The clinical work-up of patients with chest pain and dyspnoea for selected diagnoses, and the use of point-of-care testing in the process are discussed
Ulf Martin Schilling MD PhD
Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Sweden
Department of Accidents and Emergencies, University Hospital of Linköping, Sweden
The applicability of point-of-care testing (POCT) at the emergency department in the patient with undifferentiated chest pain has been documented.(1) Chest pain is the main complaint of approximately 5% of all emergency patients, and dyspnoea accounts for approximately 3.5%. In this article, we focus on the clinical work-up of patients with chest pain and dyspnoea by selected diagnoses and the use of POCT in the process.
Differential diagnoses of immediately life-threatening causes of chest pain and dyspnoea are acute myocardial infarction (AMI), cardiac tamponade, aortic dissection, perimyocarditis, tension pneumothorax, pulmonary oedema, pulmonary embolism (PE), severe pneumonia, pleural empyema and COPD/asthma (Table 1). This article focuses on acute coronary syndromes and pulmonary embolism.
Acute coronary syndromes
AMI and unstable angina pectoris (UAP), referred to as acute coronary syndromes, are potentially immediately life-threatening causes of chest pain requiring emergency care. With the diagnosis of ST-elevation myocardial infarction (STEMI) established with high fidelity on the finding of typical changes of the ECG and by the clinical picture, the diagnosis of non-STEMI (NSTEMI) and UAP might prove more difficult.
Up to 5% of AMIs were missed by emergency physicians according to the literature, and 25% of malpractice suits for emergency physicians were in the US. Whereas patients with STEMI are defined as high-risk patients and require immediate admission and therapy, patients with potential NSTEMI and UAP require workup at the ED or on admission. The workup includes the assessment of risk for a cardiac event based on the patient’s history and risk profile, the physician’s clinical experience and scoring systems, for example, the widely spread TIMI score (Table 2)(2) or the less commonly used HEART score, among others.(3)
Cardiac biomarkers and troponins
Interestingly, both scoring systems include the measurement of cardiac biomarkers for risk assessment, and the current definition of MI does include elevated cardiac markers, preferably troponins for all non-fatal MIs, as recommended by the consensus guidelines of the American College of Cardiology (ACC) and the European Society of Cardiology (ESC) (Table 3). A number of troponin subtypes exist and have been used in clinical testing for more than 15 years; however, the discussion about which subtype might prove superior in testing is still ongoing. At present, POCT for virtually all different troponins are available, allowing the clinician a rapid work-up of the patient with chest pain.
Because the common tests for troponins might be indiscriminate at the range of the cut-off level because of technical reasons, some centres have adopted the high-sensitivity troponin assays instead. In cases of repeated testing, one troponin above the recommended cut-off limit at the 99th percentile (or 10% coefficient of variation) is considered diagnostic of MI. Troponins are commonly elevated in patients with chronic renal failure, making interpretation in these patients notoriously difficult.
Thus, in these patients repeated testing might be beneficial if the clinical picture is inconclusive. Unfortunately, many patients with chronic arenal failure are elderly and suffer from concomitant disease such as hypertension, dyslipidaemia and long-standing diabetes mellitus with secondary complications, and might suffer both diabetic as uraemic polyneuropathy, defining them as patients at high risk for MI. Elevated baseline troponin levels are not infrequent in these patients, and have been shown to correlate with the long-term prognosis irrespective of any actual MI. As a clinical result, such patients are admitted to the hospital for further work-up, potentially resulting in a shortage of beds and elevated costs because of repeated admissions.
Work-up strategies in chest pain patients
Several protocols to rule out MI on the basis of biomarker testing are applied in emergency medicine; the majority of these protocols are based on serial sampling with different intervals, and result in admission to either an observation/chest-pain unit, or more intense cardiac surveillance depending on the estimated risk for MI and UAP. The three major diagnostic strategies to rule out MI are:
- Admission of the patient for serial testing, re-evaluation and stress-test in selected cases
- Rapid serial testing and stress-test(4,5)
- Combination with novel biomarkers.
Chest pain units have been shown to reduce the length of hospital stay for chest pain patients, and therefore to be cost efficient. However, by using novel protocols such as rapid serial testing, the majority of admissions can be avoided, which might result in reduced costs in the work-up of patients with chest pain, and thus might be of major interest in current practice. Novel biomarkers, in turn, might facilitate the exclusion of coronary syndromes at the emergency department on first-line testing and result in even further reduction of admissions (and thus costs), but have yet to prove their practical value.
Novel biomarkers
During recent years, several novel biomarkers to rule out MI have been tested in clinical trials. Most of these can still be considered to be at the experimental level, which is reflected in their omission in the actual guidelines. Some of these biomarkers are available in POCT, giving the potential of enhancing the processing of the patient at the emergency department. In the majority of the published trials, these novel biomarkers have been tested in combination with troponin assays to reduce the diagnostic gap during the first hours directly after MI in which troponin testing might be negative owing to the physiology of troponin release on cardiac necrosis.
Examples of biomarkers under current discussion are: heart-type fatty acid binding protein (H-FABP), a marker of myocardial stress supposedly released before final necrosis occurs and relatively specific for myocardial ischaemia(6,7); and copeptin, a precursor to the hypothalamic stress hormone arginine–vasopressin elevated in major pathologies such as AMI, PE, sepsis, severe pneumonia and stroke.(8,9)
Recently, the use of cardiac computed tomography scans has been introduced in clinical practice to visualise the coronary arteries and to exclude significant coronary artery stenosis in patients at low risk of acute coronary syndromes, which reduces the costs for admission, stress tests and invasive investigations.(10)
Pulmonary embolism
PE still poses major difficulties to the clinician, as it can present with a wide range of symptoms, from sudden cardiac arrest to non-specified general weakness in the elderly, chest pain, dyspnoea or recurrent pneumonia despite antibiotic therapy. Because of this, the exact incidence of PE in the emergency department remains uncertain, with estimates varying between 1:100 and 1:500 patients. Clinical experience and specialty seem related to the suspicion and diagnosis of PE.(11,12)
Furthermore, PE might be a manifestation of underlying severe disease, especially malignancy and coagulation disorders. While the latter can be screened by measurement of International normalised ratio and activated partial thromboplastin time, the exclusion of malignancy as the underlying cause of PE requires extensive investigation.
Beside the diagnostic difficulties in detecting PE and the broad clinical spectrum, prognosis can be difficult to judge. As a result, the detection of PE will most commonly result in initial admission, anticoagulation therapy for prolonged periods and/or thrombolysis and further work-up to exclude potential underlying causes of PE, as for example coagulation disorders and malignancy.
Because of the difficulty in ruling out PE clinically, decision rules to determine the probability of PE have been developed. The two scoring systems most discussed in the current literature are the Wells score (McMasters criteria) and the Revised Geneva Score (Wicki) (Table 4). Both these scoring systems were compared in several trials and found to be equal in their diagnostic values.(13)
Interestingly, only the Revised Geneva Score uses POCT in the scoring system (by analysis of the arterial blood gas). However, in addition to the scoring system used to assess the probability of PE in the single patient, further testing is required to rule out PE after the assessment. A current recommendation for ruling out PE is shown in Figure 1.
Essentially, it is based on the analysis of D-dimer in patients at low risk, and on the V/Q-scan or pulmonary CT-angiography for patients at moderate and high risk. Because of the requirement for IV contrast during the pulmonary CT-scan the determination of renal function, that is clearance measurements, might be useful. A common way is to estimate clearance using the Cockcroft-Gault formula, using age, weight, gender and the level of creatinine that might be determined by POCT to avoid time delays in processing at the emergency department.
D-dimer is a degradation product of fibrin and is suggestive of fibrinolysis, that is, the degradation of blood clots. Its main use is the exclusion of thrombembolism in patients with a low pretest probability of this disease, and in combination with a negative ultrasound in patients with a moderate-to-high pretest probability of deep venous thrombosis. Unfortunately, D-dimer is elevated in a number of disorders and cannot be used to diagnose thrombosis by blood analysis only (Table 5).
The combination of D-dimer, leg ultrasound and CT-scan has been shown to be one of the most cost-efficient strategies for the detection of PE.(14,15) Given the possibility of ultrasound at the emergency department to allow the diagnosis of leg deep venous thrombosis (the most common source of PE), echocardiography (presenting potential right ventricular strain suggestive of PE) and the analysis of D-dimers, the clinician can rule out PE in the majority of patients presenting with dyspnoea and chest pain, resulting in the reduction of CT- and V/Q-scans and cost-intensive (unnecessary) admissions.(16)
Conclusions
In conclusion, chest pain and dyspnoea are common presentations at the emergency department. Acute coronary syndromes and PE are frequent causes of these symptoms, and major reasons for expensive malpractice claims. Both pathologies can be detected by the application of scoring systems, the use of biomarkers and routine testing available as POCT, bedside ultrasound and stress tests combined with CT-investigations. At present, clinical guidelines and clinical practice are in a period of change and continuous revision. The technical advances in imaging modalities, and evolving new biomarkers, are currently on the brink of changing the work-up of patients with chest pain and dyspnoea, with the potential of reducing unnecessary admissions and, as a result, generating major economic savings for hospitals and emergency departments.
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