hs-cTnT Concentrations Research Articles

Troponin Levels Relate to CRP Concentrations in Patients With NAFLD on Maintenance Haemodialysis: A Retrospective Study.

IntroductionSeveral studies have shown that high sensitivity cardiac troponin (hs-cTnT) levels are elevated in patients suffering from end-stage renal disease (ESRD), even in the absence of clinical signs and instrumental features of symptomatic acute coronary syndrome (ACS). In patients undergoing haemodialysis because of ESRD, nephrologists bear witness to this increase, whose origin and clinical impact are not yet well defined.MethodsBy a retrospective study, we evaluated data from records of 70 patients with ESRD on haemodialysis, all of them with a history of NAFLD, not suffering for at least 3 months from symptomatic angina and without a history of ischemic heart disease in the same period.ResultsHs-cTnT and C-reactive protein (CRP) levels both increased and were correlated, rho = 0.34, P = 0.004. The correlation coefficient between troponin and age was significant, rho = 0.47, P = 0.0001. Serum concentrations of hs-cTnT for the whole population were positively predicted by CRP levels, P = 0.004. On separation of the population by gender, significant correlation between hs-cTnT and CRP was not found in women and was only present in men, P = 0.66 and P = 0.000, respectively.DiscussionThe assessment of hs-cTnT levels could represent a biological marker in particular subgroups of haemodialysis patients, especially for male patients with higher CRP, those at greater risk of silent myocardial ischemia and future major adverse cardiac events.ConclusionsThe evaluation of hs-cTnT in haemodialysed patients with NAFLD could indicate that men with higher CRP should undergo close monitoring in order to adopt specific therapy.

1123-P: Stress Cardiac Biomarkers and Adverse Cardiac Outcomes in the CANagliflozin CardioVascular Assessment Study (CANVAS)

SGLT2 inhibitors reduce risk of major adverse cardiovascular events (MACE) and hospitalization for heart failure (HHF) in patients with type 2 diabetes (T2D), but mechanisms remain unclear. We examined effects of canagliflozin vs. placebo on 3 prognostic biomarkers in CANVAS, as well as their predictive ability for outcomes of interest. High sensitivity cardiac troponin T (hs-cTnT; Roche Diagnostics), soluble (s)ST2 (Critical Diagnostics), and insulin-like growth factor binding protein 7 (IGFBP7; Roche Diagnostics) were measured in up to 3680 participants at baseline, 1 y, and for hs-cTnT and sST2, 6 y. Conventional statistical methods adjusting relevant covariates were used to relate biomarkers to risk for incident MACE or HHF. Higher concentration of all 3 biomarkers was associated with higher adjusted risk for incident MACE or HHF, with C-index improvements beyond covariates for MACE or HHF (Table). In terms of treatment effect, no biomarkers were differentially altered by 1 y but where data existed, both hs-cTnT (n=915; treatment coefficient [95% CI]: -0.064 [-0.121, -0.007]; p=0.027) and sST2 (n=828, treatment coefficient [95% CI]: -0.129 [-0.248, -0.010]; p=0.033) were reduced significantly at 6 y. Among patients with T2D, concentrations of hs-cTnT, sST2, and IGFBP7 were associated with risk for MACE and HHF. Canagliflozin slowed longer term (6 y) increases in hs-cTnT and sST2. Disclosure N. Sattar: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Xu: Employee; Self; Janssen Research & Development, LLC. J. Butler: Consultant; Self; Amgen, Array BioPharma, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, CVRx, G3 Pharmaceuticals, Innolife Co., Ltd., Janssen Pharmaceuticals, Inc., Luitpold Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Relypsa, Inc., VIfor. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. W. Shaw: Employee; Self; Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.E. Gutstein: Employee; Self; Janssen Research & Development, LLC. M.K. Hansen: Employee; Self; Janssen Research & Development, LLC. J. Januzzi: Consultant; Self; Roche Diagnostic USA. Research Support; Self; Janssen Pharmaceuticals, Inc. Funding Janssen Research & Development, LLC

Associations of 24-Hour Urinary Sodium and Potassium Excretion with Cardiac Biomarkers: The Maastricht Study

Background:It is a matter of debate whether sodium and potassium intake are associated with heart disease. Further, the mechanisms underlying associations of sodium and potassium intake with cardiac events, if any, are not fully understood. Objectives:We examined cross-sectional associations of 24-h urinary sodium excretion (UNaE) and potassium excretion (UKE), as estimates of their intakes, with high-sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), which are markers of cardiomyocyte injury and cardiac dysfunction. Methods:We included 2961 participants from the population-based Maastricht Study (mean SD age 59.8 8.2 y, 51.9% men), who completed the baseline survey between November 2010 and September 2013. Associations were examined with restricted cubic spline linear regression analyses and ordinary linear regression analyses, adjusted for demographics, lifestyle, and cardiovascular disease (CVD) risk factors. Results:Median [IQR] 24-h UNaE and UKE were 3.7 [2.8–4.7] g/24 h and 3.0 [2.4–3.6] g/24 h, respectively. After adjustment for potential confounders, 24-h UNaE was not associated with hs-cTnT, hs-cTnI, and NT-proBNP concentrations. In contrast, after adjustment for potential confounders, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. For example, as compared with the third/median quintile of 24-h UKE (range: 2.8–3.2 g/24 h), participants in the first quintile (range: 0.5–2.3 g/24 h) had 1.05 (95% CI: 0.99, 1.11) times higher hs-cTnT and 1.14 (95% CI: 1.03, 1.26) times higher NT-proBNP. Associations were similar after further adjustment for estimated glomerular filtration rate, albuminuria, blood pressure, and serum potassium. Conclusions:Twenty-four-hour UNaE was not associated with the studied cardiac biomarkers. In contrast, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. This finding supports recommendations to increase potassium intake in the general population. In addition, it suggests that cardiac dysfunction and/or cardiomyocyte injury may underlie previously reported associations of lower potassium intake with CVD mortality.

Cardiac troponin is associated with cardiac outcomes in men and women with atrial fibrillation, insights from the ARISTOTLE trial.

Cardiac troponin T (cTnT) and I (cTnI) concentrations provide strong prognostic information in anticoagulated patients with atrial fibrillation (AF). Whether the associations between cardiac troponin concentrations and mortality and morbidity differ by sex is not known. To assess whether men and women have different concentrations and prognostic value of cTnT and cTnI measurements in anticoagulated patients with AF. cTnT and cTnI concentrations were measured with high-sensitivity (hs) assays in EDTA plasma samples obtained from the multicentre ARISTOTLE trial, which randomized patients with AF and at least one risk factor for stroke or systemic embolic event to warfarin or apixaban. Patients were stratified according to sex and the associations between hs-troponin concentrations, and all-cause death, cardiac death, myocardial infarction, stroke or systemic embolic event and major bleeding were assessed in multivariable regression models. We found higher cardiac troponin concentrations in men (n=9649) compared to women (n=5331), both for hs-cTnT (median 11.8 [Q1-3 8.1-18.0] vs. 9.6 [6.7-14.3] ngL-1 , P<0.001) and hs-cTnI (5.8 [3.4-10.8] vs. 4.9 [3.1-8.8] ngL-1 , P<0.001). Adjusting for baseline demographics, comorbidities and medications, men still had significantly higher hs-troponin concentrations than women. C-reactive protein and N-terminal pro-B-type natriuretic peptide concentrations were higher in female patients. Both hs-cTnT and hs-cTnI concentrations were associated with all clinical outcomes similarly in men and women (p-value for interaction >0.05 for all end-points). Men have higher hs-troponin concentrations than women in AF. Regardless of sex, hs-troponin concentrations remain similarly associated with adverse clinical outcomes in anticoagulated patients with AF.

LO10: Low high-sensitivity troponin concentrations identify low-risk chest pain patients unlikely to benefit from further risk stratification

Introduction: Very low high-sensitivity troponin-T (hs-cTnT) concentrations on presentation can rule out acute myocardial infarction (AMI), but the ability to identify patients at low risk of 30-day major adverse cardiac events (MACE) is less clear. This study examines the sensitivity of low concentrations of hs-cTnT on presentation to rule out 30-day MACE. Methods: This prospective cohort study enrolled emergency department chest pain patients with non-ischemic ECGs who underwent AMI rule-out with an hs-cTnT assay. The primary outcome was 30-day MACE; secondary outcomes were individual MACE components. Because guidelines recommend using a single hs-cTnT strategy only for patients with more than 3-hours since symptom onset, a subgroup analysis was performed for this population. Outcomes were adjudicated based on review of medical records and telephone follow-up. Results: Of 1,167 patients enrolled, 125 (10.7%) experienced 30-day MACE and 97 (8.3%) suffered AMI on the index visit. More than one-third (35.6%) had presenting hs-cTnT concentrations below the limit of detection (5ng/L), which was 94.4% (95%CI 88.8-97.7%) sensitive for 30-day MACE and 99.0% (95%CI 94.5-100%) sensitive for index AMI. Of 292 (25.0%) patients with hs-cTnT &lt; 5ng/L and at least 3-hours since symptom onset, only 3 experienced 30-day MACE (sensitivity 97.6%, 95%CI 93.2-100%) and none suffered AMI within 30-days (sensitivity 100%, 95%CI 96.3-100%). Conclusion: Among patients with non-ischemic ECGs and &gt;3-hours since symptom onset, low hs-cTnT concentrations on presentation confer a very low risk of 30-day MACE. In the absence of a high risk clinical presentation, further risk stratification is likely to be low yield.

Troponin elevation: is it ischemia?

Cardiac troponin is the preferred biomarker for myocardial infarction, thanks to its sensitivity and absolute specificity for the heart. The availability of high-sensitivity assays (hs-cTnT and hs-cTnI), capable of measuring with excellent analytical precision very low levels of circulating troponin, raised the issue of whether transient ischemia is a sufficient stimulus for troponin release. For this purpose, in a series of patients submitted to a stress test (exercise ECG/echo test; dipyridamole echo test; dobutamine echo test), we measured plasma levels of hs-cTnT at baseline and 6 hours after the end of the test. Plasma concentrations of hs-cTnT significantly increased in the vast majority of patients after the test. Significant elevations were documented in response to each stressor, regardless of the test result, after both positive and negative tests. Moreover, troponin significantly increased in response to the stress, both in patients with and in patients without obstructive coronary artery disease. Despite a good sensitivity (80% and 89%), troponin showed a very low specificity (32% and 47%) for stress-induced ischemia and coronary artery disease, respectively. Myocardial release of troponin is a multifactorial process, mediated not only by cardiomyocyte necrosis, but also through several different mechanisms such as myocardial ischemia, increase in cardiac work, and hemodynamic overload. Transient elevation of high sensitivity cardiac troponin is not a useful tool for detecting spontaneous or stress-induced ischemia. L

Obesity paradox and perioperative myocardial infarction/injury in non-cardiac surgery

The impact of obesity on the incidence of perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery is not well understood. We performed a prospective diagnostic study enrolling consecutive patients undergoing non-cardiac surgery, who were considered at increased cardiovascular risk. All patients were screened for PMI, defined as an absolute increase from preoperative to postoperative sensitive/high-sensitivity cardiac troponin T (hs-cTnT) concentrations. The body mass index (BMI) was classified according to the WHO classification (underweight< 18kg/m2, normal weight 18-24.9kg/m2, overweight 25-29.9kg/m2, obesity class I 30-34.9kg/m2, obesity class II 35-39.9kg/m2, obesity class III > 40kg/m2). The incidence of PMI and all-cause mortality at 365days, both stratified according to BMI. We enrolled 4277 patients who had undergone 5413 surgeries. The median BMI was 26kg/m2 (interquartile range 23-30kg/m2). Incidence of PMI showed a non-linear relationship with BMI and ranged from 12% (95% CI 9-14%) in obesity class I to 19% (95% CI 17-42%) in the underweight group. This was confirmed in multivariable analysis with obesity class I. showing the lowest risk (adjusted OR 0.64; 95% CI 0.49-0.83) for developing PMI. Mortality at 365days was lower in all obesity groups compared to patients with normal body weight (e.g., unadjusted OR 0.54 (95% CI 0.39-0.73) and adjusted OR 0.52 (95% CI 0.38-0.71) in obesity class I). Obesity class I was associated with a lower incidence of PMI, and obesity in general was associated with a lower all-cause mortality at 365days.

Impact of training specificity on exercise-induced cardiac troponin elevation in professional athletes: A pilot study.

BACKGROUNDRelease of cardiac biomarkers is common after strenuous endurance exercise, but data on intermittent exercise are scarce. It has not been investigated whether cardiac troponin elevation is influenced depending on the type of exercise that an athlete is adapted to perform. We hypothesized that intermittent but not continuous exercise induces cardiac troponin elevation in professional athletes adapted to high-intensity intermittent exercise.AIMTo examine how training specificity impacts high-sensitivity cardiac troponin T (hs-cTnT) release.METHODSNine professional floorball players participated in the study, which comprised two different exercise tests: a continuous incremental cycle ergometer test and a Yo-Yo Intermittent Recovery 2 (Yo-Yo IR2) test. Serial assessment of hs-cTnT was performed after the cycle ergometer test and the Yo-Yo IR2 test (baseline, 0, 2, 6, and 24 h).RESULTSNo hs-cTnT elevation above the myocardial damage cutoff (≥ 14 ng/L) was shown after the cycle ergometer test, whereas hs-cTnT levels rose over the cutoff in three of nine participants after the Yo-Yo IR2 test. The hs-cTnT levels peaked at 6 h after both tests, but were significantly higher after the Yo-Yo IR2 test compared to the cycle ergometer test (median hs-cTnT concentration 10.6 ng/L vs 7.8 ng/L, P = 0.038). All levels returned to baseline within 24 h.CONCLUSIONIn professional athletes adapted to high-intensity intermittent exercise, hs-cTnT was significantly elevated after intermittent but not continuous exercise. This principle of specificity training should be considered when designing future studies to avoid misinterpretation of hs-cTnT elevation.

Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study.

The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown. To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD. Prospective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148). University hospital. 1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia. Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L). Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%). Data were generated in a large single-center diagnostic study using central adjudication. In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia. European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.

Superiority of high sensitivity cardiac troponin T vs. I for long-term prognostic value in patients with chest pain; data from the Akershus cardiac Examination (ACE) 3 study

BackgroundCardiac troponins (cTn) are essential in the diagnostic assessment of non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Elevated concentrations of cTnT and cTnI predict cardiovascular events in non-acute settings, but the individual troponin isotype association with long-term mortality in patients with suspected unstable angina pectoris (UAP) is less clear. MethodsPatients hospitalized with chest pain between June 2009 and December 2010 were included in the Akershus Cardiac Examination 3 Study and followed for median 6.6 (IQR 6.2-7.1) years. The index diagnosis was adjudicated by an independent committee as NSTE-myocardial infarction (NSTEMI), UAP or non-ACS. Blood samples were collected within 24 h of admission and analyzed with high sensitivity assays for cTnT (hs-cTnT, Roche) and cTnI (hs-cTnI, Singulex). ResultsOf 402 patients included, 74 (18%) were classified as NSTEMI, 88 (22%) UAP and 240 (60%) non-ACS. hs-cTnI concentrations were detectable in all patients (median 3 [IQR 1–11] ng/L), while hs-cTnT concentrations were above the level of blank in 205 (51%) (median 3 [IQR 3–16] ng/L). In patients with UAP, both log2-transformed hs-cTnT and hs-cTnI were associated with all-cause mortality in analyses that adjusted for other risk factors: HR 2.40 [95% CI 1.75–3.30], p < 0.001 and HR 1.44 [1.14–1.81], p = 0.002. There were no significant sex-dependent differences in the association between hs-cTnT or hs-cTnI and outcome. Time dependent receiver-operating characteristics area under the curve was 0.85 (95% CI 0.79–0.92) for hs-cTnT and 0.74 (0.64–0.84) for hs-cTnI, p = 0.008 for difference between values. ConclusionsHigher concentrations of hs-cTnT and hs-cTnI were both associated with all-cause mortality in patients with UAP, but the association with outcome was stronger for hs-cTnT than for hs-cTnI.

Causes of death in relation to stable troponin levels including chronic myocardial injury

BackgroundMany patients presenting with chest pain in the emergency department have stable concentrations of high-sensitivity cardiac troponin T (hs-cTnT) without any acute medical condition. Stable hs-cTnT levels are associated with a high risk of death. This study aimed to investigate causes of death in relation to hs-cTnT concentrations. MethodsIn a cohort of 19,460 patients with chest pain and stable hs-cTnT levels measured 2011–2014, of whom 1528 (7.9%) had chronic myocardial injury, we included all patients who died during follow-up (4.0 ± 1.3 years). Rates of cause-specific death were calculated for hs-cTnT concentrations and adjusted odds ratios (OR) estimated for causes of death at hs-cTnT 5–14 ng/l and >14 ng/l (referent hs-cTnT < 5 ng/l). ResultsThe study cohort comprised 1577 patients (8.1%), of whom 684 (43%) had chronic myocardial injury (hs-cTnT > 14 ng/l). Annual cardiovascular and non-cardiovascular death rates increased with increasing hs-cTnT from 0.07% and 0.4% (<5 ng/l) to 17% and 15% (≥50 ng/l), respectively. The ratio of cardiovascular to non-cardiovascular death increased with higher hs-cTnT. Patients with hs-cTnT 5–14 ng/l were 87% more likely to die from cardiovascular causes than those with hs-cTnT < 5 ng/l (adjusted OR: 1.87, 95% CI: 1.24–2.80). The association was similar for patients with chronic myocardial injury. ConclusionsHs-cTnT concentrations of 5–14 ng/l and >14 ng/l are associated with an almost twofold risk of cardiovascular death, whereas cardiovascular death almost never occurs in patients with undetectable troponin. Only with hs-cTnT concentrations ≥ 50 ng/l were cardiovascular diseases the predominant cause of death.

P2723Diagnosis of acute myocardial infarction in the presence of left bundle-branch block

Abstract Objective Patients with suspected acute myocardial infarction (AMI) in the setting of left bundle branch block (LBBB) present an important diagnostic and therapeutic challenge to the clinician. Methods We prospectively evaluated incidence of AMI, and diagnostic performance of specific electrocardiographic (ECG) and high-sensitivity cardiac troponin (hs-cTn) criteria in patients presenting with chest discomfort to 26 emergency departments in three international, prospective, diagnostic studies. Presence of LBBB, ECG criteria, and final diagnoses were centrally adjudicated by two independent cardiologists using the fourth universal definition of myocardial infarction. Results Among 8830 patients, LBBB was present in 247 patients (2.8%). AMI was the final diagnosis in 30% of patients with LBBB, with similar incidence in those with known LBBB versus those with presumably new LBBB (29% vs 35%, p=0.42). ECG criteria had low sensitivity (1–12%), but high specificity (95–100%). The diagnostic accuracy as quantified by the receiver-operating-characteristics curve of hs-cTnT and hs-cTnI concentrations at presentation (AUC 0.91; 95% CI 0.85–0.96 and 0.89; 95% CI 0.83–0.95) as well as that of their 0/1h and 0/2h changes was very high. A diagnostic algorithm (Figure 1) combining ECG criteria with hs-cTnT/I concentrations and their absolute changes at 1h or 2h derived in cohort 1 (45 of 45 (100%) of patients with AMI correctly identified), showed high efficacy and accuracy when externally validated in cohort 2 &amp; 3 (28 of 29 patients, 97%). Figure 1 Conclusion Most patients presenting with suspected AMI and LBBB will be found to have diagnoses other than AMI. Combining ECG criteria with Hs-cTn testing at 0/1h or 0/2h allows early and accurate diagnosis of AMI in LBBB. Acknowledgement/Funding European Union, Swiss National Foundation, University Hospital Basel, University Basel

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.

Association Between Circulating Troponin Concentrations, Left Ventricular Systolic and Diastolic Functions, and Incident Heart Failure in Older Adults

Cardiac troponin is associated with incident heart failure and greater left ventricular (LV) mass. Its association with LV systolic and diastolic functions is unclear. To define the association of high-sensitivity cardiac troponin T (hs-cTnT) with LV systolic and diastolic functions in the general population, and to evaluate the extent to which that association accounts for the correlation between hs-cTnT concentration and incident heart failure overall, heart failure with preserved LV ejection fraction (LVEF; HFpEF), and heart failure with LVEF less than 50%. This analysis of the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing epidemiologic cohort study in US communities, included participants without cardiovascular disease (n = 4111). Available hs-cTnT measurements for participants who attended ARIC Study visits 2 (1990 to 1992), 4 (1996 to 1998), and 5 (2011 to 2013) were assessed cross-sectionally against echocardiographic measurements taken at visit 5 and against incident health failure after visit 5. Changes in hs-cTnT concentrations from visits 2 and 4 were also examined. Data analyses were performed from August 2017 to July 2018. Cardiac structure and function by echocardiography at visit 5, and incident heart failure during a median 4½ years follow-up after visit 5. Of the 6538 eligible participants, 4111 (62.9%) without cardiovascular disease were included. Among these participants, 2586 (62.9%) were female, and the mean (SD) age was 75 (5) years. Median (interquartile range) hs-cTnT concentration at visit 5 was 9 (7-14) ng/L and was detectable in 3946 participants (96.0%). After adjustment for demographic and clinical covariates, higher hs-cTnT levels were associated with greater LV mass index (adjusted mean [SE] for group 1: 33.8 [0.5] vs group 5: 40.1 [0.4]; P for trend < .001) and with worse diastolic function, including lower tissue Doppler imaging e' (6.00 [0.07] vs 5.54 [0.06]; P for trend < .001), higher E/e' ratio (11.4 [0.2] vs 12.9 [0.1]; P for trend < .001), and greater left atrial volume index (23.4 [0.4] vs 26.4 [0.3]; P for trend < .001), independent of LV mass index; hs-cTnT level was not associated with measures of LV systolic function. Accounting for diastolic function attenuated the association of hs-cTnT concentration with incident HFpEF by 41% and the association with combined heart failure with midrange and reduced ejection fraction combined (LVEF <50) by 17%. Elevated hs-cTnT concentration and diastolic dysfunction were additive risk factors for incident heart failure. For any value of late-life hs-cTnT levels, longer duration of detectable hs-cTnT from midlife to late life was associated with greater LV mass in late life but not with worse LV systolic or diastolic function. This study shows that higher hs-cTnT concentrations were associated with worse diastolic function, irrespective of LV mass, but not with systolic function; these findings suggest that high levels of hs-cTnT may serve as an early marker of subclinical alterations in diastolic function that may lead to a predisposition to heart failure.

&lt;p&gt;Cardioprotective effect of transcutaneous electrical acupuncture point stimulation on perioperative elderly patients with coronary heart disease: a prospective, randomized, controlled clinical trial&lt;/p&gt;

PurposeThe purpose of this study was to evaluate the effects of transcutaneous electrical acupoint stimulation (TEAS) on postoperative autonomic nervous system function and serum biomarkers in the elderly.Patients and methodsA total of 122 American Society of Anesthesiologists class II or III patients with coronary heart disease undergoing spinal surgery were randomly divided into two groups: TEAS (received TEAS at Neiguan [PC6] and Ximen [PC4] for 30 minutes before anesthesia induction until the end of surgery) and control (received electrode plate at the same acupuncture points without any electrical stimulation). Serum was isolated for the measurement of concentration of high-sensitive troponin T (hs-cTnT), CRP, and CK. Heart rate (HR) and heart rate variability (HRV) including: total power (TP), low-frequency (LF) power, high-frequency (HF) power, and LF/HF ratio were used to assess autonomic nervous system function. The primary outcome was to evaluate whether TEAS changed the postoperative serum hs-cTnT. The secondary outcomes were to observe the effects of TEAS on HRV, circulating CK and CRP after surgery.ResultsHs-cTnT, CRP, and CK concentrations were significantly higher on first, third and fifth day after surgery than those before anesthesia induction in both groups. Hs-cTnT concentration was significantly lower on the first and third day after surgery in TEAS group than in control group. Compared with 1 day before surgery, TP, LF, and HF decreased significantly and HR, LF/HF increased significantly on first, third, and fifth day after surgery in control group. Compared with control group, HR was significantly lower on the first, third, and fifth day after surgery, LF/HF decreased and TP, LF, HF were significantly higher on the first day after surgery in TEAS group.ConclusionTEAS at PC6 and PC4 could reduce postoperative serum hs-cTnT concentration and change HRV index to improve autonomic nervous system activity.

Low High-Sensitivity Troponin Thresholds Identify Low-Risk Patients With Chest Pain Unlikely to Benefit From Further Risk Stratification

BackgroundVery low high-sensitivity cardiac troponin T (hs-cTnT) thresholds on presentation can rule out acute myocardial infarction (AMI), but the ability to identify patients at low risk of 30-day major adverse cardiac events (MACE) is less clear. This study examines the sensitivity of low concentrations of hs-cTnT on presentation to rule out 30-day MACE. MethodsThis prospective cohort study enrolled patients with chest pain presenting to the emergency department with nonischemic electrocardiograms who underwent AMI rule-out with an hs-cTnT assay. The primary outcome was 30-day MACE; secondary outcomes were individual MACE components. Because guidelines recommend using a single hs-cTnT strategy only for patients with more than 3 hours since symptom onset, a subgroup analysis was performed for this population. Outcomes were adjudicated on the basis of review of medical records and telephone follow-up. ResultsOf 1167 patients enrolled, 125 (10.7%) experienced 30-day MACE and 97 (8.3%) had AMI on the index visit. More than one-third of patients (35.6%) had presenting hs-cTnT concentrations below the limit of detection (5 ng/L), which was 94.4% (95% confidence interval [CI], 88.8-97.7) sensitive for 30-day MACE and 99.0% (95% CI, 94.5-100) sensitive for index AMI. Of 292 patients (25.0%) with hs-cTnT < 5 ng/L and at least 3 hours since symptom onset, only 3 experienced 30-day MACE (sensitivity 97.6%; 95% CI, 93.2-100) and none had AMI within 30 days (sensitivity 100%; 95% CI, 96.3-100). ConclusionsAmong patients with nonischemic electrocardiograms and > 3 hours since symptom onset, low hs-cTnT thresholds on presentation confer a very low risk of 30-day MACE. In the absence of a high-risk clinical presentation, further risk stratification is likely to be low yield.

False decrease of high-sensitivity cardiac troponin T assay in pneumatic tube system samples

BackgroundThe pneumatic tube system (PTS) is widely established in clinical laboratories. We aimed to evaluate the impacts of PTS on high-sensitivity cardiac troponin T (hs-cTnT) assays. MethodsThe hemolysis distribution of hs-cTnT PTS specimens from emergency department (ED) were determined by hemolysis index (HI). Grouped samples from 15 healthy volunteers were delivered to the laboratory via manual delivery (MD) or PTS. Interference studies were conducted to access the influence of different hemolysis degrees on hs-cTnT assays. Results7.26% PTS specimens from ED were hemolyzed in clinic. Compared with MD samples, we found highly elevated free plasma hemoglobin (Hb) in PTS samples. Hs-cTnT was interfered negatively with free Hb (R = -0.625, P < .001), and it was also validated in interference studies (R ≥ -0.820, all P ≤ .001). Clinically significant bias occurred in each hs-cTnT concentration at 100 mg/dl free Hb (Bias≥ − 13.85%, all P < .05). Moreover, bias of hs-cTnT assays at 50 mg/dl free Hb was approaching 10%, especially at 30 ng/l hs-cTnT concentration (Bias: -11.72%, P < .001). ConclusionsPTS could increase the frequency of specimen hemolysis which might cause false decrease in hs-cTnT assays. Hence, clinicians should be aware of the increased measurement bias in hs-cTnT from hemolyzed PTS samples with free Hb ≥50 mg/dl.

Relation of Dietary Sodium Intake With Subclinical Markers of Cardiovascular Disease (from MESA)

The associations between dietary sodium intake and markers of subclinical cardiovascular disease (CVD), such as high-sensitivity cardiac troponin T (hs-cTnT) and amino terminal pro b-type natriuretic peptide (NT-proBNP), may provide mechanistic insight into the relation between dietary sodium and cardiovascular events. We studied 6,131 participants of the Multi-Ethnic Study of Atherosclerosis, who were free of clinical CVD at baseline. Food frequency questionnaires were used to assess estimated sodium intake (ESI) at baseline. We tested the associations between 5 quintiles of ESI (quintile 1: 0.2 to 1.3 grams/day, quintile 2: 1.3 to 1.8 grams/day, quintile 3: 1.8 to 2.4 grams/day, quintile 4: 2.4 to 3.2 grams/day, and quintile 5: 3.2 to 9.9 grams/day) with cross-sectional and 5-year longitudinal change in hs-cTnT and NT-proBNP concentrations. Restricted cubic spline plots were utilized to explore the shape of the associations between ESI and biomarker outcomes. A cross-sectional association between baseline sodium intake and hs-cTnT (but not NT-proBNP) was observed, driven predominantly by a strong positive relation at an intake range of 0.2 to 2.4 g/day. Conversely, a longitudinal association between baseline sodium intake and NT-proBNP (but not hs-cTnT) was observed, driven predominantly by a strong positive relation at intake levels ≥2.4 g/day. In conclusion, temporal shifts in the association between increased ESI and markers of subclinical CVD, hs-cTnT in the short term and NT-proBNP in the longer term, point to the complex pathobiology of the association between sodium intake and CVD. There was also no consistent evidence supporting a J-curve (i.e., excess biomarker values at very low ESI).

Growth differentiation factor-15 and all-cause mortality in patients with suspected myocardial infarction

BackgroundTo assess the prognostic performance of Growth differentiation factor-15 (GDF-15) concentrations in unselected patients presenting with suspected acute myocardial infarction (AMI) and adjudication based on high-sensitivity cardiac troponin (hs-cTn). Methods and resultsIn an ongoing prospective multicenter diagnostic study, consecutive patients presenting with suspected AMI to the emergency department and available GDF-15 and hs-cTnT concentrations were included. Adjudication of AMI was performed central by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations. Overall, 718 patients were included, with 23% (162/718) having an adjudicated diagnosis of AMI. The cumulative incidence of death within 2 years was 19% in patients with AMI (30 deaths in 162 patients) versus 5% in patients without AMI (25 deaths in 556 patients; P < 0.001). In AMI patients, GDF-15 provided an AUC of 0.89 (95% confidence interval [CI] 0.83–0.94) for 2-year death versus 0.55 (95% CI 0.44–0.66) for hs-cTnT (P < 0.001). A GDF-15 cutoff of ≤1560 ng/L predicted 2-year survival in 47% (76/162) of AMI patients and had 100% sensitivity (95% CI 88–100%) for 2-year death. In patients without AMI, GDF-15 provided an AUC of 0.83 (95% CI 0.76–0.89) versus 0.76 (95% CI 0.67–0.85) for hs-cTnT (P = 0.096). A GDF-15 cutoff of ≤886 ng/L predicted 2-year survival in 37% (203/556) of non-AMI patients and had 100% sensitivity (95% CI 86–100%) for 2-year death. ConclusionsGDF-15 concentrations at emergency department presentation have a high predictive accuracy for all-cause death in patients with suspected AMI and allow the identification of a large proportion of AMI patients with very low mortality risk.

Associations of High-Sensitivity Cardiac Troponin and Natriuretic Peptide With Subsequent Risk of Infection in Persons Without Cardiovascular Disease: The Atherosclerosis Risk in Communities Study.

Whether persons without prevalent cardiovascular disease (CVD) but elevated levels of high-sensitivity cardiac troponin T (hs-cTnT) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) are at high risk of infection is unknown. Using 1996-2013 data from the Atherosclerosis Risk in Communities Study, we estimated hazard ratios for incident hospitalization with infection in relation to plasma hs-cTnT and NT-proBNP concentrations among participants without prevalent CVD and contrasted them with hazard ratios for persons with prevalent CVD (coronary heart disease, heart failure, or stroke). In a multivariable Cox model, prevalent CVD was significantly associated with risk of hospitalization with infection (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.19, 1.45). Among participants without prevalent CVD, hs-cTnT and NT-proBNP were independently associated with infection risk in a graded fashion (e.g., HR = 1.44 (95% CI: 1.24, 1.69) for hs-cTnT ≥14 ng/L and HR = 1.28 (95% CI: 1.14, 1.44) for hs-cTnT 9-13 ng/L vs. <3 ng/L; HR = 1.57 (95% CI: 1.35, 1.81) for NT-proBNP ≥248.1 pg/mL and HR = 1.19 (95% CI: 1.06, 1.34) for NT-proBNP 137.2-248.0 pg/mL vs. <48.1 pg/mL). The 15-year cumulative incidences of hospitalization with infection were similar for participants with prevalent CVD and participants who did not have prevalent CVD but had hs-cTnT ≥14 ng/L or NT-proBNP ≥248.1 pg/mL. Thus, hs-cTnT and NT-proBNP were independently associated with infection risk. Persons without CVD but with elevated hs-cTnT or NT-proBNP levels should be recognized to have similar infection risks as persons with prevalent CVD.