Thresholds of invasive physiological indices associated with angina and limited exercise capacity in patients with chronic coronary syndrome: SYMPTOM registry

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Abstract Background While the thresholds of fractional flow reserve (FFR) and non-pressure hyperaemic ratios (NHPR) for identifying myocardial ischemia (≤0.75 for FFR, ≤0.89 for NHPR) and guiding coronary revascularization (≤0.80 for FFR, ≤0.89 for NHPR) are well established, the values associated with anginal symptoms and impaired exercise capacity in patients with chronic coronary syndrome (CCS) remain unknown. Purpose To identify the FFR and diastolic pressure ratio (dPR) thresholds associated with anginal symptoms and impaired exercise capacity in patients with CCS. Methods This prospective multicentre registry enrolled 208 patients with suspected CCS undergoing coronary angiography with invasive intracoronary pressure measurements at five institutions in our city, Japan. Patients with normal coronary arteries (n=12), coronary anatomies unsuitable for intracoronary pressure assessments (n=21), and one patient who did not undergo intracoronary pressure measurements were excluded, leaving 174 patients for analysis. All patients underwent a 6-minute walk test before cardiac catheterization, meaning that the test results were not influenced by prior knowledge of the severities of their disease. Anginal symptoms and 6-minute walk distance were assessed, with impaired exercise capacity defined as a walk distance below the expected distance based on age, sex, height, and body weight. The Youden index with receiver operating characteristic (ROC) curve analysis was used to determine the FFR and dPR thresholds associated with anginal symptoms and impaired exercise capacity. Results The median age of the patients was 73 [67, 77], and 78% were male. The median 6-minute walk distance was 395 m [325, 447]. Anginal symptoms were reproduced in 40 (23%) patients during the 6-minute walk test, and 39 (22%) had impaired exercise capacity. The median FFR was 0.73 [0.55, 0.85], and the median dPR was 0.85 [0.56, 0.93]. In ROC curve analyses, the area under the curve (AUC) for FFR in identifying anginal symptoms during 6-minute walk test was 0.68 [0.58, 0.79] (P<0.001), while that for dPR was 0.69 [0.59, 0.79] (P<0.001) [Fig.1]. The FFR threshold associated with anginal symptom was 0.53, with a sensitivity of 46% and specificity of 91%, while dPR threshold was 0.63, with a sensitivity of 51% and specificity of 85%. The AUC for FFR in identifying impaired exercise capacity was 0.55 [0.44, 0.66], and that for dPR was 0.56 [0.45, 0.67], indicating that neither FFR nor dPR was significantly associated with impaired exercise capacity (P=0.301 for FFR, P=0.257 for dPR, respectively) [Fig.2]. Conclusion The hemodynamic severity of coronary stenoses, as assessed by FFR and dPR, was associated with anginal symptoms but not with impaired exercise capacity. The FFR and dPR thresholds associated with anginal symptoms were lower than those typically used for ischaemia detection and revascularization decisions.

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