Clinical trial NCT04827498: Myocardial Ischemia Without Obstructive Coronary Stenoses
Official title: Myocardial Ischemia Without Obstructive Coronary Stenoses: A Prospective Observational Study With Invasive Coronary Pressure and Flow Measurements and Endothelial Function Test
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myocardial Ischemia
Non-Obstructive Coronary Atherosclerosis
Microvascular Coronary Artery Disease
Vasospastic Angina
Myocardial Bridging
Lead sponsor: Hospital San Carlos, Madrid
Sponsor class: OTHER
Collaborators: name: Fundacion Investigacion Interhospitalaria Cardiovascular
First posted: 2021-04-01
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Patient-oriented composite outcome
timeFrame: Up to 5 years
measure: Vessel-oriented composite outcome
timeFrame: Up to 5 years
measure: Patient symptoms burden
timeFrame: Up to 12 months
Secondary outcomes:
measure: Cumulative incidence of any death
timeFrame: Up to 5 years
measure: Cumulative incidence of cardiac death
timeFrame: Up to 5 years
measure: Cumulative incidence of nonfatal myocardial infarction
timeFrame: Up to 5 years
measure: Cumulative incidence of ischemia-driven revascularization
timeFrame: Up to 5 years
measure: Safety of invasive comprehensive coronary functional testing with adenosine and acetylcholine
timeFrame: During procedure
measure: Emergency room visit due to angina episode
timeFrame: Up to 5 years
Other outcomes:
measure: Resting and hyperemic mean aortic pressure (mmHg)
timeFrame: During procedure
measure: Resting and hyperemic mean intracoronary distal pressure (mmHg)
timeFrame: During procedure
measure: Resting and hyperemic mean coronary flow (mean transit time or cms/sec)
timeFrame: During procedure
measure: Resting and hyperemic coronary microcirculatory resistance (units)
timeFrame: During procedure
measure: Resting Pd/Pa (units)
timeFrame: During procedure
measure: Resting full cycle ratio (units)
timeFrame: During procedure
measure: Instantaneous wave-free ratio (units)
timeFrame: During procedure
measure: Fractional flow reserve (units)
timeFrame: During procedure
measure: Coronary flow reserve (units)
timeFrame: During procedure
measure: Resistive reserve ratio (units)
timeFrame: During procedure
measure: Location of vasospasm into the coronary vessel (proximal, mid or distal)
timeFrame: During procedure
measure: Type of transient ischemic ECG changes (T wave inversion, ST depression, ST elevation)
timeFrame: During procedure
measure: Change in diameter vessel (in percentage)
timeFrame: During procedure
Locations:
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
Study officials:
affiliation: Department of Cardiology, Hospital Clinico San Carlos
name: Hernan Mejia-Renteria, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiology, Hospital Clinico San Carlos
name: Javier Escaned, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: