Novel technique for quantifying absolute coronary flow and resistance in patients with ischemia and non-obstructive coronary disease

Patients with angina but normal coronary angiogram represent 25% of cases in catheterization laboratory. The underlying pathologic substrate in ischemia and nonobstructive coronary disease (INOCA) varies between structural or functional abnormalities of coronary circulation. Coronary microvascular dysfunction may result from structural remodeling and rarefaction with consequent increase in resistance and reduced vasodilator capacity; or functional abnormalities may result in abnormal vasoconstriction of the coronary epicardial vessels or impaired vasodilatation and vasoconstriction of microcirculation. (1,2) Both vascular dysfunction mechanisms may co-exist and contribute to INOCA.

Normal coronary angiogram in a patient with documented angina/ischaemia should trigger further diagnostic pathways to elucidate INOCA endotypes. This is important for tailoring specific antianginal therapy as has been shown in CorMicA trial. (3)

ESC Guidelines recommend invasive coronary function testing (CFT) in patients with INOCA. These include acetylcholine (ACH) test for assessing endothelial dependent vasoreactiiIty and vasospasm in epicardial coronary vessels and microvasculature, and adenosine hyperemia for assessing microvascular dysfunction addressed by two standard indexes, coronary flow reserve (CFR) and index of microvascular resistance (IMR). CFR and IMR are determined by intracoronary approach by thermodilution   and Doppler flow velocity measurements. (4)

Konst R. and coauthors in their paper “Absolute Coronary Blood Flow Measured by Continuous Thermodilution in Patients With Ischemia and Nonobstructive Disease” presented a novel method for assessing microcirculation that enables direct quantification of absolute coronary blood flow (Q) and resistance (R). The absolute Q and R can be obtained by continuous thermodilution with intracoronary saline infusion at room temperature to obtain maximal hyperemia. Unlike currently used standard physiological measurments, these novel measurements of the absolute Q and R are less reliant on operator skill, have a high reproducibility and less intraobserver variability and do not require the use of adenosine, that is contraindicated in patients with chronic obstructive pulmonary disese.

In 84 patients with INOCA, reported in this paper, all recommended functional measurements were completed:

1) Endothelium dependent vasomotor function was assessed with ACH testing where epicardial spasm was diagnosed in the case of a focal or diffuse epicardial coronary diameter reduction of more than 90% compared with the relaxed state. Microvascular spasm was defined with ECG changes or provoked symptoms;

2) Endothelium independent function was assessed with adenosine where abnormal CFR value was defined as <2.0 and high index of IMR more than 25;

3) Quantification of absolute flow (Q) (ml/min), and resistance (R) (mmHg/l/min or WU) were assessed upon low-rate intracoronary infusion of saline at room temperature and continuous thermodilution. A dedicated monorail double-lumen coronary infusion catheter with side holes was used and connected to an infusion pump. Saline infusion at a rate of 20 ml/min creates steady-state maximum hyperemia within seconds. (5)

This study has several important findings. It is the first study to demonstrate the safety of newly developed invasive technology that can be used in patients with INOCA to quantify the absolute Q and R.

Main findings are : 1) Absolute R was higher in patients with the endotype of microvascular dysfunction (defined as high IMR and/or low CFR).  2) Absolute Q and R were not associated with the endotype of epicardial or microvascular spasm provoked by ACH testing. 3) The relationship between absolute Q and R and angina severity were observed for the first time.  

Although, additional studies are needed to elucidate the role of absolute flow and resistance measured by continuous thermodilution in the evaluation and prognosis in patients with INOCA, this new path and its preliminary results are promising in defining INOCA subtype and new possible guidance for patient-tailored therapy.