bims-hafaim Biomed News
on Heart failure metabolism
Issue of 2021‒10‒03
twelve papers selected by
Kyle McCommis
Saint Louis University
  1. TFEC contributes to cardiac hypertrophy by inhibiting AMPK/mTOR signaling.
  2. Enhanced Heart Failure in Redox-Dead Cys17Ser PKARIα Knock-In Mice.
  3. Ketone Ester D-β-Hydroxybutyrate-(R)-1,3 Butanediol Prevents Decline in Cardiac Function in Type 2 Diabetic Mice.
  4. Stearoyl-CoA Desaturase (SCD) Induces Cardiac Dysfunction with Cardiac Lipid Overload and Angiotensin II AT1 Receptor Protein Up-Regulation.
  5. Nicotinamide Riboside Alleviates Cardiac Dysfunction and Remodeling in Pressure Overload Cardiac Hypertrophy.
  6. Maternal Fructose Intake Exacerbates Cardiac Remodeling in Offspring with Ventricular Pressure Overload.
  7. Integrated Stress Response Couples Mitochondrial Protein Translation with Oxidative Stress Control.
  8. Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure.
  9. PUFA Supplementation and Heart Failure: Effects on Fibrosis and Cardiac Remodeling.
  10. Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction.
  11. Analysis of Metabolic Markers in Patients with Chronic Heart Failure before and after LVAD Implantation.
  12. Ketone Bodies: Universal Cardiac Response to Stress?
  1. Exp Ther Med. 2021 Nov;22(5): 1271
    TFEC contributes to cardiac hypertrophy by inhibiting AMPK/mTOR signaling.
    Ting Zhao, Zhenyu Wang, Yehong Chi, Chunmei Ni, Xudan Zheng.
      The underlying mechanism of cardiac hypertrophy has not yet been fully elucidated. The present study aimed to explore the function of transcription factor EC (TFEC) in mouse models of cardiac hypertrophy and to determine the underlying mechanism. Pressure-overload cardiac hypertrophy and angiotensin II (AngII) infusion-induced animal models of cardiac hypertrophy were established in vivo. The expression of TFEC was explored via western blotting. The results demonstrated that TFEC expression was significantly increased in the hearts of mice with pressure overload- and AngII-induced hypertrophy. Injection of rAd-short hairpin (sh)-TFEC significantly decreased the expression of TFEC in heart tissues compared with group injected with rAd-negative control (NC). Furthermore, the expression levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were increased in the hearts of AngII-treated mice; however, compared with rAd-NC transfection, transfection with rAd-sh-TFEC decreased the expression levels of ANP, BNP and β-MHC. The results from echocardiographic analysis indicated that transfection with rAd-sh-TFEC improved the cardiac function of AngII-treated mice compared with transfection with rAd-NC. In addition, the AngII-induced increase in cardiomyocyte size could be reversed by TFEC knockdown in primary cardiomyocytes. The elevated expression levels of ANP, BNP and β-MHC induced by AngII could be partially abolished following TFEC knockdown. The results from western blotting demonstrated that TFEC overexpression decreased the expression of phosphorylated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) but increased the expression of phosphorylated mechanistic target of rapamycin (mTOR). Furthermore, Compound C significantly suppressed the activation of AMPK/ACC but increased the activation of mTOR, even in primary cardiomyocytes transfected with rAd-sh-TFEC. In conclusion, the findings from this study demonstrated that TFEC was overexpressed in the hearts of mice with cardiac hypertrophy and that silencing TFEC may improve AngII-induced cardiac hypertrophy and dysfunction by activating AMPK/mTOR signaling.
    Keywords:  AMP-activated protein kinase/mechanistic target of rapamycin signaling; cardiac hypertrophy; kinase non-catalytic C-lobe domain containing 1
    DOI:  https://doi.org/10.3892/etm.2021.10706
  2. J Am Heart Assoc. 2021 Sep 29. e021985
    Enhanced Heart Failure in Redox-Dead Cys17Ser PKARIα Knock-In Mice.
    M M Towhidul Islam, Daniel Tarnowski, Min Zhang, Maximilian Trum, Simon Lebek, Julian Mustroph, Henriette Daniel, Johanna Moellencamp, Steffen Pabel, Samuel Sossalla, Ali El-Armouche, Viacheslav O Nikolaev, Ajay M Shah, Philip Eaton, Lars S Maier, Can Martin Sag, Stefan Wagner.
      Background PKARIα (protein kinase A type I-α regulatory subunit) is redox-active independent of its physiologic agonist cAMP. However, it is unknown whether this alternative mechanism of PKARIα activation may be of relevance to cardiac excitation-contraction coupling. Methods and Results We used a redox-dead transgenic mouse model with homozygous knock-in replacement of redox-sensitive cysteine 17 with serine within the regulatory subunits of PKARIα (KI). Reactive oxygen species were acutely evoked by exposure of isolated cardiac myocytes to AngII (angiotensin II, 1 µmol/L). The long-term relevance of oxidized PKARIα was investigated in KI mice and their wild-type (WT) littermates following transverse aortic constriction (TAC). AngII increased reactive oxygen species in both groups but with RIα dimer formation in WT only. AngII induced translocation of PKARI to the cell membrane and resulted in protein kinase A-dependent stimulation of ICa (L-type Ca current) in WT with no effect in KI myocytes. Consequently, Ca transients were reduced in KI myocytes as compared with WT cells following acute AngII exposure. Transverse aortic constriction-related reactive oxygen species formation resulted in RIα oxidation in WT but not in KI mice. Within 6 weeks after TAC, KI mice showed an enhanced deterioration of contractile function and impaired survival compared with WT. In accordance, compared with WT, ventricular myocytes from failing KI mice displayed significantly reduced Ca transient amplitudes and lack of ICa stimulation. Conversely, direct pharmacological stimulation of ICa using Bay K8644 rescued Ca transients in AngII-treated KI myocytes and contractile function in failing KI mice in vivo. Conclusions Oxidative activation of PKARIα with subsequent stimulation of ICa preserves cardiac function in the setting of acute and chronic oxidative stress.
    Keywords:  heart failure; pressure overload; protein kinase A; redox
    DOI:  https://doi.org/10.1161/JAHA.121.021985
  3. J Am Heart Assoc. 2021 Sep 29. e020729
    Ketone Ester D-β-Hydroxybutyrate-(R)-1,3 Butanediol Prevents Decline in Cardiac Function in Type 2 Diabetic Mice.
    Phung N Thai, Charles V Miller, M Todd King, Saul Schaefer, Richard L Veech, Nipavan Chiamvimonvat, Donald M Bers, Elena N Dedkova.
      Background Heart failure is responsible for approximately 65% of deaths in patients with type 2 diabetes mellitus. However, existing therapeutics for type 2 diabetes mellitus have limited success on the prevention of diabetic cardiomyopathy. The aim of this study was to determine whether moderate elevation in D-β-hydroxybutyrate improves cardiac function in animals with type 2 diabetes mellitus. Methods and Results Type 2 diabetic (db/db) and their corresponding wild-type mice were fed a control diet or a diet where carbohydrates were equicalorically replaced by D-β-hydroxybutyrate-(R)-1,3 butanediol monoester (ketone ester [KE]). After 4 weeks, echocardiography demonstrated that a KE diet improved systolic and diastolic function in db/db mice. A KE diet increased expression of mitochondrial succinyl-CoA:3-oxoacid-CoA transferase and restored decreased expression of mitochondrial β-hydroxybutyrate dehydrogenase, key enzymes in cardiac ketone metabolism. A KE diet significantly enhanced both basal and ADP-mediated oxygen consumption in cardiac mitochondria from both wild-type and db/db animals; however, it did not result in the increased mitochondrial respiratory control ratio. Additionally, db/db mice on a KE diet had increased resistance to oxidative and redox stress, with evidence of restoration of decreased expression of thioredoxin and glutathione peroxidase 4 and less permeability transition pore activity in mitochondria. Mitochondrial biogenesis, quality control, and elimination of dysfunctional mitochondria via mitophagy were significantly increased in cardiomyocytes from db/db mice on a KE diet. The increase in mitophagy was correlated with restoration of mitofusin 2 expression, which contributed to improved coupling between cytosolic E3 ubiquitin ligase translocation into mitochondria and microtubule-associated protein 1 light chain 3-mediated autophagosome formation. Conclusions Moderate elevation in circulating D-β-hydroxybutyrate levels via KE supplementation enhances mitochondrial biogenesis, quality control, and oxygen consumption and increases resistance to oxidative/redox stress and mPTP opening, thus resulting in improvement of cardiac function in animals with type 2 diabetes mellitus.
    Keywords:  cardiac function; glutathione peroxidase 4; ketone bodies metabolism; ketone ester; mitochondrial permeability transition; mitofusin 2; roGFP2‐GRX1; roGFP2‐ORP1; thioredoxin; type 2 diabetes mellitus
    DOI:  https://doi.org/10.1161/JAHA.120.020729
  4. Int J Mol Sci. 2021 Sep 13. pii: 9883. [Epub ahead of print]22(18):
    Stearoyl-CoA Desaturase (SCD) Induces Cardiac Dysfunction with Cardiac Lipid Overload and Angiotensin II AT1 Receptor Protein Up-Regulation.
    Joshua Abd Alla, Yahya F Jamous, Ursula Quitterer.
      Heart failure is a major cause of death worldwide with insufficient treatment options. In the search for pathomechanisms, we found up-regulation of an enzyme, stearoyl-CoA desaturase 1 (Scd1), in different experimental models of heart failure induced by advanced atherosclerosis, chronic pressure overload, and/or volume overload. Because the pathophysiological role of Scd1/SCD in heart failure is not clear, we investigated the impact of cardiac SCD upregulation through the generation of C57BL/6-Tg(MHCSCD)Sjaa mice with myocardium-specific expression of SCD. Echocardiographic examination showed that 4.9-fold-increased SCD levels triggered cardiac hypertrophy and symptoms of heart failure at an age of eight months. Tg-SCD mice had a significantly reduced left ventricular cardiac ejection fraction of 25.7 ± 2.9% compared to 54.3 ± 4.5% of non-transgenic B6 control mice. Whole-genome gene expression profiling identified up-regulated heart-failure-related genes such as resistin, adiponectin, and fatty acid synthase, and type 1 and 3 collagens. Tg-SCD mice were characterized by cardiac lipid accumulation with 1.6- and 1.7-fold-increased cardiac contents of saturated lipids, palmitate, and stearate, respectively. In contrast, unsaturated lipids were not changed. Together with saturated lipids, apoptosis-enhancing p53 protein contents were elevated. Imaging by autoradiography revealed that the heart-failure-promoting and membrane-spanning angiotensin II AT1 receptor protein of Tg-SCD hearts was significantly up-regulated. In transfected HEK cells, the expression of SCD increased the number of cell-surface angiotensin II AT1 receptor binding sites. In addition, increased AT1 receptor protein levels were detected by fluorescence spectroscopy of fluorescent protein-labeled AT1 receptor-Cerulean. Taken together, we found that SCD promotes cardiac dysfunction with overload of cardiotoxic saturated lipids and up-regulation of the heart-failure-promoting AT1 receptor protein.
    Keywords:  AGTR1; AT1 receptor; SCD; Scd1; angiotensin II; cardiac dysfunction; heart failure; lipid overload; transgenic mice
    DOI:  https://doi.org/10.3390/ijms22189883
  5. Oxid Med Cell Longev. 2021 ;2021 5546867
    Nicotinamide Riboside Alleviates Cardiac Dysfunction and Remodeling in Pressure Overload Cardiac Hypertrophy.
    Sai Ma, Jing Feng, Xiuyu Lin, Jing Liu, Yi Tang, Shinan Nie, Jianbin Gong, Lei Wang.
      Background: Cardiac hypertrophy is a compensatory response to pressure overload, which eventually leads to heart failure. The current study explored the protective effect of nicotinamide riboside (NR), a NAD+ booster that may be administered through the diet, on the occurrence of myocardial hypertrophy and revealed details of its underlying mechanism.Methods: Transverse aortic constriction (TAC) surgery was performed to establish a murine model of myocardial hypertrophy. Mice were randomly divided into four groups: sham, TAC, sham+NR, and TAC+NR. NR treatment was given daily by oral gavage. Cardiac structure and function were assessed using small animal echocardiography. Mitochondrial oxidative stress was evaluated by dihydroethidium (DHE) staining, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity. Levels of expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), IL-1β, TNF-α, and Sirtuin3 were measured by real-time PCR and ELISA. Expression levels of Caspase-1, Caspase-1 pro, cleaved Gasdermin D (GSDMD), NLRP3, ASC, Sirtuin3, ac-MnSOD, and total MnSOD were measured by Western blot.
    Results: Reductions in the heart/body mass ratio (HW/BW) and lung/body mass ratio (LW/BW) and in ANP, BNP, and LDH levels were observed in the TAC group on the administration of NR (P < 0.05). Moreover, echocardiography data showed that cardiac dysfunction and structural changes caused by TAC were improved by NR treatment (P < 0.05). NR treatment also reduced levels of the inflammatory cytokines, IL-1β and TNF-α, and attenuated activation of NLRP3 inflammasomes induced by TAC. Furthermore, changes in DHE staining, MDA content, and SOD activity indicated that NR treatment alleviated the oxidative stress caused by TAC. Data from ELISA and Western blots revealed elevated myocardial NAD+ content and Sirtuin3 activity and decreased acetylation of MnSOD after NR treatment, exposing aspects of the underlying signaling pathway.
    Conclusion: NR treatment alleviated TAC-induced pathological cardiac hypertrophy and dysfunction. Mechanically, these beneficial effects were attributed to the inhibition of NLRP3 inflammasome activation and myocardial inflammatory response by regulating the NAD+-Sirtuin3-MnSOD signaling pathway.
    DOI:  https://doi.org/10.1155/2021/5546867
  6. Nutrients. 2021 Sep 18. pii: 3267. [Epub ahead of print]13(9):
    Maternal Fructose Intake Exacerbates Cardiac Remodeling in Offspring with Ventricular Pressure Overload.
    Steve Leu, Kay L H Wu, Wei-Chia Lee, You-Lin Tain, Julie Y H Chan.
      Recent studies demonstrated that metabolic syndrome and cardiovascular diseases could be elicited by developmental programming, which is regulated by prenatal nutritional and environmental stress. In this study, we utilized a rat model to examine the effect of excessive maternal fructose intake during pregnancy and lactation on cardiac development and progression of pressure overload-induced cardiac hypertrophy in offspring. Transverse aortic constriction (TAC) was performed on 3-month-old male offspring to induce ventricular pressure overload. Four weeks post-TAC, echocardiographic assessment as well as histopathological and biochemical examinations were performed on the myocardium of the offspring. Echocardiographic and gross examinations showed that heart weight, interventricular septal thickness in diastole (IVD; d), and left ventricular posterior wall thickness in diastole (LVPW; d) were elevated in offspring with TAC and further increased by maternal fructose exposure (MFE). However, the left ventricular ejection function was not significantly affected. Myocardial histopathological examination revealed that the indices of fibrosis and oxidative stress were higher in offspring with MFE and TAC than those in animals receiving either treatment. Molecular examinations on the myocardium demonstrated an MFE-induced upregulation of p38-MAPK signaling. Next generation sequence (NGS) analysis indicated a modulation of the expression levels of several cardiac hypertrophy-associated genes, including GPR22, Myh7, Nppa, P2RX4, and Npy by MFE. Subsequent RT-PCR indicated that MFE regulated the expression levels of genes responsive to cardiac hypertrophy (i.e., Myh-7, ANP) and oxidative stress (i.e., GR, GPx, and NQO-1). In conclusion, MFE during pregnancy and lactation modulated myocardial gene expression, increased oxidative stress, and exacerbated ventricular pressure overload-induced cardiac remodeling in rat offspring.
    Keywords:  cardiac hypertrophy; developmental programming; maternal fructose exposure; oxidative stress; transverse aortic constriction
    DOI:  https://doi.org/10.3390/nu13093267
  7. Circulation. 2021 Sep 29.
    Integrated Stress Response Couples Mitochondrial Protein Translation with Oxidative Stress Control.
    Guangyu Zhang, Xiaoding Wang, Chao Li, Qinfeng Li, Yu A An, Xiang Luo, Yingfeng Deng, Thomas G Gillette, Philipp E Scherer, Zhao V Wang.
      Background: The integrated stress response (ISR) is an evolutionarily conserved process to cope with intracellular and extracellular disturbances. Myocardial infarction is a leading cause of death worldwide. Coronary artery reperfusion is the most effective means to mitigate cardiac damage of myocardial infarction, which however causes additional reperfusion injury. This study aimed to investigate the role of the ISR in myocardial ischemia/reperfusion (I/R). Methods: Cardiac-specific gain- and loss-of-function approaches for the ISR were employed in vivo. Myocardial I/R was achieved by the ligation of the cardiac left anterior descending artery for 45 minutes, followed by reperfusion for different times. Cardiac function was assessed by echocardiography. Additionally, cultured H9c2 cells, primary rat cardiomyocytes, and mouse embryonic fibroblasts were used to dissect underlying molecular mechanisms. Moreover, tandem mass tag (TMT) labeling and mass spectrometry was conducted to identify protein targets of the ISR. Pharmacological means were tested to manipulate the ISR for therapeutic exploration. Results: We show that the PERK/eIF2α axis of the ISR is strongly induced by I/R in cardiomyocytes in vitro and in vivo. We further reveal a physiological role of PERK/eIF2α signaling by showing that acute activation of PERK in the heart confers robust cardioprotection against reperfusion injury. In contrast, cardiac-specific deletion of PERK aggravates cardiac responses to reperfusion. Mechanistically, the ISR directly targets mitochondrial complexes via translational suppression. We identify NDUFAF2, an assembly factor of mitochondrial complex I, as a selective target of PERK. Overexpression of PERK suppresses the protein expression of NDUFAF2 while PERK inhibition causes an increase of NDUFAF2. Silencing of NDUFAF2 significantly rescues cardiac cell survival from PERK knockdown under I/R. Further, we show that activation of PERK/eIF2α signaling reduces mitochondrial complex-derived reactive oxygen species and improves cardiac cell survival in response to I/R. Moreover, pharmacological stimulation of the ISR protects the heart against reperfusion damage, even after the restoration of occluded coronary artery, highlighting a clinical relevance for myocardial infarction treatment. Conclusions: These studies suggest that the ISR improves cell survival and mitigate reperfusion damage by selectively suppressing mitochondrial protein synthesis and reducing oxidative stress in the heart.
    DOI:  https://doi.org/10.1161/CIRCULATIONAHA.120.053125
  8. Front Cardiovasc Med. 2021 ;8 695480
    Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure.
    Zixian Wang, Shiyu Chen, Qian Zhu, Yonglin Wu, Guifeng Xu, Gongjie Guo, Weihua Lai, Jiyan Chen, Shilong Zhong.
      Background: Heart failure (HF) is the main cause of morbidity and mortality worldwide, and metabolic dysfunction is an important factor related to HF pathogenesis and development. However, the causal effect of blood metabolites on HF remains unclear. Objectives: Our chief aim is to investigate the causal relationships between human blood metabolites and HF risk. Methods: We used an unbiased two-sample Mendelian randomization (MR) approach to assess the causal relationships between 486 human blood metabolites and HF risk. Exposure information was obtained from Sample 1, which is the largest metabolome-based genome-wide association study (mGWAS) data containing 7,824 Europeans. Outcome information was obtained from Sample 2, which is based on the results of a large-scale GWAS meta-analysis of HF and contains 47,309 cases and 930,014 controls of Europeans. The inverse variance weighted (IVW) model was used as the primary two-sample MR analysis method and followed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. Results: We observed that 11 known metabolites were potentially related to the risk of HF after using the IVW method (P < 0.05). After adding another four MR models and performing sensitivity analyses, we found a 1-SD increase in the xenobiotics 4-vinylphenol sulfate was associated with ~22% higher risk of HF (OR [95%CI], 1.22 [1.07-1.38]). Conclusions: We revealed that the 4-vinylphenol sulfate may nominally increase the risk of HF by 22% after using a two-sample MR approach. Our findings may provide novel insights into the pathogenesis underlying HF and novel strategies for HF prevention.
    Keywords:  4-vinylphenol sulfate; Mendelian randomization; blood metabolites; causal relationship; heart failure
    DOI:  https://doi.org/10.3389/fcvm.2021.695480
  9. Nutrients. 2021 Aug 26. pii: 2965. [Epub ahead of print]13(9):
    PUFA Supplementation and Heart Failure: Effects on Fibrosis and Cardiac Remodeling.
    Francesca Oppedisano, Rocco Mollace, Annamaria Tavernese, Micaela Gliozzi, Vincenzo Musolino, Roberta Macrì, Cristina Carresi, Jessica Maiuolo, Maria Serra, Antonio Cardamone, Maurizio Volterrani, Vincenzo Mollace.
      Heart failure (HF) characterized by cardiac remodeling is a condition in which inflammation and fibrosis play a key role. Dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) seems to produce good results. In fact, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory and antioxidant properties and different cardioprotective mechanisms. In particular, following their interaction with the nuclear factor erythropoietin 2 related factor 2 (NRF2), the free fatty acid receptor 4 (Ffar4) receptor, or the G-protein coupled receptor 120 (GPR120) fibroblast receptors, they inhibit cardiac fibrosis and protect the heart from HF onset. Furthermore, n-3 PUFAs increase the left ventricular ejection fraction (LVEF), reduce global longitudinal deformation, E/e ratio (early ventricular filling and early mitral annulus velocity), soluble interleukin-1 receptor-like 1 (sST2) and high-sensitive C Reactive protein (hsCRP) levels, and increase flow-mediated dilation. Moreover, lower levels of brain natriuretic peptide (BNP) and serum norepinephrine (sNE) are reported and have a positive effect on cardiac hemodynamics. In addition, they reduce cardiac remodeling and inflammation by protecting patients from HF onset after myocardial infarction (MI). The positive effects of PUFA supplementation are associated with treatment duration and a daily dosage of 1-2 g. Therefore, both the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association (ACC/AHA) define dietary supplementation with n-3 PUFAs as an effective therapy for reducing the risk of hospitalization and death in HF patients. In this review, we seek to highlight the most recent studies related to the effect of PUFA supplementation in HF. For that purpose, a PubMed literature survey was conducted with a focus on various in vitro and in vivo studies and clinical trials from 2015 to 2021.
    Keywords:  HFpEF; HFrEF; PUFAs; cardiac fibrosis; cardiac remodeling; cardioprotective mechanism; heart failure; inflammation; myocardial infarction (MI)
    DOI:  https://doi.org/10.3390/nu13092965
  10. J Am Coll Cardiol. 2021 Oct 05. pii: S0735-1097(21)05838-1. [Epub ahead of print]78(14): 1421-1432
    Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction.
    Marie-Sophie L Y de Koning, B Daan Westenbrink, Solmaz Assa, Erwin Garcia, Margery A Connelly, Dirk J van Veldhuisen, Robin P F Dullaart, Erik Lipsic, Pim van der Harst.
      BACKGROUND: Circulating ketone bodies (KBs) are increased in patients with heart failure (HF), corresponding with increased cardiac KB metabolism and HF severity. However, the role of circulating KBs in ischemia/reperfusion remains unknown.OBJECTIVES: This study sought to investigate longitudinal changes of KBs and their associations with functional outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI).
    METHODS: KBs were measured in 369 participants from a randomized trial on early metformin therapy after STEMI. Nonfasting plasma concentrations of KBs (β-hydroxybutyrate, acetoacetate, and acetone) were measured by nuclear magnetic resonance spectroscopy at presentation, at 24 hours, and after 4 months. Myocardial infarct size and left ventricular ejection fraction (LVEF) were determined by cardiac magnetic resonance imaging at 4 months. Associations of circulating KBs with infarct size and LVEF were determined using multivariable linear regression analyses.
    RESULTS: Circulating KBs were high at presentation with STEMI (median total KBs: 520 μmol/L; interquartile range [IQR]: 315-997 μmol/L). At 24 hours after reperfusion, KBs were still high compared with levels at 4-month follow-up (206 μmol/L [IQR: 174-246] vs 166 μmol/L [IQR: 143-201], respectively; P < 0.001). Increased KB concentrations at 24 hours were independently associated with larger myocardial infarct size (total KBs, per 100 μmol/L: β = 1.56; 95% confidence interval: 0.29-2.83; P = 0.016) and lower LVEF (β = -1.78; 95% CI: (-3.17 to -0.39; P = 0.012).
    CONCLUSIONS: Circulating KBs are increased in patients presenting with STEMI. Higher KBs at 24 hours are associated with functional outcomes after STEMI, which suggests a potential role for ketone metabolism in response to myocardial ischemia. (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III): a Randomized Controlled Trial; NCT01217307).
    Keywords:  ischemia/reperfusion; ketone bodies; metabolism; metformin; myocardial infarction
    DOI:  https://doi.org/10.1016/j.jacc.2021.07.054
  11. Metabolites. 2021 Sep 09. pii: 615. [Epub ahead of print]11(9):
    Analysis of Metabolic Markers in Patients with Chronic Heart Failure before and after LVAD Implantation.
    Marion S Hilse, Tom Kretzschmar, Rudin Pistulli, Marcus Franz, Tarek Bekfani, Daniela Haase, Sophie Neugebauer, Michael Kiehntopf, Jan F Gummert, Hendrik Milting, P Christian Schulze.
      Chronic heart failure (HF) is a clinical syndrome characterized by functional impairments of the myocardium. Metabolic and clinical changes develop with disease progression. In an advanced state, left ventricular assist devices (LVADs) are implanted for mechanical unloading. Our study aimed to assess the effects of LVAD implantation on the metabolic phenotypes and their potential to reverse the latter in patients with advanced HF. Plasma metabolites were analyzed by LC-MS/MS in 20 patients with ischemic cardiomyopathy (ICM), 20 patients with dilative cardiomyopathy (DCM), and 20 healthy controls. Samples were collected in HF patients before, 30 days after, and >100 days after LVAD implantation. Out of 188 measured metabolites, 63 were altered in HF. Only three metabolites returned to pre-LVAD concentrations 100 days after LVAD implantation. Pre-LVAD differences between DCM and ICM were mainly observed for amino acids and biogenic amines. This study shows a reversal of metabolite abnormalities in HF as a result of LVAD implantation. The etiology of the underlying disease plays an essential role in defining which specific metabolic parameter is altered in HF and reversed by LVAD implantation. Our findings provide a detailed insight into the disease pattern of ICM and DCM and the potential for reversibility of metabolic abnormalities in HF.
    Keywords:  DCM; ICM; LVAD; mass spectrometry; metabolomics
    DOI:  https://doi.org/10.3390/metabo11090615
  12. J Am Coll Cardiol. 2021 Oct 05. pii: S0735-1097(21)05839-3. [Epub ahead of print]78(14): 1433-1436
    Ketone Bodies: Universal Cardiac Response to Stress?
    Salva R Yurista, Anthony Rosenzweig, Christopher T Nguyen.
      
    Keywords:  cardiac stress; ischemia; ketone bodies; myocardial infarction
    DOI:  https://doi.org/10.1016/j.jacc.2021.08.002
This page is being maintained by Thomas Krichel. It was last updated on 2021‒10‒05 at 15:22:20.