Risultati per: Caratterizzazione dell'asma in base all'età di insorgenza: uno studio di coorte multi-database

Circulation, Volume 150, Issue Suppl_1, Page A4136032-A4136032, November 12, 2024. Background:Biomarkers like coronary artery calcium (CAC) and traditional risk factors are well-validated for coronary artery disease (CAD) assessment but not always available, and with limited workup efficiency and potential radiation risk. Facial features contain biological information related to atherosclerosis.Aims:We aim to extract CAC and traditional risk factor-associated digital biomarkers from facial images and evaluate their value in predicting CAD status compared with conventional clinical approaches.Methods:Suspected individuals referred for confirmatory CAD evaluation across nine centers were included. Participants in one center constituted the derivation set. External validation included one dataset of participants from a different time period in the derivation center and the other dataset from the other eight centers. We developed a multi-label deep-learning model to extract digital biomarkers from facial photos based on a multi-dimensional label of CAC score and eight traditional risk factors to comprehensively represent coronary atherosclerosis risk profile. The extracted digital biomarkers were evaluated for both effectiveness in reflecting components of the multi-dimensional label and clinical value in predicting obstructive CAD.Results:A total of 13248 facial photos from 3312 eligible participants (mean age, 58.5 years; 517 [25.9%] female) were included. In external validation, a set of digital biomarkers (FacialCAD) were extracted, effectively reflecting components of the multi-dimensional label, especially for CAC stratification (CAC >0, AUC 0.919 [0.885 – 0.949]; CAC≥100, AUC 0.906 [0.876 – 0.933]) and nearly perfect prediction for the age and sex. The performance of the FacialCAD in predicting obstructive CAD (AUC 0.721 [0.694–0.748]) significantly outperformed two guideline-recommended CAD models (0.721 vs. 0.653, P

Circulation, Volume 150, Issue Suppl_1, Page A4127990-A4127990, November 12, 2024. Background:Matrix Gla protein (MGP) inhibits arterial calcification. Higher inactive MGP, dephosphorylated-uncarboxylated (dp-ucMGP), is positively associated with vascular calcification, possibly portending cardiovascular events. The objective was to determine the association of dp-ucMGP with incident cardiovascular disease (CVD) events and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA).Methods:MESA is a cohort study of 45-84 year-old individuals enrolled between 2000-02 with adjudicated outcomes through 2019. Dp-ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000-02) and 5 (2010-12). Using age-stratified Cox proportional hazard models, adjusted for sex, race-ethnicity, body mass index, systolic blood pressure, statin use, anti-hypertensive medication use, smoking status, physical activity, alcohol use, diabetes, high density lipoprotein, low density lipoprotein, triglycerides, phosphate, and estimated glomerular filtration rate, we determined the association of dp-ucMGP with risk of all CVD (mean follow-up 16+4 years), hard CVD (17+3 years), hard CHD (17+3 years), and all-cause mortality (18+2 years).Results:The youngest age quartile (45-53-years-old) with higher dp-ucMGP levels (520-2934 pmol/L) had an increased risk of all CVD (HR 3.01 [95% CI 1.56, 5.80], p=0.001), hard CVD (HR 2.78 [95% CI 1.29, 6.02], p=0.009), hard CHD (HR 3.37 [95% CI 1.29, 8.81], p=0.013) and all-cause mortality (HR 2.69 [95% CI 1.06, 6.79], p=0.037) compared to dp-ucMGP levels between 150-519 pmol/L in maximally adjusted models. There was no relationship with any outcomes for the other age quartiles (Table).Conclusions:Middle aged individuals with elevated dp-ucMGP levels ( >520 pmol/L) had an increased risk of incident CVD, CHD, and all-cause mortality.

Circulation, Volume 150, Issue Suppl_1, Page A4139978-A4139978, November 12, 2024. Background:Discrepant transthoracic echocardiography (TTE) parameters are not infrequently observed in patients with significant aortic stenosis (AS), however, there is limited literature regarding their computed tomography (CT) characteristics and prognostic implications.Aims:We compared the multi-modality imaging characteristics and outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) by AS subtype.Methods:Patients with severe AS (defined as aortic valve area

Circulation, Volume 150, Issue Suppl_1, Page A4134249-A4134249, November 12, 2024. Background:Inflammation plays a role in the development of cardiovascular disease (CVD). We have defined various non-cardiovascular and non-cancer conditions, both infectious and non-infectious, with a common basis of inflammation; collectively termed Chronic Inflammatory-Related Disease (ChrIRD). We have previously described that ChrIRD is common, associated with baseline inflammatory marker levels, associated with high mortality, and has a bidirectional association with CVD. The clinical implications of these data require further study.Aims:We hypothesize that many traditional risk factors for CVD are also associated with ChrIRD and that ChrIRD has additional unique risk factors. We also hypothesize that the treatment of traditional CVD risk factors is associated with a decreased likelihood of ChrIRD.Methods:We studied MESA participants free of overt CVD or significant illness at baseline. ChrIRD was determined based on review of ICD codes for hospitalizations and deaths. Incident CVD was adjudicated by review of medical records. We performed proportional hazards regression (time-dependent for CVD) to identify factors associated with a first diagnosis of ChrIRD. All variables were simultaneously entered into the model.Results:Participants (n=6155) had mean age 62±10 years and 47% male gender. ChrIRD was observed in 24% and CVD in 18%; including 8% with both conditions. Participants with a diagnosis of CVD, older age, higher heart rate, higher BMI, current or ever smoking status, higher HDL, higher baseline IL6 and GlycA levels, and NSAID use had increased likelihood of ChrIRD. Whereas those with female sex, higher total cholesterol, and statin use had a decreased likelihood of ChrIRD. Participant race/ethnicity, blood pressure, diabetes status, antihypertensive use, aspirin use, baseline CRP level, and baseline D-dimer level were not associated with ChrIRD. Regression results are summarized in Table 1.Conclusions:ChrIRD shares some risk factors with CVD, while other risk factors are opposite.Better understanding of ChrIRD could eventually lead to improved patient care.

Circulation, Volume 150, Issue Suppl_1, Page A4146291-A4146291, November 12, 2024. Background:Circulatory diseases represent the primary cause of mortality in the US. Comprehending trends and potential disparities in the prevalence of circulatory conditions, such as angina pectoris (AP), myocardial infarction (MI), hypertension (HTN), and coronary heart disease (CHD), is essential for forming public health strategies.Aim:To investigate trends in the prevalence of circulatory conditions, including AP, MI, HTN, and CHD among US adults from 2019 to 2022.Methods:Prevalence percentages for all available circulatory diseases from the Centers for Disease Control and Prevention’s National Health Interview Survey (NHIS) database were retrieved for patients aged >18 years from 2019 to 2022. Annual Percentage Changes (APCs) along with their respective 95% CIs were calculated using regression analysis with Join point. The data was stratified by year, gender, age, race, nativity, veteran status, social vulnerability, employment status, metropolitan statistical area (MSA) status and census region.Results:Between 2019 and 2022, HTN was steadily the most prevalent, staying relatively constant at 27.0% (95% CI: 26.4, 27.7) in 2019 and 27.2% (95% CI: 26.5, 27.8) in 2022. Males consistently had higher prevalence than females with significant increases noted from 2019 to 2022 (APC: 1.0234). Black or African American had the highest prevalence (34.4% in 2022). The South (30.1% in 2022) and the West (22.5% in 2022) had respectively the highest and lowest rates. The second highest prevalence was seen in CHD increasing from 4.6% (95% CI: 4.3, 4.9) in 2019 to 4.9 (95% CI: 4.7, 5.2) in 2020. Males consistently exhibited a higher prevalence than females, with both genders showing significant increases in recent years (Male APC: 3.1448) (Female APC: 2.0165). For MI, a slight decrease was noted from 3.1% (95% CI:2.9, 3.4) in 2019 to 3.0% (95% CI:2.7, 3.2) in 2022. White individuals exhibited the highest prevalence (3.3% in 2022). AP had the lowest overall prevalence staying relatively consistent (1.7% in 2019 and 1.6% in 2022) (Figure 1).Conclusion:Significant trends (Figure 2) in most common circulatory diseases have been identified. Targeted interventions are imperative, particularly for high-risk demographics such as males, older adults, veterans, and unemployed individuals.

Circulation, Volume 150, Issue Suppl_1, Page A4142110-A4142110, November 12, 2024. Background:Coronary artery calcium (CAC) scans contain more actionable information than the Agatston CAC score. We have previously shown in the Multi-Ethnic Study of Atherosclerosis (MESA) that AI-enabled left atrial (LA) volumetry in CAC scans (AI-CAC) enabled prediction of atrial fibrillation (AF) as early as one year. Furthermore, we have recently shown adding AI-CAC LA volumetry to CHA2DS2-VASc risk score improved stroke prediction in MESA. In this study we evaluated the performance of AI-CAC LA volumetry versus LA measured by human experts using cardiac magnetic resonance imaging (CMRI) for predicting AF and stroke, and compared them with CHARGE-AF risk score, Agatston score, and NT-proBNP.Methods:We used 15-year outcomes data from 3552 asymptomatic individuals (52.2% women, age 61.7±10.2 years) who underwent both CAC scans and CMRI in the MESA baseline examination. We have applied the AutoChamberTM(HeartLung.AI, Houston, TX) component of AI-CAC to 3552 CAC scans. CMRI LA volume was previously measured by human experts. Data on NT-proBNP, CHARGE-AF risk score and the Agatston score were obtained from MESA. Discrimination was assessed using the time-dependent area under the curve (AUC).Results:Over 15 years follow-up, 562 cases of AF and 140 cases of stroke accrued. The AUC for 15-yearAF predictionby AI-CAC LA volume (0.801) was comparable to CMRI LA volume (0.797) and significantly higher than Agatston CAC Score (0.687) and NT-proBNP (0.704). Similarly, the AUC for 15-yearstrokepredictionfor AI-CAC volumetry (0.761) was comparable to CMRI volumetry (0.751) and significantly higher than NT-proBNP (0.631) and Agatston CAC Score (0.646). AI-CAC LA volume outperformed CHARGE AF over 1-3 years for incident AF (p

Circulation, Volume 150, Issue Suppl_1, Page A4146494-A4146494, November 12, 2024. Background:Distribution patterns for visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue are strongly associated with cardiovascular disease. Circulating metabolites and proteins are dynamic indicators of biological processes and reflect metabolic health. It is not yet clear how these analytes are associated with adiposity distribution patterns.Aims:To determine the multi-omic profiles of adiposity distribution and their associated metabolomic and proteomic measurements.Methods:MRI-derived volumes of VAT, ASAT, and GFAT adjusted for BMI were available for 40,032 UK Biobank participants. Circulating metabolites and proteins were measured using the Nightingale Health NMR biomarker platform and Olink platform, respectively. We used linear regression models to assess the association between each analyte and VAT, ASAT, and GFAT. Models were adjusted for sex, age at MRI, MRI batch, and time between enrollment and MRI. Functional protein pathway enrichment was performed using the DAVID annotation tool.Results:Among 40,032 UK Biobank participants with adiposity volumes, 22,630 (56.5%) and 5023 (12.5%) had 168 metabolomic and 2910 proteomic measurements, respectively. In the metabolomic subset, the mean (SD) age was 55.7 (7.5) years, 10,992 (48.6%) were male, and all self-reported as white. In the proteomic subset, the mean (SD) age was 54.9 (7.8) years, 2417 (48.1%) were male, and all self-reported as white. Multi-variable linear regression revealed 39, 139, and 146 significant metabolite associations (P

Circulation, Volume 150, Issue Suppl_1, Page A4124307-A4124307, November 12, 2024. Background:Obesity is considered a significant risk factor for numerous cardiovascular conditions due to its effects on cardiac structure and function. The prevalence of atrial fibrillation (AF) is elevated among patients with obesity due to the dysregulation of several mechanisms. Weight loss has been shown to reverse cardiac remodeling, leading to a lower recurrence of AF despite the better prognosis in obese patients described as the obesity paradox.Methods:We utilized the National Inpatient Sample 2016-2019 to extract patients ≥18 years of age admitted with AF as the primary diagnosis based on ICD 10 codes. We performed univariate and multivariate regression analysis for known coronary risk factors. We divided patients based on their body mass index (BMI), and our primary outcomes were determining the odds of electrical cardioversion (ECV) and cardiac ablation (CA) due to AF.Results:The analysis included 1,625,809 weighted patients. Patients include underweight (6.66%), normal BMI (4.03), overweight (6.51%), obesity class I (20.65%), obesity class II (21.45%), and obesity class III (40.7).After multivariate regression analysis, patients with obesity class I, II, or III had higher odds of ECV, irrespectively of coronary risk factors (OR 1.3, 95% CI 1.25-1.37, OR 1.3, 95% CI 1.32-1.43, OR 1.3, 95% CI1.29-1.38, respectively, with statistically significant P values). However, underweight or normal BMI patients had fewer odds of ECV (OR 0.5 95%CI 0.49-0.61 and OR 0.6 95%CI 0.58-0.74, respectively, with P values

Circulation, Volume 150, Issue Suppl_1, Page A4135861-A4135861, November 12, 2024. Background:Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown.Objectives:This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease.Methods:2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling (Table).Results:Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m2;P= 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m2;P= 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %;P= 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors (Table). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m2;P= 0.01), LV indexed mass (β 1.17 g/m2;P= 0.02) and a decrease in LV ejection fraction (β -1.01 %;P= 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 (Table- Model 3), and baseline coronary artery calcium score and interim myocardial infarction (Table- Model 4).Conclusions:In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.

Circulation, Volume 150, Issue Suppl_1, Page A4141341-A4141341, November 12, 2024. Background:Aortic valve calcification (AVC) is the primary underlying process leading to aortic stenosis. Whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors (ASCVD) is unknown.Methods:This study included 6,812 Multi-Ethnic Study of Atherosclerosis participants who had AVC measured via CT at Visit 1 and single-nucleotide polymorphism (SNP) genotype data. Using previously published PRS for coronary artery disease (CAD), coronary artery calcium (CAC), and ASCVD risk factors we calculated a weighted PRS for each participant that was standardized within each ancestry group. The cross-sectional association of the individual PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction.Results:The mean age was 62 years old, 53% were women, and 913 (13.4%) of participants had AVC >0 at baseline. The PRS for CAD (HR 1.17, 95% CI 1.07-1.26), SBP (HR 1.13, 95% CI 1.04-1.24), LDL-C (HR 1.16, 95% CI 1.07-1.26), and lipoprotein(a) [Lp(a)] (HR 1.11, 95% CI 1.02-1.20) were significantly associated with AVC, while the other PRS including CAC (HR 1.02, 95% CI 0.94-1.10) and CRP (HR 0.97, 95% CI 0.89-1.05) were not (Table). In sex stratified analyses, the PRS for CAD, LDL-C, and Lp(a) were significantly associated with AVC >0 for both women and men (p0. Additionally, the lack of association for the CAC PRS with AVC >0 demonstrates that significant differences exist in the calcification pathways for AVC and CAC.

Circulation, Volume 150, Issue Suppl_1, Page A4148114-A4148114, November 12, 2024. Introduction/Background:Use of the radial artery (RA) is associated with better clinical outcomes compared to the saphenous vein during coronary artery bypass grafting (CABG) and is strongly endorsed by society guidelines. While the safety of using the RA as a sequential T-graft from the internal mammary artery is established, evidence on the safety and efficiency of sequential radial artery grafts directly from the aorta is limited.Research Questions/Hypotheses:The use of a sequential radial artery originating on the aorta is safe and efficient and is associated with an increase in the number of arterial grafts used in patients undergoing CABG.Goals/Aims:To evaluate the safety and efficiency of using the radial artery in a sequential approach directly from the aorta during CABG.Methods:STS database analysis of patients undergoing isolated CABG with ≥1 RA by one surgeon at two centers (2001-2022). Patients with sequential vs. non-sequential RA grafting were compared. Primary outcomes included CPB and cross-clamp time, total number of arterial grafts, and incomplete revascularization. Secondary outcomes were 30-day mortality, reoperation, stroke, renal failure, sepsis, ICU length of stay, and deep sternal wound infection. Statistical methods included Mann-Whitney U test, Chi-Square test, and Optimal Matching Propensity Score analysis (1:3 ratio).Results:Of 503 patients who received an RA graft, 129 (25.6%) were sequential. Before matching, significant differences were noted in median age, BMI, CPB and cross-clamp (XC) time, and elective status between groups. Sequential RA use was associated with a higher median number of arterial grafts and total grafts (3 vs 2, and 4 vs 3, respectively, p

Circulation, Volume 150, Issue Suppl_1, Page A4146723-A4146723, November 12, 2024. Introduction:Atrial fibrillation (AF) is linked to an elevated risk of ischemic stroke (IS) and mortality. However, the performance of existing clinical scoring systems in assessing these outcomes is at best moderate. The blood proteome serves as a vital indicator of biological processes related to complex disorders. Consequently, there exists an opportunity to enhance the predictive accuracy of such risk scores by incorporating blood proteomic data.Purpose:In this study, we aim to evaluate the combined influence of genomics, proteomics, biomarkers, phenotypic, and social determinants of health (SDOH) on AF outcomes to better understand a precision health framework in managing AF.Methods:We analyzed patients with AF in the UK Biobank cohort who underwent proteomics measurements using the Olink Proximity Extension Assay. The primary endpoint was the incidence of IS.We assessed the intersection of multi-omics,comorbidities,SDOH and traditional CHA2DS2-VASc score to identify the most important factors associated with IS.We employed multi-step machine learning algorithms to evaluate 3,083 features, including Step1,which involved separate models for each feature type,followed by Step 2,where a combined model was used to assess the complex relationship between these features.The area under the curve (AUC) was used to compare the discriminative ability of the model with the addition of each feature group for predicting IS.Grid search and 10-fold cross-validation were performed to identify the best hyperparameters,and we calculated the mean AUC for the final models.SHAP values were reported for the top 30 features in the final XGBoost model (Figure1).Results:Among 4,842 patients with AF(mean age 67.2±9.5 years,61.8% female),5.2% experienced an IS within 9.9±7.5 years after AF diagnosis.The mean CHA2DS2-VASc score was 2.3±1.4, with 60.14% on anticoagulation therapy.The AUC for the CHA2DS2-VASc score at baseline was 0.493.Adding SDOH, polygenic scores, phenotypic data, proteomics, and biomarkers improved the model’s discriminative ability (Figure 1.A), with a combined model AUC of 0.619 (95% CI: 0.592-0.645)(Figure 1.B).The top 30 features in the final model, primarily proteins, are shown in Figure 1C.Conclusion:A small number of plasma proteins can substantially enhance risk prediction of IS in the setting of AF. Further validation could enable a single-source,personalized assessment of stroke risk in patients with AF as a gateway to personalized risk reduction therapy.

Circulation, Volume 150, Issue Suppl_1, Page A4124226-A4124226, November 12, 2024. Introduction:Exposure to ambient air pollution may increase the risk of cardiovascular disease events and mortality, but prior publications have primarily included administrative cohorts with outcomes that have not been individually reviewed and with air pollution estimates created without cohort-specific exposure monitoring. Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site cohort study designed specifically to prospectively collect and adjudicate cardiovascular disease (CVD) events. MESA Air recruited additional participants into sub-cohorts for enhanced air pollution variation and sample size.Research Question:The aim of this analysis was to characterize the relationship between long-term exposure to nitrogen dioxide (NO2) and fine particulate matter (PM2.5) and all-cause mortality and CVD events.Methods:Air pollution exposure was assessed using address history with a purpose-built exposure model incorporating cohort-specific monitoring including measurement and validation at participant homes. We used Cox models to assess the risk of rolling 2-year average exposures on all cause-mortality and on a composite CVD endpoint (definite angina, probable angina with revascularization, myocardial infarction, atherosclerosis or other CVD death, resuscitated cardiac arrest, and stroke). Models were stratified for baseline hazard by age, sub-cohort, and recruitment year and were additionally adjusted for age, sex, race/ethnicity, field center, smoking/second-hand smoke, pack-years, physical activity, education, income, neighborhood socioeconomic status, and statin use.Results:MESA Air participants were aged 44-87 years at enrollment between 2000 and 2007; follow-up averaged 14 years. 6,915 participants had follow-up for events, NO2exposure, and covariate information. We observed 1,442 deaths and 985 CVD events. The interquartile range over all 2-year averages was 10.5-23.1 ppb for NO2and 10.1-14.9 µ/m3for PM2.5. The adjusted hazard ratio (aHR) for a 10 ppb increment in NO2was 1.38 (95% CI: 1.17, 1.64) for all-cause mortality and 1.16 (95% CI: 0.95, 1.42) for incident CVD events. The aHR for a 5 µg/m3increment in PM2.5was 1.20 (95% CI: 0.99, 1.46) for all-cause mortality and 1.15 (95% CI: 0.95, 1.39) for incident CVD eventsConclusions:These results add to growing literature demonstrating an association between air pollution exposure, mortality, and CVD in a cohort with well-characterized clinical endpoints and cohort-specific exposure assessment.

Circulation, Volume 150, Issue Suppl_1, Page A4140940-A4140940, November 12, 2024. Background:The 4th Universal Definition of Myocardial Injury (UDMI) recognizes several categories of myocardial injury, including acute myocardial infarction (MI) which is further sub-classified into five types. However, data on these different types of myocardial injury and their risk factors is limited.Methods:In the MESA study of 6814 participants, 15905 clinical events were identified over the first 14 years, 4079 of which meet MESA criteria for physician adjudication for a possible cardiovascular event. Herein, we developed a standardized data format and a REDCap tool with an interactive robust logic algorithm to re-adjudicate all 4079 cases for the presence and classification of all 9 types of myocardial injury as defined by the 4thUDMI. Adjudication process as shown inFigure 1. The prevalence of myocardial injury types was evaluated using descriptive statistics, and adjudicator agreement was assessed using Cohen’s kappa (κ) statistics and percent agreement.Results:Out of 4079 events, adjudication is completed on 2282, of which 15% classified into subtypes of myocardial injury. Adjudication was achieved for 91% of the events in phase 1, 7% in phase 2, 2% in phase 3. The overall agreement between two adjudicators for the presence of myocardial injury was 91% (κ: 0.67), but the agreement for the specific subtype was 53% (κ: 0.38). The most common events were Type 1 MI (N= 114), followed by Type 2 MI (N= 95), and Acute non-ischemic myocardial injury (N= 85) (Figure 2). Compared to the original MESA adjudication for the presence of MI, 97% (N= 72) of probable MI and 8% (N= 174) of no MI were reclassified into five and six types of myocardial injury events respectively.Conclusion:This study highlights the complexities in identifying subtypes of myocardial injury based on current definition. This study provides a novel dataset to explore diverse correlations with these myocardial injury subtypes.

Circulation, Volume 150, Issue Suppl_1, Page A4148026-A4148026, November 12, 2024. Introduction:Multi-venous compression syndromes pose diagnostic and management dilemmas due to uncertainties in both etiology and clinical course. Clinical thresholds for surgical intervention are unclear, and systemic symptoms beyond the anatomic sites of compression are common, including exertional dyspnea, intermittent tachycardia, and fatigue. We hypothesize that multi-venous compression syndromes may represent a manifestation of autonomic dysfunction with impaired venous return to the right heart (preload failure physiology).Methods:Consecutive patients presenting to the Vascular Medicine clinic, Vascular Surgery clinic, or the vascular ultrasound laboratory at Brigham and Women’s Hospital from November 1, 2021 to May 1, 2024 with evidence of multi-vein compressions were retrospectively included in this cohort. Venous compressions evaluated were thoracic outlet syndrome, popliteal entrapment, left common iliac vein compression, and left renal vein compression. Data were analyzed from autonomic function testing and invasive cardiopulmonary exercise testing (iCPET) performed for clinical indications.Results:A total of 16 patients presented with imaging-confirmed multi-vein compressions. The average (standard deviation) number of compressed sites were 4 (2). Eleven patients (69%) had clinical symptoms of dysautonomia. Five patients (31%) underwent autonomic function testing; all had an abnormal result, most commonly manifesting as reduced orthostatic cerebral blood flow velocity. Seven patients (44%) underwent iCPET; the average right atrial pressure at peak upright exercise was abnormally low at 1 mmHg (1.5 mmHg) with a range of 0-4 mmHg. Four out of 7 patients had accompanying peak oxygen consumption less than 80% of predicted. Seven patients (44%) underwent surgery for at least one compression; the most common procedure was left common iliac vein stenting. Two patients with dysautonomia underwent venous decompression and reported no significant change in overall symptoms. Nine patients with dysautonomia were managed conservatively with medical therapy (salt/water repletion, oral pyridostigmine, beta blocker, midodrine, and/or compression garments). Eight of these patients reported improved functional status after at least 6 months.Conclusions:Patients with multi-vein compressions are enriched for autonomic dysfunction and preload failure. Medical therapy can improve overall functional status without requiring surgical intervention.

Circulation, Volume 150, Issue Suppl_1, Page A4120687-A4120687, November 12, 2024. Background:There are currently no approved medical therapies for acute fulminant myocarditis (AFM). Janus kinase (JAK) inhibitors target the JAK-STAT signaling pathway, which is crucial in immune activation. We report the first use of ruxolitinib, a JAK inhibitor, for treatment of AFM. Multi-omics single-cell technologies, including RNA-seq, T-/B-cell receptor seq, and CITE-seq, were employed to analyze immune profiles pre- and post-ruxolitinib treatment.Results:A 20-year-old female presented with AFM with cardiogenic shock and was supported by VA-ECMO and impella CP. Endomyocardial biopsy showed lymphocytic myocarditis. The patient received pulsed steroids and was listed for orthotopic heart transplant. Due to deteriorating conditions, ruxolitinib (10 mg BID) was added with immediate improvement in cardiac and inflammatory biomarkers and hemodynamics. ECMO was decannulated on day 6 and impella CP was removed on day 8. Repeat TTE on day 9 showed normalization of cardiac function (LVEF 58%, increased from 10%). She was discharged on ruxolitinib and is doing well in follow-up. Multi-omics single-cell technologies were employed on PBMCs collected at four time points: prior to ruxolitinib treatment (but after treatment with corticosteroids), and post-ruxolitinib treatment on day 5, day 8, and 2-months. At baseline, prior to treatment, scRNA-Seq and CITE-seq analysis revealed upregulated JAK-STAT signaling in pathogenic immune cells such as NK cells, CCR2+/CCR5+/HLA-DR+monocytes and activated T cells. Ruxolitinib treatment significantly decreased these pathogenic immune cells, with inhibition of STAT1/STAT3 signaling. Ruxolitinib also significantly decreased key cytotoxic genes PRF1, GZMB, and TBX21 in T and NK cells. TCR sequencing revealed clonal expansions of activated T cells with high levels of pro-inflammatory genes (IL2/IL6/IFNg) at baseline which were dramatically reduced post-treatment with ruxolitinib. Longitudinal data indicated normalization of naive T and B cell levels and clonal diversity, mirroring her clinical improvement.Conclusions:Ruxolitinib significantly modulates immune profiles and disrupts pathogenic signaling in AFM. This first reported use of ruxolitinib in AFM, coupled with our multi-omics analysis, highlights profound immune reprogramming and supports targeted immune modulation for rapid recovery, underscoring ruxolitinib’s therapeutic efficacy.