaemic and non-ischaemic aetiology of cardiomyopathy (ICM and non-ICM, respectively).

Methods And Results: The clinical response to CRT-D was assessed among ICM (n = 1046) and non-ICM (n = 774) patients enrolled in MADIT-CRT during an average follow-up of 2.

Long-term implications of cumulative right ventricular pacing among patients with an implantable cardioverter-defibrillator.

Background: Limited data regarding the effect of right ventricular pacing (RVP) on long-term survival following implantable cardioverter-defibrillator (ICD) implantation are available.

Objective: The purpose of this study was to evaluate the effect of RVP on the long-term survival benefit of primary ICD therapy.

Methods: Mortality data were obtained for all patients enrolled in the Multicenter Automatic Defibrillator Trial-II (MADIT-II) during an extended follow-up period of 8 years.

Long-term benefit of primary prevention with an implantable cardioverter-defibrillator: an extended 8-year follow-up study of the Multicenter Automatic Defibrillator Implantation Trial II.

Background: The Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) showed a significant 31 reduction in the risk of death with primary implantable cardioverter-defibrillator (ICD) therapy during a median follow-up of 1.5 years. However, currently there are no data on the long-term efficacy of primary defibrillator therapy.

Relation between renal function and response to cardiac resynchronization therapy in Multicenter Automatic Defibrillator Implantation Trial--Cardiac Resynchronization Therapy (MADIT-CRT).

Background: Cardiorenal interactions have been shown to affect outcome in heart failure patients but were not related to response to cardiac resynchronization therapy (CRT).

Objective: The purpose of this study was to test our hypothesis that assessment of markers of prerenal failure may help identify mildly symptomatic HF patients with diminished effective circulating blood volume who will benefit from CRT.

Methods: The benefit of CRT with a defibrillator (CRT-D) as compared with defibrillator-only therapy in reducing the risk of HF or death was assessed by renal function parameters (including serum creatinine [SCr], blood urea nitrogen [BUN], and the ratio of BUN to SCr [BUN:SCr], dichotomized at median values and into approximate quartiles) among 1,803 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy.

Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy.

Background: Cardiac resynchronization therapy (CRT) plus implantation of an implantable cardioverter defibrillator (ICD) reduced the risk of death or heart failure event in patients with mildly symptomatic heart failure, left ventricular dysfunction, and wide QRS complex compared with an ICD only. We assessed echocardiographic changes in patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial: Cardiac Resynchronization Therapy) to evaluate whether the improvement in outcomes with CRT plus an ICD was associated with favorable alterations in cardiac size and function.

Methods And Results: A total of 1,820 patients were randomly assigned to CRT plus an ICD or to an ICD only in a 3:2 ratio.

Cardiac-resynchronization therapy for the prevention of heart-failure events.

Background: This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex.

Methods: During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms.