Abstract
BACKGROUND: In contrast to reduced coronary flow reserve (CFR), increased minimal hyperemic microvascular resistance (hMR) lacks prognostic relevance in stable chronic coronary syndromes. OBJECTIVES: The aim of the study is to investigate the local and systemic hemodynamics, including diastolic rate constant (s(-1)) and arterial reservoir function (reservoir-excess pressure [P(r)-P(xs)] parameters), as they relate to coronary microvascular dysfunction (CMD; CFR <2.5) and hMR. METHODS: Functional CMD (CFR <2.5; hMR <2.5, n(vessel) = 82, n(patient) = 77), structural CMD (CFR <2.5; hMR ≥2.5, n(vessel) = 160, n(patient) = 149), no CMD-low hMR (CFR ≥2.5; hMR <2.5, n(vessel) = 44, n(patient) = 42), and no CMD-high hMR(CFR ≥2.5; hMR ≥2.5, n(vessel) = 26, n(patient) = 26) endotypes were compared using generalized linear mixed models adjusting for the multiple coronary arteries within same patients. RESULTS: CMD endotypes were associated with a higher diastolic rate constant (s(-1); functional-CMD: 2.0 [1.7-2.2], structural-CMD: 1.9 [1.7-2.1], no CMD-low hMR: 1.5 [1.3-1.7]; no CMD-high hMR 1.5 [1.4-1.6]; P = 0.006) and lower Pr/Pxs (functional CMD: 18.8 [17.6-20.1]; structural CMD: 19.6 [18.5-20.8]; no CMD-low hMR: 21.9 [20.1-23.8]; no CMD-high hMR: 23.8 [22.4-25.2], P < 0.001), suggesting a systemic relative hyperemic state, with lower vasotonus and arterial compliance irrespective of high hMR. Despite similar hMR, No CMD-high hMR endotype distinctively had the lowest Pxs (mm Hg) (4.0 [3.4-4.6]), whereas structural CMD (5.1 [4.8-5.4]) had the highest Pxs (P < 0.001). In no CMD, a milder increase in hMR accompanied higher basal microvascular resistance than CMD (β = 0.128 [0.106-0.149], P < 0.001; β = 0.167 [0.155-0.180], P < 0.001; P = 0.002). Higher hMR was associated with lower CFR in the CMD cases (β = -0.057 [-0.082 to -0.033], P < 0.001), but not in the no CMD group (β = 0.066 [0.013-0.118] P = 0.014). CONCLUSIONS: In this hypothesis-generating study, patients with high hMR-normal CFR exhibit favorable characteristics of coronary and aortic hemodynamics and reservoir function.