Can Pre-Ablation Biomarkers Be Used to Predict Arrhythmia Recurrence after Ablation Index-Guided Atrial Fibrillation Ablation? / Os Biomarcadores podem ser Utilizados para Prever Recorrência de Arritmia após a Ablação de Fibrilação Atrial Guiada pelo Ablation-Index?

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<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 >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). 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.

FUNDAMENTO: O software ablation index (AI) permitiu melhorar os resultados da ablação de fibrilação atrial (FA), mas as taxas de recorrência permanecem significativas. Biomarcadores séricos específicos têm sido associados a essa recorrência. OBJETIVOS: Avaliar se certos biomarcadores podem ser utilizados (individualmente ou combinados) para predizer a recorrência de FA pós ablação guiada pelo AI. MÉTODOS: Estudo multicêntrico, observacional, prospectivo de pacientes consecutivos, encaminhados para ablação de FA de janeiro de 2018 a março de 2021. Hemoglobina, peptídeo natriurético cerebral (BNP), proteína C reativa, troponina I ultrassensível, clearance de creatinina, Hormônio Tireoestimulante (TSH), e Tiroxina livre (T4) foram avaliados quanto à capacidade de prever a recorrência de arritmias durante o acompanhamento. Valores de p <0,05 foram aceitos como estatisticamente significativos. RESULTADOS: Um total de 593 pacientes foram incluídos ­ 412 com FA paroxística e 181 com FA persistente. Durante o seguimento médio de 24±6 meses, 76,4% não apresentaram recidiva após ablação. Individualmente, os biomarcadores demonstraram um valor preditivo baixo ou nulo para recorrência. No entanto, TSH >1,8 µUI/mL [HR=1,82 (IC95%, 1,89-2,80), p=0,006] foi um preditor independente de recorrência. Avaliando-se a combinação de TSH, FT4 e BNP, a adição de cada valor "anormal" foi associada a uma menor sobrevida livre de recorrência (87,1% se nenhum vs. 83,5% se um vs. 75,1% se dois vs. 43,3% se três biomarcadores, p<0,001). Doentes com três biomarcadores "anormais" apresentaram três vezes maior probabilidade de recorrência de FA, comparativamente aos que não apresentaram nenhum biomarcador "anormal" (HR=2,88 [IC95%, 1,39-5,17], p=0,003). CONCLUSÕES: Quando combinados, valores anormais de TSH, FT4 e BNP podem ser uma ferramenta útil para prever a recorrência de FA pós ablação guiada pelo AI.

Pediatric Neurogenic Pulmonary Edema After Brain Tumor Removal Complicated with Severe Myocardial Injury: A Case Report.

BACKGROUND Neurogenic pulmonary edema (NPE) is a rare complication of neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation. A high serum natriuretic (BNP) level was prolonged even after the LV contraction was improved in this case with severe myocardial injury. The overloading stress to the LV wall can last several days over the acute phase of NPE. CASE REPORT A 6-year-old boy developed NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. Simultaneously, he experienced LV dysfunction involving reduced global contraction with severe myocardial injury diagnosed by abnormally elevated cardiac troponin I level (1611.6 pg/ml) combined with a high serum BNP level (2106 pg/ml). He received mechanical ventilation for 4 days until the improvement of his pulmonary edema in the Intensive Care Unit (ICU). On the next day, after the withdrawal of mechanical ventilation, he was discharged from the ICU to the pediatric unit. Although the LV contraction was restored to an almost normal range in the early period, it took a total of 16 days for the serum BNP level to reach an approximate standard range (36.9 pg/ml). CONCLUSIONS Even in a pediatric patient with NPE, we recommend careful monitoring of the variation of cardiac biomarkers such as BNP until confirmation of return to an approximate normal value because of the possible sustained overloading stress to the LV wall.

Infliximab Limits Injury in Myocardial Infarction.

BACKGROUND: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. METHODS AND RESULTS: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P<0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P<0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05). CONCLUSIONS: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.

Systolic Blood Pressure, Diastolic Blood Pressure and Pulse Pressure and the Risk of Subclinical Myocardial Injury: The HUNT Study.

BACKGROUND: Subclinical myocardial injury expressed as higher cardiac troponin concentrations may represent an important intermediary between hypertension and the risk of cardiovascular disease. The study aimed to assess the relative strength of associations between systolic blood pressure (BP), diastolic BP, and pulse pressure, and subclinical myocardial injury, and how change in BP variables over time associates with subclinical myocardial injury. METHODS AND RESULTS: cTnl (cardiac troponin I) was measured in 32 968 participants of the fourth wave of the population-based cohort HUNT4 (Trøndelag Health Study) without a history of cardiovascular disease. An additional longitudinal analysis included participants from HUNT4 with BP measurements from HUNT3 (n=18 681). Associations between BP variables and cTnI concentrations were assessed by linear and logistic regression analyses. The median cTnI concentration was 1.6 ng/L (25th-75th percentiles, 0.6-3.1 ng/L), median age was 52 years (39.1-65.6 years), and 57% were female subjects. Cross-sectionally, only systolic BP categories ≥130 mm Hg associated with higher cTnI concentrations, compared with a reference systolic BP of <110 mm Hg. All categories of diastolic BP and pulse pressure were positively associated with higher cTnI concentrations when diastolic BP 70 to 79 mm Hg and pulse pressure <40 mm Hg were used as references, respectively. When comparing systolic BP, diastolic BP, and pulse pressure as continuous variables, cross-sectionally, pulse pressure most strongly associated with cTnI concentrations (P for all comparisons <0.001), whereas longitudinally, change in diastolic BP was most strongly associated with cTnI concentrations (P for all comparisons <0.05). CONCLUSIONS: Subjects with high pulse pressure and longitudinal increase in diastolic BP are at higher risk for subclinical myocardial injury.

Dexmedetomidine Pretreatment Confers Myocardial Protection and Reduces Mechanical Ventilation Duration for Patients Undergoing Cardiac Valve Replacement under Cardiopulmonary Bypass.

PURPOSE: The study aims to assess the effects of dexmedetomidine (Dex) pretreatment on patients during cardiac valve replacement under cardiopulmonary bypass. METHODS: For patients in the Dex group (n = 52), 0.5 µg/kg Dex was given before anesthesia induction, followed by 0.5 µg/kg/h pumping injection before aortic occlusion. For patients in the control group (n = 52), 0.125 ml/kg normal saline was given instead of Dex. RESULTS: The patients in the Dex group had longer time to first dose of rescue propofol than the control group (P = 0.003). The Dex group required less total dosage of propofol than the control group (P = 0.0001). The levels of cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) were lower in the Dex group than the control group at T4, 8 h after the operation (T5), and 24 h after the operation (T6) (P <0.01). The Dex group required less time for mechanical ventilation than the control group (P = 0.003). CONCLUSION: The study suggests that 0.50 µg/kg Dex pretreatment could reduce propofol use and the duration of mechanical ventilation, and confer myocardial protection without increased adverse events during cardiac valve replacement.

Automatic ultrasensitive lateral flow immunoassay based on a color-enhanced signal amplification strategy.

Lateral flow immunoassays (LFIAs) are an essential and widely used point-of-care test for medical diagnoses. However, commercial LFIAs still have low sensitivity and specificity. Therefore, we developed an automatic ultrasensitive dual-color enhanced LFIA (DCE-LFIA) by applying an enzyme-induced tyramide signal amplification method to a double-antibody sandwich LFIA for antigen detection. The DCE-LFIA first specifically captured horseradish peroxidase (HRP)-labeled colored microspheres at the Test line, and then deposited a large amount of tyramide-modified signals under the catalytic action of HRP to achieve the color superposition. A limit of detection (LOD) of 3.9 pg/mL and a naked-eye cut-off limit of 7.8 pg/mL were achieved for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein. Additionally, in the inactivated virus detections, LOD equivalent to chemiluminescence (0.018 TCID50/mL) was obtained, and it had excellent specificity under the interference of other respiratory viruses. High sensitivity has also been achieved for detection of influenza A, influenza B, cardiac troponin I, and human chorionic gonadotrophin using this DCE-LFIA, suggesting the assay is universally applicable. To ensure the convenience and stability in practical applications, we created an automatic device. It provides a new practical option for point-of-care test immunoassays, especially ultra trace detection and at-home testing.

Implications of High Sensitivity Troponin Levels After Lung Transplantation.

Trends in high-sensitivity cardiac troponin I (hs-cTnI) after lung transplant (LT) and its clinical value are not well stablished. This study aimed to determine kinetics of hs-cTnI after LT, factors impacting hs-cTnI and clinical outcomes. LT recipients from 2015 to 2017 at Toronto General Hospital were included. Hs-cTnI levels were collected at 0-24 h, 24-48 h and 48-72 h after LT. The primary outcome was invasive mechanical ventilation (IMV) >3 days. 206 patients received a LT (median age 58, 35.4% women; 79.6% double LT). All patients but one fulfilled the criteria for postoperative myocardial infarction (median peak hs-cTnI = 4,820 ng/mL). Peak hs-cTnI correlated with right ventricular dysfunction, >1 red blood cell transfusions, bilateral LT, use of EVLP, kidney function at admission and time on CPB or VA-ECMO. IMV>3 days occurred in 91 (44.2%) patients, and peak hs-cTnI was higher in these patients (3,823 vs. 6,429 ng/mL, p < 0.001 after adjustment). Peak hs-cTnI was higher among patients with had atrial arrhythmias or died during admission. No patients underwent revascularization. In summary, peak hs-TnI is determined by recipient comorbidities and perioperative factors, and not by coronary artery disease. Hs-cTnI captures patients at higher risk for prolonged IMV, atrial arrhythmias and in-hospital death.

Risk stratification and prognosis prediction using cardiac biomarkers in COVID-19: a single-centre retrospective cohort study.

OBJECTIVE: There is a need for a robust tool to stratify the patient's risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. METHODS: This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. RESULTS: A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI: <5.0 ng/L group; 4.3%, 5.0 ng/L-99%ile upper reference limit (URL) group; 8.8% and ≥99% ile URL group; 25.2%, p<0.001. NT-proBNP: <125 pg/mL group; 5.3%, 125-900 pg/mL group; 10.5% and ≥900 pg/mL group; 31.9%, p<0.001. CK:

Implementation of high sensitivity troponin into routine clinical practice - results of the extended CARdiac MArkers guideline uptake in Europe group (CARMAGUE) survey.

BACKGROUND: Measurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented. METHODS: A questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis. RESULTS: Responses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours. CONCLUSIONS: Measurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind.

Surface plasmon resonance biosensors for early troponin detection.

Acute myocardial infarction (AMI) is one of the life-threatening causes that decrease blood flow to the heart, leading to increased mortality and related complications. Recently, the measure of blood concentration of cardiac biomarkers has been suggested to overcome the limitations of electrocardiography (ECG) analyses for early diagnosis of this disease. Troponins, especially cardiac troponin I and cardiac troponin T, with high sensitivity and specificity, are considered the gold standards in myocardial diagnosis. Recently, the use of new biosensors such as surface plasmon resonance (SPR) for early detection of these biomarkers has been greatly appreciated. Due to the rapid, sensitive, real-time, and label-free detection of SPR-based biosensors, they can be applied for selective and nonspecific absorption that is intended to be used as an in situ cardiac biosensor. Here, we exclusively discussed the updated developments of these valuable predictors for the possible occurrence of AMI detected by SPR.

Quantitative measurement of acute myocardial infarction cardiac biomarkers by "All-in-One" immune microfluidic chip for early diagnosis of myocardial infarction.

Acute myocardial infarction (AMI) is a life-threatening condition with a narrow treatment window, necessitating rapid and accurate diagnostic methods. We present an "all-in-one" convenient and rapid immunoassay system that combines microfluidic technology with a colloidal gold immunoassay. A degassing-driven chip replaces a bulky external pump, resulting in a user-friendly and easy-to-operate immunoassay system. The chip comprises four units: an inlet reservoir, an immunoreaction channel, a waste pool, and an immunocomplex collection chamber, allowing single-channel flow for rapid and accurate AMI biomarker detection. In this study, we focused on cardiac troponin I (cTnI). With a minimal sample of just 4 µL and a total detection time of under 3 min, the chip enabled a quantitative visual analysis of cTnI concentration within a range of 0.5 âˆ¼ 60.0 ng mL-1. This all-in-one integrated microfluidic chip with colloidal gold immunoassay offers a promising solution for rapid AMI diagnosis. The system's portability, small sample requirement, and quantitative visual detection capabilities make it a valuable tool for AMI diagnostics.

Visual and quantitative lateral flow immunoassay based on Au@PS SERS tags for multiplex cardiac biomarkers.

Rapid and sensitive detection of multiple biomarkers by lateral flow immunoassay (LFIA) remains challenging for signal amplification for commonly used nanotags. Herein, we report a novel LFIA strip for visual and highly sensitive analysis of two cardiac biomarkers based on functionalized gold nanoparticles @ polystyrene microsphere (Au@PS）microcavity as surface-enhanced Raman scattering (SERS) tags. Antibody-modified Au@PS was designed as a SERS label. The evanescent waves propagating along the surface of the PS microcavity and the localized surface plasmons of the gold nanoparticles were coupled to enhance the light-matter interaction synergistically for Raman signal enhancement. In this strategy, the proposed Au@PS SERS tags-based LFIA was carried out to quantify the content of the heart failure and infarct biomarkers synchronously within 15 min and get the limits of detection of 1 pg/mL and 10 pg/mL for cardiac troponin I (cTnI) and N-terminal natriuretic peptide precursor (NT-proBNP), respectively. The results demonstrated 10-20 folds more sensitivity than that of the standard colloidal gold strip and fluorescent strip for the same biomarkers. This novel quantitative LFIA shows promise as a high-sensitive and visual sensing method for relevant clinical and forensic analysis.

l-Cysteine-Tuned the Hierarchical Structure Based on Benzimidazole: Synthesis, Characterization, and Application in Ratiometric Electrochemiluminescence Immunoassay.

Efficient and robust electrochemiluminescence (ECL) emitters are crucial for enhancing the ECL immunosensor sensitivity. This study introduces a novel ECL emitter, CoBIM/Cys, featuring a hierarchical core-shell structure. The core of the structure is created through the swift coordination between the sulfhydryl and carboxyl groups of l-cysteine (l-Cys) and cobalt ions (Co2+), while the shell is constructed by sequentially coordinating benzimidazole (BIM) with Co2+. This design yields a greater specific surface area and a more intricate porous structure compared to CoBIM, markedly enhancing mass transfer and luminophore accessibility. Moreover, the l-Cys and Co2+ core introduces Co-S and Co-O catalytic sites, which improve the catalytic decomposition of H2O2, leading to an increased production of hydroperoxyl radicals (OOH•). This mechanism substantially amplifies the ECL performance. Leveraging the competitive interaction between isoluminol and BIM for OOH• during ECL emission, we developed a ratiometric immunosensor for cardiac troponin I (cTnI) detection. This immunosensor demonstrates a remarkably broad detection range (1 pg mL-1 to 10 ng mL-1), a low detection limit (0.4 pg mL-1), and exceptional reproducibility and specificity.

Uniform or Sex-Specific Cardiac Troponin Thresholds to Rule Out Myocardial Infarction at Presentation.

BACKGROUND: Myocardial infarction can be ruled out in patients with a single cardiac troponin measurement. Whether use of a uniform rule-out threshold has resulted in sex differences in care remains unclear. OBJECTIVES: The purpose of this study was to evaluate implementation of a uniform rule-out threshold in females and males with possible myocardial infarction, and to derive and validate sex-specific thresholds. METHODS: The implementation of a uniform rule-out threshold (<5 ng/L) with a high-sensitivity cardiac troponin I assay was evaluated in consecutive patients presenting with possible myocardial infarction. The proportion of low-risk patients discharged from the emergency department and incidence of myocardial infarction or cardiac death at 30 days were determined. Sex-specific thresholds were derived and validated, and proportion of female and male patients were stratified as low-risk compared with uniform threshold. RESULTS: In 16,792 patients (age 58 ± 17 years; 46% female) care was guided using a uniform threshold. This identified more female than male patients as low risk (73% vs 62%), but a similar proportion of low-risk patients were discharged from the emergency department (81% for both) with fewer than 5 (<0.1%) patients having a subsequent myocardial infarction or cardiac death at 30 days. Compared with a uniform threshold of <5 ng/L, use of sex-specific thresholds would increase the proportion of female (61.8% vs 65.9%) and reduce the proportion of male (54.8% vs 47.8%) patients identified as low risk. CONCLUSIONS: Implementation of a uniform rule-out threshold for myocardial infarction was safe and effective in both sexes. Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited.

Derivation and Validation of Thresholds Using Synthetic Data Methods for Single-Test Screening of Emergency Department Patients with Possible Acute Myocardial Infarction Using a Point-of-Care Troponin Assay.

BACKGROUND: Single-sample (screening) rule-out of acute myocardial infarction (AMI) with troponin requires derivation of a single-test screening threshold. In data sets with small event numbers, the lowest one or two concentrations of myocardial infarction (MI) patients dictate the threshold. This is not optimal. We aimed to demonstrate a process incorporating both real and synthetic data for deriving such thresholds using a novel pre-production high-precision point-of-care assay. METHODS: cTnI concentrations were measured from thawed plasma using the Troponin I Next (TnI-Nx) assay (i-STAT; Abbott) in adults on arrival to the emergency department with symptoms suggestive of AMI. The primary outcome was an AMI or cardiac death within 30 days. We used internal-external validation with synthetic data production based on clinical and demographic data, plus the measured TnI-Nx concentration, to derive and validate decision thresholds for TnI-Nx. The target low-risk threshold was a sensitivity of 99% and a high-risk threshold specificity of >95%. RESULTS: In total, 1356 patients were included, of whom 191 (14.1%) had the primary outcome. A total of 500 synthetic data sets were constructed. The mean low-risk threshold was determined to be 5 ng/L. This categorized 38% (95% CI, 6%-68%) to low-risk with a sensitivity of 99.0% (95% CI, 98.6%-99.5%) and a negative predictive value of 99.4% (95% CI, 97.6%-99.8%). A similarly derived high-risk threshold of 25 ng/L had a specificity of 95.0% (95% CI, 94.8%-95.1%) and a positive predictive value of 74.8% (95% CI, 71.5%-78.0%). CONCLUSIONS: With the TnI-Nx assay, we successfully demonstrated an approach using synthetic data generation to derive low-risk thresholds for safe and effective screening.

Whole Blood Cardiac Troponin "Triaging" to Improve Early Detection of Myocardial Injury at a Pediatric Hospital.

BACKGROUND: The importance of offering on-site cardiac troponin (cTn) testing at pediatric hospitals may be underappreciated. We developed a rapid rule-in process for myocardial injury at a pediatric hospital experiencing delays in off-site high-sensitivity cardiac troponin T (hs-cTnT) testing. METHODS: Collect-to-verify turnaround times (TATs) for off-site testing were reviewed. Pre-analytic changes to improve TATs were devised, implemented and evaluated, after which a new analyzer was selected and evaluated for on-site cTn testing. Performance of the new analyzer's assay was compared to the off-site hs-cTnT assay, and post go-live TATs for on-site testing were assessed. RESULTS: Median collect-to-verify TAT for short turnaround-time (STAT) priority off-site plasma hs-cTnT testing was 104 min, with 35% of orders having a TAT >120 min. Eliminating serum separator tubes and requiring a separate plasma separator tube did not significantly reduce TATs. A QuidelOrtho Triage® MeterPro whole blood cardiac troponin I (cTnI) assay was implemented to "triage" time-critical and STAT priority specimens collected for off-site hs-cTnT testing. Elevated cTnI (≥0.02 µg/L) had a sensitivity of 91% for clear elevations in hs-cTnT (≥53 ng/L) but a 0% sensitivity for modest elevations (5 to 13 ng/L, 14 to 52 ng/L). An interpretive comment was auto-appended to cTnI results indicating that clinicians should wait for the hs-cTnT result if cTnI was normal. Median collect-to-verify TAT for on-site cTnI testing was <50% the TAT for off-site hs-cTnT testing. CONCLUSIONS: On-site point-of-care whole blood cTn testing can rapidly confirm significant or late-presenting myocardial injury. Combined with simultaneous off-site high-sensitivity cardiac troponin (hs-cTn) testing, this workflow is a viable interim solution for pediatric hospitals without on-site hs-cTn testing.

Temporal biomarker concentration patterns during the early course of acute coronary syndrome.

OBJECTIVES: Biomarker concentrations and their changes during acute coronary syndrome (ACS) provide clinically useful information on pathophysiological processes, e.g. myocardial necrosis, hemodynamic stress and inflammation. However, current evidence on temporal biomarker patterns early during ACS is limited, and studies investigating multiple biomarkers are lacking. METHODS: We measured concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), NT-terminal pro-B-type natriuretic peptide, C-reactive protein, and growth-differentiation factor-15 (GDF-15) in plasma samples obtained at randomization in ACS patients from the PLATelet inhibition and patient Outcomes (PLATO) trial. Linear regressions with interaction analyses were used to investigate the associations of biomarker concentrations with the time from symptom onset and to model temporal biomarker concentration patterns. RESULTS: The study population consisted of 16,944 patients (median age 62 years; 71.3 % males) with 6,853 (40.3 %) having ST-elevation myocardial infarction (STEMI) and 10,141 (59.7 %) having non-ST-elevation ACS (NSTE-ACS). Concentrations of all biomarkers were associated with time from symptom onset (pinteraction<0.001), apart for GDF-15 (pinteraction=0.092). Concentration increases were more pronounced in STEMI compared to NSTE-ACS. Temporal biomarker patterns for hs-cTnT and hs-cTnI were different depending on sex whereas biomarker patterns for the other biomarkers were similar in cohorts defined by age and sex. CONCLUSIONS: Temporal concentration patterns differ for various biomarkers early during ACS, reflecting the variability in the activation and duration of different pathophysiological processes, and the amount of injured myocardium. Our data emphasize that the time elapsed from symptom onset should be considered for the interpretation of biomarker results in ACS.

Troponin testing in routine primary care: observations from a dynamic cohort study in the Amsterdam metropolitan area.

OBJECTIVES: Troponin testing is indicated in the diagnostic work-up of acute coronary syndrome (ACS) and incorporated in risk stratification pathways. This study aims to gain insights on the use, outcomes, and diagnostic accuracy of troponin testing in routine primary care; a setting that is understudied. METHODS: Routine data were used from the academic primary care network in the Amsterdam metropolitan area (968,433 patient records). The study population included adult patients who underwent high-sensitivity troponin I or T (hs-TnI/T) testing between 2011 and 2021. The primary outcome was the reported diagnosis and the secondary outcome was the diagnostic accuracy measured by death or ACS at 30 days. RESULTS: 3,184 patients underwent hs-troponin testing, either with hsTNT (n=2,333) or hsTNI (n=851). Median patients' age was 55 (44-65) years, and 62.3 % were female. Predominant symptoms were chest pain and dyspnea (56.7 %). Additional diagnostic laboratory tests were commonly performed (CRP: 47.7 %, natriuretic peptides: 25.6 %, d-dimer: 21.5 %). Most common diagnoses were musculoskeletal symptoms (21.6 %) and coronary heart disease (7.1 %; 1.1 % ACS). Troponin testing showed sensitivity and specificity of 77.8 % (60.9-89.9) and 94.3 % (93.5-95.1), respectively. Negative and positive predictive values were 99.7 (99.5-99.9) and 13.5 (11.1-16.4), and positive and negative likelihood ratios were 13.7 (10.9-17.1) and 0.24 (0.13-0.43). CONCLUSIONS: GPs occasionally use troponin testing in very low-risk patients, often as part of a multi-marker rule-out strategy. The diagnostic characteristics of troponin tests, while promising, warrant prospective validation and implementation to facilitate appropriate use.