CT-based total vessel plaque analyses improves prediction of hemodynamic significance lesions as assessed by fractional flow reserve in patients with stable angina pectoris

BackgroundCoronary stenosis and plaque evaluation by coronary computed tomography angiography (CTA) may contribute to identify hemodynamically relevant lesions. We evaluated the most stenotic lesion including plaques proximal to it versus a total vessel analyses combined with stenosis for ischemia.MethodsPatients scheduled for clinically indicated invasive coronary angiography (ICA) for suspected coronary artery disease underwent coronary CTA and ICA including fractional flow reserve (FFR) as part of the NXT trial (clinicaltrials.gov NCT01757678). Stenoses were visually graded ≤50%, 51–70%, and >70% on coronary CTA. Semi-automated plaque analyses were performed using a proximal to the FFR pressure sensor location (including the most severe lesion to the coronary ostium) versus a total vessel (vessel diameter ≥2 mm) approach. Coronary stenosis and plaque parameters were evaluated for discrimination of ischemia by logistic regressions and combined models analyzed using receiver operating characteristics (ROC) with invasive FFR≤ 0.80 as reference standard.ResultsIn 254 patients, mean (±SD) age 64 (±10) years, 64% male, a coronary CTA stenosis >50% was present in 239 (49%) vessels. Invasive FFR was ≤0.80 in 100 (21%) vessels. Coronary stenosis severity and low-density non-calcified plaque (LD-NCP) volume were independent predictors of ischemia in the “proximal” and “total-vessel” analyses. Stenosis severity + total vessel LD-NCP assessment performed better than stenosis severity + proximal LD-NCP evaluation (Area under curve [AUC] (95%CI): 0.83 (0.78–0.87) vs 0.81 (0.76–0.86), p-value = 0.009), whereas stenosis severity + proximal LD-NCP performed better than stenosis alone (AUC (95%CI): 0.81 (0.76–0.86) vs 0.78 (0.73–0.83), p-value = 0.019).ConclusionAdding total vessel high-risk plaque volume to stenosis severity improves discrimination of ischemia in coronary CTA performed in patients with stable angina pectoris.     

Peri-coronary inflammation is associated with findings on coronary computed tomography angiography and fractional flow reserve

PurposePeri-coronary adipose tissue attenuation expressed by fat attenuation index (FAI) on coronary CT angiography (CCTA) reflects peri-coronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between FAI and whole vessel and lesion plaque quantification on CCTA in stable patients with intermediate epicardial stenosis evaluated by fractional flow reserve (FFR).MethodsA total of 187 left anterior descending arteries (LAD) with intermediate stenosis who underwent FFR measurement and CCTA were studied. FAI was assessed by the crude analysis of the mean CT attenuation value of LAD on CCTA. Determinants of FAI and FFR were explored. Furthermore, the impact of combined baseline data, CCTA-derived lesion plaque assessment, whole vessel quantification, cardiac mass and FAI on discrimination efficacy for ischemia was evaluated as FFR used for a reference standard.ResultsThe mean FAI and the median FFR values were −73.0 and 0.77, respectively. Multivariate analysis revealed that male, CCTA-derived positive remodeling, lower minimum lumen area, higher target vessel total cardiac mass, and lower FFR were independent predictors of FAI. CCTA-derived two-dimensional and three-dimensional analysis and FAI were independently and significantly associated with FFR values. Net reclassification index and integrated discrimination improvement index were both significantly improved when FAI was added to the baseline model for lesions with FFR <0.75, but not for FFR≤0.80.ConclusionsFAI was associated with FFR, CCTA-derived two-dimensional and three-dimensional lumen and plaque quantification and cardiac mass in patients with intermediate lesions in LAD, indicating that comprehensive CTA assessment may provide risk-stratification.     

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.     

Coronary CTA enhanced with CTA based FFR analysis provides higher diagnostic value than invasive coronary angiography in patients with intermediate coronary stenosis

BackgroundCTA based FFR, a software based application, enhances diagnostic value of coronary computed tomography angiography (CTA) examination. However it remains unknown whether it improves accuracy over the gold standard of invasive coronary angiography (ICA) in predicting functionally significant coronary stenosis. The aim of our study was to compare diagnostic accuracies of coronary CTA, CTA based FFR, and ICA, with invasive FFR as the reference standard in patients with intermediate stenosis on CTA.Methods96 intermediate stenoses (50–90%) from 90 subjects, with intermediate pre-test probability of CAD, who underwent coronary CTA were analyzed. Each patient had subsequent ICA with FFR. CTA based FFR (cFFR v2.1, Siemens) analysis was performed on-site. The stenoses with invasive FFR≤0.8 were considered hemodynamically significant.Results41/96 stenoses were hemodynamically significant (FFR≤0.8). While the area under ROC curves (AUC) for identification of significant stenosis evaluated on QCA (0.653), visual ICA (0.652), qCTA (0.690) and visual CTA (0.660) did not significantly differ, the AUC for CTA based FFR (0.835) was significantly higher (p = 0.004, p = 0.004, p = 0.010, p = 0.007, respectively). The accuracies of CTA based FFR, qCTA and QCA were 76%, 63% and 58% respectively.ConclusionOur results suggest that diagnostic potential of routine coronary CTA, augmented with CTA based FFR analysis, is superior to ICA in patients with intermediate stenosis.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Coronary CT angiography versus intravascular ultrasound for estimation of coronary stenosis and atherosclerotic plaque burden: A meta-analysis

BackgroundNumerous studies have compared coronary CT angiography (CTA) with quantitativecoronary angiography. However, the ability of coronary CTA to identify atherosclerosis and to accurately measure plaque and coronary area and volume measurements as compared with intravascular ultrasound (IVUS) has not been fully defined.ObjectiveWe sought to assess the ability of coronary CTA to quantify coronary and plaque measurements commonly performed with IVUS.MethodsWe searched multiple databases for diagnostic studies that directly compared coronary CTA and IVUS for coronary plaque detection, vessel luminal area, percentage of area stenosis, plaque area, and plaque volume. We used a bivariate mixed-effects binomial regression model to pool test sensitivity and specificity for detection of any coronary plaque.ResultsForty-two studies that evaluated 1360 patients (75% men; mean age, 59 years) were identified. No significant difference was found between coronary CTA and IVUS measurements of vessel lumen cross-sectional area, plaque area, percentage of area stenosis, or plaque volume within the overall cohort and no difference for the measurement of cross-sectional area (n = 5 studies) and plaque volume (n = 8 studies) among a subgroup that used automated or semiautomated measurement techniques. Sensitivity and specificity of coronary CTA to detect any plaque compared with IVUS were 93% and 92%, respectively, with an area under the receiver-operating curve of 0.97.ConclusionsCompared with IVUS, coronary CTA appears to be highly accurate for estimation of luminal area, percentage of area stenosis, plaque volume, and plaque area and for detection of plaque. The use of automated vessel and stenosis measurements appears promising in limited studies to date.     

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.     

Perivascular fat attenuation for predicting adverse cardiac events in stable patients undergoing invasive coronary angiography

BackgroundInflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown.MethodsCORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models.ResultsThirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55–68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were ?74.9, ?74.2, and ?71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75–1.22, p ?= ?0.71), 1.31 (95% CI: 0.96–1.78, p ?= ?0.09), and 0.98 (95% CI: 0.78–1.22, p ?= ?0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44–1.07), 0.85 (0.56–1.29), and 0.57 (0.41–0.80), respectively.ConclusionsIn patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.     

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.     

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.     

Comparison of quantitative atherosclerotic plaque burden from coronary CT angiography in patients with first acute coronary syndrome and stable coronary artery disease

BackgroundCoronary CTA allows characterization of non-calcified and calcified plaque and identification of high-risk plaque features.ObjectiveWe aimed to quantitatively characterize and compare coronary plaque burden from CTA in patients with a first acute coronary syndrome (ACS) and controls with stable coronary artery disease.Materials and methodsWe retrospectively analyzed consecutive patients with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina with a first ACS, who underwent CTA as part of their initial workup before invasive coronary angiography and age- and gender-matched controls with stable chest pain; controls also underwent CTA with subsequent invasive angiography (total n = 28). Culprit arteries were identified in ACS patients. Coronary arteries were analyzed by automated software to quantify calcified plaque (CP), noncalcified plaque (NCP), and low-density NCP (LD-NCP, attenuation <30 Hounsfield units) volumes, and corresponding burden (plaque volume × 100%/vessel volume), stenosis, remodeling index, contrast density difference (maximum percent difference in attenuation/cross-sectional area from proximal cross-section), and plaque length.ResultsACS patients had fewer lesions (median, 1), with higher total NCP and LD-NCP burdens (NCP: 57.4% vs 41.5%; LD-NCP: 12.5% vs 8%; P ≤ .04), higher maximal stenoses (85.6% vs 53.0%; P = .003) and contrast density differences (46.1 vs 16.3%; P < .006). Per-patient CP burden was not different between ACS and controls. NCP and LD-NCP plaque burden was higher in culprit vs nonculprit arteries (NCP: 57.8% vs 9.5%; LD-NCP: 8.4% vs 0.6%; P ≤ .0003); CP was not significantly different. Culprit arteries had increased plaque lengths, remodeling indices, stenoses, and contrast density differences (46.1% vs 10.9%; P ≤ .001).ConclusionNoninvasive quantitative coronary artery analysis identified several differences for ACS, both on per-patient and per-vessel basis, including increased NCP, LD-NCP burden, and contrast density difference.     

The association of coronary lumen volume to left ventricle mass ratio with myocardial blood flow and fractional flow reserve

BackgroundA diminished coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive disease on invasive coronary angiography (ICA).MethodsPatients underwent CCTA, and positron emission tomography (PET) prior to ICA. Matched global V/M, global, and vessel specific hyperaemic MBF (hMBF), coronary flow reserve (CFR), and, FFR were available for 431 vessels in 152 patients. The median V/M (20.71 mm³/g) was used to divide the population into patients with either a low V/M or a high V/M.ResultsOverall, a higher percentage of vessels with an abnormal hMBF and FFR (34% vs. 19%, p = 0.009 and 20% vs. 9%, p = 0.004), as well as a lower FFR (0.93 [interquartile range: 0.85–0.97] vs. 0.95 [0.89–0.98], p = 0.016) values were observed in the low V/M group. V/M was weakly associated with vessel specific hMBF (R = 0.148, p = 0.027), and FFR (R = 0.156, p < 0.001). Among vessels with non-obstructive CAD on ICA (361 vessels), no association between V/M and vessel specific hMBF nor CFR was noted. However, in the absence of obstructive CAD, V/M was associated with (R = 0.081, p = 0.027), and independently predictive for FFR (p = 0.047).ConclusionOverall, an abnormal vessel specific hMBF and FFR were more prevalent in patients with a low V/M compared to those with a high V/M. Furthermore, V/M was weakly associated with vessel specific hMBF and FFR. In the absence of obstructive CAD on ICA, V/M was weakly associated with notwithstanding independently predictive for FFR.     

Stent size selection using 64-detector coronary computed tomography angiography: a comparison to invasive coronary angiography

RATIONALE AND OBJECTIVES: Compare stent size selection using coronary computed tomography angiography (CCTA) to invasive coronary angiography (ICA). CCTA is increasingly performed before cardiac catheterization; however, the utility of incorporating these data into coronary interventions is unknown. METHODS: Retrospective study of 18 consecutive patients with 24 coronary artery lesions evaluated with 64-detector CCTA followed by ICA and resulting stent placement. Two blinded interventional cardiologists independently reviewed designated arterial segments on both CCTA and ICA during different reading sessions and determined anticipated stent length and nominal diameter, maximum stenosis, the need for postdilation of either stent margin, and final proximal and distal stent diameters. RESULTS: There was strong correlation between CCTA and ICA in the anticipated stent length (r = 0.85, P < .001) and final stent diameter (proximal end r = 0.74, P < .001; distal end r = 0.63, P = .001). Anticipated stent length was longer with CCTA compared to ICA (27.0 +/- 16.0 vs. 21.8 +/- 13.3 mm; P = .006). The final stent diameters were larger with CCTA compared to ICA, both at the proximal end (3.6 +/- 0.5 vs. 3.1 +/- 0.5 mm; P < .001) and distal end (3.2 +/- 0.6 vs. 2.9 +/- 0.4 mm; P = .004). CONCLUSIONS: Using 64-detector CCTA, interventional cardiologists select longer stents with larger final stent diameters than with ICA. Further studies are needed to determine the clinical utility of incorporating CCTA, when available, in defining interventional strategy.