Plasma amino acid metabolomic pattern in heart failure patients with either preserved or reduced ejection fraction: The relation to established risk variables and prognosis

Saleem, Tahia H.; Algowhary, Magdy; Kamel, Fatma Elzahraa M; El‐Mahdy, Reham I

doi:10.1002/bmc.5012

Cited by 8 publications

(14 citation statements)

References 44 publications

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“…Lastly, previous studies on adult Fontan patients with a dominant left ventricle reported that the observed perturbations in amino acid, phospholipid, and acylcarnitine metabolomes suggested altered cell energy metabolism, oxidative stress, endothelial dysfunction, and aberrant cell signaling as found in biventricular patients with congestive heart failure [15] , [16] . In contrast, the present study targeted adult Fontan patients exhibiting a wide variety of structural abnormalities, medications, and complications, and thus was considered to represent the heterogeneous Fontan population.…”

Section: Discussionmentioning

confidence: 75%

“…Therefore, metabolomics represents a potential tool for identifying biomarkers to understand the pathophysiological mechanism of cardiovascular diseases [14] . Several studies have addressed the metabolic alterations in patients with such cardiovascular conditions as coronary artery disease, arrhythmia, and heart failure [15] , [16] . Recently, metabolomic analysis has also been used in patients with congenital heart disease (CHD) to investigate predictors [17] .…”

Section: Introductionmentioning

confidence: 99%

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Identification of metabolomic profile related to adult Fontan pathophysiology

Motoki

Utsumi

et al. 2021

IJC Heart & Vasculature

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Background Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups. Methods and Results We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry. This observational cross-sectional study compared plasma metabolites of 14 heterogeneous adult Fontan patients with those of control groups, including 9 patients with congenital heart disease after biventricular repair and 8 normal healthy controls. Fontan patients exhibited significant differences in intermediate metabolite concentrations related to glycolysis, the tricarboxylic acid (TCA) cycle, and the urea cycle. The plasma concentrations of lactic acid, 2-oxoglutarate, isocitric acid, malic acid, cis -aconitic acid, arginine, citrulline, and the ratio of ornithine/citrulline showed significantly differences among the groups. Multiple logistic regression analysis with a stepwise selection-elimination method identified 2-oxoglutaric acid (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05–3.76) and cis -aconitic acid (OR 2.69, 95% CI 1.04–6.99) as independently associated with Fontan patients. After adjustment for the covariates of age and gender, 2-oxoglutaric acid (OR 1.97, 95% CI 0.98–3.93) and cis -aconitic acid (OR 3.88, 95% CI 0.99–15.2) showed remarkable relationships with Fontan patients. Conclusions The present findings suggest that abnormalities in the TCA cycle and amino acid metabolism are distinguishing features in the pathophysiology of Fontan patients. Future metabolomic studies will assist in developing biomarkers for the early prediction of “silent” Fontan pathophysiologies.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Identification of metabolomic profile related to adult Fontan pathophysiology

Motoki

Utsumi

et al. 2021

IJC Heart & Vasculature

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“…Indeed, even though cardiac tissues from HFpEF patients absorb and likely consume more Ile and Leu than HFrEF patients [ 26 ], their buildup in overt HFpEF suggests a relationship with endothelial dysfunction [ 130 ]. Furthermore, it was proven that Leu and Ile oxidation is more dysregulated in HFrEF than in HFpEF patients [ 72 ]. In addition, patients with at-baseline higher LV dysfunction had higher plasmatic accumulation of valine, leucine [ 72 ], and Ile [ 72 , 73 ] than controls and patients with lower LV dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, it was proven that Leu and Ile oxidation is more dysregulated in HFrEF than in HFpEF patients [ 72 ]. In addition, patients with at-baseline higher LV dysfunction had higher plasmatic accumulation of valine, leucine [ 72 ], and Ile [ 72 , 73 ] than controls and patients with lower LV dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…The plasmatic concentrations of glutamate [ 28 , 72 , 73 ], tyrosine [ 28 , 29 , 72 , 73 ], and phenylalanine [ 28 , 29 , 72 , 73 , 96 , 133 ] are lower in HFpEF, or individuals with lower LV dysfunction, and notably, other studies ascertained the opposite for Ala [ 31 , 54 , 72 , 92 ]. Alanine and glutamate are glucogenic AA, while phenylalanine and tyrosine are both glucogenic and ketogenic, and all of them are anaplerotic substrates that supply the TCA cycle [ 93 ].…”

Section: Introductionmentioning

confidence: 99%

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Understanding How Heart Metabolic Derangement Shows Differential Stage Specificity for Heart Failure with Preserved and Reduced Ejection Fraction

2022

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Heart failure (HF) is a clinical condition defined by structural and functional abnormalities in the heart that gradually result in reduced cardiac output (HFrEF) and/or increased cardiac pressures at rest and under stress (HFpEF). The presence of asymptomatic individuals hampers HF identification, resulting in delays in recognizing patients until heart dysfunction is manifested, thus increasing the chance of poor prognosis. Given the recent advances in metabolomics, in this review we dissect the main alterations occurring in the metabolic pathways behind the decrease in cardiac function caused by HF. Indeed, relevant preclinical and clinical research has been conducted on the metabolite connections and differences between HFpEF and HFrEF. Despite these promising results, it is crucial to note that, in addition to identifying single markers and reliable threshold levels within the healthy population, the introduction of composite panels would strongly help in the identification of those individuals with an increased HF risk. That said, additional research in the field is required to overcome the current drawbacks and shed light on the pathophysiological changes that lead to HF. Finally, greater collaborative data sharing, as well as standardization of procedures and approaches, would enhance this research field to fulfil its potential.

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Tyrosine to threonine ratio was related to heart failure with reduced or mildly reduced ejection fraction

Zhou,

Yang,

Dai

et al. 2024

ESC Heart Failure

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AimsWe aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF).Methods and resultsThe study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event‐free survival was determined by Kaplan–Meier curves and differences in survival were assessed using log‐rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver‐operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P < 0.001) while serum threonine (Thr) decreased (165.21 ± 40.09 μmol/L vs. 144.93 ± 44.56 μmol/L vs. 135.25 ± 41.25 μmol/L, P < 0.001). Tyr/Thr ratio was the independent risk factor for the presence of HF in all subjects [odds ratio (OR), 3.510; 95% confidence interval (CI): 2.445–5.040; P < 0.001]. After following up for a mean year (11.10 ± 2.80 months) in 269 HF subjects (75.1% males, mean age 65.2 ± 12.8 years), the higher Tyr/Thr ratio was associated with a higher risk of HF endpoint events in HF subjects [hazard ratio (HR), 2.901; 95% CI: 1.228–6.851; P = 0.015]. By comparing the area under the receiver‐operating characteristic curve (AUC), Tyr/Thr ratio was superior to Fischer's ratio (FR) in predicting HF occurrence (0.767:0.573, P < 0.001) or cardiovascular (CV) death (0.715:0.550, P = 0.047).ConclusionsCirculating elevated Tyr/Thr ratio confer an increased risk for the presence of HF and poor prognosis. Tyr/Thr index outweighs FR index in predicting HF occurrence or CV death.

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Plasma amino acid metabolomic pattern in heart failure patients with either preserved or reduced ejection fraction: The relation to established risk variables and prognosis

Cited by 8 publications

References 44 publications

Identification of metabolomic profile related to adult Fontan pathophysiology

Identification of metabolomic profile related to adult Fontan pathophysiology

Understanding How Heart Metabolic Derangement Shows Differential Stage Specificity for Heart Failure with Preserved and Reduced Ejection Fraction

Tyrosine to threonine ratio was related to heart failure with reduced or mildly reduced ejection fraction

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