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Background There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. Objectives The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. Methods The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. Results The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months’ extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). Conclusions In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555 )

INTRODUCTION Multiple risk models are used to predict the presence of obstructive coronary artery disease (CAD) in patients with chest pain. We aimed to compare the performance of these models to an experienced cardiologist's assessment utilizing coronary angiography (CA) as a reference. MATERIALS AND METHODS We prospectively enrolled patients without known CAD referred for elective CA. We assessed pretest probability of CAD using the following risk models: Diamond-Forrester (original and updated), Duke Clinical score, ACC/AHA, CAD consortium (basic and clinical) and PROMISE minimal risk tool. All patients completed self-administrative Rose angina questionnaire. Independently, an experienced cardiologist assessed the patients to provide a binary prediction of obstructive CAD prior to CA. Obstructive CAD was defined as >80% stenosis in epicardial coronary arteries by visual assessment, or fractional flow reserve

The fractional flow reserve (FFR) index is an important clinical indicator for characterizing coronary artery disease (CAD) functional significance, allowing cardiologists to decide whether intervention is required or not. Noninvasive techniques for calculating FFR are still incompletely resolved and rely heavily on time consuming numerical methods, which may hinder their clinical translation. This paper reports on the development of two fast and noninvasive methods for predicting FFR in diseased coronary arteries. The new methods are derived from physical principles and account for patient-specific physiological parameters that can be noninvasively measured. The developed algebraic equations calculate FFR without performing any tedious numerical simulations, making them attractive for clinical applications. The performance of the methods is assessed by comparing their predictions with measurements and with results obtained by full three-dimensional numerical simulations on healthy and diseased idealized coronary arteries and actual anatomical branches. Results generated by the new methodology are within 5% of measurements and in very good agreement with values obtained numerically.

BACKGROUND Based on coronary angiography and mean aortic pressure, a specially designed computational flow dynamics (CFD) method is proposed to determine contrast fractional flow reserve (cFFR) without using invasive pressure wire. This substudy assessed diagnostic performance of coronary angiography-derived cFFR in catheterization laboratory, based on a previous multicenter trial for online assessment of coronary angiography-derived FFR (caFFR). METHODS Patients with diagnosis of stable angina pectoris or unstable angina pectoris were enrolled in six centers. Wire-based FFR was measured in coronary arteries with 30-90% diameter stenosis. Offline angiography-derived cFFR was computed in blinded fashion against the wire-based FFR and caFFR at an independent core laboratory. RESULTS A total of 330 patients were enrolled to fulfill inclusion/exclusion criteria from June 26 to December 18, 2018. Offline angiography-derived cFFR and wire-based FFR results were compared in 328 interrogated vessels. The statistical analysis showed the highest diagnostic accuracy of 89.0 and 86.6% for angiography-derived cFFR with a cutoff value of 0.94 and 0.93 against the wire-based FFR with a cutoff value of 0.80 and 0.75, respectively. The corresponding sensitivity and specificity were 92.2 and 87.3% for the cutoff value of 0.94 and 80.0 and 88.4% for the cutoff value of 0.93, which are similar to those against the caFFR. The receiver-operating curve has area under the curve of 0.951 and 0.972 for the wire-based FFR with the cutoff value of 0.80 and 0.75, respectively. CONCLUSIONS Coronary angiography-derived cFFR showed higher accuracy, sensitivity, and specificity against wired-based FFR and caFFR. Hence, angiography-derived cFFR could enhance the hemodynamic assessment of coronary lesions.

Aim To evaluate the diagnostic accuracy of cardiac perfusion computed tomography (PCT) with transesophageal electrocardiostimulation (TE ECS) for detection of ischemia in patients with borderline coronary stenosis (50–75 %) compared to measurements of fractional flow reserve (FFR).Material and methods The study included 25 patients with borderline (50–75 %) coronary stenosis as per data of computed tomography angiography (CTA) or coronary angiography (CAG). Later the patients underwent invasive measurement of FFR and cardiac PCT on a 320-row detector tomograph in combination with the TE ECS stress test. FFR values Results All patients completed the study protocol. Cardiac pacing duration was 6 min for all patients. Four patients required intravenous administration of atropine sulphate. PCT with TE ECS detected significant for FFR stenoses with sensitivity, specificity, and predictive value of a positive result and predictive value for a negative result of 47, 90, 87, and 53 %, respectively.Conclusion PCT with TE ECS in combination with CTA can be considered as an informative method for simultaneous evaluation of the condition of coronary arteries and detection of myocardial ischemia. This method is particularly relevant for assessing the hemodynamic significance of borderline coronary stenoses.

BACKGROUND Optical flow ratio (OFR) is a recently developed method for functional assessment of coronary artery disease based on computational fluid dynamics of vascular anatomical data from intravascular optical coherence tomography (OCT). The purpose of this study was to investigate the relationship between OFR and fractional flow reserve (FFR) in stent-treated arteries immediately after percutaneous coronary intervention (PCI).Methods and Results:The OFR and FFR were measured in 103 coronary arteries immediately after successful PCI with a stent. An increase in the OFR and FFR values within the stent was defined as in-stent ∆OFR and ∆FFR, respectively. The values of FFR and OFR were 0.89±0.06 and 0.90±0.06, respectively. OFR was highly correlated with FFR (r=0.84, P

ObjectiveThe prognostic importance of a coronary stenosis depends on its functional severity and its depending myocardial mass. Functional severity can be assessed by fractional flow reserve (FFR), estimated non-invasively by a specific validated CT algorithm (FFRCT). Calculation of myocardial mass at risk by that same set of CT data (CTmass), however, has not been prospectively validated so far. The aim of the present study was to compare relative territorial-based CTmass assessment with relative flow distribution, which is closely linked to true myocardial mass.MethodsIn this exploratory study, 35 patients with (near) normal coronary arteries underwent CT scanning for computed flow-based CTmass assessment and underwent invasive myocardial perfusion measurement in all 3 major coronary arteries by continuous thermodilution. Next, the mass and flows were calculated as relative percentages of total mass and perfusion.ResultsThe mean difference between CTmass per territory and invasively measured myocardial perfusion, both expressed as percentage of total mass and perfusion, was 5.3±6.2% for the left anterior descending territory, −2.0±7.4% for the left circumflex territory and −3.2±3.4% for the right coronary artery territory. The intraclass correlation between the two techniques was 0.90.ConclusionsOur study shows a close relationship between the relative mass of the perfusion territory calculated by the specific CT algorithm and invasively measured myocardial perfusion. As such, these data support the use of CTmass to estimate territorial myocardium-at-risk in proximal coronary arteries.

To investigate the diagnostic performance of 70-kVp stress dynamic myocardial CT perfusion (CTP) as a low-dose, one-stop cardiac CT examination in clinical application. Consecutive symptomatic patients were prospectively recruited and scanned with stress dynamic myocardial CTP. The CTP phase with the best enhancement of the coronary arteries was selected and extracted as the CTP-derived single-phase coronary CT angiography (SP-CTA). The diagnostic performance of CTP and CTP+SP-CTA for functionally significant CAD was assessed. Invasive coronary angiography and fractional flow reserve were used as the reference standard for the myocardial ischemia evaluation. In total, 71 patients (43 men and 28 women; 63.6 ± 8.8 years old) underwent the stress dynamic myocardial CTP; 63 vessels (36.2%) from 42 of the patients (59.2%) were identified as causing ischemia. On a per-vessel basis, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy for CTP and CTP+SP-CTA were 77.8%, 93.7%, 87.5%, 88.1%, and 87.9% and 84.1%, 93.7%, 88.3%, 91.2%, and 90.2%, respectively. The area under the curve (AUC) of CTP+SP-CTA (AUC = 0.963; 95%CI, 0.938–0.989) was significantly superior to that of CTP (AUC = 0.922; 95%CI, 0.880–0.964) and that of SP-CTA (AUC = 0.833; 95%CI, 0.765–0.900) alone (all p

In patients with obstructive coronary artery disease, the functional significance of a coronary artery stenosis needs to be determined to guide treatment. This is typically established through fractional flow reserve (FFR) measurement, performed during invasive coronary angiography (ICA). We present a method for automatic and non-invasive detection of patients requiring ICA, employing deep unsupervised analysis of complete coronary arteries in cardiac CT angiography (CCTA) images. We retrospectively collected CCTA scans of 187 patients, 137 of them underwent invasive FFR measurement in 192 different coronary arteries. These FFR measurements served as a reference standard for the functional significance of the coronary stenosis. The centerlines of the coronary arteries were extracted and used to reconstruct straightened multi-planar reformatted (MPR) volumes. To automatically identify arteries with functionally significant stenosis that require ICA, each MPR volume was encoded into a fixed number of encodings using two disjoint 3D and 1D convolutional autoencoders performing spatial and sequential encodings, respectively. Thereafter, these encodings were employed to classify arteries using a support vector machine classifier. The detection of coronary arteries requiring invasive evaluation, evaluated using repeated cross-validation experiments, resulted in an area under the receiver operating characteristic curve of $0.81 \pm 0.02$ on the artery-level, and $0.87 \pm 0.02$ on the patient-level. The results demonstrate the feasibility of automatic non-invasive detection of patients that require ICA and possibly subsequent coronary artery intervention. This could potentially reduce the number of patients that unnecessarily undergo ICA., Comment: This work has been accepted to IEEE TMI for publication

To evaluate the diagnostic performance of automated quantitative analysis by coronary computed tomography angiography (CCTA) in identifying lesion-specific hemodynamic abnormality.A total of 132 patients (mean age, 61 y; 86 men) with 169 vessels (with 30% to 90% diameter stenosis), who successively underwent invasive coronary angiography with evaluation of fractional flow reserve (values ≤0.8 were defined as lesion-specific hemodynamic abnormalities), were analyzed by CCTA. CCTA images were quantitatively analyzed using automated software to obtain the following index: maximum diameter stenosis (MDS%); maximum area stenosis (MAS%); lesion length (LL); volume and burden (plaque volume×100 per vessel volume) of total plaque (total plaque volume [TPV], total plaque burden [TPB]), calcified plaque (calcified plaque volume [CPV], calcified plaque volume burden [CPB]), noncalcified plaque (noncalcified plaque volume [NCPV], noncalcified plaque volume burden [NCPB]), lipid plaque (lipid plaque volume [LPV], lipid plaque burden [LPB]), and fibrous plaque (fibrotic plaque volume [FPV], fibrotic plaque burden [FPB]); napkin-ring sign (NRS); remodeling index (RI); and eccentric index (EI). Logistic regression and area under the receiver operating characteristics (AUC) were used for statistical analysis.Fractional flow reserve ≤0.80 was found in 57 (33.73%) of the 169 vessels. Vessels with hemodynamic significance had greater MDS% (64.43%±8.69% vs. 57.33%±9.95%, P0.001), MAS% (73.18%±8.56% vs. 64.66%±8.95%, P0.001), and lipid plaque burden (12.75% [9.73%, 19.56%] vs. 9.41% [4.10%, 15.70%], P=0.01) compared with vessels with normal hemodynamics. In multivariable logistic regression analysis, MAS%68% (odds ratio: 7.20, 95% confidence interval [CI]=2.89-17.91, P0.001) and LPB10.03% (odds ratio=4.32, 95% CI=1.36-13.66, P=0.01) were significant predictors of hemodynamic abnormalities. In predicting lesion-specific hemodynamic abnormalities, the AUC was 0.77 (95% CI=0.70-0.85) for MAS% versus 0.71 (95% CI=0.63-0.79) for MDS% (P0.05), 0.66 (95% CI=0.58-0.74) for LPV (P0.05), 0.66 (95% CI=0.58-0.74) for LPB (P0.05), and 0.63 (95% CI=0.54-0.71) for TPB (P0.05). The AUC of MAS%+LPB (0.83, 95% CI=0.76-0.89) was significantly improved compared with that of MAS% (0.77, 95% CI=0.70-0.85, P0.05).Compared with MDS% and the volume burdens of plaque compositions, MAS% has a higher diagnostic accuracy for coronary hemodynamic abnormalities in the precise quantitative analysis of coronary plaques on the basis of CT. Furthermore, MAS%+LPB might improve the diagnostic accuracy beyond MAS% alone.

Contains fulltext : 229194.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices. BACKGROUND: Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR. METHODS: Of 120 patients (62% men, age 58.3 +/- 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements. RESULTS: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to >/=70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR. CONCLUSIONS: CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

The aim of this study was to evaluate a new analytical method for calculating non-invasive fractional flow reserve (FFRAM) to diagnose ischemic coronary lesions. Patients with suspected or known coronary artery disease (CAD) who underwent computed tomography coronary angiography (CTCA) and invasive coronary angiography (ICA) with FFR measurements from two sites were prospectively recruited. Obstructive CAD was defined as diameter stenosis (DS) ≥50% on CTCA or ICA. FFRAM was derived from CTCA images and anatomical features using analytical method and was compared with computational fluid dynamics (CFD)-based FFR (FFRB) and invasive ICA-based FFR. FFRAM, FFRB, and invasive FFR ≤ 0.80 defined ischemia. A total of 108 participants (mean age 60, range: 30–83 years, 75% men) with 169 stenosed coronary arteries were analyzed. The per-vessel accuracy, sensitivity, specificity, and positive predictive and negative predictive values were, respectively, 81, 75, 86, 81, and 82% for FFRAM and 87, 88, 86, 83, and 90% for FFRB. The area under the receiver operating characteristics curve for FFRAM (0.89 and 0.87) and FFRB (0.90 and 0.86) were higher than both CTCA- and ICA-derived DS (all p < 0.0001) on per-vessel and per-patient bases for discriminating ischemic lesions. The computational time for FFRAM was much shorter than FFRB (2.2 ± 0.9 min vs. 48 ± 36 min, excluding image acquisition and segmentation). FFRAM calculated from a novel and expeditious non-CFD approach possesses a comparable diagnostic performance to CFD-derived FFRB, with a significantly shorter computational time.

Cardiac transplant-related vasculopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, coronary angiography-derived vessel fractional flow reserve (vFFR) has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease. Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic coronary artery disease, data on the use of vFFR in heart transplant recipients suffering from cardiac transplant-related arteriopathy are lacking. The aim of the presented study was to validate coronary angiography-derived vessel fractional flow reserve to calculate fractional flow reserve in HTx patients with and without cardiac transplant-related vasculopathy. A prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography was conducted. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/s in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Overall, 18,059 FFR values were extracted from the FFR pullback curves from 23 HTx patients. The mean age was 59.3 ± 9.7 years, the mean time after transplantation was 5.24 years [IQR 1.20, 11.25]. A total of 39 vessels from 23 patients (24 LAD, 11 LCX, 4 RCA) were analyzed. Mean distal vFFR was 0.87 ± 0.14 whereas invasive distal FFR was 0.88 ± 0.17. An excellent correlation was found between invasive distal FFR and vFFR (r = 0.92; p < 0.001). The correlation of the pullback tracing was high, with a correlation coefficient between vFFR and invasive FFR pullback values of 0.72 (95% CI 0.71 to 0.73, p < 0.001). The mean difference between vFFR and invasive FFR pullback values was -0.01 with 0.06 of SD (limits of agreements -0.12 to 0.13). In HTx patients, coronary angiography-derived FFR correlates excellently with invasively measured wire-derived FFR. Therefore, angiography derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy. ispartof: DIAGNOSTICS vol:11 issue:10 ispartof: location:Switzerland status: published

This study aimed to examine whether the ratio of vessel-specific coronary arterial lumen volume to the fraction of myocardial mass (VR/MR) affects myocardial ischemia. We proposed a calculation method for VR/MR, and compared the ratio of total epicardial coronary arterial lumen volume to left ventricular myocardial mass (V/M) with VR/MR in predicting myocardial ischemia. VR/MR and V/M were computed using data from 205 patients with 241 stenosis vessel who underwent coronary computed tomography angiography (CTA), quantitative coronary angiography, and fractional flow reserve. The vessel-specific coronary arterial lumen volume (VR) was obtained from CTA by segmenting the coronary arterial lumen volume, while the vessel-specific fraction of myocardial mass (MR) was obtained by allometric scaling. The VR/MR was then calculated. The cut-off values of V/M (23.55 mm3/g) and VR/MR (12.98 mm3/g) were used to define equal groups of ischemic and non-ischemic patients, respectively. Using these cut-off values, the accuracy, specificity, sensitivity, positive predictive value, and negative predictive value of V/M were 60%, 76%, 45%, 57%, and 66%, and of VR/MR were 87%, 92%, 77%, 89%, and 83%, respectively. Patients have different VR/MR values in different stenotic coronary arteries. Clinically, VR/MR is a quantitative indicator of the risk of myocardial ischemia.

Purpose Several studies have demonstrated the feasibility and safety of hemodynamic assessment of non-culprit coronary arteries in setting of acute coronary syndromes (ACS) using fractional flow reserve (FFR) measurements. Quantitative flow ratio (QFR), recently introduced as angiography-based fast FFR computation, has been validated with good agreement and diagnostic performance with FFR in chronic coronary syndromes. The aim of this study was to assess the feasibility and diagnostic reliability of QFR assessment during primary PC. Methods A total of 321 patients with ACS and multivessel disease, who underwent primary PCI and were planned for staged PCI of at least one non-culprit lesion were enrolled in the analysis. Within this patient cohort, serial post-hoc QFR analyses of 513 non-culprit vessels were performed. Results The median time interval between primary and staged PCI was 49 [42–58] days. QFR in non-culprit coronary arteries did not change between acute and staged measurements (0.86 vs 0.87, p = 0.114), with strong correlation (r = 0.94, p≤0.001) and good agreement (mean difference − 0.008, 95%CI -0.013-0.003) between measurements. Importantly, QFR as assessed at index procedure had sensitivity of 95.02%, specificity of 93.59% and diagnostic accuracy of 94.15% in prediction of QFR ≤ 0.80 at the time of staged PCI. Conclusions The present study for the first time confirmed the feasibility and diagnostic accuracy of non-culprit coronary artery QFR during primary PCI. These results support QFR as valuable tool in patients with ACS to detect further hemodynamic relevant lesions with excellent diagnostic performance and therefore to guide further revascularisation therapy.

Aims The aim of this study was to evaluate the association between coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) and recurrent chest pain (CP) at 1-year follow-up in patients with stable angina pectoris (SAP). Methods and results Study of patients (n = 267) with SAP who underwent CCTA and FFRCT testing; 236 (88%) underwent invasive coronary angiography; and 87 (33%) were revascularized. Symptomatic status at 1-year follow-up was gathered by a structured interview. Three different FFRCT algorithms were applied using the following criteria for abnormality: (i) 2 cm-FFRCT ≤0.80; (ii) d-FFRCT ≤0.80; and (iii) a combination in which both a d-FFRCT ≤0.80 and a ΔFFRCT ≥0.06 must be present in the same vessel (c-FFRCT). Patients were classified into two groups based on the FFRCT test result and revascularization: completely revascularized/normal (CRN), patients in whom all coronary arteries with an abnormal FFRCT test result were revascularized or patients with completely normal FFRCT test results, and incompletely revascularized (IR), patients in whom ≥1 coronary artery with an abnormal FFRCT test result was not revascularized. Recurrent CP was present in 62 (23%) patients. Classification of patients (CRN or IR) was significantly associated with recurrent CP for all applied FFRCT interpretation algorithms. When applying the c-FFRCT algorithm, the association with recurrent CP was found, irrespective of the extent of coronary calcification and the degree of coronary stenosis. A negative association between per-patient minimal d-FFRCT and recurrent CP was demonstrated, P < 0.005. Conclusion An abnormal FFRCT test result is associated with an increased risk of recurrent CP in patients with new-onset SAP.

International audience; Vasodilator-stress CT perfusion imaging in addition to CT coronary angiography (CTCA) may provide a single-test alternative to nuclear stress testing, commonly used to assess hemodynamic significance of stenosis. Another alternative is fractional flow reserve (FFR) calculated from cardiac CT images. We studied the concordance between these two approaches and their relationship to outcomes. We prospectively studied 150 patients with chest pain, who underwent CTCA and regadenoson CT. CTCA images were interpreted for presence and severity of stenosis. Fused 3D displays of subendocardial X-ray attenuation with coronary arteries were created to detect stress perfusion defects (SPD) in each coronary territory. In patients with stenosis > 25%, CT-FFR was quantified. Significant stenosis was determined by: (1) combination of stenosis > 50% with an SPD, (2) CT-FFR ≤ 0.80. Patients were followed-up for 36 ± 25 months for death, myocardial infarction or revascularization. After excluding patients with normal arteries and technical/quality issues, in final analysis of 76 patients, CTCA depicted stenosis > 70% in 13/224 arteries, 50-70% in 24, and < 50% in 187. CT-FFR ≤ 0.80 was found in 41/224 arteries, and combination of SPD with > 50% stenosis in 31/224 arteries. Inter-technique agreement was 89%. Despite high incidence of abnormal CT-FFR (30/76 patients), only 7 patients experienced adverse outcomes; 6/7 also had SPDs. Only 1/9 patients with CT-FFR ≤ 0.80 but normal perfusion had an event. Fusion of CTCA and stress perfusion can help determine the hemodynamic impact of stenosis in one test, in good agreement with CT-FFR. Adding stress CT perfusion analysis may help risk-stratify patients with abnormal CT-FFR.

Contains fulltext : 209423.pdf (Publisher’s version ) (Open Access) OBJECTIVES: The aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)-derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BACKGROUND: In addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. METHODS: Patients with suspected coronary artery disease underwent coronary CTA and [(15)O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA-derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow

Aims Non-invasive fractional flow reserve derived from coronary CT angiography (FFRCT) has been shown to be predictive of lesion-specific ischemia as assessed by invasive fractional flow reserve (FFR). However, in practice, clinicians are often faced with an abnormal distal FFRCT in the absence of a discrete obstructive lesion. Using quantitative plaque analysis, we sought to determine the relationship between an abnormal whole vessel FFRCT (V-FFRCT) and quantitative measures of whole vessel atherosclerosis in coronary arteries without obstructive stenosis. Methods FFRCT was calculated in 155 consecutive patients undergoing coronary CTA with ≥25% but less than 70% stenosis in at least one major epicardial vessel. Semi-automated software was used to quantify plaque volumes (total plaque [TP], calcified plaque [CP], non-calcified plaque [NCP], low-density non-calcified plaque [LD-NCP]), remodeling index [RI], maximal contrast density difference [CDD] and percent diameter stenosis [%DS]. Abnormal V-FFRCT was defined as a minimum value of ≤0.75 across the vessel (at the most distal region where FFRCT was computed). Results Vessels with abnormal V-FFRCT had higher per-vessel TP (554 vs 331 mm3), CP (59 vs 25 mm3), NCP (429 vs 295 mm3), LD-NCP (65 vs 35 mm3) volume and maximum CDD (21 vs 14%) than those with normal V-FFRCT (median, p Conclusion Abnormal V-FFRCT in vessels without obstructive stenosis is associated with multiple markers of diffuse non-obstructive atherosclerosis, independent of stenosis severity. Whole vessel FFRCT may represent a novel measure of diffuse coronary plaque burden.

Background: 3D printed patient-specific coronary models have the ability to enable repeatable benchtop experiments under controlled blood flow conditions. This approach can be applied to CT-derived patient geometries to emulate coronary flow and related parameters such as Fractional Flow Reserve (FFR). Methods: This study uses 3D printing to compare such benchtop FFR results with a non-invasive CT-FFR research software algorithm and catheter based invasive FFR (I-FFR) measurements. Fifty-two patients with a clinical indication for I-FFR underwent a research Coronary CT Angiography (CCTA) prior to catheterization. CT images were used to measure CT-FFR and to generate patient-specific 3D printed models of the aortic root and three main coronary arteries. Each patient-specific model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for two coronary outflow rates ("normal", 250; and "hyperemic", 500 mL/min) by adjusting the model's distal coronary resistance. Results: Pearson correlations and ROC AUC were calculated using invasive I-FFR as reference. The Pearson correlation factor of CT-FFR and B-FFR-500 was 0.75 and 0.71, respectively. Areas under the ROCs for CT-FFR and B-FFR-500 were 0.80 (95%CI: 0.70-0.87) and 0.81 (95%CI: 0.64-0.91) respectively. Conclusion: Benchtop flow simulations with 3D printed models provide the capability to measure pressure changes at any location in the model, for ultimately emulating the FFR at several simulated physiological blood flow conditions. Clinical Trial Registration: https://clinicaltrials.gov/show/NCT03149042

Background: This study aimed to investigate the diagnostic value of comprehensive on-site coronary computed tomography angiography (CCTA) using stenosis and plaque measures and subtended myocardial mass (V sub) for fractional flow reserve (FFR) defined hemodynamically obstructive coronary artery disease (CAD). Additionally, the incremental diagnostic value of off-site CT-derived FFR (FFR CT) was assessed. Methods: Prospectively enrolled patients underwent CCTA followed by invasive FFR interrogation of all major coronary arteries. Vessels with ≥30% stenosis were included for analysis. On-site CCTA assessment included qualitative and quantitative stenosis (visual grading and minimal lumen area, MLA) and plaque measures (characteristics and volumes), and V sub. Diagnostic value of comprehensive on-site CCTA assessment was tested by comparing area under the curves (AUC). In vessels with available FFR CT, the incremental value of off-site FFR CT was tested. Results: In 236 vessels (132 patients), MLA, positive remodeling, non-calcified plaque volume, and V sub were independent on-site CCTA predictors for hemodynamically obstructive CAD (p < 0.05 for all). V sub/MLA 2 outperformed all these on-site CCTA parameters (AUC = 0.85) and V sub was incremental to all other CCTA predictors (p = 0.02). In subgroup analysis (n = 194 vessels), diagnostic performance of FFR CT and V sub/MLA 2 was similar (AUC 0.89 and 0.85 respectively, p = 0.25). Furthermore, diagnostic performance significantly albeit minimally increased when FFR CT was added to on-site CCTA assessment (ΔAUC = 0.03, p = 0.02). Conclusions: In comprehensive on-site CCTA assessment, V sub/MLA2 demonstrated greatest diagnostic value for hemodynamically obstructive CAD and V sub was incremental to all evaluated CCTA indices. Additionally, adding FFR CT only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to FFR CT. Several novel indices have been proposed to increase the diagnostic performance of coronary computed tomography angiography (CCTA). The diagnostic value of comprehensive on-site CCTA assessment using qualitative and quantitative stenosis and plaque measures and subtended myocardial mass (V sub) for fractional flow reserve (FFR) defined hemodynamically obstructive CAD was assessed in 236 vessels with ≥30% stenosis (132 patients). V sub/MLA 2 demonstrated greatest diagnostic value and V sub was incremental to all evaluated CCTA indices. The addition of off-site CT-derived FFR (FFR CT, in 192 vessels) only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to off-site assessment using FFR CT.

Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long‐term clinical outcome of patients with stable coronary artery disease but no ischemia‐inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all‐cause death, myocardial infarction, and any revascularization) after 5 years in 1122 patients without significant stenosis (all FFR >0.80; n=275) or with at least 1 significant stenosis successfully treated by percutaneous coronary intervention (ie, post–percutaneous coronary intervention FFR >0.80; n=847). The patients were stratified into low, mid, or high tertiles of global FFR (≤2.80, 2.80–2.88, and ≥2.88). Patients in the lowest tertile of global FFR showed the highest 5‐year MACE rate compared with those in the mid or high tertile of global FFR (27.5% versus 22.0% and 20.9%, respectively; log‐rank P =0.040). The higher 5‐year MACE rate was mainly driven by a higher rate of revascularization in the low global FFR group (16.4% versus 11.3% and 11.8%, respectively; log‐rank P =0.038). In a multivariable model, an increase in global FFR of 0.1 unit was associated with a significant reduction in the rates of MACE (hazard ratio [HR], 0.988; 95% CI, 0.977–0.998; P =0.023), myocardial infarction (HR, 0.982; 95% CI, 0.966–0.998; P =0.032), and revascularization (HR, 0.985; 95% CI, 0.972–0.999; P =0.040). Conclusions Even in the absence of ischemia‐producing stenoses, patients with a low global FFR, physiologic correlate of global atherosclerotic burden, present a higher risk of MACE at 5‐year follow‐up.

The aim of the present study was to examine the association of myocardial mass verified by computed tomography (CT) and invasive fractional flow reserve (FFR)—verified myocardial ischemia, or subsequent therapeutic strategy for the targeted vessels after FFR examination. We examined 333 vessels with intermediate stenoses in 297 patients (mean age 69.0 ± 9.5, 228 men) undergoing both coronary CT angiography and invasive FFR, and reviewed the therapeutic strategy after FFR. Of 333 vessels, FFR ≤ 0.80 was documented in 130 (39.0%). Myocardial volume supplied by the target vessel (MVT) was larger in those with FFR-verified ischemia than those without (53.4 ± 19.5 vs. 42.9 ± 22.2 cm3, P

Purpose Cardiac transplant-related arteriopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, vessel fractional flow reserve (vFFR) derived from coronary angiography has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease (CAD). Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic CAD, data on the use of vFFR in HTx recipients are lacking. The aim was to validate coronary angiogram-derived FFR to calculate FFR in HTx patients with and without cardiac transplant-related arteriopathy. Methods Prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/sec in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Results Overall, 13634 FFR values were extracted from the FFR pullback curves from 19 HTx patients. The mean age was 60.8 ± 9.10 years, the mean time after transplantation was 5.88 years [IQR 1.10, 12.0]. A total of 29 vessels (19 LAD, 6 LCX, 4 RCA) were analysed. Mean distal vFFR was 0.91 ± 0.05 whereas invasive distal FFR was 0.92 ± 0.07. A good correlation was found between invasive distal FFR and vFFR (r =0.635; p Conclusion In HTx patients coronary angiography-derived FFR correlates well with invasively measured wire-derived FFR. Angiography-derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy.

Coronary artery disease (CAD) remains the most common cardiovascular disease, accounting for 6% of all Emergency Department visits and 27% of all Emergency Department hospitalizations.1 Invasive coronary angiography with fractional flow reserve (FFR) remains the gold standard to assess for hemodynamically stenosis in CAD patients. However, for low- and intermediate-risk patients, noninvasive modalities have started to gain favor as patients with stable CAD who received optimal medical therapy did as well as patients who underwent percutaneous coronary intervention.2 This led to the incorporation of FFRCT. cCTA provides good spatial resolution for evaluating stenosis. FFR provides additional information regarding whether the stenosis is hemodynamically significant. FFR is the ratio of maximum blood flow in a stenotic artery to the maximum blood flow through that artery without stenosis.3 Computational fluid dynamics involved in FFRCT is based on Navier-Stokes equations, allowing the assessment of pressure and flow across coronary arteries. Limitations do exist with FFRCT which includes false-positive results due to step artifact and left ventricular hypertrophy, as well as manual segmentation and ostial stenosis, which can cause false-negative results. However, there are improvements on the horizon including artificial intelligence-driven computation of FFR and the utilization of virtual stenting for surgical planning. The purpose of this review is to describe the clinical validation, underlying mechanism, and implementation of FFRCT.

Objectives The aim of this study was to investigate the diagnostic abilities of both pericoronary adipose tissue (PCAT) CT attenuation and volume for the predication hemodynamic significance of coronary artery stenosis as evaluated by fractional flow reserve (FFR). Methods Patients with ≥ 30 % in at least 1 major epicardial coronary artery were retrospectively included. Furthermore, all eligible patients underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) as well as FFR within 1 month. PCAT CT attenuation and volume around ischemic and non-ischemic coronary stenosis were measured and compared. The diagnostic accuracy of PCAT CT attenuation and volume for the identification of hemodynamically significant stenosis was determined against the reference standard of FFR ≤ 0.80. Results A total of 61 patients (mean age, 57.8 years ± 11.8) with 77 vessels were included. Average PCAT CT attenuation of all vessels was -70.3 ± 7.4 HU. PCAT CT attenuation in coronary arteries with hemodynamically significant stenosis (FFR ≤ 0.80) (-65.6 ± 5.9 HU) was significantly higher than those with FFR > 0.80 (-75.3 ± 5.4 HU; p = 0.000). There was a strong correlation between FFR and PCAT CT attenuation (r = 0.64, p 0.80 (5.5 ± 3.7 cm3, p = 0.511). The diagnostic accuracy was significantly higher in the combination of CCTA and PCAT CT attenuation compared with CCTA alone (area under the curve: 0.869 vs. 0.569, p Conclusions PCAT CT attenuation but not volume was related to the hemodynamic significance of coronary artery stenosis. For the patients with suspected coronary artery disease, after adding of PCAT CT attenuation to CCTA, the diagnostic ability for the identification of ischemic coronary stenosis was significantly improved.

The presented clinical observation demonstrates the diagnostic capabilities of cardiac volumetric computed tomography (CT) with a pharmacological test by a vasodilator adenosine triphosphate (ATP) in the simultaneous assessment of coronary anatomy and changes in left ventricular myocardial perfusion (LV) in a patient with painless myocardial ischemia and coronary atherosclerosis. A 68-year-old patient with coronary heart disease (CHD) and atherosclerotic changes in the coronary arteries underwent cardiac volumetric CT in combination with a ATP pharmacological test. The study was performed on a Aquilion ONE 640 Vision Edition computer tomograph (Toshiba, Japan). Assessment of LV myocardial perfusion was carried out in comparison with other clinical, laboratory and instrumental examination methods. The results of clinical and instrumental examination of a patient with a low pre-test probability of coronary heart disease are presented. From the standpoint of modern recommendations on stable coronary heart disease, false-negative results of single-photon emission computed tomography of the heart and stress-echocardiography are discussed. Clinical observation demonstrates the feasibility of diagnosing LV myocardial ischemia by cardiac volumetric CT combined with ATP pharmacological test, confirmed by an invasive determination of the fractional flow reserve. The given clinical example represents the advantage of cardiac volumetric CT, combined with the ATP pharmacological test, as a method for visualizing LV myocardial perfusion in detecting myocardial ischemia.В клиническом наблюдении демонстрируются диагностические возможности объемной компьютерной томографии (КТ) сердца с фармакологической пробой вазодилататором аденозинтрифосфатом (АТФ) в одновременной оценке коронарной анатомии и изменений перфузии миокарда левого желудочка (ЛЖ) у пациентки с безболевой ишемией миокарда и атеросклерозом коронарных артерий. У пациентки 68 лет с ишемической болезнью сердца (ИБС), атеросклеротическими изменениями коронарных артерий проведена объемная КТ сердца в сочетании с фармакологической пробой АТФ. Исследование выполнено на компьютерном томографе Aquilion ONE 640 Vision Edition (Toshiba, Япония). Оценка перфузии миокарда ЛЖ осуществлялась в сопоставлении с другими клинико-лабораторными и инструментальными методами обследования. Представлены результаты клинико-инструментального обследования больной с низкой предтестовой вероятностью ИБС. С позиций современных рекомендаций по стабильной ИБС обсуждаются ложнонегативные результаты однофотонной эмиссионной КТ сердца и стресс-эхокардиографии. Клиническое наблюдение демонстрирует возможности диагностики ишемии миокарда ЛЖ методом объемной КТ сердца с фармакологической пробой АТФ, подтвержденной инвазивным определением фракционного резерва кровотока. Приведенный клинический пример представляет преимущество объемной КТ сердца, совмещенной с фармакологической пробой АТФ, как метода визуализации перфузии миокарда ЛЖ в выявлении ишемии миокарда.

AIMS The aim of this study was to investigate the diagnostic performance of quantitative flow ratio (QFR) in assessing the physiological relevance of coronary lesions in the presence of severe aortic valve stenosis (SAS). METHODS AND RESULTS A total of 115 SAS patients (138 coronary arteries) were included. Functional assessment of coronary stenoses was performed with fractional flow reserve (FFR) before transcatheter aortic valve implantation (TAVI). Subsequently, QFR was calculated at a central core laboratory, blinded to FFR results. The diagnostic yield of QFR was assessed using FFR as reference. Coronary stenoses were intermediate (diameter stenosis 48±10%, FFR 0.84 [0.77-0.89], QFR 0.82 [0.73-0.89]). Per-vessel sensitivity, specificity, area under the ROC curve and accuracy of QFR were 84% (95% CI: 71-92%), 80% (95% CI: 69-88%), 0.88 (95% CI: 0.82-0.93) and 81%, respectively. Diagnostic accuracy of QFR decreased significantly in patients with aortic valve area (AVA)

To investigate the effect of coronary calcification morphology and severity on the diagnostic performance of machine learning (ML)–based coronary CT angiography (CCTA)–derived fractional flow reserve (CT-FFR) with FFR as a reference standard. A total of 442 patients (61.2 ± 9.1 years, 70% men) with 544 vessels who underwent CCTA, ML-based CT-FFR, and invasive FFR from China multicenter CT-FFR study were enrolled. The effect of calcification arc, calcification remodeling index (CRI), and Agatston score (AS) on the diagnostic performance of CT-FFR was investigated. CT-FFR ≤ 0.80 and lumen reduction ≥ 50% determined by CCTA were identified as vessel-specific ischemia with invasive FFR as a reference standard. Compared with invasive FFR, ML-based CT-FFR yielded an overall sensitivity of 0.84, specificity of 0.94, and accuracy of 0.90 in a total of 344 calcification lesions. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of CT-FFR across different calcification arc, CRI, or AS levels. CT-FFR exhibited improved discrimination of ischemia compared with CCTA alone in lesions with mild-to-moderate calcification (AUC, 0.89 vs. 0.69, p < 0.001) and lesions with CRI ≥ 1 (AUC, 0.89 vs. 0.71, p < 0.001). The diagnostic accuracy and specificity of CT-FFR were higher than CCTA alone in patients and vessels with mid (100 to 299) or high (≥ 300) AS. Coronary calcification morphology and severity did not influence diagnostic performance of CT-FFR in ischemia detection, and CT-FFR showed marked improved discrimination of ischemia compared with CCTA alone in the setting of calcification. • CT-FFR provides superior diagnostic performance than CCTA alone regardless of coronary calcification. • No significant differences in the diagnostic performance of CT-FFR were observed in coronary arteries with different coronary calcification arcs and calcified remodeling indexes. • No significant differences in the diagnostic accuracy of CT-FFR were observed in coronary arteries with different coronary calcification score levels.

Background Congenital coronary-pulmonary fistulas (CPFs) are commonly unilateral; however, bilateral and multilateral fistulas are relatively rare. The steal phenomenon aroused from bilateral or multilateral CPFs, and was uncertain and seldom reported. We possess a new tool to assess the hemodynamic significance of coronary artery fistulas. This study aimed to describe the clinical presentation, diagnostic modalities, and management of the coincidentally detected congenital bilateral CPFs. Case presentation A case of a 52 year-old female with 10 years history of typical palpitations and chest tightness was presented. The selective coronary arteriography showed a right dominant coronary circulation without significant stenosis; however, with anomalous vessels originating from the proximal right and left anterior descending coronary arteries, draining into the pulmonary artery through a plexus of small vessels. We introduced the fractional flow reserve (FFR) to evaluate the hemodynamic significance of CPFs. The patient was successfully treated with coil embolization. Conclusions We presented the case of a female with typical palpitations and chest tightness due to the steal phenomenon that aroused from bilateral CPFs. The fistulas were safely and successfully closed by coil embolization. We showed a new tool for the sophisticated evaluation of the hemodynamic significance of CPFs using FFR measurement and temporary occlusion of the fistula with a standard balloon. FFR could be a promising means for the treatment of decision making of the CPFs.

Improvements in spatial and temporal resolution now permit robust high quality characterization of presence, morphology and composition of coronary atherosclerosis in computed tomography (CT). These characteristics include high risk features such as large plaque volume, low CT attenuation, napkin-ring sign, spotty calcification and positive remodeling. Because of the high image quality, principles of patient-specific computational fluid dynamics modeling of blood flow through the coronary arteries can now be applied to CT and allow the calculation of local lesion-specific hemodynamics such as endothelial shear stress, fractional flow reserve and axial plaque stress. This review examines recent advances in coronary CT image-based computational modeling and discusses the opportunity to identify lesions at risk for rupture much earlier than today through the combination of anatomic and hemodynamic information.

Recent efforts have demonstrated the ability of computational models to predict fractional flow reserve from coronary artery imaging without the need for invasive instrumentation. However, these models include only larger coronary arteries as smaller side branches cannot be resolved and are therefore neglected. The goal of this study was to evaluate the impact of neglecting the flow to these side branches when computing angiography-derived fractional flow reserve (vFFR) and indices of volumetric coronary artery blood flow. To compensate for the flow to side branches, a leakage function based upon vessel taper (Murray’s Law) was added to a previously developed computational model of coronary blood flow. The augmented model with a leakage function (1Dleaky) and the original model (1D) were then applied to predict FFR as well as inlet and outlet flow in 146 arteries from 80 patients who underwent invasive coronary angiography and FFR measurement. The results show that the leakage function did not significantly change the vFFR but did significantly impact the estimated volumetric flow rate and predicted coronary flow reserve. As both procedures achieved similar predictive accuracy of vFFR despite large differences in coronary blood flow, these results suggest careful consideration of the application of this index for quantitatively assessing flow. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Atherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity. Objectives: This study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively. Methods: Two hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR. Results: Atherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively). Conclusions: PR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity.