Direct Comparison of Cardiac Myosin-Binding Protein C With Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction

Kaier, Thomas E; Twerenbold, Raphael; Puelacher, Christian; Marjot, Jack; Imambaccus, Nazia; Boeddinghaus, Jasper; Nestelberger, Thomas; Badertscher, Patrick; Sabti, Zaid; Giménez, María Rubini; Wildi, Karin; Hillinger, Petra; Grimm, Karin; Loeffel, Sarah; Shrestha, Samyut; Flores, Dayana; Cupa, Janosch; Kozhuharov, Nikola; Miró, Òscar; Martín‐Sánchez, Francisco Javier; Morawiec, Beata; Rentsch, Katharina; Lohrmann, Jens; Kloos, Wanda; Oßwald, Stefan; Reichlin, Tobias; Weber, Ekkehard; Marber, Michael; Müeller, Christian

doi:10.1161/circulationaha.117.028084

Cited by 71 publications

(45 citation statements)

References 42 publications

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“…[49][50][51][52][53][54] The only additional analyte that recently was suggested to possibly provide incremental diagnostic value even if using hs-cTnT is cardiac myosin-binding protein C, a quantitative marker of cardiomyocyte injury that seems even more rapidly released from injured cardiomyocytes as compared with hs-cTnT and hs-cTnI. 55 The novel concept investigated in this study was based on recent studies documenting that there could be remarkable differences between the cTnI and the cTnT signal, and the moderate agreement between clinical decisions made on these concentrations. 20,56,57 We hypothesized that combining the 2 biochemical signals might overcome independent pathophysiological, preanalytical, and analytical differences between the individual molecules such as (auto)antibodies and sug-gested interference with troponin released from skeletal muscle, 12,15,58,59 and might therefore have higher diagnostic accuracy for AMI than either cTnI or cTnT alone.…”

Section: Discussionmentioning

confidence: 99%

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction

Linden

Wildi²,

Twerenbold³

et al. 2018

Circulation

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Section: Discussionmentioning

confidence: 99%

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction

Linden

Wildi²,

Twerenbold³

et al. 2018

Circulation

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“…Despite many years of intensified research into novel AKI biomarkers, the ideal renal serum biomarker with qualities equivalent to cardiac injury serum biomarkers such as troponin or cardiac myosin-binding protein C 21 has not yet been identified.…”

Section: Oliguria and Lack Of Aki Injury Biomarkermentioning

confidence: 99%

Intraoperative permissive oliguria – how much is too much?

Kunst

Ostermann

2017

British Journal of Anaesthesia

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Acute kidney injury (AKI) after general surgery is a serious complication. In abdominal surgery the incidence is around 13%, and it is associated with increased postoperative morbidity, length of hospital stay and a 13-fold increase in the relative risk of inhospital or 30-day mortality. 1 2 Oliguria is one of the oldest markers of AKI, and was historically described by Epheseus and Galen in 100-200 AD. 3 4 By consensus, oliguria is defined as urine output <0.5 ml kg À1 h À1. 5 Perioperative causes of oliguria include intravascular hypovolaemia, prolonged hypotension and reduced perfusion of the kidneys, but also non-renal causes such as release of anti-diuretic hormone (ADH) in response to nausea or pain. In the critical care setting, oliguria is common, and often considered as an early marker of renal injury, preceding a rise in creatinine. 6-8 Multiple studies in critical care patients with AKI demonstrated an association between oliguria and mortality. 9 10 Recently, Teixeira and colleagues 11 confirmed in an observational multicentre study of 601 critical care patients that oliguria per se was independently associated with mortality. In contrast to oliguria in the critical care setting, intraoperative oliguria appears to be less reliable in predicting AKI as was already suggested 30 yr ago in patients undergoing abdominal aortic surgery. 12 13 More recent studies indicated that oliguria during general anaesthesia was a result of reduced clearance and slower distribution of fluids administered intraoperatively and therefore potentially unrelated to renal function. 14 15 Intraoperatively, urine output is not only influenced by haemodynamics but also sympathetic tone, aldosterone and ADH levels. Increased intra-abdominal pressure independent of fluid status and blood pressure might also contribute, as shown by two studies in laparoscopic surgery. 16 17 A large retrospective study in 15-100 patients undergoing abdominal surgery demonstrated that intraoperative oliguria did not predict postoperative AKI. 18 Based on existing studies, one can conclude that the nature and impact of intraoperative oliguria or 'permissive oliguria' in anaesthetised patients undergoing elective surgery depends on patient characteristics and clinical conditions, and may not necessarily be associated with postoperative AKI. 19 20

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“…Favourable release kinetics and a higher sensitivity than hs-cTn assays are likely responsible for the better performance in patients presenting early after chest pain onset [57, 60, 61]. The greater analytic bandwidth of the assay could, in turn, be responsible for a better calibration against acute myocardial injury versus the chronic release of myocardial necrosis markers often observed in clinical practice [27]. This would explain the net reclassification benefit observed in the largest cohort study testing cMyC to date—both in all-comers and early presenters [27].…”

Section: Discussionmentioning

confidence: 99%

“…We analysed cMyC in 1954 unselected patients presenting with symptoms suggestive of AMI to emergency departments in a prospective, diagnostic multi-centre study based in Europe [27]. We focussed on studying the diagnostic properties of the presentation blood test alone and compared cMyC performance to that of hs-cTnT and hs-cTnI.…”

Section: Analysis Of Cmyc In > 1900 Patients With Suspected Ami—direcmentioning

confidence: 99%

Cardiac Myosin-Binding Protein C—From Bench to Improved Diagnosis of Acute Myocardial Infarction

Kaier

Alaour

Marber

2019

Cardiovasc Drugs Ther

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Chest pain is responsible for 6–10% of all presentations to acute healthcare providers. Triage is inherently difficult and heavily reliant on the quantification of cardiac Troponin (cTn), as a minority of patients with an ultimate diagnosis of acute myocardial infarction (AMI) present with clear diagnostic features such as ST-elevation on the electrocardiogram. Owing to slow release and disappearance of cTn, many patients require repeat blood testing or present with stable but elevated concentrations of the best available biomarker and are thus caught at the interplay of sensitivity and specificity. We identified cardiac myosin-binding protein C (cMyC) in coronary venous effluent and developed a high-sensitivity assay by producing an array of monoclonal antibodies and choosing an ideal pair based on affinity and epitope maps. Compared to high-sensitivity cardiac Troponin (hs-cTn), we demonstrated that cMyC appears earlier and rises faster following myocardial necrosis. In this review, we discuss discovery and structure of cMyC, as well as the migration from a comparably insensitive to a high-sensitivity assay facilitating first clinical studies. This assay was subsequently used to describe relative abundance of the protein, compare sensitivity to two high-sensitivity cTn assays and test diagnostic performance in over 1900 patients presenting with chest pain and suspected AMI. A standout feature was cMyC’s ability to more effectively triage patients. This distinction is likely related to the documented greater abundance and more rapid release profile, which could significantly improve the early triage of patients with suspected AMI.

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Direct Comparison of Cardiac Myosin-Binding Protein C With Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction

Abstract: Supplemental Digital Content is available in the text.

Cited by 71 publications

References 42 publications

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction

Intraoperative permissive oliguria – how much is too much?

Cardiac Myosin-Binding Protein C—From Bench to Improved Diagnosis of Acute Myocardial Infarction

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