The association between coronary physiological progression and clinical outcomes has not been investigated. A total of 421 patients who underwent serial coronary angiography at least 6 months apart were included. Total physiological atherosclerotic burden was characterized by sum of quantitative flow ratio in 3 epicardial vessels (3V-QFR). The relationships of the 3V-QFR and its longitudinal change (△3V-QFR) with major adverse cardiovascular events (MACE) were explored. 3V-QFR values derived from follow-up angiograms were slightly lower compared with baseline (2.85 [2.77, 2.90] vs 2.86 [2.80, 2.90], < .001). The median △3V-QFR value was -0.01 (-0.05, 0.02). The multivariable models demonstrated that follow-up 3V-QFR and △3V-QFR were independently associated with MACE (both < .05). Patients with both low follow-up 3V-QFR (≤2.78) and low △3V-QFR (≤-0.05) presented 3 times higher risk of MACE than those without (hazard ratio: 2.953, 95% confidence interval 1.428-6.104, = .003). Furthermore, adding patient-level 3V-QFR and △3V-QFR to clinical model significantly improved the predictability for MACE. In conclusion, total physiological atherosclerotic burden and its progression can provide incremental prognostic value over clinical characteristics, supporting the use of coronary physiology in the evaluation of disease progression and for the identification of vulnerable patients.
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