Super-resolution Multispectral Imaging Nanoimmunosensor for Simultaneous Detection of Diverse Early Cancer Biomarkers.

In medical diagnosis, relying on only one type of biomarker is insufficient to accurately identify cancer. Blood-based multicancer early detection can help identify more than one type of cancer from a single blood sample. In this study, a super-resolution multispectral imaging nanoimmunosensor (srMINI) based on three quantum dots (QDs) of different color conjugated with streptavidin was developed for the simultaneous screening of various cancer biomarkers in blood at the single-molecule level. In the experiment, the srMINI chip was used to simultaneously detect three key cancer biomarkers: carcinoembryonic antigen (CEA), C-reactive protein (CRP), and alpha-fetoprotein (AFP). The srMINI chip exhibited 108 times higher detection sensitivity of 0.18-0.5 ag/mL (1.1-2.6 zM) for these cancer biomarkers than commercial enzyme-linked immunosorbent assay kits because of the absence of interfering signals from the substrate, establishing considerable potential for multiplex detection of cancer biomarkers in blood. Therefore, the simultaneous detection of various cancer biomarkers using the developed srMINI chip with high diagnostic precision and accuracy is expected to play a decisive role in early diagnosis or community screening as a single-molecule biosensor.

Artificial intelligence-enhanced automation of left ventricular diastolic assessment: a pilot study for feasibility, diagnostic validation, and outcome prediction.

Background: Evaluating left ventricular diastolic function (LVDF) is crucial in echocardiography; however, the complexity and time demands of current guidelines challenge clinical use. This study aimed to develop an artificial intelligence (AI)-based framework for automatic LVDF assessment to reduce subjectivity and improve accuracy and outcome prediction. Methods: We developed an AI-based LVDF assessment framework using a nationwide echocardiographic dataset from five tertiary hospitals. This framework automatically identifies views, calculates diastolic parameters, including mitral inflow and annular velocities (E/A ratio, e' velocity, and E/e' ratio), maximal tricuspid regurgitation velocity, left atrial (LA) volume index, and left atrial reservoir strain (LARS). Subsequently, it grades LVDF according to guidelines. The AI-framework was validated on an external dataset composed of randomly screened 173 outpatients who underwent transthoracic echocardiography with suspicion for diastolic dysfunction and 33 individuals from medical check-ups with normal echocardiograms at Seoul National University Bundang Hospital, tertiary medical center in Korea, between May 2012 and June 2022. Additionally, we assessed the predictive value of AI-derived diastolic parameters and LVDF grades for a clinical endpoint, defined as a composite of all-cause death and hospitalization for heart failure, using Cox-regression risk modelling. Results: In an evaluation with 200 echocardiographic examinations (167 suspected diastolic dysfunction patients, 33 controls), it achieves an overall accuracy of 99.1% in identifying necessary views. Strong correlations (Pearson coefficient 0.901-0.959) were observed between AI-derived and manually-derived measurements of diastolic parameters, including LARS as well as conventional parameters. When following the guidelines, whether utilizing AI-derived or manually-derived parameters, the evaluation of LVDF consistently showed high concordance rates (94%). However, both methods exhibited lower concordance rates with the clinician's prior assessments (77.5% and 78.5%, respectively). Importantly, both AI-derived and manually-derived LVDF grades independently demonstrated significant prognostic value [adjusted hazard ratio (HR) =3.03; P=0.03 and adjusted HR =2.75; P=0.04, respectively] for predicting clinical outcome. In contrast, the clinician's prior grading lost its significance as a prognostic indicator after adjusting for clinical risk factors (adjusted HR =1.63; P=0.36). AI-derived LARS values significantly decreased with worsening LVDF (P for trend <0.001), and low LARS (<17%) was associated with increased risk for the clinical outcome (Log-rank P=0.04) relative to that for preserved LARS (≥17%). Conclusions: Our AI-based approach for automatic LVDF assessment on echocardiography is feasible, potentially enhancing clinical diagnosis and outcome prediction.

Correlations between heart sound components and hemodynamic variables.

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.

Artificial intelligence-enhanced automation for M-mode echocardiographic analysis: ensuring fully automated, reliable, and reproducible measurements.

To enhance M-mode echocardiography's utility for measuring cardiac structures, we developed and evaluated an artificial intelligence (AI)-based automated analysis system for M-mode images through the aorta and left atrium [M-mode (Ao-LA)], and through the left ventricle [M-mode (LV)]. Our system, integrating two deep neural networks (DNN) for view classification and image segmentation, alongside an auto-measurement algorithm, was developed using 5,958 M-mode images [3,258 M-mode (LA-Ao), and 2,700 M-mode (LV)] drawn from a nationwide echocardiographic dataset collated from five tertiary hospitals. The performance of view classification and segmentation DNNs were evaluated on 594 M-mode images, while automatic measurement accuracy was tested on separate internal test set with 100 M-mode images as well as external test set with 280 images (140 sinus rhythm and 140 atrial fibrillation). Performance evaluation showed the view classification DNN's overall accuracy of 99.8% and segmentation DNN's Dice similarity coefficient of 94.3%. Within the internal test set, all automated measurements, including LA, Ao, and LV wall and cavity, resonated strongly with expert evaluations, exhibiting Pearson's correlation coefficients (PCCs) of 0.81-0.99. This performance persisted in the external test set for both sinus rhythm (PCC, 0.84-0.98) and atrial fibrillation (PCC, 0.70-0.97). Notably, automatic measurements, consistently offering multi-cardiac cycle readings, showcased a stronger correlation with the averaged multi-cycle manual measurements than with those of a single representative cycle. Our AI-based system for automatic M-mode echocardiographic analysis demonstrated excellent accuracy, reproducibility, and speed. This automated approach has the potential to improve efficiency and reduce variability in clinical practice.

One-Shot Dual-Detection-Based Single-Molecule Super-Resolution Imaging Method for Real-Time Observation of Spatiotemporal Catalytic Activity Variations on the Plasmonic Gold Nanoparticle Surface.

Understanding the relationship between the surface properties of a single plasmonic nanoparticle and its catalytic performance is critical for developing highly efficient nanocatalysts. In this study, a one-shot dual-detection-based single-molecule super-resolution imaging method in the evanescent field was developed to observe real-time spatiotemporal catalytic activity on a single plasmonic gold nanoparticle (AuNP) surface. The scattering intensity of AuNPs and the fluorescence of resorufin molecules produced on the AuNP surface were obtained simultaneously to investigate the relationship between nanoparticles and catalytic reactions at a single-molecule level. Chemisorbed adsorbates (i.e., catalytic product and resorufin) changed the electron density of individual AuNPs throughout the catalytic cycle, resulting in the fluctuation of the scattering intensity of individual AuNPs, which was attributed to the electron transfer between reactant resazurin molecules and AuNPs. The increase in the electron density of individual AuNPs affected the catalytic reaction rate. Furthermore, sequential mapping of individual catalytic events at the subdiffraction limit resolution was completed for real-time surface dynamics and spatiotemporal activity variations on the single AuNP surface. The developed method can aid in understanding surface-property-dependent catalytic kinetics and facilitate the development of nanoparticle-based heterogeneous catalysts at subdiffraction limit resolution.

Reduction of moderate to severe tricuspid regurgitation after catheter ablation for atrial fibrillation.

OBJECTIVE: Tricuspid regurgitation (TR) is a progressive disease with high mortality and limited medical treatment options, and its association with atrial fibrillation (AF) has been documented. This study aimed to investigate whether successful rhythm control through catheter ablation for AF could reduce TR severity. METHODS: A total of 106 patients with drug-refractory AF with moderate to severe secondary TR who underwent AF ablation were screened from a single-centre ablation registry. Echocardiographic parameter changes (pre-procedure vs 1 day/1 year post-procedure) were analysed. Holter monitoring was performed at 3/6/12 months to assess AF recurrence. The primary outcome was at least one grade TR reduction with its main determinants evaluated. RESULTS: After excluding 36 patients (prior tricuspid valve surgery, intracardiac devices or insufficient data), 70 patients (aged 63.8±9.7 years, 50% female) were analysed. Of these, 17 (24.3%) had severe TR, 55 (78.6%) persistent AF and all restored sinus rhythm with catheter ablation. The primary outcome was achieved in 53 (75.7%) at 1-year assessment (73.6% of moderate and 82.4% of severe TR). There were significant decreases of vena contracta (6.1→3.2 mm) and tricuspid annular diameter (37.3→32.6 mm) at 1 year. Although 25 patients experienced AF recurrence within 1 year, 56 (80%) patients finally maintained sinus rhythm with medical treatment (87% in patients with TR reduction and 59% without). From the multivariate analysis, sinus rhythm maintenance was the most significant determinant of TR reduction (OR 8.3, 95% CI 1.8 to 37.4). CONCLUSION: In patients with AF with moderate to severe TR, more than two-thirds of patients experienced reduced TR severity, with notable improvements in echocardiographic parameters. Sinus rhythm maintenance was associated with significant TR reduction.

Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease.

BACKGROUND: Hypertension adds to the pressure overload on the left ventricle (LV) in combination with aortic valve (AV) disease, but the optimal blood pressure (BP) targets for patients with AV disease remain unclear. We tried to investigate whether intensive BP control reduces LV hypertrophy in asymptomatic patients with aortic stenosis (AS) or aortic regurgitation (AR). METHODS: A total of 128 hypertensive patients with mild to moderate AS (n = 93) or AR (n = 35) were randomly assigned to intensive therapy, targeting a systolic BP <130 mm Hg, or standard therapy, targeting a systolic BP <140 mm Hg. The primary end point was the change in LV mass from baseline to the 24-month follow-up. Secondary end points included changes in severity of AV disease, LV volumes, ejection fraction and global longitudinal strain (GLS). RESULTS: The treatment groups were generally well balanced regarding the baseline characteristics. The mean (±SD) age of the patients was 68 ± 8 years and 48% were men. The mean BP was 145 ± 12/81 ± 10 mm Hg at baseline. Medication at baseline was similar between the 2 groups. The 2 treatment strategies resulted in a rapid and sustained difference in systolic BP (P < .05). At 24-month, the mean systolic BP was 129 ± 12 mm Hg in the intensive therapy group and 135 ± 14 mm Hg in the standard therapy group. No patient died or underwent AV surgery during follow-up in either of the groups. LV mass was changed from 189.5 ± 41.3 to 185.6 ± 41.5 g in the intensive therapy group (P = .19) and from 183.8 ± 38.3 to 194.0 ± 46.4 g in the standard therapy group (P < .01). The primary end point of change in LV mass was significantly different between the intensive therapy and the standard therapy group (-3.9 ± 20.2 g vs 10.3 ± 20.4 g; P = .0007). The increase in LV mass index was also significantly greater in the standard therapy group (P = .01). No significant differences in secondary end points (changes in severity of AV disease, LV volumes, ejection fraction and GLS) were observed between the treatment groups. CONCLUSIONS: Among hypertensive patients with AV disease, intensive hypertensive therapy resulted in a significant reduction in LV hypertrophy, although progression of AV disease was similar between the treatment groups. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov (Number NCT03666351).

Social Mobility and Cognitive Impairment Among Korean Older Adults: Does Gender Matter?

The purpose of this study is to investigate the association between social mobility and cognitive impairment among older adults in Korea. The study sample is drawn from nationally representative data, which comes from the 2016 Korean Longitudinal Study of Ageing (KLoSA). The final sample consists of 4264 KLoSA respondents aged 65 or older. Gender-specific logistic regression models are used to examine the association between social mobility and cognitive impairment. The results show that, when compared to the reference group (stable low social mobility), women in the downward and the stable high social mobility groups were less likely to have cognitive impairment. In contrast, upward social mobility was a protective factor for cognitive impairment only among men. Gender-specific interventions may be needed to enhance cognitive health among older Koreans. Further research is needed to examine the causal relations between social mobility and cognitive health between the genders.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Tailored Planning of Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease characterized by abnormal thickening of the myocardium caused by myocardial disarray and interstitial fibrosis. HCM is associated with sudden cardiac-related events, such as ventricular fibrillation, tachycardia, and syncope. Moreover, left ventricular or midcavity obstruction due to the thickened myocardium can result in severe heart failure and mortality in patients with HCM. Surgical myectomy is a standard treatment option for patients with symptomatic obstructive HCM; however, it is a complex procedure that requires careful planning and execution to avoid complications, such as residual flow obstruction, persistent obliteration of the left ventricular cavity in systole, or iatrogenic ventricular septal defects. Therefore, a thorough understanding of the mechanics of HCM and precise evaluation of the location and extent of the hypertrophic myocardium to be removed are crucial for preoperative planning. Multiphase cardiac CT postprocessing is important for preoperative evaluation and planning of surgical myectomy in patients with HCM. In this review, the authors highlight use of multiphase cardiac CT with step-by-step postprocessing methods to simulate successful surgical myectomy. The transaortic surgeon's view on end-diastolic phase images accurately represents the surgical field. Moreover, myocardial segmentation can be used to generate volume-rendered images and three-dimensional printing. CT evaluation can also assist in identifying concurrent abnormalities, such as mitral valve or papillary muscle abnormalities. In addition to CT, other imaging modalities for preoperative evaluation of HCM and postmyectomy evaluation methods are presented. ©RSNA, 2023 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Frequency, Predictors, and Clinical Impact of Valvular and Perivalvular Thrombus After Transcatheter Aortic Valve Replacement.

BACKGROUND: Subclinical aortic valve complex (valvular and perivalvular) thrombus is not rare after transcatheter aortic valve replacement (TAVR). The risk factors and clinical implications of these findings remain uncertain. OBJECTIVES: This study sought to evaluate the frequency, predictors, and clinical outcome of aortic valve complex thrombus after TAVR. METHODS: In the ADAPT-TAVR (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement) trial comparing edoxaban vs dual antiplatelet therapy in TAVR patients without an indication for chronic anticoagulation, the frequency of valvular (subclinical leaflet thrombus) and perivalvular (supravalvular, subvalvular, and sinus of Valsalva) thrombus was evaluated by 4-dimensional computed tomography at 6 months. The association of these phenomena with new cerebral thromboembolism on brain magnetic resonance imaging, neurologic and neurocognitive dysfunction, and clinical outcomes was assessed. RESULTS: Among 211 patients with 6-month computed tomography evaluations, 91 patients (43.1%) had thrombus at any aortic valve complex, 30 (14.2%) patients had leaflet thrombus, and 78 (37.0%) patients had perivalvular thrombus. A small maximum diameter of the stent at the valve level and low body surface area were independent predictors of aortic valve complex and perivalvular thrombus, and decreased renal function was an independent predictor of leaflet thrombus. No significant differences were observed in new cerebral lesions, neurologic or neurocognitive functions, or clinical outcomes among patients with or without valvular or perivalvular thrombus. CONCLUSIONS: Subclinical aortic valve complex (valvular and perivalvular) thrombus was common in patients who had undergone successful TAVR. However, these imaging phenomena were not associated with new cerebral thromboembolism, neurologic or neurocognitive dysfunction, or adverse clinical outcomes. (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement [ADAPT-TAVR]; NCT03284827).

Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

Detection rate of brain MR and MR angiography for neuroimaging abnormality in patients with newly diagnosed left-sided infective endocarditis.

We aimed to investigate the detection rate of brain MR and MR angiography for neuroimaging abnormality in newly diagnosed left-sided infective endocarditis patients with/without neurological symptoms. This retrospective study included consecutive patients with definite or possible left-sided infective endocarditis according to the modified Duke criteria who underwent brain MRI and MR angiography between March 2015 and October 2020. The detection rate for neuroimaging abnormality on MRI was defined as the number of patients with positive brain MRI findings divided by the number of patients with left-sided infective endocarditis. Positive imaging findings included acute ischemic lesions, cerebral microbleeds, hemorrhagic lesions, and infectious aneurysms. In addition, aneurysm rupture rate and median period to aneurysm rupture were evaluated on follow-up studies. A total 115 patients (mean age: 55 years ± 19; 65 men) were included. The detection rate for neuroimaging abnormality was 77% (89/115). The detection rate in patients without neurological symptoms was 70% (56/80). Acute ischemic lesions, cerebral microbleeds, and hemorrhagic lesions including superficial siderosis and intracranial hemorrhage were detected on MRI in 56% (64/115), 57% (66/115), and 20% (23/115) of patients, respectively. In particular, infectious aneurysms were detected on MR angiography in 3% of patients (4/115), but MR angiography in 5 patients (4.3%) was insignificant for infectious aneurysm, which were detected using CT angiography (n = 3) and digital subtraction angiography (n = 2) during follow-up. Among the 9 infectious aneurysm patients, aneurysm rupture occurred in 4 (44%), with a median period of aneurysm rupture of 5 days. The detection rate of brain MRI for neuroimaging abnormality in newly diagnosed left-sided infective endocarditis patients was high (77%), even without neurological symptoms (70%).

Relationship between Preoperative Echocardiographic Parameters and the Incidence of Postoperative Complications in Patients Undergoing Clipping of Unruptured Intracranial Aneurysms: A Retrospective Cohort Study.

Background and Objectives: Preoperative echocardiography is widely performed in patients undergoing major surgeries to evaluate cardiac functions and detect structural abnormalities. However, studies on the clinical usefulness of preoperative echocardiography in patients undergoing cerebral aneurysm clipping are limited. Therefore, this study aimed to investigate the correlation between preoperative echocardiographic parameters and the incidence of postoperative complications in patients undergoing clipping of unruptured intracranial aneurysms. Materials and Methods: Electronic medical records of patients who underwent clipping of an unruptured intracranial aneurysm from September 2018 to April 2020 were retrospectively reviewed. Data on baseline characteristics, laboratory variables, echocardiographic parameters, postoperative complications, and hospital stays were obtained. Univariable and multivariable logistic regression analyses were performed to identify independent variables related to the occurrence of postoperative complications and prolonged hospital stay (≥8 d). Results: Among 531 patients included in the final analysis, 27 (5.1%) had postoperative complications. In multivariable logistic regression, the total amount of crystalloids infused (1.002 (1.001-1.003), p = 0.001) and E/e' ratio (1.17 (1.01-1.35), p = 0.031) were significant independent factors associated with the occurrence of a postoperative complication. Additionally, the maximal diameter of a cerebral aneurysm (1.13 (1.02-1.25), p = 0.024), total amount of crystalloids infused (1.001 (1.000-1.002), p = 0.031), E/A ratio (0.22 (0.05-0.95), p = 0.042), and E/e' ratio (1.16 (1.04-1.31), p = 0.011) were independent factors related to prolonged hospitalization. Conclusions: Echocardiographic parameters related to diastolic function might be associated with postoperative complications in patients undergoing clipping of unruptured intracranial aneurysms.

Impact of leaflet thrombosis on valve haemodynamic status after transcatheter aortic valve replacement.

OBJECTIVES: The effect of subclinical leaflet thrombosis, characterised by hypoattenuated leaflet thickening (HALT), on the valve haemodynamic function and durability of the bioprosthetic valve, is not yet determined. We determined the impact of HALT on valve haemodynamics after transcatheter aortic valve replacement (TAVR) and the predictors of haemodynamic structural valve deterioration (SVD). METHODS: The Anticoagulation vs Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization after Transcatheter Aortic Valve Replacement(ADAPT-TAVR) trial is a multicenter, randomised trial that compared edoxaban and dual antiplatelet therapy in patients who had undergone successful TAVR. The presence of HALT was evaluated by four-dimensional CT at 6 months and serial echocardiography performed at baseline, immediately post-TAVR and after 6 months. SVD was defined as at least one of the following: (1) mean transprosthetic gradient ≥20 mm Hg, (2) change in the mean gradient ≥10 mm Hg from baseline, or (3) new or increase in intraprosthetic aortic regurgitation of at least ≥1 grade, resulting in moderate or greater regurgitation. RESULTS: At 6 months, HALT was found in 30 of 211 (14.2%) patients. The presence of HALT did not significantly affect aortic valve mean gradients (with vs without HALT; 14.0±4.8 mm Hg vs 13.7±5.5 mm Hg; p=0.74) at 6 months. SVD was reported in 30 of 206 patients (14.6%) at 6-month follow-up echocardiography. Older age (OR: 1.138; 95% CI: 1.019 to 1.293; p=0.033), use of aortic valve size ≤23 mm (OR: 6.254; 95% CI: 2.230 to 20.569; p=0.001) and mean post-TAVR pressure gradient (OR: 1.233; 95% CI: 1.123 to 1.371; p<0.001) were independent predictors of haemodynamic SVD; however, the presence of HALT was not identified as a predictor of SVD. CONCLUSIONS: In patients who had undergone successful TAVR, aortic valve haemodynamic status was not influenced by the presence of HALT. Although HALT was not a predictor of haemodynamic SVD at 6 months, it warrants further longer-term follow-up to evaluate the effect on long-term valve durability. TRIAL REGISTRATION NUMBER: NCT03284827 (https://www. CLINICALTRIALS: gov).

Perception, performance, and detectability of conversational artificial intelligence across 32 university courses.

The emergence of large language models has led to the development of powerful tools such as ChatGPT that can produce text indistinguishable from human-generated work. With the increasing accessibility of such technology, students across the globe may utilize it to help with their school work-a possibility that has sparked ample discussion on the integrity of student evaluation processes in the age of artificial intelligence (AI). To date, it is unclear how such tools perform compared to students on university-level courses across various disciplines. Further, students' perspectives regarding the use of such tools in school work, and educators' perspectives on treating their use as plagiarism, remain unknown. Here, we compare the performance of the state-of-the-art tool, ChatGPT, against that of students on 32 university-level courses. We also assess the degree to which its use can be detected by two classifiers designed specifically for this purpose. Additionally, we conduct a global survey across five countries, as well as a more in-depth survey at the authors' institution, to discern students' and educators' perceptions of ChatGPT's use in school work. We find that ChatGPT's performance is comparable, if not superior, to that of students in a multitude of courses. Moreover, current AI-text classifiers cannot reliably detect ChatGPT's use in school work, due to both their propensity to classify human-written answers as AI-generated, as well as the relative ease with which AI-generated text can be edited to evade detection. Finally, there seems to be an emerging consensus among students to use the tool, and among educators to treat its use as plagiarism. Our findings offer insights that could guide policy discussions addressing the integration of artificial intelligence into educational frameworks.

Impact of routine brain imaging on the prognosis of patients with left-sided valve infective endocarditis without neurological manifestations.

BACKGROUND: There are limited data on the impact of routine use of brain magnetic resonance imaging (MRI) on the prognosis of neurologically asymptomatic patients with left-sided infective endocarditis (IE). METHODS: Among patients diagnosed with possible or definite IE in two tertiary referral centers between January 2005 and March 2019, we identified 527 left-sided IE patients without neurological symptoms or signs at the time of diagnosis. Patients who underwent brain MRI within 1 week after the IE diagnosis were classified as the routine brain imaging group (n = 216), and the rest were categorized as the control group (n = 311). All-cause mortality at 3 months, attributable mortality (defined as death directly related to IE), and fatal neurological events compared after adjustment using inverse probability of treatment weighting (IPTW). RESULTS: During a median follow-up of 57 months, the routine brain imaging group had a similar risk of 3-month all-cause mortality to the control group in the multivariate analysis (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.14) and IPTW-adjusted cohort (HR, 0.59; 95% CI, 0.25-1.42). The risks of attributable mortality and fatal neurological events were also similar between the two groups in the multivariable analysis and IPTW-adjusted cohort. In the subgroup analysis, the routine brain imaging group showed more favorable outcomes in cases of large vegetation (> 10 mm) or acute-onset microorganisms. CONCLUSIONS: Routine use of brain MRI in left-sided IE patients without neurological manifestations is not associated with improved clinical outcomes. However, routine brain imaging in appropriate clinical settings could improve clinical outcomes.

Effect of Edoxaban Versus Antiplatelet Therapy on Leaflet Thrombosis and Cerebral Thromboembolism After TAVI According to Major Clinical and Anatomic Factors in Prespecified Subgroup Analysis from the ADAPT-TAVR Trial.

It is unknown whether edoxaban versus dual antiplatelet therapy (DAPT) has differential treatment effects on leaflet thrombosis, cerebral thromboembolism, and neurologic or neurocognitive dysfunction according to clinical and anatomic factors after transcatheter aortic valve implantation. To investigate the relative effects of edoxaban and DAPT on leaflet and cerebral thromboembolism in patients with major risk factors. The primary end point of this study was the incidence of leaflet thrombosis on computed tomography at 6 months. The secondary end points were new cerebral lesions on brain magnetic resonance imaging and neurologic and neurocognitive dysfunction between baseline and 6-month follow-up. Cox regression models assessed the consistency of the treatment effects in the prespecified subgroups. The favorable effect of edoxaban versus DAPT on the leaflet thrombosis was consistent across multiple clinical or anatomic subgroups, without significant interaction between the drug effect and each subgroup (p for interaction for age = 0.597, gender = 0.557, body mass index = 0.866, Society of Thoracic Surgeons score = 0.307, valve type = 0.702, edoxaban reduction criteria = 0.604, and valve morphology = 0.688). However, the incidence of new cerebral lesions on brain magnetic resonance imaging and worsening of neurologic and neurocognitive function were not significantly different between the groups among the various key subgroups. The relative effects of edoxaban and DAPT on the risk of leaflet thrombosis, cerebral thromboembolism, and neurologic dysfunction were consistent across a diverse spectrum of clinical or anatomical factors. Further studies are required to define tailored antithrombotic therapy for high-risk groups with specific clinical or anatomic characteristics.

Clinical outcomes after aortic valve replacement with severe stenosis of trileaflet aortic valve and low valve calcium score.

BACKGROUND: Some patients have severe aortic valve stenosis (AS) despite a lower degree of aortic valve calcification (AVC). This study compared the clinical features and prognosis of patients undergoing aortic valve replacement (AVR) for severe AS with a low AVC score compared with those with higher AVC scores. METHODS: This study included 1002 Korean patients with symptomatic severe degenerative AS who underwent AVR. We measured AVC score before AVR and defined low AVC as AVC score of <2000 units for male patients and <1300 units for female patients. Patients with bicuspid or rheumatic aortic valve disease were excluded. RESULTS: The mean age was 75.6±7.9 years and 487 patients (48.6%) were female. Mean left ventricular ejection fraction was 59.4%±10.4%, and concomitant coronary revascularisation was performed in 96 patients (9.6%). The median aortic valve calcium score was 3122 units (IQR 2249-4289 units) among male patients and 1756 units (IQR 1192-2572) among female patients. A total of 242 patients (24.2%) had low AVC; they were significantly younger (73.5±8.7 years vs 76.3±7.5 years, p<0.001) and were more likely to be female (59.5% vs 45.1%, p<0.001) and on haemodialysis (5.4% vs 1.8%, p=0.006) than those with high AVC. During a follow-up (median: 3.8 years), the patients with low AVC had significantly higher risk of death from any cause (adjusted HR 1.60, 95% CI 1.02 to 2.52, p=0.04), mostly non-cardiac cause. CONCLUSIONS: Patients with low AVC exhibit distinct clinical characteristics and a higher risk of long-term mortality compared with those with high AVC.