High-sensitivity Troponin Research Articles

The cardio-protective effect of cardiomyopeptidin in critically ill patients with myocardial injury: a retrospective cohort study

In order to investigate the association between the use of cardiomyopeptidin (CMP) and outcomes in critically ill patients with myocardial injury, we conducted a retrospective cohort study in Nanfang hospital, Southern Medical University. Clinical data of patients with myocardial injury were collected retrospectively and adjusted for possible confounders by propensity score weighting. The main outcome was the in-hospital mortality. Secondary outcomes included the major adverse cardiovascular events (MACE) occurring during the hospital, the individual components of MACEs, changes in high sensitive troponin T (hsTnT) levels, length of stay (LOS) in ICU and hospital. A Cox proportional hazards model was constructed to examine the association between the application of CMP and in-hospital mortality. Logistic regression and linear regression are used to analyze secondary outcomes. In total, 339 critically ill patients with myocardial injury were included in the analysis. After inverse probability of treatment weighting (IPTW), the use of CMP was associated with reduced in-hospital mortality (HR: 0.64, 95%CI: 0.43–0.96, P = 0.03). No significant differences were found in change of hsTnT, the occurrence of MACE and LOS in ICU as well as hospital after IPTW. The association was more significant in the subgroup with hsTnT > 3URL (HR: 0.41, 95%CI: 0.23–0.71, P < 0.001) and APACHE II score < 25 (HR: 0.13, 95%CI: 0.17–0.59, P < 0.001). Cardiomyopeptidin was associated with reduced in-hospital mortality in critically ill patients with myocardial injury. Our study provides initial clinical basis for the application of CMP with cardio-protective effect in critically ill patients. These results need to be confirmed in future randomized controlled trails.

Evidence for stability of cardiac troponin T concentrations measured with a high sensitivity TnT test in serum and lithium heparin plasma after six-year storage at-80 °C and multiple freeze-thaw cycles.

As high-sensitivity cardiac troponin T (hs-cTnT) is making the transition from diagnostic to prognostic use, a long-term stability study of 5th generation hs-cTnT according to EFLM CRESS recommendations was set up for investigation of frozen clinical specimens (two matrices). Study samples collected in serum tubes and lithium heparin tubes with gel from patients admitted for suspected minor myocardial damage were measured directly after completion of the study (0 years), and after 3-year and 6-year storage at-80 °C, and recovery of hs-cTnT concentrations after long-term storage (%hs-cTnT concentration compared to 0-year) was calculated. Hs-cTnT changes were also compared to decisive delta changes, such as the ones proposed in the ESC NSTEMI 0 h/1 h algorithm (<3 or >5 ng/L for ruling out and ruling in suspected NSTEMI patients). Eighty-six patients were included in the study, whereof 28 both lithium heparin plasma and serum samples were collected simultaneously, in others only serum (n=30) or plasma (n=28). Multiple aliquots per patient were made, so that 479 serum and 473 plasma samples were available for analysis. Across the overall hs-cTnT measuring range, median recovery after 6 years was 105.4 % and 106.2 % for serum and plasma, respectively. Based on these decisive delta changes, serum showed consistent results upon long term storage (max 0.8 % of samples above delta threshold of >5 ng/L) as compared to heparin plasma (up to 19.2 % of samples above threshold). Over 6 years of storage at-80 °C, recovery of hs-cTnT in serum and heparin plasma was similar and within common lot-to-lot variation. Yet, when evaluating absolute delta increments around hs-cTnT clinical decision points, long-term stored sera displayed better clinical performance compared to heparin plasma samples.

Impact of combining ablation index-guided and very high-power short-duration ablation at posterior wall adjacent to esophagus during perioperative period on procedural factors.

The impact of combining ablation index (AI)-guided and very high-power short-duration (vHPSD) ablation on procedural factors at the posterior wall near the esophagus is unclear. Atrial fibrillation patients who underwent initial ablation using three-dimensional mapping were enrolled. Patients were classified into two groups: those who underwent only AI-guided pulmonary vein isolation (PVI) (AI group) and those who underwent vHPSD ablation at the posterior wall adjacent to the esophagus in addition to AI-guided PVI (AI + vHPSD group). Differences in myocardial injury, inflammation, procedural characteristics, and pulmonary vein (PV) reconnection patterns were assessed between the two groups. This study included 167 patients (AI group, 83 patients; AI+vHPSD group, 84 patients). No significant differences in high-sensitive troponin I or changes in inflammatory markers between pre- and Postablation were observed in either group. Total application time and total application energy were significantly lower in the AI+vHPSD group than in the AI group (p < 0.001 for both) despite no significant difference in the total number of applications between the groups. The incidence of esophagus temperature ≥40 degrees was significantly lower in the AI+vHPSD group than in the AI group (p = 0.036). However, the incidence of PV reconnections near the esophagus was significantly higher in the AI+vHPSD group than in the AI group (11.9% vs 3.6%, p = 0.046), despite no significant difference in the incidence of PV reconnections overall. The combination of AI-guided PVI and vHPSD adjacent to the esophagus demonstrated reduced application energy requirements and maintained safety and effectiveness during the perioperative period.

Effectiveness and Safety of the ESC-TROP (European Society of Cardiology 0h/1h Troponin Rule-Out Protocol) Trial.

European guidelines recommend the use of a 0h/1h hs-cTn (high-sensitivity cardiac troponin) protocol in patients with acute chest pain. We aimed to determine the performance of this protocol in routine care when supplemented with patient history and ECG and a recommendation to refrain from noninvasive testing in low-risk patients. This was a pre- and postimplementation study with concurrent controls. Patients with chest pain were enrolled at 5 Swedish emergency departments (EDs) during a 10-month period in both 2017 and 2018. All hospitals used a 0h/3h hs-cTnT protocol in 2017 and 3 EDs implemented a 0h/1h hs-cTnT protocol during 10 months in 2018. The 2 coprimary outcomes were the incidence of acute myocardial infarction and all-cause death within 30 days and ED length of stay. The study included 26 040 consecutive patients. In the intervention hospitals, 21 (0.40%) of the discharged patients had an acute myocardial infarction/death event during the control period (0h/3h testing) and 22 (0.45%) in the intervention period (0h/1h testing), which met the criteria for noninferiority. There was no significant difference in ED length of stay (ratio 0.99, P=0.48) or ED discharge rate between the periods in the intervention versus the control hospitals. A total of 3142 patients met low-risk 0h/1h hs-cTnT criteria and were discharged, of whom 2 had an acute myocardial infarction/death event. A 0h/1h hs-cTnT protocol incorporating patient history and ECG was as safe as using a 0h/3h protocol but did not reduce ED length of stay or increase the discharge rate. Refraining from noninvasive testing in patients identified as low risk was safe. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03421873.

Cardiac Myosin-binding Protein-C as a Biomarker in the Early Diagnosis of Acute Coronary Syndrome and Differentiation of Its Types

Abstract Background: Coronary heart disease (CHD) is primarily caused by atherosclerotic lesions within the intima of coronary arteries and acute coronary syndrome (ACS) is the main acute clinical manifestation of CHD. The ACS is manifested in one of three subtypes and it is the leading cause of mortality worldwide. The three subtypes of ACS include: acute myocardial infarction (MI) with the electrocardiogram (ECG) presenting ST-segment elevation (STEMI), MI with no ST-segment elevation on ECG (NSTEMI), and the third subtype is unstable angina (UA). The early diagnosis of is important in decreasing morbidity and mortality in ACS patients. Objective: To investigate the role of serum level of cardiac myosin-binding protein-C (cMyC), compared with high-sensitivity cardiac troponin-I (hsCTn-I) in the early diagnosis of ACS and differentiation of its subtypes. Materials and Methods: One hundred and twenty patients (72 males and 48 females), aged ≥30 years selected from those who were admitted to emergency department (ED) of Al-Yarmouk teaching hospital and diagnosed with ACS by cardiologists. The duration between the onset of chest pain and admission to ED should not exceed 3 h in any cohort. Apparenty healthy subjects as controls group for the study were recruited from those who had no current illness, particularly CHD, no other systemic disease and each had a normal ECG. For each study subject, cMybp-C and hsCT-I serum levels on admission were measured using the enzyme-linked immunosorbent assay kits. For each ACS patient, serum level of hsCTn-I level was measured 3 h after admission. Results: The comparison of cMybp-C levels among study groups revealed an overall significant difference and on paired comparison of study groups, the cMybp-C mean level was significantly higher in each ACS subgroup than in controls group (P &lt; 0.001), except in UA subgroup versus controls group. The cMybp-C levels showed a significant positive correlation with hsCT-I levels on admission in STEMI and NSTEMI subgroups but not in UA subgroup. The cMybp-C levels also showed a significant positive correlation with hscT-I levels 3 h after admission in STEMI and NSTEMI subgroups but not in UA subgroup. On receiver operating characteristic curve analysis, the cMybp-C level had a better diagnostic accuracy than hscTn-I on admission in differentiation of patients with “STEMI or NSTEMI” from those with UA or from controls. Conclusion: Serum cMybp-C mean level is significantly higher in ACS patients with STEMI and NSTEMI than in controls and the increase was more significant than hsCTn-I mean level on admission, so it could help the early diagnosis of ACS patients. The serum levels of cMybp-C also had a better diagnostic accuracy than hsCTn-I on admission in differentiation of ACS patients with STEMI or NSTEMI from those with UA or from controls.

Fastidious adherence to 0/1-hour high-sensitivity troponin T testing reduces emergency department length of stay in patients presenting with suspected acute coronary syndromes

Abstract Background High-sensitivity cardiac troponins (hs-cTn) are key clinical biomarkers in patients presenting with suspected acute coronary syndromes (ACS) to Emergency Departments (EDs). They have facilitated rapid 0h/1h troponin testing protocols, leading to safe, effective, and efficient triage of patients. However, early distinction of myocardial infarction (MI), which has a reported frequency of less than 10% in most cohorts, from the apparently stable hs-cTn elevations of chronic myocardial injury (CMI) remains a challenge. Often CMI patients require confirmation by further testing and observation, prolonging patient length of stay. Further, reliably obtaining serial hs-cTn samples at 60-minutes in a busy ED setting may be difficult. A potential explanation for only 5-6% of Australian sites adopting 0h/1h hs-cTn testing. Methods and Results We undertook a case-control study between March and August 2023 among patients with suspected ACS presenting to Liverpool Hospital ED (Sydney, Australia). 185 patients (cases) underwent hs-cTnT sampling at 30- and 60-minutes (± 5 minutes) after baseline. Diagnosis of MI was made in 8.6%, 35.7% were placed into a further observation group and MI ruled-out in 55.7%. The latter two groups were matched to 169 patients (controls) who received ‘usual’ care, which was a 0h/1h hs-cTnT testing protocol. The case and control arms were matched by age, gender, time from symptom onset and main presenting symptom. Control patients had a median sampling interval of 118 [85 to 174] minutes, rather 60 minutes as the protocol directs. When comparing the paired differences between the case and control arms, there was a mean reduction in length of stay of 104 (95% CI: 41 to 186, P = 0.01) and 47 (95% CI: 11 to 84, P = 0.01) minutes, for the observation and rule-out MI groups respectively. The figure shows the distribution of lengths of stay by group. Among the rule-out group, Wilcoxon signed rank test indicated the control arm had a longer median length of stay of 6.3 [5.1 to 8.4] hours, compared to 5.0 [4.5 to 7.1] hours in the case arm (P=0.005). Similarly, in the further observation group, control patients also had a longer median length of stay of 9.2 [6.9 to 10.4] hours compared to case patients of 8.1 [5.1 to 10.3] hours (P = 0.009). At 30-days, ED representation rates were 10.7% in controls and 8.3% in cases, rehospitalisation 3.6% in controls and 5.3% in cases, cardiac death 0% in both arms and non-cardiac death 1% in both arms. There were no differences in event rates between each arm (P &amp;gt; 0.05). Conclusion Accurate 0h/1h hs-cTnT testing reduces patient length of stay in ED and offers more personalised prediction of MI risk. The importance of adherence to protocol-directed sampling times is clear, where further studies are required regarding routine implementation in a busy ED setting.Exact 60 min TnT and LOSOutcomes at 30 days

Incidence of MINOCA in the high-sensitivity troponin era: a meta-analysis

Abstract Background and Aim Myocardial infarction with non-obstructive coronary arteries (MINOCA) is often under-recognised in clinical practice. The reported incidence of MINOCA was estimated to be 6% of MI presentations by Pasupathy et al. in the era preceding adoption of high sensitivity troponin assays. We sought to investigate the incidence of MINOCA in the high-sensitivity troponin era as compared to incidence of MINOCA during the era of traditional cardiac biomarkers (standard troponin assays, CK, CK-MB). Methods A prospective systematic review and meta-analysis using MEDLINE and EMBASE to capture relevant papers from 1996-2022 was performed. Papers detailing incidence of MI-CAD and MINOCA as well as the utilised biomarkers were included. Patient demographics, presentation and recorded biomarkers were also analysed for pre-specified analysis. Results 47 studies detailing the results of 667 850 patients were included. 53 586 patients were identified to have MINOCA with a mean weight incidence of 9.1% (7.3-11.3, 95% CI). MI-CAD patients were more likely to be male (68.5% vs 39.3%, RR (0.59, 0.74)) and had higher incidence of traditional cardiac risk factors. Notably chronic kidney disease was not associated with higher incidence of MICAD over MINOCA (RR 0.72, 0.5-1.03). There were no significant trends in incidence of MINOCA according to median year of study recruitment (ß=-0.18, (-0.76, 0.4) p=0.537). MINOCA patients were more likely to present as NSTEMI (14.5% (11.3-18.3, 95%CI)) rather than STEMI (3.5% (2.7-4.7%)). MINOCA patients had lower cardiac biomarker elevations than patients with MICAD. Conclusions The incidence of MINOCA higher than previously estimated in the era of high sensitivity troponin. MINOCA patients are less likely to have traditional cardiac risk factors and more likely to present with NSTEMI and smaller cardiac biomarker elevations than patients with MI-CAD.MINOCA RateMINOCA vs MI-CAD Risk Factors

High-sensitive cardiac troponin T in patients with idiopathic inflammatory myopathies

Abstract Introduction Patients with idiopathic inflammatory myopathies (IIM) may have positive blood tests of cardiac troponin in absence of clinically detected cardiac disease. This situation is more common using high-sensitive cardiac troponin T (hs-cTnT) but there is limited information of the expected results according to type of IIM and prognostic value of this test in this group of patients. Methods Prospective study with 32 healthy controls and 61 patients with IIM without known cardiac condition. These patients with IIM were followed for 25 months. High-sensitive cardiac troponin T (Roche Elecsys hs-cTnT) was measured at baseline in both groups and a value of 14 pg/ml was the percentile 99th and considered the upper limit of normality (ULN). Results The median value of hs-cTnT was higher in patients with myopathies [12.0 (5.0; 35.0) vs. 5.0 (4.0; 6.2) P&amp;lt; 0.001] and the frequency of abnormal values were also more common in patients with IIM compared to controls (45.9% vs 6.2%, p&amp;lt;0.001). The frequency varied according to the type of myositis: Inclusion Body Myosytis (75%), Polymyositis (66.7%) , Dermatomyositis (42.1%) and Antisynthetase syndrome (38.5%). In terms of magnitude, 57% had mild elevations (1 to 3 x ULN) while 11% had levels 3 to 5 times ULN and 32% had troponin values &amp;gt; 5x ULN (Figure 1). Among patients with IIM, elevated levels of hs-cTnT were not associated with left ventricle global longitudinal strain &amp;lt; 18% or lower ejection fraction and was not associated with cardiovascular events during 25 months of follow-up (Figure 2). Conclusion Abnormal values of high-sensitive cardiac troponin T are common in patients with idiopathic inflammatory myopathies including levels similar to myocardial infaction. This elevation was not associated with echocardiographic abnormalities or cardiovascular events in patients with IIM.Figure 1Figure 2

Enhancing the selection of heart failure patients for invasive procedures: how machine learning can predict the diagnostic yield of endomyocardial biopsy

Abstract Background Determining the etiology of heart failure (HF) is crucial for appropriate treatment. Endomyocardial biopsy (EMB) is an invasive procedure that complements clinical assessment and imaging in diagnosing various cardiac disorders. The diagnostic value of EBM depends upon the anticipated yield of the procedure. Whether results from non-invasive examinations may predict the diagnostic yield from EMB is unclear. Purpose We aimed to investigate the relative importance of clinical and instrumental features in predicting a diagnostic EMB result, using a machine learning (ML) approach. Methods We retrospectively examined 665 consecutive adult patients with HF symptoms who underwent right EBM as part of their diagnostic work-up. The primary outcome was a positive biopsy result with a clear diagnosis. The ML algorithm consisted of Gradient Boosting Machines (GBM), with computation of relative variable importance using conditional importance. We calculated the conditional variable importance for 53 clinical or instrumental variables. Model performance was evaluated using a receiver operating characteristic curve, which was compared to a logistic regression model using the same variables. Validation was performed using a 10-fold cross-validation model. Results Among the 665 patients (50±14 years, 67% male), the EMB provided a diagnosis in 138 cases (20.8%). Patients attaining diagnosis were more often older, had a shorter disease duration, presented with ventricular arrhythmia or cardiac arrest, had a pacemaker or defibrillator, displayed higher creatinine, NT-proBNP and high-sensitive troponin T levels, and had smaller ventricular volumes with higher ejection fraction at CMR. All patients with a diagnostic EMB showed late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) in the right ventricle, the right atrium or in the left atrium. The relative importance of different variables predicting outcomes is presented in Figure 1. The top six included four distinct CMR features and two circulating biomarkers (NT-proBNP and high-sensitive troponin T). LGE in the right ventricle and the presence of left ventricular hypertrophy were stronger predictors compared to the remaining variables. The GBM model performed significantly better than the logistic regression model (AUC GBM 0.98, AUC logistic regression 0.93, DeLong’s test p&amp;lt;0.001) (Figure 2). Conclusion Using a ML algorithm, CMR LGE, left ventricular hypertrophy, and elevated cardiac biomarkers, stand out as strong overall predictors of an endomyocardial biopsy with a high diagnostic yield.Figure 1Figure 2

Elevated GDF-15 is associated with stroke severity, myocardial injury and poor clinical outcome in patients after acute ischemic stroke

Abstract Background GDF-15 is emerging as a biomarker of cardiometabolic risk and disease burden. Increased concentrations of circulating GDF-15 are associated with increased mortality in patients with acute coronary syndromes or heart failure. Purpose We aimed to describe relation between GDF-15 elevation with stroke severity, myocardial injury and poor clinical outcome in patients after acute ischemic stroke (AIS). Methods Patients after AIS were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24 and 48 hours later to determine the plasma levels of GDF-15 and high-sensitive troponin I (hs-cTnI). Receiver-operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy and optimal elevation cut-off values of GDF-15 on day 1 for the severity of acute stroke defined by NIHSS score. The optimal cut off in our group was 1776 pg/ml (Sensitivity 0,8, Specificity 0,52). Myocardial injury was defined by fourth universal definition of myocardial infarction using hs-cTnI. Demographic characteristics, clinical data, functional outcome, and all-cause mortality at 1 year were compared between groups according to GDF-15 levels. National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following the patient’s discharge from the hospital were used to assess stroke severity and clinical outcome. All analyses were performed with SPSS 29.0 (SPSS Inc). Results Between August 2020 and August 2022, 177 patients after AIS were enrolled. Elevated GDF-15 was observed in 71 patients (40,1%). Most common comorbidities included arterial hypertension, dyslipidemia, type 2 DM and atrial fibrillation. In analysis, we observed a connection between elevated GDF-15 with unfavourable outcome evaluated by mRS at 90 days (HR 2.57, 95% CI 1,44 to 4,57, p=0.001) and with all-cause death at 1 year (HR 4.479, 95% CI 1,81 to 11,09, p=0.001). GDF-15 elevation was associated with myocardial injury (Figure 1C). Moreover, individuals with moderate to severe and severe strokes (NIHSS 16-42) displayed higher GDF-15 levels compared to those with minor to moderate stroke (Figure 1D). The Kaplan-Meier survival curve accentuated a significantly elevated all-cause mortality among patients with increased GDF-15 (p &amp;lt; 0.001) (Figure 2). In multivariate regression analysis elevated GDF-15 was associated with atrial fibrillation and high-sensitive troponin I elevation. Conclusion The conclusions drawn suggest that heightened GDF-15 is associated with increased stroke severity, myocardial injury and unfavourable outcome.

The prognostic utility of troponin T levels in patients undergoing PCI during initial hospitalisation for STEMI

Abstract The prognostic utility of presentation or "peak" high-sensitivity troponin T (hsTnT) levels following ST-segment elevation myocardial infarction (STEMI) has been previously reported, but hsTnT, unlike other bio-markers of myocyte damage, have a 2nd or ‘plateau-phase’ of release which lasts over a week. We have reported correlations between plateau-phase hsTnT levels, and cardiac MRI determined infarct size, though whether these levels are more highly associated with late mortality than "peak" (or highest) levels, needs clarification. Methods Hence we determined late mortality and the combination of cardiovascular death, myocardial infarction and cerebrovascular accident [CD/MI/CVA] among patients with STEMI, and an HsTnT level &amp;gt;36 hours after symptom onset (plateau phase), who underwent percutaneous coronary intervention (PCI), either primary or pharmaco-invasive, during initial hospitalisation between October 2003 and December 2021. HsTnT levels and other potential prognostic factors were determined. Results Amongst 1955 patients, 119 patients (6%) had died by 2 years and 192 (10%) patients experienced CD/MI/Stroke. The highest quartile of plateau phase hsTnT levels (³ 3786 ng/L ng/L), were more highly associated with 2-year mortality, than the highest quartile of "peak" hsTnT levels (³ 7687 ng/L ng/L). The Figure shows Peak and plateau hs-TnT levels in quartile groups were assessed by rank test to obtain p-values. Patients lost to follow-up or with less than 2-years of follow up were considered censored. Peak quartile 1; hs-TnT £ 1611 ng/L, peak quartile 2; hs-TnT 1612 – 3900 ng/L, peak quartile 3; hs-TnT 3901 – 7686 ng/L; peak quartile 4; hs-TnT ³ 7687 ng/L. Plateau quartile 1; hs-TnT £ 1060 ng/L, plateau quartile 2; hs-TnT 1061 – 2135 ng/L; plateau quartile 3; hs-cTnT 2136 – 3785 ng/L. Log rank mortality analyses are shown in the Figure. Peak quartile 1; hs-TnT &amp;lt;1611 ng/L, peak quartile 2; hs-TnT 1612 – 3900 ng/L, peak quartile 3; hs-TnT 3901 – 7686 ng/L; peak quartile 4; hs-TnT ³ 7687 ng/L. Plateau quartile 1; hs-TnT £ 1060 ng/L, plateau quartile 2; hs-TnT 1061 – 2135 ng/L; plateau quartile 3; hs-cTnT 2136 – 3785 ng/L, plateau quartile 4; hs-TnT &amp;gt;3786 ng/L. Multivariate Cox regression analysis incorporating age, sex, smoking status, hypertension, renal function, cardiogenic shock and heart failure hospitalisation found plateau hs-TnT levels (HR, 3.564; 95% CI, 1.674 – 7.590; P = 0.001) were an independent predictor of all-cause mortality at 2-years post-STEMI, whereas peak hs-cTnT levels (HR, 1.965; 95% CI, 0.959 – 4.025; P = 0.065) were not. Conclusions Plateau phase hsTnT levels were of prognostic significance in STEMI patients treated with PCI. Thus, measurement of plateau hs-cTnT levels following STEMI could be an accurate, inexpensive method of long-term prognostic risk stratification.

Comparison of rapid test for high-sensitivity troponin I with laboratory high-sensitivity troponin T in patients with acute chest pain - a prospective monocentric study

Abstract Background and purpose High-sensitivity troponin (hs-Tn) assays are recommended for routine clinical use for diagnosis of acute coronary syndrome (ACS). However, laboratory hs-TnT can be elevated due to non-cardiac conditions, such as pulmonary embolism, skeletal muscle injury or chronic kidney disease. The aim of our study was to compare the diagnostic accuracy of the bed-side rapid hs-troponin I (hs-TnI) assay with hs-TnT measured by routine laboratory. Methods This prospective monocentric study was conducted at a tertiary hospital outpatient cardiac unit with an emergency clinic for patients with acute symptoms. A total of 129 patients were included between May 2021 and August 2022. Hs-TnI was measured via a bed-side test from whole blood directly in the emergency room, while hs-TnT was measured from plasma through the routine laboratory. Definite ACS was confirmed by coronary angiography. Patients were compared by grouping them into definitive diagnosis of ACS or no ACS. Hs-TnI as well as hs-TnT values were compared for accuracy and predictive values. Routine clinical parameters and comorbidities were documented and compared as well. Agreement between hs-TnI and hs-TnT was assessed by likelihood ratios and Bland Altman plot. Results Overall, 129 patients (65.1% male, 61.8 ± 15.6 years) with acute chest pain were analysed. Median hs-TnI was 7.0 ng/L (IQR: 2.7-15.8), while median hs-TnT was 14 ng/L (IQR: 7.0-31.0). Results for TnI were available faster (average: 1:14 h ± 0:54) compared to TnT. Coronary angiography confirmed ACS in 17 patients (13.2%) displaying significant coronary stenoses requiring intervention. The relative risk of ACS patients to have an elevated hs-TnI result was 6.59 compared to that of 2.29 for the hs-TnT test, meaning that a positive hs-TnI test was a better classifier for validated ACS than that of hs-TnT. Hs-TnI exhibited equivalent negative predictive value to hs-TnT (99%) for definite ACS diagnosis, but had comparatively higher positive predictive value (50.0 vs. 25.8%). Bland Altman plot of hs-TnI versus hs-TnT showed an average difference of -4.6 ng/L (95% CI: -12.4 to 3.2) between the tests. In 39 patients with chronic kidney disease (minimum stage 3a CKD) median hs-TnT (27.0 ng/L, IQR: 16.0-55.0) values were higher than hs-TnI (11.2 ng/L, IQR: 7.5-30.7). Conclusion Bed-side hs-TnI is comparable to hs-TnT with a high degree of agreement. Measurement of troponin I using the rapid bed-side hs-TnI assay possesses a shorter blood-draw-to-result-time than routine troponin T measurement.

Imprecision and real-time clinical performance of a whole blood high sensitivity point of care troponin i: ready for prime time?

Abstract Introduction High sensitivity troponin (hs-cTn) measurement is central to rapid diagnostic algorithms in acute coronary syndrome (ACS). Point of care (POC) testing reduces turnaround time when compared to central lab (CL) testing. Currently there is very little data on the performance of POC hs-cTn assays in a clinical environment with non-expert operators. Method In a nested sub-study of a randomised controlled trial (RCT), patients with suspected ACS were randomised to either the ESC 0/1 or 0/3 hour algorithm. They underwent whole blood (WB) sampling for Siemens Atellica VTLi hs-cTnI POC (VTLi POC), CL hs-cTnI and CL hs-cTnT assays. This was for both initial and repeat samples. Assay imprecision of the VTLi POC assay was assessed by 2 runs of 10 tests with whole blood at 9 different troponin levels. 4 devices were used with samples stored at room temperature.Final diagnosis was adjudicated based on all relevant clinical and imaging data together with CL hs-cTnT as the diagnostic biomarker in clinical use (10% coefficient of variation (CV) 3-5 ng/L, 99th percentile 14 ng/L) and using the 4th universal definition of myocardial infarction (MI). Clinical performance was assessed using Receiver Operator Characteristics (ROC) curves. Results 2144 patients consented and had WB VTLi POC, CL hs-cTnI and CL hs-cTnT available. The index adjudicated type 1 MI rate was 6.1%. Assay imprecision of the VTLi POC assay demonstrated a 10% Coefficient of Variation (CV) at 9.8ng/l. This was &amp;gt;50% lower than the 99th centile of 23ng/l (average for males and females) (Figure 1). Clinical performance of the VTLi POC assay was acceptable and equivalent to CL hs-cTnT: Area Under Curve (AUC) 0.92 (0.89-0.96), 0.98 (0.96-0.99) and 0.93 (0.87-0.98) at presentation (Figure 2), 1 and 3 hours respectively. However, clinical performance was inferior to CL hs-cTnI: AUC 0.96 (0.95-0.98) and 0.96 (0.93-0.98) at presentation (p=0.0007) and 3 hours (p&amp;lt;0.0001) respectively. Conclusion The Siemens Altellica VTLi hs-cTnI POC assay has imprecision levels consistent with a high sensitivity troponin assay. It has acceptable clinical performance though inferior to the equivalent CL hs-cTnI. Further validation of this assay, particularly with optimised single sample rule-out, could facilitate its use in routine clinical practice.

Improved risk prediction in patients with atrial fibrillation and clinical intermediate-risk CHA2DS2VASc-score utilizing high sensitive troponin T

Abstract Background Guidelines of the European Society of Cardiology recommend risk assessment to identify appropriate candidates for anticoagulation in patients with atrial fibrillation (AF). However, scores such as the CHA2DS2VASc-score show only a modest performance for prediction of adverse events. Methods This retrospective single-center all-comer sub-study from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB) enrolled 9,995 consecutive patients with non-valvular AF, presenting to the emergency department (ED) from June 2009 until March 2020. We tested the performance of the CHA2DS2VASc-score with and without high sensitive cardiac troponin T (hs-cTnT) for prediction of a adverse events such as stroke or major bleedings. Per CHA2DS2VASc, stroke risk was classified as low (0 point in men, ≤1 point in females), intermediate, or high (≥2 points in men and ≥3 points in females). Results Performance of the CHA2DS2VASc-score for the prediction of the composite endpoint consisting of stroke and major bleeding was poor (AUC 0.600, 95%CI: 0.590-0.610) but improved after addition of hs-cTnT as a variable across all risk categories (AUC 0.618 95%CI: 0.608-0.628, ∆AUC 0.0182 95%CI: 0.0124-0.0240, p&amp;lt;0.0001), and particularly in patients at intermediate-risk (∆AUC 0.160 95%CI: 0.0653-0.254, p=0.0009). The absence of detectable hs-cTnT (&amp;lt; LoD) identified a cohort without incident events within patients with intermediate per CHA2DS2VASc. Conclusion Combination of hs-cTnT and clinical-based risk stratification in AF patients presenting to an ED with intermediate CHA2DS2VASc-score is simple and effective. Measurement of hs-cTnT improves prediction of stroke risk in patients with intermediate CHA2DS2VASc-score and may help guide decision for or against anticoagulation.

The coronary angiography-derived index of microcirculatory resistance predicts perioperative myocardial injury in stable coronary artery disease patients undergoing PCI

Abstract Background Coronary microvascular dysfunction (CMD) assessed by the index of microcirculatory resistance (IMR) is associated with perioperative myocardial injury(PMI).The angiography-derived index of microcirculatory resistance (caIMR) is a novel and accurate alternative of IMR. Objective This study aims to evaluate the predictive value of caIMR on PMI in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). Methods Consecutive stable CAD patients undergoing elective PCI of a single lesion were recruited. caIMR were measured before and after revascularization.Total creatine kinase-MB (CK-MB) and high sensitivity Troponin T (hsTnT) levels were measured before and within 24 hours after PCI. Results A total of 65 patients were enrolled, twenty-six patients fulfilled the diagnostic criteria of PMI. Post-PCI caIMR values in the PMI group were significantly higher than those in the control group (27.02±3.70 vs. 15.91±3.43U, P&amp;lt;0.001). Pearson correlation analysis demonstrated that increased post-PCI caIMR values have a significant positive correlation with peak hsTnT (r = 0.803, P&amp;lt;0.001) and peak CK-MB (r = 0.512, P= 0.001). Multivariate logistic regression analysis showed the post-PCI caIMR was independent predictors of PMI(OR,1.731;95% CI:1.348-2.023; P&amp;lt;0.001).The ROC analysis suggested that the best cutoff value of post-PCI caIMR was 25.17U to diagnose PMI(AUC=0.951, sensitivity 88.5%, specificity 97.1%%). Conclusions The post-PCI caIMR can accurately predict PMI in stable CAD patients receiving elective PCI, supporting its use in clinical practice.

Diagnostic potential of relative changes in high-sensitivity troponin levels during intracoronary acetylcholine provocation testing

Abstract Background Intracoronary acetylcholine (ACh) provocation testing is useful for the diagnosis of vasospastic angina (VSA). However, the positive or negative diagnosis of ACh testing is often challenging when lacking typical anginal symptoms and electrocardiographic changes during provocation tests. We hypothesized that relative changes in cardiac troponin levels during ACh provocation testing may be suggestive of myocardial ischemia and would be helpful for the VSA diagnosis. Purpose To evaluate the diagnostic potential of relative changes in high sensitivity troponin I (hs-TnI) levels during intracoronary ACh provocation test. Methods This preliminary study included a total of 29 patients undergoing invasive coronary angiography with or without ACh provocation tests. Patients were divided into three groups; no ACh provocation tests (i.e. angiography alone), negative ACh tests, and positive ACh tests. Blood samples were obtained twice, before and after angiography, through the arterial sheath to evaluate hs-TnI. The primary measure was relative changes in hs-TnI (i.e. Δhs-TnI). Positive ACh provocation test was defined as total or subtotal coronary occlusion accompanied by chest pain and/or ischemic electrocardiographic changes. Results Of the 29 patients, 10 (34.5%) underwent coronary angiography alone, while ACh provocation testing was performed in 19 (65.5%) patients, of whom 7 (36.8%) and 12 (63.2%) had negative and positive ACh test results. Overall, the mean time interval between the blood sample collections was 76 minutes. Levels of hs-TnI before angiography did not differ significantly in the no, negative, and positive ACh test groups (5.3 [2.8, 8.6] vs. 2.9 [1.3, 8.8] vs. 3.3 [1.6, 8.5] pg/ml, p=0.76), while Δhs-TnI was highest in the positive ACh test group, followed by the negative and no ACh test groups (4.2 [0.5, 8.1] vs. 0.8 [0.4, 4.6] vs. −0.3 [−0.6, 0.3], p=0.002) (Figure). Conclusions In patients undergoing intracoronary ACh testing for the VSA diagnosis, a relative increase in Δhs-TnI during angiography was observed than in those who did not undergo the provocation tests, particularly when the ACh test diagnosis was positive. Our findings suggest that Δhs-TnI has the potential to aid in the positive or negative diagnosis of ACh provocation testing.

Enhancing primary prevention: the incremental predictive value of high-sensitivity cardiac troponin T beyond ASCVD risk assessment

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) is a global health challenge, prompting widespread use of conventional risk assessment tools (SCORE2 in Europe and the ASCVD Risk calculator in the United States) to guide preventive strategies. Emerging evidence indicates that high-sensitivity cardiac troponin (hsTn) may refine risk stratification. Objective We investigate whether measuring hsTnT in primary prevention correlates with mortality and enhances prediction compared to conventional risk score stratification. Methods Utilizing National Health and Nutrition Examination Survey (NHANES) data (1999 to 2004) linked to the National Death Index, our cohort included individuals without a history of CVD at baseline and suitable for assessment of the ASCVD ACC/AHA risk score. Individuals were grouped based on computed 10-year risk (low: &amp;lt;5%; borderline: 5-7.5%; intermediate: 7.5-20%; high: ≥ 20%). hsTroponin T levels were measured (Roche assay, 99 th percentile 22ng/L for men and 17ng/L for women). Cox regression estimated association between ASCVD risk categories, with or without hsTnT, and all-cause and cardiovascular mortality. Results Among 5257 adults, 47% male, mean age 54 ± 9.1 years, the mean 10-year ASCVD risk was 8.17 ± 8.2%, grouped as: low: 53.3%; borderline: 11.5%; intermediate: 23.9%; and high: 11.3%. hsTnT above the 99 th percentile was measured in 1.1%, 2.7%, 4.9% and 13.4%, respectively (p &amp;lt; 0.001). Over 16.2 ± 3.4 years, all-cause and cardiovascular death was 22.3% and 5.6%, respectively. Compared to low-risk, the hazard ratio (HR) for all-cause death increased to 2.85 (2.2-3.7), 5.6 (4.2-7.5), and 15.3 (11.7-19.9) for borderline, intermediate, and high-risk, respectively. A significant interaction with hsTnT above 99 th percentile was observed (low: HR 3.5 (1.3-9.2); borderline: HR 4.75 (2.1-10.8); intermediate: HR 2.6 (1.8-3.7), high: HR 2.2 (1.7-2.9), p&amp;lt;0.01 for all interactions, see Fig. 1). For cardiovascular death, a significant interaction occurred in intermediate (HR 3.3 (2-5.4), p&amp;lt;0.001) and high-risk (HR 3.6 (2.2-6), p&amp;lt;0.001) groups. Conclusion Our findings suggest that hsTnT provides incremental predictive value, at least doubling the hazard of all-cause death across all risk categories, and tripling the hazard of CV death in intermediate and high-risk groups, compared to ASCVD risk stratification alone. The integration of troponin measurements into risk assessment strategies could refine primary prevention approaches.

Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T

Abstract Background Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as these patients often have elevated baseline high-sensitivity cardiac troponin T (hs-cTnT) concentrations. Methods Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with &amp;gt;1 hs-cTnT increase &amp;gt;99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2- and 6-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR &amp;lt;60 ml/min/1.73m2). Results The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 701 (82%) patients with myocardial injury, 64 (7.5%) with type 1, and 91 (11%) with type 2 MI. In CKD patients with baseline hs-cTnT thresholds of &amp;gt;52, &amp;gt;100, &amp;gt;200 or &amp;gt;300 ng/L, PPVs for acute MI were 37% [95% CI 28-46], 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 64% (95% CI 50-77), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of &amp;gt;10, &amp;gt;20 or &amp;gt;30 ng/L, the corresponding PPVs were 65% (95% CI 50-78), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 65% (95% CI 51-78), 73% (95% CI 57-86) and 75% (95% CI 58-88) (Figure). Conclusion Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in patients with CKD. It significantly improves when using higher baseline thresholds and delta values.

Comparison of multiple high sensitivity cardiac troponin assays for early low risk rule out of myocardial infarction: SCORECARD

Abstract Background/Introduction The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome. Methods In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay. Results Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from &amp;lt;2 to &amp;lt;7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days. Conclusions Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.

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 &amp;gt;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 &amp;gt;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.