Abstract P436: The Role of Free Fatty Acids in Patients With Obesity and Heart Failure With Preserved Ejection Fraction: A Post-hoc Analysis of the UFA-preserved Pilot Study

Abstract

Background: Increased circulating free fatty acids (FFA) are associated with an increased risk for heart failure (HF). Interestingly, in the setting of established HF, the failing heart relies heavily on the use of FFA as energetic substrate, and therapeutics aimed at reducing FFA in HF have been found to worsen cardiac performance. A dietary intervention aimed at increasing unsaturated fatty acids (UFA) was associated with favorable changes in cardiorespiratory fitness (CRF) in patients with obesity and HF with preserved ejection fraction (HFpEF) in the UFA-Preserved Pilot Study, although the mechanism remains largely unknown. We hypothesized that dietary UFA supplementation is associated with an increase in circulating FFA and may improve determinants of CRF such as cardiac function and body composition. Methods: Eight subjects with obesity and HFpEF engaged in 12 weeks of UFA supplementation by increasing intake of foods rich in monounsaturated fatty acids (i.e., oleic acid) and polyunsaturated fatty acids (i.e., α-linolenic acid, linoleic acid) under instruction and monitoring of a research dietitian. Measures were performed at baseline and 12 weeks. Subjects underwent venipuncture to measure circulating FFA, plasma biomarkers of UFA consumption, and NT-proBNP.. Bioelectrical impedance analysis was used to estimate skeletal muscle mass (SMM). Maximal cardiopulmonary exercise testing was performed to measure CRF defined as peak oxygen consumption (VO 2 ). Data are presented as median and interquartile range. Within group changes were assessed using Wilcoxon rank test and correlations were performed using Spearman rank test. Results: Five subjects were female and median age was 53 [50-59] years. The dietary intervention resulted in a significant increase in FFA (from 0.29 [0.20-0.43] to 0.37 [0.32-0.73] μmol/L, p=0.012) and plasmatic UFA (from 1319 [1224-1477] to 1620 [1268-2110] μg/mL, p=0.05). Changes in FFA were positively associated with changes in plasmatic UFA (R=+0.74, p=0.035). Changes in FFA were associated with a trend toward improvement in peak VO 2 , although it did not reach statistical significance (R=+0.72, p=0.068). Changes in FFA were also positively and significantly associated with an increase in SMM expressed in kg (R=+0.99, p<0.001) and % of body weight (R=+0.90, p=0.006) and inversely associated with changes in NT-proBNP (R=-0.85, p=0.007). Conclusion: In patients with obesity and HFpEF, dietary UFA supplementation increases FFA, which are associated with favorable changes in cardiac function and body composition. This supports a novel mechanism through which UFA may positively affect CRF. Ongoing randomized controlled trials (NCT03966755) are underway investigating UFA supplementation as a therapeutic strategy to improve CRF in obesity and HFpEF.