Temporal Relationship between Cardiac Myosin-Binding Protein C and Cardiac Troponin I in Type 1 Myocardial Infarction

Kaier, Thomas E; Anand, Atul; Shah, Anoop; Mills, Nicholas L; Marber, Michael

doi:10.1373/clinchem.2016.257188

Cited by 16 publications

(16 citation statements)

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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].…”

Section: Discussionmentioning

confidence: 99%

“…We investigated the performance of the novel cMyC assay (Erenna) in 174 patients with suspected AMI, presenting very early after symptom onset [61]. All patients were part of a subgroup of individuals recruited in the HighSTEACS [62] study, presenting with chest pain of less than 3 h duration prior to first blood draw—all underwent blood draws at 0, 3 and 6-12 h (late); 26 were adjudicated with type 1 myocardial infarction.…”

Section: Is the Relative Abundance And Sensitivity Relevant In Clinicmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Is the Relative Abundance And Sensitivity Relevant In Clinicmentioning

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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“…16,20 This finding is probably a result of a combination of cMyC's greater myocardial abundance, distinct sarcomeric location, and loose association with myosin and actin. 16 This biological distinctiveness of cMyC likely underpins the diagnostic advantage we observed over hs-cTnT/hs-cTnI in patients presenting <3 hours of symptom onset.…”

Section: Discussionmentioning

confidence: 99%

“…18 Using a recently developed hs assay for cMyC, 19 a pilot study in 26 patients presenting early with AMI suggested that cMyC may rise more rapidly than hs-cTnI. 20 The purpose of the current study is to compare the novel biomarker cMyC (measured on a research platform) against the most accurate currently available biochemical signals, hs-cTnI and hs-cTnT, for the early detection of AMI.…”

mentioning

confidence: 99%

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

Kaier

Twerenbold

Puelacher

et al. 2017

Journal of the American College of Cardiology

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ORIGINAL RESEARCH ARTICLE ORIGINAL RESEARCH ARTICLE BACKGROUND: Cardiac myosin-binding protein C (cMyC) is a cardiacrestricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI. METHODS:Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality. RESULTS:Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L, P<0.001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.924), hs-cTnT (AUC, 0.927), and hs-cTnI (AUC, 0.922) and superior to cTnI measured by a contemporary sensitivity assay (AUC, 0.909). The combination of cMyC with hs-cTnT or standard-sensitivity cTnI (but not hscTnI) led to an increase in AUC to 0.931 (P<0.0001) and 0.926 (P=0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categories: Net Reclassification Improvement +0.149 versus hs-cTnT, +0.235 versus hs-cTnI (P<0.001). In early presenters (chest pain <3 h), the improvement in rule-in/ruleout classification with cMyC was larger compared with hs-cTnT (Net Reclassification Improvement +0.256) and hs-cTnI (Net Reclassification Improvement +0.308; both P<0.001). Comparing the C statistics, cMyC was superior to hs-cTnI and standard sensitivity cTnI (P<0.05 for both) and similar to hs-cTnT at predicting death at 3 years.CONCLUSIONS: cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset.

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“…In another patient cohort with aortic stenosis, cMyC levels were strongly related to fibrosis (detected by cardiac magnetic resonance imaging) and clinical outcome. It is expected that cMyC will be introduced into the clinics as new diagnostic parameter, e.g., after spontaneous, type 1 MI [ 46 ] as well as in other groups of cardiac patients to obtain fast and reliable results on the degree of cardiac damage.…”

Section: Diagnosis Of Cardiac Damage and New Theranosticsmentioning

confidence: 99%

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”

et al. 2016

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In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients’ cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia–reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients’ outcome.

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Temporal Relationship between Cardiac Myosin-Binding Protein C and Cardiac Troponin I in Type 1 Myocardial Infarction

Cited by 16 publications

References 5 publications

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

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

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

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”

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