Myocardial Ischemia Without Obstructive Coronary Stenoses

Myocardial Ischemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04827498
• Other study ID #: 21/289-E
• Status: Recruiting
• Start date: November 8, 2017
• Est. completion date: December 31, 2030

Study information

• Verified date: April 2021
• Source: Hospital San Carlos, Madrid
• Contact: Hernan Mejia-Renteria, MD, PhD
• Phone: +34 913303283
• Email: hmejiarenteria[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Angina Pectoris, Variant
• Atherosclerosis
• Coronary Artery Disease
• Coronary Stenosis
• Ischemia
• Microvascular Coronary Artery Disease
• Myocardial Bridging
• Myocardial Ischemia
• Non-Obstructive Coronary Atherosclerosis
• Vasospastic Angina

Intervention

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

Locations

Country	Name	City	State
Spain	Hospital Clinico San Carlos	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Hospital San Carlos, Madrid	Fundacion Investigacion Interhospitalaria Cardiovascular

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Resting and hyperemic mean intracoronary distal pressure (mmHg)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Other	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
Other	Resting and hyperemic coronary microcirculatory resistance (units)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Other	Resting Pd/Pa (units)	Measured with the coronary physiology wire under resting conditions	During procedure
Other	Resting full cycle ratio (units)	Measured with the coronary physiology wire under resting conditions	During procedure
Other	Instantaneous wave-free ratio (units)	Measured with the coronary physiology wire under resting conditions	During procedure
Other	Fractional flow reserve (units)	Measured with the coronary physiology wire under hyperemia	During procedure
Other	Coronary flow reserve (units)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Other	Resistive reserve ratio (units)	Measured with the coronary physiology wire under adenosine administration and acetylcholine provocation test	During procedure
Other	Location of vasospasm into the coronary vessel (proximal, mid or distal)	Detected under acetylcholine provocation test	During procedure
Other	Type of transient ischemic ECG changes (T wave inversion, ST depression, ST elevation)	Observed under acetylcholine provocation test	During procedure
Other	Change in diameter vessel (in percentage)	Measured with quantitative coronary angiography under acetylcholine and nitroglycerin intracoronary administration	During procedure
Primary	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
Primary	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
Primary	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	Cumulative incidence of any death		Up to 5 years
Secondary	Cumulative incidence of cardiac death		Up to 5 years
Secondary	Cumulative incidence of nonfatal myocardial infarction		Up to 5 years
Secondary	Cumulative incidence of ischemia-driven revascularization		Up to 5 years
Secondary	Safety of invasive comprehensive coronary functional testing with adenosine and acetylcholine	Adverse events / complications linked to invasive functional testing	During procedure
Secondary	Emergency room visit due to angina episode		Up to 5 years