Ketone Bodies in Right Ventricular Failure: A Unique Therapeutic Opportunity

Blake, Madelyn; Puchalska, Patrycja; Kazmirczak, Felipe; Thenappan, Thenappan; Crawford, Peter A.; Prins, Kurt W.

doi:10.1101/2023.04.26.538410

Cited by 2 publications

(1 citation statement)

References 17 publications

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“…While our article was submitted, a non-reviewed article from the Lillehei heart institute (Minnesota university) describes that compensatory ketosis is absent in RV failure, in contrast to LV failure. The therapeutic stimulation of ketolytic activity is improving RV function, suppresses NLRP3 inflammasome activation and blunts myocardial fibrosis [ 88 ]. Those authors hypothesized an RV-liver-axis behind this specific RV dysregulation.…”

Section: Cardiac Energy Metabolismmentioning

confidence: 99%

Comparative Metabolomics in Single Ventricle Patients after Fontan Palliation: A Strong Case for a Targeted Metabolic Therapy

Renaud,

Scholl-Bürgi,

Karall

et al. 2023

Metabolites

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Most studies on single ventricle (SV) circulation take a physiological or anatomical approach. Although there is a tight coupling between cardiac contractility and metabolism, the metabolic perspective on this patient population is very recent. Early findings point to major metabolic disturbances, with both impaired glucose and fatty acid oxidation in the cardiomyocytes. Additionally, Fontan patients have systemic metabolic derangements such as abnormal glucose metabolism and hypocholesterolemia. Our literature review compares the metabolism of patients with a SV circulation after Fontan palliation with that of patients with a healthy biventricular (BV) heart, or different subtypes of a failing BV heart, by Pubmed review of the literature on cardiac metabolism, Fontan failure, heart failure (HF), ketosis, metabolism published in English from 1939 to 2023. Early evidence demonstrates that SV circulation is not only a hemodynamic burden requiring staged palliation, but also a metabolic issue with alterations similar to what is known for HF in a BV circulation. Alterations of fatty acid and glucose oxidation were found, resulting in metabolic instability and impaired energy production. As reported for patients with BV HF, stimulating ketone oxidation may be an effective treatment strategy for HF in these patients. Few but promising clinical trials have been conducted thus far to evaluate therapeutic ketosis with HF using a variety of instruments, including ketogenic diet, ketone esters, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. An initial trial on a small cohort demonstrated favorable outcomes for Fontan patients treated with SGLT2 inhibitors. Therapeutic ketosis is worth considering in the treatment of Fontan patients, as ketones positively affect not only the myocardial energy metabolism, but also the global Fontan physiopathology. Induced ketosis seems promising as a concerted therapeutic strategy.

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Section: Cardiac Energy Metabolismmentioning

confidence: 99%