Abstract 12930: Plasma Proteome Distinguishes Adaptive and Maladaptive Signaling in Repaired Tetralogy of Fallot

• Published in: Circulation (New York, N.Y.) Vol. 146; no. Suppl_1; p. A12930
• Main Authors: Jones, Andrea L, Clouthier, Katie L, Edwards, Jonathan J, Mai, Anh Duc, Fazelinia, Hossein, Reddy, Sushma, Mercer-Rosa, Laura M
• Format: Journal Article
• Language: English
• Published: Lippincott Williams & Wilkins 08.11.2022
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.12930

IntroductionPatients who have undergone tetralogy of Fallot (TOF) repair are subject to chronic volume and/or pressure overload, leading to a 40% probability of right ventricular (RV) failure by the third decade of life. We sought to identify a plasma proteome profile of the systemic response to right heart stress to better understand the mechanisms of RV failure and identify novel RV remodeling biomarkers. MethodsPatients with repaired TOF were recruited at the time of standard of care cardiac MRI (CMR) (N=14), and blood samples were collected. Plasma proteomics was assessed using data independent acquisition mass spectrometry. Proteins that were significantly affected between groups were identified and used for pathway enrichment analysis. ResultsPatients underwent primary TOF repair at median 2.9m (IQR 0.8, 4.1) and CMR at median 16yrs (IQR 15, 18). Patients were grouped based on median indexed RV end diastolic volume (RVEDVi). Group 1median RVEDVi 146ml/m2 (IQR 139, 164) (N=9); Group 2median RVEDVi 114ml/m2 (IQR 104, 130) (N=5); p<0.001. RV ejection fraction was equal between groups (mean 56% vs. 55%; p=0.68). Forty-one proteins were significantly differentially abundant19 enriched in Group 1 and 22 enriched in Group 2 (Fig 1; p<0.05). Adaptive signaling in Group 1 was characterized by upregulation of proteins involved in antioxidant mechanisms (SOD1, TXN, PRDX1&2), calcium handling (S100A6, CALM1), and proteostasis (UBB, HSPA8). Maladaptive signaling was characterized by upregulation of glycolytic pathways (MDH1, PGK1) and heme protein oxidation (ALAD) and downregulation of proteins to counter acute stress (complements, ORM1&2). ConclusionPatients with repaired TOF and moderate-severe RV dilation have a distinct maladaptive plasma proteomic profile independent of ejection fraction. These data suggest that profiling the circulating plasma proteome may be used to monitor disease progression prior to the onset of clinical heart failure.