International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial

Daniel Ang; Robin Young; Diann Taggart; David Carrick; Sudipta Chattopadhyay; Yogesh Raja; Kanarath Balachandran; Ahmed Elghamaz; John Greenwood; Stephen Hoole; James Cotton; Anirban Choudhury; Peter O'Kane; Sachin Jadhav; Ian Purcell; Rito Mitra; Ahmed Sabra; Joel Giblett; Robert Byrne; Kevin O'Gallagher; Eduardas Subkovas; Rajiv Rampat; Brijesh Anantharam; Ashwin Radhakrishnan; Colum Owens; Peter Damman; Bartłomiej Guzik; Damien Collison; Fiona Howarth; Liz Lennon; Patricia-Marielle Tolentino; Andrea Vicere; Kirsty Martin; Anna Kamdar; Robert Sykes; Rebecca Hanna; Dylan Tan; Robert Heggie; Olivia Wu; Paul Welsh; Thomas Ford; Chim Choy Lang; Vijay Kunadian; Alex McConnachie; Colin Berry

doi:10.1016/j.ahj.2026.107527

International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial

Daniel Ang
, Robin Young
, Diann Taggart
, David Carrick
, Sudipta Chattopadhyay
, Yogesh Raja
, Kanarath Balachandran
, Ahmed Elghamaz
, John Greenwood
, Stephen Hoole
, James Cotton
, Anirban Choudhury
, Peter O'Kane
, Sachin Jadhav
, Ian Purcell
, Rito Mitra
, Ahmed Sabra
, Joel Giblett
, Robert Byrne
, Kevin O'Gallagher

Eduardas Subkovas, Rajiv Rampat, Brijesh Anantharam, Ashwin Radhakrishnan, Colum Owens, Peter Damman, Bartłomiej Guzik, Damien Collison, Fiona Howarth, Liz Lennon, Patricia-Marielle Tolentino, Andrea Vicere, Kirsty Martin, Anna Kamdar, Robert Sykes, Rebecca Hanna, Dylan Tan, Robert Heggie, Olivia Wu, Paul Welsh, Thomas Ford, Chim Choy Lang, Vijay Kunadian, Alex McConnachie, Colin Berry (Lead / Corresponding author)

Cardiovascular Research

Research output: Contribution to journal › Article › peer-review

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Abstract

BACKGROUND: Angina is a debilitating condition caused by coronary artery disease and microvascular dysfunction. Following coronary angiography angina and no obstructive coronary arteries is a common outcome, and women are disproportionately affected. The objectives are first, to assess causes of angina in patients undergoing invasive management; and second, to assess effects of coronary function test-guided management on clinical outcomes.

METHODS: This is an international, multicenter, prospective, registry-based study and nested, randomized, controlled, triple-blind, and endpoint trial. Participants, community care providers, and outcomes assessors are masked. Consented participants enter the registry. Participants without obstructive coronary artery disease (luminal stenosis <50%, or fractional flow reserve >0.80) are eligible for randomization. Index of microcirculatory resistance (IMR; abnormal ≥25) and coronary flow reserve (CFR; abnormal <2.0; gray zone 2.0-2.5) are measured by bolus thermodilution, and results are disclosed (intervention) or not (control group) to the attending cardiologist.

RESULTS: The primary outcome of the registry is the Seattle Angina Questionnaire summary score at baseline described by coronary artery disease status. Secondary outcomes include the prevalence of obstructive coronary artery disease, patient reported outcome measures and clinical outcomes. The primary outcome of the randomized trial is the within-individual change in Seattle Angina Questionnaire summary score at 12-months from baseline. Secondary outcomes include safety, diagnostic accuracy, patient reported outcome measures for quality of life, physical and psychological function, cardiovascular risk, clinical outcomes, health economics and mechanistic biomarkers. The first patient was screened on December 18, 2020 and the last patient was enrolled on June 30, 2026. Forty sites were included in the United Kingdom (n = 35), Republic of Ireland (n = 2), Holland (n = 2), and Poland (n = 1). In total, 1,483 participants were enrolled into the registry of whom 1,047 were randomized and 386 were not randomized (registry-only).

CONCLUSION: This international, registry-based clinical trial will provide novel evidence on the natural history of angina and stratified therapy for angina with no obstructive coronary arteries.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04674449.

UNIQUE IDENTIFIER: NCT04674449.

Original language	English
Article number	107527
Pages (from-to)	107527
Journal	American Heart Journal
Volume	301
Early online date	6 Jul 2026
DOIs	https://doi.org/10.1016/j.ahj.2026.107527
Publication status	E-pub ahead of print - 6 Jul 2026

Keywords

Humans
Registries
Female
Microvascular Angina/diagnosis
Coronary Angiography/methods
Prospective Studies
Male
Fractional Flow Reserve, Myocardial/physiology
Middle Aged
Microcirculation/physiology

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.ahj.2026.107527Licence: CC BY

Final Published Version
© 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) https://doi.org/10.1016/j.ahj.2026.107527
Final published version, 2 MBLicence: CC BY

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Ang, D., Young, R., Taggart, D., Carrick, D., Chattopadhyay, S., Raja, Y., Balachandran, K., Elghamaz, A., Greenwood, J., Hoole, S., Cotton, J., Choudhury, A., O'Kane, P., Jadhav, S., Purcell, I., Mitra, R., Sabra, A., Giblett, J., Byrne, R., ... Berry, C. (2026). International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial. American Heart Journal, 301, 107527. Article 107527. Advance online publication. https://doi.org/10.1016/j.ahj.2026.107527

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title = "International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial",

abstract = "BACKGROUND: Angina is a debilitating condition caused by coronary artery disease and microvascular dysfunction. Following coronary angiography angina and no obstructive coronary arteries is a common outcome, and women are disproportionately affected. The objectives are first, to assess causes of angina in patients undergoing invasive management; and second, to assess effects of coronary function test-guided management on clinical outcomes.METHODS: This is an international, multicenter, prospective, registry-based study and nested, randomized, controlled, triple-blind, and endpoint trial. Participants, community care providers, and outcomes assessors are masked. Consented participants enter the registry. Participants without obstructive coronary artery disease (luminal stenosis <50\%, or fractional flow reserve >0.80) are eligible for randomization. Index of microcirculatory resistance (IMR; abnormal ≥25) and coronary flow reserve (CFR; abnormal <2.0; gray zone 2.0-2.5) are measured by bolus thermodilution, and results are disclosed (intervention) or not (control group) to the attending cardiologist.RESULTS: The primary outcome of the registry is the Seattle Angina Questionnaire summary score at baseline described by coronary artery disease status. Secondary outcomes include the prevalence of obstructive coronary artery disease, patient reported outcome measures and clinical outcomes. The primary outcome of the randomized trial is the within-individual change in Seattle Angina Questionnaire summary score at 12-months from baseline. Secondary outcomes include safety, diagnostic accuracy, patient reported outcome measures for quality of life, physical and psychological function, cardiovascular risk, clinical outcomes, health economics and mechanistic biomarkers. The first patient was screened on December 18, 2020 and the last patient was enrolled on June 30, 2026. Forty sites were included in the United Kingdom (n = 35), Republic of Ireland (n = 2), Holland (n = 2), and Poland (n = 1). In total, 1,483 participants were enrolled into the registry of whom 1,047 were randomized and 386 were not randomized (registry-only).CONCLUSION: This international, registry-based clinical trial will provide novel evidence on the natural history of angina and stratified therapy for angina with no obstructive coronary arteries.CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04674449.UNIQUE IDENTIFIER: NCT04674449.",

keywords = "Humans, Registries, Female, Microvascular Angina/diagnosis, Coronary Angiography/methods, Prospective Studies, Male, Fractional Flow Reserve, Myocardial/physiology, Middle Aged, Microcirculation/physiology",

author = "Daniel Ang and Robin Young and Diann Taggart and David Carrick and Sudipta Chattopadhyay and Yogesh Raja and Kanarath Balachandran and Ahmed Elghamaz and John Greenwood and Stephen Hoole and James Cotton and Anirban Choudhury and Peter O'Kane and Sachin Jadhav and Ian Purcell and Rito Mitra and Ahmed Sabra and Joel Giblett and Robert Byrne and Kevin O'Gallagher and Eduardas Subkovas and Rajiv Rampat and Brijesh Anantharam and Ashwin Radhakrishnan and Colum Owens and Peter Damman and Bart{\l}omiej Guzik and Damien Collison and Fiona Howarth and Liz Lennon and Patricia-Marielle Tolentino and Andrea Vicere and Kirsty Martin and Anna Kamdar and Robert Sykes and Rebecca Hanna and Dylan Tan and Robert Heggie and Olivia Wu and Paul Welsh and Thomas Ford and Lang, \{Chim Choy\} and Vijay Kunadian and Alex McConnachie and Colin Berry",

year = "2026",

month = jul,

day = "6",

doi = "10.1016/j.ahj.2026.107527",

language = "English",

volume = "301",

pages = "107527",

journal = "American Heart Journal",

issn = "0002-8703",

publisher = "Elsevier",

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Ang, D, Young, R, Taggart, D, Carrick, D, Chattopadhyay, S, Raja, Y, Balachandran, K, Elghamaz, A, Greenwood, J, Hoole, S, Cotton, J, Choudhury, A, O'Kane, P, Jadhav, S, Purcell, I, Mitra, R, Sabra, A, Giblett, J, Byrne, R, O'Gallagher, K, Subkovas, E, Rampat, R, Anantharam, B, Radhakrishnan, A, Owens, C, Damman, P, Guzik, B, Collison, D, Howarth, F, Lennon, L, Tolentino, P-M, Vicere, A, Martin, K, Kamdar, A, Sykes, R, Hanna, R, Tan, D, Heggie, R, Wu, O, Welsh, P, Ford, T, Lang, CC, Kunadian, V, McConnachie, A & Berry, C 2026, 'International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial', American Heart Journal, vol. 301, 107527, pp. 107527. https://doi.org/10.1016/j.ahj.2026.107527

TY - JOUR

T1 - International study of coronary microvascular angina (iCorMicA)

T2 - A registry-based diagnostic study and nested randomized trial

AU - Ang, Daniel

AU - Young, Robin

AU - Taggart, Diann

AU - Carrick, David

AU - Chattopadhyay, Sudipta

AU - Raja, Yogesh

AU - Balachandran, Kanarath

AU - Elghamaz, Ahmed

AU - Greenwood, John

AU - Hoole, Stephen

AU - Cotton, James

AU - Choudhury, Anirban

AU - O'Kane, Peter

AU - Jadhav, Sachin

AU - Purcell, Ian

AU - Mitra, Rito

AU - Sabra, Ahmed

AU - Giblett, Joel

AU - Byrne, Robert

AU - O'Gallagher, Kevin

AU - Subkovas, Eduardas

AU - Rampat, Rajiv

AU - Anantharam, Brijesh

AU - Radhakrishnan, Ashwin

AU - Owens, Colum

AU - Damman, Peter

AU - Guzik, Bartłomiej

AU - Collison, Damien

AU - Howarth, Fiona

AU - Lennon, Liz

AU - Tolentino, Patricia-Marielle

AU - Vicere, Andrea

AU - Martin, Kirsty

AU - Kamdar, Anna

AU - Sykes, Robert

AU - Hanna, Rebecca

AU - Tan, Dylan

AU - Heggie, Robert

AU - Wu, Olivia

AU - Welsh, Paul

AU - Ford, Thomas

AU - Lang, Chim Choy

AU - Kunadian, Vijay

AU - McConnachie, Alex

AU - Berry, Colin

PY - 2026/7/6

Y1 - 2026/7/6

N2 - BACKGROUND: Angina is a debilitating condition caused by coronary artery disease and microvascular dysfunction. Following coronary angiography angina and no obstructive coronary arteries is a common outcome, and women are disproportionately affected. The objectives are first, to assess causes of angina in patients undergoing invasive management; and second, to assess effects of coronary function test-guided management on clinical outcomes.METHODS: This is an international, multicenter, prospective, registry-based study and nested, randomized, controlled, triple-blind, and endpoint trial. Participants, community care providers, and outcomes assessors are masked. Consented participants enter the registry. Participants without obstructive coronary artery disease (luminal stenosis <50%, or fractional flow reserve >0.80) are eligible for randomization. Index of microcirculatory resistance (IMR; abnormal ≥25) and coronary flow reserve (CFR; abnormal <2.0; gray zone 2.0-2.5) are measured by bolus thermodilution, and results are disclosed (intervention) or not (control group) to the attending cardiologist.RESULTS: The primary outcome of the registry is the Seattle Angina Questionnaire summary score at baseline described by coronary artery disease status. Secondary outcomes include the prevalence of obstructive coronary artery disease, patient reported outcome measures and clinical outcomes. The primary outcome of the randomized trial is the within-individual change in Seattle Angina Questionnaire summary score at 12-months from baseline. Secondary outcomes include safety, diagnostic accuracy, patient reported outcome measures for quality of life, physical and psychological function, cardiovascular risk, clinical outcomes, health economics and mechanistic biomarkers. The first patient was screened on December 18, 2020 and the last patient was enrolled on June 30, 2026. Forty sites were included in the United Kingdom (n = 35), Republic of Ireland (n = 2), Holland (n = 2), and Poland (n = 1). In total, 1,483 participants were enrolled into the registry of whom 1,047 were randomized and 386 were not randomized (registry-only).CONCLUSION: This international, registry-based clinical trial will provide novel evidence on the natural history of angina and stratified therapy for angina with no obstructive coronary arteries.CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04674449.UNIQUE IDENTIFIER: NCT04674449.

AB - BACKGROUND: Angina is a debilitating condition caused by coronary artery disease and microvascular dysfunction. Following coronary angiography angina and no obstructive coronary arteries is a common outcome, and women are disproportionately affected. The objectives are first, to assess causes of angina in patients undergoing invasive management; and second, to assess effects of coronary function test-guided management on clinical outcomes.METHODS: This is an international, multicenter, prospective, registry-based study and nested, randomized, controlled, triple-blind, and endpoint trial. Participants, community care providers, and outcomes assessors are masked. Consented participants enter the registry. Participants without obstructive coronary artery disease (luminal stenosis <50%, or fractional flow reserve >0.80) are eligible for randomization. Index of microcirculatory resistance (IMR; abnormal ≥25) and coronary flow reserve (CFR; abnormal <2.0; gray zone 2.0-2.5) are measured by bolus thermodilution, and results are disclosed (intervention) or not (control group) to the attending cardiologist.RESULTS: The primary outcome of the registry is the Seattle Angina Questionnaire summary score at baseline described by coronary artery disease status. Secondary outcomes include the prevalence of obstructive coronary artery disease, patient reported outcome measures and clinical outcomes. The primary outcome of the randomized trial is the within-individual change in Seattle Angina Questionnaire summary score at 12-months from baseline. Secondary outcomes include safety, diagnostic accuracy, patient reported outcome measures for quality of life, physical and psychological function, cardiovascular risk, clinical outcomes, health economics and mechanistic biomarkers. The first patient was screened on December 18, 2020 and the last patient was enrolled on June 30, 2026. Forty sites were included in the United Kingdom (n = 35), Republic of Ireland (n = 2), Holland (n = 2), and Poland (n = 1). In total, 1,483 participants were enrolled into the registry of whom 1,047 were randomized and 386 were not randomized (registry-only).CONCLUSION: This international, registry-based clinical trial will provide novel evidence on the natural history of angina and stratified therapy for angina with no obstructive coronary arteries.CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04674449.UNIQUE IDENTIFIER: NCT04674449.

KW - Humans

KW - Registries

KW - Female

KW - Microvascular Angina/diagnosis

KW - Coronary Angiography/methods

KW - Prospective Studies

KW - Male

KW - Fractional Flow Reserve, Myocardial/physiology

KW - Middle Aged

KW - Microcirculation/physiology

UR - https://www.scopus.com/pages/publications/105045937972

U2 - 10.1016/j.ahj.2026.107527

DO - 10.1016/j.ahj.2026.107527

M3 - Article

C2 - 42409349

SN - 0002-8703

VL - 301

SP - 107527

JO - American Heart Journal

JF - American Heart Journal

M1 - 107527

ER -

International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial

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Keywords

ASJC Scopus subject areas

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