Association of physiological discordance between fractional flow reserve and non-hyperaemic pressure ratios with lipid-rich plaque burden

Fractional flow reserve (FFR) and non-hyperaemic pressure ratios (NHPRs) frequently yield discordant results in clinical practice, yet the mechanisms underlying this mismatch remain uncertain. Plaque composition has been suggested to influence FFR, raising the possibility that discordance reflects the features of lipid-rich plaque (LRP). This study aimed to investigate whether physiological discordance between FFR and NHPR is associated with increased lipid burden.

We retrospectively analysed 217 intermediate coronary lesions from 189 patients who underwent FFR, NHPR, and near-infrared spectroscopy with intravascular ultrasound imaging. Lesions were classified using established cut-offs for FFR (0.80) and NHPR (0.89). Lipid burden was quantified by the maximum lipid core burden index within any 4-mm segment (maxLCBI_4mm). Lipid-rich plaque was defined as maxLCBI_4mm > 400. The clinical endpoint was 3-year target vessel failure (TVF). Physiological discordance occurred in 24.0% of lesions, predominantly as an FFR+/NHPR− pattern (19.8%). FFR was independently associated with maxLCBI_4mm [β, 65.2; 95% confidence interval (CI), 29.0–101.5; P < 0.001], whereas NHPR was not (β, 16.5; 95% CI, −15.9 to 49.0; P = 0.316). The FFR+/NHPR− group demonstrated the highest maxLCBI_4mm (525 ± 201) and the greatest prevalence of LRP (65.1%; both P < 0.001). In multivariable analysis, the FFR+/NHPR− pattern independently predicted LRP [adjusted odds ratio, 6.12; 95% CI, 1.20–31.28; P = 0.030]. TVF occurrences did not differ significantly across physiological groups.

FFR+/NHPR− lesions exhibit markedly greater lipid burden, suggesting that hyperaemia-based indices better capture plaque vulnerability than resting physiology. This pattern may serve as a marker of plaque vulnerability, suggesting that deferral of FFR+/NHPR− lesions could warrant caution given their higher lipid burden.