Myocardial Ischemia Without Obstructive Coronary Stenoses

Recruiting

• Conditions: Microvascular Coronary Artery Disease; Non-Obstructive Coronary Atherosclerosis; Myocardial Bridging; Myocardial Ischemia; Vasospastic Angina
• Interventions: Diagnostic Test: Invasive coronary endothelium-dependent and non-endothelium-dependent physiological assessment

• Registration Number: NCT04827498
• Lead Sponsor: Hospital San Carlos, Madrid

Brief Summary

Coronary-related myocardial ischemia can result from obstructive epicardial stenosis or non-obstructive causes including coronary microcirculatory dysfunction and vasomotor disorders. This prospective study has been created in order to provide knowledge in the field of non-obstructive coronary artery disease.

Detailed Description

All-comer patients referred for coronary physiological assessment with pressure-flow measurements and acetylcholine endothelial function test, aimed to investigate different aspects of non-obstructive coronary artery disease, will be enrolled. Coronary hemodynamics during adenosine or acetylcholine evaluation will be measured either with a physiology wire equipped with pressure and temperature sensors (Abbott), or with a physiology wire equipped with pressure sensor and Doppler (Philips). Non-endothelium-dependent functional assessment will be performed with intravenous or intracoronary adenosine administration following the standard practice. Endothelium-dependent functional assessment will be performed with intracoronary acetylcholine bolus administration following the standard practice, which includes continuous 12-lead ECG monitorization. Microcirculatory dysfunction and vasomotor disorders will be diagnosed according to the criteria from the last European expert consensus on Ischaemia with Non-Obstructive Coronary Arteries (INOCA). Medical therapy will be adjusted on the basis of physiology study results and patients will be followed at 30 days, 1-, 2- and 5-years either at the outpatient clinic or by telephone contact. The Seattle Questionnaire of Angina will be applied during follow-up for obtaining an objective characterisation of the angina status.

OBJECTIVES OF THE STUDY:

* To investigate the coronary hemodynamics across the spectrum of coronary microcirculatory dysfunction.

* To investigate the coronary hemodynamics across the spectrum of vasomotor disorders.

* To investigate the impact of coronary microcirculatory dysfunction on clinical outcomes and patient symptoms at long-term follow-up.

* To investigate the impact of coronary vasomotor disorders on clinical outcomes and patient symptoms at long-term follow-up.

* To investigate the impact of a stratified medical therapy (guided by invasive physiology study) on patient symptoms.

* To investigate the role of microcirculatory dysfunction and vasomotor disorders in different settings of ischemic heart disease (i.e., recurrent angina despite successful percutaneous coronary intervention; myocardial infarction without obstructive coronary artery disease; left ventricular dysfunction (either systolic or diastolic) with or without heart failure).

* To develop new, alternative methods aimed to assess the coronary microcirculation.

* To investigate the role of myocardial bridging on myocardial ischemia generating mechanisms.

* To document safety of intracoronary testing in routine clinical practice.

Study Timeline

• Study Start: 2017-11-08
• Study First Submitted: 2021-03-25
• Study First Submitted QC: 2021-03-30
• Status Verified: 2021-04
• Study First Posted: 2021-04-01
• Last Update Submitted: 2021-04-23
• Last Update Posted: 2021-04-26
• Primary Completion: 2025-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

• Written informed consent available.
• Age ≥ 18 years.
• Patient eligible for invasive physiological assessment with adenosine and / or acetylcholine.

Exclusion Criteria

• Hemodynamic instability.
• Anticipated technical issues for physiology wire measurements.
• Culprit vessel of acute coronary syndrome
• Contraindications for adenosine administration.
• Contraindications for acetylcholine test.
• Reduced life expectancy (less than 1 year).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Myocardial ischemia without obstructive coronary stenosis	Invasive coronary endothelium-dependent and non-endothelium-dependent physiological assessment	-

Primary Outcome Measures

Name	Time	Method
Patient-oriented composite outcome	Up to 5 years	Incidence of a patient-oriented composite outcome, a composite of any death, nonfatal myocardial infarction, any ischemia-driven revascularization or hospitalization due to unstable angina pectoris
Vessel-oriented composite outcome	Up to 5 years	Incidence of a vessel-oriented composite outcome, a composite of cardiac death, target-vessel related myocardial infarction or target-vessel revascularization
Patient symptoms burden	Up to 12 months	Change in the Seattle questionnaire of angina scoring, associated to stratified medical treatment. Minimum is 0 and maximum is 100 and lower scores indicate worse outcome

Secondary Outcome Measures

Name	Time	Method
Cumulative incidence of any death	Up to 5 years
Cumulative incidence of cardiac death	Up to 5 years
Cumulative incidence of ischemia-driven revascularization	Up to 5 years
Safety of invasive comprehensive coronary functional testing with adenosine and acetylcholine	During procedure	Adverse events / complications linked to invasive functional testing
Emergency room visit due to angina episode	Up to 5 years
Cumulative incidence of nonfatal myocardial infarction	Up to 5 years

Trial Locations

Locations (1)

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain