This review examines the evolving role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in acute cardiac care. Originally developed as antidiabetic agents, SGLT2i have demonstrated significant and early benefits in chronic heart failure by reducing hospitalizations and cardiovascular mortality across all the ejection fraction spectrum. Recent evidence now suggests that these agents may also offer advantages in acute settings, including acute decompensated heart failure (ADHF) and post - acute myocardial infarction (AMI). Several clinical trials have explored early SGLT2i initiation during hospitalization, reporting improvements in diuretic efficiency, cardiac biomarkers, and favorable remodeling, without notable safety concerns. The present review discusses the multifaceted mechanisms underlying these benefits, which include osmotic diuresis, modulation of neurohormonal activation, anti-inflammatory effects, and direct myocardial protection. Together, these actions not only facilitate decongestion and renal preservation but also enhance cardiac energetics. Current data are promising and support a pivotal role of a SGLT2i as a therapeutic strategy in the whole acute cardiac care setting for their short and long-term benefit. Future research is essential to validate these findings and refine the best patients to be treated with early SGLT2i implementation in the acute cardiac care spectrum.

Data on the early use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with acute heart failure (HF) are conflicting, and mostly evaluating soft endpoints (i.e., indices of congestion, renal function, ejection fraction, and diuresis). The aim was to perform a meta-analysis of randomized controlled trials (RCTs) to assess their impact after an HF decompensation event.

Two electronic databases were screened for eligible studies. Efficacy endpoints were all-cause death, cardiovascular death, HF hospitalization, length of hospital stay, and N-terminal pro-B-type natriuretic peptide (nt-proBNP). Safety endpoints included acute kidney injury (AKI), volume depletion, ketoacidosis, hypotension, hypoglycemia, non-cardiovascular death, urinary tract infection, genital infections, serious adverse events (AE), and AE leading to treatment discontinuation. Two pre-specified subgroup analyses were planned according to the specific SGLT2i and clinical setting [i.e., acute myocardial infarction (MI) versus non-acute MI]. 16 RCTs enrolling 15,073 patients were considered. Early initiation of SGLT2i significantly reduced the risk of HF hospitalizations [Risk ratio (RR) 0.79, 95 % Confidence interval (CI) 0.72-0.87], AKI (RR 0.76, 95 % CI 0.59-0.99), and nt-proBNP levels (MD -354 pg/mL). No significant difference was detected for any of the other endpoints. In the pre-specified subgroup analysis, a significant interaction was found between the SGLT2i type and the risk of AKI, in favor of empagliflozin.

In patients recently hospitalized for acute HF, early administration of SGLT2i was associated with fewer readmissions for HF and AKI, as well as decongestant effects, without raising any safety concern.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent one of the main cornerstones of heart failure treatment. Nevertheless, while the cardiovascular beneficial effects of these drugs have been clearly demonstrated by several clinical trials, in clinical practice, it remains challenging to identify the appropriate timing to start SGLT2 inhibitors. The potential risk of side effects, like genito-urinary infections and interaction with other drugs, may often lead to delay the prescription of these drugs in the acute setting. However, several studies have demonstrated the safety and the prognostic impact of SGLT2 inhibitors in the hospitalized patient, suggesting that treatment initiation during hospitalization or early post-discharge may represent an ideal therapeutic option. In this review, we discuss the main trials on early administration of SGLT2 inhibitors in acute heart failure supporting early introduction of SGLT2 inhibitors to optimize heart failure treatment. The efficacy and safety of these drugs in patients with acute myocardial infarction are also discussed. Based on the review of existing evidences, a practical flowchart on early administration of SGLT2 inhibitors in the acute setting is proposed.

Observational studies and small randomized controlled trials have suggested the benefits of early introduction of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in acute heart failure (AHF). However, current evidence on their efficacy and safety in this clinical setting remains limited.

We performed a systematic review and meta-analysis to assess efficacy/safety of early use of SGLT2is in AHF. PUBMED/EMBASE/Cochrane were searched from inception to May 31, 2024, for randomized controlled trials evaluating outcomes of SGLT2i early initiation in patients with AHF. Efficacy outcomes were all-cause death and heart failure rehospitalizations. Safety outcomes included acute kidney injury, ketoacidosis, urinary tract infections, hypotension, and hypoglycemia. Early initiation was defined as performed before or shortly after discharge (within 3 days). A sensitivity analysis was conducted, including only patients with initiation before discharge.

Seven randomized controlled trials that enrolled 2320 patients were included. Early use of SGLT2is was associated with a significant reduction in all-cause death (odds ratio, 0.71 [95% CI, 0.55-0.92; 95% PI, 0.55-0.98]) and HF rehospitalizations (odds ratio, 0.73 [95% CI, 0.57-0.94; 95% PI, 0.58-0.93]), even after adjusting for follow-up duration. SGLT2i initiation before discharge yielded consistent results for efficacy outcomes. Safety outcomes could not be usefully determined because of a low events rate resulting in wide CIs. The impact of diabetic status remains basically unknown due to the small number of available randomized controlled trials investigating this population.

Early introduction of SGLT2is in AHF improves all-cause death and rehospitalization rates, can be performed before discharge, and should be offered to most patients with AHF.

Acute Heart Failure (AHF) presents as a serious pathophysiological disease with significant morbidity and mortality rates, requiring immediate medical intervention. Traditional treatment involves diuretics and vasodilators, but a subset of patients develop resistance due to acute cardiorenal syndrome. Dapagliflozin, categorized as a sodium-glucose cotransporter-2 inhibitor (SGLT2i), has emerged as a promising therapy for AHF, demonstrating substantial benefits in reducing both mortality and morbidity among patients. The purpose of this meta-analysis and systematic review is to determine dapagliflozin's safety and efficacy in AHF patients.

In accordance with PRISMA guidelines, we conducted a systematic search across several databases (PubMed, Science Direct, and Cochrane Library) up to June 2024 to identify randomized controlled trials (RCTs) that compared dapagliflozin with control treatments in patients with AHF. Key outcomes of interest included In-Hospital Cardiovascular mortality rates, duration of hospitalization, and instances of in-hospital worsening. Data extraction and quality assessment adhered to established protocols and the results were evaluated using Review Manager (RevMan Version 5.4.1) The assessment of bias risk follows the principles established in the Cochrane Handbook for Systematic Reviews and Meta-Analysis.

Five RCTs comprising 912 patients met the inclusion criteria. Dapagliflozin significantly reduced In-Hospital Cardiovascular mortality (RR 0.56, 95% CI 0.36-0.88, p = 0.01, I²=26%) and 30-day hospital readmissions (RR 0.73, CI 0.54-0.99, p = 0.05, I²=7%). However, dapagliflozin did not significantly affect the length of hospital stay (MD -0.11, CI -0.73-0.51, p = 0.72, I²=60%) or the incidence of hypotension (RR 0.82, CI 0.36-1.84, p = 0.63, I²=0%). A significant weight change was observed (MD 0.93, CI 0.03-1.83, p = 0.04, I²=95%), which was resolved upon sensitivity analysis (MD 1.34, CI 1.02-1.66, p < 0.0001, I²=0%). No significant effects were found for worsening renal failure or changes in GFR in this study.

Dapagliflozin appears to be beneficial in reducing In-Hospital Cardiovascular mortality and 30-day hospital readmissions in AHF patients. Although it demonstrates potential, additional research is needed to establish its significance in AHF management. Further investigation with larger sample sizes, different doses, and comprehensive safety and cost-effectiveness is imperative to thoroughly evaluate the safety and clinical efficacy of Dapagliflozin, underscoring the necessity for additional data to substantiate its role in managing patients with AHF.

Not applicable.

Inadequate representation of women and racial minorities in heart failure (HF) clinical trials continues to limit the generalizability of the results. This could create a disparity in treatment for future heart failure therapies and devices. The study aims to assess the representation of women and racial minorities in recent heart failure studies involving sodium-glucose cotransporter-2 (SGLT-2) inhibitors.

PubMed was used to search randomized controlled trials (RCTs) looking at SGLT-2 inhibitors and heart failure, which were published from inception to August 2024.

A total of 43 RCTs with 27,703 participants were identified. The studies were published between 2018 and 2024. Seven studies (41 %) were multi-country, with 45 countries represented. The overall proportion of women enrolled in the studies was 35.6 %. The proportion of women was 24.06 % in studies that recruited only patients with HFrEF, 44.33 % in those that recruited only patients with HFpEF, and 41.4 % in those that recruited both HFrEF and HFpEF. Data on race was partially reported in 25 studies (58 %). 76 % of the pharmaceutical industry-funded studies reported race data. However, only 33.3 % of the unfunded or non-industry-funded studies reported race data. In the studies that reported race data, 72.91 % were Caucasians, 15.48 % were Asians, 5.62 % were African-American and 4.1 % were mixed race or others.In the bivariate analysis, race was more likely to be reported in studies done in the US (p < 0.001), multi-country studies (p = 0.013), and studies sponsored by pharmaceutical companies. More than a third of the study participants were more likely to be women in more recently published studies than older studies (p < 0.001). Additionally, more than a third of the study participants were more likely to be women in studies done in the US (p = 0.055). The multivariate analysis showed an increased odds of having more than a third of the study participants being women in more recently published studies (OR 1.83, 95 % CI 1.06-3.17, p = 0.031) and in studies done in the US (OR 7.69, 95 % CI 1.53-38.59, p = 0.013).

Our study found that women and racial minority individuals have remained underrepresented in recent heart failure studies. Although some progress has been made over the years, more work is needed to improve data reporting and address barriers to enrollment for women and racial minority individuals in clinical trials.

Heart failure (HF) is a chronic disease associated with high morbidity and mortality rates. Renin-angiotensin-aldosterone system blockers (including angiotensin receptor/neprilysin inhibitors), beta-blockers, and mineralocorticoid receptor blockers remain the mainstay of pharmacotherapy for HF with reduced ejection fraction (HFrEF). However, despite the use of guideline-directed medical therapy, the mortality from HFrEF remains high. HF with preserved ejection fraction (HFpEF) comprises approximately half of the total incident HF cases; however, unlike HFrEF, there are no proven therapies for this condition. Sodium glucose cotransporter-2 inhibitors (SGLT-2is) represent a new class of pharmacological agents approved for diabetes mellitus (DM) that inhibit SGLT-2 receptors in the kidney. A serendipitous finding from seminal trials of SGLT-2is in DM was the significant improvement in renal and cardiovascular (CV) outcomes. More importantly, the improvement in HF hospitalization (HHF) in the CV outcomes trials of SGLT-2is was striking. Multiple mechanisms have been proposed for the pleiotropic effects of SGLT-2is beyond their glycemic control. However, as patients with HF were not included in any of these trials, it can be considered as a primary intervention. Subsequently, two landmark studies of SGLT-2is in patients with HFrEF, namely, an empagliflozin outcome trial in patients with chronic HF and a reduced ejection fraction (EMPEROR-Reduced) and dapagliflozin and prevention of adverse outcomes in HF (DAPA-HF), demonstrated significant improvement in HHF and CV mortality regardless of the presence of DM. These impressive results pitchforked these drugs as class I indications in patients with HFrEF across major guidelines. Thereafter, empagliflozin outcome trial in patients with chronic HF with preserved ejection fraction (EMPEROR-Preserved) and dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction HF (DELIVER) trials successively confirmed that SGLT-2is also benefit patients with HFpEF with or without DM. These results represent a watershed as they constitute the first clinically meaningful therapy for HFpEF in the past three decades of evolution of HF management. Emerging positive data for the use of SGLT-2is in acute HF and post-myocardial infarction scenarios have strengthened the pivotal role of these agents in the realm of HF. In a short span of time, these classes of drugs have captivated the entire scenario of HF.

The efficacy of dapagliflozin in patients with acute heart failure remains unclear.

To investigate the impact of dapagliflozin (DAPA) on loop diuretics use and 90-day readmission in patients with acute heart failure.

In a retrospective cohort study, patients diagnosed with acute heart failure or chronic heart failure with acute exacerbation admitted to Fuyang People's Hospital from January 2021 to April 2023, this study used DAPA (at a dose of 10 mg once daily) in combination with standard treatment. The patients were divided into DAPA group and DAPA-Free group based on whether they used DAPA in acute heart failure. To minimize the influence of confounding factors and ensure comparability between groups, we used propensity score matching (PSM).

A total of 399 patients were included, with 206 patients (51.63%) in the DAPA group and 193 patients (48.37%) in the DAPA-Free group. PSM produced 160 pairs. After PSM, there were no statistically significant differences between the DAPA and DAPA-Free groups in terms of readmission of all causes (16.88% vs. 18.12%, OR 0.9141, 95% CI 0.5385-1.552, log rank P = 0.739) or readmission for heart failure (11.88% vs. 15.0%, OR 0.9077, 95% CI 0.4441-1.469, log rank P = 0.484) after 90-day follow-up. Patients in the DAPA group had a lower mean daily dose of intravenous loop diuretics compared to the DAPA-Free group (20 mg/d vs. 30.00 mg/d, P<0.001), lower total loop diuretic dose during hospitalization (106.06 ± 31.23 mg vs. 144.50 ± 45.39 mg, P = 0.038) and a decreased number of diuretic types used (11.88% vs. 23.12%, P = 0.008).

DAPA reduced the dose of intravenous loop diuretics. However, it did not improve all-cause readmission for 90 days or readmission for heart failure after discharge.

Worsening heart failure (WHF) is a severe and dynamic condition characterized by significant clinical and hemodynamic deterioration. It is characterized by worsening HF signs, symptoms and biomarkers, despite the achievement of an optimized medical therapy. It remains a significant challenge in cardiology, as it evolves into advanced and end-stage HF. The hyperactivation of the neurohormonal, adrenergic and renin-angiotensin-aldosterone system are well known pathophysiological pathways involved in HF. Several drugs have been developed to inhibit the latter, resulting in an improvement in life expectancy. Nevertheless, patients are exposed to a residual risk of adverse events, and the exploration of new molecular pathways and therapeutic targets is required. This review explores the current landscape of WHF, highlighting the complexities and factors contributing to this critical condition. Most recent medical advances have introduced cutting-edge pharmacological agents, such as guanylate cyclase stimulators and myosin activators. Regarding device-based therapies, invasive pulmonary pressure measurement and cardiac contractility modulation have emerged as promising tools to increase the quality of life and reduce hospitalizations due to HF exacerbations. Recent innovations in terms of WHF management emphasize the need for a multifaceted and patient-centric approach to address the complex HF syndrome.