Clinical trial NCT01288560: IMAGE-HF Project I-A: Cardiac Imaging in Ischemic Heart Failure (AIMI-HF)
Official title: Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) Project I-A 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
Coronary Artery Disease
Ischemic Cardiomyopathy
Keywords: medical imaging
heart failure
morbidity and mortality
PET/CT,CMR,SPECT, echo, coronary angiography
knowledge translation
cost effectiveness
quality of life
prospective comparative effectiveness 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: 2011-02-02
Enrollment: 1390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Medical imaging is one of the fastest growing sectors in health care and increases in utilization underscore the need to ensure imaging technology is developed and used effectively. Evaluation of the clinical and economic impact of such imaging lags behind the technology development. Heart failure (HF) represents the final common pathway for most forms of heart disease and morbidity and mortality remain high. There is a need to identify imaging approaches that have a positive impact on therapy decisions, patient outcomes and costs. As well as standard methods to evaluate new and emerging techniques to better test their potential in a clinical management setting.

PRIMARY OBJECTIVES: to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, MI, resuscitated cardiac arrest and cardiac re-hospitalization (WHF, ACS, arrhythmia). Patients with an ischemic heart disease (IHD) etiology will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (is there ischemia and/or viability), in agreement with their local practices for standard and alternative imaging.

SECONDARY OBJECTIVES:

1. To evaluate the effect of imaging modalities within and between the imaging subgroups (advanced (CMR and PET), PET, MRI and standard (SPECT)) on the primary and secondary outcomes in patients being evaluated either for viability and/or ischemia.
2. To evaluate the impact of adherence to recommendations between modalities on outcomes in patients being evaluated for either viability or ischemia.
3. To compare the effect of HF imaging strategies on:

   1. The incidence of revascularization procedures (PCI, CABG, none) and the interaction of the imaging strategy and types of revascularization on outcomes
   2. LV remodeling: LV volumes, LVEF,
   3. HF symptoms, NYHA class
   4. QOL (MLHFQ, the EQ5D)
   5. The evolution of serum prognostic markers in HF (e.g. BNP, RDW, hs-cTnT, hs-CRP, ST2)
   6. Health economics: Costs estimated through regression analysis and cost effectiveness assessed through decision modeling.
   7. The safety of imaging tests measured by cumulative radiation, adverse reactions to imaging contrast agents and stress testing agents will also be determined.
   8. The evolution of renal function (eGFR) and LV remodeling-associated biomarkers (e.g. PIIINP, OPN).
   9. Event rates of each component of the composite endpoint as well as the combined endpoint of CV death and HF hospitalization
   10. All-cause mortality

Detailed description: Among patients with coronary artery disease and HF, mortality rates range from 10-60% at 1 year. Many trials have demonstrated benefit of revascularization in patients with ischemic heart disease (IHD) and LV dysfunction. Some criteria, such as severe angina or left main coronary artery stenosis may indicate the need for surgical therapy for HF patients; however, a large number of patients fall into a gray zone without clear evidence for benefit from surgical intervention. The need remains for approaches that can help better define and select the HF patients most likely to benefit from revascularization; which could be either surgical or percutaneous intervention.

Increasingly over the past three decades, information describing cardiac structure, perfusion, hemodynamics, and metabolism obtained from noninvasive cardiac imaging studies has been used to guide management decisions for patients with HF.

AIMI-HF is part of a large international team grant IMAGE-HF (Imaging Modalities to Assist with Guiding therapy and the Evaluation of patients with Heart Failure) involving 3 parallel trials addressing the role of imaging in HF patients according to HF etiology.

Primary Hypothesis of AIMI-HF:

In patients with HF due to IHD with LVEF less than or equal to 45%, a management algorithm that applies alternative advanced imaging strategies (PET or CMR) achieves a better clinical outcome measured as the composite clinical endpoint (CCE) of cardiac death, MI, resuscitated cardiac arrest and cardiac re-hospitalization (WHF, ACS, arrhythmia) than an approach with "standard care".

Secondary Hypotheses of AIMI-HF:

i) Compared to standard care, in patients with HF due to IHD with LVEF ≤ 45%, a management algorithm that applies alternative advanced imaging modalities (PET or CMR) achieves: a) more efficient use of revascularization procedures with similar complication rates than standard care imaging strategies b) better LV remodeling (including favorable evolution of serum markers associated with LV remodeling e.g. PIIINP, OPN) c) better HF and angina symptom reduction, d) better QoL, measured using MLHFQ and EQ5D, e) more favorable evolution of selected serum markers of prognosis in HF (e.g. BNP, RDW, hs-cTnT, hs-CRP), f) is economically attractive in patients with HF due to IHD with LVEF\<45%, g) reduced event rates of each components of composite endpoint; h) all-cause mortality.

ii) In patients with HF due to IHD with LVEF ≤ 45%, a HF management algorithm that applies PET or one that applies MRI, achieves a better primary composite clinical endpoint (CCE) and secondary outcomes compared to one that applies standard of care in patients assessed for ischemia and/or in patients assessed for viability.

iii) In patients with HF due to IHD with LVEF ≤ 45%, a HF management algorithm that applies PET achieves a better primary composite clinical endpoint (CCE) and secondary outcomes compared to one that applies CMR in patients assessed for ischemia and/or in patients assessed for viability.

iii) Renal function impairment is a known independent predictor of cardiovascular events in HF. Renal function may influence revascularization decisions and its evolution could be modified by revascularization procedures.

Study design AIMI-HF is the IMAGE-HF Project 1-A trial; it is a prospective comparative effectiveness study to compare the effect of HF imaging strategies in patients with HF due to IHD. Eligible patients will have LV systolic dysfunction due to IHD where evaluation of ischemia or viability is relevant. Patients will be prospectively randomized to standard (SPECT) versus advanced (PET or CMR) imaging. Patients who meet inclusion criteria but cannot be randomized due to clinical management decisions, yet undergo standard or advanced imaging (SPECT, PET/CT or CMR), will be entered into a registry. Based on site screening logs, patients who could not be randomized, who met all other inclusion criteria and underwent standard or advanced imaging, will be retrospectively enrolled, from the date of original HREB approval, into the study as registry participants. Registry recruitment will be monitored to ensure as best as possible a balanced recruitment for each modality registry.

Eligibility criteria: Inclusion criteria:

* Age \>18 years
* Known or highly suspected coronary artery disease (CAD) documented by coronary angiography or by history of previous MI or evidence of moderate ischemia or scar based on prior imaging
* LV dysfunction most likely attributable to ischemic heart disease with EF \<45% measured by any acceptable means (echo, nuclear RNA, PET or SPECT perfusion, Angiography, Cardiac MR) within the previous 6 months AND NYHA class II-IV symptoms within the past 12 months.

OR

LV dysfunction most likely attributable to ischemic heart disease with EF ≤30% measured by any acceptable means (echo, nuclear RNA, PET or SPECT perfusion, Angiography, Cardiac MR) within the previous 6 months AND NYHA class I within the past 12 months

Exclusion criteria:

* Severe medical conditions that significantly affect the patient's outcome (eg. severe COPD, active metastatic malignancy) and would preclude revascularization.
* \< 4 weeks post ST segment elevation myocardial infarction (STEMI)
* Already identified as not suitable for revascularization;
* Emergency revascularization indicated
* Severe valvular heart disease requiring surgery
* Contraindications to CMR (eg metallic implant, claustrophobia, renal failure (GFR \<30 ml/min/1.73m2),). However patients with permanent pacemakers or implanted defibrillators or GFR \<30 ml/min/1.7m2, will be randomized only to standard imaging (SPECT) versus PET or entered into the registry if only 1 modality is available
* Pregnancy
* Potential for non compliance to tests involved in this protocol
* Incapacity to provide informed consent

Primary outcomes:
measure: The time to event of the composite clinical endpoint.
timeFrame: From enrolment until date of death or up to 60 months
Secondary outcomes:
measure: The time to event of the composite clinical endpoint viability cohort.
timeFrame: From enrolment until date of death or up to 60 months
measure: The time to event of the composite clinical endpoint ischemia cohort.
timeFrame: From enrolment until date of death or up to 60 months
measure: The time to event of the composite clinical endpoint (PET vs MRI).
timeFrame: From enrolment until date of death or up to 60 months
measure: Imaging modalities: Comparing PET and MRI vs SPECT modalities and for the components of the composite
timeFrame: From enrolment until date of death or up to 60 months
measure: Imaging modalities: Comparing PET vs SPECT modalities and for the components of the composite
timeFrame: From enrolment until date of death or up to 60 months
measure: Imaging modalities: Comparing MRI vs SPECT modalities for the components of the composite
timeFrame: From enrolment until date of death or up to 60 months
measure: Imaging modalities: Comparing PET vs CMR for the components of the composite
timeFrame: From enrolment until date of death or up to 60 months
measure: Revascularization rates between advanced and standard modalities
timeFrame: 3, 12 and 24 months
measure: HF symptoms between advanced and standard modalities
timeFrame: 3, 12 and 24 months
measure: Event rates between advanced and standard modalities
timeFrame: 3, 12 and 24 months
measure: LVEF change over time
timeFrame: 3, 12 and 24 months
measure: LV volumes change over time
timeFrame: 3, 12, 24 months
measure: Cardiac biomarkers change over time
timeFrame: 3, 12, 24 months
measure: Quality of Life assessment change over time
timeFrame: 3, 12, 24 months
Other outcomes:
measure: Cost-effectiveness economic analysis of advances vs standard modalities
timeFrame: From enrolment until date of death or up to 60 months
measure: Safety Analysis between advanced and standard modalities
timeFrame: From enrolment until date of death or up to 60 months
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Buenos Aires
country: Argentina
facility: Diagnostico Maipu por Imagenes
city: Rosario
country: Argentina
facility: Diagnostico Medico Orono
city: Curitiba
country: Brazil
facility: Quanta Diagnóstico e Terapia
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Providence Health
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
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: Ottawa Heart Institute Research Corporation
name: Rob S Beanlands, MD, FRCP C
role: STUDY_DIRECTOR
affiliation: Montreal Heart Institute
name: Eileen O'Meara, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: Lisa Mielniczuk, 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: O'Meara E, Mielniczuk LM, Wells GA, deKemp RA, Klein R, Coyle D, Mc Ardle B, Paterson I, White JA, Arnold M, Friedrich MG, Larose E, Dick A, Chow B, Dennie C, Haddad H, Ruddy T, Ukkonen H, Wisenberg G, Cantin B, Pibarot P, Freeman M, Turcotte E, Connelly K, Clarke J, Williams K, Racine N, Garrard L, Tardif JC, DaSilva J, Knuuti J, Beanlands R; IMAGE HF investigators. Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial. Trials. 2013 Jul 16;14:218. doi: 10.1186/1745-6215-14-218.