Ready for rapid rule-out of acute myocardial infarction

Graphical Abstract

Pros and cons of a dual biomarker strategy for patients with a suspected acute myocardial infarction (AMI). Suspected AMI patients are transported to the emergency department (ED) to rule-in or rule-out an AMI. Chest pain is the most common reason for emergency medical contact and ED overcrowding is a growing problem worldwide. To reduce ED overcrowding, the efficiency of the diagnostic pathway of chest pain needs to improve. The AROMI study proposes an accelerated dual biomarker strategy to reduce the length of stay in the ED, which could reduce ED overcrowding. Pre-hospital strategies for rule-out of AMI could also improve the efficiency of the diagnostic pathway of chest pain. Together with pre-hospital strategies, the AROMI study further opens the door to rapid rule-out of AMI.

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This editorial refers to ‘Accelerated Rule-Out of acute Myocardial Infarction using prehospital copeptin and in-hospital troponin: The AROMI study’, by C.K. Pedersen et al., https://doi.org/10.1093/eurheartj/ehad447.

Emergency department (ED) overcrowding is a growing problem worldwide, associated with increased length of stay (LOS), worse patient outcomes, and high costs.¹ A suspected acute coronary syndrome (ACS) is the most common reason for emergency medical contact.² However, ACS is found in only a small proportion of chest pain patients at the ED, and the majority are discharged within 24 h.³ Low-risk patients in particular, in whom a true ACS is rarely found, are not likely to benefit from these expensive, resource-intensive, and lengthy ED visits.^4,5 To reduce ED overcrowding and unnecessary healthcare resource consumption, the efficiency of triage and diagnostic work-up in chest pain patients has to improve. One way to achieve this goal is by reducing the time to discharge from the ED, which is why a 0 h/1 h algorithm for rapid rule-out and rule-in of non-ST-segment elevation ACS is recommended in the 2020 European Society of Cardiology (ESC) guidelines, instead of the previously recommended 0 h/3 h algorithm.⁶ Another way to reduce the time to discharge might be the use of a dual biomarker strategy, as tested in the AROMI (Accelerated Rule-Out of AMI) trial, presented in this issue of the European Heart Journal.⁷ Pedersen and colleagues need to be commended for an excellent study, using innovative technology, implemented in a large number of patients, and conducted in the very well organized healthcare infrastructure of Denmark. Patients suspected of having an acute myocardial infarction (AMI) were randomized to either an accelerated diagnostic protocol using a dual biomarker strategy of copeptin in a pre-hospital acquired blood sample in combination with the first in-hospital high-sensitivity cardiac troponin T (hs-cTnT) measurement (hence a −1 h/0 h strategy), or a standard single biomarker strategy (0 h/3 h in-hospital hs-cTnT algorithm). The rationale of the dual biomarker strategy is that copeptin concentrations rise earlier than troponin in AMI.⁷ The primary efficacy endpoint was LOS and the primary safety endpoint was a combined endpoint of major adverse cardiac events (MACE) within 30 days after randomization (Graphical Abstract).

The study was prematurely terminated after recommendation from the study Data and Safety Monitoring Board, due to a change in the availability of hs-cTnT at two of the three recruiting hospitals, which resulted in a total of 4351 patients in the final study cohort, which was just over 90% of the calculated sample size of 4772 patients. The mean LOS was significantly shorter in the accelerated group (6.9 h), as compared with the standard group (7.8 h), with a mean difference of 0.9 h. The proportion of patients discharged within 12 h of admission was ∼47% in both groups. The accelerated diagnostic protocol was non-inferior to the standard protocol regarding MACE at 30 days (14.2% vs. 14.5%, P-value for non-inferiority = .009, absolute risk difference −0.4% [95% confidence interval −2.6 to 1.6]).

The AROMI trial is an important step towards more efficient triage and diagnostic work-up of patients with chest pain. If the pre-hospital copeptin concentration is low and only one hs-cTnT concentration is required to rule-out AMI, a diagnostic setting with a −1 h/0 h one-touch-approach could be implemented, in which the treating physician examines the patient with direct availability of all results required for rule-out. However, some important aspects need to be discussed.

First, as the authors clearly state, the standard diagnostic protocol in this study was the ESC 0 h/3 h algorithm, whereas currently the ESC 0 h/1 h algorithm is recommended.⁶ A previous randomized trial has shown that the 0 h/1 h algorithm reduces the LOS by 1 h, as compared with the 0 h/3 h algorithm, which raises the question of whether the accelerated diagnostic protocol with dual biomarker measurement will reduce LOS in the current system in which the 0 h/1 h algorithm is recommended.⁸ Maybe even more importantly, the 0 h/1 h algorithm is not yet universally implemented and should be prioritized on a wider scale to reduce LOS. Secondly, the LOS in the AROMI study was substantial and longer than previously shown in other studies, especially when compared with studies with the ESC 0 h/1 h algorithm.^8,9 When taking the turn-around time of the high sensitive troponin measurement (∼60 min) into account, patients stayed for another 6–7 h at the cardiac department until discharge. It is unclear whether this is due to administrative tasks, shortage of personnel, or additional troponin measurements and other diagnostic tests. Moreover, these were the mean LOSs of the patients who were discharged from the cardiac department within 12 h, which was only the case in 47% of the total study population. Since the other 53% were discharged from the cardiac department after 12 h, the mean LOS of the total population is expected to be much longer. Perhaps the long LOS in general could be explained by the setting in which these patients were admitted. In contrast to many other countries, suspected ACS patients in Denmark bypass the ED and are directly admitted to a cardiac department for diagnostic work-up. Third, copeptin can currently only be measured by a single analyser. Fourth, as the authors have mentioned, the generalizability of their results is currently limited to hospitals using hs-cTnT assays, not high-sensitivity troponin I assays. However, no differences in diagnostic performances are expected from a theoretical viewpoint. Fifth, copeptin is a biomarker quantifying endogenous stress, which can be elevated in several other conditions apart from AMI, such as diabetes, renal disease, heart failure, and even psychological stress.¹⁰ Therefore, using copeptin in addition to troponin could lead to higher false-positive rates for detecting AMI. At the same time, it might help to recognize alternative diagnoses as mentioned above, requiring further evaluation. Also, the reported negative predictive value of the dual biomarker approach in the present cohort was 99.6% and even 100% when lowering the threshold for hs-cTnT to the same cut-off point value as the ESC 0 h/1 h algorithm (12 ng/L instead of 14 ng/L).

Another way to reduce ED overcrowding, apart from reducing the time to discharge, is by reducing the number of patients presenting at the ED in the first place by implementation of pre-hospital rule-out of AMI. Pre-hospital risk stratification and pre-hospital rule-out strategies can reduce the number of ED admissions and lead to large cost savings by a more efficient use of healthcare resources.^11–14 The AROMI study further opens the door to pre-hospital rule-out of AMI. A strategy of pre-hospital rule-out is not yet recommended by the guidelines, but, if proven to be safe, this could lead to tremendous cost savings. We previously showed that such a strategy would lead to annual cost savings in the Netherlands alone of approximately €48 million. A recent cost analysis from Australia showed very similar results, with large cost savings after pre-hospital risk stratification and point of care (POC) troponin testing.¹⁴ Also, such a strategy would truly alleviate the pressure on emergency care services in the hospital. Previous studies have shown that 39.3% of all chest pain patients currently presenting to the ED are actually low-risk patients.^4,12 Pre-hospital rule-out with POC troponin and possibly POC copeptin measurements would greatly reduce the number of ED visits for chest pain. Future availability of POC copeptin, possibly in combination with a high-sensitivity POC troponin assay or on automatic ‘laboratory streets’, will be of potential benefit for early presenters with a symptom onset <2 h and a low clinical risk. Combining an accelerated dual biomarker strategy, like the AROMI study, and a pre-hospital rule-out strategy, like the ARTICA trial, could prove to be safe and cost-effective for millions of patients with acute chest pain worldwide.

In conclusion, improvement of the diagnostic pathway of chest pain patients could reduce ED overcrowding. Efficiency can be improved in both the pre-hospital triage and the in-hospital evaluation, so we have to pursue a combined approach, reducing the number of chest pain patients in the hospital and reducing the time patients spend at the hospital. The recently introduced 0 h/1 h algorithm has permitted rapid rule-out of AMI in hospital. The use of pre-hospital retrieved copeptin in a −1 h/0 h strategy can further reduce the LOS. Even a 1 h reduction, as shown in the AROMI study, can have massive implications on costs and availability of emergency care services, simply by the sheer number of patients. Finally, rapid rule-out of AMI outside the hospital is on the horizon, and the results of the AROMI study have certainly brought us closer.

Declarations

Disclosure of Interest

All authors declare no conflict of interest for this contribution.

References

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