MODERATE/SEVERE DIASTOLIC DYSFUNCTION IS ASSOCIATED WITH WORSE OUTCOME IN PATIENTS WITH LOW-FLOW, LOW-GRADIENT AORTIC STENOSIS AND LOW EJECTION FRACTION -Results OF THE TOPAS STUDY

Abstract

s S243 368 CIRCULATING BIOMARKER RESPONSES TO MEDICAL MANAGEMENT VERSUS MECHANICAL CIRCULATORY SUPPORT IN SEVERE INOTROPE-DEPENDENT ACUTE HEART FAILURE A Meredith, L Dai, V Chen, M Seidman, Z Hollander, R Ng, J Wilson-McManus, A Kaan, S Tebbutt, K Ramanathan, A Cheung, B McManus Vancouver, British Columbia BACKGROUND: Severe inotrope-dependent acute heart failure (AHF) is associated with poor clinical outcomes, and blood biomarkers to guide therapy could improve management of this condition. There are currently no well-defined biomarkers of response to treatment that can be used to guide treatment or evaluate recovery in this patient population. APPROACH: In the present study we characterized the levels of novel and emerging circulatingHF biomarkers of HF in patients with severe inotrope-dependent AHF over the first 30 days of medical management or mechanical circulatory support (MCS). We hypothesized that there would be a shared treatment response identifiable in both patient groups, particularly a plasma proteomic signature of inotrope-dependent AHF reversal. DESIGN AND METHODS: We enrolled a prospective cohort of 25 consecutive patients >19 years of age and supported on at least one inotrope, admitted to St. Paul’s Hospital with AHF. Peripheral blood samples were collected at days 1, 7 and 30 post-admission. Analysis of peripheral blood proteomic biomarkers was performed using semi-targeted multiple reaction monitoring mass spectrometry (MRM) and candidate marker antibody arrays. A subset of patients managed medically who survived to 30 days post-admission without the need for cardiac transplantation or mechanical circulatory support (n1⁄48), and patients receiving implantable MCS (n1⁄45) were selected for this analysis. Time course plasma samples from the first 30 days of therapy underwent biomarker analyses to generate biomarker signatures characteristic of the response to each treatment modality. Differentially expressed proteins were identified using robust limma with p <0.05 and a false discovery rate (FDR) <0.05 for MRM and antibody array data. RESULTS: We identified a set of 6 in-common plasma proteins which are differentially regulated in both treatment groups, and two proteins uniquely associated with each therapeutic intervention. Patients managed medically or with implantable MCS had increases in circulating cardiotrophin 1, cardiac troponin T, clusterin, and dickopff 1. Levels of c-reactive protein and growth differentiation factor 15 decreased in both groups over the 30-day time course. CONCLUSION: We have characterized the temporal proteomic signature of clinical recovery in AHF patients managed medically or with MCS, over the first 30 days of treatment. Changes in biomarker expression over the time course may enhance understanding of the biological basis of AHF, including the identification of novel markers and mechanisms of recovery. NCE, CECRP