Coronary Thermo-dilution Derived Flow-indices in Chronic Coronary Syndrome

March 7, 2024 updated by: Jonas Persson, Karolinska Institutet

Coronary Microvascular Dysfunction in Chronic Coronary Syndrome - Invasive Assessment With Thermo-dilution Technique in the LAD and Biobanking in an All-comer Population

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

505

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Stockholm, Sweden, 182 88
        • Danderyd University Hospital and Karolinska Institutet Danderyds University Hospital (KI DS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Subjects with stable angina pectoris or suspected angina pectoris who are scheduled for coronary angiography

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of all-cause mortality, MI and/or hospitalization due to CHF
Time Frame: Study completion, approximately 5 years
Cumulative rate of all-cause mortality, MI and/or hospitalization due to CHF at study completion
Study completion, approximately 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of all-cause mortality
Time Frame: Study completion, approximately 5 years
Cumulative rate of all-cause at study completion
Study completion, approximately 5 years
Rate of hospitalization due to CHF.
Time Frame: Study completion, approximately 5 years
Cumulative rate of hospitalization due to CHF at study completion
Study completion, approximately 5 years
Rate of all-cause mortality and/or MI
Time Frame: Study completion, approximately 5 years
Cumulative rate of all-cause mortality and MI at study completion
Study completion, approximately 5 years
Rate of MI
Time Frame: Study completion, approximately 5 years
Cumulative rate of MI at study completion
Study completion, approximately 5 years
Rate of stroke
Time Frame: Study completion, approximately 5 years
Cumulative rate of Stroke at study completion
Study completion, approximately 5 years
Rate of ischemic stroke
Time Frame: Study completion, approximately 5 years
Cumulative rate of Ischemic stroke at study completion
Study completion, approximately 5 years
Rate of unscheduled revascularization
Time Frame: Study completion, approximately 5 years
Cumulative rate of Unscheduled revascularization at study completion
Study completion, approximately 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Collaborators

Abbott

Investigators

  • Principal Investigator: JONAS PERSSON, MD, PhD, Karolinska Institutet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 2, 2015

Primary Completion (Actual)

June 7, 2021

Study Completion (Actual)

December 28, 2022

Study Registration Dates

First Submitted

February 27, 2024

First Submitted That Met QC Criteria

March 7, 2024

First Posted (Actual)

March 12, 2024

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015/962-31

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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