Blinded, randomized trial of sonographer versus AI cardiac function assessment.

Artificial intelligence (AI) has been developed for echocardiography1-3, although it has not yet been tested with blinding and randomization. Here we designed a blinded, randomized non-inferiority clinical trial (ClinicalTrials.gov ID: NCT05140642; no outside funding) of AI versus sonographer initial assessment of left ventricular ejection fraction (LVEF) to evaluate the impact of AI in the interpretation workflow. The primary end point was the change in the LVEF between initial AI or sonographer assessment and final cardiologist assessment, evaluated by the proportion of studies with substantial change (more than 5% change). From 3,769 echocardiographic studies screened, 274 studies were excluded owing to poor image quality. The proportion of studies substantially changed was 16.8% in the AI group and 27.2% in the sonographer group (difference of -10.4%, 95% confidence interval: -13.2% to -7.7%, P < 0.001 for non-inferiority, P < 0.001 for superiority). The mean absolute difference between final cardiologist assessment and independent previous cardiologist assessment was 6.29% in the AI group and 7.23% in the sonographer group (difference of -0.96%, 95% confidence interval: -1.34% to -0.54%, P < 0.001 for superiority). The AI-guided workflow saved time for both sonographers and cardiologists, and cardiologists were not able to distinguish between the initial assessments by AI versus the sonographer (blinding index of 0.088). For patients undergoing echocardiographic quantification of cardiac function, initial assessment of LVEF by AI was non-inferior to assessment by sonographers.

Alternating low-rank tensor reconstruction for improved multiparametric mapping with cardiovascular MR Multitasking.

PURPOSE: To develop a novel low-rank tensor reconstruction approach leveraging the complete acquired data set to improve precision and repeatability of multiparametric mapping within the cardiovascular MR Multitasking framework. METHODS: A novel approach that alternated between estimation of temporal components and spatial components using the entire data set acquired (i.e., including navigator data and imaging data) was developed to improve reconstruction. The precision and repeatability of the proposed approach were evaluated on numerical simulations, 10 healthy subjects, and 10 cardiomyopathy patients at multiple scan times for 2D myocardial T1/T2 mapping with MR Multitasking and were compared with those of the previous navigator-derived fixed-basis approach. RESULTS: In numerical simulations, the proposed approach outperformed the previous fixed-basis approach with lower T1 and T2 error against the ground truth at all scan times studied and showed better motion fidelity. In human subjects, the proposed approach showed no significantly different sharpness or T1/T2 measurement and significantly improved T1 precision by 20%-25%, T2 precision by 10%-15%, T1 repeatability by about 30%, and T2 repeatability by 25%-35% at 90-s and 50-s scan times The proposed approach at the 50-s scan time also showed comparable results with that of the previous fixed-basis approach at the 90-s scan time. CONCLUSION: The proposed approach improved precision and repeatability for quantitative imaging with MR Multitasking while maintaining comparable motion fidelity, T1/T2 measurement, and septum sharpness and had the potential for further reducing scan time from 90 s to 50 s.

Sex Differences in Myocardial and Vascular Aging.

It is well known that cardiovascular disease manifests differently in women and men. The underlying causes of these differences during the aging lifespan are less well understood. Sex differences in cardiac and vascular phenotypes are seen in childhood and tend to track along distinct trajectories related to dimorphism in genetic factors as well as response to risk exposures and hormonal changes during the life course. These differences underlie sex-specific variation in cardiovascular events later in life, including myocardial infarction, heart failure, ischemic stroke, and peripheral vascular disease. With respect to cardiac phenotypes, females have intrinsically smaller body size-adjusted cardiac volumes and they tend to experience greater age-related wall thickening and myocardial stiffening with aging. With respect to vascular phenotypes, sexual dimorphism in both physiology and pathophysiology are also seen, including overt differences in blood pressure trajectories. The majority of sex differences in myocardial and vascular alterations that manifest with aging seem to follow relatively consistent trajectories from the very early to the very later stages of life. This review aims to synthesize recent cardiovascular aging-related research to highlight clinically relevant studies in diverse female and male populations that can inform approaches to improving the diagnosis, management, and prognosis of cardiovascular disease risks in the aging population at large.

MR Multitasking-based multi-dimensional assessment of cardiovascular system (MT-MACS) with extended spatial coverage and water-fat separation.

PURPOSE: To extend the MR MultiTasking-based Multidimensional Assessment of Cardiovascular System (MT-MACS) technique with larger spatial coverage and water-fat separation for comprehensive aortocardiac assessment. METHODS: MT-MACS adopts a low-rank tensor image model for 7D imaging, with three spatial dimensions for volumetric imaging, one cardiac motion dimension for cine imaging, one respiratory motion dimension for free-breathing imaging, one T2-prepared inversion recovery time dimension for multi-contrast assessment, and one T2*-decay time dimension for water-fat separation. Nine healthy subjects were recruited for the 3T study. Overall image quality was scored on bright-blood (BB), dark-blood (DB), and gray-blood (GB) contrasts using a 4-point scale (0-poor to 3-excellent) by two independent readers, and their interreader agreement was evaluated. Myocardial wall thickness and left ventricular ejection fraction (LVEF) were quantified on DB and BB contrasts, respectively. The agreement in these metrics between MT-MACS and conventional breath-held, electrocardiography-triggered 2D sequences were evaluated. RESULTS: MT-MACS provides both water-only and fat-only images with excellent image quality (average score = 3.725/3.780/3.835/3.890 for BB/DB/GB/fat-only images) and moderate to high interreader agreement (weighted Cohen's kappa value = 0.727/0.668/1.000/1.000 for BB/DB/GB/fat-only images). There were good to excellent agreements in myocardial wall thickness measurements (intraclass correlation coefficients [ICC] = 0.781/0.929/0.680/0.878 for left atria/left ventricle/right atria/right ventricle) and LVEF quantification (ICC = 0.716) between MT-MACS and 2D references. All measurements were within the literature range of healthy subjects. CONCLUSION: The refined MT-MACS technique provides multi-contrast, phase-resolved, and water-fat imaging of the aortocardiac systems and allows evaluation of anatomy and function. Clinical validation is warranted.

Serological response to vaccination in post-acute sequelae of COVID.

BACKGROUND: Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. METHODS: We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. RESULTS: Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. CONCLUSION: We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.

Free-breathing, non-ECG, simultaneous myocardial T1 , T2 , T2 *, and fat-fraction mapping with motion-resolved cardiovascular MR multitasking.

PURPOSE: To develop a free-breathing, non-electrocardiogram technique for simultaneous myocardial T1 , T2 , T2 *, and fat-fraction (FF) mapping in a single scan. METHODS: The MR Multitasking framework is adapted to quantify T1 , T2 , T2 *, and FF simultaneously. A variable TR scheme is developed to preserve temporal resolution and imaging efficiency. The underlying high-dimensional image is modeled as a low-rank tensor, which allows accelerated acquisition and efficient reconstruction. The accuracy and/or repeatability of the technique were evaluated on static and motion phantoms, 12 healthy volunteers, and 3 patients by comparing to the reference techniques. RESULTS: In static and motion phantoms, T1 /T2 /T2 */FF measurements showed substantial consistency (R > 0.98) and excellent agreement (intraclass correlation coefficient > 0.93) with reference measurements. In human subjects, the proposed technique yielded repeatable T1 , T2 , T2 *, and FF measurements that agreed with those from references. CONCLUSIONS: The proposed free-breathing, non-electrocardiogram, motion-resolved Multitasking technique allows simultaneous quantification of myocardial T1 , T2 , T2 *, and FF in a single 2.5-min scan.

Cardiac microstructural alterations in immune-inflammatory myocardial disease: a retrospective case-control study.

BACKGROUND: Immune-inflammatory myocardial disease contributes to multiple chronic cardiac processes, but access to non-invasive screening is limited. We have previously developed a method of echocardiographic texture analysis, called the high-spectrum signal intensity coefficient (HS-SIC) which assesses myocardial microstructure and previously associated with myocardial fibrosis. We aimed to determine whether this echocardiographic texture analysis of cardiac microstructure can identify inflammatory cardiac disease in the clinical setting. METHODS: We conducted a retrospective case-control study of 318 patients with distinct clinical myocardial pathologies and 20 healthy controls. Populations included myocarditis, atypical chest pain/palpitations, STEMI, severe aortic stenosis, acute COVID infection, amyloidosis, and cardiac transplantation with acute rejection, without current rejection but with prior rejection, and with no history of rejection. We assessed the HS-SIC's ability to differentiate between a broader diversity of clinical groups and healthy controls. We used Kruskal-Wallis tests to compare HS-SIC values measured in each of the clinical populations with those in the healthy control group and compared HS-SIC values between the subgroups of cardiac transplantation rejection status. RESULTS: For the total sample of N = 338, the mean age was 49.6 ± 20.9 years and 50% were women. The mean ± standard error of the mean of HS-SIC were: 0.668 ± 0.074 for controls, 0.552 ± 0.049 for atypical chest pain/palpitations, 0.425 ± 0.058 for myocarditis, 0.881 ± 0.129 for STEMI, 1.116 ± 0.196 for severe aortic stenosis, 0.904 ± 0.116 for acute COVID, and 0.698 ± 0.103 for amyloidosis. Among cardiac transplant recipients, HS-SIC values were 0.478 ± 0.999 for active rejection, 0.594 ± 0.091 for prior rejection, and 1.191 ± 0.442 for never rejection. We observed significant differences in HS-SIC between controls and myocarditis (P = 0.0014), active rejection (P = 0.0076), and atypical chest pain or palpitations (P = 0.0014); as well as between transplant patients with active rejection and those without current or prior rejection (P = 0.031). CONCLUSIONS: An echocardiographic method can be used to characterize tissue signatures of microstructural changes across a spectrum of cardiac disease including immune-inflammatory conditions.

Next-Generation Hardware Advances in CT: Cardiac Applications.

Impending major hardware advances in cardiac CT include three areas: ultra-high-resolution (UHR) CT, photon-counting CT, and phase-contrast CT. Cardiac CT is a particularly demanding CT application that requires a high degree of temporal resolution, spatial resolution, and soft-tissue contrast in a moving structure. In this review, cardiac CT is used to highlight the strengths of these technical advances. UHR CT improves visualization of calcified and stented vessels but may result in increased noise and radiation exposure. Photon-counting CT uses multiple photon energies to reduce artifacts, improve contrast resolution, and perform material decomposition. Finally, phase-contrast CT uses x-ray refraction properties to improve spatial and soft-tissue contrast. This review describes these hardware advances in CT and their relevance to cardiovascular imaging.

Prediction of revascularization by coronary CT angiography using a machine learning ischemia risk score.

OBJECTIVES: The machine learning ischemia risk score (ML-IRS) is a machine learning-based algorithm designed to identify hemodynamically significant coronary disease using quantitative coronary computed tomography angiography (CCTA). The purpose of this study was to examine whether the ML-IRS can predict revascularization in patients referred for invasive coronary angiography (ICA) after CCTA. METHODS: This study was a post hoc analysis of a prospective dual-center registry of sequential patients undergoing CCTA followed by ICA within 3 months, referred from inpatient, outpatient, and emergency department settings (n = 352, age 63 ± 10 years, 68% male). The primary outcome was revascularization by either percutaneous coronary revascularization or coronary artery bypass grafting. Blinded readers performed semi-automated quantitative coronary plaque analysis. The ML-IRS was automatically computed. Relationships between clinical risk factors, coronary plaque features, and ML-IRS with revascularization were examined. RESULTS: The study cohort consisted of 352 subjects with 1056 analyzable vessels. The ML-IRS ranged between 0 and 81% with a median of 18.7% (6.4-34.8). Revascularization was performed in 26% of vessels. Vessels receiving revascularization had higher ML-IRS (33.6% (21.1-55.0) versus 13.0% (4.5-29.1), p < 0.0001), as well as higher contrast density difference, and total, non-calcified, calcified, and low-density plaque burden. ML-IRS, when added to a traditional risk model based on clinical data and stenosis to predict revascularization, resulted in increased area under the curve from 0.69 (95% CI: 0.65-0.72) to 0.78 (95% CI: 0.75-0.81) (p < 0.0001), with an overall continuous net reclassification improvement of 0.636 (95% CI: 0.503-0.769; p < 0.0001). CONCLUSIONS: ML-IRS from quantitative coronary CT angiography improved the prediction of future revascularization and can potentially identify patients likely to receive revascularization if referred to cardiac catheterization. KEY POINTS: • Machine learning ischemia risk from quantitative coronary CT angiography was significantly higher in patients who received revascularization versus those who did not receive revascularization. • The machine learning ischemia risk score was significantly higher in patients with invasive fractional flow ≤ 0.8 versus those with > 0.8. • The machine learning ischemia risk score improved the prediction of future revascularization significantly when added to a standard prediction model including stenosis.

Assessment of atherosclerosis in chronic granulomatous disease.

BACKGROUND: Patients with chronic granulomatous disease (CGD) experience immunodeficiency because of defects in the phagocyte NADPH oxidase and the concomitant reduction in reactive oxygen intermediates. This may result in a reduction in atherosclerotic injury. METHODS AND RESULTS: We prospectively assessed the prevalence of cardiovascular risk factors, biomarkers of inflammation and neutrophil activation, and the presence of magnetic resonance imaging and computed tomography quantified subclinical atherosclerosis in the carotid and coronary arteries of 41 patients with CGD and 25 healthy controls in the same age range. Univariable and multivariable associations among risk factors, inflammatory markers, and atherosclerosis burden were assessed. Patients with CGD had significant elevations in traditional risk factors and inflammatory markers compared with control subjects, including hypertension, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, and low high-density lipoprotein. Despite this, patients with CGD had a 22% lower internal carotid artery wall volume compared with control subjects (361.3±76.4 mm(3) versus 463.5±104.7 mm(3); P<0.001). This difference was comparable in p47(phox)- and gp91(phox)-deficient subtypes of CGD and independent of risk factors in multivariate regression analysis. In contrast, the prevalence of coronary arterial calcification was similar between patients with CGD and control subjects (14.6%, CGD; 6.3%, controls; P=0.39). CONCLUSIONS: The observation by magnetic resonance imaging and computerized tomography of reduced carotid but not coronary artery atherosclerosis in patients with CGD despite the high prevalence of traditional risk factors raises questions about the role of NADPH oxidase in the pathogenesis of clinically significant atherosclerosis. Additional high-resolution studies in multiple vascular beds are required to address the therapeutic potential of NADPH oxidase inhibition in cardiovascular diseases. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01063309.

Coronary Plaque Burden at Coronary CT Angiography in Asymptomatic Men and Women.

Purpose To assess the relationship between total, calcified, and noncalcified coronary plaque burdens throughout the entire coronary vasculature at coronary computed tomographic (CT) angiography in relationship to cardiovascular risk factors in asymptomatic individuals with low-to-moderate risk. Materials and Methods This HIPAA-compliant study had institutional review board approval, and written informed consent was obtained. Two hundred two subjects were recruited to an ongoing prospective study designed to evaluate the effect of HMG-CoA reductase inhibitors on atherosclerosis. Eligible subjects were asymptomatic individuals older than 55 years who were eligible for statin therapy. Coronary CT angiography was performed by using a 320-detector row scanner. Coronary wall thickness and plaque were evaluated in all epicardial coronary arteries greater than 2 mm in diameter. Images were analyzed by using dedicated software involving an adaptive lumen attenuation algorithm. Total plaque index (calcified plus noncalcified plaque) was defined as plaque volume divided by vessel length. Multivariable regression analysis was performed to determine the relationship between risk factors and plaque indexes. Results The mean age of the subjects was 65.5 years ± 6.9 (standard deviation) (36% women), and the median coronary artery calcium (CAC) score was 73 (interquartile range, 1-434). The total coronary plaque index was higher in men than in women (42.06 mm(2) ± 9.22 vs 34.33 mm(2) ± 8.35; P < .001). In multivariable analysis controlling for all risk factors, total plaque index remained higher in men than in women (by 5.01 mm(2); P = .03) and in those with higher simvastatin doses (by 0.44 mm(2)/10 mg simvastatin dose equivalent; P = .02). Noncalcified plaque index was positively correlated with systolic blood pressure (ß = 0.80 mm(2)/10 mm Hg; P = .03), diabetes (ß = 4.47 mm(2); P = .03), and low-density lipoprotein (LDL) cholesterol level (ß = 0.04 mm(2)/mg/dL; P = .02); the association with LDL cholesterol level remained significant (P = .02) after additional adjustment for the CAC score. Conclusion LDL cholesterol level, systolic blood pressure, and diabetes were associated with noncalcified plaque burden at coronary CT angiography in asymptomatic individuals with low-to-moderate risk. (©) RSNA, 2015 Online supplemental material is available for this article.

Coronary artery plaque volume and obesity in patients with diabetes: the factor-64 study.

PURPOSE: To determine the relationship between coronary plaque detected with coronary computed tomographic (CT) angiography and clinical parameters and cardiovascular risk factors in asymptomatic patients with diabetes. MATERIALS AND METHODS: All patients signed institutional review board-approved informed consent forms before enrollment. Two hundred twenty-four asymptomatic diabetic patients (121 men; mean patient age, 61.8 years; mean duration of diabetes, 10.4 years) underwent coronary CT angiography. Total coronary artery wall volume in all three vessels was measured by using semiautomated software. The coronary plaque volume index (PVI) was determined by dividing the wall volume by the coronary length. The relationship between the PVI and cardiovascular risk factors was determined with multivariable analysis. RESULTS: The mean PVI (±standard deviation) was 11.2 mm(2) ± 2.7. The mean coronary artery calcium (CAC) score (determined with the Agatston method) was 382; 67% of total plaque was noncalcified. The PVI was related to age (standardized ß = 0.32, P < .001), male sex (standardized ß = 0.36, P < .001), body mass index (BMI) (standardized ß = 0.26, P < .001), and duration of diabetes (standardized ß = 0.14, P = .03). A greater percentage of soft plaque was present in younger individuals with a shorter disease duration (P = .02). The soft plaque percentage was directly related to BMI (P = .002). Patients with discrepancies between CAC score and PVI rank quartiles had a higher percentage of soft and fibrous plaque (18.7% ± 3.3 vs 17.4% ± 3.5 [P = .008] and 52.2% ± 7.2 vs 47.2% ± 8.8 [P < .0001], respectively). CONCLUSION: In asymptomatic diabetic patients, BMI was the primary modifiable risk factor that was associated with total and soft coronary plaque as assessed with coronary CT angiography.

Machine Learning and Bias in Medical Imaging: Opportunities and Challenges.

Bias in health care has been well documented and results in disparate and worsened outcomes for at-risk groups. Medical imaging plays a critical role in facilitating patient diagnoses but involves multiple sources of bias including factors related to access to imaging modalities, acquisition of images, and assessment (ie, interpretation) of imaging data. Machine learning (ML) applied to diagnostic imaging has demonstrated the potential to improve the quality of imaging-based diagnosis and the precision of measuring imaging-based traits. Algorithms can leverage subtle information not visible to the human eye to detect underdiagnosed conditions or derive new disease phenotypes by linking imaging features with clinical outcomes, all while mitigating cognitive bias in interpretation. Importantly, however, the application of ML to diagnostic imaging has the potential to either reduce or propagate bias. Understanding the potential gain as well as the potential risks requires an understanding of how and what ML models learn. Common risks of propagating bias can arise from unbalanced training, suboptimal architecture design or selection, and uneven application of models. Notwithstanding these risks, ML may yet be applied to improve gain from imaging across all 3A's (access, acquisition, and assessment) for all patients. In this review, we present a framework for understanding the balance of opportunities and challenges for minimizing bias in medical imaging, how ML may improve current approaches to imaging, and what specific design considerations should be made as part of efforts to maximize the quality of health care for all.

Early-Onset Hypertension and Sex-Specific Residual Risk for Cardiovascular Disease in Type 2 Diabetes.

OBJECTIVE: To investigate whether the sex disparities in type 2 diabetes-associated cardiovascular disease (CVD) risks may be related to early-onset hypertension that could benefit from intensive blood pressure (BP) control. RESEARCH DESIGN AND METHODS: We analyzed intensive versus standard BP control in relation to incident CVD events in women and men with type 2 diabetes, based on their age of hypertension diagnosis. RESULTS: Among 3,792 adults with type 2 diabetes (49% women), multivariable-adjusted CVD risk was increased per decade earlier age at hypertension diagnosis (hazard ratio 1.11 [1.03-1.21], P = 0.006). Excess risk associated with early-diagnosed hypertension was attenuated in the presence of intensive versus standard antihypertensive therapy in women (P = 0.036) but not men (P = 0.76). CONCLUSIONS: Women with type 2 diabetes and early-onset hypertension may represent a higher-risk subpopulation that not only contributes to the excess in diabetes-related CVD risk for women but may benefit from intensive BP control.

Using Deep learning to Predict Cardiovascular Magnetic Resonance Findings from Echocardiography Videos.

Background: Echocardiography is the most common modality for assessing cardiac structure and function. While cardiac magnetic resonance (CMR) imaging is less accessible, CMR can provide unique tissue characterization including late gadolinium enhancement (LGE), T1 and T2 mapping, and extracellular volume (ECV) which are associated with tissue fibrosis, infiltration, and inflammation. While deep learning has been shown to uncover findings not recognized by clinicians, it is unknown whether CMR-based tissue characteristics can be derived from echocardiography videos using deep learning. We hypothesized that deep learning applied to echocardiography could predict CMR-based measurements. Methods: In a retrospective single-center study, adult patients with CMRs and echocardiography studies within 30 days were included. A video-based convolutional neural network was trained on echocardiography videos to predict CMR-derived labels including wall motion abnormality (WMA) presence, LGE presence, and abnormal T1, T2 or ECV across echocardiography views. The model performance was evaluated in a held-out test dataset not used for training. Results: The study population included 1,453 adult patients (mean age 56±18 years, 42% female) with 2,556 paired echocardiography studies occurring on average 2 days after CMR (interquartile range 2 days prior to 6 days after). The model had high predictive capability for presence of WMA (AUC 0.873 [95%CI 0.816-0.922]), however, the model was unable to reliably detect the presence of LGE (AUC 0.699 [0.613-0.780]), native T1 (AUC 0.614 [0.500-0.715]), T2 0.553 [0.420-0.692], or ECV 0.564 [0.455-0.691]). Conclusions: Deep learning applied to echocardiography accurately identified CMR-based WMA, but was unable to predict tissue characteristics, suggesting that signal for these tissue characteristics may not be present within ultrasound videos, and that the use of CMR for tissue characterization remains essential within cardiology. Clinical Perspective: Tissue characterization of the heart muscle is useful for clinical diagnosis and prognosis by identifying myocardial fibrosis, inflammation, and infiltration, and can be measured using cardiac MRI. While echocardiography is highly accessible and provides excellent functional information, its ability to provide tissue characterization information is limited at this time. Our study using a deep learning approach to predict cardiac MRI-based tissue characteristics from echocardiography showed limited ability to do so, suggesting that alternative approaches, including non-deep learning methods should be considered in future research.

Multi-Organ System Metabolic Stress and Sex-Divergent Vascular Associations.

Introduction: Women experience excess cardiovascular risk compared to men in the setting of similar metabolic disease burden. This consistent finding could be related to sex differences in the vascular response to various forms of metabolic stress. In this study we examine the association of both systemic and organ-specific metabolic stress with vascular health in women and men. Methods: We conducted an observational study of 4,299 adult participants (52% women, aged 59±13 years) of the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cohort and 110,225 adult outpatients (55% women, aged 64±16 years) of the Cedars-Sinai Medical Center (CSMC) 2019 cohort. We used natural splines to examine the association of systemic and organ-specific measures of metabolic stress including body mass index (BMI), hemoglobin A1c (HbA1c), hepatic FIB-4 score, and CKD-EPI estimated glomerular filtration rate (eGFR) on systolic blood pressure (SBP). Piecewise linear models were generated using normal value thresholds (BMI <25 kg/m 2 , HbA1c <5.7%, FIB-4 <1.3, and eGFR ≥90 ml/min), which approximated observed spline breakpoints. The primary outcome was increase in SBP (relative to a sex-specific physiologic baseline SBP) in association with increase in level of each metabolic measure. Results: Women compared to men demonstrated larger magnitudes and an earlier onset of increase in SBP per increment increase across all metabolic stress measures. The slope of SBP increase per increment of each metabolic measure was greater for women than men particularly for metabolic measures within the normal range, with slope differences of 1.71 mmHg per kg/m2 of BMI, 9.61 mmHg per %HbA1c, 6.45 mmHg per FIB-4 unit, and 0.37 mmHg per ml/min decrement of eGFR in the NHANES cohort (P difference <0.05 for all). Overall results were consistent in the CSMC cohort. Conclusions: Women exhibited greater vascular sensitivity in the setting of multiple types of metabolic stress, particularly in periods representing the transition from metabolic health to disease. These findings underscore the importance of involving early metabolic health interventions as part of efforts to mitigate vascular risks in both women and men.

Opportunistic Screening of Chronic Liver Disease with Deep Learning Enhanced Echocardiography.

Importance: Chronic liver disease affects more than 1.5 billion adults worldwide, however the majority of cases are asymptomatic and undiagnosed. Echocardiography is broadly performed and visualizes the liver; but this information is not leveraged. Objective: To develop and evaluate a deep learning algorithm on echocardiography videos to enable opportunistic screening for chronic liver disease. Design: Retrospective observational cohorts. Setting: Two large urban academic medical centers. Participants: Adult patients who received echocardiography and abdominal imaging (either abdominal ultrasound or abdominal magnetic resonance imaging) with ≤30 days between tests, between July 4, 2012, to June 4, 2022. Exposure: Deep learning model predictions from a deep-learning computer vision pipeline that identifies subcostal view echocardiogram videos and detects the presence of cirrhosis or steatotic liver disease (SLD). Main Outcome and Measures: Clinical diagnosis by paired abdominal ultrasound or magnetic resonance imaging (MRI). Results: A total of 1,596,640 echocardiogram videos (66,922 studies from 24,276 patients) from Cedars-Sinai Medical Center (CSMC) were used to develop EchoNet-Liver, an automated pipeline that identifies high quality subcostal images from echocardiogram studies and detects the presence of cirrhosis or SLD. In the held-out CSMC test cohort, EchoNet-Liver was able to detect the presence of cirrhosis with an AUC of 0.837 (0.789 - 0.880) and SLD with an AUC of 0.799 (0.758 - 0.837). In a separate test cohort with paired abdominal MRIs, cirrhosis was detected with an AUC of 0.704 (0.689-0.718) and SLD was detected with an AUC of 0.726 (0.659-0.790). In an external test cohort of 106 patients (n = 5,280 videos), the model detected cirrhosis with an AUC of 0.830 (0.738 - 0.909) and SLD with an AUC of 0.768 (0.652 - 0.875). Conclusions and Relevance: Deep learning assessment of clinical echocardiography enables opportunistic screening of SLD and cirrhosis. Application of this algorithm may identify patients who may benefit from further diagnostic testing and treatment for chronic liver disease.

Sex Differences in Association of Physical Activity With All-Cause and Cardiovascular Mortality.

BACKGROUND: Although physical activity is widely recommended for reducing cardiovascular and all-cause mortality risks, female individuals consistently lag behind male individuals in exercise engagement. OBJECTIVES: The goal of this study was to evaluate whether physical activity derived health benefits may differ by sex. METHODS: In a prospective study of 412,413 U.S. adults (55% female, age 44 ± 17 years) who provided survey data on leisure-time physical activity, we examined sex-specific multivariable-adjusted associations of physical activity measures (frequency, duration, intensity, type) with all-cause and cardiovascular mortality from 1997 through 2019. RESULTS: During 4,911,178 person-years of follow-up, there were 39,935 all-cause deaths including 11,670 cardiovascular deaths. Regular leisure-time physical activity compared with inactivity was associated with 24% (HR: 0.76; 95% CI: 0.73-0.80) and 15% (HR: 0.85; 95% CI: 0.82-0.89) lower risk of all-cause mortality in women and men, respectively (Wald F = 12.0, sex interaction P < 0.001). Men reached their maximal survival benefit of HR 0.81 from 300 min/wk of moderate-to-vigorous physical activity, whereas women achieved similar benefit at 140 min/wk and then continued to reach a maximum survival benefit of HR 0.76 also at ∼300 min/wk. Sex-specific findings were similar for cardiovascular death (Wald F = 20.1, sex interaction P < 0.001) and consistent across all measures of aerobic activity as well as muscle strengthening activity (Wald F = 6.7, sex interaction P = 0.009). CONCLUSIONS: Women compared with men derived greater gains in all-cause and cardiovascular mortality risk reduction from equivalent doses of leisure-time physical activity. These findings could enhance efforts to close the "gender gap" by motivating especially women to engage in any regular leisure-time physical activity.

Postural orthostatic tachycardia syndrome after COVID-19 vaccination.

BACKGROUND: There is an association between coronavirus disease 2019 (COVID-19) mRNA vaccination and the incidence or exacerbation of postural orthostatic tachycardia syndrome (POTS). OBJECTIVE: The purpose of this study was to characterize patients reporting new or exacerbated POTS after receiving the mRNA COVID-19 vaccine. METHODS: We prospectively collected data from sequential patients in a POTS clinic between July 2021 and June 2022 reporting new or exacerbated POTS symptoms after COVID-19 vaccination. Heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) were compared against those of 24 healthy controls. RESULTS: Ten patients (6 women and 4 men; age 41.5 ± 7.9 years) met inclusion criteria. Four patients had standing norepinephrine levels > 600 pg/mL. All patients had conditions that could raise POTS risk, including previous COVID-19 infection (N = 4), hypermobile Ehlers-Danlos syndrome (N = 6), mast cell activation syndrome (N = 6), and autoimmune (N = 7), cardiac (N = 7), neurological (N = 6), or gastrointestinal conditions (N = 4). HRV analysis indicated a lower ambulatory root mean square of successive differences (46.19 ±24 ms; P = .042) vs control (72.49 ± 40.8 ms). SKNA showed a reduced mean amplitude (0.97 ± 0.052 µV; P = .011) vs control (1.2 ± 0.31 µV) and burst amplitude (1.67 ± 0.16 µV; P = .018) vs control (4. 3 ± 4.3 µV). After 417.2 ± 131.4 days of follow-up, all patients reported improvement with the usual POTS care, although 2 with COVID-19 reinfection and 1 with small fiber neuropathy did have relapses of POTS symptoms. CONCLUSION: All patients with postvaccination POTS had pre-existing conditions. There was no evidence of myocardial injuries or echocardiographic abnormalities. The decreased HRV suggests a sympathetic dominant state. Although all patients improved with guideline-directed care, there is a risk of relapse.