Cardiac Sarcoidosis Multi-Center Prospective Cohort

Официальное название

Cardiac Sarcoidosis Multi-Center Prospective Cohort Study

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Clinically Manifest Patients [Срок оценки: On active therapy for 6 months]
• Clinically Silent and Control Patients [Срок оценки: 9 years]

Вторичные конечные точки (8)

• total mortality [Срок оценки: 6 months and 60 months]
• cardiovascular mortality [Срок оценки: 6 months and 60 months]
• heart failure hospitalization [Срок оценки: 6 months and 60 months]
• change in LVEF from baseline [Срок оценки: 6 months and 60 months]
• change in disease activity as assessed by PET imaging [Срок оценки: 6 months and 60 months]
• Atrial Fibrillation burden [Срок оценки: 6 months and 60 months]
• Ventricular arrhythmia burden [Срок оценки: 6 months and 60 months]
• % of ventricular pacing [Срок оценки: 6 months and 60 months]

Критерии участия

Критерии включения

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

Критерии исключения

• unable or unwilling to provide informed consent
• patients who are pregnant or lactating
• patients with known claustrophobia
• age < 18 years

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Канада · 13 центров

• Libin Cardiovascular Institute of Alberta — Calgary
• University of Alberta Hospital — Edmonton
• St. Paul's Hospital — Vancouver
• QEII Health Sciences Center — Halifax
• Hamilton Health Sciences Centre — Hamilton
• London Health Sciences Centre — London
• Southlake Regional Health Centre — Newmarket
• University of Ottawa Heart Institute — Ottawa
• … и ещё 5 центров

Япония · 1 центр

• Hokkaido University — Sapporo

Публикации

• Weng W, Wiefels C, Chakrabarti S, Nery PB, Celiker-Guler E, Healey JS, Hruczkowski TW, Quinn FR, Promislow S, Medor MC, Spence S, Odabashian R, Alqarawi W, Juneau D, de Kemp R, Leung E, Beanlands R, Birnie D. Atrial Arrhythmias in Clinically Manifest Cardiac Sarcoidosis: Incidence, Burden, Predictors, and Outcomes. J Am Heart Assoc. 2020 Sep;9(17):e017086. doi: 10.1161/JAHA.120.017086. Epub 2020 A PMID 32814465
• Martineau P, Pelletier-Galarneau M, Juneau D, Leung E, Nery PB, de Kemp R, Beanlands R, Birnie D. Imaging Cardiac Sarcoidosis With FLT-PET Compared With FDG/Perfusion-PET: A Prospective Pilot Study. JACC Cardiovasc Imaging. 2019 Nov;12(11 Pt 1):2280-2281. doi: 10.1016/j.jcmg.2019.06.020. Epub 2019 Aug 14. No abstract available. PMID 31422126

Идентификаторы

NCT: NCT01477359 · UOHI-04

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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