CT-derived fractional flow reserve for prediction of major adverse cardiovascular events in diabetic patients

Abstract

Objectives: To investigate the prognostic value of computed tomography fractional flow reserve (CT-FFR) in patients with diabetes and to establish a risk stratification model for major adverse cardiac event (MACE).

Methods: Diabetic patients with intermediate pre-test probability of coronary artery disease were prospectively enrolled. All patients were referred for coronary computed tomography angiography and followed up for at least 2 years. In the training cohort comprising of 957 patients, two models were developed: model1 with the inclusion of clinical and conventional imaging parameters, model2 incorporating the above parameters + CT-FFR. An internal validation cohort comprising 411 patients and an independent external test cohort of 429 patients were used to validate the proposed models.

Results: 1797 patients (mean age: 61.0 ± 7.0 years, 1031 males) were finally included in the present study. MACE occurred in 7.18% (129/1797) of the current cohort during follow- up. Multivariate Cox regression analysis revealed that CT-FFR ≤ 0.80 (hazard ratio [HR] = 4.534, p < 0.001), HbA1c (HR = 1.142, p = 0.015) and low attenuation plaque (LAP) (HR = 3.973, p = 0.041) were the independent predictors for MACE. In the training cohort, the Log-likelihood test showed statistical significance between model1 and model2 (p < 0.001). The C-index of model2 was significantly larger than that of model1 (C-index = 0.82 [0.77-0.87] vs. 0.80 [0.75-0.85], p = 0.021). Similar findings were found in internal validation and external test cohorts.

Conclusion: CT-FFR was a strong independent predictor for MACE in diabetic cohort. The model incorporating CT-FFR, LAP and HbA1c yielded excellent performance in predicting MACE.

Keywords: Coronary computed tomography angiography; Diabetes; Fractional flow reserve; High-risk plaque.

Fig. 1

Flow chart of inclusion and exclusion criteria. CAD = coronary artery disease; CCTA = coronary computed tomography angiography;

Fig. 2

Representative cases of diabetic patients with and without MACE. (A) CCTA of a 63-year-old male with stable angina showed multiple obstructive stenosis at proximal and middle LAD. Plaque characterization revealed the presence of LAP for the proximal lesion (blue content) and the distal CT-FFR value was 0.63. The total points of the proposed nomogram were 185. This patient underwent late revascularization of proximal LAD lesion 2.29 years later due to aggravated angina symptom. (B) CCTA of a 79-year-old male with stable angina showed mild stenosis at proximal LAD. Plaque characterization revealed the absence of any HRP feature and the distal CT-FFR value was 0.97. The total points of the proposed nomogram were 55. The patient did not develop MACE at a follow-up of 2.72 years. CCTA = coronary computed tomography angiography; CT-FFR = computed tomography fractional flow reserve; HRP = high-risk plaque; LAP = low-attenuation plaque; LAD = left anterior descending; MACE = major adverse cardiac events

Fig. 3

Kaplan–Meier curves for cumulative event rate of MACE according to (A) CT-FFR; (B) CAD-RADS classification; (C) HRP; (D) CACS. CACS = coronary artery calcium score; CAD-RADS = Coronary Artery Disease—Reporting and Data System; CT-FFR = computed tomography fractional flow reserve; HRP = high-risk plaque; MACE = major adverse cardiac event

Fig. 4

Nomogram for 1-, 2-, and 3-year probability of MACE. HbA1c = hemoglobin A1c; CT-FFR = computed tomography fractional flow reserve; LAP = low-attenuation plaque

Fig. 5

Calibration curves of the nomogram for 1-, 2-, and 3-year of MACE. Nomograms (A) for training cohort; (B) for internal validation cohort; and (C) for external validation cohort. MACE = major adverse cardiac event