Efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure: a meta-analysis

Objective The objective of this study is to investigate the efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure. Methods A systematic search was conducted on PubMed, Cochrane Library, and EMbase databases from inception to April 2023 to identify randomized controlled trials that compared the efficacy and safety of early ultrafiltration and conventional diuretics in patients with acute decompensated heart failure. Two investigators independently screened all eligible studies and extracted relevant data. The primary outcomes of interest were changes in body weight and creatinine levels, as well as the rate of readmission and mortality within 30 days. Meta-analysis was conducted using RevMan 5.4 software. Results This meta-analysis included eight studies and found that early ultrafiltration was effective in reducing body weight in patients with acute decompensated heart failure (RR = 1.45, 95% CI: 0.54–2.35, P = 0.002), but it also increased serum creatinine (RR = 0.1, 95% CI: 0.03–0.17, P = 0.003). However, it did not reduce the 30-day rehospitalization rate or mortality rate (30-day rehospitalization rate: RR = 0.84, 95% CI: 0.62–1.14, P = 0.28; Mortality: RR = 0.90, 95% CI: 0.57–1.44, P = 0.67). Conclusion Although early ultrafiltration is more effective in reducing body weight in patients with acute decompensated heart failure, it is associated with an increase in serum creatinine levels and does not reduce the rate of readmission or mortality within 30 days. Systematic Review Registration identifier: CRD42023416152.


Introduction
Heart failure (HF) is a critical aspect of cardiovascular disease, with device therapy, including ultrafiltration therapy, emerging as a viable option in recent years.Ultrafiltration is a treatment method that involves the passage of water and small to medium weight solutes through a semi-permeable membrane, thereby reducing the volume load (1).Both Chinese and European guidelines recommend ultrafiltration for heart failure patients with significant volume overload and poor response to conventional diuretics to quickly relieve symptoms of heart failure and fluid retention (2).The ACC/AHA guidelines are more active in recommending ultrafiltration therapy and do not emphasize diuretic resistance (3).They also consider significant fluid retention as an indication of ultrafiltration.The selection of the effect index for measurement data.The point estimate and 95% CI were reported for each effect size.Heterogeneity among the included studies was assessed using a χ 2 test (test level α = 0.1) and quantitatively determined by combining with I 2 .After excluding the influence of obvious clinical heterogeneity, a random-effects model was used for the meta-analysis.

Literature screening process and results
A total of 894 relevant literatures were retrieved and underwent a layer-by-layer screening process.Ultimately, 8 studies (4-11) were included.The literature screening process and results are illustrated in Figure 1.

Basic characteristics of included studies and results of bias risk assessment
The basic characteristics of the included studies are shown in Table 1, and the risk of bias assessment results of the included studies are shown in Figure 2.

Discussion
The study revealed that early ultrafiltration was more effective in reducing body weight in patients with acute decompensated heart failure.However, it caused an increase in creatinine and did not reduce the rate of readmission or mortality within 30 days.
It should be noted that, diuretics have a poor dose-effect relationship and cannot accurately predict urine volume.Many clinical trials have shown that ultrafiltration therapy is safe and effective (12).Ultrafiltration therapy has distinct advantages in managing fluid overload.It facilitates the  removal of body fluids, excretes a higher amount of total sodium, and has favorable hemodynamic effects.Additionally, this therapy does not cause electrolyte disturbances or activate the neuroendocrine system.Moreover, it can restore the diuretic effect in some patients who have not responded to other diuretic treatments (13).Extracorporeal ultrafiltration can be utilized for mechanical dehydration, with the amount and speed of dehydration being determined based on the patient's fluid load.Typically, the initial blood pump flow during treatment is set between 20 and 30 ml/min.It is important to note that a higher flow rate can increase the cardiac load and should not exceed 50 ml/min.The ultrafiltration speed is usually set at 200 to 300 ml/h, with a maximum limit of 500 ml/h.This speed can be adjusted according to the patient's treatment response and vital signs.It is generally recommended that the total amount of ultrafiltration should not exceed 5,000 ml within a 24-h period.However, if the patient's blood excitation dynamics are stable, the amount of ultrafiltration fluid can be increased based on the patient's actual condition.However, ultrafiltration may lead to renal hypoperfusion, which can negatively impact renal function.Patarroyo et al. ( 14) demonstrated that while early ultrafiltration improved hemodynamics, it was linked to an increased risk of subsequent CRRT and higher in-hospital mortality rates.Other studies (15)(16)(17) have also indicated that worsening renal function in heart failure patients is associated with a poor prognosis.
According to the Heart Failure Registry study, it was found that out of 2,067 patients with heart failure, 21% of them developed diuretic resistance while undergoing treatment (18).Recent studies (19,20) suggest starting ultrafiltration therapy early in patients with CHF, even before diuretic therapy becomes ineffective.This is particularly beneficial for patients with severe dyspnea symptoms of left heart failure, as ultrafiltration can effectively and regularly remove excess body fluid and improve symptoms rapidly (21), providing more reliable results than diuretics.Additionally, early use of ultrafiltration can buy time for further treatment.However, in cases of refractory heart failure or severe cardiorenal syndrome, ultrafiltration may not be effective as a "rescue" treatment.The RAPID-CHF test initiated ultrafiltration treatment within 24 h of admission for patients with acute decompensated heart failure (ADHF).The average volume of fluid removed through ultrafiltration in a 24-h period was 4,650 ml, compared to 2,838 ml in the diuretic group.This indicates that ultrafiltration was more effective than diuretic treatment in terms of fluid clearance (19).The UNLOAD study, which is the largest randomized controlled trial on ultrafiltration therapy for ADHF, divided 200 patients into an early ultrafiltration group and a routine diuresis group.The results showed that patients in the early ultrafiltration group experienced greater weight reduction, a lower rate of re-hospitalization within 90 days, similar relief of dyspnea compared to the routine diuresis group, and a lower incidence of hypokalemia (11).Previous meta-analyses ( 22) have compared ultrafiltration with diuresis in patients with heart failure and have shown that ultrafiltration is more effective in reducing volume load and   Rehospitalization rate within 30 days.rehospitalization rate, but it does not reduce the incidence of adverse events and mortality.This study's innovation lies in the timing of early ultrafiltration, which aims to determine the efficacy and safety of this approach in patients with acute decompensated heart failure.This study has some limitations that should be considered.Firstly, the sample size of 8 studies included in this research was relatively small, which may have limited the power of the evidence provided.Secondly, there was heterogeneity among the results of the different studies included, which could be due to various confounding factors, such as differences in sample sizes.
Based on current evidence, early ultrafiltration appears to be more effective in reducing body weight in patients with acute decompensated heart failure.However, it is important to note that this treatment may increase serum creatinine levels and does not necessarily reduce the rate of readmission or mortality within 30 days.It is important to acknowledge that the conclusions drawn from the available studies are limited by both the quantity and quality of the research.As such, further high-quality studies are needed to verify these findings.

TABLE 1
Basic characteristics of the included studies.
FIGURE 2Results of bias risk assessment of the included studies.Chen et al. 10.3389/fcvm.2023.1234092Frontiers in Cardiovascular Medicine 03 frontiersin.orgTABLE 2 Changes in body weight, changes in creatinine, readmission rates within 30 days and mortality.