DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design.

BACKGROUND: Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice. METHODS: This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds. CONCLUSIONS: The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Accelerated -Rule-Out of acute Myocardial Infarction using prehospital copeptin and in-hospital troponin: The AROMI study.

AIMS: The present acute myocardial infarction (AMI) rule-out strategies are challenged by the late temporal release of cardiac troponin. Copeptin is a non-specific biomarker of endogenous stress and rises early in AMI, covering the early period where troponin is still normal. An accelerated dual-marker rule-out strategy combining prehospital copeptin and in-hospital high-sensitivity troponin T could reduce length of hospital stay and thus the burden on the health care systems worldwide. The AROMI trial aimed to evaluate if the accelerated dual-marker rule-out strategy could safely reduce length of stay in patients discharged after early rule-out of AMI. METHODS AND RESULTS: Patients with suspected AMI transported to hospital by ambulance were randomized 1:1 to either accelerated rule-out using copeptin measured in a prehospital blood sample and high-sensitivity troponin T measured at arrival to hospital or to standard rule-out using a 0 h/3 h rule-out strategy. The AROMI study included 4351 patients with suspected AMI. The accelerated dual-marker rule-out strategy reduced mean length of stay by 0.9 h (95% confidence interval 0.7-1.1 h) in patients discharged after rule-out of AMI and was non-inferior regarding 30-day major adverse cardiac events when compared to standard rule-out (absolute risk difference -0.4%, 95% confidence interval -2.5 to 1.7; P-value for non-inferiority = 0.013). CONCLUSION: Accelerated dual marker rule-out of AMI, using a combination of prehospital copeptin and first in-hospital high-sensitivity troponin T, reduces length of hospital stay without increasing the rate of 30-day major adverse cardiac events as compared to using a 0 h/3 h rule-out strategy.

Non-cardiac causes of troponin elevation.

With the increased sensitivity of the newest cardiac troponin assays, the risk of false positive cardiac troponin measurements has also increased. As summarised in this review, there are multiple possible causes of cardiac troponin release including several non-cardiac illnesses, particularly kidney disease. Further, there is a risk of analytical interference in which case repeated measurements with a different assay is a good tool. When there is a discrepancy between troponin measurement and clinical presentation of the patient, the clinician should consider the possibility of analytical interference.

[Practical use of natriuretic peptides in suspected heart failure in the primary and secundary sector].

Natriuretic peptides (NP) play a key role in the regulation of the body's water and salt balance and may effectively contribute to the diagnosis of patients with heart failure. NP-measurements are increasingly used internationally, but despite being available for more than ten years, neither a rational implementation nor clinical guidelines for use exist in Denmark. In this review, we present a practical approach to the use of NP in general practice and in the emergency department based on a newly published position paper from the Danish Society of Cardiology.

Chest pain in the ambulance; prevalence, causes and outcome - a retrospective cohort study.

BACKGROUND: Chest pain is common in acute ambulance transports. This study aims to characterize and compare ambulance-transported chest pain patients to non-chest pain patients and evaluate if patient characteristics and accompanying symptoms accessible at the time of emergency call can predict cause and outcome in chest pain patients. METHODS: Retrospective, observational population-based study, including acute ambulance transports. Patient characteristics and symptoms are included in a multivariable risk model to identify characteristics, associated with being discharged without an acute cardiac diagnosis and surviving 30 days after chest pain event. RESULTS: In total, 10,033 of 61,088 (16.4%) acute ambulance transports were due to chest pain. In chest pain patients, 30-day mortality was 2.1% (95%CI 1.8-2.4) compared to 6.0% (95%CI 5.7-6.2) in non-chest pain patients. Of chest pain patients, 1054 (10.5%) were diagnosed with acute myocardial infarction, and 5068 (50.5%) were discharged without any diagnosis of disease. This no-diagnosis group had very low 30-day mortality, 0.4% (95%CI 0.2-0.9). Female gender, younger age, chronic pulmonary disease, absence of accompanying symptoms of dyspnoea, radiation, severe pain for > 5 min, clammy skin, uncomfortable, and nausea were associated with being discharged without an acute cardiac diagnosis and surviving 30 days after a chest pain event. CONCLUSION: Chest pain is a common reason for ambulance transport, but the majority of patients are discharged without a diagnosis and with a high survival rate. Early risk prediction seems to hold a potential for resource downgrading and thus cost-saving in selected chest pain patients.

A multicentre, randomized, controlled open-label trial to compare an Accelerated Rule-Out protocol using combined prehospital copeptin and in-hospital high sensitive troponin with standard rule-out in patients suspected of acute Myocardial Infarction - the AROMI trial.

BACKGROUND: Suspicion of acute myocardial infarction (AMI) is among the most common reasons for admission to hospital in Denmark. Owing to this suspicion, an estimated 50,000 patients are admitted every year. Only 15-20% are finally diagnosed with AMI, whereas 40% are discharged after rule-out of AMI and without initiation of any treatment or need for further admission. In patients discharged after rule-out, the current diagnostic protocol, using consecutive troponin measurements, results in an average length of stay (LOS) of 8-12 h. This leads to overcrowding in both the emergency departments and coronary care units. Measuring copeptin and high-sensitivity cardiac troponin (hs-cTn) upon hospital arrival has shown potential for early rule-out of AMI. However, the diagnostic performance may be improved by accelerating the copeptin measurement of blood sampled already in the pre-hospital phase. Additional evidence on LOS reduction and safety of the rule-out strategy in a large cohort of all-comers is needed. METHODS/DESIGN: The rule-out potential is being evaluated in a randomized controlled trial including 4800 patients admitted to hospital for suspicion of AMI. Patients are randomized to either standard rule-out (consecutive troponin measurements) or accelerated rule-out (copeptin measured in a blood sample acquired before hospital admission, combined with troponin measured in the first blood sample upon admission). DISCUSSION: Sampling blood for copeptin analysis already in the pre-hospital phase and combining this with a later hs-cTn measurement may be the optimal timing for achieving the best diagnostic performance in an AMI rule-out protocol/strategy. Moreover, we are directly comparing pre-hospital and in-hospital blood sample results to address this issue of timing, and we also are comparing single-marker strategies with dual-marker strategies. If the combination of copeptin and hs-cTn is confirmed to rule out AMI safely, implementation of this fast rule-out protocol could optimize patient flow, reduce health care expenses and enable allocation of resources to patients with confirmed illness. In future, when point-of-care analyses of copeptin and hs-cTn are available, hospitalization of the large proportion of patients with symptoms raising suspicion of AMI could potentially be avoided. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02666326 . Registered on January 24, 2016.

The potential of optimizing prehospital triage of patients with suspected acute myocardial infarction using high-sensitivity cardiac troponin T and copeptin.

PURPOSE: In patients with a suspected acute myocardial infarction (AMI), to evaluate the potential for early triage based on measurement of high-sensitivity cardiac troponin T (hs-cTnT) and copeptin in blood samples collected in the prehospital phase. MATERIALS AND METHODS: In this retrospective study, we measured hs-cTnT and copeptin in blood samples collected in the ambulance form 962 patients with suspected AMI. The diagnostic accuracy was estimated by receiver-operating characteristic (ROC) curve area under the curve (AUC) for both biomarkers and a combined model. Multivariable Cox regression modelling was used to estimate the predictive value of both biomarkers. RESULTS: In total, 178 (19%) cases had AMI. The AUC for hs-cTnT was 0.81. Adding copeptin increased the AUC to 0.85 (p = 0.004) and the combined model allowed a prehospital rule-out of 45% of cases without AMI (negative predictive value, NPV 98%). Both biomarkers are highly predictive of outcome. CONCLUSIONS: A future application of hs-cTnT and copeptin measurement, performed already in the prehospital phase, could potentially improve the prehospital diagnostic and prognostic classification of patients with a suspected AMI.

Prehospital diagnosis of patients with acute myocardial infarction.

Primary percutaneous intervention (PPCI) is the preferred treatment in patients with ST elevation myocardial infarction (STEMI) if this can be performed in a timely manner. The 2012 ESC Guidelines on management of AMI in patients presenting with ST-segment elevation advice that PPCI should be performed within 120 min of first medical contact. Prehospital diagnosis of patients with STEMI is performed to save time and make PPCI available to the majority of patients. Although diagnosing patients with STEMI is usually easy, there are important pitfalls and patients with STEMI are missed on occasion. In addition, it is well know that patients without ST elevation may also have a high-risk cardiac condition. The 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation stress the importance of urgent CAG in patients with high-risk non ST-segment elevation myocardial infarction (NSTEMI). Unfortunately, these patients are difficult to diagnose in the acute phase and important time may be spend establishing the correct diagnosis. Prehospital biomarker measurement has emerged as a method to gain important additional information. We review the evidence on prehospital diagnosis of patients with STEMI and, In addition, we present the current knowledge on the new diagnostic methods that could have a future role in prehospital rule-in and rule-out of cardiac disease.