Search Results (43)

High-sensitivity cardiac troponin assays are susceptible to analytical interferences, including macrotroponin, an immunoglobulin-bound complex that may cause persistent, non-dynamic, and assay-dependent elevations. This paper describes the case of a 74-year-old woman with hypertension who presented with intermittent mild chest discomfort and exertional dyspnea and exhibited persistently elevated but stable cardiac troponin I concentrations over several months, in the absence of clinical, electrocardiographic, or imaging evidence of myocardial injury. Orthogonal testing revealed discordant results across different assay platforms, and polyethylene-glycol (PEG) precipitation resulted in a substantial signal reduction, confirming macrotroponin as the source of assay-dependent analytical interference. Recognizing this phenomenon is crucial to avoid misdiagnosis, unnecessary diagnostic procedures and inappropriate management in patients with isolated troponin elevation. In conclusion, this report provides evidence-based recommendations on the optimal diagnostic strategies and laboratory approaches to adopt in cases of suspected macrotroponin-mediated interference in high-sensitivity cardiac troponin assays. Full article

Background: Coronary computed tomography angiography (CCTA) is a non-invasive imaging tool used predominantly in suspected chronic coronary artery disease (CAD) patients, due to its high negative predictive value. However, increasing focus has been placed on CCTA to manage and risk stratify acute chest pain patients in emergency departments (ED). Objective: This scoping review summarizes the available evidence on the role of CCTA to exclude acute coronary syndrome (ACS) in low-risk acute chest pain patients, focusing on its diagnostic accuracy, safety, and application in the context of high sensitivity cardiac troponin assays (hs-cTn). Methods: Articles published between January 2015 and March 2025 investigating CCTA use in low-risk acute chest pain patients were retrieved from Medline, Embase, Emcare, and Web of Science databases. Results: 22 articles (13,617 patients) were retrieved. CCTA had strong diagnostic performance, with an excellent negative predictive value (99.8–100%) and sensitivity (94–100%) for ACS diagnosis and prediction of major adverse cardiovascular events. Specificity and positive predictive values were lower and less consistent. When combined with hs-cTn, the diagnostic accuracy of CCTA for ACS was improved significantly. CCTA was associated with low rates of ACS at follow-up (0–3.5%), which were lower than or comparable to the safety outcomes of standard care and stress testing. Full article

Acute Myocardial Infarction (AMI) is a critical cardiac condition that poses a substantial threat to myocardial function. Expedient diagnosis of AMI is paramount and relies on serological assays for rapid and accurate quantification of relevant biomarkers. Electrochemical sensors have emerged as promising candidates for this application, owing to their accessibility, operational simplicity, and high specificity. In this study, we developed a paper-based electrochemical immunosensor to detect cardiac troponin I in serum and saliva specimens. The electrode was fabricated using screen-printing technology with photographic paper as the substrate, employing graphite-based ink, nail polish, and acetone as the solvent. A quasi-reference electrode was constructed using silver powder-based ink, nail polish, and acetone. The immunosensor was prepared by modifying the working electrode with gold nanoparticles (AuNP) functionalized with cardiac troponin I antibodies (anti-cTnI) and bovine serum albumin (BSA). This modified electrode was subsequently used to detect the troponin I antigen. The analyses were performed in 0.1 mol L⁻¹ phosphate buffer medium, pH 7.00, in the presence of 5.0 mmol L⁻¹ of the potassium ferrocyanide probe. The immunosensor exhibited a sensitivity of 0.006 µA/fg mL⁻¹, a limit of detection of 9.83 fg mL⁻¹, and a limit of quantification of 32.79 fg mL⁻¹. Specificity studies conducted in the presence of other macromolecules demonstrated minimal interference, with relative standard deviations (RSD) below 5.00%, indicating a specific interaction with troponin I. Furthermore, the immunosensor demonstrated excellent reproducibility and stability. Upon application to serum and saliva samples, the immunosensor presented recoveries of approximately 99–105%, suggesting its potential applicability in clinical analyses. Full article

Background: The 99th-percentile upper reference limit (99% URL) is essential for high-sensitivity cardiac troponin I (hs-cTnI) assays to diagnose acute coronary syndromes. We derived the gender-specific 99% URLs for the new Snibe hs-cTnI assay and verified its high-sensitivity performance. Methods: The Snibe hs-cTnI assay has a claimed limit of blank/detection/quantitation of 0.5/1.0/2.0 ng/L, a precision of 5.67% (@ 9.83 ng/L), 4.65% (@ 21.0 ng/L) and 3.77% (@ 174 ng/L), an analytical measuring range of 1.00–500,000 ng/L, and a claimed 99% URL of 20.1/11.8/17.5 ng/L (males/females/overall). Assay precision was evaluated using kit control materials. A total of 846 (M 444, F 402) anonymized leftover samples from healthy individuals were assessed for the derivation of 99% URLs. Results: The inter-assay CV was 6.2/4.4% (@ 10.1/20.6 ng/L). The 10/20% CV corresponded to a concentration of 5.2/3.0 ng/L. The assay recorded detectable hs-cTnI values in 64% of women and 70% of men. Hs-cTnI values were significantly lower in females than males (females vs. males median 2.6 vs. 3.2 ng/L, Mann–Whitney p = 0.005). The derived 99% URL for the population was 7.7 ng/L (90% CI 6.93–22.8 ng/L) for women and 13.7 ng/L (90% CI 10.6–41.4 ng/L) for men. When confined to subjects ≥40 years old only, males had a 99% URL of 14.8 ng/L (n = 412, 90% CI 10.6–41.4 ng/L) and 8.1 ng/L (n = 377, 90% CI 6.95–22.8 ng/L) for females, respectively. Conclusions: The Snibe hs-cTnI assay fulfills the requirements of a hs-cTn assay. Gender-specific 99% URLs are derived for this assay and they increased with age. Full article

As the leading cause of global mortality, cardiovascular diseases demand improved and innovative strategies for early detection and risk assessment to enhance prevention and timely treatment. This comprehensive review examines the potential of combining high-sensitivity cardiac troponins (hs-cTns) and homocysteine (Hcy) as complementary biomarkers for enhanced cardiovascular risk prediction. hs-cTn assays have revolutionized cardiovascular diagnostics by enabling the detection of minimal myocardial injury, improving early diagnosis of acute coronary syndrome, and providing robust prognostic information in both symptomatic and asymptomatic populations. Hcy, while established as a marker of vascular dysfunction, presents an interpretative challenge due to multiple confounding factors and inconsistent therapeutic responses. Emerging evidence demonstrates significant correlations between elevated Hcy and troponins across various clinical conditions, suggesting that their combined assessment—reflecting both myocardial injury and vascular dysfunction—may improve cardiovascular risk stratification. While initial findings are promising, additional studies are required to validate the clinical value of the combined marker approach. Future development of personalized interpretation algorithms, and multi-marker panels incorporating these biomarkers, may significantly advance cardiovascular medicine and enable more effective population-specific risk management strategies. Full article

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, underscoring the need for improved diagnostic, prognostic, and therapeutic strategies. Circulating microRNAs (c-miRNAs) have emerged as promising non-invasive biomarkers due to their stability, tissue specificity, and regulatory roles in cardiac pathophysiology. This review highlights the potential of c-miRNAs in enhancing HF diagnosis, risk stratification, and therapeutic monitoring, particularly when integrated with conventional biomarkers such as natriuretic peptides, galectin-3, soluble ST2, and high-sensitivity troponins. We explore the roles of key miRNAs in HF pathogenesis—including cardiac hypertrophy, fibrosis, inflammation, apoptosis, and vascular remodeling—and discuss their diagnostic and prognostic significance. The potential of multi-analyte liquid biopsy approaches that combine c-miRNAs with protein biomarkers is also examined within the context of precision medicine. Despite promising data, challenges related to standardization, assay variability, and clinical validation remain. Addressing these gaps through harmonized protocols and large-scale studies will be essential for translating c-miRNAs into routine HF management. Full article

Background: Atrial fibrillation (AF) is common complication of heart failure with preserved ejection fraction (HFpEF) that sufficiently intervenes in the prognosis. The aim of the study is a) to investigate the possible discriminative value of adropin for newly onset AF in patients with HFpEF without a previous history of AF and who are being treated in accordance with conventional guideline and b) to compare it with predictive potencies of conventionally used predictors. Methods: A total of 953 patients with HFpEF who had sinus rhythm on ECG were enrolled in the study. The course of the observation was 3 years. Echocardiography and assessment of conventional hematological, biochemical parameters and biomarker assay including N-terminal brain natriuretic pro-peptide (NT-proBNP), high-sensitivity cardiac troponin T, tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), galectin-3, interleukin-6, soluble suppressor tumorigenisity-2 (sST2) and adropin, were performed at baseline. Results: Incident atrial fibrillation was found in 172 patients with HFpEF, whereas 781 had sinus rhythm. In unadjusted rough Cox regression model, age ≥ 75 years, type 2 diabetes mellitus, chronic kidney disease (CKD) stages 1–3, left atrial volume index (LAVI) ≥ 40 mL/m², NT-proBNP ≥ 1440 pmol/mL, hs-CRP ≥ 5.40 mg/L, adropin ≤ 2.95 ng/mL, sST2 ≥ 15.5 ng/mL were identified as the predictors for new onset AF in HFpEF patients. After adjusting for age ≥ 75 years, a presence of type 2 diabetes mellitus and CKD stages 1–3, the levels of NT-proBNP ≥ 1440 pmol/mL and adropin ≤ 2.95 ng/mL were independent predictors of new onset AF in patients HFpEF. We also found that discriminative value of adropin was superior to NT-proBNP, while adding adropin to NT-proBNP did not improve predictive information of adropin alone. Conclusions: adropin ≤ 2.95 ng/mL presented more predictive information than NT-proBNP ≥ 1440 pmol/mL alone for new cases of AF in symptomatic patients with HFpEF, whereas the combination of both biomarkers did not improve the predictive ability of adropin alone. Full article

Background: We investigated the role of a high-sensitive cardiac troponin T (hsTnT) increase below the upper limit of normal (ULN) in patients with breast cancer (BC). hsTnT assays accurately quantify very low plasma troponin concentrations and enable the early detection of cardiomyocyte injury before a drop in the left ventricular ejection fraction (LVEF). The increase in hsTnT below the ULN in response to chemotherapy has not previously been studied. Method: This was an open-label pilot study. Female patients with newly diagnosed BC scheduled to receive systemic cancer treatment were recruited. Blood sampling and echocardiography were performed at baseline, at 3 and 6 months of cancer treatment. hsTnT concentrations were measured using the Elecsys TnT hs assay (Roche Diagnostics). The limit of blank and 99th percentile cutoff values for the hsTnT assay were 3 and 14 ng/L. We calculated the rise in hsTnT (ΔhsTnT) by the difference (%) between its baseline level and during follow-up (FU) in each patient. Results: Among eligible subjects, we excluded 4 patients before the start of treatment and 17 patients during the follow-up with values for the hsTnT >14 ng/L. Finally, 60 women with a median age of 48.6 ± 1.3 years were included in the study. The median baseline hsTnT concentration was 5.5 ± 1.4 ng/L. During 6 months of cancer treatment, hsTnT increased in all patients by up to 10–305% from baseline, with an average of 94.2%. LV EF was normal at baseline and decreased significantly compared to the value before cancer treatment (61.9 ± 3.3% vs. 56.3 ± 7.0%; p < 0.045). We correlated the hsTnT rise with a drop in LV EF ≥ 10% from its baseline level. Logistic regression analysis showed that Δ hsTnT has a good predictive value for LV dysfunction, 0.78 (p = 0.05), 95% CI (0.67–0.90). The increase in hsTnT > 81% was determined as the optimal threshold value for detecting early biochemical cardiotoxicity. Conclusion: It was investigated that hsTnT rise within the cutoff < 14 ng/L can be used as a marker of early biochemical cardiotoxicity and is valuable for predicting LV drop in 6 months of FU. We conclude that BC patients with increased hsTnT plasma concentration > 81% from the baseline value should be considered as high-risk patients for cardiotoxicity and need more precise cardiac monitoring and early preventive medical intervention strategies. Full article

Background: In the emergency setting, many diagnostic pathways incorporate change in high-sensitivity cardiac troponin (hs-cTn) concentrations (i.e., the delta) to classify patients as low-risk (rule-out) or high-risk (rule-in) for possible myocardial infarction (MI). However, the impact of analytical variation on the delta for correct classification is unknown, especially at concentrations below and around the 99th percentile. Our objective was to assess the impact of delta variation for correct risk classification across the European Society of Cardiology (ESC 0/1 h and 0/2 h), the High-STEACS, and the common change criteria (3C) pathways. Methods: A yearlong accuracy study for hs-cTnT was performed where laboratories across Canada tested three patient-based samples (level 1 target value = 6 ng/L, level 2 target value = 9 ng/L, level 3 target value = 12 ng/L) monthly across 41 different analyzers. The assigned low-delta between levels 1 and 2 was 3 ng/L (i.e., 9 − 6 = 3 ng/L) and the assigned high-delta between levels 1 and 3 was 6 ng/L (i.e., 12 − 6 = 6 ng/L). The low- and high-deltas for each analyzer were determined monthly from the measured values, with the difference calculated from the assigned deltas. The obtained deltas were then assessed via the different pathways on correct classification (i.e., percent correct with 95% confidence intervals, CI) and using non-parametric analyses. Results: The median (interquartile range) difference between the measured versus assigned low-delta (n = 436) and high-delta (n = 439) was −1 ng/L (−1 to 0). The correct classification differed among the pathways. The ESC 0/1 h pathway yielded the lowest percentage of correct classification at 35.3% (95% CI: 30.8 to 40.0) for the low-delta and 90.0% (95% CI: 86.8 to 92.6) for the high-delta. The 3C and ESC 0/2 h pathways yielded higher and equivalent estimates on correct classification: 95.2% (95% CI: 92.7 to 97.0) for the low-delta and 98.2% (95% CI: 96.4 to 99.2) for the high-delta. The High-STEACS pathway yielded 99.5% (95% CI: 98.4 to 99.9) of correct classifications for the high-delta but only 36.2% (95% CI: 31.7 to 40.9) for the low-delta. Conclusions: Analytical variation will impact risk classification for MI when using hs-cTn deltas alone per the pathways. The 3C and ESC 0/2 h pathways have <5% misclassification when using deltas for hs-cTnT in this dataset. Additional studies with different hs-cTnI assays at concentrations below and near the 99th percentile are warranted to confirm these findings. Full article

Current routine high-sensitivity cardiac troponin assays are the criterion standard for the laboratory diagnosis of myocardial injury due to their high analytical sensitivity and specificity. However, in daily clinical practice, unexpectedly elevated cardiac troponin test results without an obvious clinical correlate are becoming more frequent compared with previous cardiac troponin assay generations. In these patients, myocardial injury may sometimes be undetected by imaging techniques, including cardiac magnetic resonance imaging. This has led to an increased interest in the pathophysiology of cardiac troponin release, particularly with regard to whether troponin can be released in the absence of myocardial necrosis and thereby resulting in an increase in cardiac troponin in the systemic circulation. Although there is in vitro evidence that cardiac biomarkers are released from reversibly injured cultured cardiomyocytes, there is still a lack of evidence for cardiac troponin release apart from different forms of cell death (i.e., apoptosis or necrosis) in animal experiments. Conversely, various circulating cardiac troponin forms have been identified in human blood samples using different analytical methods, raising the question of whether the cause of myocardial injury can be reliably determined by measuring specific circulating cardiac troponin forms. Preliminary clinical data suggests that testing for specific circulating troponin forms could increase the specificity of cardiac troponin for diagnosing acute myocardial infarctions caused by an acute coronary syndrome. This review aims to provide an up-to-date overview of these current cardiac troponin research topics with their potential clinical implications. Typical clinical cases illustrate how to interpret cTn in the individual patient and how to derive a correct diagnosis. Full article

Background/Objective: The measurement of troponin is recommended for acute myocardial infarction (AMI) diagnosis. Yet, hs-cardiac troponin T (hs-cTnT) can be elevated due to non-cardiac conditions, such as skeletal muscle injury, chronic kidney disease (CKD) or pulmonary embolism. The aim of our study was to compare the diagnostic accuracy of a bedside rapid hs-cardiac troponin I (hs-cTnI) assay (Quidel TriageTrue^®) with hs-cTnT measured in a routine laboratory (Roche Elecsys). Methods: This prospective monocentric study was conducted in an acute cardiac outpatient unit at a tertiary hospital. Hs-cTnI was measured via a point-of-care test from whole blood, while hs-cTnT was measured from plasma through the routine laboratory facility. Results: In 129 patients (65.1% male, 61.8 ± 15.6 years) with acute chest pain, results for hs-cTnI were available 14 ± 11 min after the first clinical presentation, which was 74 ± 54 min earlier than for hs-cTnT. Coronary angiography confirmed AMI in 17 patients (13.28%). The relative risk of AMI patients with elevated hs-cTnI results was 6.59 compared to 2.29 for hs-cTnT. Hs-cTnI exhibited an equivalent negative predictive value to hs-cTnT (99%) for AMI but had a comparatively higher positive predictive value (50.0 vs. 25.8%). In 39 patients with at least CKD stage 3a, median hs-cTnT was pathological (27.0 ng/L), in contrast with hs-cTnI (11.2 ng/L). Further, hs-cTnI was less likely elevated in patients with CKD and no AMI. Conclusions: The diagnostic value of hs-cTnI was comparable to that of hs-cTnT, and the blood sampling-to-result time was shorter than routine hs-cTnT. Full article

(1) Background: Prompt acute coronary syndrome (ACS) recognition remains challenging. This study evaluated the diagnostic and prognostic performance of novel biomarkers for non-ST-elevation myocardial infarction (NSTEMI). (2) Methods: Patients with suspected ACS presenting to Heidelberg University Hospital’s Emergency Department between August 2014 and February 2023 were analyzed. The biomarker panel included high-sensitivity cardiac troponin T (hs-cTnT), cardiac myosin-binding protein C (cMyBP-C), pro-B-type natriuretic peptide (proBNP), total N-terminal pro-B-type natriuretic peptide (t-NtproBNP), Angiotensin II (Ang2), Bone morphogenetic protein 10 (BMP10), Endothelial cell-specific molecule 1 (ESM1), fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor 15 (GDF15), and Copeptin. Negative predictive values (NPVs), sensitivities, and area under the curve (AUC) values were calculated for NSTEMI discrimination. Effectiveness and prognostic performance were assessed based on cardiovascular events at 30 days and 1 year. (3) Results: Of 1765 patients, 212 (12%) were diagnosed with NSTEMI. The European Society of Cardiology (ESC) 0/1 h and 0/3 h algorithms achieved sensitivities of 100% and 96.8%, NPVs of 100% and 99.3%, and effectiveness values of 54.8% and 66.0%. Hs-cTnT (AUC: 0.922) and cMyBP-C (AUC: 0.917) exhibited the highest diagnostic accuracy, followed by FABP3 (AUC: 0.759) and Copeptin (AUC: 0.624). Other biomarkers had lower performance (AUC: 0.516–0.617). At 1 year, event rates ranged from 0.0% to 3.4%, with the ESC algorithms demonstrating superior prognostic performance (0.8%, 2.4%). (4) Conclusions: The ESC 0/1 h and 0/3 h algorithms remain the most effective NSTEMI diagnostic strategies, balancing high sensitivity, prognostic reliability, and effectiveness. Among novel biomarkers, only cMyBP-C demonstrated comparable accuracy to hs-cTnT, supporting its potential as an adjunct to troponin assays. Full article

Background: International guidelines recommend the use of high-sensitivity cardiac troponin (hs-cTn) I and T methods for the detection of myocardial injury as a pre-requisite for the diagnosis of acute myocardial infarction (AMI) in patients admitted to the emergency department. Recently, Mindray (Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China) has introduced a new chemiluminescence immunoassay (CLIA) for the detection of the cTn complex. The present study aims to verify and validate the hs-cTnI Mindray assay on the new automated CL2600i analyzer compared to the routine Alinity-i series instrument by Abbott (Abbott, Chicago, IL, USA). Methods: This study evaluated linearity, precision through the 5 × 5 protocol, methodological comparison on plasma and serum matrices, hs-cTnI 99th percentile imprecision, and the hs-cTnI detection rate in a healthy population. Results: The results obtained proved that the performance of the Mindray hs-cTnI test on the CL2600i platform was closely comparable to the Abbott Alinity-i system (plasma R²: 0.974; serum R²: 0.995). The CVs were consistently low, and no significant differences were reported. Excellent analytical performance, with high sensitivity, was also observed in the healthy population (overall detection rate: 79%), as well as good linearity within the measuring range (R²: 0.994). Conclusions: The Mindray hs-cTnI test confirms its robustness and utility in routine practice as an advanced assay. The new technology, with more sensitive detection methods, may improve the accuracy and reliability of cardiac biomarker testing, ultimately leading to better outcomes in the management of patients with AMI and other cardiac conditions. Full article

The management of acute heart failure (AHF) is becoming increasingly complex, especially in patients with multiple comorbidities. Endothelin-1 (ET-1), a vasoconstrictive peptide, is an important mediator of neurohormonal activation, endothelial dysfunction, and cardiac remodeling—key processes involved in the pathogenesis of AHF. The aim of our study was to evaluate the diagnostic and prognostic performance of ET-1 in multimorbid AHF patients, compared to established markers such as amino terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI). We conducted a single-center prospective study including 76 patients; 54 with AHF and 22 serving as controls. Upon admission, all patients underwent a comprehensive clinical, echocardiographic, and laboratory evaluation, including plasma ET-1 measurement using the enzyme-linked immunosorbent assay (ELISA) method. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis were performed to assess the diagnostic and prognostic performance of ET-1 in comparison to NT-proBNP and hs-cTnI. ET-1 levels were considerably higher in AHF patients than in controls (p = 0.02), with an AUC of 0.954, showing comparable diagnostic accuracy with NT-proBNP (AUC = 0.997), alongside strong correlations with signs of systemic congestion, increased hospital stay, and ventricular dysfunction. ET-1 had the strongest predictive accuracy for in-hospital mortality (AUC = 0.781, p = 0.026), outperforming NT-proBNP and hs-cTnI. For 30-day mortality, ET-1 remained a reliable predictor (AUC = 0.784, p = 0.016). However, as the follow-up period extended to one year, its predictive power declined, confirming ET-1’s prognostic efficacy only for short-term outcomes. Moreover, ET-1 levels were not influenced by the presence of comorbidities, demonstrating its potential as an independent biomarker. Our findings support that ET-1 is a valuable biomarker for both diagnosis and short-term prognosis in the assessment of multimorbid AHF patients. Full article

Background/Objectives: Patients with atrial fibrillation (AF) often have symptoms and risk factors similar to those of patients with coronary artery disease (CAD). However, the clinical criteria for identifying AF patients who would benefit from coronary angiography (CA) remain vague. We evaluated the predictive value of cardiac troponin I (cTnI), high-sensitivity cardiac troponin T (hs-cTnT), and various clinical parameters for detecting significant coronary artery stenosis. Methods: We retrospectively analyzed symptomatic AF patients admitted to the University Hospital Bonn emergency department between 2015 and 2019 undergoing CA. Out of 183 AF patients, 93 were screened with cTnI and 90 with hs-cTnT. Results: A total of 47 out of 183 (26%) AF patients were diagnosed with significant coronary artery stenosis. The sensitivity for detecting CAD requiring intervention was 62.5% [95% CI, 40.6–81.2%] for cTnI and 100% [95% CI, 85.2–100%] for hs-cTnT. Median hs-cTnT concentrations were significantly higher in the “Revascularization-group” than in the “Non-Revascularization-group” (30.05 ng/L [95% CI, 26.5–54.8 ng/L], 23 patients vs. 15.3 ng/L [95% CI, 12.7–22.5 ng/L], 67 patients, p < 0.001). The calculated regression model that includes age, history of CAD, and hs-cTnT showed the best pretest performance with an AUC of 0.83, p = 0.008. Poor performance was observed for cTnI (AUC of 0.63, p = 0.098). Conclusions: This study demonstrates that the hs-cTnT assay is superior to the contemporary cTnI assay in predicting significant CAD requiring revascularization in patients hospitalized with AF. Older age, pre-existing CAD, impaired renal function, and a higher hs-cTnT cut-off showed the highest pretest probability of relevant CAD in patients hospitalized for AF. Full article