bims-hafaim 2024-09-15 papers

Issue of 2024–09–15
three papers selected by
Kyle McCommis, Saint Louis University

Curr Heart Fail Rep. 2024 Sep 07.

Metabolic Adaptation in Heart Failure and the Role of Ketone Bodies as Biomarkers.

Michael W Foster, Joshua M Riley, Praneet C Kaki, Amine Al Soueidy, Ehson Aligholiazadeh, J Eduardo Rame.

PURPOSE OF REVIEW: The development and progression of heart failure is characterized by metabolic and physiologic adaptations allowing patients to cope with cardiac insufficiency. This review explores the changes in metabolism in heart failure and the potential role of biomarkers, particularly ketone bodies, in staging and prognosticating heart failure progression.
RECENT FINDINGS: Recent insights into myocardial metabolism shed light on the heart's response to stress, highlighting the shift towards reliance on ketone bodies as an alternative fuel source. Elevated blood ketone levels have been shown to correlate with the severity of cardiac dysfunction, emphasizing their potential as prognostic indicators. Furthermore, studies exploring therapeutic interventions targeting specific metabolic pathways offer promise for improving outcomes in heart failure. Ketones have prognostic utility in heart failure, and potentially, an avenue for therapeutic intervention. Challenges remain in deciphering the optimal balance between metabolic support and exacerbating cardiac remodeling. Future research endeavors must address these complexities to advance personalized approaches in managing heart failure.

Keywords: Biomarkers; Cardiomyopathy; Heart failure; Ketone bodies; Myocardial metabolism

DOI: https://doi.org/10.1007/s11897-024-00678-6

Physiol Rep. 2024 Sep;12(17): e70040

PKM2 regulates metabolic flux and oxidative stress in the murine heart.

Katie C Y Lee, Allison L Williams, Lu Wang, Guoxiang Xie, Wei Jia, Anastasia Fujimoto, Mariana Gerschenson, Ralph V Shohet.

Cardiac metabolism ensures a continuous ATP supply, primarily using fatty acids in a healthy state and favoring glucose in pathological conditions. Pyruvate kinase muscle (PKM) controls the final step of glycolysis, with PKM1 being the main isoform in the heart. PKM2, elevated in various heart diseases, has been suggested to play a protective role in cardiac stress, but its function in basal cardiac metabolism remains unclear. We examined hearts from global PKM2 knockout (PKM2-/-) mice and found reduced intracellular glucose. Isotopic tracing of U-13C glucose revealed a shift to biosynthetic pathways in PKM2-/- cardiomyocytes. Total ATP content was two-thirds lower in PKM2-/- hearts, and functional analysis indicated reduced mitochondrial oxygen consumption. Total reactive oxygen species (ROS) and mitochondrial superoxide were also increased in PKM2-/- cardiomyocytes. Intriguingly, PKM2-/- hearts had preserved ejection fraction compared to controls. Mechanistically, increased calcium/calmodulin-dependent kinase II activity and phospholamban phosphorylation may contribute to higher sarcoendoplasmic reticulum calcium ATPase 2 pump activity in PKM2-/- hearts. Loss of PKM2 led to altered glucose metabolism, diminished mitochondrial function, and increased ROS in cardiomyocytes. These data suggest that cardiac PKM2 acts as an important rheostat to maintain ATP levels while limiting oxidative stress. Although loss of PKM2 did not impair baseline contractility, its absence may make hearts more sensitive to environmental stress or injury.

Keywords: glucose; glycolysis; metabolism; reactive oxygen species

DOI: https://doi.org/10.14814/phy2.70040

J Cardiovasc Magn Reson. 2024 Sep 11. pii: S1097-6647(24)01122-0. [Epub ahead of print] 101095

Hyperpolarized [1-13C]pyruvate Magnetic Resonance Imaging Identifies Metabolic Phenotypes in Patients with Heart Failure.

Steen Hylgaard Joergensen, Esben Soevsoe S Hansen, Nikolaj Bøgh, Lotte Bonde Bertelsen, Rasmus Stilling Tougaard, Peter Bisgaard Staehr, Christoffer Laustsen, Henrik Wiggers.

BACKGROUND: Hyperpolarized [1-13C]pyruvate magnetic resonance imaging (HP MRI) visualizes key steps in myocardial metabolism. The present study aimed to examine patients with heart (HF) using HP MRI.
METHODS: A cross-sectional study of patients with HF and healthy controls using HP MRI. Metabolic imaging was obtained using a cardiac-gated spectral-spatial excitation with spiral read-out acquisition. The metabolite signal was analyzed for lactate, bicarbonate, and the alanine signal. Metabolite signal was normalized to the total carbon signal (TC). At the one-year follow-up, echocardiography was performed in all patients and HP MRI in two patients.
RESULTS: We included six patients with ischemic heart disease (IHD), six with dilated cardiomyopathy and six healthy controls. In patients, left ventricular ejection fraction (LVEF) correlated with lactate/bicarbonate (r = -0.6, p = 0.03) and lactate/TC (r = -0.7, p = 0.01). In patients with LVEF < 30%, lactate/TC was increased (p = 0.01) and bicarbonate/TC reduced (p = 0.03). Circumferential strain correlated with metabolite ratios: lactate/bicarbonate, r = 0.87 (p = 0.0002); lactate/TC, r = 0.85 (p = 0.0005); bicarbonate/TC, r = -0.82 (p = 0.001). In patients with IHD, a strong correlation was found between baseline metabolite ratios and the change in LVEF at follow-up: lactate/bicarbonate (p = 0.001); lactate/TC (p = 0.011); and bicarbonate/TC (p = 0.012).
CONCLUSIONS: This study highlighted the ability of HP MRI to detect changes in metabolism in HF. HP MRI has potential for metabolic phenotyping of patients with HF and for predicting treatment response.
TRIAL REGISTRATION: EUDRACT, 2018-003533-15. Registered 4 December 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-15.

Keywords: Cardiac Metabolism; Heart Failure; Hyperpolarized [1-(13)C]pyruvate Magnetic Resonance Imaging; Metabolic Imaging

DOI: https://doi.org/10.1016/j.jocmr.2024.101095