bims-hafaim 2022-10-23 papers

Issue of 2022–10–23
three papers selected by
Kyle McCommis, Saint Louis University

J Card Fail. 2022 Oct 13. pii: S1071-9164(22)00728-X. [Epub ahead of print]

Longitudinal changes in circulating ketone body levels in patients with acute heart failure: A post-hoc analysis of the EMPA-Response-AHF Trial.

S N Voorrips, E M Boorsma, J C Beusekamp, R A de Boer, M A Connelly, R P F Dullaart, P van der Meer, D J van Veldhuisen, A A Voors, K Damman, B D Westenbrink.

AIMS: Ketone bodies are endogenous fuels produced by the liver under conditions of metabolic or neurohormonal stress. Circulating ketone bodies are increased in patients with chronic heart failure (HF), yet little is known about the effect of acute HF on ketosis. We tested the hypothesis that ketogenesis is increased in patients with acute decompensated HF.
METHODS AND RESULTS: This was a post-hoc analysis of 79 acute HF patients included in the EMPA-RESPONSE-AHF trial which compared sodium-dependent glucose-cotransporter protein 2 (SGLT2) inhibitor treatment with empagliflozin for 30 days to placebo in patients with acute HF [NCT03200860]. Plasma concentrations of ketone bodies acetone, β-hydroxybutyrate and acetoacetate were measured at baseline and 5 different timepoints. Changes in ketone bodies over time were monitored using repeated measures ANOVA. In the total cohort, median total ketone body (TKB) concentration was 251 [178-377] µmol/L at baseline, which gradually decreased to 202 [156-240] µmol/L at day 30 (p=0.041). Acetone decreased from 60 [34-94] µmol/L at baseline to 30 [21-42] µmol/L (p<0.001), whereas β-hydroxybutyrate and acetoacetate remained stable over time. Higher acetone concentrations were correlated with higher NT-pro BNP levels (r=0.234; p=0.039). Circulating ketone bodies did not differ between patients treated with empagliflozin or placebo throughout the study period. Higher acetone concentration at baseline was univariately associated with a greater risk of the composite endpoint including in-hospital worsening HF, HF rehospitalizations and all-cause mortality after 30 days. However, after adjustment for age and sex, acetone did not remain an independent predictor for the combined endpoint.
CONCLUSION: Circulating ketone body concentrations, and acetone in particular, were significantly higher during an episode of acute decompensated HF compared to after stabilization. Treatment with empagliflozin did not affect ketone body concentrations in subjects with acute HF.

Keywords: Acetone; Acute Heart failure; Empagliflozin; Ketone Bodies; NT-pro BNP; SGLT2 inhibitors

DOI: https://doi.org/10.1016/j.cardfail.2022.09.009

J Cardiol. 2022 Oct 13. pii: S0914-5087(22)00256-8. [Epub ahead of print]

Tofogliflozin, a sodium-glucose cotransporter 2 inhibitor, improves pulmonary vascular remodeling due to left heart disease in mice.

Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino.

BACKGROUND: Group 2 pulmonary hypertension (PH) represents PH caused by left heart disease (PH-LHD). LHD induces left-sided filling and PH, finally leading to pulmonary vascular remodeling. Tofogliflozin (TOFO) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used in the treatment of diabetes. Recent studies have shown that SGLT2 inhibitors have beneficial effects on heart failure, but the effects of SGLT2 inhibitors on PH-LHD remain unclear. We hypothesized that TOFO has protective effects against pulmonary vascular remodeling in PH-LHD mice.
METHODS: We generated two murine models of PH-LHD: a transverse aortic constriction (TAC) model; and a high-fat diet (HFD) model. C57BL/6 J mice were subjected to TAC and treated with TOFO (3 mg/kg/day) for 3 weeks. AKR/J mice were fed HFD and treated with TOFO (3 mg/kg/day) for 20 weeks. We then measured physical data and right ventricular systolic pressure (RVSP) and performed cardiography. Human pulmonary artery smooth muscle cells (PASMCs) were cultured and treated with TOFO.
RESULTS: Mice treated with TOFO demonstrated increased urine glucose levels. TAC induced left ventricular hypertrophy and increased RVSP. TOFO treatment improved RVSP. HFD increased body weight (BW) and RVSP compared with the normal chow group. TOFO treatment ameliorated increases in BW and RVSP induced by HFD. Moreover, PASMCs treated with TOFO showed suppressed migration.
CONCLUSIONS: TOFO treatment ameliorated right heart overload and pulmonary vascular remodeling for PH-LHD models, suggesting that SGLT2 inhibitors are effective for treating PH-LHD.

Keywords: Animal models; Heart failure; Pulmonary hypertension; SGLT2 inhibitor

DOI: https://doi.org/10.1016/j.jjcc.2022.10.003

Curr Mol Pharmacol. 2022 Oct 17.

Influence of SGLT2 Inhibitors in Remodeling, Substrate and Ion Metabolism of Myocardium to Prevent Cardiovascular Risks: Recent Work and Advancement.

Nishant Johri, Prithpal S Matreja, Davis John, Shubham Dutta, Ashok Kumar Parida, Susanta Nath Sarma.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs that lower blood glucose levels while decreasing blood pressure, volume loss, and weight loss. SGLT2 inhibitors were studied to determine their effectiveness in treating cardiovascular disease and their side effects. Study outcomes related to cardiovascular and metabolic outcomes were examined in patients on SGLT2 inhibitors by searching PubMed, Embase, Cochrane, and SCOPUS. Articles related to clinical trials, reviews, and meta-analyses were considered. A review of SGLT2 inhibitors' mechanisms of action in preventing cardiovascular (CVS) disease progression was described. We then reviewed the possible effects of SGLT2 inhibitors on CVS dysfunction development, composition, and stability. In the following, we discussed the impact of SGLT2 inhibitors on CVD events, such as ischemic strokes and myocardial infarctions, and their role in treating congestive heart failure and cardiovascular mortality.

Keywords: CVS; Myocardial infarction; SGLT2.; diabetes; ischemia; stroke

DOI: https://doi.org/10.2174/1874467216666221017123333