Diuretic Regimen Research Articles

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.

Abstract 4123391: CardioMEMS and Mavacamten: A Synergistic Approach in Managing Hypertrophic Obstructive Cardiomyopathy with HFpEF Phenotype

Introduction: Mavacamten is a cardiac myosin inhibitor that has been approved for obstructive hypertrophic cardiomyopathy (oHCM). The CardioMEMS PA (pulmonary artery) sensor allows remote pulmonary artery diastolic (PAD) pressure monitoring to adjust diuresis in heart failure with preserved ejection fraction (HFpEF). We present the case of a patient with oHCM and HFpEF where data extrapolated from CardioMEMS provided valuable insight to the hemodynamic impact of cardiac myosin inhibitors. Case: A 66-year-old female with hypertension, obesity and oHCM presented with worsening dyspnea and was evaluated for septal myectomy. However, surgery was deferred because of decompensated HFpEF, as evidenced by significant leg edema on exam, and severely elevated left and right-side filling pressure, with restrictive physiology on right heart catheterization. A CardioMEMS PA sensor was implanted to guide decongestion, however, escalation of diuresis was limited due to severe left ventricular outflow tract (LVOT) obstruction. PAD remained elevated at 20-30 mmHg. Due to the refractory LVOT obstruction and despite the use of maximally tolerated beta blockers, Mavacamten was initiated and escalated according to protocol. LVOT obstruction resolved on follow up echocardiogram. Without any adjustment in her diuretic regimen, her PAD decreased to 15-20 mmHg. On follow-up visit, the patient reported improvement in dyspnea and reduction in lower extremity edema. Discussion: Managing oHCM is challenging, particularly when complicated by HFpEF. Mavacamten has shown promise in reducing LVOT gradients and improving symptoms in oHCM. However, managing fluid status in these patients can be difficult due to the risk of exacerbating LVOT obstruction while optimizing filling pressures. Our case provides direct evidence that treating LVOT obstruction with a cardiac myosin inhibitor leads to improvement in decompensated heart failure, as evidenced by the reduction in PAD. Conclusion: Addressing LVOT obstruction is key to decongesting and managing heart failure in oHCM patients. In our case, the use of CardioMEMS PA sensor system allowed a novel perspective of assessing hemodynamic impact of cardiac myosin inhibitors.

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.

Diuretic therapy strategies in decompensated acute heart failure: a systematic review and network metanalysis

Abstract Background Congestion in acute heart failure (AHF) is treated with furosemide, mainly in continuous infusion (furosemide continuous, FC) or iv boluses, and combination of different diuretics. Randomized controlled trials (RCTs) only compared the efficacy and safety of some diuretic strategies with discordant results. Purpose To provide a comprehensive synthesis of the effects of diuretic regimens in AHF. Methods The PubMed, EMBASE, SCOPUS and Cochrane databases were searched for phase III RCTs until July 31st, 2023, evaluating diuretics without any other intervention in patients admitted for AHF, with randomization within 48 hours, no run-in period and/or need of clinical stabilization. The arms assigned to iv boluses or undefined schemas of furosemide/loop diuretic (LD) were grouped together as "furosemide bolus" (FB). The endpoints were weight loss over 24 hours (WL), worsening renal function (WRF), total urine output (tUO) and net urine output (nUO) over 24 hours, hypokalemia (hypoK), and hyponatremia (hypoNa). Heterogeneity was estimated by Thompsons’ I2 statistics, and odds ratios (OR) with 95% confidence intervals were calculated by means of a random-effects model with inverse variance weighting. A leave-one-out analysis, an analysis limited to studies with specified mode of furosemide/LD administration, and an analysis of measures of congestion/decongestion were also carried out. Results Twenty-five RCTs were selected, for a total of 7,095 patients with mean age 69.2±11.1 years and mean LVEF 38.1±12.7%. In subjects treated with furosemide/LD, the mean furosemide equivalent dose was 154.7±53.0 mg/24 hours. Heterogeneity was moderate-to-high (37.3%-66.0% across the study endpoints). FC, FB plus tolvaptan, FB plus sodium-glucose cotransporter inhibitor (SGLT2i), and FB plus thiazide were associated with greater WL than FB (Figure 1A). The combination of FB and thiazide or SGLT2i also portended higher odds of WRF than FB alone, as did the combination of FB and acetazolamide (Figure 1B). tUO was greater with FC (OR 2.77 [1.98-3.88]), FB plus tolvaptan (OR 1.69 [1.22-2.35]), and FB plus SGLT2i (OR 1.95 [1.16-3.28]) than with FB, and nUO was greater with FC (OR 1.50 [1.06-2.13]) and FB plus tolvaptan (OR 1.76 [1.06-2.92]) than with FB. Compared with FB, hypoK was more frequent with FB and thiazide (OR 1.68 [1.29-2.19]), while there was a trend for less hypoK events with FB plus tolvaptan (OR 0.86 [0.69-1.08]). No differences in hypoNa rates were found. Sensitivity analyses were consistent with the main one. Thirteen (52%) and 14 (56%) studies had published information about symptoms and signs of congestion, respectively, and 6 (24%) adopted pre-specified scoring systems. Conclusions FC and most combination diuretic regimens have greater efficacy than FB in promoting WL and diuresis, but at the cost of WRF and hyoK, especially when thiazide is used. Congestion has inconsistently been evaluated in RCTs of diuretic therapy in AHF.

Efficacy and safety of ambulatory, weekly, high-intensity intravenous diuretic strategy for congestion-refractory heart failure patients: insights from the DEA-HF prospective randomized clinical trial

Abstract Background Congestion and volume overload are strongly associated with low quality of life and pose a significant risk for both rehospitalization and mortality in heart failure (HF) patients. Despite the widespread use of diuretics in HF, the use of weekly, intravenous (IV), high-intensity diuretic treatment has not been prospectively studied in the setting of ambulatory congestion-refractory patients. Purpose To assess the efficacy and safety of weekly high-intensity diuresis regimens in a practical setting of ambulatory day care for chronically congested HF patients. Methods We performed a sub-analysis on data from a prospective, randomized, cross-over controlled study (DEA-HF) originally designed to compare diuresis regimens in the setting of an HF ambulatory daycare unit who had signs of congestion or volume overload despite adherence to guideline-directed medical therapy. Each patient received three different IV diuretic regimens, in one of six randomized sequences: IV furosemide 250mg; IV furosemide 250mg + oral metolazone 5mg; and IV furosemide 250mg + IV acetazolamide 500mg. All regimens given on the same chronological week were pooled, and diuresis efficacy was assessed by measuring excreted urine volume and sodium weight 6 hours post treatment initiation. Additional assessment at one week post each treatment included serum levels of NT-ProBNP, body weight and creatinine as well as congestion score based on the presence of ascites, pleural effusion and pedal edema. Statistical analysis was based on linear mixed models while accounting for the random effect of patient identity. Results A total of 42 patients were recruited. The mean age was 72±9 years, twenty-one subjects (50%) had LVEF ≥ 50%. 74% of patients were NYHA III class. All patients were on contemporary guidelines-directed HF therapy. Analysis of excreted sodium weight and urine volume revealed values of 4202.1±180.1 mg (Mean±SEM) and 1.77±0.07 liter per visit, respectively. No significant differences in efficacy were detected among treatments given in consecutive weeks (P= 0.80 and 0.69 for differences in sodium weight and urine volume, respectively). After 4 weeks, log(NT-ProBNP) was significantly decreased (P=0.044), accompanied by a significant decrease of 2.4±0.62 kg in body weight (P=0.0004) and of 0.92±0.44 points in congestion score (P=0.037). Serum creatinine level was only slightly increased by 0.19±0.04 mg/dl (P=0.0001), demonstrating the overall safety of the high-intensity diuresis strategy. Conclusions In ambulatory, congestion refractory HF patients a strategy based on high-intensity, weekly diuresis therapy was safe and effective for three consecutive weeks. The natriuresis response to the treatments was maintained, NT-ProBNP levels and congestion score were decreased. The strategy may be instrumental for ambulatory HF patients that require diuretic therapy intensification and may allow to prevent hospitalization.

8537 Refractory Hypoglycemia Secondary To Metastatic Insulinoma Treated With Novel Insulin Receptor Antibody - A Case Report

Abstract Disclosure: J. Lloyd: None. S. Abu Omar: None. L. Lester: None. L. Wilson: None. Introduction: Insulinoma is the most common functional pancreatic neuroendocrine tumor, characterized by hypersecretion of insulin, causing hypoglycemia. Insulinomas are mostly benign, however malignant neoplasms account for 5-10 % of cases. Surgical resection is the preferred treatment for solitary tumor, however metastatic insulinoma requires a more aggressive approach with medications to prevent hypoglycemia, resection of primary tumor, resection of metastasis, and chemoembolization. We describe a case of metastatic insulinoma with refractory hypoglycemia despite treatment with multiple medications, surgical resection of tumor, embolization of liver metastasis and successfully treated with a novel monoclonal antibody that blocks insulin receptor. Clinical Case: 43-year-old female was initially diagnosed with metastatic insulinoma in 2021. The primary tumor was pancreatic with metastasis to the liver. She was treated with surgical resection of the primary tumor and three hepatic embolizations for liver metastasis. She required a progressive number of medications to treat frequent, debilitating hypoglycemia. These medications included diazoxide, verapamil, lanreotide then changed to pasireotide, everolimus, and dexamethasone. Despite these treatments, she experienced refractory hypoglycemia and was admitted to the hospital. She required continuous dextrose infusion up to 100ml/hr of D50. Due to the large volume of fluid from dextrose infusion and other medications, she developed severe edema and AKI and required aggressive diuretic regimens and briefly intermittent CRRT. As there were no additional medications to add and prospects for future liver embolization were limited, we requested use of RZ358 through the manufacturer’s Expanded Patient Access program. This medication is a monoclonal antibody that blocks the insulin receptor to counteract the effects of insulin and thereby reduce hypoglycemia. This mechanism of action is unique from medications used to manage insulinoma induced hypoglycemia. She received her first infusion of RZ358 which she tolerated well. She had baseline elevation of ALP due to liver metastasis with further rise after liver embolizations, most recently 4 weeks prior. There was a rise in ALP levels which stabilized after 3 days. She experienced no significant side effects. For the first time in two months, five days after her first infusion of RZ358, the dextrose infusion could be stopped. She received her second infusion of RZ358 one week after first infusion. She was discharged home in a stable condition shortly after the second infusion. Conclusion: The Insulin receptor blocking monoclonal antibody, RZ358, offers a promising approach to patients with metastatic insulinoma who have refractory hypoglycemia despite maximal medical and surgical therapy. Presentation: 6/1/2024

Haemodynamic effects of intra-aortic balloon pumps stratified by baseline pulmonary artery pulsatility index.

Intra-aortic balloon pump (IABP) devices are commonly used in patients with heart failure related cardiogenic shock (HF-CS), including those with out-of-proportion right ventricular (RV) dysfunction. Pulmonary artery pulsatility index (PAPi) is a haemodynamic surrogate for RV performance. We aimed to assess short-term haemodynamic changes in patients with HF-CS following IABP support stratified by baseline PAPi. This is a single-centre study of 67 consecutive patients with HF-CS who underwent IABP placement between 2020 and 2022. The primary aim was haemodynamic changes of specific variables on pulmonary artery catheter monitoring over 72h following IABP placement. Secondary aims were clinically significant changes in diuretic regimens, changes in inotropes or vasopressors at 72h following IABP, along with clinical outcomes. Prior to IABP placement, 57% of the total cohort (median age 59years [48, 69], 31% female) had Society of Cardiovascular Angiography and Interventions Stage C HF-CS. Thirty-eight (56%) patients had a PAPi <2.0. Following 72h of IABP support, the PAPi <2.0 group had an observed significant decrease in central venous pressure (CVP; 20 to 12mmHg, P<0.001) and mean pulmonary artery pressure (mPAP; 37.5 to 28.5mmHg, P=0.001), and an increase in PAPi (1 to 1.6, P=0.001). No significant change in cardiac index (CI; 2 to 2.1L/min/m2, P=0.31) was observed. The PAPi ≥2.0 group (N=29) had no observed significant change in CVP (10 to 8mmHg, P=0.47), or PAPi (2.6 to 2.8, P=0.92), but there was a significant improvement in CI (1.9 to 2.5L/min/m2, P=0.004) along with reduction in mPA (37 to 29mmHg, P=0.03). The PAPi <2.0 group had a significant increase in diuretic requirement (52.6% vs. 20.7%, P=0.01) and numerically greater addition of inotropes/vasopressors (47.3% vs. 34.4%, P=0.07) compared with the PAPi ≥2.0 group at 72h following IABP placement. Significantly more patients in the PAPi ≥2.0 group underwent left ventricular assist device (55.2% vs. 26.3%, P=0.02), with no overall significant differences observed in escalation to veno-arterial extracorporeal membrane oxygenation, 30-day mortality, renal replacement therapy post-IABP, or rates of heart transplantation. IABP devices in those with HF-CS and low or abnormal PAPi may provide modest short-term haemodynamic benefits without significant improvement in CI, along with greater need for adjustment in medical therapeutics to achieve haemodynamic optimization.

Rationale and Design of the DECONGEST (Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment) Study

To evaluate whether early combination diuretic therapy guided by serial post-diuretic urine sodium concentration (UNa+) assessments in acute heart failure (AHF) facilitates safe and effective decongestion. The Diuretic Treatment in Acute Heart Failure with Volume Overload Guided by Serial Spot Urine Sodium Assessment (DECONGEST) study is a pragmatic, 2-centre, randomized, parallel-arm, open-label study, aiming to enrol 104 patients with AHF and clinically evident fluid overload, requiring treatment with intravenous loop diuretics. Patients are randomized to receive standard of care or a bundled approach comprising: (1) systematic post-diuretic UNa+ assessments until successful decongestion, defined as no remaining clinical signs of fluid overload with a post-diuretic UNa+ ≤80 mmol/L; (2) thrice-daily intravenous loop diuretic bolus therapy, with dosing according to estimated glomerular filtration rate; (3) upfront use of intravenous acetazolamide (500 mg OD); and (4) full nephron blockade with high-dose oral chlorthalidone (100 mg OD) and intravenous canreonate (200 mg OD) for diuretic resistance, defined as persisting signs of fluid overload with a post-diuretic UNa+ ≤80 mmol/L. The primary endpoint of the DECONGEST study is a hierarchical composite of (1) survival at 30 days; (2) days alive and out of hospital or care facility up to 30 days; and (3) greater relative decrease in natriuretic peptide levels from baseline to day 30. The DECONGEST study aims to determine whether an intensive diuretic regimen focused on early combination therapy, guided by serial post-diuretic UNa+ assessments, safely enhances decongestion, warranting further evaluation in a larger trial powered for clinical events.

2024 update in heart failure.

In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4mg once weekly administered for 1year decreased body weight and significantly improved quality of life and the 6min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article.

Diuresis Efficacy in Ambulatory Congested Heart Failure Patients: Intrapatient Comparison of 3 Diuretic Regimens (DEA-HF)

BackgroundLimited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients. ObjectivesThe authors sought to compare the potency and safety of commonly used diuretic regimens in CHF patients. MethodsA prospective, randomized, open-label, crossover study conducted in NYHA functional class II to IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250 mg; IV furosemide 250 mg plus oral metolazone 5 mg; and IV furosemide 250 mg plus IV acetazolamide 500 mg. Treatments were administered once a week, in 1 of 6 randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation. ResultsA total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4,691 mg (95% CI: 4,153-5,229 mg) compared with furosemide alone, 3,835 mg (95% CI: 3,279-4,392 mg; P = 0.015) and to furosemide plus acetazolamide 3,584 mg (95% CI: 3,020-4,148 mg; P = 0.001). Furosemide plus metolazone resulted in 1.84 L of urine (95% CI: 1.63-2.05 L), compared with 1.58 L (95% CI: 1.37-1.8); P = 0.039 collected following administration of furosemide plus acetazolamide and 1.71 L (95% CI: 1.49-1.93 L) following furosemide alone. The incidence of worsening renal function was significantly higher when adding metolazone (39%) to furosemide compared with furosemide alone (16%) and to furosemide plus acetazolamide (2.6%) (P < 0.001). ConclusionsIn ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared with IV furosemide alone or furosemide plus acetazolamide.

Revisiting resistant hypertension in kidney disease.

As compared to controlled or uncontrolled hypertension, resistant hypertension in patients with chronic kidney disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage including cardiovascular disease and CKD progression. Patients with CKD have two to three times higher risk of developing resistant hypertension. True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH); however, it is usually not possible in epidemiological studies. Moreover, impact of contemporary guidelines changes in the target blood pressure (BP) goal to less than 130/80 mmHg remains to be determined. Up to half of patients with CKD meet aTRH criteria using 2017 ACC/AHA target BP less than 130/80 mmHg. Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to the treatment in CKD. Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in these patients. Management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications. Recently, renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD. This review discusses the latest in the pathophysiology, definition, identification and treatment strategies of resistant hypertension in individuals with CKD. Further investigations are required to identify the prevalence, future implication and treatment outcome data for true resistant hypertension associated with CKD.

Alcoholic Extracts of Eleusine indica as Alternative Diuretic Regimens: A Computational Based Investigation

Diuretics are widely used in current clinical practice to increase urine production and excrete electrolytes, particularly sodium and chloride ions, without affecting the absorption of protein, vitamins, carbohydrates, or amino acids. From the time of mercury chloride and organomercurials in ancient times to now (with sulphonamides, thiazides, and furosemide), a lot has changed in the field of diuretics. However, long-term use of such synthetic diuretic agents in clinical practice produces several adverse effects, such as blurred vision, loss of appetite, stomach upset, carcinomas, headaches, phototoxic impact, weakness., etc., as has been observed from recent investigations. Natural regimens can serve as potential alternatives to using nontoxic diuretic agents. Based on long-term ethnomedicinal and biological activity records, we have explored the diuretic effects of the widely known perennial herb in Pacific Islands regions and a weed in agricultural fields, Eleusine indica (L) Gaertn phytoconstituents, on a computation platform. Therefore, we conducted a bio-assay-guided crude extraction using ethanol, followed by further gas chromatography-mass spectrometry (GC-MS) analyses of the extracted crude extracts. Further selected nine constituents (EI_1 to EI_9) carried out the diuretic potency against three putative target enzymes (ACE, KCNJ1, and SLC12A1) along with three standard drugs (VU590, TSM, and FSM) through molecular docking studies using AutoDock 4.2 software. We also predict physicochemical profiles, or Lipinski Rule of Five profiles, toxicity, and pharmacokinetics using various bioinformatics and cheminformatics tools. Based on the overall investigation, it was revealed that EI_6 [Z, Z-6,28-Heptatriacontadien-2-one] was the most potential, nontoxic, and drug-able candidate. In summary, advanced computational tools play a crucial role in selecting potential preclinical candidates within limited resources to accelerate the current drug discovery process.

Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P=0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.

Post-diuretic spot urine sodium assessment in acute heart failure: a retrospective analysis

ABSTRACT Aims To provide real-world data on post-diuretic spot urine sodium concentration (UNa) assessment in acute heart failure (AHF) and its implications for treatment. Methods and Results Automated query of the electronic medical record identified patients admitted to the cardiac intensive care unit of a single tertiary care hospital between November 2018 and December 2021, who received intravenous loop diuretics. Detailed manual chart review confirmed the AHF diagnosis. Stratification was performed based on whether post-diuretic UNa was assessed within 24 h of admission. AHF was confirmed in 340/380 identified patients. Post-diuretic UNa was assessed in 117 (34%), more frequently when ejection fraction was reduced and heart failure more advanced. Patients with versus without post-diuretic UNa assessment received higher doses of intravenous loop diuretics and more frequently acetazolamide and thiazide-like diuretics (p < 0.001 for all), resulting in similar urine output despite more advanced heart failure [2,488 mL (1,740-4,033 mL) vs. 2,400 mL (1,553-3,250 mL), respectively; p = 0.170]. Diuretic therapy remained more intense at discharge in the post-diuretic UNa group, with also a higher prescription rate of angiotensin-neprilysin inhibitors (p = 0.021). Serum creatinine increases/decreases were similarly frequent irrespectively from UNa assessment, with more dynamic changes observed in patients with UNa ≤ 80 mmol/L versus ≥ 81 mmol/L. After adjustments for baseline characteristics, the risk for death or heart failure readmission was similar in patients with versus without UNa assessment [HR (95%CI) = 1.43 (0.88-2.32); p = 0.150]. Conclusion Post-diuretic UNa assessment in AHF was associated with more intense diuretic regimens, preserving urine output despite its use in a sicker population.

Diuretic activity of the hydroalcoholic extracts of rhizomes and leaves of Artemisia abyssinica sch. Bip. Ex A. Rich: In silico and in vivo study

Background/Aim: The majority of communities in developing nations utilise traditional medicine as an alternative or a combination therapy with a clinically approved diuretic regimen. The present study aimed to investigate the in vivo and in silico diuretic properties of the 80 % methanol extracts of the rhizomes and leaves of Artemisia abyssinica, an indigenous traditional diuretic medicinal plant of Ethiopia. Methods: Acute oral toxicity tests of 80 % methanol rhizome and leaf extracts of the plant were conducted in mice. For the diuretic test, six treatment groups were administered 100, 200 and 400 mg/kg doses of rhizome and leaf extracts of the plant. The negative and positive control groups were treated with distilled water (2 mL/100 g) and furosemide (10 mg/kg), respectively. Cumulative urine volume, diuretic action, diuretic activity and saluretic index were then determined. In addition, virtual screening and molecular docking study of the compounds of the genus Artemisia were done. Results: The rhizome and leaf extracts of A abyssinica were found safe at a dose of 2000 mg/kg. Moreover, both extracts showed a significant diuretic action (p &lt; 0.05). However, compared to the standard drug furosemide, the extracts had lower diuretic activity. The rhizome extract in-creased electrolyte excretion at all doses; particularly at the 200 and 400 mg/kg doses, it exhibited a profound natriuretic, chloruretic and kaliuretic effect with the concentration of 109 and 110 mmol/L for Na + , 93 and 106 mmol/L for Cl -and 79 and 86 mmol/L for K + , respectively. These sug-gested inhibition of Na + -K + -2Cl cotransporter as the potential mechanism of action of the extracts. Accordingly, virtual screening and a molecular docking analysis of the compounds of the genus Artemisia revealed that a few of them displayed a strong binding interaction with the cation-chloride cotransporter NKCC1 (PDB: 7S1Y), further indicating the cation-chloride cotransporter as a diuretic target of the constituents of the plant. Conclusion: The current study supports the traditional claim of the plant for diuresis and recommends further isolation of the active constituents.

Diuretic resistance and the role of albumin in congestive heart failure.

Diuresis with loop diuretics is the mainstay treatment for volume optimization in patients with congestive heart failure, in which perfusion and volume expansion play a crucial role. There are robust guidelines with extensive evidence for the management of heart failure; however, clear guidance is needed for patients who do not respond to standard diuretic treatment. Diuretic resistance (DR) can be defined as an insufficient quantity of natriuresis with proper diuretic therapy. A combination of diuretic regimens is used to overcome DR and, more recently, SGLT2 inhibitors have been shown to improve diuresis. Despite DR being relatively common, it is challenging to treat and there remains a notable lack of substantial data guiding its management. Moreover, DR has been linked with poor prognosis. This review aims to expose the multiple approaches for treatment of patients with DR and the importance of intravascular volume expansion in the response to therapy.

Abstract 14044: Association Between Home Diuretic Dose and Optimal Initial Intravenous Diuretic Dosing in Acute Decompensated Heart Failure

Introduction: Nearly half of adults admitted with acute decompensated heart failure (ADHF) are discharged with a patient-reported or objective physical evidence of unrelieved congestion, which increases the re-hospitalization risk. This may be due to suboptimal initial intravenous (IV) loop diuretic dosing upon admission, which is often based on a patient’s home diuretic regimen. Methods: We performed a cross-sectional analysis of adults admitted to a large, quaternary healthcare system for ADHF between Jan. 1, 2014 and Dec. 21, 2021 to determine the association between oral home loop diuretic dose and receiving optimal initial IV dosing, as well as receiving optimal initial IV dosing and hospital length of stay (LOS). Patients were categorized based on home oral loop diuretic dose: low (≤40 mg furosemide equivalents [FEs]) and high (&gt;40 mg FEs). We defined optimal initial IV dosing at least twice the home oral diuretic dose. Multivariable Poisson regression models estimated prevalence ratios (PRs) and confidence intervals (CIs) for the association between home oral diuretic dose and receiving optimal initial IV diuretic dosing. Results: Among 3,269 adults (mean age 63 years, 62% male, 82% non-Hispanic White, 51.7% ejection fraction ≤40%, mean home oral diuretic dose 71.8 mg FEs) admitted for ADHF, optimal initial IV loop diuretic dosing occurred in 2,218 (67.9%) patients. Optimal initial IV diuretic dosing was more likely to occur among patients on a low (95.5%) vs. high home dose (35.9%; PR 0.46; 95% CI 0.42-0.50). Among those who were on low oral home diuretic doses, LOS was decreased in those who received optimal initial IV dosing (estimate 0.84; 95% CI 0.77-0.91; P&lt;0.001). Conclusion: Despite loop diuretics being the primary initial therapy for ADHF, there is significant heterogeneity in practice patterns. Understanding why clinicians use suboptimal doses and patients who are at risk of undertreatment may improve outcomes for patients admitted with ADHF.

A second-generation artificial intelligence-based therapeutic regimen improves diuretic resistance in heart failure: Results of a feasibility open-labeled clinical trial

IntroductionDiuretics are a mainstay therapy for congestive heart failure (CHF); however, over one-third of patients develop diuretic resistance. Second-generation artificial intelligence (AI) systems introduce variability into treatment regimens to overcome the compensatory mechanisms underlying the loss of effectiveness of diuretics. This open-labeled, proof-of-concept clinical trial sought to investigate the ability to improve diuretic resistance by implementing algorithm-controlled therapeutic regimens. MethodsTen CHF patients with diuretic resistance were enrolled in an open-labeled trial where the Altus Care™ app managed diuretics' dosage and administration times. The app provides a personalized therapeutic regimen creating variability in dosages and administration times within pre-defined ranges. Response to therapy was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-minute walk test (SMW), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and renal function. ResultsThe second-generation, AI-based, personalized regimen alleviated diuretic resistance. All evaluable patients demonstrated clinical improvement within ten weeks of intervention. A dose reduction (based on a three-week average before and last three weeks of intervention) was achieved in 7/10 patients (70 %, p = 0.042). The KCCQ score improved in 9/10 (90 %, p = 0.002), the SMW improved in 9/9 (100 %, p = 0.006), NT-proBNP was decreased in 7/10 (70 %, p = 0.02), and serum creatinine was decreased in 6/10 (60 %, p = 0.05). The intervention was associated with reduced number of emergency room visits and the number of CHF-associated hospitalizations. SummaryThe results support that the randomization of diuretic regimens guided by a second-generation personalized AI algorithm improves the response to diuretic therapy. Prospective controlled studies are needed to confirm these findings.

Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial

BackgroundThe decongestion strategy using loop diuretics is essential for improving signs and symptoms of heart failure (HF). However, chronic use of loop diuretics in HF has been linked to worsening renal function and adverse clinical outcomes in a dose-dependent manner. Goreisan, a traditional Japanese herbal medicine, has a long history of use in Japan for regulating body fluid homeostasis and has been recognized as causing less adverse outcomes such as dehydration in contrast to loop diuretics in clinical practice. Therefore, we designed the GOREISAN-HF trial to evaluate the long-term effects of a new decongestion strategy adding Goreisan to usual care in patients with HF and volume overload. MethodsThe GOREISAN-HF trial is an investigator-initiated, multicenter, pragmatic, randomized, comparative effectiveness trial in which we will enroll 2,192 patients hospitalized for HF at 68 hospitals in Japan. All study participants will be randomly assigned to either a decongestion strategy that adds Goreisan at a dose of 7.5 g daily on top of usual care or usual care alone. Investigators have the flexibility to change the existing diuretic regimen in both groups. The primary end point is the improvement rate of cardiac edema at 12-month follow-up, and the co-primary end point is a composite of all-cause death or hospitalization up to the end of the planned follow-up period. Secondary end points include longitudinal changes in patient-reported outcomes, loop diuretics dose, and renal function. ConclusionsThe GOREISAN-HF is the first large-scale randomized pragmatic trial to assess the efficacy and safety of a new congestion control strategy adding Goreisan to usual care in patients with HF and volume overload. Registration Number: NCT04691700

Efficacy of tolvaptan on the short and mid-term prognosis in elderly patients with acute heart failure coexisting with oliguria: A retrospective cohort study.

In patients with acute heart failure (AHF) coexisting with oliguria, high doses of loop diuretics are often ineffective in increasing urine output and may adversely affect the patient's prognosis, especially in elderly patients. We investigated the efficacy of adding tolvaptan (TLV) on improving the prognosis in elderly patients with AHF coexisting with oliguria. All data for this retrospective cohort study were extracted from the electronic medical record system of the Second Medical Center of Chinese PLA General Hospital from January 2018 to December 2020. Patients diagnosed with AHF coexisting with oliguria were enrolled in this study and were divided into TLV and non-TLV groups based on the use of TLV. The primary outcome was all-cause mortality at 7 and 90-day. The secondary outcomes were the remission of AHF within 7 and 30 days or continued progression of AHF, and new-onset chronic kidney disease (CKD) after 90 days. Cox proportional hazards regression was used to assess the relationships between all-cause mortality and diuretic regimens, demographics, laboratory parameters, comorbidities, and medications. A total of 308 patients met the study criteria for the final statistical analysis, and they had a median age of 91 years (88, 95). The results showed that the addition of TLV was associated with a decreased risk of the 7 and 90-day all-cause mortality in patients with AHF with oliguria [adjusted HR, 95% CI: 0.60 (0.37, 0.98), p = 0.042; 0.56 (0.41, 0.75), p < 0.001, respectively]. Adding TLV significantly increased urine output and decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in 7 days, and alleviated the progression of AHF within 30 days. There were no statistically significant differences between the patients with or without TLV in terms of the occurrence of hypernatremia, the development of hepatic impairment within 30 days, and new-onset CKD after 90 days. This study demonstrated that the addition of TLV was clinically effective in increasing urine output, and had favorable effects on alleviating AHF progression and may reduce the risk of all-cause mortality at 7 and 90-day in elderly patients with AHF with oliguria, and TLV had a good safety profile. http://www.chictr.org.cn/showprojen.aspx?proj=148046, identifier: ChiCTR2200055518.