Elevated cTnT Research Articles

The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis

The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI) (ischemic necrosis of cardiac myocytes). Any type of reversible or irreversible cardiomyocyte injury can result in elevated serum cTnT and cTnI levels. Researchers and practitioners involved in the diagnosis and treatment of cardiovascular disease, including AMI, should know the key causes and mechanisms of elevated serum cTnT and cTnI levels. This will allow to reduce or completely avoid diagnostic errors and help to choose the most correct tactics for further patient management. The purpose of this article is to discuss the main causes and mechanisms of increase in cardiac troponins concentrations in frequently occurring physiological (physical exertion, psycho-emotional stress) and pathological conditions (inflammatory heart disease, pulmonary embolism, chronic renal failure and sepsis (systemic inflammatory response)) not related to myocardial infarction.

Association of Cardiac Troponin T Concentration on Admission with Prognosis in Critically Ill Patients without Myocardial Infarction: A Cohort Study.

PurposeTo investigate the association of cardiac Troponin T (cTnT) with prognosis in critically ill patients without myocardial infarction.MethodsAdult patients admitted to the intensive care units (ICUs) of the Beth Israel Deaconess Medical Center between 2008 and 2019 who were free of myocardial infarction with a length of ICU stay ≥24 hours and available cTnT records within 24 hours before and after ICU admission were included. The association between cTnT on ICU admission and hospital mortality was evaluated by multivariable logistic regression analysis. The discrimination capacity of cTnT on ICU admission for predicting hospital mortality was examined by receiver operating characteristic (ROC) analysis.ResultsA total of 2960 patients were included. Elevated cTnT (>0.01 ng/mL) was observed in 2730 (92.23%) patients with a higher hospital mortality compared to normal cTnT (11.21% versus 7.39%, P=0.075). There was no statistically significant association between elevated cTnT on ICU admission and hospital mortality (adjusted odds ratio 1.50, 95% confidence interval (CI) 0.88–2.57). Poor discrimination capacity was found for cTnT on ICU admission to predict hospital mortality (area under the ROC curve 0.48, 95% CI 0.44–0.53).ConclusioncTnT on ICU admission has limited prognostic value in critically ill patients without myocardial infarction.

Doğal Gelişen Şiddetli Sepsisli ve Septik Şoklu Buzağılarda Pıhtılaşma Bozuklukları ve Kardiyak Biyomarkırlarının Değerlendirilmesi

Coagulation abnormalities and myocardial injury frequently occur during sepsis. The aim of the present study was to evaluate the coagulation parameters and cardiac-specific biomarkers at set intervals in septic neonatal calves. Ten healthy calves and 20 septic calves were included in the study. For detecting coagulation parameters prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, fibrinogen, antithrombin III (AT III), thrombocyte and, for cardiac biomarkers cardiac troponin (cTn) I, T, and creatine kinase-MB (CK-MB) were evaluated on admission, 24 and 72 hours later in septic calves and once in healthy calves. The results of coagulation parameters showed a significant elevation of PT and APTT times from the time of admission until the 72nd hour and a significant reduction of AT III and fibrinogen from the time of admission until the 72nd hour. Cardiac troponin T was high in the 72nd hour, and CK-MB was high in the time of admission, 24th and 72nd hours in septic calves compare to the healthy calves. There was a correlation between PT, APTT, fibrinogen with cardiac troponin T. In conclusion, cardiac damage can develop during the hypercoagulable state of disseminated intravascular coagulation (DIC), and maybe it is responsible for the elevation of cTnT and CK-MB and worse outcome in neonatal septic calves.

Exercise-Induced Release of Cardiac Troponins in Adolescent vs. Adult Swimmers.

To examine the exercise-induced release of cardiac troponin T (cTnT) in adolescent and adult swimmers. Thirty-two trained male (18 adolescents, 14 adults) swam at maximal pace in a 45 min distance trial, and blood samples were drawn before, immediately and 3 h after exercise for subsequent cTnT analysis and comparison. Having comparable training experience and baseline values of cTnT (p = 0.78 and p = 0.13), adults exercised at lower absolute and relative intensity (p < 0.001 and p < 0.001, respectively), but presented higher immediate cTnT after exercise than adolescents (p < 0.001). Despite that, peak concentrations were observed at 3 h post exercise and peak elevations were comparable between groups (p = 0.074). Fourteen (44%) apparently healthy subjects exceeded the cutoff value for myocardial infarction (MI). Adolescents presented a delayed elevation of cTnT compared with adults, but achieved similar peak values.

Detection of myocardial injury in perinatal asphyxia by echocardiography and cardiac biomarkers

Perinatal hypoxia can induces cardiac (Cd) injury in the newborn and requires an early diagnosis. Cd troponin I (cTnI) is correlated to hypoxic myocardial lesion-may be a useful marker of it Objectives: to evaluate the utility of echocardiography(echo) and research of cTnI values for diagnosis of myocardial injury. Patients: 98 newborns (0–14 days), with perinatal hypoxia, without major Cd anomalies, to wich were performed: clinical exam, ECG, Rx.CT, echo, research of cTnT values. The patients had mainly signs of neurological post hypoxic suffering without signs of Cd distress. The Cd exam: tachycardia, systolic murmur (64 pts); RxCT: cardiomegaly (35); ECG: LV repolarization disturbances (37);. Echo at 2–7 days of life: the absence of severe Cd malformations; myocardial LV hypertrophy (42 pts); normal LV systolic function(all); LV diastolic dysfunction (45 pts).The importance of Cd involvement were correlated with signs of hypoxic ischemic encephalopathy. The pts received spironolactone 1 mg/kg/day for 1 month, then 1 mg/Kg at 2 days (the alternating pattern) for 2–3 months. Evolution: absence of new myocardial suffering signs, is maintains systolic murmur (2/3 pts); reevaluation of echo at 6 months: the reduction of the myocardial hypertrophy, normal LV diastolic function; elevated cTnT values (> 0.12 μg/l): 56% pts with perinatal hypoxic suffering. The perinatal hypoxia can induce the apparition of post hypoxic hypertrophic cardiomyopathy(HCMP)(69% pts), LV diastolic function disturbancies and normal systolic LV function, even if the signs of Cd suffering missing often; echo is the main method for diagnosis and follow up of perinatal hypoxic HCMP and is necessary from the first week of life; increased values of cTnT(> 0.12 μg/l) in perinatal asphyxia prove hypoxi c myocardial damage; traitement with spironolactone for 2–3 months induced improving of HCMP and normalising of LV diastolic disfunction and cTnI values.

The feasibility and safety of left bundle branch pacing vs. right ventricular pacing after mid-long-term follow-up: a single-centre experience.

The aim of this study is to prospectively assess the feasibility and safety of left bundle branch pacing (LBBP) when compared with right ventricular pacing (RVP) during mid-long-term follow-up in a large cohort. Patients (n = 554) indicated for pacemaker implantation were prospectively and consecutively enrolled and were non-randomized divided into LBBP group and RVP group. The levels of cTnT and N-terminal pro-B type natriuretic peptide were measured and compared within 2 days post-procedure between two groups. Implant characteristics, procedure-related complications, and clinical outcomes were also compared. Pacing thresholds, sensing, and impedance were assessed during procedure and follow-up. Left bundle branch pacing was feasible with a success rate of 94.8% with high incidence of LBB potential (89.9%), selective LBBP (57.8%), and left deviation of paced QRS axis (79.7%) with mean Sti-LVAT of 65.07 ± 8.58 ms. Paced QRS duration was significantly narrower in LBBP when compared with RVP (132.02 ± 7.93 vs. 177.68 ± 15.58 ms, P < 0.0001) and the pacing parameters remained stable in two groups during 18 months follow-up. cTnT elevation was more significant in LBBP when compared with RVP within 2 days post-procedure (baseline: 0.03 ± 0.03 vs. 0.02 ± 0.03 ng/mL, P = 0.002; 1 day post-procedure: 0.13 ± 0.09 vs. 0.04 ± 0.03 ng/mL, P < 0.001; 2 days post-procedure: 0.10 ± 0.08 vs. 0.03 ± 0.08 ng/mL, P < 0.001). The complications and cardiac outcomes were not significantly different between two groups. Left bundle branch pacing was feasible in bradycardia patients associated with stable pacing parameters during 18 months follow-up. Paced QRS duration was significantly narrower than that of RVP. Though cTnT elevation was more significant in LBBP within 2 days post-procedure, the complications, and cardiac outcomes were not significantly different between two groups.

Abstract 16397: Presence of Myocardial Injury on Admission is Associated With an Increase in All-cause Mortality in Patients With COVID-19

Introduction: COVID-19 has emerged as a global health crisis resulting in nearly half a million deaths worldwide to date. Patients with COVID-19 experience significant cardiovascular manifestations including myocardial injury. We sought to determine the risk of myocardial injury within 24 hours of admission on all-cause mortality in patients with COVID-19. Methods: This was a prospective cohort study of patients hospitalized with COVID-19 at a major academic medical center between March 1, 2020-June 1, 2020. The combination of cardiac troponin T (cTnT) elevation (defined as ≥0.01 ng/mL) within 24 hours of admission and an elevated NT-proBNP (defined as &gt;450.0 pg/mL) on admission were used as biomarker surrogates for myocardial injury. Results: There were n = 415 consecutive patients who were hospitalized with COVID-19 with a median age of 68.5 years (IQR 58-81), 44.8% were women, a median BMI of 28.8 (IQR 24.6-35.6), 5.8% of patients had end-stage renal disease on dialysis, 21.6% had a prior diagnosis of coronary artery disease and 21.8% had a prior diagnosis of congestive heart failure. Among patients with at least one positive cTnT level within 24 hours of admission, the median cTnT level was 0.04 ng/mL (IQR 0.01-0.77 ng/mL). Among those with elevated BNP, the median BNP was 1930 pg/mL (IQR 799-5826 pg/mL) on admission. Patients with COVID-19 who had an elevation in both cardiac biomarkers on admission had higher all-cause mortality than patients with COVID-19 who had negative biomarkers (38.2% vs. 7.5%, respectively, p-value &lt; 0.001), with nearly a 5-fold increase in mortality when adjusted for age, gender, BMI and renal dysfunction (adjusted OR 4.9, p-value: 0.003, 95% CI 1.7-13.9, See Figure) Conclusion: Myocardial injury is common in patients with COVID-19 and is associated with a significantly increased risk of death. Cardiac biomarkers on admission can serve as prognostic factors and may guide early management of COVID-19.

66 Comparing Conventional and High Sensitivity Troponin in Predicting a Major Acute Coronary Event in Chest Pain Patients with Intact Renal Function

This study determined whether high sensitivity troponin outperformed its predecessor in predicting a major adverse coronary event (MACE) in intact kidney function patients. This retrospective cohort study of ED patients diagnosed with chest pain, angina, unstable angina, or myocardial infarction (ICD-10 codes R07, I20, I21) was conducted from January 1 to November 27, 2018 at a tertiary care academic ED center (annual volume 95,000). Inclusion criteria was intact renal function (eGFR > 60 ml/min/1.72m2). The Roche® 4th generation conventional troponin (cTnT) was used until June 12 with a negative troponin defined as <0.06ng/mL and positive as ≥0.06ng/mL. Then, the Roche® 5th generation high sensitivity troponin (hsTnT) was used with a negative troponin defined as ≤14ng/L and a positive as ≥52ng/L. All patients were then reviewed for a MACE, defined as cardiac-related mortality, need for a coronary stent or bypass graft, or clinically diagnosed myocardial infarction type 1 or 2 within 6 weeks of initial ED visit. 6360 ED chest pain patient records were reviewed. 5063 had normal renal function. Of these, 2,655 patients (51±15 years, 56% female) had conventional troponin drawn, of which 147 patients had a MACE (prevalence = 5.5%) (see Table). 53 patients had a positive cTnT, of which 44 patients developed a MACE (PPV = 83.0%). The remaining 2,602 patients had negative cTnT, of which 103 patients developed a MACE (NPV = 96%). The positive likelihood ratio (+LR) of an elevated cTnT detecting a MACE was very high at 83 (95% CI 42, 168). The negative likelihood ratio (-LR) of a negative cTnT excluding a MACE was moderate at 0.70 (95% CI 0.63, 0.78). 2174 patients (49±15 years, 59% female) had a positive or negative high sensitivity troponin, of which 99 patients had a MACE (prevalence = 4.6%). 77 patients had a positive hsTnT of which 51 developed a MACE (PPV = 66.2%). Of the 2097 patients with a negative hsTnT, 48 developed a MACE (NPV = 97.7%). The +LR of a positive hsTnT detecting a MACE was significant at 41 (95% CI 41, 63) but lower than that of cTnT. The -LR of a negative hsTnT excluding a MACE was more significant at 0.49 (95% CI 0.40, 0.60) than that of a negative cTnT. In patients with normal renal function, a negative high sensitivity troponin is more likely than conventional troponin to exclude a MACE event. However, this comes at a slight cost, as a positive high sensitivity troponin has a lesser chance to detect MACE than a positive conventional troponin.Tabled 1Intact Renal ED CP Pts# PtsSensSpecPPV (95% CI)NPV (95% CI)+LR [95% CI]-LR [95% CI]cTnT265529.9%99.6%83.0% (81.5-84.5%)96.0% (95.2-96.8%)83 [42, 168]0.70 [0.63, 0.78]hsTnT217451.5%98.7%66.2% (64.3-68.1%)97.7% (97.1-98.3%)41 [27, 63]0.49 [0.40, 0.60] Open table in a new tab

Myocardial injury in patients with sickle cell anaemia and myocardial ischaemia in Calabar, Nigeria

ABSTRACT Background In children with sickle cell anaemia (SCA), ischaemic electrocardiogram (ECG) changes occur during both vaso-occlusive crises (VOC) and the steady state. Myocardial ischaemia evidenced by an ischaemic pattern on ECG may lead to myocardial injury which is evidenced by elevated serum cardiac troponin T (cTnT). Occasionally, the myocardial injury is fatal. Aim To determine the relationship between raised serum cTnT levels and an ischaemic ECG pattern in children with SCA. Methods This was a dual study design comprising a prospective cohort study of a group of children with SCA observed during VOC and 6 weeks later during follow-up steady state, and a case–control study of SCA children and apparently healthy children. The subjects were 34 SCA children aged 5–17 years and 34 age- and sex-matched apparently healthy controls with haemoglobin genotype AA attending University of Calabar Teaching Hospital. VOC was diagnosed by clinical examination and a history of bone pain. During VOC and follow-up steady state, an ECG was performed and blood taken for serum cTnT estimation. In the apparently healthy children, only serum cTnT was estimated. Serum cTnT was analysed by electrochemiluminescence immune-assay. Ischaemic ECG was assessed using the World Heart Federation criteria. Results Twenty-eight (82.4%) SCA children had elevated serum cTnT during VOC and it was elevated in only six (17.6%) of them during the steady state. An ischaemic ECG was observed in 25 (73.5%) and 20 (58.8%) of them during VOC and the steady state, respectively. Ischaemic ECG identified SCA children with elevated cTnT during VOC (sensitivity 75%, specificity 33.3%) and the follow-up steady state (sensitivity 50%, specificity 39.3%). Measures of agreement between ECG and cTnT in detecting myocardial injury were poor during VOC (κ 0.07, p = 0.68) and the follow-up steady state (κ − 0.06, p = 0.63). Conclusions Most SCA children have an ischaemic ECG with elevated serum cTnT, especially during VOC, which suggests ischaemic-induced cardiac injury. However, elevated serum cTnT can occur without an ischaemic ECG and vice versa. Performing only electrocardiography or cTnT to detect ischaemia-induced cardiac injury may be misleading. Therefore, when there is a high index of suspicion, both tests should be undertaken, especially during VOC, to ensure prompt, effective treatment. Abbreviations AHC, apparently healthy children; AUC, area under the ROC curve; BMI, body mass index; cTnT, cardiac troponin T; ECG, electrocardiogram; EDTA, ethylene diamine tetra-acetic acid; GFR, glomerular filtration rate; HbS, haemoglobin S; HLA, human leucocyte antigen; LVH, left ventricular hypertrophy; ROC, receiver operating characteristic; SCA, sickle cell anaemia; UCTH, University of Calabar Teaching Hospital; URL, upper reference limit; USFDA, United States Food and Drug Administration; USNIH, United States National Institutes of Health; VOC, vaso-occlusive painful crisis; WHF, World Heart Federation;

Influence of maturational status in the exercise-induced release of cardiac troponin T in healthy young swimmers

ObjectivesTo determine the influence of maturational status on the release of cardiac troponin T (cTnT) induced by a bout of 30min, high-intensity, continuous exercise. DesignQuasi-experimental, cross-sectional study. MethodsSeventy male, young, well trained swimmers (age range 7–18 years, training experience 1–11 years) were classified by maturational stages: Tanner stage I (n=14), II (n=15), III (n=15), IV (n=13), and V (n=13). Participants underwent a distance-trial of 30min continuous swimming, and cTnT was measured before, immediately after and 3h after exercise. Changes in cTnT over time were compared among groups, and associated with exercise load. ResultsBasal cTnT was higher in Tanner-V (3.8–8.1ng/L) compared with I (1.5–5.5ng/L, p<0.001), II (1.5–4.5ng/L, p<0.001) and III (1.5–6.8ng/L, p=0.003), and in IV (1.5–6.3ng/L) compared with II (p=0.036). Maximal elevations of cTnT from baseline were notable (p<0.001) and comparable among maturational stages (p=0.078). The upper reference limit for myocardial injury was exceeded in 35.7% of the participants, without differences among groups (p=0.18). Baseline cTnT correlated with participant characteristics, and maximal cTnT elevations from baseline with exercise internal load (%HRpeak, rs=0.34, p= 0.003; %HRmean, rs=0.28, p=0.02). ConclusionsMaturational status influences positively absolute pre- and post-exercise cTnT but not its elevation after a bout of 30min, high-intensity, continuous exercise.

Relationship of lipoprotein-associated phospholipase A2(Lp-PLA2) and periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention

BackgroundPercutaneous coronary intervention (PCI) is one of the dominant methods for revascularization in patients with coronary heart disease (CHD). However, periprocedural myocardial injury (PMI) is a frequent complication following PCI and is known to be a predictor of postprocedural cardiovascular morbidity and mortality. Although several studies try to identify serum markers to predict the PMI, there is a little information about the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) as a predictor of PMI. Therefore, we aimed to investigate the relationship of Lp-PLA2 levels and PMI in patients undergoing elective PCI. MethodsThis study included 265 consecutive patients with normal preprocedural cardiac troponin T(cTNT) who received elective PCI. The samples for cTNT were collected at 8, 16, and 24 h after PCI to assess perioperative myocardial injury. The Lp-PLA2 and other serum lipid parameters were measured after 12 fasting hours before PCI. ResultsThe data suggested that the patients with preprocedural high Lp-PLA2 were strongly and independently correlated with the risk of PMI. Pearson correlation analysis showed that preprocedural Lp-PLA2 was significantly positively correlated with postprocedural cTnT elevation (r = 0.694, p < 0.05). Binary logistic regression analysis was used to analyze the risk factors of PMI, we found that Lp-PLA2 was independent risk factor for postprocedural cTnT elevation. The area under Receiver Operating Characteristic curve of Lp-PLA2 was 0.757 (95%CI 0.692 ~ 0.821, p < 0.001), the best cut-off point was 185 ng/ml, sensitivity and specificity were 65.33% and 76.32%. ConclusionOur study demonstrated that preprocedural Lp-PLA2 was associated with postprocedural cTnT elevation and was the independent risk factor of PMI.

Cardiac Troponin T Release after Football 7 in Healthy Children and Adults.

The objective of this study was to compare the release of cardiac troponin T (cTnT) after a football 7 match between two cohorts of children and adult players. Thirty-six male football players (children = 24, adult = 12) played a football 7 match, and cTnT was measured before, and 3 h after exercise. Concentrations of cTnT were compared between groups and time, and correlated with participants’ characteristics, as well as internal and external exercise load. Cardiac troponin T was elevated in all participants (p < 0.001), and exceeded the upper reference limit for myocardial infarction in 25 (~70%) of them. Baseline concentrations were higher in adults (p < 0.001), but the elevation of cTnT was comparable between the groups (p = 0.37). Age (p < 0.001), body mass (p = 0.001) and height (p < 0.001), and training experience (p = 0.001) were associated to baseline cTnT values, while distance (p < 0.001), mean speed (p < 0.001), and peak (p = 0.013) and mean (p = 0.016) heart rate were associated to the elevation of cTnT. The present study suggests that a football 7 match evoked elevations of cTnT during the subsequent hours in healthy players regardless of their age. However, adults might present higher resting values of cTnT than children. In addition, results suggest that the exercise-induced elevations of cTnT might be mediated by exercise load but not participant characteristics.

Exploring the association between extra-cardiac troponin elevations and risk of future mortality.

Although the measurement of cardiac troponin I (cTnI) and T (cTnT) has now become the cornerstone for diagnosing cardiac injury, both ischemic and non-ischemic, recent evidence has become available that many patients display extra-cardiac causes of cTn elevations and carry a considerably enhanced risk of future mortality. The current literature data suggests that cTn elevations may be equally common in patients with cardiac and extra-cardiac diseases. Among the latter cohort of patients, the leading extra-cardiac diseases which may be responsible for either cTnI or cTnT elevations include infectious diseases/sepsis, pulmonary disorders, renal failure, malignancy, as well as gastrointestinal, neurological and musculoskeletal diseases. What also emerges rather clearly from the current literature data, is that the risk of dying for extra-cardiac diseases is higher (i.e., between two to three-fold) in patients with extra-cardiac cTn elevations than in those with cardiac pathologies, and that the most frequent cause of death would then be infections/sepsis, followed by malignancy, respiratory disorders, myocardial infarction, gastrointestinal and neurological diseases, heart failure, stroke, cardiac arrhythmias, renal failure, psychiatric, metabolic, urogenital and musculoskeletal disorders. These figures would lead to conclude that there is a considerable risk that the underlying pathology causing cardiac injury and cTn elevation would then become the cause of death in these patients. This important evidence shall lead the way to defining appropriate and effective strategies for managing patients with extra-cardiac cTn elevations, so that their risk of future death could be prevented or limited.

Outcomes of autologous stem cell transplant for cardiac AL-amyloidosis and cardiac light chain deposition disease.

Cardiac amyloidosis and light chain deposition disease (LCDD) are the most common cause of death in AL amyloidosis or LCDD. Our multiple myeloma database identified 50 patients with cardiac amyloidosis or LCDD between January 2004 and January 2013. Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes. The median age at diagnosis was 61 years for those who received autologous hematopoietic stem cell transplant (ASCT) and 71 years for those who received only bortezomib-based chemotherapy; 62.5% (n = 30) of patients had elevated levels of NT-proBNP ≥323 ng/L, and 29.2% (n = 14) of patients had an elevated cTnT ≥0.1 µg/L. Echocardiogram findings showed a speckled appearance in 18% (n = 9) of patients, and 60% (n = 30) of patients had an increased diastolic intra-ventricular septum (IVSD) thickness measuring ≥1.3 cm; 64.3% (n = 18) of patients who underwent cardiac MRI showed subendocardial enhancement. Out of 48 patients who received treatment, 37 patients were diagnosed with cardiac amyloidosis and 11 patients were diagnosed with cardiac LCDD. Twenty-eight patients (75.7%) with cardiac amyloidosis received ASCT, compared to 34.3% (n = 9) patients who were ineligible for ASCT and received chemotherapy only. Patients who underwent ASCT had a median OS of 4.48 years compared to 1.82 years (p = 0.69) for those receiving chemotherapy alone. Our single institution experience shows that ASCT is feasible for cardiac amyloidosis and/or cardiac LCDD. However, careful selection of proper patients and diligent supportive care are vital to decreasing transplant-related mortality.

CARDIAC TROPONIN T MEDIATED AUTOIMMUNE RESPONSE AND ITS ROLE IN SKELETAL MUSCLE AGING

Cardiac troponin T (cTnT), a key component of contractile machinery essential for muscle contraction, is also expressed in skeletal muscle under certain conditions (e.g. neuromuscular diseases and aging). We have reported that skeletal muscle cTnT regulates neuromuscular junction denervation preferentially in fast skeletal muscle of old mice. Here, we further report that cTnT is also enriched within some myofibers, and/or along microvascular walls in old mice fast skeletal muscle. Strikingly, immunoglobulin G (IgG), together with markers of complement system activation, cell death (necroptosis or apoptosis), and macrophage infiltration, were all found to be co-localized with cTnT and IgG in those areas. In addition, elevated cTnT and IgG are associated with lower dystrophin expression on muscle fiber membrane, lower muscle capillary density, and reduced muscle performance (wire hanging test). Using purified recombinant TnT proteins, we confirmed that only cTnT, but not slow or fast skeletal muscle TnT1 or TnT3, was detected by immunoblot using sera from old (but not young) mice with pre-determined elevated cTnT and IgG in their skeletal muscle, indicating the existence of anti-cTnT autoantibodies in sera (previously found in human blood) and skeletal muscle of old mice. Immunoblotting further revealed that the age related changes in skeletaI muscle cTnT and IgG are more prominent in fast skeletal muscle than in slow. Importantly, elevated cTnT and IgG were also detected in skeletal muscles from 4 older adults (65-70 yrs, IMFIT). Our finding suggests a novel autoimmune mechanism mediated by cTnT that underlies age related skeletal muscle abnormalities and dysfunction.

Cardiac Troponin T and Right Ventricular Systolic Pressure Predict Cardiovascular and Mortality Risk in Kidney Transplant Candidates

Background: Patients presenting for kidney transplant (KTx) evaluation are subject to high rates of mortality and cardiovascular (CV) events pre- and post-KTx. CV and mortality risk assessment is needed. Methods: We evaluated cardiac troponin T (cTnT) as a predictor of CV events and mortality in a racially diverse cohort with significant CV disease burden presenting for KTx evaluation. Right ventricular systolic pressure (RVSP) was also assessed in predicting these outcomes. The population consisted of 561 patients presenting for KTx evaluation from 2011 to 2013 at Mayo Clinic, Arizona. A cutoff value for cTnT and RVSP that was most associated with CV events or mortality was derived. Multivariate Cox regression analysis was used to assess cTnT, RVSP, traditional, and other risk factors for the outcomes of interest. Results: Mean age was 53.5 ± 13.7 years and the median follow-up after KTx evaluation was 48.0 months. The cohort was 70.6% (n = 392) White, 11.4% (n = 63) Black, 8.5% (n = 47) Native American, and 3.1% (n = 17) Asian. Preexisting CV disease at the time of evaluation was prevalent in 24.4% (n = 137) of patients. During follow-up, 66.3% (n = 372) received a KTx and 21.9% (n = 123) had a composite event (16.8% death, 6.6 % CV events). It was found that 70.7% (n = 87) of events occurred in patients who were not transplanted; 53.5% (n = 300) had an elevated cTnT (≥0.01 ng/mL, median 0.02 ng/mL) and 84.1% (n = 344) of patients with RVSP data had an elevated RVSP (>25 mm Hg). Time to event analysis identified a cTnT ≥0.036 ng/mL and RVSP ≥31 mm Hg to be best predictive of CV events and mortality. Smoking, CV disease, hypoalbuminemia, RVSP, and cTnT independently predicted CV events and mortality. Conclusion: Elevated cTnT and RVSP were independently predictive of CV events and mortality in the cohort. Clinicians should consider the value of RVSP and cTnT as markers of CV risk in KTx evaluation.

The impact of exercise modality and menstrual cycle phase on circulating cardiac troponin T

ObjectivesIt is unclear whether exercise modality (moderate-intensity continuous [MCE]; high-intensity interval [HIE]) and menstrual cycle phase (follicular [FP]; luteal [LP]), individually or in combination, mediate the commonly observed exercise-induced elevation in cardiac troponin T (cTnT). This study examines cTnT responses to MCE and HIE during both the FP and LP. DesignRandomised crossover study. MethodsSeventeen healthy, eumenorrheic women completed four trials including MCE (60% VO2max steady-state cycling until 300kJ) and work‐equivalent HIE (repeated 4-min cycling at 90% VO2max interspersed with 3-min rest) during both the FP and LP. The FP and LP were verified based on ovarian hormones. Serum cTnT was assessed using a high-sensitivity assay before, immediately after, and 1 (1HR), 3 (3HR) and 4 (4HR) hours after exercise. cTnT values were corrected for plasma volume changes. ResultscTnT was significantly elevated (p<0.05) post-exercise in both MCE (at 3HR and 4HR) and HIE (at 1HR, 3HR and 4HR). No statistically significant difference (p>0.05) in peak post-exercise cTnT, which mostly occurred at 3HR, was seen among the four trials (median [range], ngl−1: 5.2 [1.7–18.1] after MCE during FP; 4.8 [1.7–24.9] after MCE during LP, 8.2 [3.9–24.8] after HIE during FP and 6.9 [1.7–23.1] after HIE during LP). ConclusionsA single 300kJ bout of both MCE or HIE resulted in a significant post-exercise increase in cTnT, with no differences in peak cTnT response between menstrual cycle phases or between exercise modes, but the cTnT elevation occurs slightly earlier after HIE.

Impact of High-intensity Interval Exercise and Moderate-Intensity Continuous Exercise on the Cardiac Troponin T Level at an Early Stage of Training.

An elevation in cardiac troponin T (cTnT), as a highly specific biomarker of cardiomyocyte damage, after moderate-intensity continuous exercise (MCE) has been described. The exercise-induced cTnT response distorts the diagnostic role of the cTnT assay. Although high-intensity interval exercise (HIE) is growing in popularity and concerns remain about its safety, available data related to cTnT release after HIE is limited, which hampers the use of HIE as a health intervention. Here, we present three representative HIE protocols [traditional HIE (repeated 4 min cycling at 90% V̇O2max interspersed with 3 min rest, 200 kJ/session); sprint interval exercise (SIE, repeated 1 min cycling at 120% V̇O2max interspersed with 1.5 min rest, 200 kJ/session); and repeated sprint exercise (RSE, 40 x 6 s all-out sprints interspersed with 9 s rest)] and one representative MCE protocol (continuous cycling exercise at an intensity of 60% V̇O2max, 200 kJ/session). Forty-seven sedentary, overweight young women were randomly assigned to one of four groups (HIE, SIE, RSE, and MCE). Six bouts of respective exercise were performed by every single group, with each being 48 h apart. Meanwhile, for four groups, the duration of the entire testing period was identical, being 10 days. Before and after the first and final exercise bouts, an assessment was conducted of cTnT. The current study provides a frame of reference giving a clear picture of how a specific exercise session affects the circulating cTnT concentration at the early stage of training. The information may assist with clinical interpretations of post-exercise cTnT elevation and guide the prescription of exercise, especially for HIE.

P885Cardiovascular events in patients with suspected ST-elevation myocardial infarction and no obstructive coronary artery disease

Abstract Background Patients with suspected ST-elevation myocardial infarction (STEMI) and no obstructive coronary artery disease (CAD) comprise a heterogeneous group with varying prognoses. Purpose To evaluate the prognostic value of cardiac troponin T (cTnT) in patients with suspected STEMI and no obstructive CAD. Methods Patients with suspected STEMI and no obstructive (&lt;50% diameter stenosis) CAD were consecutively included from 2009–2014. Patients were classified as having normal cTnT, dynamic cTnT elevation, or stationary cTnT elevation. All patients were followed with respect to major adverse cardiovascular events (MACE), cardiovascular readmission, and repeat coronary procedures, until 1 year after discharge. Results The study included 502 patients with suspected STEMI and no obstructive CAD: 165 (33%) had normal cTnT, 293 (58%) had dynamic cTnT elevation and 44 (9%) had stationary cTnT elevation. Within one year after admission, 40 (8%) had MACE, 81 (16%) had cardiovascular readmission, and 8 (2%) underwent repeat coronary procedures. The risk of MACE was elevated in patients with stationary cTnT elevation compared with normal cTnT (OR 13.6, 95% CI 2.3–80.2, p=0.004). There was no statistically significant difference between those with dynamic cTnT elevation and normal cTnT (OR 2.9, 95% CI 0.6–14.0, p=0.189). Adding cTnT pattern to a conventional risk model, area under the receiver operating curve for predicting the 1-year risk of MACE improved significantly (80% vs. 85%, p=0.004, Figure 1). Figure 1 Conclusion In patients with suspected STEMI and no obstructive CAD, cTnT pattern during acute hospitalization is associated with the 1-year risk of MACE and improves risk prediction for the individual patient. Acknowledgement/Funding The Danish Heart Foundation, the A.P. Møller Foundation, the Foundation of Reinholdt W. Jorck and Wife, Rigshospitalet's Research Foundation

P4503A multi-site coronary vein sampling study on cardiac troponin T degradation in non-ST-elevation myocardial infarction

Abstract Background High-sensitivity cardiac troponin (hs-cTn) assays have reduced specificity for myocardial infarction (MI). In conditions other than MI, cardiac troponin T (cTnT) elevations have been attributed to small cTnT fragments. In search of improved cTnT assay specificity for MI, determination of the in-vivo molecular appearance of cTnT during MI is pivotal. Purpose To determine cTnT composition close to its site of release and during the course of MI by multi-site coronary venous system (CVS) and peripheral sampling. Methods Lithium-heparinized (LH) plasma and serum samples were obtained from multiple CVS locations in NSTEMI patients. Additionally, samples were drawn from a peripheral artery and vein followed by collections at 6- and 12 hours post-catheterization. cTnT concentrations were measured using the hs-cTnT immunoassay (Roche). The molecular cTnT composition was determined by gel filtration chromatography and Western blotting in an early and late presenting patient. Results CVS hs-cTnT concentrations were 28% higher than in the peripheral artery sample (n=71, p&lt;0.001). In contrast to LH plasma, serum caused pre-analytical cTn T-I-C complex disintegration and cTnT degradation. CVS samples demonstrated presence of cTn T-I-C complex, free intact cTnT, and 29 kDa and 15–18 kDa cTnT fragments in higher absolute concentrations than measured peripherally. While the proportion of cTn T-I-C complex decreased and disappeared over time, 15–18 kDa cTnT fragments increased. Moreover, cTn T-I-C complex was more prominent in the early versus the late presenting patient. Central illustration Conclusions In NSTEMI, cTnT is released as a combination of cTn T-I-C complex, free intact cTnT and multiple cTnT fragments. Over time, the composition of observed cTnT forms changes due to in-vivo degradation. These findings serve as a stepping stone to improve diagnostic accuracy of the hs-cTnT assay for MI.