Evaluation of the analytical and clinical performance of a high-sensitivity troponin I point-of-care assay in the Mersey Acute Coronary Syndrome Rule Out Study (MACROS-2).

OBJECTIVES: The objective of this study is to evaluate the analytical and diagnostic performance of a high-sensitivity point-of-care (POC) cardiac troponin I assay, the Quidel TriageTrue™ (QuidelOrtho Inc, San Diego, USA), compared to central laboratory testing (CLT) in accelerated diagnostic protocols (ADP) in real time in a clinical environment. METHODS: In a nested sub-study of a pragmatic randomised control trial, consecutive patients with suspected acute coronary syndrome (ACS) and chest pain <12 h duration were randomised to the ESC 0/1 and 0/3-h ADP. Subjects underwent sampling for Quidel TriageTrue POC hs-TnI whole blood and plasma, CLT hs-TnT Roche Elecsys and a validated, NICE approved CLT High sensitivity cardiac troponin I (hs-TnI) (Siemens Attellica) at each time point. Assay imprecision was assessed by repeat analysis of whole blood samples at three levels (low, near 10 % CV 5-10 ng/L, medium, approximating 99th percentile 15-25 ng/L and high, 3-5 times the 99th percentile, 60-100 ng/L). Final diagnosis was adjudicated at 6 weeks by Roche hs-TnT using the 4th universal definition of myocardial infarction (MI). RESULTS: A total of 1,157 patients consented and had both investigational POC whole blood and plasma and central lab hs-cTn available. The median age was 59, 47.2 % were female and 15 % had suffered a previous MI. Assay imprecision of whole blood POC TriageTrue revealed 10 % CV at 8.6 ng/L (>50 % lower than 99th percentile [20.5 ng/L]) and a 20 % CV at 1.2 ng/L. Receiver operator characteristics (ROC) curves were computed for each assay against adjudicated index type 1 MI to study clinical performance. At all-time points there were excellent performance for whole blood POC TriageTrue: area under the curve (AUC) 0.97 [95 % CI 0.94-098], 0.98 [95 % CI 0.97-1.00] and 0.95 [95 % CI 0.92-0.98] at time 0, 1 and 3 h respectively. There was statistical equivalence for performance of whole blood and plasma POC TriageTrue hs-TnI and laboratory Siemens Atellica hs-TnI. CONCLUSIONS: The whole blood POC TriageTrue hs-TnI assay demonstrates imprecision levels consistent with high sensitivity characteristics and has a clinical performance equivalent to an established, validated and NICE approved laboratory Siemens Atellica hs-TnI.

Safety and feasibility of triage and rapid discharge of patients with chest pain from emergency room: a pragmatic, randomised non-inferiority control trial of the European Society of Cardiology (ESC) 0-1 hour pathway vs. conventional 0-3 hour accelerated diagnostic protocol.

Patients presenting with chest pain represent a significant proportion of Emergency Department (ED) attendances but only a minority, typically 10%, have a final diagnosis of myocardial infarction (MI). Prompt discharge of patients without MI will alleviate ED overcrowding as well as improve patient satisfaction and reduce exposure to risk of hospital acquired infections such as Covid 19. The measurement of cardiac troponin (cTn) by a high sensitivity method is recommended by the National Institute for health and Care Excellence (NICE) for rapid categorisation of patients presenting with chest pain. Strategies proposed include measurement on admission and one hour from admission (ESC 0-1-hour pathway, the recent guideline approved pathway which has not been implemented widely), and measurement on admission and three hours from admission (0-3-hour pathway, which is conventional and widely adopted). The primary objective of this study is twofold: firstly, to assess the safety, feasibility, and impact of implementing the ESC (European Society of Cardiology) 0-1-hour pathway in clinical practice by reference to the more established ESC 0-3-hour protocol. The principal outcome measure will be the safety of the ESC 0-1-hour protocol. However, there are concerns that the time from sample draw to result availability (typically around 60 minutes) will impact on the feasibility of the ESC 0-1-hour pathway. Secondly, therefore, our goal is to evaluate whether measurement of high sensitivity troponin by a bedside analyser (point of care testing, POCT), which will produce results in 15 minutes is a feasible alternative to laboratory testing. We will compare the results produced by POCT with the laboratory results in the context of the ESC 0-1 hour and 0-3-hour pathway, as a nested controlled study in the context of a randomised controlled trial. (clinicaltrials.gov: NCT05322395).

Unstable angina in the context of high-sensitive troponins: Still a marker of high risk? A comparison of outcomes with adjudicated type 1 myocardial infarction.

BACKGROUND: Unstable angina (UA), considered historically a marker of high risk, has rarely been studied in the high sensitive troponin era. We sought to characterise this population and determine short- and medium-term outcomes for UA and compared this to both patients with musculoskeletal chest pain and adjudicated type 1 MI (NSTEMI). METHOD: We conducted a post-hoc analysis of 2 prospective cohort studies of suspected acute coronary syndrome in 2 hospitals in the northwest of England. (n = 3018) We used a dedicated symptom score to diagnose unstable angina. Type 1 MI (NSTEMI) was diagnosed by independent physician adjudication according to 3rd universal definition of MI. Follow-up was 100% complete for all patients to 1 year. RESULTS: 185 (6.1%) and 249 (8.3%) were adjudicated as suffering from UA and NSTEMI respectively. We restricted our analysis of UA to 158 (5.2%) patients with UA with high sensitive troponin T (Roche Elecsys) ≤14 ng/L (≤99th percentile). Compared to the NSTEMI population, the UA cohort were younger (59 vs 74, p < 0.002), had a lower incidence of hypertension (56.3% vs 69.1%, p = 0.009), had significantly lower composite risk scores and had fewer ECG abnormalities (ST depression >1 mm, 5.1% vs 15.6%, p = 0.001, T wave flattened, biphasic or inverted 24.1% vs 47.8%, p < 0.0001). Subsequent Type 1 MI to 30 days and 1 year in the UA cohort was 1.9% and 1.9% respectively compared to 0.8% and 2.4% in the index type 1 MI (NSTEMI cohort) respectively. However, compared to patients presenting with musculoskeletal chest pain (n = 468) there was a significantly greater incidence of subsequent MI and coronary revascularisation in patients with unstable angina. All cause death at 30 days and 1 year was 0.0% and 0.6% (n = 1) for UA patients and 2.8% (n = 7) and 16.1% (n = 40) for the NSTEMI cohort respectively. CONCLUSION: UA, defined objectively by a symptom score and absence of myocyte necrosis, is still prevalent as an entity, with a risk of subsequent MI and urgent or emergency coronary revascularisation. However, mortality is >10-fold lower when compared to NSTEMI, indicating a less severe pathology in terms of atherosclerosis or plaque burden, and implying the need for a different management strategy to that of NSTEMI.

HEART Score Recalibration Using Higher Sensitivity Troponin T.

STUDY OBJECTIVE: We examined the diagnostic performance of a recalibrated History, Electrocardiogram, Age, Risk factors, Troponin (HEART), and Thrombolysis in Myocardial Infarction (TIMI) score in patients with suspected acute cardiac syndrome (ACS). Recalibration of troponin thresholds was performed, including shifting from the 99th percentile to the limit of detection (LOD) or to the limit of quantification (LOQ) We compared the discharge potential and safety of the recalibrated composite scores using a single presentation high-sensitivity cardiac troponin (hs-cTn) T to the conventional scores and with a LOD/LOQ troponin strategy alone. METHODS: We undertook a 2-center prospective cohort study in the United Kingdom (UK) (2018) (Clinicaltrials.gov NCT03619733) to specifically assess recalibrated risk scores (shifting the troponin subset scoring from 99th percentile to LOD [UK]) and combined the results of this with secondary analyses of 2 prospective cohort studies in the UK (2011) and the United States (2018, using LOQ rather than LOD). The primary outcome was major adverse cardiovascular events (MACE), defined as adjudicated type 1 myocardial infarction (MI), urgent coronary revascularization, and all-cause death, at 30 days. We evaluated the original scores using hs-cTn below the 99th percentile and recalibrated scores using hs-cTn

Rapid diagnostic strategies using high sensitivity troponin assays: what is the evidence and how should they be implemented?

The introduction of high sensitivity measurement of cardiac troponin T (hs cTnT) and cardiac troponin I (hs cTnI) has given the laboratory the ability to measure very low levels of cardiac troponin. The limit of detection of these assays is well below the 99th percentile. These low levels can also be measured with small values of imprecision. A range of algorithms combining presentation measurement with repeat sample intervals of as little as one to 2 hours have been developed. These are able to predict with acceptable accuracy the diagnosis that would be achieved with continued repeat sampling out to six to 12 hours from presentation. In this article, we review the evidence for the diagnostic accuracy of these approaches and the practical aspects of implementation into routine clinical practice.

Characterisation of the patients with suspected heart failure: experience from the SHEAF registry.

OBJECTIVES: To characterise and risk-stratify patients presenting to a heart failure (HF) clinic according to the National Institute for health and Care Excellence (NICE) algorithm. METHODS: This is an observational study of prospectively collected data in the Sheffield HEArt Failure registry of consecutive patients with suspected HF between April 2012 and January 2020. Outcome was defined as all-cause mortality. RESULTS: 6144 patients were enrolled: 71% had HF and 29% had no HF. Patients with N-terminal pro-brain-type natriuretic peptide (NT-proBNP) >2000 pg/mL were more likely to have HF than those with NT-proBNP of 400-2000 pg/mL (92% vs 64%, respectively). Frequency of HF phenotypes include: HF with preserved ejection fraction (HFpEF) (33%), HF with reduced ejection fraction (HFrEF) (29%), HF due to valvular heart disease (4%), HF due to pulmonary hypertension (5%) and HF due to right ventricular systolic dysfunction (1%). There were 1485 (24%) deaths over a maximum follow-up of 6 years. The death rate was higher in HF versus no HF (11.49 vs 7.29 per 100 patient-years follow-up, p<0.0001). Patients with HF and an NT-proBNP >2000 pg/mL had lower survival than those with NT-proBNP 400-2000 pg/mL (3.8 years vs 5 years, p<0.0001). Propensity matched survival curves were comparable between HFpEF and HFrEF (p=0.88). CONCLUSION: Our findings support the use by NICE's HF diagnostic algorithm of tiered triage of patients with suspected HF based on their NT-proBNP levels. The two pathways yielded distinctive groups of patients with varied diagnoses and prognosis. HFpEF is the most frequent diagnosis, with its challenges of poor prognosis and paucity of therapeutic options.