BACKGROUND: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI. RESULTS: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61–0.69]; P <0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79–0.84]; P <0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50–0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00–2.97]). CONCLUSIONS: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04789317.

Background: Ultrasonic flow ratio (UFR) is a novel method for fast computation of fractional flow reserve (FFR) from intravascular ultrasound images. The objective of this study is to evaluate the diagnostic performance of UFR using wire-based FFR as the reference. Methods: Post hoc computation of UFR was performed in consecutive patients with both intravascular ultrasound and FFR measurement in a core lab while the analysts were blinded to FFR. Results: A total of 167 paired comparisons between UFR and FFR from 94 patients were obtained. Median FFR was 0.80 (interquartile range, 0.68–0.89) and 50.3% had a FFR≤0.80. Median UFR was 0.81 (interquartile range, 0.69–0.91), and UFR showed strong correlation with FFR ( r =0.87; P <0.001). The area under the curve was higher for UFR than intravascular ultrasound-derived minimal lumen area (0.97 versus 0.89, P <0.001). The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for UFR to identify FFR≤0.80 was 92% (95% CI, 87–96), 91% (95% CI, 82–96), 96% (95% CI, 90–99), 96% (95% CI, 89–99), 91% (95% CI, 93–96), 25.0 (95% CI, 8.2–76.2), and 0.10 (95% CI, 0.05–0.20), respectively. The agreement between UFR and FFR was independent of lesion locations ( P =0.48), prior myocardial infarction ( P =0.29), and imaging catheters ( P =0.22). Intraobserver and interobserver variability of UFR analysis was 0.00±0.03 and 0.01±0.03, respectively. Median UFR analysis time was 102 (interquartile range, 87–122) seconds. Conclusions: UFR had a strong correlation and good agreement with FFR. The fast computational time and excellent analysis reproducibility of UFR bears the potential of a wider adoption of integration of coronary imaging and physiology in the catheterization laboratory.

Background: In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. Methods and Results: From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all‐cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD ( P <0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HR _adjusted ], 2.88; 95% CI, 1.52–7.19; P =0.024; group 4: HR _adjusted , 4.00; 95% CI, 1.41–11.35; P =0.009). Conclusions: In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long‐term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4‐fold difference in long‐term cardiovascular events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04485234.

The role of change in fractional flow reserve derived from CT (FFR_CT) across coronary stenoses (ΔFFR_CT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown. To investigate the incremental value of ΔFFR_CT in predicting early revascularization and improving efficiency of catheter laboratory utilization. Patients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR_CT was measured 2 cm distal to stenosis. ΔFFR_CT was manually measured as the difference of FFR_CT across visible stenosis. Of 4730 patients (66 ± 10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR_CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26–1.35]; p < 0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR_CT. Among the 3 models (model 1: risk factors + stenosis type and location + CAD-RADS; model 2: model 1 + FFR_CT; model 3: model 2 + ΔFFR_CT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p < 0.001), with the greatest incremental value for FFR_CT 0.71–0.80. ΔFFR_CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR_CT ≤0.8, a diagnostic strategy incorporating ΔFFR_CT >0.13, would potentially reduce ICA by 32.2% (1638–1110, p < 0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%. ΔFFR_CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR_CT, particularly for those with FFR_CT 0.71–0.80. ΔFFR_CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.

BACKGROUND: Luminal stenosis, computed tomography–derived fractional-flow reserve (FFR _CT ), and high-risk plaque features on coronary computed tomography angiography are all known to be associated with adverse clinical outcomes. The interactions between these variables, patient outcomes, and quantitative plaque volumes have not been previously described. METHODS: Patients with coronary computed tomography angiography (n=4430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Noninvasive FFR _CT in Coronary Care) registry underwent artificial intelligence–enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume and each plaque subtype were derived using receiver-operator characteristic curve analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFR _CT , and translesional delta-FFR _CT . Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events, late revascularization, a composite of the two, and cardiovascular death and myocardial infarction. RESULTS: At one year, 55 patients (1.2%) had experienced major adverse cardiac events, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis, and FFR _CT , total plaque volume above the receiver-operator characteristic curve–derived optimal cutoff (total plaque volume >564 mm ³ ) was associated with the major adverse cardiac event/late revascularization composite (adjusted hazard ratio, 1.515 [95% CI, 1.093–2.099]; P =0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both major adverse cardiac event/late revascularization (total percent atheroma volume >24.4%; hazard ratio, 2.046 [95% CI, 1.474–2.839]; P 37.17%, hazard ratio, 4.53 [95% CI, 1.943–10.576]; P =0.0005). Calcified, noncalcified, and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/myocardial infarction in analyses stratified by median plaque volumes. CONCLUSIONS: Analysis of the ADVANCE registry using artificial intelligence–enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFR _CT . REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02499679.

High-risk plaque features and plaque burden at coronary CT angiography were associated with cardiovascular events independent of coronary hemodynamic flow parameters. Background Plaque assessments with coronary CT angiography (CCTA) and coronary flow indexes have prognostic implications. Purpose To investigate the association and additive prognostic value of pla...