NEW YORK — Siemens Healthineers recently began shipping its first Atellica VTLi Patient-side Immunoassay Analyzers with a test for troponin I, a protein biomarker of acute myocardial infarction, to hospital emergency departments in Europe.
By establishing a footprint in Europe and other regions that accept CE marking, the firm gains an early-mover advantage in the testing market for cardiac conditions at the point of care, Christoph Pedain, head of point-of-care diagnostics at Siemens Healthineers, said in an interview.
The Atellica VTLi is the first point-of-care high-sensitivity cardiac troponin I test with results comparable to laboratory performance using just a fingerstick sample, according to Pedain.
As Siemens Healthineers rolls out its test, it also is conducting a clinical validation study to prepare for a submission for 510(k) clearance of the Atellica VTLi with the US Food and Drug Administration. The timeline for the submission is uncertain, Pedain said.
Hospital emergency departments frequently use troponin assays, he noted, to test patients presenting with chest pain, but assays that can measure troponin at high levels of sensitivity near patients and rule out heart attack have eluded developers.
Troponin T and troponin I, which are subunits of the troponin protein that are involved in contracting skeletal and cardiac muscle, are expressed almost exclusively in the heart. High sensitivity laboratory assays are available to separately test for levels of troponin I and troponin T. Both types of assay are recommended in guidelines for troponin testing. They are clinically similar, and physicians can order either assay, Pedain said.
However, detecting the concentration of troponin in blood with high levels of sensitivity is difficult because of the potential for interference from red blood cells and other substances in the sample, he said. Separating red blood cells from the sample, which requires a centrifuge, works well in laboratories but is inconvenient and too time consuming at the point of care. So, the new analyzer had to be designed to handle this step on-site, Pedain noted.
Frank Peacock, an emergency department physician and cardiologist who is research director at Ben Taub Hospital in Houston, added that developing a high sensitivity point-of-care troponin assay has proven tricky because of the difficulty in repeating what can be done in a lab with such high performance. Detecting troponin with high levels of sensitivity is "like trying to find a molecule in a swimming pool, and that is very hard to do even in a central lab where you have the ultimate control," he said.
The Siemens Healthineers high sensitivity point-of-care testing platform, which the Erlangen, Germany-based firm developed after purchasing its technology for an undisclosed amount from Eindhoven, Netherlands-based Minicare in 2019, combines a washing step, magnetic beads, and light detection and has a turnaround time of eight minutes.
"In the laboratory, you have the luxury of being able to centrifuge samples to separate red blood cells and then run highly accurate tests," Pedain said. "But [for near-patient testing] we need to use fingerstick whole blood because it saves on the time taken for sample preparation, and this point-of-care analyzer allows you to do that."
The testing platform includes a handheld analyzer, analytical software, and a single-use disposable cartridge to test for troponin I. Inside the cartridge, particles capture target analytes that are bound to a surface with antibodies by magnetic beads, and the weakly bound or unbound particles are washed away from the surface. The instrument then detects the concentration of target analytes bound to the cartridge by emitting light through a translucent surface and capturing the amount of reflected light as an indicator of the analyte's concentration.
For CE marking, Siemens compared the performance of its point-of-care test with that of the firm's high sensitivity troponin I test running on its Atellica Solution analyzer and Abbott's high sensitivity troponin I test running on its laboratory analyzer, Pedain said, adding, "We see extremely high concordance among test results, meaning this point-of-care machine working from fingerstick blood is basically equivalent to those two laboratory machines."
Siemens Healthineers' FDA-cleared Atellica IM TnIH assay, one of the tests used to validate the performance of its point-of-care assay, has a limit of detection — defined as the lowest concentration of cardiac troponin I that can be detected with 95 percent probability — of 1.60 pg/mL.
Ruling out heart attack
Emergency department clinicians rely on laboratory tests with high sensitivity, but variables such as the transportation of samples to the lab, the processing of tests, and the reporting and validation of test results can result in too long time-to-results.
The wait can be especially concerning when an emergency room is overcrowded or a patient is in danger of going into cardiac arrest, Peacock said in an interview.
To diagnose patients with chest pain, emergency department physicians also conduct tests with an earlier generation of point-of-care troponin assays that aren't considered high-sensitivity. The tests do a good job of detecting high levels of troponin, signifying a high risk of heart attack, but they are unable to accurately and repeatedly detect levels of troponin low enough to rule out heart attack, said Peacock.
By comparison, a test that can provide a rapid result and help quickly rule out heart attack has the potential to reduce overcrowding in emergency departments, a significant global problem, said Peacock, who is not affiliated with Siemens Healthineers but provided clinical advice for the early design of the point-of-care test under Philips Handheld Diagnostics prior to its further development by Minicare.
A disproportionately high percentage of people present with chest pain to emergency departments and between one-third and one-half of them do not develop a heart attack. "If we can save just one hour of time for everybody on which we need to run a troponin test, that's a huge deal," Peacock said. "It is not going to cure ER overcrowding, but it is going to take it down a notch."
The availability of Siemen's high sensitivity test for troponin I could also be important for patients who present to the emergency department without chest pain or who are not at risk of heart attack. These patients tend to wait longer for care because they don't appear to have serious symptoms. A high-sensitivity troponin test that enables clinicians to quickly decide on treatments for patients with chest pain provides time that can be devoted to treating patients without chest pain. As a result, patients that present to the emergency department without chest pain can get faster treatment, Peacock said.
Further, a test that can detect even slightly elevated troponin level — something a high-sensitivity troponin test can accomplish — is important, Peacock said. While a slightly elevated level of troponin might not signify the risk of a heart attack, the mortality rate is higher for all patients with elevated troponin, and that includes patients with conditions such as renal failure, sepsis, and various infections, among many other conditions, Peacock added.
Siemens Healthineers is planning a geographic rollout of the Atellica VTLi patient-side analyzer for cardiac conditions beyond countries that accept the CE mark, including the US, dependent on it receiving regulatory approval.
The company is also developing additional cardiac biomarkers for its point-of-care platform, including BNP and NT-proBNP.
With a new point-of-care technology in hand, Siemens Healthineers is developing tests to run on the analyzer for conditions other than heart attack, including for sepsis, another condition for which clinicians urgently need fast results in the emergency department, Pedain said, adding that the firm does not disclose timelines for its products in development. "The important piece for us is that the analyzer is capable of highly accurate detection for troponin I, and we are looking to get that same level of performance for other indications," he said.
Still, there are advantages to using lab-based tests over point-of-care tests for chest pain diagnosis. For example, laboratory tests are almost always less expensive, and they can be run at high volumes, Peacock said.
Further, many POC analyzers may be needed to cover the demand for testing in the emergency room. To ensure adequate coverage for patients, Peacock has 10 Abbott i-Stat POC cardiac troponin analyzers in his emergency room, which do not have the high sensitivity label.
Nonetheless, among the many positive outcomes associated with high sensitivity POC troponin testing, the most significant is "shorter serial testing times in comparison to older assays," Louise Cullen, a clinician specialist in acute cardiac care at the Royal Brisbane Hospital, Queensland, Australia, said in an email. The "time benefit truly leads to overall shorter evaluation periods, and earlier discharge of patients who have not had a myocardial infarction. The added benefit of ruling out a [myocardial infarction] in up to one in three such patients with a single test is only possible due to the precision of these assays at very low concentrations."