Association of Hemodynamic Disease Severity and Distribution With Risk of Future Acute Coronary Syndrome

Although physiological assessment has been used in decision-making for revascularization, its role in predicting the future risk of acute coronary syndrome (ACS) remains underexplored.

This study aims to investigate the independent and combined prognostic significance of hemodynamic disease severity and distribution in identifying ACS culprit vessels, in conjunction with lumen and plaque characteristics.

The EMERALD-II study is an international, multicenter, internal case-control study enrolling 351 patients with ACS who underwent coronary computed tomography angiography (CTA) 1 month to 3 years before the event. Culprit and nonculprit vessels were identified by matching invasive coronary angiography with coronary CTA findings. High-risk plaque (HRP) characteristics, including minimum lumen area <4 mm², plaque burden ≥70%, low-attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign, were assessed by a core laboratory, with HRP defined as ≥3 HRP characteristics. From coronary CTA, the authors derived both the hemodynamic severity of the disease (fractional flow reserve derived from computed tomography [FFR_CT]) and its spatial distribution (diffuse vs focal), as assessed by the pullback pressure gradient derived from coronary CTA (PPG_CT). Vessels were categorized into 4 hemodynamic disease patterns: nonischemic (FFR_CT >0.80), hemodynamic diffuse (FFR_CT ≤0.80 and PPG_CT ≤0.50), mixed (FFR_CT ≤0.80 and 0.50 < PPG_CT ≤0.60), and focal disease (FFR_CT ≤0.80 and PPG_CT >0.60).

Among 873 vessels, the mean FFR_CT was 0.74 ± 0.17 and the mean PPG_CT was 0.54 ± 0.14. Both lower FFR_CT and higher PPG_CT were independently associated with higher ACS risk (OR per 0.1 increase in FFR_CT: 0.71 [95% CI: 0.65-0.77]; P < 0.001; OR per 0.1 increase in PPG: 1.22 [95% CI: 1.09-1.37]; P < 0.001). Among the 4 subgroups of hemodynamic disease pattern, hemodynamic focal disease showed the highest risk of ACS (relative risk [RR]: 2.02 [95% CI: 1.74-2.36]; P < 0.001), myocardial infarction (RR: 1.75 [95% CI: 1.43-2.14]; P < 0.001), and unstable angina (RR: 2.54 [95% CI: 2.00-3.22]; P < 0.001). It remained a predictor for ACS in nonobstructive lesions (OR: 3.56 [95% CI: 1.43-8.84]), obstructive lesions (OR: 3.16 [95% CI: 1.96-5.07]), non-HRP (OR: 6.69 [95% CI: 3.59-12.5]), and HRP (OR: 2.98 [95% CI: 1.83-4.87]). Although the maximal lesion-level ΔFFR_CT (differences in FFR_CT across the lesion) demonstrated superior model performance compared with models incorporating FFR_CT and PPG_CT, higher PPG_CT was additionally associated with increased ACS risk, particularly among vessels with maximal ΔFFR_CT ≥0.10.

Hemodynamic disease distribution, as measured by PPG_CT, complements FFR_CT in predicting ACS risk. The integration of hemodynamic disease patterns provides additional prognostic value beyond lumen and plaque characteristics, with hemodynamic focal disease emerging as an independent predictor and a potential therapeutic target for ACS prevention. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamics II [EMERALD II]; NCT03591328).