Cardiac Sarcoidosis Multi-Center Prospective Cohort
- Conditions
- Cardiac Sarcoidosis
- Registration Number
- NCT01477359
- Lead Sponsor
- Ottawa Heart Institute Research Corporation
- Brief Summary
Recent data has shown that sarcoidosis, presenting initially with cardiac manifestations (CS) of either conduction system disease or cardiomyopathy and sustained VT, is not uncommon. A Canadian physician survey found that most physicians do not investigate for CS as a possibility in these situations. Thus many patients with clinically important CS are going un-diagnosed. A study from Finland showed that missing the diagnosis of CS in these patients' leads to significant mortality and morbidity.
There are no published clinical consensus guidelines on treatment of CS. Corticosteroid therapy is advocated by most experts. This is based on very modest data from small retrospective observational studies using variable definitions of clinical response. The effect of corticosteroid treatment on the clinical course of CS has not been studied in prospective studies and will be one of the aims of this project. Recent physician surveys regarding CS, in Canada and the US, found that current clinical practice varies widely. The 2008 American College of Cardiology/American Heart Association/Heart Rhythm society guidelines recommend implantation of a defibrillator (Class IIa recommendation) to prevent sudden cardiac death. The most recent Canadian device therapy guidelines do not mention CS.
A multi-center collaborative approach to study CS is greatly needed." The investigators propose exactly that i.e. a multi-center prospective cohort to start to answer clinical questions. The investigators have formed the CANADIAN CARDIAC SARCOIDOSIS RESEARCH GROUP. The group includes respirologists with an interest in sarcoidosis, cardiac electrophysiologists, cardiac imaging specialists with extensive experience in imaging of sarcoidosis and biostatisticians. The research will be in two phases; a registry of current diagnostic approaches, treatment and prognosis, and a randomized clinical trial of the effect of corticosteroid treatment on the clinical course of cardiac sarcoidosis.
- Detailed Description
Baseline assessment of Clinically Manifest CS patients consists of: history, echocardiogram, ECG, chest CT scan, FDG-PET scan, blood for biomarkers within 2 months of the PET scan, cardiac MRI and possibly a signal average ECG and biopsy (encouraged-either endomyocardial or extra-cardiac).
Follow-up and clinical management of clinically manifest patients diagnosed with CS will occur at 3-6 months with a repeat FDG-PET scan and blood biomarkers. Follow-up will then be annually with an echo and ECG. Treatment with steroids/immunosuppressants and device therapy will be at the discretion of the treating physician.
Baseline assessment of patients diagnosed with extra-cardiac sarcoidosis and being screened for CS consists of: history, echocardiogram, ECG, holter, chest CT scan, biopsy, and cardiac MRI (CMR). If the CMR is suggestive of CS the patient will be have a FDG-PET scan done and be followed as a Clinically Silent patient. They will be contacted every 2 years. If the CMR is negative the patient will be followed as a extra-cardiac sarcoidosis patient with no evidence of CS and be in the control group. They will be contacted at 5 years and at the time of study completion.
All patients will be followed until the last patient recruited has been followed for 4 years.
The occurrence of the primary and secondary outcomes will be assessed in treated and untreated patients.
There will be 2 imaging core labs. The PET core lab will be located at UOHI under the direction of Dr. Robert Beanlands. The CMR core lab will be under the direction of Dr. Mathias Friedrich (McGill University). All scans will be read in the core labs by physicians who are blinded to the clinical details of the patients.
The Biomarker core lab will be at The University of Ottawa Heart Institute under the leadership of Dr P Liu.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1500
To diagnose Clinically Manifest CS all following criteria must be met:
(i) Positive biopsy* for Sarcoid (either EMB or extra-cardiac) AND/OR (ii) CT Chest highly suggestive of pulmonary sarcoidosis AND (iii) one or more of the following clinical features:
- advanced conduction system disease (sustained Mobitz II AV block or third degree AV block)
- non- sustained or sustained ventricular arrhythmia
- ventricular dysfunction (LVEF < 50% and/or RVEF < 40%) AND (iv) No alternative explanation for clinical features AND (v) FDG-PET suggestive of active CS
To diagnose clinically silent CS all of the following criteria must be met
(i) Biopsy proven extra-cardiac sarcoidosis
AND/OR (ii) CT Chest highly suggestive of pulmonary sarcoidosis
AND (iii) CMR suggestive of cardiac sarcoidosis
AND (iv) Does not have criteria for clinically manifest CS ie. should not have any of following
- advanced conduction system disease (sustained Mobitz II AV block or third degree AV block)
- non- sustained or sustained ventricular arrhythmia
- ventricular dysfunction (LVEF < 50% and/or RVEF < 40%)
Patients with negative CMR will be designated as 'extra-cardiac sarcoidosis with no evidence of CS' and followed as control
- unable or unwilling to provide informed consent
- patients who are pregnant or lactating
- patients with known claustrophobia
- age < 18 years
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Clinically Silent and Control Patients 9 years Cardiac death or cardiac transplantation or sustained VT/VF or sustained second or third degree AV block or development of clinical congestive heart failure (with documented LVEF \< 50%).
Clinically Manifest Patients On active therapy for 6 months "Clinically improved" if they are alive and not had a heart transplant and have not had heart failure hospitalization and no sustained VT/VF and meet one or more of following
(i) No sustained VT (if presented with sustained VT) (ii) Improvement in LV function (defined as 10% decrease in LV end systolic volume or 5% absolute increase in LVEF) (iii) Resolution of conduction system disease (if presented with sustained heart block)
failure hospitalization and have not had sustained VT and one or both of: a. LV function improvement (defined as 10% decrease in LV end systolic volume) b. Resolution of conduction system disease.
- Secondary Outcome Measures
Name Time Method cardiovascular mortality 6 months and 60 months total mortality 6 months and 60 months change in disease activity as assessed by PET imaging 6 months and 60 months comparing pre-treatment to 6 month scans
change in LVEF from baseline 6 months and 60 months heart failure hospitalization 6 months and 60 months Atrial Fibrillation burden 6 months and 60 months from defibrillator diagnostics
Ventricular arrhythmia burden 6 months and 60 months from defibrillator diagnostics
% of ventricular pacing 6 months and 60 months
Trial Locations
- Locations (14)
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
QEII Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Southlake Regional Health Centre
🇨🇦Newmarket, Ontario, Canada
Centre Hospitalier de l"Universite de Montreal-Hotel Dieu
🇨🇦Montreal, Quebec, Canada
Hokkaido University
🇯🇵Sapporo, Japan
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Libin Cardiovascular Institute of Alberta
🇨🇦Calgary, Alberta, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Hamilton Health Sciences Centre
🇨🇦Hamilton, Ontario, Canada
University of Ottawa Heart Institute
🇨🇦Ottawa, Ontario, Canada
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Prairie Vascular Research Inc-Regina General Hospital
🇨🇦Regina, Saskatchewan, Canada