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BackgroundAmong individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels.Methods and resultsA total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (

The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) European Society of Cardiology (ESC) 0/1-h algorithm in sex and race subgroups of US Emergency Department (ED) patients is unclear. A pre-planned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 1-h hs-cTnT measures from eight US EDs (1/2017 to 9/2018) were stratified into rule-out, observation, and rule-in zones using the hs-cTnT ESC 0/1 algorithm. The primary outcome was adjudicated 30-day cardiac death or MI. The proportion with the primary outcome in each zone was compared between subgroups with Fisher's exact tests. The negative predictive value (NPV) of the ESC 0/1 rule-out zone for 30-day CDMI was calculated and compared between subgroups using Fisher's exact tests. Of the 1422 patients enrolled, 54.2% (770/1422) were male and 58.1% (826/1422) white with a mean age of 57.6 ± 12.8 years. At 30 days, cardiac death or myocardial infarction (MI) occurred in 12.9% (183/1422) of participants. Among patients stratified to the rule-out zone, 30-day cardiac death or MI occurred in 1.1% (5/436) of women versus 2.1% (8/436) of men (p = .40) and 1.2% (4/331) of non-white patients versus 1.8% (9/490) of white patients (p = .58). The NPV for 30-day cardiac death or MI was similar among women versus men (98.9% [95% confidence interval, CI: 97.3-99.6] vs. 97.9% [95% CI: 95.9-99.1]; p = .40) and among white versus non-white patients (98.8% [95% CI: 96.9-99.7] vs. 98.2% [95% CI: 96.5-99.2]; p = .39). NPVs

Background: Postoperative acute kidney injury (AKI) in patients undergoing heart valve surgery is a common complication requiring special treatment, including renal replacement therapy (RRT). Effective prevention remains the most effective tool to reduce this important clinical problem. The aim of the study was to evaluate the predictive abilities of selected perioperative parameters in predicting AKI requiring RRT in the early postoperative period in patients undergoing cardiac valve surgery. Methods: Prospective study on a group of patients undergoing cardiac valve surgery. The primary endpoint was postoperative AKI requiring RRT. The secondary endpoint was death in the RRT group. Logistic regression analysis was used to assess which variables predicted the primary and secondary endpoints. Results: 603 patients were included in the study. The primary endpoint occurred in 43 patients. At multivariable analysis, age (p < 0.001), preoperative CRP level (p = 0.007), troponin T measured one day after surgery (TnT II) (p < 0.001) and prolonged postoperative use of catecholamines (p = 0.001) were independent predictors of the primary endpoint. In turn, death in the group of patients requiring RRT occurred in 32 patients. Age (p < 0.001), preoperative CRP level (p = 0.002), TnT II (p = 0.009), and prolonged postoperative use of catecholamines (p = 0.001) remained independent predictors of the secondary endpoint. Conclusions: The results of this study indicate that older age, elevated values of preoperative levels of CRP, as well as increasing levels of postoperative troponin T and the need for a prolonged supply of catecholamines, are independent predictors of postoperative AKI requiring RRT as well as death. Accurate identification of patients at increased postoperative risk of AKI could facilitate preoperative patient informed consent and optimize the process of qualification and cardiac surgical treatment. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is associated with increased fracture risk in the general population. Few data exist on the association between cardiovascular health and incident fracture risk in patients with advanced CKD, a high-risk population for fractures. We aimed to assess the link between fracture risk and cardiovascular health in a prospective cohort of 210 patients with CKD stage G4–5. Incident fractures were recorded during a prospective follow-up of 5 years. Laboratory parameters, abdominal aortic calcification score, echocardiography, ultrasound assessment of brachial artery flow-mediated dilatation and carotid intima-media thickness, and maximal stress ergometry were obtained at baseline. A total of 51 fractures were observed in 40 (19%) patients during follow-up. In separate multivariable Cox proportional hazards models adjusted for age, gender, and baseline eGFR, TnT (HR 1.007, CI 95% 1.003–1.010, p < 0.001) and ProBNP (HR 1.000, CI 95% 1.000–1.000, p = 0.017) were associated with incident fractures and the association persisted after adjusting for coronary artery disease (CAD). The patients unable to perform the ergometry test had a higher risk of incident fractures compared to others (36.1% vs 15.5%, p = 0.009). A cardiovascular composite risk score summarizing TnT, ProBNP, and ergometry data was independently associated with incident fractures in a multivariable Cox model (HR 1.373, CI 95% 1.180–1.599, p < 0.001). Patients with the lowest score were observed with no fractures, while patients with the highest score were observed with a fracture risk of 40.5% during follow-up. Risk of incident fractures is associated with biomarkers of cardiovascular health and a composite cardiovascular risk score in patients with advanced CKD. [ABSTRACT FROM AUTHOR]

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Abstract 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

Abstract This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI. Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal.

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. [ABSTRACT FROM AUTHOR]

Background/Objectives: Previous preclinical studies have shown that desflurane might have the most significant cardioprotective effect of all volatile anesthetics. However, data regarding the cardioprotective effects of desflurane versus sevoflurane are lacking. Therefore, we evaluated the effect of the maintenance of anesthesia using desflurane versus sevoflurane on the postoperative maximum concentrations of cardiac biomarkers in older adults undergoing low- to moderate-risk noncardiac surgery. Methods: In this secondary analysis of a prospective randomized trial, we included all 190 older adults undergoing low- to moderate-risk noncardiac surgery. Patients were randomized to receive desflurane or sevoflurane for the maintenance of anesthesia. We administered desflurane or sevoflurane, aiming at a BIS value of 50 ± 5. The cardiac-specific biomarkers included troponin T, NT-proBNP, and copeptin, which were measured preoperatively, within one hour after surgery, and on the second postoperative day. Results: There were no significant differences between the desflurane and sevoflurane groups in the postoperative maximum concentrations of troponin T (11 ng.L−1 [8; 16] versus 13 ng.L−1 [9; 18]; p = 0.595), NT-proBNP (196 pg.mL−1 [90; 686] versus 253 pg.mL−1 [134; 499]; p = 0.288), or copeptin (19 pmol.L−1 [7; 58] versus 12 pmol.L−1 [6; 41]; p = 0.096). We also observed no significant differences in the troponin T, NT-proBNP, or copeptin concentrations between the desflurane and sevoflurane groups at any measured timepoint (all p > 0.05). Conclusions: In contrast to preclinical studies, we did not observe a significant difference in the postoperative maximum concentrations of cardiac biomarkers. It seems likely that desflurane does not exert significant clinical meaningful cardioprotective effects in older adults. Thus, our results do not support the use of desflurane in patients undergoing low- to moderate-risk noncardiac surgery. [ABSTRACT FROM AUTHOR]

Introduction The relationship between mortality and troponin in non-ST-elevation myocardial infarction (NSTEMI) patients with a history of renal failure is quite limited. This study investigated the relationship between blood delta troponin T levels and 30-day mortality in patients with chronic renal dysfunction and NSTEMI. Materials and Methods This study was conducted prospectively by including patients with chronic renal dysfunction and clinical findings of NSTEMI between February 1, 2021, and August 1, 2022. Demographics, medical history, laboratory parameters, and mortality data were noted. Thirty-day morbidity data was used for mortality. Delta troponin T was calculated using initial and first-hour troponin T values. Patients were grouped as healthy and deceased. Data were evaluated using univariant analysis and receiver operating characteristics analysis. Results Of the 73 patients included in the study, 29 were female. The mean age of the patients was 67.3 years. The 30-day mortality rate was 9.5%. The sensitivity of the initial troponin T value was 85.7% (42.1–99.6), the specificity was 68.2% (55.6–79.1), and the accuracy was 69.9% (58–80.1), and the sensitivity of the first-hour troponin T value was 85.7% (42.1–99.6), specificity was 75.8% (63.6–85.5), and accuracy was 76.7% (65.4–85.8). The delta troponin T median of the mortality group was 56 (24.2–286.4), and the delta troponin median of the surviving patients was 29.4 (10.7–79.6). The difference was not statistically significant (p = 0.072). Conclusion The current study's results show that delta troponin T (initial and first hour) is not associated with short-term mortality in patients with chronic renal dysfunction and NSTEMI. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets. METHODS: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories. RESULTS: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; Pinteraction=0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively. CONCLUSIONS: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar. [ABSTRACT FROM AUTHOR]

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI. Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal. [ABSTRACT FROM AUTHOR]

Troponin is the American College of Cardiology and American Heart Association preferred biomarker for diagnosing acute myocardial infarction (MI). We provide a modeling framework for high sensitivity cardiac Troponin I (hs-cTnI) detection in chromatographic immunoassays (flow displacement mode) with an analytical limit of detection, i.e., LOD

BACKGROUND: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hs-cTn)-based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays. METHODS: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability (ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients. RESULTS: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline-recommended strategy. CONCLUSION: We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care. TRIAL REGISTRATION NUMBERS: Data of following cohorts were used for this project: BACC ( www. CLINICALTRIALS: gov ; NCT02355457), stenoCardia ( www. CLINICALTRIALS: gov ; NCT03227159), ADAPT-BSN ( www.australianclinicaltrials.gov.au ; ACTRN12611001069943), IMPACT ( www.australianclinicaltrials.gov.au , ACTRN12611000206921), ADAPT-RCT ( www.anzctr.org.au ; ANZCTR12610000766011), EDACS-RCT ( www.anzctr.org.au ; ANZCTR12613000745741); DROP-ACS ( https://www.umin.ac.jp , UMIN000030668); High-STEACS ( www. CLINICALTRIALS: gov ; NCT01852123), LUND ( www. CLINICALTRIALS: gov ; NCT05484544), RAPID-CPU ( www. CLINICALTRIALS: gov ; NCT03111862), ROMI ( www. CLINICALTRIALS: gov ; NCT01994577), SAMIE ( https://anzctr.org.au ; ACTRN12621000053820), SEIGE and SAFETY ( www. CLINICALTRIALS: gov ; NCT04772157), STOP-CP ( www. CLINICALTRIALS: gov ; NCT02984436), UTROPIA ( www. CLINICALTRIALS: gov ; NCT02060760).

BACKGROUND: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. METHODS: We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry. RESULTS: Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P=0.03 versus cTnT), and 43 of 57 ([75%] P

Background: In prospective studies employing troponin assays in ACS, troponin-T and troponin-I have demonstrated to predict long-term risk for adverse cardiac events and to have diagnostic accuracy on par with, if not superior to, creatine kinase-MB. Recent prognostic studies have demonstrated that myocardial injury at initial presentation has a major role in determining both short- and long-term mortality as well as the probability of future reinfarction. Assays for cardiac-specific troponin-T (TnT) and troponin-I are very sensitive in identifying cardiac injury. Aims: To study the prognostic significance of troponin T in patients diagnosed to have unstable angina during their study in the hospital. Methods: A prospective longitudinal study was conducted in the medicine department of Vinayaka Missions Kirupananda Variyar Medical College Hospital, Salem, for a period of one year between May 2020 and April 2021. All patients over the age of 18 with chest pain or symptoms suggestive of unstable angina and a blood sample showing troponin positivity were included in the study. A total of 50 patients were included in the study. A semi-structured questionnaire was designed to collect information regarding socio-demographic details and symptoms related to their presenting illness at the time of admission. All the routine blood investigations were performed. An ECG was taken on all the study subjects to confirm the feature of unstable angina. Troponin T levels were measured in all the study subjects. The cut-off used in our study for a positive TnT assay was > 0.05 ng/ml. All the cardiac events that occurred during their hospital stay were recorded. Results: The majority of the study subjects had troponin T levels between 0.11 and 0.15 ng/ml, and only 6% of the subjects had troponin levels >0.2 ng/ml, and the mean troponin T level was 0.14 ng/ml. There was a statistically significant association between the troponin T levels and the occurrence of cardiac events; as the levels of troponin T increased, the incidence of infarction also increased. A statistically significant association was seen between death and high troponin T levels. This proves that troponin T levels predict the prognosis of patients with unstable angina. Conclusion: Our study concluded that an increased troponin T substantially increases the short-term risk of cardiac events, such as mortality and MI, in individuals with unstable angina or suspected myocardial ischemia. [ABSTRACT FROM AUTHOR]

Patients admitted for acute medical conditions and major noncardiac surgery are at risk of myocardial injury. This is frequently asymptomatic, especially in the context of concomitant pain and analgesics, and detection thus relies on cardiac biomarkers. Continuous single‐lead ST‐segment monitoring from wireless electrocardiogram (ECG) may enable more timely intervention, but criteria for alerts need to be defined to reduce false alerts. This study aimed to determine optimal ST‐deviation thresholds from wireless single‐lead ECG for detection of myocardial injury following major abdominal cancer surgery and during acute exacerbation of chronic obstructive pulmonary disease. Patients were monitored with a wireless single‐lead ECG patch for up to 4 days and had daily troponin measurements. Single‐lead ST‐segment deviations of <0.255 mV and/or >0.245 mV (based on previous study comparison with 0.1 mV 12‐lead ECG and variation in single‐lead ECG) were analyzed for relation to myocardial injury defined as hsTnT elevation of 20–64 ng/L with an absolute change of ≥5 ng/L, or a hsTnT level ≥ 65 ng/L. In total, 528 patients were included for analysis, of which 15.5% had myocardial injury. For corrected ST‐thresholds lasting ≥10 and ≥ 20 min, we found specificities of 91% and 94% and sensitivities of 17% and 13% with odds ratios of 2.0 (95% CI: 1.1; 3.9) and 2.4 (95% CI: 1.1; 5.1) for myocardial injury. In conclusion, wireless single‐lead ECG monitoring with corrected ST thresholds detected patients developing myocardial injury with specificities >90% and sensitivities <20%, suggesting increased focus on sensitivity improvement. [ABSTRACT FROM AUTHOR]

Cardiomyopathies have unresolved genotype-phenotype relationships and lack disease-specific treatments. Here we provide a framework to identify genotype-specific pathomechanisms and therapeutic targets to accelerate the development of precision medicine. We use human cardiac electromechanical in-silico modelling and simulation which we validate with experimental hiPSC-CM data and modelling in combination with clinical biomarkers. We select hypertrophic cardiomyopathy as a challenge for this approach and study genetic variations that mutate proteins of the thick (MYH7R403Q/+) and thin filaments (TNNT2R92Q/+, TNNI3R21C/+) of the cardiac sarcomere. Using in-silico techniques we show that the destabilisation of myosin super relaxation observed in hiPSC-CMs drives disease in virtual cells and ventricles carrying the MYH7R403Q/+ variant, and that secondary effects on thin filament activation are necessary to precipitate slowed relaxation of the cell and diastolic insufficiency in the chamber. In-silico modelling shows that Mavacamten corrects the MYH7R403Q/+ phenotype in agreement with hiPSC-CM experiments. Our in-silico model predicts that the thin filament variants TNNT2R92Q/+ and TNNI3R21C/+ display altered calcium regulation as central pathomechanism, for which Mavacamten provides incomplete salvage, which we have corroborated in TNNT2R92Q/+ and TNNI3R21C/+ hiPSC-CMs. We define the ideal characteristics of a novel thin filament-targeting compound and show its efficacy in-silico. We demonstrate that hybrid human-based hiPSC-CM and in-silico studies accelerate pathomechanism discovery and classification testing, improving clinical interpretation of genetic variants, and directing rational therapeutic targeting and design.

Background and Aim: Acute sports activities can lead to damage to some tissues of the body (e.g., heart) due to the generation of oxidizing substances, resulting in an increase in troponins I and T levels. This study aimed to investigate the impact of two weeks of ginseng extract (Panax ginseng) supplementation on troponins I and T in male rats in response to acute swimming exercise. Methods: In this experimental study, 40 male Wistar rats (8 weeks old, mean weight of 239.48 ± 6.7 grams) were randomly assigned to four groups: placebo, placebo + acute swimming exercise, ginseng extract supplement, and acute swimming exercise + ginseng extract supplement. The supplement groups received 0.02 ml of ginseng supplement per day for two weeks via gavage. The acute swimming exercise groups engaged in swimming activity until exhaustion in water after the supplementation period. Blood samples were collected from the rats' hearts two hours after acute swimming exercise to measure troponin I and T proteins. Results: Troponin I and T levels significantly increased after acute swimming exercise in both groups compared to pre-activity levels (P < 0.001). Ginseng extract supplementation resulted in a significant decrease in troponin I (P < 0.001) and troponin T (P = 0.019) levels compared to the placebo group following acute swimming exercise. Conclusion: The findings suggest that acute swimming exercise can induce heart damage in rats, and a two-week regimen of ginseng supplementation may mitigate these effects.

Abstract 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.

BACKGROUND: Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death. OBJECTIVES: The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences. METHODS: A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type natriuretic peptide ≥125 pg/mL) at baseline. The effects of intensive vs standard SBP lowering on rates of acute decompensated heart failure (ADHF) events and death and on the incidence and regression of malignant LVH were determined. RESULTS: Randomization to intensive SBP lowering led to similar relative reductions in ADHF events and death across the combined LVH/biomarker groups (P for interaction = 0.68). The absolute risk reduction over 4 years in ADHF events and death was 4.4% (95% CI: -5.2% to 13.9%) among participants with baseline malignant LVH (n = 449) and 1.2% (95% CI: 0.0%-2.5%) for those without LVH and nonelevated biomarkers (n = 4,361). Intensive SBP lowering also reduced the incidence of malignant LVH over 2 years (2.5% vs 1.1%; OR: 0.44; 95% CI: 0.30-0.63). CONCLUSIONS: Intensive SBP lowering prevented malignant LVH and may provide substantial absolute risk reduction in the composite of ADHF events and death among SPRINT participants with baseline malignant LVH.

Background: Troponin I and T are biomarkers to diagnose myocardial infarction and damage. Studies indicate that strenuous physical activity can cause transient increases in these troponin levels, typically considered physiological. However, current data show differences in the exercise-induced increase in troponin I and T in elite athletes. Method: This prospective clinical study aimed to determine troponin I and T levels in 36 top cross-country skiers of the German national team (18 male, 18 female) after a standardized competition load over two days. All study participants underwent a comprehensive sports medical and cardiological evaluation, including ECG and echocardiography. A multivariable regression analysis was utilized to identify possible predictors of increased troponin I levels. Results: Only three male athletes (8.1%) showed an isolated increase in Troponin I (Ø 112.49 ng/L, cut off < 45.2 ng/L), while no increase in troponin T in the study population was detected. Conclusions: The analysis suggested several potential predictors for increased troponin I levels, such as height, weight, weekly training hours, and indications of an enlarged sports heart, though none achieved statistical significance. Knowing the different exercise-induced detectability of the various troponins in the clinical setting is essential. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases are the most common cause of sudden natural deaths. Cardiac troponin T is a specific biochemical marker of myocardial injury. It may help in diagnosis of early myocardial ischemia when macroscopic or microscopic evidence of necrosis is not available after autopsy. Aim of this study was to assess the effectiveness of pericardial fluid troponin T in predicting the cause of death in sudden natural death and in estimating the post mortem interval. Materials and methods: It was a pilot study. Sudden natural deaths brought to Forensic Medicine department of GMCH Nagpur for autopsy were included in this observational cross sectional study. Deaths were grouped into cardiac and non cardiac deaths. Pericardial fluid samples were collected by opening pericardial sac with sterile syringe and processed on Roche Cobas e411 autoanalyzer for estimation of levels of Troponin T. Results: There was a statistically significant difference seen for the values between the groups (p<0.05) for Trop-T (ng/ml) with higher values in Cardiac cause. There was a statistically non significant correlation between postmortem interval vs Trop T (p>0.05). Conclusion: Estimation of pericardial fluid Troponin-T may be used to predict the cause of death in sudden natural death. [ABSTRACT FROM AUTHOR]

The N-terminal region of troponin T (TnT) does not bind any protein of the contractile machinery and the role of its hypervariability remains uncertain. In this review we report the evidence of the interaction between TnT and AMP deaminase (AMPD), a regulated zinc enzyme localized on the myofibril. In periods of intense muscular activity, a decrease in the ATP/ADP ratio, together with a decrease in the tissue pH, is the stimulus for the activation of the enzyme that deaminating AMP to IMP and NH3 displaces the myokinase reaction towards the formation of ATP. In skeletal muscle subjected to strong tetanic contractions, a calpain-like proteolytic activity produces the removal in vivo of a 97-residue N-terminal fragment from the enzyme that becomes desensitized towards the inhibition by ATP, leading to an unrestrained production of NH3. When a 95-residue N-terminal fragment is removed from AMPD by trypsin, simulating in vitro the calpain action, rabbit fast TnT or its phosphorylated 50-residue N-terminal peptide binds AMPD restoring the inhibition by ATP. Taking in consideration that the N-terminus of TnT expressed in human as well as rabbit white muscle contains a zinc-binding motif, we suggest that TnT might mimic the regulatory action of the inhibitory N-terminal domain of AMPD due to the presence of a zinc ion connecting the N-terminal and C-terminal regions of the enzyme, indicating that the two proteins might physiologically associate to modulate muscle contraction and ammonia production in fast-twitching muscle under strenuous conditions. [ABSTRACT FROM AUTHOR]

PURPOSE: Both immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor (VEGFR) inhibitors are approved for advanced renal cell carcinoma treatment and can cause cardiovascular events (CVs); thus, combination therapy could lead to major adverse CV events (MACE). Cardiac serum biomarker assessment and imaging, including left ventricular ejection fraction (LVEF) monitoring, can be used to evaluate MACE. METHODS: To our knowledge, the JAVELIN Renal 101 trial, assessing avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma, is the first randomized study of ICI plus VEGFR inhibitor treatment to include prospective serial cardiac monitoring of LVEF and serum cardiac biomarkers. RESULTS: MACE (defined as grade ≥ 3 CV AEs) occurred in 31 patients (7.1%) in the combination arm and 17 patients (3.9%) in the sunitinib arm. Patients in the combination arm who had high baseline troponin T values were at higher risk of MACE versus patients with low values (MACE in 6/35 v 7/135, respectively; relative risk, 3.31; 95% CI, 1.19 to 9.22). This association was not observed in patients treated with sunitinib. Other CV baseline risk factors and serum cardiac biomarkers were not significantly predictive for MACE, although a trend toward an association with dyslipidemia was seen in the combination arm. No clinical value of on-treatment routine monitoring of LVEF in relation to MACE was observed. Although LVEF decline was significantly more frequent in the combination arm, most patients recovered, and decline was not associated with other significant cardiac events or symptoms. CONCLUSION: Patients with high baseline troponin T levels receiving ICI and VEGFR combinations may need to be monitored more closely for MACE. Routine monitoring of LVEF in asymptomatic patients is not recommended.

ObjectivesThe analytical sensitivity of high-sensitivity cardiac troponin T (hsTnT) assays has enabled rapid myocardial infarction rule-out algorithms for emergency department (ED) presentations. Few studies have analyzed the real-world impact of hsTnT algorithms on outcomes and operations.MethodsComparison of ED length of stay (LOS) and 30-day outcomes (return to ED, inpatient admission, and mortality) for patients presenting with chest pain during 2 separate 208-day periods using a 0/1-hour hsTnT-enabled algorithm or fourth-generation TnT.ResultsDischarge, 30-day readmission, and 30-day mortality rates were not significantly different with fourth-generation TnT vs hsTnT. Thirty-day return rates were significantly decreased with hsTnT (17.4% vs 14.9%; P

Background Assessing the risk of serious adverse events (SAEs) during hypertension treatment is important for understanding the benefit-harm trade-offs of lower blood pressure goals. It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) provide information about SAEs. Methods and Results In SPRINT (Systolic Blood Pressure Intervention Trial), hs-cTnT and NT-proBNP were measured at baseline in 8828 (94.3%) and 8836 (94.4%) participants, respectively. Multivariable Cox proportional hazards models were used to evaluate hs-cTnT and NT-proBNP associations with a composite of SPRINT's SAEs of interest: hypotension, syncope, bradycardia, acute kidney injury, electrolyte abnormalities, and injurious falls. Elevations in hs-cTnT and NT-proBNP were associated with increased composite SAE risk (hazard ratio [HR] per 2-fold higher hs-cTnT: 1.15; 95% CI, 1.06‒1.25; HR per 2-fold higher NT-proBNP: 1.09; 95% CI, 1.05‒1.14). Compared with both hs-cTnT and NT-proBNP in the lower tertiles, both biomarkers in the highest tertile was associated with increased composite SAE risk (HR, 1.56; 95% CI, 1.32‒1.84). Composite SAE risk was higher in the intensive-treatment group than in the standard-treatment group for participants with both biomarkers in the lower tertiles, but similar between treatment groups for participants with both biomarkers in the highest tertile (P for interaction=0.008). Conclusions Elevations in hs-cTnT and NT-proBNP individually and in combination are associated with higher composite SAE risk in SPRINT. The differential impact of blood pressure treatment on SAE risk across combined biomarker categories may have implications for identifying individuals with more favorable benefit-harm profiles for intensive blood pressure lowering.

IntroductionWe investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle-brachial index (ABI).MethodsHs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI 0.9 at baseline and at least one follow-up ABI measurement 3-10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively.ResultsOverall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes.ConclusionsNT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD.

BackgroundElevated cardiac troponin levels in blood are associated with increased risk of cardiovascular diseases and mortality. Cardiac troponin levels are heritable, but their genetic architecture remains elusive.MethodsWe conducted a transethnic genome-wide association analysis on high-sensitivity cTnT (cardiac troponin T; hs-cTnT) and high-sensitivity cTnI (cardiac troponin I; hs-cTnI) levels in 24 617 and 14 336 participants free of coronary heart disease and heart failure from 6 population-based cohorts, followed by a series of bioinformatic analyses to decipher the genetic architecture of hs-cTnT and hs-cTnI.ResultsWe identified 4 genome-wide significant loci for hs-cTnT including a novel locus rs3737882 in PPFIA4 and 3 previously reported loci at NCOA2, TRAM1, and BCL2. One known locus at VCL was replicated for hs-cTnI. One copy of C allele for rs3737882 was associated with a 6% increase in hs-cTnT levels (minor allele frequency, 0.18; P=2.80×10-9). We observed pleiotropic loci located at BAG3 and ANO5. The proportions of variances explained by single-nucleotide polymorphisms were 10.15% and 7.74% for hs-cTnT and hs-cTnI, respectively. Single-nucleotide polymorphisms were colocalized with BCL2 expression in heart tissues and hs-cTnT and with ANO5 expression in artery, heart tissues, and whole blood and both troponins. Mendelian randomization analyses showed that genetically increased hs-cTnT and hs-cTnI levels were associated with higher odds of atrial fibrillation (odds ratio, 1.38 [95% CI, 1.25-1.54] for hs-cTnT and 1.21 [95% CI, 1.06-1.37] for hs-cTnI).ConclusionsWe identified a novel genetic locus associated with hs-cTnT in a multiethnic population and found that genetically regulated troponin levels were associated with atrial fibrillation.

Background and objectives: As part of the LIFE Child study, we previously described the associations between N-terminal-pro-hormone brain natriuretic peptide (NT-proBNP) and hs-troponin T (hs-TnT) levels and an individual’s sex, age and pubertal status, as well as with body mass index (BMI) and serum lipid levels. For NT-proBNP, we found inverse associations with advancing puberty, increasing BMI and serum lipid levels. These findings led us to further question the putative influences of the developing individual’s metabolic and growth status as represented by levels of insulin-like growth factor-1 (IGF-1) and IGF-1- binding protein-3 (IGF-BP3) as well as hemoglobin A1c (HbA1c) and Cystatin C (CysC). Material and methods: Serum values, medical history and anthropometric data provided by 2522 children aged 0.25–18 years were collected and analyzed as per study protocol. Results: A strong negative association between NT-proBNP values and IGF-1, IGF-BP3 and HbA1c levels was identified. For IGF-BP3, this interaction was m odulated by sex and age, for HbA1c only by age. For hs-TnT, a positive association was found with IGF-BP3, IGF-1 and CysC. The association between hs-TnT and IGF-1 was sex dependent. The association between CysC and hs-TnT was stronger in girls, but the interaction with age was only seen in boys. Between hs-TnT and HbA1c, the association was sig nificantly negative and modulated by age. Conclusion: Based on our large pediatric cohort, we could identify age- and sex-dependent interactions between the metabolic status represented by IGF-1, IGF-BP3, CysC and HbA1c levels and the cardiac markers NT-proBNP and hs-TnT.

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. [ABSTRACT FROM AUTHOR]

Coronary low-attenuation plaque (LAP) burden is a strong predictor of myocardial infarction in patients with stable chest pain. We aimed to assess the relationship between LAP burden and circulating levels of high-sensitivity cardiac troponin T (hs-cTnT), and to explore the potential underlying etiology in patients undergoing clinically indicated coronary CT angiography (CCTA). A comprehensive metabolic and lipid panel, as well as C-reactive protein (CRP) and hs-cTnT tests were obtained from consecutive patients with stable chest pain at the time of CCTA. Qualitative and quantitative coronary plaque analysis, CT-derived fractional flow reserve (FFR) calculation, and pericoronary adipose tissue (PCAT) attenuation measurement around the right coronary artery were performed on CCTA images. Linear regression analyses were performed to identify independent associations with hs-cTnT concentration and mediation analysis was used to assess whether ischemia or markers of inflammation mediate hs-cTnT elevation. In total, 114 patients (56.3 ​± ​10.6 years, 44.7 ​% female) were enrolled. In multivariable analysis, age (β ​= ​0.04 [95%CI: 0.02; 0.06], p ​< ​0.001), female sex (β ​= ​−0.77 [95%CI: −1.20; 0.33], p ​< ​0.001), and LAP burden (β ​= ​0.03 [95%CI: 0.001; 0.06], p ​= ​0.04) were independently associated with hs-cTnT levels. Mediation analysis, on the other hand, did not identify a significant mediating effect of lesion-specific ischemia based on CT-FFR, circulating CRP levels, or PCAT values between LAP burden and hs-cTnT levels (all p ​> ​0.05). Although ischemia and inflammation have previously been proposed to mediate the association between LAP burden and hs-cTnT levels, our results did not confirm the role of these pathophysiological pathways in patients with stable chest pain. Recent evidence has shed light on the relationship between cardiac troponin and coronary low-attenuation plaque burden in patients presenting to the emergency department with acute chest pain. According to our results, circulating levels of high-sensitivity troponin T are associated with total low-attenuation plaque volume even in patients with stable chest pain. This association is not mediated by previously proposed pathways, such as the presence of hemodynamically significant stenosis or systemic/pericoronary inflammation, further supporting the concept of vulnerable plaques. Measurement of high-sensitivity troponin T in chronic coronary syndromes may allow the more accurate risk stratification of patients. [ABSTRACT FROM AUTHOR]

Objective: It has been stated that colchicine can reduce the cytokine storm and inflammation in cardiac myocytes during COVID-19 infection. This study aims to investigate the effect of colchicine treatment on cardiac and inflammatory markers in COVID-19 patients followed in the intensive care Unit (ICU) of a tertiary center. Materials and Methods: Patients followed up in the ICU with the diagnosis of COVID-19 between April 2020 and June 2020 were evaluated retrospectively. Patients who received standard treatment in moderate-to-severe COVID-19 patients were analyzed by classifying them as the control group and patients who were added to the standard treatment within the first 48 h as the colchicine group. Results: A total of 79 patients, 39 in the colchicine group and 40 in the control group, were included in the study. Demographic data and the presence of comorbid disease were similar between groups. The mean length of stay in the ICU was 19.4±8 days in the colchicine group and 14.7±7 days in the control group. The length of stay in the ICU was found to be significantly higher in the colchicine group (p=0.017). There was no significant difference between the groups in terms of C-reactive protein, Interleukin-6, troponin T and D-dimer levels, and 28-day mortality (94.9% vs. 95%, p>0.05). Conclusion: Adding oral colchicine to the standard treatment within the first 48 h after hospitalization in moderate-to-severe COVID-19 patients followed in the ICU did not improve the clinical status of the patients. It did not reduce cardiac and inflammatory markers and mortality rates. [ABSTRACT FROM AUTHOR]

Background: A novel beta-Coronavirus related to Severe Adult Distress Syndrome, named SARS-CoV was the cause of pandemic with more than 24 million people contaminated. COVID-19, the disease provoked by the virus, resulted in more than 80,000 deaths in quite 200 countries worldwide. Several cardiovascular complications were reported in literature like arrhythmias, myocarditis, pericarditis, heart failure, myocardial ischemia, myocardial infarction, and Takotsubo syndrome. To our knowledge several cases of myocarditis associated with SARS-CoV-2 have been reported so far; nevertheless, to date, there is a knowledge gap regarding the real prevalence of this cardiac involvement, its pathologic pathway and specific characteristics of patients who experience this complication. Thus, we will analyze the data of covid 19 cases on the basis of appropriate sample size of the patients admitted in our hospital. Objectives: 1. Study of hospital related outcome of Covid 19 patients with suspected myocarditis, 2. Correlation of NT-PROBNP levels, TROPONIN T in suspected case of myocarditis with outcomes. Methods: Study Design: Hospital based retrospective study Setting: Patients admitted in ICU in SMS Medical College and attached hospitals Result: Patients with myocarditis had significantly more prolonged hospitalization 14.75±8.53 days as compare to without myocarditis 10.44±4.16 days (P value .009), they had the non-significant values of IL-6 level, NT-pro-BNP and T-troponin patients without myocarditis Conclusion: Myocarditis is a severe cardiac complication in SARS-CoV-2 infection. Present study showed that in COVID-19 patients myocarditis was associated with more severe infection and a higher need for oxygen therapy, a higher rate of cardiac disease, and a longer hospitalization. [ABSTRACT FROM AUTHOR]

The identification and appropriate management of patients at risk of suffering from acute chest pain (ACP) in prehospital care are not straightforward. This task could benefit, as occurs in emergency departments (EDs), from cardiac enzyme assessment. The aim of the present work was to derive and validate a scoring system based on troponin T (cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP), and D-dimer to predict 1-year mortality in patients with ACP. This was a prospective, multicenter, ambulance-based cohort study of adult patients with a prehospital ACP diagnosis who were evacuated by ambulance to the ED between October 2019 and July 2021. The primary outcome was 365-day cumulative mortality. A total of 496 patients fulfilled the inclusion criteria. The mortality rate was 12.1% (60 patients). The scores derived from cTnT, NT-proBNP, and D-dimer presented an AUC of 0.802 (95% CI: 0718-0.886) for 365-day mortality. This AUC was superior to that of each individual cardiac enzyme. Our study provides promising evidence for the predictive value of a risk score based on cTnT, NT-proBNP, and D-dimer for the prediction of 1-year mortality in patients with ACP. The implementation of this score has the potential to benefit emergency medical service care and facilitate the on-scene decision-making process. [ABSTRACT FROM AUTHOR]

BackgroundCardiac involvement among hospitalized patients with severe coronavirus disease 2019 (COVID-19) is common and associated with adverse outcomes. This study aimed to determine the prevalence and clinical implications of COVID-19 cardiac involvement in young competitive athletes.MethodsIn this prospective, multicenter, observational cohort study with data from 42 colleges and universities, we assessed the prevalence, clinical characteristics, and outcomes of COVID-19 cardiac involvement among collegiate athletes in the United States. Data were collected from September 1, 2020, to December 31, 2020. The primary outcome was the prevalence of definite, probable, or possible COVID-19 cardiac involvement based on imaging definitions adapted from the Updated Lake Louise Imaging Criteria. Secondary outcomes included the diagnostic yield of cardiac testing, predictors for cardiac involvement, and adverse cardiovascular events or hospitalizations.ResultsAmong 19 378 athletes tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 3018 (mean age, 20 years [SD, 1 year]; 32% female) tested positive and underwent cardiac evaluation. A total of 2820 athletes underwent at least 1 element of cardiac triad testing (12-lead ECG, troponin, transthoracic echocardiography) followed by cardiac magnetic resonance imaging (CMR) if clinically indicated. In contrast, primary screening CMR was performed in 198 athletes. Abnormal findings suggestive of SARS-CoV-2 cardiac involvement were detected by ECG (21 of 2999 [0.7%]), cardiac troponin (24 of 2719 [0.9%]), and transthoracic echocardiography (24 of 2556 [0.9%]). Definite, probable, or possible SARS-CoV-2 cardiac involvement was identified in 21 of 3018 (0.7%) athletes, including 15 of 2820 (0.5%) who underwent clinically indicated CMR (n=119) and 6 of 198 (3.0%) who underwent primary screening CMR. Accordingly, the diagnostic yield of CMR for SARS-CoV-2 cardiac involvement was 4.2 times higher for a clinically indicated CMR (15 of 119 [12.6%]) versus a primary screening CMR (6 of 198 [3.0%]). After adjustment for race and sex, predictors of SARS-CoV-2 cardiac involvement included cardiopulmonary symptoms (odds ratio, 3.1 [95% CI, 1.2, 7.7]) or at least 1 abnormal triad test result (odds ratio, 37.4 [95% CI, 13.3, 105.3]). Five (0.2%) athletes required hospitalization for noncardiac complications of COVID-19. During clinical surveillance (median follow-up, 113 days [interquartile range=90 146]), there was 1 (0.03%) adverse cardiac event, likely unrelated to SARS-CoV-2 infection.ConclusionsSARS-CoV-2 infection among young competitive athletes is associated with a low prevalence of cardiac involvement and a low risk of clinical events in short-term follow-up.

Abstract Background Sepsis-induced myocardial injury (SIMI) is a common organ dysfunction and is associated with higher mortality in patients with sepsis. We aim to construct a nomogram prediction model to assess the 28-day mortality in patients with SIMI. . Method We retrospectively extracted data from Medical Information Mart for Intensive Care (MIMIC-IV) open-source clinical database. SIMI was defined by Troponin T (higher than the 99th percentile of upper reference limit value) and patients with cardiovascular disease were excluded. A prediction model was constructed in the training cohort by backward stepwise Cox proportional hazards regression model. The concordance index (C-index), area under the receiver operating characteristics curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting and decision-curve analysis (DCA) were used to evaluate the nomogram. Results 1312 patients with sepsis were included in this study and 1037 (79%) of them presented with SIMI. The multivariate Cox regression analysis in all septic patients revealed that SIMI was independently associated with 28-day mortality of septic patients. The risk factors of diabetes, Apache II score, mechanical ventilation, vasoactive support, Troponin T and creatinine were included in the model and a nomogram was constructed based on the model. The C-index, AUC, NRI, IDI, calibration plotting and DCA showed that the performance of the nomogram was better than the single SOFA score and Troponin T. Conclusion SIMI is related to the 28-day mortality of septic patients. The nomogram is a well-performed tool to predict accurately the 28-day mortality in patients with SIMI.

BackgroundWe examined the association of objective and subjective oral health markers with inflammatory, hemostatic, and cardiac biomarkers in older age.MethodsCross-sectional analyses were based on the British Regional Heart Study (BRHS) comprising British men aged 71-92 years (n = 2,147), and the Health, Aging and Body Composition (HABC) Study comprising American men and women aged 71-80 years (n = 3,075). Oral health markers included periodontal disease, tooth count, dry mouth. Inflammatory biomarkers included C-reactive protein (CRP), interleukin-6 (IL-6) in both studies, and tissue plasminogen activator (t-PA), von Willebrand Factor (vWF), fibrin D-dimer, high-sensitivity Troponin T (hsTnT), and N-terminal pro-brain natriuretic peptide (NTproBNP) only in the BRHS.ResultsIn both studies, tooth loss, was associated with the top tertile of CRP-odds ratios (ORs) (95% confidence interval [CI]) are 1.31 (1.02-1.68) in BRHS; and 1.40 (1.13-1.75) in the HABC Study, after adjusting for confounders. In the HABC Study, cumulative (≥3) oral health problems were associated with higher levels of CRP (OR [95% CI] =1.42 [1.01-1.99]). In the BRHS, complete and partial tooth loss was associated with hemostatic factors, in particular with the top tertile of fibrin D-dimer (OR [95% CI] = 1.64 [1.16-2.30] and 1.37 [1.05-1.77], respectively). Tooth loss and periodontal disease were associated with increased levels of hsTnT.ConclusionsPoor oral health in older age, particularly tooth loss, was consistently associated with some inflammatory, hemostatic, and cardiac biomarkers. Prospective studies and intervention trials could help understand better if poor oral health is causally linked to inflammatory, hemostatic, and cardiac biomarkers.

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiovascular disease and often results in cardiac remodeling and an increased incidence of sudden cardiac arrest (SCA) and death, especially in youth and young adults. Among thousands of different variants found in HCM patients, variants of TNNT2 (cardiac troponin T-TNNT2) are linked to increased risk of ventricular arrhythmogenesis and sudden death despite causing little to no cardiac hypertrophy. Therefore, studying the effect of TNNT2 variants on cardiac propensity for arrhythmogenesis can pave the way for characterizing HCM in susceptible patients before sudden cardiac arrest occurs. In this study, a TNNT2 variant, I79N, was generated in human cardiac recombinant/reconstituted thin filaments (hcRTF) to investigate the effect of the mutation on myofilament Ca2+ sensitivity and Ca2+ dissociation rate using steady-state and stopped-flow fluorescence techniques. The results revealed that the I79N variant significantly increases myofilament Ca2+ sensitivity and decreases the Ca2+ off-rate constant (k off). To investigate further, a heterozygous I79N+/- TNNT2 variant was introduced into human-induced pluripotent stem cells using CRISPR/Cas9 and subsequently differentiated into ventricular cardiomyocytes (hiPSC-CMs). To study the arrhythmogenic properties, monolayers of I79N+/- hiPSC-CMs were studied in comparison to their isogenic controls. Arrhythmogenesis was investigated by measuring voltage (V m) and cytosolic Ca2+ transients over a range of stimulation frequencies. An increasing stimulation frequency was applied to the cells, from 55 to 75 bpm. The results of this protocol showed that the TnT-I79N cells had reduced intracellular Ca2+ transients due to the enhanced cytosolic Ca2+ buffering. These changes in Ca2+ handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. While wild-type (WT) hiPSC-CMs were accurately entrained to frequencies of at least 150 bpm, the I79N hiPSC-CMs demonstrated clear patterns of alternans for both V m and Ca2+ transients at frequencies >75 bpm. Lastly, a transcriptomic analysis was conducted on WT vs. I79N+/- TNNT2 hiPSC-CMs using a custom NanoString codeset. The results showed a significant upregulation of NPPA (atrial natriuretic peptide), NPPB (brain natriuretic peptide), Notch signaling pathway components, and other extracellular matrix (ECM) remodeling components in I79N+/- vs. the isogenic control. This significant shift demonstrates that this missense in the TNNT2 transcript likely causes a biophysical trigger, which initiates this significant alteration in the transcriptome. This TnT-I79N hiPSC-CM model not only reproduces key cellular features of HCM-linked mutations but also suggests that this variant causes uncharted pro-arrhythmic changes to the human action potential and gene expression.

Upper reference limits of high-sensitivity cardiac troponin T (hs-cTnT) are derived from healthy, population-based cohorts, and are frequently exceeded in hospitalized patients. In this study we aim to systematically examine the differences between in-hospital patients with no diagnosed cardiac diseases and a population-based cohort. Retrospective analyses were performed in two independent cohorts. We included 5,652 participants of the prospective population-based LIFE cohort as well as 9,300 patients having been treated at our hospital between 2014 and 2021. In both cohorts, subjects with diagnosed or suspected cardiac diseases were excluded. We used Spearman's rank correlation for correlation analyses of hs-cTnT serum concentrations and age. Sex- and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained in both cohorts. In both cohorts, hs-cTnT serum concentrations positively correlated with age. Male sex was associated with higher hs-cTnT serum concentrations. Persons treated in hospital showed significantly higher hs-cTnT concentrations in females and males aged above 50. While in the population-based cohort only 99th percentile hs-cTnT results of females aged above 70 and males aged above 60 years exceeded the assay's upper reference limit, the 99th percentiles of in-hospital females over 40 years and males of all age groups exceeded this threshold. Besides age and sex, hospitalization per se is correlated with higher serum concentrations of hs-cTnT in most age groups. Our results indicate, that unconditionally applying current hs-cTnT cut-offs to inpatients might overestimate myocardial infarction and potentially lead to overdiagnosis. [ABSTRACT FROM AUTHOR]

Background Elevated troponin T (cTnT) and/or troponin I (cTnI) can be ascribed to multiple causes, mostly resulting from cardiac tissue damage and in lesser numbers resulting from non-cardiac related causes. The presence of macrotroponins is easily overlooked, with potentially negative consequences. Case summary This case report presents a case study of a 12-year-old child known to have MYH7 gene–associated hypertrophic cardiomyopathy with acute chest pain combined with an unexpected high cTnT and cTnI. A cardiac cause was deemed unlikely after additional investigation, as these showed no abnormalities. After consulting a laboratory specialist, it could be concluded that the high cTnT and cTnI were a result of macrotroponin complexes, a protein complex consisting of circulating protein and endogenous autoantibodies against that protein, resulting in elevated values with misguiding and uncertain clinical significance. Discussion Awareness of the existence of macrotroponins could have prevented costly diagnostics and prolonged hospital admission with grave psychological impact, especially in children. [ABSTRACT FROM AUTHOR]

Study objectiveOur objective is to describe the rates of diagnostic reclassification between conventional cardiac troponin I (cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) and between combined and sex-specific hs-cTnT thresholds in adult emergency department (ED) patients in the United States.MethodsWe conducted a prospective, single-center, before-and-after, observational study of ED patients aged 18 years or older undergoing single or serial cardiac troponin testing in the ED for any reason before and after hs-cTnT implementation. Conventional cTnI and hs-cTnT results were obtained from a laboratory quality assurance database. Combined and sex-specific thresholds were the published 99th percentile upper reference limits for each assay. Cases underwent physician adjudication using the Fourth Universal Definition of Myocardial Infarction. Diagnostic reclassification occurred when a patient received a diagnosis of myocardial infarction or myocardial injury with one assay but not the other assay. Our primary outcome was diagnostic reclassification between the conventional cTnI and hs-cTnT assays. Diagnostic reclassification probabilities were assessed with sample proportions and 95% confidence intervals for binomial data.ResultsWe studied 1,016 patients (506 men [50%]; median age 60 years [25th, 75th percentiles 49, 71]). Between the conventional cTnI and hs-cTnT assays, 6 patients (0.6%; 95% confidence interval 0.2% to 1.3%) underwent diagnostic reclassification regarding myocardial infarction (5/6 reclassified as no myocardial infarction) and 166 patients (16%; 95% confidence interval 14% to 19%) underwent diagnostic reclassification regarding myocardial injury (154/166 reclassified as having myocardial injury) by hs-cTnT.ConclusionCompared with conventional cTnI, the hs-cTnT assay resulted in no clinically relevant change in myocardial infarction diagnoses but substantially more myocardial injury diagnoses.

Objectives Biotin >20.0 ng/mL (81.8 nmol/L) can reduce Elecsys® Troponin T Gen 5 (TnT Gen 5; Roche Diagnostics) assay recovery, potentially leading to false-negative results in patients with suspected acute myocardial infarction (AMI). We aimed to determine the prevalence of elevated biotin and AMI misclassification risk from biotin interference with the TnT Gen 5 assay. Methods Biotin was measured using an Elecsys assay in two cohorts: (i) 797 0-h and 646 3-h samples from 850 US emergency department patients with suspected acute coronary syndrome (ACS); (ii) 2023 random samples from a US laboratory network, in which biotin distributions were extrapolated for higher values using pharmacokinetic modeling. Biotin >20.0 ng/mL (81.8 nmol/L) prevalence and biotin 99th percentile values were calculated. AMI misclassification risk due to biotin interference with the TnT Gen 5 assay was modeled using different assay cutoffs and test timepoints. Results ACS cohort: 1/797 (0.13%) 0-h and 1/646 (0.15%) 3-h samples had biotin >20.0 ng/mL (81.8 nmol/L); 99th percentile biotin was 2.62 ng/mL (10.7 nmol/L; 0-h) and 2.38 ng/mL (9.74 nmol/L; 3-h). Using conservative assumptions, the likelihood of false-negative AMI prediction due to biotin interference was 0.026% (0-h result; 19 ng/L TnT Gen 5 assay cutoff). US laboratory cohort: 15/2023 (0.74%) samples had biotin >20.0 ng/mL (81.8 nmol/L); 99th percentile biotin was 16.6 ng/mL (68.0 nmol/L). Misclassification risk due to biotin interference (19 ng/L TnT Gen 5 assay cutoff) was 0.025% (0-h), 0.0064% (1-h), 0.00048% (3-h), and

BackgroundTo assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry.MethodsWe sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3634), compared findings with additional populations and White HCM cohorts (n=6179), and performed in vitro functional studies.ResultsSingaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (pathogenic/likely pathogenic: 18%, P

Background Current strategies for cardiovascular disease (CVD) risk assessment focus on 10-year or longer timeframes. Shorter-term CVD risk is also clinically relevant, particularly for high-risk occupations, but is under-investigated. Methods and Results We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi-Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N-terminal pro-B-type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high-sensitivity cardiac troponin T (abnormal >5 ng/L); high-sensitivity C-reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima-media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3-year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3-year multivariable-adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2-, 3-, 4.5- and 8-fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non-fatal myocardial infarction or stroke). Conclusions A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3-year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

BackgroundThe accuracy and speed by which acute myocardial infarction (AMI) is excluded are an important determinant of emergency department (ED) length of stay and resource utilization. While high-sensitivity troponin I (hsTnI) >99th percentile (upper reference level [URL]) represents a "rule-in" cutpoint, our purpose was to evaluate the ability of the Beckman Coulter hsTnI assay, using various level-of-quantification (LoQ) cutpoints, to rule out AMI within 3 hours of ED presentation in suspected acute coronary syndrome (ACS) patients.MethodsThis multicenter evaluation enrolled adults with >5 minutes of ACS symptoms and an electrocardiogram obtained per standard care. Exclusions were ST-segment elevation or chronic hemodialysis. After informed consent was obtained, blood samples were collected in heparin at ED admission (baseline), ≥1 to 3, ≥3 to 6, and ≥6 to 9 hours postadmission. Samples were processed and stored at -20°C within 1 hour and were tested at three independent clinical laboratories on an immunoassay system (DxI 800, Beckman Coulter). Analytic cutpoints were the URL of 17.9 ng/L and two LoQ cutpoints, defined as the 10 and 20% coefficient of variation (5.6 and 2.3 ng/L, respectively). A criterion standard MI diagnosis was adjudicated by an independent endpoint committee, blinded to hsTnI, and using the universal definition of MI.ResultsOf 1,049 patients meeting the entry criteria, and with baseline and 1- to 3-hour hsTnI results, 117 (11.2%) had an adjudicated final diagnosis of AMI. AMI patients were typically older, with more cardiovascular risk factors. Median (IQR) presentation time was 4 (1.6-16.0) hours after symptom onset, although AMI patients presented ~0.5 hour earlier than non-AMI. Enrollment and first blood draw occurred at a mean of ~1 hour after arrival. To evaluate the assay's rule-out performance, patients with any hsTnI > URL were considered high risk and were excluded. The remaining population (n = 829) was divided into four LoQ relative categories: both hsTnI  LoQ (Lo-Hi cohort); first > LoQ and second  LoQ (Hi-Hi cohort). In patients with any hsTnI result 3 hours after the onset of suspected ACS symptoms, with at least two Beckman Coulter Access hsTnI LoQ had inadequate sensitivity and NPV.