Optimized interpretation of fractional flow reserve derived from computed tomography: Comparison of three interpretation methods

BackgroundAn optimal system for interpreting fractional flow reserve (FFR) values derived from CT (FFRCT) is lacking. We sought to evaluate performance of three FFR_CT measurements in detecting ischemia by comparing them with invasive FFR.MethodsFor 73 vessels in 50 patients who underwent coronary CT angiography (CCTA) and FFR_CT analysis followed by invasive FFR, the greatest diameter stenosis on CCTA, FFR_CT difference between distal and proximal to the stenosis (ΔFFR_CT), FFR_CT 2 cm distal to the stenosis (lesion-specific FFR_CT), and the lowest FFR_CT in distal vessel tip were calculated. Significant obstruction (≥50% diameter stenosis) and ischemia (lesion-specific FFR_CT ≤0.80, the lowest FFR_CT ≤0.80, or ΔFFR_CT ≥0.12 based on the greatest Youden index) were compared with invasive FFR (≤0.80).ResultsForty (55%) vessels demonstrated ischemia during invasive FFR. On multivariable generalized estimating equations, ΔFFR_CT (odds ratio [OR] 10.2, p < 0.01) remained a predictor of ischemia over CCTA (OR 2.9), lesion-specific FFR_CT (OR 3.1), and the lowest FFR_CT (OR 0.9) (p > 0.05 for all). Area under the curve (AUC) of ΔFFR_CT (0.86) was higher than CCTA (0.66), lesion-specific FFR_CT (0.71), and the lowest FFR_CT (0.65) (p < 0.01 for all). Addition of each FFR_CT measure to CCTA showed improvement of AUC and significant net reclassification improvement (NRI): ΔFFR_CT (AUC 0.84, NRI 1.24); lesion-specific FFR_CT (AUC 0.77, NRI 0.83); and the lowest FFR_CT (AUC 0.76, NRI 0.59) (p < 0.01 for all).ConclusionsCompared with diameter stenosis, ΔFFR_CT, lesion-specific FFR_CT, and the lowest FFR_CT improved ischemia discrimination and reclassification, with ΔFFR_CT being superior in identifying and discriminating ischemia.     

Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry

BackgroundThe 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.ObjectivesTo investigate the incremental value of ΔFFR_CT in predicting early revascularization and improving efficiency of catheter laboratory utilization.MaterialsPatients 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.ResultsOf 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%.ConclusionsΔFFR_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.     

Prognostic value of computed tomography derived fractional flow reserve for predicting cardiac events and mortality in kidney transplant candidates

BackgroundCardiac screening using coronary computed tomography angiography (CCTA) in kidney transplant candidates before transplantation yields both diagnostic and prognostic information. Whether CT-derived fractional flow reserve (FFRCT) analysis provides prognostic information is unknown.This study aimed to assess the prognostic value of FFR_CT for predicting major adverse cardiac events (MACE) and all-cause mortality in kidney transplant candidates.MethodsAmong 553 consecutive kidney transplant candidates, 340 CCTA scans (61%) were evaluated with FFR_CT analysis. Patients were categorized into groups based on lowest distal FFR_CT; normal >0.80, intermediate 0.80–0.76, and low ≤0.75. In patients with ≥50% stenosis, a lesion-specific FFR_CT was defined as; normal >0.80 and abnormal ≤0.80.The primary endpoint was MACE (cardiac death, resuscitated cardiac arrest, myocardial infarction or revascularization). The secondary endpoint was all-cause mortality.ResultsMedian follow-up was 3.3 years [2.0–5.1]. MACE occurred in 28 patients (8.2%), 29 patients (8.5%) died.When adjusting for risk factors and transplantation during follow-up, MACE occurred more frequently in patients with distal FFR_CT ≤0.75 compared to patients with distal FFR_CT >0.80: Hazard Ratio (HR): 3.8 (95%CI: 1.5–9.7), p ?< ?0.01.In the lesion-specific analysis with <50% stenosis as reference, patients with lesion-specific FFR_CT >0.80 had a HR for MACE of 1.5 (95%CI: 0.4–4.8), p ?= ?0.55 while patients with lesion-specific FFR_CT ≤0.80 had a HR of 6.0 (95%CI: 2.5–14.4), p ?< ?0.01.Abnormal FFR_CT values were not associated with increased mortality.ConclusionIn kidney transplant candidates, abnormal FFR_CT values were associated with increased MACE but not mortality. Use of FFR_CT may improve cardiac evaluation prior to transplantation.     

The clinical utility of FFRCT stratified by age

BackgroundCT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFR_CT) is a safe alternative to invasive coronary angiography. A negative FFR_CT has been shown to have low cardiac event rates compared to those with a positive FFR_CT. However, the clinical utility of FFR_CT according to age is not known.MethodsPatients’ in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those ≥65 or <65 years of age. The impact of FFR_CT on clinical decision-making, as assessed by patient age, was determined by evaluating patient management using CTA results alone, followed by site investigators submitting a report on the treatment plan based upon the newly provided FFR_CT data. Outcomes at 1-year post CTA were assessed, including major adverse cardiovascular events (myocardial infarction, all-cause mortality or unplanned hospitalization for ACS leading to revascularisation) and total revascularisation. Positive FFR_CT was deemed to be ?≤ ?0.8.ResultsFFR_CT was calculated in 1849 (40.6%) subjects aged <65 and 2704 (59.4%) ?≥ ?65 years of age. Subjects ≥65 years were more likely to have anatomic obstructive disease on CTA (≥50% stenosis), compared to those aged <65 (69.7% and 73.2% respectively, p ?= ?0.008). There was a similar graded increase in recommended and actual revascularisation with either CABG or PCI, with declining FFR_CT strata for subjects above and below the age of 65. MACE and revascularisation rates were not significantly different for those ?≥ ?or <65, regardless of FFR_CT positivity or stenosis severity <50% or ≥50%. With a negative FFR_CT result, and anatomical stenosis ≥50%, those ?≥ ?and <65 years of age, had similar rates of MACE (0.2% for both, p ?= ?0.1) and revascularisation (8.7% and 10.4% respectively p ?= ?0.4).Logistic regression analysis, with age as a continuous variable, and adjustment for Diamond Forrester Risk, baseline FFR_CT and treatment (CABG, PCI, medical therapy), indicated a statistically significant, but small increase in the odds of a MACE event with increasing age (OR 1.04, 95% CI 1.006–1.08, p ?= ?0.02). Amongst patients with a FFR_CT > 0.80, there was no effect of age on the odds of revascularisation.ConclusionThe findings of this study point to a low risk of MACE events or need for revascularisation in those aged ?≥ ?or <65 with a FFR_CT>0.80, despite the higher incidence of anatomic obstructive CAD in those ≥65 years. The findings show the clinical usefulness and outcomes of FFR_CT are largely constant regardless of age.     

Temporal changes in FFRCT-Guided Management of Coronary Artery Disease – Lessons from the ADVANCE Registry

BackgroundThe ADVANCE registry is a large prospective study of outcomes and resource utilization in patients undergoing coronary computed tomography angiography (CCTA) and CT-based fractional flow reserve (FFR_CT). As experience with new technologies and practices develops over time, we investigated temporal changes in the use of FFR_CT within the ADVANCE registry.Methods5083 patients with coronary artery disease (CAD) on CCTA were prospectively enrolled in the ADVANCE registry and were divided into 3 equally sized cohorts based on the temporal order of enrollment per site. Demographics, CCTA and FFR_CT findings, and clinical outcomes through 1-year follow-up, were recorded and compared between tertiles.ResultsThe number of patients with a ≥70% stenosis on CCTA was similar over time (33.6%, 30.9%, and 33.8% for cohort 1–3). The rate of positive FFR_CT ≤0.80 was higher for cohorts 2 (67.3%) and 3 (74.6%) than for cohort 1 (57.1%, p < 0.001). Invasive FFR rates decreased from 25.8% to 22.4% between cohort 1 and 3 (p = 0.023). Moreover, patients with a FFR_CT ≤0.80 were less frequently referred for invasive coronary angiography (ICA) (from 62.9% to 52.9%, p < 0.001), and underwent fewer revascularizations between cohort 1 and 3 (from 41.9% to 32.0%, p < 0.001). The prevalence of major events was low (1.2%) and similar between cohorts.ConclusionsGrowing experience with FFR_CT improved the likelihood of identifying hemodynamically significant CAD and safely reduced the need for ICA and revascularization in patients with anatomically significant disease even in the instance of an abnormal FFR_CT.     

Diagnostic value of comprehensive on-site and off-site coronary CT angiography for identifying hemodynamically obstructive coronary artery disease

BackgroundThis 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.MethodsProspectively 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.ResultsIn 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/MLA² 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/MLA² 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).ConclusionsIn 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.     

Diagnostic concordance and discordance between angiography-based quantitative flow ratio and fractional flow reserve derived from computed tomography in complex coronary artery disease

BackgroundBoth quantitative flow ratio (QFR) and fractional flow reserve derived from computed tomography (FFR_CT) have shown significant correlations with invasive wire-based fractional flow reserve. However, the correlation between QFR and FFR_CT is not fully investigated in patients with complex coronary artery disease (CAD). The aim of this study is to investigate the correlation and agreement between QFR and FFR_CT in patients with de novo three-vessel disease and/or left main CAD.MethodsThis is a post-hoc sub-analysis of the international, multicenter, and randomized SYNTAX III REVOLUTION trial, in which both invasive coronary angiography and coronary computed tomography angiography were prospectively obtained prior to the heart team discussion. QFR was performed in an independent core laboratory and compared with FFR_CT analyzed by HeartFlow?. The correlation and agreement between QFR and FFR_CT were assessed per vessel. Furthermore, independent factors of diagnostic discordance between QFR and FFR_CT were evaluated.ResultsOut of 223 patients, 40 patients were excluded from this analysis due to the unavailability of FFR_CT and/or QFR, and a total of 469 vessels (183 patients) were analyzed. There was a strong correlation between QFR and FFR_CT (R ?= ?0.759; p ?< ?0.001), and the Bland-Altman analysis demonstrated a mean difference of ?0.005 and a standard deviation of 0.116. An independent predictor of diagnostic concordance between QFR and FFR_CT was the lesion location in right coronary artery (RCA) (odds ratio 0.395; 95% confidence interval 0.174–0.894; P ?= ?0.026).ConclusionIn patients with complex CAD, QFR and FFR_CT were strongly correlated. The location of the lesion in RCA was associated with the highest diagnostic concordance between QFR and FFR_CT.     

Coronary CT-based FFR in patients with acute myocardial infarction might predict follow-up invasive FFR: The XPECT-MI study

BackgroundWe aimed to evaluate whether invasive fractional flow reserve (FFRi) of non-infarction related (non-IRA) lesions changes over time in ST-elevation myocardial infarction (STEMI) patients. Moreover, we assessed the diagnostic performance of coronary CT angiography-derived FFR(FFR_CT) following the index event in predicting follow-up FFRi.MethodsWe prospectively enrolled 38 STEMI patients (mean age 61.6 ​± ​9 years, 23.1% female) who underwent non-IRA baseline and follow-up FFRi measurements and a baseline FFR_CT (within ≤10 days after STEMI). Follow-up FFRi was performed at 45–60 days (FFRi and FFR_CT value of ≤0.8 was considered positive).ResultsFFRi values showed significant difference between baseline and follow-up (median and interquartile range (IQR) 0.85 [0.78–0.92] vs. 0.81 [0.73–0.90] p ​= ​0.04, respectively). Median FFR_CT was 0.81 [0.68–0.93]. In total, 20 lesions were positive on FFR_CT. A stronger correlation and smaller bias were found between FFR_CT and follow-up FFRi (ρ ​= ​0.86,p ​< ​0.001,bias:0.01) as compared with baseline FFRi (ρ ​= ​0.68, p ​< ​0.001,bias:0.04). Comparing follow-up FFRi and FFR_CT, no false negatives but two false positive cases were found. The overall accuracy was 94.7%, with sensitivity and specificity of 100.0% and 90.0% for identifying lesions ≤0.8 on FFRi. Accuracy, sensitivity, and specificity were 81.5%, 93.3%, and 73.9%, respectively, for identifying significant lesions on baseline FFRi using index FFR_CT.ConclusionFFR_CT in STEMI patients close to the index event could identify hemodynamically relevant non-IRA lesions with higher accuracy than FFRi measured at the index PCI, using follow-up FFRi as the reference standard. Early FFR_CT in STEMI patients might represent a new application for cardiac CT to improve the identification of patients who benefit most from staged non-IRA revascularization.     

Non-invasive fractional flow reserve in vessels without severe obstructive stenosis is associated with coronary plaque burden

AimsNon-invasive fractional flow reserve derived from coronary CT angiography (FFR_CT) 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 FFR_CT in the absence of a discrete obstructive lesion. Using quantitative plaque analysis, we sought to determine the relationship between an abnormal whole vessel FFR_CT (V-FFR_CT) and quantitative measures of whole vessel atherosclerosis in coronary arteries without obstructive stenosis.MethodsFFR_CT 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-FFR_CT was defined as a minimum value of ≤0.75 across the vessel (at the most distal region where FFR_CT was computed).ResultsVessels with abnormal V-FFR_CT 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-FFR_CT (median, p < 0.05 for all). Using a multivariate analysis to adjust for CDD and %DS, all measures of plaque volume were predictive of abnormal V-FFR_CT (OR 2.09, 1.36, 1.95, 1.95 for TP, CP, NCP and LD-NCP volume, respectively; p < 0.05 for all).ConclusionAbnormal V-FFR_CT in vessels without obstructive stenosis is associated with multiple markers of diffuse non-obstructive atherosclerosis, independent of stenosis severity. Whole vessel FFR_CT may represent a novel measure of diffuse coronary plaque burden.     

Incidence and predictors of lesion-specific ischemia by FFRCT: Learnings from the international ADVANCE registry

BackgroundTo date, the clinical utility of coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT) has been limited to trials and single center experiences. We herein report the incidence of abnormal FFRCT (≤0.80) and the relationship of lesion-specific ischemia to subject demographics, symptoms, and degree of stenosis in the multicenter, prospective ADVANCE registry.MethodsOne thousand patients with suspected angina having documented coronary artery disease on coronary CTA and clinically referred for FFRCT were prospectively enrolled in the registry. Patient demographics, symptom status, coronary CTA and FFRCT findings were recorded. Univariate and multivariate analyses were performed to investigate the predictors related to abnormal FFR_CT.ResultsFFR_CT data were analyzed in 952 patients (95.2%). Overall, 51.1% patients had a positive FFR_CT value (≤0.80). Patients with ≥3 risk factors had a significantly higher rate of abnormal FFR_CT than those with <3 risk factors (60.2% vs. 43.9%, p = 0.0001). On multivariate analysis, baseline diabetes (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.04–2.21, p = 0.030) and hypertension (OR 1.56, 95%CI 1.14–2.14, p = 0.005) were both predictive of abnormal FFR_CT. In addition, >70% stenosis was significantly associated with low FFR_CT (OR 31.16, 95%CI 12.25–79.22, p < 0.0001) vs. <30% stenosis. Notably, stenosis 30–49% vs. <30% had an increased likelihood of ischemia (OR 3.74, 95%CI 1.52–9.17, p < 0.0001).ConclusionsIn this real-world registry, CT angiographic stenosis severity in addition to baseline cardiovascular risk factors conferred an increased likelihood of an abnormal FFR_CT. Importantly, however, mild CT angiographic stenoses were noted to have an increased hazard for ischemia and the converse holding true for more severe stenoses as well.     

Non-invasive fractional flow reserve derived from coronary computed tomography angiography in patients with acute chest pain: Subgroup analysis of the ROMICAT II trial

BackgroundNon-invasive fractional flow reserve (FFR_CT) derived from coronary computed tomography angiography (CTA) permits hemodynamic evaluation of coronary stenosis and may improve efficiency of assessment in stable chest pain patients. We determined feasibility of FFR_CT in the population of acute chest pain patients and assessed the relationship of FFR_CT with outcomes of acute coronary syndrome (ACS) and revascularization and with plaque characteristics.MethodsWe included 68 patients (mean age 55.8 ± 8.4 years, 71% men) from the ROMICAT II trial who had ≥50% stenosis on coronary CTA or underwent additional non-invasive stress test. We evaluated coronary stenosis and high-risk plaque on coronary CTA. FFR_CT was measured in a core laboratory.ResultsWe found correlation between anatomic severity of stenosis and FFR_CT ≤0.80 vs. FFR_CT >0.80 (severe stenosis 84.8% vs. 15.2%; moderate stenosis 33.3% vs. 66.7%; mild stenosis 33.3% vs. 66.7% patients). Patients with severe stenosis had lower FFR_CT values (median 0.64, 25th-75th percentile 0.50–0.75) as compared to patients with moderate (median 0.84, 25th-75th percentile, p < 0.001) or mild stenosis (median 0.86, 25th-75th percentile 0.78–0.88, p < 0.001). The relative risk of ACS and revascularization in patients with positive FFR_CT ≤0.80 was 4.03 (95% CI 1.56–10.36) and 3.50 (95% CI 1.12–10.96), respectively. FFR_CT ≤0.80 was associated with the presence of high-risk plaque (odds ratio 3.91, 95% CI 1.55–9.85, p = 0.004) after adjustment for stenosis severity.ConclusionAbnormal FFR_CT was associated with the presence of ACS, coronary revascularization, and high-risk plaque. FFR_CT measurements correlated with anatomic severity of stenosis on coronary CTA and were feasible in population of patients with acute chest pain.     

Fractional flow reserve derived from coronary CT angiography: Variation of repeated analyses

BackgroundFractional flow reserve (FFR) is the standard of reference for assessing the hemodynamic significance of coronary stenoses in patients with stable coronary artery disease. Noninvasive FFR derived from coronary CT angiography (FFR_CT) is a promising new noninvasive method for assessing the physiologic significance of epicardial stenoses. The reproducibility of FFR_CT has not yet been established.ObjectiveThe aim of this study was to evaluate the variation of repeated analyses of FFR_CT per se and in the context of the reproducibility of repeated FFR measurements.MethodsCoronary CT angiography and invasive coronary angiography with repeated FFR measurements were performed in 28 patients (58 vessels) with suspected stable coronary artery disease. Based on the coronary CT angiography data set, FFR_CT analyses were performed twice by 2 independent blinded analysts.ResultsIn 12 of 58 (21%) vessels FFR was ≤0.80. The standard deviation for the difference between first and second FFR_CT analyses was 0.034 vs 0.033 for FFR repeated measurements (P = .722). Limits of agreement were −0.06 to 0.08 for FFR_CT and −0.07 to 0.06 for FFR. The coefficient of variation of FFR_CT (CV_FFRct) was 3.4% (95% confidence interval [CI], 1.4%–4.6%) vs 2.7% (95% CI, 1.8%–3.3%) for FFR. In vessels with mean FFR ranging between 0.70 and 0.90 (n = 25), the difference between the first and second FFR_CT analyses was 0.035 and FFR repeated measurements was 0.043 (P = .357), whereas CV_FFRct was 3.3% (95% CI, 1.5%–4.3%) and coefficient of variation for FFR was 3.6% (95% CI, 2.3%–4.6%).ConclusionsThe reproducibility of both repeated FFR_CT analyses and repeated FFR measurements is high.     

Rationale and design of the HeartFlowNXT (HeartFlow analysis of coronary blood flow using CT angiography: NeXt sTeps) study

IntroductionCoronary CT angiography (CTA) is an established noninvasive method for visualization of coronary artery disease. However, coronary CTA lacks physiological information; thus, it does not permit differentiation of ischemia-causing lesions. Recent advances in computational fluid dynamic techniques applied to standard coronary CTA images allow for computation of fractional flow reserve (FFR), a measure of lesion-specific ischemia. The diagnostic performance of computed FFR (FFR_CT) compared with invasively measured FFR is not yet fully established.Methods/DesignHeartFlowNXT (HeartFlow analysis of coronary blood flow using coronary CT angiography: NeXt sTeps) is a prospective, international, multicenter study designed to evaluate the diagnostic performance of FFR_CT for the detection and exclusion of flow-limiting obstructive coronary stenoses, as defined by invasively measured FFR as the reference standard. FFR values ≤0.80 will be considered to be ischemia causing. All subjects (N = 270; 10 investigative sites) will undergo coronary CTA (single- or dual-source CT scanners with a minimum of 64 slices) and invasive coronary angiography with FFR. Patients with insufficient quality of coronary CTA will be excluded. Blinded core laboratory interpretation will be performed for FFR_CT, invasive coronary angiography, and FFR. Stenosis severity by coronary CTA will be evaluated by the investigative site in addition to a blinded core laboratory interpretation. The primary objective of the study is to determine the diagnostic performance of FFR_CT compared with coronary CTA alone to noninvasively determine the presence of hemodynamically significant coronary lesions. The secondary end point comprises assessment of diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR_CT.     

Non obstructive high-risk plaque but not calcified by coronary CTA,and the G-score predict ischemia

BackgroundThe association of plaque morphology with ischemia in non-obstructive lesions has not been fully eludicated: Calcium density and high-risk plaque features have not been explored.Objectives: to assess whether high-risk plaque or calcified, and global mixed including non-calcified plaque burden (G-score) by coronary CTA predict ischemia in non-obstructive lesions using non-invasive fractional flow reserve (FFR_CT).MethodsIn 106 patients with low-to-intermediate pre-test probability referred to coronary 128-slice dual source CTA, lesion-based and distal FFR_CT were computated.The 4 high-risk-plaque criteria: Low-attenuation-plaque, Napkin Ring Sign, positive remodelling and spotty calcification were recorded. Plaque density (HU) and stenosis (MLA,MLD,%area,%diameter stenosis) were quantified. Plaque composition was classified as type 1–4:1 = calcified, 2 = mixed (calcified > non-calcified), 3 = mixed (non-calcified > calcified), 4 = non-calcified, and expressed by the G-score: Z = Sum of type 1–4 per segment. The total plaque segment involvement score (SIS) and the Coronary Calcium Score (Agatston) were calculated.Results89 non–obstructive lesions were included. Both lesion-based and distal FFR_CT were lower in high-risk-plaque as compared to calcified (0.85 vs 0.93, p < 0.001 and 0.79 vs 0.86, p = 0.002). The prevalence of lesion-based ischemia (FFR_CT<0.8) was higher in high-risk-plaque as compared to calcified (25% vs. 2.5%, p = 0.007). Similarly, the rate of distal ischemia (40% vs 17.5%) was higher, respectively.Lower plaque density (HU) indicating higher lipid plaque component (p = 0.024) predicted lesion based FFR_CT in low attenuation plaque. For all lesions (n = 89) including calcified (p = 0.003), the correlation enhanced.Positive remodelling and an increasing non-calcified plaque burden (G-score) in relation to calcified were associated with lower FFR_CT distal (p = 0.042), but not the SIS and calcium score.ConclusionHigh-risk-plaque but not calcified, an increasing lipid-necrotic-core component and non-calcified mixed plaque burden (G-score) predict ischemia in non-obstructive lesions (INOCA), while an increasing calcium compactness acts contrary.     

Assessment of lesion-specific ischemia using fractional flow reserve (FFR) profiles derived from coronary computed tomography angiography (FFRCT) and invasive pressure measurements (FFRINV): Importance of the site of measurement and implications for patient referral for invasive coronary angiography and percutaneous coronary intervention

BackgroundFractional flow reserve (FFR)-derived from computed tomography angiography (CTA; FFRCT) and invasive FFR (FFRINV) are used to assess the need for invasive coronary angiography (ICA) and percutaneous coronary intervention (PCI). The optimal location for measuring FFR and the impact of measurement location have not been well defined.Methods930 patients (age 60.7 + 10 years, 59% male) were included in this study. Normal and diseased coronary arteries were classified into stenosis grades 0–4 in the left anterior descending artery (LAD, n = 518), left circumflex (LCX, n = 112) and right coronary artery (RCA, n = 585). FFRCT (n = 1215 arteries) and FFRINV (n = 26 LAD) profiles were developed by plotting FFR values (y-axis) versus site of measurement (x-axis: ostium, proximal, mid, distal segments). The best location to measure FFR was defined relative to the distal end of the stenosis. FFR ≤0.8 was considered positive for ischemia.ResultsIn normal and stenotic coronary arteries there are significant declines in FFRCT and FFRINV from the ostium to the distal vessel (p < 0.001), due to lesion-specific ischemia and to effects unrelated to the lesion. A reliable location (distal to the stenosis) is 10.5 mm [IQR 7.3–14.8 mm] for FFRCT and within 20–30 mm for FFRINV. Rates of positive FFR (from the distal vessel) reclassified to negative FFR (distal to the stenosis) are 61% (FFRCT) and 33% (FFRINV).ConclusionFFRCT and FFRINV values are influenced by stenosis severity and the site of measurement. FFR measurements from the distal vessel may over-estimate lesion-specific ischemia and result in unnecessary referrals for ICA and PCI.     

Ethnic differences in coronary anatomy,left ventricular mass and CT-derived fractional flow reserve

BackgroundStudies have observed higher incidence of cardiovascular mortality in South Asians (SA), and lower prevalence in East Asians (EA), compared with Caucasians. These observations are not entirely explained by ethnic differences in cardiovascular risk factors and mechanistic factors such as variations in cardiac anatomy and physiology may play a role. This study compared ethnic differences in CT-assessed left ventricular (LV) mass, coronary anatomy and non-invasive fractional flow reserve (FFRCT).MethodsThree-hundred symptomatic patients (age 59 ± 7.9, male 51%) underwent clinically-mandated CT-coronary-angiography (CTA) were matched for age, gender, BMI and diabetes (100 each ethnicity). Assessment of coronary stenosis, luminal dimensions and vessel dominance was performed by independent observers. LV mass, coronary luminal volume and FFRCT were quantified by blinded core-laboratory. A sub-analysis was performed on patients (n = 187) with normal/minimal disease (0–25% stenosis).ResultsStenosis severity was comparable across ethnic groups. EA demonstrated less left-dominant circulation (2%) compared with SA (8.2%) and Caucasians (10.1%). SA compared with EA and Caucasians demonstrated smallest indexed LV mass, coronary luminal volumes and dimensions. EA compared with Caucasians had comparable indexed LV mass, coronary luminal dimensions and highest luminal volumes. The latter was driven by higher prevalence of right-dominance including larger and longer right posterior left ventricular artery. FFR_CT in the left anterior descending artery (LAD) was lowest in SA (0.87) compared with EA (0.89; P = 0.009) and Caucasians (0.89; P < 0.001), with no difference in other vessels. All observed differences were consistent in patients with minimal disease.ConclusionThis single-centre study identified significant ethnic differences in CT-assessed LV mass, coronary anatomy and LAD FFR_CT. These hypotheses generating results may provide a mechanistic explanation for ethnic differences in cardiovascular outcomes and require validation in larger cohorts.     

Evaluation of epicardial coronary resistance using computed tomography angiography: A Proof of Concept

AimsFractional flow reserve (FFR) pullback allows to assess the distribution of pressure loss along the coronary vessels. FFR derived from CT (FFRCT) provides a virtual pullback curve that may also aid in the assessment of the distribution of epicardial coronary resistance in the non-invasive setting. The present study aims to determine the accuracy of the virtual FFR_CT pullback curve using a motorized invasive FFR pullback as reference in patients with stable coronary artery disease.Methods and resultsFFR values were extracted from coronary vessels at approximately 1 mm to generate pullback curves. Invasive motorized FFR pullbacks were acquired using a dedicated device at a speed of 1 mm/s. A total of 3172 matched FFR_CT and FFR values were obtained in 24 vessels. The correlation coefficient between FFR_CT and FFR was 0.76 (95%CI 0.75 to 0.78; p < 0.001). The area under the pullback curve was similar between FFR_CT and invasive FFR (79.0 ± 16.1 vs. 85.3 ± 16.4, p = 0.097). The mean difference in lesion gradient between FFR_CT and FFR was −0.07 (LOA -0.26 to 0.13) whereas in non-obstructive segments was −0.01 (LOA -0.06 to 0.05).ConclusionThe evaluation of epicardial coronary resistance using coronary CT angiography with FFR_CT was feasible. FFR_CT virtual pullback appears to be accurate for the evaluation of pressure gradients. FFR_CT has the potential to identify the pathophysiological pattern of coronary artery disease in the non-invasive setting.     

Value of semiquantitative assessment of high-risk plaque features on coronary CT angiography over stenosis in selection of studies for FFRct

IntroductionThe degree of stenosis on coronary CT angiography (CCTA) guides referral for CT-derived flow reserve (FFRct). We sought to assess whether semiquantitative assessment of high-risk plaque (HRP) features on CCTA improves selection of studies for FFRct over stenosis assessment alone.MethodsPer-vessel FFRct was computed in 1,395 vessels of 836 patients undergoing CCTA with 25–99% maximal stenosis. By consensus analysis, stenosis severity was graded as 25–49%, 50–69%, 70–89%, and 90–99%. HRPs including low attenuation plaque (LAP), positive remodeling (PR), and spotty calcification (SC) were assessed in lesions with maximal stenosis. Lesion FFRct was measured distal to the lesion with maximal stenosis, and FFRct<0.80 was defined as abnormal. Association of HRP and abnormal lesion FFRct was evaluated by univariable and multivariable logistic regression models.ResultsThe frequency of abnormal lesion FFRct increased with increase of stenosis severity across each stenosis category (25–49%:6%; 50–69%:30%; 70–89%:54%; 90–99%:91%, p ?< ?0.001). Univariable analysis demonstrated that stenosis severity, LAP, and PR were predictive of abnormal lesion FFRct, while SC was not. In multivariable analyses considering stenosis severity, presence of PR, LAP, and PR and/or LAP were independently associated with abnormal FFRct: Odds ratio 1.58, 1.68, and 1.53, respectively (p ?< ?0.02 for all). The presence of PR and/or LAP increased the frequency of abnormal FFRct with mild stenosis (p ?< ?0.05) with a similar trend with 70–89% stenosis. The combination of 2 HRP (LAP and PR) identified more lesions with FFR < 0.80 than only 1 HRP.ConclusionsSemiquantitative visual assessment of high-risk plaque features may improve the selection of studies for FFRct.     

Implications of computed tomography reconstruction algorithms on coronary atheroma quantification: Comparison with intravascular ultrasound

BackgroundAdvances in coronary computed tomography angiography (CCTA) reconstruction algorithms are expected to enhance the accuracy of CCTA plaque quantification. We aim to evaluate different CCTA reconstruction approaches in assessing vessel characteristics in coronary atheroma using intravascular ultrasound (IVUS) as the reference standard.MethodsMatched cross-sections (n ?= ?7241) from 50 vessels in 15 participants with chronic coronary syndrome who prospectively underwent CCTA and 3-vessel near-infrared spectroscopy-IVUS were included. Twelve CCTA datasets per patient were reconstructed using two different kernels, two slice thicknesses (0.75 ?mm and 0.50 ?mm) and three different strengths of advanced model-based iterative reconstruction (IR) algorithms. Lumen and vessel wall borders were manually annotated in every IVUS and CCTA cross-section which were co-registered using dedicated software. Image quality was sub-optimal in the reconstructions with a sharper kernel, so these were excluded. Intraclass correlation coefficient (ICC) and repeatability coefficient (RC) were used to compare the estimations of the 6 CT reconstruction approaches with those derived by IVUS.ResultsSegment-level analysis showed good agreement between CCTA and IVUS for assessing atheroma volume with approach 0.50/5 (slice thickness 0.50 ?mm and highest strength 5 ADMIRE IR) being the best (total atheroma volume ICC: 0.91, RC: 0.67, p ?< ?0.001 and percentage atheroma volume ICC: 0.64, RC: 14.06, p ?< ?0.001). At lesion-level, there was no difference between the CCTA reconstructions for detecting plaques (accuracy range: 0.64–0.67; p ?= ?0.23); however, approach 0.50/5 was superior in assessing IVUS-derived lesion characteristics associated with plaque vulnerability (minimum lumen area ICC: 0.64, RC: 1.31, p ?< ?0.001 and plaque burden ICC: 0.45, RC: 32.0, p ?< ?0.001).ConclusionCCTA reconstruction with thinner slice thickness, smooth kernel and highest strength advanced IR enabled more accurate quantification of the lumen and plaque at a segment-, and lesion-level analysis in coronary atheroma when validated against intravascular ultrasound. Clinicaltrials.gov (NCT03556644)     

Randomized comparison of chest pain evaluation with FFRCT or standard care: Factors determining US costs

BackgroundFFR_CT assesses the functional significance of lesions seen on CTCA, and may be a more efficient approach to chest pain evaluation. The FORECAST randomized trial found no significant difference in costs within the UK National Health Service, but implications for US costs are unknown. The purpose of this study was to compare costs in the FORECAST trial based on US healthcare cost weights, and to evaluate factors affecting costs.MethodsPatients with stable chest pain were randomized either to the experimental strategy (CTCA with selective FFR_CT), or to standard clinical pathways. Pre-randomization, the treating clinician declared the planned initial test. The primary outcome was nine-month cardiovascular care costs.ResultsPlanned initial tests were CTCA in 912 patients (65%), stress testing in 393 (28%), and invasive angiography in 94 (7%). Mean US costs did not differ overall between the experimental strategy and standard care (cost difference +7% (+$324), CI ?12% to +26%, p ?= ?0.49). Costs were 4% lower with the experimental strategy in the planned invasive angiography stratum (p for interaction ?= ?0.66). Baseline factors independently associated with costs were older age (+43%), male sex (+55%), diabetes (+37%), hypertension (+61%), hyperlipidemia (+94%), prior angina (+24%), and planned invasive angiography (+160%). Post-randomization cost drivers were coronary revascularization (+348%), invasive angiography (267%), and number of tests (+35%).ConclusionsInitial evaluation of chest pain using CTCA with FFR_CT had similar US costs as standard care pathways. Costs were increased by baseline coronary risk factors and planned invasive angiography, and post-randomization invasive procedures and the number of tests.Registration at ClinicalTrials.gov (NCT03187639).