Plasma myo-inositol elevation in heart failure: clinical implications and prognostic significance. Results from the BElgian and CAnadian MEtabolomics in HFpEF (BECAME-HF) research projectResearch in context
Anne-Catherine Pouleur,
Nassiba Menghoum,
Julien Cumps,
Alice Marino,
Maria Badii,
Sibille Lejeune,
Julie Thompson Legault,
Gabrielle Boucher,
Damien Gruson,
Clotilde Roy,
Sylvain Battault,
Louiza Mahrouche,
Valérie Pedneault-Gagnon,
Daniel Charpentier,
Alexandra Furtos,
Julie Hussin,
David Rhainds,
Jean-Claude Tardif,
Luc Bertrand,
Christine Des Rosiers,
Sandrine Horman,
Christophe Beauloye
Affiliations
Anne-Catherine Pouleur
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium; Department of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Nassiba Menghoum
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
Julien Cumps
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
Alice Marino
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
Maria Badii
Department of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Sibille Lejeune
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
Julie Thompson Legault
Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada
Gabrielle Boucher
Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada
Damien Gruson
Department of Clinical Biology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Clotilde Roy
Department of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Sylvain Battault
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
Louiza Mahrouche
Department of Chemistry, Université de Montréal, Montréal, QC H3T IJ4, Canada
Valérie Pedneault-Gagnon
Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada
Daniel Charpentier
Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada
Alexandra Furtos
Department of Chemistry, Université de Montréal, Montréal, QC H3T IJ4, Canada
Julie Hussin
Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada
David Rhainds
Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada
Jean-Claude Tardif
Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada; Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada
Luc Bertrand
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium
Christine Des Rosiers
Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada; Department of Nutrition, Université de Montréal, Montréal, QC H3T 1J4, Canada
Sandrine Horman
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
Christophe Beauloye
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium; Department of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Department of Cardiovascular Intensive Care, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Corresponding author. Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, UCLouvain, 55, Avenue Hippocrate B1.55.03.1322, Brussels BE-1200, Belgium.
Summary: Background: The metabolic environment plays a crucial role in the development of heart failure (HF). Our prior research demonstrated that myo-inositol, a metabolite transported by the sodium-myo-inositol co-transporter 1 (SMIT-1), can induce oxidative stress and may be detrimental to heart function. However, plasmatic myo-inositol concentration has not been comprehensively assessed in large cohorts of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Methods: Plasmatic myo-inositol levels were measured using mass spectrometry and correlated with clinical characteristics in no HF subjects and patients with HFrEF and HFpEF from Belgian (male, no HF, 53%; HFrEF, 84% and HFpEF, 40%) and Canadian cohorts (male, no HF, 51%; HFrEF, 92% and HFpEF, 62%). Findings: Myo-inositol levels were significantly elevated in patients with HF, with a more pronounced increase observed in the HFpEF population of both cohorts. After adjusting for age, sex, body mass index, hypertension, diabetes, and atrial fibrillation, we observed that both HFpEF status and impaired kidney function were associated with elevated plasma myo-inositol. Unlike HFrEF, abnormally high myo-inositol (≥69.8 μM) was linked to unfavourable clinical outcomes (hazard ratio, 1.62; 95% confidence interval, [1.05–2.5]) in patients with HFpEF. These elevated levels were correlated with NTproBNP, troponin, and cardiac fibrosis in this subset of patients. Interpretation: Myo-inositol is a metabolite elevated in patients with HF and strongly correlated to kidney failure. In patients with HFpEF, high myo-inositol levels predict poor clinical outcomes and are linked to markers of cardiac adverse remodelling. This suggests that myo-inositol and its transporter SMIT1 may have a role in the pathophysiology of HFpEF. Funding: BECAME-HF was supported by Collaborative Bilateral Research Program Québec – Wallonie-Brussels Federation.
