High-sensitivity troponin-T Research Articles

Evidence for stability of cardiac troponin T concentrations measured with a high sensitivity TnT test in serum and lithium heparin plasma after six-year storage at-80 °C and multiple freeze-thaw cycles.

As high-sensitivity cardiac troponin T (hs-cTnT) is making the transition from diagnostic to prognostic use, a long-term stability study of 5th generation hs-cTnT according to EFLM CRESS recommendations was set up for investigation of frozen clinical specimens (two matrices). Study samples collected in serum tubes and lithium heparin tubes with gel from patients admitted for suspected minor myocardial damage were measured directly after completion of the study (0 years), and after 3-year and 6-year storage at-80 °C, and recovery of hs-cTnT concentrations after long-term storage (%hs-cTnT concentration compared to 0-year) was calculated. Hs-cTnT changes were also compared to decisive delta changes, such as the ones proposed in the ESC NSTEMI 0 h/1 h algorithm (<3 or >5 ng/L for ruling out and ruling in suspected NSTEMI patients). Eighty-six patients were included in the study, whereof 28 both lithium heparin plasma and serum samples were collected simultaneously, in others only serum (n=30) or plasma (n=28). Multiple aliquots per patient were made, so that 479 serum and 473 plasma samples were available for analysis. Across the overall hs-cTnT measuring range, median recovery after 6 years was 105.4 % and 106.2 % for serum and plasma, respectively. Based on these decisive delta changes, serum showed consistent results upon long term storage (max 0.8 % of samples above delta threshold of >5 ng/L) as compared to heparin plasma (up to 19.2 % of samples above threshold). Over 6 years of storage at-80 °C, recovery of hs-cTnT in serum and heparin plasma was similar and within common lot-to-lot variation. Yet, when evaluating absolute delta increments around hs-cTnT clinical decision points, long-term stored sera displayed better clinical performance compared to heparin plasma samples.

High-Sensitivity Troponin-T and heart failure risk in individuals with suspected acute coronary syndrome

Abstract Background In individuals with suspected acute coronary syndrome (ACS), serial assessments of high-sensitivity cardiac troponin-T (hsTnT) levels demonstrate associations with both short- and long-term mortality and recurrent ischemic events. Nonetheless, the relationship with subsequent heart failure remains inadequately characterized. Purpose We investigated the association between single and serial hsTnT levels and subsequent hospitalization or outpatient medical encounters related to heart failure in individuals presenting with suspected ACS. Methods Utilizing Danish national registries from 2012 to 2019, we identified individuals without known heart failure who underwent dual hsTnT assessments ( 99th percentile upper reference limit: 13.5 ng/l), spaced 1-7 hours apart during hospitalization for myocardial infarction (MI), unstable angina, observation for suspected MI, or chest pain. Participants were categorized based on their hsTnT concentration patterns from the first to the second measurement (primary groups: normal, rising, persistently elevated, or falling) and the extent of hsTnT concentration alterations (secondary groups: &amp;lt;20%, &amp;gt;20 to 50%, or &amp;gt;50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (&amp;lt;=9 ng/l, 10-15 ng/l, 16-66 ng/l, &amp;gt;=67 ng/l) to assess whether heightened hsTnT concentrations correlated with an increased risk of heart failure. Standardized risks of hospitalization or outpatient contacts for heart failure were computed using multivariable logistic regression with average treatment effect modeling. Results The study encompassed 26,835 individuals, of whom 38.9% received discharge diagnoses of MI, 5.1% were diagnosed with unstable angina, and 56.1% with observation for suspected MI or chest pain. Median age was 64.2 years, with 59.5% males. Prevalence of known cardiovascular disease included coronary disease in 18.1% of cases, prior revascularization in 7.2%, atrial fibrillation or flutter in 7.9%, and a history of stroke in 6.3%. Within the initial 30 days, 628 persons received a heart failure diagnosis, with an additional 960 diagnosed between days 31-365. Subjects displaying two normal hsTnT values exhibited the lowest standardized absolute risk (0.39% in days 0-30; 0.58% in days 31-365), while those with persistently elevated concentrations demonstrated the highest risk (6.45% in days 0-30; 7.05% in days 31-365) (Figure). Notably, the magnitude of hsTnT within each primary group did not affect heart failure risk. Conversely, heart failure risk exhibited a positive association with hsTnT concentrations measured in the initial sample. Conclusions In individuals presenting with suspected ACS, subjects with a sustained elevation in hsTnT levels showed the highest risk of subsequent heart failure events. Moreover, a dose-response association was observed between hsTnT concentrations and heart failure risk.Figure

Long-term outcomes in patients with dual pathology aortic stenosis and cardiac amyloidosis referred for valve intervention

Abstract Background The coexistence of aortic stenosis (AS) and cardiac amyloidosis (CA) is common. If treated with transcatheter aortic valve implantation (TAVI), patients with the combined phenotype (AS-CA) have a comparable short term survival to those with lone AS, whereas data on longer term outcomes is currently lacking. Purpose This study aimed to evaluate the clinical outcomes of AS-CA compared to lone AS over a 5-year follow-up. Methods Using a prospective, multicentre, observational, case-control design, we screened consecutive patients with severe AS referred for TAVI for co-existing CA. CA screening included blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) with additional SPECT/CT and light chain assessment prior to intervention. Transthyretin CA (ATTR) was diagnosed by bone scintigraphy and unremarkable light chain assessment, light-chain CA (AL) by endomyocardial biopsy. Mortality (all-cause and cardiovascular [CV]) and hospitalisation for heart failure (HHF) were captured as clinical endpoints. Results 376 patients (83±7 years, 52% female, EuroSCORE-II 4.9±2.9) were recruited, of which 43 (11.4%) had AS-CA (42 ATTR, 1 AL). Compared to lone AS, patients with AS-CA were older with higher cardiac biomarkers (NT-proBNP, high-sensitive Troponin-T) and a higher prevalence of atrial fibrillation. Heart team decision yielded valve replacement in 320 (85%) and conservative management in 56 (15%) patients, without differences between AS-CA and lone AS. Over a median follow-up of 5.4 (Q1: 4.9; Q3: 5.7) years, 230 (61.1%) patients died and 67 (17.8%) experienced HHF (with a total HHF number of 91). AS-CA was associated with higher all-cause mortality (crude HR 1.64, 95%CI 1.15-2.35; log-rank, p=0.006), which remained significant after multivariate adjustment for clinical confounders (EuroSCORE-II, valve replacement; adjusted HR 1.63, 95%CI 1.15-2.32; p=0.006). AS-CA was not associated with CV mortality (log-rank, p=0.18) or time to first HHF (log-rank, p=0.43), but the rate of HHF was significantly higher in AS-CA compared to lone AS (5.7 versus 3.5 per 1,000 patient years, p=0.022). Conclusions Among elderly patients referred for TAVI, long-term outcomes of AS-CA are characterized by higher mortality and a higher rate of heart failure hospitalisations compared to patients with lone AS. Studies evaluating the role of CA-specific treatments are warranted in this population.

Characterisation of plasma proteins and circulating microRNAs in out-of-hospital cardiac arrest patients - approaches for predicting outcome

Abstract Rationale: Early prognostication after out-of-hospital cardiac arrest (OHCA) is an unmet clinical need. There is limited data on serial release kinetics of cardiac, brain and systemic biomarkers such as Neuron Specific Enolase (NSE) and S-100B. miRNAs are sensitive biomarker candidates in acute myocardial infarction (MI). Objective The objective was to characterise circulating biomolecules in the early release kinetics after OHCA, compared with a STEMI control group and assessed with clinical outcome. Methods and Results Serial blood samples of patients with OHCA with STEMI (n=20) and STEMI control (n=20) were collected at baseline and at 6, 12, 24 and 48h after admission. Untargeted plasma proteomics were performed using data-independent acquisition–mass spectrometry (DIA–MS). Candidate proteins and miRNAs were quantified. Proteomics returned n=156 proteins with significantly different kinetics between OHCA and STEMI. Six clusters, depicting distinct biological pathways, with characteristic differences between OHCA and STEMI were identified. The most distinct and significant differences between OHCA and STEMI patients were seen for acute phase reactants LBP, AACT, CRP and the lipid metabolite A2GL as well as endothelial and platelet miR-126 and cardiomyocyte-apoptosis/ischemia-reperfusion related miR-320a. Cardiogenic shock was best characterised by differential kinetics of coagulation and complement related proteins FA9, HRG, FHR1 and inflammation related miR-146. The primary endpoint was poor neurological recovery at 30-days. Individuals with good outcome showed distinct differences in adaptive immune response, complement and coagulation cascades and hemostasis. Circulating plasma levels of hypoxia-associated miR-101, miR-210 and S-100B protein were significantly elevated at baseline in OHCA patients. These molecules further showed higher baseline values in patients with poor outcome. For current prognosis marker NSE, this difference only develops after 48h. Cardiac/muscle miRNAs followed an early release-pattern similar to high-sensitivity cardiac troponin-T (hs-cTnT). Machine learning models were used to calculate the AUC for the prediction of poor neurological outcome at baseline. This was highest for hypoxia-induced miR-210 (AUC: 0.854), which performed significantly better than the protein biomarkers NSE (AUC: 0.646) and S-100B (AUC:0.656). Conclusions Untargeted mass spectrometry reveals distinct biological pathways and candidate biomolecules affected in patients suffering from OHCA compared with STEMI controls, in patients developing cardiogenic shock and in those with adverse versus good neurological outcome. Platelet-, inflammation and hypoxia associated miRNAs are associated with OHCA, cardiogenic shock and prognostication of adverse neurological outcome. Pronounced differences in early release kinetics of RNA and protein biomarkers may improve identification of OHCA patients at risk of poor outcome.

Gender-related differences in clinical characteristics of patients with hypertrophic cardiomyopathy in our city

Abstract Background Female patients with hypertrophic cardiomyopathy (HCM) tend to display a higher rate of heart failure as well as lower survival compared to male patients. Despite this, gender-related differences in the clinical characteristics of HCM patients remain unclear. Methods and Aim Consecutive HCM patients were prospectively enrolled at a tertiary referral center. The primary objective of this study was to investigate and emphasize gender differences in clinical characteristics including imaging and laboratory parameters. Results Between May 2018 and January 2024, a total of 301 HCM patients were included, of which 41.9% were female (n=125). Female patients were significantly older and more symptomatic than male counterparts (59 years [IQR 47-67] vs. 53 years [IQR 39-61], p=0.001; New York Heart Association functional class ³III: 28.8% vs. 17.6%, p=0.002, respectively). No significant differences in body mass index were found (28.4 kg/m² [IQR 24.9-31.6] vs. 28.4 kg/m² [IQR 25.9-31.8], p=0.8). With respect to echocardiographic parameters, although interventricular septal thickness was comparable (19.0 mm [IQR 16.0-22.0] vs. 19.5 mm [IQR 17.0-22.0], p=0.4) left atrial as well as right atrial volume index were higher in women (30.0 cm³/m² [IQR 27.0-35.0] vs. 27.0 cm³/m² [IQR 24.0-30.0], p&amp;lt;0.001; 27.1 cm³/m² [IQR 25.4-29.3] vs. 24.7 cm³/m² [IQR 22.5-28.2], p&amp;lt;0.001). These findings were further supported by elevated filling pressures in female patients reflected by E/e’ ratio (16 [IQR 14-22] vs. 10 [IQR 9-12], p&amp;lt;0.001). Moreover, these patients showed more frequent left ventricular (LV) outflow tract obstruction (50% vs. 33%, p=0.029) which is accompanied by a slightly higher LV ejection fraction compared to men (69% [IQR 62-74] vs. 62% [IQR 55-67], p=0.004). In terms of cardiac biomarkers, female HCM patients presented with higher levels of serum N-terminal pro brain natriuretic peptide (671 pg/ml [IQR 333-1613] vs. 357 pg/ml [IQR 115-959], p&amp;lt;0,001) as well as lower concentrations of serum creatinine (0.84 mg/dl [IQR 0.75-0.95] vs. 0.98 mg/dl [IQR 0.87-1.15], p&amp;lt;0.001) whereas no differences regarding high-sensitive troponin-T levels were observed. Conclusion This single-center analysis illustrates profound gender-related differences among HCM patients in Vienna. Female patients tend to present in a more advanced clinical status, rather reflecting the phenotype of heart failure with preserved ejection fraction. Whether these findings should prompt an early HCM diagnosis in female patients with unspecific symptoms, or may result in early treatment initiation of e.g. sodium-glucose-transporter 2 inhibitors, should be part of future research.

Increased circulating levels of standardized inflammatory and endothelial dysfunction biomarkers in patients with myocardial infarction with nonobstructive coronary arteries

Abstract Introduction Around 10% of patients with acute myocardial infarction (AMI) present with nonobstructive coronary arteries (MINOCA), for which the underlying pathophysiology is often uncertain. Our aim was to evaluate inflammatory burden and endothelial dysfunction in MINOCA patients by assessing biomarkers in both acute and stable phases. Methods An analytical and observational study at a University Hospital involving 166 MI patients admitted over the past 3years. Following ESC guidelines, patients were categorized into MINOCA or myocardial infarction with significant coronary artery disease (MI-CAD) groups. Circulating levels of inflammatory biomarkers (interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and high-sensitivity C-reactive protein(hs-CRP)) and of endothelial dysfunction (asymmetric dimethylarginine (ADMA)) were measured in 44 MINOCA patients and 122 MI-CAD patients at acute phase (admission and discharge) and stable phase (2months after MI). As biomarker levels may vary with MI size, each value was standardized by dividing it by the peak troponin, resulting in a biomarker/troponinT ratio. We evaluated the effects of standardized (SB) and non-standardized (NSB) biomarker values using a multivariate regression model adjusted for age and sex. Results We analyzed 166 patients (median age:68 years, 70% males). MI-CAD patients had higher peak high-sensitive troponinT (hs-TnT) levels upon admission compared to those with MINOCA (1491ng/L vs 247ng/L,p&amp;lt;0.001),likely due to larger infarctions generating higher levels of inflammation. When examining the association between infarct size, as measured by peak hs-TnT values, and biomarker levels, we observed a significant dose-response relationship for hs-CRP at admission (βcoefficient 0.16 [95%CI,0.02-0.29],p0.02) and IL-6 at admission (βcoefficient 0.15 [95%CI,0.04-0.27],p0.01). Significant positive associations were found between MINOCA and all SBs, both during the acute phase and in follow-up. During the acute phase ORs ranged from 1.35to2.7 (p&amp;lt;0.05) for inflammatory biomarkers and from 2.34 to 2.76 (p&amp;lt;0.01) for ADMA. In the stable phase ORs ranged from 1.49to3.06 (p&amp;lt;0.05) for inflammatory biomarkers, and OR was 2.79(p&amp;lt;0.01) for ADMA (Figure 1). In contrast, none of the NSBs were associated with MINOCA. Regarding temporal biomarker changes, during the acute phase of MI and 2 months post-event, both MINOCA and MI-CAD patients showed similar trends. However, MINOCA patients consistently maintained elevated inflammatory activity and ADMA concentrations only when biomarkers were standardized by infarct size (Figure 2). Conclusions Higher levels of SBs were consistently associated with MINOCA, both during the acute phase of the event and in follow-up, compared to MI-CAD. Consequently, this study suggests that the inflammatory burden, measured by heightened levels of standardized inflammatory biomarkers, and endothelial dysfunction, as measured by ADMA, may play a role in the pathophysiology of MINOCA.Boxplots for SBs at three time points.Temporal changes in biomarker levels.

Prognostic utility of heart-type fatty acid binding protein in patients with cardiac amyloidosis

Abstract Background Heart-type fatty acid binding protein (H-FABP) is a biomarker that has been shown to provide long-term prognostic information in patients with heart failure (HF), yet its role in patients with cardiac amyloidosis (CA) is unknown. Purpose We aim to investigate the association of H-FABP levels with prognosis in patients with CA. Methods Consecutive patients diagnosed with cardiac amyloidosis from October 2015 to May 2022 at Heart Failure Center, of our hospital were enrolled. Patients were categorized into 2 categories based on H-FABP levels measured in the baseline blood sample: &amp;lt; or = 7 ng/ml (low H-FABP), &amp;gt;7 ng/ml (high H-FABP). Univariate and multivariate Cox models were used to identify predictors of survival. Kaplan-Meier analysis was performed to compare survival between patients with low or high H-FABP. Results Overall, ninety-five patients were included. H-FABP was elevated (&amp;gt;7 ng/ml) in 37 patients (39%). Patients with high H-FABP were more likely to present with higher levels of high-sensitivity troponin-T (hs-TNT)(0.17ng/mL vs. 0.11ng/mL, p =0.01) and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (18098.76pg/mL vs. 6211.69pg/mL, p&amp;lt;0.001). Patients were followed for an average follow-up period of 440 days, in which 53 (56%) patients died. Univariate and multivariate analysis demonstrated that H-FABP levels (HR 1.48, 95% CI 1.03-2.13, per 1-SD greater) was independently associated with prognosis, even after adjusting for NT-proBNP, hs-TNT and renal function. Conclusions Elevation of H-FABP is associated with an increased risk of death in patients with cardiac amyloidosis. H-FABP can serve as a novel biomarker independent of other established predictors for prognosis in cardiac amyloidosis.Kaplan-Meier curves for overall survival

Intercoronary communication: a rare coronary anomaly.

Intercoronary communication also known as coronary arcade or coronary cascade is a rare coronary artery anomaly with an incidence of only 0.002% in patients undergoing angiography. This case emphasizes the importance of recognizing this rare anomaly and highlights its clinical significance. We report a case of intercoronary communication in a 56-year-old female who presented with acute chest pain and ST-segment depression in the lateral leads. High-sensitivity troponin-T was elevated and transthoracic echocardiography revealed normal left ventricular function with no regional wall motion abnormality. Hence, the diagnosis of acute coronary syndrome - non-st-elevation myocardial infarction was considered. Coronary angiography revealed a 95% focal stenosis in the major obtuse marginal artery (OM). The right coronary artery (RCA) angiogram revealed a single abnormal channel communicating the right posterolateral branch (PLV) and the distal left circumflex artery (LCX) with retrograde opacification of the proximal LCX, left main coronary artery (LMCA) and left aortic sinus. After she underwent revascularization with the drug-eluting stent to the OM. CT-coronary angiography confirmed the presence of intercoronary communication (ICC) between the right posterolateral branch and the distal LCX artery. No active intervention was done for the ICC. Over a year of follow-up, our patient remained asymptomatic. Angiographically and anatomically, collaterals and intercoronary communications should be differentiated. Obstructive coronary artery disease leads to the development of collaterals, which are typically less than 1mm in diameter, multiple and tortuous. However, ICC tends to be single and straight, usually seen without obstructive disease with unidirectional or bidirectional flow. Histologically, collaterals consist of endothelium supported by poorly organized collagen, muscle and elastic fibers. Meanwhile, ICCs resemble epicardial vessels in that they have a well-defined muscular layer. This case emphasizes the importance of recognizing this rare coronary anomaly and distinguishing it from collaterals to help in accurate diagnosis. Although they can provide an efficient blood supply to the jeopardized myocardium and can aid as a channel during coronary interventions, they can also cause myocardial ischemia by coronary steal.

A-004 Clinical and Laboratory Validation of the Atellica® vTLi Analyzer for Diagnosis of Myocardial Infarction Through High Sensitivity Cardiac Troponin I (hs-cTnI) Measurement

Abstract Background Most deaths resulting from Acute Myocardial Infarction (AMI) occur within the initial hours following the onset of clinical symptoms. Troponins serve as the preferred biomarkers and can be utilized for screening individuals presenting with chest pain, referring them towards appropriate clinical interventions based on the 0-hour/1-hour algorithm. The Atellica® vTLi Patient-side analyzer (POC), employing the methodology based Magnotech™ Technology, allows the quantification of hs-cTnI levels using a small sample volume. This capability enables the prompt evaluation and management of patients with chest pain. Use POCT troponin assays may allow for faster decision-making in this high-risk population and reduce the burden on emergency facilities. This study evaluated the analytical and clinical performance of a POCT hs-cTnI from Atellica® VTLi compared to hs-cTnT Roche Diagnostics and hs-cTnI Atellica® IM 1300. Objectives Clinical and analytical validation of the Atellica® vTLi analyzer for the measurement of hs-cTnI in patients with suspected AMI compared to the reference methodologies on the market. Methods The study is being conducted in the department of critically patient, the Cardiology program and the clinical laboratory of the Hospital Israelita Albert Einstein. In the first phase of the study, samples from 108 volunteers were analyzed for analytical comparability between hs-cTnI of the Analyzer Atellica® vTLi and hs-cTnT Cobas®. A study was then carried out of precision with samples of commercial controls with three evaluation levels, with five replicates, for 5 days in the Analyzer Atellica® vTLi. The second phase of the study was performed with samples from 51 patients who report to the emergency department with chest pain for a clinical prospective evaluation and correlation between the hs-cTnI assays of the Analyzer Atellica® vTLi, hs-cTnT Cobas® and Atellica IM 1300. Results The results show a great correlation (Pearson’s correlation greater than 0.75, p&amp;lt;0.0001) between the Atellica® vTLi, hs-cTnT Cobas® platforms in the sample group. Of the patients included in the second phase of study, the average age was 61 years, with 60% of patients having systemic arterial hypertension, 35% diabetics, 53% dyslipidemic patients and none of the patients were smokers. When assessing cardiovascular risk using the heart score, 55% of patients were at moderate or high risk. In this group there was also a strong correlation between the Atellica® vTLi platforms, hs-cTnT Cobas® serum, hs-cTnT Cobas® plasma, Atellica IM 1300 serum and Atellica IM 1300 plasma in the second phase (p&amp;lt;0.0001 in all cases. Pearson correlation), considering the reference values for laboratory stratification in the rapid chest pain protocol (time 0 h and 1 h) and the biochemical differences of troponin I and troponin T molecules. Conclusions In the present study, the Siemens POCT Atellica® vTLi device showed excellent performance in laboratory validation and strong correlation with the high-sensitivity TnT assay in different troponin concentration ranges. Additionally, Atellica® vTLi demonstrated a strong clinical correlation between hs-cTnI Atellica® IM 1300 and hs-cTnT Cobas® platforms present in a central laboratory, being considered safe for use in 0-1h protocols in patients with chest pain and suspected heart attack.

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. ClinicalTrials.gov Identifier: NCT01000701.

Machine Learning to Predict Disease Severity and Progression in Hospitalized COVID-19 Patients Using Laboratory Data on Admission

Background: Herein, we aimed to develop and test machine learning (ML) models to predict disease severity and/or progression in hospitalized COVID-19 patients through baseline laboratory features. Methods: In this retrospective study of hospitalized COVID-19 patients admitted to a tertiary care center, we evaluated routine admission data to determine the accuracy rates of different ML algorithms: k-nearest neighbor classifier, bagging classifier, random forest (RF), and decision tree. These models were compared over three outcomes: those who needed oxygen supplementation vs. who did not on admission (Analysis 1, n: 180), those who later developed oxygen requirement vs. those who did not (Analysis 2, n: 112), and those who needed invasive mechanical ventilation vs. those who did not during hospitalization (Analysis 3, n: 164). Results: The median age of the patients was 55 (44-68) years, with males constituting 47.2% of the subjects. At admission, 37.8% of the patients required oxygen supplementation. During hospitalization, 17.5% needed mechanical ventilation, and 8.3% died. For all analyses, RF had the highest accuracy in classifying the need for oxygen supplementation on admission (89.4%) or during hospitalization (91.1%) and for invasive mechanical ventilation (92.2%). These were followed by a bagging classifier for Analysis 1 (88.3%) and Analysis 3 (91.0%) and by a decision tree for Analysis 2 (88.4%). C-reactive protein, monocyte distribution width, and high-sensitive troponin-T were the most crucial laboratory contributors to Analysis 1, Analysis 2, and Analysis 3, respectively. Conclusion: Our study showed that ML algorithms could predict the need for oxygen supplementation and mechanical ventilation during hospitalization using baseline laboratory data, suggesting a slight superiority of RF, among others.

Mean arterial pressure versus cardiac index for haemodynamic management and myocardial injury after hepatopancreatic surgery: A randomised controlled trial.

Myocardial injury after noncardiac surgery (MINS) frequently complicates the peri-operative period and is associated with increased mortality. We hypothesised that cardiac index (CI) based haemodynamic management reduces peri-operative high-sensitive troponin-T (hsTnT) elevation and MINS incidence in patients undergoing hepatic/pancreatic surgery compared to mean arterial pressure. A randomised controlled study. A single-centre study conducted in a university-affiliated tertiary hospital between June 2022 and March 2023. Ninety-one patients, who were ≥ 65 years old or ≥ 45 years old with a history of at least one cardiac risk factor were randomised to either mean arterial pressure (MAP) based (n = 45) or CI-based (n = 46) management groups, and completed the study. In group-MAP, patients received fluid boluses and/or a noradrenaline infusion to maintain MAP above the predefined threshold. In group-CI, patients received fluid boluses and/or dobutamine infusion to keep CI above the predefined threshold. When a low MAP was observed despite a normal CI, a noradrenaline infusion was started. The primary outcome was peri-operative hsTnT elevation. The secondary outcomes were MINS incidence and 90-day mortality. The median absolute troponin elevation was 4.3 ng l-1 (95% CI 3.4 to 6) for the CI-based group, and 9.4 ng l-1 (95% CI 7.7 to 12.7) for the MAP-based group (median difference: 5.1 ng l-1, 95% CI 3 to 7; P < 0.001). MINS occurred in 8 (17.4%) patients in the CI-based group and 17 (37.8%) patients in the MAP-based group (relative risk: 0.46, 95% CI: 0.22 to 0.96; P = 0.029). Two patients in group-MAP died from cardiovascular-related causes. One patient in group-CI and two in group-MAP died from sepsis-related complications (for all-cause mortality: χ2 = 1.98, P = 0.16). MAP-AUC and CI-AUC values of the CI- and MAP-based groups were 147 vs. 179 min × mmHg (P = 0.85) and 8.4 vs. 43.2 l m-2 min-1 × min (P < 0.001), respectively. CI-based haemodynamic management assures sufficient flow and consequently is associated with peri-operative hsTnT elevation and the incidence of MINS compared to MAP. Clinicaltrials.gov identifier: NCT05391087.

Trimethylamine-N-oxide and 5-year mortality: the role of gut microbiota-generated metabolite from the CORE-Thailand cohort

The gut microbiota metabolite trimethylamine-N-oxide (TMAO)—derived from dietary phosphatidylcholine—is mechanistically linked to cardiovascular disease (CVD) and increased cardiovascular risk. This study examined the relationship between fasting plasma TMAO levels and 5-year all-cause mortality in a cohort of patients at high risk of cardiovascular events (CORE-Thailand Registry). Of the 134 patients, 123 (92%) had established cardiovascular disease, and 11 (8%) had multiple risk factors. Fasting plasma TMAO levels were measured using nuclear magnetic resonance spectroscopy. Within this prospective cohort study, the median TMAO was 3.81 μM [interquartile range (IQR) 2.89–5.50 μM], with a mean age of 65 ± 11 years; 61% were men, and 39.6% had type II diabetes. Among 134 patients, 65 (49%) were identified as the high-TMAO group (≥ 3.8 μM), and 69 (51%) were identified as the low-TMAO group (< 3.8 μM). After a median follow-up of 58.8 months, the high-TMAO group was associated with a 2.88-fold increased mortality risk. Following adjustment for traditional risk factors, high-sensitivity cardiac troponin-T, estimated glomerular filtration rate, angiotensin-converting enzyme (ACEI), or angiotensin-receptor blocker (ARB) use, the high-TMAO group remained predictive of 5-year all-cause mortality risk (the high-TMAO vs. the low-TMAO group, adjusted hazard ratio 2.73, 95% CI 1.13–6.54; P = 0.025). Among Thai patients at high risk of cardiovascular events, increased plasma TMAO levels portended greater long-term mortality risk.

Monitoring of myocardial injury by serial measurements of QRS area and T area: The MaastrICCht cohort.

Manually derived electrocardiographic (ECG) parameters were not associated with mortality in mechanically ventilated COVID-19 patients in earlier studies, while increased high-sensitivity cardiac troponin-T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were. To provide evidence for vectorcardiography (VCG) measures as potential cardiac monitoring tool, we investigated VCG trajectories during critical illness. All mechanically ventilated COVID-19 patients were included in the Maastricht Intensive Care Covid Cohort between March 2020 and October 2021. Serum hs-cTnT and NT-proBNP concentrations were measured daily. Conversion of daily 12-lead ECGs to VCGs by a MATLAB-based script provided QRS area, T area, maximal QRS amplitude, and QRS duration. Linear mixed-effect models investigated trajectories in serum and VCG markers over time between non-survivors and survivors, adjusted for confounders. In 322 patients, 5461 hs-cTnT, 5435 NT-proBNP concentrations and 3280 ECGs and VCGs were analyzed. Non-survivors had higher hs-cTnT concentrations at intubation and both hs-cTnT and NT-proBNP significantly increased compared with survivors. In non-survivors, the following VCG parameters decreased more when compared to survivors: QRS area (-0.27 (95% CI) (-0.37 to -0.16, p < .01) μVs per day), T area (-0.39 (-0.62 to -0.16, p < .01) μVs per day), and maximal QRS amplitude (-0.01 (-0.01 to -0.01, p < .01) mV per day). QRS duration did not differ. VCG-derived QRS area and T area decreased in non-survivors compared with survivors, suggesting that an increase in myocardial damage and tissue loss play a role in the course of critical illness and may drive mortality. These VCG markers may be used to monitor critically ill patients.

Systemic and cerebro-cardiac biomarkers following traumatic brain injury: an interim analysis of randomized controlled clinical trial of early administration of beta blockers

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal.

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study

PurposeThe aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. Materials and MethodsBlood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. ResultsHS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. ConclusionSignificant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints.

External Validation of the Recalibrated HEART Score for Evaluation of Possible Acute Coronary Syndrome

A single high-sensitivity troponin-T (hs-TnT) measurement may be sufficient to risk-stratify emergency department (ED) patients with possible acute coronary syndrome (ACS) using the recalibrated History, Electrocardiogram, Age, Risk Factors, Troponin (rHEART) score. We sought to validate this approach in a multiethnic population of United States patients and investigate gender-specific differences in performance. We conducted a secondary analysis of a prospective cohort study of adult ED patients with possible ACS at a single, urban, academic hospital. We investigated the diagnostic performance of rHEART for the incidence of type-1 acute myocardial infarction (AMI) and other major adverse cardiac events (MACE) at 30 days, using both single (19 ng/L) and gender-specific (14 ng/L for women, 22 ng/L for men) 99th percentile hs-TnT thresholds. The 821 patients included were 54% women, 57% Hispanic, and 26% Black. Overall, 4.6% of patients had MACE, including 2.4% with AMI. Single-threshold rHEART ≤3 had a sensitivity of 94.4% (95% confidence interval 81% to 99%) and negative predictive values of 99.3% (98% to 100%) for MACE; gender-specific thresholds performed nearly identically. Sensitivity and negative predictive values for AMI were 90.0% (67% to 98%) and 99.3% (97% to 100%). Excluding patients presenting <3 hours from symptom onset improved sensitivity for MACE and AMI to 97.0% (84% to 100%) and 94.1% (71% to 100%). Logistic regression demonstrated odds of MACE increased with higher rHEART scores at a similar rate for men and women. In conclusion, a single initial hs-TnT and rHEART score can be used to risk-stratify male and female ED patients with possible ACS, especially when drawn >3 hours after symptom onset.

D-dimer/high sensitive troponin I ratio is useful in predicting in-hospital mortality in pulmonary embolism patients.

Pulmonary embolism requires careful differential diagnosis as it is associated with a wide range of symptoms that may suggest different diseases such as chest pain, shortness of breath and syncope. Since the disease can be fatal, especially in cases where right ventricular failure and hemodynamic instability develop, prognostic markers are great importance in terms of monitoring the patient during the treatment process. We aimed in our study to compare the relationship between the ratio of D-dimer and High Sensitive Troponin T (HsTnT) values ​​with short-term mortality and to compare this relationship with Pulmonary Embolism Severity Index (PESI) scoring. Our study was conducted with patients who applied to the emergency department of our hospital between 01/01/2022 and 01/01/2023 and were definitively diagnosed withPulmonary thromboembolismafter their evaluation. The success of D-dimer/HsTroponin, D-dimer/CK-MB and troponin/D-dimer indices calculated from the laboratory test results of the cases in predicting mortality was examined, and a comparison was made with the success of the PESI score in predicting mortality. Among these indices, D-dimer/CK-MB was found to be the most successful index in predicting 7-day mortality (AUC: 0.734; 95% CI: 0.653-0.815; p < 0.001). Additionally, the D-dimer/HsTroponin ratio was found to be statistically significant as a successful index in predicting 7-day mortality (AUC: 0.697; 95% CI: 0.621-0.774; p < 0.001). FD-dimer/HsTroponin ratio, which is a powerful, fast, low-cost, easy and simple test, can be used especially in emergency services instead of the PESI score as a mortality marker in pulmonary embolism, which has a high mortality rate.

Clinical impact and predictors of periprocedural myocardial injury among patients undergoing left bundle branch area pacing.

The clinical impact of Periprocedural myocardial injury (PMI) in patients undergoing permanent pacemaker implantation with Left Bundle Branch Area Pacing (LBBAP) is unknown. 130 patients undergoing LBBAP from January 2020 to June 2021 and completing 12months follow up were enrolled to assess the impact of PMI on composite clinical outcome (CCO) defined as any of the following: all-cause death, hospitalization for heart failure (HHF), hospitalization for acute coronary syndrome (ACS) and ventricular arrhythmias (VAs). High sensitivity Troponin T (HsTnT) was measured up to 24-h after intervention to identify the peak HsTnT values. PMI was defined as increased peak HsTnT values at least > 99th percentile of the upper reference limit (URL: 15pg/ml) in patients with normal baseline values. PMI occurred in 72 of 130 patients (55%). ROC analysis yielded a post-procedural peak HsTnT cutoff of fourfold the URL for predicting the CCO (AUC: 0.692; p = 0.023; sensitivity 73% and specificity 71%). Of the enrolled patients, 20% (n = 26) had peak HsTnT > fourfold the URL. Patients with peak HsTnT > fourfold the URL exhibited a higher incidence of the CCO than patients with peak HsTnT ≤ fourfold the URL (31% vs. 10%; p = 0.005), driven by more frequent hospitalizations for ACS (15% vs. 3%; p = 0.010). Multiple (> 2) lead repositions attempts, the use of septography and stylet-driven leads were independent predictors of higher risk of PMI with peak HsTnT > fourfold the URL. PMI seems common among patients undergoing LBBAP and may be associated with an increased risk of clinical outcomes in case of more pronounced (peak HsTnT > fourfold the URL) myocardial damage occurring during the procedure.

Application of magnetocardiography for myocarditis assessment in a testosterone-substituted female-to-male individual

BackgroundThe diagnosis of myocarditis remains challenging due to its diverse clinical manifestations. We recently demonstrated the ability of magnetocardiography (MCG) to screen for myocarditis and applied it successfully to detect myocarditis in this case study of a female-to-male (FtM) patient who had undergone sexual reassignment surgery. This case highlights two significant points: first, sex differences in myocarditis may be promoted by higher levels of testosterone, and second, the ability of MCG to diagnose myocarditis. Case presentationWe report on a 38-year-old FtM patient who was hospitalized for chest pain following testosterone therapy. The patient received testosterone every 2 weeks for 6 months following his FtM surgery. Two days after the last administration of testosterone, he developed chest pain. Electrocardiography identified non-significant ST elevations in V3–6, II and aVF and echocardiography revealed reduced left ventricular ejection fraction and apical hypokinesia. High-sensitivity troponin-T (539 ng/L to 676 ng/L) and creatine kinase elevation (592 U/L) were elevated. Coronary CT angiography ruled out coronary artery disease. Cardiac magnetic resonance imaging confirmed suspected myocarditis.Additionally, we used MCG to detect abnormalities in the electromagnetic field. A pathologic vector (0.179) supported the diagnosis of myocarditis in this patient. During therapy with ibuprofen the vector improved to 0.067 after 3 weeks accompanied by symptom improvement. ConclusionTestosterone treatment may have promoted myocarditis in a FtM individual. Additional MCG assessment was consistent with a diagnosis of myocarditis and highlights the promising potential of this method to facilitate diagnostic screening for cardiomyopathy in the future.