Search Results (251)

Background: We evaluated the Sysmex Highly Integrated Single-Cartridge Luminescence Immunoassay System (HISCL) hs-cTnT assay, and compared its performance to the Roche assay, with derivation of 99th-percentile upper reference limits (99% URLs) for healthy subjects. We assessed the effect of increasing age/decreasing eGFR on the HISCL hs-cTnT. Methods: We verified assay limits of blank/detection, precision and the functional sensitivity. Samples were analyzed on both the Sysmex HISCL and Roche Elecsys analyzers for method comparison. Results: The HISCL assay limit of blank/detection was 1.3/1.9 ng/L, and concentrations corresponding to 20/10% CVs were 1.8/3.3 ng/L. Assay precision of kit controls at 3253 ng/L was 2.2% and at 106 ng/L was 2.5%. Linear regression analysis (n = 2151) showed good agreement (r = 0.95) with the Roche hs-cTnT. Bland–Altman (Roche/HISCL) analysis for samples with hs-cTnT ≤ 52 ng/L showed a mean absolute difference of 3.5 ng/L; for hs-cTnT > 52 ng/L, the mean difference was 2.8%. In a cardio-renal healthy population (n = 1004), the 99% URLs were 14.4/17.0/13.9 ng/L for overall/male/female, respectively; assay CV% was below 10% at these levels. More than 50% of the hs-cTnT in the healthy male and female subjects were measurable above the limit of detection. Hs-cTnT increased with increasing age and decreasing eGFR. Conclusions: In conclusion, the Sysmex HISCL hs-cTnT fulfils the criteria for a high-sensitivity assay, with specific 99th URLs for males and females. Expectedly, the baseline Sysmex hs-cTnT increases with age and decreasing eGFR. 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: Prolonged stays in the postoperative intensive care unit (ICU) for patients undergoing heart valve surgery are mainly caused by the development of complications. In turn, with the extension of the ICU stay, there is a risk of developing further serious postoperative complications. The main aim of the present study was to evaluate selected biomarkers in terms of their predictive potential for a prolonged postoperative stay in the ICU. Methods: This prospective study was conducted on a group of patients undergoing heart valve surgery. The primary endpoint was prolonged postoperative intensive care unit stay beyond 3 days (above the median). Logistic regression analysis was used to assess the predictors of the occurrence of the primary endpoint. Results: A total of 631 patients were included in the study. The median stay in the ICU was 3 days (2–5). A total of 265 patients required a prolonged stay in the ICU. In multivariate logistic regression analysis troponin T measured before surgery (p = 0.014), EuroSCORE II operative risk score (p = 0.004), troponin T measured the day after surgery (p = 0.005), preoperative RDW level (p = 0.005) and the presence of preoperative atrial fibrillation (p = 0.002) were independent predictors of the primary endpoint. Conclusions: Patients with elevated troponin T values determined both before the procedure and in the early postoperative period should be given special attention, because this group of patients is burdened with an increased risk of prolonged stay in the postoperative ward, the occurrence of serious postoperative complications and ultimately worse prognosis. Full article

Unplanned postoperative coronary angiography (uCAG) following isolated coronary artery bypass grafting (CABG) represents a significant clinical challenge, reflecting postoperative myocardial ischemia (PMI) with substantial impact on outcomes. The incidence of uCAG varies from 0.39 to 5.3%, depending on institutional protocols and diagnostic thresholds. Elevated cardiac biomarkers (high-sensitivity troponin and CK-MB), ECG changes, and hemodynamic instability are key indicators guiding uCAG. While associated with increased short-term mortality and morbidity, timely identification and treatment of graft-related complications via uCAG can improve midterm survival. Percutaneous coronary intervention (PCI) often emerges as the preferred therapeutic strategy over redo CABG. Future efforts should focus on refining risk stratification models, expanding the role of non-invasive imaging modalities, and validating early intervention strategies through prospective studies. Establishing standardized criteria for diagnosing and managing PMI remains critical to enhance outcomes and healthcare efficiency. Full article

Background: Intra-aortic balloon pump (IABP) augments coronary perfusion during high-risk percutaneous coronary interventions (PCI). We sought to identify patients who benefited from prophylactic IABP (P-IABP) compared to rescue-IABP (R-IABP). Methods: All consecutive non-cardiogenic shock patients undergoing high-risk PCI with IABP support at Ulm University Hospital, Germany, between 2012 and 2020 were grouped based on the timing of IABP insertion in the pre-interventional P-IABP or peri-interventional R-IABP group. We compared the primary endpoint peri-interventional high-sensitivity Troponin T (hsTnT) increase, sought baseline characteristics associated with the endpoint in the R-IABP group, and compared their correlation strengths between the groups. Results: Interventional outcomes of 44 patients with P-IABP implantation were compared with those of 15 patients with R-IABP implantation. P-IABP was associated with a lower peri-interventional hsTnT increase (p = 0.008, r = 0.390). In the R-IABP group, the presence of ST-segment elevation (p = 0.037, r = 0.631), low systolic blood pressure (RRsyst) (p = 0.007, r = 0.893 (inverse correlation)), and elevated NT-proBNP levels (p < 0.001, r = 0.953) were associated with higher hsTnT increases. HsTnT increase was significantly smaller in the P-IABP group in patients with low RRsyst (IZI = 2.6) and high NT-proBNP levels (IZI = 3.36). Patients with RRsyst < 120 mmHg (p = 0.007) and NT-proBNP levels ≥ 900 pg/mL (Cohen’s d = 0.70, respectively 1.17 for ≥5000 pg/mL and 5.01 for ≥10,000 pg/mL) showed lower peri-interventional hsTnT increase when treated with P-IABP compared to R-IABP, while patients with NT-proBNP levels < 900 pg/mL showed a contrary effect (Cohen’s d = −0.90). Cox regression analysis showed that a high peri-interventional hsTnT increase was significantly associated with a shorter survival time (p = 0.046). Conclusions: P-IABP use in high-risk PCI was associated with reduced peri-interventional myocardial injury, as measured by lower hsTnT increase, which was associated with improved survival in patients with low systolic blood pressure and elevated NT-proBNP levels. Thus, these conditions should be considered for indicating P-IABP. 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

Heart failure with preserved ejection fraction (HFpEF) shows diverse disease patterns, with various combinations of comorbidities and symptoms. A common hallmark is exercise intolerance, caused by alterations in the peripheral skeletal muscle (SKM) including a recently indicated titin hyperphosphorylation. Our aim is to compare a metabolic syndrome- (ZSF-1 rats) and a hypertension-driven (Dahl salt-sensitive (DSS) rats) HFpEF rat-model in relation to SKM function and titin phosphorylation. Obese ZSF-1 and high-salt fed DSS rats (HFpEF) were compared to lean ZSF-1 and low-salt fed rats (con). HFpEF was confirmed by echocardiography and invasive haemodynamic measurements. SKM atrophy, in vitro force measurements, titin- and contractile protein expression were evaluated. Obese ZSF-1 HFpEF rats showed muscle atrophy, reduced muscle force and increased titin phosphorylation compared to controls, which was not detected in hypertensive DSS rats. Fiber type specific troponins, myostatin and four and a half LIM domain 1 were differently regulated between the two models. Altogether, our results show that both animal models of HFpEF exhibit different SKM phenotypes, probably based on the divergent disease etiologies, which may help to define the most suitable animal model for HFpEF to test potential treatment regimens. Full article

Background/Objectives: The aim of this study is to identify markers and develop a multifactorial model for characterizing extensive scar tissue after revascularization in patients with myocardial infarction (MI). Methods: A total of 123 patients with MI were examined. The patients underwent contrast-enhanced cardiac magnetic resonance imaging (MRI) with a 1.5 Tesla GE SIGNA Voyager (GE HealthCare, Chicago, IL, USA) on the 7th–10th days from the onset of the disease. At the first stage, we performed a comparative analysis and built a multifactorial model based on the examination results of 92 (75%) patients enrolled from April 2021 to October 2023. These patients formed the group used for model development, or the “modeling group”. The mass of the scar was calculated, including relative to the left ventricular (LV) myocardium mass (M_scar/LVMM, in %). Results: The first subgroup consisted of 36 (39%) patients with a large scar, denoted as “LS” (M_scar/LVMM > 20%). The second subgroup included 56 (61%) patients with a smaller scar, referred to as “SS” (M_scar/LVMM ≤ 20%). Logistic regression was used to identify independent factors affecting scar tissue size. A multifactorial model was created. This model predicts M_scar/LVMM > 20% on MRI. It uses readily available clinical parameters: high-sensitivity troponin I (HscTn I) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and LV relative wall thickness (RWT). We tested the multifactorial model on the “modeling group” (n = 31). The sensitivity was 63.6% and the specificity was 85.7%. Conclusions: These indicates the feasibility of its application in clinical practice. Full article

Background: The diagnostic accuracy of the exercise treadmill test (ETT) remains suboptimal in premenopausal women. Menstrual cycle phases display hormonal variations and biological effects in premenopausal women. The early and late follicular phases of the menstrual cycle demonstrate nearly four-fold differences in estrogen levels. Methods: This study assessed the variability in ETT results between the early and late follicular phases in premenopausal women. This study included premenopausal females with regular menstrual cycles and chest pain. As per the study protocol, patients underwent two separate ETTs at the early and late follicular phases of the menstrual cycle. Hormones and high-sensitivity cardiac troponin T (hs-cTnT) were measured. The primary endpoint was the ST segment/heart rate (HR) index. The secondary endpoints were maximum ST/HR slope, ST segment depression, HR and blood pressure (BP) response, exercise capacity, and hs-cTnT change after ETT. Results: False-positive ETT results were common in premenopausal women. The early follicular phase displayed significantly higher hs-cTnT and BP responses to ETT compared to the late follicular phase. This study reports that ETT results are similar between the early and late follicular phases of the menstrual cycle in premenopausal women. Biological variability is observed in the BP and hs-cTnT response to ETT between the two phases. Conclusions: The menstrual cycle phase (early versus late follicular phase) did not affect the ETT results. The consideration of estrogen and hormonal status when evaluating the diagnostic test results can improve our understanding of cardiovascular disease in women. 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

Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality rates globally, presenting a severe threat to human health and life. Acute myocardial infarction (AMI) is one of the most common and extremely severe disorders within CVDs, causing an estimated 17.5 million deaths each year. Cardiac troponin I (cTnI) is considered a biomarker for myocardial infarction and a “gold standard” method for diagnosing AMI due to its high specificity and sensitivity. The ability to rapidly detect cTnI with high sensitivity is critical throughout the diagnosis and treatment process of AMI. It is a necessary precursor for doctors to quickly assess the disease and initiate subsequent therapies. This work comprehensively explores various techniques for the analysis and detection of cTnI. We systematically review current cutting-edge technologies used for cTnI detection. According to optical, electrical, and intelligent technology dimensions, this study meticulously classifies and elaborates on the research progress of related sensors. Based on current research findings and technological development trends, we further project the future research directions and application prospects of cTnI sensors. This is geared towards providing valuable references for the further development of this field. Full article

Anthracyclines and human epidermal growth factor receptor 2 (HER-2) inhibitors are cornerstone therapies for breast cancer but are associated with significant cardiotoxicity. While sodium–glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin have demonstrated cardio–renal protective effects during anthracycline treatment, their efficacy in preventing cardiotoxicity from sequential anthracycline and HER-2 blockade remains poorly understood. This study investigates the cardioprotective role of dapagliflozin in a preclinical model of chemotherapy-induced cardiotoxicity. Female C57Bl/6 mice were divided into four groups and treated for 10 days as follows: (1) a normal control group receiving saline (sham); (2) a model control group receiving doxorubicin (2.17 mg/kg/day for 5 days) followed by HER-2-blocking monoclonal antibody (2.25 mg/kg/day for 5 days); (3) a dapagliflozin-only group (10 mg/kg/day via oral gavage); and (4) a treatment group receiving the combination of doxorubicin, HER-2 inhibitor, and dapagliflozin. Cardiac function was assessed using echocardiography (VEVO 2100). Biomarkers of myocardial injury and inflammation (NLRP3, MyD88, CXCR4, H-FABP, troponin-T, and cytokines) were quantified via ELISA and immunohistochemistry. Circulating markers such as mitofusin-2, cardiac myosin light chain, malondialdehyde (MDA), and 4-hydroxy-2-nonenal (4-HNE) were also measured. Dapagliflozin significantly preserved the ejection fraction and reduced both radial and longitudinal strain impairment in mice treated with the doxorubicin–HER-2 inhibitor combination (p < 0.001). Levels of myocardial NLRP3, MyD88, CXCR4, H-FABP, interleukin-1β, and troponin-T were significantly lower in the dapagliflozin-treated group compared to the chemotherapy-only group. Serum markers of oxidative stress and cardiac injury, including mitofusin-2, MDA, 4-HNE, BNP, and high-sensitivity C-reactive protein (hs-CRP), were also reduced by dapagliflozin treatment. Our findings demonstrate that dapagliflozin effectively mitigates early cardiac dysfunction and injury in a preclinical model of sequential doxorubicin and HER-2 inhibitor therapy. 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

This study introduces a cutting-edge, aptamer-based, planar electric, double-layer field-effect transistor (FET) system that offers both high sensitivity and specificity for the detection of troponin I (TnI). The proposed sensing platform leverages the signal amplification capabilities of FETs alongside the unique attributes of a planar electric double-layer design to address the limitations inherent in traditional ion-sensitive detectors, which are impacted by Debye length effects. By integrating TnI-specific aptamers, the system markedly enhances molecular recognition and transduction efficiency, achieving an impressive detection limit of $0.0001467 \mathrm{d}\mathrm{e}\mathrm{c}\mathrm{a}\mathrm{d}\mathrm{e}$. Furthermore, the sensor demonstrates a strong exponential linear response across a clinically relevant concentration range of 1 ng/mL to 100 ng/mL. This innovative approach underscores the potential of electric double-layer FET systems to advance biomarker detection technologies for medical diagnostics and point-of-care applications. Full article

Background/Objectives: Endovascular aneurysm repair (EVAR) of the aorta may trigger an inflammatory response that affects coagulation. In the EVAR of para-renal and thoraco-abdominal aortic aneurysms, the implants are more complex and the duration of surgery is longer. However, the exact pathophysiological mechanisms of coagulation activation are not yet well understood. The primary aim of this study is to investigate the effects of complex EVAR of para-renal and thoraco-abdominal aortic aneurysms on the coagulation status of patients. Methods: This prospective observational study (STROBE), approved and registered by the Ethics Committee of the University Hospital of Larissa (UHL) (NCT06432387), will enroll consecutive patients undergoing elective EVAR of para-renal and thoraco-abdominal aortic aneurysms. Exclusion criteria: Refusal to participate, previous surgery within 3 months, American Society of Anesthesiologists physical status (ASA PS) > 3, known history of thrombophilia or functional platelet dysfunction. Perioperative laboratory tests will be performed according to institutional guidelines. These include a complete blood count, conventional coagulation tests, and kidney and liver function tests. In addition, the following parameters will be determined: von Willebrand factor, factors VIII and XI, D-dimers, fibrinogen, Adamts-13, anti-Xa, platelet activation (multiplate), and high-sensitivity troponin. Blood samples will be taken pre-operatively before induction of anesthesia (01), on postoperative day 1 (02), and on postoperative day 3–4 (03). During hospitalization, myocardial injury after non-cardiac surgery (MINS), major adverse cardiovascular events after non-cardiac surgery (MACE), acute kidney injury (AKI), post-implantation syndrome (PIS), and death from any cause will be recorded. In addition, our patients will be reviewed at 30 days, 3, 6, and 12 months for MACE, implant failure, or death from any cause. All enrolled patients will be treated by the same medical team at UHL according to the indications. According to our power analysis, for a cohort of patients with three consecutive measurements, 58 patients should be included in the study. To compensate for possible dropouts, the sample size was increased to 65 patients. Conclusions: The results of the present study could help physicians to better understand the effects of complex EVAR of para-renal and thoraco-abdominal aortic aneurysms on blood coagulation and platelet activation. Full article