Plasma Myo-Inositol Elevation in Heart Failure: Clinical Implications and Prognostic Significance. Results from the BElgian and CAnadian MEtabolomics in HFpEF (BECAME-HF) Research Project

Anne-Catherine Pouleur,Nassiba Menghoum，Sandrine Horman,Christophe Beauloye

EBioMedicine（2024）

Pôle de Recherche Cardiovasculaire (CARD) | Clin Univ St Luc | Montreal Heart Inst | Univ Montreal

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Abstract

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 (SMIT1), 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 fi cantly 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 fi brillation, 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 >= 69.8 mu M) was linked to unfavourable clinical outcomes (hazard ratio, 1.62; 95% confidence fi dence interval, [1.05-2.5]) - 2.5]) in patients with HFpEF. These elevated levels were correlated with NTproBNP, troponin, and cardiac fi brosis 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 Qu & eacute;bec - Wallonie-Brussels Federation.

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Key words

Heart failure,HFpEF,Myo-inositol,Prognosis,Metabolites,Kidney

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