Elevated hs-cTnT Research Articles

Acute kidney injury in relation to high-sensitivity cardiac troponin T levels in the emergency department

Abstract Background The clinical implications of high-sensitivity cardiac troponin T (hs-cTnT) measurements in all-comers with AKI in the emergency department (ED) is largely unknown. Purpose To investigate the prevalence of myocardial injury, associations between serum-creatinine concentrations (SCC) and hs-cTnT kinetics, and the accuracy of established hs-cTnT-based myocardial infarction (MI) risk stratification algorithm criteria in patients with AKI. Methods This observational cohort study was based on patient visits to 7 EDs in Sweden from December 9, 2010 to August 31, 2017. All visits by patients ≥18 years fulfilling criteria for AKI with ≥1 hs-cTnT measurement and the exposure was dynamic change in SCC (ΔSCC) during the visits. Linear mixed models were used to estimate linear predictors of kinetic change in hs-cTnT (Δhs-cTnT). Logistic regression models were applied to calculate odds ratios (ORs) for Δhs-cTnT indicative of acute myocardial injury (Δhs-cTnT >20% and elevated hs-cTnT) in relation to ΔSCC among patients without MI, and to assess the diagnostic performance of hs-cTnT for MI in a subgroup of patients presenting with chest pain. Results A total of 15,211 visits by patients with AKI were included, of whom 1174 (8%) had an MI. Four of five (81%) patients without MI had myocardial injury (hs-cTnT >14 ng/l), and almost one of three (31%) had acute myocardial injury. These entities were common in both cardiac and non-cardiac conditions. The Δhs-cTnT in non-MI patients was 1.8-fold (β: 1.78, 95% CI: 1.62-1.96) in the highest quartile of ΔSCC and was paralleled by a 2-fold risk of acute myocardial injury (OR: 2.32, 95% CI: 2.08-2.59), compared with the lowest ΔSCC quartile. Using a 0 h hs-cTnT cut-off ≥52 ng/l assigned 627 (26%) patients to a high-risk group in whom the specificity and positive predictive value (PPV) for MI was low (78.5% (95% CI: 76.7-80.2) and 27.6% (95% CI: 24.1-31.3), respectively). Conclusions Hs-cTnT concentrations indicative of acute myocardial injury are frequently observed among all-comers with AKI in the ED and are associated with dynamic changes in SCC. These observations are accompanied by poor performance of recommended hs-cTnT-based algorithms for MI risk stratification in patients with chest pain.

Prognostic importance of persistent elevations in high-sensitivity troponin T in the early convalescent phase (two weeks) following high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p<0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Increased index of microcirculatory resistance, capillary rarefaction, elevated troponin levels, and their association with transthyretin amyloidosis cardiomyopathy

Abstract Background The pathophysiology of coronary microvascular disease (CMD) in patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) remains unclear. Objective This study aims to functionally and pathologically assess coronary microvasculature to elucidate the underlying mechanisms of myocardial injury in patients with ATTR-CM. Methods Fifty patients (median age, 74 years; men, n=46, 92%) with echocardiographic evidence of left ventricular hypertrophy (≥12 mm) who underwent endomyocardial biopsy (EMB) and invasive coronary physiological assessments following coronary angiography were enrolled between October 2021 and September 2023 and divided into ATTR-CM (n=30) and non-cardiac amyloidosis (CA) (n=20) groups according to EMB results. All patients with ATTR-CM exhibited positive heart-to-contralateral (H/CL) ratios (>1.5) on technetium 99m pyrophosphate scintigraphy. Fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were measured using the PressureWire X guidewire in the left anterior descending artery. Capillary density (/mm2) was determined with EMB tissues by counting the number of CD31 immunopositive luminal structures, whereas the amyloid deposition burden was assessed by measuring the transthyretin immunopositive areas. Circulating cardiac troponin T (hs-cTnT) and brain natriuretic peptide (BNP) were measured. Results Compared to the non-CA group, the ATTR-CM group exhibited lower CFR (2.4±0.3 vs. 3.6±0.4, p=0.01), higher IMR (35.4±3.0 vs. 18.7±3.7, p=0.0009), lower capillary density (255.3±24.9 /mm2 vs. 408.6±29.5 /mm2 , p=0.0002), and elevated hs-cTnT levels (0.056±0.006 ng/mL vs. 0.036±0.004 ng/mL, p=0.01), with similar FFR (0.87±0.015 vs. 0.84±0.013, p=0.1) and BNP levels (229.6±38.1 pg/mL vs. 210.2±46.7 pg/mL, p=0.75). In the overall and ATTR-CM groups, capillary density had no significant correlation with IMR (r=0.16, p=0.41 and r=0.04, p=0.84, respectively) and a significant inverse correlation with hs-cTnT (r=-0.47, p=0.001, and r=-0.48, p=0.009, respectively). In the ATTR-CM group, capillary density was not significantly correlated with the H/CL ratio (r=-0.23, p=0.09); nevertheless, transthyretin immunopositive areas were positively correlated with the H/CL ratio (r=0.47, p=0.01). Conclusion Capillary rarefaction correlates with elevated hs-cTnT levels but not with elevated IMR, and H/CL ratios, suggesting that CMD is involved at the capillary level in ATTR-CM-related myocardial injury independent of the amyloid deposition burden.

Comprehensive remote myocardium characterisation using T1 mapping in patients with ST-segment elevation myocardial infarction

Abstract Background Myocardial tissue injury due to acute myocardial infarction (AMI) does not only occur in the myocardium that is supplied by the culprit lesion, but can also extend to the remote, non-infarcted myocardium. The prognostic implications of remote myocardium changes assessed by cardiac magnetic resonance (CMR) are not fully understood. The aim was to investigate the prognostic relevance of remote myocardium alterations assessed by CMR T1 mapping (native T1 and extracellular volume (ECV)) in patients after ST-segment elevation myocardial infarction (STEMI). Methods This study analyzed 491 STEMI patients treated with primary percutaneous coronary intervention (PCI) that were included in the prospective MARINA-STEMI study (NCT04113356). CMR imaging was performed 4 (Interquartile range [IQR]: 3-5) days after PCI. CMR images were analyzed for left ventricular (LV) function, standard infarct characteristics as well as native remote T1 and remote ECV. The primary clinical endpoint was the composite of all-cause mortality, re-infarction and new congestive heart failure (Major adverse cardiovascular events, MACE). Results Remote native T1 (median: 1009 [IQR: 979-1044] ms) was associated with female sex, peak NT-pro-BNP levels, peak hs-cTnT elevations, TIMI-risk score, admission Killip class, anterior infarct location, post-interventional TIMI-flow, LV ejection fraction and microvascular injury. Remote ECV (median: 26.37 [IQR: 24.28-29.27] %) was associated with age, female sex, peak NT-pro-BNP levels, diabetes, TIMI-risk score, admission Killip class, anterior infarct location, LV ejection fraction and microvascular injury. Over a median follow-up of 12 months (IQR: 12-13) after STEMI, 42 MACE outcomes occurred. Higher native remote T1-times (1018.5 [IQR: 997.0-1064.0] ms vs. 1007.0 [IQR: 977.0-1041.5] ms, p=0.033) as well as a higher remote ECV-values (28.07 vs. 26.27 %, p=0.009) were observed in patients with MACE. Multivariable Cox regression analysis demonstrated that remote ECV (hazard ratio (HR): 1.53 [confidence interval (CI): 1.07-2.19], p=0.020) but not native remote T1 associated with MACE. Conclusions A comprehensive assessment of the remote myocardium with native T1 and ECV provides prognostic information in a contemporary cohort of low risk STEMI patients. Remote ECV, but not remote native T1, was found to be an independent predictor of MACE.

Validation and correlation of high-sensitive troponin I and troponin T in the emergency department

BackgroundTroponin elevation is frequently observed in various scenarios in the Emergency Department (ED), yet there is a paucity of studies investigating simultaneously measured high-sensitivity cardiac troponin T (hs-cTnT) and troponin I (hs-cTnI) within a diverse cohort in a clinical setting.MethodsAll patients who underwent troponin testing at a single center were eligible for this study. Only patients with simultaneous samples with hs-cTnI (Siemens) and hs-cTnT (Roche) were included, regardless of chief complaint.ResultsAnalysis of 1987 samples from 1134 patients showed a significant correlation between hs-cTnT and hs-cTnI (r = 0.86, p < 0.01). Of these samples, 65% exceeded the upper reference limit (URL) for hs-cTnT, and 30% for hs-cTnI with 39% who exhibited elevated hs-cTnT levels alongside normal hs-cTnI levels. The area under the curve (AUC) for acute myocardial infarction (AMI) for the index visit was 0.80 (95% CI; 0.75–0.85) for hs-cTnT and 0.87 (95% CI; 0.83–0.91) for hs-cTnI. Sensitivity and specificity were 91% and 39% for hs-cTnT, and 80% and 80% for hs-cTnI. Positive predictive value (PPV) and negative predictive value (NPV) was 9.3% and 98.5% for hs-cTnT respectively, corresponding for hs-cTnI was 21.3% and 98.3% respectively. Hazard ratios for 1-year mortality were 1.52 (95% CI; 1.40–1.66) for hs-cTnT and 1.26 (95% CI; 1.18–1.34) for hs-cTnI.ConclusionElevated troponins above the URL were very common in this diverse cohort, particularly for hs-cTnT, which was twice as frequent compared to hs-cTnI, resulting in low specificity and PPV for AMI.

Elevated high-sensitive cardiac troponin T in emergency department patients: insights from a retrospective descriptive cohort study

BackgroundHigh-sensitive cardiac troponin T (hs-cTnT) assessments are routinely conducted in German emergency departments (EDs). However, data describing a large number of ED patients with pathological hs-cTnT levels and subsequent clinical outcomes are limited.MethodsThis retrospective descriptive analysis included 141.892 patients who presented to the interdisciplinary ED at Klinikum rechts der Isar in Munich, Germany, between January 2019 and December 2021. Patients with trauma diagnoses were excluded, focusing on those with elevated hs-cTnT levels. These patients were categorized into three groups based on the International Classification of Procedures in Medicine (ICPM): those with elevated hs-cTnT who received no coronary angiography (NCA), those who underwent diagnostic coronary angiography (DCA), and those who received percutaneous coronary intervention (PCI). The objective of this study was to characterize a large emergency department patient cohort and assess their subsequent clinical outcomes.ResultsAfter initial Manchester Triage Sytem (MTS) categorization, 32.6% (46.307/141.892) of patients were identified as non-trauma cases. Of these, 9.9% (4.587/46.307) had hs-cTnT levels exceeding 14 ng/L. Within this subset, 70.4% (3.230/4.587) did not undergo coronary angiography, 15.4% (705/4.587) underwent DCA and 14.2% (652/4.587) received PCI. Chest pain occurred more frequently in the PCI group (28.0%, 160/652) compared to the DCA group (18.3%, 113/705) or NCA group (5.7%, 159/3230), p < 0.001. However, breathing problems occurred more frequently in the NCA group (23.2%, 647/3230) compared to the PCI group (17.7%, 101/652) or DCA group (21.8%, 135/705), p < 0.001. Also, collapse was more frequent in patients in the NCA group (4.0%, 112/3230) compared to the DCA group (3.4%, 21/705) or PCI group (3.5%, 20/652), p < 0.001. Overall, in-hospital mortality was significantly higher in the NCA group (7.9%, 256/3230) compared to the DCA group (2.3%, 16/705) or PCI group (4.1%, 27/652), p < 0.001.ConclusionEmergency patients with elevated hs-cTnT who did not undergo coronary angiography faced a higher risk of in-hospital mortality in our retrospective descriptive study. Given the heterogeneous nature of presenting complaints in emergency departments, identifying at-risk patients can pose challenges for treating physicians.

Prospective Multicenter Screening With High-Sensitivity Cardiac Troponin T for Wild-Type Transthyretin Cardiac Amyloidosis in Outpatient and Community-Based Settings.

High-sensitivity cardiac troponin T (hs-cTnT) was proposed as a simple and useful diagnostic tool for cardiac amyloidosis (CA). We performed exploratory systemic screening using hs-cTnT to detect wild-type transthyretin CA (ATTRwt-CA) in outpatient and community-based settings. This study was a prospective multicenter study including 8 internal medicine clinics in Kochi Prefecture, Japan. Consecutive individuals aged ≥70 years who visited those clinics as outpatients were enrolled. Patients with a prior diagnosis of CA or a history of heart failure hospitalization were excluded. We measured hs-cTnT levels in the enrolled individuals at each clinic, and those with elevated hs-cTnT levels (≥0.03ng/mL) received further detailed examination, including remeasurement of hs-cTnT. The diagnosis of ATTRwt-CA was confirmed by biopsy-proven transthyretin. Of 1,141 individuals enrolled in the study, 55 (4.8%) had elevated hs-cTnT levels. Of the 33 patients who underwent further examination, 22 had elevated hs-cTnT levels at remeasurement. Finally, 2 men were diagnosed with ATTRwt-CA. The prevalence of ATTRwt-CA was 9.1% (2/22) among patients with elevated hs-cTnT levels at two examinations, and at least 0.18% (2/1,141) in the whole study population. Measurement of hs-cTnT will help to screen for patients with undiagnosed ATTRwt-CA in primary care practice.

Improved diagnostic performance of high-sensitivity cardiac troponins in muscle dystrophies using comprehensive definition criteria for cardiac involvement: A longitudinal study on 35 patients.

Sparse information is available on the correct interpretation of elevated high-sensitivity cardiac troponin (hs-cTn) in confirmed muscular dystrophies. Serum concentrations of hs-cTn T (hs-cTnT) and hs-cTn I (hs-cTnI) were determined in 35 stable outpatients with confirmed skeletal muscle dystrophies. We calculated sensitivities, specificities, and positive and negative predictive values of hs-cTnT and hs-cTnI for identification of cardiac involvement using a comprehensive definition that included diastolic left ventricular and right ventricular function, strain analysis using two-dimensional transthoracic echocardiogram and magnetic resonance imaging, myocardial biopsies, and consideration of a variety of triggers for cardiac injury, including arrhythmias, conduction disorders, and hypoxemia due to respiratory failure. Cardiac involvement was diagnosed in 34 of 35 cases. Specificities of hs-cTnT increased from 12.5% to 100% (p = 0.0006) applying the comprehensive definition compared to a definition based on electrocardiography and echocardiography alone. At the recommended 99th percentile upper limit of normal, sensitivities were significantly lower for hs-cTnI than for hs-cTnT (29.4% vs. 100%, p = 0.0164). Conversely, the specificities of hs-cTnT and hs-cTnI increased to 100% when using the comprehensive definition criteria for diagnosing cardiac involvement. Elevated hs-cTnT but not hs-cTnI discriminates cardiac involvement in cases with confirmed skeletal muscle dystrophies with very high sensitivity and 100% specificity. Prior reports on worse performance may be explained by the use of less sensitive imaging methods or incomplete assessment of cardiac involvement.

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

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

Acute Kidney Injury and High-Sensitivity Cardiac Troponin T Levels in the Emergency Department

The clinical implications of high-sensitivity cardiac troponin T (hs-cTnT) measurements in patients with acute kidney injury (AKI) in the emergency department (ED) are largely unknown. To investigate associations between serum creatinine (SCr) concentrations and hs-cTnT kinetics, as well as the clinical accuracy of hs-cTnT for myocardial infarction (MI) in patients with AKI. This retrospective cohort study included 15 111 patient visits to 7 EDs in Sweden from December 9, 2010, to August 31, 2017, by patients 18 years or older fulfilling AKI criteria with 2 or more SCr measurements and 1 or more hs-cTnT measurement. Statistical analysis was performed from October 2, 2022, to September 28, 2023. Dynamic change in SCr during the ED visits. Linear mixed-effects models were used to estimate the log-linear regression of kinetic change in hs-cTnT. Logistic regression models were applied to calculate odds ratios (ORs) for change in hs-cTnT indicating acute myocardial injury (Δhs-cTnT >20% and elevated hs-cTnT >14 ng/L) in association with change in SCr, and to assess the diagnostic performance of hs-cTnT for MI in patients with chest pain. There was a total of 15 211 visits by 13 638 patients (median age, 74 years [IQR, 64-83 years]; 8709 men [57%]), of whom 1174 (8%) had an MI. Overall, 11 353 of patients at 14 037 visits without an MI diagnosis (81%) had myocardial injury, and 4396 patients at 14 037 visits (31%) had acute myocardial injury. The change in hs-cTnT among patients without MI was 1.8-fold higher in the highest vs the lowest change in SCr quartile (64.7% [95% CI, 58.4%-71.5%] vs 36.3% [95% CI, 32.4%-40.7%]; exponentiated β coefficient, 1.78 [95% CI, 1.62-1.96]). Patients in the former group were twice as likely to have acute myocardial injury (39% [1378 of 3516 visits] vs 23% [817 of 3507 visits]; adjusted OR, 2.32 [95% CI, 2.08-2.59]). Using a 0 hours hs-cTnT cutoff value of 52 ng/L or higher assigned 627 of 2388 patients (26%) with chest pain to a high-risk group in whom the specificity and positive predictive value for MI was low (78.5% [95% CI, 76.7%-80.2&] and 27.6% [95% CI, 24.1%-31.3%], respectively). This cohort study of patients in the ED suggests that dynamic change in SCr among patients with AKI was associated with hs-cTnT concentrations indicative of acute myocardial injury. These observations were accompanied by poor performance of recommended hs-cTnT-based algorithms for MI risk stratification.

Interpretation of elevated baseline concentrations and serial changes of high-sensitivity cardiac troponin T in confirmed muscular dystrophies.

Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. Hs-cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1h and after 6-12months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1h algorithm and assessed biological variation at 6-12months using two established methods: reference change value (RCV) and minimal important difference (MID). Median baseline hs-cTnT concentrations were 34.4ng/L [inter-quartile range (IQR): 17.5-46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow-up of 6.6months (IQR: 6-7). Median concentration change was 1.9ng/L (IQR: 0.7-3.2) and 0.8ng/L (IQR: 0-7.0) at 60min and 6-9months, respectively. Applying the criteria of the ESC 0/1h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs-cTnT values. No patient would qualify for rule-out based on hs-cTnT less than the limit of detection, whereas five cases would qualify for rule-in based on hs-cTnT≥52ng/L. Biological variabilities at 6-12months per MID and RCV were 1.2ng/L [95% confidence interval (CI): 0.7-2.1] and 28.6% (95% CI: 27.9-29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. The high prevalence of elevated hs-cTnT could negatively impact the effectiveness of rule-out and rule-in strategies based on a single hs-cTnT value. Knowledge of the physiological and biological variation of hs-cTnT after 6-12months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

Homocysteine Metabolism, Subclinical Myocardial Injury, and Cardiovascular Mortality in the General Population

BackgroundHomocysteine (Hcy) is a recognized cardiovascular disease (CVD) risk factor linked with atherosclerosis. However, the association between Hcy and myocardial injury is little known. ObjectivesThis study aimed to examine the associations between Hcy metabolism, subclinical myocardial injury, and cardiovascular mortality. MethodsWe included 10,871 participants without diagnosed CVD. Generalized linear regression was used to investigate the relationship between Hcy-related indicators (plasma total Hcy [tHcy], vitamin B12, and folate) and myocardial injury biomarkers (high-sensitivity troponin T [hs-cTnT], high-sensitivity troponin I [hs-cTnI] measured using 3 assays [Abbott, Siemens, and Ortho], and N-terminal pro–B-type natriuretic peptide [NT-proBNP]). ResultsAmong 10,871 participants, the weighted mean levels for tHcy, folate, and vitamin B12 were 8.58 μmol/L, 32.43 nmol/L, and 447.08 pmol/L, respectively. Plasma tHcy levels were positively associated with elevated hs-cTnT, hs-cTnI, and NT-proBNP, whereas folate and vitamin B12 were not inversely related to myocardial injury biomarkers. Multivariable-adjusted odds ratios for elevated hs-cTnT (19 ng/L) and NT-proBNP (125 pg/mL) per doubling of tHcy were 2.80 (95% CI: 1.17-6.73; P < 0.001) and 1.58 (95% CI: 1.20-2.08; P < 0.001), respectively. The associations of tHcy levels with elevated hs-cTnI (Abbott: 28 ng/L; Siemens: 46.5 ng/L; Ortho: 11 ng/L) were consistent. Indirect effects of tHcy on cardiovascular mortality risk via hs-cTnT and NT-proBNP explained up to 26.6% and 12.3% of the total effect, respectively. ConclusionsPlasma tHcy, not folate or vitamin B12, is significantly associated with elevated hs-cTnT, hs-cTnI, and NT-proBNP in adults without CVD. Subclinical myocardial injury may substantially mediate Hcy-related cardiovascular mortality risk.

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

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

Modeling the Impact of Biomarker-Guided Versus ASCVD Risk-Guided Drug Treatment in US Adults With Stage 1 Hypertension: The National Health and Nutrition Examination Survey, 1999 to 2004.

Guidelines recommend antihypertensive medication for adults with both stage 1 hypertension (systolic blood pressure, 130-139 mm Hg or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%. Cardiac biomarkers could facilitate a more targeted approach to the treatment of stage 1 hypertension. We studied 1999 to 2004 National Health and Nutrition Examination Survey participants aged ≥20 years with untreated stage 1 hypertension without heart failure or ASCVD. We measured hs-cTnI (high-sensitivity cardiac troponin I), hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in stored serum. We used the Pooled Cohort Equations to predict 10-year ASCVD risk. All participants had linked mortality follow-up through December 31, 2019. Overall, 17.5% of US adults (32.2 million) had untreated stage 1 hypertension. Among these 32.2 million persons, 15.7% had ASCVD risk ≥10%, 5.6% had elevated hs-cTnI, 4.7% had elevated hs-cTnT, and 9.5% had elevated NT-proBNP. Among adults aged 65 to 79 years with untreated stage 1 hypertension, 80.5% had ASCVD risk ≥10%, 13.0% had elevated hs-cTnI, 15.2% had elevated hs-cTnT, and 29.4% had elevated NT-proBNP. Less than half of the adults aged ≥80 years with untreated stage 1 hypertension had elevated biomarkers. The cardiovascular disease mortality rates among all adults with untreated stage 1 hypertension and with either ASCVD risk ≥10%, elevated hs-cTnI, elevated hs-cTnT, or elevated NT-proBNP were 7.51, 7.74, 8.75, and 5.87 per 1000 person-years, respectively. Cardiac biomarkers may be more selective for informing risk-based treatment decisions in stage 1 hypertension, particularly among adults aged ≥65 years.

Diagnostic and prognostic value of cardiac troponins in emergency department patients presenting after a fall: A prospective, multicenter study.

Emergency department (ED) presentations after a ground-level fall (GLF) are common. Falls were suggested to be another possible presenting feature of a myocardial infarction (MI), as unrecognized MIs are common in older adults. Elevated high-sensitivity cardiac troponin (hs-cTn) concentrations could help determine the etiology of a GLF in ED. We investigated the prevalence of both MI and elevated high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), as well as the diagnostic accuracy of hs-cTnT and hs-cTnI regarding MI, and their prognostic value in older ED patients presenting after a GLF. This was a prospective, international, multicenter, cohort study with a follow-up of up to 1 year. Patients aged 65 years or older presenting to the ED after a GLF were prospectively enrolled. Two outcome assessors independently reviewed all discharge records to ascertain final gold standard diagnoses. Hs-cTnT and hs-cTnI levels were determined from thawed samples for every patient. In total, 558 patients were included. Median (IQR) age was 83 (77-89) years, and 67.7% were female. Elevated hs-cTnT levels were found in 384 (68.8%) patients, and elevated hs-cTnI levels in 86 (15.4%) patients. Three patients (0.5%) were ascertained the goldstandard diagnosis MI. Within 30 days, 18 (3.2%) patients had died. Nonsurvivors had higher hs-cTnT and hs-cTnI levels compared with survivors (hs-cTnT 40 [23-85] ng/L in nonsurvivors and 20 [13-33] ng/L in survivors; hs-cTnI 25 [14-54] ng/L in nonsurvivors and 8 [4-16] ng/L in survivors; p < 0.001 for both). A majority of patients (n = 364, 68.8%) presenting to the ED after a fall had elevated hs-cTnT levels and 86 (15.4%) elevated hs-cTnI levels. However, the incidence of MI in these patients was low (n = 3, 0.5%). Our data do not support the opinion that falls may be a common presenting feature of MI. We discourage routine troponin testing in this population. However, hs-cTnT and hs-cTnI were both found to have prognostic properties for mortality prediction up to 1 year.

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

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

Associations of High-Sensitive Cardiac Troponin T in Healthy Newborns and Prolonged Second Stage of Labor, Neonatal and Maternal Factors: A Prospective Study

Introduction: High-sensitivity cardiac troponin T (hs-cTnT) is not used routinely as a diagnostic biomarker in newborns. The high precision of hs-cTnT assays increases the ability to determine small differences in cTnT over time and to detect troponin T elevation; thus, we believe that hs-cTnT assays might improve clinical care. We explored the plausible association between hs-cTnT levels (ng/L) in healthy newborns and prolonged second stage of labor, neonatal, and maternal factors. Methods: A prospective study was performed among healthy newborns in the Obstetrics and Gynecology Department at Hillel Yaffe Medical Center in Israel in January–June 2021. The sociodemographic characteristics of the participants, maternal age, gravidity, parity, Pitocin use, epidural analgesia, and neonatal anemia were obtained from the electronic medical records. Gestational age was determined by ultrasound biometric measurements. We classified second-stage labor as normal or prolonged using the WHO guidelines. Samples from umbilical cord blood were drawn using syringes rinsed with anticoagulant by a specialist in pediatrics. The remaining blood was used to determine hs-cTnT levels (ng/L), which was defined as a continuous quantitative variable with the median value and the 25th–75th percentiles. Results: Overall, 184 cord blood samples were performed from healthy newborns (60.6% males) with a median hs-cTnT of 39.03 (25th–75th percentiles = 30.53–54.09) ng/L. A multivariable linear regression model showed no significant association between neonatal anemia and hs-cTnT levels (ng/L) (p = 0.8). Gestational age (B coefficient −4.24, p < 0.001) and gravidity (B coefficient −2.41, p = 0.03) were negatively associated with hs-cTnT levels (ng/L), while Pitocin use (B coefficient 6.91, p = 0.04) and prolonged second stage of labor (B coefficient 18.07, p = 0.02) were positively associated with hs-cTnT levels (ng/L). Conclusions: High hs-cTnT levels (ng/L) were documented in the cord blood of healthy newborns. Hs-cTnT levels were positively correlated with a prolonged second stage of labor and Pitocin use and negatively correlated with longer gestational age and higher gravidity. Hs-cTnT may signify labor-related fetal distress. A larger surveillance study is mandatory to establish this correlation and assess for possible prognostic significance of elevated hs-cTnT in this context.

Cardiological parameters predict mortality and cardiotoxicity in oncological patients.

Oncological patients suspected at risk for cardiotoxicity are recommended to undergo intensified cardiological surveillance. We investigated the value of cardiac biomarkers and patient-related risk factors [age, cardiovascular risk factors (CVRFs), and cardiac function] for the prediction of all-cause mortality (ACM) and the development of cardiotoxicity. Between January 2016 and December 2020, patients with oncological diseases admitted to the Cardio-Oncology Unit at the Heidelberg University Hospital were included. They were evaluated by medical history, physical examination, 12-lead electrocardiogram, 2D echocardiography, and cardiac biomarkers [high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP)]. The primary endpoint was defined as ACM and the secondary endpoint was defined as cardiotoxicity, as defined by the European Society of Cardiology. Of the 1971 patients enrolled, the primary endpoint was reached by 490 patients (25.7%) with a median of 363.5 [interquartile range (IQR) 121.8, 522.5] days after presentation. Hs-cTnT of ≥ 7ng/L [odds ratio (OR) 1.82, P<0.001] and NT-proBNP (OR 1.98, P<0.001) were independent predictors of ACM, while reduced left ventricular ejection fraction was not associated with increased ACM (P=0.85). The secondary endpoint was reached by 182 patients (9.2%) with a median of 793.5 [IQR 411.2, 1165.0] days. Patients with multiple CVRFs (defined as high risk, n=886) had an increased risk of cardiotoxicity (n=100/886, 11.3%; hazard ratio 1.57, P=0.004). They showed elevated baseline values of hs-cTnT (OR 1.60, P=0.006) and NT-proBNP (OR 4.00, P<0.001) and had an increased risk of ACM (OR 1.43, P=0.031). In cancer patients, CVRF accumulation predicts cardiotoxicity whereas elevated hs-cTnT or NT-proBNP levels are associated with ACM. Accordingly, less intensive surveillance protocols may be warranted in patients with low cardiac biomarker levels and absence of CVRFs.

Different diagnostic value of risk factors for ACS in relation to initial troponin level and early dynamic change

Abstract Introduction/background Early rule in/rule out algorithms using high sensitivity cardiac troponin T (hs-cTnT) have improved the evaluation for acute coronary syndrome (ACS) and facilitated the care of chest pain patients in the emergency department (ED). It is still unknown whether risk factors and comorbidities provide additional diagnostic information for ACS to one-hour hs-cTnT dynamics in the ED. Purpose To evaluate whether cardiovascular risk factors and comorbidities are associated with ACS in chest pain patients with elevated and normal initial hs-cTnT, and with and without early dynamic change. Methods 48,283 unique patients with chest pain and a measured hs-cTnT were identified at 4 university hospitals during 2013-2016 where a one-hour algorithm was implemented during the study period. Among these, 7903 patients had two hs-cTnT measurements obtained within 105 minutes. Clinical information was cross-linked to national registers to obtain previous diagnoses, outcomes and prescriptions. Early dynamics of hs-cTnT was defined as a change by 3ng/l or more if the first hs-cTnT was at or below 14 ng/l, or otherwise a change by more than 20% if the first hs-cTnT was above 14ng/l. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between risk factors and ACS in subgroups by different hs-cTnT levels and with or without dynamic change. Results 516 out of 39777 (1.3%) patients with normal and 1999 out of 8506 (23.5%) with elevated hs-cTnT levels were diagnosed with ACS. In patients with normal initial hs-cTnT 55 out of 5936 (0.9%) without and 44 out of 186 patients (23.7%) with dynamic change were diagnosed with ACS. In patients with elevated hs-cTnT 196 out of 1464 (13.4%) without and 202 out of 317 patients (63.7%) with dynamic change had ACS. In patients with normal hs-cTnT, hypertension (OR 3.24, 95% CI, 2.72-3.87), hyperlipidaemia (OR 3.21, 95% CI 2.67-3.85), diabetes (OR 3.46, 95% CI, 2.81-4.27) and atherosclerotic cardiovascular disease (ASCVD) (OR 2.92, 95% CI 3.24-4.70) were associated with increased risk for ACS (figure 1), whereas the opposite or no association for ACS was shown for these conditions when the initial hs-TnT was elevated. Among patients with normal initial hs-cTnT, hypertension (OR 2.52, 95% CI, 1.47-4.30) and hyperlipidaemia (OR 2.63. 95% CI, 1.51-4.57) were only associated with ACS in patients without early dynamic change (p-value for interaction &amp;lt;0.001 and p=0.02 respectively) whereas diabetes and ASCVD were associated with ACS irrespective of early dynamics (figure 2). Conclusion Cardiovascular risk factors and comorbidities have different diagnostic value for ACS depending on whether the initial hs-cTnT level is elevated and whether an early dynamic change in hs-cTnT is present. Further investigations of combined comorbidities, hs-cTnT levels and its correlation with ACS could refine risk stratifying algorithms among these patients.Figure 1troponin - ACSFigure 2troponin, dynamics - ACS

Abstract 12969: Role of Elevated High-Sensitivity Cardiac Troponin T in Determining the Clinical and Angiographic Outcomes in Patients With Chronic Total Occlusion Undergoing Percutaneous Intervention: A Meta-Analysis

Background: Percutaneous Coronary Intervention of Chronic Total Occlusion (CTO-PCI) leads to higher periprocedural myocardial injury (PMI); however, the prognostic value of high-sensitive-Cardiac Troponin T (Hs-cTnT) in CTO-PCI outcomes is not well studied. This review evaluated the association of Hs-cTnT with major adverse cardiovascular events (MACE) following CTO-PCI. Methods: We conducted a thorough literature search in PubMed, Scopus, Embase, and Google Scholar, using relevant keywords, to identify studies up to 2022. The primary outcome of interest was MACE, which included all-cause mortality, PMI, target vessel revascularization (TVR), and target vessel re-occlusion (TVRO). Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated using binary random-effects models. Heterogeneity was assessed using I 2 statistics. Results: Our analysis included four studies investigating 1499 post-CTO-PCI patients (mean age 66.77±10.09 years, 81.5% male). Patients with multivessel disease, retrograde approach, and previous PCI or coronary artery bypass graft procedures were more likely to present with elevated Hs-cTnT levels due to the complexity of the procedure. No difference in baseline comorbidities was noted in patients with and without elevated Hs-cTnT, including diabetes and hypertension. There was no significant association between Hs-cTnT levels and MACE (OR:1.56 p=0.25), TVR (OR:2.03, p=0.22), PMI (OR:3.45, p=0.07), and mortality (OR:2.35, p=0.14) ( Figure 1) . However, a significant association was found between Hs-cTnT levels and TVRO [OR:8.78 (95% C.I. 3.64-21.17) p&lt;0.01, I2 0%]. Conclusion: Patients with elevated Hs-cTnT levels have a nine-fold higher risk of TVRO than those with normal levels in CTO-PCI. Periprocedural Hs-cTnT measurement can be utilized for risk stratification of TVRO after CTO-PCI with no association with MACE. Overall smaller sample size warrants more randomized studies to substantiate the results.