Myocardial Ischemia Without Obstructive Coronary Stenoses

Myocardial Ischemia Without Obstructive Coronary Stenoses: A Prospective Observational Study With Invasive Coronary Pressure and Flow Measurements and Endothelial Function Test

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.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Ischemia; Vasospastic Angina; Non-Obstructive Coronary Atherosclerosis; Microvascular Coronary Artery Disease; Myocardial Bridging
• Intervention / Treatment: Diagnostic test: Invasive coronary endothelium-dependent and non-endothelium-dependent physiological assessment

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 Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: Hernan Mejia-Renteria, MD, PhD; Phone Number: +34 913303283; Email: hmejiarenteria@gmail.com

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The target population consists of patients with clinically indicated invasive physiological measures of coronary pressure and flow with adenosine and acetylcholine for the assessment of myocardial ischemia.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Myocardial ischemia without obstructive coronary stenosis	Diagnostic test: Invasive coronary endothelium-dependent and non-endothelium-dependent physiological assessment; Coronary hemodynamics and vessel anatomical measures obtained during adenosine and acetylcholine evaluation with a dedicated physiology wire

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-oriented composite outcome	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	Up to 5 years
Vessel-oriented composite outcome	Incidence of a vessel-oriented composite outcome, a composite of cardiac death, target-vessel related myocardial infarction or target-vessel revascularization	Up to 5 years
Patient symptoms burden	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	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of any death		Up to 5 years
Cumulative incidence of cardiac death		Up to 5 years
Cumulative incidence of nonfatal myocardial infarction		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	Adverse events / complications linked to invasive functional testing	During procedure
Emergency room visit due to angina episode		Up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting and hyperemic mean aortic pressure (mmHg)	Measured with the coronary guiding catheter during physiology assessment under adenosine administration and acetylcholine provocation test	During procedure
Resting and hyperemic mean intracoronary distal pressure (mmHg)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Resting and hyperemic mean coronary flow (mean transit time or cms/sec)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Resting and hyperemic coronary microcirculatory resistance (units)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Resting Pd/Pa (units)	Measured with the coronary physiology wire under resting conditions	During procedure
Resting full cycle ratio (units)	Measured with the coronary physiology wire under resting conditions	During procedure
Instantaneous wave-free ratio (units)	Measured with the coronary physiology wire under resting conditions	During procedure
Fractional flow reserve (units)	Measured with the coronary physiology wire under hyperemia	During procedure
Coronary flow reserve (units)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Resistive reserve ratio (units)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Location of vasospasm into the coronary vessel (proximal, mid or distal)	Detected under acetylcholine provocation test	During procedure
Type of transient ischemic ECG changes (T wave inversion, ST depression, ST elevation)	Observed under acetylcholine provocation test	During procedure
Change in diameter vessel (in percentage)	Measured with quantitative coronary angiography under acetylcholine and nitroglycerin intracoronary administration	During procedure

Collaborators and Investigators

• Sponsor: Hospital San Carlos, Madrid
• Collaborators: Fundacion Investigacion Interhospitalaria Cardiovascular
• Investigators: Principal Investigator: Hernan Mejia-Renteria, MD, PhD, Department of Cardiology, Hospital Clinico San Carlos; Principal Investigator: Javier Escaned, MD, PhD, Department of Cardiology, Hospital Clinico San Carlos

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2017
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2030

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Congenital Abnormalities; Coronary Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Chest Pain; Angina, Unstable; Angina Pectoris; Coronary Vessel Anomalies; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Atherosclerosis; Angina Pectoris, Variant; Coronary Stenosis; Myocardial Bridging
• Other Study ID Numbers: 21/289-E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The study contemplates the possibility of sharing data with other researchers who have similar objectives. IPD to be shared includes demographic data, vessel characteristics, invasive coronary physiology data and outcome measures, appropriately anonymized.
• IPD Sharing Time Frame: Throughout the development of the study
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)

Drug and device information, study documents

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