Giuseppe, Esposito (2024) A comprehensive assessment of the coronary circulation: redefinition of physiological approaches and exploration of clinical settings. [Tesi di dottorato]

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Abstract

Invasive coronary angiography has been uniformly accepted as the gold standard for assessing the presence of coronary artery disease (CAD) by defining its extension and guiding revascularization (1). However considering the severity of stenosis reported as percentage of minimal lumen diameter, an intrinsic limitation based on the nature of 2-dimensional images affect the estimation of them. Because of this, correct visual evaluation is often not standardized and influenced by inter and intra operator variability, especially for intermediate stenosis (30-80%) or in challenging anatomies (tortuosity, diffuse CAD, branch overlap or eccentric/calcified lesion). Nowadays, in the “precision medicine” era, clinical decision making based only on a visual estimation affected by not negligible share of variability is inconceivable, even more in uncertain clinical scenario with asymptomatic patients or in absence of non-invasive ischemia test. However, the introduction of fractional flow reserve (FFR) has overcome the previous limitations by making the assessment reproducible and standardized, adding variables such as stenotic segment dependent myocardial mass and microvascular function that angiography alone cannot account for. The ability of FFR in ischemia detection were proved with randomized trial that shown the clear prognostic benefit in terms of death and MACCE of an FFR-guided PCI compared with the angiography-guided approach (FAME II, DEFER). The rising of interest around coronary physiology beyond epicardial evaluation, starts from procedural and clinical observation. Failure of coronary flow reserve (CFR) increase after PCI together with clinical scenario of angina or ischemia in patients with normal coronary artery, helps the researcher to clarify that our ability investigation involved only the 50% of the coronary circulation, the epicardial vessels. The microvascular compartment represented the missing part of the equation able to explain both phenomena and the study of which, expands the indications of coronary physiology assessment. However, by definition, CFR express the flow status in both epicardial and micro circulation and theoretically it might be influenced from the resting hemodynamics condition. The new index called IMR (index microcirculatory resistance) developed form Fearon WF et colleagues, is specific for the microvasculature and is independent from the hemodynamic variability, providing information about the vascular resistance without requiring additional equipment due to the possibility of a simultaneous measurement using the same pressure wire for FFR evaluation. However, during IMR assessment an intrinsic variability of resting mean transit time (Tmnrest) of 7- 10%, and Tmnhyp of 4-8% have been reported. Bearing this in mind, an operators independent microcirculation assessment was achieved with the discovery of the continuous thermodilution method through a dedicated monorail catheter (Rayflow™, Hexacath, Paris, France), able to measure absolute coronary flow (Q) and microvascular resistance (R) in the cathlab. This technology based on saline hyperemia mechanism is completely operator independent and demonstrated higher reproducibility. In this thesis we report the comparison of the two different thermodilution- based method (bolus vs thermodilution) in the context of angina with non- obstructive coronary disease (ANOCA) and the application of this technology in different clinical settings. The aim of the following study is to describe how in less than 5 minutes with a single catheter using saline infusion, is possible to investigate the entire coronary circulation and collect fundamental information with clinical and prognostic impact.

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