L-Carnitine prevents the development of ventricular fibrosis and heart failure with preserved ejection fraction in hypertensive heart disease

Omori, Yosuke; Ohtani, Tomohito; Sakata, Yasushi; Mano, Toshiaki; Takeda, Yasuharu; Tamaki, Shunsuke; Tsukamoto, Yasumasa; Kamimura, Daisuke; Aizawa, Yoshihiro; Miwa, Takeshi; Komuro, Issei; Soga, Tomoyoshi; Yamamoto, Keiji

doi:10.1097/hjh.0b013e3283569c5a

Cited by 53 publications

(30 citation statements)

References 59 publications

(73 reference statements)

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“…In a recent study, cardiac collagen production was diminished by increased activation of fads1/2 and elevated ARA accumulation in a rat model of hypertension. Not surprisingly, such effects were also down-regulated by knockdown of fads1 or fads2 in cultured cardiac fibroblasts in the same study (53). Based on such results, investigations of fads SNPs in clinical populations may reveal significant associations with cardiac fibrosis and remodeling.…”

Section: Discussionsupporting

confidence: 58%

Excess Linoleic Acid Increases Collagen I/III Ratio and “Stiffens” the Heart Muscle Following High Fat Diets

Beam

Botta

et al. 2015

Journal of Biological Chemistry

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Background: Dietary n-6 polyunsaturated fats (n-6 PUFA) like linoleic acid (LA) may worsen cardiac remodeling after injury. Results: Excess LA increased cardiac collagen I/III ratio and lysyl oxidase causing early diastolic dysfunction. In vitro experiments in fibroblasts with genetic manipulation confirmed such mechanisms. Conclusion: LA promotes noncompliant collagen and cardiac stiffening. Significance: This study demonstrates a novel, cardiac-specific lipotoxic pathway of n-6 PUFAs.

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Section: Discussionsupporting

confidence: 58%

Excess Linoleic Acid Increases Collagen I/III Ratio and “Stiffens” the Heart Muscle Following High Fat Diets

Beam

Botta

et al. 2015

Journal of Biological Chemistry

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“…On the other hand, carnitine supplementation attenuates cardiac fibrosis in HFpEF model rats14 and improves echocardiographic diastolic parameters and symptoms in HFpEF patients 15. Thus, the impact of the AC/FC on the prognosis of HFpEF may be greater than that of HFrEF.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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“…L-carnitine prevents the development of ventricular fibrosis and heart failure with preserved EF in hypertensive heart disease [22]. L-carnitine also blocks dietary vitamin B deficiency-induced left ventricular dysfunction and attenuates the diet-caused increase in serum BNP [23].…”

Section: Effects On Cardiac Parametersmentioning

confidence: 99%

Effects of L-carnitine supplementation on nutritional, immunological, and cardiac parameters in hemodialysis patients: a pilot study

et al. 2015

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Background: L-carnitine is an essential compound that facilitates the transport of long-chain fatty acid across the inner mitochondrial membrane for β-oxidation. However, the effect of L-carnitine supplementation remains to be fully explored in patients with chronic kidney disease. We aimed in this study to determine the multidirectional effects of L-carnitine supplementation on clinical parameters in more detail. Methods: We orally administered L-carnitine to maintain serum-free carnitine levels within the normal range (30 to 70 μmol/L) for 6 months in 21 hemodialysis (HD) patients (age, 74 ± 11 years; time on HD, 60 ± 84 months).

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L-Carnitine prevents the development of ventricular fibrosis and heart failure with preserved ejection fraction in hypertensive heart disease

Cited by 53 publications

References 59 publications

Excess Linoleic Acid Increases Collagen I/III Ratio and “Stiffens” the Heart Muscle Following High Fat Diets

Excess Linoleic Acid Increases Collagen I/III Ratio and “Stiffens” the Heart Muscle Following High Fat Diets

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

Effects of L-carnitine supplementation on nutritional, immunological, and cardiac parameters in hemodialysis patients: a pilot study

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