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

Carnitine is a friend in HFpEF and foe in HFrEF

Huiqing Wang  1 , Haoran Wei  2 , Mingming Zhao  3 , Junfang Wu  2 , Min Fei  4 , Nan Lin  4 , Rui Zhan  5 , Qingyuan Liu  6 , Qi Zhang  1 , Xiaodong Yao  7 , Yufei Wu  1 , Wenxin Shan  1 , Hongtu Cui  3 , Liang Ji  1 , Bing Pan  1 , Lu Fang  1 , Yujie Zhu  1 , Xin Li  1 , Yansong Guo  4 , Dao Wen Wang  2 , Lemin Zheng  1   6
Affiliations

Carnitine is a friend in HFpEF and foe in HFrEF

Huiqing Wang et al. iScience. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Metabolic differences of carnitine between heart failure and control groups were explored based on an improved pseudotargeted metabolomics technology (A) The improved pseudotargeted metabolomics technology research process. (B) Principal component analysis of the control, HFpEF, and HFrEF groups. (C and D) Supervised orthogonal partial least squares discriminant analyses (OPLS-DA) of HFpEF and HFrEF in positive and negative ion modes separately. (E) Pathway enrichment analysis between HFpEF and HFrEF.
Figure 2
Figure 2
Metabolic differences of carnitine between different groups in learning and validation populations (A and B) Distribution of carnitine in different groups (learning population). (C, D) Verification of the absolute quantitative analysis of carnitine in different groups (validation population). Data are represented as medians (interquartile range). ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
Figure 3
Figure 3
Survival and nonlinear analysis of carnitine between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) (A and B) The changing trend of carnitine in the HFpEF and HFrEF groups was characterized by a non-linear statistical analysis. (C and D) Prognostic analysis of HFpEF and HFrEF.
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