HiSTORIC Validates Single High-Sensitivity Troponin Test to Rule Out MI

Patrice Wendling

September 04, 2019

PARIS — A single cardiac troponin measurement by high-sensitivity cardiac troponin I (hs-cTnI) assay can safely and effectively rule out myocardial infarction (MI) at presentation, results from more than 30,000 consecutive patients in the High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction (HiSTORIC) study show.

Implementing the early-rule-out pathway for all comers at seven hospitals across Scotland reduced the time in the emergency department (ED) by just over 3 hours (from 10.1 to 6.8 hours; P < .001), compared with standard care.

Further, the proportion of patients discharged directly from the ED increased by 57% (from 53% to 74%; P < .001).

"So overall, three quarters of all patients with suspected acute coronary syndrome were managed in our outpatient setting," chief investigator Nicholas Mills, MD, PhD, University of Edinburgh, Scotland, said during a hotline session here at the European Society of Cardiology (ESC) Congress 2019, World Congress of Cardiology.

This acceleration of the diagnostic pathway did not appear to come at the cost of patient safety. Although the investigators were unable to show noninferiority for the early-rule-out pathway vs standard care for the primary safety outcome of MI or cardiac death at 30 days (0.3% vs 0.4%), there was no evidence of an increase in events at 1 year (1.8% vs 2.7%), he said.

The HiSTORIC study used a stepped-wedge cluster design with randomization at the level of the hospital, not the patient. The study had three phases, during which all seven hospitals initially used a standard-care pathway (6- to 9-month validation phase), transitioned to the High-STEACS early-rule-out pathway (6-month randomization phase), and then used the early-rule-out pathway (6-month implementation phase). Troponin I was measured using the ARCHITECT STAT   high-sensitivity troponin I assay (Abbott Laboratories).

Using the High-STEACS pathway, patients whose hs-cTnI concentration at presentation was <5 ng/L were considered to be at low risk and were sent home. That hs-cTnI concentration level has been shown to have a negative predictive value of at least 99.5% for ruling out MI at 30 days. Patients with a value that was higher than the sex-specific 99th centile at presentation were considered to be at high risk and were admitted for further testing. Intermediate-risk patients with values between 5 ng/L and the 99th centile were retested after 3 hours and were sent home if the change in troponin concentration was <3 ng/L; they were admitted if it was ≥3 ng/L.

Overall, 31,492 patients (mean age, 59 years; 45% women) with troponin I concentrations less than the 99th centile were enrolled and were followed for 1 year. The scientific basis for the early-rule-out pathway used in the trial was published simultaneously in Circulation.

Landmark Study

Speaking with theheart.org | Medscape Cardiology about the results, Mills and Roxanna Mehran, MD, acknowledged that cardiologists have a love-hate relationship with troponin testing.

"We say if you cough, you get a troponin release, so I do think your study is the landmark study and will make a very big difference in how we look at that, especially given that it used risk stratification," Mehran said. "It's not a dichotomous value, yay or nay; it's this spectrum of risk.

"I also like that it was sort of like an algorithm, and I think that's something we clinicians can follow," she said.

Mills replied: "Anything that can help clinicians make practical decisions based on robust evidence when you're faced with a new test which is potentially quite complicated and confusing is going to be of value.

"I think what we've learned over the last 5 years using these tests is that it's a fabulous test to identify low-risk patients who you can plan to evaluate as an outpatient and allows you to concentrate your efforts on the complicated ones," he said. "That makes a big difference and also moves us away from the idea that every positive troponin is a heart attack."

What "absolutely blew me away" about the pathway, Mills said, was that among hundreds of different clinicians at seven hospitals, "with no one standing over them, 92%, using a prespecified adherence criteria, followed it. Can you believe it?"

"I believe it because it's very difficult to evaluate what to do with those troponins, so we want some sort of structure," Mehran said.

During the formal presentation, invited discussant Hugo Katus, MD, PhD, Heidelberg University Hospital, Germany, said HiSTORIC was an "urgently needed and well-conducted trial" that used validated cardiac troponin I discriminators. He said the results show that early rule-out with high-sensitivity troponin I is "efficient and safe."

Although not every troponin I assay is validated, "high-sensitivity troponin protocols are here to stay," he said.

During a media briefing earlier that morning, Mills observed that practice in Scotland has already changed to early-rule-out with a single test for patients with suspected acute coronary syndrome and that other countries are following suit.

"It is the most common presentation worldwide, with 20 million presentations in the US alone every year," he said. "If we can make an evaluation that is safe with a single test on presentation to hospital, avoiding hospital admission and all the downstream investigations that certainly in many healthcare systems are standard practice, then the cost savings of this single test when used effectively could be absolutely enormous."

Katus questioned, however, whether HiSTORIC really evaluated an early-rule-out protocol, because the time from presentation to the first blood sampling was 66 minutes, not 60 minutes, as recommended by the ESC guidelines. The standard-care protocol also "very conservatively" defined with regard to time for retesting, at 6 to 12 hours after symptom onset, whereas ESC guidelines recommend a rapid-rule-out protocol with testing at presentation and at 3 hours, if high-sensitivity troponin tests are available. "This will increase inappropriately length of stay in hospital in the comparator group," he noted.

He said that it is also notable that, independently of the standard-care or early-rule-out pathway, the all-cause death rate was more than 5% in both groups and the reattendance rate was about 39% at 1 year. "So are we, by discharging the patients as rule out, cardiovascular rule out, ignoring other life-threatening conditions?" Katus questioned.

"HiSTORIC does not prohibit careful clinical workup," he concluded.

The study was sponsored by the University of Edinburgh, National Health Service (NHS) Lothian, and NHS Greater Glasgow and Clyde. Mills has acted as a consultant for Abbott Diagnostics, Siemens Healthineers, and LumiraDx; his institution has received grants from Abbott Diagnostics and Siemens Healthineers. Katus reports holding a US patent on a cardiac troponin T assay.

European Society of Cardiology (ESC) Congress 2019, World Congress of Cardiology: Presentation 2309, presented September 1, 2019.

Circulation. Published online September 1, 2019. Abstract

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