Coronary Thermo-dilution Derived Flow-indices in Chronic Coronary Syndrome
- Conditions
- Coronary Artery DiseaseMicrovascular AnginaCoronary Microvascular Dysfunction
- Registration Number
- NCT06306066
- Lead Sponsor
- Karolinska Institutet
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 505
- Subjects with stable angina pectoris or suspected angina pectoris who are scheduled for coronary angiography
- Age 18 years - 85 years
- Life expectancy >2 years
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Rate of all-cause mortality, MI and/or hospitalization due to CHF Study completion, approximately 5 years Cumulative rate of all-cause mortality, MI and/or hospitalization due to CHF at study completion
- Secondary Outcome Measures
Name Time Method Rate of all-cause mortality Study completion, approximately 5 years Cumulative rate of all-cause at study completion
Rate of hospitalization due to CHF. Study completion, approximately 5 years Cumulative rate of hospitalization due to CHF at study completion
Rate of all-cause mortality and/or MI Study completion, approximately 5 years Cumulative rate of all-cause mortality and MI at study completion
Rate of MI Study completion, approximately 5 years Cumulative rate of MI at study completion
Rate of stroke Study completion, approximately 5 years Cumulative rate of Stroke at study completion
Rate of ischemic stroke Study completion, approximately 5 years Cumulative rate of Ischemic stroke at study completion
Rate of unscheduled revascularization Study completion, approximately 5 years Cumulative rate of Unscheduled revascularization at study completion
Trial Locations
- Locations (1)
Danderyd University Hospital and Karolinska Institutet Danderyds University Hospital (KI DS)
🇸🇪Stockholm, Sweden