NEW YORK (360Dx) – European researchers said recently that the diagnostic accuracy and clinical utility of a new Siemens high-sensitivity Advia Centaur troponin I assay are comparable to that of established high-sensitivity troponin assays developed by Abbott and Roche.
The investigators noted that the results of their large multicenter study and subsequent launch of the Siemens assay enables more institutions to introduce high-sensitivity cardiac troponin testing into treatment of patients with suspected acute myocardial infarction. It also enables clinicians to adopt the assay and follow European clinical guideline recommendations "without the logistic challenges and costs of introducing an additional analyzer exclusively for the measurement of [high sensitivity cardiac troponin]," they added.
In the study published recently in Clinical Chemistry, the researchers said that the assay — which received CE marking in May but is not yet available in the US — performed well in the context of several comparisons, including negative predictive value, positive predictive value, and overall diagnostic accuracy.
The clinical validation of the assay was performed by the researchers in Switzerland, Germany, Spain, Poland, and Italy. It makes available to European healthcare centers and others that accept the CE designation another highly sensitive troponin test that clinicians can use to enable quick release of patients as appropriate that present with chest pain but don't have acute myocardial infarction, Raphael Twerenbold, one of the researchers who validated the assay, said in an interview.
Lower-sensitivity assays are still used in hospitals throughout the world and especially in the US where the US Food and Drug Administration has cleared one high-sensitivity troponin assay, Roche's Elecsys Troponin T Gen 5 Stat blood test, said Twerenbold, who is a physician in the department of cardiology at the University Hospital Basel in Switzerland.
Siemens said that its high sensitivity troponin I assay is under active review by the FDA, but it couldn't predict the timing of clearance. The assay is used for the quantitative measurement of cadiac troponin I in human serum or plasma using the firm's Advia Centaur XP and Advia Centaur XPT immunoassay systems.
High-sensitivity troponin assays enable clinicians to detect acute myocardial infarction earlier, and "to detect small infarctions that would be missed using the old generation troponin assays," Twerenbold said.
In their study, the researchers enrolled 1,755 patients that presented to the emergency department with symptoms suggestive of acute myocardial infarction. They validated all clinical information twice using the Roche-Elecsys and Abbott Architect high sensitivity troponin assays.
They conducted troponin measurements using the Siemens-hs-cTnI-Centaur at presentation of the patient in the emergency room, and after one and two hours. They diagnosed acute myocardial infarction in 318 of 1,755 patients. The area under the curve reading at presentation for Siemens-hs-cTnI Centaur was 0.94, comparable with 0.95 for the Roche-hs-cTnT Elecsys and 0.93 for the Abbott-hscTnI Architect, the researchers said.
Of 1,755 patients, 156 had unstable angina; 238 had a cardiac condition of origin other than coronary artery disease, such as tachyarrhythmia, heart failure, and myocarditis; 968 had a non-cardiac condition; and 75 had an unknown condition.
Importantly, during their work, the researchers also developed and published 0/1-hour and 0/2-hour algorithms for emergency departments using the Siemens assay, Twerenbold said. With the algorithms, clinicians establish a baseline troponin level by drawing blood when the patient presents at the emergency room and they compare it with troponin levels taken after one or two hours have elapsed.
By applying the Siemens-hs-cTnICentaur 0/1-h algorithm to a validation cohort, the medical researchers ruled out 46 percent of patients for acute myocardial infarction. Survival in patients assigned to the rule-out zone by the 0/1-h algorithm was 100 percent after 30 days and 98.4 percent after 2 years. That demonstrated the safety of providing early discharge from the emergency department for most patients classified as rule-out, the researchers said.
US Clearances Anticipated
Until the completion of the multicenter trial, the clinical performance of the Siemens high sensitivity cardiac troponin I assay was unknown, Twerenbold said.
Highly sensitive troponin T and I tests have been clinically available in Europe and other countries outside the US since 2010, including tests by Singulex and Beckman Coulter in addition to Roche and Abbott.
In January 2017, Roche announced that the FDA had cleared the company's next generation troponin test for helping diagnose patients suspected of having a heart attack. The 510(k) clearance made Roche the first in vitro diagnostic firm in the US to offer the next-generation troponin test for patients as an aid in diagnosing myocardial infarction.
At the time, the test had been available in the rest of the world for seven years and its clinical diagnostic utility had been supported by more than 600 peer-reviewed publications, Roche said. The higher sensitivity of the Elecsys Troponin T Gen 5 Stat test "can significantly accelerate decision-making, and allows the detection of smaller infarctions, thereby maximizing the potential for effective treatment," the firm added.
It's a perspective that many, if not most, cardiologists share, Twerenbold said.
He noted that in the US, Europe, and elsewhere, clinicians record a baseline troponin level and take a second blood drop later to compare the rise or fall in troponin. However, the length of time between blood draws in Europe differs significantly from the US. In Europe, using the high-sensitivity tests, clinicians usually draw blood a second time after one, two, or three hours. In the US, clinicians draw blood a second time after six or 12 hours.
Consequently, in the US, patients can wait in the emergency department for up to 12 hours, or more, without knowing whether they are suffering from myocardial infarction, Twerenbold said. Apart from the obvious psychological effect on patients, "this is also of major relevance to the distribution of healthcare resources in the emergency department," he said.
Chest pains and other symptoms associated with acute myocardial infarction account for about 8 million emergency room visits in the US, but no more than 20 percent of such cases turn out to have actual AMIs. That means that with high sensitivity troponin tests, "between 80 percent of patients could be sent home after a one hour blood draw," Twerenbold said.
The FDA is expected to approve additional high-sensitivity cardiac troponin assays for use in the US this year, according to Alan H.B. Wu, professor of laboratory medicine at University of California, San Francisco, and clinical chemistry laboratory chief at Zuckerberg San Francisco General Hospital. To get ahead of anticipated clearances, the American Association for Clinical Chemistry has published practice recommendations for the use of high sensitivity troponin tests in clinical laboratories.
Medical researchers are also investigating the use of point-of-care instruments and assays for chest pain diagnosis.
In the US, a research group recently conducted a study of chemistry and troponin point-of-care tests at the at Touro Infirmary in New Orleans, Louisiana, that has about 34,000 emergency department visits annually. They reported that implementing some point-of-care testing in the emergency room reduced the overall time to receive a test result by 20 minutes and contributed to improving the overall quality of care.
In the UK, meanwhile, King's College London researchers are developing a point-of-care blood test to diagnose heart attacks that uses cardiac myosin-binding protein C as an alternative biomarker to high-sensitivity troponin used in laboratory testing.
Presenting the results of a study recently at the British Cardiovascular Society Conference, the researchers said that levels of cMyC in the blood increased more rapidly after patients had a heart attack than in the lab-based troponin tests, which take a few hours to show results.
Roche declined to comment for this article, and Abbott did not respond to a request for comment.