Identifying proteomic profiles as indicators of disease severity in arrhythmogenic cardiomyopathy

Abstract Introduction Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease characterized by progressive fibrofatty replacement of the myocardium and ventricular arrhythmias. Biventricular (BiV) involvement may lead to failure. This study aimed investigate characteristic proteomic patterns in plasma ACM patients, correlated them with clinical outcome as well physical exercise, assess if key soluble molecules serve specific biomarkers for ACM, whether mechanical stress induced exercise alter patients. Methods In 38 patients parameters major adverse cardiovascular events (MACE defined presence sustained tachycardia, fibrillation, appropriate therapy from implantable cardioverter defibrillator, sudden cardiac death, death related end-stage failure or transplant) were obtained prospectively during a mean follow-up period 36 months. All received genetic testing using next generation DNA sequencing. Plasma protein expression was analysed Proximity Extension Assay (PEA) technology, where pair oligonucleotide-labelled antibody probe binds each targeted protein. subgroup 11 blood drawn immediately before 3 hours after standardised bicycle testing, compared. Results 12 had BiV involvement, 26 isolated right (RV) involvement. During period, 34 MACE (30% RV 14% BiV). Over 360 proteins assessed all compared 24 healthy controls. The signature differed significantly controls, 32 upregulated (Figure 1). profiles also those Most importantly, over 40 specifically including pro-inflammatory, adipogenic markers fibrosis. Conclusion Our shows that have different Furthermore we able demonstrate that, several pro-inflammatory pathways are further elucidating molecular associated arrhythmogenicity progression highlighting role stress. results enable identification potential future diagnosis risk stratification pave way personalized patient treatments. Funding Acknowledgement Type funding sources: Foundation. Main source(s): Baugarten Foundation ZurichSwiss National