TY - JOUR
T1 - Natural History of Patients with Ischemia and No Obstructive Coronary Artery Disease
T2 - The CIAO-ISCHEMIA Study
AU - Reynolds, Harmony R.
AU - Picard, Michael H.
AU - Spertus, John A.
AU - Peteiro, Jesus
AU - Lopez Sendon, Jose Luis
AU - Senior, Roxy
AU - El-Hajjar, Mohammad C.
AU - Celutkiene, Jelena
AU - Shapiro, Michael D.
AU - Pellikka, Patricia A.
AU - Kunichoff, Dennis F.
AU - Anthopolos, Rebecca
AU - Alfakih, Khaled
AU - Abdul-Nour, Khaled
AU - Khouri, Michel
AU - Bershtein, Leonid
AU - De Belder, Mark
AU - Poh, Kian Keong
AU - Beltrame, John F.
AU - Min, James K.
AU - Fleg, Jerome L.
AU - Li, Yi
AU - Maron, David J.
AU - Hochman, Judith S.
N1 - Funding Information:
This work received funding from National Institutes of Health grants R01HL119153, U01HL105907, U01HL105462, U01HL105561, and U01HL105565.
Funding Information:
Dr Reynolds reports grants from National Heart, Lung and Blood Institute during the conduct of the study; nonfinancial support from Abbott Vascular, Siemens, and BioTelemetry, outside the submitted work. Dr Picard reports grants from National Heart, Lung and Blood Institute during the conduct of the study. Dr Spertus reports grants from 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, outside the submitted work; In addition, Dr Spertus has a patent copyright to Seattle Angina Questionnaire with royalties paid and Board of Directors for Blue Cross Blue Shield of Kansas City and Equity in Health Outcomes Sciences. Dr Peteiro reports grants from National Heart, Lung and Blood Institute during the conduct of the study. Dr Sendon reports grants from National Heart, Lung and Blood Institute during the conduct of the study; he also reports grants from Merck, Pfizer, and Boehringer Ingelheim outside the submitted work. Dr Senior reports grants from National Heart, Lung and Blood Institute during the conduct of the study; he also reports speaker fees from Lantheus Medical Imaging,, Bracco, and Philips Healthcare. Drs El-Hajjar, and Celutkiene report grants from National Heart, Lung and Blood Institute during the conduct of the study. Dr Shapiro reports grants from National Heart, Lung and Blood Institute during the conduct of the study; he serves on the Scientific Advisory Board for Regeneron and Amgen. Dr Pellikka, Alfakih, Abdul-Nour, Khouri, Bershtein, de Belder, Poh, and Beltrame, D. Kunichoff, and Y. Li report grants from National Heart, Lung and Blood Institute during the conduct of the study. Dr Min reports grants from National Heart, Lung, and Blood Institute, during the conduct of the study; other from CLEERLY INC, grants and other from GE HEALTHCARE, other from ARINETA, outside the submitted work. Dr Fleg reports no conflict of interest. Dr Maron reports grants from National Heart, Lung and Blood Institute during the conduct of the study. Dr Hochman reports grants from National Heart, Lung, and Blood Institute during the conduct of the study; other from AstraZeneca Pharmaceuticals LP, Arbor Pharmaceuticals LLC, Abbott Vascular, Medtronic Inc, St. Jude Medical Inc, Volcano Corp, Merck Sharp & Dohme Corp, Omron Healthcare Inc, and Amgen Inc, during the conduct of the study.
Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/9/28
Y1 - 2021/9/28
N2 - Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (P=0.46) or ISCHEMIA stress echocardiography participants (P=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). Conclusions: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.
AB - Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (P=0.46) or ISCHEMIA stress echocardiography participants (P=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). Conclusions: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.
KW - coronary artery disease
KW - exercise test
KW - ischemia
KW - microvascular angina
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U2 - 10.1161/CIRCULATIONAHA.120.046791
DO - 10.1161/CIRCULATIONAHA.120.046791
M3 - Article
C2 - 34058845
AN - SCOPUS:85113484019
SN - 0009-7322
VL - 144
SP - 1008
EP - 1023
JO - Circulation
JF - Circulation
IS - 13
ER -