Doses Of Furosemide Research Articles

Comparative efficacy of different drugs in acute heart failure with renal dysfunction: a systematic review and network meta-analysis

ObjectiveThis network meta-analysis was to compare the efficacy of different drugs on cardiac function, renal function, and clinical outcomes in patients with acute heart failure (AHF) accompanied by renal dysfunction.MethodsPubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of AHF between January 1st 2001 and March 31th 2024. The primary outcome measures were N-terminal pro-B type natriuretic peptide (NT-proBNP), B-type natriuretic peptide (BNP), glomerular filtration rate (GFR), blood urea nitrogen, serum creatinine, all-cause mortality within 60 days, and cardiovascular mortality.ResultsAfter screening 30,697 citations, 13 studies (21,745 patients) were included, and drugs including nesiritide, dopamine, tolvaptan, levosimendan, dobutamine, furosemide, and spirolactone, and high dose of diuretics (HDD, furosemide, and spirolactone) were estimated. The results indicated that HDD had the best efficacy in reducing NT-proBNP levels. In detail, HDD notably reduced NT-proBNP levels compared to conventional treatment or placebo (PLC) [MD = −950.24; 95% CrI (−1,832.21, −64.12)]. Levosimendan significantly increased GFR levels compared to PLC [MD = 14.46; 95% CrI (3.88, 25.97)] and tolvaptan [MD = 13.83; 95% CrI (2.31, 25.33)]. No significant difference was found in 60-day all-cause mortality and cardiovascular mortality across drugs.ConclusionHDD showed the best efficacy in reducing NT-proBNP levels compared with dopamine and nesiritide, and levosimendan could significantly improve GFR levels, with no marked difference in the effect of various drugs on 60-day all-cause mortality. Hence, HDD and levosimendan may be optimal agents in the treatment of AHF with renal dysfunction.Systematic Review RegistrationPROSPERO, identifier (CRD42023454616).

Characterization of Renal OAT3 and Hepatic CYP3A Activities in Pregnant Women with Acute Pyelonephritis Using the Endogenous Biomarker Cortisol and 6β-Hydroxycortisol.

This study evaluates the impact of acute pyelonephritis in pregnant women on the in vivo activity of renal OAT3 using the endogenous biomarker (EB) 6β-hydroxycortisol (6β-OHF) renal clearance (CLrenal 6β-OHF) and AUC6β-OHF validated by correlating with the secretion clearance (CLsec) of the probe drug furosemide. Additionally, 6β-OHF formation clearance (CLformation 6β-OHF) as well as urinary (Ae6β-OHF/AeF) and plasma (AUC6βOHF/AUCF) ratios were also evaluated as EB for hepatic CYP3A activity. Pregnant women in their third trimester of gestation, diagnosed with acute pyelonephritis, were recruited before (pre-treatment, n = 8) and after (post-treatment, n = 8) cefuroxime treatment and resolution of acute pyelonephritis. All participants received a single dose of furosemide 40 mg for evaluation of OAT3 in vivo activity on both occasions followed by collection of urine and serial blood samples for 24 h. The CLrenal 6β-OHF (geometric mean and 95% CI) increased from 1.81 L/h (0.86-3.83) to 11.82 L/h (6.58-21.24), whereas the AUC6β-OHF decreased from 44.85 ng h/mL (30.96-64.98) to 24.20 ng h/mL (16.05-36.48) pre- and post-treatment. Significant statistical correlations were observed between furosemide CLsec and CLrenal 6β-OHF (R = 0.88, P =.01) and AUC6β-OHF (R = -0.66, P >.001). Additionally, the CLformation 6β-OHF was lower in pre-treatment 26.81 L/h (10.18-70.59) than in post-treatment 96.18 L/h (64.21-144.09), whereas AUC6βOHF/AUCF ratios were decreased from 0.014 (0.010-0.019) pre-treatment to 0.009 (0.006-0.013) post-treatment. Regarding Ae6β-OHF/AeF ratios, no differences were observed between pre-treatment and post-treatment. In conclusion, CLrenal 6β-OHF evaluates renal OAT3 activity when CYP3A is inhibited, whereas CLformation 6β-OHF evaluates hepatic CYP3A when OAT3 is inhibited, such as in pregnant women with acute pyelonephritis.

A Systematic Review and Meta-Analysis of an Angiotensin Receptor-Neprilysin Inhibitor in Patients Using a Durable Left Ventricular Assist Device.

Introduction: Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) drug used to treat patients with heart failure and has shown improvement in outcomes. Different studies reported the use of an ARNI in patients using left ventricular assist devices (LVADs). However, there are limited data on the use of ARNIs in this population. We aimed to assess the efficacy of ARNIs in LVAD patients. Methods: A systematic search was performed in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to November 2024. We used all relevant words for "ARNI" and "LVAD" to search, and we included studies that assessed ARNIs in patients with LVAD. Efficacy and safety outcomes were extracted from the included studies. R software version 4.4.2 was used for a meta-analysis. Results: Seven studies totaling 249 patients were included. The ARNI was found to be effective in improvements from baseline in the New York Heart Association (NYHA), B-type natriuretic peptide (BNP) (mean = -630.07 pg/mL, 95% CI [-1113.13, -147.01]), diuretic dose (furosemide equivalents) (mean= -76.05 mg/day, 95% CI [-145.11, -6.99]), left ventricular end-diastolic diameter (LVEED) (mean = -7.3 mm, 95% CI [-11.4, -3.1]), and left ventricular ejection fraction (LVEF) (mean =5, 95% CI [3.52, 6.48]). No improvement was found in the creatinine (Cr) level. However, a slight increase in the potassium level was noticed (mean= 0.17 mEq/L, 95% CI [0.02, 0.34]). The overall mortality in patients using the ARNI was 5%, 95% CI [0.00, 20], and discontinuation was found in 25%, 95% CI [0, 100]. Conclusions: The ARNI improved several cardiac structural and hemodynamic parameters in patients on LVAD support.

The Impact of Postoperative Albumin Levels on Furosemide Efficacy in Infants with Congenital Heart Disease.

Postoperative fluid overload is associated with increased mortality and morbidity in infants with congenital heart disease (CHD). Loop diuretics, such as furosemide, are commonly used to prevent fluid overload in the postoperative period. This study aimed to investigate the effect of postoperative albumin levels on the efficacy of furosemide after surgery in infants with CHD. From 1 January 2017 to 31 December 2022, postoperative albumin levels, total furosemide doses, and three-day postoperative diuresis levels were retrospectively analyzed in 186 patients aged 0-1 years who underwent cardiopulmonary bypass at the Pediatric Intensive Care Unit, Diyarbakır Gazi Yaşargil Training and Research Hospital. Demographic and clinical parameters, along with urine output in the first 6 h, first 24 h, 24-48 h, and 48-72 h postoperatively, were recorded. Patients were divided into two groups based on their albumin levels: normal albumin (≥30 g/dL) and hypoalbuminemia (<30 g/dL). A common protein interaction network for albumin and furosemide was constructed using Cytoscape software (version 3.10.2). Of the 186 patients, 79 (42.5%) were male and 107 (57.5%) were female, with a median age of 97.5 days (range 1-360 days). Furosemide doses were higher in hypoalbuminemic patients on postoperative days 1 and 2 compared to normoalbuminemic patients. On postoperative day 1, hypoalbuminemia was more prevalent in patients with oliguria, whereas normoalbuminemia was significantly higher in patients with normouria and polyuria. Furosemide doses were significantly higher in patients with oliguria than in those with normouria in the first 6 h and lower in patients with polyuria compared to those with normouria. A positive correlation was observed between albumin levels and furosemide efficacy on postoperative day 2. Additionally, a positive correlation existed between albumin levels on postoperative day 1 and urine output in the first 6 and 24 h postoperatively. Furosemide efficacy and urine output were positively correlated in the postoperative period. Mortality risk was significantly higher in hypoalbuminemic patients on postoperative days 1 and 2, as well as in patients with oliguria in the first 6 and 24 h postoperatively. Network analysis revealed that albumin was directly involved in furosemide's target network, along with six other proteins within the common interaction network. Diuresis levels were significantly lower in hypoalbuminemic patients. We suggest that the effectiveness of furosemide is reduced because it cannot bind to albumin at sufficient levels. The effective management of albumin levels may enhance furosemide efficacy and improve postoperative outcomes in infants with CHD.

Observational study for multiparametric assessment of cardiac congestion in outpatient worsening heart failure (EVOLUTION).

We sought to characterize the clinical course of patients following worsening heart failure (WHF) treated in an outpatient setting and to identify factors associated with a poor response to standard of care with loop diuretics. Between September 2022 and March 2023, 44 eligible patients (mean age 66.3 years, 84% male) with ejection fraction <50% and with WHF symptoms in the preceding week treated in an outpatient setting were enrolled. Patients were assessed weekly over 4 weeks following the WHF episode. At week 4, responses to fluid expansion and furosemide administration were assessed in 39 patients to unmask persistent subclinical congestion. Patients were on stable doses of guideline-directed medical therapy (GDMT) with a mean daily furosemide dose of 47.4 mg. Patient-reported and physician-assessed symptoms and quality of life improved over the 4 weeks. At 1 h following 1 L Ringer solution infused over 2 h, the median (interquartile range) urine volume and urine sodium excreted over 3 h were 300 (200.0-500.0) ml and 39.6 (12.4-63.0) mEq, respectively. Receiver-operating characteristic curves suggest that cystatin C >1.2 ng/ml, N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1500 pg/ml, and high-sensitivity troponin T >20 pg/ml represent good predictors of non-response to a fluid challenge (diuresis, natriuresis, and rales) following an outpatient WHF, with having all three markers associated with the worst response. Patients with high levels of troponin, or NT-proBNP, or cystatin C who develop WHF despite being treated with a loop diuretic, need novel therapies for WHF.

Door-to-Diuretic Time and Outcomes in Acute Heart Failure: A Scoping Review.

Inadequate decongestion remains an unmet need in the management of patients with heart failure. The concept of door-to-diuretic (D2D) time to improve outcomes has been proposed for patients with heart failure (HF), but the trial results have been mixed. We utilized Preferred Reporting Instrument for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) for scoping reviews with an extensive a priori search strategy for databases: PubMed and Scopus between January 2015 and November 2023. We used the key search terms "door-to-diuretic time" OR "door-to-furosemide time" OR "acute heart failure decongestion". Early D2D time was defined as intravenous (IV) diuretic administration within 30-120 min of patient arrival to the healthcare facility. Articles were included if they met our criteria, were written in the English language, and investigated door-to-diuretic or furosemide time as a decongestive strategy to improve outcomes in patients with acute HF. From 588 articles, 13 articles fulfilled the inclusion criteria after excluding duplicates and articles that did not meet our inclusion criteria. Of these studies, there was 1 meta-analysis and 12 observational cohort/registry-based studies (10 were positive trials and 2 were neutral). The most common outcomes examined were mortality and rehospitalization with early diuretic administration. First, early treatment was associated with lower in-hospital mortality and shorter hospital length of stay. Second, higher doses of furosemide were associated with improved HF symptoms and decreased hospitalization, at the cost of transiently worsening renal function. Third, the evidence is mixed for long-term mortality benefits. Although the impact of early D2D time on HF outcomes is mixed, early diuretic administration appears to be an effective and safe strategy that warrants further investigation in large-scale pragmatic comparative effectiveness trials. Future trials should consider utilizing diuretic efficiency-guided dose escalation and augmented diuresis using high-dose or combination diuretic therapy.

MELD score predicts outcomes in patients with advanced heart failure: A longitudinal evaluation.

Advanced heart failure (AHF) is characterized by recurrent episodes of haemodynamic instability and frequent hospitalizations, leading to a progressive decline in quality of life and high mortality rates. The objectives of this study were to evaluate the effect of the model for end-stage liver disease (MELD) score and its variations in predicting adverse outcomes [death, urgent heart transplant, and left ventricular assist device (LVAD) implant] among patients with AHF to assess the clinical associations of the MELD score in this population and to compare the efficacy of this tool with other prognostic scores in AHF. In this longitudinal prospective study, 162 patients with advanced heart failure (AHF) were enrolled; all patients included in the study were receiving the maximum tolerated medical therapy according to guidelines. The MELD score was measured at baseline and every 6months during follow-up. All patients underwent echocardiographic assessment and cardiopulmonary testing, which included the evaluation of maximal oxygen uptake (VO2max) and the minute ventilation/carbon dioxide production (VE/VCO2) slope. The mean age of the study group was 57.7±11.6years. There were 26 deaths, 5 urgent transplants, and 1 LVAD implantation during a follow-up period of 31.4±15.6months. The mean New York Heart Association (NYHA) class was 2.8±0.5, ejection fraction (EF) was 26.3±6.5%, the mean VO2max was 11.7±3.5mL/kg/min. Multiple regression analysis revealed a positive correlation between the MELD score and NT-proBNP (β=0.215; P=0.041) and furosemide dosage (β=0.187; P=0.040). Conversely, a negative correlation was observed between the MELD score and TAPSE (β=-0.204; P=0.047). Multivariate Cox regression on combined outcome shows a HR of 1.094 (95% CI 1.003-1.196) for unit increase in MELD considered as a continuous variable. The predictive role is independent by the effect of covariates considered in the analysis such as age, sex, NYHA class, EF, TAPSE, PASP, VO2max, NT-proBNP, MELD score worsening, and NT-proBNP increase. Changes in MELD score percentage, considered as a dichotomous variable (≤100% and >100%), were found to be predictors of mortality, urgent heart transplant and LVAD implant. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.887 for MELD score and composite outcome of death, urgent transplant, and need for LVAD. The predictive performance of MELD was even superior compared with MELD-Na, MELD-XI, MAGGIC risk score, and MECKI. The MELD score and its longitudinal changes are effective predictors of adverse outcomes in AHF.

Comparison of Urine Output Response of Intravenous Bumetanide and Furosemide in Acute Decompensated Heart Failure: an observational analysis.

Loop diuretics are a fundamental cornerstone in management of hypervolemia encountered in acute decompensated heart failure. There is variation in literature describing relative potency of loop diuretic agents, and very limited available data specific to the heart failure population. In this retrospective cohort study, we aimed to compare the urine output response between intravenous furosemide and bumetanide in patients with acute decompensated heart failure. Patients were eligible for inclusion if they were admitted between July 1, 2021 and June 30, 2022, with acute decompensated heart failure and received intravenous bumetanide or furosemide within 48 hours of admission. Propensity matching was utilized to determine comparison groups. The primary outcome was total urine output for 24 hours following initiation of the diuretic regimen. A total of 120 patients (60 in each group) were matched after exclusion criteria were applied. The total urine output was similar between groups. The bumetanide group did demonstrate a greater urine output: furosemide equivalent response (52 ± 46 mL/mg versus 33 ± 25 mL/mg; p=0.007). Based on our analysis, similar urine output may be achieved with either intravenous bumetanide or furosemide in acute decompensated heart failure; however a higher dose of furosemide may be required than what has been previously established as an equivalent dose to bumetanide to achieve a similar diuretic effect. These results should warrant further investigation to better establish dose-response relationships with loop diuretics in the acute decompensate heart failure.

Diuretic efficiency of a single dose of subcutaneous versus oral furosemide after heart failure hospitalization across diuretic resistance strata: A pilot randomized controlled trial

AimsDiuretic resistance (DR) in heart failure (HF) is associated with worse outcomes. Furoscix®, a self‐administered subcutaneous (sc) furosemide injection administered via on‐body infusor, is approved for HF congestion relief. However, its efficacy in patients with DR post‐HF hospitalization remains unknown.Methods and resultsIn this open‐label pilot randomized controlled trial, 70 participants were randomized within 14 days post‐HF hospitalization to receive a single dose of 80 mg sc furosemide or home oral dose furosemide. Enrolment was stratified by presence of DR (admission BAN‐ADHF score ≥12) with a 2:1 enrolment of those with versus without DR. Key outcomes included diuretic efficiency, the total urine output per mg of diuretic administered, and peak urine sodium within 8 h of dose administration. Treatment effects were calculated as the difference in estimated marginal means across study groups and DR strata using linear mixed‐effect models. Overall, 70 participants were enrolled (57 years, 27% female, 70% Black, 79% with HF with reduced ejection fraction). Participants with DR (n = 46) had worse kidney function, higher N‐terminal pro‐B‐type natriuretic peptide, and higher home diuretic dose. Among participants with DR, sc furosemide versus oral furosemide led to significantly greater diuretic efficiency (34.0 vs. 22.6 ml/mg, p = 0.002) and peak urine sodium (100 vs. 83 mmol/L, p = 0.029), while participants without DR had similar diuretic efficiency (29.8 vs. 30.1 ml/mg, p = 0.94) and peak urine sodium (96 vs. 95 mmol/L, p = 0.93) across both treatments. DR significantly modified the effect of sc versus oral furosemide on diuretic efficiency (pinteraction: treatment × diuretic resistance = 0.022).ConclusionSingle‐dose sc furosemide was associated with greater diuretic efficiency and peak urine sodium than oral furosemide in participants with DR discharged following recent HF hospitalization.

The Relationship of Diuretics and Dietary Sodium in Patients with Heart Failure: An Analysis of the SODIUM-HF Trial

BackgroundSODIUM-HF was a large clinical trial testing dietary sodium restriction compared to usual care in patients with heart failure that showed no reduction in clinical events. It has been suggested that diuretic doses in response to dietary sodium modification may have influenced the trial results. ObjectiveWe assessed the effects of baseline diuretic dose and diuretic dose changes on clinical outcomes in the SODIUM-HF trial. MethodsDiuretics were converted to furosemide-equivalent diuretic total daily doses. Furosemide dose was treated as a continuous variable and also stratified into 0 mg, 1–39 mg, 40 mg, 41–80 mg, and >80 mg daily. The baseline diuretic dose and change in diuretic dose were assessed and correlated with dietary sodium restriction and changes in dietary sodium intake. We then examined the relationship between diuretic dosing and the primary outcomes of SODIUM-HF (cardiovascular-related emergency department visit, cardiovascular-related hospitalization, and all-cause mortality). ResultsOf the 806 patients enrolled in the SODIUM-HF trial, 784 had known diuretic status at baseline: 209 patients (26.7%) with 0 mg, 134 patients (17%) with 1-39 mg, 205 patients (26.1%) with 40 mg, 118 patients (15.1%) with 41-80 mg, and 118 patients (15.1%) with >80 mg. No correlation was found between dietary sodium intake and diuretic dose, either at baseline or change throughout the study (P>0.05). For the primary outcomes, the 2-year risk of primary outcomes was strongly correlated with diuretic dose at baseline across the overall SODIUM-HF population (P<0.001). No significant association was found between the treatment arm and the risk of primary outcomes, within each baseline diuretic dose range or with change in diuretic dose (both P>0.05). ConclusionsAlthough a higher baseline diuretic dose was associated with worse clinical outcomes, no association was found between dietary sodium restriction, baseline or change in diuretic dose and the primary outcomes.

Эффективность алгоритма назначения диуретической терапии под контролем натрийуреза у пациентов с острой декомпенсацией сердечной недостаточности в отделении реанимации и интенсивной терапии: проспективное интервенционное контролируемое исследование

INTRODUCTION: The European Society of Cardiology suggests using early and repeated assessment of sodium content in urine in patients admitted with heart failure to evaluate diuretic therapy. OBJECTIVES: Evaluation of the effectiveness of the algorithm for diuretic therapy under the control of natriuresis in patients with acute decompensation of chronic heart failure (ADCHF) in the intensive care unit (ICU). MATERIALS AND METHODS: A prospective study included 150 patients hospitalized in the ICU with ADCHF. All patients underwent standard physical, laboratory and instrumental examinations. The starting dose of furosemide was 20 mg i/v. After 2 hours, a quantitative assessment of sodium in urine was performed. If the natriuresis was ≥ 70 mmol/l, furosemide was continued at the same dose every 12 hours. If the natriuresis was &lt; 70 mmol/L, the dose of furosemide was doubled. Natriuresis was monitored every 12 hours. RESULTS: In the natriuresis-controlled group the duration of patients' stay in the ICU was significantly shorter (3 vs. 5 days, p = 0.01), achieving euvolemia was significantly more frequent (42 % vs. 12 %, p &lt; 0.05), the daily diuresis in patients was significantly higher on more daily (120 mg vs. 80 mg, p &lt; 0.05) and the total dose of furosemide (420 mg vs. 240 mg, p &lt; 0.05). There was a pronounced decrease in congestion in the group of patients with natriuresis control with less pulmonary (number of B-lines 9.6 ± 1.2 versus 23.4 ± 2.5) and venous congestion (GRADE 0–56 %, 1–20 %, 2–24 %, 3–0 % against 0–20 %, 1–35 %, 2–18 %, 3–27 %) on the 3rd day of hospitalization. CONCLUSION: The inclusion of an algorithm for diuretic therapy under the control of natriuresis in patients with ADCHF in the ICU is effective and contributes to a more pronounced and rapid reduction of congestion, as well as a 1.5-fold reduction of time in the ICU.

Frequency and progression of azotemia during acute and chronic treatment of congestive heart failure in cats.

Azotemia is common in cats with congestive heart failure (CHF) and might be exacerbated by diuretic therapy. Determine frequency, risk factors, and survival impact of progressive azotemia in cats treated for CHF. One hundred and sixteen client-owned cats with kidney function testing performed at least twice during acute or chronic CHF treatment. Serum creatinine (sCr) and electrolyte concentrations were determined at multiple clinical timepoints to detect azotemia and kidney injury (KI; sCr increase ≥0.3 mg/dL). Furosemide dosage between timepoints was calculated. Multivariable modeling was performed to identify predictors of KI, change in serum biochemistry results, and survival. Azotemia was common at all timepoints, including initial CHF diagnosis (44%). Kidney injury was documented in 66% of cats. Use of a furosemide continuous rate infusion was associated with increased risk of KI during hospitalization (odds ratio, 141.6; 95% confidence interval [CI], 12.1-6233; P = .01). Higher furosemide dosage was associated with increase in sCr during hospitalization (P = .03) and at first reevaluation (P = .01). Treatment with an angiotensin converting enzyme inhibitor was associated with fewer lifetime KI events (P = .02). Age in years was the only variable associated with shorter survival (hazard ratio, 1.1; 95% CI, 1.0-1.1; P = .03). Neither sCr nor KI were associated with long-term outcome. Azotemia and KI were common in cats during CHF treatment but did not impact survival.

The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better

BackgroundSodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles.MethodsFrom January 2022 to June 2023, we enrolled 240 patients with chronic HF and reduced ejection fraction (HFrEF) on optimal medical therapy, according to 2021 ESC guidelines, that added treatment with Dapagliflozin from the HF Clinics of 6 Italian University Hospitals. Clinical, biochemical, and echocardiographic parameters were collected before and after 6 months of Dapagliflozin introduction. Moreover, the HFrEF population was classified according to hemodynamic profiles (A: SV ≥ 35 ml/m2; E/e′ < 15; B: SV ≥ 35 ml/m2; E/e′ ≥ 15; C: SV < 35 ml/m2; E/e′ < 15; D: SV < 35 ml/m2; E/e′ ≥ 15). Then, we compared the Dapagliflozin population with two retrospective HF cohorts, hereinafter referred to as Guide Line 2012 (GL 2012) group and Guide Line 2016 (GL 2016) group, in accordance with the HF ESC guidelines in force at the time of patients enrolment. Precisely, we evaluated the changes to baseline in clinical, functional, biochemical, and echocardiographic parameters and compared them to the GL 2012 and GL 2016 groups.ResultsDapagliflozin population (67.18 ± 11.11 years) showed a significant improvement in the echocardiographic and functional parameters (left ventricular ejection fraction [LVEF], LV end-diastolic volume [LVEDV], LVEDV index, stroke volume index [SVi], left atrium volume index [LAVi], filling pressure [E/e′ ratio], tricuspid annular plane systolic excursion [TAPSE], tricuspid annular S′ velocity [RVs’], fractional area change [FAC], inferior vena cava [IVC diameter], pulmonary artery systolic pressure [sPAP], NYHA class, and quality of life) compared to baseline. In particular, TAPSE and right ventricle diameter (RVD1) ameliorate in congestive profiles (B and D); accordingly, the furosemide dose significantly decreased in these profiles. Comparing the three populations, the analysis of echocardiographic parameters (baseline vs follow-up) highlighted a significant decrease of sPAP in the Dapagliflozin population (p < 0.05), while no changes were recorded in the GL 2012 and GL 2016 population. Moreover, at the baseline evaluation, the GL 2012 and 2016 groups needed a higher significant dose of furosemide compared to Dapagliflozin group. Finally, Dapagliflozin patients had significantly fewer rehospitalizations (1.25%) compared with the other two groups (GL 2012 18.89%, p 0.0097; GL 2016 15.32%, p 0.0497).ConclusionsWe demonstrate that Dapagliflozin is rapidly effective in an HFrEF real-world population; furthermore, the more significant effect is recorded in HFrEF patients with a congestive profile (B and D), supporting the introduction of Dapagliflozin in patients with a congestive profile and a worse prognosis. In conclusion, our data suggest evaluating the patient's hemodynamic state beyond LVEF in HFrEF.

Abstract 4136654: Urine Output Response to a Furosemide Infusion is Associated with Acute Kidney Injury in Infants Following Cardiac Surgery

Background: Acute kidney injury (AKI) following cardiac surgery in infants is common and associated with longer mechanical ventilation times and length of stay. Prior studies have shown that a lack of responsiveness to bolus dose furosemide has been associated with increased incidence of AKI. However, these studies have excluded patients on continuous furosemide infusions who are often younger, more hemodynamically unstable, and at higher risk for AKI. Hypothesis: Decreased urine output after initiation of a furosemide infusion predicts development of AKI. Methods: A retrospective cohort study of infants (&lt;1 year of age) was conducted who underwent cardiac surgery requiring cardiopulmonary bypass from 2020-2023 and were on a furosemide infusion post-operatively. The primary outcome was post-operative AKI as defined using KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. A furosemide response score (FRS) was calculated using the total urine output divided by the total dose of furosemide administered over a given time. Univariate and multivariate analyses were performed, and receiver operating characteristic curves used to determine the discriminatory ability of the FRS with regards to the primary outcome. Results: A total of 155 infants (median age at surgery 9 days) were included. Overall, 77% of infants met definition for the primary outcome of AKI; 32% stage 1, 30% stage 2, and 15% stage 3. Lower FRS at 4, 10, and 24 hours after infusion initiation were associated with AKI development (p&lt;0.0001). Younger age, smaller weight at surgery, lack of pre-operative feedings, pre-operative inotropic use and higher surgical complexity were also associated with a higher risk of AKI. An FRS (mL/mg/kg) cutoff of &lt;11.3 at 4 hours, &lt;25.5 at 10 hours, and &lt;55.3 at 24 hours had good discriminatory ability (area under the curve 0.7-0.75) in predicting AKI stage 2 or 3 (p&lt;0.001). Controlling for the significant univariate variables listed above, the FRS cutoffs remained an independent risk factor for the development of AKI stage 2 or 3, (p&lt;0.01) and were significantly associated with longer mechanical ventilation days and length of stay. Conclusion: Lack of responsiveness to a furosemide infusion (as measured by urine output corrected for dose of furosemide) is associated with the development of AKI in a high-risk cohort of infants. These novel findings may be helpful to predict those at risk and allow for further investigations for modifiable risk factors.

Co-administration of albumin and loop diuretic may be associated with reduced mortality in septic shock patients: A retrospective study with PSM analysis

BackgroundThis study aimed to investigate the potential impact of administering albumin and loop diuretics together on in-hospital mortality in septic shock patients. MethodsData from the MIMIC-IV database was used for a retrospective cohort study analyzing 3,298 adult septic shock patients. The Cox proportional hazards model and propensity score matching (PSM) were utilized to assess the relationship between loop diuretic administration and in-hospital mortality. ResultsThe study found that septic shock patients who received albumin in combination with loop diuretic had a significantly lower in-hospital mortality rate compared to those who received albumin alone (19.4% vs 33.1%, p < 0.001). Administering diuretics after albumin infusion was associated with lower mortality rates. Optimal furosemide dosages of 10 to 40 mg daily were linked to the lowest mortality rates. ConclusionCo-administering albumin and loop diuretics in septic shock patients receiving high-dose crystalloids may be associated with reduced in-hospital mortality. Further investigation through a prospective randomized controlled trial is recommended to validate these findings.

Outcomes of Bolus Dose Furosemide Versus Continuous Infusion in Patients With Acute Decompensated Left Ventricular Failure and Atrial Fibrillation.

This prospective, randomized trial aimed to compare the efficacy and safety of different intravenous diuretic regimens in acute decompensated heart failure (ADHF) patients. ADHF patients were enrolled and randomized into three groups: continuous intravenous furosemide infusion (cIV), bolus furosemide injection (bI), and furosemide plus hypertonic saline solution (HSS). Clinical outcomes were assessed over 48 h. In a study involving 1276 patients admitted for ADHF, three therapeutic regimens (T × 1, T × 2, and T × 3) were compared. T × 1 administered an 80 mg furosemide intravenous bolus infusion twice daily to 479 patients, while T × 2 involved a continuous 16-h infusion of 160 mg furosemide daily to 420 patients. T × 3 treated 377 patients with 160 mg furosemide combined with 150 mL of HSS containing 1.95% NaCl over 30 min. Yet, overall changes in renal markers such as BUN, Na, K, and serum creatinine did not differ significantly. Analysis of prespecified study endpoints revealed notable variations in hospitalization length among the treatment arms. T × 1 demonstrated a significantly shorter hospital stay (3.7 days) compared to T × 2 (6.6 days) and T × 3 (7.9 days). Conversely, alterations in serum creatinine at 48 h, overall changes in serum creatinine, body weight loss, and serum potassium levels did not significantly differ among the treatment groups. While intravenous bolus of furosemide showed potential benefits in reducing hospitalization duration, limitations such as a small sample size and short-term observation emphasize the need for larger studies to validate these outcomes further.

Hypertonic Saline in acute decompensated Heart Failure (HSHF)

Hypertonic saline with high dose furosemide improves refractory heart failure. In this case series of 10 patients of refractory acute decompensated heart failure, effect of HSS with furosemide was compared with furosemide alone. Patients responded to the therapy better, with faster decongestion, without significant adverse effects or worsening renal function. Hence an adequately powered, randomized study is required to assess the veracity of findings in this case series of hypertonic saline in diuretic resistant acute decompensated heart failure on optimal therapy. Based on present study, hypertonic saline looks like a promising option in the management of refractory heart failure.

Diuretic dosing and outcomes with torsemide and furosemide following hospitalization for heart failure: the TRANSFORM-HF trial

Abstract Background The TRANSFORM-HF trial found no significant difference in all-cause mortality and all-cause hospitalization following hospitalization for heart failure (HF) with a diuretic strategy of torsemide versus furosemide. However, the impact of diuretic dosing on the trial results and whether the relationship between dosing and outcomes differs between torsemide and furosemide is unclear. Purpose To assess and compare the associations between diuretic dosing and outcomes with torsemide and furosemide. Methods TRANSFORM-HF was an open-label, pragmatic trial that randomized 2859 patients hospitalized for HF in the United States to a diuretic strategy of torsemide versus furosemide after discharge. These post-hoc analyses categorized patients according to investigator-selected discharge dose tertile of torsemide and furosemide, i.e. tertile 1) ≤40 mg, 2) &amp;gt;40-80 mg and 3) &amp;gt;80 mg of furosemide equivalents using a 2:1 conversion with torsemide. Study endpoints were all-cause mortality, all-cause hospitalization, composite all-cause mortality or hospitalization, and change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results Dosing data were available for 2379 (83%) of patients with median age 65 years (IQR: 56, 75), 883 (37.1%) were women, and 812 (34.2%) were Black. When categorized by discharge dose, a total of 1136 (47.8%) patients were included in dose tertile 1, 696 (29.2%) in tertile 2 and 547 (23.0%) in tertile 3. For all-cause mortality, furosemide showed adjusted hazard ratios (aHR) of 1.21 (95% CI: 0.91, 1.59) for tertile 2 and 1.40 (95% CI: 1.04, 1.88) for tertile 3 compared with tertile 1. For torsemide aHR for all-cause mortality were 1.74 (95% CI: 1.32, 2.30) for tertile 2 and 1.58 (95% CI: 1.14, 2.19) for tertile 3 compared with tertile 1 (Table 1). The risk of adverse events increased similarly with dose for both diuretics and no statistically significant interaction between loop diuretic and dose was observed (Pinteraction=0.17). Likewise, for the endpoints of all-cause hospitalization and the composite of all-cause mortality and hospitalization, higher doses of furosemide and torsemide aligned with higher risk of both endpoints, and interaction p-values that did not demonstrate statistical significance by loop diuretic (all-cause hospitalization: Pinteraction= 0.28, all-cause mortality and hospitalization: Pinteraction=0.38) (Table 1). Changes in KCCQ-CSS were similar across the range of dose tertiles from baseline to month 12 for both furosemide and torsemide (Table 2). Conclusions Following hospitalization for HF, no clinical differences were observed across the dosing spectrum in all-cause mortality, all-cause hospitalization, or KCCQ-CSS at 12-mornths between torsemide and furosemide. Irrespective of diuretic agent used, increasing dose of loop diuretics correlates with worse clinical outcomes.

Basal natriuresis as a predictor of diuretic resistance and clinical evolution in acute heart failure

Abstract Introduction Current clinical guidelines recommend serial measurement of natriuresis to detect diuretic resistance (DR) and to adjust the dose of furosemide in patients with acute heart failure (AHF) (1-5). However, multiple natriuretic dosages could make more complex the AHF management. Our objective was to correlate a single measurement of basal natriuresis (BN) on admission with the development of DR and cardiovascular (CV) events in patients hospitalized for AHF and during early outpatient follow-up (6-11). Methodology Prospective, multicenter study that included patients admitted to the coronary care unit (CCU) for AHF. Patients in shock or with creatinine &amp;gt;2.5 mg% at admission were excluded. Patients included received 40 mg of intravenous furosemide on admission, BN was measured in the first urination (the result was blinded to the treating physician), and subsequent diuretic treatment was guided by a pre-established protocol. The BN was considered low if it was &amp;lt;70 meq/L. The DR was defined as a combined endpoint composed of the requirement for intravenous furosemide ≥240 mg/day, tubular diuretic blockade (TB), hypertonic saline solution (HSS) or renal replacement therapy (RRT). In-hospital CV mortality was evaluated, as well as CV mortality and AHF readmissions at 60-day post-discharge follow-up. Results 157 patients were included, 56% men, with a median age of 74 years. The median BN was 103 meq/L (IQR 74-122), and BN was low in 22% of the cohort (N=34). DR was presented in 19% (N=30), 12.7% (N=20) required furosemide ≥240 mg/day, 8% (N=13) TB, 1 patient HSS and 4% (N=6) RRT. In-hospital CV mortality was 5.7%, CV mortality at 60-day follow-up 6.8%, and AHF readmissions at 60-day follow-up 12.2%. The group with low BN presented more DR (44% vs 12%; p 0.0001; RR 0.27; 95% CI 0.15-0.5), persistence of congestion at 48 hs (26.5% vs 11.4%; p 0.05; RR 0.48; IC 95% 0.22-1), administration of furosemide ≥240 mg/day (29% vs 8%; RR 0.27; 95% CI 0.12-0.61; p 0.003), more cumulative dose of furosemide at 72 hours (220mg [IQR 180-440] vs 160mg [IQR 100-180]; p 0.0001), use of TB (20.6 vs 4.9%; p 0.008; RR 0.23; 95%CI 0.08-0.65) and RRT (11.8 vs 1.6%; p 0.02; RR 0.14; 95%CI 0.02-0.72). Low BN was associated with in-hospital worsening of AHF (26.5% vs 9%; p 0.016; RR 0.34; 95%CI 0.15-0.74), inotropics use (21% vs 7%; p 0.048; RR 0.36; 95%CI 0.14 -0.88) or mechanical respiratory assistance (12% vs 2%; p 0.02; RR 0.14; 95%CI 0.02-0.72). Low BN presented higher in-hospital CV mortality (12% vs 4%; p 0.1), without association with endpoints in outpatient 60-day follow-up. Conclusions In patients hospitalized for AHF, low BN was associated with DR, persistence of congestion, need for more aggressive decongestion strategies, and a worse in-hospital clinical outcome

The dynamics of urine sodium concentration after intra-venous furosemide in patients with acute heart failure

Abstract Background The urine sodium concentration measured at 2 hours after the administration of intravenous (IV) furosemide in patients with acute heart failure (AHF) is recommended as a marker to assess the responsiveness to IV furosemide. However, little is known regarding the dynamics of natriuresis in the very acute phase after IV furosemide and its association with prognosis in patients with AHF. Purpose The aim of this study is to investigate the dynamics of natriuresis in the very acute phase after IV furosemide and its prognostic implication in patients with AHF. Methods DIURESIS-AHF (Diuretic Resistance Measured by Sodium Excretion and Urine Output in Acute Heart Failure) is a multicenter, prospective, and observational study that evaluated the urine samples at the time of 0h, 1h, 2h, 6h, and 24h after the first administration of IV furosemide in hospitalized patients with AHF. Results After excluding 20 patients who needed additional IV furosemide within the first 6 hours, and 9 patients with missing data about 1h-spot urine sample, 84 patients with AHF (79±8 years, 55% men) were analyzed. Median N-terminal pro-brain natriuretic peptide levels at admission were 4722 [interquartile: 2616-8095] pg/mL, and median first IV furosemide doses were 20 [interquartile:20-20] mg. 29 combined event of all-cause death and heart failure rehospitalization were observed during a 1-year follow-up after registration. Urine sodium concentration corrected for urine creatinine concentration peaked 1 hour and decreased at 2 hours after IV furosemide. Kaplan-Meier curve analysis indicated that 1h urine sodium concentration below 50 mEq/L was significantly associated with a high incidence of composite endpoint (Log-rank P=0.033), and this association was retained even after adjusting for age and sex (hazard ratio, 2.37 [95% CI, 1.03-5.45]; P=0.042), but 2h urine sodium below 50 mEq/L was not associated with a poor prognosis (Log-rank; P=0.630). Conclusions Urinary sodium excretion after IV furosemide administration peaked at 1 hour after IV furosemide and decreased at 2 hours in patients with AHF. The urine sodium concentration below 50 mEq/L at 1 hour, but not 2 hours, was associated with adverse events.Urine Na trajectoriesKaplan Meier curves