Abstract 15246: Sex-Biased Preoperative Circulating MicroRNA Levels in Patients Who Developed Postoperative Heart Failure With Preserved Ejection Fraction

Abstract

Introduction: Acute postoperative heart failure (PoHF) is encountered in 20-35% of elderly patients after cardiac surgery but predictors are not well defined. Circulating microRNAs (miRNAs) predict HF or postoperative atrial fibrillation, yet, their role in identifying those at risk for PoHF with preserved LV function and gender-related differences is not known. Hypothesis: miRNAs involved in CVD can identify patients who develop PoHF in gender-specific manner. Methods: Preoperative blood samples from patients with preserved LV function undergoing cardiac surgery with no prior history of HF, supraventricular, or ventricular tachycardia was used for RNA isolation. Differences in relative plasma levels of miRNA between PoHF vs. No-PoHF were assessed using qPCR. Univariate and multiple logistic regressions were performed to assess risk factors for PoHF. Results: Out of 68 patients (mean age 68.3±12.4), 13 (19%) developed PoHF (54% males; mean age 64.1±15.1; p=0.23), while 55 (51% males; mean age 69.3y ± 11.6) remained free of PoHF. Although all patients had preserved LV function, those who developed PoHF had lower LVEF, (52 vs 58; P<0.05). No significant differences were observed in the prevalence of hypertension, diabetes, myocardial infarction, heart failure, stroke, COPD, or the use of cardiac medications. Out of 13 miRNAs analyzed, stepwise discriminant analysis showed miR-423 (11-fold), -187 (6-fold), -26a2 (4-fold), and -15b (-1.9-fold) were significantly (p<0.05) altered in patients who developed PoHF. When miRNAs were assessed for gender differences, levels of only four miRNAs [miR-423(P<0.01), -23b2(p<0.05), -15b1(p<0.01), and -29b (p<0.05)] principally involved in TGFβ1-SMAD 2/3 regulated extracellular matrix (ECM) turnover pathways were significantly altered in male but not in female patients who developed PoHF compared to No-PoHF group. Conclusions: The differences in preoperative miRNA expression in pathways involved in ECM turnover in male patients who develop PoHF is suggestive of pathophysiological substrate differences between males and females and identifies a group at risk of PoHF with preserved LV function.