Carbohydrate antigen-125 (CA125): a marker of right ventricular dysfunction and poor prognosis in heart failure with preserved ejection fraction.

Background: Right ventricular (RV) dysfunction (RVD) in heart failure (HF) with preserved ejection fraction (HFpEF) is recognised late and associated with poor outcomes. We aimed to identify biomarkers associated with RV dysfunction in HFpEF and evaluate their prognostic significance. Methods: 77 patients with HFpEF were enrolled from a prospective, multicentre study. At baseline, patients underwent echocardiography, cardiac magnetic resonance (CMR) imaging and laboratory testing. They were followed up for the composite outcome parameter of all-cause mortality and HF hospitalisation. RVD was defined as RV ejection fraction (RVEF) < 45 % on CMR. Proteomics analysis was performed using Olink proteomics multiplex panels (CVDII, CVDIII, Inflammatory and Immuno-oncology) with further verification on immunoassay analysis. Results: 19 patients with HFpEF (25 %) had RVD. The Olink proteomic analysis identified carbohydrate antigen 125 (CA125) as the most differentially abundant in plasma of patients with HFpEF and RVD as compared to those without RVD, which corroborated with further immunoassay analysis - median CA125 in patients with RVD was 23 kU/L [21-47] vs. 16 [[12], [13], [14], [15], [16], [17], [18], [19], [20]] in patients without RVD (p < 0.001). Log-normalised CA125 (LnCA125) was associated with worse RVEF (r = -0.29, p = 0.03) and predicted worse clinical outcomes [HR 2.28 (1.28-4.07) for the composite outcome of all-cause mortality and HF hospitalisation] adjusted for age, gender, body mass index, LVEF, RVD, atrial fibrillation, renal function and NTproBNP. Conclusion: Targeted proteomic analysis reveals CA125 as a biomarker for RVD in a HFpEF population. Higher serum CA125 concentration, but not NTproBNP, was associated with an increased risk of all-cause mortality and HF hospitalisation.Word Count: 249.