Microvascular Dysfunction in Patients With Type II Diabetes Mellitus: Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance Reserve

Abstract

Background: Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups. Methods: In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results: The median FFR value was 0.83 [0.79-0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, [p < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 0.05). Conclusions: Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.

Keywords: continuous thermodilution technique; coronary flow reserve (CFR); coronary microvascular dysfunction (CMD); diabetes mellitus; microcirculatory resistance.

Figure 1

Example of tracings of phasic and mean central aortic pressure (Pa), distal coronary pressure (Pd) and thermodilution during the infusion of 10 mL/min (A) and of 20 mL/min (B) in the LAD of a 77-year-old male patients with mild wall irregularities. (A) after the start and during the next 70 s of the infusion of saline at 10 mL/min through the RayFlow^TM catheter located in the proximal LAD, no changes in Pd / Pa were observed. Resting flow is 67 mL/min. (B) in contrast, after the start and during the next 70 s, the infusion of saline at 20 mL/min through the RayFlow^TM catheter located in the proximal LAD, was paralleled by a decrease in Pd and in Pd/Pa. Hyperemic flow is 230 mL/min. CFR and MRR are 3.43 and 4.03 respectively. Q, Absolute Flow; Qnorm, Normalized Absolute Flow (Q/FFR); R, Absolute Microvascular Resistance; CFR, Coronary Flow Reserve; MRR, Microvascular resistance Reserve.

Figure 2

Box Plot and Cumulative Frequency of CFR (A,B) and MRR (C,D) in diabetic and non-diabetic patients. In the (B) the dashed green line corresponds to a CFR = 2.5. DM, Diabetes Mellitus; CFR, Coronary Flow Reserve; MRR, Microvascular resistance Reserve.

Figure 3

Histograms and median values (dotted line) of the hemodynamic parameters [(A) Pd/Pa, (B) fractional flow reserve – FFR, (C) resting flow, (D) hyperemic flow, (E) resting resistance, (F) hyperemic resistance, (G) coronary flow reserve – CFR, (H) microvascular resistance reserve – MRR] in both diabetic and non-diabetic patients.