Baseline Characteristics of Patients With HF With Mildly Reduced and Preserved Ejection Fraction

Solomon, Scott D.; Vaduganathan, Muthiah; Claggett, Brian; Boer, Rudolf A. de; DeMets, David L.; Hernandez, Adrian F.; Inzucchi, Silvio E.; Kosiborod, Mikhail; Lam, Carolyn S.P.; Martínez, Felipe A.; Shah, Sanjiv J.; Bělohlávek, Jan; Chiang, Chern‐En; Borleffs, C. Jan Willem; Comín‐Colet, Josep; Dobreanu, Dan; Dróżdż, Jarosław; Fang, James C.; Gamba, Marco Antonio Alcocer; Habeeb, Waleed Al; Han, Yaling; Honorio, Jose Walter Cabrera; Janssens, Stefan; Katova, Tsvetana; Kitakaze, Masafumi; Merkely, Béla; O’Meara, Eileen; Saraiva, José Francisco Kerr; Tereschenko, Sergey N.; Thierer, Jorge; Vardeny, Orly; Verma, Subodh; Vinh, Pham Nguyễn; Wilderäng, Ulrica; Zaozerska, Natalia; Lindholm, Daniel; Petersson, Magnus; McMurray, John J.V.

doi:10.1016/j.jchf.2021.11.006

Cited by 102 publications

(107 citation statements)

References 22 publications

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“…With the release of PRESERVED-HF [ 13 ], CANVAS [ 14 ], CHIEF-HF [ 15 ], and VERTIS CV [ 16 ], SGLT2is seem a potential promising therapy for patients with HFpEF. In addition to the recently published EMPEROR-Preserved trial [ 12 ], the efficacy of SGLT2is in HFpEF is investigated in 2 additional still ongoing phase 3 trials: DELIVER [ 42 ] and CANONICAL [ 43 ]. The exact underlying mechanisms of action of SGLT2is in HFpEF have not yet been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological mechanisms of sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction

Liang

2022

BMC Cardiovasc Disord

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Background More and more evidence indicates sodium-glucose co-transporter 2 inhibitors (SGLT2is) may display clinical benefits for heart failure with preserved ejection fraction (HFpEF). However, the mechanisms of the action remain unclear. Methods A systematic pharmacology-based strategy was applied for predicting the potential molecular mechanisms of SGLT2is in HFpEF. The potential targets of SGLT2is and HFpEF were contained from diverse databases. After networks were constructed, Metascape was applied to functional enrichment. Moreover, the key findings were validated through molecular docking. Results We obtained 487 SGLT2is related targets and 1505 HFpEF related targets. The networks showed the complex relationship of HFpEF-target-HFpEF. The results of functional enrichment analysis suggested that several biological processes, including muscle system process, inflammatory response, vasculature development, heart development, regulation of MAPK cascade, positive regulation of ion transport, negative regulation of cell population proliferation, cellular response to nitrogen compound, apoptotic signaling pathway, multicellular organismal homeostasis, response to oxidative stress, regulation of cell adhesion, positive regulation of cell death, response to growth factor, and cellular response to lipid, and signaling pathways, such as cardiomyopathy, cAMP signaling pathway, cytokine-cytokine receptor interaction, apoptosis, MAPK signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and NF-kappa B signaling pathway. Finally, we validated the interactions and combinations of SGLT2is and core targets. Conclusion SGLT2is play the potential role of anti-HFpEF through the direct or indirect synergy of multiple targets and pathways. Our study promotes the explanation of the molecular mechanisms of SGLT2is in HFpEF.

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Section: Discussionmentioning

confidence: 99%

Pharmacological mechanisms of sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction

Liang

2022

BMC Cardiovasc Disord

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“…[ 16 ] DELIVER should further clarify the possibility of SGLT2is reducing CV death in HFpEF patients. [ 17 ] As stated earlier, uncertainty still remains regarding the effect of SGLT2is on mortality in HFpEF patients, as SOLOIST-WHF had a small sample size representing EF ≥50 (n=256), and EMPEROR-Preserved met its primary outcome mostly due to a reduction in the risk of hospitalisations, not mortality. [ 1 , 3 ] DELIVER was also designed to recognise heterogeneity in the HF population at the higher end of the EF spectrum, and is powered with large sample sizes across the EF spectrum (41–49%, n=2,111; 50–59%, n=2,256; ≥60%, n=1,892).…”

Section: Randomised Controlled Trials Of Sglt2 Inhibitors In Patients...mentioning

confidence: 99%

“…[ 1 , 3 ] DELIVER was also designed to recognise heterogeneity in the HF population at the higher end of the EF spectrum, and is powered with large sample sizes across the EF spectrum (41–49%, n=2,111; 50–59%, n=2,256; ≥60%, n=1,892). [ 17 ] This should further elucidate the effect of SGLT2is in those at the higher end of the EF spectrum, where EMPEROR-Preserved data showed attenuation of benefit versus those with HFmrEF in reducing hospitalisations. [ 3 ]…”

Section: Randomised Controlled Trials Of Sglt2 Inhibitors In Patients...mentioning

confidence: 99%

Clinical Evidence and Proposed Mechanisms of Sodium–Glucose Cotransporter 2 Inhibitors in Heart Failure with Preserved Ejection Fraction: A Class Effect?

2022

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Effective treatment for heart failure with preserved ejection fraction (HFpEF) is an unmet need in cardiovascular medicine. The pathophysiological drivers of HFpEF are complex, differing depending on phenotype, making a one-size-fits-all treatment approach unlikely. Remarkably, sodium–glucose cotransporter 2 inhibitors (SGLT2is) may be the first drug class to improve cardiovascular outcomes in HFpEF. Randomised controlled trials suggest a benefit in mortality, and demonstrate decreased hospitalisations and improvement in functional status. Limitations in trials exist, either due to small sample sizes, differing results between trials or decreased efficacy at higher ejection fractions. SGLT2is may provide a class effect by targeting various pathophysiological HFpEF mechanisms. Inhibition of SGLT2 and Na+/H+ exchanger 3 in the kidney promotes glycosuria, osmotic diuresis and natriuresis. The glucose deprivation activates sirtuins – protecting against oxidation and beneficially regulating metabolism. SGLT2is reduce excess epicardial adipose tissue and its deleterious adipokines. Na+/H+ exchanger 1 inhibition in the heart and lungs reduces sodium-induced calcium overload and pulmonary hypertension, respectively.

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“…To date, empagliflozin represents the first drug to significantly improve outcomes in HFpEF. It will be exciting to see whether these effects apply equally to other SGLT2i, in particular dapagliflozin, which will be clarified in the DELIVER trial [ 58 ]. Overall, the authors are convinced that empagliflozin should be the cornerstone of any HFpEF medical treatment, especially due to the lack of other evidence-based options.…”

Section: Therapy Of Hfpefmentioning

confidence: 99%

Management strategies in heart failure with preserved ejection fraction

Wintrich

Abdin

Böhm

2022

Herz

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The diagnosis and therapy of heart failure with preserved ejection fraction (HFpEF) remain challenging. Currently, there are ongoing discussions on whether the diagnosis of HFpEF should be based solely on left ventricular ejection fraction, which may not account for the heterogeneity of HFpEF syndrome. This aspect has been addressed by the recently proposed HFA-PEFF and the H2FPEF algorithms, which take numerous diagnostic modalities into account to establish the diagnosis of HFpEF. Moreover, this review focuses on the adequate treatment of comorbidities and risk factors in HFpEF that should be an essential part of any HFpEF therapy. Furthermore, the management of fluid level in HFpEF patients is pointed out, as it plays an important role in symptom control. In addition, the value of LCZ696 therapy in HFpEF is discussed. Although LCZ696 had neutral effects in the large PARAGON-HF trial, it had previously been granted an extended indication by the Food and Drug Administration. Since the publication of the EMPEROR-Preserved trial, empagliflozin now represents the first drug to significantly improve the prognosis of HFpEF patients. Therefore, the role of SGLT2 inhibitors in HFpEF management is highlighted. Overall, this review aims to enhance the knowledge on the diagnostic processes and best treatments available for HFpEF patients.

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Baseline Characteristics of Patients With HF With Mildly Reduced and Preserved Ejection Fraction

Cited by 102 publications

References 22 publications

Pharmacological mechanisms of sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction

Pharmacological mechanisms of sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction

Clinical Evidence and Proposed Mechanisms of Sodium–Glucose Cotransporter 2 Inhibitors in Heart Failure with Preserved Ejection Fraction: A Class Effect?

Management strategies in heart failure with preserved ejection fraction

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