OPEN Research Support

MD, DMSci, PhD, Professor, Interventional Cardiolo
Lisette Okkels Jensen
Department of Cardiology, Odense University hospital

Projekt styring
Projekt status    Open
Data indsamlingsdatoer
Start 01.03.2022  
Slut 31.01.2023  

The Influence of the microcirculation on pressure and flow measurements in coronary arteries in patients with coronary artery disease

Short summary

Coronary artery disease can lead to stenosis and inadequate coronary perfusion causing stable angina, acute myocardial infarction or death. Fractional flow reserve (FFR) and instantaneous wave free (iFR) are invasive measurements to assess the need for revascularisation. Microcirculatory disease can be determined using index of microcurculatory resistance (IMR) and may influence on FFR and iFR. Aim: to investigate the influence of IMR on FFR and iFR measurements. 200 patients will be enrolled.


Cardiovascular disease is the leading cause of death according to WHO. [1] Coronary artery disease can lead to stenosis and occlusion of the vessel leading to inadequate coronary perfusion. This could lead to diseases like stabile angina, acute myocardial infarction or death. Coronary angiography is used to visualize these changes to the coronary arteries. Stenosis and occlusion can be treated with percutaneous coronary intervention. The decision to do so is based on the angiographic morphology and the patient's symptoms. Though is the visual assessment subjective and not always in accordance with the physiological importance of the stenosis. [1] [2]

Fractional flow reserve (FFR) is a more objective measurement of the significance of the stenosis. It represents the maximal flow with the presence of the stenosis compared to the hypothetical maximal flow without the stenosis. It is measured during medically induced maximal hyperemia with adenosine [3] Due to the need for maximal hyperemia to measure FFR, it has been developed measurement without the need for adenosine like instantaneous wave free ratio(iFR), that can be calculated without the need for medication. [4]

The existence of disease in the microcirculation is likely to influence the measurement and importance of a stenosis or occlusion. It can be determined using Index of microcirculatory resistance (IMR) which also is measured using maximal hyperemia. A Value of less than 0.24 is considered to be normal. [5] There have been studies regarding the FFR and IMR. IMR was found to be an independent predictor of FFR, and patient with a high IMR was found to have a higher FFR. Such studies have not been conducted for iFR. [6]


The aim of the project is to investigate the influence of microcirculatory disease on the cut off value for IFR.


Patient referred to supplementary flow and pressure measurements and that have either stabil angina or an non-ST elevation myocardial infarction will be included. During the produce FFR, IFR and IMR will be measured by conventional standards.

The project is a pilot study and 200 patients will be enrolled.

There will be calculated a receiver-operator curve (ROC) to predict FFR <= 0.80 for the groups with normal microcirculation and for the group with microcirculatory disease defined as having a IMR >= 0.24.

[1] Pijls NH, van Scaardenburgh P, Manoharan G et al.: Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER study. J Am Coll Cardiol, 2007 May; 49 (21), 2105- 11.

[2] Tonino PA, De Bruyne B, Pijls NH et al.: Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med, 2009 Jan; 360 (3): 213-24.doi: 10.1056/NEJMoa0807611.

[3] De Bruyne B, Pijls NH, Barbato E et al.: Intracoronary and intravenous adenosine 5'-triphosphate, adenosine, papaverine and contrast medium to assess fractional flow reserve in humans. Cirkulation 2003 Apr 15; 107 (14):1877-83.

[4] van't Veer M, Pijls N, Hennigan B, Watkins S, Ali Z, De Bruyne B et al. Comparison of Different Diastolic Resting Indexes to iFR. Journal of the American College of Cardiology. 2017;70(25):3088-3096.

[5] Martin K.C., Alan Yeung, William Fearon: Invasive Assessment of the Coronary Microcirkulation. American Heart Association, 2006 March; 2054-2061.

[6] Park SD, Lee MJ, Woo SI, et al. Epicardial Artery Stenosis with a High Index of Microcirculatory Resistance Is Frequently Functionally Insignificant as Estimated by Fractional Flow Reserve (FFR). Intern Med. 2016;55(2):97-103.

Description of the cohort

Patient referred to supplementary flow and pressure measurements and that have either stabil angina, unstable angina or an non-ST elevation myocardial infarction will be included.

Data and biological material

During the coronary angiography produce FFR, IFR and IMR will be measured as part of routine procedure.

Collaborating researchers and departments

Department of oncology, Aarhus University hospital,

  • Christian Hviid

Department of oncology, Aalborg University hospital.

  • Signe Christensen

Dpartment of oncology, Odense University hospital.

  • Thea Otto Mattsson