Metabolomic fingerprint of heart failure in humans: A nuclear magnetic resonance spectroscopy analysis

Tenori, Leonardo; Hu, Xiaoyu; Pantaleo, Pietro; Alterini, Brunetto; Castelli, Gabriele; Olivotto, Iacopo; Bertini, Ivano; Luchinat, Claudio; Gensini, Gian Franco

doi:10.1016/j.ijcard.2013.08.042

Cited by 61 publications

(60 citation statements)

References 8 publications

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“…The plasma levels of glycerol, linoleate, myristate, and cholesterol, which were reduced in HF patients, may indicate reduced lipid metabolism. Similarly others using different analytical platforms and patient groups found altered metabolomic profiles in heart failure and identified candidate disease biomarkers 19, 29, 49, 50 . Consistent with derangement in different metabolic pathways at a systemic level, as we observed in our study, HF patients had higher serum concentrations of phenylalanine, tyrosine, isoleucine, creatine, and lower serum levels of lactate, citrate and lysine 49 .…”

Section: Discussionmentioning

confidence: 82%

“…Similarly others using different analytical platforms and patient groups found altered metabolomic profiles in heart failure and identified candidate disease biomarkers 19, 29, 49, 50 . Consistent with derangement in different metabolic pathways at a systemic level, as we observed in our study, HF patients had higher serum concentrations of phenylalanine, tyrosine, isoleucine, creatine, and lower serum levels of lactate, citrate and lysine 49 . In patients with heart failure significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate 19 and 2-oxoglutarate and pseudouridine, 51 was demonstrated.…”

Section: Discussionmentioning

confidence: 82%

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Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Nemutlu

Zhang

et al. 2015

Journal of Cardiac Failure

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Background Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value for the response to CRT. Methods This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed using gas chromatography–mass spectrometry and nuclear magnetic resonance. Results The plasma metabolomic profile was altered in the HF patients, with a distinct panel of metabolites, including Krebs cycle and lipid, amino acid, and nucleotide metabolism. CRT improved the metabolic profile. The succinate/glutamate ratio, an index of Krebs cycle activity, improved from 0.58±0.13 to 2.84±0.60 (P<.05). The glucose/palmitate ratio, an indicator of the balance between glycolytic and fatty acid metabolism, increased from 0.96±0.05 to 1.54±0.09 (P<.01). Compared with the nonresponders to CRT, the responders had a distinct baseline plasma metabolomic profile, including higher isoleucine, phenylalanine, leucine, glucose, and valine levels and lower glutamate levels at baseline (P<.05). Conclusion CRT improves plasma metabolomic profile of HF patients indicating harmonization of myocardial energy substrate metabolism. CRT responders may have a favorable metabolic profile as a potential biomarker for predicting CRT outcome.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 82%

Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Nemutlu

Zhang

et al. 2015

Journal of Cardiac Failure

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“…Although these metabolites represent a small portion of the human metabolome in terms of absolute numbers, they report on pathways critical for cellular and organism‐level homeostasis: fatty acid, carbohydrate, amino acid, and urea metabolism. These particular metabolites were chosen for several reasons: (1) An expanding body of evidence has implicated impairments in fatty acid and carbohydrate oxidation in HF pathophysiology, which could be reflected in acylcarnitine elevations13, 50, 73, 74, 75, 76, 77; (2) previous metabolomics investigations have identified derangements in plasma levels of these metabolites in HF patients49, 50, 78, 79, 80; and (3) acylcarnitines and their derivatives have been suggested to have intrinsic physiological effects that could contribute to the HF phenotype 66, 67, 68, 81, 82…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Hunter

Kelly

McGarrah

et al. 2016

JAHA

186

137

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BackgroundMetabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF).Methods and ResultsWe identified HFpEF cases, HFrEF controls, and no‐HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No‐HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long‐chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no‐HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance.ConclusionsWe identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.

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“…Previous studies identified several metabolomic features in plasma and tissue samples that were related to HF or cardiovascular pathologies such as coronary artery disease (CAD) (11,17,18 ). Recently, Cheng et al identified biomarker panels comprising metabolomic features from several ontology classes in a large metabolomics study on HF patients (19 ).…”

Section: Metabolomic Features As Novel Diagnostic Biomarkers For Hfrefmentioning

confidence: 99%

A Novel Lipid Biomarker Panel for the Detection of Heart Failure with Reduced Ejection Fraction

et al. 2017

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OBJECTIVES:In this study we aimed to identify novel metabolomic biomarkers suitable for improved diagnosis of heart failure with reduced ejection fraction (HFrEF). METHODS:We prospectively recruited 887 individuals consisting of HFrEF patients with either ischemic (ICMP, n ϭ 257) or nonischemic cardiomyopathy (NICMP, n ϭ 269), healthy controls (n ϭ 327), and patients with pulmonary diseases (n ϭ 34). A singlecenter identification (n ϭ 238) was followed by a multicenter confirmation study (n ϭ 649). Plasma samples from the single-center study were subjected to metabolite profiling analysis to identify metabolomic features with potential as HFrEF biomarkers. A dedicated analytical protocol was developed for the routine analysis of selected metabolic features in the multicenter cohort. RESULTS:In the single-center study, 92 of 181 metabolomic features with known chemical identity (51%) were significantly changed in HFrEF patients compared to healthy controls (P Ͻ0.05). Three specific metabolomic features belonging to the lipid classes of sphingomyelins, triglycerides, and phosphatidylcholines were selected as the cardiac lipid panel (CLP) and analyzed in the multicenter study using the dedicated analytical protocol. The combination of the CLP with N-terminal pro-B-type natriuretic peptide (NT-proBNP) distinguished HFrEF patients from healthy controls with an area under the curve (AUC) of 0.97 (sensitivity 80.2%, specificity 97.6%) and was significantly superior compared to NTproBNP alone (AUC ϭ 0.93, sensitivity 81.7%, specificity 88.1%, P Ͻ0.001), even in the subgroups with mildly reduced left ventricular EF (0.94 vs 0.87; P Ͻ0.001) and asymptomatic patients (0.95 vs 0.91; P Ͻ0.05). CONCLUSIONS:The new metabolomic biomarker panel has the potential to improve HFrEF detection, even in mild and asymptomatic stages. The observed changes further indicate lipid alterations in the setting of HFrEF.

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Metabolomic fingerprint of heart failure in humans: A nuclear magnetic resonance spectroscopy analysis

Cited by 61 publications

References 8 publications

Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

A Novel Lipid Biomarker Panel for the Detection of Heart Failure with Reduced Ejection Fraction

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