Resynchronization/Defibrillation for Ambulatory Heart Failure Trial
Resynchronization/Defibrillation for Ambulatory Heart Failure Trial
Congestive heart failure (CHF) is a common health problem that leads to frequent
 hospitalizations and an increased death rate. In spite of advances in drug therapy, it
 remains a significant public health problem. Recently, a new therapy has been developed for
 advanced heart failure patients with a ventricular conduction abnormality. This new therapy,
 called cardiac resynchronization (CRT), is a device which stimulates the atrium, the right
 ventricle, and the left ventricle providing synchronization of the contraction of the heart
 chambers. It is the addition of this therapy to an implantable cardioverter defibrillator
 (ICD) that will be evaluated in this study. This study will compare whether the implantation
 of this new therapy device, in combination with an implantable cardioverter defibrillator,
 will reduce total mortality and hospitalizations for CHF.
Cardiovascular mortality is decreasing in most industrial countries, however mortality for
 congestive heart failure is increasing. The most important predictors of mortality in heart
 failure patients are depressed left ventricular function, severity of symptoms (NYHA class),
 and ventricular conduction abnormality manifested as wide QRS. Recent advances in
 pharmacological therapy including ACE inhibitors, beta-blocker and spironolactone have
 resulted in improvement of symptoms and reduction in mortality. Population epidemiological
 studies demonstrated that mortality and hospitalization rate for heart failure remains very
 high despite recent pharmacological therapeutic progress. Recent short-term clinical trials
 demonstrated that cardiac resynchronization therapy (CRT) is effective in improving symptoms
 of heart failure, functional capacity and quality of life in patients with moderate to severe
 heart failure and conduction abnormality optimally treated with drug therapy. However, the
 data for morbidity and mortality in mild to moderate heart failure is lacking.

 The objective of this trial is to determine if the addition of CRT to optimal pharmacological
 therapy and ICD is effect in reducing mortality and morbidity in patients with poor LV
 function, wide QRS and mild to moderate heart failure symptoms.

 This is a double-blinded randomized control trial. A total of 1800 patients with mild to
 moderate heart failure symptoms, LVEF ≤ 30%, and QRS ≥ 120 ms will be included in the study.
 Patients will be randomized to either "ICD plus Optimal Medical Therapy (control)" or
 "CRT/ICD plus Optimal Medical Therapy (experimental)" in a 1:1 randomization ratio. Patients
 in the control group will be implanted with a single or dual chamber ICD. Patients in the
 experimental group will receive a device with the capabilities of CRT and ICD. Optimal
 Medical Therapy will include ACE inhibitors and beta-blockers. Patients will be followed on a
 regular basis and will have clinical evaluation, quality of life assessment, and six minute
 walk tests performed. The primary outcome is a composite of total mortality and heart failure
 hospitalization. Secondary outcome measures will include total mortality, cardiovascular
 mortality, sudden arrhythmic death, health related quality of life and cost economics.
 Patient accruement is scheduled for 4.5 years and a minimum follow of 18 months.

 DFT sub study:

 Overview of sub-study Design Patients participating in the RAFT trial, at participating
 sites, will be randomized to have DFT testing or no testing at the time of device implant. Up
 to 450 patients will be eligible for enrollment at Canadian and European centres. The study
 will have two primary outcomes: a short-term safety outcome and a long-term efficacy outcome.
 The safety outcome will be a composite of all adverse events potentially related to DFT that
 occur within 30 days following ICD implant. The long-term efficacy outcome will be a
 composite of failed first appropriate clinical ICD shock and sudden death. This pilot study
 is intended primarily to confirm the anticipated rates of events and to demonstrate
 feasibility of enrollment, but will not have statistical power to determine if
 intra-operative DFT testing is associated with significant short-term risk. If complication
 rates are as high as predicted and enrollment is feasible, then a larger study would be
 justified to determine the impact of intra-operative DFT testing on long-term rates of failed
 appropriated ICD shocks and sudden death. Events rates determined in this pilot study would
 then be used to estimate the sample size of this larger study.
Inclusion Criteria:

 -  New York Heart Association (NYHA) Class II

 -  Left ventricular ejection fraction (LVEF) less than or equal to 30% by multigated
 acquisition scan (MUGA)/catheterization OR LVEF less than or equal to 30% and LV end
 diastolic dimension ≥ 60 mm (by echocardiogram) within 6 months prior to randomization

 -  Intrinsic QRS complex width ≥ 120 ms OR paced QRS measurement ≥ 200 ms

 -  ICD indication for primary or secondary prevention

 -  Optimal heart failure pharmacological therapy

 -  Normal sinus rhythm; OR chronic persistent atrial tachyarrhythmia with resting
 ventricular heart rate ≤ 60 beats per minute (bpm) and 6 minute hall walk ventricular
 heart rate of ≤ 90 bpm; OR chronic persistent atrial tachyarrhythmia with resting
 ventricular heart rate > 60 bpm and 6 minute hall walk ventricular heart rate of > 90
 bpm and booked for atrioventricular junction ablation.

 Exclusion Criteria:

 -  Intravenous inotropic agent in the last 4 days

 -  Patients with a life expectancy of less than one year from non-cardiac cause

 -  Expected to undergo cardiac transplantation within one year (status I)

 -  In hospital patients who have acute cardiac or non-cardiac illness that requires
 intensive care

 -  Uncorrected or uncorrectable primary valvular disease

 -  Restrictive, hypertrophic, or reversible form of cardiomyopathy

 -  Severe primary pulmonary disease such as cor pulmonale

 -  Tricuspid prosthetic valve

 -  Patients with an existing ICD (patients with an existing pacemaker may be included if
 the patients satisfy all other inclusion/exclusion criteria)

 -  Coronary revascularization (coronary artery bypass graft surgery [CABG] or
 percutaneous coronary intervention [PCI]) < 1 month if previously determined LVEF >
 30%. Patients with a more recent revascularization can be included if a previously
 determined LVEF was ≤ 30%.

 -  Patients with an acute coronary syndrome including myocardial infarction (MI) can be
 included if the patients have had a previous MI with LV dysfunction (LVEF ≤ 30%).

 -  Patients included in another clinical trial that will affect the objectives of this
 study

 -  History of noncompliance to medical therapy

 -  Unable or unwilling to provide informed consent