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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Advanced computed tomographic anatomical and morphometric plaque analysis for prediction of fractional flow reserve in intermediate coronary lesions

Objective

To determine the application of advanced coronary computed tomography angiography (CCTA) plaque analysis for predicting invasive fractional flow reserve (FFR) in intermediate coronary lesions.

Methods

Sixty-one patients with 71 single intermediate coronary lesions (≥50–80% stenosis) on CCTA prospectively underwent coronary angiography and FFR. Advanced anatomical and morphometric plaque analysis was performed based on CCTA data set to determine optimal criteria for significant flow impairment. A significant stenosis was defined as FFR ≤ 0.80.

Results

FFR averaged 0.85 ± 0.09, and 19 lesions (27%) were functionally significant. FFR correlated with minimum lumen area (MLA) (r = 0.456, p < 0.001), minimum lumen diameter (MLD) (r = 0.326, p = 0.006), reference lumen diameter (RLD) (r = 0.245, p = 0.039), plaque burden (r = −0.313, p = 0.008), lumen area stenosis (r = −0.305, p = 0.01), lesion length (r = −0.692, p < 0.001), and plaque volume (r = −0.668, p < 0.001). There was no relationship between FFR and CCTA morphometric plaque parameters. By multivariate analysis the independent predictors of FFR were lesion length (beta = −0.581, p < 0.001), MLA (beta = 0.360, p = 0.041), and RLD (beta = −0.255, p = 0.036). The optimal cutoffs for lesion length, MLA, MLD, RLD, and lumen area stenosis were >18.5 mm, ≤3.0 mm², ≤2.1 mm, ≤3.2 mm, and >69%, respectively (max. sensitivity: 100% for MLA, max. specificity: 79% for lumen area stenosis).

Conclusions

CCTA predictors for FFR support the mathematical relationship between stenosis pressure drop and coronary flow. CCTA could prove to be a useful rule-out test for significant hemodynamic effects of intermediate coronary stenoses.     

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.     

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.     

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.     

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.     

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.     

Sex differences in computed tomography angiography-derived coronary plaque burden in relation to invasive fractional flow reserve

BackgroundDistinct sex-related differences exist in coronary artery plaque burden and distribution. We aimed to explore sex differences in quantitative plaque burden by coronary CT angiography (CCTA) in relation to ischemia by invasive fractional flow reserve (FFR).MethodsThis post-hoc analysis of the PACIFIC trial included 581 vessels in 203 patients (mean age 58.1 ​± ​8.7 years, 63.5% male) who underwent CCTA and per-vessel invasive FFR. Quantitative assessment of total, calcified, non-calcified, and low-density non-calcified plaque burden were performed using semiautomated software. Significant ischemia was defined as invasive FFR ≤0.8.ResultsThe per-vessel frequency of ischemia was higher in men than women (33.5% vs. 7.5%, p ​< ​0.001). Women had a smaller burden of all plaque subtypes (all p ​< ​0.01). There was no sex difference on total, calcified, or non-calcified plaque burdens in vessels with ischemia; only low-density non-calcified plaque burden was significantly lower in women (beta: -0.183, p ​= ​0.035). The burdens of all plaque subtypes were independently associated with ischemia in both men and women (For total plaque burden (5% increase): Men, OR: 1.15, 95%CI: 1.06–1.24, p ​= ​0.001; Women, OR: 1.96, 95%CI: 1.11–3.46, p ​= ​0.02). No significant interaction existed between sex and total plaque burden for predicting ischemia (interaction p ​= ​0.108). The addition of quantitative plaque burdens to stenosis severity and adverse plaque characteristics improved the discrimination of ischemia in both men and women.ConclusionsIn symptomatic patients with suspected CAD, women have a lower CCTA-derived burden of all plaque subtypes compared to men. Quantitative plaque burden provides independent and incremental predictive value for ischemia, irrespective of sex.     

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.     

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.     

Comparison of invasively measured FFR with FFR derived from coronary CT angiography for detection of lesion-specific ischemia: Results from a PC-based prototype algorithm

BackgroundWe evaluated the diagnostic accuracy of a novel prototype for on-site determination of CT-based FFR (cFFR) on a standard personal computer (PC) compared to invasively measured FFR in patients with suspected coronary artery disease.MethodsA total of 91 vessels in 71 patients (mean age 65 ± 9 years) in whom coronary CT angiography had been performed due to suspicion of coronary artery disease, and who subsequently underwent invasive coronary angiography with FFR measurement were analyzed. For both cFFR and FFR, a threshold of ≤0.80 was used to indicate a hemodynamically relevant stenosis. The mean time needed to calculate cFFR was 12.4 ± 3.4 min. A very close correlation between cFFR and FFR could be shown (r = 0.85; p < 0.0001) with Bland-Altman analysis showing moderate agreement between FFR and cFFR with mild systematic overestimation of FFR values in CT (mean difference 0.0049, 95% limits of agreement ±2SD −0.007 to 0.008). Compared to FFR, the sensitivity of cFFR to detect hemodynamically significant lesions was 91% (19/21, 95% CI: 70%–99%), specificity was 96% (67/70, 95% CI: 88%–99%), positive predictive value 86% (95% CI: 65%–97%) and negative predictive value was 97% (95% CI: 90%–100%) with an accuracy of 93%.ConclusioncFFR obtained using an on-site algorithm implemented on a standard PC shows high diagnostic accuracy to detect lesions causing ischemia as compared to FFR. Importantly, the time needed for analysis is short which may be useful for improving clinical workflow.     

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.