Key result
Higher fatty acid-to-glucose utilization ratio predicts ≥10% LVEF improvement post-LVAD in advanced heart failure.
Why the study?
Perturbations of myocardial metabolism and energy depletion are hallmarks of heart failure, but methods for their systematic assessment in humans remain limited.
Does the ratio of fatty acid to glucose utilization predict reverse cardiac remodeling after LVAD implantation in patients with advanced heart failure?
Does the ratio of fatty acid to glucose utilization predict reverse cardiac remodeling after LVAD implantation in patients with advanced heart failure?
Computational modelling of myocardial metabolism reveals that a higher fatty acid to glucose utilization ratio predicts functional recovery and reverse remodeling after LVAD implantation in advanced heart failure.
May identify LVAD responders via metabolic phenotyping in advanced HF; leaves open need for prospective validation before clinical adoption.
Aims Perturbations of myocardial metabolism and energy depletion are well‐established hallmarks of heart failure (HF), yet methods for their systematic assessment remain limited in humans. This study aimed to determine the ability of computational modelling of patient‐specific myocardial metabolism to assess individual bioenergetic phenotypes and their clinical implications in HF. Methods and results Based on proteomics‐derived enzyme quantities in 136 cardiac biopsies, personalised computational models of myocardial metabolism were generated in two independent cohorts of advanced HF patients together with sex‐ and body mass index‐matched non‐failing controls. The bioenergetic impact of dynamic changes in substrate availability and myocardial workload were simulated, and the models' ability to predict the myocardial response following left ventricular assist device (LVAD) implantation was assessed. Compared to controls, HF patients had a reduced ATP production capacity ( p < 0.01), although there was remarkable interindividual variance. Utilisation of glucose relative to fatty acids was generally higher in HF patients, depending on substrate availability and myocardial workload. The ratio of fatty acid to glucose utilisation was associated with reverse cardiac remodelling after LVAD implantation and highly predictive of an improvement in left ventricular ejection fraction ≥10% (C‐index 0.94 [0.81–1.00], p < 0.01). System‐level simulations identified fatty acid administration and carnitine supplementation in those with low mitochondrial carnitine content as potential pharmacological interventions to restore myocardial substrate utilisation. Conclusions Computational modelling identified a subset of advanced HF patients with preserved myocardial metabolism despite a similar degree of systolic dysfunction. Substrate preference was associated with the myocardial response after LVAD implantation, which suggests a role for substrate manipulation as a therapeutic approach. Computational assessment of myocardial metabolism in HF may improve understanding of disease heterogeneity, individual risk stratification, and guidance of personalised clinical decision‐making in the future.
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Beyhoff et al. (2025) studied this question. In advanced heart failure patients, a higher fatty acid to glucose utilisation ratio predicted an improvement in left ventricular ejection fraction ≥10% post-LVAD implantation (C-index 0.94).
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