Assessment of Specific Biomarkers' Profile and Structural, Functional Parameters of the Left Ventricle in Patients With Lymphomas Undergoing Antitumor Therapy.

AIM: To evaluate the dynamics of specific biomarkers for cardiotoxicity, endothelial dysfunction, fibrosis, systemic inflammation, and morpho-functional alterations in the left ventricular (LV) myocardium in patients with newly diagnosed lymphomas during 6 courses of polychemotherapy (PCT). MATERIAL AND METHODS: The study included 30 patients with newly diagnosed lymphomas. All patients were evaluated for laboratory markers of cardiotoxicity at baseline and after 6 courses of chemotherapy (6 months), including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), endothelin-1 (ET-1), circulating cardiac biomarker ST-2, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and LV structural and functional echocardiographic (EchoCG) parameters. RESULTS: The changes in NT-proBNP and hsTnI concentrations during 6 courses of PCT were not statistically significant. Comparison of the baseline values with those after 6 courses of PCT showed increases in the median concentrations of ET-1 (3.38 and 5.5 pg/ml, respectively; p=0.438) and ST-2 (12.21 and 26.75 ng/ml, respectively; p=0.687). Markers of systemic inflammation were significantly decreased after 6 courses of PCT: the median CRP decreased from 15.2 to 0.72 mg/ml (p=0.006), and the median IL-6 decreased from 12.2 to 5.1 pg/ml (p=0.034). EchoCG data revealed a statistically significant impairment of the LV diastolic function parameters (E/A; E/e' lateral; E/e' average; left atrial volume index; isovolumic relaxation time). A moderate direct correlation was found between the ET-1 concentration and the isovolumic relaxation time at baseline and after 6 courses of PCT, respectively (r1 = 0.387, p=0.047 and r2 = 0.391, p=0.035). No changes in the LV systolic function were observed. CONCLUSION: The study showed that patients with lymphoproliferative diseases had no signs of cardiotoxicity during PCT according to the accepted criteria. This study described and highlighted for the first time the interrelation of endothelial dysfunction, profibrotic status, and LV diastolic dysfunction as manifestations of cardiovascular toxicity in patients with lymphoproliferative diseases. It is advisable to supplement the integrated strategies for the prevention and monitoring of PCT cardiovascular toxicity with a thorough evaluation of instrumental parameters of diastolic dysfunction for timely initiation/correction of cardioprotective therapy.

SARS-CoV2 mRNA vaccine intravenous administration induces myocarditis in chronic inflammation.

The current COVID-19 mRNA vaccines were developed and applied for pandemic-emergent conditions. These vaccines use a small piece of the virus's genetic material (mRNA) to stimulate an immune response against COVID-19. However, their potential effects on individuals with chronic inflammatory conditions and vaccination routes remain questionable. Therefore, we investigated the effects of mRNA vaccines in a mouse model of chronic inflammation, focusing on their cardiac toxicity and immunogenicity dependent on the injection route. mRNA vaccine intravenous administration with or without chronic inflammation exacerbated cardiac pericarditis and myocarditis; immunization induced mild inflammation and inflammatory cytokine IL-1beta and IL-6 production in the heart. Further, IV mRNA vaccination induced cardiac damage in LPS chronic inflammation, particularly serum troponin I (TnI), which dramatically increased. IV vaccine administration may induce more cardiotoxicity in chronic inflammation. These findings highlight the need for further research to understand the underlying mechanisms of mRNA vaccines with chronic inflammatory conditions dependent on injection routes.

Acoustic Streaming Tunnel Enables Particle Velocity Stretching in Multiplex Flow Cytometry.

Multiplexed flow cytometry, known for its powerful high-throughput identification capability, is widely applied across various biomedical and clinical fields. However, classical flow cytometry relies on multichannel lasers and detectors, which are significant in cost and size, limiting their application in miniaturized assays. Herein, we developed an acoustic streaming-based flow cytometry technique that focuses on multisized microbeads flowing sheathlessly. This method enables the discrimination of particle types and the quantification of target protein concentrations using only a single detector. Microbeads of different sizes exhibit distinct behaviors in the continuous acoustic streaming tunnel, leading to an increased velocity difference during their transition under the laser spot. Consequently, a size detection method based on "velocity stretching" has been established. A multiplex assay of three proteins: cardiac troponin I, creatine kinase-MB and myoglobin, in acute myocardial infarction is performed to validate the feasibility and evaluate the performance of the system. This new multiplexed flow cytometry strategy is expected to enable low-cost and onsite detection of multiple biomarkers.

Validation and correlation of high-sensitive troponin I and troponin T in the emergency department.

BACKGROUND: Troponin elevation is frequently observed in various scenarios in the Emergency Department (ED), yet there is a paucity of studies investigating simultaneously measured high-sensitivity cardiac troponin T (hs-cTnT) and troponin I (hs-cTnI) within a diverse cohort in a clinical setting. METHODS: All patients who underwent troponin testing at a single center were eligible for this study. Only patients with simultaneous samples with hs-cTnI (Siemens) and hs-cTnT (Roche) were included, regardless of chief complaint. RESULTS: Analysis of 1987 samples from 1134 patients showed a significant correlation between hs-cTnT and hs-cTnI (r = 0.86, p < 0.01). Of these samples, 65% exceeded the upper reference limit (URL) for hs-cTnT, and 30% for hs-cTnI with 39% who exhibited elevated hs-cTnT levels alongside normal hs-cTnI levels. The area under the curve (AUC) for acute myocardial infarction (AMI) for the index visit was 0.80 (95% CI; 0.75-0.85) for hs-cTnT and 0.87 (95% CI; 0.83-0.91) for hs-cTnI. Sensitivity and specificity were 91% and 39% for hs-cTnT, and 80% and 80% for hs-cTnI. Positive predictive value (PPV) and negative predictive value (NPV) was 9.3% and 98.5% for hs-cTnT respectively, corresponding for hs-cTnI was 21.3% and 98.3% respectively. Hazard ratios for 1-year mortality were 1.52 (95% CI; 1.40-1.66) for hs-cTnT and 1.26 (95% CI; 1.18-1.34) for hs-cTnI. CONCLUSION: Elevated troponins above the URL were very common in this diverse cohort, particularly for hs-cTnT, which was twice as frequent compared to hs-cTnI, resulting in low specificity and PPV for AMI.

Novel SOI-Biosensor Topology for the Detection of an Acute Myocardial Infarction Marker - Troponin I.

A biosensor based on field-effect transistors on silicon-on-insulator structures (SOI-biosensor) is a high-potential device for detection of biological molecules, for instance, such as troponin I; the biosensor allows conducting label-free real-time analysis. The aim of the study is the development of SOI-biosensor design for detection of acute myocardial infarction marker - troponin I. A notable feature of this design was the integration of two grounding electrodes directly onto the biosensor surface, which effectively nullified the static potential of the liquid sample and minimized physical breakdowns of biosensor elements. Materials and Methods: The highly specific anti-troponin I DNA aptamer was used as a receptor for specific detection of protein marker. Aptamer immobilization on the biosensor surface was carried out by physical adsorption. The analyzed range of target troponin I molecules concentration in the sample varied within 10-11 to 10-9 mol/L, mirroring clinical levels observed in myocardial infarction cases. During the experiment, a constant voltage of Vds=0.15 V was maintained. Results: The developed SOI-biosensor successfully detected target troponin I molecules at a concentration of 10-11 mol/L. The detection process exhibited an effective time of approximately 200-300 s per sample. Moreover, analysis of the detection process revealed a noticeable decrease in current within the source-drain circuit, indicative of the negatively charged complex formed by troponin I and anti-troponin I DNA-aptamer at the "liquid sample-nanowire" phase interface.

Deep Learning-Enhanced Paper-Based Vertical Flow Assay for High-Sensitivity Troponin Detection Using Nanoparticle Amplification.

Successful integration of point-of-care testing (POCT) into clinical settings requires improved assay sensitivity and precision to match laboratory standards. Here, we show how innovations in amplified biosensing, imaging, and data processing, coupled with deep learning, can help improve POCT. To demonstrate the performance of our approach, we present a rapid and cost-effective paper-based high-sensitivity vertical flow assay (hs-VFA) for quantitative measurement of cardiac troponin I (cTnI), a biomarker widely used for measuring acute cardiac damage and assessing cardiovascular risk. The hs-VFA includes a colorimetric paper-based sensor, a portable reader with time-lapse imaging, and computational algorithms for digital assay validation and outlier detection. Operating at the level of a rapid at-home test, the hs-VFA enabled the accurate quantification of cTnI using 50 µL of serum within 15 min per test and achieved a detection limit of 0.2 pg/mL, enabled by gold ion amplification chemistry and time-lapse imaging. It also achieved high precision with a coefficient of variation of <7% and a very large dynamic range, covering cTnI concentrations over 6 orders of magnitude, up to 100 ng/mL, satisfying clinical requirements. In blinded testing, this computational hs-VFA platform accurately quantified cTnI levels in patient samples and showed a strong correlation with the ground truth values obtained by a benchtop clinical analyzer. This nanoparticle amplification-based computational hs-VFA platform can democratize access to high-sensitivity point-of-care diagnostics and provide a cost-effective alternative to laboratory-based biomarker testing.

The effects of inspiratory muscle training on biomarkers of muscle damage in recovered COVID-19 patients after weaning from mechanical ventilation.

Background: COVID-19 patients experience respiratory muscle damage, leading to reduced respiratory function and functional capacity often requiring mechanical ventilation which further increases susceptibility to muscle weakness. Inspiratory muscle training (IMT) may help mitigate this damage and improve respiratory function and functional capacity. Methods: We studied the effects of IMT on muscle damage biomarkers, respiratory function, and functional capacity in COVID-19 recovered young adults, successfully weaned from mechanical ventilation. Participants were randomly allocated to either an IMT (n = 11) or control (CON; n = 11) intervention for 4 weeks. The IMT group performed 30 dynamic inspiratory efforts twice daily, at 50% of their maximal inspiratory mouth pressure (PMmax) while the CON group performed 60 inspiratory efforts at 10% of pMmax daily. Serum was collected at baseline, week two, and week four to measure creatine kinase muscle-type (CKM), fast skeletal troponin-I (sTnI) and slow sTnI. Results: Time × group interaction effects were observed for CKM and slow sTnI, but not for fast sTnI. Both were lower at two and 4 weeks for the IMT compared to the CON group, respectively. Time × group interaction effects were observed for forced expiratory volume in 1s, forced vital capacity, PMmax and right- and left-hand grip strength. These were higher for the IMT compared to the CON group. Conclusion: Four weeks of IMT decreased muscle damage biomarkers and increased respiratory function and grip strength in recovered COVID-19 patients after weaning from mechanical ventilation.

Bioinformatics design of peptide binding to the human cardiac troponin I (cTnI) in biosensor development for myocardial infarction diagnosis.

Cardiovascular disease has reached a mortality rate of 470,000 patients each year. Myocardial infarction accounts for 49.2% of these deaths, and the cTnI protein is a crucial target in diagnosing myocardial infarction. A peptide-based bioreceptor design using a computational approach is a good candidate to be developed for a rapid, effective, and selective detection method for cTnI although it is still lacking in study. Hence, to address the scientific gap, we develop a new candidate peptide for the cTnI biosensor by bioinformatics method and present new computational approaches. The sequential point mutations were made to the selected peptide to increase its stability and affinity for cTnI. Next, molecular docking was performed to select the mutated peptide, and one of the best results was subjected to the molecular dynamics simulation. Finally, the results showed that the best peptide showed the lowest affinity and good stability among other mutated peptide designs for interacting with the cTnI protein. In addition, the peptide has been tested to have a higher specificity towards cTnI than its major isomer, sTnI, through molecular docking and molecular dynamics simulation. Therefore, the peptide is considered a good potential bioreceptor for diagnosing myocardial infarction diseases.

[Severe cardiotoxic characteristics associated with allogeneic hematopoietic stem cell transplantation preconditioning in patients with aplastic anemia].

Objective: To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA). Methods: This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People's Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method. Results: In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days (n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases (n=26). Most patients (n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions: Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.

Aptamer-Based Electrochemical Biosensing Platform for Analysis of Cardiac Biomarkers.

Monitoring biomarkers secreted by cardiomyocytes is critical to evaluate anticancer drug-induced myocardial injury (MI). Cardiac troponin I (cTnI) is considered the gold standard biomarker for MI. Herein, an electrochemical aptasensor is engineered for cTnI detection based on lanthanide europium metal-organic frameworks (Eu-MOFs) and a hybridization chain reaction-directed DNAzyme strategy. Three types of Eu-MOF morphologies were easily synthesized by changing the solvent, and the Eu-MOF modulated by mixing the solvent of dimethylformamide and H2O (D-Eu-MOF) exhibited the best performance compared to other morphologies of the Eu-MOFs. Multifunctional nanoprobes were constructed from D-Eu-MOF@Pt loaded with natural horseradish peroxidase and combined with an aptamer-initiated nuclear acid hybridization chain reaction to form G-quadruplex/hemin DNAzymes for signal amplification. A novel capture probe is constructed on the basis of DNA nanotetrahedrons modified on screen-printed gold electrodes to enhance the capture of the target and multifunctional nanoprobes for signal amplification. It exhibits a detection limit of 0.17 pg mL-1 and a linear range from 0.5 pg mL-1 to 15 ng mL-1. The practicality of the platform is evaluated by measuring cTnI in real samples and secreted by cardiomyocytes after drug treatment, which provides great potential in drug-induced MI evaluation for clinical application.

Predicting troponin biomarker elevation from electrocardiograms using a deep neural network.

BACKGROUND: Elevated troponin levels are a sensitive biomarker for cardiac injury. The quick and reliable prediction of troponin elevation for patients with chest pain from readily available ECGs may pose a valuable time-saving diagnostic tool during decision-making concerning this patient population. METHODS AND RESULTS: The data used included 15 856 ECGs from patients presenting to the emergency rooms with chest pain or dyspnoea at two centres in Sweden from 2015 to June 2023. All patients had high-sensitivity troponin test results within 6 hours after 12-lead ECG. Both troponin I (TnI) and TnT were used, with biomarker-specific cut-offs and sex-specific cut-offs for TnI. On this dataset, a residual convolutional neural network (ResNet) was trained 10 times, each on a unique split of the data. The final model achieved an average area under the curve for the receiver operating characteristic curve of 0.7717 (95% CI±0.0052), calibration curve analysis revealed a mean slope of 1.243 (95% CI±0.075) and intercept of -0.073 (95% CI±0.034), indicating a good correlation between prediction and ground truth. Post-classification, tuned for F1 score, accuracy was 71.43% (95% CI±1.28), with an F1 score of 0.5642 (95% CI±0.0052) and a negative predictive value of 0.8660 (95% CI±0.0048), respectively. The ResNet displayed comparable or surpassing metrics to prior presented models. CONCLUSION: The model exhibited clinically meaningful performance, notably its high negative predictive accuracy. Therefore, clinical use of comparable neural networks in first-line, quick-response triage of patients with chest pain or dyspnoea appears as a valuable option in future medical practice.

Clinical effects of dexmedetomidine on patients with sepsis and myocardial injury.

This study aimed to explore the organ-protective effects of dexmedetomidine in patients with sepsis combined with myocardial injury. From December 2021 to December 2023, 263 sepsis patients with myocardial injury were included based on inclusion and exclusion criteria. They were divided into an experimental group (n = 122), who had previously received dexmedetomidine, and a control group (n = 141), who had received midazolam. After matching baseline characteristics, the treatment outcomes between the 2 groups were compared. In a propensity score-matched cohort of 263 patients, each group had 62 individuals with balanced baseline characteristics. The experimental group showed significantly lower heart rates on days 1, 3, and 7 compared to the control (P < .05). Biomarkers high-sensitivity troponin I and creatine kinase-MB decreased significantly by days 3 and 7, with lower levels in the experimental group. B-type natriuretic peptide levels were also lower in the experimental group on days 3 and 7. Heart function improved in both groups, with the experimental group showing better outcomes. Inflammatory markers decreased significantly after 7 days, with the experimental group having lower levels. Hospitalization duration was similar between groups. Dexmedetomidine reduces heart rate and inflammatory markers, protects myocardial cells, and improves cardiac function in patients with sepsis and myocardial injury. It shows potential as a treatment option, with future research needed to assess its long-term efficacy and safety.

Cardioprotective Effects of Ursodeoxycholic Acid in Isoprenaline-Induced Myocardial Injury in Rats.

Patients suffering from cholelithiasis have an increased risk of developing cardiovascular complications, particularly ischemic myocardial disease. Ursodeoxycholic acid (UDCA), already used in clinical practice for the treatment of cholelithiasis and related conditions, has proven antioxidative, anti-inflammatory, and cytoprotective effects. Therefore, the aim of this study was to investigate the cardioprotective effect of UDCA pre-treatment on isoprenaline-induced myocardial injury in rats. Male Wistar albino rats were randomized into four groups. Animals were pre-treated for 10 days with propylene glycol + saline on days 9 and 10 (control), 10 days with propylene glycol + isoprenaline on days 9 and 10 (I group), 10 days with UDCA + saline on days 9 and 10 (UDCA group), and 10 days with UDCA + isoprenaline on days 9 and 10 (UDCA + I group). UDCA pre-treatment significantly reduced values of high-sensitivity troponin I (hsTnI) and aspartate aminotransferase (AST) cardiac markers (p < 0.001 and p < 0.01, respectively). The value of thiobarbituric acid reactive substances (TBARS) was also decreased in the UDCA + I group compared to the I group (p < 0.001). UDCA also significantly increased glutathione (GSH) levels, while showing a tendency to increase levels of superoxide dismutase (SOD) and catalase (CAT). The level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, a key regulatory gene of inflammation, was diminished when UDCA was administered. A reduction of cardiac damage was also observed in the UDCA pre-treated group. In conclusion, UDCA pre-treatment showed a cardioprotective effect on isoprenaline-induced myocardial injury in rats, primarily by reducing oxidative stress and inflammation.

The efficacy of levosimendan and dobutamine on reducing peripheral blood interleukin-6 levels and improving cardiac function in patients with septic cardiomyopathy: a comparative study.

In patients with severe septic cardiomyopathy, levosimendan has been found to improve myocardial contractility more effectively than dobutamine, although the underlying mechanisms remain unclear. This study aims to compare the effects of levosimendan and dobutamine on cardiac function and inflammatory markers in patients with septic cardiomyopathy, and to further investigate the advantages and disadvantages of both treatments. We included 40 patients with septic cardiomyopathy treated in the intensive care unit of our hospital from September 2020 to September 2023. The patients were randomly divided into a levosimendan group (n=20) and a dobutamine group (n=20). Plasma concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) were measured by immunofluorescence at the start of treatment, 24 hours, and 48 hours. Cardiac troponin I (cTnI) concentrations were determined by chemiluminescence, and left ventricular ejection fraction (LVEF) was measured using the Simpson method. After 24 hours of treatment, there were no significant differences in IL-6, IL-1ß, and TNFα levels between the two groups (P>0.05). However, at 48 hours, the IL-6 level in the levosimendan group was significantly lower than that in the dobutamine group (319.43±226.05 pg/ml vs. 504.57±315.20 pg/ml, P=0.039), while IL-1ß and TNF-α levels showed no significant differences (P>0.05). Additionally, the cTnI level in the levosimendan group was significantly lower than that in the dobutamine group (1.01±0.54 ng/ml vs. 1.40±0.63 ng/ml, P=0.042), and LVEF was significantly higher in the levosimendan group (50.60±6.11% vs. 46.90±4.95%, P=0.042). These findings suggest that levosimendan may reduce plasma IL-6 levels, alleviate myocardial injury, and improve myocardial contractility in patients with septic cardiomyopathy compared to dobutamine.

Perioperative Change of High-Sensitive Cardiac Troponin I Concentration in Cats According to Three Different Anaesthesia Protocols.

BACKGROUND: Cardiac troponin I, a particular biomarker, is released into the bloodstream in response to myocardial injury. OBJECTIVES: To evaluate perioperative changes in high-sensitivity cardiac troponin I (hs-cTnI) concentration during ovariohysterectomy in cats undergoing three different anaesthesia protocols. METHODS:  Twenty-one female mixed-breed cats owned by clients aged (2.2 ± 0.7 years) and weight (3.2 ± 0.5 kg) were included in our study. The cats were divided into three groups: propofol-isoflurane (PI) group (n = 7), xylazine-ketamine (XK) group (n = 7) and xylazine-isoflurane (XI) group (n = 7). After pre-anaesthetic propofol (6 mg/kg IV) was administered to cats in Group PI, a mask was placed, and anaesthesia was maintained with 3.0% isoflurane in oxygen. Cats in Group XK underwent general anesthetization with xylazine hydrochloride (2 mg/kg IM) and, 10 min later, ketamine hydrochloride (10 mg/kg IM). Cats in Group XI were administered xylazine hydrochloride (2 mg/kg IM), and then anaesthesia (3.0% isoflurane and oxygen) was continued with a mask. Blood samples were collected from all cats; preoperatively and postoperatively at 0 and 12 h (Pre-, Post-0 h and Post-12 h, respectively). Serum hs-cTnI concentrations were measured with the Advia Centaur TnI-Ultra. RESULTS: In all 21 cats, hs-cTnI concentration increased at Post-0 h and 12 h measurement points compared to Pre-. In the XK group, hs-cTnI concentrations exhibited a significant increase at the Post-0 h (51.30 ng/L) and Post-12 h (157.70 ng/L) time points compared to Pre- (6.70 ng/L) (p < 0.05). CONCLUSIONS: The XK group increased the concentration of hs-cTnI more than other protocols. In the PI group, the increase in hs-cTnI concentrations at Post-0 and 12 h increased less than the other two groups (p < 0.05). The PI group was found to induce less myocardial damage.

Genetic excision of the regulatory cardiac troponin I extension in high-heart rate mammal clades.

Mammalian cardiac troponin I (cTnI) contains a highly conserved amino-terminal extension harboring protein kinase A targets [serine-23 and -24 (Ser23/24)] that are phosphorylated during ß-adrenergic stimulation to defend diastolic filling by means of an increased cardiomyocyte relaxation rate. In this work, we show that the Ser23/24-encoding exon 3 of TNNI3 was pseudoexonized multiple times in shrews and moles to mimic Ser23/24 phosphorylation without adrenergic stimulation, facilitating the evolution of exceptionally high resting heart rates (~1000 beats per minute). We further reveal alternative exon 3 splicing in distantly related bat families and confirm that both cTnI splice variants are incorporated into cardiac myofibrils. Because exon 3 of human TNNI3 exhibits a relatively low splice strength score, our findings offer an evolutionarily informed strategy to excise this exon to improve diastolic function during heart failure.

Association between peak troponin level and prognosis among patients admitted to intensive cardiovascular care unit.

INTRODUCTION: High-sensitivity cardiac troponin (hs-cTn) is a key biomarker for myocardial injury, yet its prognostic value in intensive cardiovascular care units (ICCU) remains poorly understood. We aimed to assess the association between peak hs-cTn levels and prognosis in ICCU patients. METHODS: All patients admitted to a tertiary care center ICCU between July 2019 - July 2023 were prospectively enrolled. Patients were divided into five groups according to their peak hs-cTnI levels: A) hs-cTnI <100 ng/L; B) hs-cTnI of 100-1000 ng/L; C) hs-cTnI of 1000-10,000 ng/L; D) hs-cTnI of 10,000-100,000 ng/L and E) hs-cTnI ≥100,000 ng/L. The primary outcome was all-cause mortality at one year. RESULTS: A total of 4149 patients (1273 females [30.7 %]) with a median age of 69 (IQR 58-79) were included. Group E was highly specific for myocardial infarction (97.4 %) and especially for ST segment elevation myocardial infarction (STEMI) (87.5 %). Patients in group E were 56 % more likely to die at 1-year in an adjusted Cox model (95 % CI 1.09-2.23, p = 0.014) as compared with group A. Subgroup analyses revealed that among STEMI patients, higher peak hs-cTnI levels were not associated with higher mortality rate (HR 1.04, 95 % CI 0.4-2.72, p = 0.9), in contrast to patients with NSTEMI (HR 7.62, 95 % CI 1.97-29.6, p = 0.003). CONCLUSIONS: Peak hs-cTnI levels ≥100,000 ng/L were linked to higher one-year mortality, largely indicative of large myocardial infarctions. Notably, the association between elevated hs-cTnI levels and mortality differed between STEMI and NSTEMI patients, warranting further investigation.

Significance of an Early Repeat Troponin Measurement Upon Presentation to the Hospital for Acute Heart Failure.

BACKGROUND: Higher cardiac troponin is associated with worse outcomes in patients with acute heart failure. The significance of repeat measurements over hours remains unclear. We assessed whether a repeat measurement and the Δ between measurements of high-sensitivity cardiac troponin I (hs-cTnI) were associated with outcomes in hypervolemic patients with acute heart failure without acute coronary syndrome. METHODS AND RESULTS: We analyzed 582 individuals from AKINESIS (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) with hs-cTnI measured ≤12 hours from admission and repeated ≤6 hours thereafter. Associations between hs-cTnI levels and their Δ with short-term (death, intensive care unit admission, receipt of inotropes, or positive pressure ventilation during hospitalization) and long-term (death or heart failure readmission within 1 year) outcomes were assessed. The average age was 69±13 years, 62% were men, 65% were White, 46% had coronary artery disease, and 22% had chest pain. Median hs-cTnI levels were 27 (interquartile range [IQR], 13-62) ng/L initially and 28 (IQR, 14-68) ng/L subsequently, with a Δ of 0 [IQR, -2 to 4] ng/L over 3.4±1 hours. Only the second measurement was associated with short-term outcomes (odds ratio, 1.14 per 2-fold higher [95% CI, 1.02-1.28]). Both individual measurements and the Δ were associated with long-term outcomes (hazard ratios, 1.09, 1.12, and 1.16 for first, second, and Δ, respectively). Associated risk for the first and second measurements were not constant over the year but highest early after being measured and decreased over 1 year. CONCLUSIONS: Repeat measurements of hs-cTnI over hours can identify individuals with acute heart failure without acute coronary syndrome at risk for short- and long-term outcomes.

Functional cardiac consequences of ß-adrenergic stress-induced injury in a model of Duchenne muscular dystrophy.

Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD); however, in the mdx mouse model of DMD, the cardiac phenotype differs from that seen in DMD-associated cardiomyopathy. Although some have used pharmacologic stress to stimulate injury and enhance cardiac pathology in the mdx model, many methods lead to high mortality with variable cardiac outcomes, and do not recapitulate the structural and functional cardiac changes seen in human disease. Here, we describe a simple and effective method to enhance the cardiac phenotype model in mdx mice using advanced 2D and 4D high-frequency ultrasound to monitor cardiac dysfunction progression in vivo. mdx and wild-type mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathological assessment showed that isoproterenol treatment increased myocyte injury, elevated serum cardiac troponin I levels and enhanced fibrosis in mdx mice. Ultrasound revealed reduced ventricular function, decreased wall thickness, increased volumes and diminished cardiac reserve in mdx compared to wild-type mice. Our findings highlight the utility of challenging mdx mice with low-dose isoproterenol as a valuable model for exploring therapies targeting DMD-associated cardiac pathologies.

Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans.

BACKGROUND: Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans. METHODS: Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays. RESULTS: Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0-6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180-679 mL) autologous plasma, the concentration of cTn in participants' blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8-168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7-295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0-44.9) to 52.7 mL/min (95% CI, 42.2-57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2-95.0). CONCLUSIONS: This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury.