Impact of baseline kidney dysfunction on oral diuretic efficacy following hospitalization for heart failure - insights from TRANSFORM-HF.

AIM: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half-life, but direct supportive evidence is lacking. METHODS AND RESULTS: The TRANSFORM-HF trial randomized patients hospitalized for HF to a long-term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post-hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30-<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30-<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all-cause mortality and all-cause (re)-hospitalizations, both when assessing eGFR categorically or continuously (p-value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ-CSS (p-value for interaction all >0.052) when assessing eGFR categorically or continuously. CONCLUSION: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient-reported outcomes between torsemide and furosemide, irrespective of renal function.

Clinical effect of torsemide in a horse with congestive heart failure and atrial fibrillation.

In this case report, a high dose of torsemide (6mg/kg, every 12 hours for 3 days followed by 12mg/kg, every 12 hours for 4 days) was administered orally to a horse with congestive heart failure (CHF) and atrial fibrillation. Blood samples for measurement of plasma torsemide concentrations were obtained one hour after each drug administration. Pharmacodynamic effects of oral torsemide were evaluated by daily physical examination, electrocardiography, and serum biochemistry. The horse tolerated administration of torsemide. A decrease in ventral oedema and venous congestion was subjectively noted at day 7. Torsemide plasma concentration markedly increased at day 5 (peak concentration of 15.41 µg/mL). Evidence of an increase in renal markers was observed throughout the study period. Electrolyte measurements revealed mild hyponatremia and hypochloremia, and moderate hypokalaemia. No electrocardiographic changes related to torsemide administration were observed. After seven days of treatment, the horse was euthanised due to his disease stage and poor prognosis. Results indicate that torsemide was absorbed after oral administration and was well tolerated in this horse. Furthermore, clinical improvement in this single case indicates that torsemide might be utilized as an oral alternative to furosemide in the management of equine patients in CHF. The high doses of torsemide used in this case report should be reserved for cases without clinical response to lower doses and with close monitoring of electrolytes and renal function parameters. Further investigation of torsemide clinical efficacy and safety in horses with CHF with a larger cohort and prolonged administration is warranted.

Torsemide vs Furosemide Among Patients With New-Onset vs Worsening Chronic Heart Failure: A Substudy of the TRANSFORM-HF Randomized Clinical Trial.

Importance: Differences in clinical profiles, outcomes, and diuretic treatment effects may exist between patients with de novo heart failure (HF) and worsening chronic HF (WHF). Objectives: To compare clinical characteristics and treatment outcomes of torsemide vs furosemide in patients hospitalized with de novo HF vs WHF. Design, Setting, and Participants: All patients with a documented ejection fraction who were randomized in the Torsemide Comparison With Furosemide for Management of Heart Failure (TRANSFORM-HF) trial, conducted from June 18 through March 2022, were included in this post hoc analysis. Study data were analyzed March to May 2023. Exposure: Patients were categorized by HF type and further divided by loop diuretic strategy. Main Outcomes and Measures: End points included all-cause mortality and hospitalization outcomes over 12 months, as well as change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results: Among 2858 patients (mean [SD] age, 64.5 [14.0] years; 1803 male [63.1%]), 838 patients (29.3%) had de novo HF, and 2020 patients (70.7%) had WHF. Patients with de novo HF were younger (mean [SD] age, 60.6 [14.5] years vs 66.1 [13.5] years), had a higher glomerular filtration rate (mean [SD], 68.6 [24.9] vs 57.0 [24.0]), lower levels of natriuretic peptides (median [IQR], brain-type natriuretic peptide, 855.0 [423.0-1555.0] pg/mL vs 1022.0 [500.0-1927.0] pg/mL), and tended to be discharged on lower doses of loop diuretic (mean [SD], 50.3 [46.2] mg vs 63.8 [52.4] mg). De novo HF was associated with lower all-cause mortality at 12 months (de novo, 65 of 838 [9.1%] vs WHF, 408 of 2020 [25.4%]; adjusted hazard ratio [aHR], 0.50; 95% CI, 0.38-0.66; P < .001). Similarly, lower all-cause first rehospitalization at 12 months and greater improvement from baseline in KCCQ-CSS at 12 months were noted among patients with de novo HF (median [IQR]: de novo, 29.94 [27.35-32.54] vs WHF, 23.68 [21.62-25.74]; adjusted estimated difference in means: 6.26; 95% CI, 3.72-8.81; P < .001). There was no significant difference in mortality with torsemide vs furosemide in either de novo (No. of events [rate per 100 patient-years]: torsemide, 27 [7.4%] vs furosemide, 38 [10.9%]; aHR, 0.70; 95% CI, 0.40-1.14; P = .15) or WHF (torsemide 212 [26.8%] vs furosemide, 196 [24.0%]; aHR, 1.08; 95% CI, 0.89-1.32; P = .42; P for interaction = .10), In addition, no significant differences in hospitalizations, first all-cause hospitalization, or total hospitalizations at 12 months were noted with a strategy of torsemide vs furosemide in either de novo HF or WHF. Conclusions and Relevance: Among patients discharged after hospitalization for HF, de novo HF was associated with better clinical and patient-reported outcomes when compared with WHF. Regardless of HF type, there was no significant difference between torsemide and furosemide with respect to 12-month clinical or patient-reported outcomes.

Comparative Effect of Loop Diuretic Prescription on Mortality and Heart Failure Readmission.

Loop diuretics are a standard pharmacologic therapy in heart failure (HF) management. Although furosemide is most frequently used, torsemide and bumetanide are increasingly prescribed in clinical practice, possibly because of superior bioavailability. Few real-world comparative effectiveness studies have examined outcomes across all 3 loop diuretics. The study goal was to compare the effects of loop diuretic prescribing at HF hospitalization discharge on mortality and HF readmission. We identified patients in Medicare claims data initiating furosemide, torsemide, or bumetanide after an index HF hospitalization from 2007 to 2017. We estimated 6-month risks of all-cause mortality and a composite outcome (HF readmission or all-cause mortality) using inverse probability of treatment weighting to adjust for relevant confounders. We identified 62,632 furosemide, 1,720 torsemide, and 2,389 bumetanide initiators. The 6-month adjusted all-cause mortality risk was lowest for torsemide (13.2%), followed by furosemide (14.5%) and bumetanide (15.6%). The 6-month composite outcome risk was 21.4% for torsemide, 24.7% for furosemide, and 24.9% for bumetanide. Compared with furosemide, the 6-month all-cause mortality risk was 1.3% (95% confidence interval [CI]: -3.7, 1.0) lower for torsemide and 1.0% (95% CI: -1.2, 3.2) higher for bumetanide, and the 6-month composite outcome risk was 3.3% (95% CI: -6.3, -0.3) lower for torsemide and 0.2% (95% CI: -2.5, 2.9) higher for bumetanide. In conclusion, the findings suggested that the first prescribed loop diuretic following HF hospitalization is associated with clinically important differences in morbidity in older patients receiving torsemide, bumetanide, or furosemide. These differences were consistent for the effect of all-cause mortality alone, but were not statistically significant.

Effect of Furosemide Versus Torsemide on Hospitalizations and Mortality in Patients With Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

Loop diuretics are essential in the treatment of patients with heart failure (HF) who develop congestion. Furosemide is the most commonly used diuretic; however, some randomized controlled trials (RCTs) have shown varying results associated with torsemide and furosemide in terms of hospitalizations and mortality. We performed an updated meta-analysis of currently available RCTs comparing furosemide and torsemide to see if there is any difference in clinical outcomes in patients treated with these loop diuretics. PubMed, MEDLINE, Cochrane, and Embase databases were searched for RCTs comparing the outcomes in patients with HF treated with furosemide versus torsemide. The primary end points included all-cause mortality, all-cause hospitalizations, cardiovascular-related hospitalizations, and HF-related hospitalizations. A random-effects meta-analysis was performed to estimate the risk ratio (RR) with a 95% confidence interval (CI). A total of 10 RCTs with 4,127 patients (2,088 in the furosemide group and 2,039 in the torsemide group) were included in this analysis. A total of 56% of the patients were men and the mean age was 68 years. No significant difference was noted in all-cause mortality between the furosemide and torsemide groups (RR 1.02, 95% CI 0.91 to 1.15, p = 0.70); however, patients treated with furosemide compared with torsemide had higher risks of cardiovascular hospitalizations (RR 1.36, 95% CI 1.13 to 1.65, p = 0.001), HF-related hospitalizations (RR 1.65, 95% CI 1.21 to 2.24, p = 0.001), and all-cause hospitalizations (RR 1.06, 95% CI 1.01 to 1.11, p = 0.02). In conclusion, patients with HF treated with torsemide have a reduced risk of hospitalizations compared with those treated with furosemide, without any difference in mortality. These data indicate that torsemide may be a better choice to treat patients with HF.

Clinical Outcomes With Furosemide Versus Torsemide in Patients With Heart Failure: An Updated Systematic Review and Meta-Analysis.

Despite potential advantages of torsemide over furosemide, <10% of the patients with heart failure (HF) are on torsemide in clinical practice. Prior studies comparing furosemide to torsemide in patients with HF have shown conflicting findings, regarding hospitalizations and mortality. We aimed to pool all the studies conducted to date and provide the most updated and comprehensive evidence, regarding the effect of furosemide vs torsemide in reducing mortality and hospitalizations in patients with HF. We conducted a comprehensive literature search of the PubMed/Medline, Cochrane Library and Scopus from inception till June 2023, for randomized and nonrandomized studies comparing furosemide to torsemide in adult patients (>18 years) with acute or chronic HF. Data about all-cause mortality, HF-related hospitalizations and all-cause hospitalizations was extracted, pooled, and analyzed. Forest plots were created based on the random effects model. A total of 17 studies (n = 11,996 patients) were included in our analysis with a median follow-up time of 8 months. Our pooled analysis demonstrated no difference in all-cause mortality between furosemide and torsemide groups in HF patients (OR = 0.98, 95% CI: 0.75-1.29, P = 0.89). However, torsemide was associated with a significantly lesser incidence of HF-related hospitalizations (OR = 0.73, 95% CI: 0.54-0.99, P = 0.04), and all-cause hospitalizations (OR = 0.84, 95% CI: 0.73-0.98, P = 0.03), as compared to furosemide. Torsemide significantly reduces HF-related and all-cause hospitalizations as compared to furosemide, with no difference in mortality. We recommend transitioning from furosemide to torsemide in HF patients who are not attaining symptomatic control.

Effect of Torsemide Versus Furosemide on Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.

BACKGROUND: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. METHODS: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0-100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0-6; score ≥3 supporting evaluation for depression) over 12 months. RESULTS: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27-60) in the torsemide group and 40 (24-59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, -2.26 to 2.37]; P=0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P=0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, -0.64 to 3.36]; P=0.18) and 6-month follow-up (adjusted mean difference, -0.37 [95% CI, -2.52 to 1.78]; P=0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. CONCLUSIONS: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03296813.

Torsemide increases arsenic concentrations by inhibition of multidrug resistance protein 4 in arsenic trioxide treated acute promyelocytic leukemia patients.

Torsemide is commonly used to relieve edema during the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). We explored the effect of torsemide on the plasma concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMAV) and dimethyarsinic acid (DMAV) in APL patients treated with ATO and clarified its molecular mechanism in rats and cells. The study included 146 APL patients treated with ATO. 60（41.1 %) of these 146 patients were co-administered with torsemide. The treatment of torsemide increased plasma concentrations of iAs (P < 0.05) and DMAV (P < 0.05) in APL patients. The single co-administration of ATO and torsemide in rats significantly increased the plasma concentrations and AUC(0-t) of iAs (P < 0.05) and MMAV (P < 0.05), decreased the urinary excretion rates and the urine concentrations of iAs (P < 0.05) and DMAV (P < 0.05), and enhanced iAs (P < 0.05) and MMAV (P < 0.05) concentrations in the kidneys of rats. In addition, torsemide decreased the expression of multidrug resistance protein 4 (MRP4) in rat kidneys after 7 days of continuous co-administration (P < 0.05). We also treated MRP4-overexpressing HEK293T cells with ATO and different concentrations of torsemide. Torsemide markedly increased the concentrations of iAs, MMAV and DMAV by inhibiting MRP4 compared with ATO alone (P < 0.05). In conclusion, torsemide increased the plasma concentrations of arsenic metabolites in APL patients treated with ATO by inhibiting the transporter MRP4 in a dose-dependent manner.

Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.

Importance: Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. Objective: To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure. Design, Setting, and Participants: TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022. Interventions: Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage. Main Outcomes and Measures: The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide. Results: TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction. Conclusions and Relevance: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Trial Registration: ClinicalTrials.gov Identifier: NCT03296813.

Torasemide-induced Vascular Purpura in the Course of Eosinophilic Granulomatosis with Polyangiitis.

Torasemide is a loop diuretic with a molecule that is chemically similar to the sulphonamides described as eosinophilic granulomatosis with polyangiitis (EGPA) triggering drugs. The presented case is probably the first description of torasemide-induced vascular purpura in the course of EGPA. Any diagnosis of vasculitis should be followed by an identification of drugs that may aggravate the disease. A 74-year-old patient was admitted to the Department of Dermatology with purpura-like skin lesions on the upper, and lower extremities, including the buttocks. The lesions had appeared around the ankles 7 days before admission to the hospital and then started to progress upwards. The patient complained on lower limb paresthesia and pain. Other comorbidities included bronchial asthma, chronic sinusitis, ischemic heart disease, mild aortic stenosis, arterial hypertension, and degenerative thoracic spine disease. The woman had previously undergone nasal polypectomy twice. She was on a constant regimen of oral rosuvastatin 5 mg per day, spironolactone 50 mg per day, metoprolol 150 mg per day, inhaled formoterol 12 µg per day, and ipratropium bromide 20 µg per day. Ten days prior to admission, she was commenced on torasemide at a dose of 50 mg per day prescribed by a general practitioner due to high blood pressure. Doppler ultrasound upon admission to the hospital excluded deep venal thrombosis. The laboratory tests revealed leukocytosis (17.1 thousand per mm3) with eosinophilia (38.6%), elevated plasma level of C-reactive protein (119 mg per L) and D-dimers (2657 ng per mm3). Indirect immunofluorescent test identified a low titer (1:80) of antinuclear antibodies, but elevated (1:160) antineutrophil cytoplasmic antibodies (ANCA) in the patient's serum. Immunoblot found them to be aimed against myeloperoxidase (pANCA). A chest X-ray showed increased vascular lung markings, while high-resolution computed tomography revealed peribronchial glass-ground opacities. Microscopic evaluation of skin biopsy taken from the lower limbs showed perivascular infiltrates consisting of eosinophils and neutrophils, fragments of neutrophil nuclei, and fibrinous necrosis of small vessels. Electromyography performed in the lower limbs because of their weakness highlighted a loss of response from both sural nerves, as well as slowed conduction velocity of the right tibial nerve and in both common peroneal nerves. Both clinical characteristics of skin lesions and histopathology suggested a diagnosis of EGPA, which was later confirmed by a consultant in rheumatology. The patient was commenced on prednisone at a dose of 0.5 mg per kg of body weight daily and mycophenolate mofetil at a daily dose of 2 g. The antihypertensive therapy was modified, and torasemide was replaced by spironolactone 25 mg per day. The treatment resulted in a gradual regression of skin lesions within a few weeks. The first report of EGPA dates back to 1951. Its authors were Jacob Churg and Lotte Strauss. They described a case series of 13 patients who had severe asthma, fever, peripheral blood eosinophilia, and granulomatous vasculitis in microscopic evaluation of the skin. Three histopathological criteria were then proposed, and Churg-Strauss syndrome was recognized when eosinophilic infiltrates in the tissues, necrotizing inflammation of small and medium vessels, and the presence of extravascular granulomas were observed together in a patient (1). Only 17.4% of patients met all three histopathological criteria, and the diagnosis of the disease was frequently delayed despite of its overt clinical picture (2). In 1984, Lanham et al. proposed new diagnostic criteria which included the presence of bronchial asthma, eosinophilia in a peripheral blood smear >1.5 thousand per mm3, and signs of vasculitis involving at least two organs other than the lungs (3). Lanham's criteria could also delay the recognition of the syndrome before involvement of internal organs, and the American College of Rheumatology therefore established classification criteria in 1990. These included the presence of bronchial asthma, migratory infiltrates in the lungs as assessed by radiographs, the presence of abnormalities in the paranasal sinuses (polyps, allergic rhinitis, chronic inflammation), mono- or polyneuropathy, peripheral blood eosinophilia (>10% of leukocytes must be eosinophils), and extravascular eosinophilic infiltrates in a histopathological examination. Patients who met 4 out of 6 criteria were classified as having Churg-Strauss syndrome (4). The term EGPA was recommended to define patients with Churg-Strauss syndrome in 2012 (5). EGPA is a condition with low incidence (0.11-2.66 cases per million) and morbidity. It usually occurs in the fifth decade of life (6,7), although 65 cases reports of EGPA in people under 18 years of age could be found in the PubMed and Ovid Medline Database at the end of 2020 (8). The etiopathogenesis of the disease has not been fully explained so far. Approximately 40-60% of patients are positive to pANCA (9), but the role of these antibodies in the pathogenesis of EGPA remains unclear. They are suspected to mediate binding of the Fc receptor to MPO exposed on the surface of neutrophils. Subsequently, this may active neutrophils and contribute to a damage of the vascular endothelium (9,10). Glomerulonephritis, neuropathy, and vasculitis are more common in patients with EGPA who have detectable pANCA when compared with seronegative patients. There are at least several drugs which potentially may EGPA. The strongest association with the occurrence of EGPA was found with the use of leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast), although they are commonly used in the treatment of asthma, which is paradoxically one of the complications of the syndrome (13). Although no relationship has been demonstrated so far between the occurrence of EGPA and the intake of drugs from the groups used by the presented patient, a clear time relationship can be observed between the commencement of torasemide and the onset of symptoms in our patient. To date, only three cases of leukocytoclastic vasculitis have been reported after the administration of torasemide. Both of them developed cutaneous symptoms of the disease within 24 hours of the administration of torasemide in patients with no previous history of drug hypersensitivity, but they disappeared quickly within 8-15 days after drug discontinuation (14,15). The chemical structure of torasemide is similar to the molecule of sulfonamides which were previously found to be a triggering factors for EGPA (12). This drug belongs to the group of loop diuretics classified as sulfonamide derivatives. A comparison of the chemical structure of torasemide and sulphanilamide molecules is presented in Figure 1. The clear time relationship between starting the administration of torasemide and the occurrence of purpura-like lesions suggests that it was an aggravating factor for EGPA in our patient. A coexistence of several disorders (asthma, nasal polyps, symptoms of peripheral neuropathy) in our patient suggest EGPA could have developed in her years before oral intake of torasemide. The sudden onset of skin symptoms shows torasemide to be possible inducing factor for the development of vascular purpura in patients suffering from EGPA but without previous cutaneous involvement.

Ascertaining Death Events in a Pragmatic Clinical Trial: Insights From the TRANSFORM-HF Trial.

BACKGROUND: Death ascertainment can be challenging for pragmatic clinical trials that limit site follow-up activities to usual clinical care. METHODS AND RESULTS: We used blinded aggregate data from the ongoing ToRsemide comparison with furoSemide FOR Management of Heart Failure (TRANSFORM-HF) pragmatic clinical trial in patients with heart failure to evaluate the agreement between centralized call center death event identification and the United States National Death Index (NDI). Of 2284 total patients randomized through April 12, 2021, 1480 were randomized in 2018-2019 and 804 in 2020-2021. The call center identified 416 total death events (177 in 2018-2019 and 239 in 2020-2021). The NDI 2018-2019 final file identified 178 death events, 165 of which were also identified by the call center. The study's inter-rater reliability metric (Cohen's kappa coefficient, 0.920; 95% confidence interval, 0.889-0.951) demonstrates a high level of agreement. The time between a death event and its identification was less for the call center (median, 47 days; interquartile range, 11-103 days) than for the NDI (median, 270 days; interquartile range, 186-391 days). CONCLUSIONS: There is substantial agreement between deaths identified by a centralized call center and the NDI. However, the time between a death event and its identification is significantly less for the call center.

90-year-old man • dyspnea • lower extremity edema • limitations in daily activities • Dx?

► Dyspnea ► Lower extremity edema ► Limitations in daily activities.

Efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure with volume overload: a prospective, randomized, controlled clinical trial.

BACKGROUND: Ultrafiltration decreases total body water and improves the alveolar to arterial oxygen gradient. The aims of the study were to investigate the efficacy and safety of early ultrafiltration in acute decompensated heart failure (ADHF) patients. METHODS: 100 patients with ADHF within 24 h of admission were randomly assigned into early ultrafiltration (n = 40) or torasemide plus tolvaptan (n = 60) groups. The primary outcomes were weight loss and an increase in urine output on days 4 and 8 of treatment. RESULTS: Patients who received early ultrafiltration for 3 days achieved a greater weight loss (kg) (- 2.94 ± 3.76 vs - 0.64 ± 0.91, P < 0.001) and urine increase (mL) (198.00 ± 170.70 vs 61.77 ± 4.67, P < 0.001) than the torasemide plus tolvaptan group on day 4. From days 4 to 7, patients in the early ultrafiltration group received sequential therapy of torasemide and tolvaptan. Better control of volume was reflected in a greater weight loss (- 3.72 ± 3.81 vs - 1.34 ± 1.32, P < 0.001) and urine increase (373.80 ± 120.90 vs 79.5 ± 52.35, P < 0.001), greater reduction of B-type natriuretic peptide (BNP) (pg/mL) (- 1144 ± 1435 vs - 654.02 ± 889.65, P = 0.037), NYHA (New York Heart Association) functional class (- 1.45 ± 0.50 vs - 1.17 ± 0.62, P = 0.018), jugular venous pulse (JVP) score (points) (- 1.9 ± 1.13 vs - 0.78 ± 0.69, P < 0.001), inferior vena cava (IVC) diameter (mm) (- 15.35 ± 11.03 vs - 4.98 ± 6.00, P < 0.001) and an increase in the dyspnea score (points) (4.08 ± 3.44 vs 2.77 ± 2.03, P = 0.035) in the early ultrafiltration group on day 8. No significant differences were found in the readmission and mortality rates in the 2 patient groups at the 1-month and 3-month follow-ups. Both groups had a similar stable renal profile. CONCLUSION: Early ultrafiltration is superior to diuretics for volume overload treatment initiation of ADHF patients. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030696, Registered 10 March 2020-Retrospectively registered, https://www.chictr.org.cn/showproj.aspx?proj=29099 .

Tolerance of torasemide in cats with congestive heart failure: a retrospective study on 21 cases (2016-2019).

BACKGROUND: In dogs with congestive heart failure (CHF), the efficacy of torasemide, a loop diuretic, has been demonstrated. However, unlike in dogs and humans little has been described about the use of torasemide in the cat with spontaneous CHF. The objectives of this retrospective study were therefore to describe the therapeutic use of oral torasemide in cats with spontaneous CHF, document its potential adverse effects while reporting the clinical course of this feline population following torasemide administration in addition to standard medical therapy. RESULTS: Medical records of 21 client-owned cats with CHF (median age = 10.6 years [interquartile range (IQR) = 6.5-11.2]) receiving torasemide were reviewed. Data collected included torasemide dosages, other concurrent medications, physical examination features, echocardiographic data, and potential adverse effects during follow-up. A survival analysis was performed to estimate the time from diagnosis to cardiac death. Dyspnea related to CHF was identified in all cats (pleural effusion [8/21], pulmonary edema [5/21] or both [8/21]), associated with ascites in 4/21 cats. The CHF cause was determined by echocardiography in all cats: hypertrophic (n = 10), restrictive (n = 6), arrhythmogenic right ventricular (n = 3), dilated (n = 1) cardiomyopathies, and aortic valve abnormality (n = 1). At initiation, median torasemide dosage was 0.21 mg/kg [IQR = 0.17-0.23] q24h. Clinical signs declined in most cats (20/21) during the first 2 weeks with no remarkable adverse events. Median survival time after torasemide prescription was 182 days [IQR = 46-330]. A contemporary control group including 54 cats with CHF, receiving furosemide as sole loop diuretic treatment was compared with the study group. Median (IQR) survival time of cats in the control group was not significatively different (p = 0.962) from that of the torasemide group, i.e., 148 days (9-364), although the torasemide group included significantly more cats with recurrent episodes of CHF (52%) that the control group (19%). CONCLUSIONS: This case series demonstrates that torasemide can be used in cats with spontaneous CHF. This therapeutic interest needs to be confirmed by prospective clinical trials.

Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure.

Although torsemide's oral bioavailability and half-life theoretically render it a more efficient diuretic than furosemide, the clinical outcomes of torsemide compared with furosemide remain unclear. We performed a systematic review and meta-analysis, including all published studies that compared torsemide and furosemide use in heart failure patients from January 1996 through August 2019. Nineteen studies (9 randomized control trials [RCTs] and 10 observational studies) with a total of 19,280 patients were included. During a mean follow-up duration of 15 months, torsemide was associated with a numerically lower risk of hospitalization due to heart failure (10.6% vs 18.4%; odds ratio [OR] 0.72, 95% confidence interval [CI] [0.51, 1.03], p = 0.07, I2 = 18%; number needed to treat [NNT] = 23) compared with furosemide. Torsemide was associated with statistically significant more improvement in functional status from New York Heart Association (NYHA) class III/IV to I/II (72.5% vs 58%; OR 2.32, 95% CI (1.32, 4.1), p = 0.004, I2 = 27%; NNT = 5) and lower risk of cardiac mortality (1.5% vs 4.4%; OR 0.37, 95% CI (0.20, 0.66), p <0.001, I2 = 0%, NNT = 40) compared with furosemide. However, there was no difference in all-cause mortality or medication side effects between the 2 groups. In conclusion, compared with furosemide, torsemide use was associated with significant more improvement in functional status and lower cardiac mortality; and numerically fewer hospitalizations in patients with heart failure.