Troponin I Tyrosine Phosphorylation Beneficially Accelerates Diastolic Function.

BACKGROUND: A healthy heart is able to modify its function and increase relaxation through post-translational modifications of myofilament proteins. While there are known examples of serine/threonine kinases directly phosphorylating myofilament proteins to modify heart function, the roles of tyrosine (Y) phosphorylation to directly modify heart function have not been demonstrated. The myofilament protein TnI (troponin I) is the inhibitory subunit of the troponin complex and is a key regulator of cardiac contraction and relaxation. We previously demonstrated that TnI-Y26 phosphorylation decreases calcium-sensitive force development and accelerates calcium dissociation, suggesting a novel role for tyrosine kinase-mediated TnI-Y26 phosphorylation to regulate cardiac relaxation. Therefore, we hypothesize that increasing TnI-Y26 phosphorylation will increase cardiac relaxation in vivo and be beneficial during pathological diastolic dysfunction. METHODS: The signaling pathway involved in TnI-Y26 phosphorylation was predicted in silico and validated by tyrosine kinase activation and inhibition in primary adult murine cardiomyocytes. To investigate how TnI-Y26 phosphorylation affects cardiac muscle, structure, and function in vivo, we developed a novel TnI-Y26 phosphorylation-mimetic mouse that was subjected to echocardiography, pressure-volume loop hemodynamics, and myofibril mechanical studies. TnI-Y26 phosphorylation-mimetic mice were further subjected to the nephrectomy/DOCA (deoxycorticosterone acetate) model of diastolic dysfunction to investigate the effects of increased TnI-Y26 phosphorylation in disease. RESULTS: Src tyrosine kinase is sufficient to phosphorylate TnI-Y26 in cardiomyocytes. TnI-Y26 phosphorylation accelerates in vivo relaxation without detrimental structural or systolic impairment. In a mouse model of diastolic dysfunction, TnI-Y26 phosphorylation is beneficial and protects against the development of disease. CONCLUSIONS: We have demonstrated that tyrosine kinase phosphorylation of TnI is a novel mechanism to directly and beneficially accelerate myocardial relaxation in vivo.

Cardiac biomarker responses following high-intensity interval and continuous exercise: the influence of ACE-I/D gene polymorphism and training status in men.

This study aimed to investigate the relationship between pre- and postexercise cardiac biomarker release according to athletic status (trained vs. untrained) and to establish whether the I/D polymorphism in the angiotensin-converting enzyme (ACE) gene had an influence on cardiac biomarkers release with specific regard on the influence of the training state. We determined cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in 29 trained and 27 untrained male soccer players before and after moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) running tests. Trained soccer players had higher pre (trained: 0.014 ± 0.007 ng/mL; untrained: 0.010 ± 0.005 ng/mL) and post HIIE (trained: 0.031 ± 0.008 ng/mL; untrained: 0.0179 ± 0.007) and MICE (trained: 0.030 ± 0.007 ng/mL; untrained: 0.018 ± 0.007) cTnI values than untrained subjects, but the change with exercise (ΔcTnI) was similar between groups. There was no significant difference in baseline and postexercise NT-proBNP between groups. NT-proBNP levels were elevated after both HIIE and MICE. Considering three ACE genotypes, the mean pre exercise cTnI values of the trained group (DD: 0.015 ± 0.008 ng/mL, ID: 0.015 ± 0.007 ng/mL, and II: 0.014 ± 0.008 ng/mL) and their untrained counterparts (DD: 0.010 ± 0.004 ng/mL, ID: 0.011 ± 0.004 ng/mL, and II: 0.010 ± 0.006 ng/mL) did not show any significant difference. To sum up, noticeable difference in baseline cTnI was observed, which was related to athletic status but not ACE genotypes. Neither athletic status nor ACE genotypes seemed to affect the changes in cardiac biomarkers in response to HIIE and MICE, indicating that the ACE gene does not play a significant role in the release of exercise-induced cardiac biomarkers indicative of cardiac damage in Iranian soccer players.NEW & NOTEWORTHY Our study investigated the impact of athletic status and angiotensin-converting enzyme (ACE) gene I/D polymorphism on cardiac biomarkers in soccer players. Trained players showed higher baseline cardiac troponin I (cTnI) levels, whereas postexercise ΔcTnI remained consistent across groups. N-terminal pro-brain natriuretic peptide increased after exercise in both groups, staying within normal limits. ACE genotypes did not significantly affect pre-exercise cTnI. Overall, athletic status influences baseline cTnI, but neither it nor ACE genotypes significantly impact exercise-induced cardiac biomarker responses in this population.

Kiwi-Inspired Rational Nanoarchitecture with Intensified and Discrete Magneto-Fluorescent Functionalities for Ultrasensitive Point-of-Care Immunoassay.

Fluorescent lateral flow immunoassays (FLFIA) is a well-established rapid detection technique for quantitative analysis. However, achieving accurate analysis of biomarkers at the pg mL-1 level using FLFIA still poses challenges. Herein, an ultrasensitive FLFIA platform is reported utilizing a kiwi-type magneto-fluorescent silica nanohybrid (designated as MFS) that serves as both a target-enrichment substrate and an optical signal enhancement label. The spatially-layered architecture comprises a Fe3O4 core, an endocarp-fibers like dendritic mesoporous silica, seed-like quantum dots, and a kiwi-flesh like silica matrix. The MFS demonstrates heightened fluorescence brightness, swift magnetic response, excellent size uniformity, and dispersibility in water. Through liquid-phase capturing and fluorescence-enhanced signal amplification, as well as magnetic-enrichment sample amplification and magnetic-separation noise reduction, the MFS-based FLFIA is successfully applied to the detection of cardiac troponin I that achieved a limit of detection at 8.4 pg mL-1, tens of times lower than those of previously published fluorescent and colorimetric lateral flow immunoassays. This work offers insights into the strategic design of magneto-fluorescent synergetic signal amplification on LFIA platform and underscores their prospects in high-sensitive rapid and on-site diagnosis of biomarkers.

Advances in the diagnosis of myocarditis in idiopathic inflammatory myopathies: an overview of diagnostic tests.

Cardiac involvement in idiopathic inflammatory myopathies (IIM) purports to worse clinical outcomes, and therefore early identification is important. Research has focused on blood biomarkers and basic investigations such as ECG and echocardiography, which have the advantage of wide availability and low cost but are limited in their sensitivity and specificity. Imaging the myocardium to directly look for inflammation and scarring has therefore been explored, with a number of new methods for doing this gaining wider research interest and clinical availability. Cardiovascular magnetic resonance (CMR) with contemporary multiparametric mapping techniques and late gadolinium enhancement imaging, is an extremely valuable and increasingly used non-invasive imaging modality for the diagnosis of myocarditis. The recently updated CMR-based Lake Louise Criteria for the diagnosis of myocarditis incorporate the newer T1 and T2 mapping techniques, which have greatly improved the diagnostic accuracy for IIM myocarditis.18F-FDG-PET/CT is a well-utilized imaging modality in the diagnosis of malignancies in IIM, and it also has a role for the diagnosis of myocarditis in multiple systemic inflammatory diseases. Endomyocardial biopsy, however, remains the gold standard technique for the diagnosis of myocarditis and is necessary for the diagnosis of specific cases of myocarditis. This article provides an overview of the important tests and imaging modalities that clinicians should consider when faced with an IIM patient with potential myocarditis.

Clinical relevance and advances in detection of translational biomarker cardiac troponin.

Cardiovascular diseases (CVD) are a range of diseases, pointing the functional hindrances in the heart and blood vessels of the human system that contributes to 48.6 % of the world's adult death rate. The diagnosis of CVD relies upon the Electro Cardio Gram (ECG) and detection of muscle markers such as troponins. Among the cardiac trio, Cardiac Troponin I (cTnI) weighing 23 KiloDalton (kDa) is a sorted biomarker for CVD. cTnI remains high in the blood after 1-2 weeks of myocardial damage. Testing of cTnI in CVD patients aids in diagnosis and risk stratification of the disease. Different determination systems including optical, electrochemical, and acoustic have been put forward for monitoring the cTnI which are Point of Care (POC) that promotes simple and sensitive detection of cTnI. The modern era has paved way to high-sensitivity Troponin I (hscTnI) devices that can detect up to 0.01 ng/ml in human blood/plasma/serum. Yet, the practice of hscTnI is impracticable due to cost inefficiency. Development of new hscTnI devices with minimal investment and maximal detection range will meet the global requirement. This review gives an over view on different detection systems of cardiac troponin I which stands as a translational detection molecule for CVDs.

Intra-amniotic infection and/or inflammation is associated with fetal cardiac concentric hypertrophy and diastolic dysfunction in preterm labor and preterm prelabor rupture of membranes.

BACKGROUND: Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero. OBJECTIVE: We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation. STUDY DESIGN: In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared. RESULTS: From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group. CONCLUSION: Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.

Assessment of the role of N-terminal pro-B-type natriuretic peptide as a predictive biomarker of mortality in acute aluminum phosphide poisoning.

BACKGROUND: In Egypt, aluminum phosphide (ALP) is a known lethal poison due to its cardiotoxicity. This study aimed to evaluate the predictive ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality in ALP-poisoned patients. METHODS: This prospective study was conducted on patients with ALP poisoning admitted to the Poison Control Center Ain Shams University Hospitals between July and December 2022. Upon admission, all patients were followed up and had their levels of NT-proBNP, troponin I (cTnI), and creatine kinase myocardial band (CK-MB) analyzed. RESULTS: Thirty patients were enrolled in the study and were divided into survivors and non-survivors. The initial NT-proBNP levels were significantly higher among non-survivors in contrast to the initial cTnI and CK-MB levels. The study identified that the best cutoff point of NT-proBNP for predicting mortality was ≥72 pg/ml, with AUC (0.869). CONCLUSION: It can be concluded that NT-proBNP can serve as an early predictor of mortality in ALP poisoning.

Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome.

OBJECTIVES: Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. METHODS: A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. RESULTS: There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. CONCLUSIONS: The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.

Evaluation of the analytical and clinical performance of a new high-sensitivity cardiac troponin I assay: hs-cTnI (CLIA) assay.

OBJECTIVES: Cardiac troponin (cTn) is the key biomarker for diagnosis of acute coronary syndrome (ACS). We performed a complete assessment of the high-sensitivity cardiac troponin I (hs-cTnI) (CLIA) assay on the analytical performance and clinical diagnostic performance, which was compared with Abbott ARCHITECT hs-cTnI assay. METHODS: Sex-specific 99th percentile upper reference limits (URLs) were determined from a healthy population of 424 males and 408 females. High-sensitivity performance was assessed by examining the imprecision at sex-specific URLs and the detectable results above LoD in a cohort of healthy population. The diagnostic performance of the hs-cTnI (CLIA) assay was validated in a population of 934 patients with suspected ACS. RESULTS: The 99th percentile URLs were 15.3 ng/L for female, 31.3 ng/L for male and 24.2 ng/L for overall population. The total imprecision near the sex-specific 99th percentile URLs were <5 %. 76.74 % of females, 97.12 % of males and 86.69 % of overall population had cTnI values exceeding the LoD, which met the criteria of high-sensitivity troponin assay. No cross-reactivity or interference was identified. The diagnostic sensitivity, specificity, PPV, NPV, and AUC of hs-cTnI (CLIA) assay were 97.97 , 90.70, 79.02, 99.21 % and 0.9885, respectively, which were comparable to ARCHITECT hs-cTnI assay. CONCLUSIONS: hs-cTnI (CLIA) assay is a high-sensitivity troponin I method with high precision, sensitivity and specificity. The clinical diagnostic performance of hs-cTnI (CLIA) is comparable to the established ARCHITECT hs-cTnI assay. Mindray's hs-cTnI (CLIA) assay is an attractive alternative for diagnosis of myocardial infarction with a high level of accuracy and safety.

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.

Cardiac troponins and coronary artery calcium score: a systematic review.

An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery calcification (CAC) nature in radiation exposure, finding biomarkers associated with CAC could be useful in identifying individuals at high risk of CAC score. In this review, we focused on the association of cardiac troponins (hs-cTns) and CAC to achieve insight into the pathophysiology of CAC. In October 2022, we systematically searched Web of Science, Scopus, PubMed, and Embase databases to find human observational studies which have investigated the association of CAC with cardiac troponins. To appraise the included articles, we used the Newcastle Ottawa scale (NOS). Out of 520 records, 10 eligible studies were included. Based on findings from longitudinal studies and cross-sectional analyses, troponin T and I were correlated with occurrence of CAC and its severity. Two of the most important risk factors that affect the correlation between hs-cTns serum levels and CAC were age and gender. The elevation of cardiac troponins may affect the progression of CAC and future cardiovascular diseases. Verifying the association between cardiac troponins and CAC may lead to identify individuals exposed to enhanced risk of cardiovascular disease (CVD) complications and could establish innovative targets for pharmacological therapy.

An unusual etiology in an 8-year-old girl with chest pain and elevated troponin-I.

Acute post-streptococcal glomerulonephritis (APSGN) is the most common glomerulonephritis of childhood, and clinical presentation can vary widely. This case report presents an atypical manifestation of APSGN in an 8-year-old female patient with pleuritic chest pain and elevated troponin-I, despite lacking classical kidney symptoms. Imaging studies showed cardiomegaly and interstitial lung opacities. Further investigations revealed hematuria and proteinuria, and the diagnosis was confirmed through elevated antistreptolysin-O (ASO) titers and low complement 3 (C3) levels. The patient was successfully managed with fluid restriction, diuretics, and antihypertensives, resulting in the resolution of symptoms and normalization of laboratory values. This case highlights the significance of recognizing atypical manifestations of APSGN for ensuring prompt diagnosis and proper management in the pediatric population.

Troponin I as a Predictor of Transcranial Doppler Sonography Defined Vasospasm in Intensive Care Unit Patients After Spontaneous Subarachnoid Hemorrhage.

OBJECTIVE: Elevation of Troponin I (TnI) in spontaneous subarachnoid hemorrhage (SAH) patients is a well-known phenomenon and associated with cardiopulmonary complications and poor outcome. The present study was conducted to investigate the association of the TnI value on admission, and the occurrence of cerebral vasospam in SAH patients. PATIENTS AND METHODS: A total of 142 patients with SAH, who were admitted to the neurosurgical intensive care unit (ICU) between December 2014 and January 2021 were evaluated. Blood samples were drawn on admission to determine TnI value. Each patient's demographic, radiological and medical data on admission, the modified Ranking Scale score at discharge as well as continuous measurements of transcranial Doppler sonography were analyzed. A maximum mean flow velocity (MMFV) > 120 cm/sec was defined as any vasospasm. These were stratified into severe vasospasms, which were defined as at least two measurements of MMFVs > 200 cm/sec or an increase of MMFV > 50 cm/sec/24 h over two consecutive days or a new neurological deterioration and mild vasospasm defined as MMFVs > 120 cm/sec in absence of severe vasospasm criteria. The total study population was dichotomized into patients with an initially elevated TnI (>0.05 µg/L) and without elevated TnI (≤0.05 µg/L). RESULTS: A total of 52 patients (36.6%) had an elevated TnI level upon admission, which was significantly associated with lower GCS score (p < 0.001), higher WFNS score (p < 0.001) and higher Fisher grade (p = 0.01) on admission. In this context a higher rate of ischemic brain lesions (p = 0.02), a higher modified Rankin Scale score (p > 0.001) and increased mortality (p = 0.02) at discharge were observed in this group. In addition, TnI was identified as an independent predictor for the occurrence of any vasospasm and severe vasospasm. CONCLUSION: An initially elevated TnI level is an independent predictor for the occurrence of any and severe vasospasm in patients with SAH.

Long-term exposures to low concentrations of source-specific air pollution, road-traffic noise, and systemic inflammation and cardiovascular disease biomarkers.

OBJECTIVES: Air pollution and traffic noise are detrimental to cardiovascular health. However, the effects of different sources of these exposures on cardiovascular biomarkers remain unclear. We explored the associations of long-term exposure to source-specific air pollution (vehicular exhausts and residential woodsmoke) at low concentrations and road-traffic noise with systemic inflammation and cardiovascular disease biomarkers. MATERIAL AND METHODS: Modeled outdoor exposure to fine particulate matter (aerodynamic diameter ≤2.5 µm; PM2.5) from vehicular exhausts and residential woodsmoke, nitrogen dioxide (NO2) from road traffic, and road-traffic noise were linked to the home addresses of the participants (Finnish residents aged 25-74) in the FINRISK study 1997-2012. The participants were located in the cities of Helsinki, Vantaa, and the region of Turku, Finland. The outcomes were high-sensitivity C-reactive protein (CRP), a biomarker for systemic inflammation, and cardiovascular disease biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I. We performed cross-sectional analyses with linear and additive models and adjusted for potential confounders. RESULTS: We found no association between PM2.5 from vehicular exhausts (% CRP difference for 1 µg/m3 increase in PM2.5: -0.9, 95% confidence interval, CI: -7.2, 5.8), or from residential woodsmoke (% difference: -8.1, 95% CI: -21.7, 7.9) and CRP (N = 4147). Road-traffic noise >70 dB tended to be positively associated with CRP (% CRP difference versus noise reference category of ≤45 dB: 18.3, 95% CI: -0.5, 40.6), but the association lacked significance and robustness (N = 7142). Otherwise, we found no association between road-traffic noise and CRP, nor between NO2 from road traffic and NT-proBNP (N = 1907) or troponin I (N = 1951). CONCLUSION: Long-term exposures to source-specific, fairly low-level air pollution from vehicular exhausts and residential woodsmoke, or road-traffic noise were not associated with systemic inflammation and cardiovascular disease biomarkers in this urban area.

Effectiveness of Dexmedetomidine as Myocardial Protector in Children With Classic Tetralogy of Fallot Having Corrective Surgery: A Randomized Controlled Trial.

OBJECTIVES: Efficacy of dexmedetomidine (DEX) as a cardioprotective agent in Indonesian children undergoing classic tetralogy of Fallot (TOF) repair with cardiopulmonary bypass (CPB). DESIGN: A prospective, parallel trial using block randomization along with double-blinded preparation of treatment agents by other parties. SETTING: National Cardiovascular Center Harapan Kita, Indonesia. PARTICIPANTS: Sixty-six children with classic TOF scheduled for corrective surgery. No children were excluded. All patients had fulfilled the criteria for analysis. INTERVENTIONS: A total of 0.5 µg/kg bolus of DEX was added to the CPB priming solution, followed by 0.25 µg/kg/h maintenance during bypass. The placebo group used normal saline. Follow-ups were up to 30 days. MEASUREMENTS AND MAIN RESULTS: Troponin I was lower in the DEX group at 6 hours (30.48 ± 19.33 v 42.73 ± 27.16, p = 0.039) and 24 hours after CPB (8.89 ± 5.42 v 14.04 ± 11.17, p = 0.02). Within a similar timeframe, DEX successfully lowered interleukin-6 (p = 0.03; p = 0.035, respectively). Lactate was lower in the Dex group at 1, 6, and 24 hours after CPB (p < 0.01; p = 0.048; p = 0.035; respectively). Dexmedetomidine increased cardiac output and index from 6 hours after bypass, but vice versa in systemic vascular resistance. Reduction of vasoactive inotropic score was seen during intensive care unit monitoring in the Dex group (p = 0.049). Nevertheless, DEX did not significantly affect the length of ventilation (p = 0.313), intensive care unit stay (p = 0.087), and mortality (p > 0.99). CONCLUSIONS: Dexmedetomidine during CPB is an effective cardioprotective agent in TOF children having surgery. Postoperative mortality was comparable across groups.

Photoelectrochemical immunoassay of cardiac troponin I based on ZnTCPP/CdIn2S4 type-II heterojunction and co-catalyzed precipitation biolabeling.

CdIn2S4 and zinc tetrakis(4-carboxyphenyl)porphyrin (ZnTCPP) were synthesized by hydrothermal method, and an organic dye-sensitized inorganic semiconductor ZnTCPP/CdIn2S4 type II heterojunction was constructed on a fluorine-doped tin oxide (FTO) substrate electrode. A sandwich immunostructure for signal-attenuation photoelectrochemical (PEC) detection of cardiac troponin I (cTnI) was constructed using the ZnTCPP/CdIn2S4/FTO photoanode and a horseradish peroxidase (HRP)-ZnFe2O4-Ab2-bovine serum albumin (BSA) immunolabeling complex. The bioenzyme HRP and the HRP-like nanozyme ZnFe2O4 can co-catalyze the oxidation of 4-chloro-1-naphthol (4-CN) by H2O2 to produce an insoluble precipitate on the photoanode, thus notably reducing the anodic photocurrent for quantitative determination of cTnI. Under the optimal conditions, the photocurrent at 0 V vs. SCE in 0.1 M phosphate buffer solution (pH 7.40) containing 0.1 M ascorbic acid was linear with the logarithm of cTnI concentration from 500 fg mL-1 to 50.0 ng mL-1, and the limit of detection (LOD, S/N = 3) is 0.15 pg mL-1. Spiked recoveries were 95.1% ~ 104% for assay of cTnI in human serum samples.

A Portable Readout System for Biomarker Detection with Aptamer-Modified CMOS ISFET Array.

Biosensors based on ion-sensitive field effect transistors (ISFETs) combined with aptamers offer a promising and convenient solution for point-of-care testing applications due to the ability for fast and label-free detection of a wide range of biomarkers. Mobile and easy-to-use readout devices for the ISFET aptasensors would contribute to further development of the field. In this paper, the development of a portable PC-controlled device for detecting aptamer-target interactions using ISFETs is described. The device assembly allows selective modification of individual ISFETs with different oligonucleotides. Ta2O5-gated ISFET structures were optimized to minimize trapped charge and capacitive attenuation. Integrated CMOS readout circuits with linear transfer function were used to minimize the distortion of the original ISFET signal. An external analog signal digitizer with constant voltage and superimposed high-frequency sine wave reference voltage capabilities was designed to increase sensitivity when reading ISFET signals. The device performance was demonstrated with the aptamer-driven detection of troponin I in both reference voltage setting modes. The sine wave reference voltage measurement method reduced the level of drift over time and enabled a lowering of the minimum detectable analyte concentration. In this mode (constant voltage 2.4 V and 10 kHz 0.1Vp-p), the device allowed the detection of troponin I with a limit of detection of 3.27 ng/mL. Discrimination of acute myocardial infarction was demonstrated with the developed device. The ISFET device provides a platform for the multiplexed detection of different biomarkers in point-of-care testing.

Differences in Troponin I and Troponin T Release in High-Performance Athletes Outside of Competition.

Troponin I and troponin T are critical biomarkers for myocardial infarction and damage and are pivotal in cardiological and laboratory diagnostics, including emergency settings. Rapid testing protocols have been developed for urgent care, particularly in emergency outpatient clinics. Studies indicate that strenuous physical activity can cause transient increases in these troponin levels, which are typically considered benign. This research focused on 219 elite athletes from national teams, evaluating their troponin I and T levels as part of routine sports medical exams, independent of competition-related physical stress. The results showed that 9.2% (18 athletes) had elevated troponin I levels above the reporting threshold, while their troponin T levels remained within the normal range. Conversely, only 0.9% (two athletes) had normal troponin I but raised troponin T levels, and 2.3% (five athletes) exhibited increases in both markers. No significant cardiovascular differences were noted between those with elevated troponin levels and those without. This study concludes that elevated troponin I is a common response to the intense physical training endured by high-performance endurance athletes, whereas troponin T elevation does not seem to be directly linked to physical exertion in this group. For cardiac assessments, particularly when ruling out cardiac damage in these athletes, troponin T might be a more reliable indicator than troponin I.

Elevated Cardiac Troponin I as a Mortality Predictor in Hospitalised COVID-19 Patients.

Background and Objectives: SARS-CoV-2 affects multiple organ systems, including the cardiovascular system, leading to immediate and long-term cardiovascular complications. Acute myocardial injury is one of the earliest and most common cardiac issues in the acute phase of COVID-19. This study aimed to evaluate the prognostic value of cardiac troponin I (cTnI) levels in predicting in-hospital mortality among hospitalised COVID-19 patients. Materials and Methods: A retrospective observational cohort study included 2019 adult patients hospitalised with a confirmed COVID-19 infection stratified by cTnI levels on admission into three groups: <19 ng/L (1416 patients), 19-100 ng/L (431 patients), and >100 ng/L (172 patients). Myocardial injury was defined as blood serum cTnI levels increased above the 99th percentile upper reference limit. Depersonalised datasets were extracted from digital health records. Statistical analysis included multivariable binary logistic and Cox proportional hazards regressions. Results: Overall, 29.87% of patients experienced acute myocardial injury, which development was associated with age, male sex, chronic heart failure, arterial hypertension, obesity, and chronic kidney disease. Among patients with cTnI levels of 19-100 ng/L, the odds ratio for requiring invasive mechanical ventilation was 3.18 (95% CI 2.11-4.79) and, for those with cTnI > 100 ng/L, 5.38 (95% CI 3.26-8.88). The hazard ratio for in-hospital mortality for patients with cTnI levels of 19-100 ng/L was 2.58 (95% CI 1.83-3.62) and, for those with cTnI > 100 ng/L, 2.97 (95% CI 2.01-4.39) compared to patients with normal cTnI levels. Conclusions: Increased cardiac troponin I, indicating myocardial injury, on admission is associated with a more adverse clinical disease course, including a higher likelihood of requiring invasive mechanical ventilation and increased risk of in-hospital mortality. This indicates cardiac troponin I to be a beneficial biomarker for clinicians trying to identify high-risk COVID-19 patients, choosing the optimal monitoring and treatment strategy for these patients.

HEART Score: Prospective Evaluation of Its Accuracy and Applicability.

Background: The History, Electrocardiogram, Age, Risk factors, and Troponin I (HEART) score is a simple method to risk stratify patients with chest pain according to the risk for incidence of major adverse cardiac events (MACEs). Materials and methods: A 202-patient prospective, single center study at Sri Siddhartha Medical College, Tumkur. Patients included were those who were presented to the emergency department (ED) due to non-traumatic chest pain, irrespective of age or any previous medical treatments, and were later referred to the cardiac care unit (CCU), cardiology department (CD). The end point of the study was the incidence of MACE. Results: There was a high occurrence of endpoint-myocardial infarction (MI) as MACE among patients with a high-risk HEART score (p < 0.001). About 52 patients (81.3%) who had MI had a high-risk score and 2 patients (3.1%) who had an endpoint of MI had a low-risk score. Sensitivity of HEART score to anticipate MACE was 91%, and the specificity was 80%. Conclusions: Our prospective study demonstrates the high sensitivity of the HEART score to effectively risk stratify patients and project the phenomenon of MACE. We support the use of the HEART score as a fast and accurate risk stratification tool in the ED. How to cite this article: Anwar I, Sony D. HEART Score: Prospective Evaluation of Its Accuracy and Applicability. Indian J Crit Care Med 2024;28(8):748-752.