Ultrafiltration for acute decompensated heart failure: A systematic review and meta-analysis of randomized controlled trials

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Abstract

Background

Current clinical guidelines recommend ultrafiltration (UF) for patients with acute decompensated heart failure (ADHF) who are unresponsive or resistant to diuretics. We systematically reviewed the latest randomized evidence on the efficacy and safety of UF in ADHF.

Methods

MEDLINE, EMBASE and the Cochrane database were searched in January 2013 for eligible randomized controlled trials (RCTs) evaluating UF in patients with ADHF. A Mantel–Haenszel random-effects model was used to calculate mean differences (MDs) and odds ratios (ORs) for continuous and dichotomous data, respectively, with 95% confidence intervals (CIs).

Results

Data of 12 studies (n = 659) were meta-analyzed; follow-up duration ranged from 36 h to 12 months. Compared to control, treatment of UF was associated with significant fluid removal (MD 1.28, 95% CI 0.43 to 2.12, P = 0.003) and weight loss (MD 1.23, 95% CI 0.03 to 2.44, P = 0.04), with no significant effects on all-cause mortality (OR 1.08, 95% CI 0.63 to 1.86, P = 0.77) or all-cause rehospitalization (OR 0.89, 95% CI 0.39 to 2.00, P = 0.77). No significant differences were observed in the analyses of change in serum creatinine or unscheduled medical care; analysis of adverse effects was inconclusive since only one study provided usable data.

Conclusions

For patients with ADHF, UF is effective in reducing fluid retention and body weight, with no significant benefits in mortality or rehospitalization. The current limited randomized evidence highlights the need for further well-conducted randomized studies of adequate power to establish the role of UF in ADHF patients for whom conventional HF treatment is unsuccessful or contraindicated.

Introduction

An estimated 5.1 million Americans over the age of 20 years have heart failure (HF) [1]. By 2030, the prevalence of HF will increase by 25% and the consequent total cost of HF will increase almost 120% to $70 billion [1]. Acute decompensated heart failure (ADHF) is a sudden deterioration of chronic stable HF characterized by sodium retention leading to volume overload, and congestive symptoms such as edema and dyspnea occur [2], [3]. ADHF is an emerging public health problem with high hospitalization rate and poor prognosis [4]. In the EuroHeart Failure Survey II (EHFS II; n = 3580), ADHF was found to be the predominant classification (62.9%) of all hospitalized acute HF cases with an inhospital mortality rate of 5.8% [5]. The large, multicenter Acute Decompensated Heart Failure National Registry (ADHERE; n = 105,388) also indicated that ADHF-related hospital admissions were associated with high inhospital mortality rate (4%), with a higher rate observed among patients admitted to intensive care settings (11%) [6]. Intravenous (IV) loop diuretics are recommended first-line treatment for significant pulmonary congestion and fluid retention in the latest clinical guidelines [7], [8]. However, the effectiveness of diuretics in ADHF is hindered by several factors such as the elimination of hypotonic urine, diuretic resistance, electrolyte disturbances and impaired glomerular filtration rate [9], [10], [11]. Extracorporeal ultrafiltration (UF) is proposed as an alternative treatment strategy for patients with ADHF who are unresponsive or resistant to loop diuretics and remain in pulmonary edema (urine output < 20 mL/h) [7]. During UF, a hydrostatic pressure gradient triggers the mechanical removal of fluid across a filter membrane and isotonic plasma water is separated from blood without affecting serum electrolytes and other solutes [9], [10], [11]. A systematic review in 2011 revealed that initial evidence on the clinical effectiveness of UF was mostly derived from small, non-randomized case series [12]. However, a number of randomized controlled trials (RCTs) have since become available and we consequently conducted a systematic review and meta-analysis of randomized studies exploring the efficacy and safety of UF in patients with ADHF.

Section snippets

Study selection

We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) in January 2013 to identify eligible randomized controlled trials (RCTs) evaluating the use of UF in patients with ADHF, using the search terms: “ultrafiltration AND heart failure”. No language restrictions were applied. Reference lists of retrieved records and relevant reviews, editorials and letters were also screened. Ongoing studies were identified in ClinicalTrials.gov (www.Clinicaltrials.gov).

Description of studies

Our study selection process is illustrated in Fig. 1. Of the 989 records identified from literature search, 930 clearly did not meet the inclusion criteria and were thus excluded. Full-texts of the remaining 59 records were retrieved for further evaluation. A total of 13 RCTs were eligible for inclusion in our systematic review; [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33] one study (n = 10), available as a conference abstract,

Discussion

This meta-analysis of 12 studies shows that UF is effective in reducing volume overload and weight loss, with no benefits in all-cause mortality or rehospitalization. The nonsignificant differences in renal function and incidence of unscheduled medical care are inconclusive due to limited trial data. Safety profile of UF remains to be ascertained due to a lack of adverse event data in the included studies. Currently available RCTs exploring the effects of UF in ADHF are of small size and

Conclusions

Currently available knowledge on the efficacy and safety of UF in patients with ADHF is inconclusive, where published studies are of small size and reporting of relevant outcome measures is suboptimal. Well-conducted randomized trials with adequate power and carefully selected endpoints are much warranted to enrich the existing body of evidence on the role of UF in patients with refractory HF and resistance to standard diuretic therapy or in whom such therapy is contraindicated.

Acknowledgment

This study was supported by a research grant from the University Grants Committee of Hong Kong (RGC Collaborative Research Fund 2010/11: CUHK9/CRF/10). We also acknowledge support from the Lui Che Woo Foundation.

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