Dr Rachel Bastiaenen, PhD, St George's University of London, St George's Hospital London, UK

Chest pain is a common presenting complaint in the emergency department (ED) and investigation of acute cardiovascular disease is a major resource intensive public health challenge. The current standard of care involves troponin testing to ‘rule out’ a cardiac event. Recent advances in the sensitivity of troponin have led to a focus on earlier detection of events. In the ED, ruling out an acute coronary syndrome has been shown to be safe and effective within two hours.

The Providing Rapid Out of hospital Acute Cardiovascular Treatment 4 (PROACT-4) trial sought to answer whether pre-hospital point-of-care (POC) troponin testing in the ambulance further accelerated the time to diagnosis in patients with chest pain (excluding those with ST-elevation myocardial infarction and those with non-cardiac symptoms). 601 patients were randomised to usual care with troponin testing in the ED or POC-Troponin in the ambulance. The first troponin was available within 38 minutes in the POC-Troponin arm and within 139 minutes in the usual care arm. There was a borderline significant reduction in the primary endpoint (time from first medical contact to discharge from ED or admission to hospital) in the POC-Troponin patients compared with those receiving usual care (median 8.8 hours (6.2-10.8) vs median 9.1 hours (6.7-11.2); p=0.05).(1) There were no differences in clinical outcomes at 30 days.

Overall POC-Troponin testing reduced time to final disposition by 23 minutes in this Canadian patient population with chest pain. The reduction in time to final disposition was significant in patients discharged from the ED (in both intention to treat and per protocol analyses) but not in those admitted to hospital. POC-Troponin testing shows some potential as a method to reduce the bottleneck of chest pain patients in the ER. This approach could be valuable in countries with limited ER facilities, but it requires universal availability of ambulance POC-Troponin testing as well as a high level of pre-hospital expertise with paramedics trained to identify relevant patients. Geographical differences in usual care exist and putting this into practice would be more difficult in countries with fragmented healthcare systems in place. The choice of troponin assay is also important. Newer more sensitive assays exist and future randomised trials will be needed to assess these within the pre-hospital setting.

References

  • Ezekowitz JA, Welsh RC, Weiss D et al. Providing rapid out of hospital acute cardiovascular treatment (PROACT-4). J Am Heart Assoc 2015;4(12):e002859.
Cardio Debate Expert Comments

Cardiac troponins(cTnT, cTnI) for the diagnosis of acute coronary syndrome (ACS) is the accepted gold standard biochemical partner to clinical symptoms and associated electrocardiographic changes. Recently high sensitivity assays have been developed for routine immunoassay technology. The utility of high sensitivity assays can result in shorter testing protocols of admission and three hours, or even admission and 1 hour repeated testing. High sensitivity assays also identify patients without a final diagnosis of ACS but who have a positive cTn above the 99th percentile reference interval with an associated adverse risk. Therefore the evolving role of cTn testing is from a diagnostic confirmatory marker but in addition, a cardiovascular risk marker.

There are very limited data using point of care testing (POCT) for cTn in the pre-hospital setting. The majority utilised the initial rapid Trop T assay from Roche Diagnostics 1;2 3 which was far less sensitive than we are used to in current laboratory diagnostics. The cut off for AMI was 0.1 mg/L which equates to 100 ng/L in new units. By contrast, the current hs-cTnT assay has a 99th percentile cut off value of 14ng/L. There are even less published data utilising POCT cTnI 4 5;6.

What is important to remember is that the current POCT technology for cTn is not suitably analytically sensitive enough when compared to laboratory based immunoassay. To this end, they are reliable as rule in tests if patients are positive for cTn; however their role as a rule out marker is questionable due to the equivalent high cut off values employed.

In urban areas were patients receive rapid response to emergency calls within minutes with subsequent rapid transfer, the value of POCT is questionable. However, if a suitable sensitive POCT could be developed, this may have major benefit in rural areas where patients can be triaged to appropriate cardiac centres that offer immediate primary coronary interventional surgery. Furthermore, it is not common practice to draw venous blood samples in the prehospital setting by paramedical staff. There are a number of companies that are investing in new technology with the hope of delivering a sensitive POCT troponin test with the added benefit of possibly using finger prick testing rather than venepuncture. At present, it’s a case of watch this space.

References

  1. Newman J, Aulick N, Cheng T, Faynor S, Curtis R, Mercer D et al. Prehospital identification of acute coronary ischemia using a troponin T rapid assay. Prehosp.Emerg.Care 1999;3:97-101.
  2. Schuchert A, Hamm C, Scholz J, Klimmeck S, Goldmann B, Meinertz T. Prehospital testing for troponin T in patients with suspected acute myocardial infarction. Am.Heart J 1999;138:45-8.
  3. Sorensen JT, Terkelsen CJ, Steengaard C, Lassen JF, Trautner S, Christensen EF et al. Prehospital troponin T testing in the diagnosis and triage of patients with suspected acute myocardial infarction. Am.J.Cardiol. 2011;107:1436-40.
  4. Dumas F, Manzo-Silberman S, Fichet J, Mami Z, Zuber B, Vivien B et al. Can early cardiac troponin I measurement help to predict recent coronary occlusion in out-of-hospital cardiac arrest survivors? Crit Care Med. 2012;40:1777-84.
  5. Venturini JM, Stake CE, Cichon ME. Prehospital point-of-care testing for troponin: are the results reliable? Prehosp.Emerg.Care 2013;17:88-91.
  6. Ezekowitz JA, Welsh RC, Weiss D, Chan M, Keeble W, Khadour F et al. Providing Rapid Out of Hospital Acute Cardiovascular Treatment 4 (PROACT-4). J.Am.Heart Assoc. 2015;4.

Troponins (Tns) have a pivotal role in acute myocardial infarction (AMI) diagnosis. According to the Third Universal Definition of Myocardial Infarction, AMI is defined as evidence of myocardial necrosis (diagnosed with Tns) in a clinical setting consistent with AMI (according to symptoms, ECG findings or imaging evidence). The introduction of the high sensitivity tests for cardiac troponins (hs-cTns) increased both sensitivity and specificity for acute myocardial necrosis, while decreasing at the same time the specificity for AMI. The list of non-AMI and non-cardiac causes of increased hs-cTns has become progressively longer in conjunction with the increase in test sensitivity.

In STEMI patients to measure hs-cTns is not useful neither for diagnosis nor for risk stratification: the diagnosis is based on clinical data and ECG findings and treatment is independent from hs-cTns levels. On the contrary, in the case of NSTEACS, hs-cTns are very important, firstly to differentiate unstable angina from NSTEMI, secondly to stratify the risk (patients with elevated hs-cTns are at high risk by definition) and thirdly to suggestthe therapeutic strategy.

However, the pre-hospital determination of hs-cTns could not be useful, for several reasons. Among the subjects with chest pain, the proportion of patients with NSTEMI is about 10% only: the rule-in and rule-out of NSTEMI frequently need repeated ECGs, multiple hs-cTns determinations and imaging investigations; moreover, reperfusion treatment is NSTEMI is rarely urgent (≤ 2 hrs) and in the vast majority of cases is indicated within 24 hrs. In NSTEMI there is no indication to skip the ER and to go directly to the ICCU or cath lab: we can not expect a significant decrease in the crowding of ER. Finally, the point-of care (POC) tests for hs-cTns have a reduced sensitivity in comparison with the laboratory determinations and false negative tests could not be infrequent.

Therefore, it is not only difficult (particularly with a POC test) but probably useless to diagnose NSTEMI in the pre-hospital setting: if the test is positive, we still have to rule out the non-AMI and non-cardiac causes of hs-cTns elevations; if the test is negative, we have to repeat it in the hospital laboratory, also to exclude a lack of sensitivity.