Munhoz, Daniel (2024) Characterisation of Pathophysiological Patterns of Coronary Artery Disease. [Tesi di dottorato]

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Abstract

In part B of this thesis, we expand the understanding of pathophysiological patterns of CAD by assessing the PPG’s accuracy and reproducibility when derived from different techniques (manual versus motorised). We further evaluate the association between PPG and PCI outcomes and study the influence of PPG on revascularisation decisions. Chapter 1 describes the reproducibility and repeatability of PPG when derived from manual pullbacks, showing an excellent agreement with motorised pullbacks. This finding permitted the integration of PPG into clinical practice. Chapter 2 addresses the performance of PPG in serial stenoses. Part C delves into the intricacies of PPG according to specific anatomical characteristics. Chapter 3 deepens the understanding of the mechanistic relationship between vessel volume, myocardial mass and post-PCI FFR. Chapter 4 describes anatomical correlates (vessel types) influencing the relationship between post-PCI FFR and PCI outcomes. This observation of lower post-PCI FFR in the Left Anterior Descending (LAD) artery is validated against clinical outcomes in an individual patient-level (IPD) meta-nalysis presented in Chapter 5. Chapter 6 describes the impact of PPG on PCI optimisation based on coronary physiology. Part D of this thesis describes novel associations between PPG and atherosclerotic plaque characteristics. Chapter 7 describes the association between focal CAD (high PPG) plaque burden, lipid-rich plaque and thin-cap fibroatheroma (TCFA). Chapter 8 explores the interaction between hemodynamic forces and atherosclerotic plaque phenotypes, particularly concerning plaque rupture. We aimed to establish the association between intracoronary pressure gradients in focal and diffuse CAD and wall shear stress (WSS). Vessels with focal CAD had significantly higher WSS than those with diffuse CAD. Chapter 9 describes the impact of PPG on post-PCI FFR and minimal stent area, and Chapter 10 shows the impact of PPG on patient-reported outcomes, as measured by the 7-item Seattle angina questionnaire(SAQ-7). In Part E, we present a large-scale prospective validation of the PPG concept starting in Chapter 11 with the rationale and design of the PPG Global study. A single-arm, investigator-initiated, multicenter international study enrolled patients with at least one major epicardial lesion with a distal FFR ≤0.80 and intended to be treated with PCI. The primary endpoint was the predictive capacity of PPG for Post-PCI FFR. The key secondary outcomes included the impact of PPG on treatment decisions, the relationship between baseline PPG and improvement of angina symptoms one year after PCI (assessed by SAQ-7) and rates of TVF at follow-up. Chapter 12 provides an example of a subject included on PPG Global, aimed at clarifying the role of PPG in cases of discordance between FFR and non-hyperemic pressure indices (NHPR) assessment. The results of the primary endpoint of PPG Global are presented in Chapter 13. PPG demonstrated excellent predictive capacity for optimal revascularisation and PPG influenced treatment decisions. Interestingly, periprocedural MI occurred more frequently in patients with diffuse disease (low PPG) compared to those with focal disease.

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