Publications by authors named "Allan S Jaffe"

457 Publications

High-Sensitivity Cardiac Troponin T for the Detection of Myocardial Injury and Risk Stratification in COVID-19.

Clin Chem 2021 Apr 16. Epub 2021 Apr 16.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.

Methods: We conducted a multicenter, retrospective, observational, US-based study of COVID-19 patients undergoing hs-cTnT. Outcomes included short-term mortality (in-hospital and 30-days post-discharge) and a composite of major adverse events including respiratory failure requiring mechanical ventilation, cardiac arrest, and shock within the index presentation and/or mortality during the index hospitalization or within 30-days post-discharge.

Results: Among 367 COVID-19 patients undergoing hs-cTnT, myocardial injury was identified in 46%. They had a higher risk for mortality (20% vs. 12%, P<0.0001; unadjusted HR 4.44, 95% CI 2.13-9.25, P<0.001) and major adverse events (35% vs. 11%, P<0.0001; unadjusted OR 4.29, 95% CI 2.50-7.40, P<0.0001). Myocardial injury was associated with major adverse events (adjusted OR 3.84, 95% CI 2.00-7.36, P<0.0001) but not mortality. Baseline (adjusted OR 1.003, 95% CI 1.00-1.007, P=0.047) and maximum (adjusted OR 1.005, 95% CI 1.001-1.009, P=0.0012) hs-cTnT were independent predictors of major adverse events. Most (95%) increases were due to myocardial injury, with 5% (n = 8) classified as type 1 or 2 myocardial infarction. A single hs-cTnT <6 ng/L identified 26% of patients without mortality, with a 94.9% (95% CI 87.5-98.6) negative predictive value and 93.1% sensitivity (95% CI 83.3-98.1) for major adverse events in those presenting to the ED.

Conclusions: Myocardial injury is frequent and prognostic in COVID-19. While most hs-cTnT increases are modest and due to myocardial injury, they have important prognostic implications. A single hs-cTnT <6 ng/L at presentation may facilitate the identification of patients with a favorable prognosis.
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http://dx.doi.org/10.1093/clinchem/hvab062DOI Listing
April 2021

Prediction of Death After Noncardiac Surgery: Potential Advantage of Using High-Sensitivity Troponin T as a Continuous Variable.

J Am Heart Assoc 2021 Mar 4;10(6):e018008. Epub 2021 Mar 4.

Cardiovascular Department and Department of Laboratory Medicine and Pathology Mayo Clinic MN.

Background Increased high-sensitivity cardiac troponin T (hs-cTnT) above the upper reference limit (URL) after noncardiac surgery identifies patients at risk for mortality. Prior studies have not analyzed hs-cTnT as a continuous variable or probed age- and sex-specific URLs. This study compared the prediction of 30-day mortality using continuous postoperative hs-cTnT levels to the use of the overall URL and age- and sex-specific URLs. Methods and Results Patients (876) >40 years of age who underwent noncardiac surgery were included. Hs-cTnT was measured on postoperative day 1. Cox proportional hazards models were used to compare associations between 30-day mortality and using hs-cTnT as a continuous variable, or above the overall or age- and sex-specific URLs. Comparisons were performed by the area under the receiver operating characteristic curve analysis. Mortality was 4.2%. For each 1 ng/L increase in postoperative hs-cTnT, there was a 0.3% increase in mortality (<0.001). Patients with postoperative hs-cTnT >14 ng/L were 37% of the cohort, while those above age- and sex-specific URLs were 25.3%. Both manifested higher mortality (hazard ratio [HR], 3.19; 95% CI, 1.20-8.49; =0.020) and (HR, 2.76; =0.009) than those with normal levels. The area under receiver operating characteristic curve was 0.89 using hs-cTnT as a continuous variable, 0.87 for age- and sex-specific URLs, and 0.86 for the overall URL. Conclusions Hs-cTnT as a continuous variable was independently associated with 30-day mortality and had the highest accuracy. Hs-cTnT elevations using overall and/or age- and sex-specific URLs were also associated with higher mortality.
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http://dx.doi.org/10.1161/JAHA.120.018008DOI Listing
March 2021

Cardiovascular biomarkers in patients with COVID-19.

Eur Heart J Acute Cardiovasc Care 2021 Feb 28. Epub 2021 Feb 28.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.
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http://dx.doi.org/10.1093/ehjacc/zuab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989520PMC
February 2021

Biomarkers of coagulation and fibrinolysis in acute myocardial infarction: a joint position paper of the Association for Acute CardioVascular Care and the European Society of Cardiology Working Group on Thrombosis.

Eur Heart J Acute Cardiovasc Care 2020 Nov 7. Epub 2020 Nov 7.

Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 161, 8200 Aarhus N, Denmark.

The formation of a thrombus in an epicardial artery may result in an acute myocardial infarction (AMI). Despite major advances in acute treatment using network approaches to allocate patients to timely reperfusion and optimal antithrombotic treatment, patients remain at high risk for thrombotic complications. Ongoing activation of the coagulation system as well as thrombin-mediated platelet activation may both play a crucial role in this context. Whether measurement of circulating biomarkers of coagulation and fibrinolysis could be useful for risk stratification in secondary prevention is currently not fully understood. In addition, measurement of such biomarkers could be helpful to identify thrombus formation as the leading mechanism for AMI. The introduction of biomarkers of myocardial injury such as high-sensitivity cardiac troponins made rule-out of AMI even more precise. However, elevated markers of myocardial injury cannot provide proof of a type 1 AMI, let alone thrombus formation. The combined measurement of markers of myocardial injury with biomarkers reflecting ongoing thrombus formation might be helpful for the fast and correct diagnosis of an atherothrombotic type 1 AMI. This position paper gives an overview of the current knowledge and possible role of biomarkers of coagulation and fibrinolysis for the diagnosis of AMI, risk stratification, and individualized treatment strategies in patients with AMI.
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http://dx.doi.org/10.1093/ehjacc/zuaa025DOI Listing
November 2020

Adjusting the MI Codes Into the Framework of the Universal Definition of Myocardial Infarction.

J Am Coll Cardiol 2021 Feb;77(7):858-860

Department of Medicine and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.01.003DOI Listing
February 2021

Ceramide Scores Predict Cardiovascular Risk in the Community.

Arterioscler Thromb Vasc Biol 2021 Apr 18;41(4):1558-1569. Epub 2021 Feb 18.

Department of Laboratory Medicine and Pathology (V.C.V., J.W.M., L.J.D., A.S.J.), Mayo Clinic College of Medicine, Rochester, MN.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.315530DOI Listing
April 2021

Using high sensitivity cardiac troponin values in patients with SARS-CoV-2 infection (COVID-19): The Padova experience.

Clin Biochem 2021 Apr 30;90:8-14. Epub 2021 Jan 30.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: The spectrum of Coronavirus Disease 2019 (COVID-19) is broad and thus early appropriate risk stratification can be helpful. Our objectives were to define the frequency of myocardial injury using high-sensitivity cardiac troponin I (hs-cTnI) and to understand how to use its prognostic abilities.

Methods: Retrospective study of patients with COVID-19 presenting to an Emergency Department (ED) in Italy in 2020. Hs-cTnI was sampled based on clinical judgment. Myocardial injury was defined as values above the sex-specific 99th percentile upper reference limits (URLs). Most data is from the initial hospital value.

Results: 426 unique patients were included. Hs-cTnI was measured in 313 (73.5%) patients; 85 (27.2%) had myocardial injury at baseline. Patients with myocardial injury had higher mortality during hospitalization (hazard ratio = 9 [95% confidence interval (CI) 4.55-17.79], p < 0.0001). Multivariable analysis including clinical and laboratory variables demonstrated an AUC of 0.942 with modest additional value of hs-cTnI. Myocardial injury was associated with mortality in patients with low APACHE II scores (<13) [OR (95% CI): 4.15 (1.40, 14.22), p = 0.014] but not in those with scores > 13 [OR (95% CI): 0.48 (0.08, 2.65), p = 0.40]. Initial hs-cTnI < 5 ng/L identified 33% of patients that were at low risk with 97.8% sensitivity (95% CI 88.7, 99.6) and 99.2% negative predictive value. Type 1 myocardial infarction (MI) and type 2 MI were infrequent.

Conclusions: hs-cTnI at baseline is a significant predictor of mortality in COVID-19 patients. A value < 5 ng/L identified patients at low risk.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847286PMC
April 2021

Sex-Specific 99th Percentile URLs for Cardiac Troponin Assays-Their Time Has Come.

Clin Chem 2021 Jan;67(1):197-200

Department of Cardiology, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1093/clinchem/hvaa204DOI Listing
January 2021

Temporal Trends, Predictors, and Outcomes of Acute Ischemic Stroke in Acute Myocardial Infarction in the United States.

J Am Heart Assoc 2021 Jan 5;10(2):e017693. Epub 2021 Jan 5.

Department of Cardiovascular Medicine Mayo Clinic Rochester MN.

Background There are limited contemporary data prevalence and outcomes of acute ischemic stroke (AIS) complicating acute myocardial infarction (AMI). Methods and Results Adult (>18 years) AMI admissions using the National Inpatient Sample database (2000-2017) were evaluated for in-hospital AIS. Outcomes of interest included in-hospital mortality, hospitalization costs, length of stay, discharge disposition, and use of tracheostomy and percutaneous endoscopic gastrostomy. The discharge destination was used to classify survivors into good and poor outcomes. Of a total 11 622 528 AMI admissions, 183 896 (1.6%) had concomitant AIS. As compared with 2000, in 2017, AIS rates increased slightly among ST-segment-elevation AMI (adjusted odds ratio, 1.10 [95% CI, 1.04-1.15]) and decreased in non-ST-segment-elevation AMI (adjusted odds ratio, 0.47 [95% CI, 0.46-0.49]) admissions (<0.001). Compared with those without, the AIS cohort was on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias. The AMI-AIS admissions received less frequent coronary angiography (46.9% versus 63.8%) and percutaneous coronary intervention (22.7% versus 41.8%) (<0.001). The AIS cohort had higher in-hospital mortality (16.4% versus 6.0%; adjusted odds ratio, 1.75 [95% CI, 1.72-1.78]; <0.001), longer hospital length of stay, higher hospitalization costs, greater use of tracheostomy and percutaneous endoscopic gastrostomy, and less frequent discharges to home (all <0.001). Among AMI-AIS survivors (N=153 318), 57.3% had a poor functional outcome at discharge with relatively stable temporal trends. Conclusions AIS is associated with significantly higher in-hospital mortality and poor functional outcomes in AMI admissions.
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http://dx.doi.org/10.1161/JAHA.120.017693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955313PMC
January 2021

The IFCC Clinical Application of Cardiac Biomarkers Committee's Appraisal of the 2020 ESC Guidelines for the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-segment Elevation: Getting Cardiac Troponin Right.

Clin Chem 2020 Dec 30. Epub 2020 Dec 30.

Departments of Laboratory Medicine and Pathology and Cardiology, Mayo Clinic, Rochester, MN, USA.

The Committee on the Clinical Application of Cardiac Biomarkers (C-CB) of the International Federation of Clinical Chemistry (IFCC) represents international groups from laboratory medicine, cardiology and emergency medicine involved in providing global educational guidance pertaining to the analytical and clinical applications of cardiac biomarkers. For that reason, most of the members are involved with national and international studies and trials pertaining to high sensitivity (hs) cardiac troponins I and T (cTnI and cTnT) (1-3). Although the recently published '2020 European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation' present some topics very well, the current special report was developed to delineate our specific concerns regarding the ESB guidance for the use of hs-cardiac troponin (hs-cTn) (4).
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http://dx.doi.org/10.1093/clinchem/hvaa337DOI Listing
December 2020

Corrigendum to "Measuring the contribution of Lp(a) cholesterol towards LDL-C interpretation" [Clin. Biochem. 86 (2020) 45-51].

Clin Biochem 2021 Feb 19;88:56-57. Epub 2021 Jan 19.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States. Electronic address:

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http://dx.doi.org/10.1016/j.clinbiochem.2020.12.008DOI Listing
February 2021

Influence of primary payer status on the management and outcomes of ST-segment elevation myocardial infarction in the United States.

PLoS One 2020 18;15(12):e0243810. Epub 2020 Dec 18.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.

Background: There are limited contemporary data on the influence of primary payer status on the management and outcomes of ST-segment elevation myocardial infarction (STEMI).

Objective: To assess the influence of insurance status on STEMI outcomes.

Methods: Adult (>18 years) STEMI admissions were identified using the National Inpatient Sample database (2000-2017). Expected primary payer was classified into Medicare, Medicaid, private, uninsured and others. Outcomes of interest included in-hospital mortality, use of coronary angiography and percutaneous coronary intervention (PCI), hospitalization costs, hospital length of stay and discharge disposition.

Results: Of the 4,310,703 STEMI admissions, Medicare, Medicaid, private, uninsured and other insurances were noted in 49.0%, 6.3%, 34.4%, 7.2% and 3.1%, respectively. Compared to the others, the Medicare cohort was older (75 vs. 53-57 years), more often female (46% vs. 20-36%), of white race, and with higher comorbidity (all p<0.001). The Medicare and Medicaid population had higher rates of cardiogenic shock and cardiac arrest. The Medicare cohort had higher in-hospital mortality (14.2%) compared to the other groups (4.1-6.7%), p<0.001. In a multivariable analysis (Medicare referent), in-hospital mortality was higher in uninsured (adjusted odds ratio (aOR) 1.14 [95% confidence interval {CI} 1.11-1.16]), and lower in Medicaid (aOR 0.96 [95% CI 0.94-0.99]; p = 0.002), privately insured (aOR 0.73 [95% CI 0.72-0.75]) and other insurance (aOR 0.91 [95% CI 0.88-0.94]); all p<0.001. Coronary angiography (60% vs. 77-82%) and PCI (45% vs. 63-70%) were used less frequently in the Medicare population compared to others. The Medicare and Medicaid populations had longer lengths of hospital stay, and the Medicare population had the lowest hospitalization costs and fewer discharges to home.

Conclusions: Compared to other types of primary payers, STEMI admissions with Medicare insurance had lower use of coronary angiography and PCI, and higher in-hospital mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243810PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748387PMC
January 2021

Cardiac procedural myocardial injury, infarction, and mortality in patients undergoing elective percutaneous coronary intervention: a pooled analysis of patient-level data.

Eur Heart J 2021 Jan;42(4):323-334

The Hatter Cardiovascular Institute, University College London, London, UK.

Aims: The prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated.

Methods And Results: We analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84-1.77), P = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32-3.97), P = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42-7.27), P = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin).

Conclusion: Our analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect 'major' procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia.
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http://dx.doi.org/10.1093/eurheartj/ehaa885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850039PMC
January 2021

Return-to-Play Guidelines for Athletes After COVID-19 Infection.

JAMA Cardiol 2021 04;6(4):479

Department of Cardiology, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1001/jamacardio.2020.5348DOI Listing
April 2021

Ceramides improve atherosclerotic cardiovascular disease risk assessment beyond standard risk factors.

Clin Chim Acta 2020 Dec 12;511:138-142. Epub 2020 Oct 12.

Zora Biosciences Oy, Espoo, Finland; Finnish Cardiovascular Research Center, Tampere University, Tampere, Finland.

Ceramides are bioactive lipids that act as secondary messengers for both intra- and inter-cellular signaling. Elevated plasma concentrations of ceramides are associated with multiple risk factors of atherosclerotic cardiovascular diseases and comorbidities including obesity, insulin resistance and diabetes mellitus. Furthermore, atherosclerotic plaques have been shown to be highly enriched with ceramides. Increases in ceramide content may accelerate atherosclerosis development by promoting LDL infiltration to the endothelium and aggregation within the intima of artery walls. Thus, ceramides appear to play a key role in the development of cardiometabolic disease due to their central location in major metabolic pathways that intersect lipid and glucose metabolism. Recently published data have shown that ceramides are not only of scientific interest but may also have diagnostic value. Their independent prognostic value for future cardiovascular outcomes over and above LDL cholesterol and other traditional risk factors have consistently been shown in numerous clinical studies. Thus, ceramide testing with a mass spectrometer offers a simple, reproducible and cost-effective blood test for risk stratification in atherosclerotic cardiovascular diseases.
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http://dx.doi.org/10.1016/j.cca.2020.10.005DOI Listing
December 2020

Measuring the contribution of Lp(a) cholesterol towards LDL-C interpretation.

Clin Biochem 2020 Dec 28;86:45-51. Epub 2020 Sep 28.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States. Electronic address:

Background: Lipoprotein(a) [Lp(a)] is a pro-atherogenic and pro-thrombotic LDL-like particle recognized as an independent risk factor for cardiovascular disease (CVD). The cholesterol within Lp(a) (Lp(a)-C) contributes to the reported LDL-cholesterol (LDL-C) concentration by nearly all available methods. Accurate LDL-C measurements are critical for identification of genetic dyslipidemias such as familial hypercholesterolemia (FH). FH diagnostic criteria, such as the Dutch Lipid Clinic Network (DLCN) criteria, utilize LDL-C concentration cut-offs to assess the likelihood of FH. Therefore, failure to adjust for Lp(a)-C can impact accurate FH diagnosis and classification, appropriate follow-up testing and treatments, and interpretation of cholesterol-lowering treatment efficacy.

Objective: In this study, we use direct Lp(a)-C measurements to assess the potential misclassification of FH from contributions of Lp(a)-C to reported LDL-C in patient samples submitted for advanced lipoprotein profiling.

Methods: A total of 31,215 samples submitted for lipoprotein profiling were included. LDL-C was measured by beta quantification or calculated by one of three equations. Lp(a)-C was measured by quantitative lipoprotein electrophoresis. DLCN LDL-C cut-offs were applied to LDL-C results before and after accounting for Lp(a)-C contribution.

Results: Lp(a)-C was detected in 8665 (28%) samples. A total of 940 subjects were reclassified to a lower DLCN LDL-C categories; this represents 3% of the total patient series or 11% of subjects with measurable Lp(a)-C.

Conclusion: Lp(a)-C is present in a significant portion of samples submitted for advanced lipid testing and could cause patient misclassification when using FH diagnostic criteria. These misclassifications could trigger inappropriate follow-up, treatment, and cascade testing for suspected FH.
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http://dx.doi.org/10.1016/j.clinbiochem.2020.09.007DOI Listing
December 2020

Sex Disparities in the Management and Outcomes of Cardiogenic Shock Complicating Acute Myocardial Infarction in the Young.

Circ Heart Fail 2020 10 29;13(10):e007154. Epub 2020 Sep 29.

Department of Cardiovascular Medicine (S.V., M.S., M.R.B., R.G., A.S.J., B.J.G., D.R.H., G.W.B.), Mayo Mayo Clinic, Rochester, MN.

Background: There are limited data on how sex influences the outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in young adults.

Methods: A retrospective cohort of AMI-CS admissions aged 18 to 55 years, during 2000 to 2017, was identified using the National Inpatient Sample. Use of coronary angiography, percutaneous coronary intervention, mechanical circulatory support and noncardiac interventions was identified. Outcomes of interest included in-hospital mortality, use of cardiac interventions, hospitalization costs, and length of stay.

Results: A total 90 648 AMI-CS admissions ≤55 years of age were included, of which 26% were women. Higher rates of CS were noted in men (2.2% in 2000 to 4.8% in 2017) compared with women (2.6% in 2000 to 4.0% in 2017; <0.001). Compared with men, women with AMI-CS were more frequently of Black race, from a lower socioeconomic status, with higher comorbidity, and admitted to rural and small hospitals (all <0.001). Women had lower rates of ST-segment elevation presentation (73.0% versus 78.7%), acute noncardiac organ failure, cardiac arrest (34.3% versus 35.7%), and received less-frequent coronary angiography (78.3% versus 81.4%), early coronary angiography (49.2% versus 54.1%), percutaneous coronary intervention (59.2% versus 64.0%), and mechanical circulatory support (50.3% versus 59.2%; all <0.001). Female sex was an independent predictor of in-hospital mortality (23.0% versus 21.7%; adjusted odds ratio, 1.11 [95% CI, 1.07-1.16]; <0.001). Women had lower hospitalization costs ($156 372±$198 452 versus $167 669±$208 577; <0.001) but comparable lengths of stay compared with men.

Conclusions: In young AMI-CS admissions, women are treated less aggressively and experience higher in-hospital mortality than men.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578068PMC
October 2020

99th Percentile Upper-Reference Limit of Cardiac Troponin and the Diagnosis of Acute Myocardial Infarction.

Clin Chem 2020 09;66(9):1167-1180

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.

Background: Concerns exist regarding how the 99th percentile upper reference limit (URL) of cardiac troponin (cTn) is determined and whether it should be derived from normal healthy individuals.

Content: The 99th percentile URL of cTn is an important criterion to standardize the diagnosis of myocardial infarction (MI) for clinical, research, and regulatory purposes. Statistical heterogeneity in its calculation exists but recommendations have been proposed. Some negativity has resulted from the fact that with some high-sensitivity (hs) cTn assays, a greater number of increases above the 99th percentile are observed when transitioning from a contemporary assay. Increases reflect acute or chronic myocardial injury and provide valuable diagnostic and prognostic information. The etiology of increases can sometimes be difficult to determine, making a specific treatment approach challenging. For those reasons, some advocate higher cutoff concentrations. This approach can contribute to missed diagnoses. Contrary to claims, neither clinical or laboratory guidelines have shifted away from the 99th percentile. To support the diagnosis of acute MI, the 99th percentile URL remains the best-established approach given the absence of cTn assay standardization. Importantly, risk stratification algorithms using hs-cTn assays predict the possibility of MI diagnoses established using the 99th percentile.

Summary: The 99th percentile of cTn remains the best-established criterion for the diagnosis of acute MI. While not perfect, it is analytically and clinically evidence-based. Until there are robust data to suggest some other approach, staying with the 99th percentile, a threshold that has served the field well for the past 20 years, appears prudent.
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http://dx.doi.org/10.1093/clinchem/hvaa158DOI Listing
September 2020

Sex and Gender Disparities in the Management and Outcomes of Acute Myocardial Infarction-Cardiogenic Shock in Older Adults.

Mayo Clin Proc 2020 09;95(9):1916-1927

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.

Objective: To evaluate outcomes by sex in older adults with cardiogenic shock complicating acute myocardial infarction (AMI-CS).

Materials And Methods: A retrospective cohort of older (≥75 years) AMI-CS admissions during January 1, 2000, to December 31, 2014, was identified using the National Inpatient Sample. Interhospital transfers were excluded. Use of angiography, percutaneous coronary intervention (PCI), mechanical circulatory support (MCS), and noncardiac interventions was identified. The primary outcome was in-hospital mortality stratified by sex, and secondary outcomes included temporal trends of prevalence, in-hospital mortality, use of cardiac and noncardiac interventions, hospitalization costs, and length of stay.

Results: In this 15-year period, there were 134,501 AMI-CS admissions 75 years or older, of whom 51.5% (n=69,220) were women. Women were on average older, were more often Hispanic or nonwhite race, and had lower comorbidity, acute organ failure, and concomitant cardiac arrest. Compared with older men (n=65,281), older women (n=69,220) had lower use of coronary angiography (55.4% [n=35,905] vs 49.2% [n=33,918]), PCI (36.3% [n=23,501] vs 34.4% [n=23,535]), MCS (34.3% [n=22,391] vs 27.2% [n=18,689]), mechanical ventilation, and hemodialysis (all P<.001). Female sex was an independent predictor of higher in-hospital mortality (adjusted odds ratio, 1.05; 95% CI, 1.02-1.08; P<.001) and more frequent discharges to a skilled nursing facility. In subgroup analyses of ethnicity, presence of cardiac arrest, and those receiving PCI and MCS, female sex remained an independent predictor of increased mortality.

Conclusion: Female sex is an independent predictor of worse in-hospital outcomes in older adults with AMI-CS in the United States.
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http://dx.doi.org/10.1016/j.mayocp.2020.01.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582223PMC
September 2020

Intracranial Hemorrhage Complicating Acute Myocardial Infarction: An 18-Year National Study of Temporal Trends, Predictors, and Outcomes.

J Clin Med 2020 Aug 22;9(9). Epub 2020 Aug 22.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Background: There is a paucity of contemporary data on the burden of intracranial hemorrhage (ICH) complicating acute myocardial infarction (AMI). This study sought to evaluate the temporal trends, predictors, and outcomes of ICH in AMI.

Methods: The National Inpatient Sample (2000-2017) was used to identify adult (>18 years) AMI admissions with ICH. In-hospital mortality, hospitalization costs, length of stay, and measure of functional ability were the outcomes of interest. The discharge destination along with use of tracheostomy and percutaneous endoscopic gastrostomy were used to estimate functional burden.

Results: Of a total 11,622,528 AMI admissions, 23,422 (0.2%) had concomitant ICH. Compared to those without, the ICH cohort was on average older, female, of non-White race, had greater comorbidities, and had higher rates of arrhythmias (all < 0.001). Female sex, non-White race, ST-segment elevation AMI presentation, use of fibrinolytics, mechanical circulatory support, and invasive mechanical ventilation were identified as individual predictors of ICH. The AMI admissions with ICH received less frequent coronary angiography (46.9% vs. 63.8%), percutaneous coronary intervention (22.7% vs. 41.8%), and coronary artery bypass grafting (5.4% vs. 9.2%), as compared to those without ( < 0.001). ICH was associated with a significantly higher in-hospital mortality (41.4% vs. 6.1%; adjusted OR 5.65 (95% CI 5.47-5.84); < 0.001), longer hospital length of stay, higher hospitalization costs, and greater use of percutaneous endoscopic gastrostomy (all < 0.001). Among ICH survivors ( = 13, 689), 81.3% had a poor functional outcome at discharge.

Conclusions: ICH causes a substantial burden in AMI due to associated higher in-hospital mortality and poor functional outcomes.
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http://dx.doi.org/10.3390/jcm9092717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565584PMC
August 2020

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

Circulation 2020 Oct 21;142(16):1532-1544. Epub 2020 Aug 21.

University of California, San Diego, La Jolla (Y.H., N.W., M.P.P., S.-X.N., G.M.V., L.B.D., A.M.).

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, =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.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046682DOI Listing
October 2020

Management and outcomes of uncomplicated ST-segment elevation myocardial infarction patients transferred after fibrinolytic therapy.

Int J Cardiol 2020 Dec 15;321:54-60. Epub 2020 Aug 15.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States of America.

Background: This study sought to assess the contemporary outcomes of patients transferred after receiving fibrinolytic therapy ('drip-and-ship') for ST-segment elevation myocardial infarction (STEMI) in the United States.

Methods: During 2009-2016, adults (>18 years) with STEMI (>18 years) without cardiac arrest and cardiogenic shock that received fibrinolytic therapy and were subsequently transferred were identified using the National Inpatient Sample (NIS). These admissions were divided into those undergoing fibrinolysis alone, subsequent coronary angiography (CA) without revascularization and subsequent CA with revascularization. Outcomes of interest included in-hospital mortality, resource utilization, and discharge disposition.

Results: A total of 27,454 STEMI admissions receiving a 'drip-and-ship strategy', 96.3% and 85.8% received subsequent coronary angiography and revascularization Admissions receiving CA and revascularization were younger, male, and with lower comorbidity. The fibrinolysis alone cohort had higher rates of organ failure, hemorrhagic sequelae, and intracranial hemorrhage. Compared to the fibrinolysis cohort, CA with revascularization (adjusted odds ratio [aOR] 0.17 [95% confidence interval {CI} 0.11-0.27]; p < .001) but not CA without revascularization (OR 0.72 [95% CI 0.42-1.21]; p = .21) was associated with lower in-hospital mortality. The fibrinolysis alone cohort had higher use of do-not-resuscitate status (12.8%) and fewer discharges to home (56.6%) compared to cohorts undergoing CA without (1.7%; 86.9%) and with (0.3% and 91.2%) revascularization, respectively. Presence of complications, do-not-resuscitate status, and higher comorbidity were predictive of lower CA and revascularization use.

Conclusion: Fibrinolysis with subsequent revascularization is associated with excellent outcomes in STEMI. Admissions receiving fibrinolysis alone were systematically different, sicker and had poorer outcomes.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.012DOI Listing
December 2020

Weekend Effect in the Management and Outcomes of Acute Myocardial Infarction in the United States, 2000-2016.

Mayo Clin Proc Innov Qual Outcomes 2020 Aug 12;4(4):362-372. Epub 2020 Jun 12.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.

Objective: To assess the effects of weekend admission vs weekday admission on the management and outcomes of acute myocardial infarction (AMI).

Methods: Adult ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) hospital admissions were identified using the National (Nationwide) Inpatient Sample (2000-2016). Interhospital transfers were excluded. Timing of coronary angiography (CA) and percutaneous coronary intervention (PCI) relative to the day of admission was identified. Outcomes of interest included in-hospital mortality, receipt of early CA, timing of CA and PCI, resource utilization, and discharge disposition for weekend vs weekday admissions.

Results: Of the 9,041,819 AMI admissions, 2,406,876 (26.6%) occurred on weekends. Compared with 2000, in 2016 there was an increase in weekend STEMI (adjusted odds ratio [aOR], 1.12; 95% CI, 1.08-1.16; <.001) but not NSTEMI (aOR, 1.01; 95% CI, 0.98-1.02; =.21) admissions. Compared with weekday admissions, weekend admissions received comparable CA (59.9% vs 58.8%) and PCI (38.4% vs 37.6%) and specifically lower rates of early CA (hospital day 0) (26.0% vs 20.8%; <.001). There was a steady increase in CA and PCI use during the 17-year period. Mean ± SD time to CA was higher in the weekend group vs the weekday group (1.2±1.8 vs 1.0±1.8 days; <.001). Weekend admission did not influence in-hospital mortality (aOR, 1.01; 95% CI, 1.00-1.01; =.05) but had fewer discharges to home (58.7% vs 59.7%; <.001).

Conclusion: Despite small differences in CA and PCI, there were no differences in in-hospital mortality of AMI admissions on weekdays vs weekends in the United States in the contemporary era.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411160PMC
August 2020

Influence of Human Immunodeficiency Virus Infection on the Management and Outcomes of Acute Myocardial Infarction With Cardiogenic Shock.

J Acquir Immune Defic Syndr 2020 11;85(3):331-339

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.

Background: There are limited data on the outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in patients with HIV infection and AIDS.

Setting: Twenty percent sample of all US hospitals.

Methods: A retrospective cohort of AMI-CS during 2000-2017 from the National Inpatient Sample was evaluated for concomitant HIV and AIDS. Outcomes of interest included in-hospital mortality and use of cardiac procedures. A subgroup analysis was performed for those with and without AIDS within the HIV cohort.

Results: A total 557,974 AMI-CS admissions were included, with HIV and AIDS in 1321 (0.2%) and 985 (0.2%), respectively. The HIV cohort was younger (54.1 vs. 69.0 years), more often men, of non-White race, uninsured, from a lower socioeconomic status, and with higher comorbidity (all P < 0.001). The HIV cohort had comparable multiorgan failure (37.8% vs. 39.0%) and cardiac arrest (28.7% vs. 27.4%) (P > 0.05). The cohorts with and without HIV had comparable rates of coronary angiography (70.2% vs. 69.0%; P = 0.37) but less frequent early coronary angiography (hospital day zero) (39.1% vs. 42.5%; P < 0.001). The cohort with HIV had higher unadjusted but comparable adjusted in-hospital mortality compared with those without [26.9% vs. 37.4%; adjusted odds ratio 1.04 (95% confidence interval: 0.90 to 1.21); P = 0.61]. In the HIV cohort, AIDS was associated with higher in-hospital mortality [28.8% vs. 21.1%; adjusted odds ratio 4.12 (95% confidence interval: 1.89 to 9.00); P < 0.001].

Conclusions: The cohort with HIV had comparable rates of cardiac procedures and in-hospital mortality; however, those with AIDS had higher in-hospital mortality.
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http://dx.doi.org/10.1097/QAI.0000000000002442DOI Listing
November 2020

Atherosclerotic Cardiovascular Disease Risk Stratification Based on Measurements of Troponin and Coronary Artery Calcium.

J Am Coll Cardiol 2020 07;76(4):357-370

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jacc.2020.05.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513421PMC
July 2020

Cardiac Troponin for Assessment of Myocardial Injury in COVID-19: JACC Review Topic of the Week.

J Am Coll Cardiol 2020 Sep 8;76(10):1244-1258. Epub 2020 Jul 8.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death. These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations. The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients. Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury. The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.
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http://dx.doi.org/10.1016/j.jacc.2020.06.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833921PMC
September 2020

Epidemiological Trends in the Timing of In-Hospital Death in Acute Myocardial Infarction-Cardiogenic Shock in the United States.

J Clin Med 2020 Jul 3;9(7). Epub 2020 Jul 3.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Background: There are limited data on the epidemiology and timing of in-hospital death (IHD) in patients with acute myocardial infarction-cardiogenic shock (AMI-CS).

Methods: Adult admissions with AMI-CS with IHDs were identified using the National Inpatient Sample (2000-2016) and were classified as early (≤2 days), mid-term (3-7 days), and late (>7 days). Inter-hospital transfers and those with do-not-resuscitate statuses were excluded. The outcomes of interest included the epidemiology, temporal trends and predictors for IHD timing.

Results: IHD was noted in 113,349 AMI-CS admissions (median time to IHD 3 (interquartile range 1-7) days), with early, mid-term and late IHD in 44%, 32% and 24%, respectively. Compared to the mid-term and late groups, the early IHD group had higher rates of ST-segment-elevation AMI-CS (74%, 63%, 60%) and cardiac arrest (37%, 33%, 29%), but lower rates of acute organ failure (68%, 79%, 89%), use of coronary angiography (45%, 56%, 67%), percutaneous coronary intervention (33%, 36%, 42%), and mechanical circulatory support (31%, 39%, 50%) (all < 0.001). There was a temporal increase in the early (adjusted odds ratio (aOR) for 2016 vs. 2000 2.50 (95% confidence interval (CI) 2.22-2.78)) and a decrease in mid-term (aOR 0.75 (95% CI 0.71-0.79)) and late (aOR 0.34 (95% CI 0.31-0.37)) IHD. ST-segment-elevation AMI-CS and cardiac arrest were associated with the increased risk of early IHD, whereas advanced comorbidity and acute organ failure were associated with late IHD.

Conclusions: Early IHD after AMI-CS has increased between 2000 and 2016. The populations with early vs. late IHD were systematically different.
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http://dx.doi.org/10.3390/jcm9072094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408956PMC
July 2020

Implementing High-Sensitivity Cardiac Troponin T in a US Regional Healthcare System.

Circulation 2020 Jun 8;141(23):1937-1939. Epub 2020 Jun 8.

Department of Cardiovascular Diseases (Y.S., J.W.A., A.S.J.), Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.045480DOI Listing
June 2020