Clinical implications of non-hyperemic pressure ratio and change in Pd/Pa to evaluate coronary microvascular dysfunction in patients with angina and non-obstructive coronary arteries

Background A reduced coronary flow reserve (CFR) in patients with angina and non-obstructive coronary arteries (ANOCA) harbors coronary microvascular dysfunction (CMD). Recent studies classify CMD into structural and functional subtypes based on an IMR threshold of ≥25 or <25mmHg·sec. Given its phenotypic variations, clinical needs exist to develop a better approach for evaluating phenotypes of CMD. The wire-based non-hyperemic pressure ratio (NHPR) has been reported to correlate with CFR. Additionally, we reported change in Pd/Pa during hyperemia [(Pd/Pa at rest – Pd/Pa at hyperemia (=fractional flow reserve, FFR)] as a novel measure associated with microvascular reactivity. We hypothesized that these two measures may help differentiate CMD subtypes in ANOCA. Purpose To evaluate the association of NHPR and change in Pd/Pa with CMD phenotypes in ANOCA. Methods The current study investigated 112 patients with anginal chest pain. Pressure-wire was used to measure coronary physiological indices (CFR, IMR, NHPR, FFR, and the change in Pd/Pa) in 112 coronary arteries with <50% stenosis (LAD/non-LAD=108/4) (Figure 1). Clinical characteristics and physiological indices were compared in subjects stratified into CMD and non-CMD groups according to a CFR threshold of <2.5 or ≥2.5. Results 34% (=38/112) of study subjects presented CMD, including 6 structural and 32 functional CMD (Figure 1). Patients with CMD were more likely to be female (58% vs. 38%, P=0.04) with a greater frequency of ACS (37% vs. 15%, P=0.008) and hypertension (87% vs. 66%, P=0.02). On physiological analysis, patients with CMD exhibited lower NHPR (0.88 vs. 0.92, P<0.001) and CFR (1.6 vs. 4.7, P<0.001) but higher IMR (17.9 vs. 11.8 mmHg·sec, P=0.02), whereas the change in Pd/Pa was similar (0.08 vs. 0.08, P=0.80). (Table 1). Multivariable analysis demonstrated NHPR (OR=1.25, 95%CI=1.10-1.42, P<0.001) and female (OR=2.84, 95%CI=1.12-7.20, P=0.03) as independent factors associated with CFR<2.5 (Table 2A). Receiver operating characteristic (ROC) analysis showed NHPR≤0.89 optimally predicted CFR<2.5 (AUC=0.74, P<0.001, sensitivity=78%, specificity=62%) and was more prevalent in functional CMD (P<0.001, Figure 3A). Further analysis identified change in Pd/Pa as an independent predictor of IMR≥25mmHg·sec (OR=1.24, 95% CI=1.02–1.51, P=0.04) (Table 2B). ROC analysis showed change in Pd/Pa≤0.08 as an optimal cut-off value to predict IMR≥25mmHg·sec (AUC=0.69, P=0.03, sensitivity=36%, specificity=100%). In contrast to NHPR, a greater frequency of change in Pd/Pa≤0.08 was observed in patients with structural than functional CMD (Figure 3B). Conclusion In ANOCA patients, reduced NHPR was a potential physiological measure of CMD, especially in functional CMD. In contrast, structural CMD was characterized as a reduced change in Pd/Pa. These observations indicate NHPR and change in Pd/Pa as potential measures to stratify CMD and then select optimal therapeutic management in the setting of ANOCA.