Carnitine is a friend in HFpEF and foe in HFrEF

Huiqing Wang; Haoran Wei; Mingming Zhao; Junfang Wu; Min Fei; Nan Lin; Rui Zhan; Qingyuan Liu; Qi Zhang; Xiaodong Yao; Yufei Wu; Wenxin Shan; Hongtu Cui; Liang Ji; Bing Pan; Lu Fang; Yujie Zhu; Xin Li; Yansong Guo; Dao Wen Wang; Lemin Zheng

doi:10.1016/j.isci.2024.111018

Carnitine is a friend in HFpEF and foe in HFrEF

iScience. 2024 Sep 23;27(10):111018. doi: 10.1016/j.isci.2024.111018. eCollection 2024 Oct 18.

Authors

Huiqing Wang¹, Haoran Wei², Mingming Zhao³, Junfang Wu², Min Fei⁴, Nan Lin⁴, Rui Zhan⁵, Qingyuan Liu⁶, Qi Zhang¹, Xiaodong Yao⁷, Yufei Wu¹, Wenxin Shan¹, Hongtu Cui³, Liang Ji¹, Bing Pan¹, Lu Fang¹, Yujie Zhu¹, Xin Li¹, Yansong Guo⁴, Dao Wen Wang², Lemin Zheng^{1

6}

Affiliations

¹ The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing 100191, China.
² Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
⁴ Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, P.R. China.
⁵ Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China.
⁶ Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing 100050, China.
⁷ School of Pharmacy North Sichuan Medical College, Nanchong, China.

Abstract

Heart failure (HF) is a global concern, particularly HF with preserved ejection fraction (HFpEF), lacking effective treatments. Understanding the differences of metabolic profiles between HFpEF and HFrEF (heart failure with reduced ejection fraction) patients is crucial for therapeutic advancements. In this study, pseudotargeted metabolomics was employed to analyze for disparities of plasma metabolic profiles between HFpEF and HFrEF in two cohorts: discovery (n = 514) and validation (n = 3368). Plasma-free carnitine levels were significant changed in HF patients. A non-linear and U-shaped (for HFpEF) or J-shaped (for HFrEF) association between circulating free carnitine levels and the composite risk of cardiac events were observed. Interestingly, HFpEF patients with low free carnitine (≤40.18 μmol/L) displayed a poorer survival, contrasting with HFrEF where higher levels (≥35.67 μmol/L) were linked to poorer outcomes, indicating distinct metabolism pathways. In conclusion, these findings offer insights into HFpEF metabolic profiles, suggesting potential therapeutic targets.

Keywords: Cardiovascular medicine; Health sciences; Human physiology; Metabolomics.