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BACKGROUND: There was no scientific evidence about the initial treatment of hypertonic saline solution (HSS) in acutely decompensated heart failure (ADHF). OBJECTIVES: This study assessed the impact of using HSS along with a loop diuretic (LD) as the first diuretic treatment for ADHF, focusing on renal function, electrolyte levels, and clinical outcomes. METHODS: In this retrospective case-control study, 171 adult patients (93 females/78 males) with ADHF were included between January 1, 2022, and December 31, 2022. Patients were allocated into two groups: upfront combo HSS+LD and standardized LD. The primary endpoint was worsening renal function (WRF). Hospitalization for HF and all-cause mortality were evaluated during 6 months of follow-up. The significance level adopted in the statistical analysis was 5%. RESULTS: The groups exhibited similarities in baseline characteristics.A significantly higher diuresis on the 1st day (3975 [3000-5150] vs. 2583 [2000-3250], p=0.001) and natriuresis on the 2nd hour (116.00 [82.75-126.00] vs. 68.50 [54.00-89.75], p=0.001) in the initial upfront combo HSS+LD were found in comparison with the standardized LD.When compared to the standardized LD, the utilization of HSS led to an increase in serum Na+ (137.00 [131.75-140.00] vs. 140.00 [136.00-142.25], p=0.001 for upfront combo HSS, 139.00 [137.00-141.00] vs. 139.00 [136.00-140.00], p=.0470 for standardized LD), while chloride (99.00 [94.00-103.25] vs. 99.00[96.00-103.00], p=0.295), GFR (48.50 [29.75-72.50 vs. 50.00 [35.50-63.50, p=0.616), and creatinine (1.20 [0.90-1.70] vs. 1.20 [1.00-1.50], p=0.218) remained stable in the upfront combo HSS group when compared to standardized LD group (Cl-: 102.00 [99.00-106.00] vs. 98.00 [95.00-103.00], p=0.001, eGFR: 56.00 [41.00-71.00] vs. 55.00 [35.00-71.00], p=0.050, creatinine:1.10 [0.90-1.40] vs. 1.20 [0.90-1.70], p=0.009). Worsening renal function (16.1% vs 35.5%, p=0.007), and length of stay in the hospital (4 days [3-7] vs. 5 days [4-7], p=0.004) were lower in the upfront combo HSS+LD in comparison with the standardized LD. In-hospital mortality, hospitalization for HF, and all-cause mortality were similar between the two groups. CONCLUSION: HSS as an initial therapy, when combined with LD, may provide a safe and effective diuresis without impairing renal function in ADHF. Therefore, HSS may lead to a shorter length of stay in the hospital for these patients.

FUNDAMENTO: Não houve evidência científica sobre o tratamento inicial com solução salina hipertônica (SSH) na insuficiência cardíaca agudamente descompensada (ICAD). OBJETIVOS: Este estudo avaliou o impacto do uso de SSH junto com um diurético de alça (DA) como o primeiro tratamento diurético para ICAD, com foco na função renal, níveis de eletrólitos e resultados clínicos. MÉTODOS: Neste estudo retrospectivo de caso-controle, 171 pacientes adultos (93 mulheres/78 homens) com ICAD foram incluídos entre 1º de janeiro de 2022 e 31 de dezembro de 2022. Os pacientes foram alocados em dois grupos: combinação inicial de SSH+DA e DA padronizada. O desfecho primário foi piora da função renal (PFR). A hospitalização por IC e a mortalidade por todas as causas foram avaliadas durante 6 meses de acompanhamento. O nível de significância adotado na análise estatística foi de 5%. RESULTADOS: Os grupos exibiram semelhanças nas características basais. Diurese significativamente maior no 1º dia (3975 [3000-5150] vs. 2583 [2000-3250], p=0,001) e natriurese na 2ª hora (116,00 [82,75-126,00] vs. 131,75-140,00] vs. 94,00-103,25] vs. 99,00 [96,00-103,00], p=0,295), TFG (48,50 [29,75-72,50 vs. 50,00[35,50-63,50, p=0,616) e creatinina (1,20 [0,90-1,70] vs. 1,20 [1,00-1,50], p=0,218) permaneceu estável no grupo SSH combinado inicial quando comparado ao grupo DA padronizado (Cl-: 102,00[99,00-106,00] vs. 98,00[95,00-103,00], p=0,001, TFGe: 56,00 [41,00-71,00] vs. 55,00[35,00-71,00], p=0,050, creatinina: 1,10[0,90-1,40] vs. 1,20 [0,90-1,70], p=0,009). A piora da função renal (16,1% vs. 35,5%, p = 0,007) e o tempo de internação hospitalar (4 dias [3-7] vs. 5 dias [4-7], p = 0,004) foram menores na combinação inicial SSH+DA em comparação com o DA padronizado. A mortalidade hospitalar, a hospitalização por IC e a mortalidade por todas as causas foram semelhantes entre os dois grupos. CONCLUSÃO: SSH como terapia inicial, quando combinada com DA, pode proporcionar uma diurese segura e eficaz sem prejudicar a função renal na ICAD. Portanto, a SSH pode levar a um menor tempo de internação hospitalar para esses pacientes.

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Consider IV Acetazolamide in addition to standard IV loop diuretic therapy in patients hospitalized for acute decompensated heart failure.1.

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INTRODUÇÃO: Amiloidose é uma doença de deposição multissistêmica de proteínas como a transtirretina (TTR), tendo o coração como um dos órgãos mais afetados. Em 2018, foi publicado o estudo ATTR-ACT que evidenciou que o tafamidis muda a história natural da amiloidose cardíaca, reduzindo a mortalidade e necessidade de internação hospitalar, tanto na dose de 20 mg e 80 mg, porém, esta última esteve associada a melhores desfechos. MÉTODOS: Estudo observacional retrospectivo de coorte de pacientes (p) portadores de amiloidose com fenótipo misto, cardiomiopatia e polineuropatia, que fizeram uso por período mínimo de 16 meses de tafamidis na dose de 20mg/dia. RESULTADOS: Da amostra total de 12 p, 9 utilizaram o tafamidis ininterruptamente, sendo que 4 foram a óbito, destes, apenas 1 utilizou tafamidis por 16 meses. A amostra foi composta por 75% masculino e 25% feminino, com média de 71 anos. A variante patogênica no gene da TTR mais prevalente da amostra foi a Val142Ile (58,3%), sendo os p que foram a óbito, portadores dessa mesma mutação. Em relação à classe funcional (CF), 9 p estavam em CF I/II e 3 p em CF III. 50% dos p estavam em uso de furosemida oral na avaliação inicial. A fração de ejeção (FE) dos 9 p vivos variou de 27% a 73% com média de 54,33% e o NT pro BNP variou de 7 a 7000 pg/ml. Após o uso do tafamidis, os p que se encontravam em CF I/II permaneceram estáveis, exceto 1 que evoluiu para CF IV, enquanto os que iniciaram em CF III foram a óbito. Em relação ao uso do diurético de alça, 4 p utilizaram até óbito, 2 permaneceram e outros 2 que não usavam inicialmente passaram a usar na evolução final, ou seja, apesar da CF ter se mantido a mesma ao longo da evolução, observamos que houve necessidade de uso de diurético em maior número de p. Os níveis iniciais de NT pro BNP estavam elevados em 7 p, apenas em 1 p houve diminuição em 67% e os p que tinham valores dentro da normalidade mantiveram níveis baixos ao longo da evolução. Não houve diferença da FE entre a média inicial e final da evolução de 53,84%. CONCLUSÃO: O uso da dose de tafamidis 20mg/dia em pacientes com a forma mista de amiloidose pelo período mínimo de 16 meses foi associado a estabilização do quadro clínico, da FE nos p que se encontravam em CF baixa. Em contrapartida, p com CF alta não foi associado a melhores desfechos.

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BACKGROUND: We sought to compare cardiovascular outcomes, renal function, and diuresis in patients receiving standard diuretic therapy for acute heart failure (AHF) with or without the addition of SGLT2i. METHODS AND RESULTS: Systematic search of three electronic databases identified nine eligible randomized controlled trials involving 2,824 patients. The addition of SGLT2i to conventional therapy for AHF reduced all-cause death (odds ratio [OR] 0.75; 95% CI 0.56-0.99; p = 0.049), readmissions for heart failure (HF) (OR 0.54; 95% CI 0.44-0.66; p < 0.001), and the composite of cardiovascular death and readmissions for HF (hazard ratio 0.71; 95% CI 0.60-0.84; p < 0.001). Furthermore, SGLT2i increased mean daily urinary output in liters (mean difference [MD] 0.45; 95% CI 0.03-0.87; p = 0.035) and decreased mean daily doses of loop diuretics in mg of furosemide equivalent (MD -34.90; 95% CI [- 52.58, - 17.21]; p < 0.001) without increasing the incidence worsening renal function (OR 0.75; 95% CI 0.43-1.29; p = 0.290). CONCLUSION: SGLT2i addition to conventional diuretic therapy reduced all-cause death, readmissions for HF, and the composite of cardiovascular death or readmissions for HF. Moreover, SGLT2i was associated with a higher volume of diuresis with a lower dose of loop diuretics.

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BACKGROUND: The co-administration of loop diuretics with thiazide diuretics is a therapeutic strategy in patients with hypertension and volume overload. The aim of this study was to assess the efficacy and safety of treatment with bumetanide plus chlorthalidone in patients with chronic kidney disease (CKD) stage 4-5 KDIGO. METHODS: A double-blind randomized study was conducted. Patients were randomized into two groups: bumetanide plus chlorthalidone group (intervention) and the bumetanide plus placebo group (control) to evaluate differences in TBW, ECW and ECW/TBW between baseline and 30 Days of follow-up. Volume overload was defined as 'bioelectrical impedance analysis as fluid volume above the 90th percentile of a presumed healthy reference population. The study's registration number was NCT03923933. RESULTS: Thirty-two patients with a mean age of 57.2 ± 9.34 years and a median estimated glomerular filtration rate (eGFR) of 16.7 ml/min/1.73 m2 (2.2-29) were included. There was decreased volume overload in the liters of total body water (TBW) on Day 7 (intervention: -2.5 vs. control: -0.59, p = 0.003) and Day 30 (intervention: -5.3 vs. control: -0.07, p = 0.016); and in liters of extracellular water (ECW) on Day 7 (intervention: -1.58 vs. control: -0.43, p < 0.001) and Day 30 (intervention: -3.05 vs. control: -0.15, p < 0.000). There was also a decrease in systolic blood pressure on Day 7 (intervention: -18 vs. control: -7.5, p = 0.073) and Day 30 (intervention: -26.1 vs. control: -10, p = 0.028) and in diastolic blood pressure on Day 7 (intervention: -8.5 vs. control: -2.25, p = 0.059) and Day 30 (intervention: -13.5 vs. control: -3.4, p = 0.018). CONCLUSION: In CKD stage 4-5 KDIGO without renal replacement therapy, bumetanide in combination with chlorthalidone is more effective in treating volume overload and hypertension than bumetanide with placebo.

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OBJECTIVES: To measure between-center variation in loop diuretic use in infants developing severe bronchopulmonary dysplasia (BPD) in US children's hospitals, and to compare mortality and age at discharge between infants from low-use centers and infants from high-use centers. STUDY DESIGN: We performed a retrospective cohort study of preterm infants at <32 weeks of gestational age with severe BPD. The primary outcome was cumulative loop diuretic use, defined as the proportion of days with exposure between admission and discharge. Infant characteristics associated with loop diuretic use at P < .10 were included in multivariable models to adjust for center differences in case mix. Hospitals were ranked from lowest to highest in adjusted use and dichotomized into low-use centers and high-use centers. We then compared mortality and postmenstrual age at discharge between the groups through multivariable analyses. RESULTS: We identified 3252 subjects from 43 centers. Significant variation between centers remained despite adjustment for infant characteristics, with use present in an adjusted mean range of 7.3% to 49.4% of days (P < .0001). Mortality did not differ significantly between the 2 groups (aOR, 0.98; 95% CI, 0.62-1.53; P = .92), nor did postmenstrual age at discharge (marginal mean, 47.3 weeks [95% CI, 46.8-47.9 weeks] in the low-use group vs 47.4 weeks [95% CI, 46.9-47.9 weeks] in the high-use group; P = .96). CONCLUSIONS: A marked variation in loop diuretic use for infants developing severe BPD exists among US children's hospitals, without an observed difference in mortality or age at discharge. More research is needed to provide evidence-based guidance for this common exposure.

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BACKGROUND: Interstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2 h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST. METHODS: This study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6 h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation. RESULTS: The mean age of the participants was 38 years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p = 0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r = - 0.245, p = 0.02) was observed. CONCLUSIONS: Our findings indicate that interstitial fibrosis correlates with total urine output and FEM. Further studies are needed to determine if UO and FST could be a non-invasive tool to evaluate interstitial fibrosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02417883.

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