Endotypes of coronary microvascular dysfunction in patients with and without Diabetes Mellitus

Abstract

Abstract Background Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of ventricular 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). Recently, two different endotypes of CMD, structural and functional were identified, based on CFR and minimal resistance (Rm-hyp) values. Purpose To compare the patterns of CMD among patients with and without diabetes mellitus by continuous intracoronary thermodilution. Methods Consecutive patients with angina and non-obstructive coronary artery disease undergoing absolute flow measurement with continuous intracoronary thermodilution between 2020 and 2022 were included. Considering a CFR threshold of 2.5, patients were divided into 4 groups, CMD with and without diabetes (DM-CMD and NDM-CMD respectively), and two control groups with and without diabetes (DM-Control and NDM-Control group, respectively). Rm-hyp threshold of 390 (median value) was used to divide structural and functional endotypes (Rm-hyp above or below the threshold respectively). Results 204 patients were included (NDM-CMD=62 vs NDM-Control=77 and dm-CMD=38 vs dm-Control=27). The prevalence of CMD among diabetic patients was 58%. Both CFR and MRR were significantly reduced in both CMD groups compared to the control groups. DM-CMD and NDM-CMD patients had both lower Rm-hyp and higher Rm-rest as compared to the control groups. Among patients with CMD, DM-CMD had higher Rm-hyp compared to NDM-CM patients (480±163 vs 420±124 WU, respectively, p=0.04) and had a higher prevalence of structural endotype (78% vs 58%), p=0.03) which was higher among patients with insulin-dependent diabetes than in those without. Conclusions In patients with DM structural microvascular dysfunction is the most prevalent endotype. Functional endotype is more frequent among those with non-insuline dependent DM. Therefore, CMD in diabetic patients appears to be a continuum, evolving from a functional pattern to a structural one as the disease progresses.