CardioExchange Archive

CardioExchange welcomes Dr. Martin Than, lead author of the Lancet article on ASPECT, an observational study of a 2-hour diagnostic protocol to assess chest pain in the emergency department. CardioExchange’s Dr. James de Lemos asks Than about the nuances of the protocol. We welcome you to offer your own questions and opinions.

Background: The accelerated diagnosis protocol (ADP) evaluated in ASPECT was designed to identify which chest-pain patients in the ED have low short-term risk for a major adverse cardiac event (MACE) and, therefore, may be suitable for early discharge. The protocol comprises the TIMI score, ECG, and a point-of-care biomarker panel of troponin, creatine-kinase MB, and myoglobin. Of 3582 consecutive chest-pain patients at 14 EDs in the Asia-Pacific region, 9.8% had negative results on all 3 tests and were therefore classified by the ADP as “low risk.” The MACE rate was 11.8% in the entire population, versus 0.9% in the ADP-identified low-risk group — yielding a sensitivity of 99.3%, a negative predictive value of 99.1%, and a specificity of 11.0% for the ADP.

de Lemos: The integration of risk scoring with ECG and biomarkers is a logical approach to countering overuse of resources in low-risk chest-pain patients. A downside might be that only about 10% of assessed patients would be eligible for early discharge. Did you evaluate whether the cost savings of shortening the observation period by 4 hours in this subgroup made up for the additional laboratory costs of applying your strategy to the larger group of patients? And in your hospital, are you using all three biomarkers or a different biomarker approach?

Than: We believe that the ADP should be used only for patients with a TIMI score of 0 and no new ECG-identified ischemia. Based on the ASPECT cohort, that would mean doing biomarker testing in only 13% of patients at 0 and 2 hours. The ADP would still require testing of three point-of-care (POC) biomarkers for some patients (with some resultant increased cost). A preplanned ASPECT subanalysis revealed that if only the POC troponin was used, the sensitivity was 98.5%.

We have observationally tested other biomarkers in ASPECT. For example, in the Christchurch Hospital cohort (1000 patients), use of just our central laboratory’s contemporary troponin assay (99th percentile at 0.028 µg/L) within the protocol would have yielded a sensitivity of 99.6%. This analysis has persuaded us that a contemporary troponin-only approach would work best in Christchurch. As a consequence, we have begun local implementation as part of a 500-patient, pragmatic randomized controlled trial aimed at testing the effectiveness (early discharge rate and cost utility) of the strategy in real-world practice. The primary outcome is the safe discharge rate at 6 hours after hospital admission. We are approaching the trial’s halfway point, and the early-discharge rate in the experimental arm is about 17%.

de Lemos: At UT Southwestern in Dallas, most of the “action” with the biomarkers is at the first draw. Did you evaluate whether the 2-hour draw was necessary? I suspect that the rate of “rule in” at the 2-hour draw would be low among those with a TIMI risk score of 0, negative baseline markers, and no ECG changes. Could the second measurement be eliminated in low-risk patients?

Than: We definitely found that the initial investigation provided most of the value, but there were 11 false negatives (sensitivity, 97.4%) when the 2-hour set of biomarkers was not used. There were still extra false negatives even if a high-sensitivity troponin assay was used. So, for now, we believe that a second draw is required.

de Lemos: Did you explore other definitions of “low risk”? That might expand the pool of patients who are eligible for early discharge, if the negative predictive value were still high.

Than: The primary hypothesis was based on the TIMI score, but we did test other risk tools (Vancouver Chest Pain Rule, a chest-pain rule for young adults from Marsan and colleagues, GRACE, and PURSUIT). As it happens, using a TIMI score of 0 with the ECG and other biomarkers had the best sensitivity. We are currently working with the dataset to produce a risk tool more focused on a rule-out strategy for “all comers to the ER with chest pain.”

de Lemos: One concern for cardiologists will be what to do with patients identified as “not low risk.” An isolated abnormal-myoglobin test, in particular, will present a conundrum. What, if any, evaluation do you recommend when the myoglobin result is abnormal?

Than: The ADP evaluated in ASPECT is a screening tool that may allow “screen out” and early discharge (or next test — e.g., stress test) for 10% to 15% of patients. If any of the protocol parameters are abnormal, then investigations should continue as usual, following a conservative “late” approach (≥6 hours for the second troponin). We would not advocate extra investigations for an elevated myoglobin level if troponins remained normal. If CK-MB is used, then we advise that further investigations are required for a positive result, because CK-MB is a specific marker of myocardial necrosis. In fact, in Christchurch Hospital we had been provided for many years (until recently) with myoglobin, in addition to troponin, results. I can’t remember anyone ever acting on the results!