Angiography-based Fractional Flow Reserve for the Prediction of Clinical Outcomes After Drug-coated Balloon or Plain Old Balloon Angioplasty.

BACKGROUND: AccuFFRangio is a novel method for fast computation of fractional flow reserve (FFR) based on coronary angiography and computational fluid dynamics. The association between the AccuFFRangio and clinical outcomes after drug-coated balloon (DCB) or plain old balloon angioplasty (POBA) remains to be investigated. METHODS: This study included consecutive patients who underwent balloon angioplasty from December 2016 to October 2020. AccuFFRangio was calculated retrospectively based on the post-procedural angiography obtained immediately after angioplasty. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, vessel-related myocardial infarction, and repeat target vessel revascularization. RESULTS: A total of 169 patients were retrospectively analyzed in this study. Post-procedural AccuFFRangio (hazard ratio [HR] per 0.1 increase 0.33, 95% confidence interval [CI] 0.22-0.48, p < 0.001) was an independent predictor for MACE at 2-year follow-up. Post-procedural AccuFFRangio ≤ 0.87 was determined as the optimal cutoff value to predict MACE with an area under the curve (AUC) of 0.872 (95% CI 0.813-0.919, p < 0.001). CONCLUSIONS: AccuFFRangio measured immediately after balloon angioplasty is a promising predictor of unfavorable clinical outcomes.

Transcriptional regulation of TacL-mediated lipoteichoic acids biosynthesis by ComE during competence impacts pneumococcal transformation.

Competence development is essential for bacterial transformation since it enables bacteria to take up free DNA from the surrounding environment. The regulation of teichoic acid biosynthesis is tightly controlled during pneumococcal competence; however, the mechanism governing this regulation and its impact on transformation remains poorly understood. We demonstrated that a defect in lipoteichoic acid ligase (TacL)-mediated lipoteichoic acids (LTAs) biosynthesis was associated with impaired pneumococcal transformation. Using a fragment of tacL regulatory probe as bait in a DNA pulldown assay, we successfully identified several regulatory proteins, including ComE. Electrophoretic mobility shift assays revealed that phosphomimetic ComE, but not wild-type ComE, exhibited specific binding to the probe. DNase I footprinting assays revealed the specific binding sequences encompassing around 30 base pairs located 31 base pairs upstream from the start codon of tacL. Expression of tacL was found to be upregulated in the ΔcomE strain, and the addition of exogenous competence-stimulating peptide repressed the tacL transcription in the wild-type strain but not the ΔcomE mutant, indicating that ComE exerted a negative regulatory effect on the transcription of tacL. Mutation in the JH2 region of tacL upstream regulatory sequence led to increased LTAs abundance and displayed higher transformation efficiency. Collectively, our work identified the regulatory mechanisms that control LTAs biosynthesis during competence and thereby unveiled a repression mechanism underlying pneumococcal transformation.

The protease caspase-1: Activation pathways and functions.

Caspase-1 is one of the main mediators of inflammatory caspases and has become a correspondent with inflammation, cell death, and several inflammatory diseases. In this review, we systematically summarize both original and recent advances in caspase-1 to provide references for a better understanding of the molecular mechanisms in its activation and functions. This study investigates and summarizes the published articles concerning caspase-1, inflammation, pyroptosis, apoptosis, and cell death by searching academic search systems, including the PubMed, Web of Science, and Google Scholar. Caspase-1 is one of the main mediators of inflammatory caspases and has become a correspondent with inflammation and cell death. In cell death, caspase-1 was originally found to cause apoptosis in fibroblasts. Importantly, caspase-1 was later reported to execute programmed cell death, including pyroptosis and apoptosis, in many immune cells in response to diverse stimuli. It is widely established that different pathways can activate caspase-1 and subsequently mediate cell death and inflammation. It has become increasingly clear that caspase-1 is responsible for the initiation and control of pyroptosis, apoptosis, and inflammation in addition to its well-known function in cleaving IL-1ß. The significant advancement in the understanding of caspase-1-controlled cell death and novel substrates inspires new therapeutic approaches in the future.

Hemodynamic assessment for intracranial atherosclerosis from angiographic images: a clinical validation study.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of ischemic stroke. Conventional anatomical analysis by CT angiography, MRI, or digital subtraction angiography can provide valuable information on the anatomical changes of stenosis; however, they are not sufficient to accurately evaluate the hemodynamic severity of ICAS. The goal of this study was to assess the diagnostic performance of the pressure ratio across intracranial stenoses (termed as fractional flow (FF)) derived from cerebral angiography for the diagnosis of hemodynamically significant ICAS defined by pressure wire-derived FF. METHODS: This retrospective study represents a feasible and reliable method for calculating the FF from cerebral angiography (AccuFFicas). Patients (n=121) who had undergone wire-based measurement of FF and cerebral angiography were recruited. The accuracy of the computed pressure ratio was evaluated using wire-based FF as the reference standard. RESULTS: The mean value of wire-based FF was 0.78±0.19, while the computed AccuFFicas had an average value of 0.79±0.18. Good correlation (Pearson's correlation coefficient r=0.92, P<0.001) between AccuFFicas and FF was observed. Bland-Altman analysis showed that the mean difference between AccuFFicas and FF was -0.01±0.07, indicating good agreement. The area under the curve (AUC) of AccuFFicas in predicting FF≤0.70, FF≤0.75, and FF≤0.80 was 0.984, 0.986, and 0.962, respectively. CONCLUSION: Angiography-based FF computed from cerebral angiographic images could be an effective computational tool for evaluating the hemodynamic significance of ICAS.

Diagnostic accuracy of a novel optical coherence tomography-based fractional flow reserve algorithm for assessment of coronary stenosis significance.

BACKGROUND: This study aimed to introduce a novel optical coherence tomography-derived fractional flow reserve (FFR) computational approach and assess the diagnostic performance of the algorithm for assessing physiological function. METHODS: The fusion of coronary optical coherence tomography and angiography was used to generate a novel FFR algorithm (AccuFFRoct) to evaluate functional ischemia of coronary stenosis. In the current study, a total of 34 consecutive patients were included, and AccuFFRoct was used to calculate the FFR for these patients. With the wire-measured FFR as the reference standard, we evaluated the performance of our approach by accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Per vessel accuracy, sensitivity, specificity, PPV, and NPV for AccuFFRoct in identifying hemodynamically significant coronary stenosis were 93.8%, 94.7%, 92.3%, 94.7%, and 92.3%, respectively, were found. Good correlation (Pearson's correlation coefficient r = 0.80, p < 0.001) between AccuFFRoct and FFR was observed. The Bland-Altman analysis showed a mean difference value of -0.037 (limits of agreement: -0.189 to 0.115). The area under the receiver-operating characteristic curve (AUC) of AccuFFRoct in identifying physiologically significant stenosis was 0.94, which was higher than the minimum lumen area (MLA, AUC = 0.91) and significantly higher than the diameter stenosis (%DS, AUC = 0.78). CONCLUSIONS: This clinical study shows the efficiency and accuracy of AccuFFRoct for clinical implementation when using invasive FFR measurement as a reference. It could provide important insights into coronary imaging superior to current methods based on the degree of coronary artery stenosis.

Cisplatin-activated ERß/DCAF8 positive feedback loop induces chemoresistance in non-small cell lung cancer via PTEN/Akt axis.

High levels of the estrogen receptor ß (ERß) predict poor prognosis following platinum-containing adjuvant chemotherapies in patients with non-small cell lung cancer (NSCLC). However, the precise role of ERß remains elusive. In this study, we demonstrated that targeting ERß could significantly increase the cytotoxicity of cisplatin both in vitro and in vivo. Mechanically, cisplatin directly binds to ERß, which facilitates its homodimerization and nuclear translocation. ERß activation transcriptionally represses the expression of DCAF8, an adaptor of CRL4 E3 ubiquitin ligase, which in turn attenuates the proteasomal degradation of ERß, leading to ERß accumulation; this positive feedback loop results in Akt activation and eventually cisplatin resistance in NSCLC through PTEN inhibition. Moreover, low expression of DCAF8 and high expression of ERß are associated with treatment resistance in patients receiving cisplatin-containing adjuvant chemotherapy. The present results provide insights into the underlying mechanism of ERß-induced cisplatin resistance and offer an alternative therapeutic strategy to improve the efficacy of platinum-based chemotherapy in patients with NSCLC.

Nanomaterial-based biosensors for the detection of foodborne bacteria: a review.

Ensuring food safety is a critical concern for the development and well-being of humanity, as foodborne illnesses caused by foodborne bacteria have increasingly become a major public health concern worldwide. Traditional food safety monitoring systems are expensive and time-consuming, relying heavily on specialized equipment and operations. Therefore, there is an urgent need to develop low-cost, user-friendly and highly sensitive biosensors for detecting foodborne bacteria. In recent years, the combination of nanomaterials with optical biosensors has provided a prospective future platform for the detection of foodborne bacteria. By harnessing the unique properties of nanomaterials, such as their high surface area-to-volume ratio and exceptional sensitivity, in tandem with the precision of optical biosensing techniques, a new prospect has opened up for the rapid and accurate identification of potential bacterial contaminants in food. This review focuses on recent advances and new trends of nanomaterial-based biosensors for the detection of foodborne pathogens, which mainly include noble metal nanoparticles (NMPs), metal organic frameworks (MOFs), graphene nanomaterials, quantum dot (QD) nanomaterials, upconversion fluorescent nanomaterials (UCNPs) and carbon dots (CDs). Additionally, we summarized the research progress of color indicators, nanozymes, natural enzyme vectors and fluorescent dye biosensors, focusing on the advantages and disadvantages of nanomaterial-based biosensors and their development prospects. This review provides an outlook on future technological directions and potential applications to help identify the most promising areas of development in this field.

Calculation of left ventricular ejection fraction using an 8-layer residual U-Net with deep supervision based on cardiac CT angiography images versus echocardiography: a comparative study.

Background: Accurate segmentation of the left ventricle (LV) is an important step in assessing cardiac function. Cardiac CT angiography (CCTA) has become an important means of clinical diagnosis of cardiovascular diseases (CVDs) because of its advantages of non-invasive, short examination time and low cost. In order to obtain the segmentation of LV in CCTA scans, we propose a deep learning method based on 8-layer residual U-Net with deep supervision. In this study we compared the left ventricular ejection fraction (LVEF) calculated by deep learning (DL) method (AccuLV) from CCTA to LVEF by conventional two-dimensional echocardiography (EC). Methods: This was a retrospective cross-sectional study, and consecutive patients who had undergone CCTA and EC in our hospital from February 2021 to May 2021 were recruited. The current study included 180 patients who had undergone CCTA and EC. To obtain LVEF, we used an 8-layer residual U-Net with deep supervision to segment LV contours from CCTA images and compute LVEF (DL-LVEF). The EC and DL-LVEF measurements were compared. A 50% EC-LVEF cut-off value was used as a reference standard to assess the diagnostic performance of AccuLV in assessing LV function. Results: The overall mean EC-LVEF and DL-LVEF values were 64.0% (52.3%, 69.0%) and 73.0% (52.3%, 77.0%), respectively. Three patient groups were studied: (I) hypertensive patients, (II) postmenopausal women, and (III) diabetes. EC-LVEF and DL-LVEF were found to be positively correlated for all of the included patients (r=0.82, P<0.001), with the detailed results for the three groups as follows: hypertensive patients (r=0.77, P<0.001), postmenopausal women (r=0.92, P<0.001) and diabetes (r=0.88, P<0.001). The diagnostic accuracy, sensitivity, and specificity of the DL method in predicting EC-LVEF <50% for all patients were 93.9%, 92.3%, and 94.3%, and for hypertensive patients were 95.4%, 93.8%, and 95.8%, for postmenopausal women were 87.0%, 100%, and 84.2%, for diabetes were 97.4%, 100%, and 96.6%. Conclusions: In comparison to echocardiography, which is commonly used in clinical setting, AccuLV may be a promising, fully automated tool for rapid and accurate quantification of LV function and thus for making reliable clinical decisions.

Are baseline conditions of coronary arteries sufficient for calculating angio-based index of microcirculatory resistance and fractional flow reserve?

Background: Angio-based index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) have been developed, however, the differences between baseline and hyperemic data and their effects on their computation have not yet been discussed. This study aimed to compare the diagnostic performance of a novel method for calculating IMR and FFR from coronary angiography under baseline and hyperemic conditions. Methods: We performed a retrospective study to investigate the diagnostic performance of angiography-derived IMR (AccuIMR) and FFR (AccuFFRangio) computed from the hyperemic condition (AccuIMRhyp, AccuFFRangiohyp) and baseline condition (AccuIMRbase, AccuFFRangiobase) in 101 consecutive patients with chronic coronary syndrome (CCS) who underwent measurements of IMR and FFR at a single center, using wire-based IMR and FFR as the reference standard. Results: AccuIMRhyp showed much better correlation with IMR than AccuIMRbase (r=0.77 vs. 0.47, P<0.001). The diagnostic accuracy and area under the curve (AUC) for identifying significant microvascular dysfunction was higher for AccuIMRhyp than AccuIMRbase [92.1% (95% CI: 85.0-96.5%) vs. 83.2% (95% CI: 74.4-89.9%), P=0.012; 0.942 (95% CI: 0.877-0.979) vs. 0.815 (95% CI: 0.726-0.886), P=0.003]. The computed AccuFFRangio showed good correlations with FFR and good diagnostic performance under both hyperemic and baseline conditions [r=0.68 vs. 0.68, P>0.99; diagnostic accuracy =95.9% (95% CI: 89.8-98.9%) vs. 94.9% (95% CI: 88.4-98.3%), P=0.728; AUC =0.989 (95% CI: 0.942-1.000) vs. 0.973 (95% CI: 0.919-0.995), P=0.381]. The net reclassification index (NRI) demonstrated that hyperemic group had improved reclassification ability compared to the baseline group in identification of IMR >25 (NRI =0.20, P<0.001) and FFR ≤0.8 (NRI =0.11, P<0.001). Conclusions: By comparing the calculated angio-derived IMR and FFR under the baseline and hyperemic conditions, this study demonstrates that AccuIMR calculation is more accurate using the hyperemic condition, while AccuFFRangio calculation is accurate under both conditions.

Intravascular Ultrasound-Based Fractional Flow Reserve for Predicting Prognosis after Percutaneous Coronary Intervention.

AccuFFRivus is an alternative to fractional flow reserve (FFR) based on intravascular ultrasound (IVUS) images for functional assessment of coronary stenosis. However, its prognostic impact in patients undergoing percutaneous coronary intervention (PCI) is still unclear. This retrospective study aimed to investigate the capability of AccuFFRivus in predicting prognosis. AccuFFRivus was calculated based on postoperative angiographic and IVUS images. Vessel-oriented clinical events (VOCE) at 2 years were recorded and analyzed. A total of 131 participants with 131 vessels were included in the study. VOCE occurred in 15 patients during 2-year follow-up. AccuFFRivus after PCI (post-AccuFFRivus) was significantly higher in the non-VOCE group than in the VOCE group (0.95 ± 0.03 vs. 0.91 ± 0.02, p < 0.001). Multivariate Cox regression showed that AccuFFRivus ≤ 0.94 was a strong independent predictor of VOCE during 2-year follow-up (hazard ratio 23.76, 95% confidence interval: 3.04-185.81, p < 0.001). The left panel displays the Receiver operating characteristics (ROC) curves of postoperative parameters (post-AccuFFRivus and post-MLA) versus vessel-oriented clinical events (VOCE) occurrence within 2-year follow-up. The right panel demonstrates Kaplan-Meier curves of VOCE stratified by the optimal cut-off of post-AccuFFRivus.

Angiography-based index of microcirculatory resistance (AccuIMR) for the assessment of microvascular dysfunction in acute coronary syndrome and chronic coronary syndrome.

Background: To assess the diagnostic accuracy of AccuIMR, a newly proposed, pressure wire-free index, in identifying coronary microvascular dysfunction (CMD) among patients with acute coronary syndrome [including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI)] and chronic coronary syndrome (CCS). Methods: A total of 163 consecutive patients (43 with STEMI, 59 with NSTEMI, and 61 with CCS), who underwent invasive coronary angiography (ICA) and for whom the index of microcirculatory resistance (IMR) was measured, were retrospectively enrolled at a single center. IMR measurements were made in 232 vessels. The AccuIMR based on computational fluid dynamics (CFD) was calculated from coronary angiography. The diagnostic performance of AccuIMR was assessed using wire-based IMR as a reference standard. Results: AccuIMR correlated well with IMR (overall r=0.76, P<0.001; STEMI r=0.78, P<0.001; NSTEMI r=0.78, P<0.001; CCS r=0.75, P<0.001) and had good diagnostic performance in detecting abnormal IMR [overall diagnostic accuracy, sensitivity, and specificity were 94.83% (91.14% to 97.30%), 92.11% (78.62% to 98.34%), and 95.36% (91.38% to 97.86%), respectively]. Using a cutoff value of IMR >40 U for AccuIMR in STEMI and IMR >25 U in NSTEMI and CCS, the area under the receiver operating characteristic (ROC) curve (AUC) of AccuIMR for predicting abnormal IMR value was 0.917 (0.874 to 0.949) in all patients, 1.000 (0.937 to 1.000) in patients with STEMI, 0.941 (0.867 to 0.980) in patients with NSTEMI, and 0.918 (0.841 to 0.966) in patients with CCS. Conclusions: The use of AccuIMR in the evaluation of microvascular diseases could provide valuable information and potentially increase the application of physiological assessment for microcirculation in patients with ischemic heart disease.

Accuracy of intravascular ultrasound-derived virtual fractional flow reserve (FFR) and FFR derived from computed tomography for functional assessment of coronary artery disease.

BACKGROUND: Coronary computed tomography-derived fractional flow reserve (CT-FFR) and intravascular ultrasound-derived fractional flow reserve (IVUS-FFR) are two functional assessment methods for coronary stenoses. However, the calculation algorithms for these methods differ significantly. This study aimed to compare the diagnostic performance of CT-FFR and IVUS-FFR using invasive fractional flow reserve (FFR) as the reference standard. METHODS: Six hundred and seventy patients (698 lesions) with known or suspected coronary artery disease were screened for this retrospective analysis between January 2020 and July 2021. A total of 40 patients (41 lesions) underwent intravascular ultrasound (IVUS) and FFR evaluations within six months after completing coronary CT angiography were included. Two novel CFD-based models (AccuFFRct and AccuFFRivus) were used to compute the CT-FFR and IVUS-FFR values, respectively. The invasive FFR ≤ 0.80 was used as the reference standard for evaluating the diagnostic performance of CT-FFR and IVUS-FFR. RESULTS: Both AccuFFRivus and AccuFFRct demonstrated a strong correlation with invasive FFR (R = 0.7913, P < 0.0001; and R = 0.6296, P < 0.0001), and both methods showed good agreement with FFR. The area under the receiver operating characteristic curve was 0.960 (P < 0.001) for AccuFFRivus and 0.897 (P < 0.001) for AccuFFRct in predicting FFR ≤ 0.80. FFR ≤ 0.80 were predicted with high sensitivity (96.6%), specificity (85.7%), and the Youden index (0.823) using the same cutoff value of 0.80 for AccuFFRivus. A good diagnostic performance (sensitivity 89.7%, specificity 85.7%, and Youden index 0.754) was also demonstrated by AccuFFRct. CONCLUSIONS: AccuFFRivus, computed from IVUS images, exhibited a high diagnostic performance for detecting myocardial ischemia. It demonstrated better diagnostic power than AccuFFRct, and could serve as an accurate computational tool for ischemia diagnosis and assist in clinical decision-making.

Hydrogen bonding-induced high-performance stretchable organic semiconductors: a Review.

Semiconductors are widely used in electron devices. With the development of wearable soft-electron devices, conventional inorganic semiconductors are unable to meet the demand because of their high rigidity and high cost. Thus, scientists construct organic semiconductors with high charge mobility, low cost, eco-friendly, stretchable, etc. Due to the excellent performance of stretchable organic semiconductors, they can be widely used as wearable soft-electron devices, such as stretchable organic field-effect transistors (OFETs), organic solar cells (OSCs), etc. Contains flexible display devices and flexible power sources, which are of great interest for applications of future electron devices. However, there are still some challenges that need to be solved. Commonly, enhancing the stretchability may cause the degradation of charge mobility, because of the destruction of the conjugated system. Currently, scientists find that hydrogen bonding can enhance the stretchability of organic semiconductors with high charge mobility. Thus in this review, based on the structure and design strategies of hydrogen bonding, various hydrogen bonding induced stretchable organic semiconductors are introduced. In addition, the applications of the hydrogen bonding induced stretchable organic semiconductors are reviewed. Finally, the stretchable organic semiconductors design concept and potential evolution trends are discussed. The final goal is to outline a theoretical scaffold for the design of high-performance wearable soft-electron devices, which can also further advance the development of stretchable organic semiconductors for applications.

[Protective mechanism of electroacupuncture combined with acellular nerve allografts on spinal ganglia in rats with sciatic nerve injury].

OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with acellular nerve allograft (ANA) on the morphological structure of spinal ganglion cells and the protein expressions of nerve growth factor (NGF) and phosphorylated protein kinase B (p-Akt) in rats with sciatic nerve injury (SNI), so as to explore the protective mechanism of EA combined with ANA on spinal ganglia. METHODS: SPF male SD rats were randomly divided into normal, model, single ANA bridging (bridging) and EA + ANA (combination) groups， with 10 rats in each group. The SNI rat model was established by right sciatic nerve transection. Rats in the bridging group were bridged with ANA to the two broken ends of injured sciatic nerves. Rats in the combination group were treated with EA at "Yanglingquan" (GB34) and "Huantiao" (GB30) 2 d after ANA bridging, with dilatational wave, frequency of 1 Hz/20 Hz, intensity of 1 mA, 15 min/d, 7 d as a course of treatment for 4 consecutive courses. Sciatic function index (SFI) was observed by footprint test. Wet weight ratio of tibialis anterior muscle was calculated after weighing. Morphology of rat spinal ganglion cells was observed after Nissl staining. The protein expressions of NGF and p-Akt were detected by immunofluorescence and Western blot. RESULTS: Compared with the normal group, the SFI and wet weight ratio of tibialis anterior muscle were significantly decreased (P<0.05), the number of Nissl bodies in spinal ganglion cells was significantly reduced (P<0.05) with dissolution and incomplete structure， the protein expressions of NGF and p-Akt in ganglion cells were significantly decreased (P<0.05) in the model group. Following the interventions and in comparison with the model group, the SFI and the wet weight ratio of tibialis anterior muscle were significantly increased (P<0.05), the damage of Nissl bodies in ganglion cells was reduced and the number was obviously increased (P<0.05), and the protein expressions of NGF and p-Akt in ganglion cells were significantly increased (P<0.05) in the bridging and combination groups. Compared with the bridging group, the SFI and the wet weight ratio of tibialis anterior muscle were increased (P<0.05), the morphology of Nissl bodies in ganglion cells was more regular and the number was increased (P<0.05), the protein expressions of NGF and p-Akt in spinal ganglion cells were significantly increased (P<0.05) in the combination group. CONCLUSION: EA combined with ANA can improve the SFI and the wet weight ratio of tibialis anterior muscle in SNI rats, improve the morphology and structure of Nissl bodies in spinal ganglion cells, and increase the protein expressions of NGF and p-Akt in spinal ganglion, so as to play a protective role on spinal ganglia.

The diagnostic performance of AccuFFRangio for evaluating coronary artery stenosis under different computational conditions.

Background: A computational method (AccuFFrangio) based on invasive coronary angiography (ICA) and computational fluid dynamics (CFD) to calculate fractional flow reserve (FFR) without a pressure wire has been devised to clarify the physiological significance of coronary stenosis. This study aimed to evaluate the diagnostic performance of AccuFFRangio computation under different boundary conditions and vessel reconstruction approaches. Methods: Consecutive patients with stable angina pectoris who underwent ICA and FFR assessment from 2 centers were analyzed retrospectively. Using wire-based FFR as the reference standard, the diagnostic performances of AccuFFRangio and its variations were evaluated and compared. The calculation of AccuFFRangio involves several key boundary conditions, including patient-specific aortic pressure, contrast flow velocity derived from the thrombolysis in myocardial infarction (TIMI) frame count method, and vessel reconstruction based on 2 angiographic views. We considered the following 3 variations: (I) a fixed aortic pressure [fixed pressure AccuFFRangio (pAccuFFRangio)], (II) an empirical hyperemic velocity [fixed velocity AccuFFRangio (vAccuFFRangio)], and (III) vessel reconstruction using a single angiographic view [single view AccuFFRangio (sAccuFFRangio)]. Results: A total of 230 patients with 230 vessels were included in the final analysis. The accuracy for standard AccuFFRangio, pAccuFFRangio, vAccuFFRangio, and sAccuFFRangio was 93.91%, 86.52%, 81.74%, and 83.48%, respectively; the sensitivity was 90.74%, 51.85%, 83.33%, and 46.30%, respectively; the specificity was 94.89%, 97.16%, 81.25%, and 94.89%, respectively; and the area under the receiver operating characteristic curve was 0.971, 0.928, 0.892, and 0.870, respectively. Conclusions: The comparison suggested that the overall performance of the standard AccuFFRangio was superior to other variations and had the highest accuracy among all the cases.

Diagnostic performance of computational fluid dynamics (CFD)-based fractional flow reserve (FFR) derived from coronary computed tomographic angiography (CCTA) for assessing functional severity of coronary lesions.

Background: Fractional flow reserve (FFR) is the gatekeeper for lesion-specific revascularization decision-making in patients with stable coronary artery disease (CAD). The potential of noninvasive calculation of FFR from coronary computed tomographic angiography (CCTA) to identify ischemia-causing lesions has not been sufficiently assessed. The objective of this study was to evaluate the feasibility and diagnostic accuracy of a novel computational fluid dynamics (CFD)-based technology, termed as AccuFFRct, for the diagnosis of functionally significant lesions from CCTA, using wire-based FFR as a reference standard. Methods: A total of 191 consecutive patients who underwent CCTA and FFR measurement for suspected or known CAD were retrospectively enrolled at 2 medical centers. Three-dimensional anatomic model of coronary tree was extracted from CCTA data, CFD was applied subsequently with a novel strategy for the computation of FFR in a blinded fashion by professionals. Results were compared to invasive FFR, a threshold of ≤0.80 was used to indicate the hemodynamically relevant stenosis. Results: On a per-patient basis, the overall accuracy, sensitivity, specificity of AccuFFRct for detecting ischemia were 91.78% (95% CI: 86.08% to 95.68%), 92.31% (95% CI: 81.46% to 97.86%) and 91.49% (95% CI: 83.92% to 96.25%), respectively; those for per-vessel basis were 91.05% (95% CI: 86.06% to 94.70%), 92.73% (95% CI: 82.41% to 97.98%) and 90.37% (95% CI: 84.10% to 94.77%), respectively. The AccuFFRct and FFR was well correlated on per-patient (r=0.709, P<0.001) and per-vessel basis (r=0.655, P<0.001). The AUC of AccuFFRct determination was 0.935 (95% CI: 0.881 to 0.969) and 0.927 (95% CI: 0.880 to 0.960) on per-patient and per-vessel basis. Conclusions: This novel CFD-based CCTA-derived FFR shows good diagnostic performance for detecting hemodynamic significance of coronary stenoses and may potentially become a new gatekeeper for invasive coronary angiography (ICA).

Functional Assessment of Coronary Artery Stenosis from Coronary Angiography and Computed Tomography: Angio-FFR vs. CT-FFR.

This study was designed to compare the diagnostic performance of angio-FFR and CT-FFR for detecting hemodynamically significant coronary stenosis. Angio-FFR and CT-FFR were measured in 110 patients (139 vessels) with stable coronary disease using invasive FFR as the reference standard. On per-patient basis, angio-FFR was highly correlated with FFR (r =0.78, p <0.001), while the correlation was moderate between CT-FFR and FFR (r =0.68, p <0.001). Diagnostic accuracy, sensitivity, and specificity for angio-FFR were 94.6%, 91.4%, and 96.0%, respectively; and those of CT-FFR were 91.8%, 91.4%, and 92%, respectively. Bland-Altman analysis showed that angio-FFR had a larger average difference and a smaller root mean squared deviation than CT-FFR compared with FFR (-0.014±0.056 vs. 0.0003±0.072). Angio-FFR had a slightly higher AUC than that of CT-FFR (0.946 vs. 0.935, p =0.750). Angio-FFR and CT-FFR computed from coronary images could be accurate and efficient computational tools for detecting lesion-specific ischemia of coronary artery stenosis. Angio-FFR and CT-FFR calculated based on the two types of images can both accurately diagnose functional ischemia of coronary stenosis. CT-FFR can act as a gatekeeper to the catheter room, assisting doctors in determining whether patients need to be screened by coronary angiography. Angio-FFR can be used in the catheter room to determine the functional significant stenosis for helping decision-making in revascularization.

A novel CFD-based computed index of microcirculatory resistance (IMR) derived from coronary angiography to assess coronary microcirculation.

OBJECTIVES: This study sought to present a novel approach for computation of the index of microcirculatory resistance (IMR) and to evaluate its diagnostic performance. BACKGROUND: IMR is a quantitative assessment to identify coronary microvascular dysfunction. However, its clinical use remains extremely limited. Calculation of IMR from coronary angiography images may increase the utility of coronary microvasculature assessment. METHODS: 203 patients with 203 vessels were included in this study. Physiology measurements were obtained with pressure-wire in the whole cohort. The computational fluid dynamics (CFD)-based AccuIMR was computed and evaluated in a blinded fashion using wire-based IMR as the reference standard. RESULTS: The overall diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AccuIMR for detecting coronary microvascular disease were 91.1% (95% CI: 86.4% to 94.7%), 89.4% (95% CI: 80.9% to 95.0%), 92.4% (95% CI: 86.0% to 96.5%), 89.4% (95% CI: 81.8% to 94.1%), and 92.2% (95% CI: 86.7% to 95.8%), respectively. The correlation coefficient equaled to 0.81 (p < 0.001) between AccuIMR and wire-based IMR with the receiver-operating curve had area under the curve of 0.924 (95% CI: 0.878 to 0.956). CONCLUSIONS: AccuIMR is a novel pressure-wire free approach to assess coronary microvascular disease with great diagnostic performance, which can be a valid, efficient, and cost-reducing tool to provide an easier routine assessment of coronary microcirculation.

Diagnostic performance of deep learning and computational fluid dynamics-based instantaneous wave-free ratio derived from computed tomography angiography.

BACKGROUND AND OBJECTIVES: Both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are widely used to evaluate ischemia-causing coronary lesions. A new method of CT-iFR, namely AccuiFRct, for calculating iFR based on deep learning and computational fluid dynamics (CFD) using coronary computed tomography angiography (CCTA) has been proposed. In this study, the diagnostic performance of AccuiFRct was thoroughly assessed using iFR as the reference standard. METHODS: Data of a total of 36 consecutive patients with 36 vessels from a single-center who underwent CCTA, invasive FFR, and iFR were retrospectively analyzed. The CT-derived iFR values were computed using a novel deep learning and CFD-based model. RESULTS: Mean values of FFR and iFR were 0.80 ± 0.10 and 0.91 ± 0.06, respectively. AccuiFRct was well correlated with FFR and iFR (correlation coefficients, 0.67 and 0.68, respectively). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of AccuiFRct ≤ 0.89 for predicting FFR ≤ 0.80 were 78%, 73%, 81%, 73%, and 81%, respectively. Those of AccuiFRct ≤ 0.89 for predicting iFR ≤ 0.89 were 81%, 73%, 86%, 79%, and 82%, respectively. AccuiFRct showed a similar discriminant function when FFR or iFR were used as reference standards. CONCLUSION: AccuiFRct could be a promising noninvasive tool for detection of ischemia-causing coronary stenosis, as well as facilitating in making reliable clinical decisions.