Mechanistic Insights of Empagliflozin in Nondiabetic Patients With HFrEF

Requena-Ibáñez, Juan Antonio; Santos‐Gallego, Carlos G.; Rodriguez-Cordero, Anderly; Vargas-Delgado, Ariana P.; Mancini, Donna; Sartori, Samantha; Atallah-Lajam, Farah; Giannarelli, Chiara; Macaluso, Frank; Lala, Anuradha; Sanz, Javier; Fuster, Valentín; Badimón, Juan J.

doi:10.1016/j.jchf.2021.04.014

Cited by 166 publications

(129 citation statements)

References 27 publications

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“…However, we did not find differences among groups regarding diabetes treatment or presence. The findings of this manuscript complement recent findings around the mechanisms of the benefits of SGLT2i in HF ( Requena-Ibáñez et al, 2021 ). In this article, SGLT2i both reduce epicardial adipose tissue (which would result in increased omentin levels) and cause an anti-inflammatory effect (which would be translated as lower levels of orosomucoid).…”

Section: Discussionsupporting

confidence: 86%

“…In this article, SGLT2i both reduce epicardial adipose tissue (which would result in increased omentin levels) and cause an anti-inflammatory effect (which would be translated as lower levels of orosomucoid). Therefore, the OROME score perfectly captures the benefits of SGLT2i in HF ( Santos-Gallego et al, 2021 ) given that higher levels of omentin and lower levels of orosomucoid both predict improved outcomes (as per the OROME score) and are also a consequence of SGLT2i treatment (as demonstrated in Requena-Ibáñez et al (2021) .…”

Section: Discussionmentioning

confidence: 97%

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A New Biomarker Tool for Risk Stratification in “de novo” Acute Heart Failure (OROME)

et al. 2022

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Background: Inflammation is one of the mechanisms involved in heart failure (HF) pathophysiology. Thus, the acute phase reactant protein, orosomucoid, was associated with a worse post-discharge prognosis in de novo acute HF (AHF). However, the presence of anti-inflammatory adipokine, omentin, might protect and reduce the severity of the disease. We wanted to evaluate the value of omentin and orosomucoid combination for stratifying the risk of these patients.Methods and Results: Two independent cohorts of patients admitted for de novo AHF in two centers were included in the study (n = 218). Orosomucoid and omentin circulating levels were determined by ELISA at discharge. Patients were followed-up for 317 (3–575) days. A predictive model was determined for the primary endpoint, death, and/or HF readmission. Differences in survival were evaluated using a Log-rank test. According to cut-off values of orosomucoid and omentin, patients were classified as UpDown (high orosomucoid and low omentin levels), equal (both proteins high or low), and DownUp (low orosomucoid and high omentin levels). The Kaplan Meier determined a worse prognosis for the UpDown group (Long-rank test p = 0.02). The predictive model that includes the combination of orosomucoid and omentin groups (OROME) + NT-proBNP values achieved a higher C-index = 0.84 than the predictive model with NT-proBNP (C-index = 0.80) or OROME (C-index = 0.79) or orosomucoid alone (C-index = 0.80).Conclusion: The orosomucoid and omentin determination stratifies de novo AHF patients into the high, mild, and low risk of rehospitalization and/or death for HF. Its combination with NT-proBNP improves its predictive value in this group of patients.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 97%

A New Biomarker Tool for Risk Stratification in “de novo” Acute Heart Failure (OROME)

et al. 2022

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“… 26 , 27 In another randomized controlled trial analysing the effect of canagliflozin compared with perindopril on vascular function in patients with type 2 diabetes and arterial hypertension, a significant decrease in SBP and DBP under office conditions and 24 h ambulatory conditions as well as in office cSBP was observed, supporting our findings with empagliflozin in patients with stable HF. 28 In a post hoc analysis of pooled data from four phase 3 studies, patients with type 2 diabetes showed a reduction of SBP and DBP as well as pulse pressure after 26 weeks treatment with canagliflozin. 29 After 6 months treatment with tofogliflozin, an improved arterial stiffness was observed in patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Effects of the sodium‐glucose cotransporter 2 inhibitor empagliflozin on vascular function in patients with chronic heart failure

et al. 2021

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Aims Impairment of vascular function contributes to the progression of chronic heart failure (HF) by increasing the afterload. Treatment with selective sodium-glucose cotransporter 2 (SGLT2) inhibitors improves the prognosis of HF, but the precise mechanisms remain unclear. The aim of this study was to analyse the effect of empagliflozin on vascular function in patients with HF. Methods and resultsIn an investigator initiated, double-blind, randomized, placebo-controlled, parallel-group, clinical study, patients with HF NYHA II-III and an ejection fraction of 49% or less were randomized 2:1 to receive empagliflozin 10 mg once daily or placebo for 3 months. A total of 74 patients (15% female), aged 66 ± 9 years, with a mean ejection fraction of 39 ± 8% and a median NTproBNP of 558 pg/mL (IQR 219-1051 pg/mL), were included. Vascular parameters such as central systolic blood pressure (cSBP), central pulse pressure (cPP), forward (FPH), and reflected pressure pulse height (RPH) decreased under resting conditions after 1 and 3 months (1 month: cSBP À6.4 ± 8.3 mmHg, P < 0.001, cPP À3.0 ± 6.6 mmHg, P = 0.004, FPH À2.5 ± 4.5 mmHg, P = 0.001, RPH À1.6 ± 3.0 mmHg, P = 0.001; 3 months: cSBP À4.6 ± 8.4 mmHg, P = 0.001, cPP À3.1 ± 4.8 mmHg, P < 0.001, FPH À1.7 ± 3.7 mmHg, P = 0.004, RPH À1.4 ± 2.5 mmHg, P = 0.001) in patients treated with empagliflozin (n = 45). In accordance, cSBP and cPP decreased in patients with empagliflozin treatment under 24 h ambulatory conditions after 1 and 3 months (1 month: cSBP À4.8 ± 10.1 mmHg, P = 0.003, cPP À2.0 ± 5.7 mmHg, P = 0.026; 3 months: cSBP À4.7 ± 9.0 mmHg, P = 0.002, cPP À2.1 ± 6.4 mmHg, P = 0.044). In the placebo group, there was no significant change after 1 and 3 months. The decrease in cSBP under resting conditions (À5.7 ± 2.4 mmHg, P = 0.019) after 1 month and in cSBP (À6.0 ± 2.6, P = 0.027) as well as in pulse wave velocity (À0.5 ± 0.2 m/s, P = 0.021) under 24 h ambulatory conditions after 3 months was greater in the empagliflozin group than in the placebo group. Conclusions We found an improvement of vascular function after treatment with empagliflozin that indicates decreased afterload of the left ventricle and may contribute to the beneficial effects of SGLT2 inhibition in HF.

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“…There is no proven treatment to improve RV function by targeting RV fibrosis, although preclinical studies have shown that Sodium-glucose transport protein 2 inhibitors have also demonstrated a positive effect in cardiac fibrosis [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

The Interplay between Myocardial Fibrosis, Strain Imaging and Collagen Biomarkers in Adults with Repaired Tetralogy of Fallot

et al. 2021

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Background: We sought to assess the interplay between right ventricle (RV) fibrosis, biventricular dysfunction based on global longitudinal strain (GLS) analysis, and biomarkers such as Galectin-3 (Gal-3), procollagen type III (PCIII), and NTproBNP. Methods: We studied 35 adult patients with rToF. All patients underwent a cardiac magnetic resonance (CMR) scan including feature tracking for deformation imaging. Blood biomarkers were measured. Results: LGE RV was detected in all patients, mainly at surgical sites. Patients with the highest RV LGE scoring had greater RV dilatation and dysfunction whereas left ventricular (LV) function was preserved. LV GLS correlated with RV total fibrosis score (p = 0.007). A LV GLS value of −15.9% predicted LGE RV score > 8 (AUC 0.754 (p = 0.02)). Neither RV GLS nor biomarker levels were correlated with the extent of RV fibrosis. A cut-off value for NTproBNP of 145.25 pg/mL predicted LGE RV score > 8 points (AUC 0.729, (p = 0.03)). A cut-off value for Gal-3 of 7.42 ng/mL predicted PR Fraction > 20% [AUC 0.704, (p = 0.05)]. Conclusions: A significant extent of RV fibrosis was mainly detected at surgical sites of RV, affecting RV performance. CMR-FT reveals subtle LV dysfunction in rToF patients, due to decreased performance of the fibrotic RV. Impaired LV function and elevated NTproBNP in rToF reflect a dysfunctional fibrotic RV.

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Mechanistic Insights of Empagliflozin in Nondiabetic Patients With HFrEF

Cited by 166 publications

References 27 publications

A New Biomarker Tool for Risk Stratification in “de novo” Acute Heart Failure (OROME)

A New Biomarker Tool for Risk Stratification in “de novo” Acute Heart Failure (OROME)

Effects of the sodium‐glucose cotransporter 2 inhibitor empagliflozin on vascular function in patients with chronic heart failure

The Interplay between Myocardial Fibrosis, Strain Imaging and Collagen Biomarkers in Adults with Repaired Tetralogy of Fallot

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