Associations between acylcarnitine to free carnitine ratio and adverse prognosis in heart failure patients with reduced or preserved ejection fraction

Abstract

AimsThe failing heart is accompanied by disturbed energy metabolism with mitochondrial dysfunction. Carnitine transports fatty acids into mitochondria for β‐oxidation. Decreased myocardial carnitine levels accompanied by increased plasma carnitine levels in heart failure (HF) have been reported. The plasma acylcarnitine to free carnitine ratio (AC/FC) is recognized as a marker of carnitine deficiency. We aimed to investigate the impact of the AC/FC on HF prognosis, taking into consideration differences between HF patients with preserved ejection fraction (HFpEF) and those with reduced ejection fraction (HFrEF).Methods and resultsConsecutive 168 HF patients were divided into three groups based on their AC/FC: first to third tertiles (n = 56, respectively). We followed up all patients for cardiac events including cardiac death and/or worsening HF. During the follow‐up period (1004 days), there were 23 cardiac deaths and 28 worsening HF. In the Kaplan–Meier analysis, the cardiac event rate of the third group was highest among the three groups (P = 0.022). In the Cox proportional hazard analysis, AC/FC was a predictor of cardiac events (P = 0.007). When HFpEF (n = 79) and HFrEF (n = 89) were analysed separately, the cardiac event rate of the third group was highest with regard to HFpEF (P = 0.008), but not HFrEF (P = 0.321). In the Cox proportional hazard analysis, AC/FC was a predictor of cardiac events with regard to HFpEF (P = 0.031), but not HFrEF (P = 0.095). Therefore, the impact of the AC/FC on cardiac events was different between HFpEF and HFrEF (P = 0.042 for interaction).ConclusionsThe AC/FC can identify high risk HF patients, especially in HFpEF.

A pilot study investigating circulating trimethylamineN‐oxide and its precursors in dogs with degenerative mitral valve disease with or without congestive heart failure

“…Furthermore, total carnitine, carnitine esters, and E/F ratio were significantly higher in dogs with DMVD/CHF compared to those with asymptomatic DMVD. In people, increased carnitine esters and E/F ratio have been shown to be associated with the presence of heart failure, increased risk for worsening heart failure, and CV‐related death . In contrast to studies in humans, our results did not show a difference in choline concentrations between dogs with DMVD/CHF and those with asymptomatic DMVD.…”

Impaired β-Oxidation and Altered Complex Lipid Fatty Acid Partitioning with Advancing CKD

“…In the literature, the ratio of acylcarnitine to L-carnitine is used as a prognostic biomarker. 20 We also found that alterations of L-carnitine were comparable with intermediate acylcarnitine, and therefore, the trend of long-to-intermediate acylcarnitine ratio was similar to long-to-L-carnitine ratio by stage of CKD (Supplemental Figure 2).…”

The importance of registries in today's heart failure therapies

“…We continue to gain more insight into these HF syndromes from contemporary registries [4][5][6]. While one-year and five-year mortality rates of patients with HF remain unacceptably high at about 15% and 50%, respectively [7][8][9][10], awareness about HF management and prognosis in the general population is still low [11].…”