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Review

How Close Are We to Patient-Side Troponin Testing?

by
Aaron Goldberg
1,
Samuel McGrath
2 and
Michael Marber
2,*
1
Stoke Mandeville Hospital, Aylesbury HP21 8AL, UK
2
BHF Centre of Research Excellence, The Rayne Institute, King’s College London, 4th Floor, Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2024, 13(24), 7570; https://doi.org/10.3390/jcm13247570
Submission received: 25 November 2024 / Revised: 8 December 2024 / Accepted: 9 December 2024 / Published: 12 December 2024
(This article belongs to the Section Cardiology)
Browse Figure
Review Reports Versions Notes

Abstract

:
Laboratory-based high-sensitivity cardiac troponin testing has been the pillar for emergency stratification of suspected acute coronary syndrome for well over a decade. Point-of-care troponin assays achieving the requisite analytical sensitivity have recently been developed and could accelerate such assessment. This review summarises the latest assays and describes their potential diverse clinical utility in the emergency department, community healthcare, pre-hospital, and other hospital settings. It outlines the current clinical data but also highlights the evidence gap, particularly the need for clinical trials using whole blood, that must be addressed for safe and successful implementation of point-of-care troponin analysis into daily practice. Additionally, how point-of-care troponin testing can be coupled with advances in biosensor technology, cardiovascular screening, and triage algorithms is discussed.

1. Introduction

Acute coronary syndrome (ACS) has a major impact on patients, healthcare services, and clinicians. Ischaemic heart disease causes nine million annual deaths globally [1], and suspected ACS accounts for 10% of emergency department (ED) visits [2]. Timely, accurate, and safe triage of such patients is thus imperative. Since their advent in the 1980s [3], immunoassays for cardiac troponin (cTn) as myocardial injury indicators have played a central and increasingly dominant role in ACS assessment. Cardiomyocytes are the sole source of cTnI and the main source of cTnT; hence, these assays have high biological specificity and are the only recommended biomarker for acute myocardial infarction (AMI) diagnosis in the Fourth Universal Definition of Myocardial Infarction [4]. Central laboratory testing (CLT) has been the mainstay of this cTn measurement. However, CLT’s drawbacks include result turnaround times of up to one hour [5], the need for trained laboratory personnel, and accessibility issues in resource-poor healthcare settings. Promisingly, point-of-care (POC) analysers seem adept to address these challenges.
Older cTn assays had optimum sensitivity 10–12 h after AMI onset, resulting in patients needing admission for observation and serial troponin measurement. High-sensitivity cardiac troponin (hs-cTn) measurement by CLT was developed in 2009 [6]. These platforms can detect lower troponin concentrations occurring earlier in AMI, and so have been the focus of ACS biochemical diagnosis. These hs-cTn assays are defined by two key analytical attributes [7]. Firstly, their minimal variation at the cut-off cTn value for diagnosing AMI amongst a healthy reference cohort (coefficient of variation (CV) at 99th percentile upper reference limit is ≤10%). Secondly, they are sensitive enough to detect very low cTn levels in more than half of healthy individuals (measurable concentrations above limit of detection (LoD) for >50% healthy population). Trials have evidenced CLT-based hs-cTn measurements’ ability to rule in AMI with a single high cTn level, rule out AMI with a single low result, and then triage those with intermediate levels using the change in concentration on repeat measurements [8]. Accordingly, international guidelines, such as the European Society of Cardiology (ESC), recommend the use of such testing in rapid algorithms for patients presenting with suspected non-ST-segment elevation myocardial infarction (NSTEMI) [9].
POC cTn testing can be performed faster and closer to the patient than CLT, presenting an exciting potential solution for accelerating suspected NSTEMI work-up. The first contemporary POC assays were rightfully usurped by the superior sensitivity of hs-cTn CLT, but POC instruments with improved analytical abilities have recently been developed. This review aims to provide non-specialist clinicians with an overview of how these new high-sensitivity POC troponin tests may benefit the chest pain management armamentarium. We discuss what is already known about their clinical performance and what key clinical information is still needed for their safe and effective implementation into daily practice.

2. What Is Meant by POC

POC testing is a diagnostic measurement performable at or near the patient by non-laboratory staff with swift results, potentially influencing the care provided. It needs to be operator-friendly and capable of utilising whole-blood samples. This negates the need for preparatory steps common in CLT such as pipetting and centrifugation which are required to process serum or plasma samples. Compared to the longer turnaround times of conventional CLT, POC analysis can yield results in 5–15 min [10]. POC testing has been utilised to assess a range of biochemical parameters, such as electrolytes, full blood counts, and infection markers. This has been shown to generate faster management and disposition decisions that can reduce the length of patients’ ED stay [11].
Translating these benefits into suspected ACS assessment is very attractive. The rationale for POC cTn testing is to directly give results faster to the responsible clinician and facilitate testing in a wider range of healthcare settings. A key sequela would hopefully be quicker clinical decision-making that expedites patients to the correct care pathway, enabling faster discharge of low-risk patients to alleviate crowded EDs. It could also allow for quicker provision of therapeutic intervention when needed for confirmed NSTEMI and prevent unindicated ED visits altogether if utilised effectively in the community. POC cTn instruments vary in scale from smaller portable battery-powered devices to desktop machines which can be situated within the clinical workspace but may need a wired power supply [12]. They are immunoassays, using labelled antibodies to detect cTnI or cTnT, and some can also run simultaneous assays for other biochemical markers. Table 1 summarises the specifications of the three current hs-cTn POC devices.

3. The Concentration Problem

POC cTn assays are ideally suited for rapidly ruling in AMI diagnosis. It has been demonstrated that POC can reliably rule in MI by detecting 99th percentile upper reference limit troponin levels with a high predictive value [14,15]. However, safely and effectively ruling out AMI is the crux of managing patients presenting with ACS symptoms. In the context of a normal or unchanged ECG, this necessitates either an undetectably low troponin level close to or below the assay’s LoD or a measurably low level which shows unchanging repeat measurements. The LoD is defined as the lowest analyte concentration reliably distinguishable from a blank sample and at which detection is feasible [16]. These requirements are agreed by international guidelines, albeit with variation in the advised timing for serial measurement (e.g., 0/1 h or 0/3 h to rule out) [9,17]. Laboratory hs-cTn assays are the current gold standard for accomplishing this, setting the benchmark for POC tests. Achieving this degree of clinical sensitivity presents POC assays, using a single approximately 100-microlitre droplet of blood, with an analytical concentration problem. POC analysers measure concentrations of cTnI, which has an AMI rule-out concentration of 2 ng/L [18]. This equates to an incredibly small 10–100 femtomolar (10–100 × 10−15 molar) concentration in the POC sample volume. Therefore, to detect this very low level of cTnI, POC assays must surmount the challenge of achieving the requisite high sensitivity with just a drop of blood.
Previously available POC assays could not perform such high-sensitivity analyses necessary to rule out MI on a single admission blood test. They may even have had a diagnostic performance worse than a triage decision aid alone [19]. Instead, these contemporary assays required serial sampling at three to six hours post-presentation to attain sufficient rule-out sensitivity [20]. Therefore, CLT is clearly preferable to exclude or diagnose NSTEMI within one to three hours of admission compared to the extra time requirements of a POC instrument’s repeat measurements. The advantage of a 10–15 min turnaround time of a conventional POC cTn assay is swamped by the delay needed to match the diagnostic sensitivity of CLT hs-cTn assays. However, as per the IFCC C-CB [13], there are now currently three POC machines meeting hs-cTn assay analytical criteria, namely Atellica VTLi (Siemens Helathineers, Erlangen, Germany), PATHFAST (LSI Medicine Corporation, Tokyo, Japan), and TriageTrue (QuidelOrtho, San Diego, CA, USA); their assay characteristics are outlined in Table 1.
Studies of Atellica VTLi’s diagnostic performance indicate that it is comparable with hs-cTn CLT and suggest that it could be utilised in rapid rule-out algorithms [21,22,23]. Similar studies have been performed for PATHFAST [24] and TriageTrue [25]. These initial analyses do unfortunately have a significant drawback; they were performed on biobanked or processed plasma samples under controlled laboratory conditions. Therefore, such results have dubious applicability to the ED setting, in which non-laboratory clinicians would use whole-blood samples for POC analysis without preparatory steps. The National Institute for Health and Care Excellence similarly emphasises the importance of assessing POC’s diagnostic performance with whole-blood samples [26]. However, there are very recent studies attempting to bridge this applicability gap to real-world practice. Compared to the CLT hs-cTn gold standard, Atellica VTLi has shown a strong correlation using whole-blood samples over a wide range of cTnI concentrations [27,28,29] and concordant NSTEMI diagnostic performance for non-traumatic chest pain in the ED [30]. Furthermore, it has shown good equivalence with CLT for accurate MI diagnosis within a 0/2 h serial testing protocol of whole blood from patients presenting to the ED with suspected cardiac ischaemia [31,32]. Similar whole-blood analytical correlation with a CLT benchmark has also been demonstrated for PATHFAST [33]. Furthermore, there are other POC assays that are close to achieving the required degree of clinical sensitivity [34,35,36]. However, there is a need to bridge the evidence gap pertaining to whether the equivalence in analytic performance between POC testing and CLT translates to better economic or health outcomes. This requires prospective clinical trials where the two systems drive clinical decisions.

4. Potential Advantages of POC Testing

4.1. Ambulance Triage

The portability of POC cTn assays means that there is certainly scope for their use in ambulance triage of acute chest pain cases. The collection of cTn levels with concomitant ECG analysis by paramedics is feasible [37]. This prevents the need for secondary inter-hospital transfer as high-risk NSTEMI patients are identified earlier and transported initially to centres with percutaneous coronary intervention facilities. Recent trials demonstrate that in comparison to ED transfer, the utilisation of ambulance POC cTn assays to identify patients as low-risk for ACS reduces incurred healthcare costs without increasing major adverse cardiovascular event (MACE) outcomes at 30 days [38,39,40]. Furthermore, studies have conveyed that incorporating POC cTn results into the pre-hospital History, ECG, Age, Risk, and Troponin (preHEART) score performs better than other triage scores without POC results and POC cTn testing alone [41,42]. This enables a significant proportion of low-risk patients to avoid hospitalisation [43]. However, there is conflicting evidence that whilst pre-hospital POC cTn shows high specificity, it lacks sensitivity compared to CLT, and hence cannot safely rule out MI [44]. Ambulance crews attend to patients sooner from symptom onset than when venepuncture is performed in the ED for CLT; thus, the low sensitivity in these studies may arise from the troponin-blind period during ACS progression. Additionally, the ability to rule in AMI alone would still help guide pre-hospital management, such as antiplatelet administration, transport urgency decisions, and conveying patients directly to cardiac catheterisation centres. The above studies all used either Cobas h232 (Roche Instr, Basel, Switzerland) or i-STAT (Abbott Point of Care, Princeton, NJ, USA) POC assays, which, whilst they can be handheld, do not meet hs-cTn analytical standards. Therefore, pre-hospital studies assessing the utility and safety of hs-cTn POC assays small enough to be deployed in ambulances, such as Atellica VTLi and TriageTrue, are needed.

4.2. Primary Care and Other Community Healthcare Settings

There are other community settings whereby POC cTn testing could be advantageous. Primary care physicians commonly encounter patients presenting with chest pain [45]. Amongst these patients, those at a low risk of ACS could avoid unnecessary urgent hospital transfer via risk stratification incorporating POC cTn in primary care, provided other severe acute differential diagnoses are not clinically suspected. An accelerated diagnostic chest pain pathway in general practice using POC cTn identified over 60% of patients as low-risk who were resultingly managed in the community safely without 30-day MACE [46]. POC testing could prove similarly beneficial for rural or resource-poor healthcare settings with more limited access to CLT. In rural Australia, a cardiac support model, in which tertiary centre specialists remotely reviewed ECGs and POC cTn results to advise on management and onwards referral, reduced missed AMI diagnoses and improved rates of primary reperfusion therapy and 30-day mortality [47,48]. A similar chest pain management pathway involving POC cTn testing demonstrated safe and effective identification of low-risk ACS patients in rural New Zealand too [49]. However, these benefits need to be considered in country-specific healthcare contexts and do not necessarily translate into lower-income countries. For example, the HEART triage score including POC cTn could not safely identify low-risk patients in Tanzania. This was possibly due to patients presenting later, worse access to coronary angiography, and lesser uptake of evidence-based treatment and secondary prevention for ACS [50]. Figure 1 summarises the various community healthcare settings in which POC cTn testing may prove valuable.

4.3. ED

We must first consider the current landscape of suspected ACS work-up in the ED to appreciate how POC cTn testing could be a beneficial addition. There is clear and strong evidence that rapid rule-out pathways incorporating hs-cTn assays, which can be on a 0/1 [51], 0/2 [9], or 0/3 h basis [52], safely accelerate triage without harming patient outcomes, hence their recommendation in international guidelines. Such protocols can shorten the length of stay for patients in the ED and increase the rate of direct ED discharge when AMI is ruled out, without excess diagnostic resource utilisation [53]. Moreover, clinical scoring systems containing hs-cTn values, such as HEART [54] and Emergency Department Assessment of Chest Pain Score (EDACS) [55] pathways, have demonstrated consistent reductions of 20–45% in suspected ACS admissions. These decreased admission rates, combined with shorter subsequent inpatient stays, translate to significant cost savings for hospitals [56]. Additionally, economic benefits are further enhanced by reduced rates of downstream diagnostic procedures, such as functional testing [57] and anatomic imaging including invasive coronary angiography [58]. This swifter assessment does not compromise patient outcomes, with multicentre studies illustrating that using hs-cTn strategies to triage patients as low-risk for ACS does not impact the incidence of mortality or MI at 30 days [18,59,60]. The clinical reliability, safety, and benefits of hs-cTn algorithms have additionally been affirmed via meta-analysis [8,61].
Despite this clear evidence of benefits, such protocols are not universally deployed day-to-day in EDs. A survey of 1902 medical centres across five continents in 2019 revealed that only 41% utilise hs-cTn assays and less than 10% implement 0/1 or 0/2 h algorithms [62]. In fact, when accelerated protocols are indeed implemented, significant intracentre variation in ED stay duration has been highlighted [53]. A likely explanation for this is the infrastructural challenge of CLT hs-cTn, including delays portering blood samples to a centralised lab from busy EDs, sample processing, available access to sensitive analysers, and clinical teams being aware of the results (push versus in-record notification). POC instruments, with their short result turnaround times of under 20 min [31] and ability to be located within the ED itself, appear ideally suited to circumvent such barriers and help expedite patient flow.
Older POC tests, which as aforementioned require serial cTn testing, have yielded mixed findings regarding their benefits in the ED. Contrasting inter-hospital results arose for successful discharge and cost savings from using a panel POC assay including troponin [63], and POC cTn testing only minimally reduced the time from first medical contact to ED discharge by 0.3 h [64]. However, more recent studies indicate that incorporating POC cTn testing, including assays meeting hs-cTn criteria, into the ED triage process is safe, accurate, and timely. The inclusion of POC results in the troponin-only Manchester ACS decision aid may facilitate ruling out suspected ACS within three hours for nearly one-third of ED patients without missing any AMIs [65]. A prospective observational study of two large ED cohorts has derived and validated a 0/2-hour strategy using Atellica VTLi, enabling earlier clinical decision-making without augmenting 30-day MACE [66]. Figure 1 portrays how POC cTn assays could be beneficial within EDs in this way. POC testing may be especially adept for supporting self-contained dedicated chest pain units, which have been previously shown to decrease hospital admissions and costs and improve patient outcomes and satisfaction [67,68].
There are caveats to ED POC cTn testing that would need to be carefully considered for widespread implementation. Firstly, indiscriminate troponin testing is a potential by-product of the increased accessibility afforded by POC testing in the ED. This can lead to uncertain diagnosis and further unneeded investigations. A sizeable trial highlighted this; the implementation of an hs-cTnI lab assay reclassified a significant proportion of suspected ACS patients as higher risk, but only a third of these did indeed have type 1 MI and there was no improvement in adverse cardiovascular outcomes [69]. Secondly, the potential advantages need to be regarded in the context of other hurdles to POC implementation in the ED. Notably, these include the costs of establishing POC analysers in situ and maintaining them, the analytical errors arising from operation by clinicians not trained in laboratory medicine, and the increased workload for busy ED staff [70,71]. These factors are likely to be prominent during initial implementation and would improve over time as the ED staff’s familiarity with the analysers grows. Thirdly, cTn analysis is not inherently the rate-limiting step in chest pain assessment because appropriate work-up for other differentials, such as performing d-dimer, chest X-ray, and pulmonary angiogram for pulmonary embolism, is crucial. Additional investigation results, such as haemoglobin, electrolytes, and renal function, are also imperative in triaging ACS patients. Thus, POC testing’s faster result times will not translate into more efficient clinical practice unless it is well integrated into wider patient management systems.

4.4. Elsewhere in Hospitals

POC cTn testing may also have advantageous roles in hospitals outside of the ED ACS triage setting. The ESC guidelines recommend perioperative troponin measurement for patients undergoing intermediate- or high-risk surgery because myocardial injury in this setting can increase long-term morbidity and mortality risk [72]. Troponin levels are also a suggested component of monitoring during cardiotoxic cancer therapy [73]. Therefore, POC cTn analysers may benefit specialist surgical or oncological centres with more limited access to a central laboratory. Additionally, a POC instrument could serve as an efficient back-up analyser in the case of hs-cTn CLT malfunction or when lab-trained staff are not available overnight. It must be emphasised that different cTn assays are not harmonised and have non-standardised individual cut-offs; thus, lab and POC results should not be directly compared [74] and need to be clearly flagged in the patient’s record.

5. Trial Experience

There is clearly evidence from observational studies, as described above, that there are now POC assays reaching hs-cTn analytical standards, and that utilising POC cTn testing in pre-hospital and ED environments could be safe and effective for ACS triage. However, these findings are limited by observational studies’ increased bias and inability to prove causality [75]. RCTs comparing POC testing with standard CLT in clinical practice can reveal how the former’s rapid result turnaround time directly impacts clinical decision-making and patient outcomes; the handful of such trials currently published are summarised in Table 2. Crucially, they were all performed on pre-hs-cTn POC assays. The findings are variable, particularly regarding POC testing’s impact on shortening the decision time from admission to disposition for suspected ACS patients. Within multicentre RCTs, disparate effects on length of stay were found between EDs [63,76]. The lack of standardised chest pain protocols between hospitals, such as different assessment time targets, could explain the inconsistent trial findings. This highlights that POC cTn testing implementation needs to be well integrated within the wider ED triage pathway [71]. Understandably, these RCTs were designed pragmatically, and thus it was not possible to blind clinicians to which assay produced the provided cTn result. This may have attenuated POC testing’s actual impact as irrespective of a swift POC result, clinicians might have waited for the validating CLT value [77] or gone on to order further lab tests anyway. Regardless of these limitations, the RCTs indicate significant scope for POC cTn testing to accelerate suspected ACS assessment, and none identified any major risks for patient safety in doing so.

6. What the Future May Bring

Going forwards, there is a clear need for RCTs that compare hs-cTn testing with POC and laboratory assays in the clinical ED setting using unspun whole-blood samples. The ICare-FASTER trial is such a study of the Atellica VTLi analyser; it has been protocolised [82] and will hopefully provide invaluable information on POC hs-cTn’s actual clinical impact on ED length of stay, morbidity, and mortality. The POB HELP RCT is also underway to assess how using the Atellica VTLi assay with fingerstick samples impacts patient flow and ACS rule-out in primary care [83]. Factors specific to POC instruments will need to be borne in mind in such studies. For example, pre-analytical errors can arise from haemolysis, which is more common with unspun whole blood [84], and the relationship between venous and fingerstick capillary cTn levels needs to be better understood [12].
In the future, POC cTn measurement may be deployed for detecting chronic cardiovascular disease risk in asymptomatic populations. It has been well demonstrated that cTn is a strong predictor for cardiovascular morbidity and mortality; cTnT has been suggested as a better predictor for all-cause mortality [85] and cTnI for future AMI [86]. There are no consensus-agreed preventative interventions once such increased risk has been identified, and thus routine troponin screening is not recommended. However, should screening and specific interventions be shown to lower chronic cardiovascular risk, POC cTn analysers in the community would be ideal for accomplishing this. Detecting early cTn elevations in this way could reveal subclinical cardiac disease and therefore provide an opportunity to deliver targeted preventative therapy [87].
Technological advances could make POC cTn testing even more accessible and easy-to-operate. In comparison to more traditional biomarker methods like enzyme-linked immunosorbent assays, considerable progress has been made in the field of microfluidic biosensors. These have the potential to usher in more cost-effective, miniaturised, and ergonomic detection systems [88]. For example, a wrist-worn transdermal infrared spectrophotometric sensor has been shown to accurately detect elevated cTnI levels amongst inpatients with confirmed ACS [89]. Additionally, there is mixed evidence that saliva can provide samples for rapid and simple troponin analysis [90]. These technologies could enable easy POC cTn measurements in a broader range of settings, including possible “plug-and-play” style and smartphone-compatible systems [91,92]. However, they all certainly still need further validation studies and regulatory clearance. As mentioned earlier, POC cTn can be beneficially incorporated into ACS triage scores, but given machine learning progress, they can also be implemented into more complex stratification tools. Compared to international guideline-recommended pathways, a recent artificial intelligence algorithm integrated single POC hs-cTn measurements alongside other clinical variables, such as ischaemic ECG changes, smoking status, and family history of ACS, to identify more patients suitable for ACS rule-out while maintaining high safety [93]. Going forwards, these algorithms should not be used in isolation to guide management but rather should help guide shared decision-making with patients.

7. Conclusions

POC instruments meeting hs-cTn assay criteria are now available. This makes them viable alternatives to the CLT recommended in international ACS guidelines, with their added benefits of faster result turnaround times, operability closer to the patient, and user-friendly form factor. Therefore, potential avenues for POC cTn testing to benefit AMI diagnosis in community and ED settings are evident. They are also well suited for integration with advances in biosensor, artificial intelligence, and screening tools. However, prospective device evaluation using whole blood in collaborative RCTs between manufacturers and researchers is still required for POC testing’s future safe clinical deployment. Hopefully, these trials will demonstrate that POC hs-cTn testing can safely and effectively accelerate ACS triage, leading to improved patient outcomes and galvanising further progress in this field.

Author Contributions

A.G., literature review and writing—original draft preparation; S.M., writing—review and editing; M.M., supervision and writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

This study was supported by the King’s BHF Centre of Research Excellence [RE/24/130035]. Dr Samuel McGrath is undergoing a clinical research training fellowship (CRTF) funded by the British Heart Foundation [FS/CRTF/22/24187].

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Khan, M.A.; Hashim, M.J.; Mustafa, H.; Baniyas, M.Y.; Al Suwaidi, S.K.B.M.; Alkatheeri, R.; Alblooshi, F.M.K.; Almatrooshi, M.E.A.H.; Alzaabi, M.E.H.; Al Darmaki, R.S.; et al. Global Epidemiology of Ischemic Heart Disease: Results from the Global Burden of Disease Study. Cureus 2020, 12, e9349. [Google Scholar] [CrossRef] [PubMed]
  2. Anderson, J.L.; Morrow, D.A. Acute Myocardial Infarction. N. Engl. J. Med. 2017, 376, 2053–2064. [Google Scholar] [CrossRef] [PubMed]
  3. Cummins, B.; Auckland, M.L.; Cummins, P. Cardiac-specific troponin-I radioimmunoassay in the diagnosis of acute myocardial infarction. Am. Heart J. 1987, 113, 1333–1344. [Google Scholar] [CrossRef] [PubMed]
  4. Thygesen, K.; Alpert, J.S.; Jaffe, A.S.; Chaitman, B.R.; Bax, J.J.; Morrow, D.A.; White, H.D.; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation 2018, 138, e618–e651. [Google Scholar] [CrossRef]
  5. Apple, F.S.; Fantz, C.R.; Collinson, P.O.; The IFCC Committee on Clinical Application of Cardiac Bio-Markers. Implementation of High-Sensitivity and Point-of-Care Cardiac Troponin Assays into Practice: Some Different Thoughts. Clin. Chem. 2021, 67, 70–78. [Google Scholar] [CrossRef]
  6. Apple, F.S. A new season for cardiac troponin assays: It’s time to keep a scorecard. Clin. Chem. 2009, 55, 1303–1306. [Google Scholar] [CrossRef]
  7. Wu, A.H.B.; Christenson, R.H.; Greene, D.N.; Jaffe, A.S.; Kavsak, P.A.; Ordonez-Llanos, J.; Apple, F.S. Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine. Clin. Chem. 2018, 64, 645–655. [Google Scholar] [CrossRef]
  8. Arslan, M.; Dedic, A.; Boersma, E.; Dubois, E. Serial high-sensitivity cardiac troponin T measurements to rule out acute myocardial infarction and a single high baseline measurement for swift rule-in: A systematic review and meta-analysis. Eur. Heart J. Acute Cardiovasc. Care 2020, 9, 14–22. [Google Scholar] [CrossRef]
  9. Collet, J.P.; Thiele, H.; Barbato, E.; Barthélémy, O.; Bauersachs, J.; Bhatt, D.L.; Dendale, P.; Dorobantu, M.; Edvardsen, T.; Folliguet, T.; et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur. Heart J. 2021, 42, 1289–1367. [Google Scholar] [CrossRef]
  10. Abel, G. Current status and future prospects of point-of-care testing around the globe. Expert Rev. Mol. Diagn. 2015, 15, 853–855. [Google Scholar] [CrossRef]
  11. Goyder, C.; Tan, P.S.; Verbakel, J.; Ananthakumar, T.; Lee, J.J.; Hayward, G.; Turner, P.J.; Bruel, A.V.D. Impact of point-of-care panel tests in ambulatory care: A systematic review and meta-analysis. BMJ Open 2020, 10, e032132. [Google Scholar] [CrossRef] [PubMed]
  12. Collinson, P.; Aakre, K.M.; Saenger, A.; Body, R.; Hammarsten, O.; Jaffe, A.S.; Kavsak, P.; Omland, T.; Ordonez-Lianos, J.; Karon, B.; et al. Cardiac troponin measurement at the point of care: Educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB). Clin. Chem. Lab. Med. (CCLM) 2023, 61, 989–998. [Google Scholar] [CrossRef] [PubMed]
  13. High-Sensitivity* Cardiac Troponin I and T Assay Analytical Characteristics Designated by Manufacturer. IFCC Committee on Clinical Applications of Cardiac BioMarkers (C-CB) v052022. Available online: https://ifccfiles.com/2024/03/Point-of-Care-Cardiac-Troponin-I-and-T-Assay-Analytical-Characteristics-Designated-By-Manufacturer-v062024.pdf (accessed on 19 November 2024).
  14. Venge, P.; van Lippen, L.; Blaschke, S.; Christ, M.; Geier, F.; Giannitsis, E.; Hagström, E.; Hausfater, P.; Khellaf, M.; Mair, J.; et al. Equal clinical performance of a novel point-of-care cardiac troponin I (cTnI) assay with a commonly used high-sensitivity cTnI assay. Clin. Chim. Acta 2017, 469, 119–125. [Google Scholar] [CrossRef] [PubMed]
  15. Rasmussen, M.B.; Stengaard, C.; Sørensen, J.T.; Riddervold, I.S.; Hansen, T.M.; Giebner, M.; Rasmussen, C.-H.; Bøtker, H.E.; Terkelsen, C.J. Predictive value of routine point-of-care cardiac troponin T measurement for prehospital diagnosis and risk-stratification in patients with suspected acute myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care 2019, 8, 299–308. [Google Scholar] [CrossRef]
  16. Armbruster, D.A.; Pry, T. Limit of Blank, Limit of Detection and Limit of Quantitation. Clin. Biochem. Rev. 2008, 29, S49. [Google Scholar]
  17. Writing Committee Members; Gulati, M.; Levy, P.D.; Mukherjee, D.; Amsterdam, E.; Bhatt, D.L.; Birtcher, K.K.; Blankstein, R.; Boyd, J.; Bullock-Palmer, R.P.; et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021, 144, e368–e454. [Google Scholar]
  18. Bularga, A.; Lee, K.K.; Stewart, S.; Ferry, A.V.; Chapman, A.R.; Marshall, L.; Strachan, F.E.; Cruickshank, A.; Maguire, D.; Berry, C.; et al. High-Sensitivity Troponin and the Application of Risk Stratification Thresholds in Patients With Suspected Acute Coronary Syndrome. Circulation 2019, 140, 1557–1568. [Google Scholar] [CrossRef]
  19. Alghamdi, A.; Reynard, C.; Morris, N.; Moss, P.; Jarman, H.; Hardy, E.; Harris, T.; Horner, D.; Parris, R.; Body, R. Diagnostic accuracy of the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid with a point-of-care cardiac troponin assay. Emerg. Med. J. 2020, 37, 223–228. [Google Scholar] [CrossRef]
  20. Suh, D.; Keller, D.I.; Hof, D.; von Eckardstein, A.; Gawinecka, J. Rule-out of non-ST elevation myocardial infarction by five point of care cardiac troponin assays according to the 0 h/3 h algorithm of the European Society of Cardiology. Clin. Chem. Lab. Med. (CCLM) 2018, 56, 649–657. [Google Scholar] [CrossRef]
  21. Pickering, J.W.; Young, J.M.; George, P.M.; Watson, A.S.; Aldous, S.J.; Troughton, R.W.; Pemberton, C.J.; Richards, A.M.; Cullen, L.A.; Than, M.P. Validity of a Novel Point-of-Care Troponin Assay for Single-Test Rule-Out of Acute Myocardial Infarction. JAMA Cardiol. 2018, 3, 1108–1112. [Google Scholar] [CrossRef]
  22. Mion, M.M.; Bragato, G.; Casarotti, A.; Cosma, C.; Vigolo, S.; Vettore, G.; Tosato, F.; Zaninotto, M.; Plebani, M. Clinical performance of cardiac Troponin I: A comparison between the POCT AQT90 FLEX and the Dimension Vista analyzer in an emergency setting. Clin. Biochem. 2017, 50, 763–767. [Google Scholar] [CrossRef] [PubMed]
  23. De Iuliis, V.; Gabriele, A.R.; De Santis, F.; De Rugeriis, R.; Di Quinzio, L.; Aloisi, S.; Rosati, A.C.; Benvenuto, M.; Fabiani, D.; Ranieri, S.C. Diagnostic performance of a point of care high-sensitivity cardiac troponin I assay and single measurement evaluation to rule out and rule in acute coronary syndrome. Clin. Chem. Lab. Med. (CCLM) 2024, 62, 2326–2334. [Google Scholar] [CrossRef] [PubMed]
  24. Sörensen, N.A.; Neumann, J.T.; Ojeda, F.; Giannitsis, E.; Spanuth, E.; Blankenberg, S.; Westermann, D.; Zeller, T. Diagnostic Evaluation of a High-Sensitivity Troponin I Point-of-Care Assay. Clin. Chem. 2019, 65, 1592–1601. [Google Scholar] [CrossRef] [PubMed]
  25. Boeddinghaus, J.; Nestelberger, T.; Koechlin, L.; Wussler, D.; Lopez-Ayala, P.; Walter, J.E.; Troester, V.; Ratmann, P.D.; Seidel, F.; Zimmermann, T.; et al. Early Diagnosis of Myocardial Infarction With Point-of-Care High-Sensitivity Cardiac Troponin I. J. Am. Coll. Cardiol. 2020, 75, 1111–1124. [Google Scholar] [CrossRef]
  26. Body, R.; Chuter, A.; Collinson, P.; Mills, N.; Reid, A.; Timmis, A.; Titu, H. High-Sensitivity Troponin Tests for the Early Rule out of NSTEMI. National Institute for Health and Care Excellence Diagnostics Guidance [DG40]; NICE: London, UK, 2020. [Google Scholar]
  27. Christenson, R.H.; Frenk, L.D.S.; de Graaf, H.J.; van Domburg, T.S.Y.; Wijnands, F.P.G.; Foolen, H.W.J.; Kemper, D.W.M.; Bruinen, A.L.; Meijering, B.D.M.; Fonville, J.M.; et al. Point-of-Care: Roadmap for Analytical Characterization and Validation of a High-Sensitivity Cardiac Troponin I Assay in Plasma and Whole Blood Matrices. J. Appl. Lab. Med. 2022, 7, 971–988. [Google Scholar] [CrossRef]
  28. Florkowski, C.M.; Buchan, V.; Li, B.V.; Taylor, F.; Phan, M.; Than, M.; Pickering, J.W. Analytical verification of the Atellica VTLi point of care high sensitivity troponin I assay. Clin. Chem. Lab. Med. 2024; ahead of print. [Google Scholar] [CrossRef]
  29. Xiong-Hang, K.; Schulz, K.; Sandoval, Y.; Smith, S.W.; Saenger, A.K.; Apple, F.S. Analytical performance comparing siemens whole blood point of care Atellica VTLi to the central laboratory plasma Atellica IM high-sensitivity cardiac troponin I assays. Clin. Biochem. 2023, 114, 79–85. [Google Scholar] [CrossRef]
  30. Zalama-Sánchez, D.; del Pozo Vegas, C.; Sanz-García, A.; de Santos-Castro, P.; Presencio-Dominguez, J.; González-Izquierdo, P.; Sánchez-Ramón, S.; Pinilla-Arribas, L.T.; Baladrón-Segura, M.; Cheayeb-Morán, J.; et al. Diagnostic Performance of Point-of-Care High-Sensitivity Troponin in the Exclusion of Non-ST-Elevation Myocardial Infarction in the Emergency Department. J. Pers. Med. 2024, 14, 762. [Google Scholar] [CrossRef]
  31. Apple, F.S.; Smith, S.W.; Greenslade, J.H.; Sandoval, Y.; Parsonage, W.; Ranasinghe, I.; Gaikwad, N.; Schulz, K.; Stephensen, L.; Schmidt, C.; et al. Single High-Sensitivity Point-of-Care Whole-Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk. Circulation 2022, 146, 1918–1929. [Google Scholar] [CrossRef]
  32. Gunsolus, I.L.; Schulz, K.; Sandoval, Y.; Smith, S.W.; Lindgren, B.; Okeson, B.; Apple, F.S. Diagnostic performance of a rapid, novel, whole blood, point of care high-sensitivity cardiac troponin I assay for myocardial infarction. Clin. Biochem. 2022, 105–106, 70–74. [Google Scholar] [CrossRef]
  33. Osredkar, J.; Krivic, K.; Fabjan, T.; Kumer, K.; Tršan, J.; Poljančič, L.; Finderle, P.; Možina, H. Point-of-care high-sensitivity assay on PATHFAST as the backup in the emergency room. Med. Access Point Care 2021, 5, 23992026211055095. [Google Scholar] [CrossRef]
  34. Pittie, G.; Lukas, P.; Massart, M.; Cavalier, E.; Le Goff, C. Evaluation of analytical and clinical performance of the AFIAS Tn-I plus assay—A new point-of-care. Acta Cardiol. 2024, 79, 351–357. [Google Scholar] [CrossRef] [PubMed]
  35. Zhang, R.; Hong, Y.; Shi, J.; Zhao, R.; Song, Y.; Li, Z.; Wang, Q.; Yue, Y. Analytical characterization and clinical performance evaluation of a new point-of-care testing system for high-sensitivity cardiac troponin I assay. Ann. Clin. Biochem. 2021, 58, 579–585. [Google Scholar] [CrossRef] [PubMed]
  36. Koechlin, L.; Boeddinghaus, J.; Lopez-Ayala, P.; Reber, C.; Nestelberger, T.; Wildi, K.; Spagnuolo, C.C.; Strebel, I.; Glaeser, J.; Bima, P.; et al. Clinical and Analytical Performance of a Novel Point-of-Care High-Sensitivity Cardiac Troponin I Assay. J. Am. Coll. Cardiol. 2024, 84, 726–740. [Google Scholar] [CrossRef] [PubMed]
  37. Jacobsen, L.; Grenne, B.; Olsen, R.B.; Jortveit, J. Feasibility of prehospital identification of non-ST-elevation myocardial infarction by ECG, troponin and echocardiography. Emerg. Med. J. 2022, 39, 679–684. [Google Scholar] [CrossRef]
  38. Aarts, G.W.A.; Camaro, C.; Adang, E.M.M.; Rodwell, L.; van Hout, R.; Brok, G.; Hoare, A.; de Pooter, F.; de Wit, W.; Cramer, G.E.; et al. Pre-hospital rule-out of non-ST-segment elevation acute coronary syndrome by a single troponin: Final one-year outcomes of the ARTICA randomised trial. Eur. Heart J.—Qual. Care Clin. Outcomes 2024, 10, 411–420. [Google Scholar] [CrossRef]
  39. Camaro, C.; Aarts, G.W.A.; Adang, E.M.M.; van Hout, R.; Brok, G.; Hoare, A.; Rodwell, L.; de Pooter, F.; de Wit, W.; Cramer, G.E.; et al. Rule-out of non-ST-segment elevation acute coronary syndrome by a single, pre-hospital troponin measurement: A randomized trial. Eur. Heart J. 2023, 44, 1705–1714. [Google Scholar] [CrossRef]
  40. Dawson, L.P.; Nehme, E.; Nehme, Z.; Zomer, E.; Bloom, J.; Cox, S.; Anderson, D.; Stephenson, M.; Ball, J.; Zhou, J.; et al. Chest Pain Management Using Prehospital Point-of-Care Troponin and Paramedic Risk Assessment. JAMA Intern. Med. 2023, 183, 203–211. [Google Scholar] [CrossRef]
  41. Sagel, D.; Vlaar, P.J.; van Roosmalen, R.; Waardenburg, I.; Nieuwland, W.; Lettinga, R.; van Barneveld, R.; Jorna, E.; Kijlstra, R.; van Well, C.; et al. Prehospital risk stratification in patients with chest pain. Emerg. Med. J. 2021, 38, 814–819. [Google Scholar] [CrossRef]
  42. Demandt, J.P.A.; Koks, A.; Sagel, D.; Haest, R.; Heijmen, E.; Thijssen, E.; el Farissi, M.; Eerdekens, R.; van der Harst, P.; van’t Veer, M.; et al. External validation of the preHEART score and comparison with current clinical risk scores for prehospital risk assessment in patients with suspected NSTE-ACS. Emerg. Med. J. 2024, 41, 610–616. [Google Scholar] [CrossRef]
  43. Tolsma, R.T.; Fokkert, M.J.; van Dongen, D.N.; Badings, E.A.; van der Sluis, A.; Slingerland, R.J.; Riet, E.v.; Ottervanger, J.P.; van’t Hof, A.W. Referral decisions based on a pre-hospital HEART score in suspected non-ST-elevation acute coronary syndrome: Final results of the FamouS Triage study. Eur. Heart J. Acute Cardiovasc. Care 2022, 11, 160–169. [Google Scholar] [CrossRef]
  44. Stopyra, J.P.; Snavely, A.C.; Scheidler, J.F.; Smith, L.M.; Nelson, R.D.; Winslow, J.E.; Pomper, G.J.; Ashburn, N.P.; Hendley, N.W.; Riley, R.F.; et al. Point-of-Care Troponin Testing during Ambulance Transport to Detect Acute Myocardial Infarction. Prehospital Emerg. Care 2020, 24, 751–759. [Google Scholar] [CrossRef] [PubMed]
  45. Hoorweg, B.B.; Willemsen, R.T.; Cleef, L.E.; Boogaerts, T.; Buntinx, F.; Glatz, J.F.; Dinant, G.J. Frequency of chest pain in primary care, diagnostic tests performed and final diagnoses. Heart 2017, 103, 1727–1732. [Google Scholar] [CrossRef] [PubMed]
  46. Norman, T.; Young, J.; Jones, J.S.; Egan, G.; Pickering, J.; Du Toit, S.; Hamilton, F.; Miller, R.; Frampton, C.; Devlin, G.; et al. Implementation and evaluation of a rural general practice assessment pathway for possible cardiac chest pain using point-of-care troponin testing: A pilot study. BMJ Open 2022, 12, e044801. [Google Scholar] [CrossRef]
  47. Dee, F.; Savage, L.; Leitch, J.W.; Collins, N.; Loten, C.; Fletcher, P.; French, J.; Weaver, N.; Watson, O.; Orvad, H.; et al. Management of Acute Coronary Syndromes in Patients in Rural Australia: The MORACS Randomized Clinical Trial. JAMA Cardiol. 2022, 7, 690–698. [Google Scholar] [CrossRef] [PubMed]
  48. Tideman, P.A.; Tirimacco, R.; Senior, D.P.; Setchell, J.J.; Huynh, L.T.; Tavella, R.; Aylward, P.E.G.; Chew, D.P.B. Impact of a regionalised clinical cardiac support network on mortality among rural patients with myocardial infarction. Med. J. Aust. 2014, 200, 157–160. [Google Scholar] [CrossRef]
  49. Miller, R.; Nixon, G.; Pickering, J.W.; Stokes, T.; Turner, R.M.; Young, J.; Gutenstein, M.; Smith, M.; Norman, T.; Watson, A.; et al. A prospective multi-centre study assessing the safety and effectiveness following the implementation of an accelerated chest pain pathway using point-of-care troponin for use in New Zealand rural hospital and primary care settings. Eur. Heart J. Acute Cardiovasc. Care 2022, 11, 418–427. [Google Scholar] [CrossRef]
  50. Grisel, B.; Adisa, O.; Sakita, F.M.; Tarimo, T.G.; Kweka, G.L.; Mlangi, J.J.; Maro, A.V.; Yamamoto, M.; Coaxum, L.; Arthur, D.; et al. Evaluating the performance of the HEART score in a Tanzanian emergency department. Acad. Emerg. Med. 2024, 31, 361–370. [Google Scholar] [CrossRef]
  51. Twerenbold, R.; Costabel, J.P.; Nestelberger, T.; Campos, R.; Wussler, D.; Arbucci, R.; Cortes, M.; Boeddinghaus, J.; Baumgartner, B.; Nickel, C.H.; et al. Outcome of Applying the ESC 0/1-hour Algorithm in Patients with Suspected Myocardial Infarction. J. Am. Coll. Cardiol. 2019, 74, 483–494. [Google Scholar] [CrossRef]
  52. Wildi, K.; Nelles, B.; Twerenbold, R.; Giménez, M.R.; Reichlin, T.; Singeisen, H.; Druey, S.; Haaf, P.; Sabti, Z.; Hillinger, P.; et al. Safety and efficacy of the 0 h/3 h protocol for rapid rule out of myocardial infarction. Am. Heart J. 2016, 181, 16–25. [Google Scholar] [CrossRef]
  53. Stoyanov, K.M.; Hund, H.; Biener, M.; Gandowitz, J.; Riedle, C.; Löhr, J.; Mueller-Hennessen, M.; Vafaie, M.; Katus, H.A.; Giannitsis, E. RAPID-CPU: A prospective study on implementation of the ESC 0/1-hour algorithm and safety of discharge after rule-out of myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care 2020, 9, 39–51. [Google Scholar] [CrossRef]
  54. Mahler, S.A.; Riley, R.F.; Hiestand, B.C.; Russell, G.B.; Hoekstra, J.W.; Lefebvre, C.W.; Nicks, B.A.; Cline, D.M.; Askew, K.L.; Elliott, S.B.; et al. The HEART Pathway Randomized Trial. Circ. Cardiovasc. Qual. Outcomes 2015, 8, 195–203. [Google Scholar] [CrossRef] [PubMed]
  55. Than, M.P.; Pickering, J.W.; Aldous, S.J.; Cullen, L.; Frampton, C.M.; Peacock, W.F.; Jaffe, A.S.; Goodacre, S.W.; Richards, A.M.; Ardagh, M.W.; et al. Effectiveness of EDACS Versus ADAPT Accelerated Diagnostic Pathways for Chest Pain: A Pragmatic Randomized Controlled Trial Embedded Within Practice. Ann. Emerg. Med. 2016, 68, 93–102.e1. [Google Scholar] [CrossRef] [PubMed]
  56. Parsonage, W.A.; Milburn, T.; Ashover, S.; Skoien, W.; Greenslade, J.H.; McCormack, L.; Cullen, L. Implementing change: Evaluating the Accelerated Chest pain Risk Evaluation (ACRE) project. Med. J. Aust. 2017, 207, 201–205. [Google Scholar] [CrossRef]
  57. Twerenbold, R.; Jaeger, C.; Rubini Gimenez, M.; Wildi, K.; Reichlin, T.; Nestelberger, T.; Boeddinghaus, J.; Grimm, K.; Puelacher, C.; Moehring, B.; et al. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur. Heart J. 2016, 37, 3324–3332. [Google Scholar] [CrossRef]
  58. Greenslade, J.H.; Parsonage, W.; Foran, L.; McCormack, L.; Ashover, S.; Milburn, T.; Berndt, S.; Than, M.; Brain, D.; Cullen, L. Widespread Introduction of a High-Sensitivity Troponin Assay: Assessing the Impact on Patients and Health Services. J. Clin. Med. 2020, 9, 1883. [Google Scholar] [CrossRef]
  59. Pickering, J.W.; Than, M.P.; Cullen, L.; Aldous, S.; ter Avest, E.; Body, R.; Carlton, E.W.; Collinson, P.; Dupuy, A.M.; Ekelund, U.; et al. Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection. Ann. Intern. Med. 2017, 166, 715–724. [Google Scholar] [CrossRef]
  60. Chew, D.P.; Lambrakis, K.; Blyth, A.; Seshadri, A.; Edmonds, M.J.R.; Briffa, T.; Cullen, L.A.; Quinn, S.; Karnon, J.; Chuang, A.; et al. A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes. Circulation 2019, 140, 1543–1556. [Google Scholar] [CrossRef]
  61. Chiang, C.H.; Chiang, C.H.; Lee, G.H.; Gi, W.T.; Wu, Y.K.; Huang, S.S.; Yeo, Y.H.; Giannitsis, E.; Lee, C.C. Safety and efficacy of the European Society of Cardiology 0/1-hour algorithm for diagnosis of myocardial infarction: Systematic review and meta-analysis. Heart 2020, 106, 985–991. [Google Scholar] [CrossRef]
  62. Anand, A.; Shah, A.S.V.; Beshiri, A.; Jaffe, A.S.; Mills, N.L. Global Adoption of High-Sensitivity Cardiac Troponins and the Universal Definition of Myocardial Infarction. Clin. Chem. 2019, 65, 484–489. [Google Scholar] [CrossRef]
  63. Bradburn, M.; Goodacre, S.W.; Fitzgerald, P.; Coats, T.; Gray, A.; Hassan, T.; Humphrey, J.; Kendall, J.; Smith, J.; Collinson, P.; et al. Interhospital variation in the RATPAC Trial (Randomised Assessment of Treatment using Panel Assay of Cardiac markers). Emerg. Med. J. 2012, 29, 233–238. [Google Scholar] [CrossRef]
  64. Ezekowitz, J.A.; Welsh, R.C.; Weiss, D.; Chan, M.; Keeble, W.; Khadour, F.; Sharma, S.; Tymchak, W.; Sookram, S.; Brass, N.; et al. Providing Rapid Out of Hospital Acute Cardiovascular Treatment 4 (PROACT-4). J. Am. Heart Assoc. 2015, 4, e002859. [Google Scholar] [CrossRef] [PubMed]
  65. Body, R.; Almashali, M.; Morris, N.; Moss, P.; Jarman, H.; Appelboam, A.; Parris, R.; Chan, L.; Walker, A.; Harrison, M.; et al. Diagnostic accuracy of the T-MACS decision aid with a contemporary point-of-care troponin assay. Heart 2019, 105, 768–774. [Google Scholar] [CrossRef] [PubMed]
  66. Cullen, L.; Greenslade, J.; Parsonage, W.; Stephensen, L.; Smith, S.W.; Sandoval, Y.; Ranasinghe, I.; Gaikwad, N.; Bayat, M.K.; Mahmoodi, E.; et al. Point-of-care high-sensitivity cardiac troponin in suspected acute myocardial infarction assessed at baseline and 2 h. Eur. Heart J. 2024, 45, 2508–2515. [Google Scholar] [CrossRef] [PubMed]
  67. Goodacre, S.; Nicholl, J.; Dixon, S.; Cross, E.; Angelini, K.; Arnold, J.; Revill, S.; Locker, T.; Capewell, S.J.; Quinney, D.; et al. Randomised controlled trial and economic evaluation of a chest pain observation unit compared with routine care. BMJ 2004, 328, 254. [Google Scholar] [CrossRef]
  68. Goodacre, S.W.; Quinney, D.; Revill, S.; Morris, F.; Capewell, S.; Nicholl, J. Patient and Primary Care Physician Satisfaction with Chest Pain Unit and Routine Care. Acad. Emerg. Med. 2004, 11, 827–833. [Google Scholar] [CrossRef]
  69. Shah, A.S.V.; Anand, A.; Strachan, F.E.; Ferry, A.V.; Lee, K.K.; Chapman, A.R.; Sandeman, D.; Stables, C.L.; Adamson, P.D.; Andrews, J.P.M.; et al. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: A stepped-wedge, cluster-randomised controlled trial. Lancet 2018, 392, 919–928. [Google Scholar] [CrossRef]
  70. Quinn, A.D.; Dixon, D.; Meenan, B.J. Barriers to hospital-based clinical adoption of point-of-care testing (POCT): A systematic narrative review. Crit. Rev. Clin. Lab. Sci. 2016, 53, 1–12. [Google Scholar] [CrossRef]
  71. Florkowski, C.; Don-Wauchope, A.; Gimenez, N.; Rodriguez-Capote, K.; Wils, J.; Zemlin, A. Point-of-care testing (POCT) and evidence-based laboratory medicine (EBLM)—Does it leverage any advantage in clinical decision making? Crit. Rev. Clin. Lab. Sci. 2017, 54, 471–494. [Google Scholar] [CrossRef]
  72. Halvorsen, S.; Mehilli, J.; Cassese, S.; Hall, T.S.; Abdelhamid, M.; Barbato, E.; De Hert, S.; de Laval, I.; Geisler, T.; Hinterbuchner, L.; et al. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery: Developed by the task force for cardiovascular assessment and management of patients undergoing non-cardiac surgery of the European Society of Cardiology (ESC) Endorsed by the European Society of Anaesthesiology and Intensive Care (ESAIC). Eur. Heart J. 2022, 43, 3826–3924. [Google Scholar] [CrossRef]
  73. Lyon, A.R.; Lopez-Fernandez, T.; Couch, L.S.; Asteggiano, R.; Aznar, M.C.; Bergler-Klein, J.; Boriani, G.; Cardinale, D.; Cordoba, R.; Cosyns, B.; et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur. Heart J. 2022, 43, 4229–4361. [Google Scholar] [CrossRef]
  74. Saenger, A.K. Pick a Number, Any Number…Choosing Your Troponin Cutoff Wisely. J. Appl. Lab. Med. 2019, 3, 753–755. [Google Scholar] [CrossRef] [PubMed]
  75. Boyko, E.J. Observational Research—Opportunities and Limitations. J. Diabetes Its Complicat. 2013, 27, 642–648. [Google Scholar] [CrossRef] [PubMed]
  76. Ryan, R.J.; Lindsell, C.J.; Hollander, J.E.; O’Neil, B.; Jackson, R.; Schreiber, D.; Christenson, R.; Gibler, W.B. A multicenter randomized controlled trial comparing central laboratory and point-of-care cardiac marker testing strategies: The Disposition Impacted by Serial Point of Care Markers in Acute Coronary Syndromes (DISPO-ACS) trial. Ann. Emerg. Med. 2009, 53, 321–328. [Google Scholar] [CrossRef] [PubMed]
  77. Asha, S.E.; Cooke, A.; Walter, E.; Weaver, J. Three-month outcome of patients with suspected acute coronary syndrome using point-of-care cardiac troponin-T testing compared with laboratory-based cardiac troponin-T testing: A randomised trial. Emerg. Med. J. 2015, 32, 601–607. [Google Scholar] [CrossRef]
  78. Goodacre, S.; Bradburn, M.; Fitzgerald, P.; Cross, E.; Collinson, P.; Gray, A.; Hall, A. The RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial: A randomised controlled trial of point-of-care cardiac markers in the emergency department. Health Technol. Assess. 2011, 15, 1–102. [Google Scholar] [CrossRef]
  79. Collinson, P.; John, C.; Lynch, S.; Rao, A.; Canepa-Anson, R.; Carson, E.; Cramp, D. A prospective randomized controlled trial of point-of-care testing on the coronary care unit. Ann. Clin. Biochem. 2004, 41, 397–404. [Google Scholar] [CrossRef]
  80. Loten, C.; Attia, J.; Hullick, C.; Marley, J.; McElduff, P. Point of care troponin decreases time in the emergency department for patients with possible acute coronary syndrome: A randomised controlled trial. Emerg. Med. J. 2010, 27, 194–198. [Google Scholar] [CrossRef]
  81. Renaud, B.; Maison, P.; Ngako, A.; Cunin, P.; Santin, A.; Hervé, J.; Salloum, M.; Calmettes, M.; Boraud, C.; Lemiale, V.; et al. Impact of Point-of-care Testing in the Emergency Department Evaluation and Treatment of Patients with Suspected Acute Coronary Syndromes. Acad. Emerg. Med. 2008, 15, 216–224. [Google Scholar] [CrossRef]
  82. Pickering, J.W.; Devlin, G.; Body, R.; Aldous, S.; Jaffe, A.S.; Apple, F.S.; Mills, N.; Troughton, R.W.; Kavsak, P.; Peacock, W.F.; et al. Protocol for Improving Care by FAster risk-STratification through use of high sensitivity point-of-care troponin in patients presenting with possible acute coronary syndrome in the EmeRgency department (ICare-FASTER): A stepped-wedge cluster randomised quality improvement initiative. BMJ Open 2024, 14, e083752. [Google Scholar] [CrossRef]
  83. Van Den Bulk, S.; Petrus, A.H.J.; Willemsen, R.T.A.; Boogers, M.J.; Meeder, J.G.; Rahel, B.M.; Van Den Akker-Van, M.E.; Numans, M.E.; Dinant, G.J.; Bonten, T.N. Ruling out acute coronary syndrome in primary care with a clinical decision rule and a capillary, high-sensitive troponin I point of care test: Study protocol of a diagnostic RCT in the Netherlands (POB HELP). BMJ Open 2023, 13, e071822. [Google Scholar] [CrossRef]
  84. O’Hara, M.; Wheatley, E.G.; Kazmierczak, S.C. The Impact of Undetected In Vitro Hemolysis or Sample Contamination on Patient Care and Outcomes in Point-of-Care Testing: A Retrospective Study. J. Appl. Lab. Med. 2020, 5, 332–341. [Google Scholar] [CrossRef] [PubMed]
  85. Lyngbakken, M.N.; Røsjø, H.; Holmen, O.L.; Nygård, S.; Dalen, H.; Hveem, K.; Omland, T. Gender, High-Sensitivity Troponin I, and the Risk of Cardiovascular Events (from the Nord-Trøndelag Health Study). Am. J. Cardiol. 2016, 118, 816–821. [Google Scholar] [CrossRef] [PubMed]
  86. Parikh, R.H.; Seliger, S.L.; de Lemos, J.; Nambi, V.; Christenson, R.; Ayers, C.; Sun, W.; Gottdiener, J.S.; Kuller, L.H.; Ballantyne, C.; et al. Prognostic Significance of High-Sensitivity Cardiac Troponin T Concentrations between the Limit of Blank and Limit of Detection in Community-Dwelling Adults: A Metaanalysis. Clin. Chem. 2015, 61, 1524–1531. [Google Scholar] [CrossRef] [PubMed]
  87. Seliger, S.L.; Hong, S.N.; Christenson, R.H.; Kronmal, R.; Daniels, L.B.; Lima, J.A.; De Lemos, J.A.; Bertoni, A.; Defilippi, C.R. High-Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure: MESA (Multi-Ethnic Study of Atherosclerosis). Circulation 2017, 135, 1494–1505. [Google Scholar] [CrossRef]
  88. Chen, Q.; Wu, W.; Wang, K.; Han, Z.; Yang, C. Methods for detecting of cardiac troponin I biomarkers for myocardial infarction using biosensors: A narrative review of recent research. J. Thorac. Dis. 2023, 15, 5112–5121. [Google Scholar] [CrossRef]
  89. Sengupta, S.; Biswal, S.; Titus, J.; Burman, A.; Reddy, K.; Fulwani, M.C.; Khan, A.; Deshpande, N.; Shrivastava, S.; Yanamala, N.; et al. A novel breakthrough in wrist-worn transdermal troponin-I-sensor assessment for acute myocardial infarction. Eur. Heart J.—Digit. Health 2023, 4, 145–154. [Google Scholar] [CrossRef]
  90. Domenico, T.; Rita, A.; Giacomo, S.; Diego, A.; Thelma, P.; Mariana, G.; Giampaolo, N.; Francesco, N.; Maria, G.; Francesco, F.; et al. Salivary biomarkers for diagnosis of acute myocardial infarction: A systematic review. Int. J. Cardiol. 2023, 371, 54–64. [Google Scholar] [CrossRef]
  91. Hu, X.; Li, J.; Li, Y.-T.; Zhang, Y.; Xiao, M.-M.; Zhang, Z.; Liu, Y.; Zhang, Z.-Y.; Zhang, G.-J. Plug-and-play smart transistor bio-chips implementing point-of-care diagnosis of AMI with modified CRISPR/Cas12a system. Biosens. Bioelectron. 2024, 246, 115909. [Google Scholar] [CrossRef]
  92. Chuang, E.-Y.; Ho, T.-L.; Wang, Y.-C.; Hsiao, Y.-C. Smartphone and home-based liquid crystal sensor for rapid screening of acute myocardial infarction by naked-eye observation and image analysis. Talanta 2022, 250, 123698. [Google Scholar] [CrossRef]
  93. Toprak, B.; Solleder, H.; Di Carluccio, E.; Greenslade, J.H.; Parsonage, W.A.; Schulz, K.; Cullen, L.; Apple, F.S.; Ziegler, A.; Blankenberg, S.; et al. Diagnostic accuracy of a machine learning algorithm using point-of-care high-sensitivity cardiac troponin I for rapid rule-out of myocardial infarction: A retrospective study. Lancet Digit. Health 2024, 6, e729–e738. [Google Scholar] [CrossRef]
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Figure 1. Summary of POC cTn assays’ varied potential beneficial healthcare applications going forwards.
Figure 1. Summary of POC cTn assays’ varied potential beneficial healthcare applications going forwards.
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Table 1. Specifications and analytical characteristics of current hs-cTn POC analysers as per International Federation of Clinical Chemistry Committee of Clinical Application of Cardiac Bio-Markers (IFCC C-CB) [13].
Table 1. Specifications and analytical characteristics of current hs-cTn POC analysers as per International Federation of Clinical Chemistry Committee of Clinical Application of Cardiac Bio-Markers (IFCC C-CB) [13].
AnalyserInstrument Size (Width × Length × Height in cm) *AssaySample TypeTime to Results (Minutes)LoD (ng/L)% Measured > LoD in Healthy
Population		99th Percentile (ng/L)%CV at 99th
Percentile
(Under Optimised Lab Conditions)
Atellica
VTLi
(Siemens Healthineers, Erlangen, Germany)		Portable
desktop
system;
8.5 × 25 × 5.2		hs-TnIHeparin-Li whole blood, plasma, or capillary blood≈81.2 (plasma), 1.6 (whole blood)Overall 84,
females 80,
males 87		Overall 22.9,
females 18.5, males 27.1		6.5 (plasma),
6.1 (whole blood)
PATHFAST (LSI Medicine Corporation, Tokyo, Japan)Compact
desktop
system;
34 × 57 × 48		hs-TnIHeparin-Na, heparin-Li, or EDTA whole blood or plasma<172.9Overall 66.3,
females 52.8, males 78.8		Overall 27.9,
females 20.3, males 29.7		6.1
TriageTrue (QuidelOrtho, San Diego, CA, USA)Portable bedside system;
no dimensions provided		hs-TnIEDTA whole blood or plasma<200.7–1.6 (plasma), 1.5–1.9 (whole blood)Overall ≥50Overall 20.5,
females 14.4, males 25.7		5.0–5.9 (plasma), 5.9–6.5 (whole blood)
* Where available, analysers’ dimensions taken from respective manufacturers’ websites. hs-TnI, high-sensitivity troponin I; LoD, limit of detection; CV, coefficient of variation.
Table 2. Published RCTs comparing POC testing and CLT of cTn in clinical practice.
Table 2. Published RCTs comparing POC testing and CLT of cTn in clinical practice.
TrialcTn Assays
Compared (POC vs. CLT) *		MI Diagnosis
Protocol		Outcomes
Measured		ResultsKey Limitations
Multicentre RCT of EDs in USA [76] Abbott i-Stat cTnI (Abbott Point of Care, Princeton, NJ, USA) vs. unspecified CLT cTnI
assay		Serial cTn testing over 6, 8, or 12 h; no cut-off value specifiedTime from
admission to discharge or transfer to inpatient
cardiology ward		Inconsistent changes in length of ED stay
between EDs		Sampling bias
introduced by exclusion of large proportion of
patients after
randomisation
Single-centre RCT in
Australian ED [77] 		AQT Flex cTnT (Radiometer, Copenhagen, Denmark) vs. Roche hs-cTnTAt least one 0/6-h cTn value > 14 ng/LMACE at 3 monthsNo significant
difference		Small sample size and unblinded
clinicians
RATPAC
multicentre RCT in UK EDs [78] 		Siemens Stratus CS panel (Dade Behring, Milton Keynes, UK) vs. Siemens cTnI ultra, Abbott cTnI, Beckman Accu TnI, or Roche cTnTAny cTn value > 0.07 μg/L or delta change between tests on admission and
after 90 min		Successful ED
discharge < 4 h, MACE at 3
months, and length of hospital stay		More early
discharges, fewer admissions, and no
significant
difference in MACE		Unblinded
clinicians
Single-centre RCT of coronary care unit admissions in UK [79] Roche Cardiac T test (Roche Diagnostics, Lewes, UK) vs. Bayer Axon cTnT (Bayer Diagnostics, Newbury, UK)cTn > 0.2 μg/L at 12 h after
admission		Length of hospital stay and 6-month mortalityShortened hospital stays with no
significant
difference in mortality		Small sample size
Two-centre cluster RCT in Australian EDs [80] Abbott i-Stat cTnI (Abbott Point of Care, Princeton, NJ, USA) vs. Beckman Coulter Accu TnI assay (Beckman Coulter, Fullerton, CA, USA)Not providedLength of ED stayInsignificant
reduction in length of ED stay		Underpowered as intervention not mandated so
significant proportion of patients did not receive POC testing
Single-centre RCT in ED in France [81] Siemens Stratus CS cTnI (Stratus CS Test Systems, Dade Behring, Marburg, Germany) vs. Dimension RxL-HM cTnI (Dade Behring, Newark, DE, USA)cTn > 0.1 μg/L but
timing not
provided		Time to NSTEMI therapy initiation and length of stay in EDReduced time to treatment commencement but no reduction in ED stay lengthSmall sample size and unblinded
clinicians
* Manufacturer names and locations provided when exact POC or CLT cTn testing device specified in RCT. cTn, cardiac troponin; MACE, major adverse cardiovascular event; NSTEMI, non-ST elevated myocardial infarction.
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Goldberg, A.; McGrath, S.; Marber, M. How Close Are We to Patient-Side Troponin Testing? J. Clin. Med. 2024, 13, 7570. https://doi.org/10.3390/jcm13247570

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Goldberg A, McGrath S, Marber M. How Close Are We to Patient-Side Troponin Testing? Journal of Clinical Medicine. 2024; 13(24):7570. https://doi.org/10.3390/jcm13247570

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Goldberg, Aaron, Samuel McGrath, and Michael Marber. 2024. "How Close Are We to Patient-Side Troponin Testing?" Journal of Clinical Medicine 13, no. 24: 7570. https://doi.org/10.3390/jcm13247570

APA Style

Goldberg, A., McGrath, S., & Marber, M. (2024). How Close Are We to Patient-Side Troponin Testing? Journal of Clinical Medicine, 13(24), 7570. https://doi.org/10.3390/jcm13247570

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