Sensitive Cardiac Troponin Research Articles

Complexity of coronary artery disease and the release of cardiac biomarkers after CABG.

In patients with complex coronary artery disease (CAD) undergoing cardiac surgery, myocardial protection might be impaired due to microvascular obstruction, resulting in myocardial injury and subsequent biomarker release. Therefore, this study investigated the correlation between the complexity of CAD, reflected by the SYNTAX Score, and the release of cardiac biomarkers after CABG. In a consecutive series of 919 patients undergoing isolated CABG SYNTAX scores I and II were calculated to assess the complexity of CAD. Levels of high sensitivity cardiac troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) were routinely measured once before and serially after surgery. Patients were divided into tertiles according to their SYNTAX Scores I and II. Spearman correlations and regression models were performed to measure the degree of association between the release of hs-cTnT and CK-MB and the SYNTAX Scores. Patients with a higher SYNTAX Score I had more comorbidities reflected in a higher EuroSCORE II. Preoperatively, higher levels of cardiac biomarkers were found in patients with higher SYNTAX Score II. No correlation was observed between hs-cTnT, CK-MB and SYNTAX Score I or II. Regression models did not show any association between cardiac biomarkers and the complexity of CAD. The complexity of CAD is not associated with the release of cardiac biomarkers after CABG. Factors influencing postoperative biomarker release need to be elucidated in future trials to include postoperative biomarker release into risk stratification models predicting outcome after cardiac surgery.

Four high sensitivity troponin assays and mortality in US adults with cardiovascular disease: The national health and nutrition examination survey, 1999–2004

ObjectiveHigh sensitivity cardiac troponin (hs-cTn) may be useful to monitor residual risk in secondary prevention. Our objective was to study the correlations and comparative associations with mortality of four hs-cTn assays in US adults with known cardiovascular disease (CVD). MethodsWe studied 1,211 adults with a history of CVD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Using stored samples, we measured hs-cTnT (Roche) and three hs-cTnI assays (Abbott, Siemens, and Ortho). Outcomes were all-cause and CVD mortality, with follow-up through December 31, 2019. ResultsMean age was 64 years, 48 % were female, and 80 % identified as non-Hispanic White. Pearson's correlation coefficients between hs-cTn assays ranged from 0.67 to 0.85. There were 848 deaths (365 from CVD). Among adults with a history of prior non-fatal CVD, each hs-cTn assay (log-transformed, per 1-SD) was independently associated with CVD death (HRs ranging from 1.55 to 2.16 per 1-SD, all p-values <0.05) and with all-cause death (HRs ranging from 1.31 to 1.62 per 1-SD, all p-values <0.05). Associations of hs-cTnT and all-cause and CVD death remained significant after adjusting for hs-cTnI (and vice versa). Associations between hs-cTnI and CVD death remained significant after mutually adjusting for other individual hs-cTnI assays: e.g., HR 2.21 (95 % CI 1.60, 3.05) for Ortho (hs-cTnI) after adjustment for Siemens (hs-cTnI) and HR 1.81 (95 % CI 1.35, 2.43) for Ortho (hs-cTnI) after adjustment for Abbott (hs-cTnI). ConclusionIn US adults with a history of CVD, we found modest correlations between 4 hs-cTn assays. All assays were associated with all-cause and CVD mortality. The hs-cTnT assay was associated with mortality independent of the hs-cTnI assays. Hs-cTnI assays also appeared to be independent of each other. Thus, hs-cTn assays may provide distinct information for residual risk in secondary prevention adults.

Analytical evaluation of the novel Mindray high sensitivity cardiac troponin I immunoassay on CL-1200i.

The current study was designed to evaluate the analytical performance of the new Mindray highly sensitive cardiac troponin I (hs-cTnI) chemiluminescent immunoassay on Mindray CL-1200i, as a thorough validation of novel hs-cTnI methods is required before introduction into clinical practice. The evaluation of the analytical performance of this hs-cTnI immunoassay encompassed the calculation of the limit of blank (LOB), limit of detection (LOD), functional sensitivity, imprecision, linearity, 99th percentile upper reference limit (URL) and concordance with another previously validated hs-cTnI chemiluminescent immunoassay. The LOB and LOD were 0.32 and 0.35 ng/L, whilst the functional sensitivity (expressed as cTnI value with <10 % imprecision), was 0.35 ng/L. The linearity was excellent throughout a wide range of clinically measurable values (r=1.00 between 0.8 and 9,726.9 ng/mL). The intra-assay, inter-assay and total imprecision were 1.1-1.3 %, 5.5-8.1 % and 5.6-8.2 %, respectively. The 99th percentile URL calculated using residual plasma from 246 ostensibly healthy blood donors was 9.2 ng/L (4.3 ng/L in women vs. 12.3 ng/L in men). The Spearman's correlation between Mindray hs-cTnI and Access hs-TnI was 0.97, with mean bias of 7.2 % (95 % CI, 2.6-11.9 %). Although we failed to confirm the very optimistic analytical characteristics previously reported for this method, our evaluation of the novel Mindray hs-cTnI immunoassay on CL-1200i demonstrated that the overall performance is comparable to that of other commercially available hs-cTnI techniques, making it a viable alternative to other methods.

Can Pre-Ablation Biomarkers Be Used to Predict Arrhythmia Recurrence after Ablation Index-Guided Atrial Fibrillation Ablation?

Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of<0.05. A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value >1.8 μUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional "abnormal" biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p<0.001). Patients with three "abnormal" biomarkers had a threefold higher risk of AF recurrence compared with no "abnormal" biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.

Os Biomarcadores podem ser Utilizados para Prever Recorrência de Arritmia após a Ablação de Fibrilação Atrial Guiada pelo Ablation-Index?

Abstract Background: Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. Objectives: To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. Methods: Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of&lt;0.05. Results: A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value &gt;1.8 μUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional “abnormal” biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p&lt;0.001). Patients with three “abnormal” biomarkers had a threefold higher risk of AF recurrence compared with no “abnormal” biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). Conclusions: When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.

Determination of sex and age specific 99th percentile upper reference limit of high sensitivity cardiac Troponin I in a sample of apparently healthy Iraqi adults

Determination of sex and age specific 99th percentile upper reference limit of high sensitivity cardiac Troponin I in a sample of apparently healthy Iraqi adults

Subclinical cardiovascular remodelling in HIV-infection: A multimodal case study of 2 serodiscordant, monozygotic twins.

Cardiovascular abnormalities are increasingly recognised among people newly diagnosed with HIV, but subclinical pathology may be challenging to diagnose. We present a case study of subtle cardiovascular changes in identical twins, one without HIV-infection and the other recently diagnosed with HIV (serodiscordant). We hypothesise that cardiovascular parameters would be similar between the twins, unless non-genetic (environmental) factors are at play. These differences likely represent occult pathology secondary to the effects of early HIV-infection. A 25-year-old female incidentally diagnosed with HIV, and her HIV-uninfected identical twin, living with her since birth, underwent comprehensive cardiovascular assessments. The HIV-positive twin exhibited a globular left ventricle (LV), larger LV volumes, decreased LV strain, peak atrial longitudinal strain (PALS) and higher native T1 and T2 mapping values compared to her sister. Cardiac biomarkers high sensitivity cardiac troponin T and N-terminal proBNP, as well as the novel markers of fibrosis and remodelling, galectin-3 and soluble-ST2, were higher in the HIV-infected twin. Given the twins' shared environment and genetic makeup, these differences likely stem from HIV-infection. Our study supports previous findings and suggests potential screening markers for HIV-associated cardiovascular disease, including PALS. Further research is warranted to explore PALS' utility in this context.

BIOMARKERS OF CARDIOVASCULAR COMPLICATIONS ASSOCIATED WITH COVID-19 DISEASE

The coronavirus disease (COVID-19), which caused a global pandemic in the world, is now becoming an endemic, seasonal disease. Therefore, the search for new biomarkers to predict the course of the disease and its outcomes remains extremely important. It has been found that COVID-19 affects not only the respiratory system but also other organs and systems of the body. In particular, the target of the SARS-CoV-2 virus is the cardiovascular system. Because the severity of COVID-19 disease is highly variable, laboratory biomarkers can provide important prognostic information already at the emergency stage, especially in patients with atypical manifestations. It has been demonstrated that viral infections, and in particular COVID-19, can cause changes in the host's lipid profile. Changes in the processes of intracellular cholesterol biosynthesis and its transport in the bloodstream of patients with COVID-19 have been reported. Thus, in patients suffering from COVID-19, significantly reduced levels of total іукгь cholesterol (C), HDL, and LDL cholesterol, and an increased ratio of triglycerides/C have been recorded. Patients with COVID-19 are characterized by an increased content of residual (remnant) cholesterol, which is defined as cholesterol present in residual lipoproteins rich in triglycerides and, as shown by the results of genetic, observational, and clinical studies, is associated with the development of atherosclerosis and overall mortality. Several peptide cardiac biomarkers have become other predictors of cardiovascular prognosis in patients with COVID-19: highly sensitive cardiac troponin – successfully used in clinical practice as a marker of myocyte damage for diagnosis and prognostic assessment of acute coronary syndrome; N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of myocardial stretch; peptide ST2 – a marker of remodeling of myocardial extracellular matrix, which prevents fibrosis, cardiac hypertrophy and apoptosis; copeptin is a biomarker of neurohumoral activation. The review provides a concise analysis of currently known cardiac biomarkers in COVID-19 and their prognostic significance.

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

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

Adequate Interval between Matches in Elite Female Soccer Players.

The present study compared four different intervals between three simulated soccer matches for changes in muscle damage and performance parameters. Thirteen well-trained female university soccer players performed three bouts of 90-min Loughborough Intermittent Shuttle Test (LIST) with four different intervals between bouts; one (1d), two (2d), three (3d) and four days (4d), with >12-weeks between conditions in a counterbalanced order. Heart rate, blood lactate, rating of perceived exertion and distance covered in each LIST were measured. Changes in several muscle damage markers (e.g., maximal voluntary isometric torque of the knee extensors: MVC-KE, muscle soreness), performance parameters (e.g., Yo-Yo intermittent recovery test level 1: Yo-Yo IR1), and blood measures (e.g., osmolality, high sensitivity cardiac troponin T) before the first LIST, 1 h after each LIST, and one to five days after the third LIST were compared among the conditions. The total distance covered during the first two LISTs was not different among the conditions, but that during the third LIST was shorter (P < 0.05) for the 1d (9,416 ± 885 m) and 2d conditions (9,737 ± 246 m) than the 3d (10,052 ± 490 m) and 4d conditions (10,432 ± 538 m). Changes in all measures were smaller (P < 0.05) in the 3d and 4d conditions (e.g., the decrease in MVC-KE at one day after the third LIST was -13 ± 4% and -10 ± 3%, respectively) when compared with the 1d and 2d conditions (-20 ± 7%, -18 ± 5%). Performance parameters showed smaller (P < 0.05) changes in the 4d (e.g., the decrease in Yo-Yo IR1 at one day after the third LIST was -9 ± 3%) and 3d (-13 ± 6%) conditions when compared with the 1d (-19 ± 4%) and 2d (-20 ± 8%) conditions. These results suggest that muscle damage and fatigue accumulate when soccer matches are performed three consecutive days or every other day, but if more than three days are inserted between matches, this could be minimized.

Implementation of the European Society of Cardiology 0/3-hour accelerated diagnostic protocol, using high sensitive troponin T: a clinical practice evaluation of safety and effectiveness involving 3003 patients with suspected acute coronary syndrome

BackgroundThere have been relatively few studies detailing the real-world effectiveness and safety of accelerated diagnostic protocols (ADP), using high sensitivity cardiac troponin (hs-cTn).ObjectiveTo analyse the safety and effectiveness of early...

Implementation of a high sensitivity cardiac troponin I assay and risk of myocardial infarction or death at five years: observational analysis of a stepped wedge, cluster randomised controlled trial

ObjectiveTo evaluate the impact of implementing a high sensitivity assay for cardiac troponin I on long term outcomes in patients with suspected acute coronary syndrome.DesignSecondary observational analysis of a stepped...

Introduction of a high sensitivity troponin reduces ED length of stay

BackgroundHigh sensitivity cardiac troponins (hs-cTn) allow earlier identification and exclusion of acute myocardial infarction. We determined if transitioning from contemporary to high sensitivity troponin T (hs-cTnT) would reduce ED length of stay in chest pain (CP) patients. MethodsWe conducted a pragmatic, prospective, before and after study of implementing a hs-cTnT by reviewing the electronic health records in all adult ED patients presenting to a large, suburban academic medical center during the 3 months before and after transitioning from a 4th generation troponin to a 5th generation hs-cTnT (Elecsys® Troponin T-high sensitive, Roche Diagnostics, Indianapolis, IN). ResultsThere were 1431 and 1437 CP patients before and after the intervention. Mean (SD) age was 51.5 (18) yrs. and 54.3% were female. The median (IQR) ED LOS for chest pain patients directly discharged to home was 6.2 (4.7–8.4) and 5.3 (4.0–7.2) hours before and after introducing hs-cTn respectively; difference 47 min (95%CI, 35–59); P < 0.001. The median (IQR) ED LOS for chest pain patients admitted to the hospital was 9.5 (6.6–13.8) and 8.1 (5.7–11.2) hours before and after introducing hs-cTn respectively; difference 77 min (95%CI, 35–121); P < 0.001. Overall admission rates (22 vs 21% both before and after) did not change during the study. The rates of computed tomography coronary angiography before and after the intervention were 21 and 20.4% respectively. The rates of invasive coronary angiography before and after the intervention were 5.8 and 5.6% respectively. ConclusionsTransitioning to a hs-cTnT is associated with a clinically relevant and statistically significant reduction in ED LOS for both discharged and admitted patients with and without CP with no increase in admission or coronary angiography rates.

Prevalence and outcome of clinical misdiagnosis of non-ST-elevation myocardial infarction

Abstract Background The prevalence of clinical misdiagnosis of non-ST-elevation myocardial infarction (NSTEMI) and its impact on patient outcomes is largely unknown. Methods We prospectively enrolled adult patients presenting with suspected acute coronary syndromes at 12 sites in five European countries. All patients provided written informed consent and were managed as per local clinical care using conventional, sensitive or high-sensitivity cardiac troponin (hs-cTn) assays. Study blood samples were taken at presentation and serially thereafter for measurements of hs-cTn concentrations. Final diagnoses were adjudicated by two independent cardiologists according to current guidelines and the 4th universal definition of myocardial infarction using all information including serial hs-cTnT measurements and imaging. The primary diagnostic endpoint was the prevalence of clinical NSTEMI misdiagnosis. Co-primary prognostic endpoints were 30 day and two year all-cause and cardiovascular (CV) death. Results In 7,678 patients (median age 61 [IQR 48-73], 34% women), the prevalence of adjudicated and clinical NSTEMI was 17.8% and 12.3%, respectively (P&amp;lt;0.001). Among 1,363 patients with an adjudicated NSTEMI (77% type 1 MI, 23% type 2 MI), 470/1,363 (34%) had a clinical NSTEMI misdiagnosis. These patients were older, more often female, had lower median cTn concentrations, and were more likely managed at centers using non-hs-cTn assays at time of enrolment. Compared to patients with an adjudicated and clinical NSTEMI diagnosis, missed patients were less likely to undergo coronary angiography or revascularization and less often discharged on evidence-based treatment (dual antiplatelet therapy 24% vs 79%, statin 64% vs 92%, betablocker 68% vs 81%, all P&amp;lt;0.001). Finally, patients with a clinical NSTEMI misdiagnosis were at much higher risk of premature all-cause (HR 1.51, 95% CI 1.18-1.94, P&amp;lt;0.001) and CV (HR 1.93, 95%CI 1.42-2.63, P&amp;lt;0.001) death. Conclusion One out of three adjudicated NSTEMI patients was misdiagnosed in routine clinical care. Clinical NSTEMI misdiagnosis was associated with lower use of guideline-recommended therapies and a substantial increase in premature death.Alluvial plotAll-cause death at 2-years

Predictive Value of high-sensitivity cardiac troponin T in patients undergoing 99mTc pyrophosphate scintigraphy for suspected transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (1,2). 99mTc- pyrophosphate cardiac scintigraphy (PYP) enables accurate, noninvasive diagnosis of ATTR-CM when coupled with appropriate clinical and laboratory evaluations to rule out light chain amyloidosis (3,4). High sensitivity cardiac troponin T (hs-cTnT) is routinely assessed for diagnostic purposes when ATTR-CM is suspected in clinical practice. Purpose To investigate the diagnostic performance of hs-cTnT in patients undergoing PYP for suspected ATTR-CM. Methods Observational study of patients undergoing PYP at a United States (US) cardiac amyloidosis referral center from 2013 to September 2022 and with at least one hs-cTnT value available within 1 year. 3-hour planar imaging followed by single photon-emission computed tomography with computed tomography was performed. Final diagnoses of ATTR-CM were validated using all clinical information. The lowest reportable clinical value for hs-cTnT in the US is &amp;lt;6 ng/L (limit of quantitation). Results A total of 1572 patients underwent PYP and had a hs-cTnT value available within the study period. Of these, ATTR-CM was diagnosed in 475 patients (30%). Median (IQR) hs-cTnT was 48 (31-67) ng/L in patients with ATTR-CM and 26 (13-48) ng/L in those without. The area under the curve of hs-cTnT for the diagnosis of ATTR-CM was 0.69 (0.67-0.72). Among patients with a very low hs-cTnT value, i.e. &amp;lt;6 ng/L (n=100, 6.4% of the overall cohort), 7 (7%) patients had a final ATTR-CM diagnosis while 93 (93%) did not. Therefore, a threshold of &amp;lt;6 ng/L demonstrated a negative predictive value (NPV) of 93% (IQR 88, 98) and a sensitivity of 99% (97, 100) for ruling out ATTR-CM. The highest NPV was achieved with a threshold of 12 ng/L; 269 (17%) patients had hs-cTnT below this value and, of those, only 16 (6%) had a final diagnosis of ATTR-CM. This resulted in a NPV of 94% (91, 97) and a sensitivity of 97% (95, 98) for ruling out ATTR-CM. When considering progressively increasing hs-cTnT values as potential thresholds to aid in the prediction of ATTR-CM (Figure), we observed a progressive increase in specificity (above 90% for hs-cTnT values &amp;gt; 95 ng/L), but the positive predictive value (PPV) remained low (below 50%). Conclusions Among patients undergoing PYP for suspected ATTR-CM at a US referral center, a very low hs-cTnT value was present in a minority of patients but demonstrated good performance in ruling out ATTR-CM. The highest NPV (94%) was achieved with a threshold of &amp;lt; 12 ng/L. Higher hs-cTnT values showed a good specificity, but PPV remained low. Therefore, while a very low hs-cTnT might be of help in identifying those at low risk of ATTR-CM, the ubiquitous presence of increased hs-cTnT in many of these patients suggests the need for a multiparametric diagnostic approach to make the diagnosis.hs-cTnT in patients undergoing PYP scan

The incremental value of non-necrosis biomarkers to risk stratification in acute chest pain, with MI excluded: the first prospective long term cohort study in the high sensitive troponin era

Abstract Background Approximately 90% of patients presenting to ED (Emergency Department) with suspected Acute Coronary Syndrome (ACS) have Myocardial Infarction (MI) excluded. Long term outcome and risk stratification for this cohort has rarely been studied. Purpose To study long term cardiovascular outcomes in patients with acute Chest Pain (CP) in whom MI is excluded, and to investigate the incremental value of biomarkers of inflammation, myocardial ischaemia and stress, for risk stratification, to that of existing methods of stratifying risk including absolute values of two high sensitive troponins below the 99th percentile. Methods A prospective observational study in a large university teaching hospital with a median follow-up of 5.8-year. Cardiovascular outcomes studied included adjudicated type 1 MI (to 4th universal definition), unstable angina requiring urgent revascularisation and cardiovascular death. Inclusion criteria included CP with features of ischaemia but with MI excluded (High sensitive cardiac troponin [hs-cTn] T ≤99th percentile). Exclusion criteria included non-cardiac chest pain, chronic atrial fibrillation, heart failure and recent ACS. The biomarkers HFABP, GDF-15, NT-proBNP, Galectin-3, HS-CRP taken on first venepuncture for high sensitive cardiac troponins were investigated using univariable and multivariable backward stepwise elimination logistic modelling, receiver operator characteristic (ROC) analysis, and Net Reclassification Indices (NRI). They were compared to absolute values of both sub-99th percentile hs-cTnT (Roche Elecsys) and hs-cTnI (Abbot Architect) both as a single entity or when the troponin values were incorporated with HEART and TIMI scores. Results 487 consented patients were enrolled. The mean age of the population was 56 years (SD 11.8), 44% were female, 16.2% were diabetic, 20.9% had a previous MI, 13.8% previous PCI and 5.1% coronary artery bypass grafting. 100% follow-up was achieved. There were 48 events in follow-up. (event rate 9.9%). Multivariable Cox Proportional Hazards analysis including hs-cTnT or hs-cTnI (below 99th percentile) demonstrated incremental improvement in risk stratification with absolute values of either hs-cTn below the 99th percentile when added to either TIMI or HEART risk score. The results were consistent with NRI analysis. Only GDF-15 demonstrated significance in multivariable analysis when analysed with the HEART score regardless of troponin assay and the TIMI score with HS-cTnI but not with HS-cTnT. Conclusion Absolute values of hs-cTnT or I, below 99th percentiles, significantly improve risk modelling for cardiovascular outcomes in acute CP patients, presenting to ED, who have MI excluded. No other biomarker retains independent risk with the exception of GDF-15. Effective dichotomisation of sub99th percentile hstnT or I, used alone or incorporated into risk scores, could allow improved targeting of resources for investigation and management for this large pool of patients.

Growth differentiation factor-15 is associated with myocardial infarction and death at 30 and 90 days in ED patients with suspected acute coronary syndrome

Abstract Background Growth differentiation factor (GDF)-15 is a novel biomarker of cardiac stress that may be an accurate predictor of mortality and acute myocardial infarction (AMI) in patients with acute chest pain. However, data from US populations are lacking. Purpose Our objective was to determine whether GDF-15 is an independent predictor of index, 30-day, and 90-day day AMI and death in a U.S cohort of ED patients with possible acute coronary syndrome. Methods This study was a secondary analysis of the STOP-CP (High Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification) trial, which prospectively enrolled adults (≥ 21 years) presenting to eight emergency departments in the US with suspected AMI (1/25/2017-9/6/2018). Blood sampling was performed at baseline and 3 hours later, and hs-TnT, NT-pro-BNP, and GDF-15 assays were performed at a central laboratory. The primary outcome was the composite of AMI and all-cause death at index visit, 30 days, and 90 days and secondary outcomes were AMI and death separately. Multivariable logistic regression models were fitted for the outcomes at each timepoint with the following independent variables: age, sex, number of cardiac risk factors, ECG findings, hs-TnT, and NT-pro-BNP. Odds ratios (ORs) are reported per 100 ng/L increase in GDF-15 levels. Results In 1,428 patients the median age was 58 (IQR: 49, 66) years and 25% (353/1,428) had a history of coronary artery disease. The median GDF-15 level was 1,233 pg/mL (IQR: 754, 2206) at baseline and 1,363 pg/mL (IQR: 851, 2434) at 3 hours. The composite outcome of AMI or death occurred in 12% (169) at index visit, an additional 2% (34) at 30 days, and an additional 3% (37) at 90 days. In multivariable regression models, GDF-15 was independently associated with the composite outcome of AMI or death at 30 days (OR ng/L 1.01, 95% CI 1.00-1.02) and 90 days (OR 1.01, 95% CI 1.01-1.02), but not during the index visit (OR 1.00, 95% CI 1.00-1.00). It was also associated with both AMI (OR 1.01, 95% CI 1.00-1.02) and death (OR 1.01, 95% CI 1.01-1.02) separately at 90 days, but was only associated with death (OR 1.01, 95% CI 1.01-1.02) at 30 days. Conclusion Among adult ED patients with suspected AMI, GDF-15 was independently associated with subsequent 30-day and 90-day AMI or death. These data suggest a potential role for GDF-15 in risk stratifying ED patients with regard to future cardiac events.

High sensitivity cardiac troponin I in response to handgrip in women with signs and symptoms of ischemia with no obstructive coronary arteries

Abstract Background Women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) are suspected to have myocardial ischemia, ∼10% have prior myocardial scar often in the absence of acute myocardial infarction (AMI) diagnosis and the development of heart failure with preserved ejection fraction (HFpEF) is relatively frequent. The mechanisms contributing to AMI and HFpEF progression are poorly understood in INOCA. Purpose To compare clinical, invasive, and high sensitivity cardiac troponin I (hsTnI) parameters in women with INOCA at rest and in response to isometric handgrip exercise. Methods Women with suspected INOCA underwent cannulation of the coronary sinus (CS), handgrip exercise testing and serial CS plasma sampling before, after 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction, and after 5 minutes of recovery. hsTnI was measured using a commercial immunoassay (R-PLEX, Meso Scale Discovery, Rockville, MD) and compared using t-tests. Results A total of 54 women with complete invasive data were included with a mean age of 53 ± 10 years, mean body mass index 28 ± 7 kg/m2. 20 women (37% of the cohort) had detectable CS hsTnI from baseline. Among these women, median values were elevated in response to handgrip (Figure) (baseline median 33.75 (IQR 18.12-67.75) pg/mL vs peak handgrip median 56.23 (IQR 32.84-97.83) pg/mL, signed rank p=0.0007, baseline vs recovery median 52.35 (IQR 32.59-106.27) pg/mL, signed rank p=0.0002). Conclusion Among women with INOCA, handgrip stress leads to an increase in hsTnI in more than a third, demonstrating objective evidence of myocardial injury. More work is needed to better understand contribution of coronary microvascular dysfunction to HFpEF progression.

Prognostic value and determinants of high sensitive cardiac Troponin levels in patients with a systemic right ventricle: insights from the SERVE-Trial

Abstract Background The prognostic value of high-sensitivity cardiac Troponin T (hs-cTnT) in patients with a systemic left ventricle is well-established. However, the determinants and prognostic value of hs-cTnT among patients with a systemic right ventricle (sRV) are largely unknown. Purpose We aimed to assessed the determinants and prognostic value of hs-cTnT among patients with sRV. Methods Ninety-eight patients from the randomized-controlled SERVE-trial were included. The correlation between baseline hs-cTnT concentrations and bi-ventricular volumes and function quantified by cardiac magnetic resonance was assessed by adjusted linear regression models. The prognostic value of hs-cTnT and other established prognostic markers were assessed by adjusted cox proportional hazards models, survival analysis and c-statistics. The primary outcome was the composite of clinically relevant arrhythmia, hospitalization for heart failure or all-cause death. Results Median age [interquartile range, IQR] was 39 [32, 48] years and 32% were female. Median hs-cTnT concentration was 7 [IQR, 4-11] ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index, (RVESVi) and ejection fraction (RVEF) were +0.368, p=0.046; and -0.381, p=0.018, respectively. The sex and aged adjusted hazard ratio [95%, confidence interval, CI] of hs-cTnT at 2- and 4-times the reference level (5 ng/l) for the primary outcome were 2.89 [1.14-7.29] and 4.42 [1.21-16.15], respectively (Figure 1). Patients with hs-cTnT concentrations ≤7 ng/L (median) had better event-free survival (89% vs. 67%, p=0.004). The prognostic performance quantified by the C-statistics [95%, CI] for age and sex adjusted models based on hs-cTnT, RVEF, and peak VO2 predicted (%) were comparable: 0.71 [0.61-0.82], 0.72 [0.59-0.84], and 0.71 [0.59-0.83], respectively (Figure 2). Conclusion Hs-cTnT concentration was significantly correlated with RVEF and RVESVi in patients with a sRV. The prognostic accuracy of this biomarker was comparable to that of the current gold standards (RVEF and peak VO2 predicted).Figure 1Figure 2

Does a high baseline high sensitivity cardiac troponin T allow for the early diagnosis of acute myocardial infarction?

Abstract Background Guidelines suggest that the diagnosis of acute myocardial infarction (MI) is likely when high concentrations of high-sensitivity cardiac troponin (hs-cTn) are present in the initial sample. These concentration thresholds are much higher than the 99th percentile and are said to provide a high positive predictive value (PPV) for acute MI1. Purpose Evaluate the PPV of recommended baseline hs-cTnT thresholds (&amp;gt;52 and &amp;gt;100 ng/L) for the diagnosis of acute MI from our multi-center United States (US) experience. Methods Retrospective, multicenter (n=22), observational biomarker study involving consecutive, adult patients presenting to the emergency department (ED) in whom at least 1 hs-cTnT measurement was obtained within 12 hours of presentation (CV DataMart Biomarker cohort). The primary endpoint was also evaluated in an adjudicated cohort of consecutive patients presenting to the ED with at least 1 hs-cTnT &amp;gt;99th percentile (ACTION cohort). These cases were adjudicated based on the Fourth Universal Definition of MI by trained physicians. The primary efficacy endpoint was the PPV of acute MI (type 1 or 2), type 1 MI and type 2 MI during index hospitalization using baseline hs-cTnT thresholds of &amp;gt;52 ng/L and &amp;gt;100 ng/L. Results The CV DataMart Biomarker cohort consisted of 143,709 patients, amongst whom 3,003 (2.1%) were diagnosed with acute MI using ICD codes. In the CV DataMart Biomarker cohort, baseline hs-cTnT concentrations of &amp;gt;52 ng/L and &amp;gt;100 ng/L resulted in PPVs of 12% (95% CI: 11, 12) and 17% (95% CI: 17, 19) for acute MI, respectively. In patients with chest pain and baseline hs-cTnT concentrations &amp;gt;52 ng/L, PPV for acute MI was 17% (95% CI: 15, 18), and in those with hs-cTnT concentrations &amp;gt;100 ng/L, PPV was 22% (95% CI: 19, 25). The adjudicated ACTION cohort consisted of 2,107 patients, amongst whom 155 (7.4%) were diagnosed with acute MI including 64 (41%) with type 1 MI and 91 (59%) with type 2 MI. In the ACTION cohort, baseline hs-cTnT concentrations of &amp;gt;52 ng/L and &amp;gt;100 ng/L resulted in PPVs of 46% (95% CI: 40, 53) and 62% (95% CI: 53, 70) for acute MI, respectively. In patients with chest pain and baseline hs-cTnT concentrations &amp;gt;52 ng/L, PPV was 67% (95% CI: 57, 76) for acute MI, 52% (95% CI: 41, 62) for type 1 MI and 15% (95% CI: 8.4, 24) for type 2 MI. In those with chest pain and baseline hs-cTnT concentrations &amp;gt;100 ng/L, PPV was 77% (95% CI: 65, 87) for acute MI, 64% (95% CI: 51, 75) for type 1 MI and 14% (95% CI 6.4, 24) for type 2 MI (Figure). Conclusion Using previously recommended high-risk hs-cTnT thresholds of 52 and 100 ng/L in US patients provides reasonable performance to rule-in acute MI when used in patients with chest pain. When used more broadly across all-comers, the diagnostic performance is poor.