Cardiac Myosin-Binding Protein C in the Diagnosis and Risk Stratification of Acute Heart Failure

BASEL V investogators

doi:10.1002/ejhf.2094

Cardiac Myosin-Binding Protein C in the Diagnosis and Risk Stratification of Acute Heart Failure

BASEL V investogators

Cardiovascular Research

University of Basel
King's College London BHF Centre, The Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London, UK. [email protected]
King's College London and Guy's & St Thomas' PET Centre, St Thomas' Hospital, London, United Kingdom.
University Children's Hospital
Department of Cardiology, University Heart Centre, University Zurich, Zurich, Switzerland.
Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, Sofia 1431, Bulgaria.

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Abstract

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.

Original language	English
Pages (from-to)	716-725
Number of pages	10
Journal	EUROPEAN JOURNAL OF HEART FAILURE
Volume	23
Issue number	5
Early online date	9 Jan 2021
DOIs	https://doi.org/10.1002/ejhf.2094
Publication status	Published - May 2021

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@article{7d593474e5054d7585cc3805c63ecd4b,

title = "Cardiac Myosin-Binding Protein C in the Diagnosis and Risk Stratification of Acute Heart Failure",

abstract = "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.",

author = "{BASEL V investogators} and Nikola Kozhuharov and Desiree Wussler and Thomas Kaier and Ivo Strebel and Samyut Shrestha and Dayana Flores and Albina Nowak and Zaid Sabti and Thomas Nestelberger and Tobias Zimmermann and Joan Walter and Maria Belkin and Eleni Michou and {Lopez Ayala}, Pedro and Gualandro, {Danielle M} and Keller, {Dagmar I} and Assen Goudev and Tobias Breidthardt and Christian Mueller and Michael Marber",

note = "Funding Information: N.K. has received research grants from the Swiss National Science Foundation (P400PM‐194 477), Gottfried und Julia Bangerter‐Rhyner‐Stiftung, and the European Society of Cardiology. T.K. has received speaker honoraria from AstraZeneca. T.N. received speaker/consulting honoraria from Beckman‐Coulter, Bayer, Orion Pharma and Ortho Clinical Diagnostics. A.G. received speaker honoraria from Pfizer, Novartis, AstraZeneca, and Amgen. T.B. has received research grants from the Swiss National Science Foundation (PASMP3‐134362), the University Hospital Basel, the Department of Internal Medicine, University Hospital Basel, Abbott, and Roche as well as speaker honoraria from Roche. C.M. has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the University Hospital Basel, the Cardiovascular Research Foundation Basel, the KTI, the University of Basel, Abbott, Beckman Coulter, BRAHMS, Ortho Critical Diagnostics, Novartis, Quidel, Roche, Siemens, Singulex, and Sphingotec, as well as speaker/consulting honoraria from Amgen AstraZeneca, BMS, Boehringer Ingelheim, BRAHMS, Bayer, Osler, Novartis, Roche, and Sanofi. M.M. is named as an inventor on a patent held by King's College London for the detection of cMyC as a biomarker of myocardial injury. All other authors have nothing to disclose. Conflict of interest: Funding Information: This work was supported by research grants from the European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, the University Hospital Basel, Critical Diagnostics, Abbott, Alere, BRAHMS, Roche, and Singulex. This work was further supported by grants from the Medical Research Council (UK) (G1000737), Guy's and St Thomas' Charity (R060701, R100404), the British Heart Foundation (TG/15/1/31518, FS/15/13/31320), and the United Kingdom Department of Health through the National Institute for Health Research Biomedical Research Center award to Guy's and St Thomas' National Health Service Foundation Trust. Funding Information: This work was supported by research grants from the European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, the University Hospital Basel, Critical Diagnostics, Abbott, Alere, BRAHMS, Roche, and Singulex. This work was further supported by grants from the Medical Research Council (UK) (G1000737), Guy's and St Thomas' Charity (R060701, R100404), the British Heart Foundation (TG/15/1/31518, FS/15/13/31320), and the United Kingdom Department of Health through the National Institute for Health Research Biomedical Research Center award to Guy's and St Thomas' National Health Service Foundation Trust. Publisher Copyright: {\textcopyright} 2021 European Society of Cardiology Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = may,

doi = "10.1002/ejhf.2094",

language = "English",

volume = "23",

pages = "716--725",

journal = "EUROPEAN JOURNAL OF HEART FAILURE",

issn = "1388-9842",

publisher = "John Wiley & Sons, Ltd",

number = "5",

}

TY - JOUR

T1 - Cardiac Myosin-Binding Protein C in the Diagnosis and Risk Stratification of Acute Heart Failure

AU - BASEL V investogators

AU - Kozhuharov, Nikola

AU - Wussler, Desiree

AU - Kaier, Thomas

AU - Strebel, Ivo

AU - Shrestha, Samyut

AU - Flores, Dayana

AU - Nowak, Albina

AU - Sabti, Zaid

AU - Nestelberger, Thomas

AU - Zimmermann, Tobias

AU - Walter, Joan

AU - Belkin, Maria

AU - Michou, Eleni

AU - Lopez Ayala, Pedro

AU - Gualandro, Danielle M

AU - Keller, Dagmar I

AU - Goudev, Assen

AU - Breidthardt, Tobias

AU - Mueller, Christian

AU - Marber, Michael

N1 - Funding Information: N.K. has received research grants from the Swiss National Science Foundation (P400PM‐194 477), Gottfried und Julia Bangerter‐Rhyner‐Stiftung, and the European Society of Cardiology. T.K. has received speaker honoraria from AstraZeneca. T.N. received speaker/consulting honoraria from Beckman‐Coulter, Bayer, Orion Pharma and Ortho Clinical Diagnostics. A.G. received speaker honoraria from Pfizer, Novartis, AstraZeneca, and Amgen. T.B. has received research grants from the Swiss National Science Foundation (PASMP3‐134362), the University Hospital Basel, the Department of Internal Medicine, University Hospital Basel, Abbott, and Roche as well as speaker honoraria from Roche. C.M. has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the University Hospital Basel, the Cardiovascular Research Foundation Basel, the KTI, the University of Basel, Abbott, Beckman Coulter, BRAHMS, Ortho Critical Diagnostics, Novartis, Quidel, Roche, Siemens, Singulex, and Sphingotec, as well as speaker/consulting honoraria from Amgen AstraZeneca, BMS, Boehringer Ingelheim, BRAHMS, Bayer, Osler, Novartis, Roche, and Sanofi. M.M. is named as an inventor on a patent held by King's College London for the detection of cMyC as a biomarker of myocardial injury. All other authors have nothing to disclose. Conflict of interest: Funding Information: This work was supported by research grants from the European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, the University Hospital Basel, Critical Diagnostics, Abbott, Alere, BRAHMS, Roche, and Singulex. This work was further supported by grants from the Medical Research Council (UK) (G1000737), Guy's and St Thomas' Charity (R060701, R100404), the British Heart Foundation (TG/15/1/31518, FS/15/13/31320), and the United Kingdom Department of Health through the National Institute for Health Research Biomedical Research Center award to Guy's and St Thomas' National Health Service Foundation Trust. Funding Information: This work was supported by research grants from the European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, the University Hospital Basel, Critical Diagnostics, Abbott, Alere, BRAHMS, Roche, and Singulex. This work was further supported by grants from the Medical Research Council (UK) (G1000737), Guy's and St Thomas' Charity (R060701, R100404), the British Heart Foundation (TG/15/1/31518, FS/15/13/31320), and the United Kingdom Department of Health through the National Institute for Health Research Biomedical Research Center award to Guy's and St Thomas' National Health Service Foundation Trust. Publisher Copyright: © 2021 European Society of Cardiology Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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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U2 - 10.1002/ejhf.2094

DO - 10.1002/ejhf.2094

M3 - Article

C2 - 33421273

SN - 1388-9842

VL - 23

SP - 716

EP - 725

JO - EUROPEAN JOURNAL OF HEART FAILURE

JF - EUROPEAN JOURNAL OF HEART FAILURE

IS - 5

ER -

Cardiac Myosin-Binding Protein C in the Diagnosis and Risk Stratification of Acute Heart Failure

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