bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid rule-out of acute myocardial infarction using the 0/1-hour algorithm for cardiac troponins in emergency primary care: the OUT-ACS implementation study
Authors: Johannessen T R , Vallersnes O M , Atar D , Halvorsen S , Larstorp A C K , Nilsen B , Ruud S E 
Published: October 2024

Abstract

Background
Acute chest pain in primary care often results in defensive and unnecessary hospital referrals due to the limited ability to rule out an acute myocardial infarction (AMI) outside of hospital. In a previous prospective observational study (OUT-ACS; One-hoUr Troponin in a low-prevalence population of Acute Coronary Syndrome), we demonstrated that the ESC 0/1-hour algorithm for high-sensitivity cardiac troponin T (hs-cTnT) would be safe and cost-effective if implemented to assess low-risk patients with chest pain in emergency primary care.

Purpose
We evaluated the real-world applicability, personnel adherence, and disposition of low-risk patients with chest pain following the implementation of the ESC 0/1-hour algorithm in emergency primary care.

Methods
In April 2023, the ESC 0/1-hour algorithm for hs-cTnT was implemented at a large emergency primary care clinic in Norway. The clinic is located close to a hospital, enabling the patient to wait at the clinic while blood samples are analysed for hs-cTnT at the hospital laboratory. For the following six months, all patients ≥18 years with acute non-traumatic chest discomfort, offered hs-cTnT measurements at the clinic, were anonymously registered, including their discharge diagnoses and disposition from the clinic. By applying the ESC 0/1-hour algorithm, patients were assigned to rule-out, rule-in or further observation. Patients in the observation group were offered a 4-hour hs-cTnT measurement before a final decision.

Results
During the six-month period, 10.3% (n=3,053/29,631) of the clinic's consultations involved chest complaints. Hs-cTnT measurements were conducted in 32.6% (n=995/3,053) with a median age of 58 years (IQR 45-68), 50.6% being female. A single hs-cTnT &lt;5 ng/L, sampled ≥3 hours since symptom onset, triaged 24.1% (n=240/995) of the patients towards the rule-out group, increasing to 63.8% after adding a 1-hour measurement. In the rule-in group (n=42/995, 4.2%), 16 patients were diagnosed with an AMI. The intermediate observation group (n=318/995, 32.0%, 4 AMIs) was reduced to 23.0 % after a 4-hour hs-cTnT measurement. Healthcare personnel adhered well to the algorithm, with a median sampling interval of 63 minutes (IQR 60-66) and 4.5 hours (IQR 4.1-5.5) for the 1- and 4-hour measurements, respectively. The algorithm was misinterpreted or overruled in 8.8% of the cases. Ultimately, only 14.8% required hospital transfer following troponin assessment at the clinic. The remaining patients were sent home or managed in the outpatient setting.

Conclusions
The OUT-ACS strategy, utilizing a 0/1/4-hour algorithm for hs-cTnT measurements in emergency primary care, is safe, effective and applicable, and the strategy contributes to reduced hospital referrals for low-risk patients with chest pain.0/1/4-hour algorithm for hs-cTnTDisposition
Identifying low-risk chest pain in out-of-hours primary care: the diagnostic performance of preHEAR and preHEART scores based on two European cohorts
Authors: Johannessen T R , Melessen I M , Vallersnes O M , Manten A , Halvorsen S , Atar D , Harskamp R E 
Published: October 2024

Abstract

Background
Distinguishing cardiac from non-cardiac acute chest pain presents a diagnostic challenge. Risk stratification tools, such as the HEART score, have been developed for decision support for hospital-based settings. For prehospital settings, the preHEART score was developed as an alternative to the HEART score, with refinements made to meet prehospital conditions, as illustrated in Figure 1. While promising for use by emergency medical services, the diagnostic performance in primary care is unknown.

Purpose
In this study, we aim to evaluate the preHEART score (with and without high-sensitivity cardiac troponin (hs-cTn)) as a risk stratification tool to rule out acute myocardial infarction (MI) in patients evaluated in out-of-hours primary care.

Methods
We relied on retrospective data from two cohorts, namely, the OUT-ACS study involving 1,711 consecutive patients (47.7% female, median age: 56 (25th-75th percentiles: 45-68)) evaluated at a Norwegian primary care emergency centre from 2016-2018; and the TRACE study involving 664 consecutive patients (56.9% female, median age: 48 (25th-75th percentiles: 32-67) from a Dutch primary care emergency centre in 2017. We evaluated the preHEAR (OUT-ACS & TRACE without hs-cTn) and preHEART scores (OUT-ACS). The threshold of ≤3 points was considered low-risk and previously determined as optimal for rule-out purposes. The primary outcome was the diagnostic performance for ruling out MI at the index episode, and the secondary outcome was the composite of 90-day all-cause death or MI.

Results
In the OUT-ACS cohort, 61 (3.6%) patients were diagnosed with an MI; for the TRACE study, MI was diagnosed in 20 (3.0%) patients. The percentage of patients deemed at low risk by preHEAR was 49.3% (n=843) and 82.7% (n=549) for OUT-ACS and TRACE, respectively. For preHEART, only 33.6% (n=575) of OUT-ACS patients were deemed low-risk. As shown in Figure 2, the corresponding sensitivity/specificity indices for index MI were 63.9%/49.8% (OUT-ACS) and 65.0%/84.2% (TRACE) for preHEAR and 93.4%/34.6% for preHEART. Positive predictive values were low (preHEAR 5.0-11.3%, preHEART 5.0%), whereas negative predictive values were high (preHEAR 97.4-98.7%, preHEART 99.3%). For the secondary outcome, similar diagnostic performance metrics were found. All missed MI cases (n=4) in the low-risk preHEART group were female.

Conclusion
The preHEAR and preHEART scores did not result in adequate rule-out safety for an emergency primary care setting despite a low a priori MI risk. Moreover, the score appears to underestimate the risk for MI in females.preHEAR(T) risk scoresPerformance of the risk scores
Comparison of multiple high sensitivity cardiac troponin assays for early low risk rule out of myocardial infarction: SCORECARD
Authors: Apple F , Mills N L , Vasile V C , Schulz K , Sexter A , Jaffe A S 
Published: October 2024

Abstract

Background/Introduction
The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome.

Methods
In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay.

Results
Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from &lt;2 to &lt;7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days.

Conclusions
Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.
Multi-biomarker approach for predicting cardiac magnetic resonance parameters at 30 days after ST-segment elevation myocardial infarction
Authors: Horbach T , Wenzl F A , Manka R , Raeber L , Pedrazzini G , Carballo D , Keller T , Sossalla S , Von Eckardstein A , Matter C M , Ruschitzka F , Luescher T F , Staehli B E , Klingenberg R 
Published: October 2024

Abstract

Background
Prior data showed associations of circulating Proprotein Convertase Subtilisin / Kexin type 9 (PCSK9) and inflammatory/anti-fibrotic Cellular Communication Network factor 1 (CCN1) at index ST-segment elevation acute myocardial infarction (STEMI) with left ventricular ejection fraction at 6 and 12 months, respectively and for CCN1 also with infarct size.

Purpose
PCSK-9, CCN1 and reference biomarkers high-sensitivity Troponin T (hsTNT) and N-terminal pro-brain natriuretic peptide (NTproBNP) were measured in patients from the CLEVER-ACS trial (clinicaltrials.gov NCT01529554) at presentation with STEMI and correlated with clinically relevant cardiac magnetic resonance (CMR) parameters at 30 days.

Methods
Associations between baseline biomarkers (PCSK-9, CCN1, hsTNT, NTproBNP) and CMR parameters at 30 days were evaluated using Spearman correlation and linear regression analysis (dichotomised at their median). Receiver operating characteristic (ROC) and area under the curve (AUC) were determined for significant values based on correlation analysis; AUC &gt; 0,7 considered relevant. CMR parameters comprised left ventricular structural and functional parameters including scar mass and microvascular obstruction.

Results
We identified 56 STEMI patients (mean age 61.7 ± 11.2 (SD) years) who completed 30 days follow-up with biomarker data. Among biomarkers, significant associations with CMR parameters were only found for hsTNT, and NTproBNP. The strongest associations were found for left ventricular ejection fraction (LVEF; hsTNT RSp =-0.66; NTproBNP RSp =-0.57), left ventricular scar (LVSCAR; hsTNT RSp =0.58; NTproBNP RSp =0.56) and scar mass (SM; hsTNT RSp =0.65; NTproBNP RSp =0.55). Conversely, left ventricular end-diastolic volume index (LVEDVI; hsTNT RSp =0.47; NTproBNP RSp =0.32), left ventricular end-systolic volume index (LVESVI; hsTNT RSp =0.51; NTproBNP RSp =0.39) and microvascular obstruction (MVO; hsTNT RSp =0.34; NTproBNP RSp =0.34) were significantly, albeit only modestly associated.
ROC and AUC analysis yielded relevant associations of biomarkers with CMR parameters LVEF (hsTNT=0.79; NTproBNP=0.81), LVSCAR (hsTNT=0.84; NTproBNP=0.76) and scar mass (hsTNT=0.83; NTproBNP=0.78). Furthermore, relevant associations of biomarkers with CMR were found for LVEDVI (hsTNT=0.79; NTproBNP=0.72), LVESVI (hsTNT=0.84; NTproBNP=0.72) and MVO (hsTNT=0.72; NTproBNP=0.71).

Conclusion
Baseline levels of hsTNT and NT-proBNP are strong predictors for functional and dimensional CMR parameters of the left ventricle including clinically relevant imaging surrogates of myocardial injury shortly after STEMI.ROC LVEF
Circulating nucleases degrade high-molecular-weight cell-free DNA in coronary vessels during acute myocardial infarction
Authors: Artner T , Ondracek A S , Hofbauer T M , Scherz T , Sharma S , Rinderer J , Panzenboeck A , Testori C , Beitzke D , Mangold A , Lang I M 
Published: October 2024

Abstract

Introduction
Extracellular cell-free DNA (cfDNA) originates from various biological processes, including cell turnover, apoptosis, necrosis, NETosis, and other forms of cell death. In healthy individuals, highly fragmented cfDNA is elevated in the bloodstream due to infection, cancer, inflammation and thrombosis. In thrombotic vascular diseases, neutrophils release elongated, high-molecular-weight DNA with bioactive and prothrombotic properties in a process termed NETosis. Circulating nucleases are thought to counteract pathogenic properties of NETs. However, attempts to connect total cfDNA concentration to nuclease activity have failed.

Purpose
We aimed to elucidate the in vivo connection between extracellular DNA and circulating nucleases in thrombotic vascular diseases by investigating DNA length as a potential novel biomarker in cardiovascular disease.

Methods
Citrated plasma from healthy volunteers (n=363) and from ST-elevation myocardial infarction (MI) coronary aspirates (n=59) and peripheral arterial sites (n=96) were analyzed for DNA concentration, length, and nuclease activity. Total DNA concentration was measured with a fluorescent DNA binding dye, and elongated DNA assessed using qPCR and Agilent bioanalyzer high-sensitivity DNA chip. Nuclease activity was measured by single radial enzyme-diffusion (SRED) assay. Cardiac MRI assessed infarct size acutely and six months after the event.

Results
Coronary aspirates exhibited an elevation in total DNA, with a significant rise in high-molecular weight cell-free DNA in addition to an increase in sub-nucleosome fragmentation (Figure 1). Peripheral and coronary plasma samples from individuals with myocardial infarction (MI) showed elevated levels of total and elongated cfDNA. When compared to healthy individuals, the integrity of cfDNA was lower in peripheral samples and higher in coronary aspirates. During myocardial infarction, circulating nuclease activity was elevated systemically but low at the coronary culprit lesion site. Elongated high-molecular-weight cfDNA accumulates primarily in coronary vessels but is also elevated systemically. In coronary aspirates, nuclease activity negatively correlated with elongated DNA and DNA integrity (rs=0.6255, p&lt;0.0001).

Conclusions
Elongated DNA accumulates during MI at the culprit lesion site. Its inverse correlation with nuclease activity underscores the role of nucleases in cleaving elongated DNA to shorter, soluble fragments. This study establishes DNA length and integrity as novel biomarkers in thrombotic cardiovascular disease.Figure 1:Coronary cfDNA lengthFigure 2:Nuclease activity and cfDNA
Troponin T as a risk marker for recurrent cardiovascular events in the post-discharge setting one month after acute coronary syndrome: a TRACER substudy
Authors: Batra G , Wassberg C , Westerbergh J , Lindback J , Lopes R D , Leonardi S , Mahaffey K W , Harrington R A , Held C , Wallentin L 
Published: October 2024

Abstract

Background
Troponin T (TnT) is a protein found in cardiac myocytes that is released during myocardial injury, such as myocardial infarction (MI). TnT levels rapidly rise during an MI, remain elevated for several days, and are a key criterion for diagnosing MI. Additionally, circulating TnT levels may offer prognostic information later, particularly during the rehabilitation phase after an acute coronary syndrome (ACS).

Purpose
To examine the relationship between circulating TnT at one month after hospitalisation for ACS and subsequent cardiovascular (CV) events.

Methods
The TRACER trial randomly assigned 12,944 patients diagnosed with non-ST-segment elevation ACS (NSTE-ACS) to receive either vorapaxar or placebo. Plasma samples were obtained after one month, and high-sensitivity (hs)-TnT was measured among 5,313 patients using the Elecsys electrochemiluminescence immunoassays. In this sub-study, the primary composite endpoint was the one-year risk of CV mortality, MI, or ischaemic stroke. Associations with outcomes were evaluated using Cox regression models, both unadjusted and adjusted for clinical baseline characteristics.

Results
The median concentration of hs-TnT was 11 ng/L one month after hospitalisation for ACS. Higher levels of hs-TnT at one month were associated with older age, coronary artery bypass surgery during the index ACS, male sex, a history of heart failure, renal disease, and diabetes mellitus. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 381 patients (incidence rate 5.4 per 100 person-years). Hs-TnT at one month after ACS was independently associated with the risk of the composite CV endpoint (relative hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 2.40 [1.80 – 3.20]) (see Figure 2). Similarly, hs-TnT, when added to a model including established risk factors, increased the concordance index of the multivariable model from 0.711 to 0.740 (p&lt;0.001). The results were consistent across the different components of the composite endpoint.

Conclusions
The level of hs-TnT provides useful information on the risk of future CV events in patients when measured one month after an ACS. This information might be useful for optimising secondary preventive treatment following an ACS.Figure.Hs-TnT and composite CV outcome
Comparison of the clinical chemistry score to other biomarker algorithms for rapid rule-out of acute myocardial infarction and risk stratification
Authors: Yildirim M , Salbach C , Milles B R , Reich C , Biener M , Frey N , Giannitsis E , Mueller-Hennessen M 
Published: October 2024

Abstract

Background
The clinical chemistry score (CCS) comprising high-sensitivity (hs) cardiac troponins (cTn), glucose and estimated glomerular filtration rate has been previously validated with superior accuracy for detection and risk stratification of acute myocardial infarction (AMI) compared to hs-cTn alone.

Methods
The CCS was directly compared to other biomarker-based algorithms for rapid rule-out and prognostication of AMI including the hs-cTnT limit-of-blank (LOB, &lt;3 ng/L) or limit-of-detection (LOD, &lt;5 ng/L) and the dual marker strategy (DMS) (copeptin &lt;10 pmol/L and hs-cTnT ≤14 ng/L) in 1506 patients presenting to the emergency department (ED) with symptoms suggestive of acute coronary syndrome. Negative predictive values (NPV) and sensitivities for rule-out of AMI were assessed and outcomes included rates of the combined end-point of all-cause mortality, myocardial re-infarction and stroke within 12 months.

Results
NPVs of 100% (98.3-100%) could be found for a CCS=0, hs-cTnT LoB and hs-cTnT LoD with rule-out efficacies of 11.1%, 7.6% and 18.3% as well as specificities of 13.0% (9.9-16.6%), 8.8% (7.3-10.5%) and 21.4% (19.2-23.8%), respectively. A CCS≤ 1 achieved a rule-out in 32.2% of all patients with a NPV of 99.6% (98.4-99.9%) and specificity of 37.4% (34.2-40.5%) compared to a rule-out efficacy of 51.2%, NPV of 99.0 (98.0-99.5) and specificity of 59.7% (57.0-62.4%) for the DMS. Rates of the combined end-point of death/AMI within 30 days ranged between 0.0% and 0.5% for all fast-rule-out protocols.

Conclusions
The CCS enables a reliable rule-out of AMI with low outcome rates in short and long-term follow-up for a specific population of ED patients. However, compared to a single or dual biomarker strategy, the CCS rule-out is attenuated by a loss of specificity and lower efficacy. Thus, the clinical benefit of the CCS in clinical practice seems to be negligible.
Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T
Authors: Knott J , Ola O , De Michieli L , Akula A , Slusser J , Mehta R , Crockford E , Lobo R , Hodge D , Grube E , Tak T , Cagin C , Gulati R , Sandoval Y , Jaffe A 
Published: October 2024

Abstract

Background
Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as these patients often have elevated baseline high-sensitivity cardiac troponin T (hs-cTnT) concentrations.

Methods
Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with &gt;1 hs-cTnT increase &gt;99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2- and 6-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR &lt;60 ml/min/1.73m2).

Results
The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 701 (82%) patients with myocardial injury, 64 (7.5%) with type 1, and 91 (11%) with type 2 MI. In CKD patients with baseline hs-cTnT thresholds of &gt;52, &gt;100, &gt;200 or &gt;300 ng/L, PPVs for acute MI were 37% [95% CI 28-46], 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 64% (95% CI 50-77), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of &gt;10, &gt;20 or &gt;30 ng/L, the corresponding PPVs were 65% (95% CI 50-78), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 65% (95% CI 51-78), 73% (95% CI 57-86) and 75% (95% CI 58-88) (Figure).

Conclusion
Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in patients with CKD. It significantly improves when using higher baseline thresholds and delta values.
The prognostic utility of troponin T levels in patients undergoing PCI during initial hospitalisation for STEMI
Authors: Ediriweera T E , Nguyen T N , Jamal J J , Tam G T , Wang A W , Long M , Leung A , Yang K , Faour A K , French J K 
Published: October 2024

Abstract

The prognostic utility of presentation or "peak" high-sensitivity troponin T (hsTnT) levels following ST-segment elevation myocardial infarction (STEMI) has been previously reported, but hsTnT, unlike other bio-markers of myocyte damage, have a 2nd or ‘plateau-phase’ of release which lasts over a week. We have reported correlations between plateau-phase hsTnT levels, and cardiac MRI determined infarct size, though whether these levels are more highly associated with late mortality than "peak" (or highest) levels, needs clarification.

Methods
Hence we determined late mortality and the combination of cardiovascular death, myocardial infarction and cerebrovascular accident [CD/MI/CVA] among patients with STEMI, and an HsTnT level &gt;36 hours after symptom onset (plateau phase), who underwent percutaneous coronary intervention (PCI), either primary or pharmaco-invasive, during initial hospitalisation between October 2003 and December 2021. HsTnT levels and other potential prognostic factors were determined.

Results
Amongst 1955 patients, 119 patients (6%) had died by 2 years and 192 (10%) patients experienced CD/MI/Stroke. The highest quartile of plateau phase hsTnT levels (³ 3786 ng/L ng/L), were more highly associated with 2-year mortality, than the highest quartile of "peak" hsTnT levels (³ 7687 ng/L ng/L). The Figure shows Peak and plateau hs-TnT levels in quartile groups were assessed by rank test to obtain p-values. Patients lost to follow-up or with less than 2-years of follow up were considered censored. Peak quartile 1; hs-TnT £ 1611 ng/L, peak quartile 2; hs-TnT 1612 – 3900 ng/L, peak quartile 3; hs-TnT 3901 – 7686 ng/L; peak quartile 4; hs-TnT ³ 7687 ng/L. Plateau quartile 1; hs-TnT £ 1060 ng/L, plateau quartile 2; hs-TnT 1061 – 2135 ng/L; plateau quartile 3; hs-cTnT 2136 – 3785 ng/L. Log rank mortality analyses are shown in the Figure. Peak quartile 1; hs-TnT &lt;1611 ng/L, peak quartile 2; hs-TnT 1612 – 3900 ng/L, peak quartile 3; hs-TnT 3901 – 7686 ng/L; peak quartile 4; hs-TnT ³ 7687 ng/L. Plateau quartile 1; hs-TnT £ 1060 ng/L, plateau quartile 2; hs-TnT 1061 – 2135 ng/L; plateau quartile 3; hs-cTnT 2136 – 3785 ng/L, plateau quartile 4; hs-TnT &gt;3786 ng/L. Multivariate Cox regression analysis incorporating age, sex, smoking status, hypertension, renal function, cardiogenic shock and heart failure hospitalisation found plateau hs-TnT levels (HR, 3.564; 95% CI, 1.674 – 7.590; P = 0.001) were an independent predictor of all-cause mortality at 2-years post-STEMI, whereas peak hs-cTnT levels (HR, 1.965; 95% CI, 0.959 – 4.025; P = 0.065) were not.

Conclusions
Plateau phase hsTnT levels were of prognostic significance in STEMI patients treated with PCI. Thus, measurement of plateau hs-cTnT levels following STEMI could be an accurate, inexpensive method of long-term prognostic risk stratification.