In suspected ACS, hs-cTnI- vs. c-cTnI-guided care was associated with improved outcomes at 5 y in certain subgroups.

SOURCE CITATION: Lee KK, Doudesis D, Ferry AV, et al; High-STEACS Investigators. Implementation of a high sensitivity cardiac troponin I assay and risk of myocardial infarction or death at five years: observational analysis of a stepped wedge, cluster randomised controlled trial. BMJ. 2023;383:e075009. 38011922.

Trajectory of cardiac troponin T following moderate-to-severe COVID-19 and the association with cardiac abnormalities.

BACKGROUND: COVID-19 has been associated with cardiac troponin T (cTnT) elevations and changes in cardiac structure and function, but the link between cardiac dysfunction and high-sensitive cardiac troponin T (hs-cTnT) in the acute and convalescent phase is unclear. OBJECTIVE: To assess whether hs-cTnT concentrations are associated with cardiac dysfunction and structural abnormalities after hospitalization for COVID-19, and to evaluate the performance of hs-cTnT to rule out cardiac pathology. METHODS: Patients hospitalized with COVID-19 had hs-cTnT measured during the index hospitalization and after 3-and 12 months, when they also underwent an echocardiographic study. A subset also underwent cardiovascular magnetic resonance imaging (CMR) after 6 months. Cardiac abnormalities were defined as left ventricular hypertrophy or dysfunction, right ventricular dysfunction, or CMR late gadolinium. RESULTS: We included 189 patients with hs-cTnT concentrations measured during hospitalization for COVID-19, and after 3-and 12 months: Geometric mean (95%CI) 13 (11-15) ng/L, 7 (6-8) ng/L and 7 (6-8) ng/L, respectively. Cardiac abnormalities after 3 months were present in 45 (30%) and 3 (8%) of patients with hs-cTnT ≥ and < 5 ng/L at 3 months, respectively (negative predictive value 92.3% [95%CI 88.5-96.1%]). The performance was similar in patients with and without dyspnea. Hs-cTnT decreased from hospitalization to 3 months (more pronounced in intensive care unit-treated patients) and remained unchanged from 3 to 12 months, regardless of the presence of cardiac abnormalities. CONCLUSION: Higher hs-cTnT concentrations in the convalescent phase of COVID-19 are associated with the presence of cardiac pathology and low concentrations (< 5 ng/L) may support in ruling out cardiac pathology following the infection.

Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Department.

BACKGROUND COVID-19 increases the risk of acute cardiovascular diseases (CVDs), including acute coronary syndrome (ACS), acute pulmonary embolism (APE), and acute myocarditis (AMyo). The actual impact of CVDs on mortality of patients with COVID-19 remains unknown. This study aimed to determine whether CVDs influence the course of COVID-19 pneumonia and if they can be easily detected by using common tests and examinations. MATERIAL AND METHODS Data of 249 consecutive patients with COVID-19 hospitalized in a dedicated cardiology department were analyzed. On admission, clinical status, biomarkers, computed tomography, and bedside echocardiography were performed. RESULTS D-dimer level predicted APE (AUC=0.850 95% CI [0.765; 0.935], P<0.001) with sensitivity of 69.4% and specificity of 96.2% for a level of 4968.0 ng/mL, and NT-proBNP predicted AMyo (AUC=0.692 95% CI [0.502; 0.883], P=0.004) and showed sensitivity of 54.5%, with specificity of 86.5% for the cut-off point of 8970 pg/mL. Troponin T levels were not useful for diagnostic differentiation between CVDs. An extent of lung involvement predicted mortality (OR=1.03 95% CI [1.01;1.04] for 1% increase, P<0.001). After adjusting for lung involvement, ACS increased mortality, compared with COVID-19 pneumonia only (OR=5.27 95% CI [1.76; 16.38] P=0.003), while APE and AMyo did not affect risk for death. CONCLUSIONS D-dimer and NT-proBNP, but not troponin T, are useful in differentiating CVDs in patients with COVID-19. ACS with COVID-19 increased in-hospital mortality independently from extent of lung involvement, while coexisting APE or AMyo did not.

Comparison of troponin and natriuretic peptides in Takotsubo syndrome and acute coronary syndrome: a meta-analysis.

OBJECTIVE: Takotsubo syndrome (TTS) is an acute heart failure syndrome which resembles acute coronary syndrome (ACS) at presentation. Differentiation requires coronary angiography, but where this does not occur immediately, cardiac biomarkers may provide additional utility. We performed a meta-analysis to compare troponin and natriuretic peptides (NPs) in TTS and ACS to determine if differences in biomarker profile can aid diagnosis. METHODS: We searched five literature databases for studies reporting NPs (Brain NP (BNP)/NT-pro-BNP) or troponin I/T in TTS and ACS, identifying 28 studies for troponin/NPs (5618 and 1145 patients, respectively). RESULTS: Troponin was significantly lower in TTS than ACS (standardised mean difference (SMD) -0.86; 95% CI, -1.08 to -0.64; p<0.00001), with an absolute difference of 75 times the upper limit of normal (×ULN) higher in ACS than TTS. Conversely, NPs were significantly higher in TTS (SMD 0.62; 95% CI, 0.44 to 0.80; p<0.00001) and 5.8×ULN greater absolutely. Area under the curve (AUC) for troponin in ACS versus TTS was 0.82 (95% CI, 0.70 to 0.93), and 0.92 (95% CI, 0.80 to 1.00) for ST-segment elevation myocardial infarction versus TTS. For NPs, AUC was 0.69 (95% CI, 0.48 to 0.89). Combination of troponin and NPs with logistic regression did not improve AUC. Recursive Partitioning and Regression Tree analysis calculated a troponin threshold ≥26×ULN that identified 95% cases as ACS where and specificity for ACS were 85.71% and 53.57%, respectively, with 94.32% positive predictive value and 29.40% negative predictive value. CONCLUSIONS: Troponin is lower and NPs higher in TTS versus ACS. Troponin had greater power than NPs at discriminating TTS and ACS, and with troponin ≥26×ULN patients are far more likely to have ACS.

In emergency hypertension, could biomarkers change the guidelines?

BACKGROUND: Hypertension may cause target organ damage (TOD). Target blood pressure (BP) management may not be appropriate in some conditions. AIM: We aim to assess the impact of targeted BP management in severe hypertension on renal TOD. PATIENTS & METHODS: This is a prospective cohort study involving patients admitted due to severe hypertension (BP > 180/120) associated with any symptoms. The study involved patients referred to the ICU in our tertiary center during the period between August 2017 and February 2018. All patients underwent target BP treatment according to recent guidelines. Hs-Troponin T (hs-TNT) and serum creatinine (s.creat) were measured in all patients on admission and 24 h later. Patients were divided into Group A (with initial normal hs-TNT) and Group B (with initial high hs-TNT). The main outcome was in-hospital renal-related morbidity (including renal failure). RESULTS: Four hundred seventy consecutive patients with hypertensive crises were involved in the study. Group B had a significantly higher incidence of in-hospital mortality (4 patients) and renal TOD (acute renal dysfunction) than Group A (P value = 0.001 and 0.000 respectively). There was a significant difference between initial s.creat on admission and follow-up s.creat values in Group B with significant elevation of their s.creat on the following 24 h (P = 0.002), while this difference is insignificant in Group A (P = 0.34). There was a significant positive correlation between hs-TNT and the follow-up s.creat (P = 0.004). CONCLUSION: In severe HTN, hs-TNT may be elevated due to marked afterload. Patients with severe HTN and high hs-TNT have higher s.creat values, which are associated with an increased risk of renal failure and in-hospital mortality if their BP decreases acutely to the guideline-target BP. Using biomarkers during the management of emergency HTN should be considered before following clinical guidelines. However, our findings do underscore the potential utility of hs-TNT as an indicator for risk stratification in patients with severe or emergency HTN.

Non-Canonical Localization of Cardiac Troponins: Expanding Functions or Causing Pathologies?

The troponin complex-consisting of three subunits: troponin C (TnC), cardiac troponin I (cTnI) and cardiac troponin T (cTnT)-plays a key role in the regulation of myocardial contraction. Troponins are preferentially localized in the cytoplasm and bind to myofibrils. However, numerous, albeit scattered, studies have shown the presence of troponins in the nuclei of muscle cells. There is increasing evidence that the nuclear localization of troponins may be functionally important, making troponins an important nuclear player in the pathogenesis of various diseases including cancer and myopathies. Further studies in this area could potentially lead to the development of treatments for certain pathologies. In this review, we collected and discussed recent data on the properties of non-canonically localized cardiac troponins, the molecular mechanisms leading to this non-canonical localization, and the possible functions or pathological effects of these non-canonically localized troponins.

The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination.

BACKGROUND: Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis. METHODS: Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and T cells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls. FINDINGS: Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1ß (IL-1ß), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57+ NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57+ NK subset was particularly prominent in males and in those after the second dose of vaccination. Genotypically, killer cell immunoglobulin-like receptor (KIR) KIR2DL5B(-)/KIR2DS3(+)/KIR2DS5(-)/KIR2DS4del(+) was a risk haplotype, in addition to single-nucleotide polymorphisms related to the NK cell-specific expression quantitative trait loci DNAM-1 and FuT11, which also correlated with cardiac troponin T levels in post-vaccination patients with myocarditis. CONCLUSION: Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects. FUNDING: This work was funded by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and the CRF Coronavirus and Novel Infectious Diseases Research Exercises (reference no. C7149-20G).

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

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

High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study.

BACKGROUND: Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin)  levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown. METHODS AND RESULTS: We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study. Patients underwent neuropsychological testing 6 and 12 months after the index event. Test results were classified into 5 cognitive domains (language, memory, executive function, attention, and visuospatial function). SVD markers (lacunes, cerebral microbleeds, white matter hyperintensities, and enlarged perivascular spaces) were assessed on cranial magnetic resonance imaging to constitute a global SVD score. We examined the association between hs-cTnT (hs-cTn T levels) and cognitive domains as well as the global SVD score and individual SVD markers, respectively. Measurement of cognitive and SVD-marker analyses were performed in 385 and 466 patients with available hs-cTnT levels, respectively. In analyses adjusted for demographic characteristics, cardiovascular risk factors, and cognitive status at baseline, higher hs-cTnT was negatively associated with the cognitive domains "attention" up to 12 months of follow-up (beta-coefficient, -0.273 [95% CI, -0.436 to -0.109]) and "executive function" after 12 months. Higher hs-cTnT was associated with the global SVD score (adjusted odds ratio, 1.95 [95% CI, 1.27-3.00]) and the white matter hyperintensities and lacune subscores. CONCLUSIONS: In patients with stroke, hs-cTnT is associated with a higher burden of SVD markers and cognitive function in domains linked to vascular cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01334749.

Early Detection and Prediction of Anthracycline-Induced Cardiotoxicity　- A Prospective Cohort Study.

BACKGROUND: In the present study, we aimed to investigate whether early cardiac biomarker alterations and echocardiographic parameters, including left atrial (LA) strain, can predict anthracycline-induced cardiotoxicity (AIC) and thus develop a predictive risk score.Methods and Results: The AIC registry is a prospective, observational cohort study designed to gather serial echocardiographic and biomarker data before and after anthracycline chemotherapy. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) ≥10 percentage points from baseline and <55%. In total, 383 patients (93% women; median age, 57 [46-66] years) completed the 2-year follow-up; 42 (11.0%) patients developed cardiotoxicity (median time to onset, 292 [175-440] days). Increases in cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) and relative reductions in the left ventricular global longitudinal strain (LV GLS) and LA reservoir strain [LASr] at 3 months after anthracycline administration were independently associated with subsequent cardiotoxicity. A risk score containing 2 clinical variables (smoking and prior cardiovascular disease), 2 cardiac biomarkers at 3 months (TnT ≥0.019 ng/mL and BNP ≥31.1 pg/mL), 2 echocardiographic variables at 3 months (relative declines in LV GLS [≥6.5%], and LASr [≥7.5%]) was generated. CONCLUSIONS: Early decline in LASr was independently associated with subsequent cardiotoxicity. The AIC risk score may provide useful prognostication in patients receiving anthracyclines.

Intensive Blood Pressure Lowering in Individuals With Low Diastolic Blood Pressure and Elevated Troponin Levels in SPRINT.

BACKGROUND: Among 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 RESULTS: A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (<70 mm Hg) were further stratified by elevated hs-cTnT (≥14 ng/L) at baseline. The effects of intensive versus standard BP lowering on a cardiovascular disease composite end point, all-cause death, and 1-year change in hs-cTnT were determined. The combination of low DBP/high hs-cTnT was independently associated with a higher risk for cardiovascular disease and all-cause death, as well as greater 1-year increases in hs-cTnT, compared with DBP ≥70 mm Hg. However, randomization to intensive versus standard BP lowering led to similar reductions in cardiovascular disease risk among individuals with low DBP/high hs-cTnT (hazard ratio [HR], 0.82 [95% CI, 0.57-1.19]), low DBP/low hs-cTnT (HR, 0.48 [95% CI, 0.29-0.79]), and DBP ≥70 mm Hg (HR, 0.73 [95% CI, 0.60-0.89]; P for interaction=0.20). Intensive BP lowering also led to a reduction in all-cause death that was similar across groups (P for interaction=0.57). CONCLUSIONS: In this nonprespecified subgroup analysis of SPRINT, individuals with low DBP and elevated hs-cTnT, low DBP and nonelevated hs-cTnT, and DBP ≥70 mm Hg derived similar cardiovascular disease and mortality benefits from intensive BP lowering. These findings warrant confirmation in other studies.

High-sensitivity cardiac troponin T in detecting obstructive coronary artery disease in hemodialysis patients listed for kidney transplantation.

BACKGROUND: Cardiovascular diseases are the leading cause of morbidity and mortality in patients with end-stage renal disease. AIMS: This study aimed to assess the prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) in identifying patients with obstructive coronary artery disease (CAD) among patients on hemodialysis listed for kidney transplantation. METHODS: The study prospectively enrolled consecutive adult hemodialysis patients listed for kidney transplantation. They underwent laboratory tests and a standardized set of imaging and functional tests, including coronary angiography, according to patient characteristics. RESULTS: The study included 100 consecutive patients (72 men)at a median age of 56.5 years. Ultimately, 48% of the patients were diagnosed with obstructive CAD. Age and plasma hs-cTnT levels predicted the diagnosis of obstructive CAD (OR, 1.13; 95% CI, 1.08-1.20; P < 0.001 and OR, 1.03; 95% CI, 1.01-1.05; P = 0.001, respectively). The calculated cut-off value for age was 53 years, which showed sensitivity of 87.5% and specificity of 76.9% for obstructive CAD diagnosis. The calculated value for hs-cTnT was 0.067 ng/ml, which showed sensitivity of 61.4% and specificity of 82.2% for the detection of obstructive CAD. In patients aged >52 years, 79.2% were diagnosed with obstructive CAD. However, in the group of patients ≤52 years and with hs-cTnT >0.069 ng/ml, the incidence of obstructive CAD was significantly higher than in the group with hs-cTnT level ≤0.069 ng/ml. CONCLUSIONS: Baseline hs-cTnT level is a useful prognostic biomarker in the diagnosis of obstructive CAD in hemodialysis patients listed for kidney transplantation.

Troponin T is elevated in a relevant proportion of patients with 5q-associated spinal muscular atrophy.

Troponin T concentration (TNT) is commonly considered a marker of myocardial damage. However, elevated concentrations have been demonstrated in numerous neuromuscular disorders, pointing to the skeletal muscle as a possible extracardiac origin. The aim of this study was to determine disease-related changes of TNT in 5q-associated spinal muscular atrophy (SMA) and to screen for its biomarker potential in SMA. We therefore included 48 pediatric and 45 adult SMA patients in this retrospective cross-sequential observational study. Fluid muscle integrity and cardiac markers were analyzed in the serum of treatment-naïve patients and subsequently under disease-modifying therapies. We found a TNT elevation in 61% of SMA patients but no elevation of the cardiospecific isoform Troponin I (TNI). TNT elevation was more pronounced in children and particularly infants with aggressive phenotypes. In adults, TNT correlated to muscle destruction and decreased under therapy only in the subgroup with elevated TNT at baseline. In conclusion, TNT was elevated in a relevant proportion of patients with SMA with emphasis in infants and more aggressive phenotypes. Normal TNI levels support a likely extracardiac origin. Although its stand-alone biomarker potential seems to be limited, exploring TNT in SMA underlines the investigation of skeletal muscle integrity markers.

Incidence, presentation and outcome of acute aortic dissection: results from a population-based study.

OBJECTIVES: To describe the incidence of acute aortic dissection in a clearly defined population, to assess onset symptoms and admission biochemical marker levels and to analyse variables potentially associated to mortality. METHODS: Medical records and CT angiograms of all patients hospitalised for acute aortic dissection in the Stockholm County during the 5-year period 2012-2016 were reviewed. The patients were followed until date of death or until 31 December 2020. The annual incidence was determined. Associations between clinical and biochemical variables and 30-day mortality, respectively, were analysed using multivariable logistic regression models. RESULTS: A total of 344 patients were included. The mean annual incidence of acute aortic dissection was 4.1 per 100 000. Median age was 67 years (range 24-91) and 34% (n=118) were women. Type A dissection was predominant; 220 patients (64%) had type A and 124 (36%) had type B. Painless dissection was more common in type A than in type B (18% vs 15%, p=0.003). Type A dissection patients also more commonly had elevated plasma troponin T (44% vs 21%, p<0.001) and thrombocytopenia (26% vs 15%, p=0.010) than type B dissection patients on admission. Overall, 30-day mortality was 28% in type A and 11% in type B (p<0.001). Both painless dissection (OR 4.30, 95% CI 1.80 to 10.28, p=0.001) and elevated troponin T (OR 3.78, 95% CI 2.01 to 7.12, p<0.001), respectively, were associated with increased 30-day mortality in all acute aortic dissection patients. Thrombocytopenia was associated with elevated 30-day mortality only in patients with type A (OR 3.09, 95% CI 1.53 to 6.21, p=0.002). CONCLUSIONS: Nearly two-thirds of acute aortic dissection patients had type A. Levels of troponin T and platelets, respectively, paired with presence or absence of typical symptoms may become useful adjuncts in risk stratification of patients with acute aortic dissection.

Troponin efficacy in the diagnosis of acute coronary syndrome in patients with chronic renal failure.

There is no consensus on whether cardiac troponins with high reliability values should be different diagnostic criteria for acute myocardial infarction in patients with and without renal dysfunction. Although it is often emphasized that the etiology of elevated troponin levels in chronic kidney disease (CKD) remains unclear, elevated cardiac troponin (cTnT) levels have been associated with increased subclinical cardiac damage in these patient groups. In this study, we investigated the value of cTnT value in diagnosing acute coronary syndrome in CKD patients with high clinical suspicion of acute coronary syndrome and without acute ST segment elevation on electrocardiogram. The aim was to prevent cardiac ischemia from being overlooked in CKD patients. Coronary angiography revealed vessel occlusion in 192 patients, and the mortality rate after treatment decisions was 6.7%. The first measured troponin results showed a significant difference in patients who did not survive, indicating the prognostic value of troponin levels. Troponin values were compared with cardiovascular pathologies obtained by angiography, and elevated troponin levels strongly correlated with pathologic angiography results. The conclusion highlighted that despite prognostic uncertainties, biomarkers used for acute myocardial infarction diagnosis in patients with renal insufficiency are reliable in those with renal dysfunction. Elevated cTnT levels in CKD patients are considered a clear marker of cardiac ischemia, emphasizing the need for careful consideration of troponin values in this population.

Influence of a 7-day Transalpine Trail Run on cardiac biomarkers and myocardial function.

Intense physical exercise is known to increase cardiac biomarkers; however, it is unclear, whether this phenomenon is physiological, or if it indicates myocardial tissue injury. The aim of our study was to investigate the effects of seven consecutive days of excessive endurance exercise on continuous assessment of cardiac biomarkers, function, and tissue injury. During a 7-day trail-running competition (Transalpine Run, distance 267.4 km, altitude ascent/descent 15556/14450 m), daily blood samples were obtained for cardiac biomarkers (hs-TnT, NT-proBNP, and suppression of tumorigenicity-2 protein (ST2)) at baseline, after each stage and 24-48 h post-race. In addition, echocardiography was performed every second day, cardiac magnetic resonance imaging (CMR) before (n = 7) and after (n = 16) the race. Twelve (eight males) out of 17 healthy athletes finished all seven stages (average total finish time: 43 ± 8 h). Only NT-proBNP increased significantly (3.6-fold, p = 0.009) during the first stage and continued to increase during the race. Hs-TnT revealed an incremental trend during the first day (2.7-fold increase, p = 0.098) and remained within the pathological range throughout the race. ST2 levels did not change during the race. All cardiac biomarkers completely returned to physiological levels post-race. NT-proBNP kinetics correlated significantly with mild transient reductions in right ventricular function (assessed by TAPSE, tricuspid annular plane systolic function; r = -0.716; p = 0.014). No significant echocardiographic changes in LV dimensions, LV function, or relevant alterations in CMR were observed post-race. In summary, this study shows that prolonged, repetitive, high-volume exercise induced a transient, significant increase in NT-proBNP associated with right ventricular dysfunction without corresponding left ventricular functional or structural impairment.

Evaluation of a new Electrochemiluminescence Immunoassay System for Measuring High-Sensitivity Cardiac Troponin T.

BACKGROUND: The aim of this study was to verify the analytical performance of the UD90DT electrochemiluminescence immunoassay system (the UD90DT system) for measuring high-sensitivity cardiac troponin T (hs-cTnT). METHODS: According to the Clinical and Laboratory Standards Institute guidelines, the imprecision, linearity, reference interval, limit of blank (LoB), limit of detection (LoD), and functional sensitivity (FS) of hs-cTnT using the UD90DT system were verified. The trueness was validated using the Proficiency Testing (PT) materials. RESULTS: The within-run and between-run coefficients of variations (CVs) of two hs-cTnT levels were 7.2% and 1.5%, and 7.1% and 2.6%, respectively. The biases of the PT samples (n = 6) all fell within the allowable total error. The linearity satisfied the requirements, with a slope of 0.9963 and an R12 value of 0.9998. The hs-cTnT levels of the healthy volunteers (n = 20) ranged from 3.0 ng/L to 7.7 ng/L. All blank calibrator measurements (n = 20) fell within the LoD claim, and none of the samples (n = 25) had a LoB value ≤ 3.0 ng/L. The FS was 5.3 ng/L. Furthermore, a good correlation between the UD90DT system and the Cobas e 601 module was observed for hs-cTnT. CONCLUSIONS: The analytical performance of hs-cTnT using the UD90DT system is acceptable and satisfies clinical needs.

Efficacy of propofol-supplemented cardioplegia on biomarkers of organ injury in patients having cardiac surgery using cardiopulmonary bypass: a statistical analysis plan for the ProMPT-2 randomised controlled trial.

BACKGROUND: The ProMPT-2 trial (Propofol for Myocardial Protection Trial #2) aims to compare the safety and efficacy of low- and high-dose propofol supplementation of the cardioplegia solution during adult cardiac surgery versus sham supplementation. This update presents the statistical analysis plan, detailing how the trial data will be analysed and presented. Outlined analyses are in line with the Consolidated Standards of Reporting Trials and the statistical analysis plan has been written prior to database lock and the final analysis of trial data to avoid reporting bias (following recommendations from the International Conference on Harmonisation of Good Clinical Practice). METHODS/DESIGN: ProMPT-2 is a multi-centre, blinded, parallel three-group randomised controlled trial aiming to recruit 240 participants from UK cardiac surgery centres to either sham cardioplegia supplementation, low dose (6 µg/ml) or high dose (12 µg/ml) propofol cardioplegia supplementation. The primary outcome is cardiac-specific troponin T levels (a biomarker of cardiac injury) measured during the first 48 h following surgery. The statistical analysis plan describes the planned analyses of the trial primary and secondary outcomes in detail, including approaches to deal with missing data, multiple testing, violation of model assumptions, withdrawals from the trial, non-adherence with the treatment and other protocol deviations. It also outlines the planned sensitivity analyses and exploratory analyses to be performed. DISCUSSION: This manuscript prospectively describes, prior to the completion of data collection and database lock, the analyses to be undertaken for the ProMPT-2 trial to reduce risk of reporting and data-driven analyses. TRIAL REGISTRATION: ISRCTN ISRCTN15255199. Registered on 26 March 2019.