Oxylipins are Associated With Poor Right Ventricular to Pulmonary Artery Coupling and Adverse Outcomes in Heart Failure With Preserved Ejection Fraction

Right ventricular (RV) coupling to pulmonary artery (PA) pressure is a key parameter in heart failure with preserved ejection fraction (HFpEF). Oxylipins, a class of fatty acid signaling molecules that regulate inflammation, may be associated with RV-PA uncoupling. We sought to determine the association of RV-PA uncoupling with clinical outcomes in HFpEF and to discover oxylipins associated with RV-PA uncoupling. A prospective HFpEF cohort study was established. Echocardiogram and right heart catheterization were performed and venous and arterial blood samples were collected. 234 oxylipins were measured in all participants. Kaplan Meier curves were used to assess the relationship between the tricuspid annular plane systolic excursion (TAPSE) to RV systolic pressure (RVSP) ratio and mortality or heart failure (HF) hospitalizations. Volcano plots were used to determine the relationship between oxylipins and RV-PA uncoupling. The primary endpoint was a composite of all-cause mortality and HF hospitalizations. 83 patients (mean age 68.69 ± 10.7 years, 67.5% female) in our cohort study had TAPSE/RVSP data and entered the analysis. Receiver operating characteristic (ROC) analysis determined an optimal cutpoint of TAPSE/RVSP of 0.31. TAPSE/RVSP <0.31 was associated with higher risk of the primary endpoint (HR = 2.61, 95% CI = 1.28 to 5.33, p = 0.008). Arterial oxylipins 19(R)-OH PGF2a and 20-OH PGF2a, and venous oxylipin 7(8)-EpDPE were associated with an increased odds of TAPSE/RVSP <0.31, while arterial oxylipin 20-HETE was associated with decreased odds of TAPSE/RVSP <0.31. In conclusion, RV-PA uncoupling is associated with higher risk of all-cause mortality or HF hospitalizations in patients with HFpEF. Specific oxylipins were associated with RV-PA uncoupling.