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UnlabelledVitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.IntroductionVitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.MethodsWe tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.ResultsIL-6 was lower in men with higher 25OHD (-0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) -0.07 to -0.38 μg/mL) and with higher 1,25(OH)2D (-0.20 μg/mL, 95 % CI -0.0004 to -0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)2D).ConclusionsAssociations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)2D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

Background and aimsTo investigate the associations between selected adipokines and the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP).Methods and resultsAs many as 1489 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis were evaluated at 4 clinic visits about every 2 years. The evaluation included fasting venous blood, which was analyzed for NT-proBNP (at visits 1 and 3) and the adipokines adiponectin and leptin (at visits 2 and 3). The mean age was 64.8 ± 9.6 years and 48% were female. After multivariable adjustment, a 1-SD increment in adiponectin was associated with a 14 pg/ml higher NT-proBNP level (p < 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles had 28, 45 and 67% higher NT-proBNP levels (p < 0.01 for all). For changes in NT-proBNP over the follow-up period, and after multivariable adjustment including baseline NT-proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml absolute increase in NT-proBNP (p < 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated with increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and

Background: Giant coronary artery aneurysms and myocardial fibrosis after Kawasaki disease may lead to devastating cardiovascular outcomes. We characterised the vascular and myocardial outcomes in five selected Kawasaki disease patients with a history of giant coronary artery aneurysms that completely regressed., Methods: Five patients were selected who had giant coronary artery aneurysm in early childhood that regressed when studied 12-33 years after Kawasaki disease onset. Coronary arteries were imaged by coronary CT angiography, and coronary artery calcium volume scores were determined. We used endocardial strain measurements from CT imaging to assess myocardial regional wall function. Calprotectin and galectin-3 (gal-3) as biomarkers of inflammation and myocardial fibrosis were measured by enzyme-linked immunosorbent assay., Results: The five selected patients with regressed giant coronary artery aneurysms had calcium scores of zero, normal levels of calprotectin and gal-3, and normal appearance of the coronary arteries by coronary computed tomography angiography. CT strain demonstrated normal peak systolic and diastolic strain patterns in four of five patients. In one patient with a myocardial infarction at the time of Kawasaki disease diagnosis at the age of 10 months, CT strain showed altered global longitudinal strain, reduced segmental peak strain, and reduced diastolic relaxation patterns in multiple left ventricle segments., Conclusions: These patients illustrate that regression of giant aneurysms after Kawasaki disease is possible with no detectable calcium, normal biomarkers of inflammation and fibrosis, and normal myocardial function. Individuals with regressed giant coronary artery aneurysm still require longitudinal surveillance to assess the durability of this favourable outcome.

Background: We evaluated the Vitros® Immunodiagnostic Products N-terminal pro B-type natriuretic peptide (NT-proBNP) II assay for aiding in diagnosis of heart failure (HF) in patients with acute dyspnea., Methods: Serum concentrations of NT-proBNP were measured in patient samples from 20 emergency departments across the United States. Study endpoints included sensitivity, specificity, likelihood ratios, and predictive values for diagnosis of acute HF according to age-stratified cutoffs (450, 900, and 1800 pg/mL), and a rule-out age-independent cutoff (300 pg/mL). Additional measures were area under the curve (AUC) for receiver operating characteristic (ROC) curves. Results were also interpreted in patient subgroups with relevant comorbidities, and gray zone/intermediate assay values., Results: Of 2200 patients, 1095 (49.8%) were diagnosed with HF by clinical adjudication. Sensitivity and specificity for Vitros NT-proBNP II ranged from 84.0% to 92.1%, and 81.4% to 86.5%, respectively, within and across age groups, and positive predictive values were 80.4% to 85.7%. Using the rule-out cutoff, the negative predictive value was 97.9%, with a negative likelihood ratio of 0.02. In subgroups with comorbidities potentially affecting NT-proBNP concentrations, sensitivities ranged from 82.6% to 89.5%, and AUCs for ROC curves were 0.899 to 0.915., Conclusions: The Vitros NT-proBNP II assay demonstrated excellent clinical performance using age-stratified cutoffs along with other clinical information for supporting diagnosis of HF, and can rule out HF with a high negative predictive value using the age-independent cutoff. The assay retained utility in patient subgroups with conditions that influence NT-proBNP concentration, and for those with gray zone results., Clinicaltrials.gov Registration Number: NCT03548909., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Breast arterial calcification (BAC) on mammograms has emerged as a biomarker of women's cardiovascular disease (CVD) risk, but there is a lack of quantification tools and clinical outcomes studies., Objectives: This study assessed the association of BAC (both presence and quantity) with CVD outcomes., Methods: This single-center, retrospective study included women with a screening mammogram from 2007 to 2016. BAC was quantified using an artificial intelligence-generated score, which was assessed as both a binary and continuous variable. Regression analyses evaluated the association between BAC and mortality and a composite of acute myocardial infarction, heart failure, stroke, and mortality. Analyses were adjusted for age, race, diabetes, smoking, blood pressure, cholesterol, and history of CVD and chronic kidney disease., Results: A total of 18,092 women were included in this study (mean age 56.8 ± 11.0 years; diabetes [13%], hypertension [36%], hyperlipidemia [40%], and smoking [5%]). BAC was present in 4,223 (23%). Over a median follow-up of 6 years, death occurred in 7.8% and 2.3% of women with and without BAC, respectively. The composite occurred in 12.4% and 4.3% of women with and without BAC, respectively. Compared to those without, women with BAC had adjusted HRs of 1.49 (95% CI: 1.33-1.67) for mortality and 1.56 (95% CI: 1.41-1.72) for the composite. Each 10-point increase in the BAC score was associated with higher risk of mortality (HR: 1.08 [95% CI: 1.06-1.11]) and the composite (HR: 1.08 [95% CI: 1.06-1.10]). BAC was especially predictive of future events among younger women., Conclusions: BAC is independently associated with mortality and CVD, especially among younger women. Measurement of BAC beyond presence adds incremental risk stratification. Quantifying BAC using an artificial intelligence algorithm is feasible, clinically relevant, and may improve personalized CVD risk stratification., Competing Interests: This research was in part funded by the National Heart, Lung, and Blood Institute T32 HL079891-11. Drs Bui, Nerlekar, Eghtedari, and Daniels have served as consultants to CureMetrix. Drs Mantey and Wang are employees of CureMetrix. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: The prognostic implications of phenotypes along the preshock to cardiogenic shock (CS) continuum remain uncertain., Objectives: This study sought to better characterize pre- or early shock and normotensive CS phenotypes and examine outcomes compared to those with conventional CS., Methods: The CCCTN (Critical Care Cardiology Trials Network) is a registry of contemporary cardiac intensive care units. Consecutive admissions (N = 28,703 across 47 sites) meeting specific criteria based on hemodynamic variables, perfusion parameters, and investigator-reported CS were classified into 1 of 4 groups or none: isolated low cardiac output (CO), heart failure with isolated hypotension, normotensive CS, or SCAI (Society of Cardiovascular Angiography and Intervention) stage C CS. Outcomes of interest were in-hospital mortality and incidence of subsequent hypoperfusion among pre- and early shock states., Results: A total of 2,498 admissions were assigned to the 4 groups with the following distribution: 4.8% isolated low CO, 4.4% isolated hypotension, 12.1% normotensive CS, and 78.7% SCAI stage C CS. Overall in-hospital mortality was 21.3% (95% CI: 19.7%-23.0%), with a gradient across phenotypes (isolated low CO 3.6% [95% CI: 1.0%-9.0%]; isolated hypotension 11.0% [95% CI: 6.9%-16.6%]; normotensive CS 17.0% [95% CI 13.0%-21.8%]; SCAI stage C CS 24.0% [95% CI: 22.1%-26.0%]; global P < 0.001). Among those with an isolated low CO and isolated hypotension on admission, 47 (42.3%) and 56 (30.9%) subsequently developed hypoperfusion., Conclusions: In a large contemporary registry of cardiac critical illness, there exists a gradient of mortality for phenotypes along the preshock to CS continuum with risk for subsequent worsening of preshock states. These data may inform refinement of CS definitions and severity staging., Competing Interests: Funding Support and Author Disclosures Dr Patel is supported by T32 postdoctoral training grant T32HL007604 from the National Heart, Lung and Blood Institute. Dr Solomon has received research support from the National Institutes of Health Clinical Center intramural research funds. Dr Thompson is supported by National Institutes of Health-NHLBI grant K08HL163328]and by the Michigan Biology of Cardiovascular Aging (M-BoCA) at the University of Michigan. Drs Patel, Berg, Bohula, Park, and Morrow and Ms Baird-Zars are members of the TIMI study group that has received research grant support through Brigham and Women’s Hospital from Abbott Laboratories, Abiomed, Amgen, Anthos Therapeutics, AstraZeneca, Daiichi-Sankyo, Intarcia, Janssen, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Regeneron, Roche, Siemens, and Zora Biosciences. Dr Patel has received consulting fees from Janssen. Dr Berg has received honoraria from the Medical Education Speakers Network and USV Private Limited; consulting fees from AstraZeneca, MobilityBio, Pfizer, and Youngene Therapeutics; and serves on clinical endpoint committees for studies sponsored by Beckman Coulter, Kowa Pharmaceuticals, and Tosoh Biosciences. Dr Bohula has received consulting fees from Novo Nordisk and Kowa Pharmaceuticals. Dr Morrow has received consulting fees from Abbott Laboratories, InCarda, Merck, Novartis, Regeneron, and Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objective: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied., Design/setting/participants/interventions/outcome Measures: Using the American Heart Association's Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19., Results: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20-3/24/21) and 26,459 patients were admitted in the year prior (2/16/19-2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p < 0.0001) and BB (56.9 % vs 62.4 %, p < 0.0001) use was lower among admitted HFrEF patients during the pandemic when compared to the year prior. Rates of ACEI/ARB/ARNI, MRA, and triple therapy (ACE/ARB/ARNI + BB + MRA) prescription at discharge were higher during the pandemic compared to the year prior. Among a subgroup of those with HFrEF and COVID-19 (n = 333), prior to admission GDMT use was not associated with in-hospital mortality or severe COVID-19., Conclusion: We found no association between prior to admission GDMT use and in-hospital mortality or severe COVID-19 among HFrEF patients admitted with ADHF and COVID-19. GDMT prescription at discharge for HFrEF patients overall has remained either similar or improved during the pandemic., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GCF reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Eli Lilly, Johnson&Johnson, Medtronic, Merck, Novartis, and Pfizer. EHY reports research grants/funding from CSL Behring, Boehringer Ingelheim, Eli Lilly, and Bristol Meyers Squibb, and consulting fees from Pfizer. LBD reports consulting for Abbott, Quidel, and Roche; research funding from Vifor; and serves on a clinical endpoint adjudication committee for Applied Therapeutics. RVP receives unrelated research support from Infraredx, Abbott Vascular, and Bayer, and consulting fees from Abbott Vascular., (© 2024 The Authors.)

Background: Sex disparities exist in the management and outcomes of various cardiovascular diseases. However, little is known about sex differences in cardiogenic shock (CS). We sought to assess sex-related differences in the characteristics, resource utilization, and outcomes of patients with CS., Methods: The Critical Care Cardiology Trials Network is a multicenter registry of advanced cardiac intensive care units (CICUs) in North America. Between 2018 and 2022, each center (N=35) contributed annual 2-month snapshots of consecutive CICU admissions. Patients with CS were stratified as either CS after acute myocardial infarction or heart failure-related CS (HF-CS). Multivariable logistic regression was used for analyses., Results: Of the 22 869 admissions in the overall population, 4505 (20%) had CS. Among 3923 patients with CS due to ventricular failure (32% female), 1235 (31%) had CS after acute myocardial infarction and 2688 (69%) had HF-CS. Median sequential organ failure assessment scores did not differ by sex. Women with HF-CS had shorter CICU lengths of stay (4.5 versus 5.4 days; P <0.0001) and shorter overall lengths of hospital stay (10.9 versus 12.8 days; P <0.0001) than men. Women with HF-CS were less likely to receive pulmonary artery catheters (50% versus 55%; P <0.01) and mechanical circulatory support (26% versus 34%; P <0.0001) compared with men. Women with HF-CS had higher in-hospital mortality than men, even after adjusting for age, illness severity, and comorbidities (34% versus 23%; odds ratio, 1.76 [95% CI, 1.42-2.17]). In contrast, there were no significant sex differences in utilization of advanced CICU monitoring and interventions, or mortality, among patients with CS after acute myocardial infarction., Conclusions: Women with HF-CS had lower use of pulmonary artery catheters and mechanical circulatory support, shorter CICU lengths of stay, and higher in-hospital mortality than men, even after accounting for age, illness severity, and comorbidities. These data highlight the need to identify underlying reasons driving the differences in treatment decisions, so outcomes gaps in HF-CS can be understood and eliminated., Competing Interests: Drs Berg, Bohula, Park, and Morrow are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Ltd, The Medicines Company, and Zora Biosciences. Dr Katz reports modest research funding from Abbott Corporation. The other authors report no conflicts.

Background: Previous studies have suggested that there is wide variability in cardiac intensive care unit (CICU) length of stay (LOS); however, these studies are limited by the absence of detailed risk assessment at the time of admission. Thus, we evaluated inter-hospital differences in CICU LOS, and the association between LOS and in-hospital mortality., Methods: Using data from the Critical Care Cardiology Trials Network (CCCTN) registry, we included 22,862 admissions between 2017 and 2022 from 35 primarily tertiary and quaternary CICUs that captured consecutive admissions in annual 2-month snapshots. The primary analysis compared inter-hospital differences in CICU LOS, as well as the association between CICU LOS and all-cause in-hospital mortality using a Fine and Gray competing risk model., Results: The overall median CICU LOS was 2.2 (1.1-4.8) days, and the median hospital LOS was 5.9 (2.8-12.3) days. Admissions in the longest tertile of LOS tended to be younger with higher rates of pre-existing comorbidities, and had higher Sequential Organ Failure Assessment (SOFA) scores, as well as higher rates of mechanical ventilation, intravenous vasopressor use, mechanical circulatory support, and renal replacement therapy. Unadjusted all-cause in-hospital mortality was 9.3%, 6.7%, and 13.4% in the lowest, intermediate, and highest CICU LOS tertiles. In a competing risk analysis, individual patient CICU LOS was correlated (r 2 = 0.31) with a higher risk of 30-day in-hospital mortality. The relationship remained significant in admissions with heart failure, ST-elevation myocardial infarction and non-ST segment elevation myocardial infarction., Conclusions: In a large registry of academic CICUs, we observed significant variation in CICU LOS and report that LOS is independently associated with all-cause in-hospital mortality. These findings could potentially be used to improve CICU resource utilization planning and refine risk prognostication in critically ill cardiovascular patients., Competing Interests: Disclosure DMK, MWD, DAG, DH, SL, MJP, SWR, PAS, JS JW, LBD, SvD, none. JNK reports 1) Research support from Abbott and as a data safety and monitoring committee member for Abiomed; RP reports consulting fees from Abiomed; LKN reports research funding and consulting from Medtronic and research funding from Roche Diagnostics. EAB/DAM/JGP are members of the TIMI Study Group which has received institutional research grant support through Brigham and Women's Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, The Medicines Company, Zora Biosciences. DAM has received consulting fees from Abbott Laboratories, ARCA Biopharma, InCarda, Inflammatix, Merck, Novartis and Roche Diagnostics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Risk stratification has potential to guide triage and decision-making in cardiogenic shock (CS). We assessed the prognostic performance of the IABP-SHOCK II score, derived in Europe for acute myocardial infarct-related CS (AMI-CS), in a contemporary North American cohort, including different CS phenotypes., Methods: The critical care cardiology trials network (CCCTN) coordinated by the TIMI study group is a multicenter network of cardiac intensive care units (CICU). Participating centers annually contribute ≥2 months of consecutive medical CICU admissions. The IABP-SHOCK II risk score includes age > 73 years, prior stroke, admission glucose > 191 mg/dl, creatinine > 1.5 mg/dl, lactate > 5 mmol/l, and post-PCI TIMI flow grade < 3. We assessed the risk score across various CS etiologies., Results: Of 17,852 medical CICU admissions 5,340 patients across 35 sites were admitted with CS. In patients with AMI-CS (n = 912), the IABP-SHOCK II score predicted a >3-fold gradient in in-hospital mortality (low risk = 26.5%, intermediate risk = 52.2%, high risk = 77.5%, P < .0001; c-statistic = 0.67; Hosmer-Lemeshow P = .79). The score showed a similar gradient of in-hospital mortality in patients with non-AMI-related CS (n = 2,517, P < .0001) and mixed shock (n = 923, P < .001), as well as in left ventricular (<0.0001), right ventricular (P = .0163) or biventricular (<0.0001) CS. The correlation between the IABP-SHOCK II score and SOFA was moderate (r 2 = 0.17) and the IABP-SHOCK II score revealed a significant risk gradient within each SCAI stage., Conclusions: In an unselected international multicenter registry of patients admitted with CS, the IABP- SHOCK II score only moderately predicted in-hospital mortality in a broad population of CS regardless of etiology or irrespective of right, left, or bi-ventricular involvement., (Copyright © 2023. Published by Elsevier Inc.)

Background: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers., Methods: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability., Results: The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively., Conclusions: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites., Competing Interests: Disclosures Dr Barnett reports clinical trial enrollment for Acceleron, Merck, Merck Shape & Dohme, and Aerovate Therapeutics. Dr Bohula, Dr Morrow, and J. Guo are members of the TIMI study group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, and Zora Biosciences. Dr Morrow has received consulting fees from Abbott Laboratories, ARCA Biopharma, InCarda, Inflammatix, Merck, Novartis, and Roche Diagnostics. Dr Daniels reports consulting income from Roche Diagnostics and QuidelOrtho serves on clinical end point adjudication committees for Abbottand Applied Therapeutics. Dr Prasad reports advisory board for Abiomed and NIH R01 grant. Dr Teuteberg reports consulting with Abbott, Abiomed advisory board, CareDx advisory board and speaking fees, Cytokinetics speaking fees, Medtronic advisory board, speaking and consulting fees, Paragonix speaking fees, and Takeda advisory board. The other authors report no conflicts.

Aims: Invasive haemodynamic assessment with a pulmonary artery catheter is often used to guide the management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting haemodynamic parameters in CS., Methods and Results: The Critical Care Cardiology Trials Network is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018-2022) who underwent invasive haemodynamic assessment within 24 h of CICU admission were included. Associations of haemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score. Among the 3603 admissions with CS, 1473 had haemodynamic data collected within 24 h of CICU admission. The median cardiac index was 1.9 (25th-75th percentile, 1.6-2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66-86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for the intensity of background pharmacologic and mechanical haemodynamic support. These parameters were also associated with higher presenting serum lactate., Conclusion: In a contemporary CS population, presenting haemodynamic parameters reflecting decreased systemic arterial tone and right ventricular dysfunction are associated with adverse outcomes and systemic hypoperfusion., Competing Interests: Conflict of interest: D.D.B., E.A.B., V.M.B-Z., J.G., S.M.P., and D.A.M. are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, The Medicines Company, Zora Biosciences. M.A.S. receives research support from the National Institutes of Health Clinical Center intramural research funds. A.D.T. is supported by NIH-NHLBI (K08HL163328)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The appropriate use of pulmonary artery catheters (PACs) in critically ill cardiac patients remains debated., Objectives: The authors aimed to characterize the current use of PACs in cardiac intensive care units (CICUs) with attention to patient-level and institutional factors influencing their application and explore the association with in-hospital mortality., Methods: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Between 2017 and 2021, participating centers contributed annual 2-month snapshots of consecutive CICU admissions. Admission diagnoses, clinical and demographic data, use of PACs, and in-hospital mortality were captured., Results: Among 13,618 admissions at 34 sites, 3,827 were diagnosed with shock, with 2,583 of cardiogenic etiology. The use of mechanical circulatory support and heart failure were the patient-level factors most strongly associated with a greater likelihood of the use of a PAC (OR: 5.99 [95% CI: 5.15-6.98]; P < 0.001 and OR: 3.33 [95% CI: 2.91-3.81]; P < 0.001, respectively). The proportion of shock admissions with a PAC varied significantly by study center ranging from 8% to 73%. In analyses adjusted for factors associated with their placement, PAC use was associated with lower mortality in all shock patients admitted to a CICU (OR: 0.79 [95% CI: 0.66-0.96]; P = 0.017)., Conclusions: There is wide variation in the use of PACs that is not fully explained by patient level-factors and appears driven in part by institutional tendency. PAC use was associated with higher survival in cardiac patients with shock presenting to CICUs. Randomized trials are needed to guide the appropriate use of PACs in cardiac critical care., Competing Interests: Funding Support and Author Disclosures Dr Solomon has received research support from the National Institutes of Health Clinical Center intramural research funds. Dr Morrow has received research grant support to Brigham and Women’s Hospital from Abbott and Abiomed; and has received consulting fees from Abbott Laboratories. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Purpose: Sleep disordered breathing in decompensated heart failure has physiological consequences (e.g., intermittent hypoxemia) that may predispose to subclinical myocardial injury, yet a temporal relationship between sleep apnea and troponin elevation has not been established., Methods: We assessed the feasibility of performing respiratory polygraphy and measuring overnight high-sensitivity cardiac troponin T change in adults admitted to the hospital with acutely decompensated heart failure. Repeat sleep apnea tests (SATs) were performed to determine response to optimal medical heart failure therapy. Multivariable logistic regression was used to identify associations between absolute overnight troponin change and sleep apnea characteristics., Results: Among the 19 subjects with acutely decompensated heart failure, 92% of SATs demonstrated sleep disordered breathing (apnea-hypopnea index [AHI] > 5 events/h). For those with repeat SATs, AHI increased in 67% despite medical management of heart failure. Overnight troponin increase was associated with moderate to severe sleep apnea (vs. no to mild sleep apnea, odds ratio (OR = 18.4 [1.51-224.18]), central apnea index (OR = 1.11 [1.01-1.22]), and predominantly central sleep apnea (vs. obstructive, OR = 22.9 [1.29-406.32])., Conclusions: Sleep apnea severity and a central apnea pattern may be associated with myocardial injury. Respiratory polygraphy with serial biomarker assessment is feasible in this population, and combining this approach with interventions (e.g., positive airway pressure) may help establish if a link exists between sleep apnea and subclinical myocardial injury., (© 2022. The Author(s).)

Background: The pathobiology of inflammation, thrombosis, and myocardial injury associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may be assessed by circulating biomarkers. However, their relative prognostic importance has been incompletely described., Methods: We analyzed data from patients hospitalized with COVID-19 from January 2020, to April 2021, at 122 US hospitals in the American Heart Association (AHA) COVID-19 cardiovascular (CV) disease registry. Patients with data for D-dimer, C-reactive protein (CRP), ferritin, natriuretic peptides [NP], or cardiac troponin (cTn) at admission were included. cTn quintiles were indexed to the assay-specific 99th percentile reference limits. Using multivariable logistic regression, we assessed the association between each biomarker by quintile [Q] and odds of in-hospital death and a cardiovascular and thrombotic composite outcome., Results: Of 32,636 registry patients, 26,424 (81%) had admission values for ≥1 of the key biomarkers, of which 4,527 (17%) had admission values for all 5 biomarkers. Each biomarker revealed a significant gradient for in-hospital mortality from Q1 to Q5: D-dimer 14% to 35%, CRP 11%-32%, ferritin 11% to 30%, cTn 13% to 43%, and NPs 7% to 35% (P trend for each <.001). After adjustment for other biomarkers and clinical variables, Q5 for NPs (OR:4.67, 95% CI: 3.05-7.14) retained the greatest relative odds for death; cTn (OR:2.68, 95% CI: 2.00-3.59) and NPs (OR:7.14, 95% CI: 4.92-10.37) were associated with the greatest odds of the CV composite. Q5 for D-dimer was associated with the highest risk of thrombotic events (OR: 9.02, 95% CI: 5.36-15.18)., Conclusions: Among patients hospitalized with COVID-19, cTn and NPs identified patients at high risk for an in-hospital adverse cardiovascular outcome, while elevations in D-dimer identified patients at risk for thrombotic complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Elevated cardiac troponin (cTn) levels in patients with COVID-19 has been associated with worse outcomes. Guidelines on best practices of those patients remain uncertain., Methods: We included patients with COVID-19 and cTn above the assay-specific upper limit of normal (ULN) enrolled in the American Heart Association's COVID-19 registry between March 2020-January 2021. Site-level variability in invasive coronary angiography, LVEF assessment, ICU utilization, and inpatient mortality were determined by calculating adjusted median odds ratio (MOR) using hierarchical logistic regression models. Temporal trends were assessed with Cochran-Armitage trend test., Results: Among 32,636 patients, we included 6234 (19.4 %) with cTn above ULN (age 68.7 ± 16.0 years, 56.5 % male, 51.5 % Caucasian), of whom 1365 (21.6 %) had ≥5-fold elevations. Across 55 sites, the median rate of invasive coronary angiography was 0.1 % with adjusted MOR 1.5(1.0,2.3), median LVEF assessment was 25.5 %, MOR 3.0(2.2,3.9), ICU utilization was 41.7 %, MOR 2.2(1.8,2.6), and mortality was 20.9 %, MOR 1.7(1.5,2.0). Over time, we noted a significant increase in invasive coronary angiography (p-trend = 0.001), and LVEF assessment (p-trend<0.001), and reduction in mortality (p-trend<0.001), without significant change in ICU admissions (p-trend = 0.08). Similar variability and temporal trends were seen among patients with ≥5-fold cTn elevation., Conclusions: The use of invasive coronary angiography among patients with COVID-19 and myocardial injury was very low during the early pandemic. We found moderate institutional variability in processes of care with an uptrend in invasive catheterization and LVEF assessment, and downtrend in mortality. Comparative effectiveness studies are needed to examine whether variability in care is associated with differences in outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Subclinical abnormalities in myocardial structure (stage B heart failure) may be identified by cardiac and non-organ specific biomarkers. The associations of high-sensitivity cardiac troponin T (hs-cTnT) and growth differentiation factor-15 (GDF-15) with cardiac magnetic resonance imaging (CMR) interstitial fibrosis (extracellular volume [ECV]) is unknown and for GDF-15 the association with replacement (late gadolinium enhancement [LGE]) is also unknown. GDF-15 is a systemic biomarker also released by myocytes associated with fibrosis and inflammation. We sought to define the associations of hs-cTnT and GDF-15 with these CMR fibrosis measures in the MESA cohort., Methods: We measured hs-cTnT and GDF-15 in MESA participants free of cardiovascular disease at exam 5. CMR measurements were complete in 1737 for LGE and 1258 for ECV assessment. We estimated the association of each biomarker with LGE and increased ECV (4th quartile) using logistic regression, adjusted for demographics and risk factors., Results: Mean age of the participants was 68 ± 9 years. Unadjusted, both biomarkers were associated with LGE, but after adjustment only hs-cTnT concentrations remained significant (4th vs. 1st quartile OR] 7.5, 95% CI: 2.1, 26.6). For interstitial fibrosis both biomarkers were associated with 4th quartile ECV, but the association was attenuated compared to replacement fibrosis. After adjustment, only hs-cTnT concentrations remained significant (1st to 4th quartile OR 1.7, 95%CI: 1.1, 2.8)., Conclusion: Our findings identify that both interstitial and replacement fibrosis are associated with myocyte cell death/injury, but GDF-15 a non-organ specific biomarker prognostic for incident cardiovascular disease is not associated with preclinical evidence of cardiac fibrosis., Competing Interests: CdF received research funding to Inova from Abbott Diagnostics, Fujirebio, Ortho Clinical Diagnostics, Quidel, Roche Diagnostics, and Siemens Healthineers; independent of Inova he consults for Fujirebio, Ortho Diagnostics, Quidel, Roche Diagnostics, and Siemens Healthineers. CdF also receives unrelated research funding from the NIH R01HL154768, R01HL151293, R21AG072095, and 1UL1TR003015. RC received research funding to the University of Maryland from Roche Diagnostics, Siemens Healthineers, Becton Dickinson, Abbott, Beckman Coulter, and PixCell Medical; consulting/honoraria for Roche Diagnostics, Siemens Healthineers, Becton Dickinson, Beckman Coulter, SphingoTec, and PixCell Medical. LD was consulting for Quidel, Roche, and Siemens; has served on clinical endpoint adjudication committees for Abbott, Applied Therapeutics, Quidel, and Siemens. SS received research funding to the University of Maryland funding from Roche Diagnostics. SS, RC, and CdF were co-owners on a patent awarded to the University of Maryland (US Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure”. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 deFilippi, Tran, Gattani, Daniels, Shah, Ilkhanoff, Christenson, Lima and Seliger.)

Purpose of Review: To review the role of cardiac troponin (cTn) for prognosis in acute and chronic heart failure, and for predicting heart failure; and to explore the association between troponin and response to heart failure therapies, with an eye toward a possible role for troponin in a personalized approach to heart failure management, beyond prognosis., Recent Findings: A number of therapies, including the neprilysin inhibitor sacubitril/valsartan and sodium-glucose cotransporter-2 inhibitors, have recently been shown to improve outcomes in heart failure patients. Most studies suggest that these agents improve outcomes regardless of baseline cTn concentration, but have greater absolute benefit among patients with highest cTn and baseline risk. Troponin is prognostic across the heart failure spectrum, but whether it can significantly help with heart failure prevention and with tailoring and guiding heart failure treatments and interventions remains unknown., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Few data exist regarding the implementation of high-sensitivity cardiac troponin (hs-cTn) assays in the United States since their approval., Objectives: This study sought to explore trends in hs-cTn assay implementation over time and assess the association of their use with in-hospital cardiac testing and outcomes., Methods: The study examined trends in implementation of hs-cTn assays among participating hospitals in the National Cardiovascular Data Registry Chest Pain-MI [Myocardial Infarction] Registry from January 1, 2019 through September 30, 2021. Associations among hs-cTn use, use of in-hospital diagnostic imaging, and patient outcomes were assessed using generalized estimating equation models with logistic or gamma distributions., Results: Among 550 participating hospitals (N = 251,000), implementation of hs-cTn assays increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (P trend  < 0.001). Use of hs-cTn was associated with more echocardiography among persons with non-ST-segment elevation acute coronary syndrome (NSTE-ACS; 82.4% vs 75.0%; adjusted odds ratio: 1.43; 95% CI: 1.19-1.73) but not among low-risk chest pain individuals. Use of hs-cTn was associated with less invasive coronary angiography among low-risk patients (3.7% vs 4.5%; adjusted odds ratio: 0.73; 95% CI: 0.58-0.92) but similar use for patients with NSTE-ACS. There was no association between hs-cTn use and noninvasive stress testing or coronary computed tomography angiography testing. Among individuals with NSTE-ACS, hs-cTn use was not associated with revascularization or in-hospital mortality. Use of hs-cTn was associated with a shorter length of stay (median 47.6 hours vs 48.0 hours; ratio: 0.94; 95% CI: 0.90-0.98)., Conclusions: Implementation of hs-cTn among U.S. hospitals is increasing, but most U.S. hospitals continue to use less sensitive assays. The use of hs-cTn was associated with modestly shorter length of stay, greater use of echocardiography for NSTE-ACS, and less use of invasive angiography among low-risk patients., Competing Interests: Funding Support and Author Disclosures This research was supported by the American College of Cardiology’s National Cardiovascular Data Registry (NCDR). The views expressed in this manuscript represent those of the author(s) and do not necessarily represent the official views of the NCDR or its associated professional societies identified at CVQuality.ACC.org/NCDR. Dr McCarthy has received support from the National Heart, Lung, and Blood Institute (NHLBI) T32 postdoctoral training grant (5T32HL094301-12); and has received consulting income from Abbott Laboratories. Dr Wang has received research grants to the Duke Clinical Research Institute from Abbott, AstraZeneca, Bristol Myers Squibb, Boston Scientific, Cryolife, Chiesi, Merck, Portola, and Regeneron; and has received consulting honoraria from AstraZeneca, Bristol Myers Squibb, Cryolife, and Novartis. Dr Sandoval has served on advisory boards for Roche Diagnostics and Abbott Diagnostics without personal financial compensation; and has also been a speaker without personal financial compensation for Abbott Diagnostics. Dr Smilowitz has received partial support from a Career Development Award from NHLBI (K23HL150315); and has received consulting honoraria from Abbott Vascular. Dr Wasfy has received support from the American Heart Association (18 CDA 34110215). Dr de Lemos has received grant support from Abbott Diagnostics and Roche Diagnostics; and has received consulting income from Ortho Clinical Diagnostics, Quidel, Beckman Coulter, and Siemens’s Health Care Diagnostics. Dr Kontos has served as chair of the Chest Pain-MI Steering committee. Dr Apple has served as an Associate Editor of Clinical Chemistry; has participated in the advisory boards of Werfen, Siemens Healthineers, and Qorvo Biotechnology; has received consulting income from AWE Medical and Hytest; and has received cardiac biomarker grant support (nonsalaried) through his institutional research institute from Abbott Diagnostics, Abbott POC, Siemens Healthcare, Ortho-Clinical Diagnostics, Roche Diagnostics, Beckman Coulter, BD, and Quidel. Dr Daniels has received consulting income from Quidel, Roche, and Siemens; and has participated in clinical endpoint committees or data safety monitoring boards for Abbott, Applied Therapeutics, and Quidel. Dr Newby has received research grant support from Roche Diagnostics and BioKier; and has received consulting honoraria from Beckman-Coulter, CSL, and Medtronic. Dr Jaffe has served as a consultant for Abbott, Beckman-Coulter, Siemens, Roche, Ortho Diagnostics, Radiometer, ET Healthcare, Sphingotec, Astellas, RCE Technologies, Amgen, and Novartis. Dr Januzzi has served as a Trustee of the American College of Cardiology; has received grant support from Abbott, Applied Therapeutics, HeartFlow Inc, Innolife, and Roche Diagnostics; has received consulting income from Abbott, Janssen, Novartis, Merck, and Roche Diagnostics; and has participated in clinical endpoint committees or data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Pfizer, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Algorithmic application of the 2019 Society of Cardiovascular Angiography and Intervention (SCAI) shock stages effectively stratifies mortality risk for patients with cardiogenic shock. However, clinician assessment of SCAI staging may differ. Moreover, the implications of the 2022 SCAI criteria update remain incompletely defined., Methods: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Between 2019 and 2021, participating centers (n=32) contributed at least a 2-month snapshot of consecutive medical CICU admissions. In-hospital mortality was assessed across 3 separate staging methods: clinician assessment, Critical Care Cardiology Trials Network algorithmic application of the 2019 SCAI criteria, and a revision of the Critical Care Cardiology Trials Network application using the 2022 SCAI criteria., Results: Of 9612 admissions, 1340 (13.9%) presented with cardiogenic shock with in-hospital mortality of 35.2%. Both clinician and algorithm-based staging using the 2019 SCAI criteria identified a stepwise gradient of mortality risk (stage C-E: 19.0% to 83.7% and 14.6% to 52.2%, respectively; P trend <0.001 for each). Clinician assignment of SCAI stages identified higher risk patients compared with algorithm-based assignment (stage D: 49.9% versus 29.3%; stage E: 83.7% versus 52.2%). Algorithmic application of the 2022 SCAI criteria, with incorporation of the vasoactive-inotropic score, more closely approximated clinician staging (mortality for stage C-E: 21.9% to 70.5%; P trend <0.001)., Conclusions: Both clinician and algorithm-based application of the 2019 SCAI stages identify a stepwise gradient of mortality risk, although clinician-staging may better allocate higher risk patients into advanced SCAI stages. Updated algorithmic staging using the 2022 SCAI criteria and vasoactive-inotropic score further refines risk stratification.

Aims: The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicentre research network to conduct randomised clinical trials (RCTs) in patients with cardiac critical illness., Methods and Results: The CCCTN was founded in 2017 with 16 centres and has grown to a research network of over 40 academic and clinical centres in the United States and Canada. Each centre enters data for consecutive cardiac intensive care unit (CICU) admissions for at least 2 months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterised utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicentre collaboration, the CCCTN has established a robust research network to facilitate multicentre registry-based randomised trials in patients with cardiac critical illness., Conclusion: The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomised controlled trials in this important patient population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiac troponin (cTn) can be elevated in many patients presenting to the emergency department (ED) with chest pain but without a diagnosis of acute coronary syndrome (ACS). We compared the prognostic significance of cTn in these different populations., Methods: We retrospectively analyzed the CHOPIN study, which enrolled patients who presented to the ED with chest pain. Patients were grouped as ACS, non-ACS cardiovascular disease, noncardiac chest pain and chest pain not otherwise specified (NOS). We examined the prognostic ability of cTnI for the clinical endpoints of mortality and major adverse cardiovascular event (MACE; a composite of acute myocardial infarction, unstable angina, revascularization, reinfarction, and congestive heart failure and stroke) at 180-day follow-up., Results: Among 1982 patients analyzed, 14% had ACS, 21% had non-ACS cardiovascular disease, 31% had a noncardiac diagnosis and 34% had chest pain NOS. cTnI elevation above the 99th percentile was observed in 52, 18, 6 and 7% in these groups, respectively. cTnI elevation was associated with mortality and MACE, and their relationships were more prominent in noncardiac diagnosis and chest pain NOS than in ACS and non-ACS cardiovascular diagnoses for mortality, and in non-ACS patients than in ACS patients for MACE (hazard ratio for doubling of cTnI 1.85, 2.05, 8.26 and 4.14, respectively; P for interaction 0.011 for mortality; 1.04, 1.23, 1.54 and 1.42, respectively; P for interaction <0.001 for MACE)., Conclusion: In patients presenting to the ED with chest pain, cTnI elevation was associated with a worse prognosis in non-ACS patients than in ACS patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: With the improvement in outcomes for acute coronary syndrome (ACS), the practice of routine admission to cardiac intensive care units (CICUs) is evolving. We aimed to describe the epidemiology of patients with ACS admitted to contemporary CICUs., Methods: Using the CCCTN (Critical Care Cardiology Trials Network) Registry for consecutive medical CICU admissions across 26 advanced CICUs in North America between 2017 and 2020, we identified patients with a primary diagnosis of ACS at CICU admission and compared patient characteristics, resource utilization, and outcomes to patients admitted with a non-ACS diagnosis and across sub-populations of patients with ACS, including by indication for CICU admission., Results: Of 10 118 CICU admissions, 29.4% (n=2978) were for a primary diagnosis of ACS, with significant interhospital variability (range, 13.4%-56.6%). Compared with patients admitted with a diagnosis other than ACS, patients with ACS had fewer comorbidities, lower acute severity of illness with less utilization of advanced CICU therapies (41.3% versus 66.1%, P <0.0001), and lower CICU mortality (5.4% versus 9.9%, P <0.0001). Monitoring alone, without another CICU indication at the time of admission, was the most frequent admission indication in patients with ACS (53.8%); less common indications in patients with ACS included respiratory insufficiency, shock, or the need for vasoactive therapy. Of patients with ACS admitted for monitoring alone, 94.8% did not subsequently require advanced intensive care unit therapies and had a low CICU length of stay (1.5 days [0.9-2.4] versus 2.6 [1.4-5.1], P <0.0001) and CICU mortality (0.6% versus 11.0%, P <0.0001), compared with patients with ACS with an admission indication beyond monitoring., Conclusions: In a registry of tertiary care CICUs, ACS represent ≈1/3 of all admissions with significant variability across hospitals. More than half of the ACS admissions to the CICU were for routine monitoring alone, with a low rate of complications and mortality. This observation highlights an opportunity for prospective studies to refine triage strategies for lower risk patients with ACS.

The clinical sequalae of SARS-CoV-2 infection are in part dependent upon age and pre-existing health conditions. Although the use of tobacco products decreases cardiorespiratory fitness while increasing susceptibility to microbial infections, limited information is available on how smoking affects COVID-19 severity. Therefore, we examined whether smokers hospitalized for COVID-19 are at a greater risk for developing severe complications than non-smokers. Data were from all hospitalized adults with SARS-CoV-2 infection from the American Heart Association's Get-With-The-Guidelines COVID-19 Registry, from January 2020 to March 2021, which is a hospital-based voluntary national registry initiated in 2019 with 122 participating hospitals across the United States. Patients who reported smoking at the time of admission were classified as smokers. Severe outcome was defined as either death or the use of mechanical ventilation. Of the 31,545 patients in the cohort, 6,717 patients were 1:2 propensity matched (for age, sex, race, medical history, medications, and time-frame of hospital admission) and classified as current smokers or non-smokers according to admission data. In multivariable analyses, after adjusting for sociodemographic characteristics, medical history, medication use, and the time of hospital admission, patients self-identified as current smokers had higher adjusted odds of death (adjusted odds ratio [aOR], 1.41; 95% CI, 1.21-1.64), the use of mechanical ventilation (aOR 1.15; 95% CI 1.01-1.32), and increased risk of major adverse cardiovascular events (aOR, 1.27; 95% CI 1.05-1.52). Independent of sociodemographic characteristics and medical history, smoking was associated with a higher risk of severe COVID-19, including death., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine the utility of a highly sensitive troponin assay when utilized in the emergency department., Methods: The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician's clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible., Trial Registration: ClinicalTrials.gov Identifier NCT00880802.

Background: We compared the long-term health of adults with prior Kawasaki disease (KD) to controls and determined whether outcomes varied by coronary artery (CA) status., Methods: We conducted a prospective cohort study of 258 KD subjects (mean 19 ± 9 years since KD) and 148 age-similar controls who completed extensive health questionnaires. KD subjects were divided into 2 groups, Cohort 1: 109 subjects followed since KD diagnosis at our institution; Cohort 2: 149 KD subjects diagnosed elsewhere., Results: KD subjects and controls were of similar age at the time of questionnaire completion (p = 0.50). Overall, 128 subjects (including 60 in Cohort 1) reported normal CAs during and after KD. Compared to controls, KD subjects with normal CAs reported several medical conditions with increased prevalence including migraine headaches, shortness of breath, and leg pain with walking, among others. When limited to Cohort 1, KD subjects were significantly more likely to report chest pain (47% vs 16%, p < 0.001) or palpitations (23% vs 10%, p = 0.01) compared to controls. Prevalence of depression was similar (7% vs 5%, p = 0.73)., Conclusions: Despite always having normal CAs in the acute and subacute phases of KD, young adults with a history of KD with normal coronaries were more likely than controls to experience cardiovascular symptoms. These differences could be influenced by anxiety or depression, but report of depression was similar between groups. Whether these health differences reflect a heightened awareness of symptoms among KD subjects, or underlying vascular pathology (i.e. vasospasm, microvascular dysfunction, other) merits further study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Objectives: The analytical sensitivity of high-sensitivity cardiac troponin T (hsTnT) assays has enabled rapid myocardial infarction rule-out algorithms for emergency department (ED) presentations. Few studies have analyzed the real-world impact of hsTnT algorithms on outcomes and operations., Methods: Comparison of ED length of stay (LOS) and 30-day outcomes (return to ED, inpatient admission, and mortality) for patients presenting with chest pain during 2 separate 208-day periods using a 0/1-hour hsTnT-enabled algorithm or fourth-generation TnT., Results: Discharge, 30-day readmission, and 30-day mortality rates were not significantly different with fourth-generation TnT vs hsTnT. Thirty-day return rates were significantly decreased with hsTnT (17.4% vs 14.9%; P < .01). For encounters with TnT measured at least twice and resulting in discharge, median ED LOS decreased by 61 minutes with the use of hsTnT (488 vs 427 minutes; P < .0001). Median time between first and second TnT results decreased by 82 minutes with hsTnT (202 vs 120 minutes; P < .0001), suggesting that the 0/1-hour algorithm was incompletely adopted., Conclusions: Implementation of the hsTnT algorithm was associated with decreased 30-day return rates and decreased ED LOS for a subset of patients, despite incomplete adoption of the 0/1-hour algorithm., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Acute heart failure (HF) is an important complication of coronavirus disease 2019 (COVID-19) and has been hypothesized to relate to inflammatory activation., Methods: We evaluated consecutive intensive care unit (ICU) admissions for COVID-19 across 6 centers in the Critical Care Cardiology Trials Network, identifying patients with vs without acute HF. Acute HF was subclassified as de novo vs acute-on-chronic, based on the absence or presence of prior HF. Clinical features, biomarker profiles and outcomes were compared., Results: Of 901 admissions to an ICU due to COVID-19, 80 (8.9%) had acute HF, including 18 (2.0%) with classic cardiogenic shock (CS) and 37 (4.1%) with vasodilatory CS. The majority (n = 45) were de novo HF presentations. Compared to patients without acute HF, those with acute HF had higher cardiac troponin and natriuretic peptide levels and similar inflammatory biomarkers; patients with de novo HF had the highest cardiac troponin levels. Notably, among patients critically ill with COVID-19, illness severity (median Sequential Organ Failure Assessment, 8 [IQR, 5-10] vs 6 [4-9]; P = 0.025) and mortality rates (43.8% vs 32.4%; P = 0.040) were modestly higher in patients with vs those without acute HF., Conclusions: Among patients critically ill with COVID-19, acute HF is distinguished more by biomarkers of myocardial injury and hemodynamic stress than by biomarkers of inflammation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Contemporary cardiac intensive care unit (CICU) outcomes remain highly heterogeneous. As such, a risk-stratification tool using readily available lab data at time of CICU admission may help inform clinical decision-making., Methods and Results: The primary derivation cohort included 4352 consecutive CICU admissions across 25 tertiary care CICUs included in the Critical Care Cardiology Trials Network (CCCTN) Registry. Candidate lab indicators were assessed using multivariable logistic regression. An integer risk score incorporating the top independent lab indicators associated with in-hospital mortality was developed. External validation was performed in a separate CICU cohort of 9716 patients from the Mayo Clinic (Rochester, MN, USA). On multivariable analysis, lower pH [odds ratio (OR) 1.96, 95% confidence interval (CI) 1.72-2.24], higher lactate (OR 1.40, 95% CI 1.22-1.62), lower estimated glomerular filtration rate (OR 1.26, 95% CI 1.10-1.45), and lower platelets (OR 1.18, 95% CI 1.05-1.32) were the top four independent lab indicators associated with higher in-hospital mortality. Incorporated into the CCCTN Lab-Based Risk Score, these four lab indicators identified a 20-fold gradient in mortality risk with very good discrimination (C-index 0.82, 95% CI 0.80-0.84) in the derivation cohort. Validation of the risk score in a separate cohort of 3888 patients from the Registry demonstrated good performance (C-index of 0.82; 95% CI 0.80-0.84). Performance remained consistent in the external validation cohort (C-index 0.79, 95% CI 0.77-0.80). Calibration was very good in both validation cohorts (r = 0.99)., Conclusion: A simple integer risk score utilizing readily available lab indicators at time of CICU admission may accurately stratify in-hospital mortality risk., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Rationale & Objective: The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population., Study Design: Observational study., Setting & Participants: We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease., Exposure: Estimated glomerular filtration rate (eGFR)., Outcome: NT-proBNP and hsTnT at baseline., Analytical Approach: We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT., Results: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above the conventional URL, respectively. In those with eGFR <30mL/min/1.73m 2 , 71% and 68% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, respectively. Among all CKD participants, the 99th percentile for NT-proBNP was 3,592 (95% CI, 2,470-4,849) pg/mL and for hsTnT it was 126 (95% CI, 100-144) ng/L. Each 15mL/min/1.73m 2 decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60])., Limitations: Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting., Conclusions: In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background Currently, there is limited research on the prognostic value of NT-proBNP (N-terminal pro-B-type natriuretic peptide) as a biomarker in COVID-19. We proposed the a priori hypothesis that an elevated NT-proBNP concentration at admission is associated with increased in-hospital mortality. Methods and Results In this prospective, observational cohort study of the American Heart Association's COVID-19 Cardiovascular Disease Registry, 4675 patients hospitalized with COVID-19 were divided into normal and elevated NT-proBNP cohorts by standard age-adjusted heart failure thresholds, as well as separated by quintiles. Patients with elevated NT-proBNP (n=1344; 28.7%) were older, with more cardiovascular risk factors, and had a significantly higher rate of in-hospital mortality (37% versus 16%; P <0.001) and shorter median time to death (7 versus 9 days; P <0.001) than those with normal values. Analysis by quintile of NT-proBNP revealed a steep graded relationship with mortality (7.1%-40.2%; P <0.001). NT-proBNP was also associated with major adverse cardiac events, intensive care unit admission, intubation, shock, and cardiac arrest ( P <0.001 for each). In subgroup analyses, NT-proBNP, but not prior heart failure, was associated with increased risk of in-hospital mortality. Adjusting for cardiovascular risk factors with presenting vital signs, an elevated NT-proBNP was associated with 2-fold higher adjusted odds of death (adjusted odds ratio [OR], 2.23; 95% CI, 1.80-2.76), and the log-transformed NT-proBNP with other biomarkers projected a 21% increased risk of death for each 2-fold increase (adjusted OR, 1.21; 95% CI, 1.08-1.34). Conclusions Elevated NT-proBNP levels on admission for COVID-19 are associated with an increased risk of in-hospital mortality and other complications in patients with and without heart failure.

Introduction: We investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle-brachial index (ABI)., Methods: Hs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3-10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively., Results: Overall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes., Conclusions: NT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown., Methods and Results: We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P < 0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P < 0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P < 0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02)., Conclusions: Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Myocardial histology from autopsies of young adults with giant coronary artery aneurysms following Kawasaki disease (KD) shows bridging fibrosis beyond the territories supplied by the aneurysmal arteries. The etiology of this fibrosis is unknown, but persistent, low-level myocardial inflammation and microcirculatory ischemia are both possible contributing factors. To investigate the possibility of subclinical myocardial inflammation or fibrosis, we measured validated biomarkers in young adults with a remote history of KD., Methods: We measured plasma calprotectin, galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and serum procollagen type 1C-terminal propeptide (P1CP) in 91 otherwise healthy young adults with a remote history of KD and in 88 age-similar, healthy controls. KD subjects were stratified by coronary artery aneurysm (CAA) status and history of remote myocardial infarction (MI)., Results: After correction for multiple testing, calprotectin, Gal-3, and GDF-15 levels were significantly higher in subjects with persistent CAA (n = 26) compared with KD subjects with remodeled CAA (n = 20, p = 0.005, 0.001, 0.0036, respectively). In a multivariable regression model with CA status as the main predictor and adjusting for sex, MI history, and interval from KD onset, CA status was a significant predictor (Persistent CAA vs KD Normal CA) of calprotectin, Gal-3, GDF-15 and sST2 levels (p = 0.004, <0.001, 0.007, and 0.049, respectively)., Conclusions: These results suggest that ongoing inflammation and fibrosis may be occurring in individuals with persistent CAA. Longitudinal follow-up is needed to clarify the clinical significance of these elevated biomarker levels in this patient population that requires life-long monitoring., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Statins have anti-inflammatory and immunomodulatory effects that may reduce the severity of coronavirus disease 2019 (COVID-19), in which organ dysfunction is mediated by severe inflammation. Large studies with diverse populations evaluating statin use and outcomes in COVID-19 are lacking., Methods and Results: We used data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease (CVD) Registry to evaluate the associations between statin use and outcomes. Prior to admission, 42% of subjects (n = 4,449) used statins (7% on statins alone, 35% on statins plus anti-hypertensives). Death (or discharge to hospice) occurred in 2,212 subjects (21%). Outpatient use of statins, either alone or with anti-hypertensives, was associated with a reduced risk of death (adjusted odds ratio [aOR] 0.59, 95% CI 0.50-0.69), adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications by logistic regression. In propensity-matched analyses, use of statins and/or anti-hypertensives was associated with a reduced risk of death among those with a history of CVD and/or hypertension (aOR 0.68, 95% CI 0.58-0.81). An observed 16% reduction in odds of death among those without CVD and/or hypertension was not statistically significant., Conclusions: Patients taking statins prior to hospitalization for COVID-19 had substantially lower odds of death, primarily among individuals with a history of CVD and/or hypertension. These observations support the continuation and aggressive initiation of statin and anti-hypertensive therapies among patients at risk for COVID-19, if these treatments are indicated based upon underlying medical conditions., Competing Interests: The authors have declared that no competing interests exist.

Background: Coronavirus Disease-2019 (COVID-19) is associated with cardiovascular injury, but left ventricular (LV) function is largely preserved. We aimed to evaluate for subclinical LV dysfunction in patients with COVID-19 through myocardial strain analysis., Methods: We performed a single-center retrospective cohort study of all patients hospitalized with COVID-19 who underwent echocardiography. Traditional echocardiographic and global longitudinal strain (GLS) values were compared with prior and subsequent echocardiograms., Results: Among 96 patients hospitalized with COVID-19 with complete echocardiograms, 67 (70%) had adequate image quality for strain analysis. The cohort was predominantly male (63%) and 18% had prevalent cardiovascular disease (CVD). Echocardiograms were largely normal with median [IQR] LV ejection fraction (EF) 62% [56%, 68%]. However, median GLS was abnormal in 91% (-13.5% [-15.0%, -10.8%]). When stratified by CVD, both groups had abnormal GLS, but presence of CVD was associated with worse median GLS (-11.6% [-13.4%, -7.2%] vs -13.9% [-15.0%, -11.3%], p = 0.03). There was no difference in EF or GLS when stratified by symptoms or need for intensive care. Compared to pre-COVID-19 echocardiograms, EF was unchanged, but median GLS was significantly worse (-15% [-16%, -14%] vs -12% [-14%, -10%], p = 0.003). Serial echocardiograms showed no significant changes in GLS or EF overall, however patients who died had stable or worsening GLS, while those who survived to discharge home showed improved GLS., Conclusions: Patients with COVID-19 had evidence of subclinical cardiac dysfunction manifested by reduced GLS despite preserved EF. These findings were observed regardless of history of CVD, presence of COVID-19 symptoms, or severity of illness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V.)

Background: At the University of California, San Diego, routine coronary angiography has generally been performed in men 40 years of age and older and women 45 years of age and older before pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (CTEPH). The prevalence of significant coronary artery disease (CAD) in this population has not been evaluated, however, and the optimal screening strategy has not been established. This study sought to evaluate whether the current approach may be better optimized on the basis of cardiac risk factors., Methods: This study included 462 consecutive patients with CTEPH who were undergoing preoperative coronary angiography for pulmonary thromboendarterectomy. Baseline demographic and medical information was recorded. Major cardiac risk factors included: diabetes, hypertension, hyperlipidemia, body mass index 25 kg/m 2 or greater, tobacco use, and family history of CAD. Charts were then reviewed for presence of significant CAD and revascularization., Results: Significant CAD was found in 13.4% of patients who underwent routine preoperative coronary angiography; it was present in only 5% of patients younger than 50 years of age, compared with 16% of patients 50 years old and older. No patient younger than 50 years of age without cardiac risk factors was found to have significant CAD. Furthermore, in patients younger than 50 years of age, significant CAD was found only among those with 3 or more major risk factors., Conclusions: In patients younger than 50 years of age with CTEPH, the prevalence of significant CAD was low. Omitting preoperative coronary angiography in this subset of patients is reasonable when no coronary risk factors are present. Preoperative coronary angiography is warranted in individuals 50 years of age and older, as well as in those younger than 50 years who have significant risk factors for CAD., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The impact of statins, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) severity and recovery is important given their high prevalence of use among individuals at risk for severe COVID-19. We studied the association between use of statin/angiotensin-converting enzyme inhibitors/ARB in the month before hospital admission, with risk of severe outcome, and with time to severe outcome or disease recovery, among patients hospitalized for COVID-19. We performed a retrospective single-center study of all patients hospitalized at University of California San Diego Health between February 10, 2020 and June 17, 2020 (n = 170 hospitalized for COVID-19, n = 5,281 COVID-negative controls). Logistic regression and competing risks analyses were used to investigate progression to severe disease (death or intensive care unit admission), and time to discharge without severe disease. Severe disease occurred in 53% of COVID-positive inpatients. Median time from hospitalization to severe disease was 2 days; median time to recovery was 7 days. Statin use prior to admission was associated with reduced risk of severe COVID-19 (adjusted OR 0.29, 95%CI 0.11 to 0.71, p < 0.01) and faster time to recovery among those without severe disease (adjusted HR for recovery 2.69, 95%CI 1.36 to 5.33, p < 0.01). The association between statin use and severe disease was smaller in the COVID-negative cohort (p for interaction = 0.07). There was potential evidence of faster time to recovery with ARB use (adjusted HR 1.92, 95%CI 0.81 to 4.56). In conclusion, statin use during the 30 days prior to admission for COVID-19 was associated with a lower risk of developing severe COVID-19, and a faster time to recovery among patients without severe disease., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers., Methods: Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated., Results: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P =0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI., Conclusions: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

Background: Despite differing underlying pathophysiology, type 1 and type 2 myocardial infarction share many of the same diagnostic criteria and can be challenging to differentiate in clinical practice. Correctly differentiating type 1 from type 2 myocardial infarction is important because they are managed differently. The aim of this study was to compare the patterns of rise of cardiac troponin (cTn) and creatine kinase MB (CK-MB) in type 1 and type 2 myocardial infarction., Methods: We analyzed retrospective data on 200 patients with myocardial infarction (97 with type 1, 103 with type 2), excluding patients with ST-segment elevation myocardial infarction. The percentage rise from trough to peak values and the ratio of the peak to the upper limit of normal (RULN) were calculated for both cardiac troponin T (cTnT) and CK-MB. The ratio of peak cTnT to peak CK-MB was also calculated before and after adjusting for sex, glomerular filtration rate (GFR), and infarct size., Results: Type 1 myocardial infarction tended to be larger than type 2 myocardial infarction, with a significantly higher mean percentage rise for both cTnT and CK-MB as well as higher mean RULN (207 vs 86 for cTnT, P = 0.02; 9 vs 4 for CK-MB, P = 0.002). There was a trend toward a higher rise of cTnT than CK-MB in type 2 compared with type 1 myocardial infarction, as demonstrated by the ratio of peak cTnT to peak CK-MB (0.09 in type 2 myocardial infarction vs 0.06 in type 1 myocardial infarction, P = 0.06). This difference persisted after adjusting for sex, GFR, and infarct size (P = 0.05)., Conclusion: Both cTnT and CK-MB rise higher in type 1 than in type 2 myocardial infarction. Meanwhile, cTnT tends to rise out of proportion to CK-MB in type 2 myocardial infarction. These patterns may have considerable implications for the differentiation and subsequent treatment of patients with type 1 versus type 2 myocardial infarction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Sterile tissue injury is thought to locally activate innate immune responses via damage-associated molecular patterns (DAMPs). Whether innate immune pathways are remotely activated remains relatively unexplored. Here, by analyzing ~145,000 single-cell transcriptomes at steady state and after myocardial infarction (MI) in mice and humans, we show that the type I interferon (IFN) response, characterized by expression of IFN-stimulated genes (ISGs), begins far from the site of injury, in neutrophil and monocyte progenitors within the bone marrow. In the peripheral blood of patients, we observed defined subsets of ISG-expressing neutrophils and monocytes. In the bone marrow and blood of mice, ISG expression was detected in neutrophils and monocytes and their progenitors, intensified with maturation at steady-state and after MI, and was controlled by Tet2 and Irf3 transcriptional regulators. Within the infarcted heart, ISG-expressing cells were negatively regulated by Nrf2 activation in Ccr2 - steady-state cardiac macrophages. Our results show that IFN signaling begins in the bone marrow, implicate multiple transcriptional regulators (Tet2, Irf3, and Nrf2) in governing ISG expression, and provide a clinical biomarker (ISG score) for studying IFN signaling in patients., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Prior studies have demonstrated the importance of diversity among physicians. Identifying trends in diversity within the most competitive internal medicine (IM) fellowships can guide focused efforts to address barriers to equal representation., Objective: To examine the racial and gender composition of resident applicants and accepted fellows to the top five most competitive IM specialties., Design: Survey data from the AAMC, JAMA, and NRMP were obtained. Fisher's exact tests were conducted to compare differences in representation between fellows in the most competitive specialties, resident applicants into those specialties, and categorical IM residents. Linear regression was used to analyze trends within each group., Participants: Categorical IM residents and fellows at ACGME-accredited M.D. programs in the USA., Main Measures: Proportion of each population by gender and race/ethnicity KEY RESULTS: Women saw an increase in representation among accepted fellows to the most competitive IM fellowships from 2008 to 2013 (+ 4.4%, p < 0.011), but the trend has since plateaued at a level (34%) significantly lower than their representation among IM residents (43%, p < 0.001). Black representation among accepted fellows (4.6%) has been increasing from 2008 to 2018 (+ 1.2%, p = 0.001), but is still significantly lower than their representation among IM residents (5.6%, p < 0.001). Hispanic resident applicant and fellow representation have seen minimal change., Conclusion: Despite trends towards better representation among women and underrepresented minorities (URMs) among fellows in the most competitive IM specialties from 2008 to 2013, there has been a stagnation in both gender and racial diversity over the past 5 years. Further efforts must be undertaken to address barriers to entry and advocate for better representation of women and URMs in fellowship programs.

Background: Low values of high-sensitivity cardiac troponin (hs-cTn) and coronary artery calcium (CAC) scores of zero are associated with a low risk for atherosclerotic cardiovascular disease (ASCVD)., Objectives: The purpose of this study was to evaluate baseline hs-cTnT and CAC in relation to ASCVD., Methods: Baseline hs-cTnT (limit of detection [LoD] 3 ng/l) and CAC measurements were analyzed across participants age 45 to 84 years without clinical cardiovascular disease from the prospective MESA (Multi-Ethnic Study of Atherosclerosis) in relationship to incident ASCVD., Results: Among 6,749 participants, 1,002 ASCVD events occurred during a median follow-up of 15 years. Participants with detectable CAC (20.1 vs. 5.0 events per 1,000 person-years; adjusted hazard ratio [HR]: 2.35; 95% confidence interval [CI]: 2.0 to 2.76; p < 0.001) and detectable hs-cTnT (15.4 vs. 5.2 per 1,000 person-years; adjusted HR: 1.47; 95% CI: 1.21 to 1.77; p < 0.001) had higher rates of ASCVD than those with undetectable results. Individuals with undetectable hs-cTnT (32%) had similar risk for ASCVD as did those with a CAC of zero (50%) (5.2 vs. 5.0 per 1,000 person-years). Together, hs-cTnT and CAC (discordance 38%) resulted in the following ASCVD event rates: hs-cTnT < LoD/CAC = 0: 2.8 per 1,000 person-years (reference), hs-cTnT ≥ LoD/CAC = 0: 6.8 per 1,000 person-years (HR: 1.59; 95% CI: 1.17 to 2.16; p = 0.003), hs-cTnT < LoD/CAC > 0: 11.1 per 1,000 person-years (HR: 2.74; 95% CI: 1.96 to 3.83; p < 0.00001), and hs-cTnT ≥ LoD/CAC > 0: 22.6 per 1,000 person-years (HR: 3.50; 95% CI: 2.60 to 4.70; p < 0.00001)., Conclusions: An undetectable hs-cTnT identifies patients with a similar, low risk for ASCVD as those with a CAC score of zero. The increased risk among those with discordant results supports their conjoined use for risk prediction., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)