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).     

Influence of operator expertise and coronary luminal segmentation technique on diagnostic performance,precision and reproducibility of reduced-order CT-derived fractional flow reserve technique

BackgroundOnsite workstation-based CT-derived Fractional-Flow-Reserve (CT-FFR) is accurate in assessing hemodynamic-significance of coronary stenoses. We aim to describe the influence of operator expertise and luminal-segmentation technique on the diagnostic performance, precision and reproducibility of CT-FFR in identifying hemodynamically-significant stenosis (FFR≤0.8).MethodsForty-eight consecutive stable-patients (86 vessels) with suspected CAD underwent research indicated invasive-FFR and 320-detector CT-coronary-angiography (CTA). CT-FFR was derived using reduced-order model on standard desktop-computer. Semi-automated coronary luminal segmentation was performed using focused-technique with manual adjustments at regions of stenosis and calcification or comprehensive-technique with manual adjustments along the entire course of the vessel. CT-FFR analysis was performed using 3 blinded operators; core-laboratory engineer using focused-technique and radiographer and cardiologist using the comprehensive-technique. Diagnostic performance was assessed by area under receiver-operating-curve (AUC). Precision with invasive FFR was determined by Bland-Altman analysis, and reproducibility by intraclass-correlation-coefficient (ICC).ResultsDiagnostic performance was comparable among operators (Engineer: AUC = 0.88, Radiographer 0.84; Cardiologist 0.87; P = 0.59). Coronary luminal-segmentation time was shortest using focused technique (engineer 6:17 ± 2.43 min), compared with comprehensive technique (cardiologist 14.83 ± 7.09, radiographer 24.74 ± 12.65; P < 0.001). Use of focused technique was associated with widest limits of agreement (LOA) with FFR and moderate intra-operator reproducibility (engineer LOA -0.20-0.33; ICC 0.66), when compared with the comprehensive technique which demonstrated narrower LOA and excellent reproducibility [radiographer (LOA -0.17-0.20, ICC = 0.91) and cardiologist (LOA-0.15-0.23, ICC = −0.93)]ConclusionA workstation-based CT-FFR technique was reproducible with high and comparable diagnostic performance among operators with different expertise. A comprehensive luminal segmentation technique was the most time-consuming and associated with the highest reproducibility and precision with FFR.     

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.     

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.     

Importance of measurement site on assessment of lesion-specific ischemia and diagnostic performance by coronary computed tomography Angiography-Derived Fractional Flow Reserve

BackgroundValues of fractional flow reserve (FFR_CT) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFR_CT impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFR_INV).Methods1484 patients underwent FFR_CT; 1910 vessels were stratified by stenosis severity (normal; <25%, 25–50%, 50–70%, and >70% stenosis). The rates of positive FFR_CT (≤0.8) were determined by measuring FFR_CT from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFR_CT were calculated. Diagnostic performance of FFR_CT relative to FFR_INV was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves.ResultsPositive FFR_CT was identified in 24.9% of vessels using terminal vessel FFR_CT and 10.1% using FFR_CT distal-to-the-lesion (p ?< ?0.001). FFR_CT obtained distal-to-the-lesion resulted in reclassification of 59.6% of positive terminal FFR_CT to negative FFR_CT. Relative to FFR_INV, there were improvements in specificity (50% to 86%, p ?< ?0.001), diagnostic accuracy (65% to 88%, p ?< ?0.001), positive predictive value (50% to 78%, p ?< ?0.001), and area-under-the-curve (AUC, 0.83 to 0.91, p ?< ?0.001) when FFR_CT was measured distal-to-the-lesion.ConclusionFFR_CT values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFR_CT measured distal-to-the-lesion improves the diagnostic performance of FFR_CT relative to FFR_INV, ensures that FFR_CT values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures.     

Comparison of coronary CT angiography-based and invasive coronary angiography-based quantitative flow ratio for functional assessment of coronary stenosis: A multicenter retrospective analysis

BackgroundThe aim of this study was to evaluate the diagnostic performance of coronary CT angiography (CTA)-based quantitative flow ratio (QFR), namely CT-QFR, and compare it with invasive coronary angiography (ICA)-based Murray law QFR (μQFR), using fractional flow reserve (FFR) as the reference standard.MethodsPatients who underwent coronary CTA, ICA and pressure wire-based FFR assessment within two months were retrospectively analyzed. CT-QFR and μQFR were computed in blinded fashion and compared with FFR, all applying the same cut-off value of ≤0.80 to identify hemodynamically significant stenosis.ResultsPaired comparison between CT-QFR and μQFR was performed in 191 vessels from 167 patients. Average FFR was 0.81 ?± ?0.10 and 42.4% vessels had an FFR ≤0.80. CT-QFR had a slightly lower correlation with FFR compared with μQFR, although statistically non-significant (r ?= ?0.87 versus 0.90, p ?= ?0.110). The vessel-level diagnostic performance of CT-QFR was slightly lower but without statistical significance than μQFR (AUC ?= ?0.94 versus 0.97, difference: ?0.03 [95%CI: ?0.00-0.06], p ?= ?0.095), and substantially higher than diameter stenosis by CTA (AUC difference: 0.17 [95%CI: ?0.10-0.23], p ?< ?0.001). The patient-level diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio for CT-QFR to identify FFR value ?≤ ?0.80 was 88%, 90%, 86%, 86%, 91%, 6.59 and 0.12, respectively. The diagnostic accuracy of CT-QFR was 84% in extensively calcified lesions, while in vessels with no or less calcification, CT-QFR showed a comparable diagnostic accuracy with μQFR (91% versus 92%, p ?= ?0.595). Intra- and inter-observer variability in CT-QFR analysis was ?0.00 ?± ?0.04 and 0.00 ?± ?0.04, respectively.ConclusionsPerformance in diagnosis of hemodynamically significant coronary stenosis by CT-QFR was slightly lower but without statistical significance than μQFR, and substantially higher than CTA-derived diameter stenosis. Extensively calcified lesions reduced the diagnostic accuracy of CT-QFR.     

Influence of coronary stenosis location on diagnostic performance of machine learning-based fractional flow reserve from CT angiography

BackgroundCompared with invasive fractional flow reserve (FFR), coronary CT angiography (cCTA) is limited in detecting hemodynamically relevant lesions. cCTA-based FFR (CT-FFR) is an approach to overcome this insufficiency by use of computational fluid dynamics. Applying recent innovations in computer science, a machine learning (ML) method for CT-FFR derivation was introduced and showed improved diagnostic performance compared to cCTA alone. We sought to investigate the influence of stenosis location in the coronary artery system on the performance of ML-CT-FFR in a large, multicenter cohort.MethodsThree hundred and thirty patients (75.2% male, median age 63 years) with 502 coronary artery stenoses were included in this substudy of the MACHINE (Machine Learning Based CT Angiography Derived FFR: A Multi-Center Registry) registry. Correlation of ML-CT-FFR with the invasive reference standard FFR was assessed and pooled diagnostic performance of ML-CT-FFR and cCTA was determined separately for the following stenosis locations: RCA, LAD, LCX, proximal, middle, and distal vessel segments.ResultsML-CT-FFR correlated well with invasive FFR across the different stenosis locations. Per-lesion analysis revealed improved diagnostic accuracy of ML-CT-FFR compared with conventional cCTA for stenoses in the RCA (71.8% [95% confidence interval, 63.0%–79.5%] vs. 54.8% [45.7%–63.8%]), LAD (79.3 [73.9–84.0] vs. 59.6 [53.5–65.6]), LCX (84.1 [76.0–90.3] vs. 63.7 [54.1–72.6]), proximal (81.5 [74.6–87.1] vs. 63.8 [55.9–71.2]), middle (81.2 [75.7–85.9] vs. 59.4 [53.0–65.6]) and distal stenosis location (67.4 [57.0–76.6] vs. 51.6 [41.1–62.0]).ConclusionIn a multicenter cohort with high disease prevalence, ML-CT-FFR offered improved diagnostic performance over cCTA for detecting hemodynamically relevant stenoses regardless of their location.     

Repeatability of quantitative pericoronary adipose tissue attenuation and coronary plaque burden from coronary CT angiography

BackgroundHigh pericoronary adipose tissue (PCAT) attenuation and non-calcified plaque burden (NCP) measured from coronary CT angiography (CTA) have been implicated in future cardiac events. We aimed to evaluate the interobserver and intraobserver repeatability of PCAT attenuation and NCP burden measurement from CTA, in a sub-study of the prospective SCOT-HEART trial.MethodsFifty consecutive CTAs from participants of the CT arm of the prospective SCOT-HEART trial were included. Two experienced observers independently measured PCAT attenuation and plaque characteristics throughout the whole coronary tree from CTA using semi-automatic quantitative software.ResultsWe analyzed proximal segments in 157 vessels. Intraobserver mean differences in PCAT attenuation and NCP plaque burden were ?0.05HU and 0.92% with limits of agreement (LOA) of ±1.54 and ± 5.97%. Intraobserver intraclass correlation coefficients (ICC) for PCAT attenuation and NCP burden were excellent (0.999 and 0.978). Interobserver mean differences in PCAT attenuation and NCP plaque burden were 0.13HU [LOA ±1.67HU] and ?0.23% (LOA ±9.61%). Interobserver ICC values for PCAT attenuation and NCP burden were excellent (0.998 and 0.944).ConclusionPCAT attenuation and NCP burden on CTA has high intraobserver and interobserver repeatability, suggesting they represent a repeatable and robust method of quantifying cardiovascular risk.     

Artificial intelligence machine learning-based coronary CT fractional flow reserve (CT-FFRML): Impact of iterative and filtered back projection reconstruction techniques

BackgroundThe influence of computed tomography (CT) reconstruction algorithms on the performance of machine-learning-based CT-derived fractional flow reserve (CT-FFR_ML) has not been investigated. CT-FFR_ML values and processing time of two reconstruction algorithms were compared using an on-site workstation.MethodsCT-FFR_ML was computed on 40 coronary CT angiography (CCTA) datasets that were reconstructed with both iterative reconstruction in image space (IRIS) and filtered back-projection (FBP) algorithms. CT-FFR_ML was computed on a per-vessel and per-segment basis as well as distal to lesions with ≥50% stenosis on CCTA. Processing times were recorded. Significant flow-limiting stenosis was defined as invasive FFR and CT-FFR_ML values ≤ 0.80. Pearson's correlation, Wilcoxon, and McNemar statistical testing were used for data analysis.ResultsPer-vessel analysis of IRIS and FBP reconstructions demonstrated significantly different CT-FFR_ML values (p ≤ 0.05). Correlation of CT-FFR_ML values between algorithms was high for the left main (r = 0.74), left anterior descending (r = 0.76), and right coronary (r = 0.70) arteries. Proximal and middle segments showed a high correlation of CT-FFR_ML values (r = 0.73 and r = 0.67, p ≤ 0.001, respectively), despite having significantly different averages (p ≤ 0.05). No difference in diagnostic accuracy was observed (both 81.8%, p = 1.000). Of the 40 patients, 10 had invasive FFR results. Per-lesion correlation with invasive FFR values was moderate for IRIS (r = 0.53, p = 0.117) and FBP (r = 0.49, p = 0.142). Processing time was significantly shorter using IRIS (15.9 vs. 19.8 min, p ≤ 0.05).ConclusionCT reconstruction algorithms influence CT-FFR_ML analysis, potentially affecting patient management. Additionally, iterative reconstruction improves CT-FFR_ML post-processing speed.     

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.     

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.     

Dynamic CT myocardial perfusion imaging

Cardiac CT offers several approaches to establish the hemodynamic severity of coronary artery obstructions. Dynamic myocardial perfusion CT (MPI_CT) is based on serial CT imaging to measure the inflow of contrast medium into the myocardium and calculate absolute measures of myocardial perfusion. This review describes the MPI_CT acquisition protocol, post-image acquisition processing and calculation of quantitative parameters, the diagnostic performance of MPI_CT and the potential incremental value of this technique in comparison to alternative approaches. Further technical innovation using different scanner platforms and establishment of reproducible diagnostic thresholds to differentiate significant coronary artery disease will be crucial in the path to broader clinical implementation.     

Increased coronary pericoronary adipose tissue attenuation in diabetic patients compared to non-diabetic controls: A propensity score matching analysis

BackgroundPericoronary adipose tissue (PCAT) attenuation is an indicator of active inflammation of perivascular adipose tissue, which is supposed to increase in diabetic patients. We aimed to investigate the PCAT attenuation values and high-risk plaque (HRP) features in diabetic and non-diabetic subjects with different stenotic extents.MethodsConsecutive type 2 diabetes patients and non-diabetic patients with chest pain and intermediate pre-test probability of coronary artery disease (CAD) were prospectively enrolled and underwent coronary computed tomography angiography (CCTA). At per-patient level, PCAT attenuation values of three major epicardial coronary vessels, as well as HRP features were measured. PCAT attenuation values and HRP features were compared between diabetic and non-diabetic subjects according to the presence or absence of obstructive stenosis.Results1700 patients (mean age: 65.5 ?± ?11.7, 940 males) were divided into two groups according to presence of obstructive stenosis on CCTA. Propensity score matching was performed in further analysis. RCA_PCAT was significantly higher in diabetic subjects than that in non-diabetic subjects, regardless of the presence of obstructive stenosis (?83.60 ?± ?9.51 HU vs. ?88.58 ?± ?9.37 HU, p ?< ?0.001) or absence of obstructive stenosis (?83.70 ?± ?10.32 HU vs. ?88.76 ?± ?8.28 HU, p ?< ?0.001). In contrast, HRP features were more commonly presented in diabetic patients with obstructive stenosis than in those without obstructive stenosis. According to subgroup analysis based on acquisition tube voltage, RCA_PCAT was the only parameter showing consistent difference between diabetic and non-diabetic patients.ConclusionsRCA_PCAT was significantly higher in diabetic patients than that in non-diabetic patients regardless of stenotic severity and plaque vulnerability.     

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.     

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.     

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.     

A comparative assessment of the performance of a state-of-the art small footprint dedicated cardiovascular CT scanner

IntroductionWith increasing adoption of CT coronary angiography (CTA) there is increasing demand for cost-effective, small footprint, dedicated cardiac scanners. We compared a state-of-the-art, small footprint dedicated cardiac scanner (DCCT) to a standard multidetector scanner (MDCT).MethodsThe study was a retrospective unblinded single centre study. A total of 800 patients were included, with 400 undergoing a DCCT and MDCT coronary CTA scanning, respectively. Image quality was assessed using a 4-point grading score. Image noise and artifact, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), and acceptance rate for CT-derived fractional flow reserve (FFRct) were recorded.ResultsOverall image quality was higher in the DCCT group (3.8 ± 0.55 vs 3.6 ± 0.69; p = 0.042). There was no difference in overall image noise (p = 0.131) or artifact (p = 0.295). SNR was superior in the DCCT group (14.2 ± 6.85 vs 11.4 ± 3.32; p < 0.005) as was CNR (12.7 ± 6.77 vs 11.9 ± 3.29; p < 0.005). The heart rate was lower in the DCCT group (56 ± 9.1 vs 59 ± 8.1; p < 0.005). No difference in the dose length product (DLP median 244.53 (IQR 105.6) vs 237.63 (IQR 160.1); p = 0.313) or FFR_CT acceptance rate (100 vs 97.7%; p > 0.05) was noted. Independent predictors of excellent quality regardless of scanner type were age (p = 0.011), heart rate <65 bpm (p < 0.005), and body mass index < 35 (p < 0.005).ConclusionA DCCT scanner is capable of image quality similar to modern current generation general purpose CT technology. Such technology appears to be a viable option to serve the increasing demand for CTCA imaging.     

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.     

Age related compositional plaque burden by CT in patients with future ACS

BackgroundWe examined age differences in whole-heart volumes of non-calcified and calcified atherosclerosis by coronary computed tomography angiography (CCTA) of patients with future ACS.MethodsA total of 234 patients with core-lab adjudicated ACS after baseline CCTA were enrolled. Atherosclerotic plaque was quantified and characterized from the main epicardial vessels and side branches on a 0.5 ?mm cross-sectional basis. Calcified plaque and non-calcified plaque were defined by above or below 350 Hounsfield units. Patients were categorized according to their age by deciles. Also, coronary artery calcium scores (CACS) were evaluated when available.ResultsPatients were on average 62.2 ?± ?11.5 years old. On the pre-ACS CCTA, patients showed diffuse, multi-site, predominantly non-obstructive atherosclerosis across all age categories, with plaque being detected in 93.5% of all ACS cases. The proportion calcified plaque from the total plaque burden increased significantly with older presentation (10% calcification in those <50 years, and 50% calcification in those >80 years old). Patients with ACS <50 years had remarkably lower atherosclerotic burden compared with older patients, but a high proportion of high risk markers such as low-attenuation plaque. CACS was >0 in 85% of the patients older than 50 years, and in 57% of patients younger than 50 years.ConclusionThe proportion of calcified plaque varied depending on patient age at the time of ACS. Only a small proportion of plaque was calcified when ACS occurred at <50 years old, while this increased gradually with older age. Purely non-calcified atherosclerotic plaque was not uncommon in patients <50 years.     

Accuracy of RESOLVE score derived from coronary computed tomography versus visual angiography to predict side branch occlusion in percutaneous bifurcation intervention

IntroductionVisually estimated angiographic V-RESOLVE score was developed as a simple and accurate prediction tool for side branch (SB) occlusion in patients undergoing coronary bifurcation intervention. Data on the use of coronary computed tomography angiography (coronary CTA) for guiding percutaneous coronary intervention in bifurcation lesions is scarce.ObjectivesWe aimed to validate the ability of quantitative CTA-derived RESOLVE score for predicting SB occlusion in coronary bifurcation intervention and to compare its predictive value with that of the angiography-based V-RESOLVE score.MethodsWe included 363 patients with 400 bifurcation lesions. Angiographic V-RESOLVE score and CTA-derived RESOLVE score were calculated utilizing the weights from the QCA-based RESOLVE score. The scoring systems were divided into quartiles, and classified as the non-high-risk group and the high-risk group. Accuracy was assessed using areas under the receiver-operator characteristic curve (AUC). SB occlusion was defined as any decrease in Thrombolysis in Myocardial Infarction flow grade (including the absence of flow) in the SB after main vessel stenting.ResultsIn total, 28 SB occlusions (7%) occurred. CTA-derived RESOLVE and V-RESOLVE scores achieved comparable predictive accuracy (0.709 vs. 0.752, respectively, p = 0.531) for predicting SB occlusion, and the analysis of AUC for each constituent element of the scores did not show any significant difference between CTA and visual angiography. The total net reclassification index was −18.6% (p = 0.194), and there were no significant differences in the rates of SB occlusion in the non-high-risk group (4.9% vs. 3.8%, p = 0.510) and the high-risk group (13.8% vs. 18.6%, p = 0.384) between CTA-derived RESOLVE and V-RESOLVE scores.ConclusionsThe quantitative CTA-derived RESOLVE score is an accurate and reliable alternative to the visually estimated angiographic V-RESOLVE score for prediction of SB occlusion in coronary bifurcation intervention.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT03709836.