Furosemide and torsemide are the primary treatment strategies for AHF to eliminate congestion. Both medications are loop diuretics that promote renal sodium and water excretion with a rapid onset of action, helping to achieve a euvolemic state. As loop diuretics, they share the same mechanism of action. However, torsemide has a higher degree of protein binding and longer half-life, resulting in more stable natriuresis and urine output compered to furosemide. Moreover, torsemide demonstrates benefits beyond diuresis, including the inhibition of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous activity. Because of its anti-aldosterone effect, torsemide carries a lower risk of hypokalemia. Furthermore, torsemide-treated patients showed decreased serum concentrations of the C-terminal propeptide of procollagen type I, a biochemical marker of myocardial fibrosis. Torsemide also has a neutral metabolic action, meaning it does not affect bicarbonate and lipid metabolism (McDonagh et al., 2021; Erratum, 2020; Diez et al., 2009; Lopez et al., 2004; Cuthbert et al., 2024; Felker et al., 2020). Nevertheless, the superiority of one diuretic over the other in managing AHF or chronic HF (CHF) remains unproven. A few head-to-head comparisons of loop diuretic drugs in CHF suggest a lower rate of hospitalization and cardiac mortality in torsemide treatment, along with improvements in fatigue, symptoms, and quality of life (Mullens et al., 2019; Cosín and Díez, 2002; Balsam et al., 2019; Mentz et al., 2016; Murray et al., 2001; Müller et al., 2003; Abraham et al., 2020). In contrast, other studies have shown no differences between the medications regarding hospitalization rates and 1-year all-cause mortality reduction (Mentz et al., 2016; Yao et al., 2018). To date, there have only been a limited number of studies comparing IV furosemide with torsemide in the treatment of AHF (Stroobandt et al., 1982; Paterna et al., 2011).

Diuresis and natriuresis, which occur after diuretic administration, are key indicators of diuretic response. Urine output or changes in body weight are used to assess diuresis, while measurement of sodium in a spot urine sample helps to assess natriuresis (Mullens et al., 2019). In the PUSH-AHF (Pragmatic Urinary Sodium-based Algorithm in Acute Heart Failure) and ENACT-HF (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) studies, patients with AHF requiring treatment with IV loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care. Even though no significant differences were observed between the two arms regarding all-cause mortality or first HF rehospitalization, the authors concluded that natriuresis-guided loop diuretic treatment was safe and improved natriuresis and diuresis without impacting long-term clinical outcomes (Ter Maaten et al., 2022; Dauw et al., 2024; Biegus et al., 2024). A good diuretic response within the first 24 h of AHF treatment is associated with better outcomes. Conversely, patients with poor diuretic response have worse prognosis (Cuthbert et al., 2024; Cuthbert and Clark, 2024; Felker et al., 2020; Mullens et al., 2019; Cosín and Díez, 2002). A decrease in sodium excretion during loop diuretic treatment is indicative of diuretic resistance, which refers to insufficient diuresis and natriuresis despite the administration of an adequate dose of diuretics (Paterna et al., 2011; Ter Maaten et al., 2022). The primary mechanism of resistance is intense sodium reabsorption in the distal part of the nephron, driven by high urine sodium concentration and hypochloremic alkalosis (Cox and Testani, 2020; Mullens et al., 2009; Felker et al., 2011). In the ROSE-HF (Renal Optimisation Strategies Evaluation in Acute Heart Failure) trial evaluating diuretic resistance, a lower level of urinary sodium was associated with higher 6-month mortality, unless water balance was achieved (Hodson et al., 2019). Urinary sodium levels below 50–70 mmol/L also correlate with an increased risk of renal failure and late complications (Mullens et al., 2009; Felker et al., 2011). To compare the efficacy of IV furosemide and torsemide, we assessed changes in spot urinary sodium levels during the initial treatment of AHF. Imaging modalities and clinical assessment tools play a complementary role in evaluating the efficacy of diuretic therapy. LUS has emerged as a reliable, non-invasive method to monitor pulmonary congestion by quantifying B-lines, which are reverberation artifacts representing interstitial edema. B-lines are useful for the diagnosis, monitoring, and prognostic assessment of patients with HF (Čelutkienė et al., 2020; Platz et al., 2017). A reduction in the number of B-lines over time reflects effective decongestion and has improved outcomes in HF patients (He et al., 2022). Clinical assessment tools, such as the Borg scale and the Killip-Kimball classification, offer practical insights into the severity of dyspnea and the degree of hemodynamic compromise, respectively. These tools, in conjunction with urine output, enable a multidimensional assessment of treatment response.

Numerous clinical trials have compared the effects of torsemide and furosemide in CHF; however, relatively few have focused on AHF. The TORIC (Torsemide in Congestive HF) trial found that patients on torsemide had lower total and cardiac mortality with RRR (Relative Risk Reduction) of 51.5% and 59.7%, respectively, than those on furosemide, and presented better clinical improvement assessed by NYHA classification (Cosín and Díez, 2002). The TORNADO (Torsemide in Hemodynamic and Neurohormonal Stress and Cardiac Remodelling in HF) study demonstrated improvement of NYHA class in the torsemide group among patients with CHF (Balsam et al., 2019). Conversely, the TRANSFORM (Torsemide Comparison with Furosemide for Management of HF), a trial comparing furosemide to torsemide in CHF, suggested no difference in all-cause hospitalization or all-cause mortality (Mentz et al., 2023). Similarly, a post hoc analysis of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial compering patients discharged on torsemide versus furosemide showed no significant difference in 30-day mortality or HF rehospitalization (Mentz et al., 2016). Clasen et al. (1988) found that the diuretics had similar effects on fluid and sodium excretion, but torsemide led to less RAAS activation. In turn, analyzing features of IV loop diuretics, Paterna et al. (2011), concluded that high-doses of IV torsemide are equivalent to high-doses of IV furosemide in the treatment of refractory CHF. They included 87% of patients (n = 3,620) on furosemide and 13% (n = 557) on torsemide. Torsemide was associated with similar outcomes on unadjusted analysis and nominally lower events on adjusted analysis (30-day mortality/HF hospitalization). The other study, which included twelve patients with AHF, revealed that the effects of both drugs on urinary electrolyte and water excretion were similar (Stroobandt et al., 1982). These data suggest the potential additional value of torsemide in the treatment of CHF, possibly due to its ability to inhibit myocardial fibrosis, RAAS, and sympathetic nervous activity. However, this therapeutic advantage was not evident during the initial phase of AHF management in our study, consistent with the observations reported by Paterna and Stroobandt. Considering that furosemide performs better in sodium excretion and urine output in our study, it may point to its ability to overcome diuretic resistance in AHF, but clinical effect, that is reduction of B-lines, changes in the Borg scale, and the Killip-Kimball classification, do not vary compared to torsemide. This might imply that while furosemide could potentially be more effective at promoting sodium and urine excretion, the lack of universal statistical significance calls for cautious interpretation. The 2021 European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of AHF and CHF emphasize early and effective decongestion, recommending the prompt use of IV loop diuretics to alleviate symptoms and reduce pulmonary and systemic congestion (McDonagh et al., 2021; Erratum, 2020). Both furosemide and torsemide are recommended, although furosemide remains the most widely studied and utilized agent. Our study aligns with these guideline-directed principles, showing that both IV furosemide and torsemide achieved decongestive effects across multiple parameters, including urinary sodium excretion, reduction in B-lines, and clinical congestion scoring without significant differences. This reflects the ESC’s emphasis on monitoring the response to diuretics, such as changes in dyspnea and natriuresis, to guide therapy titration. Notably, the ESC also endorses the use of natriuresis-guided diuretic strategies to improve short-term decongestion, as seen in the ENACT-HF trial, which is mirrored in our study design through repeated urinary sodium assessments to optimize dosing (Dauw et al., 2024). The findings from our study suggest that while both agents fit within guideline-recommended decongestion strategies, the choice between furosemide and torsemide may be individualized based on patient phenotype, including comorbid conditions like AF and COPD, which in our study were associated with better urine output with furosemide. This personalized approach is consistent with the ESC’s call for tailoring therapy to individual patient characteristics and treatment response.

This study has several noteworthy limitations. First, the open-label design may have introduced performance and detection bias, as awareness of treatment allocation could have influenced both clinical decision-making and outcome assessment. Second, based on the primary endpoint that is change in urinary spot sodium levels at 24 h, we performed a sample size estimation using an assumed standard deviation of 25 mmol/L and a mean difference of 21 mmol/L between groups, as observed in our preliminary results. We estimated that approximately 23 patients per group would be required to achieve 80% power at a p-value of 0.05. However, in a post hoc power analysis using observed medians and interquartile ranges, we estimated standard deviations of 56.3 mmol/L and 31.85 mmol/L for the torsemide and furosemide groups, respectively. This yielded a moderate effect size (Cohen’s d ≈ 0.54), but a reduced power of approximately 48%. This suggests that the study may have been underpowered to detect a statistically significant difference, despite a clinically meaningful trend (p = 0.097). Third, baseline imbalances were observed, particularly in the prevalence of COPD (24% vs. 61.5%, p = 0.007) and BMI (28.6 kg/m² vs. 25.5 kg/m², p = 0.013) between the torsemide and furosemide groups. However, multivariate analysis of these parameters did not reveal any differences in treatment outcomes between the two drugs. Fourth, this was a single-center study, which may limit the external validity and generalizability of the findings. Finally, the study focused exclusively on short-term clinical outcomes, without evaluating the impact on HF rehospitalization or mortality. Future investigations should aim to address the limitations of the present study by including larger patient populations, implementing blinding, and extending the observation period beyond 24 h. A longer evaluation window may better elucidate any delayed or sustained effects of torsemide that were not apparent during 24 h of treatment.

Given these results, the choice between furosemide and torsemide should be guided by clinical context and individualized patient characteristics, as the two drugs may not be equally effective in all patients. While overall differences did not consistently reach statistical significance, observed trends and subgroup variations suggest that furosemide and torsemide may exert differential effects on fluid reduction. These findings are preliminary and require validation, but they highlight the potential importance of a personalized approach to diuretic therapy in AHF and underscore the need for further research to clarify the comparative effectiveness of these agents.