Cardiac Troponin Levels Research Articles

Abstract 4138606: Toll-like Receptor 4 Signaling Establishes Trained Innate Immunity Through Interferon-Mediated Epigenetic Modifications Leading to Cardioprotection in a Stress-induced Cardiomyopathy Model

Introduction: The mechanisms responsible for establishing preconditioning-induced cardioprotection remain unknown. We have shown that a high dose of isoproterenol (ISO) induces cardioprotection against a second ISO dose in mice. The durability of protection and the lack of an innate immune response suggests trained immunity as a novel cardioprotective mechanism. Hypothesis: We hypothesize that cardioprotection is conferred through trained immunity, by interferon signaling downstream of necrotic cardiac material-mediated Toll-like receptor 4 (TLR4) activation. Methods: Wild-type C57BL/6J mice were intraperitoneally injected with TLR agonists or diluent, and challenged with 300 mg/kg ISO 7 days later. Mice were assessed by 2-D echocardiography, serum cardiac troponin levels, flow cytometry immune cell counts, and Multiome (single nuclei RNA+ATAC) sequencing. Results: The TLR4 agonist lipopolysaccharide (LPS) induced cardioprotection against ISO injury, with mice having enhanced survival (P=0.049) and no changes in cardiac troponin levels (P>0.99), cardiac neutrophil influx (P>0.99) or left ventricular motion (P=0.057) relative to baseline values before injury. Treating LPS-injected mice with β-glucan reversed the effects of LPS on immune cells and abolished cardioprotection. Multiome analysis of genes linked to chromatin peaks with increased accessibility in LPS+vehicle (protected) compared to LPS+β-glucan and diluent control (non-protected) hearts revealed the interferon pathway to be up-regulated across all major cell types. Modulation of interferon signaling with monoclonal antibodies against type 1+2 interferon receptors abolished cardioprotection in LPS-treated mice, whereas pre-treatment with recombinant type 1+2 interferons induced cardioprotection. Importantly, interferon-treated hearts shared similar chromatin accessibility features and enriched transcription factor motifs, including interferon-specific motifs, with LPS-protected hearts across cell types, particularly among non-cardiomyocytes. Conclusions: TLR4-induced interferon signaling is sufficient and in part necessary for cardioprotection against ISO injury. Moreover, our findings show that epigenetic modifications downstream of interferon signaling lead to cardioprotection consistent with trained innate immunity.

Abstract 4132820: S-nitrosylation of cardiac Cx43 hemichannels at Cys271 promotes arrhythmogenicity and myocardial injury upon cardiac stress in Duchenne Muscular Dystrophy

Connexin-43 (Cx43) plays a critical role in the propagation of action potentials among cardiomyocytes and proper cardiac contractility. In healthy cardiomyocytes, Cx43 is located at the intercalated disk; however, Cx43 remodeling is observed in cardiac pathologies and is linked with arrhythmogenesis and sudden cardiac death. Utilizing a mouse model of Duchenne muscular dystrophy (DMD mdx ), we have previously demonstrated that cardiac Cx43 is laterally localized, forming undocked hemichannels that activate via S-nitrosylation in response to isoproterenol-evoked cardiac stress. This activation leads to the disruption of cardiac membrane permeability, triggered activity, and deadly arrhythmogenic behaviors. To establish the direct role of S-nitrosylated Cx43 in DMD cardiomyopathy, we developed a specific knock-in mouse line in which the single Cx43 site for S-nitrosylation, cysteine 271 (Cys271), was substituted with a serine (C271S +/- ). Here, we developed a DMD mdx :C271S +/- line (4–6 months old), exhibiting reduced levels of S-nitrosylated Cx43 after crossing DMDmdx mice and C271S +/- mouse lines to assess the effect of β-adrenergic stimulation-induced cardiac stress and heart dysfunction. We show that cardiac Cx43 remodeling was not prevented in DMD mdx :C271S +/- , similar to what was shown in DMD mdx mice via immunofluorescence analysis. In addition, DMD mdx mice displayed an increased number of deadly arrhythmogenic events, increased Ca 2+ signaling, and prolonged action potentials in Langendorff-perfused whole hearts via optical mapping, compared to wild-type and DMD mdx :C271S +/- mice. Similarly, isoproterenol treatment evoked severe myocardial injury, increased levels of plasmatic cardiac troponin I (cTnI), and 40% mortality in DMD mdx mice. Notably, DMD mdx :C271S +/- mice, similar to DMD mdx mice treated with the Cx43 hemichannel blocker Gap19, exhibited cardioprotection compared to the cardiac dysfunction observed in DMD mdx mice. Therefore, these findings strongly suggest that S-nitrosylation of Cx43 proteins at site Cys271 represents a fundamental NO-mediated mechanism involved in the induction of arrhythmias and myocardial injury in DMD mdx after β-adrenergic stress.

Abstract 4137155: Relationship between Subclinical Myocardial Injury and Global Cognitive Performance: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: With demographic trends transitioning towards older adults, dementia and cognitive impairment are predicted to increase dramatically. We aim to elucidate the relationship between subclinical myocardial injury, as indicated by asymptomatic increased levels of high-sensitivity cardiac Troponin (hs-cTnT), and cognitive performance. Methods: We studied MESA participants from Exam 1 (2000-02) to Exam 6 (2016-18), categorizing them based on baseline hs-cTnT at Exam 1. Cognitive decline was defined as a decrease of ≥5 units in CASI between Exam 5&6. We used Pearson correlation and linear regression to analyze the association of hs-cTnT levels with CASI scores, and logistic regression to examine the association with cognitive decline. We also explored the relationship between different hs-cTnT categories and cognitive measures. Models were adjusted for demographics, lifestyle, APOE status, comorbidities, and medication use ( Figure ). Results: 4445 participants had both baseline hs-cTnT and valid Exam 5 CASI scores while only 1776 participants had valid Exam 6 CASI scores. Cohort was predominantly female (53%), mean age of 60 years, and 27% had at least one APOE e4 allele. Median hs-cTnT was 6.32 ng/L, and median CASI scores were 89 at Exam 5 and 91.5 at Exam 6. We found a negative correlation between the log-hs-cTnT at Exam 1 and Exam 5 with CASI scores at Exam 5. An increase of one unit in log-hs-cTnT level was associated with a decrease of 0.67 (CI -1.17, -0.17) in CASI and corresponded to higher odds (OR: 1.44; CI 1.05-1.95) of cognitive decline, after adjusting for covariates. When comparing various categories of hs-cTnT with category 1, we observe that the odd of cognitive decline increases as the category increases. However, this trend does not hold for category 5 with significantly lower sample size ( Figure ). Conclusion: Our findings indicate an inverse relationship between hs-cTnT and cognitive function years later, which is significantly attenuated by known risk factors for cognitive decline. Further research is needed to determine hs-cTnT as a predictor of future global cognitive functions.

Taurine and enzymatically modified isoquercitrin synergistically protect against the methotrexate-induced cardiotoxicity in rats: antioxidant and antiapoptotic effects

This study aimed to evaluate the protective potential of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ), both individually and in combination, against MTX-induced cardiotoxicity in male rats. A total of 36 rats were randomly divided into six groups (six animals each): control (vehicle), MTX alone (20 mg/kg, single dose), EMIQ+MTX (EMIQ at 26 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), Tau + MTX (Tau at 500 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), (EMIQ+Tau)+MTX, and (EMIQ+Tau)½+MTX. MTX treatment resulted in elevated levels of cardiac creatine phosphokinase-myocardial band, troponin I, nitric oxide, malondialdehyde, and serum IL-6, while decreasing levels of cardiac myeloperoxidase, catalase, and superoxide dismutase. MTX also reduced expression of BMI-1, induced DNA laddering and fragmentation, and increased cleaved caspase-3 protein expression in cardiac tissue. Both Tau and EMIQ showed equivalent effectiveness in protecting the heart against MTX-induced damage due to their antioxidant, anti-inflammatory, and antiapoptotic properties. Notably, combined treatment with half-doses of Tau and EMIQ offered superior protection compared to full doses of each agent alone. The full-dose combination showed similar efficacy to the half-dose combination, with a few exceptions. Overall, these results suggest a synergistic effect of Tau and EMIQ in mitigating MTX-induced cardiotoxicity, warranting further investigation into the underlying mechanisms.

Moderate-intensity training can ameliorate the process of cardiac apoptosis induced by lithium drug consumption in male Wistar rats

Background and objectiveLithium medication, given its significant role in the treatment or reduction of psychiatric disorders, may exert adverse effects on cardiac tissue. Therefore, this study aimed to investigate the effects of different exercise training intensities on the process of cardiac apoptosis and serum levels of cardiac troponin I (cTnI) resulting from lithium administration in male Wistar rats. MethodologyIn the present experimental study, 35 male Wistar rats were randomly divided into five groups (n=7); Control (CTL), Lithium (Li), High-Intensity training + lithium (HIT-Li), Moderate-Intensity training + lithium (MIT-Li), and Low-Intensity training + lithium (LIT-Li). Lithium drug (dose of 40mmol/kg dry food weight) and exercise training (5 days per week) were administered for eight weeks. Serum levels of cTnI, mRNA expression of Bcl-2, Bax, and Caspase-3, and histopatholigical changes were assessed by using the ELISA method, Real-Time PCR, and H&E staining, respectively. ResultsThe expression of the Bcl-2 gene was significantly increased in the LIT-Li group compared to the Li group (P = 0.003). Serum levels of cTnI were considereably higher in the Li group compared to the MIT-Li group (P = 0.0001). The expression of the Bax gene, in the LIT-Li, HIT-L, and Li groups, significantly increased compared to the MIT-Li group (P = 0.0001). Histopathological scores decreased in MIT-Li compared to Li group (P = 0.001). ConclusionIt seems that among different exercise intensities, the greatest protective effect against lithium consumption can be observed with moderate exercise intensity, which may potentially modulate factors influencing cardiac apoptosis and reduce lithium toxicity in the cardiac tissue of rats.

Diagnostic potential of relative changes in high-sensitivity troponin levels during intracoronary acetylcholine provocation testing

Abstract Background Intracoronary acetylcholine (ACh) provocation testing is useful for the diagnosis of vasospastic angina (VSA). However, the positive or negative diagnosis of ACh testing is often challenging when lacking typical anginal symptoms and electrocardiographic changes during provocation tests. We hypothesized that relative changes in cardiac troponin levels during ACh provocation testing may be suggestive of myocardial ischemia and would be helpful for the VSA diagnosis. Purpose To evaluate the diagnostic potential of relative changes in high sensitivity troponin I (hs-TnI) levels during intracoronary ACh provocation test. Methods This preliminary study included a total of 29 patients undergoing invasive coronary angiography with or without ACh provocation tests. Patients were divided into three groups; no ACh provocation tests (i.e. angiography alone), negative ACh tests, and positive ACh tests. Blood samples were obtained twice, before and after angiography, through the arterial sheath to evaluate hs-TnI. The primary measure was relative changes in hs-TnI (i.e. Δhs-TnI). Positive ACh provocation test was defined as total or subtotal coronary occlusion accompanied by chest pain and/or ischemic electrocardiographic changes. Results Of the 29 patients, 10 (34.5%) underwent coronary angiography alone, while ACh provocation testing was performed in 19 (65.5%) patients, of whom 7 (36.8%) and 12 (63.2%) had negative and positive ACh test results. Overall, the mean time interval between the blood sample collections was 76 minutes. Levels of hs-TnI before angiography did not differ significantly in the no, negative, and positive ACh test groups (5.3 [2.8, 8.6] vs. 2.9 [1.3, 8.8] vs. 3.3 [1.6, 8.5] pg/ml, p=0.76), while Δhs-TnI was highest in the positive ACh test group, followed by the negative and no ACh test groups (4.2 [0.5, 8.1] vs. 0.8 [0.4, 4.6] vs. −0.3 [−0.6, 0.3], p=0.002) (Figure). Conclusions In patients undergoing intracoronary ACh testing for the VSA diagnosis, a relative increase in Δhs-TnI during angiography was observed than in those who did not undergo the provocation tests, particularly when the ACh test diagnosis was positive. Our findings suggest that Δhs-TnI has the potential to aid in the positive or negative diagnosis of ACh provocation testing.

Predictors of periprocedural myocardial infarction following percutaneous coronary intervenction in NSTEMI

Abstract Background Percutaneous coronary intervention (PCI) has demonstrated a significant positive prognostic impact on outcomes in patients with Non-ST-elevation myocardial infarction (NSTEMI). However, PCI is associated with an increased risk of periprocedural complications, among which periprocedural myocardial infarction (PMI). Although risk factors of periprocedural events are only well established in patients undergoing PCI for chronic coronary syndrome with normal baseline cardiac troponin (cTn) levels, evidence on predictors of additional post-PCI myocardial infarction in patients with acute coronary syndrome who present elevated cTn levels at baseline (pre-PCI) is missing. Purpose To identify the predictors of PMI in patients affected by NSTEMI undergoing PCI. Methods We prospectively evaluated all NSTEMI patients admitted to our coronary care unit from 2017 to 2022 who underwent PCI. NSTEMI patients were managed according to the current European guidelines criteria. The diagnosis of PMI (type 4a myocardial infarction) was based on the Fourth Universal Definition of Myocardial Infarction. We only enrolled patients with stable (≤ 20% variation) or falling pre-procedure baseline cTn values. A multivariable logistic regression analysis was performed to investigate the factors independently associated with the occurrence of PMI after PCI. For the analysis, we selected the main known predictors of PMI after elective PCI, specifically age, serum creatinine, GRACE score > 140, multivessel disease, coronary bifurcation PCI, left main or proximal left anterior descending PCI, multivessel PCI and stent length ≥ 60 mm. Results The final court of the study included 1412 patients. PMI was recognized in 240 patients (17.0%). Although the patients who developed PMI had a higher risk profile as documented by a higher mean age, a higher complexity of atherosclerotic disease, and thus a significant technical difficulty of PCI compared to other patients, according to the multivariable model, only age [OR: 1.02 (95% CI: 1.01-1.04); p=0.006], coronary bifurcation PCI [OR: 3.71 (95% CI: 2.70-5.10); p<0.001], and stent length ≥ 60 mm [OR: 1.87 (95% CI: 1.30-2.68); p=0.001] were independent predictors of PMI. Interestingly, despite previous studies have demonstrated a predictive role of procedural complexity features, this was not completely confirmed by our analysis, in which left main or proximal left anterior descending PCI [OR: 0.92 (95% CI: 0.66-1.26); p=0.596] and multivessel PCI [OR: 0.83 (95% CI: 0.56-1.23); p=0.357] were not associated with an increased risk of periprocedural ischemic complications. Conclusions Among NSTEMI patients undergoing PCI, age, coronary bifurcation PCI and stent length ≥ 60 mm represent independent predictive factors of type 4a MI. This finding may have important clinical implications for clinical practice, providing valuable insights for the identification of higher-risk patients that can benefit from a more aggressive treatment.

Clinical and experimental evidence for differences between cardiac troponin I and T in acute and chronic cardiovascular conditions

Abstract Background Clinical and scientific practice operate under the assumption that systemic levels of cardiac troponin I (cTnI) and troponin T (cTnT) are indicative of the same underlying pathophysiological mechanisms and can be utilized interchangeably. Purpose To assess cTnI and cTnT levels and their ratio for differences in various cardiovascular conditions. Methods Individuals from three prospective clinical studies with a centrally adjudicated diagnosis were categorized into three groups: no known cardiac disease, chronic cardiac disease, and acute cardiac disease. Circulating cTnI and cTnT concentrations were measured using high-sensitivity assays (hs-cTnI-Architect, hs-cTnT-Elecsys) and the cTnI/cTnT ratio was calculated. Findings were validated using a second hs-cTnI assay (hs-cTnI-Clarity) and externally validated in independent cohorts. The cTnI/cTnT ratio was also assessed in five different non-lethal and lethal experimental models of cardiomyocyte injury. Results Of the 9704 included individuals, 9% had no known cardiac disease, 69% chronic cardiac disease, and 22% acute cardiac disease. No known cardiac disease and chronic cardiac disease were associated with a disproportional increase in cTnT compared to cTnI (cTnI/cTnT ratio, median 0.50, IQR 0.38-0.69 and 0.53, IQR 0.37-0.80). In contrast, cTnI concentrations were increased compared to cTnT in patients with acute cardiac disease, resulting in a cTnI/cTnT ratio of 1.62 (IQR 0.77-4.31). Findings were consistent using an alternative cTnI assay and in external validation cohorts (n=2776) where the cTnI/cTnT ratio was lower in those without cardiac disease (0.33 (IQR 0.25-0.50), 0.64 (IQR 0.40-1.05)) and with chronic cardiac disease (0.50 (IQR 0.32-0.75), 0.60 (IQR 0.38-1.00)), compared to those with acute cardiac disease (2.22 (IQR 1.08-5.27), 2.28 (IQR 1.01-5.67)). Non-lethal cardiomyocyte injury models showed a predominant release of cTnT with cTnI/cTnT ratios <0.5, and lethal injury models a predominant release of cTnI with cTnI/cTnT ratios >1. Conclusion Differences in cTnI and cTnT levels were observed in individuals with chronic and acute cardiac conditions, leading to distinct cTnI/cTnT ratios in both clinical and experimental settings. As a result, the interchangeability of cTnI and cTnT in present-day clinical and scientific settings needs to be reevaluated.Central illustration

Comparison of ultrasound-assisted thrombolysis and mechanical thrombectomy in patients with intermediate-high-risk pulmonary embolism

Abstract Background Pulmonary embolism (PE) can cause right heart failure and is associated with a high mortality. Early risk stratification is critical for individualized management. In patients with intermediate-high-risk PE, guidelines recommend to consider a percutaneous catheter-directed treatment (CDT). While different techniques are available, comparisons between treatments regarding right heart function and outcome are still scarce. Purpose To compare changes in right heart function as well as outcome in patients with intermediate-high-risk PE after catheter-directed treatment with ultrasound-assisted thrombolysis as compared to mechanical thrombectomy. Methods This is a retrospective, single-center study in intermediate-high-risk PE. According to the ESC guidelines, all patients had PESI class III-V, RV dysfunction and elevated cardiac troponin levels, but were hemodynamically stable. PE was confirmed by CT angiography. All patients underwent a catheter-directed treatment. One group received an ultrasound-assisted thrombolysis (USAT), while the other had a large-bore mechanical thrombectomy (MT). Right heart function (RV-Diameter, RV-/LV-Ratio, TAPSE) assessed via transthoracic echocardiography before and after CDT as well as interventional characteristics and postinterventional hospital stay were compared. Results From June 2022 to January 2024, 27 patients (43% female; aged 62 ± 14 years) were diagnosed with pulmonary embolism with intermediate-high-risk and underwent a catheter-directed treatment. Most patients (89%) had bilateral pulmonary embolisms. 15 patients (55%) received an ultrasound-assisted thrombolysis. 12 patients (45%) had a mechanical thrombectomy via a large-bore aspiration system. The mean procedural time was 41 ± 19 minutes for USAT and 106 ± 33 minutes for MT (p < 0.001). Right ventricular / left ventricular ratio reduction was -0.48 ± 0.25 in the USAT group (p < 0.001) and -0.34 ± 0.14 in the MT group (p < 0.001) (between group difference p = 0.2). TAPSE increased by 8 mm ± 4.4 mm in the USAT group (p < 0.001) and by 8.7mm ± 3.8 mm in the MT group (p < 0.001) (between group difference p = 0.7). The median postinterventional hospital stay was 7 days for the USAT patients and 7 days for the MT patients (between group difference p = 1). Conclusions In patients with intermediate-high-risk PE both ultrasound-assisted thrombolysis and large-bore mechanical thrombectomy lead to an improved right heart function with both interventions leading to a similar length of postprocedural hospital stay. Further randomized data have to discriminate differential impact of novel tools for the treatment of intermediate risk PE.

Comprehensive echocardiographic and biomarker assessment of patients with diabetic ketoacidosis

BackgroundSystemic stress, inflammation, and hydroelectrolytic and acid‒base abnormalities observed during diabetic ketoacidosis (DKA) can cause changes in the heart and even induce cardiovascular damage. We aimed to evaluate the structure and function of the heart during and after a DKA episode via echocardiography and biomarker assessment.MethodsWe performed a transthoracic echocardiogram (TTE) in subjects with an episode of DKA in the first 4–6 h of treatment. We evaluated left ventricular wall thickness, diameters and volumes, as well as systolic and diastolic function using tissue Doppler imaging, pulsed wave Doppler and left ventricular ejection fraction (LVEF). Left ventricular function was also assessed with global longitudinal strain (GLS). We obtained cardiac troponin levels in the first 24 h after admission. A second TTE was performed following the same protocol 6–12 h after the resolution of the DKA episode.ResultsWe included a total of 20 subjects. The mean age was 33 ± 13.6 years; 70% were female, and 70% had type 1 DM. 75% of the patients experienced severe episodes, and the rest experienced moderate episodes. Left ventricular isovolumetric contraction and ejection time were significantly shorter during DKA and prolonged after the resolution of the episodes (47.6 ± 9.9 vs. 62.2 ± 14.1, p = < 0.001) and (218.6 ± 37.9 vs. 265.06 ± 34.7). The isovolumetric relaxation time was also shorter during DKA, (41.72 ± 8.29 vs. 59.32 ± 17.98, p = < 0.001). Volumes and diameters of the left ventricle increased significantly after DKA resolution. We found no difference between LVEF or GLS during and after DKA resolution. 20% of the participants had troponin elevations, half of whom had moderate episodes and half of whom had severe episodes. 35% had LV dysfunction, 28.5% both in GLS and LVEF. 28.5% occurred after DKA resolution, with alterations in GLS.ConclusionsDiabetic ketoacidosis induces changes in the structure and function of the heart, which are mostly transient, reflect the presence of a hyperdynamic state and resolve after the resolution of the episode. Some subjects present with evidence of myocardial injury with elevated cardiac troponin and left ventricular dysfunction.Graphical abstractIcons in the graphical abstract are made by Freepik from www.flaticon.com.

Novel troponin fragmentation assay to discriminate between Takotsubo syndrome and acute myocardial infarction.

Cardiac troponin levels are elevated in Takotsubo syndrome (TTS) with significant overlap to acute myocardial infarction (MI). Long and intact cardiac troponin T (cTnT) forms are typical for MI. This study sought to assess whether the fragmentation composition of cTnT release in TTS differs from MI. The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence immunoassay and total cTnT with a commercial high-sensitivity cTnT assay in 24 TTS patients and in 84 Type 1 MI patients. The ratio of long to total cTnT (troponin ratio) was determined as a measure of cTnT fragmentation. Troponin ratio was lower in TTS patients 0.13 [0.10-0.20] vs. 0.62 [0.29-0.96], p<0.001). In the ROC curve analyses, troponin ratio showed a better predictive power than total cTnT in discriminating TTS and MI patients (AUC 0.869 [CI95% 0.789-0.948)] vs. 0.766 [CI95% 0.677-0.855], p=0.047). When restricting the analysis to patients with total cTnT below 1200 ng/L (maximal value in TTS patients), the respective AUC values for total cTnT and troponin ratio were 0.599 (CI 95% 0.465-0.732) and 0.816 (CI95% 0.712-0.921), p =0.003). At a cutoff point of 0.12, troponin ratio correctly identified 95% of MI patients and 50% of TTS patients. In contrast to Type 1 MI, only a small fraction of circulating cTnT in TTS exists in intact or long molecular forms. This clear difference in troponin composition could be of diagnostic value when evaluating patients with cTnT elevations and suspicion of TTS. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465591.

Cardiac Troponin Levels in Patients with Chronic Kidney Disease: "Markers of High Risk or Just Noise''?

Kidney disease is linked to the development of cardiovascular disorders, further increasing morbidity and mortality in this high-risk population. Thus, early detection of myocardial damage is imperative in order to prevent devastating cardiovascular complications within this patient group. Over the years, cardiac biomarkers have been identified and are now widely used in everyday clinical practice. More specifically, available data suggest that cardiac troponin and its regulatory subunits (TnT, TnI, and TnC) reflect the injury and necrosis of myocardial tissue. While cTnC is identical in cardiac and skeletal muscle, TnT and TnI constitute cardiac-specific forms of troponin, and, as such, they have been established by international societies as biomarkers of cardiac damage and diagnostic indicators for acute myocardial infarction. Elevations in the levels of both cardiac troponins (cTnT and cTnI) have been also reported in asymptomatic patients suffering from chronic kidney disease. Therefore, if abnormal, they often generate confusion among clinicians regarding the interpretation and clinical significance of their numerical values in emergency settings. The aim of this review is to explore the reasons behind elevated troponin levels in patients with chronic kidney disease and identify when these elevated levels of biomarkers indicate the need for urgent intervention, considering the high cardiovascular risk in this patient group.

The Hidden Heart: Exploring Cardiac Damage Post-Stroke: A Narrative Review

Stroke–heart syndrome (SHS), a critical yet underrecognized condition, encompasses a range of cardiac complications that arise following an ischemic stroke. This narrative review explores the pathophysiology, clinical manifestations, and implications of SHS, focusing on the complex interplay between the brain and the heart. Acute ischemic stroke (AIS) triggers autonomic dysfunction, leading to a surge in catecholamines and subsequent myocardial injury. Our review highlights the five cardinal manifestations of SHS: elevated cardiac troponin (cTn) levels, acute myocardial infarction, left ventricular dysfunction, arrhythmias, and sudden cardiac death. Despite the significant impact of these complications on patient outcomes, there is a notable absence of specific guidelines for their management. Through a comprehensive literature search, we synthesized findings from recent studies to elucidate the mechanisms underlying SHS and identified gaps in the current understanding. Our findings underscore the importance of early detection and multidisciplinary management of cardiac complications post-stroke. Future research should focus on establishing evidence-based protocols to improve clinical outcomes for stroke patients with SHS. Addressing this unmet need will enhance the care of stroke survivors and reduce mortality rates associated with cardiac complications.

A magnetic SERS-imprinted sensor for the determination of cardiac troponin I based on proteolytic peptide technology

Acute myocardial infarction is a sudden and high-mortality disease that can be accurately diagnosed by measuring the level of cardiac troponin I in the blood. Currently, cTnI commonly used clinical detection methods usually have excellent sensitivity and are suitable for large-scale sample detection analysis. However, most of these methods are operated through multiple steps of fixation, incubation, reaction and separation, and most of them require professionals to operate complex instruments, which greatly limits their applicability in real-time rapid detection. Therefore, a method that requires low professional skills and can perform rapid detection is necessary. We presents an alternative strategy to quantify cTnI in clinical serum samples using a combination of SERS and magnetic molecularly imprinted polymers (MMIP). MMIPs was synthesized under Polyvinyl Pyrrolidone (PVP) conditions without vinyl modification using characteristic peptide as template, MAA and DMAm as functional monomers. The internal Raman probe 4-MBA was connected through Ag-SH bonds in MMIPs to solve the problem that the target object had no Raman characteristic peak. MMIPs with high magnetic and adsorptive properties showed characteristic absorption peaks at the Raman shift of 1582 cm−1 after specific capture of the target templates. The Raman signals of the 4-MBA were reduced due to shielding effects and the detection range of this method was 0.001–100 ng mL−1. The recoveries and relative standard deviations (RSDs) of the spiked experiments were 103.1%–106.3 % and 3.54 %–7.38 %, respectively. In summary, this work had appropriate sensitivity and specificity, and there was no significant difference in detection results after ELISA verification. It provided a flexible and practical analysis method for detecting cTnI based on SERS technology. In addition, the imprinting materials of other disease markers can be prepared by changing the template molecules, which provides a new idea for the detection of other biomarkers.

GIANT CELL MYOCARDITIS: AUTOPSY CONFIRMATION OF A DIAGNOSTIC DILEMMA - A RARE CASE REPORT

Abstract Introduction/Objective Giant cell myocarditis (GCM) is a rare and rapidly progressive form of myocarditis, commonly leading to fulminant heart failure (HF), refractory ventricular arrhythmias or conduction system abnormalities and carrying a high mortality rate without prompt treatment. Due to its rarity, there is limited data on its prevalence, although studies show an incidence of 0.007–0.053% among autopsied cases. This entity primarily affects the heart, exhibiting a rapid clinical course and a poor prognosis necessitating immunosuppressive therapy and, in most instances, heart transplantation to improve survival rates. Methods/Case Report We present a case of a 62-year-old male with a prior history of complete heart block status post permanent pacemaker placement, presenting with acute decompensated heart failure. Laboratory investigations revealed elevated cardiac troponin levels (&amp;gt;35000) with echocardiography showing a reduced ejection fraction of 25% and an initial diagnosis of non-ST elevation myocardial infarction (NSTEMI) was made. Endomyocardial biopsy revealed GCM. Despite aggressive management, including immunosuppressive therapy and mechanical circulatory support, his condition deteriorated rapidly, leading to multiorgan failure and eventual death. The diagnosis was confirmed on autopsy. The diagnostic challenge of GCM lies in its clinical or pathologic overlap with other myocardial disorders such as cardiac sarcoidosis, viral myocarditis, and cardiac amyloidosis. Endomyocardial biopsy (EMB) remains the gold standard for diagnosing this entity which is characterized by a widespread inflammatory cell infiltrate with multinucleated giant cells in association with myocyte damage. The etiology of GCM remains unclear, but it is believed to be immune-mediated, possibly triggered by an autoimmune response. Results (if a Case Study enter NA) NA Conclusion Pathologists should give importance to consider GCM in the differential diagnosis of patients presenting with acute heart failure refractory to standard therapy. Early recognition and prompt initiation of immunosuppressive therapy are crucial for improving outcomes in patients with GCM. Awareness of this entity is crucial to make a timely diagnosis.

2-[18F]Fluoropropionic Acid PET Imaging of Doxorubicin-induced Cardiotoxicity.

Purpose Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA). Therefore, we explored the utility of 2-[ 18 F]fluoropropionic acid ([ 18 F]FPA), an SCFA analog, as an imaging biomarker of cardiac injury in mice exposed to doxorubicin. Procedures : Cardiotoxicity and cardiac dysfunction were induced in mice by an 8-dose regimen of doxorubicin (cumulative dose 24 mg/kg) administered over 14 days. The effects of doxorubicin exposure were assessed by measurement of heart weights, left ventricular ejection fractions, and blood cardiac troponin levels. Whole body and cardiac [ 18 F]FPA uptakes were determined by PET and tissue gamma counting in the presence or absence of AZD3965, a pharmacological inhibitor of monocarboxylate transporter 1 (MCT1). Radiation absorbed doses were estimated using tissue time-activity concentrations. Results Significantly higher cardiac [ 18 F]FPA uptake was observed in doxorubicin-treated animals. This uptake remained constant from 30 min to 120 min post-injection. Pharmacological inhibition of MCT1-mediated transport by AZD3965 selectively decreased the uptake of [ 18 F]FPA in tissues other than the heart. Co-administration of [ 18 F]FPA and AZD3965 enhanced the imaging contrast of the diseased heart while reducing overall exposure to radioactivity. Conclusions [ 18 F]FPA, especially when co-administered with AZD3965, is a new tool for imaging changes in fatty acid metabolism occurring in response to doxorubicin-induced cardiomyopathy by PET.

Elevated Cardiac Troponin Levels as a Predictor of Increased Mortality Risk in Non-Cardiac Critically Ill Patients Admitted to a Medical Intensive Care Unit.

Background: Cardiac troponin I (TnI) is a specific marker of myocardial damage used in the diagnosis of acute coronary syndrome (ACS). TnI levels can also be elevated in patients without ACS, which is linked to a worse prognosis and mortality. We evaluated the clinical implications and prognostic significance of serum TnI levels in critically ill non-cardiac patients admitted to the intensive care unit (ICU) at a tertiary-level hospital. Materials and Methods: A three-year retrospective study including the years 2017-2020 was conducted to evaluate in-hospital mortality during ICU stay and mortality rates at 28 and 90 days, as well as one and two years after admission, in 557 patients admitted to the medical ICU for non-cardiac causes. Results: TnI levels were elevated in 206 (36.9%) patients. Patients with elevated TnI levels were significantly older and had higher rates of comorbidities, including chronic heart failure, coronary heart disease, and chronic kidney disease (p < 0.05 for all). Patients with elevated TnI levels required more invasive mechanical ventilation, vasopressor infusion, and dialysis in the ICU and experienced more shock within the first 72 h (p = 0.001 for all). High TnI levels were associated with higher Acute Physiological and Chronic Health Evaluation (APACHE) II (27.6 vs. 20.3, p = 0.001) and Sequential Organ Failure assessment (8.8 vs. 5.26, p = 0.001) scores. Elevated TnI levels were associated with higher mortality rates at 28 days (58.3% vs. 19.4%), 90 days (69.9% vs. 35.0%), one year (78.6% vs. 46.2%), and two years (82.5% vs. 55.6%) (p < 0.001 for all). Univariate logistic regression analysis revealed that high TnI levels were a strong independent predictor of mortality at all time points: 28 days (OR = 1.2, 95% CI: 1.108-1.3, p < 0.001), 90 days (OR = 1.207, 95% CI: 1.095-1.33, p = 0.001), one year (OR = 1.164, 95% CI: 1.059-1.28, p = 0.002), and two year (OR = 1.119, 95% CI: 1.026-1.22, p = 0.011). Multivariate analysis revealed that age, albumin level, APACHE II score, and requirements for dialysis and vasopressor use in the ICU were important predictors of mortality across all timeframes, but elevated TnI levels were not. Conclusions: Elevated TnI levels in critically ill non-cardiac patients are markers of disease severity. While elevated TnI levels were significant predictors of mortality in the univariate analysis, they lost significance in the multivariate model when adjusted for other factors. Patients with elevated TnI levels had higher mortality rates across all timeframes, from 28 days to two years.

A-019 Unexpectedly High Cardiac Troponin Values in Healthy Athletes after SARS-CoV-2 Infection

Abstract Background Elevated levels of cardiac troponin I or T (cTnI, cTnT) in general have immediate clinical consequences including invasive cardiac imaging and rhythm monitoring. Macro-troponin is a complex of antitroponin autoantibodies and cTnI or cTnT and may result in falsely elevated values. In athletes, a reliable exclusion of cardiac disease is crucial to allow for intensive exercise. The prevalence and causes of falsely elevated cTn in professional athletes after SARS-CoV-2 infection are unknown. Methods These are preliminary results of an observational study including 35 professional athletes (16 -75 years old, median 24 years; 19 females, 16 males) who had post-Covid-19 check-ups at their practicing sports physician mostly in the year 2022 (6 athletes in 2023). One female athlete did not have a proven SARS-CoV-2 infection but vaccination. Divergences in high sensitivity (hs) cTn concentrations were investigated according to the sex-specific cut-off values of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostics, Atellica/Siemens Healthineers, Access/Beckman Coulter and hs-cTnT: Cobas/Roche Diagnostics). All athletes were advised to stop training 48h before routine blood drawing and if required underwent electrocardiography (ECG), echocardiography and magnetic resonance imaging to exclude myocardial involvement, particularly when suspicious symptoms were present. Athletes with divergent hs-cTn assay results were further analyzed for the presence of macro-troponin using the reference method sucrose gradient ultracentrifugation. Results The two main professional sports were cycling (mountain biking or road biking) and soccer, further sports comprised curling, swimming, running including marathon, floorball, cross-country skiing or rhythmic gymnastics. Athletes mostly suffered from postviral exhaustion, mild infectious symptoms like headache, sore throat, dry cough, subfebrile temperature, or sniffles or had atypical thoracic pain. There were two males with known secondary diagnoses, one 25 years old with diabetes mellitus type 1 and one 75 years old with atherosclerosis and hypercholesterolemia. Eighteen (18/35) athletes had hs-cTn concentrations within the sex-specific cut-off values in all assays and did not undergo further investigation for macro-troponin by sucrose gradient ultracentrifugation. However, in 17 athletes (17/35) hs-cTn was increased in at least one assay method which was mostly a hs-cTnI method (for 2/17 all assays elevated). The sucrose-gradient ultracentrifugation method proved macro-troponin in 15/17 with original hs-cTn values for Abbott Alinity: 5 - 170 ng/L; Siemens Atellica: 9.6 - 376 ng/L; Beckman Access: 0.5 - 55 ng/L and Roche Cobas 4 - 77 ng/L. However, 2/17 had the free troponin form, one with only a minor hs-cTnT increase above the sex-specific cut-off and the other with increased values in all hs-cTn assays but normal values in a 2- and 4-days control follow-up measurement. Notably, there were no ECG or cardiac imaging findings including echocardiography or cardiac magnetic resonance imaging suggestive of myocarditis in the investigated athletes. Conclusions After SARS-CoV-2 infection, cTn might be increased in athletes without a correlate in ECG or imaging reports. This should prompt physicians to consider an assay interference by macro-troponin, particularly if a second troponin method such as hs-cTnT remains normal. AHL &amp; CK share first and OH &amp; CM share last authorship

Network Pharmacology and Experimental Verification: SanQi-DanShen Treats Coronary Heart Disease by Inhibiting the PI3K/AKT Signaling Pathway.

To employee network pharmacology to predict the components and pathways of SanQi-DanShen (SQDS) in treating coronary heart disease, followed by in vitro experiments to validate the molecular mechanism of SQDS in treating coronary heart disease. We sourced the active ingredients and targets of Panax notoginseng and Danshen from the Traditional Chinese Medicine Systems Pharmacology database. Coronary heart disease related genes were retrieved from the OMIM, Genecards, and Therapeutic Target databases. Using Cytoscape 3.7.2 software, we constructed a network diagram illustrating the components and targets of SQDS. The associated targets were then imported into the STRING database to build a protein-protein interaction network. The Metascape database and WeChat software were utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Lastly, we performed molecular docking between the key components and related targets using AutoDock Vina. To validate the potential mechanism of SQDS in treating coronary heart disease, we established an acute coronary heart disease rat model via tail vein injection of pituitrin. Network pharmacology analysis revealed that 65 active ingredients and 167 targets of SQDS are implicated in the treatment of coronary heart disease. The key targets identified include AKT1, TNF, TP53, IL6, and VEGFA. Notably, the PI3K/AKT signaling pathway emerged as the primary pathway. Furthermore, animal experiments showed that, compared to the model group, SQDS significantly reduced levels of TNF-α, IL-6, Bax, and cardiac troponin I, while increasing Bcl-2 content. It also notably suppressed the expression of p-PI3K and p-AKT, thereby offering protection to myocardial tissue. Through the integrated approach of network pharmacology and molecular docking, we have established that SQDS exerts a multi-component, multi-target, and multi-pathway synergistic therapeutic effect on coronary heart disease. Its mechanism may involve the inhibition of the PI3K/AKT signaling pathway and the reduction of inflammatory factor expression.

Exploring strategies to rapidly identify false positives in high-sensitivity cardiac troponin I assay: A prospective study

BackgroundCardiac troponin is the pivotal biomarker of myocardial injury, playing a central role in the diagnosis of acute coronary syndrome and various clinical situations. Nevertheless, challenges arise when patients exhibit elevated cardiac troponin levels in the absence of evident cardiac origin, as evidenced by extensive cardiac exploration, which suggests the presence of an interfering factor. Despite the high performance of high-sensitive cardiac troponin immunoassays, these tests remain susceptible to interferences that may lead to false-positives. MethodsIn the period between July 2021 and July 2024, 8129 patients were hospitalized in the cardiology departments of Bordeaux University Hospital with positive results for high-sensitivity cardiac troponin I. Among them, 15 patients were suspected of having false-positive results, based on clinical and biological observations. ResultsIn this subpopulation, we evaluated prospectively various techniques, including serial dilutions, antibody-binding tubes, and alternative immunoassays (for cardiac troponin I and T) with the objective of identifying any potential analytical interference in their high-sensitive cardiac troponin I measurements. Our investigations revealed that 12 out of 15 suspected cases exhibited an interference on the high-sensitive cardiac troponin I assay. ConclusionIn conclusion, we propose an original algorithm designed to identify high-sensitive cardiac troponin I false-positives. This algorithm can help clinicians to make prompt and informed decisions about patient care, and to avoid erroneous clinical interventions that may result from such interferences.