Deconstructing coronary microvascular resistance: From reperfusion injury to adaptive Haemodynamics

The prognostic meaning of elevated coronary microvascular resistance (MR) differs between acute and chronic coronary syndromes (ACS and CCS). After reperfusion in ACS, high MR, measured invasively as the index of microcirculatory resistance (IMR) or hyperaemic microvascular resistance (hMR), is an established marker of microvascular injury, microvascular obstruction and adverse outcomes. In CCS, elevated hMR or IMR alone has not consistently been associated with adverse cardiovascular events, whereas a reduced coronary flow reserve (CFR) has. We examine the physiological basis of MR and the assumption that high resistance is uniformly pathological. Using adenosine-derived haemodynamic endotypes defined by CFR and hMR, we describe an endotype without coronary microvascular dysfunction (CMD) in which a preserved CFR coexists with high hMR and a higher resting resistance. In this endotype, wave-intensity and reservoir-pressure analyses show preserved hyperaemic augmentation of accelerating wave energy, favourable aortic reservoir function and low excess pressure. We discuss the hypothesis that the higher resting microvascular tone reflects a compensatory myogenic response to pulsatile load, and the evidence still needed to distinguish adaptation from association. The absence of excess events does not exclude clinically relevant disease, because angina and quality of life are separate outcomes. Since microvascular resistance dynamically sets resting flow and its augmentation, a high MR may reflect pathology that limits flow or autoregulation that adjusts it. Its interpretation should therefore consider mechanism and vasodilator capacity rather than a single threshold, and endotyping by CFR, MR and, where indicated, acetylcholine testing may improve patient selection for targeted therapies.