The recently published 2024 European Society of Cardiology (ESC) Guidelines on the management of chronic coronary syndromes (CCS) highlighted the role of investigating the presence and diagnosis of ischemia with non-obstructed coronary arteries (INOCA), suggesting invasive coronary function testing with a Class I, Level of Evidence B recommendation1. Coronary flow reserve (CFR) is one of the key indices assessed, showing the dynamic capacity of the coronary circulation to increase blood flow, in response to pharmaceutically-induced maximal demand. However, it is well-known that the invasive assessment of CFR is subject to several limitations, as it is influenced by the presence and extent of epicardial stenoses, resting hemodynamics, pharmacotherapy used to induce maximal vasodilation and baseline coronary blood flow2. In this context, assessment of microvascular resistance reserve (MRR) has been recently introduced3, in order to characterize the vasodilator reserve capacity of the coronary microcirculation. MRR is not influenced by epicardial CAD4, while recent data show that it is independently associated with 5-year MACE and target vessel failure rates5 in INOCA patients.
A recently published study6 aimed to evaluate whether MRR is associated with health status outcomes in patients with moderate stenoses, undergoing revascularization. The study included patients with stable, new-onset chest pain and moderate coronary stenoses of initially unknown functional significance. Revascularization decisions were made based on fractional flow reserve (FFR), while the presence of coronary microvascular dysfunction (CMD) was determined by CFR/MRR. The cut-off for considering an MRR value pathologic was MRR≤3.0. Health status was assessed with the Seattle Angina Questionnaire. Improvement in health status was noted only in patients with normal FFR and CFR/MRR (not undergoing revascularization) and in patients with abnormal FFR and CFR/MRR (undergoing revascularization). This indicates that patients with significant stenoses and CMD may benefit from revascularization, to a similar extent of patients with normal FFR and CFR/MRR, as elimination of the epicardial ischemia component could result in enhanced blood flow and significant symptom benefit. Moreover, the authors note that the absence of a similar benefit in those without significant epicardial disease, but abnormal CFR/MRR, could indicate inadequate initiation of CMD-directed pharmacotherapy.
This study has significant implications for revascularization decision-making in CCS patients. To date, despite studies7,8 showed a benefit of revascularization in the health status of CCS patients, FFR could not predict symptom relief post-revascularization9. This investigation provides a novel insight, showing that MRR, a specific indicator of microvascular physiology regardless of epicardial disease, along with prognosticating long-term cardiovascular outcomes5, could also predict a benefit of revascularization in health status and angina relief. Therefore, MRR could be potentially used as a CCS phenotype stratification tool, identifying those CCS patients that are expected to benefit from revascularization. Further, larger randomized clinical trials are needed, though, in order to evaluate this interesting hypothesis and result in clinical use.
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