Overview of Quantitative Flow Ratio and Optical Flow Ratio in the Assessment of Intermediate Coronary Lesions

Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improves clinical outcome compared with angiography-guided PCI. Advances in computational technology have resulted in the development of solutions, enabling fast derivation of FFR from imaging data in the catheterization laboratory. The quantitative flow ratio is currently the most validated approach to derive FFR from invasive coronary angiography, while the optical flow ratio allows faster and more automation in FFR computation from intracoronary optical coherence tomography. The use of quantitative flow ratio and optical flow ratio has the potential for swift and safe identification of lesions that require revascularization, optimization of PCI, evaluation of plaque features, and virtual planning of PCI

Reproducibility of quantitative flow ratio: An inter-core laboratory variability study

Background: Quantitative flow ratio (QFR) is a novel approach to derive fractional flow reserve (FFR) from coronary angiography. This study sought to evaluate the reproducibility of QFR when analyzed in independent core laboratories. Methods: All interrogated vessels in the FAVOR II China Study were separately analyzed using the AngioPlus system (Pulse medical imaging technology, Shanghai) by two independent core laboratories, following the same standard operation procedures. The analysts were blinded to the FFR values and online QFR values. For each interrogated vessel, two identical angiographic image runs were used by two core laboratories for QFR computation. In both core laboratories QFR was successfully obtained in 330 of 332 vessels, in which FFR was available in 328 vessels. Thus, 328 vessels ended in the present statistical analysis. Results: The mean difference in contrast-flow QFR between the two core laboratories was 0.004 ± 0.03 (p = 0.040), which was slightly smaller than that between the online analysis and the two core laboratories (0.01 ± 0.05, p < 0.001 and 0.01 ± 0.05, p = 0.038). The mean difference of QFR with re­spect to FFR were comparable between the two core laboratories (0.002 ± 0.06, p = 0.609, and 0.002 ± 0.06, p = 0.531). Receiver operating characteristic curve analysis showed that diagnostic accuracies of QFR analyzed by the two core laboratories were both excellent (area under the curve: 0.970 vs. 0.963, p = 0.142), when using FFR as the reference standard. Conclusions: The present study showed good inter-core laboratory reproducibility of QFR in assessing functionally-significant stenosis. It suggests that QFR analyses can be carried out in different core labo­ratories if, and only if, highly standardized conditions are maintained

Optimal diagnostic approach for using CT-derived quantitative flow ratio in patients with stenosis on coronary computed tomography angiography

Background: Coronary computed tomography angiography (CCTA)-derived quantitative flow ratio (CT-QFR) is an on-site non-invasive technique estimating invasive fractional flow reserve (FFR). This study assesses the diagnostic performance of using most distal CT-QFR versus lesion-specific CT-QFR approach for identifying hemodynamically obstructive coronary artery disease (CAD).Methods: Prospectively enrolled de novo chest pain patients (n ​= ​445) with ≥50 ​% visual diameter stenosis on CCTA were referred for invasive evaluation. On-site CT-QFR was analyzed post-hoc blinded to angiographic data and obtained as both most distal (MD-QFR) and lesion-specific CT-QFR (LS-QFR). Abnormal CT-QFR was defined as ≤0.80. Hemodynamically obstructive CAD was defined as invasive FFR ≤0.80 or ≥70 ​% diameter stenosis by 3D-quantitative coronary angiography.Results: In total 404/445 patients had paired CT-QFR and invasive analyses of whom 149/404 (37 ​%) had hemodynamically obstructive CAD. MD-QFR and LS-QFR classified 188 (47 ​%) and 165 (41 ​%) patients as abnormal, respectively. Areas under the receiver-operating characteristic curve for MD-QFR was 0.83 vs. 0.85 for LS-QFR, p ​= ​0.01. Sensitivities for MD-QFR and LS-QFR were 80 ​% (95%CI: 73-86) vs. 77 ​% (95%CI: 69-83), p ​= ​0.03, respectively, and specificities were 73 ​% (95%CI: 67-78) vs. 80 ​% (95%CI: 75-85), p ​< ​0.01, respectively. Positive predictive values for MD-QFR and LS-QFR were 63 ​% vs. 69 ​%, p ​< ​0.01, respectively, and negative predictive values for MD-QFR and LS-QFR were 86 ​% vs. 85 ​%, p ​= ​0.39, respectively).Conclusion: Using a lesion-specific CT-QFR approach has superior discrimination of hemodynamically obstructive CAD compared to a most distal CT-QFR approach. CT-QFR identified most cases of hemodynamically obstructive CAD while a normal CT-QFR excluded hemodynamically obstructive CAD in the majority of patients

Prognostic value of microvascular resistance and its association to fractional flow reserve:a DEFINE-FLOW substudy

OBJECTIVE: This study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary artery disease. METHODS: This is a substudy of the DEFINE-FLOW cohort (NCT02328820), which evaluated the prognosis of lesions (n=456) after combined FFR and coronary flow reserve (CFR) assessment in a prospective, non-blinded, non-randomised, multicentre study in 12 centres in Europe and Japan. Participants (n=430) were evaluated by wire-based measurement of coronary pressure, flow and vascular resistance (ComboWire XT, Phillips Volcano, San Diego, California, USA). RESULTS: Mean FFR and CFR were 0.82±0.10 and 2.2±0.6, respectively. When divided according to FFR and CFR thresholds (above and below 0.80 and 2.0, respectively), HMR was highest in lesions with FFR>0.80 and CFR<2.0 (n=99) compared with lesions with FFR≤0.80 and CFR≥2.0 (n=68) (2.92±1.2 vs 1.91±0.64 mm Hg/cm/s, p<0.001). The FFR value was proportional to the ratio between HMR and the HMR+HSR (total resistance), 95% limits of agreement (−0.032; 0.019), bias (−0.003±0.02) and correlation (r(2)=0.98, p<0.0001). Cox regression model using HMR as continuous parameter for target vessel failure showed an HR of 1.51, 95% CI (0.9 to 2.4), p=0.10. CONCLUSIONS: Increased HMR was not associated with a higher rate of adverse clinical events, in this population of mainly stable patients. FFR can be equally well expressed as HMR/HMR+HSR, thereby providing an alternative conceptual formulation linking epicardial severity with microvascular resistance. TRIAL REGISTRATION NUMBER: NCT02328820

Characterization of quantitative flow ratio and fractional flow reserve discordance using doppler flow and clinical follow-up

The physiological mechanisms of quantitative flow ratio and fractional flow reserve disagreement are not fully understood. We aimed to characterize the coronary flow and resistance profile of intermediate stenosed epicardial coronary arteries with concordant and discordant FFR and QFR. Post-hoc analysis of the DEFINE-FLOW study. Anatomical and Doppler-derived physiological parameters were compared for lesions with FFR+QFR− (n = 18) vs. FFR+QFR+ (n = 43) and for FFR−QFR+ (n = 34) vs. FFR−QFR− (n = 139). The association of QFR results with the two-year rate of target vessel failure was assessed in the proportion of vessels (n = 195) that did not undergo revascularization. Coronary flow reserve was higher [2.3 (IQR: 2.1–2.7) vs. 1.9 (IQR: 1.5–2.4)], hyperemic microvascular resistance lower [1.72 (IQR: 1.48–2.31) vs. 2.26 (IQR: 1.79–2.87)] and anatomical lesion severity less severe [% diameter stenosis 45.5 (IQR: 41.5–52.5) vs. 58.5 (IQR: 53.1–64.0)] for FFR+QFR− lesions compared with FFR+QFR+ lesions. In comparison of FFR−QFR+ vs. FFR-QFR- lesions, lesion severity was more severe [% diameter stenosis 55.2 (IQR: 51.7–61.3) vs. 43.4 (IQR: 35.0–50.6)] while coronary flow reserve [2.2 (IQR: 1.9–2.9) vs. 2.2 (IQR: 1.9–2.6)] and hyperemic microvascular resistance [2.34 (IQR: 1.85–2.81) vs. 2.57 (IQR: 2.01–3.22)] did not differ. The agreement and diagnostic performance of FFR using hyperemic stenosis resistance (> 0.80) as reference standard was higher compared with QFR and coronary flow reserve. Disagreement between FFR and QFR is partly explained by physiological and anatomical factors. Clinical Trials Registration https://www.clinicaltrials.gov; Unique identifier: NCT01813435. Graphical abstract: Changes in central physiological and anatomical parameters according to FFR and QFR match/mismatch quadrants

Diagnostic performance of an acoustic-based system for coronary artery disease risk stratification

ObjectiveDiagnosing coronary artery disease (CAD) continues to require substantial healthcare resources. Acoustic analysis of transcutaneous heart sounds of cardiac movement and intracoronary turbulence due to obstructive coronary disease could potentially change this. The aim of this study was thus to test the diagnostic accuracy of a new portable acoustic device for detection of CAD.MethodsWe included 1675 patients consecutively with low to intermediate likelihood of CAD who had been referred for cardiac CT angiography. If significant obstruction was suspected in any coronary segment, patients were referred to invasive angiography and fractional flow reserve (FFR) assessment. Heart sound analysis was performed in all patients. A predefined acoustic CAD-score algorithm was evaluated; subsequently, we developed and validated an updated CAD-score algorithm that included both acoustic features and clinical risk factors. Low risk is indicated by a CAD-score value ≤20.ResultsHaemodynamically significant CAD assessed from FFR was present in 145 (10.0%) patients. In the entire cohort, the predefined CAD-score had a sensitivity of 63% and a specificity of 44%. In total, 50% had an updated CAD-score value ≤20. At this cut-off, sensitivity was 81% (95% CI 73% to 87%), specificity 53% (95% CI 50% to 56%), positive predictive value 16% (95% CI 13% to 18%) and negative predictive value 96% (95% CI 95% to 98%) for diagnosing haemodynamically significant CAD.ConclusionSound-based detection of CAD enables risk stratification superior to clinical risk scores. With a negative predictive value of 96%, this new acoustic rule-out system could potentially supplement clinical assessment to guide decisions on the need for further diagnostic investigation.Trial registration numberClinicalTrials.gov identifier NCT02264717; Results.</jats:sec

Danish study of Non-Invasive Testing in Coronary Artery Disease 3 (Dan-NICAD 3):study design of a controlled study on optimal diagnostic strategy

Introduction Current guideline recommend functional imaging for myocardial ischaemia if coronary CT angiography (CTA) has shown coronary artery disease (CAD) of uncertain functional significance. However, diagnostic accuracy of selective myocardial perfusion imaging after coronary CTA is currently unclear. The Danish study of Non-Invasive testing in Coronary Artery Disease 3 trial is designed to evaluate head to head the diagnostic accuracy of myocardial perfusion imaging with positron emission tomography (PET) using the tracers 82Rubidium (82Rb-PET) compared with oxygen-15 labelled water PET (15O-water-PET) in patients with symptoms of obstructive CAD and a coronary CT scan with suspected obstructive CAD.Methods and analysis This prospective, multicentre, cross-sectional study will include approximately 1000 symptomatic patients without previous CAD. Patients are included after referral to coronary CTA. All patients undergo a structured interview and blood is sampled for genetic and proteomic analysis and a coronary CTA. Patients with possible obstructive CAD at coronary CTA are examined with both 82Rb-PET, 15O-water-PET and invasive coronary angiography with three-vessel fractional flow reserve and thermodilution measurements of coronary flow reserve. After enrolment, patients are followed with Seattle Angina Questionnaires and follow-up PET scans in patients with an initially abnormal PET scan and for cardiovascular events in 10 years.Ethics and dissemination Ethical approval was obtained from Danish regional committee on health research ethics. Written informed consent will be provided by all study participants. Results of this study will be disseminated via articles in international peer-reviewed journal.Trial registration number NCT04707859

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  0.05, 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.Danish Heart Foundation (grant no. 15-R99-A5837-22920)Health Research Fund of Central Denmark Regio