RAFT-PermAF: Resynchronization/Defibrillation for Ambulatory Heart Failure Trial in Patients With Permanent Atrial Fibrillation
Study Details
Study Description
Brief Summary
Atrial fibrillation (AF) and heart failure (HF) are two common heart conditions that are encountered with an increase in death and suffering. When both these two conditions occur in a patient, the patient's prognosis is poor with a reduced quality of life and impaired heart function. These patients have enlarged hearts, specifically the left ventricle (major pumping chamber), which impairs the heart's pumping capacity, leading to symptoms such as fatigue, shortness of breath from any type of exertion, and swelling, usually of the feet and ankles.
In these HF patients who are in AF all of the time, who would otherwise be a suitable candidate for an implantable defibrillator to prevent sudden cardiac death, we would like to determine whether adding pacing of both ventricles will reduce heart size (left ventricular end systolic volume index LVESVi) as measured by ultrasound, which can improve its function and help the heart pump more efficiently.
Other studies have shown that adding pacing to both ventricles is of benefit in HF patients with mild to moderate symptoms and have a regular heart rhythm. The Investigators now want to explore if this therapy will benefit those patients with a permanent irregular heart rhythm (AF).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
NEW:
Heart failure (HF) is increasing in prevalence and incidence, and is the most common reason for hospital admissions of patients over the age of 65. Therapy for HF has evolved over the last two decades. Cardiac resynchronization therapy (CRT) is a therapy that attempts to resynchronize the sequence of ventricular contraction in heart failure (HF) patients with left ventricular (LV) systolic dysfunction and ventricular dyssynchrony. CRT is achieved by stimulating both RV and LV together, synchronized to right atrial excitation to achieve atrio-ventricular synchrony. Clinical trials have demonstrated that CRT reduced heart size (left ventricular end systolic volume index LVESVi), improved survival and reduced HF hospitalization in mild to advanced HF patients. In addition, CRT reversed the remodeling process such that it was associated with a reduction of LV size, and an increase of LV ejection fraction (EF). This knowledge translated to a change in practice guidelines and the adoption of CRT into clinical practice benefitting many HF patients CRT is now an important state-of-the-art therapy for HF patients with LV systolic dysfunction, low LVEF, and prolonged QRS duration in sinus rhythm, since the vast majority of the CRT clinical research was performed in patients in sinus rhythm. However, in the ~25% of HF patients with permanent atrial fibrillation (AF), the effectiveness of CRT is not clear. It is therefore timely to address the question of whether the addition of CRT to optimal HF treatment, rate control and an ICD is beneficial in reducing LVESVi in HF patients in permanent AF with LV systolic dysfunction and prolonged QRS duration
Objectives: To determine whether cardiac resynchronization therapy will reduce Left Ventricular End-Systolic Volume index (LVESVi) for heart failure patients with permanent atrial fibrillation, mild to moderate heart failure, left ventricular systolic dysfunction, and prolonged QRS duration, when compared to implantable cardioverter defibrillator (ICD) therapy alone.
Methods: This is a multi-centre randomized controlled trial of two treatment groups. The patients, primary physicians and the heart failure caregivers will be blinded to the treatment allocation. The device follow-up caregivers will not be blinded. Patients with NYHA Class II and III HF symptoms, LVEF HF ≤ 35% , permanent AF, on optimal medical therapy and QRS durations ≥ 130 ms when the QRS morphology is LBBB, or QRS durations ≥ 150 ms when the QRS morphology is non-LBBB, or Paced QRS will be included in the trial. Patients should be suitable candidates for either of the 2 treatment strategies. There will be 200 patients randomized in 1:1 ratio to two groups: 1) ICD-CRT, 2) ICD only. All patients will undergo baseline clinical evaluation, echocardiogram measurements, quality of life assessment, medication assessment, and NT-proBNP. The patients will be followed at 1 month, 3 months, 6 months and then every 6 months. Follow up echocardiograms will be done at 6 and 12 month follow ups to evaluate LVESVi. Quality of life assessment, and 6-minute walk distance will also be performed at baseline and at follow-up visits.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Optimal Medical therapy plus ICD Patients randomized to the (ICD) Implantable-Defibrillator-Cardioverter only group will receive an ICD + optimal medical therapy |
Device: Optimal Medical therapy plus ICD
|
| Active Comparator: Optimal Medical therapy plus CRT/ICD Patients randomized to the (ICD) Implantable-Defibrillator-Cardioverter plus cardiac resynchronisation therapy (CRT) group will receive an ICD + CRT and optimal medical therapy |
Device: Optimal Medical therapy plus CRT/ICD
|
Outcome Measures
Primary Outcome Measures
- The primary outcome is a reduction of Left Ventricular End Systolic Volume index (LVESVi) [Baseline to a minimum of 18 months]
Echocardiogram Measures of LVESVi
Secondary Outcome Measures
- All-cause mortality [Baseline to a minimum of 18 months]
Death all cause
- Hospitalization for Heart Failure [Baseline to a minimum of 18 months]
Admission to Hospital > 24 hours for Heart Failure
- Cardiovascular mortality [Baseline to a minimum of 18 months]
Cardiovascular Death
- Cost-effectiveness [Baseline to a minimum of 18 months]
Readmission for Heart Failure
- Quality of Life Questionnaire [Baseline to a minimum of 18 months]
Minnesota Living with Heart Failure
- 6 Minute walk distance [Baseline to a minimum of 18 months]
Hall walk distance over 6 minute timeframe
- Cardiovascular hospitalizations [Baseline to a minimum of 18 months]
Cardiovascular Admission to Hospital > 24 hours
- Composite of all-cause mortality and heart failure [Baseline to a minimum of 18 months]
All cause death and admission to to Hospital > 24 hours for Heart Failure
- Quality of Life Questionnaire [Baseline to a minimum of 18 months]
EQ5D-5L
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with NYHA Class II or III HF symptoms (assessment in the last 3 months)
-
Permanent AF
-
Optimal Medical Therapy for HF of at least 3 months (according to 2009 ACCF/AHA and ESC 2012 recommendations,)
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LVEF ≤ 35% (assessment in the last 6 months)
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Candidacy for an ICD for primary or secondary prevention of sudden cardiac death
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QRS durations ≥ 130 ms when the QRS morphology is LBBB, or QRS durations ≥ 150 ms when the QRS morphology is non-LBBB or Paced QRS
Exclusion Criteria:
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In-hospital patients who have acute cardiac or non-cardiac illness that requires intensive care
-
Intra-venous inotropic agent in the last 4 days
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Patients with a life expectancy of less than one year from non-cardiac cause.
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Expected to undergo cardiac transplantation within one year (status I)
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Acute coronary syndrome (including MI) < 4 weeks
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Unable or unwilling to provide informed consent
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Uncorrected or uncorrectable primary valvular disease
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Restrictive, hypertrophic or reversible form of cardiomyopathy
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Severe primary pulmonary disease such as cor pulmonale
-
Tricuspid prosthetic valve
-
Patients included in other clinical trial that will affect the objectives of this study
-
Coronary revascularization (CABG or PCI) < 3 months
-
Patients with an existing ICD or CRT pacemaker
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Libin Cardiovascular Institute of Alberta | Calgary | Alberta | Canada | |
| 2 | Vancouver General Hospital | Vancouver | British Columbia | Canada | |
| 3 | Victoria Cardiac Arrhythmia Trials | Victoria | British Columbia | Canada | V8R 4R2 |
| 4 | St. Boniface General Hospital | Winnipeg | Manitoba | Canada | |
| 5 | Queen Elizabeth II Health Science | Halifax | Nova Scotia | Canada | |
| 6 | Hamilton Health Sciences | Hamilton | Ontario | Canada | |
| 7 | Kingston General Hospital | Kingston | Ontario | Canada | |
| 8 | London Health Sciences Centre | London | Ontario | Canada | N6A 5A5 |
| 9 | University of Ottawa Heart Institute | Ottawa | Ontario | Canada | K1W 4W7 |
| 10 | St. Michael's General Hospital | Toronto | Ontario | Canada | |
| 11 | McGill Health Science Centre | Montreal | Quebec | Canada | |
| 12 | Montreal Heart Institute | Montreal | Quebec | Canada | |
| 13 | CHUM Centre hospitalier universitaire de Montréal | Montréal | Quebec | Canada | |
| 14 | Hôpital du Sacré-Cœur de Montréal | Montréal | Quebec | Canada | |
| 15 | Institut universitaire de cardiologie et de pneumologie de Quebec | Quebec City | Quebec | Canada | |
| 16 | Le Centre hospitalier universitaire de Sherbrooke | Sherbrooke | Quebec | Canada |
Sponsors and Collaborators
- Ottawa Heart Institute Research Corporation
- Canadian Institutes of Health Research (CIHR)
Investigators
- Principal Investigator: Anthony SL Tang, MD, Ottawa Heart Institute Research Corporation
Study Documents (Full-Text)
None provided.More Information
Publications
- RN00208414