Cardiac biomarkers are associated with increased risks of adverse clinical outcomes after ischemic stroke.

BACKGROUND: Impaired cardiac function was suggested to be implicated in the functional recovery after ischemic stroke, but the prognostic value of cardiac biomarkers among ischemic stroke patients remains unclear. We aimed to prospectively explore the associations of serum lactate dehydrogenase (LDH), plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), and plasma high-sensitivity cardiac troponin T (hs-cTnT) with adverse clinical outcomes after ischemic stroke in a large-scale cohort study. METHODS: We measured serum LDH, plasma NT-proBNP, and plasma hs-cTnT levels at baseline among 5056 ischemic stroke patients from the Minhang Stroke Cohort study. All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was composite outcome of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and ordered 7-level categorical score of the mRS. RESULTS: During 3 months of follow-up, 1584 patients developed the primary outcome. Baseline serum LDH, plasma NT-proBNP, and plasma hs-cTnT were positively associated with the risk of adverse outcomes after ischemic stroke. The multivariable-adjusted odds ratios of primary outcome for the highest versus lowest quartile of LDH, NT-proBNP, and hs-cTnT were 1.37 (95% CI 1.13-1.66; Ptrend = 0.001), 2.51 (95% CI, 2.00-3.16; Ptrend < 0.001), and 2.24 (95% CI 1.77-2.83; Ptrend < 0.001), respectively. Each SD increase of log-transformed cardiac biomarker score was associated with a 49% (95% CI 37-62%; P < 0.001) increased risk of primary outcome. Multivariable-adjusted spline regression analyses showed linear relationships between cardiac biomarkers and the risk of primary outcome (all P for linearity < 0.001). Moreover, adding LDH, NT-proBNP, hs-cTnT, or cardiac biomarker score to conventional risk factors significantly improved the risk reclassification of primary outcome after ischemic stroke (all P < 0.05). CONCLUSION: High LDH, NT-proBNP, hs-cTnT, and cardiac biomarker score were independently associated with increased risks of adverse clinical outcomes among ischemic stroke patients, suggesting that cardiac biomarkers might be potential prognostic biomarkers for ischemic stroke.

Association Between High-Sensitivity Troponin (hs-cTnT) and Diagnosis of Myocarditis in Previously Healthy Pediatric Patients.

Cardiac troponin is commonly used to screen for cardiac diagnoses in pediatric patients, as it is only released by myocardial tissue. There is limited data regarding high-sensitivity troponin T in pediatric populations and its clinical interpretation. We sought to determine how high-sensitivity troponin values are associated with myocarditis diagnosis. High sensitivity troponin levels were reviewed for pediatric patients at our center from February 2022 to February 2023. Basic demographic and presenting data (including age, gender, body mass index), and diagnoses (cardiac diagnosis, including myocarditis, vs non-cardiac) were compared for patients with elevated initial troponin levels (≥ 12 ng/L) vs. those with non-elevated values. Of the 308 patients included, 91 (29.5%) had elevated hs-cTnT and 45 (14.6%) had a cardiac diagnosis, of whom 8 (2.5%) were ultimately diagnosed with acute myocarditis. There was no meaningful difference in demographic characteristics between the elevated and non-elevated hs-cTnT groups. For patients with diagnosis of myocarditis (n = 8), median peak levels were 506.5 ng/L (182.0 to 1184.0) versus 6.0 ng/L (< 6.0 to 13.5) for those with all other diagnoses (n = 300) (p < 0.001). A high sensitivity troponin cut-off value of 90 ng/dL was established for diagnosis of myocarditis, providing high sensitivity (100%) and specificity of (95%).

High-Sensitivity Cardiac Troponin T and Cardiovascular Risk After Ischemic Stroke or Transient Ischemic Attack.

Background: High-sensitivity cardiac troponin T (hs-cTnT) is associated with cardiovascular disease (CVD) risk in general and various high-risk populations. Objectives: The purpose of this study was to precisely characterize the association of hs-cTnT with CVD risk in patients following acute ischemic stroke or transient ischemic attack. Methods: We conducted post hoc analyses of data from the STROKE-CARD trial (NCT02156778), a pragmatic randomized controlled trial of a disease management program in patients with acute ischemic stroke or transient ischemic attack (ABCD2 score ≥3). We measured hs-cTnT on admission (Roche Elecsys, detection limit 5 ng/L) and quantified HRs for a composite CVD outcome (ie, stroke, myocardial infarction, CVD death) adjusted for age, sex, prior coronary heart disease, prior heart failure, diabetes, smoking, systolic blood pressure, and low- and high-density-lipoprotein cholesterol. Results: Among 1,687 patients (mean age, 69.3 ± 13.7 years; 40.7% female), hs-cTnT was detectable in 80.7%. Median hs-cTnT was 10 ng/L (IQR: 6-18 ng/L). Over a median follow-up of 12.1 months, 110 patients had a CVD event. The association of hs-cTnT level with CVD risk was of log-linear shape, with a multivariable-adjusted HR of 1.40 (95% CI: 1.15-1.70; P < 0.001) per 1-SD higher log-transformed hs-cTnT value. The strength of association was similar when further adjusted for other potential confounders and across clinically relevant subgroups. Corresponding outcome-specific HRs were 1.33 (95% CI: 1.06-1.68; P = 0.016) for stroke, 1.28 (95% CI: 0.69-2.37; P = 0.430) for myocardial infarction, 1.98 (95% CI: 1.43-2.73; P < 0.001) for CVD death, and 1.93 (95% CI: 1.54-2.41; P < 0.001) for all-cause death. Conclusions: High hs-cTnT is associated with increased CVD risk in ischemic stroke and transient ischemic attack patients.

Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T.

AIMS: Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations. METHODS AND RESULTS: Observational US cohort study of emergency department patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase > 99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of ≥52, >100, >200, or >300 ng/L, positive predictive values (PPVs) for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89), and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82), and 54% (95% CI 25-81). In CKD patients with a 2 h hs-cTnT delta of ≥10, >20, or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96), and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86), and 75% (95% CI 58-88). CONCLUSION: Diagnostic performance of standard baseline and serial 2 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.

High-Sensitivity Troponin T, NT-proBNP, and Cognitive Outcomes in SPRINT.

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.

Masked ECG Changes in Wolff-Parkinson-White Syndrome Coexisting With Myocardial Infarction: A Case Report.

Wolff-Parkinson-White (WPW) syndrome, known for episodes of tachycardia and distinctive electrocardiographic (ECG) patterns, often makes it harder to diagnose myocardial infarction (MI) because it can hide the usual ECG signs of MI. Early use of high-sensitivity troponin levels and echocardiography to detect myocardial injury in WPW is important, facilitates timely intervention and improves patient outcomes. This report presents the case of a 39-year-old Caucasian male with no chronic disease history who presented to a family health center with intermittent mild chest pain localized to the left side, characterized by a burning and dull ache, for one week. On the day of presentation, the patient experienced increased pain accompanied by palpitations and mild sweating. An ECG at the family health center showed findings of WPW. Due to the presence of typical chest pain and WPW pattern on the ECG, the patient was referred to a tertiary hospital emergency department. At the tertiary hospital, repeat ECGs showed no changes, but blood tests revealed elevated troponin T levels (495 ng/ml initially, 485 ng/ml after 4 hours). The patient was admitted to the cardiology critical care ward. Echocardiography indicated regional wall motion abnormalities in specific segments. Coronary angiography revealed ectasia in vessels with slow flow but no obstructed vessels. This case underscores the diagnostic challenges posed by WPW syndrome in the context of MI and highlights the importance of using high-sensitivity troponin levels and echocardiography for early diagnosis to improve patient outcomes.

Cardiovascular medications, high-sensitivity cardiac troponin T concentrations, and long-term outcome in non-ST segment elevation acute coronary syndrome.

AIMS: Cardiac troponin plays an essential role in the management of non-ST segment elevation acute coronary syndrome (NSTE-ACS). However, it is not clear whether troponin concentrations provide guidance regarding the initiation of prognostically beneficial cardiovascular medications [i.e. betablockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and statins] in NSTE-ACS. METHODS AND RESULTS: Registry-based study investigating three NSTE-ACS cohorts (n = 43 075, 40 162, and 46 698) with elevated high-sensitivity cardiac troponin concentrations >14 ng/L. Cox proportional regression models with the addition of interaction terms were used to analyse the interrelations of high-sensitivity cardiac troponin T (hs-cTnT) concentrations, new initiated medications with the respective three drug classes, and long-term risk of all-cause mortality and major adverse events (MAE). Betablockers were associated with risk reductions of 8 and 5% regarding all-cause mortality and MAE, respectively. There was no evidence of an interaction with hs-cTnT concentrations. RAAS inhibitors were associated with 13 and 8% risk reductions, respectively, with a weak interaction between hs-cTnT and MAE (Pinteraction = 0.016). However, no increasing prognostic benefit was noted at hs-cTnT concentrations >100 ng/L. Statins were associated with 38 and 32% risk reductions, respectively, with prognostic benefit across the entire range of hs-cTnT concentrations, and with a weak interaction regarding MAE (Pinteraction = 0.011). CONCLUSION: Cardiovascular medications provide different prognostic benefit in patients with NSTE-ACS with elevated hs-cTnT, and there was some evidence of greater treatment effects regarding MAE along with higher hs-cTnT concentrations. However, hs-cTnT appears only to have limited value overall for customizing such treatments.

RNA Sequencing Screens the Key Genes and Pathways in a Mouse Model of HFpEF.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality but without available evidence-based therapies. It is essential to investigate changes in gene expression profiles in preclinical HFpEF animal models, with the aim of searching for novel therapeutic targets. METHODS: Wild-type male C57BL/6J mice were administrated with a combination of high-fat diet (HFD) and inhibition of constitutive nitric oxide synthase using N-nitro-l-arginine methyl ester (l-NAME) for 5 and 7 weeks. RNA sequencing was conducted to detect gene expression profiles, and bioinformatic analysis was performed to identify the core genes, pathways, and biological processes involved. RESULTS: A total of 1,347 genes were differentially expressed in the heart at week 5 and 7 post-intervention. Gene Ontology enrichment analysis indicated that these greatly changed genes were involved mainly in cell adhesion, neutrophil chemotaxis, cell communication, and other functions. Using hierarchical cluster analysis, these differentially expressed genes were classified into 16 profiles. Of these, three significant profiles were ultimately identified. Gene co-expression network analysis suggested troponin T type 1 (Tnnt1) directly regulated 31 neighboring genes and was considered to be at the core of the associated gene network. CONCLUSION: The combined application of RNA sequencing, hierarchical cluster analysis, and gene network analysis identified Tnnt1 as the most important gene in the development of HFpEF.

Effects of mild hypercapnia on myocardial injury after out-of-hospital cardiac arrest. A sub-study of the TAME trial.

PURPOSE: Mild hypercapnia did not improve neurological outcomes for resuscitated out-of-hospital cardiac arrest (OHCA) patients in the Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial. However, the effects of hypercapnic acidosis on myocardial injury in patients with cardiac arrest is unexplored. We investigated whether mild hypercapnia compared to normocapnia, following emergency coronary intervention, increased myocardial injury in comatose OHCA-patients with AMI. METHODS: Single-centre, prospective, pre-planned sub-study of the TAME trial. Patients were randomised to targeted mild hypercapnia (PaCO2 = 6.7-7.3 kPa) or normocapnia (PaCO2 = 4.7-6.0 kPa) for 24 h. Myocardial injury was assessed with high-sensitive cardiac troponin T (hs-cTnT) measured at baseline, 24, 48 and 72 h. Haemodynamics were assessed with right heart catheterisation and blood-gas analyses every 4th hour for 48 h. RESULTS: We included 125 OHCA-patients. 57 (46%) had an AMI, with 31 and 26 patients randomised to hypercapnia and normocapnia, respectively. Median peak hs-cTnT in AMI-patients was 58% lower in the hypercapnia-group: 2136 (IQR: 861-4462) versus 5165 ng/L (IQR: 2773-7519), p = 0.007. Lower average area under the hs-cTnT curve was observed in the hypercapnia-group: 2353 (95% CI 1388-3319) versus 4953 ng/L (95% CI 3566-6341), P-group = 0.002. Hypercapnia was associated with increased cardiac power output (CPO) and lower lactate levels in patients with AMI (P-group < 0.05). hs-cTnT, lactate and CPO were not significantly different between intervention groups in OHCA-patients without AMI (p > 0.05). CONCLUSIONS: Mild hypercapnia was not associated with increased myocardial injury in resuscitated OHCA-patients. In AMI-patients, mild hypercapnia was associated with lower hs-cTnT and lactate, and improved cardiac performance. TRIAL REGISTRATION NUMBER: NCT03114033.

Association of high-sensitivity troponin T with left ventricular dysfunction in prediabetes.

BACKGROUND: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are an increasingly serious problem worldwide. Tissue Doppler imaging (TDI), a non-invasive technique, may evaluate both systolic and diastolic function during the first phases of cardiovascular disease (CVD). High-sensitivity cardiac troponin T (hs-cTnT) can detect subclinical myocardial injury in asymptomatic prediabetic patients. AIM: We aimed to investigate the relationship between left ventricular (LV) function and hs-cTnT in prediabetic patients. METHODS: Between 1 October 2021 and 1 October 2022, we recruited 96 prediabetic and an equal number of age- and gender-matched healthy volunteers prospectively. TDI was used to evaluate both systolic and diastolic functions. Hs-cTnT levels were obtained and compared between groups. RESULTS: It was found that the values for mitral annular plane systolic excursion (MAPSE), E, the rapid filling wave, E/Em, and the peak annular velocities of systolic excursion in the ejection period (Sm) were all significantly higher in these patients compared to healthy individuals (p < .001). Hs-cTnT was an independent predictor of left ventricular diastolic dysfunction (LVDD) and left ventricular systolic dysfunction (LVSD) (odds ratio [OR] = 2.625, 95% confidence interval [CI] = 1.324-4.308, p < .001, and OR = 1.922, 95% CI = 0.454-3.206, p = .004). CONCLUSIONS: Prediabetics had higher hs-cTnT levels than controls. We showed that LVSD and LVDD functions were negatively affected in prediabetic patients. Our results proved that hs-cTnT levels may be associated with subclinical LV dysfunction in prediabetes.

The Role of High-Sensitivity Troponin T Regarding Prognosis and Cardiovascular Outcome across Heart Failure Spectrum.

Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02-0.078) and 0.031 ng/mL (IQR 0.02-0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median (p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization (p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02-4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006-3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH (p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events (p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events.

Effects of preparticipating hypohydration on cardiac burden in recreational athletes.

The global temperature rise will have extensive consequences on our organ systems, but hypohydration caused by reduced water intake or increased water loss through sweating plays the most relevant role. Many studies have already demonstrated the association between hypohydration and impaired exercise performance, but data related to the cardiac burden of hypohydration are scarce. This study is a sub-investigation of our large, prospective, self-controlled trial on the effects of hypohydration on cardiopulmonary exercise capacity with previously published results. In the current sub-study, we analyzed the impact of hypohydration on cardiac burden in this cohort of fifty healthy, recreational athletes during cardiopulmonary exercise test.Therefore, each participant underwent cardiopulmonary exercise test with a standardized ramp protocol twice, once in hypohydrated state and once in euhydrated state as control, and the cardiac markers Troponin T, NT-pro-BNP and Chromogranin A were measured before and after the exercise test at each state. Mean age was 29.7 years and 34% of probands were female. Hypohydration led to a reduced body water, a significant decrease in oxygen uptake and lower levels of power output. Yet, Troponin T, NT-proBNP, Chromogranin A and lactate levels did not significantly differ between the two conditions.In this study cohort, decreased exercise capacity during hypohydration was more likely due to impaired cardiac output with diminished plasma volume rather than measurable cardiac stress from fluid deprivation. However, whether these data are generalizable to a diseased cohort is left unanswered and should be addressed in future randomized controlled trials.

Prognostic Value and Determinants of High-Sensitivity Cardiac Troponin T in Patients With a Systemic Right Ventricle: Insights From the SERVE Trial.

BACKGROUND: The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown. METHODS AND RESULTS: Ninety-eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (P=0.046) and -0.381 (P=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively. CONCLUSIONS: Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.

Frequency of periprocedural myocardial injury and infarction stratified by cardiac troponin I and cardiac troponin T.

BACKGROUND: There are different definitions of periprocedural myocardial infarction (PPMI) both in terms of thresholds for cardiac biomarkers and the ancillary criteria for myocardial ischemia. Cardiac Troponin I (cTnI) and cardiac Troponin T (cTnT) are used interchangeably to diagnose PPMI. OBJECTIVES: This study evaluated the frequency of periprocedural myocardial injury and infarction as defined by the Society of Cardiovascular Angiography & Interventions (SCAI), the Academic Research Consortium-2 (ARC-2), and the 4th Universal definition of MI (4UDMI) stratified using cTnT versus cTnI, among patients with chronic coronary syndrome (CCS) and unstable angina. RESULTS: Among 830 patients, PPMI rates according to the SCAI, ARC2 and 4UDMI criteria were 4.34 %, 2.05 %, and 4.94 % respectively, with higher rates seen for all definitions when using cTnI versus cTnT (SCAI: 9.84 % vs. 1.91 %, p < 0.001; ARC 2: 3.15 % vs. 1.56 %, p = 0.136; and 4UDMI 5.91 % vs. 4.51 %, p = 0.391). Minor and major periprocedural myocardial injury was respectively observed in 58.31 % and 27.10 % of patients, with rates of both significantly higher when using cTnI versus cTnT (Minor: 69.29 % vs. 53.47 %, p < 0.001, Major: 49.21 % vs. 17.36 %, p < 0.001). CONCLUSIONS: Among patients with CCS and unstable angina, PPMIs defined by SCAI occurred more frequently when using cTnI as opposed to cTnT, whereas the type of troponin had no impact on the incidence of PPMIs according to the ARC-2 and 4UDMI.

Low Level of First Morning Urine Cardiac Troponin I: A Specific Hallmark of Aortic Stenosis Severity.

Background: It has recently been shown that cardiac-specific troponin I concentrations in first morning urine samples can be measured with commercially available tests. Due to their accumulation in the first morning urine, scientific papers indicate a potential predictive value for cardiovascular diseases. Therefore, the aim of this study was to compare the concentration of cardiac troponin I in the first morning urine in patients with severe aortic stenosis and the healthy population. Patients and Methods: Blood and first morning urine samples were collected from 34 healthy individuals (17 female) at University Hospital Merkur and 25 patients with severe aortic stenosis (14 female) before surgical treatment at University Hospital Dubrava. Cardiac troponin I and T values were determined using high-sensitivity assays using commercially available Abbott and Roche tests. Results: Patients with severe aortic stenosis had significantly lower troponin I concentrations in the first morning urine samples (0.3 ng/L (0.1-0.6)) as compared to the healthy population (15.2 ng/L (8.4-19.9)) (p < 0.001). There was no statistically significant difference in troponin T concentrations between healthy individuals and patients with severe aortic stenosis. In parallel, both I and T plasma troponin concentrations were significantly higher in patients with severe aortic stenosis. Conclusions: In patients with severe aortic stenosis, cardiac troponin I values in the first morning urine are significantly lower than in healthy subjects.

Cardiac Biomarker Change at 1 Year After Tafamidis Treatment and Clinical Outcomes in Patients With Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Although tafamidis treatment improves prognosis in patients with wild-type transthyretin amyloid cardiomyopathy, an optimal surrogate marker monitoring its therapeutic effect remains unclear. This study investigated the association between changes in cardiac biomarkers, high-sensitivity cardiac troponin T (hs-cTnT) and B-type natriuretic peptide (BNP) during the first year after tafamidis treatment and clinical outcomes. METHODS AND RESULTS: In 101 patients with wild-type transthyretin amyloid cardiomyopathy receiving tafamidis at our institution, change in cardiac biomarkers from baseline to 1 year after tafamidis administration and its association with composite outcomes (composite of all-cause death and hospitalization attributable to heart failure) was assessed. During the follow-up period (median, 17 months), 16 (16%) patients experienced composite outcomes. The hs-cTnT level significantly decreased at 1 year after tafamidis treatment, unlike the BNP level. The frequencies of increased hs-cTnT and BNP levels were significantly higher in those with composite outcomes than in those without (44% versus 15%; P=0.01). Kaplan-Meier survival analysis showed that patients in whom both hs-cTnT and BNP levels increased at 1 year after tafamidis had a higher probability of composite outcomes compared with those with decreased hs-cTnT and BNP levels (log-rank P<0.01). Cox regression analysis identified increased hs-cTnT and BNP levels at 1 year after tafamidis administration as an independent predictor of higher cumulative risk of composite outcomes. CONCLUSIONS: Deterioration in cardiac biomarkers during the first year after tafamidis treatment predicted a worse prognosis, suggesting the utility of serial assessment of cardiac biomarkers for monitoring the therapeutic response to tafamidis in patients with wild-type transthyretin amyloid cardiomyopathy.

Surface plasmon resonance biosensors for early troponin detection.

Acute myocardial infarction (AMI) is one of the life-threatening causes that decrease blood flow to the heart, leading to increased mortality and related complications. Recently, the measure of blood concentration of cardiac biomarkers has been suggested to overcome the limitations of electrocardiography (ECG) analyses for early diagnosis of this disease. Troponins, especially cardiac troponin I and cardiac troponin T, with high sensitivity and specificity, are considered the gold standards in myocardial diagnosis. Recently, the use of new biosensors such as surface plasmon resonance (SPR) for early detection of these biomarkers has been greatly appreciated. Due to the rapid, sensitive, real-time, and label-free detection of SPR-based biosensors, they can be applied for selective and nonspecific absorption that is intended to be used as an in situ cardiac biosensor. Here, we exclusively discussed the updated developments of these valuable predictors for the possible occurrence of AMI detected by SPR.

Tricuspid Regurgitation and TAVR: Outcomes, Risk Factors and Biomarkers.

Background. The significance of concomitant tricuspid regurgitation (TR) in the context of transcatheter aortic valve replacement (TAVR) remains unclear. This study aimed to analyze the severity of TR before and after TAVR with regard to short- and long-term survival and to analyze the influencing factors. Methods. In our retrospective analysis, TR before and after TAVR was examined and patients were classified into groups accordingly. Special attention was paid to patients with post-interventional changes in TR. Mortality after TAVR was considered the primary endpoint of the analysis and major complications according to the Valve Academic Research Consortium 3 (VARC3) were compared. Moreover, biomarkers and risk factors for worsening or improvement of TR through TAVR were analyzed. Results. Among 775 patients who underwent TAVR in our center between January 2009 and December 2019, 686 patients (89%) featured low- and 89 patients (11%) high-grade TR. High-grade pre-TAVR TR was associated with worse short- (30-day), mid- (2-year) and long-term survival up to 8 years. Even though in nearly half of the patients with high-grade TR the regurgitation improved within seven days after TAVR (n = 42/89), this did not result in a survival benefit for this subgroup. On the other hand, a worsening of low-grade TR was seen in more than 10% of the patients (n = 73/686), which was also associated with a worse prognosis. Predictors of worsening of TR after TAVR were adipositas, impaired right ventricular function and the presence of mild TR. Age, atrial fibrillation, COPD, impaired renal function and elevated cardiac biomarkers were risk factors for mortality after TAVR independent from the grade of TR. Conclusions. Not only pre-interventional, but also post-TAVR high-grade TR is associated with a worse prognosis after TAVR. TAVR can change concomitant tricuspid regurgitation, but improvement does not have any impact on short- and long-term survival. Worsening of TR after TAVR is possible and impairs the prognosis.

Myocardial extracellular volume derived from contrast-enhanced chest computed tomography in longitudinal evaluation of cardiac toxicity in patients treated with immune checkpoint inhibitors.

Background: The immune-related adverse effects after immune checkpoint inhibitors (ICIs) treatment have always been a hot topic. Although the incidence of myocarditis is not high among the related adverse effects, the mortality rate is extremely high once it occurs. In the past, the risk of cancer therapy-related cardiac dysfunction (CTRCD) after drug treatment was evaluated based on imaging examinations, but this evaluation still had certain limitations. Currently, the extracellular volume (ECV) score measurement calculated using cardiac magnetic resonance T1 mapping has become a reliable method for evaluating myocardial toxicity and computed tomography (CT) examination may become an alternative. This study aimed to longitudinally evaluate the cardiac toxicity of patients treated with ICIs using myocardial ECV derived from contrast-enhanced chest CT. Methods: A total of 500 patients with III-IV lung cancer and esophageal cancer treated with ICIs were evaluated. Participants underwent baseline examination and at least 1 follow-up examination after treatment. Contrast-enhanced chest CT-ECV, left ventricular ejection fraction (LVEF), and measurement of cardiac troponin T (cTnT) were conducted before the first treatment, 3-6 months after the first treatment, and about 12 months after the first treatment, respectively. The ECV value of the middle part of the left ventricular septum was evaluated on CT venography and plain scan, the LVEF value was evaluated by color Doppler ultrasound, and the quantity of cTnT was detected by chemiluminescence. Cancer therapy-related cardiac dysfunction was recorded. Results: The mean baseline LVEF value was 68.51%±4.81% (N0=500), and those of LVEF1, LVEF2, and LVEF3 were 68.77%±4.30%, 68.16%±3.59%, and 66.23%±4.20%, respectively (N1=500, N2=467, and N3=361, respectively). There was no significant difference between LVEF1, LVEF2, and LVEF0 (P1=0.095, P2=0.062), whereas LVEF3 was significantly lower than LVEF0 (P<0.001). The average baseline cTnT0 value was 7.42±3.95 (N0=500). The values of cTnT1, cTnT2, and cTnT3 were 10.05±11.40, 12.24±13.59, and 14.54±14.49, respectively (N1=500, N2=467, N3=361). The values of cTnT1, cTnT2, and cTnT3 were significantly higher than cTnT0 (P1<0.001, P2<0.001, P3<0.001). The average ECV0 was 47.14%±7.48% (N0=500). ECV1, ECV2, and ECV3 were 50.85%±6.79%, 53.44%±6.96% and 52.64%±7.58% respectively (N1=500, N2=467 and N3=361). ECV1, ECV2, and ECV3 were significantly higher than ECV0 (P1<0.001, P2<0.001, P3<0.001). CTRCD occurred in 49 patients. There were significant differences between the CTRCD (+) group and the CTRCD (-) group in cTnT1, cTnT2, and cTnT3 (P1<0.001, P2<0.001, and P3<0.001, respectively) and in ECV1, ECV2, and ECV3 (P1=0.039, P2=0.041, and P3=0.013, respectively). Conclusions: CT-ECV began to increase at the early stage after the treatment of ICIs. CT-ECV is a potential biomarker for dynamically monitoring the cardiac toxicity of tumor patients after receiving ICIs. ECV may be used to speculate the CTRCD caused by the treatment of ICIs.