CompREhensive Diagnostic Assessment of Coronary Endothelial Function Impairment and Vasospasm With CoNtinuous ThErmodilution in Patients With Suspected Coronary Microvascular and Vasomotor Dysfunction (REDEFINE-CMD)

The goal of this observational study is to learn more about the diagnosis of coronary endothelium function and coronary vasospasm using a dedicated invasive protocol in patients who has angina without obstruction in their main heart arteries. The main question it aims to answer is the feasibility, reproducibility, and safety of this invasive protocol:

Does this invasive protocol diagnose coronary endothelial dysfunction and vasospasm without issues?

Participants already having invasive coronary angiogram and physiological studies will undergo additional physiological measurements during the same procedure.

Participants will enrol in a symptoms and quality of life questionnaire using dedicated questionnaires and a mobile application to assess the burden of their symptoms before and after the invasive procedure and up to 12 months follow up.

A subset of participants will undergo a repeat set of these measurements to assess reproducibility of the invasive protocol.

A subset of the participants will also undergo a cardiac MRI to assess correlation with the invasive protocol measurements.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Microvascular Dysfunction (CMD); Vasospasm, Coronary
• Intervention / Treatment: Procedure: Invasive coronary physiological measurements

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with symptoms suggestive of angina.
2. Evidence of unobstructed coronary arteries on invasive or non-invasive coronary angiography (coronary stenosis <50% and /or FFR >0.80).
3. Above the age of 18.
4. The subject has been informed of the nature of the study, agrees to its provisions and has signed written informed consent.

Exclusion Criteria:

1. Pregnancy.
2. Contraindication to angiography and/or physiological assessment with adenosine or acetylcholine.
3. Previous coronary artery bypass graft (CABG).
4. Moderate to severe valvular heart disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Invasive Coronary function Assessment arm; Invasive coronary endothelial function and vasospasm assessment	Procedure: Invasive coronary physiological measurements; Invasive assessment of changes in coronary blood flow, resistance, and distal pressure in response to acetylcholine infusion. These will be measured during a clinical indicated invasive coronary angiogram procedure and physiological studies using a standard coronary pressure wire and a dedicated infusion catheter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility outcome	Proportion of patients in whom the full invasive protocol (baseline and post-stimulation measurements) is successfully completed without major technical issues or protocol deviations.	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reproducibility outcome	Intra- and inter-operator variability of measurements quantified using intraclass correlation coefficients and Bland-Altman plots in a predefined reproducibility subset.	At baseline
Safety outcome	Incidence of adverse events related to the procedure or medications.	At Baseline and up to 12 months
Correlation between invasive and non-invasive measures of endothelial-dependent coronary microvascular dysfunction.	Strength of correlation (unit of measure = correlation coefficient, r) between invasive indices of endothelial-dependent coronary microvascular function obtained during the study protocol (absolute coronary blood flow and absolute microvascular resistance measured by continuous thermodilution during intracoronary acetylcholine testing) and non-invasive measures of myocardial perfusion (myocardial perfusion reserve obtained from cardiac stress perfusion imaging). Diagnostic agreement for identifying endothelial-dependent microvascular dysfunction will also be assessed (unit of measure = area under ROC curve, sensitivity, and specificity), using the invasive assessment as the reference standard.	From baseline and up to 3 months
Correlation between invasive physiological indices of coronary microvascular function and symptom burden at baseline.	The strength of correlation (Pearson or Spearman correlation coefficient; unit of measure = correlation coefficient, r) between invasive physiological measurements of coronary microvascular function obtained during the study protocol (e.g., absolute coronary blood flow and absolute microvascular resistance derived by continuous thermodilution during acetylcholine testing) and patient-reported symptom burden assessed at baseline using validated questionnaires (Seattle Angina Questionnaire-7 [SAQ-7] and EQ-5D-5L scores).	Baseline (at time of invasive coronary function testing).
Change in symptoms, quality of life, and need for further investigation or treatment during follow-up.	Change from baseline to follow-up in patient-reported symptoms and quality of life (unit of measure = change in questionnaire score) as assessed using the SAQ-7 and EQ-5D-5L questionnaires, and the proportion of patients (%) requiring additional cardiac investigations or treatment changes during follow-up.	From baseline to 12 months follow-up

Collaborators and Investigators

• Sponsor: Mid and South Essex NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Estimated): December 15, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 18, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 13, 2026

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Ischemia; Coronary Vasospasm
• Other Study ID Numbers: IRAS 356198

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No