Evidence map›Paper›PMID 34058845›Full record

ArticleCirculation2021

Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

Harmony R Reynolds, Michael H Picard, John A Spertus, Jesus Peteiro, Jose Luis Lopez Sendon, Roxy Senior, Mohammad C El-Hajjar, Jelena Celutkiene, Michael D Shapiro, Patricia A Pellikka and 14 more

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02347215 (Changes in Ischemia and Angina Over One Year Among ISCHEMIA Trial Screen Failures), which is not on this map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
9.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02347215 nacompletednot on this map

Changes in Ischemia and Angina Over One Year Among ISCHEMIA Trial Screen Failures

TypeinterventionalSponsorNYU Langone HealthRan2014 to 2019Enrolled212ConditionsMicrovascular Angina, Angina PectorisArmsQuality of Life assessment, Stress imaging
3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Interpreting ECG-Based Risk Stratification in Women With INOCA: Methodological Considerations From the WISE Cohort.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2026
    Article
  8. Article
  9. Electrocardiographic Predictors of Major Adverse Cardiovascular Events in Women With Suspected Ischemia and no Obstructive Coronary Artery Disease: Results of the Women's Ischemia Syndrome Evaluation.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
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  17. Societal, occupational, and economic considerations for women with (M)INOCA: a narrative review.International journal of occupational medicine and environmental health · 2025
    Review
  18. The role of cardiac imaging in the post-ISCHEMIA world.The British journal of radiology · 2025
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 19 institutions in 10 countries.

Harmony R ReynoldsNew York University Grossman School of Medicine (H.R.R., D.F.K., R.A., Y.L., J.S.H.).ORCID 0000-0003-0284-0655
Michael H PicardMassachusetts General Hospital, Boston (M.H.P.).ORCID 0000-0002-9264-3243
John A SpertusSaint Luke's Mid America Heart Institute/University of Missouri - Kansas City (J.A.S.).ORCID 0000-0002-2839-2611
Jesus PeteiroCHUAC, Universidad de A Coruña,/CIBER-CV, Spain (J.P.).ORCID 0000-0002-8457-6351
Jose Luis Lopez SendonHospital Universitario La Paz, IdiPaz, CIBER-CV, Madrid, Spain (J.L.L.S.).ORCID 0000-0002-0871-9197
Roxy SeniorRoyal Brompton Hospital, London, United Kingdom (R.S.).ORCID 0000-0001-6579-7039
Mohammad C El-HajjarAlbany Medical Center, New York (M.C.E.-H.).
Jelena CelutkieneClinic of Cardiac and Vascular Diseases, Faculty of Medicine/State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania (J.C.).
Michael D ShapiroWake Forest University Baptist Medical Center, Winston-Salem, NC (M.D.S.).ORCID 0000-0002-9071-3287
Patricia A PellikkaMayo Clinic, Rochester, MN (P.A.P.).ORCID 0000-0001-6800-3521
Dennis F KunichoffNew York University Grossman School of Medicine (H.R.R., D.F.K., R.A., Y.L., J.S.H.).
Rebecca AnthopolosNew York University Grossman School of Medicine (H.R.R., D.F.K., R.A., Y.L., J.S.H.).
Khaled AlfakihKing's College Hospital, London, United Kingdom (K.A.).
Khaled Abdul-NourHenry Ford Health System, Grosse Pointe Farms, MI (K.A.-N.).
Michel KhouriDuke University Medical Center, Durham, NC (M.K.).
Leonid BershteinNorth-Western State Medical University n.a. I.I Mechnikov, Saint Petersburg, Russia (L.B.).ORCID 0000-0002-9444-159X
Mark De BelderBarts Health National Health Service Trust, London, United Kingdom (M.D.B.).
Kian Keong PohNational University Heart Centre, Singapore (K.K.P.).
John F BeltrameYong Loo Lin School of Medicine, National University of Singapore (K.K.P., J.F.B.).ORCID 0000-0002-4294-6510
James K MinCleerly, Inc., New York (J.K.M.).
Jerome L FlegNational Heart, Lung, and Blood Institute, Bethesda, MD (J.L.F.).
Yi LiNew York University Grossman School of Medicine (H.R.R., D.F.K., R.A., Y.L., J.S.H.).
David J MaronDepartment of Medicine, Stanford University, CA (D.J.M.).
Judith S HochmanNew York University Grossman School of Medicine (H.R.R., D.F.K., R.A., Y.L., J.S.H.).ORCID 0000-0002-5889-5981
New York University · USNational University of Singapore · SGAlbany Medical Center Hospital · USAtrium Health Wake Forest Baptist · USBarts Health NHS Trust · GBDuke Medical Center · USHenry Ford Health System · USHospital Universitario La Paz · ESJambi University · IDKing Khaled Hospital · SAMayo Clinic in Arizona · USNational Heart Lung and Blood Institute · USNorth-Western State Medical University named after I.I. Mechnikov · RUNorthwick Park Hospital · GBSaint Luke's Hospital · USStanford University · USState Research Institute Centre for Innovative Medicine · LTTwitter (United States) · USUniversidade da Coruña · ES

Funding

The Ischemia Trial - CCCU01HL105907 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HOCHMAN, JUDITH S · 2011 to 2019
$100.1M
The ISCHEMIA Trial - SDCCU01HL105462 · NHLBI · DUKE UNIVERSITY · PI ALEXANDER, KAREN P, O'BRIEN, SEAN M · 2011 to 2019
$17.8M
THE ISCHEMIA TRIAL - IICCU01HL105561 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI SHAW, LESLEE J · 2011 to 2018
$6.5M
The ISCHEMIA Trial - EQOLU01HL105565 · NHLBI · DUKE UNIVERSITY · PI MARK, DANIEL B · 2011 to 2017
$2.4M
CIAO-ISCHEMIA - Resubmission - 1R01HL119153 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI REYNOLDS, HARMONY R. · 2014 to 2017
$1.8M
NHLBI NIH HHS R01 HL119153NHLBI NIH HHS U01 HL105462NHLBI NIH HHS U01 HL105561NHLBI NIH HHS U01 HL105565NHLBI NIH HHS U01 HL105907
6 · The paper itself

Abstract

backgroundIschemia 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.

methodsCIAO-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.

resultsINOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease,

conclusionsImprovement 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.

Indexed as

AgedCoronary Artery DiseaseFemaleHumansIschemiaMaleMiddle AgedNatural Historycoronary artery diseaseexercise testischemiamicrovascular angina

Identifiers

PMID34058845
PMCPMC8478858
OpenAlexW3164263546

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.