Harmony R Reynolds1, Michael H Picard2, John A Spertus3, Jesus Peteiro4, Jose Luis Lopez Sendon5, Roxy Senior6,7, Mohammad C El-Hajjar8, Jelena Celutkiene9, Michael D Shapiro10, Patricia A Pellikka11, Dennis F Kunichoff1, Rebecca Anthopolos1, Khaled Alfakih12, Khaled Abdul-Nour13, Michel Khouri14, Leonid Bershtein15, Mark De Belder16, Kian Keong Poh17,18, John F Beltrame18,19, James K Min20, Jerome L Fleg21, Yi Li1, David J Maron22, Judith S Hochman1. 1. New York University Grossman School of Medicine (H.R.R., D.F.K., R.A., Y.L., J.S.H.). 2. Massachusetts General Hospital, Boston (M.H.P.). 3. Saint Luke's Mid America Heart Institute/University of Missouri - Kansas City (J.A.S.). 4. CHUAC, Universidad de A Coruña,/CIBER-CV, Spain (J.P.). 5. Hospital Universitario La Paz, IdiPaz, CIBER-CV, Madrid, Spain (J.L.L.S.). 6. Royal Brompton Hospital, London, United Kingdom (R.S.). 7. Northwick Park Hospital, Harrow, United Kingdom (R.S.). 8. Albany Medical Center, New York (M.C.E.-H.). 9. Clinic of Cardiac and Vascular Diseases, Faculty of Medicine/State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania (J.C.). 10. Wake Forest University Baptist Medical Center, Winston-Salem, NC (M.D.S.). 11. Mayo Clinic, Rochester, MN (P.A.P.). 12. King's College Hospital, London, United Kingdom (K.A.). 13. Henry Ford Health System, Grosse Pointe Farms, MI (K.A.-N.). 14. Duke University Medical Center, Durham, NC (M.K.). 15. North-Western State Medical University n.a. I.I Mechnikov, Saint Petersburg, Russia (L.B.). 16. Barts Health National Health Service Trust, London, United Kingdom (M.D.B.). 17. National University Heart Centre, Singapore (K.K.P.). 18. Yong Loo Lin School of Medicine, National University of Singapore (K.K.P., J.F.B.). 19. University of Adelaide/Central Adelaide Local Health Network, South Australia (J.F.B.). 20. Cleerly, Inc., New York (J.K.M.). 21. National Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.). 22. Department of Medicine, Stanford University, CA (D.J.M.).
Abstract
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.
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.
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