FASTEST - Fast ASsessment of Thoracic pain with EcTomography.
Patients presenting with chest pain or other symptoms suggestive of an acute coronary syndrome (ACS) amount today to about 20% of all visits to the emergency department 1. Of the two thirds who will be admitted, approximately 60% will be found to have ACS, whereas the remaining 40% will be diagnosed with other cardiac or non-cardiac causes. In the low- and moderate risk groups the rate of ACS is much lower (4-8%). However, 2-4 % of the patients with ACS are mistakenly sent home from the emergency department, and these patients have a worse outcome than those who are hospitalized 2-4. Thus, the early assessment of these patients is still a difficult task for the clinician and a major health issue for the community. Although new biomarkers of myocardial damage, such as cardiac troponins, have improved the early detection of ischemia, levels of these biomarkers do not rise until several hours after the ischemic event and normal levels do not exclude the presence of ACS. Thus, exclusion of ACS is often a time- and resource-consuming process. Therefore, new and faster strategies for early rule-in or rule-out ACS are needed.
According to present guidelines 5-7 the initial assessment of patients with possible ACS should include history, physical examination, ECG and cardiac markers (troponin T or I). If presence of symptoms reproducing prior documented angina, signs of heart failure, new significant ST-T changes or elevated cardiac markers, the diagnosis of ACS is very likely and current guidelines regarding treatment of ACS should usually be applied. If these signs are absent but a diagnosis of ACS is still possible or probable the patient is observed with repeated ECGs (or continuous ST-monitoring) and repeated measurements of cardiac markers 6-12 hours after admission and in some patients for even longer time period. If there are no new ECG-changes and cardiac markers are normal these patients may be evaluated by a stress-test before discharge.
Myocardial Perfusion Scintigraphy
Several studies have shown that strategies using myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) after injection of technetium-99m at rest have a high sensitivity (90-100%) to detect myocardial infarction in this population, and that patients discharged home with negative scans have a low likelihood of subsequent cardiac events 8-14. Myocardial perfusion imaging at rest for assessment of myocardial risk in possible ACS patients with non-diagnostic ECG and normal initial cardiac markers was therefore a "class IA-recommendation" in the latest guidelines from the American college of cardiology and American heart association regarding cardiac radionuclide imaging 15. However, the clinical use of MPI has so far been limited, mainly because SPECT is not easily available in the clinical routine and patients need to be transported to the camera.
By the use of ectomograhy, which is a limited-view angle method for acquisition of images, a mobile gamma camera has been developed. This gamma camera has been shown to provide information similar to that obtained by SPECT 16. However, the usefulness of this mobile gamma camera for early rule-in or rule-out in chest pain patients has so far not been tested.
Echocardiography has been proven efficient in risk stratification of patients with suspected ACS in several studies 17-19. Traditional echocardiography, using visual assessment of regional wall motion abnormalities, has however a serious limitations in being subjective and user dependent. The technical development has provided means for both assessment of myocardial perfusion; an approach that has been proven superior to clinical assessment and TIMI scoring in risk stratification of suspected ACS, and different quantitative methods for detection of regional ischemia based on either tissue Doppler imaging (TDI) or a new reflector based technique, speckle tracking (SpT). There is an ongoing debate about which of these approaches is the most accurate, feasible and cost-effective for detection of regional ischemia. Up to date there are no published data comparing these two principally different approaches.
Although current guidelines recommend serial measurement of cardiac markers 6-12 hours after admission and in some patients for even longer time period, several recent studies have shown that a more expedited exclusion of myocardial infarction is possible by the use more frequent early testing and analysis of changes in levels of cardiac markers 20-22. In two well performed studies using newly developed troponin assays, myocardial infarction could be safely excluded already at 2 hours from admission (or 6 hours from chest pain) 21, 22. Moreover, the use of change in troponin-level may further improve the ability to detect or exclude myocardial infarction 23. Still, the clinical consequences of applying these findings have not been sufficiently explored.
In the present study we want to compare a diagnostic strategy based on early MPI with a mobile gamma camera (with ectomographic image acquisition), ECG, early serial sampling of troponin, and clinical judgment, with a traditional diagnostic strategy according to the current guidelines.
In patients with intermediate or low probability/risk of ACS, to determine whether a diagnostic strategy based early MPI with a mobile gamma camera, ECG, early serial sampling of troponin, and clinical judgment:
- reduces the time to detection or exclusion of ACS.
- reduces the time to discharge in patients proven not to have ACS.
- reduces average costs.
- is equally accurate to detect and exclude ACS and to risk stratify patients.
In patients with intermediate or low probability/risk of ACS, to examine the value of different echocardiographic methods, including contrast echocardiography, TDI and SpT, for early detection and exclusion of ACS.
- 1. Age?40 if male, and ?50 if female.
- 2. Chest pain
- a. ? 15 minutes
- b. Suggestive of ACS and admission for observation needed.
- c. On-going or terminated within 2 hours.
- 3. Randomization is possible.
- Previous myocardial infarction
- Chest pain that is similar to previously documented angina pectoris.
- ST-segment elevation or new (previously unknown) left bundle branch block (STEMI).
- Admission-ECG considered diagnostic for myocardial ischemia (ST-depression ?1mm or pathological T-wave inversions ?2mm)
- Troponin I-positive (>0.11 ?g/L) on admission.
- Signs of congestive heart failure or significant arytmhia
Eligible patients will be randomized to a diagnostic strategy based on early MPI with a mobile gamma camera, ECG, early serial sampling of troponin, and clinical judgment (strategy 1), or a traditional diagnostic strategy according to the current guidelines (strategy 2) (See figure).
If randomized to strategy 1, bedside scintigraphy will be performed as quickly as possible and a second troponin I will be measured 3 hours from admission (and at least 6 hours from onset of symptoms). If the examination is normal, 2nd troponin I <0.11 ?g/L, there is no increase of troponin I ?0.02 ?g/L from the 1st to the 2nd measurement, the patient is free of chest pain, and there is no suspicion of other serious condition, the patient can be discharged. A stress test can also be performed before discharge. All decisions regarding further examinations, time for observation and discharge are made by the discerning physician. If the result from the bedside-scintigraphy is positive or equivocal further management is decided by the discerning physician.
If randomized to strategy 2, the local guidelines (based on ESC and ACC/AHA guidelines) will be applied. Patients will be observed with serial or continuous 12-lead ECG and troponin will be measured after 6 and 12 hours. If no signs of ischemia during monitoring and normal levels of troponin, an exercise test is recommended before discharge.
All patients discharged without troponin measurement at least 12 hours after admission are asked to return 24-72 hours later for a new troponin I measurement. All patients discharged without a stress test or coronary angiography during hospital stay are asked to return within 72 hours for a stress test.
Approximately 400 MBq 99mTc-tetrofosmin will be injected intravenously as soon as possible. Acquisition of images by a mobile bedside gamma camera will be started within 1 hour from injection. An evaluation will be performed by an experienced observer within 1 hour from acquisition of images. Results will classified normal, equivocal or abnormal.
In strategy 1: laboratory tests according to local guidelines, but a 2nd troponin I (Stratus CS) will be measured after 3 hours from admission and at least 6 hours from onset of symptoms.
In strategy 2: laboratory testes according to local guidelines with a 2nd troponin measurement 6 hours from admission and a 3rd troponin measurement 12 hours from admission.
Echocardiography images will be collected at the earliest possible time from randomization. Grayscale images, optimized for SpT analysis, and color coded TDI images will be recorded and digitally stored for later analysis of regional hypokinesia. An intravenous infusion of the contrast agent Luminity®, 1.5 ml diluted to 20 ml, will be given as an infusion with an infusion rate of 1.6 ml/min, and perfusion-replenishment sequences using a dedicated low mechanical index (M I) real time perfusion technique following a high MI flash will be collected in apical views both in real time and triggered imaging. Apical two, three and four chamber view will be recorded in all three modalities, additional parasternal short axis views at basal, mid chamber and apical levels will be recorded for SpT analysis.
Data that will be collected:
- Age, gender
- Other risk factors: current or previous smoking, hyperlipidemia, diabetes, hypertension, family history.
- Previous cardiovascular disease: Angina, PCI, CABG, stroke, heart failure, arythmias
- Other disease: Chronic kidney disease, chronic pulmonary obstructive disease, pulmonary embolisms.
- Medications on admission.
- Chest pain: time of onset of last chest pain, time of maximum intensity of last chest pain, time of termination of last chest pain, intensity, localization, radiation, related to breathing or certain movements, tenderness etc.
- Arrival time at emergency department, time when ACS is detected or excluded, time when other condition is diagnosed, time of discharge.
- Documentation of all examinations performed.
- ECG:s are stored and interpreted centrally.
- Time of troponin measurements and results of these analyses.