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Identification of a Multiplex Biomarker Panel for Hypertrophic Cardiomyopathy Using Quantitative Proteomics and
Gabriella Captur1, Wendy E Heywood2, Caroline Coats3
1UCL MRC Unit for Lifelong Health and Ageing, 1-19 Torrington Place, Fitzrovia, London WC1E 7HB, UK; Barts Heart Center, The Cardiovascular Magnetic Resonance Imaging Unit and The Inherited Cardiovascular Diseases Unit, St. Bartholomew's Hospital, West Smithfield, London, EC1A 7BE, UK.
New plasma biomarkers for hypertrophic cardiomyopathy (HCM) can improve disease monitoring and sudden cardiac death (SCD) risk assessment. Six peptides identified show promise in detecting HCM and stratifying risk, aiding early intervention for this inherited cardiac condition.
Area of Science:
- Cardiovascular Medicine
- Proteomics
- Biomarker Discovery
Background:
- Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition characterized by left ventricular hypertrophy (LVH).
- Current methods for monitoring HCM progression and stratifying sudden cardiac death (SCD) risk rely on imaging and patient history, with a need for improved plasma biomarkers.
- A significant number of high-risk HCM cases remain undetected, leading to potential SCD events.
Purpose of the Study:
- To identify novel plasma biomarkers for HCM to enhance disease monitoring and SCD risk stratification.
- To validate identified peptide biomarkers using a targeted liquid chromatography-tandem mass spectrometry assay.
- To assess the association of these biomarkers with clinical phenotypes and SCD risk in HCM patients.
Main Methods:
- Exploratory myocardial and plasma proteomics screens were conducted to identify potential peptide biomarkers.
- A multiplexed targeted liquid chromatography-tandem mass spectrometry assay was developed for validation.
- Plasma samples from 110 LVH+ HCM patients, 97 controls, and 16 subclinical HCM patients were analyzed.
Main Results:
- Six peptides (aldolase fructose-bisphosphate A, complement C3, glutathione S-transferase omega 1, Ras suppressor protein 1, talin 1, and thrombospondin 1) were significantly elevated in LVH+ HCM patients compared to controls.
- These six biomarkers correlated with imaging markers of disease severity, including LV wall thickness, mass, and myocardial scar.
- The six-biomarker panel demonstrated high accuracy (AUC ≥ 0.87) in differentiating LVH+ HCM from controls and correlated with SCD risk factors.
Conclusions:
- Six circulating plasma biomarkers have been discovered that are associated with myocardial substrate changes in HCM.
- These biomarkers show potential for refining disease monitoring and improving SCD risk stratification in HCM patients.
- The identified biomarkers may aid in earlier detection and more effective management of hypertrophic cardiomyopathy.
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