Cardiac Myosin-binding Protein C: Improving chest pain triage by using a novel marker of myocardial injury

Thomas Kaier

The diagnosis of acute myocardial infarction and, therefore, chest pain triage has become increasingly complicated. Cardiac troponins (cTn) have emerged as the gold standard cardiac necrosis biomarker for patients presenting with chest pain and are incorporated into the universal definition of myocardial infarction; they are also now endorsed by European and US guidelines.1–3 In this commentary, Thomas Kaier discusses the data for a new option.

The slow rise of cTn after cardiac injury results in delayed rule-out, and rule-in, of acute myocardial infarction extending hospital stay.4 To overcome this biological hurdle, assay manufacturers have painstakingly increased sensitivity to develop high-sensitivity assays—which allow detection of even the tiniest release of the muscle protein (potentially as little as necrosis of 9mg of myocardial tissue).5,6 Therefore, the perceived specificity-gap widens as by the very definition of a “high-sensitivity assay”, almost all individuals ought to have a quantifiable biomarker level—resulting in a reality in which many people test cTn-positive but only about 10% are “acute myocardial infarction positive”.7,8 In a prospective cohort study undertaken at our institution (St Thomas’ Hospital, London, UK), my colleagues and I observed that up to 50% of patients require ongoing observation and further testing after the initial blood draw.9

In the pursuit of a better solution for this very common problem—chest pain accounts for at least 6% of all visits to emergency departments—we have developed a novel biomarker of myocardial injury, cardiac Myosin-binding Protein C (cMyC).10–14 cMyC is as specific to the human heart as cTn, but is a much more abundant protein and it rises to 19-fold its baseline level after only five minutes of ischaemia.6,14,15 A relatively insensitive in-house sandwich immunoassay facilitated first clinical studies: in patients undergoing alcohol septal ablation—for the reduction of septal hypertrophy in individuals with hypertrophic cardiomyopathy—cMyC rises in shorter time-to-peak concentration, with a brisker rate of rise to higher levels than high-sensitivity cardiac Troponin T (hs-cTnT).16 While cMyC  was clearly more dynamic, the assay required optimisation as we were only able to detect the 99th centile of cMyC (87ng/L). As a consequence, we migrated our best performing monoclonal antibody pair onto the Singulex Erenna analyser (Merck) and achieved sensitivity and analytical precision not seen before (LoD 0.4ng/L, <10% coefficient of variation from 4.6ng/L).17

With this in place, we were first able to conduct clinical studies—in patients with adjudicated acute myocardial infarction presenting early (within three hours of symptom onset), cMyC levels were significantly higher than cTnI at first blood draw.18 In a multicentre study, investigating >1,900 patients presenting to the emergency department with chest pain, cMyC matched the diagnostic accuracy of hs-cTnT and hs-cTnI but performed better in patients who presented early. This enables better triage, as the earlier, more dynamic rise of cMyC facilitates discharge of 7–23% more patients than with hs-cTnT/I.19

In work that was presented at the 2018 annual meeting of the British Cardiovascular Society (4–6 June, Manchester, UK), we analysed blood samples obtained from 776 patients enrolled in a study investigating the use of prehospital biomarkers to guide triage in suspected myocardial infarction. In tandem, we contracted a point of care (POCT) diagnostics device manufacturer to migrate cMyC onto their platform. While preliminary, signal differentiation was achieved for 10, 50 and 100ng/L of recombinant cMyC; thus, the required limit of detection (10ng/L) on a handheld device is realistic (with a coefficient of variation ≤10%). Notably, despite a median symptom time of only 70 minutes, cMyC levels were significantly higher than hs-cTnT at this early time point.

If the migration of cMyC onto POCT succeeds, we could reliably identify 95% of patients with acute myocardial infarction in the ambulance—whereas cTnT is currently only able to rule-in 40% of patients. This is probably a result of the greater abundance and earlier rise of the novel biomarker, which breaks down some of the technological barriers many manufacturers face: miniaturising assays capable of detecting a few molecules of analyte per sample is no simple feast!

We aim to make cMyC available on both laboratory and hand-held devices to facilitate further clinical studies and add to the arsenal physicians can rely upon when testing for myocardial injury. Our research demonstrates that cMyC can markedly enhance chest pain triage, allowing earlier reassurance of more individuals than currently possible. This can free up scarce healthcare resources, add to a better patient-experience and save hospitals from costly admissions for ongoing observation and repeat blood testing. Considering the potential impact on one of the most common complaints in emergency departments worldwide; a worthy goal to pursue.


  1. Thygesen et al. Circulation 2012; 126 :2020–35.
  2. Roffi et al. Eur Heart J 2016; 37: 267–315.
  3. Amsterdam et al. J Am Coll Cardiol 2014; 64: e139–228.
  4. Katus et al. Circulation 1991; 83: 902–12.
  5. Apple et al. Clin Chem 2012; 58: 1574–81.
  6. Marjot et al. Clin Chem 2017; 63: 990–96.
  7. Apple et al. Clin Chem 2011; 58: 54–61.
  8. McManus et al. Am J Med 2011; 124: 40–47.
  9. Marjot et al. Eur Heart J Acute Cardiovasc Care 2017;2048872617746850.
  10. Goodacre et al. Heart 2005; 91 :229–30.
  11. Murphy. BMJ 2004; 328: 1413–14.
  12. Blatchford et al. Br J Gen Pract 1999; 49: 551–54.
  13. Harris et al. Emerg Med J 2014; 31: 970–74.
  14. Jacquet et al. Mol Cell Proteomics 2009; 8: 2687–99.
  15. Aye et al. Mol Biosyst 2010; 6: 1917–27.
  16. Baker et al. Basic Res Cardiol 2015; 1–14
  17. Marjot et al. Transl Res 2016; 170: 17–25.
  18. Kaier et al. Clin Chem 2016; 62: 1153–55.
  19. Kaier et al. Circulation 2017; 136: 1495–1508.

Thomas Kaier is at The Rayne Institute, Department of Cardiology, St Thomas’ Hospital, London, UK.


Please enter your comment!
Please enter your name here