Stress Cardiac Magnetic Resonance Ischemia Burden and Cardiovascular Events: Post-Hoc Analysis From the ISCHEMIA Trial.
| Title: | Stress Cardiac Magnetic Resonance Ischemia Burden and Cardiovascular Events: Post-Hoc Analysis From the ISCHEMIA Trial. |
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| Authors: | Kwong RY; Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: rykwong@bwh.harvard.edu.; Heydari B; Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Abbasi S; Amegen, Thousand Oaks, California, USA.; Mongeon FP; Department of Specialized Medicine, Division of Non-Invasive Cardiology, Montreal Heart Institute, Montreal, Quebec, Canada.; Marcotte F; Mayo Clinic, Phoenix, Arizona, USA.; Friedrich M; Department of Specialized Medicine, Division of Non-Invasive Cardiology, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.; Shaw LJ; Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Xu Y; NYU Grossman School of Medicine, New York, New York, USA.; Anthopolos R; NYU Grossman School of Medicine, New York, New York, USA.; Bekeredjian R; Robert Bosch Medical Center, Stuttgart, Germany.; Monti L; Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.; Selvanayagam J; Flinders Medical Centre, Adelaide, South Australia, Australia.; Lesiak M; University Hospital of the Lords Transfiguration, Poznan, Poland.; Picard MH; Department of Medicine, Cardiovascular Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Berman DS; Cedars Sinai Medical Center, Los Angeles, California, USA.; Bangalore S; Duke Clinical Research Institute, Durham, North Carolina, USA.; Spertus JA; Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA; University of Missouri-Kansas City's Healthcare Institute for Innovations in Quality, Kansas City, Missouri, USA.; Stone GW; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Boden WE; VA New England Healthcare System, Bedford, Massachusetts, USA.; Min J; Cleerly Inc, New York, New York, USA.; Mancini GBJ; University of British Columbia, Vancouver, British Columbia, Canada.; Leipsic J; University of British Columbia, Vancouver, British Columbia, Canada.; Budoff M; Lundquist Institute, Harbor-UCLA Medical Center, Torrance, California, USA.; Hague C; Cleerly Inc, New York, New York, USA.; Hochman JS; Cardiovascular Clinical Research Center, Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA.; Maron DJ; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.; Reynolds HR; Cardiovascular Clinical Research Center, Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. |
| Corporate Authors: | ISCHEMIA Research Group |
| Source: | JACC. Cardiovascular imaging [JACC Cardiovasc Imaging] 2026 Mar; Vol. 19 (3), pp. 326-341. Date of Electronic Publication: 2025 Dec 05. |
| Publication Type: | Journal Article; Randomized Controlled Trial; Comparative Study; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 101467978 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1876-7591 (Electronic) Linking ISSN: 18767591 NLM ISO Abbreviation: JACC Cardiovasc Imaging Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York : Elsevier |
| MeSH Terms: | Myocardial Ischemia*/mortality ; Myocardial Ischemia*/therapy ; Myocardial Ischemia*/diagnostic imaging ; Myocardial Ischemia*/diagnosis ; Myocardial Ischemia*/complications ; Tomography, Emission-Computed, Single-Photon* ; Echocardiography, Stress* ; Magnetic Resonance Imaging* ; Magnetic Resonance Imaging, Cine*; Myocardial Infarction/mortality ; Myocardial Infarction/etiology ; Myocardial Infarction/therapy ; Angina, Unstable/etiology ; Angina, Unstable/mortality ; Heart Failure/etiology ; Heart Failure/mortality ; Humans ; Male ; Female ; Middle Aged ; Predictive Value of Tests ; Aged ; Time Factors ; Severity of Illness Index ; Risk Factors ; Prognosis ; Hospitalization ; Risk Assessment |
| Abstract: | Background: Research comparing the prognostic value of stress cardiac magnetic resonance (CMR) to other stress modalities in patients with coronary disease is limited.; Objectives: The authors compared the prognostic value of stress CMR vs alternative testing by either single-photon emission computed tomography or stress echocardiography (SPECT/echo) in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial.; Methods: CMR vs SPECT/echo was compared in 3,909 patients randomized in ISCHEMIA after sites' interpretation of moderate to severe ischemia. Ischemia and infarct extent, measured by either CMR or SPECT/echo, were each associated with the trial's primary outcome of cardiovascular death, nonfatal myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, at a median follow-up of 3.37 years (Q1-Q3: 2.20-4.56 years).; Results: Compared with SPECT/echo (n = 5,627), CMR participants (n = 313) were not different in key demographic factors but were more likely to have severe ischemia (57% vs 38%; P < 0.001) and to be randomized (n = 257, 82%, vs n = 3,652, 65%; P < 0.001). Ischemia severity (no/mild, moderate, severe) by CMR core laboratory was associated with cumulative 4-year event rates of all trial-specific endpoints, including the primary outcome (P = 0.042), cardiovascular death/MI (P = 0.041), and nonfatal MI (P = 0.03), but SPECT/echo ischemia severity was not. No/mild, moderate, and severe ischemia by CMR were associated with 0%, 14%, and 23% 4-year primary outcome rates, respectively, compared with 18%, 15%, and 16%, by SPECT/echo. After adjustment for age, estimated glomerular filtration rate, and diabetes, the association between ischemia extent and the primary endpoint differed by imaging modality, with each additional ischemic segment on CMR associated with a 13% increase in hazard (interaction P = 0.02). In participants assigned to initial conservative management who had no/mild ischemia on imaging, 4-year rates of invasive referral and coronary revascularization were lower in the CMR than SPECT/echo group (16.7% and 0%, respectively, for CMR; and 31% and 13.3%, respectively, for SPECT/echo).; Conclusions: Ischemia severity by CMR had a stronger association with all ISCHEMIA trial endpoints compared with SPECT/echo. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).; (Copyright © 2026 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Funding Support and Author Disclosures This study was funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (grant numbers U01HL105907, U01HL105462, U01HL105561, U01HL105565). Dr Kwong has received grants from the NHLBI during the conduct of the trial. Dr Abbasi is an employee and shareholder of Amegen. Dr Shaw has received grants from the NHLBI during the conduct of the trial and currently. Dr Anthopolos, Mr Xu, and Dr Selvanayagam have received grants from the NHLBI during the conduct of the study. Dr Lesiak has received personal fees from AstraZeneca, Pfizer, and Terumo outside of the submitted work. Dr Picard has received grants from the NHLBI during the conduct of the trial. Dr Berman has received software royalties from Cedars-Sinai Medical Center outside of the submitted work; and grants from the NHLBI during the conduct of the trial. Dr Bangalore has received grants from the NHLBI during the conduct of the study; grants and personal fees from Abbott Vascular; and personal fees from Biotronik, Pfizer, Amgen, and Reata outside of the submitted work. Dr Spertus has received grants from the NHLBI during the conduct of the study and the American College of Cardiology; personal fees from Bayer, Novartis, AstraZeneca, Amgen, Janssen, United Healthcare, and Blue Cross Blue Shield of Kansas City outside of the submitted work; and has a patent copyright to Seattle Angina Questionnaire with royalties paid and Equity in Health Outcomes Sciences. Dr Stone has received grants and personal fees from the NHLBI during the conduct of the study; speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; consulting fees from Abbott, Daiichi-Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, and HighLife; has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; his employer, Mount Sinai Hospital, has received research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave; and his daughter is an employee at IQVIA. Dr Boden has received grants from the NHLBI during the conduct of the study; grants from Abbvie, Amarin, and Amgen; and personal fees from Amgen, Cleveland Clinic Clinical Coordinating Center, and Janssen, outside of the submitted work. Dr Min is an employee of Cleerly, Inc and retains equity. Dr Mancini has received grants from the NHLBI during the conduct of the study; grants and personal fees from Amgen, Sanofi, Boehringer Ingelheim, AstraZeneca, Bayer, Janssen, Novo Nordisk, and HLS Therapeutics; and grants from Novartis, outside of the submitted work. Dr Leipsic has received consulting fees and has stock options with HeartFlow and Circle CVI; and a research grant from GE HealthCare outside of the submitted work. Dr Budoff has received grant support from General Electric outside of the submitted work. Dr Hochman has been the primary investigator for the ISCHEMIA trial for which, in addition to support by the NHLBI grant, devices and medications were provided by Abbott Vascular, Medtronic Inc, Abbott Laboratories (formerly St Jude Medical, Inc), Royal Philips NV (formerly Volcano Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck Sharp & Dohme Corp, and Omron Healthcare, Inc; and has received financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP; and she is primary investigator for ISCHEMIA-EXTEND. Dr Maron has received grants from the NHLBI during the conduct of the study; independent contractor fees from Abiomed; has stock in Ablative Solutions; has received research funding from Cleerly; and has received consulting fees from Regeneron. Dr Reynolds has received grants from the NHLBI during the conduct of the study; consulting fees from HeartFlow; and support from Abbott Vascular (donation of optical coherence tomography catheters for an unrelated research study) and Biotelemetry Inc (donation of telemetry monitors for an unrelated research study). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. |
| Grant Information: | U01 HL105462 United States HL NHLBI NIH HHS; U01 HL105561 United States HL NHLBI NIH HHS; U01 HL105565 United States HL NHLBI NIH HHS; U01 HL105907 United States HL NHLBI NIH HHS |
| Contributed Indexing: | Keywords: ISCHEMIA trial; cardiovascular events; stress cardiac magnetic resonance imaging |
| Molecular Sequence: | ClinicalTrials.gov NCT01471522 |
| Entry Date(s): | Date Created: 20251206 Date Completed: 20260306 Latest Revision: 20260509 |
| Update Code: | 20260509 |
| PubMed Central ID: | PMC13155462 |
| DOI: | 10.1016/j.jcmg.2025.10.015 |
| PMID: | 41351610 |
| Database: | MEDLINE |
Journal Article; Randomized Controlled Trial; Comparative Study; Multicenter Study