Higher troponin T serum concentrations in hospital patients without diagnosed cardiac diseases compared to a population-based cohort.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Significance of postmortem biomarkers and multimarker strategy in sudden cardiac death.

The most common cause in the etiology of sudden cardiac death (SCD) is ischemic heart disease due to atherosclerosis. Postmortem diagnosis can be made by histopathological examinations, but routine histopathological examinations are limited, especially in the early period of postmortem ischemia. For this reason, many methods are being investigated for the postmortem diagnosis of ischemia, and postmortem biochemical studies are promising. In our study, we evaluated the biochemical markers; hs-cTnT, NT-proBNP, H-FABP, pentraxin-3, copeptin, ischemic modified albumin (IMA), and PAPP-A in postmortem serums. In forensic pathology practice, it was investigated whether it would be useful to go to the diagnosis by measuring more than one marker in a single biological fluid in SCD cases. The study included 35 sudden cardiac death cases and 24 control cases and as a result of our study, hs-cTnT, NT-proBNP, and H-FABP values were found to be significantly higher in the SCD group than in the control group. Within the scope of the multi-marker strategy, models were tried to be developed in which the markers were used together, and it was concluded that the model consisting of the myocardial ischemia marker hs-cTnT, the myocardial stress marker NT-proBNP, and the inflammation marker pentraxin 3 was the most accurate combination by correctly classifying the cases at a rate of 94.9%. As a result, it was thought that it would be appropriate to use the multi-marker strategy which is widely used in clinical applications, also in forensic medicine applications.

Heart Failure: Is There an Ideal Biomarker?

An always-rising prevalence of heart failure (HF), formerly classified as an emerging epidemic in 1997 and still representing a serious problem of public health, imposes on us to examine more in-depth the pathophysiological mechanisms it is based on. Over the last few years, several biomarkers have been chosen and used in the management of patients affected by HF. The research about biomarkers has broadened our knowledge by identifying some underlying pathophysiological mechanisms occurring in patients with both acute and chronic HF. This review aims to provide an overview of the role of biomarkers previously identified as responsible for the pathophysiological mechanisms subtending the disease and other emerging ones to conduct the treatment and identify possible prognostic implications that may allow the optimization of the therapy and/or influence a closer follow-up. Taking the high prevalence of HF-associated comorbidities into account, an integrated approach using various biomarkers has shown promising results in predicting mortality, a preferable risk stratification, and the decrease of rehospitalizations, reducing health care costs as well.

Diagnostic value of high sensitivity cardiac troponin T (hs-cTnT) in dialysis patients with myocardial infarction.

Background: As a sensitive diagnostic marker for myocardial infarction (MI) in people with normal renal function, elevated high sensitivity cardiac troponin T (hs-cTnT) was often found in chronic kidney disease (CKD) patients requiring dialysis. However, the accuracy of baseline hs-cTnT in the diagnosis of MI (including Type 1 MI (T1MI) and Type 2 MI (T2MI)) in dialysis patients is still controversial. The aim of this study was to retrospectively explore whether there were any clinical indices that could increase the predictive value of hs-cTnT on admission for MI occurrence in dialysis patients. Methods: Here, 136 patients with uremia who underwent regular dialysis with coronary angiography in the First Affiliated Hospital of Nanjing Medical University from August 2017 to October 2021 were enrolled. According to the coronary angiography results and the presence of clinical symptoms, the patients were divided into: (1). AMI group (n = 69; angiography positive) and Control group (n = 67; angiography negative); (2). T1MI group (n = 69; angiography positive), T2MI group (n = 7; angiography negative & symptomatic), and Control group (n = 60; angiography negative & asymptomatic). Results: Here, we found the mean hs-cTnT on admission in the Control group was much lower than that in the AMI group. Hs-cTnT alone had a mediocre predictive performance, with an AUROC of 0.7958 (95% CI: 0.7220, 0.8696). Moreover, the ROC curve of hs-cTnT combined with the Triglyceride (TG), Time of dialysis, and Albumin (Alb) showed a higher sensitivity area [0.9343 (95% CI: 0.8901, 0.9786)] than that of single hs-cTnT. Next, hs-cTnT combined with the TG, Time of dialysis, and Alb also presented a better performance in predicting T1MI [0.9150 (95% CI: 0.8678, 0.9621)] or T2MI (0.9167 [0.9167 (95% CI: 0.8427, 0.9906)] occurrences. Last, these combined variables could better distinguish patient between T1MI and T2MI group than hs-cTnT alone. Conclusions: On admission, a combination of hs-cTnT, TG, Time of dialysis, and Alb presented a higher sensitivity than hs-cTnT alone in predicting MI occurrence in dialysis patients, suggesting a better diagnostic approach for future clinical applications.

Frequency, associated variables, and outcomes of acute myocardial injury according to the fourth Universal Definition of Myocardial Infarction in patients with acute ischemic stroke.

Background: Myocardial injury as indicated by elevation of cardiac troponin levels is common after acute ischemic stroke (AIS) and linked to poor outcomes. Previous studies rarely reported on serial hs-cTn measurements to distinguish whether myocardial injury is acute or chronic. Thus, little is known about frequency, associated variables, and outcome of acute myocardial injury in AIS. Methods and patients: In this single-centered observational cohort study, from 01/2019 to 12/2020, consecutive patients with neuroimaging-confirmed AIS <48 h after symptom onset, and serial troponin measurements within the first 2 days after admission (Roche Elecsys®, hs-cardiac troponin T) were prospectively registered. Acute myocardial injury was defined according to the fourth Universal Definition of Myocardial Infarction (troponin above the upper reference limit and rise/fall>20%). Outcomes of interest were in-hospital mortality and unfavorable functional status at discharge (modified Rankin Scale >1). Results: Out of 1067 analyzed patients, 25.3% had acute myocardial injury, 40.4% had chronic myocardial injury and 34.3% had no myocardial injury. Older age, higher stroke severity, thrombolytic treatment, and impaired kidney function were independently associated with acute myocardial injury. In-hospital mortality was higher in patients with acute myocardial injury than in those without (13% vs 3%, adjusted OR, 2.9% [95% CI, 1.6-5.5]). Compared with no myocardial injury, both acute and chronic myocardial injury were associated with unfavorable functional status at discharge (adjusted OR, 1.6 [95% CI, 1.1-2.5] and OR, 1.7 [95% CI, 1.2-2.4], respectively). Conclusions: A quarter of patients with AIS have evidence of acute myocardial injury according to the fourth Universal Definition of Myocardial Infarction. The strong association with in-hospital mortality highlights the need for clinical awareness and future studies on underlying mechanisms.

High-Sensitivity Cardiac Troponin T in Prediction and Diagnosis of Early Postoperative Hypoxemia after Off-Pump Coronary Artery Bypass Grafting.

To investigate the relationship of preoperative high-sensitivity cardiac troponin T (hs-cTnT) with early postoperative hypoxemia (EPH) following off-pump coronary artery bypass grafting (OPCAB). Records of patients undergoing OPCAB between 2018 and 2022 were reviewed. Baseline characteristics and postoperative arterial blood gas analysis were derived from the cardiovascular surgery electronic medical records. Preoperative hs-cTnT levels were measured routinely in all patients. Logistic regression analyses were performed to test the association of preoperative hs-cTnT with EPH. A total of 318 OPCAB patients were included, who had a preoperative hs-cTnT test available for review. Before surgery, 198 patients (62%) had a rise in hs-cTnT level (≥14 ng/L) and 127 patients (40%) had a more severe hs-cTnT level (≥25 ng/L). The preoperative hs-cTnT level was associated with EPH (odds ratio per ng/L, 1.86; 95% confidence interval 1.30−2.68; p < 0.001), prolonged intensive care unit stay (odds ratio, 1.58; 95% confidence interval 1.08−2.32; p = 0.019), and delayed extubating time (odds ratio, 1.63; 95% confidence interval 1.15−2.34; p = 0.007). On multivariable analysis, adjusted for BMI, hypertension, smoking status, serum creatinine, and cardiac function, preoperative hs-cTnT remained an independent factor associated with EPH. Elevation of hs-cTnT concentrations are significantly associated with EPH after OPCAB. Review of presurgical hs-cTnT concentration may help identify patients who would benefit from OPCAB to improve surgical risk assessment.

Recreational drug use among young, hospitalized patients with acute coronary syndrome: A retrospective study.

Background: Cocaine use is a well-established risk factor for acute coronary syndrome (ACS) although other recreational drugs (RD), are increasingly considered as potential cardiac risk factors. Compared to ACS without RD use, worse outcomes have been described for RD-associated ACS. Objective: The aim of this study was to explore the use of RD in a contemporary cohort of young ACS patients. Methods: Between June 2016 and October 2019, ACS patients aged 18-50 years, admitted to OLVG Hospital in Amsterdam, were retrospectively analysed. Medical chart review was performed to obtain patient and clinical characteristics, RD use, cardiac risk factors, outcome and follow up. Results: A total of 229 patients were included in the study. Recreational drug use prior to ACS was present in 24.9% of all patients, with cannabis (16.2%), cocaine (4.8%), or both (2.6%) most commonly observed. RD users were predominantly young men (87.7%) and had a significantly higher tobacco use compared to non-RD users (89.5% vs. 62.8%, P < 0.001), also after adjusting for age and sex. RD use was associated with larger myocardial infarctions with significantly higher CK-MB levels (104 ± 116 U/L vs 62 ± 96, P = 0.040) and poorer left ventricular function measured by echocardiography as compared to non-users (P = 0.007). Conclusion: Recreational drug use was present in almost 25% of all young ACS patients evaluated for drug use and was associated with larger myocardial infarction resulting in poorer left ventricular function as compared to non-users. Additionally, RD-users were younger and were more often tobacco users, compared to non-users.

Outcomes by Cardiac Stage in Patients With Newly Diagnosed AL Amyloidosis: Phase 3 ANDROMEDA Trial.

Background: Patients with amyloid light chain amyloidosis and severe cardiac dysfunction have a poor prognosis. Treatment options that induce rapid and deep hematologic and organ responses, irrespective of cardiac involvement, are needed. Objectives: The aim of this study was to evaluate the impact of baseline cardiac stage on efficacy and safety outcomes in the phase 3 ANDROMEDA trial. Methods: Rates of overall complete hematologic response and cardiac and renal response at 6 months and median major organ deterioration-progression-free survival and major organ deterioration-event-free survival were compared across cardiac stages (I, II, or IIIA) and treatments (daratumumab, bortezomib, cyclophosphamide, and dexamethasone [D-VCd] or bortezomib, cyclophosphamide, and dexamethasone [VCd]). Rates of adverse events (AEs) were summarized for patients with and without baseline cardiac involvement and by cardiac stage. Results: Median follow-up duration was 15.7 months. The proportions of stage I, II, and IIIA patients were 23.2%, 40.2%, and 36.6%. Across cardiac stages, hematologic and organ response rates were higher and major organ deterioration-progression-free survival and major organ deterioration-event-free survival were longer with D-VCd than VCd. AE rates were similar between treatments and by cardiac stage; serious AE rates were higher in patients with cardiac involvement and increased with increasing cardiac stage. The incidence of cardiac events was numerically greater with D-VCd vs VCd, but the rate of grade 3 or 4 events was similar. The exposure-adjusted incidence rate for cardiac events was lower with D-VCd than VCd (median exposure 13.4 and 5.3 months, respectively). Conclusions: These findings demonstrate the efficacy of D-VCd over VCd in patients with newly diagnosed amyloid light chain amyloidosis across cardiac stages, thus supporting its use in patients with cardiac involvement. (NCT03201965).

A comparison of modelled serum cTnT and cTnI kinetics after 60 min swimming.

Post-exercise elevations of cardiac troponin T (cTnT) and I (cTnI) are often used in isolation but interpreted interchangeably. Research suggests, however, that post-exercise cTn kinetic might differ with each isoform. In this cross-sectional observational study, we collected blood samples before, immediately after (5 minutes), and at 1-, 3-, 6-, 12-, and 24-hour post-exercise in a mixed cohort of 56 participants after a distance-trial of 60 min continuous swimming (age range from 14 to 22, 57.1% female). Cardiac troponin kinetics were modelled using Bayesian mixed-effects models to estimate time to peak (TTP) and peak concentration (PC) for each isoform, while controlling for participants sex, tanner stage and average relative heart rate during the test. Exercise induced an elevation of cTnT and cTnI in 93% and 75% of the participants, respectively. Cardiac troponin T peaked earlier, at 2.9 h (CI: 2.6 - 3.2 h) post-exercise, whereas cTnI peaked later, at 4.5 h (CI: 4.2 - 4.9 h). Peak concentrations for cTnT and cTnI were 2.5 ng/L, CI: 0 - 11.2 ng/L and 2.16 ng/L, CI: 0 - 22.7 ng/L, respectively. Additionally, we did not observe a systematic effect of sex and maturational status mediating cTn responses.

NT-proBNP, hs-cTnT, and CRP predict the risk of cardiopulmonary outcomes in systemic sclerosis: Findings from the Canadian Scleroderma Research Group.

Objective: The aim of this study was to determine the independent value of N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein to predict onset of cardiopulmonary disease in a large, multi-center systemic sclerosis cohort followed prospectively. Methods: Subjects from the Canadian Scleroderma Research Group registry with data on N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein were identified. Outcomes of interest were death, systolic dysfunction (left ventricular ejection fraction < 50% or medications for heart failure), pulmonary arterial hypertension by right heart catheterization, pulmonary hypertension by cardiac echocardiography (systolic pulmonary artery pressures ⩾ 45 mmHg), arrhythmias (pacemaker/implantable cardiac defibrillator or anti-arrhythmic medications), and interstitial lung disease. Multivariate Cox proportional hazard models were generated for each outcome. Results: A total of 675 subjects were included with a mean follow-up of 3.0 ± 1.8 years. Subjects were predominantly women (88.4%) with mean age of 58.2 ± 11.3 years and mean disease duration of 13.7 ± 9.1 years. One hundred and one (101, 15%) subjects died during follow-up, 37 (6.4 %) developed systolic dysfunction, 18 (2.9%) arrhythmias, 34 (5.1%) pulmonary arterial hypertension, 43 (7.3%) pulmonary hypertension, and 48 (12.3%) interstitial lung disease. In multivariate analyses, elevated levels of N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein were associated with increased risk of death, while elevated levels of N-terminal pro b-type natriuretic peptide and C-reactive protein were associated with increased risk of developing pulmonary hypertension. Conclusion: In systemic sclerosis, N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein have independent predictive value for death and pulmonary hypertension. A larger study would be required to determine the predictive value of these biomarkers for less common systemic sclerosis outcomes.

Clinical and prognostic implications of high-sensitivity cardiac troponin T concentrations in type 2 non-ST elevation myocardial infarction.

BACKGROUND: While the clinical importance of cardiac troponin is well-known in type 1 myocardial infarction (MI), evidence on this topic in type 2 MI is limited. We assessed the clinical and prognostic implications of high-sensitivity cardiac troponin (hs-cTnT) concentrations in a large sample of patients with type 2 MI. METHODS: Retrospective registry-based cohort study (SWEDEHEART) including 4607 patients with type 2 MI and 43,405 patients with type 1 MI, used for comparisons. Patients with ST-elevation MI were excluded. Multivariable-adjusted regressions were applied to investigate the associations of hs-cTnT concentrations (highest measured value during each hospitalization) with clinical variables and prognosis during a median follow-up of up to 1.9 years. RESULTS: Hs-cTnT concentrations (median 264 [25th, 75th percentiles 112-654] ng/L) were significantly associated with various cardiovascular risk factors and comorbidities in type 2 non-ST elevation MI (NSTEMI) but only weakly with the underlying triggering condition. Most of these findings including the magnitude of hs-cTn release were similar to type 1 NSTEMI. Hs-cTnT (ln) independently predicted all-cause mortality (hazard ratio 1.13 [95% confidence interval 1.09-1.17]) and major adverse events (hazard ratio 1.13 [95% confidence interval 1.10-1.17]) in type 2 NSTEMI, similar as for type 1 NSTEMI according to interaction analysis. The associations of hs-cTnT (ln) with poor prognosis tended to be stronger in type 2 NSTEMI patients without known cardiovascular disease. CONCLUSIONS: Hs-cTnT concentrations independently predict adverse outcome in type 2 NSTEMI. The similarities to type 1 NSTEMI however, are striking and emphasize the difficulty to distinguish both MI types.

[Current characteristics of methods for determining cardiac troponins and their diagnostic value: a mini-review] / Característica actual de los métodos para la determinación de troponinas cardíacas y su valor diagnóstico: minirrevisión.

The expansion and discovery of new diagnostic possibilities for the use of many biomarkers of cardiovascular diseases (CVDs), including cardiospecific troponin isoforms (cTnI, cTnT), is due to improved laboratory methods for their determination. Throughout a long history of the creation and improvement of immunochemical methods for the determination of cTnI and cTnT, significant changes were observed in the concept of biology and its diagnostic value as CVD biomarkers. The obsolete methods of detection of cTnI, cTnT, named low sensitivity and moderate, were distinguished by a relatively low sensitivity, which led to the confirmation late in the diagnosis of acute myocardial infarction (AMI) and, therefore, such methods were gradually replaced by new methods of high and moderate sensitivity, such as definitions of methods, ultra-sensitive (hs-cTnI, hs-cTnT). With the introduction of hs-cTnI and hs-cTnT in clinical practice, the possibility of early diagnosis and exclusion of AMI through the evaluation of the kinetics of the concentration of hs-cTnI and hs-cTnT in the first hours (0-1 hour, 0-2 hours, 0-3 hours) from the moment the patient enters the emergency room. In addition, some of our ideas about the biology of cardiac troponins have changed, and promising new opportunities for their use in medicine have emerged. This manuscript analyzes the key analytical characteristics of hs-cTnI and hs-cTnT detection methods compared to moderately sensitive methods, and reports on new biological data and some new diagnostic possibilities for the use of hs-cTnI and hs-cTnT in modern clinical practice.

La expansión y el descubrimiento de nuevas posibilidades de diagnóstico para el uso de muchos biomarcadores de enfermedades cardiovasculares (ECV), incluidas las isoformas de troponina cardioespecíficas (cTnI, cTnT), se debe a la mejora de los métodos de laboratorio para su determinación. A lo largo de una prolongada historia de la creación y mejora de métodos inmunoquímicos para la determinación de cTnI y cTnT, se observaron cambios significativos en el concepto de biología y su valor diagnóstico como biomarcadores de ECV. Los métodos obsoletos de detección de cTnI, cTnT, llamados de sensibilidad baja y moderada, se distinguieron por una sensibilidad relativamente baja, lo que llevó a la confirmación tardía del diagnóstico de infarto agudo de miocardio (IAM) y, por lo tanto, dichos métodos fueron reemplazados gradualmente por nuevos métodos de alta y moderada sensibilidad, como definiciones de métodos ultrasensibles (hs-cTnI, hs-cTnT). Con la introducción de hs-cTnI y hs-cTnT en la práctica clínica, la posibilidad de diagnóstico precoz y exclusión del IAM mediante la evaluación de la cinética de la concentración de hs-cTnI y hs-cTnT en las primeras horas (0-1 hora, 0-2 horas, 0-3 horas) desde el momento en que el paciente ingresa a urgencias. Además, algunas de nuestras ideas sobre la biología de las troponinas cardíacas han cambiado, y han surgido nuevas oportunidades prometedoras para su uso en medicina. En este artículo se discuten las características analíticas clave de los métodos de detección de hs-cTnI y hs-cTnT en comparación con métodos moderadamente sensibles, e informa sobre nuevos datos biológicos y algunas nuevas posibilidades de diagnóstico para el uso de hs-cTnI y hs-cTnT en la práctica clínica moderna.

The Prognostic Value of Cardiac Biomarkers and Echocardiography in Critical COVID-19.

Background: Early risk stratification is crucial in critically ill COVID-19 patients. Myocardial injury is associated with worse outcome. This study aimed to evaluate cardiac biomarkers and echocardiographic findings in critically ill COVID-19 patients and to assess their association with 30-day mortality in comparison to other biomarkers, risk factors and clinical severity scores. Methods: Prospective, single-center, cohort study in patients with PCR-confirmed, critical COVID-19. Laboratory assessment included high sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission to ICU: a hs-cTnT ≥ 14 pg/mL and a NT-proBNP ≥ 450 pg/mL were considered as elevated. Transthoracic echocardiographic evaluation was performed within the first 48 h of ICU admission. The primary outcome was 30-day all-cause mortality. Predictive markers for mortality were assessed by ROC analysis and cut-off values by the Youden Index. Results: A total of 100 patients were included. The median age was 63.5 years, the population was predominantly male (66%). At the time of ICU admission, 47% of patients had elevated hs-cTnT and 39% had elevated NT-proBNP. Left ventricular ejection fraction was below 50% in 19.1%. Elevated cardiac biomarkers (hs-cTnT P-value < 0.001, NT-proBNP P-value = 0.001) and impaired left ventricular function (P-value = 0.011) were significantly associated with mortality, while other biomarkers (D-dimer, ferritin, C-reactive protein) and clinical scores (SOFA) did not differ significantly between survivors and non-survivors. An optimal cut-off value to predict increased risk for 30-day all-cause mortality was 16.5 pg/mL for hs-cTnT (OR 8.5, 95% CI: 2.9, 25.0) and 415.5 pg/ml for NT-proBNP (OR 5.1, 95% CI: 1.8, 14.7). Conclusion: Myocardial injury in COVID-19 is common. Early detection of elevated hs-cTnT and NT-proBNP are predictive for 30-day mortality in patients with critical COVID-19. These markers outperform other routinely used biomarkers, as well as clinical indices of disease severity in ICU. The additive value of routine transthoracic echocardiography is disputable and should only be considered if it is likely to impact therapeutic management.

Kounis Syndrome Associated With Takotsubo Syndrome in an Adolescent With Peutz-Jeghers Syndrome.

We describe the case of a 15-year-old female patient with Peutz-Jeghers syndrome who presented with vomiting and abdominal pain secondary to ileoileal invagination. Initial analgesic treatment was not effective, and subsequent tramadol infusion resulted in clinical manifestations compatible with Kounis and Takotsubo syndromes. However, the patient had an excellent recovery. (Level of Difficulty: Advanced.).

6-year change in high sensitivity cardiac troponin T and the risk of atrial fibrillation in the Atherosclerosis Risk in Communities cohort.

BACKGROUND: Circulating high sensitivity cardiac troponin T (hs-cTnT) is associated with incidence of atrial fibrillation (AF), but the association of changes in hs-cTnT over time on incident AF has not been explored. HYPOTHESIS: Six-year increase in circulating hs-cTnT will be associated with increased risk of AF and will contribute to improved prediction of incident AF. METHODS: We conducted a prospective cohort analysis of 8431 participants from the Atherosclerosis Risk in Communities (ARIC) study. hs-cTnT change was categorized at visit 2 and 4 as undetectable (<5 ng/L), detectable (≥5 ng/L, <14 ng/L), or elevated (≥14 ng/L). We used Cox regression to examine the association between the combination of hs-cTnT categories at two visits and incident AF. We also assessed the impact of adding absolute hs-cTnT change on risk discrimination for AF by C-statistics and net reclassification improvement (NRI). RESULTS: Over a mean follow-up of 16.5 years, 1629 incident AF cases were diagnosed. Among participants with undetectable hs-cTnT at visit 2, the multivariable HR of AF was 1.28 (95% CI 1.12-1.48) among those with detectable or elevated hs-cTnT at visit 4 compared to those in which hs-cTnT remained undetectable. Among those with detectable hs-cTnT at visit 2, compared to those who remained in the detectable hs-cTnT group, reduction to undetectable at visit 4 was associated with lower risk of AF (HR 0.74, 95% CI 0.59-0.94), while increment to elevated was associated with higher AF risk (HR 1.30, 95% CI 1.01-1.68). Adding hs-cTnT change to our main model with baseline hs-cTnT did not result in significant improvement in the C-statistic or substantial NRI. CONCLUSION: Six-year increase in circulating hs-cTnT was associated with elevated risk of incident AF.

Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan'an district.

OBJECTIVE: To detect the concentration of high-sensitivity cardiac troponin T (hs-cTnT) in healthy children aged 0-14 years by electrochemiluminescence immunoassay (ECLIA), so as to explore the differences in different ages and genders. The aim of this study is to establish the reference interval for hs-cTnT in healthy children aged 0-14 years. METHODS: After screening, 3463 healthy children, including 1924 boys and 1539 girls, were selected from 4617 children aged 0-14 years. They were divided into nine groups: one day (umbilical cord blood; 'UCB'), one day (venous blood; 'VB'), 2-28 days, 29 days-<3 months, 3-<6 months, 6 months-<1 year old, 1-< 3 years old, 3-< 6 years old and 6-14 years old. A nonparametric test was used to detect the hs-cTnT concentration. The upper limit of the reference interval is the mean of the 99th percentile after bootstrap sampling. RESULTS: Hs-cTnT levels conformed to a non-Gaussian distribution. There was no significant difference in the concentration of hs-cTnT between boys and girls in the general data, but there were differences between boys and girls in the 3-<6 years old and 6-14 years old age groups. Except for UCB and 2-28 days, the concentration of hs-cTnT was significantly different in other age groups. The level of hs-cTnT in neonatal serum (2-28 days) was the highest. In other groups, it decreased gradually with age and dropped to the reference range of adults (0-14ng/L) at one-year old. The upper limit of reference interval of hs-cTnT concentration in each group was, respectively, 60.8, 78.8, 96.6, 58.6, 34.2, 16.2, 11.4, 8.0 (7.8 female), and 7.9 (7.3 female) ng/L. CONCLUSIONS: Referring to WS/T 402-2012 establishment of reference intervals for clinical laboratory testing projects and CLSI (Clinical and Laboratory Standards Institute) C28-A3 documents and the joint expert consensus of ESC (European Society of Cardiology) and ACC (American College of Cardiology) in 2007, we established the reference interval of hs-cTnT concentration in children aged 0-14 years in Chongqing Nan'an district of China which can provide certain reference value for clinical diagnosis and treatment of myocarditis and myocardial (micro) injury in children.

Relationship between high-sensitivity cardiac troponin T, B-type natriuretic peptide, and physical function in patients with heart failure.

AIMS: High-sensitivity cardiac troponin T (hs-cTnT) and B-type natriuretic peptide (BNP) are associated with prognosis and severity in patients with heart failure (HF); however, their association with physical function is unclear. This study aimed to investigate whether hs-cTnT and BNP levels are associated with physical function in patients with HF. METHODS AND RESULTS: Hs-cTnT, BNP, and physical function (maximal quadriceps isometric strength [QIS], usual gait speed, and 6-min walk distance [6MWD]) were evaluated in 363 consecutive patients with HF (median age, 70 [60-78] years). Patients were divided into four groups according to their median hs-cTnT and BNP levels. After adjusting for demographic characteristics, laboratory levels, and HF severity, higher hs-cTnT and BNP levels were significantly associated with lower physical function (log hs-cTnT, ß = -0.162, P = 0.001, for maximal QIS; ß = -0.175, P = 0.002, for usual gait speed, and ß = -0.129, P = 0.004, for 6MWD; log BNP, ß = -0.090, P = 0.092, for maximal QIS, ß = 0.038, P = 0.516, for usual gait speed, and ß = -0.108, P = 0.023, for 6MWD). In addition, the high hs-cTnT and high BNP group had significantly lower physical function (all P < 0.05) than the low hs-cTnT and low BNP group. CONCLUSIONS: Higher hs-cTnT and BNP levels are both associated with lower physical function in patients with HF, but hs-cTnT levels showed a more consistent association. The combination of hs-cTnT and BNP may be effective for the stratification of physical function in patients with HF.

Biopsy Evidence of Sequential Transthyretin and Immunoglobulin Light-Chain Cardiac Amyloidosis in the Same Patient.

Currently adopted diagnostic flow charts consider transthyretin and light-chain cardiac amyloidosis as mutually exclusive. Here, we report for the first time, to our knowledge, the demonstration of a biopsy-proven dual pathology in an 80-year-old man with sequential development of both wild-type transthyretin amyloidosis and light-chain cardiac amyloidosis cardiomyopathy over a 3-year timespan. (Level of Difficulty: Intermediate.).

Cardiac Troponins: Contemporary Biological Data and New Methods of Determination.

Laboratory diagnosis plays one of the key roles in the diagnosis of many diseases, including cardiovascular diseases (CVD). The methods underlying the in vitro study of many CVD biomarkers, including cardiac troponins (cTnI and cTnT), are imperfect and are continually being improved to enhance their analytical performance, with sensitivity and specificity being the most important. Recently developed improved cTnI and cTnT detection methods, referred to as highly sensitive methods (hs-cTnI, hs-cTnT), have changed many of our ideas about the biology of cardiac troponins and opened up a number of additional diagnostic capabilities for practical healthcare. This article systematizes some relevant data on the biology of cardiac troponins as well as on methods for determining cTnI and cTnT with an analysis of the diagnostic value of their analytical characteristics (limit of blank, limit of detection, 99th percentile, coefficient of variation, and others). Data on extracardiac expression of cTnI and cTnT, mechanisms of formation and potential clinical significance of gender, age, and circadian characteristics of hs-cTnI and hs-cTnT content in serum are discussed. Considerable attention is paid to the discussion of new diagnostic capabilities of hs-cTnI, hs-cTnT, including consideration of promising possibilities for their study in biological fluids that can be obtained by non-invasive methods. Also, some possibilities of using hs-cTnI and hs-cTnT as prognostic laboratory biomarkers in healthy people (for example, to assess the risk of developing CVD) and in patients suffering from a number of pathological conditions that cause damage to cardiomyocytes are examined, and the potential mechanisms underlying the increase in hs-cTnI and hs-cTnT are discussed.