The left main coronary artery (LMCA) physiology study: comprehensive clinical haemodynamic evaluation of physiology and pathophysiology
Authors: Demir O M , Sinha A , Rahman H , Scannell C , Alfakih K , O'gallagher K , Ryan M , Li Kam Wa M , Ellis H , Webb I , Melikian N , De Silva K , Chiribiri A , Plein S , Perera D 
Published: November 2023

Abstract

Background & Purpose
At present, physiological evaluation of left main coronary artery (LMCA) disease is based on the assumption that pressure-based indices are agnostic to the vessel being assessed. We conducted mechanistic studies to determine whether pressure-based indices in the left anterior descending (LAD) and left circumflex (LCx) arteries are different and if so, the basis of this discrepancy, in patients with normal coronary arteries (LMCA Physiology Study) and in those with isolated LMCA disease (LMCA Pathophysiology Study).

Methods
Patients with exertional angina were prospectively enrolled after baseline investigation of computed tomography or invasive angiography and those with left ventricular impairment were excluded. Eligibility for the Physiology Study required the absence of epicardial disease on angiography and/or fractional flow reserve or significant coronary microvascular disease (LAD coronary flow reserve (CFR) &lt;2.0). Simultaneous intracoronary pressure and Doppler measurements were performed in the LAD and LCx arteries, at rest and adenosine mediated hyperaemia. A subset also underwent 3-Tesla quantitative stress perfusion cardiac magnetic resonance imaging. Eligibility for the Pathophysiology Study required isolated LMCA disease, which was verified physiologically by pressure wire pullback according to predefined criteria of 1) ≥80% of total FFR arising from the left main coronary artery disease and 2) ≤0.05 FFR gradient distal to the left main coronary artery disease in both vessels. A paired 2-tailed test for significance was performed for all analyses. The protocols were approved by the UK National research ethics committee.

Results
71 patients were prospectively enrolled, 28 in the Physiology Study and 43 in the Pathophysiology Study (Table 1). In the LMCA Physiology Study, CFR was higher and hyperaemic microvascular resistance (hMR) lower in the LAD compared to the LCx. In the LMCA Pathophysiology Study, the contribution to total FFR of downstream disease was negligible and comparable in both branches. Moreover, hyperaemic, and non-hyperaemic pressure-based indices were all significantly lower in the LAD, compared to the LCx. In addition, CFR was higher and hMR lower in the LAD compared to the LCx. Correlations are outlined in Figure 1. Differences in pressure-derived measurements remained after correction for the influence of hydrostatic pressures. However, when adjusted for subtended myocardial mass, there was no significant difference in invasive hemodynamic indices or quantitative perfusion analysis-derived myocardial perfusion reserve index.

Conclusions
Commonly used indices of stenosis severity are not agnostic to the vessel assessed due to differences in myocardial mass and microvascular resistances. The need for vessel-specific thresholds has significant implications on LMCA disease assessment and potentially, interpretation of the existing evidence base on physiological assessment of non-LMCA disease.Table 1Figure 1