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Hugo A. Katus: Pioneer of the cardiac specific troponin T immunoassay

ESC Congress News 2018 - Munich, Germany

The cardiac-specific troponin T (c-TnT) immunoassay revolutionised the diagnosis and management of myocardial injury. Professor Hugo Katus (Heidelberg University Hospital, Heidelberg, Germany), President of the German Cardiac Society and the man behind decades of work that led to the development and commercialisation of the c-TNT assay, explains why it has been so successful and what is important for the future.

Myocardial Disease
Basic Science


katus-esc-congress-news-2018.jpgProf. Katus’ 40-year career began with a research fellowship in the laboratory of Edgar Haber at Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA, where he started to develop highly specific immunoassays to measure myofibrillar proteins in blood as a diagnostic tool for myocardial cellular necrosis. The initial development of a myosin light chain assay was eventually abandoned due to the insufficient cardiac specificity of these proteins, which are also expressed in slow skeletal muscle. However, in the 1980s he discovered that c-TNT could be distinguished from skeletal troponin T isoforms by monoclonal antibodies, which led to the development of a truly cardiac-specific assay.

What are the key factors that made development of the c-TnT assay possible? “Most importantly, we knew that troponin was an ideal marker,” says Prof. Katus. “What was needed was translation of our laboratory-based ideas and work into clinical practice, and for that to happen we realised that industrial support was critical.” Pharmaceutical company collaboration resulted in the joint protection of his original work by European and international patents and the necessary investment for the development of a highly sensitive c-TnT assay.

It took over ten years of further work before c-TnT was established as a cardiac marker in the clinical setting, and Prof. Katus acknowledges that the translation of a novel idea to a clinical application is not without frustrations. “Initially, there was some scepticism as to the value of the novel c-TnT assay,” he says. “People are not always willing to accept new ideas and I remember when we were trying publish our novel results one reviewer commenting that it is already known how to diagnose myocardial injury, and that our work would just confuse the clinical community.” Persistence in demonstrating that the c-TnT assay was better than the existing enzyme assays was important, as was ensuring independent evaluation of his team’s research through multicentre trials to confirm their laboratory findings. What finally convinced the clinical community was the finding that a positive test result had therapeutic consequences, because troponin-positive (but creatinine kinase-MB-negative) patients gained benefit from targeted and more aggressive treatment. Also significant was that in early 2000 a working group of the ESC/ACC/AHA redefined acute myocardial infarction, endorsing the diagnostic use of cardiac troponins instead of cardiac enzymes or creatinine kinase-MB mass.(1)

“Troponin transformed the way we think about biomarkers. Its clinical significance is huge; it is at least as important in the diagnostic work-up as ECG.”

When asked why he thinks cardiac troponin is such a successful biomarker, Prof. Katus is clear, “It’s successful because of its unique characteristics. As well as it being cardiac-specific, we knew from our work on myosin light chain that the intracellular concentration of troponin was high and so the protein pool was large. Furthermore, many troponin T epitopes are well preserved in their protein structure once released into the circulation—it is a good, stable analyte.”

In its early clinical use to test for myocardial injury, the c-TnT assay led to nearly twice as many cases being detected. Soon afterwards, it was realised that any insult to the heart, e.g. myocardial infarction or toxicity after chemotherapy, resulted in elevated troponin levels and clinicians were able to detect damage due to ongoing disease and also predict poor outcome. The next diagnostic level is that high-sensitivity assays can detect even less injury, and troponin levels can now be measured in apparently healthy people, potentially indicating earlier-stage disease.

Is this the future direction for the troponin assay? Prof. Katus thinks so. “The future is even greater sensitivity and faster assays. Work in this area is ongoing to gain more understanding with high-sensitivity tests and the detection of very early stages of cardiovascular diseases associated with troponin levels in the blood.” So, a lifetime of experience has brought about great changes in diagnostic capabilities. Prof. Katus emphasises, “This assay is the result of decades of work; the process of development generates data that are not always acceptable by high-impact journals but which, for the troponin assay, ultimately demonstrated its reproducibility and confirmed its clinical impact in furthering progress in medicine—and that is what is most important.”

1. Katus HA. Clin Chem 2008;54:1576–1577.

 

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Notes to editor

About the European Society of Cardiology

The European Society of Cardiology brings together healthcare professionals from more than 150 countries, working to advance cardiovascular medicine and help people lead longer, healthier lives.

About ESC Congress 2018

ESC Congress is the world’s largest and most influential cardiovascular event contributing to global awareness of the latest clinical trials and breakthrough discoveries. ESC Congress 2018 takes place 25 to 29 August at the Messe München in Munich, Germany. Explore the scientific programme