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    Expediting the confirmation of acute myocardial infarction with point of care troponin and heart fatty acid binding protein testing to facilitate early intervention in emergency department

    Almashali, Malak Ataaalah (2018) Expediting the confirmation of acute myocardial infarction with point of care troponin and heart fatty acid binding protein testing to facilitate early intervention in emergency department. Doctoral thesis (PhD), Manchester Metropolitan University.


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    Cardiac troponin is the reference standard biomarker for the diagnosis of acute myocardial infarction (AMI). In the appropriate clinical context, the detection of a rise and/or fall of cardiac troponin is highly sensitive and specific for this diagnosis. However, troponin testing has two key limitations. First, as levels in serum or plasma can take several hours to rise, the diagnostic sensitivity of troponin testing is insufficient to allow acute coronary syndromes to be safely ‘ruled out’ and serial testing remains necessary. Second, because of the need to detect a rise and/or fall of troponin, serial testing is essential to differentiate chronic troponin elevations from those related to AMI. As a result, international guidance currently recommends serial testing over 6-12 hours. Recent evidence suggests that, with contemporary sensitive troponin assays, AMI can often be ‘ruled out’ and/or ‘ruled in’ with serial testing over as little as 1 to 3 hours However, as the turnaround time of laboratory-based testing is typically 1-2 hours, these results may still be unavailable at the time key decisions about initial treatment and patient disposition are made in the Emergency Department (ED). Point of care troponin (POCT) testing at the patient’s bedside has a shorter turnaround time than laboratory-based assays and eliminates the need to transport the sample to a central laboratory. When patient pathways are appropriately designed to accommodate point of care testing, key management decisions may be expedited, potentially reducing ED length of stay. If the accuracy and safety of rapid diagnostic strategies using point of care troponin testing over 3 hours can be demonstrated, there are tremendous potential benefits for ED throughput, healthcare resource use and for patients (both in terms of receiving appropriate reassurance with avoidance of hospital admission and receiving appropriate early treatment for acute coronary syndromes). In this study, we will evaluate several promising strategies that may enable clinicians to make accurate diagnoses based on information available in the ED and a single blood test for cardiac markers at the POC. During the study period of February 2015 to March 2017 there were 1,613 patients enrolled. Of this cohort, some patients were excluded for missing i-Stat on arrival, and the patients who did not have an ECG recorded were excluded. This left 733 patients in the final group for analysis consisting of 457 men (62.3%) and 276 women (37.7%). The mean age was 58 years (standard deviation 16). In a pragmatic study we determined the interobserver reliability of Heart-type fatty acid–binding protein (h-FABP) the absolute agreement between investigators was 93.0% with a kappa of 0.81 (95% CI 0.6–1.0), indicating near perfect agreement. In total there were three (7.0%) disagreements. The diagnostic accuracy of POC h-FABP lateral flow immunoassay (True Rapid, FABPulous BV) device for diagnosing or excluding AMI using a single test at the time of patient presentation to the ED and three hours later has been evaluated, the sensitivity and NPV to rule out AMI were 48.24% (95%CI: 37.26% to 59.34%) and 92.48 % (95%CI: 90.91% to 93.80%) respectively. While Specificity and PPV were 89.27 % (95%CI: 86.53%to 91.62%) and 38.68% (95%CI: 31.45% to 46.44%) respectively. However, this strategy would allow 85 % of patients to be discharged (rule out percentage). The diagnostic accuracy of a contemporary POC cTn assay used on arrival and 3 hours later in patients with suspected ACS, at the conventional 99th percentile and novel LoD cut-offs was also evaluated. Finally, we were validated the T-MACS with a contemporary POC cTn assay (i-Stat, Abbott Point of Care, New Jersey) in order to investigate the clinical diagnostic accuracy of i-Stat device to rule out AMI in EDs. By setting the cut off levels of POC at 10ng/ml and functional sensitivity at 10% CV, the T-MACS rule has successfully ‘ruled out’ > 41.8% of patients with suspected cardiac chest pain following a single blood test, with a sensitivity of 97.4% (90.8 - 99.7%) and NPV of 99.3% (97.1 – 99.8%), in a very short turnaround time of 5-10 minutes. On the other hand T-MACS has risk stratified the patients who were at high risk to have AMI with a specificity of 93.56% (91.27% to 95.40%) and a PPV of 50.00% (42.08% to 57.92%). To our knowledge, this is the first successful validation of a single test ‘rule out strategy’ using a POC cTn assay. With a 5-10 minute turnaround time, this assay could help to unburden crowded EDs by enabling almost immediate reassurance and discharge for >40% of patients with suspected cardiac chest pain.

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