Coronary Artery Stenosis Evaluation by Angiography-Derived FFR: Validation by Positron Emission Tomography and Invasive Thermodilution.

BACKGROUND: Fractional flow reserve (FFR) derived from invasive coronary angiography (QFR) is promising for evaluation of intermediate coronary artery stenosis. OBJECTIVES: The authors aimed to compare the diagnostic performance of QFR and the guideline-recommended invasive FFR using 82Rubidium positron emission tomography (82Rb-PET) myocardial perfusion imaging as reference standard. METHODS: This is a prospective, observational study of symptomatic patients with suspected obstructive coronary artery disease on coronary computed tomography angiography (≥50% diameter stenosis in ≥1 vessel). All patients were referred to 82Rb-PET and invasive coronary angiography with FFR and QFR assessment of all intermediate (30%-90% diameter stenosis) stenoses. Main analyses included a comparison of the ability of QFR and FFR to identify reduced myocardial blood flow (<2 mL/g/min) during vasodilation and/or relative perfusion abnormalities (summed stress score ≥4 in ≥2 adjacent segments). RESULTS: A total of 250 patients (320 vessels) with indication for invasive physiological assessment were included. The continuous relationship of 82Rb-PET stress myocardial blood flow per 0.10 increase in FFR was +0.14 mL/g/min (95% CI: 0.07-0.21 mL/g/min) and +0.08 mL/g/min (95% CI: 0.02-0.14 mL/g/min) per 0.10 QFR increase. Using 82Rb-PET as reference, QFR and FFR had similar diagnostic performance on both a per-patient level (accuracy: 73%; 95% CI: 67%-79%; vs accuracy: 71%; 95% CI: 64%-78%) and per-vessel level (accuracy: 70%; 95% CI: 64%-75%; vs accuracy: 68%; 95% CI: 62%-73%). The per-vessel feasibility was 84% (95% CI: 80%-88%) for QFR and 88% (95% CI: 85%-92%) for FFR by intention-to-diagnose analysis. CONCLUSIONS: With 82Rb-PET as reference modality, the wire-free QFR solution showed similar diagnostic accuracy as invasive FFR in evaluation of intermediate coronary stenosis. (DAN-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease; NCT02264717).

Quantitative flow ratio versus fractional flow reserve for guiding percutaneous coronary intervention: design and rationale of the randomised FAVOR III Europe Japan trial.

Quantitative flow ratio (QFR) is a computation of fractional flow reserve (FFR) based on invasive coronary angiographic images. Calculating QFR is less invasive than measuring FFR and may be associated with lower costs. Current evidence supports the call for an adequately powered randomised comparison of QFR and FFR for the evaluation of intermediate coronary stenosis. The aim of the FAVOR III Europe Japan trial is to investigate if a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with a standard FFR-guided strategy in the evaluation of patients with intermediary coronary stenosis. FAVOR III Europe Japan is an investigator-initiated, randomised, clinical outcome, non-inferiority trial scheduled to randomise 2,000 patients with either 1) stable angina pectoris and intermediate coronary stenosis, or 2) indications for functional assessment of at least 1 non-culprit lesion after acute myocardial infarction. Up to 40 international centres will randomise patients to either a QFR-based or a standard FFR-based diagnostic strategy. The primary endpoint of major adverse cardiovascular events is a composite of all-cause mortality, any myocardial infarction, and any unplanned coronary revascularisation at 12 months. QFR could emerge as an adenosine- and wire-free alternative to FFR, making the functional evaluation of intermediary coronary stenosis less invasive and more cost-effective.

Polygenic Risk Score-Enhanced Risk Stratification of Coronary Artery Disease in Patients With Stable Chest Pain.

BACKGROUND: Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but the clinical potential of using PRSs at the single-patient level for risk stratification has yet to be established. We investigated whether adding a PRS to clinical risk factors (CRFs) improves risk stratification in patients referred to coronary computed tomography angiography on a suspicion of obstructive CAD. METHODS: In this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease), we included 1617 consecutive patients with stable chest symptoms and no history of CAD referred for coronary computed tomography angiography. CRFs used for risk stratification were age, sex, symptoms, prior or active smoking, antihypertensive treatment, lipid-lowering treatment, and diabetes. In addition, patients were genotyped, and their PRSs were calculated. All patients underwent coronary computed tomography angiography. Patients with a suspected ≥50% stenosis also underwent invasive coronary angiography with fractional flow reserve. A combined end point of obstructive CAD was defined as a visual invasive coronary angiography stenosis >90%, fractional flow reserve <0.80, or a quantitative coronary analysis stenosis >50% if fractional flow reserve measurements were not feasible. RESULTS: The PRS was associated with obstructive CAD independent of CRFs (adjusted odds ratio, 1.8 [95% CI, 1.5-2.2] per SD). The PRS had an area under the curve of 0.63 (0.59-0.68), which was similar to that for age and sex. Combining the PRS with CRFs led to a CRF+PRS model with area under the curve of 0.75 (0.71-0.79), which was 0.04 more than the CRF model (P=0.0029). By using pretest probability (pretest probability) cutoffs at 5% and 15%, a net reclassification improvement of 15.8% (P=3.1×10-4) was obtained, with a down-classification of risk in 24% of patients (211 of 862) in whom the pretest probability was 5% to 15% based on CRFs alone. CONCLUSIONS: Adding a PRS improved risk stratification of obstructive CAD beyond CRFs, suggesting a modest clinical potential of using PRSs to guide diagnostic testing in the contemporary clinical setting. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02264717.

Prediction of Coronary Revascularization in Stable Angina: Comparison of FFRCT With CMR Stress Perfusion Imaging.

OBJECTIVES: This study was designed to compare head-to-head fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) and cardiac magnetic resonance (CMR) stress perfusion imaging for prediction of standard-of-care-guided coronary revascularization in patients with stable chest pain and obstructive coronary artery disease by coronary CTA. BACKGROUND: FFRCT is a novel modality for noninvasive functional testing. The clinical utility of FFRCT compared to CMR stress perfusion imaging in symptomatic patients with coronary artery disease is unknown. METHODS: Prospective study of patients (n = 110) with stable angina pectoris and 1 or more coronary stenosis ≥50% by coronary CTA. All patients underwent invasive coronary angiography. Revascularization was FFR-guided in stenoses ranging from 30% to 90%. FFRCT ≤0.80 in 1 or more coronary artery or a reversible perfusion defect (≥2 segments) by CMR categorized patients with ischemia. FFRCT and CMR were analyzed by core laboratories blinded for patient management. RESULTS: A total of 38 patients (35%) underwent revascularization. Per-patient diagnostic performance for identifying standard-of-care-guided revascularization, (95% confidence interval) yielded a sensitivity of 97% (86% to 100%) for FFRCT versus 47% (31% to 64%) for CMR, p < 0.001; corresponding specificity was 42% (30% to 54%) versus 88% (78% to 94%), p < 0.001; negative predictive value of 97% (91% to 100%) versus 76% (67% to 85%), p < 0.05; positive predictive value of 47% (36% to 58%) versus 67% (49% to 84%), p < 0.05; and accuracy of 61% (51% to 70%) versus 74% (64% to 82%), p > 0.05, respectively. CONCLUSIONS: In patients with stable chest pain referred to invasive coronary angiography based on coronary CTA, FFRCT and CMR yielded similar overall diagnostic accuracy. Sensitivity for prediction of revascularization was highest for FFRCT, whereas specificity was highest for CMR.

Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II).

BACKGROUND: Quantitative flow ratio (QFR) is a novel diagnostic modality for functional testing of coronary artery stenosis without the use of pressure wires and induction of hyperemia. QFR is based on computation of standard invasive coronary angiographic imaging. The purpose of WIFI II (Wire-Free Functional Imaging II) was to evaluate the feasibility and diagnostic performance of QFR in unselected consecutive patients. METHODS AND RESULTS: WIFI II was a predefined substudy to the Dan-NICAD study (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease), referring 362 consecutive patients with suspected coronary artery disease on coronary computed tomographic angiography for diagnostic invasive coronary angiography. Fractional flow reserve (FFR) was measured in all segments with 30% to 90% diameter stenosis. Blinded observers calculated QFR (Medis Medical Imaging bv, The Netherlands) for comparison with FFR. FFR was measured in 292 lesions from 191 patients. Ten (5%) and 9 patients (5%) were excluded because of FFR and angiographic core laboratory criteria, respectively. QFR was successfully computed in 240 out of 255 lesions (94%) with a mean diameter stenosis of 50±12%. Mean difference between FFR and QFR was 0.01±0.08. QFR correctly classified 83% of the lesions using FFR with cutoff at 0.80 as reference standard. The area under the receiver operating characteristic curve was 0.86 (95% confidence interval, 0.81-0.91) with a sensitivity, specificity, negative predictive value, and positive predictive value of 77%, 86%, 75%, and 87%, respectively. A QFR-FFR hybrid approach based on the present results enables wire-free and adenosine-free procedures in 68% of cases. CONCLUSIONS: Functional lesion evaluation by QFR assessment showed good agreement and diagnostic accuracy compared with FFR. Studies comparing clinical outcome after QFR- and FFR-based diagnostic strategies are required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.

Quantitative Flow Ratio Identifies Nonculprit Coronary Lesions Requiring Revascularization in Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Disease.

BACKGROUND: The nonculprit lesion (NCL) management in ST-segment-elevation myocardial infarction patients with multivessel disease is debated. We sought to assess whether quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, may be reliable in this scenario. METHODS AND RESULTS: The present proof-of-concept study is based on a 3-step process: (1) identification of the QFR reproducibility in NCLs assessment (cohort A, n=31); (2) prospective validation of QFR diagnostic accuracy in respect to fractional flow reserve (cohort B, n=45); and (3) investigation of long-term clinical outcomes of NCLs stratified according to QFR (cohort C, n=110). A blinded core laboratory computed QFR values for all NCLs. Cohort A showed a good correlation and agreement between QFR values at index (acute) and at staged (subacute, 3-4 days later) procedures (r=0.98; 95% confidence interval, 0.96-0.99; mean difference, 0.004 [-0.027 to 0.34]). The inter-rater agreement was κ=0.9. In cohort B, fractional flow reserve and QFR identified 16 (33%) and 17 (35%) NCLs potentially flow limiting. Sensitivity, specificity, negative, and positive predictive values were 88%, 97%, 94%, and 94%. The area under the receiver operating characteristics curve was 0.96 (95% confidence interval, 0.89-0.99). Finally, in cohort C, we identified 110 ST-segment-elevation myocardial infarction patients where at least 1 NCL was left untreated. Patients with NCLs showing a QFR value ≤0.80 were at higher risk of adverse events (hazard ratio, 2.3; 95% confidence interval, 1.2-4.5; P=0.01). CONCLUSIONS: In a limited and selected study population, our study showed that QFR computation may be a safe and reliable tool to guide coronary revascularization of NCLs in ST-segment-elevation myocardial infarction patients.

Diagnostic Accuracy of Fast Computational Approaches to Derive Fractional Flow Reserve From Diagnostic Coronary Angiography: The International Multicenter FAVOR Pilot Study.

OBJECTIVES: The aim of this prospective multicenter study was to identify the optimal approach for simple and fast fractional flow reserve (FFR) computation from radiographic coronary angiography, called quantitative flow ratio (QFR). BACKGROUND: A novel, rapid computation of QFR pullbacks from 3-dimensional quantitative coronary angiography was developed recently. METHODS: QFR was derived from 3 flow models with: 1) fixed empiric hyperemic flow velocity (fixed-flow QFR [fQFR]); 2) modeled hyperemic flow velocity derived from angiography without drug-induced hyperemia (contrast-flow QFR [cQFR]); and 3) measured hyperemic flow velocity derived from angiography during adenosine-induced hyperemia (adenosine-flow QFR [aQFR]). Pressure wire-derived FFR, measured during maximal hyperemia, served as the reference. Separate independent core laboratories analyzed angiographic images and pressure tracings from 8 centers in 7 countries. RESULTS: The QFR and FFR from 84 vessels in 73 patients with intermediate coronary lesions were compared. Mean angiographic percent diameter stenosis (DS%) was 46.1 ± 8.9%; 27 vessels (32%) had FFR ≤ 0.80. Good agreement with FFR was observed for fQFR, cQFR, and aQFR, with mean differences of 0.003 ± 0.068 (p = 0.66), 0.001 ± 0.059 (p = 0.90), and -0.001 ± 0.065 (p = 0.90), respectively. The overall diagnostic accuracy for identifying an FFR of ≤0.80 was 80% (95% confidence interval [CI]: 71% to 89%), 86% (95% CI: 78% to 93%), and 87% (95% CI: 80% to 94%). The area under the receiver-operating characteristic curve was higher for cQFR than fQFR (difference: 0.04; 95% CI: 0.01 to 0.08; p < 0.01), but did not differ significantly between cQFR and aQFR (difference: 0.01; 95% CI: -0.04 to 0.06; p = 0.65). Compared with DS%, both cQFR and aQFR increased the area under the receiver-operating characteristic curve by 0.20 (p < 0.01) and 0.19 (p < 0.01). The positive likelihood ratio was 4.8, 8.4, and 8.9 for fQFR, cQFR, and aQFR, with negative likelihood ratio of 0.4, 0.3, and 0.2, respectively. CONCLUSIONS: The QFR computation improved the diagnostic accuracy of 3-dimensional quantitative coronary angiography-based identification of stenosis significance. The favorable results of cQFR that does not require pharmacologic hyperemia induction bears the potential of a wider adoption of FFR-based lesion assessment through a reduction in procedure time, risk, and costs.