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Randomized Controlled Trial
. 2024 Dec;17(12):e013743.
doi: 10.1161/CIRCINTERVENTIONS.123.013743. Epub 2024 Dec 17.

Relationship Between Severity of Ischemia and Coronary Artery Disease for Different Stress Test Modalities in the ISCHEMIA Trial

Harmony R Reynolds  1 , Courtney B Page  2 , Leslee J Shaw  3 , Daniel S Berman  4 , Bernard R Chaitman  5 , Michael H Picard  6   7 , Raymond Y Kwong  8 , James K Min  9 , Jonathon Leipsic  10 , G B John Mancini  10 , Matthew J Budoff  11 , Cameron J Hague  12 , Roxy Senior  13 , Hanna Szwed  14 , Balram Bhargava  15 , Jelena Celutkiene  16   17 , Milind Gadkari  18 , Kevin R Bainey  19 , Rolf Doerr  20 , Ruben B Ramos  21 , Peter Ong  22 , Sudhir R Naik  23 , Philippe Gabriel Steg  24 , Kaatje Goetschalckx  25 , Benjamin J W Chow  26 , Marielle Scherrer-Crosbie  27 , Lawrence Phillips  1 , Daniel B Mark  2 , John A Spertus  28 , Karen P Alexander  2 , Sean M O'Brien  2 , William E Boden  29   30 , Sripal Bangalore  1 , Gregg W Stone  3 , David J Maron  31 , Judith S Hochman  1 ; ISCHEMIA Research Group
Collaborators, Affiliations
Randomized Controlled Trial

Relationship Between Severity of Ischemia and Coronary Artery Disease for Different Stress Test Modalities in the ISCHEMIA Trial

Harmony R Reynolds et al. Circ Cardiovasc Interv. 2024 Dec.

Abstract

Background: The relationship between the extent and severity of stress-induced ischemia and the extent and severity of anatomic coronary artery disease (CAD) in patients with obstructive CAD is multifactorial and includes the intensity of stress achieved, type of testing used, presence and extent of prior infarction, collateral blood flow, plaque characteristics, microvascular disease, coronary vasomotor tone, and genetic factors. Among chronic coronary disease participants with site-determined moderate or severe ischemia, we investigated associations between ischemia severity on stress testing and the extent of CAD on coronary computed tomography angiography.

Methods: Clinically indicated stress testing included nuclear imaging, echocardiography, cardiac magnetic resonance imaging, or nonimaging exercise tolerance test. Among those with preserved renal function who underwent coronary computed tomography angiography, we examined relationships between ischemia and CAD by coronary computed tomography angiography, overall, and by stress test modality, regardless of subsequent randomization. Core laboratories categorized ischemia as severe, moderate, mild, or none, while the extent and severity of anatomic CAD were categorized based on the modified Duke prognostic index.

Results: Among 3601 participants with interpretable stress tests and coronary computed tomography angiography, ischemia severity was weakly associated with CAD extent/severity (r=0.27), with modest variability in strength of association by modality: nuclear (n=1532; r=0.40), echocardiography (n=827; r=0.15), cardiac magnetic resonance imaging (n=108; r=0.31), and exercise tolerance test (n=1134; r=0.18). The extent of infarction on nuclear imaging and echocardiography was weakly associated with CAD extent/severity.

Conclusions: Overall, ischemia severity on stress testing showed weak to moderate associations with the anatomic extent of CAD in this cohort with moderate or severe ischemia on local interpretation and controlled symptoms.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Keywords: angiography; coronary artery disease; infarction; ischemia; plaque, atherosclerotic.

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Conflict of interest statement

Dr Reynolds reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study, and consulting fees from HeartFlow; she receives 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). Dr Berman receives software royalties from Cedars-Sinai Medical Center, outside the submitted work. Dr Chaitman reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study and personal fees from Merck, Novo Nordisk, Sanofi, Lilly, Johnson and Johnson, Daiichi Sankyo, Tricida, Relypsa, Imbria, and Xylocor, outside the submitted work. Dr Kwong reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Min reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study; other from Cleerly, Inc, grants; and other from GE Healthcare and Arineta, outside the submitted work. Dr Leipsic is a consultant and has stock options in HeartFlow and Circle CVI and received research grant from GE Healthcare, outside the submitted work. Dr Mancini reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study; grants and personal fees from Amgen, grants and personal fees from Sanofi, Boehringer Ingelheim, AstraZeneca, Bayer, Janssen, Novo Nordisk, and HLS Therapeutics; and grants from Novartis, outside the submitted work. Dr Budoff reports grant support from General Electric, outside the submitted work. Dr Hague reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Senior reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study and speaker fees from Bracco, Lantheus Medical Imaging Boston USA, and Philips Healthcare, outside the submitted work. Dr Bhargava reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Celutkiene reported personal fees from Boehringer Ingelheim, AstraZeneca, Bayer, and Novartis. Dr Bainey received unrestricted research grant support from the Heart and Stroke Foundation of Canada, AstraZeneca, and Bayer; speaker honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer Alliance, and Boehringer Ingelheim-Eli Lilly Alliance; consultancy and advisory board memberships in AstraZeneca, Abbott Vascular, Bayer, Bristol-Myers Squibb-Pfizer Alliance, and Boehringer Ingelheim-Eli Lilly Alliance; and proctorship honoraria from Abbott Vascular. Dr Doerr reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Ong reports speaker honoraria from Abbott Medical, Phillips, Bayer Healthcare, Pfizer, and Medtronic and research funding from the Berthold Leibinger Foundation, Ditzingen, Germany. Dr Steg reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study and research grants from Amarin, Bayer, Sanofi, and Servier; he serves as a member of the Steering Committee, Clinical Events Committee, or Data and Safety Monitoring Board for clinical trials conducted in Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Idorsia, Myokardia, Novartis, Pfizer, Sanofi, and Servier; consulting or speaker’s fees from Amgen, Novo Nordisk, and Regeneron. Dr Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research; receives research support from TD Bank, CV Diagnostix and AusculSciences, and Siemens Healthineers; and has equity interest in General Electric. Dr Phillips has served as a consultant for Novo Nordisk. Dr Mark reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study, and grants from HeartFlow and Merck, outside the submitted work. Dr Spertus reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study; personal fees from Bayer, Novartis, AstraZeneca, Amgen, Janssen, and United Healthcare; grants from the American College of Cardiology; and personal fees from Blue Cross Blue Shield of Kansas City, outside the submitted work; in addition, Dr Spertus has a patent Copyright to Seattle Angina Questionnaire with royalties paid and Equity in Health Outcomes Sciences. Dr O’Brien reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Boden reports grants from the National Heart, Lung, and Blood Institute, 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 the submitted work. Dr Bangalore reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study; grants and personal fees from Abbott Vascular; and personal fees from Biotronik, Pfizer, Amgen, and Reata, outside the submitted work. Dr Stone reports grants and personal fees from the National Heart, Lung, and Blood Institute during the conduct of the study; speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; is a consultant to 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; and equity/options in Ancora, Cagent, Applied Therapeutics, Biostar Family of Funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Institutional disclosures: Dr Stone’s employer, Mount Sinai Hospital; Dr Stone receives research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Inc, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Family disclosure: Dr Stone’s daughter is an employee at IQVIA. Dr Maron reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Hochman was the PI for the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) for which, in addition to support by the National Heart, Lung, and Blood Institute 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 Corporation; and Omron Healthcare, Inc; and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. She is a PI for ISCHEMIA-EXTEND (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches Extended Follow-Up). The other authors report no conflicts.

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