The University of Toledo Translation Journal of Medical Sciences 
Cardiology Abstract, Department of Medicine Research Symposium UTJMS 2023 May 05; 11(1):e1-e1 

A Novel Lipidomics Approach to Predicting Pulmonary 
Hypertension in Human Heart Failure 

Vaishnavi Aradhyula, M11*, Prabhatchandra Dube, PhD1, Sadik A. Khuder, PhD2, 
Krishna Rao Maddipati, PhD1, Steven T. Haller, PhD1, David J. Kennedy, PhD1, 
Samer J. Khouri, MD1

1Division of Cardiology, Department of Medicine, The University of Toledo, Toledo, 
OH 43614 
2Division of Internal Medicine, Department of Medicine, The University of Toledo, 
Toledo, OH 43614 

*Corresponding author: Vaishnavi.Aradhyula@rockets.utoledo.edu

Published: 05 May 2023 

Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is associated 
with high morbidity and mortality; however, the pathophysiology of disease is unknown. 
Polyunsaturated Fatty Acid (PUFA) metabolites play a vital role in cardiovascular health by regulating 
balance between anti-inflammation and pro-resolution processes. An imbalance of these metabolites can 
lead to PH. We hypothesize that a PUFA-derived mediator score can be created using lipidomics 
analysis to accurately predict PH in patients with HFpEF.  Pulmonary venous and arterial serum samples 
were collected during right heart catheterization from 88 HFpEF patients without PH (control, n=40), 
HFpEF with isolated postcapillary PH (pc-PH, n=30), and HFpEF with combined post- and precapillary 
PH (cpc-PH, n=18). A total of 143 PUFA metabolites were analyzed by mass spectroscopy with 
Multiple Reaction Monitoring. A series of regression models was conducted to assess which metabolites 
were predictive of PH. Low arterial 7(S)-Maresin1, a pro-resolution molecule, was significantly more 
predictive of HFpEF with pc-PH (p=0.0003) and HFpEF with cpc-PH (p=0.004) when compared to 
control. Low venous 11(12)-EpETrE, an anti-inflammatory molecule, was more predictive of HFpEF 
with pc-PH (p=0.02) compared to control. Elevated arterial 19(R)- OH PGF2 alpha and 20-OH PGF2 
alpha both pro- and anti-inflammatory molecules, were more significant predictors of HFpEF with cpc-
PH compared to pc-PH (p=0.006). These findings support the hypothesis that distinct PUFA metabolites 
play a significant role in mediating PH in HFpEF. Our study introduces a novel lipidomics framework 
and approach for the diagnostic assessment of PH in patients with HFpEF. 

https://dx.doi.org/10.46570/utjms.vol11-2023-639 

https://dx.doi.org/10.46570/utjms.vol11-2023-639
mailto:Vaishnavi.Aradhyula@rockets.utoledo.edu