All of a sudden, it’s become vogue to send home chest pain. After a decade of horror stories regarding the diagnostic errors and medicolegal consequences of discharging chest pain, there is no shortage now of strategies for rapid disposition. Do you like HEART? Go ahead and use it. Do you like CCTA? Please, no – but, OK. Do you like high-sensitivity troponin? Then this is for you.
From Switzerland, Spain and Italy, these authors prospectively evaluated the sensitivity and area under the receiving operator curve for a 1-hour rule-out. Analyzing 1,320 patients with acute chest pain of onset within 12 hours, after excluding STEMI and those with missing data. Final adjudication of MI was performed by two independent cardiologists and based additionally on 3- and 6-hour conventional troponins for each patient. 3, 12, and 24-month follow-up was attempted on each patient. As with each of these new studies, the devil is in the assay – in this case, the Roche Elecsys 2010 hsTnT with a 99th percentile healthy reference cut-off of 14ng/L.
The algorithm for rule-in and rule-out entailed the following:
- Out: hsTnT less than 12 ng/L and a less than 3 ng/L 1-hour delta.
- In: hsTnT greater than 52 ng/L or a greater than 5 ng/L 1-hour delta.
- Who knows (the “observation zone”): Everyone else!
This resulted in 786 (59.5%) patients classified as “rule out”, with 1 patient ultimately falling out with a diagnosis of acute MI. “Rule in” occurred in 216 (16.4%) of cases, with 169 (78.2%) true positives. 318 (24.1%) remained in the Danger Zone, where 59 (18.6%) ultimately ruled-in. The AUC of the algorithm – based on the rule in/rule out – was 0.96 for the 1-hour strategy, as compared to 0.93 for just an initial measurement, or 0.96 for a 2-hour delta. 30-day follow-up showed zero mortality for the “rule out” patients, and even 24-month follow-up with less than 1% all-cause mortality.
These results are fairly consistent with prior strategies incorporating the use of high-sensitivity troponins, which inevitably produce a “gray area” of sorts between the rule-in and rule-out requiring further observation. An area of continued concern, as well, remains the false-positives – nearly a quarter of the “rule in” cohort. The authors provide a small breakdown of these patients, and most were suffering from some acute cardiopulmonary condition – heart failure, myocarditis, acute pulmonary embolism, etc.
However, not mentioned in the paper, but noted on the last page of the appendix, is the full accounting of final adjudicated diagnoses. In addition to the 229 with a final diagnosis of acute MI, another 109 received a diagnosis of unstable angina and 194 “cardiac but non-coronary disease”. Unstable angina, per the authors definition, was a bit of a catch-all category, including those with positive functional testing, cardiac catheterization, and acute MI within 60 days. More detailed information on this heterogeneous endpoint, and their distribution within the “rule out”/“observation zone”/“rule in” cohorts would be helpful.
From a pragmatic standpoint, I think most groups will have success with these accelerated rule-out strategies. The key, as always, is intelligent disposition and management of those in the ambiguous range – in which additional resource utilization associated with troponin measurements above the 99th percentile can torpedo any advantages to this strategy. Regardless, these assays are certainly proliferating, and clinicians need be familiar with their advantages and disadvantages.
Naturally, there were diverse conflicts-of-interest with the makers of the assay involved.
“Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay”
http://www.cmaj.ca/content/early/2015/04/13/cmaj.141349.full.pdf+html