Clinical trial NCT01281384: Routine vs Selective Cardiac Magnetic Resonance in Non-Ischemic Heart Failure
Official title: Routine vs Selective Cardiac Magnetic Resonance in Non-Ischemic Heart Failure (OUTSMART-HF) Project I-B of Imaging Modalities to Assist With Guiding Therapy and the Evaluation of Patients With Heart Failure (IMAGE-HF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: cardiac magnetic resonance imaging
echocardiography
heart failure
imaging
cost effectiveness
quality of life
definitive diagnosis
prospective comparative effectiveness randomized clinical trial
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: The Finnish Funding Agency for Technology and Innovation (TEKES)
First posted: 2011-01-21
Enrollment: 518
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Uncovering the underlying cause of heart failure can be quite challenging and doctors often rely on imaging tests such as echo (heart ultrasound) to provide the answers. Cardiac MRI is emerging as another promising test because it gives very precise information on heart function and the amount of scarring in the muscle. Heart failure patients are increasingly being sent for cardiac MRI but the potential advantage that this test offers over others such as echo has not been fully explored.

The purpose of this study is to determine if cardiac MRI provides more information on the cause of heart failure than traditional tests such as echo. In addition, if the information provided by this test always leads to an overall improvement in a patient's heart condition over time.

This is a randomized study where subjects referred for clinically indicated heart failure workup to determine the best clinical management will undergo standard heart failure testing (including echo) OR standard testing PLUS cardiac MRI.

Detailed description: Primary objective: to compare the effect of routine cardiac magnetic resonance (CMR) versus standard care (i.e. echocardiography with only selective use of CMR) on the etiological diagnosis in patients with a non-ischemic heart failure (HF). The proposed categories of HF to be considered in this study include: idiopathic dilated cardiomyopathy, infiltrative cardiomyopathy, inflammatory, hypertrophic cardiomyopathy, heart failure with preserved ejection fraction (HFPEF), ischemic cardiomyopathy, mixed etiology and other (eg. pericardial, congenital, non-compaction, right ventricular failure).

Primary hypothesis: Routine use of CMR (vs. selective use) will lead to a more specific diagnostic characterization of the underlying etiology of non-ischemic heart failure. This will lead to a reduction in the diagnosis of idiopathic dilated cardiomyopathy and HFPEF.

Secondary objectives: Determine the effects that routine use of CMR in non-ischemic HF has on therapeutic decisions, on the Composite Clinical Endpoint (CCE), cardiac function, symptoms, quality of life (QoL), and costs. Ancillary measurements will include the safety of imaging tests and adverse reactions to gadolinium contrast agent.

Secondary hypothesis: Routine use of CMR will have significant impact on treatment decisions, (1) lead to more disease specific therapies and/or (2) cause a significant change in the number and class of HF meds, during follow-up. The routine CMR group will also have improved clinical outcomes (CCE), symptoms and QoL and decreased costs to the standard of care group during follow-up.

Design

Methods: Randomized controlled trial comparing i) routine CMR vs. ii) echocardiography with selective CMR in patient with HF due to NICM and/or HFPEF.

Among patients enrolled in Level I of IMAGE-HF, it is expected that 504 will have known NICM (or strongly suspected based on young age, absent risk factors and presenting history) and/or HFPEF.

Tertiary care sites (in Canada and Finland) with dedicated HF programs will participate in the study. Consecutive patients will be enrolled at sites with dedicated CMR programs (defined as minimum 200 cases/year and maximum 2 weeks waiting time in the majority of patients) and randomized to routine CMR or selective CMR. Non-ischemic HF patients from sites without dedicated CMR programs will be included in a registry of patients undergoing routine HF care (i.e. selective use of CMR). Participants in the selective CMR arm may ONLY undergo CMR for a suspicion of: 1) infiltrative myocardial disease, 2) arrhythmogenic right ventricular cardiomyopathy, 3) adult congenital heart disease or 4) pericardial disease following standard HF care including echocardiography. Other tertiary sites may be added in year 2-3 depending on recruitment needs and registry sites may become randomization sites if the experience and wait-time criteria are met.

Eligibility criteria: The study population includes patients with either

1. Newly diagnosed HF within the past 12 months

   OR
2. Established HF patients with deterioration/decompensation within the past 12 months

Inclusion Criteria: Patients with new or worsening HF as above AND

1. Age \> 18
2. Working clinical diagnosis (known or highly suspected) of non-ischemic cardiomyopathy (NICM) OR Clinical diagnosis of HFPEF (Signs or symptoms of heart failure with a LVEF ≥ 40%)
3. Documented history of Class II-IV NYHA HF symptoms within the past 12 months

Exclusion Criteria:

1. Prior CMR and no major change in clinical condition
2. Well-documented specific etiology (eg known amyloidosis or hemochromatosis)
3. MD considers cause of heart failure is attributable to obstructive CAD.
4. Documented previous STEMI (any territory) or NSTEMI in LAD territory
5. Severe medical conditions that significantly affect the patient's outcome (eg. active malignancy)
6. Ongoing need for advanced cardiac life support (eg IABP)
7. Severe valvular heart disease requiring surgery within the next 6 months
8. Contraindications to CMR (e.g. certain metallic implants, severe claustrophobia)
9. Contraindications to gadolinium contrast agent (GFR \< 30ml/min/1,72m2, pregnancy)
10. Inability to give informed consent
11. Evidence of multivessel ischemia on stress imaging

Primary outcomes:
measure: Frequency of definitive diagnoses
timeFrame: 3 and 12 months
Secondary outcomes:
measure: Treatment effects
timeFrame: 3 and 12 months
measure: Clinical Endpoints
timeFrame: 3 and 12 months
measure: Resource utilization and costs
timeFrame: 3 and 12 months
measure: HF Diagnosis Variability:
timeFrame: 3 and 12 months
measure: Echo/CMR variability:
timeFrame: baseline
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Quebec City
country: Canada
facility: University of Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Université de Sherbrooke
state: Quebec
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital,
city: Kuopio
country: Finland
facility: University of Kuopio
city: Turku
country: Finland
facility: University of Turku
Study officials:
affiliation: Universityof Ottawa Heart Institute
name: Rob SB Beanlands, MD, FRCP C
role: STUDY_DIRECTOR
affiliation: University of Alberta
name: Ian Paterson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Paterson DI, OMeara E, Chow BJ, Ukkonen H, Beanlands RS. Recent advances in cardiac imaging for patients with heart failure. Curr Opin Cardiol. 2011 Mar;26(2):132-43. doi: 10.1097/HCO.0b013e32834380e7.
citation: Paterson I, Wells GA, Ezekowitz JA, White JA, Friedrich MG, Mielniczuk LM, O'Meara E, Chow B, DeKemp RA, Klein R, Dennie C, Dick A, Coyle D, Dwivedi G, Rajda M, Wright GA, Laine M, Hanninen H, Larose E, Connelly KA, Leong-Poi H, Howarth AG, Davies RA, Duchesne L, Yla-Herttuala S, Saraste A, Farand P, Garrard L, Tardif JC, Arnold M, Knuuti J, Beanlands R, Chan KL. Routine versus selective cardiac magnetic resonance in non-ischemic heart failure - OUTSMART-HF: study protocol for a randomized controlled trial (IMAGE-HF (heart failure) project 1-B). Trials. 2013 Oct 12;14:332. doi: 10.1186/1745-6215-14-332.
citation: Paterson DI, Wells G, Erthal F, Mielniczuk L, O'Meara E, White J, Connelly KA, Knuuti J, Radja M, Laine M, Chow BJW, Kandolin R, Chen L, Dick A, Dennie C, Garrard L, Ezekowitz J, Beanlands R, Chan KL; IMAGE-HF Investigators. OUTSMART HF: A Randomized Controlled Trial of Routine Versus Selective Cardiac Magnetic Resonance for Patients With Nonischemic Heart Failure (IMAGE-HF 1B). Circulation. 2020 Mar 10;141(10):818-827. doi: 10.1161/CIRCULATIONAHA.119.043964. Epub 2020 Jan 8.