Cardiac Myosin‐Binding Protein C to Diagnose Acute Myocardial Infarction in the Pre‐Hospital Setting

Kaier, Thomas E; Stengaard, Carsten; Marjot, Jack; Sørensen, Jacob Thorsted; Alaour, Bashir; Stavropoulou-Tatla, Stavroula; Terkelsen, Christian Juhl; Williams, Lindsey W.; Thygesen, Kristian; Weber, Ekkehard; Marber, Michael; Bøtker, Hans Erik

doi:10.1161/jaha.119.013152

Cited by 15 publications

(14 citation statements)

References 26 publications

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“…This myosin-binding protein isoform is exclusively expressed at the level of the heart, making it a specific marker of myocardial injury; it is more rapidly released into the bloodstream as a result of myocardial necrosis than troponin, allowing earlier detection of myocardial injury and disease [ 43 ]. The cardiac myosin-binding protein C myocardial concentration is almost twice that of cTn, which makes cMyC a more sensitive AMI biomarker than troponin, and the addition of cMyC to high-sensitive cardiac troponin T provides supplementary AMI-related diagnostic information [ 44 ].…”

Section: Newer Biomarkers For Laboratory Diagnosis Of Acute Myocardial Infarctionmentioning

confidence: 99%

Past, Present, and Future of Blood Biomarkers for the Diagnosis of Acute Myocardial Infarction—Promises and Challenges

Ţilea

Varga

Șerban³

2021

Diagnostics

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Despite important advancements in acute myocardial infarction (AMI) management, it continues to represent a leading cause of mortality worldwide. Fast and reliable AMI diagnosis can significantly reduce mortality in this high-risk population. Diagnosis of AMI has relied on biomarker evaluation for more than 50 years. The upturn of high-sensitivity cardiac troponin testing provided extremely sensitive means to detect cardiac myocyte necrosis, but this increased sensitivity came at the cost of a decrease in diagnostic specificity. In addition, although cardiac troponins increase relatively early after the onset of AMI, they still leave a time gap between the onset of myocardial ischemia and our ability to detect it, thus precluding very early management of AMI. Newer biomarkers detected in processes such as inflammation, neurohormonal activation, or myocardial stress occur much earlier than myocyte necrosis and the diagnostic rise of cardiac troponins, allowing us to expand biomarker research in these areas. Increased understanding of the complex AMI pathophysiology has spurred the search of new biomarkers that could overcome these shortcomings, whereas multi-omic and multi-biomarker approaches promise to be game changers in AMI biomarker assessment. In this review, we discuss the evolution, current application, and emerging blood biomarkers for the diagnosis of AMI; we address their advantages and promises to improve patient care, as well as their challenges, limitations, and technical and diagnostic pitfalls. Questions that remain to be answered and hotspots for future research are also emphasized.

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Section: Newer Biomarkers For Laboratory Diagnosis Of Acute Myocardial Infarctionmentioning

confidence: 99%

Past, Present, and Future of Blood Biomarkers for the Diagnosis of Acute Myocardial Infarction—Promises and Challenges

Ţilea

Varga

Șerban³

2021

Diagnostics

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“…The assay has a limit of detection of 0.4 ng/L and a lower limit of quantification of 1.2 ng/L with a ≤20% coefficient of variation at limits of quantification, and ≤10% coefficient of variation at the 99th centile. Assay precision is not affected by freeze/thaw cycles 23 . The 99th percentile concentration determined previously in patients without obstructive coronary artery disease on invasive angiography is 87 ng/L 11,13 .…”

Section: Methodsmentioning

confidence: 74%

Cardiac myosin‐binding protein C in the diagnosis and risk stratification of acute heart failure

Kozhuharov

Wussler

Kaier

et al. 2021

European J of Heart Fail

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Aims Cardiac myosin‐binding protein C (cMyC) seems to be even more sensitive in the quantification of cardiomyocyte injury vs. high‐sensitivity cardiac troponin, and may therefore have diagnostic and prognostic utility. Methods and results In a prospective multicentre diagnostic study, cMyC, high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) plasma concentrations were measured in blinded fashion in patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists centrally adjudicated the final diagnosis. Diagnostic accuracy for acute heart failure (AHF) was quantified by the area under the receiver operating characteristic curve (AUC). All‐cause mortality within 360 days was the prognostic endpoint. Among 1083 patients eligible for diagnostic analysis, 51% had AHF. cMyC concentrations at presentation were higher among AHF patients vs. patients with other final diagnoses [72 (interquartile range, IQR 39–156) vs. 22 ng/L (IQR 12–42), P < 0.001)]. cMyC's AUC was high [0.81, 95% confidence interval (CI) 0.78–0.83], higher than hs‐cTnT's (0.79, 95% CI 0.76–0.82, P = 0.081) and lower than NT‐proBNP's (0.91, 95% CI 0.89–0.93, P < 0.001). Among 794 AHF patients eligible for prognostic analysis, 28% died within 360 days; cMyC plasma concentrations above the median indicated increased risk of death (hazard ratio 2.19, 95% CI 1.66–2.89; P < 0.001). cMyC's prognostic accuracy was comparable with NT‐proBNP's and hs‐cTnT's. cMyC did not independently predict all‐cause mortality when used in validated multivariable regression models. In novel multivariable regression models including medication, age, left ventricular ejection fraction, and discharge creatinine, cMyC remained an independent predictor of death and had no interactions with medical therapies at discharge. Conclusion Cardiac myosin‐binding protein C may aid physicians in the rapid triage of patients with suspected AHF.

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“…However, it differed in two important details: first, while the ESC hs-cTnT/I 0/1h-algorithm does not allow for direct rule-out based on a single hs-cTnT measurement in patients presenting very early (≤3 h) after chest pain onset due to concerns of delayed release of hs-cTnT/I in NSTEMI, 23 the cMyC 0/1h-algorithm offered a direct rule-out option based on a single measurement irrespective of the time since chest pain onset (based on prior research describing an earlier rise and shorter time-to-peak concentration 11 , 13 , 16 ) as well as favourable pilot data in patients presenting very early (≤3 h) after chest pain onset. 24 Second, the ESC hs-cTnT/I 0/1h-algorithm considered dynamic changes as absolute, unsigned changes (not differentiating between rise or fall) between the 0h- and 1h-sample, whereas the cMyC 0/1h-algorithm considers absolute, signed changes (differentiating between rise or fall; based on prior insights into the release kinetics of cMyC). 11 , 13 …”

Section: Methodsmentioning

confidence: 99%

“…Prior publications have evaluated the cut-off concentrations in the presentation samples only. 16 , 24 For integration of cMyC into ESC algorithms, see Supplementary material online .…”

Section: Methodsmentioning

confidence: 99%

A 0/1h-algorithm using cardiac myosin-binding protein C for early diagnosis of myocardial infarction

Kaier

Twerenbold

Lopez-Ayala

et al. 2022

European Heart Journal. Acute Cardiovascular Care

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Aims Cardiac myosin-binding protein C (cMyC) demonstrated high diagnostic accuracy for the early detection of non-ST-elevation myocardial infarction (NSTEMI). Its dynamic release kinetics may enable a 0/1h-decision algorithm that is even more effective than the ESC hs-cTnT/I 0/1 h rule-in/rule-out algorithm. Methods and results In a prospective international diagnostic study enrolling patients presenting with suspected NSTEMI to the emergency department, cMyC was measured at presentation and after 1 h in a blinded fashion. Modelled on the ESC hs-cTnT/I 0/1h-algorithms, we derived a 0/1h-cMyC-algorithm. Final diagnosis of NSTEMI was centrally adjudicated according to the 4th Universal Definition of Myocardial Infarction. Among 1495 patients, the prevalence of NSTEMI was 17%. The optimal derived 0/1h-algorithm ruled-out NSTEMI with cMyC 0 h concentration below 10 ng/L (irrespective of chest pain onset) or 0 h cMyC concentrations below 18 ng/L and 0/1 h increase <4 ng/L. Rule-in occurred with 0 h cMyC concentrations of at least 140 ng/L or 0/1 h increase ≥15 ng/L. In the validation cohort (n = 663), the 0/1h-cMyC-algorithm classified 347 patients (52.3%) as ‘rule-out’, 122 (18.4%) as ‘rule-in’, and 194 (29.3%) as ‘observe’. Negative predictive value for NSTEMI was 99.6% [95% confidence interval (CI) 98.9–100%]; positive predictive value 71.1% (95% CI 63.1–79%). Direct comparison with the ESC hs-cTnT/I 0/1h-algorithms demonstrated comparable safety and even higher triage efficacy using the 0h-sample alone (48.1% vs. 21.2% for ESC hs-cTnT-0/1 h and 29.9% for ESC hs-cTnI-0/1 h; P < 0.001). Conclusion The cMyC 0/1h-algorithm provided excellent safety and identified a greater proportion of patients suitable for direct rule-out or rule-in based on a single measurement than the ESC 0/1h-algorithm using hs-cTnT/I. Trial registration ClinicalTrials.gov number, NCT00470587.

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Cardiac Myosin‐Binding Protein C to Diagnose Acute Myocardial Infarction in the Pre‐Hospital Setting

Cited by 15 publications

References 26 publications

Past, Present, and Future of Blood Biomarkers for the Diagnosis of Acute Myocardial Infarction—Promises and Challenges

Past, Present, and Future of Blood Biomarkers for the Diagnosis of Acute Myocardial Infarction—Promises and Challenges

Cardiac myosin‐binding protein C in the diagnosis and risk stratification of acute heart failure

A 0/1h-algorithm using cardiac myosin-binding protein C for early diagnosis of myocardial infarction

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