Artificial intelligence guided screening for cardiomyopathies in an obstetric population: a pragmatic randomized clinical trial.

Nigeria has the highest reported incidence of peripartum cardiomyopathy worldwide. This open-label, pragmatic clinical trial randomized pregnant and postpartum women to usual care or artificial intelligence (AI)-guided screening to assess its impact on the diagnosis left ventricular systolic dysfunction (LVSD) in the perinatal period. The study intervention included digital stethoscope recordings with point of-care AI predictions and a 12-lead electrocardiogram with asynchronous AI predictions for LVSD. The primary end point was identification of LVSD during the study period. In the intervention arm, the primary end point was defined as the number of identified participants with LVSD as determined by a positive AI screen, confirmed by echocardiography. In the control arm, this was the number of participants with clinical recognition and documentation of LVSD on echocardiography in keeping with current standard of care. Participants in the intervention arm had a confirmatory echocardiogram at baseline for AI model validation. A total of 1,232 (616 in each arm) participants were randomized and 1,195 participants (587 intervention arm and 608 control arm) completed the baseline visit at 6 hospitals in Nigeria between August 2022 and September 2023 with follow-up through May 2024. Using the AI-enabled digital stethoscope, the primary study end point was met with detection of 24 out of 587 (4.1%) versus 12 out of 608 (2.0%) patients with LVSD (intervention versus control odds ratio 2.12, 95% CI 1.05-4.27; P = 0.032). With the 12-lead AI-electrocardiogram model, the primary end point was detected in 20 out of 587 (3.4%) versus 12 out of 608 (2.0%) patients (odds ratio 1.75, 95% CI 0.85-3.62; P = 0.125). A similar direction of effect was observed in prespecified subgroup analysis. There were no serious adverse events related to study participation. In pregnant and postpartum women, AI-guided screening using a digital stethoscope improved the diagnosis of pregnancy-related cardiomyopathy. ClinicalTrials.gov registration: NCT05438576.

Reliability of MR Enterography Features for Describing Fibrostenosing Crohn Disease.

Background Clinical decision making and drug development for fibrostenosing Crohn disease is constrained by a lack of imaging definitions, scoring conventions, and validated end points. Purpose To assess the reliability of MR enterography features to describe Crohn disease strictures and determine correlation with stricture severity. Materials and Methods A retrospective study of patients with symptomatic terminal ileal Crohn disease strictures who underwent MR enterography at tertiary care centers (Cleveland Clinic: September 2013 to November 2020; Mayo Clinic: February 2008 to March 2019) was conducted by using convenience sampling. In the development phase, blinded and trained radiologists independently evaluated 26 MR enterography features from baseline and follow-up examinations performed more than 6 months apart, with no bowel resection performed between examinations. Follow-up examinations closest to 12 months after baseline were selected. Reliability was assessed using the intraclass correlation coefficient (ICC). In the validation phase, after five features were redefined, reliability was re-estimated in an independent convenience sample using baseline examinations. Multivariable linear regression analysis identified features with at least moderate interrater reliability (ICC ≥0.41) that were independently associated with stricture severity. Results Ninety-nine (mean age, 40 years ± 14 [SD]; 50 male) patients were included in the development group and 51 (mean age, 45 years ± 16 [SD]; 35 female) patients were included in the validation group. In the development group, nine features had at least moderate interrater reliability. One additional feature demonstrated moderate reliability in the validation group. Stricture length (ICC = 0.85 [95% CI: 0.75, 0.91] and 0.91 [95% CI: 0.75, 0.96] in development and validation phase, respectively) and maximal associated small bowel dilation (ICC = 0.74 [95% CI: 0.63, 0.80] and 0.73 [95% CI: 0.58, 0.87] in development and validation group, respectively) had the highest interrater reliability. Stricture length, maximal stricture wall thickness, and maximal associated small bowel dilation were independently (regression coefficients, 0.09-3.97; P < .001) associated with stricture severity. Conclusion MR enterography definitions and scoring conventions for reliably assessing features of Crohn disease strictures were developed and validated, and feature correlation with stricture severity was determined. © RSNA, 2024 Supplemental material is available for this article. See also the article by Rieder and Ma et al in this issue. See also the editorial by Galgano and Summerlin in this issue.

Dapagliflozin Enhances Arterial and Venous Compliance During Exercise in Heart Failure With Preserved Ejection Fraction: Insights From the CAMEO-DAPA Trial.

BACKGROUND: Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. METHODS: In this secondary analysis from the CAMEO-DAPA trial (Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial), 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model. RESULTS: There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P=0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m2 [95% CI, 0.003-0.11] P=0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P=0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P=0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P=0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P=0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P<0.001). CONCLUSIONS: In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04730947.

Peripheral liver metastases are more frequently missed than central metastases in contrast-enhanced CT: insights from a 25-reader performance study.

PURPOSE: Subtle liver metastases may be missed in contrast enhanced CT imaging. We determined the impact of lesion location and conspicuity on metastasis detection using data from a prior reader study. METHODS: In the prior reader study, 25 radiologists examined 40 CT exams each and circumscribed all suspected hepatic metastases. CT exams were chosen to include a total of 91 visually challenging metastases. The detectability of a metastasis was defined as the fraction of radiologists that circumscribed it. A conspicuity index was calculated for each metastasis by multiplying metastasis diameter with its contrast, defined as the difference between the average of a circular region within the metastasis and the average of the surrounding circular region of liver parenchyma. The effects of distance from liver edge and of conspicuity index on metastasis detectability were measured using multivariable linear regression. RESULTS: The median metastasis was 1.4 cm from the edge (interquartile range [IQR], 0.9-2.1 cm). Its diameter was 1.2 cm (IQR, 0.9-1.8 cm), and its contrast was 38 HU (IQR, 23-68 HU). An increase of one standard deviation in conspicuity index was associated with a 6.9% increase in detectability (p = 0.008), whereas an increase of one standard deviation in distance from the liver edge was associated with a 5.5% increase in detectability (p = 0.03). CONCLUSION: Peripheral liver metastases were missed more frequently than central liver metastases, with this effect depending on metastasis size and contrast.

Dapagliflozin and Right Ventricular-Pulmonary Vascular Interaction in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Increases in pulmonary capillary wedge pressure (PCWP) during exercise reduce pulmonary artery (PA) compliance, increase pulsatile right ventricular (RV) afterload, and impair RV-PA coupling in patients with heart failure with preserved ejection fraction (HFpEF). The effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on pulmonary vascular properties and RV-PA coupling are unknown. Objective: To test the effect of dapagliflozin on right ventricular performance and pulmonary vascular load during exertion in HFpEF. Design, Setting, and Participants: Evaluation of the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction (CAMEO-DAPA) randomized clinical trial demonstrated improvement in PCWP at rest and exercise over 24 weeks with dapagliflozin compared with placebo with participants recruited between February 2021 and May 2022. This secondary analysis evaluates the effects of dapagliflozin on pulsatile pulmonary vascular load and RV-PA coupling using simultaneous echocardiography and high-fidelity invasive hemodynamic testing with exercise. This was a single-center study including patients with hemodynamically confirmed HFpEF with exercise PCWP of 25 mm Hg or greater. Interventions: Dapagliflozin or placebo for 24 weeks. Main Outcomes and Measures: Pulsatile pulmonary vascular load (PA compliance and elastance) and right ventricular performance (PA pulsatility index, RV systolic velocity [s']/PA mean) during rest and exercise. Results: Among 37 randomized participants (mean [SD] age, 67.4 [8.5] years; 25 female [65%]; mean [SD] body mass index, 34.9 [6.7]; calculated as weight in kilograms divided by height in meters squared), there was no effect of dapagliflozin on PA loading or RV-PA interaction at rest. However, with exercise, dapagliflozin improved PA compliance (placebo-corrected mean difference, 0.57 mL/mm Hg; 95% CI, 0.11-1.03 mL/mm Hg; P = .02) and decreased PA elastance (stiffness; -0.17 mm Hg/mL; 95% CI, -0.28 to -0.07 mm Hg/mL; P = .001). RV function during exercise improved, with increase in PA pulsatility index (0.33; 95% CI, 0.08-0.59; P = .01) and increase in exercise RV s' indexed to PA pressure (0.09 cm·s-1/mm Hg; 95% CI, 0.02-0.16 cm·s-1/mm Hg; P = .01). Improvements in pulsatile RV load and RV-PA coupling were correlated with reduction in right atrial (RA) pressure (PA elastance Pearson r = 0.55; P =.008; RV s'/PA elastance Pearson r = -0.60; P =.002) and PCWP (PA elastance Pearson r = 0.58; P <.001; RV s'/PA elastance Pearson r = -0.47; P = .02). Dapagliflozin increased resistance-compliance time (dapagliflozin, median [IQR] change, 0.06 [0.03-0.15] seconds; placebo, median [IQR] change, 0.01 [-0.02 to 0.05] seconds; P =.046), resulting in higher PA compliance for any exercise pulmonary vascular resistance. Conclusions and Relevance: Results of this randomized clinical trial reveal that treatment with dapagliflozin for 24 weeks reduced pulsatile pulmonary vascular load and enhanced dynamic RV-PA interaction during exercise in patients with HFpEF, findings that are related to the magnitude of PCWP reduction. Benefits on dynamic right ventricular-pulmonary vascular coupling may partially explain the benefits of SGLT2 inhibitors in HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04730947.

An evidence-based screening tool for heart failure with preserved ejection fraction: the HFpEF-ABA score.

Heart failure with preserved ejection fraction (HFpEF) is under-recognized in clinical practice. Although a previously developed risk score, termed H2FPEF, can be used to estimate HFpEF probability, this score requires imaging data, which is often unavailable. Here we sought to develop an HFpEF screening model that is based exclusively on clinical variables and that can guide the need for echocardiography and further testing. In a derivation cohort (n = 414, 249 women), a clinical model using age, body mass index and history of atrial fibrillation (termed the HFpEF-ABA score) showed good discrimination (area under the curve (AUC) = 0.839 (95% confidence interval (CI) = 0.800-0.877), P < 0.0001). The performance of the model was validated in an international, multicenter cohort (n = 736, 443 women; AUC = 0.813 (95% CI = 0.779-0.847), P < 0.0001) and further validated in two additional cohorts: a cohort including patients with unexplained dyspnea (n = 228, 136 women; AUC = 0.840 (95% CI = 0.782-0.900), P < 0.0001) and a cohort for which HF hospitalization was used instead of hemodynamics to establish an HFpEF diagnosis (n = 456, 272 women; AUC = 0.929 (95% CI = 0.909-0.948), P < 0.0001). Model-based probabilities were also associated with increased risk of HF hospitalization or death among patients from the Mayo Clinic (n = 790) and a US national cohort across the Veteran Affairs health system (n = 3076, 110 women). Using the HFpEF-ABA score, rapid and efficient screening for risk of undiagnosed HFpEF can be performed in patients with dyspnea using only age, body mass index and history of atrial fibrillation.

Artificial intelligence-based screening for cardiomyopathy in an obstetric population: A pilot study.

Background: Cardiomyopathy is a leading cause of pregnancy-related mortality and the number one cause of death in the late postpartum period. Delay in diagnosis is associated with severe adverse outcomes. Objective: To evaluate the performance of an artificial intelligence-enhanced electrocardiogram (AI-ECG) and AI-enabled digital stethoscope to detect left ventricular systolic dysfunction in an obstetric population. Methods: We conducted a single-arm prospective study of pregnant and postpartum women enrolled at 3 sites between October 28, 2021, and October 27, 2022. Study participants completed a standard 12-lead ECG, digital stethoscope ECG and phonocardiogram recordings, and a transthoracic echocardiogram within 24 hours. Diagnostic performance was evaluated using the area under the curve (AUC). Results: One hundred women were included in the final analysis. The median age was 31 years (Q1: 27, Q3: 34). Thirty-eight percent identified as non-Hispanic White, 32% as non-Hispanic Black, and 21% as Hispanic. Five percent and 6% had left ventricular ejection fraction (LVEF) <45% and <50%, respectively. The AI-ECG model had near-perfect classification performance (AUC: 1.0, 100% sensitivity; 99%-100% specificity) for detection of cardiomyopathy at both LVEF categories. The AI-enabled digital stethoscope had an AUC of 0.98 (95% CI: 0.95, 1.00) and 0.97 (95% CI: 0.93, 1.00), for detection of LVEF <45% and <50%, respectively, with 100% sensitivity and 90% specificity. Conclusion: We demonstrate an AI-ECG and AI-enabled digital stethoscope were effective for detecting cardiac dysfunction in an obstetric population. Larger studies, including an evaluation of the impact of screening on clinical outcomes, are essential next steps.

Nimodipine-associated standard dose reductions and neurologic outcomes after aneurysmal subarachnoid hemorrhage: the era of pharmacogenomics.

Nimodipine, an L-type cerebroselective calcium channel antagonist, is the only drug approved by the US Food and Drug Administration for the neuroprotection of patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized, placebo-controlled trials of nimodipine demonstrated clinical improvement over placebo; however, these occurred before precision medicine with pharmacogenomics was readily available. The standard enteral dose of nimodipine recommended after aSAH is 60 mg every 4 h. However, up to 78% of patients with aSAH develop systemic arterial hypotension after taking the drug at the recommended dose, which could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure and cerebral blood flow, particularly when concomitant vasospasm is present. We investigated the association between nimodipine dose changes and clinical outcomes in a consecutive series of 150 patients (mean age, 56 years; 70.7% women) with acute aSAH. We describe the pharmacogenomic relationship of nimodipine dose reduction with clinical outcomes. These results have major implications for future individualized dosing of nimodipine in the era of precision medicine.

Unlocking the potential of artificial intelligence in electrocardiogram biometrics: age-related changes, anomaly detection, and data authenticity in mobile health platforms.

Aims: Mobile devices such as smartphones and watches can now record single-lead electrocardiograms (ECGs), making wearables a potential screening tool for cardiac and wellness monitoring outside of healthcare settings. Because friends and family often share their smart phones and devices, confirmation that a sample is from a given patient is important before it is added to the electronic health record. Methods and results: We sought to determine whether the application of Siamese neural network would permit the diagnostic ECG sample to serve as both a medical test and biometric identifier. When using similarity scores to discriminate whether a pair of ECGs came from the same patient or different patients, inputs of single-lead and 12-lead medians produced an area under the curve of 0.94 and 0.97, respectively. Conclusion: The similar performance of the single-lead and 12-lead configurations underscores the potential use of mobile devices to monitor cardiac health.

Midbrain dopaminergic degeneration differentially modulates primary motor cortex activity and motor behavior in hemi-parkinsonian rats.

Parkinson's disease (PD) is marked by degeneration in the nigrostriatal dopaminergic pathway, affecting motor control via complex changes in the cortico-basal ganglia-thalamic motor network, including the primary motor cortex (M1). The modulation of M1 neuronal activity by dopaminergic inputs, particularly from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), plays a crucial role in PD pathophysiology. This study investigates how nigrostriatal dopaminergic degeneration influences M1 neuronal activity in rats using in vivo calcium imaging. Histological analysis confirmed dopaminergic lesion severity, with high lesion level rats showing significant motor deficits. Levodopa treatment improved fine motor abilities, particularly in high lesion level rats. Analysis of M1 calcium signals based on dopaminergic lesion severity revealed distinct M1 activity patterns. Animals with low dopaminergic lesion showed increased calcium events, while high lesion level rats exhibited decreased activity, partially restored by levodopa. These findings suggest that M1 activity is more sensitive to transient fluctuations in dopaminergic transmission, rather than to chronic high or low dopaminergic signaling. This study underscores the complex interplay between dopaminergic signaling and M1 neuronal activity in PD symptoms development. Further research integrating behavioral and calcium imaging data can elucidate mechanisms underlying motor deficits and therapeutic responses in PD.

Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease.

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy. Design, Setting, and Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses. Main Outcomes and Measures: Clinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET). Results: Of the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02). Conclusions and Relevance: Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.

Machine Learning for Diagnosis of Pulmonary Hypertension by Echocardiography.

OBJECTIVE: To evaluate a machine learning (ML)-based model for pulmonary hypertension (PH) prediction using measurements and impressions made during echocardiography. METHODS: A total of 7853 consecutive patients with right-sided heart catheterization and transthoracic echocardiography performed within 1 week from January 1, 2012, through December 31, 2019, were included. The data were split into training (n=5024 [64%]), validation (n=1275 [16%]), and testing (n=1554 [20%]). A gradient boosting machine with enumerated grid search for optimization was selected to allow missing data in the boosted trees without imputation. The training target was PH, defined by right-sided heart catheterization as mean pulmonary artery pressure above 20 mm Hg; model performance was maximized relative to area under the receiver operating characteristic curve using 5-fold cross-validation. RESULTS: Cohort age was 64±14 years; 3467 (44%) were female, and 81% (6323/7853) had PH. The final trained model included 19 characteristics, measurements, or impressions derived from the echocardiogram. In the testing data, the model had high discrimination for the detection of PH (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.80 to 0.85). The model's accuracy, sensitivity, positive predictive value, and negative predictive value were 82% (1267/1554), 88% (1098/1242), 89% (1098/1241), and 54% (169/313), respectively. CONCLUSION: By use of ML, PH could be predicted on the basis of clinical and echocardiographic variables, without tricuspid regurgitation velocity. Machine learning methods appear promising for identifying patients with low likelihood of PH.

Peer review of clinical and translational research manuscripts: Perspectives from statistical collaborators.

Research articles in the clinical and translational science literature commonly use quantitative data to inform evaluation of interventions, learn about the etiology of disease, or develop methods for diagnostic testing or risk prediction of future events. The peer review process must evaluate the methodology used therein, including use of quantitative statistical methods. In this manuscript, we provide guidance for peer reviewers tasked with assessing quantitative methodology, intended to complement guidelines and recommendations that exist for manuscript authors. We describe components of clinical and translational science research manuscripts that require assessment including study design and hypothesis evaluation, sampling and data acquisition, interventions (for studies that include an intervention), measurement of data, statistical analysis methods, presentation of the study results, and interpretation of the study results. For each component, we describe what reviewers should look for and assess; how reviewers should provide helpful comments for fixable errors or omissions; and how reviewers should communicate uncorrectable and irreparable errors. We then discuss the critical concepts of transparency and acceptance/revision guidelines when communicating with responsible journal editors.

Hyperglycemia Suppresses Lactate Clearance During Exercise in Type 1 Diabetes.

CONTEXT: Circulating lactate concentration is an important determinant of exercise tolerance. OBJECTIVE: This work aimed to determine the role of hyperglycemia on lactate metabolism during exercise in individuals with type 1 diabetes (T1D). METHODS: The protocol at the University of Virginia compared 7 T1D participants and 7 participants without diabetes (ND) at euglycemia (5.5 mM) or hyperglycemia (9.2 mM) in random order in T1D and at euglycemia in ND. Intervention included [1-13C] lactate infusion, exercise at 65% maximal oxygen uptake (VO2max), euglycemia, and hyperglycemia visits. The main outcome measure was lactate turnover before, during, and after 60 minutes of exercise at 65% VO2max. RESULTS: A 2-compartment model with loss only from the peripheral compartment described lactate kinetics. Volume of distribution of the accessible compartment was similar between T1D and ND individuals (P = .76) and concordant with plasma volume (∼40 mL/kg). Circulating lactate concentrations were higher (P < .001) in T1D participants during exercise at hyperglycemia than euglycemia. Exercise-induced lactate appearance did not differ (P = .13) between hyperglycemia and euglycemia. However, lactate clearance (CL) was lower (P = .03) during hyperglycemia than euglycemia in T1D participants. There were no differences in any of the aforementioned parameters between T1D and ND participants during euglycemia. CONCLUSION: Hyperglycemia modulates lactate metabolism during exercise by lowering CL, leading to higher circulating lactate concentrations in T1D individuals. This novel observation implies that exercise during hyperglycemia can lead to higher circulating lactate concentrations thus increasing the likelihood of reaching the lactate threshold sooner in T1D, and has high translational relevance both for providers and recreationally active people with T1D.

Artificial intelligence-enabled ECG for left ventricular diastolic function and filling pressure.

Assessment of left ventricular diastolic function plays a major role in the diagnosis and prognosis of cardiac diseases, including heart failure with preserved ejection fraction. We aimed to develop an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to identify echocardiographically determined diastolic dysfunction and increased filling pressure. We trained, validated, and tested an AI-enabled ECG in 98,736, 21,963, and 98,763 patients, respectively, who had an ECG and echocardiographic diastolic function assessment within 14 days with no exclusion criteria. It was also tested in 55,248 patients with indeterminate diastolic function by echocardiography. The model was evaluated using the area under the curve (AUC) of the receiver operating characteristic curve, and its prognostic performance was compared to echocardiography. The AUC for detecting increased filling pressure was 0.911. The AUCs to identify diastolic dysfunction grades ≥1, ≥2, and 3 were 0.847, 0.911, and 0.943, respectively. During a median follow-up of 5.9 years, 20,223 (20.5%) died. Patients with increased filling pressure predicted by AI-ECG had higher mortality than those with normal filling pressure, after adjusting for age, sex, and comorbidities in the test group (hazard ratio (HR) 1.7, 95% CI 1.645-1.757) similar to echocardiography and in the indeterminate group (HR 1.34, 95% CI 1.298-1.383). An AI-enabled ECG identifies increased filling pressure and diastolic function grades with a good prognostic value similar to echocardiography. AI-ECG is a simple and promising tool to enhance the detection of diseases associated with diastolic dysfunction and increased diastolic filling pressure.

Targeted Training Reduces Search Errors but Not Classification Errors for Hepatic Metastasis Detection at Contrast-Enhanced CT.

RATIONALE AND OBJECTIVES: Methods are needed to improve the detection of hepatic metastases. Errors occur in both lesion detection (search) and decisions of benign versus malignant (classification). Our purpose was to evaluate a training program to reduce search errors and classification errors in the detection of hepatic metastases in contrast-enhanced abdominal computed tomography (CT). MATERIALS AND METHODS: After Institutional Review Board approval, we conducted a single-group prospective pretest-posttest study. Pretest and posttest were identical and consisted of interpreting 40 contrast-enhanced abdominal CT exams containing 91 liver metastases under eye tracking. Between pretest and posttest, readers completed search training with eye-tracker feedback and coaching to increase interpretation time, use liver windows, and use coronal reformations. They also completed classification training with part-task practice, rating lesions as benign or malignant. The primary outcome was metastases missed due to search errors (<2 seconds gaze under eye tracker) and classification errors (>2 seconds). Jackknife free-response receiver operator characteristic (JAFROC) analysis was also conducted. RESULTS: A total of 31 radiologist readers (8 abdominal subspecialists, 8 nonabdominal subspecialists, 15 senior residents/fellows) participated. Search errors were reduced (pretest 11%, posttest 8%, difference 3% [95% confidence interval, 0.3%-5.1%], P = .01), but there was no difference in classification errors (difference 0%, P = .97) or in JAFROC figure of merit (difference -0.01, P = .36). In subgroup analysis, abdominal subspecialists demonstrated no evidence of change. CONCLUSION: Targeted training reduced search errors but not classification errors for the detection of hepatic metastases at contrast-enhanced abdominal CT. Improvements were not seen in all subgroups.