Sex Differences in Coronary Computed Tomography Angiography–Derived Fractional Flow Reserve: Lessons From ADVANCE

ObjectivesThis study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)–derived fractional flow reserve (FFR_CT) according to sex.BackgroundWomen are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFR_CT improves sex-based patient management decisions compared to CCTA alone is unknown.MethodsSubjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFR_CT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFR_CT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates.ResultsA total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFR_CT. Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFR_CT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFR_CT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFR_CT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFR_CT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm³/g vs. 24.76 ± 7.22 mm³/g; p < 0.0001) that is associated with higher FFR_CT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFR_CT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284).ConclusionsFFR_CT differs between the sexes, as women have a higher FFR_CT for the same degree of stenosis. In FFR_CT-positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFR_CT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679)     

Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement

ObjectivesThis study sought to evaluate the prognostic value of stress dynamic computed tomography (CT) perfusion (CTP) with CT delayed enhancement (CTDE) in patients with suspected or known coronary artery disease (CAD) and in subgroups of patients with stent, heavy calcification, or stenosis.BackgroundThe prognostic value of stress dynamic CTP with CTDE is unknown.MethodsParticipants were 540 patients with suspected or known CAD. Major adverse cardiac event(s) (MACE) consisted of cardiac death, nonfatal myocardial infarction, unstable angina, or hospitalization for congestive heart failure. Ischemic score was calculated by scoring the reduction of normalized myocardial blood flow in 16 segments excluding areas of myocardial scarring. Ischemic perfusion defect (IPD) was defined as Ischemic score ≥4. Scar score was also calculated by scoring the transmural extent of scarring in each segment on CTDE.ResultsDuring a median follow-up of 2.9 years, 43 MACEs occurred. By adding IPD to obstructive CAD (≥50% stenosis) on coronary CT angiography, the concordance index for predicting MACEs increased from 0.73 to 0.82 in patients with suspected CAD (p = 0.028) and from 0.61 to 0.73 in patients with known CAD (p = 0.004). IPD and scar score of ≥4 were independent predictors when adjusted for each other in patients with suspected (adjusted hazard ratios: 7.5 [p < 0.001] and 3.0 [p = 0.034], respectively) or known CAD (adjusted hazard ratios: 4.4 [p = 0.001] and 3.2 [p = 0.024], respectively). Patients with IPD had a higher annualized event rate than those without IPD in subgroups of those with stent (11.5% vs. 2.6%; p < 0.001), heavy calcification (13.3% vs. 3.1%; p < 0.001), 50% to 69% stenosis (8.8% vs. 1.0%; p < 0.001), or ≥70% stenosis (12.4% vs. 3.6%; p < 0.001).ConclusionsStress dynamic CTP with CTDE had incremental prognostic value over CT angiography in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification.     

Prognostic Value of Computed Tomography-Derived Fractional Flow Reserve Comparison With Myocardial Perfusion Imaging

ObjectivesThe aim of this study was to compare the incremental prognostic value of coronary computed tomography (CT) angiography (CCTA)-derived machine learning fractional flow reserve CT (ML-FFRct) versus that of ischemia detected on single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) on incident cardiovascular outcomes.BackgroundSPECT MPI and ML-FFRct are noninvasive tools that can assess the hemodynamic significance of coronary atherosclerotic disease.MethodsWe studied a retrospective cohort of consecutive patients who underwent clinically indicated CCTA and SPECT MPI. ML-FFRct was computed using a ML prototype. The primary outcome was all-cause mortality and nonfatal myocardial infarction (D/MI), and the secondary outcome was D/MI and unplanned revascularization, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) occurring more than 90 days postimaging. Multiple nested multivariate cox regression was used to model a scenario wherein an initial anatomical assessment was followed by a functional assessment.ResultsA total of 471 patients (mean age: 64 ± 13 year; 53% males) were included. Comorbidities were prevalent (78% hypertension, 66% diabetes, 81% dyslipidemia). ML-FFRct was <0.8 in at least 1 proximal/midsegment was present in 41.6% of patients, and ischemia on MPI was present in 13.8%. After a median follow-up of 18 months, 7% of patients (n = 33) experienced D/MI. On multivariate Cox proportional analysis, the presence of ischemia on MPI but not ML-FFRct significantly predicted D/MI (HR: 2.3; 95% CI: 1.0-5.0; P = 0.047; or HR: 0.7; 95% CI: 0.3-1.4; P = 0.306 respectively) when added to CCTA obstructive stenosis. Furthermore, the model with SPECT ischemia had higher global chi-square result and significantly improved reclassification. Results were similar using the secondary outcome and on several sensitivity analyses.ConclusionsIn a high-risk patient cohort, SPECT MPI but not ML-FFRct adds independent and incremental prognostic information to CCTA-based anatomical assessment and clinical risk factors in predicting incident outcomes.     

Optical Coherence Tomography Fractional Flow Reserve and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome

BackgroundOptical coherence tomography–derived fractional flow reserve (OCT-FFR) correlates strongly with wire-based FFR; however, its clinical significance remains uncertain.ObjectivesThis study sought to investigate the relationship between post–percutaneous coronary intervention (PCI) OCT-FFR and long-term clinical outcomes in acute coronary syndrome (ACS).MethodsThis retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent OCT-guided emergency PCI. We analyzed post-PCI OCT images and calculated OCT-FFR to identify independent factors associated with target vessel failure (TVF) after PCI.ResultsAmong 364 enrolled patients, 54 experienced TVF during a median follow-up of 36 (IQR: 26-48) months. Vessel-level OCT-FFR was significantly lower in the TVF group than in the non-TVF group (0.87 vs 0.94; P < 0.001). In the multivariable Cox regression analysis, low vessel-level OCT-FFR (HR per 0.1 increase: 0.38; 95% CI: 0.29-0.49; P < 0.001) and thin-cap fibroatheroma in the nonculprit lesion were independently associated with TVF. The TVF rate of vessels with both low vessel-level OCT-FFR (<0.90) and thin-cap fibroatheroma in the nonculprit lesion was 8.1 times higher than that of all other vessels (69.3% vs 12.4%; HR: 8.13; 95% CI: 4.33-15.25; log-rank P < 0.001). Furthermore, adding vessel-level OCT-FFR to baseline characteristics and post-PCI OCT findings improved discriminatory and reclassification ability in identifying patients with subsequent TVF.ConclusionsVessel-level OCT-FFR was an independent factor associated with TVF after PCI in patients with ACS. Adding the OCT-FFR measurement to post-PCI OCT findings may enable better discrimination of patients with subsequent TVF after PCI for ACS. (Relationship between Intracoronary Optical Coherence Tomography Derived Virtual Fractional Flow Reserve and cardiovascular outcome on Acute coronary syndrome; UMIN000043858)     

Implementing Coronary Computed Tomography Angiography in the Catheterization Laboratory

Coronary computed tomography angiography (CCTA) is now an established tool in the diagnostic work-up of patients suspected to have coronary artery disease. Yet, its usefulness beyond this phase has not been fully explored. The current review focuses on the implementation of CCTA as a tool to plan and guide coronary interventions in the catheterization laboratory. Specifically, we explore the potential of CCTA to improve patient selection for percutaneous revascularization, provide the rationale for better resource use, and present a novel approach to incorporate 3-dimensional CT guidance for percutaneous coronary interventions.     

AI Evaluation of Stenosis on Coronary CTA,Comparison With Quantitative Coronary Angiography and Fractional Flow Reserve: A CREDENCE Trial Substudy

BackgroundClinical reads of coronary computed tomography angiography (CTA), especially by less experienced readers, may result in overestimation of coronary artery disease stenosis severity compared with expert interpretation. Artificial intelligence (AI)-based solutions applied to coronary CTA may overcome these limitations.ObjectivesThis study compared the performance for detection and grading of coronary stenoses using artificial intelligence–enabled quantitative coronary computed tomography (AI-QCT) angiography analyses to core lab–interpreted coronary CTA, core lab quantitative coronary angiography (QCA), and invasive fractional flow reserve (FFR).MethodsCoronary CTA, FFR, and QCA data from 303 stable patients (64 ± 10 years of age, 71% male) from the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia) trial were retrospectively analyzed using an Food and Drug Administration–cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination.ResultsDisease prevalence was high, with 32.0%, 35.0%, 21.0%, and 13.0% demonstrating ≥50% stenosis in 0, 1, 2, and 3 coronary vessel territories, respectively. Average AI-QCT analysis time was 10.3 ± 2.7 minutes. AI-QCT evaluation demonstrated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94%, 68%, 81%, 90%, and 84%, respectively, for ≥50% stenosis, and of 94%, 82%, 69%, 97%, and 86%, respectively, for detection of ≥70% stenosis. There was high correlation between stenosis detected on AI-QCT evaluation vs QCA on a per-vessel and per-patient basis (intraclass correlation coefficient = 0.73 and 0.73, respectively; P < 0.001 for both). False positive AI-QCT findings were noted in in 62 of 848 (7.3%) vessels (stenosis of ≥70% by AI-QCT and QCA of <70%); however, 41 (66.1%) of these had an FFR of <0.8.ConclusionsA novel AI-based evaluation of coronary CTA enables rapid and accurate identification and exclusion of high-grade stenosis and with close agreement to blinded, core lab–interpreted quantitative coronary angiography. (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia [CREDENCE]; NCT02173275)     

Superior Risk Stratification With Coronary Computed Tomography Angiography Using a Comprehensive Atherosclerotic Risk Score

ObjectivesThis study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS).BackgroundCurrent risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification.MethodsA total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and ≥70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971).ResultsThe mean age of patients was 55 ± 13 years, mean follow-up 3.6 ± 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort.ConclusionsThe new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/)     

Radiomics-Based Precision Phenotyping Identifies Unstable Coronary Plaques From Computed Tomography Angiography

ObjectivesThe aim of this study was to precisely phenotype culprit and nonculprit lesions in myocardial infarction (MI) and lesions in stable coronary artery disease (CAD) using coronary computed tomography angiography (CTA)-based radiomic analysis.BackgroundIt remains debated whether any single coronary atherosclerotic plaque within the vulnerable patient exhibits unique morphology conferring an increased risk of clinical events.MethodsA total of 60 patients with acute MI prospectively underwent coronary CTA before invasive angiography and were matched to 60 patients with stable CAD. For all coronary lesions, high-risk plaque (HRP) characteristics were qualitatively assessed, followed by semiautomated plaque quantification and extraction of 1,103 radiomic features. Machine learning models were built to examine the additive value of radiomic features for discriminating culprit lesions over and above HRP and plaque volumes.ResultsCulprit lesions had higher mean volumes of noncalcified plaque (NCP) and low-density noncalcified plaque (LDNCP) compared with the highest-grade stenosis nonculprits and highest-grade stenosis stable CAD lesions (NCP: 138.1 mm³ vs 110.7 mm³ vs 102.7 mm³; LDNCP: 14.2 mm³ vs 9.8 mm³ vs 8.4 mm³; both P_trend < 0.01). In multivariable linear regression adjusted for NCP and LDNCP volumes, 14.9% (164 of 1,103) of radiomic features were associated with culprits and 9.7% (107 of 1,103) were associated with the highest-grade stenosis nonculprits (critical P < 0.0007) when compared with highest-grade stenosis stable CAD lesions as reference. Hierarchical clustering of significant radiomic features identified 9 unique data clusters (latent phenotypes): 5 contained radiomic features specific to culprits, 1 contained features specific to highest-grade stenosis nonculprits, and 3 contained features associated with either lesion type. Radiomic features provided incremental value for discriminating culprit lesions when added to a machine learning model containing HRP and plaque volumes (area under the receiver-operating characteristic curve 0.86 vs 0.76; P = 0.004).ConclusionsCulprit lesions and highest-grade stenosis nonculprit lesions in MI have distinct radiomic signatures compared with lesions in stable CAD. Within the vulnerable patient may exist individual vulnerable plaques identifiable by coronary CTA-based precision phenotyping.     

Comparison of Coronary Computed Tomography Angiography,Fractional Flow Reserve,and Perfusion Imaging for Ischemia Diagnosis

Background

Fractional flow reserve (FFR) computation from coronary computed tomography angiography (CTA) datasets (FFR_CT) has emerged as a promising noninvasive test to assess hemodynamic severity of coronary artery disease (CAD), but has not yet been compared with traditional functional imaging.

CT Coronary Angiography and Dynamic CT Myocardial Perfusion for Detection of Cardiac Allograft Vasculopathy

BackgroundCardiac allograft vasculopathy (CAV) is a major obstacle limiting long-term graft survival. Effective noninvasive surveillance modalities reflecting both coronary artery and microvascular components of CAV are needed.ObjectivesThe authors evaluated the diagnostic performance of dynamic computed tomography–myocardial perfusion imaging (CT-MPI) and coronary computed tomography angiography (CCTA) for CAV.MethodsA total of 63 heart transplantation patients underwent combined CT-MPI and CCTA plus invasive coronary angiography (ICA) with intravascular ultrasonography (IVUS) between December 2018 and October 2021. The median interval between CT-MPI and heart transplantation was 4.3 years. Peak myocardial blood flow (MBF) of the whole myocardium (MBF_global) and minimum MBF (MBF_min) among the 16 segments according to the American Heart Association model, except the left ventricular apex, were calculated from CT-MPI. CCTA was assessed qualitatively, and the degree of coronary artery stenosis was recorded. CAV was diagnosed based on both ICA (ISHLT criteria) and IVUS. Patients were followed up for a median time of 2.3 years after CT-MPI and a median time of 5.7 years after transplantation.ResultsAmong the 63 recipients, 35 (55.6%) had diagnoses of CAV. The median MBF_global and MBF_min were significantly lower in patients with CAV (128.7 vs 150.4 mL/100 mL/min; P = 0.014; and 96.9 vs 122.8 mL/100 mL/min; P < 0.001, respectively). The combined use of coronary artery stenosis on CCTA and MBF_min showed the highest diagnostic performance with an area under the curve of 0.886 (sensitivity: 74.3%, specificity: 96.4%, positive predictive value: 96.3%, and negative predictive value: 75.0%).ConclusionsThe combination of CT-MPI and CCTA demonstrated excellent diagnostic performance for the detection of CAV. One-stop evaluation of the coronary artery and microvascular components involved in CAV using combined CCTA and CT-MPI may be a potent noninvasive screening method for early detection of CAV.     

Fractional Flow Reserve or Optical Coherence Tomography to Guide Management of Angiographically Intermediate Coronary Stenosis: A Single-Center Trial

ObjectivesThe aim of this study was to compare optical coherence tomographic (OCT) guidance and fractional flow reserve (FFR) guidance in patients with angiographically intermediate coronary lesions (AICLs) in a single-center, prospective, 1:1 randomized trial.BackgroundFFR and OCT imaging may help both in the assessment of AICLs and in percutaneous coronary intervention optimization.MethodsPatients with AICLs were randomized to FFR or OCT imaging. In the FFR arm, PCI was performed if FFR was ≤0.80. In the OCT imaging arm, PCI was performed if area stenosis was ≥75% or 50% to 75% with minimal luminal area <2.5 mm² or plaque rupture. Angina (evaluated using the Seattle Angina Questionnaire), major adverse cardiac events, and cost were assessed at the end of follow-up. The pre-defined primary endpoint was the composite of major adverse cardiac events or significant angina (defined as Seattle Angina Questionnaire frequency scale score <90) at 13 months.ResultsA total of 350 patients (with 446 AICLs) were enrolled (176 randomized to FFR and 174 to OCT imaging). The primary endpoint of major adverse cardiac events or significant angina at 13 months occurred in 14.8% of patients in the FFR arm and in 8.0% in the OCT imaging arm (p = 0.048). This result was driven by a statistically nonsignificant lower occurrence of all primary endpoint components. Up to 13 months, the rate of medically managed patients was significantly higher (p < 0.001) and total cost significantly lower (p < 0.001) with FFR in comparison with OCT imaging.ConclusionsIn patients with AICLs, OCT guidance is associated with lower occurrence of the composite of major adverse cardiac events or significant angina. FFR guidance is associated with a higher rate of medical management and lower costs. FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty [FORZA]; NCT01824030)     

Myocardial Flow Reserve and Coronary Calcification in Prognosis of Patients With Suspected Coronary Artery Disease

ObjectivesThe aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).BackgroundAdvances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.MethodsConsecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables.ResultsA total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.)ConclusionsIn this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.     

Coronary Access After TAVR With a Self-Expanding Bioprosthesis: Insights From Computed Tomography

ObjectivesThe authors sought to estimate possible interference of the Medtronic Evolut R/Pro transcatheter heart valve (THV) frame with coronary access using multislice computed tomography (MSCT) data.BackgroundLower-risk patients undergoing transcatheter aortic valve replacement (TAVR) endure a high cumulative risk of coronary events, but coronary access can be challenging.MethodsIn 101 patients who received an Evolut R/Pro THV, post-TAVR MSCT (performed at a median of 30 days after TAVR) was used to assess possible interference of the elements of the THV frame with coronary access.ResultsThe closest cell of the THV frame vertically aligned with the coronary ostium was located opposite the ostium in 58% and 63%, below the ostium in 22% and 30%, or above the ostium in 20% and 7% of left and right coronary arteries, respectively. The free sinus of Valsalva space between the THV frame and the coronary ostium was 0.45 ± 0.17 cm and 0.44 ± 0.17 cm for the left and right coronary arteries, respectively, and showed a stepwise decrease with decreasing THV size (p < 0.001). Bioprosthetic valve commissures were antianatomic (i.e., not aligned with native commissures) in 45 patients (47%), and the commissural post was overlapping a coronary ostium in 15 patients (16%). Two patients (2.0%) had a possible interference of the paravalvular sealing skirt with coronary access.ConclusionsUsing post-TAVR MSCT data, the main mechanism of potential interference of Evolut R/Pro frame with coronary access was an antianatomic commissural post overlapping the coronary ostium.     

CT Perfusion Versus Coronary CT Angiography in Patients With Suspected In-Stent Restenosis or CAD Progression

ObjectivesThe goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard.BackgroundDiagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation.MethodsConsecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses.ResultsIn the 150 enrolled patients (132 men; mean age 65.1 ± 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 ± 1.5 mSv.ConclusionsIn patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard.     

Prediction of Coronary Revascularization in Stable Angina: Comparison of FFRCT With CMR Stress Perfusion Imaging

ObjectivesThis study was designed to compare head-to-head fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFR_CT) and cardiac magnetic resonance (CMR) stress perfusion imaging for prediction of standard-of-care–guided coronary revascularization in patients with stable chest pain and obstructive coronary artery disease by coronary CTA.BackgroundFFR_CT is a novel modality for noninvasive functional testing. The clinical utility of FFR_CT compared to CMR stress perfusion imaging in symptomatic patients with coronary artery disease is unknown.MethodsProspective study of patients (n = 110) with stable angina pectoris and 1 or more coronary stenosis ≥50% by coronary CTA. All patients underwent invasive coronary angiography. Revascularization was FFR-guided in stenoses ranging from 30% to 90%. FFR_CT ≤0.80 in 1 or more coronary artery or a reversible perfusion defect (≥2 segments) by CMR categorized patients with ischemia. FFR_CT and CMR were analyzed by core laboratories blinded for patient management.ResultsA total of 38 patients (35%) underwent revascularization. Per-patient diagnostic performance for identifying standard-of-care–guided revascularization, (95% confidence interval) yielded a sensitivity of 97% (86% to 100%) for FFR_CT versus 47% (31% to 64%) for CMR, p < 0.001; corresponding specificity was 42% (30% to 54%) versus 88% (78% to 94%), p < 0.001; negative predictive value of 97% (91% to 100%) versus 76% (67% to 85%), p < 0.05; positive predictive value of 47% (36% to 58%) versus 67% (49% to 84%), p < 0.05; and accuracy of 61% (51% to 70%) versus 74% (64% to 82%), p > 0.05, respectively.ConclusionsIn patients with stable chest pain referred to invasive coronary angiography based on coronary CTA, FFR_CT and CMR yielded similar overall diagnostic accuracy. Sensitivity for prediction of revascularization was highest for FFR_CT, whereas specificity was highest for CMR.     

Risk Stratification With the Use of Coronary Computed Tomographic Angiography in Patients With Nonobstructive Coronary Artery Disease

ObjectivesThe purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD.BackgroundAmong stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed.MethodsIn PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD.ResultsOf 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007).ConclusionsAdvanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events.     

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

BackgroundIn patients with non–ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease.ObjectivesThe purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS.MethodsThe VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard.ResultsCoronary CTA was conducted in 1,023 patients—very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group.ConclusionsCoronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.     

Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics

ObjectivesThe authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS).BackgroundACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known.MethodsSeventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR_CT], change in FFR_CT across the lesion [△FFR_CT], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR_CT, △FFR_CT, WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC).ResultsThe culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFR_CT and higher △FFR_CT, WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001).ConclusionsNoninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775)     

Utilization and Outcomes of Measuring Fractional Flow Reserve in Patients With Stable Ischemic Heart Disease

BackgroundThe use and clinical outcomes of fractional flow reserve (FFR) measurement in patients with stable ischemic heart disease (SIHD) are uncertain, as prior studies have been based on selected populations.ObjectivesThis study sought to evaluate contemporary, real-world patterns of FFR use and its effect on outcomes among unselected patients with SIHD and angiographically intermediate stenoses.MethodsThe authors used data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program to analyze patients who underwent coronary angiography between January 1, 2009, and September 30, 2017, and had SIHD with angiographically intermediate disease (40% to 69% diameter stenosis on visual inspection). The authors documented trends in FFR utilization and evaluated predictors using generalized mixed models. They applied Cox proportional hazards models to determine the association between an FFR-guided revascularization strategy and all-cause mortality at 1 year.ResultsA total of 17,989 patients at 66 sites were included. The rate of FFR use gradually increased from 14.8% to 18.5% among all patients with intermediate lesions, and from 44% to 75% among patients who underwent percutaneous coronary intervention. One-year mortality was 2.8% in the FFR group and 5.9% in the angiography-only group (p < 0.0001). After adjustment for patient, site-level, and procedural factors, FFR-guided revascularization was associated with a 43% lower risk of mortality at 1 year compared with angiography-only revascularization (hazard ratio: 0.57; 95% confidence interval: 0.45 to 0.71; p < 0.0001).ConclusionsIn patients with SIHD and angiographically intermediate stenoses, use of FFR has slowly risen, and was associated with significantly lower 1-year mortality.     

Mortality Prediction by Quantitative PET Perfusion Expressed as Coronary Flow Capacity With and Without Revascularization

ObjectivesThis study sought to determine the relationship between the severity of reduced quantitative perfusion parameters and mortality with and without revascularization.BackgroundThe physiological mechanisms for differential mortality risk of coronary flow reserve (CFR) and coronary flow capacity (CFC) before and after revascularization are unknown.MethodsGlobal and regional rest-stress (ml/min/g), CFR, their regional per-pixel combination as CFC, and relative stress in ml/min/g were measured as percent of LV in all serial routine 5,274 diagnostic PET scans with systematic follow-up over 10 years (mean 4.2 ± 2.5 years) for all-cause mortality with and without revascularization.ResultsSeverely reduced CFR of 1.0 to 1.5 and stress perfusion ≤1.0 cc/min/g incurred increasing size-dependent risks that were additive because regional severely reduced CFC (CFCsevere) was associated with the highest major adverse cardiac event rate of 80% (p < 0.0001 vs. either alone) and a mortality risk of 14% (vs. 2.3% for no CFCsevere; p = 0.001). Small regions of CFCsevere ≤0.5% predicted high risk (p < 0.0001 vs. no CFCsevere) related to a wave front of border zones at risk around the small most severe center. By receiver-operating characteristic analysis, relative stress topogram maps of stress (ml/min/g) as a fraction of LV defined these border zones at risk or for mildly reduced CFC (area under the curve [AUC]: 0.69) with a reduced relative tomographic subendocardial-to-subepicardial ratio. CFCsevere incurred the highest mortality risk that was reduced by revascularization (p = 0.005 vs. no revascularization) for artery-specific stenosis not defined by global CFR or stress perfusion alone.ConclusionsCFC is associated with the size-dependent highest mortality risk resulting from the additive risk of CFR and stress (ml/min/g) that is significantly reduced after revascularization, a finding not seen for global CFR. Small regions of CFCsevere ≤0.5% of LV also carry a high risk because of the surrounding border zones at risk defined by relative stress perfusion and a reduced relative subendocardial-to-subepicardial ratio.