Effects of intracoronary nitrates administration on the invasive assessment of coronary microcirculation: insights from the INOCA NA registry

Abstract Background In patients presenting with non obstructive coronary artery disease, myocardial ischemia may result from coronary microvascular dysfunction (CMD) and epicardial or microvascular spasm. Invasive functional assessment is necessary to correctly identify both mechanisms according to the #FullPhysiology approach. There are concerns about the timing for intracoronary (i. c. ) administration of nitrates (NTG). This study aimed to evaluate whether preventive i. c. administration of NTG significantly affects hemodynamic parameters and the diagnostic accuracy of functional coronary angiography (FCA). Methods: Clinical, angiographic and hemodynamic features were analysed from patients undergoing FCA in our Institution. Patients presenting with typical angina, evidence of myocardial ischemia, and absence of angiographically or functionally significant epicardial stenoses were included. During the invasive functional assessment, mean aortic pressure (Pa), distal pressure (Pd) and mean Transit Time at rest were measured both before (PaREST, PdREST and mTTREST) and after i. c. NTG administration (PaNTG, PdNTGmTTNTG). Equally, the baseline resistance index was derived both before (BRI) and after NTG administration (BRINTG). Maximal hyperaemia was achieved by i. v. adenosine administration (140μg/kg/min) and hyperaemic mean transit time (mTTHYP) was measured. IMR was calculated only after NTG administration, since it has been previously demonstrated that NTG does not influence IMR values, the latter being independent of the epicardial compartment. CFR was calculated both before (CFR) and after NTG administration (CFRNTG). The former was virtually assessed as the ratio between mTTREST and mTTHYP. Equally, microvascular resistance reserve (MRR) was calculated both before (MRR) and after NTG administration (MRRNTG). The former, representing the microvascular resistance reserve which would have been measured if nitrate had not been administered, was defined as the ratio between the CFR and FFR multiplied for the ratio between PaREST and PaHYP. The presence of VSA was diagnosed with the acetylcholine test. Finally, INOCA patients were stratified into different endotypes: CMD, including structural CMD (SCMD, CFR 2 and IMR 25), functional CMD (FCMD, CFR 2 and IMR 25), and compensated microvascular disfunction (CCMD, CFR 2 and IMR 25). Some patients presented with both CMD and VSA. Patients without any disease were considered with Non-Cardiac Chest Pain. Results 61 patients were included. mTTRESTand BRI significantly increased after NTG administration (mTTREST: 0. 560. 38–0. 91 and BRI: 5632 – 89 vs mTTNTG: 0. 780. 47–1. 27 and BRINTG 7239–105, p0. 001). Equally, CFR and MRR significantly increased after NTG administration (CFR: 2. 7±1. 3 and MRR: 3. 3±1. 6 vs CFRNTG: 3. 3±1. 5 and MRRNTG: 4. 1±2. 0 p0. 001). NTG administration significantly changed endotypes distribution. Conclusions I. c. NTG administration prior to FCA prevents CMD overestimation. Endotypes reclassificationFor image description, please refer to the figure legend and surrounding text.