Master's Candidate McGill University Montreal, Quebec, Canada
Background: Dilated cardiomyopathy (DCM) is a leading cause of nonischemic heart failure, affecting approximately 1 in 250 individuals and accounting for 60% of cardiomyopathy cases worldwide. Characterized by progressive ventricular dilation and systolic dysfunction, DCM often leads to advanced heart failure, arrhythmias, and the need for heart transplantation or mechanical circulatory support. The disease arises from a broad range of etiologies—including genetic mutations, familial inheritance, toxic exposures, metabolic derangements, tachyarrhythmias, and autoimmune conditions—making accurate diagnosis and risk stratification particularly challenging. Current methods for identifying the etiology of DCM are often invasive or lack specificity, and widely used biomarkers such as N-terminal pro–B-type natriuretic peptide do not differentiate between underlying causes. There is an urgent need for noninvasive, etiology-driven tools. This study aimed to identify both universal and subtype-specific plasma protein biomarkers to enhance diagnostic precision and support personalized management of DCM.
METHODS AND RESULTS: Plasma samples were collected from 50 participants, including patients with clinically diagnosed DCM across six etiologies—idiopathic, familial, genetic, tachyarrhythmic, chemotherapeutic, and alcohol-related—and matched healthy controls. All patients were enrolled from a tertiary care center with echocardiographic confirmation of systolic dysfunction and clinical evidence of nonischemic cardiomyopathy. Plasma was isolated, and high-abundance proteins were depleted using magnetic bead–based affinity enrichment. Enriched samples underwent proteomic profiling by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Protein identification and quantification were performed using Scaffold 5. Statistical comparisons included Student’s t-test and one-way ANOVA, with multiple hypothesis correction using the Benjamini-Hochberg method. Functional enrichment and pathway analyses were conducted using g:Profiler, STRING, and Reactome. A total of 1,056 unique plasma proteins were identified. Serum amyloid P component was significantly downregulated in DCM compared to controls (adjusted p < 0.05), emerging as a potential general diagnostic candidate. Additionally, subtype-specific protein expression patterns were identified. These proteins were involved in key biological processes, including mitochondrial dysfunction, oxidative stress, calcium handling, immune activation, protein folding, lysosomal integrity, and myocardial remodeling. Their differential expression provides insight into shared and distinct molecular pathways across DCM etiologies and supports the development of etiology-specific, noninvasive diagnostic strategies.
Conclusion: Plasma proteomic profiling enables accurate diagnosis and molecular stratification of DCM across diverse etiologies. The identification of distinct subtype-specific biomarkers supports the development of noninvasive, etiology-driven diagnostic tools and targeted therapies. These findings promote the integration of precision medicine in cardiology and underscore the translational potential of proteomics to improve clinical decision-making, risk stratification, and outcomes in patients with cardiomyopathy.
