Clinical trial NCT06306066: Coronary Thermo-dilution Derived Flow-indices in Chronic Coronary Syndrome
Official title: Coronary Microvascular Dysfunction in Chronic Coronary Syndrome - Invasive Assessment With Thermo-dilution Technique in the LAD and Biobanking in an All-comer Population
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Microvascular Angina
Coronary Microvascular Dysfunction
Keywords: coronary microvascular dysfunction
microvascular angina
coronary artery disease
microcirculation
index of microcirculatory dysfunction
coronary flow reserve
baseline resistance index
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2024-03-12
Enrollment: 505
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with stable angina pectoris or suspected angina pectoris who are scheduled for coronary angiography

Brief summary: Patients scheduled for elective coronary angiography due to chronic coronary syndrome are recruited at admission to hospital before the coronary anatomy is known. Immediately after coronary angiography measures thermo-dilution derived flow indices are obtained in the left left anterior descending artery (LAD). The patients are followed through telephone-calls and medical records at 1 and 2 years after inclusion and at completion of the study. The hypothesis is that elevated index of microcirculatory resistance (IMR),(\>25) is associated with all-cause death, myocardial infarction (MI) and hospitalization due to congestive heart failure (CHF).

The primary analysis is the relationship between IMR and the composite outcome all-cause death, MI and hospitalization due to CHF.

Detailed description: Patients scheduled for elective coronary angiography due to chronic coronary syndrome are recruited at admission to hospital after written informed consent has been obtained and before the coronary anatomy is known. Blood sampling is performed from the arterial sheath before coronary angiography. The coronary angiography is done according to clinical practice. Immediately after coronary angiography measures thermo-dilution derived flow indices are obtained in the LAD (methods below). Interventions of epicardial lesions are then performed at the percutaneous coronary intervention (PCI)-operators discretion.

Fractional Flow Reserve (FFR), Coronary Flow Reserve(CFR) and IMR measurements

All indices FFR, CFR and IMR are measured in the left anterior descending artery (LAD). The flow measurements shall be obtained before PCI in the LAD. Further assessment of flow in LAD after PCI are optional. Flow measurements in the right coronary artery and circumflex lesions are optional.

Flow measurements:

A coronary guidewire with pressure and temperature sensors (PressurewireX, Abbott Inc, Calif., USA) is advanced in the LAD. The thermistor is placed \> 70 mm from the catheter-tip and three millilitres of cold saline is injected into the LAD three times through the guiding catheter and thermo-dilution resting curves in triplicate are obtained. The patient then receives an intravenous infusion of adenosine (167 µg/kg/min) during approximately two minutes to induce stable hyperaemia. Again, three millilitres of cold saline is injected into the LAD through the guiding catheter and hyperaemic thermos-dilution curves in triplicate are obtained.

FFR is calculated as the ratio of distal coronary pressure (Pd) to proximal coronary pressure (Pa) at hyperaemia. CFR will be calculated through as the ratio of mean transit time of resting thermo-dilution curves (Tmnbas) divided by mean transit time of hyperaemic thermos-dilution curves (Tmnhyp). IMR is calculated as the product of Pd and Tmnhyp during stable hyperaemia. If FFR is \<0.75 IMR can be overestimated and will be calculated differently (Yong et al.); Corrected index of microcirculatory resistance (IMRcorr) = Pa x Tmnhyp x (\[1.35 x Pd/Pa\] - 0.32).

Recordings of systolic blood pressure, diastolic blood pressure, Tmnbas, Tmnhyp, Pa, Pd, IMR, CFR will be saved and analysed off-line by a dedicated physician.

Follow-up The patients are followed through telephone-calls and medical records at 1 and 2 years and after inclusion and at completion of the study December 2022.

Patients with extensive atherosclerotic disease in the left main or the LAD with risk of complications when advancing a pressure wire making flow-measures not possible will be followed according to the protocol but excluded from the primary analysis. Patients with chronic total occlusions (CTO) in the LAD making flow-measures impossible in the LAD will be followed according to the protocol but excluded from the primary analysis.

Survival analysis The null hypothesis is that subjects with IMR \>25 have the same outcome (death, MI, and hospitalization due to CHF) as subjects with IMR≤25. Assumptions are that 30% of subjects have IMR \>25, the hazard ratio is 2.0, the event rate is 0.09 per year, censoring rate 0.3/year, average follow-up 3 years. With 395 subjects the power is 80% to reject the null hypothesis. α=0.05.

Biomarkers in relation to IMR Post-hoc power calculation; the null hypothesis is that no variables are associated with IMR. Assumptions; effect-size (R2) = 0.20; maximum variables in the regression analysis = 15; α = 0.05. With a power of 0.80 a sample size of 89 subjects are needed to reject the null hypothesis.

Eligibility criteria: Inclusion Criteria:

* Subjects with stable angina pectoris or suspected angina pectoris who are scheduled for coronary angiography
* Age 18 years - 85 years
* Life expectancy \>2 years

Exclusion Criteria:

* Acute coronary syndrome (ST-elevation myocardial infarction \[STEMI\], non-ST-elevation myocardial infarction \[NSTEMI\] and unstable angina pectoris)
* Known CHF
* Prior heart transplantation
* Prior coronary artery by-pass grafting
* Hypertrophic cardiomyopathy (Septum \>15 mm)
* Valvular disease
* Not eligible for coronary angiogram
* Cancer within three years of admission
* Peri-myocarditis
* Atrial fibrillation with heart beats per minute \>120
* Asthma

Primary outcomes:
measure: Rate of all-cause mortality, MI and/or hospitalization due to CHF
timeFrame: Study completion, approximately 5 years
Secondary outcomes:
measure: Rate of all-cause mortality
timeFrame: Study completion, approximately 5 years
measure: Rate of hospitalization due to CHF.
timeFrame: Study completion, approximately 5 years
measure: Rate of all-cause mortality and/or MI
timeFrame: Study completion, approximately 5 years
measure: Rate of MI
timeFrame: Study completion, approximately 5 years
measure: Rate of stroke
timeFrame: Study completion, approximately 5 years
measure: Rate of ischemic stroke
timeFrame: Study completion, approximately 5 years
measure: Rate of unscheduled revascularization
timeFrame: Study completion, approximately 5 years
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Danderyd University Hospital and Karolinska Institutet Danderyds University Hospital (KI DS)
Study officials:
affiliation: Karolinska Institutet
name: JONAS PERSSON, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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