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.     

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

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

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

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

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.     

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.     

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.     

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).     

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.     

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.     

Higher coronary artery calcium score is associated with increased risk of atrial fibrillation recurrence after catheter ablation

BackgroundCoronary artery calcium score (CACS) is associated with an increased risk of atrial fibrillation (AF) development, but scarce data are available regarding the impact on AF recurrence. This study aims to assess the impact of CACS on AF recurrence following catheter ablation.MethodsRetrospective study of patients with AF undergoing cardiac computed tomography (CCT) before ablation (2017–2019). Patients with coronary artery disease (CAD), significant valvular heart disease and previous catheter ablation were excluded. A cut-off of CACS ≥ 100 was used according to literature.ResultsA total of 311 patients were included (median age 57 [48, 64] years, 65% men and 21% with persistent AF). More than half of the patients had a CACS > 0 (52%) and 18% a CACS ≥ 100. Patients with CACS ≥ 100 were older (64 [59, 69] vs 55 [46, 63] years, p ?< ?0.001), had more frequently hypertension (68% vs 42%, p ?< ?0.001) and diabetes mellitus (21% vs 10%, p ?= ?0.020). During a median follow-up of 34 months (12–57 months), 98 patients (32%) had AF recurrence. CACS ≥ 100 was associated with increased risk of AF recurrence (unadjusted Cox regression: hazard ratio [HR] 2.0; 95% confidence interval [CI], 1.3–3.1, p ?= ?0.002). After covariate adjustment, CACS ≥ 100 and persistent AF remained independent predictors of AF recurrence (HR, 1.7; 95% CI, 1.0–2.8, p ?= ?0.039 and HR, 2.0; 95% CI, 1.3–3.2, p ?= ?0.004, respectively).ConclusionAn opportunistic evaluation of CACS could be an important tool to improve clinical care considering that CACS ≥ 100 was independently associated with a 69% increase in the risk of AF recurrence after first catheter ablation.     

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.     

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.     

Impact of coronary artery calcium testing on patient management

BackgroundCoronary artery calcium (CAC) scoring can identify individuals who may benefit from aggressive prevention therapies. However, there is a paucity of contemporary data on the impact of CAC testing on patient management.MethodsRetrospective cohort study of adults who underwent CAC testing at Brigham and Women's Hospital between 2015 and 2019. Information on baseline medications, follow-up medications, lifestyle modification, and downstream cardiovascular testing within one-year post-CAC were obtained from electronic health records.ResultsOf the 839 patients with available baseline and follow-up data, 376 (45%) had a CAC ?= ?0, 289 (34%) had CAC ?= ?1–99, and 174 (21%) had CAC≥100. The mean age at time of CAC testing was 59 ?± ?9.7 years. Patients with higher CAC scores were more likely to be male, have diabetes and hypertension, and have higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol. A non-zero CAC score was associated with initiation of aspirin (41% increase, p ?< ?0.001), anti-hypertensives (9% increase, p ?= ?0.031), and lipid-lowering therapies (114% increase, p ?< ?0.001), whereas CAC ?= ?0 was not. Among individuals with CAC≥100, 75% were started on new or more intense lipid-lowering therapy. Higher calcium scores correlated with increased physician recommendations for diet (p ?= ?0.008) and exercise (p ?= ?0.004). The proportion of cardiovascular downstream testing following CAC was 9.1%, and the majority of patients who underwent additional testing post-CAC had CAC scores ≥100.ConclusionApproximately half of individuals referred for CAC testing had evidence of calcified coronary plaque, and of those who had significant calcifications (CAC≥100), nearly 90% were prescribed lipid-lowering therapies post-CAC. Rates of downstream non-invasive testing were low and such testing was mostly performed in patients who had at least moderate CAC.     

Mitral annular calcification in the elderly – Quantitative assessment

PurposeTo determine the reliability of subjective and objective quantification of mitral annular calcification (MAC) in elderly patients with severe aortic stenosis, to define quantitative sex- and age-related reference values of MAC, and to correlate quantitative MAC with mitral valve disease.MethodsIn this retrospective, IRB-approved study, we included 559 patients (268 females, median age 81 years, inter-quartile range 77–85 years) with severe aortic stenosis undergoing CT. Four independent readers performed subjective MAC categorization as follows: no, mild, moderate, and severe MAC. Two independent readers performed quantitative evaluation of MAC using the Agatston score method (Agatston_MAC). Mitral valve disease was determined by echocardiography.ResultsSubjective MAC categorization showed high inter-reader agreement for no (k ?= ?0.88) and severe MAC (k ?= ?0.75), whereas agreement for moderate (k ?= ?0.59) and mild (k ?= ?0.45) MAC was moderate. Intra-reader agreement for subjective MAC categorization was substantial (k ?= ?0.69 and 0.62). Inter- and intra-reader agreement for Agatston_MAC were excellent (ICC ?= ?0.998 and 0.999, respectively), with minor inconsistencies in MAC involving the left ventricular outflow tract/aortic valve. There were significantly more women than men with MAC (n ?= ?227, 85% versus n ?= ?209, 72%; p ?< ?0.001), with a significantly higher Agatston_MAC (median 597, range 81–2055 versus median 244; range 0–1565; p ?< ?0.001), particularly in patients ≥85 years of age. Agatston_MAC showed an area-under-the-curve of 0.84 to diagnose mitral stenosis, whereas there was no association of Agatston_MAC with mitral regurgitation (p ?> ?0.05).ConclusionsOur study in elderly patients with severe aortic stenosis shows that quantitative MAC scoring is more reliable than subjective MAC assessment. Women show higher Agatston_MAC scores than men, particularly in the elderly population. Agatston_MAC shows high accuracy to diagnose mitral 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.     

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.     

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.     

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.     

CT multivessel aggregate stenosis score: A novel point-of-care tool for predicting major adverse cardiac events

BackgroundWe evaluated the utility of a novel 15-point multivessel aggregate stenosis (MVAS) score for predicting major adverse cardiac events (MACE) in low-risk patients with suspected ischaemic symptoms undergoing CTCA. Prognostic performance was compared with the Coronary Artery Disease Reporting and Data System (CAD-RADS) classification and the 16-point Segment Involvement Score (SIS).Methods772 consecutive patients underwent CTCA and coronary artery calcification scoring (CACS) from 2010 to 2015. Coronary artery disease severity was calculated according to CAD-RADS class (0–5 ?± ?vulnerability modifier), the SIS (0–16), and an MVAS score (0–15) based on the aggregate stenosis severity in all 4 coronary vessels (maximum 12 points) plus the presence of any high-risk plaque features (additional 3 points). 52 patients were referred directly for coronary angiography based on CTCA findings and were excluded; the remainder were followed-up for 64.6 ?± ?19.1 months.Results54 ?MACE were observed in 720 patients (7.5%); MACE patients had higher CAD-RADS class (3.92 ?± ?0.7 vs 0.91 ?± ?1.2, p ?< ?0.0001), SIS (4.59 ?± ?2.7 vs 0.79 ?± ?1.2, p ?< ?0.0001), and MVAS scores (10.1 ?± ?1.7 vs 1.7 ?± ?2.1, p ?< ?0.0001). Adjusted Cox proportional hazards analysis identified CAD-RADS class (HR 2.96 (2.2–4), p ?< ?0.0001), SIS (HR 1.29 (1.2–1.4, p ?< ?0.0001), and MVAS score (HR 1.82 (1.6–2.1), p ?< ?0.0001) as predictors of MACE. Adjusted receiver operating characteristic (ROC) analysis found MVAS a more powerful predictor of MACE than CAD-RADS and SIS (AUC: 0.92 vs 0.84 vs 0.83, p ?= ?0.018).ConclusionsCAD-RADS and SIS are reliable predictors of MACE, and the MVAS score provided incremental prognostic data. MVAS may potentiate risk stratification, particularly in institutions without advanced plaque analysis software.