bims-hafaim Biomed News
on Heart failure metabolism
Issue of 2021‒11‒21
twelve papers selected by
Kyle McCommis
Saint Louis University
  1. The mitochondrial regulator PGC1α is induced by cGMP-PKG signaling and mediates the protective effects of phosphodiesterase 5 inhibition in heart failure.
  2. Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway.
  3. Renal denervation ameliorates cardiac metabolic remodeling in diabetic cardiomyopathy rats by suppressing renal SGLT2 expression.
  4. Comparing Sacubitril/Valsartan Against Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure: A Systematic Review and Network Meta-analysis.
  5. Combined effects of ARNI and SGLT2 inhibitors in diabetic patients with heart failure with reduced ejection fraction.
  6. Ser9 phosphorylation of GSK-3β promotes aging in the heart through suppression of autophagy.
  7. Beneficial Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Left Ventricular Function.
  8. Metformin Prevents Low-dose Isoproterenol-induced Cardiac Dilatation and Systolic Dysfunction in Male Sprague-Dawley Rats.
  9. Proteome dynasmics and bioinformatics reveal major alterations in the turnover rate of functionally related cardiac and plasma proteins in a dog model of congestive heart failure.
  10. Effect of sodium-glucose cotransporter-2 inhibitors on cardiac remodelling: a systematic review and meta-analysis.
  11. A Meta-Analysis of the Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Heart Failure and Preserved Ejection Fraction.
  12. Cardiovascular benefit of SGLT2 inhibitors.
  1. FEBS Lett. 2021 Nov 14.
    The mitochondrial regulator PGC1α is induced by cGMP-PKG signaling and mediates the protective effects of phosphodiesterase 5 inhibition in heart failure.
    Guangshuo Zhu, Kazutaka Ueda, Masaki Hashimoto, Manling Zhang, Masayuki Sasaki, Taro Kariya, Hideyuki Sasaki, Nina Kaludercic, Dong-Ik Lee, Djahida Bedja, Matthew Gabrielson, Yuan Yuan, Nazareno Paolocci, Robert M Blanton, Richard H Karas, Michael E Mendelsohn, Brian O'Rourke, David A Kass, Eiki Takimoto.
      Phosphodiesterase 5 inhibition (PDE5i) activates cGMP-dependent protein kinase (PKG) and ameliorates heart failure; however, its impact on cardiac mitochondrial regulation has not been fully determined. Here, we investigated the role of the mitochondrial regulator peroxisome proliferator-activated receptor γ co-activator-1α (PGC1α) in the PDE5i-conferred cardioprotection, utilizing PGC1α null mice. In PGC1α+/+ hearts exposed to 7 weeks of pressure overload by transverse aortic constriction, chronic treatment with the PDE5 inhibitor sildenafil improved cardiac function and remodeling, with improved mitochondrial respiration and upregulation of PGC1α mRNA in the myocardium. By contrast, PDE5i-elicited benefits were abrogated in PGC1α-/- hearts. In cultured cardiomyocytes, PKG overexpression induced PGC1α, while inhibition of the transcription factor CREB abrogated the PGC1α induction. Together, these results suggest that the PKG-PGC1α axis plays a pivotal role in the therapeutic efficacy of PDE5i in heart failure.
    Keywords:  PGC1α; cyclic guanosine monophosphate; heart failure; mitochondria
    DOI:  https://doi.org/10.1002/1873-3468.14228
  2. Front Pharmacol. 2021 ;12 739615
    Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway.
    Wen-Jing Chen, Yan Cheng, Wen Li, Xiao-Kang Dong, Jian-Liang Wei, Chuan-Hua Yang, Yue-Hua Jiang.
      Cardiac hypertrophy is an important characteristic in the development of hypertensive heart disease. Mitochondrial dysfunction plays an important role in the pathology of cardiac hypertrophy. Recent studies have shown that sirtuin 3 (SIRT3)/poly (ADP-ribose) polymerase-1 (PARP-1) pathway modulation inhibits cardiac hypertrophy. Quercetin, a natural flavonol agent, has been reported to attenuate cardiac hypertrophy. However, the molecular mechanism is not completely elucidated. In this study, we aimed to explore the mechanism underlying the protective effect of quercetin on cardiac hypertrophy. Spontaneously hypertensive rats (SHRs) were treated with quercetin (20 mg/kg/d) for 8 weeks to evaluate the effects of quercetin on blood pressure and cardiac hypertrophy. Additionally, the mitochondrial protective effect of quercetin was assessed in H9c2 cells treated with Ang II. SHRs displayed aggravated cardiac hypertrophy and fibrosis, which were attenuated by quercetin treatment. Quercetin also improved cardiac function, reduced mitochondrial superoxide and protected mitochondrial structure in vivo. In vitro, Ang II increased the mRNA level of hypertrophic markers including atrial natriuretic factor (ANF) and β-myosin heavy chain (β-MHC), whereas quercetin ameliorated this hypertrophic response. Moreover, quercetin prevented mitochondrial function against Ang II induction. Importantly, mitochondrial protection and PARP-1 inhibition by quercetin were partly abolished after SIRT3 knockdown. Our results suggested that quercetin protected mitochondrial function by modulating SIRT3/PARP-1 pathway, contributing to the inhibition of cardiac hypertrophy.
    Keywords:  Sirtuin3; cardiac hypertrophy; mitochondrial function; poly (ADP-ribose) polymerase-1; quercetin
    DOI:  https://doi.org/10.3389/fphar.2021.739615
  3. Lab Invest. 2021 Nov 13.
    Renal denervation ameliorates cardiac metabolic remodeling in diabetic cardiomyopathy rats by suppressing renal SGLT2 expression.
    Jun-Yu Huo, Wan-Ying Jiang, Shi-Geng Zhang, Yi-Ting Lyu, Jie Geng, Meng Chen, Yuan-Yuan Chen, Zhi-Xin Jiang, Qi-Jun Shan.
      This study aimed to investigate the effects of renal denervation (RDN) on diabetic cardiomyopathy (DCM) and explore the related mechanisms. Male Sprague-Dawley rats were fed high-fat chow and injected with low-dose streptozotocin to establish a DCM model. Six rats served as controls. The surviving rats were divided into three groups: control group, DCM group and DCM + RDN group. RDN surgery was performed in the fifth week. At the end of the experiment, all rats were subjected to 18F-FDG PET/CT and metabolic cage studies. Cardiac function and structure were evaluated by echocardiography and histology. Myocardial substrate metabolism and mitochondrial function were assessed by multiple methods. In the 13th week, the DCM rats exhibited cardiac hypertrophy and interstitial fibrosis accompanied by diastolic dysfunction. RDN ameliorated DCM-induced cardiac dysfunction (E/A ratio: RDN 1.07 ± 0.18 vs. DCM 0.93 ± 0.12, P < 0.05; E/E' ratio: RDN 10.74 ± 2.48 vs. DCM 13.25 ± 1.99, P < 0.05) and pathological remodeling (collagen volume fraction: RDN 5.05 ± 2.05% vs. DCM 10.62 ± 2.68%, P < 0.05). Abnormal myocardial metabolism in DCM rats was characterized by suppressed glucose metabolism and elevated lipid metabolism. RDN increased myocardial glucose uptake and oxidation while reducing the absorption and utilization of fatty acids. Meanwhile, DCM decreased mitochondrial ATP content, depolarized the membrane potential and inhibited the activity of respiratory chain complexes, but RDN attenuated this mitochondrial damage (ATP: RDN 30.98 ± 7.33 μmol/gprot vs. DCM 22.89 ± 5.90 μmol/gprot, P < 0.05; complexes I, III and IV activity: RDN vs. DCM, P < 0.05). Furthermore, both SGLT2 inhibitor and the combination treatment produced similar effects as RDN alone. Thus, RDN prevented DCM-induced cardiac dysfunction and pathological remodeling, which is related to the improvement of metabolic disorders and mitochondrial dysfunction.
    DOI:  https://doi.org/10.1038/s41374-021-00696-1
  4. Clin Drug Investig. 2021 Nov 19.
    Comparing Sacubitril/Valsartan Against Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure: A Systematic Review and Network Meta-analysis.
    Yao Neng Teo, Yao Hao Teo, Nicholas L Syn, Celine Shuen Yin Yoong, Alex Jia Yang Cheong, Caitlin Fern Wee, Yoke-Ching Lim, Chi-Hang Lee, Tiong-Cheng Yeo, Ping Chai, Raymond C C Wong, Weiqin Lin, Ching-Hui Sia.
      BACKGROUND AND OBJECTIVE: In recent trials, sodium-glucose cotransporter 2 (SGLT2) inhibitors proved effective as treatment for heart failure. However, the relative efficacy of sacubitril/valsartan against SGLT2 inhibitor in patients with heart failure remains unknown. Hence, we performed a network meta-analysis to compare the effects of sacubitril/valsartan against SGLT2 inhibitors on cardiovascular outcomes in patients with heart failure.METHODS: Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched for randomised-controlled trials (RCTs) published from 1st January 2000 to 25th September 2021. Two additional systematic reviews were conducted for RCTs of enalapril and valsartan to establish a common comparator arm. Frequentist network meta-analysis models were utilised to summarise the studies.
    RESULTS: Twenty-five RCTs were included, comprising a combined cohort of 47,275 patients. Network meta-analysis demonstrated that compared to SGLT2 inhibitors, sacubitril/valsartan achieved a larger hazard rate reduction in the composite of heart failure hospitalisation and cardiovascular death (hazard ratio [HR]: 0.86; 95% CI 0.75-0.98), cardiovascular death (HR: 0.78; 95% CI 0.65-0.94), and a larger mean change in systolic blood pressure at 8 or more months (weighted mean difference [WMD]: - 7.08 mmHg; 95% CI - 8.28 to - 5.89). There were no significant differences in treatment effects across heart failure hospitalisation, all-cause mortality, diastolic blood pressure at 12 weeks, and systolic blood pressure at 2-4 months. In patients with heart failure with reduced ejection fraction, sacubitril/valsartan achieved a 20% hazard rate reduction for cardiovascular death compared to SGLT2 inhibitors.
    CONCLUSIONS: In patients with heart failure, sacubitril/valsartan was demonstrated to be superior to SGLT2 inhibitors in the treatment effect for the composite of heart failure hospitalisation and cardiovascular death, cardiovascular death, and long-term blood pressure.
    DOI:  https://doi.org/10.1007/s40261-021-01098-3
  5. Sci Rep. 2021 Nov 16. 11(1): 22342
    Combined effects of ARNI and SGLT2 inhibitors in diabetic patients with heart failure with reduced ejection fraction.
    Hyue Mee Kim, In-Chang Hwang, Wonsuk Choi, Yeonyee E Yoon, Goo-Yeong Cho.
      Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose co-transporter-2 inhibitor (SGLT2i) have shown benefits in diabetic patients with heart failure with reduced ejection fraction (HFrEF). However, their combined effect has not been revealed. We retrospectively identified diabetic patients with HFrEF who were prescribed an ARNI and/or SGLT2i. The patients were divided into groups treated with both ARNI and SGLT2i (group 1), ARNI but not SGLT2i (group 2), SGLT2i but not ARNI (group 3), and neither ARNI nor SGLT2i (group 4). After propensity score-matching, the occurrence of hospitalization for heart failure (HHF), cardiovascular mortality, and changes in echocardiographic parameters were analyzed. Of the 206 matched patients, 92 (44.7%) had to undergo HHF and 43 (20.9%) died of cardiovascular causes during a median 27.6 months of follow-up. Patients in group 1 exhibited a lower risk of HHF and cardiovascular mortality compared to those in the other groups. Improvements in the left ventricular ejection fraction and E/e' were more pronounced in group 1 than in groups 2, 3 and 4. These echocardiographic improvements were more prominent after the initiation of ARNI, compare to the initiation of SGLT2i. In diabetic patients with HFrEF, combination of ARNI and SGT2i showed significant improvement in cardiac function and prognosis. ARNI-SGLT2i combination therapy may improve the clinical course of HFrEF in diabetic patients.
    DOI:  https://doi.org/10.1038/s41598-021-01759-5
  6. J Cardiovasc Aging. 2021 ;pii: 9. [Epub ahead of print]1
    Ser9 phosphorylation of GSK-3β promotes aging in the heart through suppression of autophagy.
    Yanbin Chen, Yasuhiro Maejima, Akihiro Shirakabe, Takanobu Yamamoto, Yoshiyuki Ikeda, Junichi Sadoshima, Peiyong Zhai.
      Introduction: Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase and a negative regulator of cardiac hypertrophy. Phosphorylation of GSK-3β at Ser9 negatively regulates its kinase activity. The role of GSK-3β in cardiac aging remains poorly understood.Aim: The study aimed to elucidate the role of GSK-3β Ser9 phosphorylation in mediating cardiac aging and the underlying mechanism.
    Methods and Results: Phosphorylation of GSK-3β at Ser9 and the levels of β-catenin and Mcl-1 were increased in the mouse heart during aging, suggesting that GSK-3β is inactivated during aging in the heart. Age-induced cardiac hypertrophy, fibrosis, left ventricular dysfunction, and increases in cardiomyocyte apoptosis and senescence were all attenuated in constitutively active GSK-3βS9A knock-in (KI) mice compared to littermate wild type mice. Although autophagy is inhibited in the heart during aging, KI of GSK-3βS9A reversed the age-associated decline in autophagy in the mouse heart. GSK-3β directly phosphorylates Ulk1, a regulator of autophagy, at Ser913, thereby stimulating autophagy in cardiomyocytes. Ulk1Ser913A KI mice exhibited decreased autophagic flux and increased senescence in cardiomyocytes.
    Conclusion: Our results suggest that GSK-3β is inactivated during aging through Ser9 phosphorylation, which in turn plays an important role in mediating cardiac aging. GSK-3β promotes autophagy through phosphorylation of Ulk1 at Ser913, which in turn prevents aging in the heart.
    Keywords:  GSK-3; Ulk1; aging; autophagy; senescence
    DOI:  https://doi.org/10.20517/jca.2021.13
  7. J Clin Endocrinol Metab. 2021 Nov 15. pii: dgab834. [Epub ahead of print]
    Beneficial Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Left Ventricular Function.
    Fang-Hong Shi, Hao Li, Long Shen, Li Xu, Heng Ge, Zhi-Chun Gu, Hou-Wen Lin, Jun Pu.
      BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients.METHODS: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to 9 July 2021. Randomised clinical trials and cohort studies that reported LV function-related variables were included.
    RESULTS: Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing seven RCTs with 640 individuals and six cohort studies with 797 individuals were included in this meta-analysis. LV regression (LV mass, LVM), LV ejection fractions (LVEF), LV volumes (LV end-diastolic volumes and -systolic volumes, LVEDV and LVESV), and LV diastolic function (mitral inflow E velocity to tissue Doppler e' ratio, E/e' and left atrial volume index, LAVI) were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% confidence interval, LVM: ‒6.319 g, ‒10.850 to ‒1.789; LVEF: 2.458 %, 0.693 to 4.224; LVEDV: ‒9.134 mL, ‒15.808 to ‒2.460; LVESV: ‒8.440 mL, ‒15.093 to ‒1.787; LAVI: ‒2.791 mL/m 2, ‒4.554 to ‒1.027; E/e': ‒1.567, ‒2.440 to ‒0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment.
    CONCLUSIONS: Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).
    Keywords:  cardiovascular disease; heart failure; left ventricular function; meta-analysis; sodium-glucose co-transporter 2 inhibitors
    DOI:  https://doi.org/10.1210/clinem/dgab834
  8. J Cardiovasc Pharmacol. 2021 Nov 03.
    Metformin Prevents Low-dose Isoproterenol-induced Cardiac Dilatation and Systolic Dysfunction in Male Sprague-Dawley Rats.
    Vernice R Peterson, Gavin R Norton, M T Madziva, S Makaula.
      ABSTRACT: Myocardial metabolic abnormalities are well recognized alterations in chronic heart failure, effects that may contribute to progressive cardiac dysfunction. However, whether metabolic alterations in-part mediate their deleterious effects by modifying the chronic impact of excess low dose sympathetic stimulation on cardiac chamber dilatation, is uncertain. We therefore aimed to determine the effect of metformin administration on cardiac function and mitochondrial architectural changes in a rat model of chronic sympathetic-induced left ventricular (LV) remodeling and systolic dysfunction (daily subcutaneous isoproterenol [ISO] injection at a low-dose of 0.02 mg/kg for 7 months). Echocardiography was used to assess in vivo LV dimensions and function, and mitochondrial and myofibril arrangement was assessed using transmission electron microscopy. 7 months of low-dose ISO administration increased left ventricular diastolic diameter (in mm) (CONT: 7.29±0.19 vs. ISO: 8.76±0.21; p=0.001), an effect that was attenuated by metformin (ISO+MET: 7.63±0.29 vs ISO: p=0.001) administration. Similarly, ISO increased LV end systolic diameter (CONT: 4.43±0.16 vs ISO: 5.49±0.16: p<0.0001) an effect prevented by metformin (ISO+MET: 4.04±0.25 vs. ISO: p<0.0001). Moreover, chronic ISO administration reduced LV endocardial fractional shortening (p=0.0001), midwall fractional shortening (p=0.0001) and ejection fraction (p=0.0001), effects similarly prevented by metformin administration. Furthermore, changes in mitochondrial arrangement and relative mitochondrial area (CONT: 37.7±2.2 vs. ISO: 28.1±2.9; p=0.05) were produced by ISO administration, effects prevented by metformin. In conclusion, metformin offers cardiac protection against chronic sympathetic-induced LV dilatation and systolic dysfunction. These data support a role for myocardial metabolic changes in mediating LV dilatation and LV dysfunction produced by chronic neurohumoral activation in cardiac disease.
    DOI:  https://doi.org/10.1097/FJC.0000000000001172
  9. J Card Fail. 2021 Nov 13. pii: S1071-9164(21)00471-1. [Epub ahead of print]
    Proteome dynasmics and bioinformatics reveal major alterations in the turnover rate of functionally related cardiac and plasma proteins in a dog model of congestive heart failure.
    Khatia Gabisonia, Gia Burjanadze, Felix Woitek, Ayse Keles, Mitsuru Seki, Nikoloz Gorgodze, Lucia Carlucci, Serguei Ilchenko, Clara Kurishima, Kenneth Walsh, Helen Piontkivska, Fabio A Recchia, Takhar Kasumov.
      Protein pool turnover is a critically important cellular homeostatic component, yet it has been little explored in the context of heart failure (HF) pathophysiology. We employed in vivo 2H labeling/ proteome dynamics for non-biased discovery of turnover alterations involving functionally linked cardiac and plasma proteins in canine tachypacing-induced HF, an established preclinical model of dilated cardiomyopathy. Compared to control, dogs with congestive HF displayed bidirectional turnover changes of 28 cardiac proteins, i.e. reduced half-life of several key enzymes involved in glycolysis, homocysteine metabolism and glycogenesis, and increased half-life of proteins involved in proteolysis. Changes in plasma proteins were more modest: only 5 proteins, involved in various functions including proteolysis inhibition, hemoglobin, calcium and ferric-iron binding, displayed increased or decreased turnover rates. In other dogs undergoing cardiac tachypacing, we infused for 2 weeks the myokine Follistatin-like protein 1 (FSTL1), known for its ameliorative effects on HF-induced alterations. Proteome dynamics proved very sensitive in detecting the partial or complete prevention, by FSTL1, of cardiac and plasma protein turnover alterations. In conclusion, our study unveiled, for the first time in a large mammal, numerous HF-related alterations that may serve as the basis for future mechanistic research and/or as conceptually new molecular markers.
    Keywords:  ATIC, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase /IMP cyclohydrolase; BNP, brain natriuretic peptide; CLTC, Clathrin heavy chain; CRP, Pentraxin; CYB5R3, NADH-cytochrome b5 reductase; DPYSL2, Dihydropyrimidinase Like 2; FDR, false discovery rate; FSTL1, Follistatin-like protein 1; GAPDHS, Glyceraldehyde-3-phosphate dehydrogenase; GYS1, Glycogen synthase; HF, Heart failure; HSP90, Heat shock protein 90; HSP90AB1, Heat shock protein 90 alpha family class B member 1; HSPA1A, Heat Shock Protein A1; LC-MS, liquid chromatography-mass spectrometry; LFQ, Label-free quantification; LOC479668, Haptoglobin; LTAH4, Leukotriene A (4) hydrolase; LV, Left ventricle; PCA, Principal Component Analysis; PDHA1, Pyruvate dehydrogenase E1 component subunit alpha; PDHB, Pyruvate dehydrogenase E1 component subunit beta; PGM, Phosphoglucomutase 1; PSMD2, Proteasome 26S subunit, non-ATPase 2; STIP1, Stress induced phosphoprotein; TF, Transferrin; proteome dynamics, bioinformatics, cardiac disease, heart failure, List of abbreviations: ANP, atrial natriuretic peptide
    DOI:  https://doi.org/10.1016/j.cardfail.2021.11.011
  10. Eur J Prev Cardiol. 2021 Nov 18. pii: zwab173. [Epub ahead of print]
    Effect of sodium-glucose cotransporter-2 inhibitors on cardiac remodelling: a systematic review and meta-analysis.
    Nan Zhang, Yueying Wang, Gary Tse, Panagiotis Korantzopoulos, Konstantinos P Letsas, Qingpeng Zhang, Guangping Li, Gregory Y H Lip, Tong Liu.
      AIMS: To examine the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiac remodelling in patients with type 2 diabetes mellitus (T2DM) and/or heart failure (HF), and to explore the subsets of patients who may have greater benefit from SGLT2i therapy.METHODS AND RESULTS: Four electronic databases were searched for randomized controlled trials (RCTs) that evaluated the effects of SGLT2i on parameters reflecting cardiac remodelling in patients with T2DM and/or HF. Standardized mean differences (SMDs) or mean differences (MDs) were pooled. Subgroup analyses were performed according to the baseline HF and T2DM, HF type, SGLT2i agent, follow-up duration, and imaging modality. A total of 13 RCTs involving 1251 patients were analysed. Sodium-glucose cotransporter-2 inhibitors treatment significantly improved left ventricular (LV) ejection fraction [SMD, 0.35; 95% confidence interval (CI) (0.04, 0.65); P = 0.03], LV mass [SMD, -0.48; 95% CI (-0.79, -0.18); P = 0.002], LV mass index [SMD, -0.27; 95% CI (-0.49, -0.05); P = 0.02], LV end-systolic volume [SMD, -0.37; 95% CI (-0.71; -0.04); P = 0.03], LV end-systolic volume index [MD, -0.35 mL/m2; 95% CI (-0.64, -0.05); P = 0.02], and E-wave deceleration time [SMD, -0.37; 95% CI (-0.70, -0.05); P = 0.02] in the overall population. Subgroup analyses showed that the favourable effects of SGLT2i on LV remodelling were only significant in HF patients, especially HF with reduced ejection fraction (HFrEF), regardless of glycaemic status. Among the four included SGLT2i, empagliflozin was associated with a greater improvement of LV mass, LV mass index, LV end-systolic volume, LV end-systolic volume index, LV end-diastolic volume, and LV end-diastolic volume index (all P < 0.05).
    CONCLUSIONS: Sodium-glucose cotransporter-2 inhibitors treatment significantly reversed cardiac remodelling, improving LV systolic and diastolic function, LV mass and volume, especially in patients with HFrEF and amongst those taking empagliflozin compared with other SGLT2i. Reversed remodelling may be a mechanism responsible for the favourable clinical effects of SGLT2i on HF.
    Keywords:  Cardiac remodelling; HFrEF; Heart failure; Sodium-glucose cotransporter-2 inhibitors; Type 2 diabetes mellitus
    DOI:  https://doi.org/10.1093/eurjpc/zwab173
  11. Am J Cardiol. 2021 Nov 16. pii: S0002-9149(21)01036-5. [Epub ahead of print]
    A Meta-Analysis of the Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Heart Failure and Preserved Ejection Fraction.
    Ahmad Al-Abdouh, Mohammed Mhanna, Mahmoud Barbarawi, Waiel Abusnina, Vedant A Gupta.
      
    DOI:  https://doi.org/10.1016/j.amjcard.2021.10.017
  12. Crit Rev Clin Lab Sci. 2021 Nov 17. 1-14
    Cardiovascular benefit of SGLT2 inhibitors.
    Reza Mohebi, James L Januzzi.
      Patients with type 2 diabetes mellitus (T2D) are at increased risk of cardiovascular (CV) disease. Sodium glucose cotransporter 2 (SGLT2) inhibitors, also known as gliflozins, are a class of medications used to treat T2D by preventing the reabsorption of glucose filtered through the kidney and thereby facilitating glucose excretion in the urine. Over the past 5 years, many cardiovascular outcome trials (CVOTs) have evaluated the safety and efficacy of SGLT2 inhibitors in preventing CV events. The results of 7 CVOTs have provided solid evidence that the use of SGLT2 in patients with T2D and at high CV risk significantly reduced the risk of death from CV causes. Moreover, in patient with heart failure with reduced ejection fraction, regardless of the presence or absence of T2D, SGLT2 inhibitors use significantly reduced the risk of worsening heart failure and death from CV causes. Although the exact mechanism of the cardiorenal benefit of SGLT2 inhibitors is still unknown, studies have shown that the beneficial effect of these drugs cannot be exclusively explained by their glucose lowering effect, and several possible mechanisms have been proposed. This review will explore the changing role of SGLT2 inhibitors from a diabetes drug to clinical practice guideline-supported therapy for the prevention and treatment of CV diseases, including heart failure.
    Keywords:  SGLT-2 inhibitor; cardiovascular risk; chronic kidney disease; heart failure; type 2 diabetes mellitus
    DOI:  https://doi.org/10.1080/10408363.2021.1993439
This page is being maintained by Thomas Krichel. It was last updated on 2021‒11‒23 at 15:26:12.