Positive pediatric exercise capacity trajectory predicts better adult Fontan physiology rationale for early establishment of exercise habits

Ohuchi, Hideo; Negishi, Jun; Miike, Hikari; Toyoshima, Yuka; Morimoto, Yoshihito; Fukuyama, Midori; Iwasa, Takeshi; Sakaguchi, Heima; Miyazaki, Aya; Shiraishi, Isao; Kurosaki, Kenichi; Nakai, Michikazu

doi:10.1016/j.ijcard.2018.06.067

Cited by 41 publications

(50 citation statements)

References 33 publications

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“…Echocardiography followed, and, after a defined snack rich in carbohydrates, exercise capacity was tested. We correlated metabolic results with routine laboratory parameters and exercise capacity parameters 51 . All patients underwent symptom-limited treadmill exercise capacity testing with expiratory gas analysis 52 .…”

Section: Methodsmentioning

confidence: 99%

Targeted metabolomic analysis of serum amino acids in the adult Fontan patient with a dominant left ventricle

Michel

Dubowy

Entenmann

et al. 2020

Sci Rep

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Growing interest lies in the assessment of the metabolic status of patients with a univentricular circulation after Fontan operation, especially in changes of amino acid metabolism. Using targeted metabolomic examinations, we investigated amino acid metabolism in a homogeneous adult Fontanpatient group with a dominant left ventricle, seeking biomarker patterns that might permit better understanding of fontan pathophysiology and early detection of subtle ventricular or circulatory dysfunction. We compared serum amino acid levels (42 analytes; AbsoluteIDQ p180 kit, Biocrates Life Sciences, Innsbruck, Austria) in 20 adult Fontan patients with a dominant left ventricle and those in age-and sex-matched biventricular controls. Serum concentrations of asymmetric dimethylarginine, methionine sulfoxide, glutamic acid, and trans-4-hydroxyproline and the methionine sulfoxide/ methionine ratio (Met-SO/Met) were significantly higher and serum concentrations of asparagine, histidine, taurine, and threonine were significantly lower in patients than in controls. Met-SO/ Met values exhibited a significant negative correlation with oxygen uptake during exercise. The alterations in amino acid metabolome that we found in fontan patients suggest links between fontan pathophysiology, altered cell energy metabolism, oxidative stress, and endothelial dysfunction like those found in biventricular patients with congestive heart failure. Studies of extended amino acid metabolism may allow better understanding of fontan pathophysiology that will permit early detection of subtle ventricular or circulatory dysfunction in Fontan patients. Ventricular dysfunction and circulatory failure with progressing end-organ impairment like renal or liver dysfunction are an important cause of morbidity and mortality in adults with complex congenital heart disease (CHD), especially in patients with single-ventricle types of CHD and Fontan circulation 1,2. Besides limited cardiac output, alterations that mark Fontan hemodynamics are passive flow to the lungs, chronically elevated venous pressures, and congestion. Unfortunately, the clinical use of traditional markers such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels for non-invasive diagnostics and monitoring in such patients is limited 3,4. Thus, for early detection of cardiac and circulatory derangement and for evaluation and tailoring of treatment options, regular functional assessment of these patients is crucial, with complete clinical examination, electrocardiogram, imaging studies, determination of values for traditional laboratory markers, or exercise capacity testing.

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Section: Methodsmentioning

confidence: 99%

Targeted metabolomic analysis of serum amino acids in the adult Fontan patient with a dominant left ventricle

Michel

Dubowy

Entenmann

et al. 2020

Sci Rep

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show abstract

“…To exclude metabolites below the limit of detection (LOD), the raw data (µmol/l) were cleaned applying a modified 80% rule; thus, for statistical analy- 20 Fontan patients and 20 age-and sex-matched controls were enrolled ( Figure 1). Data were complete for all of them.…”

Section: Statisticsmentioning

confidence: 99%

Targeted metabolomic analysis of serum phospholipid and acylcarnitine in the adult Fontan patient with a dominant left ventricle

Michel

Dubowy

Zlamy

et al. 2020

Therapeutic Advances in Chronic Disease

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Background: Patients with a Fontan circulation have altered cholesterol and lipoprotein values. We analysed small organic molecules in extended phopsholipid and acylcarnitine metabolic pathways (‘metabolomes’) in adult Fontan patients with a dominant left ventricle, seeking differences between profiles in baseline and Fontan circulations. Methods: In an observational matched cross-sectional study, we compared phosphatidylcholine (PC), sphingomyelin (SM), and acylcarnitine metabolomes (105 analytes; AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) in 20 adult Fontan patients having a dominant left ventricle with those in 20 age- and sex-matched healthy controls. Results: Serum levels of total PC ( q-value 0.01), total SM ( q-value 0.0002) were significantly lower, and total acylcarnitines ( q-value 0.02) were significantly higher in patients than in controls. After normalisation of data, serum levels of 12 PC and 1 SM Fontan patients were significantly lower ( q-values <0.05), and concentrations of 3 acylcarnitines were significantly higher than those in controls ( q-values <0.05). Conclusion: Metabolomic profiling can use small specimens to identify biomarker patterns that track derangement in multiple metabolic pathways. The striking alterations in the phospholipid and acylcarnitine metabolome that we found in Fontan patients may reflect altered cell signalling and metabolism as found in heart failure in biventricular patients, chronic low-level inflammation, and alteration of functional or structural properties of lymphatic or blood vessels. Trial registration number: ClinicalTrials.gov Identifier NCT03886935

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“…This is particularly significant because systemic venous pressure may rise considerably during periods of vigorous activity, in contrast to the normal circulation [116]. It is unclear whether transient increases in venous pressure for short periods predispose to end-organ damage or if exercise-induced flow improves pulmonary vascular physiology and overall reduces resting venous pressure, as suggested by recent data [117].…”

Section: Safetymentioning

confidence: 99%

Management of People With a Fontan Circulation: a Cardiac Society of Australia and New Zealand Position statement

Zentner

Celermajer

Gentles

et al. 2020

Heart, Lung and Circulation

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The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as individuals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival.

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Positive pediatric exercise capacity trajectory predicts better adult Fontan physiology rationale for early establishment of exercise habits

Cited by 41 publications

References 33 publications

Targeted metabolomic analysis of serum amino acids in the adult Fontan patient with a dominant left ventricle

Targeted metabolomic analysis of serum amino acids in the adult Fontan patient with a dominant left ventricle

Targeted metabolomic analysis of serum phospholipid and acylcarnitine in the adult Fontan patient with a dominant left ventricle

Management of People With a Fontan Circulation: a Cardiac Society of Australia and New Zealand Position statement

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