Beyond the biomarker, from signal to action: Insights from Roche’s ACS Summit 2026

• Various factors can impact the interpretation of cardiac troponin assays; diagnostic pathways that use validated hs-cTnT assays provide a strong foundation for clinical decision-making

• hs-cTnT Gen 6 builds on the successes of the previous generation assay, with molecular refinements enhancing precision, sensitivity, and resistance to interference

• Innovation in diagnostic technologies, including clinical decision support tools and additional cardiac biomarkers, can help to optimize the chest pain triage pathway

The summit covered topics from analytical performance and interpretation of results to innovation that could enhance the use of cardiac biomarkers. The unique mix of attendees ensured perspectives were captured from all those directly involved in the triage and diagnosis of suspected myocardial infarction (MI).

Decades of research, evidence generation, and experience have led to high-sensitivity cardiac troponin T (hs-cTnT) being established as a fundamental step in MI diagnostic pathways. The hs-cTnT Gen 6 assay is an example of continued innovation and another important step toward confident, efficient clinical decision-making​​. 

This article summarizes the latest science and changing paradigms, as well as expert insights from the summit, and explores how they could enhance the diagnosis of MI and bring optimal care to patients.

ED overcrowding is a major global healthcare challenge.^1–4 Around 10% of patients at EDs are there for chest pain,⁵ but just 5% of them will be diagnosed with MI.⁶ This means a large proportion of chest pain patients could, in theory, be safely discharged via rapid rule-out pathways.

The high number of patients visiting EDs due to chest pain can impact clinical outcomes. Delays caused by overcrowding lead to higher mortality and ED readmission rates. For every 82 patients delayed in the ED for 6–8 hours before admission, one additional death occurs at 30 days.⁷

Validated rapid diagnostic algorithms, for example, single-sample rule-out, support safe, efficient triage of patients, which helps to accelerate patient flow and optimize healthcare resource use. The challenge now is to ensure hospitals and institutions have the tools they need to implement rapid pathways consistently.

Clinical and laboratory teams also face analytical complexities. With approximately 50% of chest pain patients falling into the “gray” zone, steps should be taken to act on opportunities for improved clinical interpretation. 

Unlike in clinical trials, patients at the ED are not clinically pre-selected, tending to be older and affected by chronic renal or cardiac conditions. These confounding factors are associated with increased cTn concentrations, which can alter patients’ triage classification. 

When blood samples are taken in the ED, hemolysis is a frequent occurrence.⁸ It is associated with reduced ​​cTnT concentrations, and laboratories are required to request re-sampling before analysis, which delays clinical decision-making and treatment initiation.

Hospitals and institutions use assays that may be based on either cTnT or cardiac troponin I (cTnI). This can influence another type of interference, macrotroponins, which form when cTn binds to immunoglobulin G (IgG) to prevent clearance via the kidneys.⁹

In the DANSPOT study, macrotroponins were highly prevalent with high-sensitivity cTnI (hs-cTnI) assays and significantly ​​influenced 99th percentiles,⁹ which can have a major impact on clinical decision-making. ​​In contrast, they were not present in any hs-cTnT samples,⁹ increasing confidence in clinical interpretation.

Importantly, clinical and laboratory teams are aware of these factors and experienced in successfully managing them by following validated diagnostic algorithms. At the summit, attendees discussed adjusted cut-offs for confounders and “cleaning” samples for macrotroponins—and ongoing innovation will provide even more tools and solutions.

One of the most hotly debated topics at the summit was whether sex-specific thresholds should be implemented. Current upper reference limits (URLs) are clinically validated and supported by extensive evidence, but the scientific community continues to explore the possibility and incremental benefits of personalization. 

Dr Aakre highlighted that men and women have different cTn profiles. From the age of 20 until around 50 years, males have approximately twice the circulating cTn of females. Moreover, healthy females have smaller hearts and lower baseline cTn, so a single cut-off risks missing MI in women.

In response, Dr Rubini pointed to sex-specific cut-offs not resulting in significant reclassification of patients for MI in clinical trials. Furthermore, implementing sex-based thresholds adds operational complexity, with ED and laboratory teams having to adjust their workflows.

Additionally, the discussion raised the question of why sex should be prioritized over other confounding factors that have a greater impact on cTn levels, such as age and renal function. Ideally, all relevant confounders would be considered when interpreting cTn levels, and this is where artificial intelligence could help in the future.

High-sensitivity cardiac Troponin T (hs-cTnT) Gen 5 has been a cornerstone of acute cardiac diagnostics. Building on its well-established clinical performance and trust among clinical and laboratory teams, the hs-cTnT Gen 6 assay offers improved sensitivity and robustness through key molecular refinements:¹⁰

• Affinity maturation of the M11.7 monoclonal antibody: hs-cTnT Gen 6 recognizes the same epitopes as hs-cTnT Gen 5 but binds with greater affinity. 

• High sensitivity even at the limit of detection: Optimized buffer composition and advanced antibody design achieve a limit of blank of 1.0 ng/L. 

• Robust resistance to interference: 10-fold improvement in resistance to hemolysis and 2-fold improvement in resistance to bilirubin versus hs-cTnT Gen 5; hs-cTnT Gen 6 also incorporates anti-streptavidin antibodies.

• A three-level quality control system: Per the latest International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations; hs-cTnT Gen 6 is in line with the lowest and highest sex-specific 99th percentile URLs. 

• State-of-the-art metrological traceability: Decoupled from hs-cTnT Gen 5 and standardized to recombinant human cTnT rather than bovine cTnT.

hs-cTnT Gen 6 has been extensively investigated in the global TSIX study program, which recruited over 13,000 participants from China, Japan, the US, and the EU.^11,12 The REF-TSIX study established standard URLs for cTn levels in the blood; 99th percentiles for the overall population, males, and females were consistent with IFCC recommendations.¹¹

To validate the clinical performance, PERFORM-TSIX enrolled 5,631 participants across  50 sites.¹² hs-cTnT Gen 6 was highly effective at detecting MI, meeting its primary endpoint using the universal 99th percentile URLs at 3 hours post ED presentation.¹³ Moreover, 56.6% of patients were discharged in the first hours after presentation with a negative predictive value of 99.7%.¹³

Together, the molecular refinements and extensive study program demonstrate that hs-cTnT Gen 6 provides consistent, reliable results, which should support fast, accurate diagnosis and decision-making. hs-cTnT Gen 6 continues to be investigated in robust studies, which will add further validation of its clinical performance and utility. 

Chest pain triage still requires refinement; there is still a need to streamline workflows and eliminate protocol deviations. The development of clinical decision support tools and uncovering cardiac biomarkers could help to achieve this.

​​Overcrowding and unpredictable delays make it difficult for EDs to manage patients and organize resources. Currently, there are no standardized assays between the laboratory and Point of Care. However, many attendees expressed that harmonization across different settings could offer pathway flexibility, which could help healthcare systems cope with high patient volume. In response, next-generation developments center on near-patient hs-cTnT testing platforms designed to be standardized against the hs-cTnT Gen 6 assay, bringing lab-equivalent performance to the bedside and enabling consistent clinical decision-making. 

Professor Giannitsis introduced the ​​CAD-1 clinical decision support tool, which was developed in line with European Society of Cardiology guidelines. It provides dynamic time correction and real-time tracking for automated and standardized 0/1-hour and 0/2-hour algorithms. CAD-1 has received a CE-mark and is part of an ongoing prospective study with hs-cTnT Gen 6.¹⁴

To support single-sample rule-out, additional cardiac biomarkers are being investigated for use in combination with hs-cTn. Dr Lopez Ayala explained that cardiac Myosin-Binding Protein C (cMyBP-C) is a highly abundant cardiac-specific protein that is rapidly released into the circulation during myocardial ischemia.¹⁵

In cohorts from the APACE and TRAPID-MI studies, combining hs-cTnT and cMyBP-C doubled the number of patients safely and immediately ruled out, while also reducing the size of the “gray” zone.¹⁶ This could be particularly valuable for early presenters in whom cTn has not reached detectable levels.

There is also the potential for additional intended uses of cTn. Throughout the summit, it was highlighted that cTn can do more than rule in or out MI; instead, it has shown that it can be a powerful marker of myocardial injury and vulnerability.

Dr Noordzij discussed postoperative myocardial injury (pMI), a serious complication that affects ~20% of non-cardiac surgeries.¹⁷ Although most patients exhibit no symptoms initially, high postoperative cTn is associated with a high risk of 30-day mortality. In the BIGPROMISE study, active surveillance with hs-cTnT Gen 6 before, during, and after surgery is under investigation.¹⁸

The perspectives gathered during the summit gave a real insight into what it is like for cardiologists, ED physicians, and lab managers leading chest pain triage in hospitals and institutions around the world. It is clear that cTn will remain central to triage workflows, but challenges to its clinical interpretation exist. 

Clinical and laboratory teams have shown they can navigate these challenges by following validated diagnostic algorithms supported by robust evidence. The arrival of innovations, such as the hs-cTnT Gen 6 assay, clinical decision support tools, near-patient hs-cTnT testing, and new cardiac biomarkers, can build on this to further increase confidence in clinical decision-making and improve patient care.

The ACS summit brought together a unique group of experts who shared their time and expertise and celebrated the progress that has been made so far, while focusing on areas for improvement, as everyone works towards our shared goal of fast, accurate diagnosis of MI across the patient pathway.