Clinical Likelihood Prediction of Hemodynamically Obstructive Coronary Artery Disease in Patients With Stable Chest Pain.

BACKGROUND: Selection for invasive angiography is recommended to be based on pretest probabilities (PTPs), and physiological measures of hemodynamical impairment by, for example, fractional flow reserve (FFR) should guide revascularization. The risk factor-weighted clinical likelihood (RF-CL) and coronary artery calcium score-weighted clinical likelihood (CACS-CL) models show superior discrimination of patients with suspected obstructive coronary artery disease (CAD), but validation against hemodynamic impairment is warranted. OBJECTIVES: The aim of this study was to validate the RF-CL and CACS-CL models against hemodynamically obstructive CAD. METHODS: Stable de novo chest pain patients (N = 4,371) underwent coronary computed tomography angiography and subsequently invasive coronary angiography with FFR measurements. Hemodynamically obstructive CAD was defined as invasive FFR ≤0.80 or high-grade stenosis by visual assessment (>90% diameter stenosis). For comparison, a guideline-endorsed basic PTP model was calculated based on age, sex, and symptom typicality. The RF-CL model additionally included the number of risk factors, and the CACS-CL model incorporated the coronary artery calcium score into the RF-CL. RESULTS: In total, 447 of 4,371 (10.9%) patients had hemodynamically obstructive CAD. Both the RF-CL and CACS-CL models classified more patients with a very low clinical likelihood (≤5%) of obstructive CAD compared to the basic PTP model (33.0% and 53.7% vs 12.0%; P < 0.001) with a preserved low prevalence of hemodynamically obstructive CAD (<5% for all models). Against hemodynamically obstructive CAD, calibration and discrimination of the RF-CL and CACS-CL models were superior to the basic PTP model. CONCLUSIONS: The RF-CL and CACS-CL models are well calibrated and superior to a currently recommended basic PTP model to predict hemodynamically obstructive CAD. (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease [Dan-NICAD]; NCT02264717; Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 [Dan-NICAD 2]; NCT03481712, Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 3 [Dan-NICAD 3]; NCT04707859).

Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial.

BACKGROUND AND OBJECTIVES: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. METHODS: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. RESULTS: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). CONCLUSIONS: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02673424.

Invasive fractional-flow-reserve prediction by coronary CT angiography using artificial intelligence vs. computational fluid dynamics software in intermediate-grade stenosis.

Coronary computed angiography (CCTA) with non-invasive fractional flow reserve (FFR) calculates lesion-specific ischemia when compared with invasive FFR and can be considered for patients with stable chest pain and intermediate-grade stenoses according to recent guidelines. The objective of this study was to compare a new CCTA-based artificial-intelligence deep-learning model for FFR prediction (FFRAI) to computational fluid dynamics CT-derived FFR (FFRCT) in patients with intermediate-grade coronary stenoses with FFR as reference standard. The FFRAI model was trained with curved multiplanar-reconstruction CCTA images of 500 stenotic vessels in 413 patients, using FFR measurements as the ground truth. We included 37 patients with 39 intermediate-grade stenoses on CCTA and invasive coronary angiography, and with FFRCT and FFR measurements in this retrospective proof of concept study. FFRAI was compared with FFRCT regarding the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for predicting FFR ≤ 0.80. Sensitivity, specificity, PPV, NPV, and diagnostic accuracy of FFRAI in predicting FFR ≤ 0.80 were 91% (10/11), 82% (23/28), 67% (10/15), 96% (23/24), and 85% (33/39), respectively. Corresponding values for FFRCT were 82% (9/11), 75% (21/28), 56% (9/16), 91% (21/23), and 77% (30/39), respectively. Diagnostic accuracy did not differ significantly between FFRAI and FFRCT (p = 0.12). FFRAI performed similarly to FFRCT for predicting intermediate-grade coronary stenoses with FFR ≤ 0.80. These findings suggest FFRAI as a potential non-invasive imaging tool for guiding therapeutic management in these stenoses.

Longitudinal Evaluation of Coronary Arteries and Myocardium in Breast Cancer Using Coronary Computed Tomographic Angiography.

BACKGROUND: The association of coronary computed tomography angiography (CTA) and left ventricular (LV) myocardium measurements with cancer therapy-related cardiac dysfunction (CTRCD) is limited. OBJECTIVES: In this study, the authors sought to evaluate the changes in coronary arteries and LV myocardium in patients with left breast cancer (BC) receiving anthracycline with or without radiotherapy, with the use of coronary CTA. METHODS: Participants with left BC receiving anthracycline with or without radiotherapy were prospectively included. All participants underwent coronary CTA before and after treatment, including nonenhanced calcium-scoring scan, computed tomography angiography, and dual-energy late enhancement scan. Computed tomographic fractional flow reserve (CT-FFR), pericoronary adipose tissue (PCAT) CT attenuation, and LV segments' extracellular volume (ECV) before and after treatment were compared. Logistic regression analysis was used to assess the association between baseline coronary CTA parameters and CTRCD. RESULTS: Eighty participants receiving anthracycline and 59 participants receiving anthracycline with radiotherapy were included. CT-FFR decreased and PCAT CT attenuation and LV global and segments' ECV increased after treatment (all P < 0.05). After chemoradiotherapy, CT-FFR was lower and PCAT CT attenuation and LV myocardial ECV were higher than after chemotherapy. Twenty-four participants developed CTRCD. After adjustment by Heart Failure Association-International Cardio-Oncology Society risk in multivariable logistic regression analysis, baseline stenosis of the left anterior descending artery (LAD) (OR: 1.987 [95% CI: 1.322-2.768]; P = 0.021), left circumflex artery (LCX) (OR: 1.895 [95% CI: 1.281-2.802]; P = 0.031), and right coronary artery (RCA) (OR: 1.920 [95% CI: 1.405-2.811]; P = 0.028), and baseline CT-FFR of the LAD (OR: 3.425 [95% CI: 1.621-9.434]; P < 0.001), LCX (OR: 2.058 [95% CI: 1.030-5.076]; P = 0.006), and RCA (OR: 2.469 [95% CI: 1.232-6.944]; P = 0.004) were associated with CTRCD. CONCLUSIONS: Multiparameter coronary CTA contributes to comprehensive assessment of the coronary arteries and myocardium in patients with left BC receiving anthracycline with or without radiotherapy. Baseline coronary artery stenosis and CT-FFR might be imaging markers for predicting CTRCD in these patients.

Accuracy of subtraction fractional flow reserve with computed tomography in identifying early revascularization in patients with coronary artery disease.

OBJECTIVES: The diagnostic performance of fractional flow reserve with computed tomography (FFR-CT) is affected by the presence of calcified plaque. Subtraction can remove the influence of calcification in coronary computed tomography angiography (CCTA) to increase confidence in the diagnosis of coronary artery stenosis. Our purpose is to investigate the accuracy of post-subtraction FFR-CT in predicting early revascularization. DESIGN: Based on CCTA data of 237 vessels from 79 patients with coronary artery disease, subtraction CCTA images were obtained at a local post-processing workstation, and the conventional and post-subtraction FFR-CT measurements and the difference in proximal and distal FFR-CT values of the narrowest segment of the vessel (ΔFFR-CT) were analyzed for their accuracy in predicting early coronary artery hemodynamic reconstruction. RESULTS: With FFR-CT ≤ 0.8 as the criterion, the accuracy of conventional and post-subtraction FFR-CT measurements in predicting early revascularization was 73.4% and 77.2% at the patient level, and 64.6% and 72.2% at the vessel level, respectively. The specificity of post-subtraction FFR-CT measurements was significantly higher than that of conventional FFR-CT at both the patient and vessel levels (P of 0.013 and 0.015, respectively). At the vessel level, the area under the curve of receiver operating characteristic was 0.712 and 0.797 for conventional and post-subtraction ΔFFR-CT, respectively, showing a difference (P = 0.047), with optimal cutoff values of 0.07 and 0.11, respectively. CONCLUSION: The post-subtraction FFR-CT measurements enhance the specificity in predicting early revascularization. The post-subtraction ΔFFR-CT value of the stenosis segment > 0.11 may be an important indicator for early revascularization.

Pd/Pa fluctuation with continuous ATP administration indicates inaccurate FFR measurement caused by insufficient hyperemia.

Continuous intravenous adenosine triphosphate (ATP) administration is the standard method for inducing maximal hyperemia in fractional flow reserve (FFR) measurements. Several cases have demonstrated fluctuations in the ratio of mean distal coronary pressure to mean arterial pressure (Pd/Pa) value during ATP infusion, which raised our suspicions of FFR value inaccuracy. This study aimed to investigate our hypothesis that Pd/Pa fluctuations may indicate inaccurate FFR measurements caused by insufficient hyperemia. We examined 57 consecutive patients with angiographically intermediate coronary lesions who underwent fractional flow reverse (FFR) measurements in our hospital between November 2016 and September 2018. Pd/Pa was measured after continuous ATP administration (150 µg/kg/min) via a peripheral forearm vein for 5 min (FFRA); and we analyzed the FFR value variation in the final 20 s of the 5 min, defining 'Fluctuation' as variation range > 0.03. Then, 2 mg of nicorandil was administered into the coronary artery during continued ATP infusion, and the Pd/Pa was remeasured (FFRA+N). Fluctuations were observed in 23 of 57 patients. The cases demonstrating discrepancies of > 0.05 between FFRA and FFRA+N were observed more frequently in the fluctuation group than in the non-fluctuation group (12/23 vs. 1/34; p < 0.0001). The discrepancy between FFRA and FFRA+N values was smaller in the non-fluctuation group (mean difference ± SD; -0.00026 ± 0.04636 vs. 0.02608 ± 0.1316). Pd/Pa fluctuation with continuous ATP administration could indicate inaccurate FFR measurements caused by incomplete hyperemia. Additional vasodilator administration may achieve further hyperemia when Pd/Pa fluctuations are observed.

Modeling cardiac microcirculation for the simulation of coronary flow and 3D myocardial perfusion.

Accurate modeling of blood dynamics in the coronary microcirculation is a crucial step toward the clinical application of in silico methods for the diagnosis of coronary artery disease. In this work, we present a new mathematical model of microcirculatory hemodynamics accounting for microvasculature compliance and cardiac contraction; we also present its application to a full simulation of hyperemic coronary blood flow and 3D myocardial perfusion in real clinical cases. Microvasculature hemodynamics is modeled with a compliant multi-compartment Darcy formulation, with the new compliance terms depending on the local intramyocardial pressure generated by cardiac contraction. Nonlinear analytical relationships for vessels distensibility are included based on experimental data, and all the parameters of the model are reformulated based on histologically relevant quantities, allowing a deeper model personalization. Phasic flow patterns of high arterial inflow in diastole and venous outflow in systole are obtained, with flow waveforms morphology and pressure distribution along the microcirculation reproduced in accordance with experimental and in vivo measures. Phasic diameter change for arterioles and capillaries is also obtained with relevant differences depending on the depth location. Coronary blood dynamics exhibits a disturbed flow at the systolic onset, while the obtained 3D perfusion maps reproduce the systolic impediment effect and show relevant regional and transmural heterogeneities in myocardial blood flow (MBF). The proposed model successfully reproduces microvasculature hemodynamics over the whole heartbeat and along the entire intramural vessels. Quantification of phasic flow patterns, diameter changes, regional and transmural heterogeneities in MBF represent key steps ahead in the direction of the predictive simulation of cardiac perfusion.

Non-invasive fractional flow reserve estimation in coronary arteries using angiographic images.

Coronary artery disease is the leading global cause of mortality and Fractional Flow Reserve (FFR) is widely regarded as the gold standard for assessing coronary artery stenosis severity. However, due to the limitations of invasive FFR measurements, there is a pressing need for a highly accurate virtual FFR calculation framework. Additionally, it's essential to consider local haemodynamic factors such as time-averaged wall shear stress (TAWSS), which play a critical role in advancement of atherosclerosis. This study introduces an innovative FFR computation method that involves creating five patient-specific geometries from two-dimensional coronary angiography images and conducting numerical simulations using computational fluid dynamics with a three-element Windkessel model boundary condition at the outlet to predict haemodynamic distribution. Furthermore, four distinct boundary condition methodologies are applied to each geometry for comprehensive analysis. Several haemodynamic features, including velocity, pressure, TAWSS, and oscillatory shear index are investigated and compared for each case. Results show that models with average boundary conditions can predict FFR values accurately and observed errors between invasive FFR and virtual FFR are found to be less than 5%.

Intentional coronary revascularization versus conservative therapy in patients after peripheral artery revascularization due to critical limb ischemia: the INCORPORATE trial.

OBJECTIVES: INCORPORATE trial was designed to evaluate whether default coronary-angiography (CA) and ischemia-targeted revascularization is superior compared to a conservative approach for patients with treated critical limb ischemia (CLI). Registered at clinicaltrials.gov (NCT03712644) on October 19, 2018. BACKGROUND: Severe peripheral artery disease is associated with increased cardiovascular risk and poor outcomes. METHODS: INCORPORATE was an open-label, prospective 1:1 randomized multicentric trial that recruited patients who had undergone successful CLI treatment. Patients were randomized to either a conservative or invasive approach regarding potential coronary artery disease (CAD). The conservative group received optimal medical therapy alone, while the invasive group had routine CA and fractional flow reserve-guided revascularization. The primary endpoint was myocardial infarction (MI) and 12-month mortality. RESULTS: Due to COVID-19 pandemic burdens, recruitment was halted prematurely. One hundred eighty-five patients were enrolled. Baseline cardiac symptoms were scarce with 92% being asymptomatic. Eighty-nine patients were randomized to the invasive approach of whom 73 underwent CA. Thirty-four percent had functional single-vessel disease, 26% had functional multi-vessel disease, and 90% achieved complete revascularization. Conservative and invasive groups had similar incidences of death and MI at 1 year (11% vs 10%; hazard ratio 1.21 [0.49-2.98]). Major adverse cardiac and cerebrovascular events (MACCE) trended for hazard in the Conservative group (20 vs 10%; hazard ratio 1.94 [0.90-4.19]). In the per-protocol analysis, the primary endpoint remained insignificantly different (11% vs 7%; hazard ratio 2.01 [0.72-5.57]), but the conservative approach had a higher MACCE risk (20% vs 7%; hazard ratio 2.88 [1.24-6.68]). CONCLUSION: This trial found no significant difference in the primary endpoint but observed a trend of higher MACCE in the conservative arm.

Temporal changes in CT-derived fractional flow reserve in patients after heart transplantation.

BACKGROUND: Adding functional information by CT-derived fractional flow reserve (FFRct) to coronary CT angiography (CCTA) and assessing its temporal change may provide insight into the natural history and physiopathology of cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients. We assessed FFRct changes as well as CAV progression over a 2-year period in HTx patients undergoing serial CT imaging. METHODS: HTx patients from Erasmus MC and Mount Sinai Hospital, who had consecutive CCTAs 2 years apart were evaluated. FFRct analysis was performed for both scans. FFRct values at the most distal point in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) were measured after precisely matching the anatomical locations in both analyses. Also, the number of anatomical coronary stenoses of > 30% was scored. RESULTS: In total, 106 patients (median age 57 [interquartile range 47-67] years, 67% male) at 9 [6-13] years after HTx at the time of the baseline CCTA were included. Median distal FFRct values significantly decreased from baseline to follow-up for the LAD from 0.85 [0.79-0.90] to 0.84 [0.76-0.90] (p = 0.001), LCX from 0.92 [0.88-0.96] to 0.91 [0.85-0.95] (p = 0.009), and RCA from 0.92 [0.86-0.95] to 0.90 [0.86-0.94] (p = 0.004). The number of focal anatomical stenoses of > 30% increased from a median of 1 [0-2] at baseline to 2 [0-3] at follow-up (p = 0.009). CONCLUSIONS: The distal coronary FFRct values in post-HTX patients in each of the three major coronary arteries decreased, and the number of focal coronary stenoses increased over a 2-year period. Temporal FFRct change rate may become an additional parameter in the follow-up of HTx patients, but more research is needed to elucidate its role. CLINICAL RELEVANCE STATEMENT: CT-derived fractional flow reserve (FFRct) is important post-heart transplant because of additional information on coronary CT angiography for cardiac allograft vasculopathy (CAV) detection. The decrease and degree of reduction in distal FFRct value may indicate progression in anatomic CAV burden. KEY POINTS: CT-derived fractional flow reserve (FFRct) is important for monitoring cardiac allograft vasculopathy (CAV) in heart transplant patients. Over time, transplant patients showed a decrease in distal FFRct and an increase in coronary stenoses. Temporal changes in FFRct could be crucial for transplant follow-up, aiding in CAV detection.

Cardiovascular Imaging for Coronary Artery Disease in Patients with Diabetes Mellitus.

In patients with diabetes mellitus, accelerated progression of atherosclerosis can lead to worse clinical outcomes. Determining the best diagnostic strategy to identify patients with increased cardiovascular risk is challenging. Current guidelines recommend using both functional imaging and CT angiography to detect myocardial ischemia and coronary artery disease based on pre-test probability. Functional imaging is suggested for patients with a higher clinical likelihood due to its higher rule-in diagnostic capacity. On the other hand, CT angiography is preferred for patients with lower pre-test probability because of its excellent negative predictive value. The optimal management strategy for asymptomatic diabetic patients remains unclear. In asymptomatic diabetic patients, previous randomized trials have not shown benefits from diagnostic testing over standard care. However, these trials were methodologically inconsistent and lacked clear stratification of cardiovascular risk. In terms of invasive evaluation, a combined invasive functional and anatomic imaging approach for angiographically intermediate coronary stenosis appears to be the best, most effective decision pathway for managing diabetic patients.

Rapid and Precise Computation of Fractional Flow Reserve from Routine Two-Dimensional Coronary Angiograms Based on Fluid Mechanics: The Pilot FFR2D Study.

Objective: To present a novel pipeline for rapid and precise computation of fractional flow reserve from an analysis of routine two-dimensional coronary angiograms based on fluid mechanics equations (FFR2D). Material and methods: This was a pilot analytical study that was designed to assess the diagnostic performance of FFR2D versus the gold standard of FFR (threshold ≤ 0.80) measured with a pressure wire for the physiological assessment of intermediate coronary artery stenoses. In a single academic center, consecutive patients referred for diagnostic coronary angiography and potential revascularization between 1 September 2020 and 1 September 2022 were screened for eligibility. Routine two-dimensional angiograms at optimal viewing angles with minimal overlap and/or foreshortening were segmented semi-automatically to derive the vascular geometry of intermediate coronary lesions, and nonlinear pressure-flow mathematical relationships were applied to compute FFR2D. Results: Some 88 consecutive patients with a single intermediate coronary artery lesion were analyzed (LAD n = 74, RCA n = 9 and LCX n = 5; percent diameter stenosis of 45.7 ± 11.0%). The computed FFR2D was on average 0.821 ± 0.048 and correlated well with invasive FFR (r = 0.68, p < 0.001). There was very good agreement between FFR2D and invasive-wire FFR with minimal measurement bias (mean difference: 0.000 ± 0.048). The overall accuracy of FFR2D for diagnosing a critical epicardial artery stenosis was 90.9% (80 cases classified correctly out of 88 in total). FFR2D identified 24 true positives, 56 true negatives, 4 false positives, and 4 false negatives and predicted FFR ≤ 0.80 with a sensitivity of 85.7%, specificity of 93.3%, positive likelihood ratio of 13.0, and negative likelihood ratio of 0.15. FFR2D had a significantly better discriminatory capacity (area under the ROC curve: 0.95 [95% CI: 0.91-0.99]) compared to 50%DS on 2D-QCA (area under the ROC curve: 0.70 [95% CI: 0.59-0.82]; p = 0.0001) in predicting wire FFR ≤ 0.80. The median time of image analysis was 2 min and the median time of computation of the FFR2D results was 0.1 s. Conclusion: FFR2D may rapidly derive a precise image-based metric of fractional flow reserve with high diagnostic accuracy based on a single two-dimensional coronary angiogram.

Simulation of coronary fractional flow reserve and whole-cycle flow based on optical coherence tomography in individual patients with coronary artery disease.

Computer simulations of coronary fractional flow reserve (FFR) based on coronary imaging have emerged as an attractive alternative to invasive measurements. However, most methods are proprietary and employ non-physiological assumptions. Our aims were to develop and validate a physiologically realistic open-source simulation model for coronary flow, and to use this model to predict FFR based on intracoronary optical coherence tomography (OCT) data in individual patients. We included patients undergoing elective coronary angiography with angiographic borderline coronary stenosis. Invasive measurements of coronary hyperemic pressure and absolute flow and OCT imaging were performed. A computer model of coronary flow incorporating pulsatile flow and the effect of left ventricular contraction was developed and calibrated, and patient-specific flow simulation was performed. Forty-eight coronary arteries from 41 patients were included in the analysis. Average FFR was 0.79 ± 0.14, and 50% had FFR ≤ 0.80. Correlation between simulated and measured FFR was high (r = 0.83, p < 0.001). Average difference between simulated FFR and observed FFR in individual patients was - 0.009 ± 0.076. Overall diagnostic accuracy for simulated FFR ≤ 0.80 in predicting observed FFR ≤ 0.80 was 0.88 (0.75-0.95) with sensitivity 0.79 (0.58-0.93) and specificity 0.96 (0.79-1.00). The positive predictive value was 0.95 (0.75-1.00) and the negative predictive value was 0.82 (0.63-0.94). In conclusion, realistic simulations of whole-cycle coronary flow can be produced based on intracoronary OCT data with a new, computationally simple simulation model. Simulated FFR had moderate numerical agreement with observed FFR and a good diagnostic accuracy for predicting hemodynamic significance of coronary stenoses.

Increasing the rate of datasets amenable to CTFFR and quantitative plaque analysis: Value of software for reducing stair-step artifacts demonstrated in photon-counting detector CT.

Purpose: To determine the value of an algorithm for reducing stair-step artifacts for advanced coronary analyses in sequential mode coronary CT angiography (CCTA). Methods: Forty patients undergoing sequential mode photon-counting detector CCTA with at least one stair-step artifact were included. Twenty patients (14 males; mean age 57±17years) with 45 segments showing stair-step artifacts and without atherosclerosis were included for CTFFR analysis. Twenty patients (20 males; mean age 74±13years) with 22 segments showing stair-step artifacts crossing an atherosclerotic plaque were included for quantitative plaque analysis. Artifacts were graded, and CTFFR and quantitative coronary plaque analyses were performed in standard reconstructions and in those reconstructed with a software (entitled ZeeFree) for artifact reduction. Results: Stair-step artifacts were significantly reduced in ZeeFree compared to standard reconstructions (p<0.05). In standard reconstructions, CTFFR was not feasible in 3/45 (7 %) segments but was feasible in all ZeeFree reconstructions. In 9/45 (20 %) segments without atherosclerosis, the ZeeFree algorithm led to a change of CTFFR values from pathologic in standard to physiologic values in ZeeFree reconstructions. In one segment (1/22, 5 %), quantitative plaque analysis was not feasible in standard but only in ZeeFree reconstruction. The mean overall plaque volume (111±60 mm3), the calcific (77±47 mm3), fibrotic (31±28 mm3), and lipidic (4±3 mm3) plaque components were higher in standard than in ZeeFree reconstructions (overall 75±50 mm3, p<0.001; calcific 51±42 mm3, p<0.001; fibrotic 22±19 mm3, p<0.05; lipidic 3±3 mm3, p=0.055). Conclusion: Despite the lack of reference standard modalities for CTFFR and coronary plaque analysis, initial evidence indicates that an algorithm for reducing stair-step artifacts in sequential mode CCTA increases the rate and quality of datasets amenable to advanced coronary artery analysis, hereby potentially improving patient management.

The pressure-derived microvascular resistance reserve and its correlation to Doppler MRR measurement-a proof of concept study.

Background: Microvascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from coronary flow reserve (CFR) assessment, provided that intracoronary pressure data are also available. The previously proposed pressure-bounded CFR (CFRpb) defines the possible CFR interval on the basis of resting and hyperemic pressure gradients in the epicardial vessel, however, its correlation to the Doppler wire measurement was reported to be rather poor without the correction for hydrostatic pressure. Purpose: We aimed to determine the pressure-bounded coronary MRR interval with hydrostatic pressure correction according to the previously established equations of CFRpb adapted for the MRR concept. Furthermore, we also aimed to design a prediction model using the actual MRR value within the pressure-bounded interval and validate the results against the gold-standard Doppler wire technique. Methods: Hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. In the derivation cohort the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined solely from hydrostatic pressure-corrected intracoronary pressure data. The actual MRR was calculated by simple hemodynamic equations incorporating the anatomical data of the three-dimensionally reconstructed coronary artery (MRRp-3D). These results were analyzed by regression analyses to find relations between the MRRpb bounds and the actual MRRp-3D. Results: In the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpbmax and MRRp-3D (r 2 = 0.74, p < 0.0001). Using this relation (MRRp-3D = 1.04 + 0.51 × MRRpbmax), the linear prediction of the MRR was tested in the validation cohort of 19 measurements against the gold standard Doppler wire technique. A significant correlation was found between the linearly predicted and the measured values (r = 0.54, p = 0.01). If the area stenosis (AS%) was included to a quadratic prediction model, the correlation was improved (r = 0.63, p = 0.004). Conclusions: The MRR can be predicted reliably to assess microvascular function by our simple model. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement provides a simultaneous physiological assessment of the macro- and microvasculature.

The Plaque Analysis Classifies the Coronary Artery Disease-Reporting and Data System (CAD-RADS) Stenosis and Plaque Burden Categories: Association of the Plaque Features, Fat Attenuation Index, Coronary Computed Tomography Fractional Flow Reserve, and the Combination of Stenosis and Calcification.

BACKGROUND: The coronary artery disease-reporting and data system (CAD-RADS) 2.0 is used to standardize the reporting of coronary computed tomography angiography (CCTA) results. Artificial intelligence software can quantify the plaque composition, fat attenuation index, and fractional flow reserve. OBJECTIVE: To analyze plaque features of varying severity in patients with a combination of CAD-RADS stenosis and plaque burden categorization and establish a random forest classification model. METHODS: The data of 100 patients treated between April 2021 and February 2022 were retrospectively collected. The most severe plaque observed in each patient was the target lesion. Patients were categorized into three groups according to CAD-RADS: CAD-RADS 1-2 + P0-2, CAD-RADS 3-4B + P0-2, and CAD-RADS 3-4B + P3-4. Differences and correlations between variables were assessed between groups. AUC, accuracy, precision, recall, and F1 score were used to evaluate the diagnostic performance. RESULTS: A total of 100 patients and 178 arteries were included. The differences of computed tomography fractional flow reserve (CT-FFR) (H = 23.921, p < 0.001), the volume of lipid component (H = 12.996, p = 0.002), the volume of fibro-lipid component (H = 8.692, p = 0.013), the proportion of lipid component volume (H = 22.038, p < 0.001), the proportion of fibro-lipid component volume (H = 11.731, p = 0.003), the proportion of calcification component volume (H = 11.049, p = 0.004), and plaque type (χ2 = 18.110, p = 0.001) was statistically significant. CONCLUSION: CT-FFR, volume and proportion of lipid and fibro-lipid components of plaques, the proportion of calcified components, and plaque type were valuable for CAD-RADS stenosis + plaque burden classification, especially CT-FFR, volume, and proportion of lipid and fibro-lipid components. The model built using the random forest was better than the clinical model (AUC: 0.874 vs. 0.647).

Cardiac computed tomography-derived coronary artery volume to myocardial mass in patients with severe coronary artery disease.

BACKGROUND: Coronary artery lumen volume (V) to myocardial mass (M) ratio (V/M) can show the mismatch between epicardial coronary arteries and the underlying myocardium. METHODS: The V, M and V/M were obtained from the coronary computed tomography angiography (CCTA) of patients in the FAST-TRACK CABG study, the first-in-human trial of coronary artery bypass grafting (CABG) guided solely by CCTA and fractional flow reserve derived from CCTA (FFRCT) in patients with complex coronary artery disease (CAD). The correlations between V/M ratios and baseline characteristics were determined and compared with those from the ADVANCE registry, an unselected cohort of historical controls with chronic CAD. RESULTS: The V/M ratio was obtained in 106 of the 114 pre-CABG CCTAs. Mean age was 65.6 years and 87% of them were male. The anatomical SYNTAX score from CCTA was significantly higher than the functional SYNTAX score derived using FFRCT [43.1 (15.2) vs 41.1 (16.5), p â€‹< â€‹0.001]. Mean V, M, and V/M were 2204 â€‹mm3, 137 â€‹g, and 16.5 â€‹mm3/g, respectively. There were weak negative correlations between V and anatomical and functional SYNTAX scores (Pearson's r â€‹= â€‹-0.26 and -0.34). V and V/M had a strong correlation (r â€‹= â€‹0.82). The V/M ratio in the current study was significantly lower than that in the ADVANCE registry (median 16.1 vs. 24.8 [1st quartile 20.1]). CONCLUSION: Systematically smaller V/M ratios were found in this population with severe CAD requiring CABG compared to an unselected cohort with chronic CAD. The V/M ratio could provide additional non-invasive assessment of CAD especially when combined with FFRCT.

Sex Differences in Coronary Artery Disease Characteristics Among Patients With Type 2 Myocardial Infarction.

Background: Type 2 myocardial infarction (MI) results from coronary supply and demand imbalance and has a poor prognosis. It is crucial to identify potential sex-based differences in the prevalence and nature of coronary artery disease (CAD) within this population. Objectives: The purpose of this study was to evaluate sex-based disease differences in type 2 MI among patients evaluated with coronary computed tomography angiography and fractional flow reserve. Methods: In a single-center, prospective study, patients with strictly adjudicated type 2 MI underwent coronary computed tomography angiography with fractional flow reserve. Results: Among 50 study participants enrolled, 50% were women. A similar mix of MI precipitants was present in both sexes. ST-segment depression was more common in women (64% vs 32%), while men were more likely to have T wave inversion (68% vs 36%). Women and men had comparable coronary artery calcium scores (median: 152 [Q1, Q3: 45, 762] vs 234 [Q1, Q3: 56, 422]). Prevalence of any CAD (84% vs 100%), obstructive CAD (24% vs 28%), and hemodynamically significant focal stenosis (20% vs 32%) were similar between sexes. Total plaque volume was similar between sexes, but women had significantly lower levels of low-attenuation plaque (median: 3 [Q1, Q3: 1, 7] vs 9 [Q1, Q3: 3, 14]). Conclusions: Among patients with type 2 MI, prevalence of any CAD and obstructive CAD did not differ according to sex. Total plaque volume was similar between sexes, but women had a lower volume of low-attenuation plaque (DEFINing the PrEvalence and Characteristics of Coronary Artery Disease Among Patients With TYPE 2 Myocardial Infarction Using CT-FFR [DEFINE TYPE2MI]; NCT04864119).

Additional prognostic impact of plaque characterization with on-site CT-derived fractional flow reserve in coronary CT angiography.

BACKGROUND: On-site computed tomography-derived fractional flow reserve (CT-FFR) is a feasible method for examining lesion-specific ischemia, and plaque analysis of coronary CT angiography (CCTA) is useful for predicting future cardiac events. However, their utility and association on a per-vessel level remain unclear. METHODS: We analyzed vessels showing 50-90 % stenosis on CCTA where planned revascularization was not performed after CCTA within 90 days. Relevant features, including CT-FFR and the plaque burden [necrotic core to the total plaque volume (% necrotic core), and non-calcified plaque (NCP) to vessel volume (% NCP)] using a novel algorithm for analyzing plaque to predict vessel-oriented composite outcomes (VOCO), including cardiac death, non-fatal myocardial infarction, and unplanned vessel-related revascularization, were assessed. RESULTS: In 256 patients (68.7 ±â€¯9.4 years; 73.8 % male) with 354 vessels (10.5 % CT-FFR ≤ 0.80), VOCO occurred in 24 vessels (6.8 %) during a median follow-up of 3.6 years. Multivariable Cox analysis revealed CT-FFR ≤ 0.80 had the pronounced impact on VOCO, and moreover, higher % necrotic core and % NCP were independently associated with VOCO [adjusted hazard ratio 3.43 (95 % confidence interval 1.42-8.29) and 4.05 (1.19-13.71), respectively], especially for vessels with CT-FFR > 0.80. CONCLUSIONS: In vessels without planned revascularization, per-vessel CT-FFR ≤ 0.80 was the notable predictor of future cardiac events. Additionally, necrotic core volume and NCP were identified as independent predictors along with CT-FFR.