Heart failure, a complex clinical syndrome, poses a significant burden on healthcare systems worldwide [13, 14]. The current study aimed to compare the effects of adding empagliflozin or doubling the dose of loop diuretics in patients with HFrEF who presented to the emergency department with decompensated heart failure. The findings shed light on the potential benefits of SGLT2 inhibitors beyond their established role in glycemic control, extending to improved echocardiographic and clinical outcomes compared to traditional diuretic escalation.
The study’s cohort comprised individuals diagnosed with HFrEF already receiving GDMT, including ACEi or ARBs, beta-blockers, and MRA. Furosemide, a loop diuretic, was the standard diuretic therapy [15]. During the study, patients experiencing decompensated heart failure were randomized into two groups: one receiving empagliflozin, an SGLT2 inhibitor, in addition to GDMT, and the other with a doubled dose of furosemide.
Echocardiographic parameters, including LVEF, estimated RVSP), and the ratio of mitral (E/A), were evaluated as key indicators of cardiac function [16]. Additionally, clinical outcomes such as the 6 MWD distance and HR were assessed. The results demonstrated that both treatment arms exhibited significant improvements in various echocardiographic parameters and clinical outcomes at the end of the 1-month follow-up [17, 18].
Interestingly, the empagliflozin group displayed notable reductions in the mitral E/A ratio, mitral Doppler tissue E/e’ ratio, and TRV, suggesting improved left ventricular filling pressure and reduced right ventricular pressure. Furthermore, the increase in 6 MWD distance and decrease in HR in this group indicated enhanced exercise tolerance and reduced sympathetic activity. This conclusion was not confirmed by direct measurement of sympathetic activity parameters. While sympathetic activity can be assessed by various methods, such as measuring plasma levels of catecholamines such as norepinephrine or using heart rate variability analysis, the observed changes in 6 MWD and HR may be indirect indicators of improved exercise capacity and reduced sympathetic tone without direct measurement of sympathetic activity. Similar improvements were observed in the group where the furosemide dose was increased, highlighting the effectiveness of both interventions in alleviating cardiac strain and enhancing functional capacity.
Importantly, the study’s primary endpoint focused on rehospitalization within the first month, a crucial metric in evaluating the efficacy of interventions in managing acute heart failure exacerbations [19]. The results demonstrated a statistically significant reduction in rehospitalization rates for patients receiving empagliflozin compared to those with a doubled diuretic dose. Our study’s results are consistent with other important studies, including the ’Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction’ (DAPA-HF) trial, the ‘Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction’ (EMPEROR-Reduced) trial, and the EMPULSE study comparing empagliflozin treatment with placebo after stabilization in acute heart failure patients. These trials collectively emphasize the efficacy of SGLT2 inhibitors in reducing heart failure-related hospitalizations and improving clinical outcomes [7, 8, 20,21,22]. Additionally, studies investigating dapagliflozin treatment during acute decompensated heart failure have shown significant weight loss and lower diuretic doses during hospitalization, while studies involving early addition of empagliflozin to standard diuretic therapy have demonstrated increased urine output without impacting renal function in acute heart failure patients [23, 24]. Moreover, research has indicated that empagliflozin treatment reduces markers of tubular injury in patients with acute decompensated heart failure, further supporting the beneficial effects of SGLT2 inhibitors in this patient population [25].
The reduced hospitalization rate observed in the SGLT2 inhibitor (SGLT2-I) group can be attributed primarily to the effect of empagliflozin rather than the doubling of the furosemide dose. This conclusion is supported by several key findings in the study. First, the empagliflozin group showed significant improvements in echocardiographic parameters such as the mitral E/A ratio, mitral Doppler tissue E/e’ ratio, and tricuspid regurgitation velocity (TRV), indicating enhanced cardiac function and reduced ventricular pressures. Additionally, the empagliflozin group demonstrated notable reductions in rehospitalization rates compared to the group with escalated furosemide dosage, aligning with previous trials highlighting the efficacy of SGLT2 inhibitors in reducing heart failure-related hospitalizations. These findings collectively suggest that empagliflozin plays a substantial role in mitigating acute heart failure episodes and contributing to the observed decrease in rehospitalization rates.
High-dose loop diuretics may potentially have a negative impact on outcomes in patients with heart failure [26, 27]. While loop diuretics are essential for managing volume overload and symptoms of heart failure exacerbations, their high doses can lead to electrolyte imbalances, renal dysfunction, and neurohormonal activation, contributing to adverse events such as worsening renal function, electrolyte disturbances, and neurohormonal activation, which are associated with increased morbidity and mortality in heart failure patients. Therefore, careful dose titration and monitoring of electrolytes and renal function are crucial to optimizing the therapeutic benefits of loop diuretics while minimizing their potential adverse effects on outcomes.
In heart failure management, the decision regarding the dosage of diuretics depends on the clinical context, including the severity of symptoms, volume status, renal function, and response to initial treatment. In acute decompensated heart failure cases requiring recompensation, an increased dosage of diuretics may be necessary to achieve adequate volume reduction and symptom relief. This approach aims to address acute volume overload and congestion promptly. On the other hand, in stable outpatient settings, a lower dosage of diuretics is often preferred to maintain euvolemia while minimizing the risk of electrolyte imbalances, renal impairment, and neurohormonal activation associated with high-dose diuretic therapy. Tailoring diuretic dosing strategies to individual patient needs and closely monitoring response and tolerability are essential aspects of optimizing heart failure management [28].
The study’s reliance on data from a single center may limit the generalizability of the results to broader patient populations across different healthcare settings. Future research should aim for multicenter studies to validate the findings in diverse patient cohorts. The relatively short 1-month follow-up period might not capture long-term outcomes and sustainability of treatment effects. Extending the follow-up duration in future studies could provide insights into the durability of improvements observed. The study primarily focused on empagliflozin, and while it provided valuable insights into this specific SGLT2 inhibitor, caution should be exercised when extrapolating these findings to other SGLT2 inhibitors. Future studies comparing different SGLT2 inhibitors could elucidate potential differences in efficacy and safety profiles.
The study’s findings highlighted the extended benefits of SGLT2 inhibitors beyond glycemic control, showing improvements in echocardiographic parameters, clinical outcomes, and reduced rehospitalization rates compared to traditional diuretic escalation. This expands the understanding of SGLT2 inhibitors in managing heart failure patients with reduced ejection fraction. The observed reductions in mitral E/A ratio, mitral Doppler tissue E/e’ ratio, and TRV in the empagliflozin group provide mechanistic insights into improved cardiac function, reduced ventricular pressures, enhanced exercise tolerance, and reduced sympathetic activity. These mechanistic findings contribute to a deeper understanding of the effects of SGLT2 inhibitors on heart failure pathophysiology.
Conducting multicenter studies involving diverse patient populations and healthcare settings can enhance the external validity and generalizability of findings. Extending the follow-up duration to assess long-term outcomes, including mortality and major adverse cardiovascular events, can provide a comprehensive understanding of the sustained effects of interventions. Considering comparative studies among different SGLT2 inhibitors and other heart failure therapies can elucidate potential differences in efficacy, safety, and tolerability profiles, guiding clinical decision-making.
By acknowledging these limitations, emphasizing the novelty of findings, and providing advice for future research directions, the study’s contributions to the field of heart failure management can be effectively contextualized and further advanced.
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