Medical Policy

This document addresses ultrafiltration, (also referred to as aquapheresis), a treatment for refractory congestive heart failure (CHF, also referred to as heart failure [HF]) that involves the removal of excess fluid. The technique utilizes pressure differentials during treatment with a dialysis machine or similar filtration device. Proponents suggest that this treatment may offer the potential for greater and more expeditious volume and sodium removal compared with conventional therapies for hospitalized individuals. Ultrafiltration is generally used for decompensated HF where fluid overload is unresponsive to conventional medical management with use of diuretics.

Investigational and Not Medically Necessary:

The use of ultrafiltration is considered investigational and not medically necessary for the treatment of heart failure.

Ultrafiltration (UF) differs from dialysis in that it acts via convection rather than diffusion, which lowers the risk for induced metabolic abnormalities. Conventional UF devices required central venous access with a double lumen catheter, monitoring by a dialysis technician, and specialized hospital units. Devices have been developed that allow UF to be carried out via large peripheral venous catheters that potentially allow for continuous UF in ambulatory individuals. UF techniques are performed primarily in hospitalized individuals or in facility-based ambulatory settings, such as specialized dialysis clinics.

Clinical studies of UF techniques on human participants have been limited regarding the impact of this technology on survival, hospitalization, complication rates, and quality of life, compared to conventional treatment options. Studies of UF include underpowered, randomized trials (Bart, 2005; Bart, 2012; Costanzo, 2007; Costanzo, 2016; Rogers, 2008), case series (Costanzo, 2005; Dahle, 2006) and a retrospective case series (Jaski, 2008).

Results of the UNLOAD trial (Ultrafiltration vs. Intravenous Loop Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure) were published in 2007. A total of 200 individuals hospitalized for CHF at 28 sites were randomized to receive either UF or standard care. The primary endpoints included weight loss and dyspnea measured at 48 hours on a 7-point Likert scale. While the UF group reported a 30-40% greater fluid and weight loss, there was no difference in dyspnea between the two groups at 48 hours. Among the secondary outcomes, quality of life and other functional assessments were also similar between the two groups. However, the rehospitalization rates were lower in the UF group (18% vs. 32%). Study design and methodologic concerns have been raised and call into question the validity of the results from the UNLOAD trial. There were discrepancies between the improvement in intermediate outcomes, such as weight loss, and the key reported outcomes, such as dyspnea scores and walking distance, which did not differ between the two groups. The reduction in hospital admissions in the UF group was unexpected and is not explained by the intermediate measures of HF severity. The design of this industry-sponsored trial did not include blinding for participants, investigators, or staff. In addition, there was inadequate reporting of recruitment and follow-up. Only 83 of 100 individuals randomized to the UF group and 84 of 100 individuals randomized to the standard care group were included in measures of the primary outcomes. This high rate of incomplete data at 48 hours after randomization of inpatient cohorts was unexplained. In addition, only 72 of the 100 individuals receiving UF had failed prior diuretic therapies, which is the U.S. Food and Drug Administration (FDA) labeled indication for peripheral UF in CHF (Costanzo, 2007).

Post-hoc analysis of the UNLOAD trial results investigated the primary outcomes of individuals randomized to UF (n=100), which were compared with those treated with continuous (n=32) or bolus (n=68) IV diuretics. In this analysis, the two primary outcome measures (dyspnea scores and weight loss at 48 hours) were compared across the three groups. Dyspnea scores at 48 hours did not differ between the three groups (p=0.608). Pair-wise comparisons showed the weight loss to be similar in the UF and IV continuous diuretic infusion groups (5 ± 3.1 vs. 3.6 ± 3.5 kg; p=0.145) but greater in the UF than in the IV bolus diuretic group (5 ± 3.1 vs. 2.9 ± 3.5 kg; p=0.001), although similar between the continuous IV diuretic infusion and bolus IV diuretic groups (3.6 ± 3.5 kg vs. 2.9 ± 3.5 kg; p=0.358). At 90 days, a secondary outcome measure of “rehospitalization equivalents” (rehospitalization plus unscheduled visits for HF) were fewer in the UF group (0.65 vs. 2.29; p=0.016) than in the continuous diuretic infusion group and the bolus diuretic group (0.65 vs. 1.31; p=0.05) (Costanzo, 2010).

In 2010, an assessment of UF for HF was conducted by the Veterans Health Administration Technology Assessment Program in the United Kingdom (UK), which found no recently published evidence to materially change conclusions from a previous report by the Centre for Evidence-based Purchasing (CEP) of the UK National Health Services, that noted, “CEP finds that ultrafiltration has significant potential to become a routine therapy for excess fluid removal in patients with congestive heart failure. However, further work is needed to establish the patient groups who would benefit most” (Flynn, 2010).

Results of the Effectiveness of Ultrafiltration in Treating People With Acute Decompensated Heart Failure (ADHF) and Cardiorenal Syndrome (CARRESS-HF) trial were published in 2012, which was a large, multicenter study sponsored by the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and Duke University, in collaboration with CHF Solutions^®, Inc (the manufacturer of the UF device evaluated in the study). The primary purpose of this trial was to investigate the safety and effectiveness of UF compared to standard medical drug therapy in improving renal function and relieving fluid buildup in people hospitalized with ADHF and cardiorenal syndrome. Participants with ADHF, worsening renal function, and persistent congestion were randomized to a strategy of stepped pharmacologic therapy (n=94) or UF (n=94). The primary endpoint was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Study participants were followed for 60 days. The results showed that UF was inferior to pharmacologic therapy with respect to the bivariate endpoint of the change in the serum creatinine level and body weight at 96 hours after enrollment (p=0.003), owing primarily to an increase in the creatinine level in the UF group. At 96 hours, the mean change in the creatinine level was -0.04 ± 0.53 mg per deciliter (-3.5 ± 46.9 μmol per liter) in the pharmacologic-therapy group, as compared with +0.23 ± 0.70 mg per deciliter (20.3 ± 61.9 μmol per liter) in the UF group (p=0.003). There was no significant difference in weight loss at 96 hours after enrollment between participants in the pharmacologic-therapy group and those in the UF group (a loss of 5.5 ± 5.1 kg [12.1 ± 11.3 lb] and 5.7 ± 3.9 kg [12.6 ± 8.5 lb], respectively; p=0.58). A higher percentage of participants in the UF group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, p=0.03). The investigators concluded that the use of a stepped pharmacologic-therapy algorithm was superior to UF for the preservation of renal function at 96 hours, with similar amounts of weight loss for both approaches. UF was associated with a higher rate of adverse events (Bart, 2012).

Results of a retrospective, single center review included 63 consecutive adult participants with ADHF who were admitted to the Heart Failure Intensive Care Unit at the Cleveland Clinic from 2004 through 2009 and who required slow continuous ultrafiltration (SCUF) because of congestion that had been refractory to hemodynamically guided intensive medical therapy. The mean creatinine level was 1.9 ± 0.8 mg/dl on admission and 2.2 ± 0.9 mg/dl at SCUF initiation. After 48 hours of SCUF, there were significant improvements in hemodynamic variables (mean pulmonary arterial pressure: 40 ± 12 mm Hg vs. 33 ± 8 mm Hg, p=0.002; central venous pressure: 20 ± 6 mm Hg vs. 16 ± 8 mm Hg, p=0.007; mean pulmonary wedge pressure: 27 ± 8 mm Hg vs. 20 ± 7 mm Hg, p=0.02; Fick cardiac index: 2.2 l/min/m² [interquartile range: 1.87 to 2.77 l/min/m²] vs. 2.6 l/min/m² [interquartile range: 2.2 to 2.9 l/min/m²], p=0.0008); and weight loss (102 ± 25 kg vs. 99 ± 23 kg, p=0.0001). However, there were no significant improvements in serum creatinine levels (2.2 ± 0.9 mg/dl vs. 2.4 ± 1 mg/dl, p=0.12) or blood urea nitrogen (60 ± 30 mg/dl vs. 60 ± 28 mg/dl, p=0.97). Fifty-nine percent of study participants receiving SCUF required conversion to continuous hemodialysis during their hospital course and 14% were dependent on dialysis at hospital discharge. Thirty percent died during hospitalization, and 6 individuals were discharged to hospice care. The authors concluded that SCUF after admission for ADHF refractory to standard medical therapy was associated with high incidence of subsequent transition to renal replacement therapy and high in-hospital mortality, despite significant improvement in hemodynamics (Patarroyo, 2012).

Cheng and colleagues (2015) published a systematic review and meta-analysis of seven randomized controlled trials (RCTs) (total n=569 participants) that evaluated UF in decompensated HF with renal insufficiency. A pooled analysis of five of these trials did not find a significant difference between groups in all-cause mortality (odds ratio [OR] 0.95; 95% confidence interval [CI], 0.58 to 1.55; p=0.83). There was significantly more 48-hour weight loss (WMD 1.59; 95% CI, 0.32 to 2.86; p=0.01; I2=68%) and 48-hour fluid removal (WMD 1.23; 95% CI, 0.63 to 1.82; p<0.0001; I2=43%) in the UF group. Serum creatinine and serum creatinine changes were similar between the UF and control groups. All-cause mortality (OR 0.95; 95% CI, 0.58 to 1.55; p=0.83; I2=0.0%) and all-cause rehospitalization (OR 0.97; 95% CI, 0.49 to 1.92; p=0.94; I2=52%) were also similar between the UF and control groups. Adverse events, such as anemia, infection, hemorrhage, worsening HF, and other cardiac disorders did not differ significantly between the UF and control groups.

Siddiqui and colleagues (2017) performed a systematic review and meta-analysis to determine the role of ultrafiltration for individuals with ADHF. The authors analyzed nine RCTs (n=820) that compared UF (n=403) to conventional diuretics (n=417). The primary endpoints were cumulative heart failure readmissions, cumulative heart failure readmissions at 90 days, and cumulative all-cause admissions. Cumulative hospital readmissions secondary to heart failure were less in the UF group than the diuretic group (77 vs.111, risk ratio [RR] 0.71; 95% CI, 0.49 to 1.02; p=0.07). Likewise, at 90 days there were less readmissions in the UF group than the diuretic group (43 vs. 67, RR 0.65; 95% CI, 0.47 to 0.90; p=0.01). However, there were no differences between the UF group and the diuretic group for all-cause readmissions (56 vs. 58, RR 0.65; 95% CI, 0.18 to 2.38; p=0.52). Hypotension was more common in the UF group than the diuretic group (24 vs. 13, OR 2.06; 95% CI, 0.98 to 4.32; p=0.06). The cumulative mortality, length of hospital stays, and renal function between the two groups was similar. The study was limited by the heterogeneity of the RCTs. The authors concluded that ultrafiltration “remains a plausible treatment option” for ADHF and larger RCTs with extended follow-up are needed.

Kabach and colleagues (2017) performed a meta-analysis to compare UF to conventional diuretic therapy for ADHF. They used pooled data from nine RCTs (n=605) and compared UF to diuretics in a 1:1 ratio. They found that UF was associated with a reduced risk of clinical worsening (OR 0.57; 95% CI, 0.38 to 0.86; p=0.007) and better clinical decongestion (OR 2.32; 95% CI, 1.09 to 4.91; p=0.03). However, they did not find that UF improved the risk of re-hospitalization (OR 0.92; 95% CI, 0.62 to 1.38; p=0.70) or mortality (OR 0.99; 95% CI, 0.60 to 1.62; p=0.97). The authors noted that the study was limited by the heterogeneity of the RCTs. They concluded that although UF improves symptoms, “many questions concerning the indications of UF, as a unique decision-making tool in ADHF are still unanswered.”

Grodin and colleagues (2018) performed a per-protocol analysis on the CARESS-HF study (Bart, 2012) to better understand the effect of UF on clinical biomarkers and neurohormonal activation. They included participants who were randomized to the UF group and had UF output collected or were randomized to the pharmacological group and had urine but not UF collected. A total of 106 participants were included at 96 hours. The researchers found that UF was associated with higher cumulative fluid loss, net fluid loss, and relative reduction in weight. Additionally, UF was associated with higher serum creatinine and blood urea nitrogen by 72 hours, lower serum sodium by 48 hours, and increased plasma renin activity by 96 hours. The pharmacological group was associated with higher serum bicarbonate after 24 hours. The two 60-day composite endpoints ([i] death, heart failure hospitalization, or unscheduled emergency department or clinic visit; and [ii] death, any hospitalization, or unscheduled emergency department or clinic visit) were not significantly different between the UF and pharmacological groups. The researchers concluded that UF was associated with more efficient decongestion compared to the pharmacological group, but the UF group had a rise in serum creatinine and neurohormonal activation. The study was limited by the per-protocol design.

Rao and colleagues (2019) performed an analysis of the CARRESS-HF trial. This trial randomized individuals with acute decompensated heart failure and preexisting worsening renal function (WRF) to intensive volume removal with stepped pharmacological therapy (SPT) or fixed rate ultrafiltration. The trial included 188 participants who were hospitalized for ADHF and had pre-enrollment WRF (defined as an increase in creatinine concentration of ≥ 0.3 mg/dL) in addition to persistent congestion. Of the 188 participants enrolled in the CARRESS-HF trial, 105 participated in the urinary renal tubular injury biomarker sub study N-acetyl- b-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). The baseline characteristics of those participants were similar to those of the overall trial population and the severity of prerandomization WRF was unrelated to baseline renal tubular injury biomarkers (r=0.14; P=0.17). During randomized intensive volume removal, creatinine further worsened in 53% of individuals. Researchers concluded that intensive volume removal resulted in additional worsening of creatinine approximately half of the time, a finding associated with a rise in tubular injury biomarkers. Decongestion and renal function recovery at 60 days were superior in participants with increased tubular injury markers. Neither WRF nor worsening renal tubular injury biomarkers was associated with an increased risk of post-discharge death or rehospitalization. However, several limitations of the study were identified. CARRESS-HF was not specifically designed to determine if escalation of decongestion is safe in individuals with WRF as there was no control group receiving standard care. Researchers were unable to know if renal outcomes would have been inferior or superior had further aggressive decongestion not been attempted. Due to the small study population, researchers were unable to definitely examine the impact of ultrafiltration versus SPT on cardiorenal parameters. Researchers had no data on renal function beyond 60 days and were unable to discern whether renal injury may have set up adverse or potentially self-perpetuating renal pathophysiology.

Hu and colleagues (2020) published a study investigating the efficacy and safety of early UF in ADHF. The study included 100 individuals who were randomly assigned within 24 hours of admission into early UF (n=40) or torasemide plus tolvaptan (n=60) groups. The primary outcomes were weight loss and an increase in urine output on days 4 and 8 of treatment. The results showed that participants who received UF for 3 days achieved a greater weight loss (kg) (- 2.94 ± 3.76 vs - 0.64 ± 0.91, P<0.001) and urine increase (mL) (198.00 ± 170.70 vs 61.77 ± 4.67, P<0.001) than the torasemide plus tolvaptan group on day 4. From days 4 to 7, participants in the early UF group received sequential therapy of torasemide and tolvaptan. Better control of volume was reflected in a greater weight loss (−3.72 ± 3.81 vs −1.34 ± 1.32, P<0.001) and urine increase (373.80 ± 120.90 vs 79.5 ± 52.35, P<0.001), greater reduction of B-type natriuretic peptide (BNP) (pg/mL) (−1144 ± 1435 vs −654.02 ± 889.65, P=0.037), NYHA (New York Heart Association) functional class (−1.45 ± 0.50 vs −1.17 ± 0.62, P=0.018), jugular venous pulse (JVP) score (points) (−1.9 ± 1.13 vs −0.78 ± 0.69, P<0.001), inferior vena cava (IVC) diameter (mm) (−15.35 ± 11.03 vs −4.98 ± 6.00, P<0.001) and an increase in the dyspnea score (points) (4.08 ± 3.44 vs 2.77 ± 2.03, P=0.035) in the early UF group on day 8. The researchers concluded that early UF effectively and safely reduces volume overload in individuals with ADHF. It was noted that future studies should focus on understanding the effect of UF on the progress of HF, identification of population most likely to benefit and select the best indication and best timing of UF.

Wang and colleagues (2021) performed a systematic review and meta-analysis on a total of 12 studies with 1197 participants. Individuals were required to be ≥ 18 years old and meet the criteria of diagnosis for heart failure; the intervention group was UF and the comparison group was diuretics. The results showed a reduction in heart failure rehospitalization (risk ratio [RR] 0.67; 95% CI: 0.52–0.87; p=0.003) and all-cause rehospitalization (RR 0.62; 95% CI: 0.42–0.92; p=0.02), an increase in fluid loss (1.47 L, 95% CI: 0.95–1.99 L; p<0.001) and weight loss (1.65 kg, 95% CI: 0.90–2.41 kg; p<0.001). There was no difference in mortality (RR 1.09; 95% CI: 0.78–1.51; p=0.62). There were inconsistent agreements about which group had more total adverse events. Subgroup analysis showed that UF with larger mean fluid-remove rate (≥ 200 mL/h) could significantly remove more fluid, lose more weight, and decrease heart failure rehospitalization. A limitation of the study was the high heterogeneity in the amount of weight loss. Additionally, most RCTs did not provide enough information to assess for bias. Because of the heterogeneity of the kinds of adverse events in all studies, the researchers were unable to make a consistent conclusion about the safety of UF. In addition, researchers noted that although UF is more effective in removing fluid than diuretics and decreases rehospitalization for heart failure and all causes, there was not enough evidence to compare rates of adverse events and mortality between UF and diuretic treatment.

Wobbe and colleagues (2021) performed a meta-analysis to assess the impact of UF therapy in individuals with ADHF. The meta-analysis included eight randomized controlled trials and involved 801 participants comparing UF with standard diuretic therapy. Data provided by four of the studies addressed individuals suffering from worsened HF during follow-up. Heart failure worsening occurred in 76 individuals (34.2%) in the UF group and in 101 (45.7%) individuals treated with diuretics. The researchers indicated that ultrafiltration was associated with a significantly decreased risk of worsening HF (OR 0.632; 95% CI, 0.426 to 0.936; p=0.022, I²=67.4%). It was also noted that treatment with UF led to a significantly larger net volume of fluid removal compared to usual care (difference in means: 1372.5 mL; 95% CI, 849.6 to 1895.4 mL; p<0.001, I²=48.41%). Heart failure rehospitalization was reported in four studies and was noted for 50 out of 316 individuals in the UF group and for 88 out of 320 individuals randomized to the usual care group, a significant reduction (p=0.003). The hospital follow-up duration for evaluation of hospital readmission ranged from 30 days, 60 days, 90 days, and to 1 year. Weight loss in the UF group was significantly greater than weight loss in individuals treated with usual care (difference in means 1.592 kg; 95% CI, 1.039 to 2.144 kg; p<0.001, I²=65.88%). Renal impairment incidence and all-cause mortality rates were found to be similar between the 2 groups. The researchers’ findings indicated UF treatment effectively removed larger volumes of fluid without significant changes in serum creatinine levels. The authors concluded that UF is a safe and effective treatment alternative to diuretics in ADHF individuals. However, the authors of the meta-analysis identified four limitations of the analysis. There were differences in the intervention protocols and time of measurement across the included studies. Second, the researchers found possible risks of bias within studies. Third, the analysis found evidence of heterogeneity for certain outcomes which might be explained by the small number of studies. Fourth, different search terms were used to identify suitable studies during the selection process and were individually adapted to the databases to obtain a higher number of results.

A 2009 focused update from the American College of Cardiology Foundation (ACCF), American Heart Association (AHA) Task Force on Practice Guidelines has been incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults (Hunt, 2005). Within this focused update, the following recommendation was given a Class IIa, Level of Evidence: B – “Ultrafiltration is reasonable for patients with refractory congestion not responding to medical therapy” (Jessup, 2009). This recommendation was repeated in another 2009 update to the ACC/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults (Hunt, 2009). Additional excerpted comments from these documents are as follows:

If all diuretic strategies are unsuccessful, ultrafiltration or another renal replacement strategy may be reasonable. Ultrafiltration moves water and small- to medium-weight solutes across a semipermeable membrane to reduce volume overload. Because the electrolyte concentration is similar to plasma, relatively more sodium can be removed than by diuretics…Consultation with a kidney specialist may be appropriate before opting for any mechanical strategy to affect diuresis. (Hunt, 2009; Jessup, 2009).

An updated 2013 ACCF/AHA Guideline for the Management of Heart Failure downgraded its recommendations to Class IIb for UF as renal replacement therapy in hospitalized individuals based on the limited evidence demonstrating safety/efficacy as follows:

Ultrafiltration may be considered for patients with obvious volume overload to alleviate congestive symptoms and fluid weight.(Level of Evidence: B);

Ultrafiltration may be considered for patients with refractory congestion not responding to medical therapy (Level of Evidence: C) (Yancy, 2013).

The 2022 updated AHA/ACC/HFSA “Guideline for the Management of Heart Failure” replaced the 2013 Guideline and the 2017 “Focused Update of the 2013 ACCF/AHA Guidelines for the Management of Heart Failure.” Regarding UF as renal replacement therapy in hospitalized individuals it states:

Bedside ultrafiltration initiated early after admission increased fluid loss, which decreased rehospitalizations in some studies when compared with use of diuretics without systematic escalation and was also associated with adverse events related to the intravenous catheters required. Many aspects of ultrafiltration including patient selection, fluid removal rates, venous access, prevention of therapy-related complications, and cost require further investigation. (Heidenreich, 2022).

The European Society of Cardiology (ESC) Task Force guidelines developed with contribution from the Heart Failure Association (HFA) (McDonagh, 2021) on the diagnosis and treatment of acute and chronic heart failure state the following:

In patients who fail to respond to diuretic-based strategies, renal replacement therapies should be considered. Ultrafiltration is one of the most common approaches. It may be considered in those with diuretic resistance even if data about its effects on outcomes are unsettled. (l1b./C).

In 2023 the ESC and HFA published a “Focused Update” on the previous (2021) guidelines, the new guidelines did not include recommendations relevant to the use of ultrafiltration in heart failure.

In 2022 the Heart Failure Society of America's 2010 Comprehensive Heart Failure Practice Guideline was replaced with the new joint guideline previously cited.

Published evidence is insufficient to show net improvement in health outcomes through the use of UF (aquapheresis) techniques for the treatment of refractory ADHF, as compared to conventional treatment modalities. Although recent reviews and meta-analyses have shown favorable clinical results from use of UF in ADHF, most investigators concur that additional large, well-designed trials are needed to establish the role of UF in refractory ADHF (DeVecchis, 2014; Ebrahim, 2015; Kwong, 2014; Wen, 2013; Zhi, 2013).

In February 2020, the Aquadex FlexFlow^® System 2.0 (CHF Solutions, Inc., Eden Prairie, MN) received clearance from the FDA through the 510(k) clearance process, as substantially equivalent to prior predicate devices that perform UF/aquapheresis techniques. The current FDA approved indications for use are as follows:

• Temporary (up to 8 hours) UF treatment of patients with fluid overload who have failed diuretic therapy, and
• Extended (longer than 8 hours) UF treatment of patients with fluid overload who have failed diuretic therapy and require hospitalization.

“All treatments must be administered by a health care provider, under physician prescription, both of whom having received training in extracorporeal therapies” (FDA, 2020).

Aquapheresis^™: The trademarked term for removal of salt and water with the Aquadex FlexFlow  System which was classified by the FDA as a high permeability dialysis system.

Heart failure (HF; also referred to as congestive heart failure [CHF]): The term used for a clinical syndrome characterized by systemic perfusion that is inadequate to meet the body’s metabolic demands as a result of impaired cardiac pump function. The heart is unable to pump sufficient oxygenated blood to vital organs and there is congestion/pooling of blood in the extremities and lungs with resultant symptoms, such as dyspnea (shortness of breath).

New York Heart Association (NYHA) Definitions:

The NYHA classification of heart failure is a 4-tier system that categorizes based on subjective impression of the degree of functional compromise. The four NYHA functional classes are as follows:

• Class I - individuals with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; symptoms only occur on severe exertion;
• Class II - individuals with cardiac disease resulting in slight limitation of physical activity; they are comfortable at rest; ordinary physical activity, (for example, moderate physical exertion, such as carrying shopping bags up several flights of stairs) results in fatigue, palpitation, dyspnea, or anginal pain;
• Class III - individuals with cardiac disease resulting in marked limitation of physical activity; they are comfortable at rest; less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain;
• Class IV - individuals with cardiac disease resulting in inability to carry on any physical activity without discomfort; symptoms of heart failure or the anginal syndrome may be present even at rest; if any physical activity is undertaken, discomfort is increased.

Ultrafiltration (UF): A term for a technique that moves water and small-to-medium weight solutes across a semi-permeable membrane to reduce volume overload.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:

Peer Reviewed Publications:

1. Badawy SS, Fahmy A. Efficacy and cardiovascular tolerability of continuous veno-venous hemodiafiltration in acute decompensated heart failure: a randomized comparative study. J Crit Care. 2012; 27(1):106 e7-13.
2. Bart BA, Boyle A, Bank AJ, et al. Ultrafiltration vs. usual care for hospitalized patients with heart failure: the Relief for Acutely Fluid-Overloaded Patients with Decompensated Congestive Heart Failure (RAPID-CHF) trial. J Am Coll Cardiol. 2005; 46(11):2043-2046.
3. Bart BA, Goldsmith SR, Lee KL, et al.; Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012; 367(24):2296-2304.
4. Cheng Z, Wang L, Gu Y, et al. Efficacy and safety of ultrafiltration in decompensated heart failure patients with renal insufficiency. Int Heart J. 2015; 56(3):319-323.
5. Costanzo MR, Guglin ME, Saltzberg MT, et al. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure (UNLOAD). J Am Coll Cardiol. 2007; 49(6):675-683.
6. Costanzo MR, Jessup M. Treatment of congestion in heart failure with diuretics and extracorporeal therapies: effects on symptoms, renal function, and prognosis. Heart Fail Rev. 2012; 17(2):313-324.
7. Costanzo MR, Negoianu D, Jaski BE, et al. Aquapheresis versus intravenous diuretics and hospitalizations for heart failure. JACC Heart Fail. 2016; 4(2):95-105.
8. Costanzo MR, Saltzberg MT, Jessup M, et al. Ultrafiltration is associated with fewer rehospitalizations than continuous diuretic infusion in patients with decompensated heart failure: results from UNLOAD. J Card Fail. 2010; 16(4):277-284.
9. Costanzo MR, Saltzberg M, O’Sullivan, et al. Early ultrafiltration in patients with decompensated heart failure and diuretic resistance. J Am Coll Cardiol. 2005; 46(11):2047-2051.
10. Dahle TG, Bladke D, Ali SS, et al. Large volume ultrafiltration for acute decompensated heart failure using standard peripheral intravenous catheters. J Card Fail. 2006; 12(5):349-352.
11. Dahle TG, Sobotka PA, Boyle AJ. A practical guide for ultrafiltration in acute decompensated heart failure. Congest Heart Fail. 2008; 14(2):83-88.
12. De Maria E, Pignatti F, Patrizi G, et al. Ultrafiltration for the treatment of diuretic-resistant, recurrent, acute decompensated heart failure: experience in a single center. J Cardiovasc Med (Hagerstown). 2010; 11(8):599-604.
13. De Vecchis R, Esposito C, Ariano C. Efficacy and safety assessment of isolated ultrafiltration compared to intravenous diuretics for acutely decompensated heart failure: a systematic review with meta-analysis. Minerva Cardioangiol. 2014; 62(2):131-146.
14. Ebrahim B, Sindhura K, Okoroh J, et al. Meta-analysis of ultrafiltration versus diuretics treatment option for overload volume reduction in patients with acute decompensated heart failure. Arq Bras Cardiol. 2015; 104(5):417-425.
15. Giglioli C, Landi D, Cecchi E, et al. Effects of ULTRAfiltration vs. DIureticS on clinical, biohumoral and hemodynamic variables in patients with deCOmpensated heart failure: the ULTRADISCO study. Eur J Heart Fail. 2011; 13(3):337-346.
16. Grodin JL, Carter S, Bart BA, et al. Direct comparison of ultrafiltration to pharmacological decongestion in heart failure: a per-protocol analysis of CARRESS-HF. Eur J Heart Fail. 2018; 20(7):1148-1156.
17. Hanna MA, Tang WH, Teo BW, et al. Extracorporeal ultrafiltration vs. conventional diuretic therapy in advanced decompensated heart failure. Congest Heart Fail. 2012; 18(1):54-63.
18. Hu J, Wan Q, Zhang Y, et al. Efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure with volume overload: a prospective, randomized, controlled clinical trial. BMC Cardiovasc Disord. 2020; 20(1):447.
19. Jaski BE, Romeo A, Ortiz B, et al. Outcomes of volume-overloaded cardiovascular patients treated with ultrafiltration. J Card Fail. 2008; 14(6):515-520.
20. Kabach M, Alkhawam H, Shah S, et al. Ultrafiltration versus intravenous loop diuretics in patients with acute decompensated heart failure: a meta-analysis of clinical trials. Acta Cardiol. 2017; 72(2):132-141.
21. Kazory A, Ross EA. Ultrafiltration for decompensated heart failure: renal implications. Heart. 2009; 95(13):1047-1051.
22. Kitai T, Grodin JL, Kim YH, Tang WH. Impact of ultrafiltration on serum sodium homeostasis and its clinical implication in patients with acute heart failure, congestion, and worsening renal function. Circ Heart Fail. 2017 Feb; 10(2):e003603.
23. Kwong JS, Yu CM. Ultrafiltration for acute decompensated heart failure: a systematic review and meta-analysis of randomized controlled trials. Int J Cardiol. 2014; 172(2):395-402.
24. Liang KV, Williams AW, Greene EL, Redfield MM. Acute decompensated heart failure and the cardiorenal syndrome. Crit Care Med. 2008; 36(1 Suppl):S75-88.
25. Marenzi G, Muratori M, Cosentino ER et al. Continuous ultrafiltration for congestive heart failure: the CUORE trial. J Card Fail. 2014; 20(1):9-17.
26. Mentz RJ, Stevens SR, DeVore AD, et al. Decongestion strategies and renin-angiotensin-aldosterone system activation in acute heart failure. JACC Heart Fail. 2015; 3(2):97-107.
27. Patarroyo M, Wehbe E, Hanna M, et al. Cardiorenal outcomes after slow continuous ultrafiltration therapy in refractory patients with advanced decompensated heart failure. J Am Coll Cardiol. 2012; 60(19):1906-1912.
28. Rao VS, Ahmad T, Brisco-Bacik MA, et al. Renal effect of intensive volume removal in heart failure patients with preexisting worsening renal function. Circ Heart Fail. 2019; 12(6): e00552.
29. Rogers HL, Marshall J, Bock J, et al. A randomized, controlled trial of the renal effects of ultrafiltration as compared to furosemide in patients with acute decompensated heart failure. J Card Fail. 2008; 14(1):1-5.
30. Shi X, Jiating B, Haili Z, et al. Patients with high-dose diuretics should get ultrafiltration in the management of decompensated heart failure: a meta-analysis. Heart Fail Rev. 2019; 24(6):927-940.
31. Siddiqui WJ, Kohut AR, Hasni SF, et al. Readmission rate after ultrafiltration in acute decompensated heart failure: a systematic review and meta-analysis. Heart Fail Rev. 2017; (6):685-698.
32. Wang MJ, Zheng YM, Jin HX. Ultrafiltration for patients with acute decompensated heart failure: a systematic review and meta-analysis. Medicine (Baltimore). 2021; 100(50):e28029.
33. Wen H, Zhang Y, Zhu J, et al. Ultrafiltration versus intravenous diuretic therapy to treat acute heart failure: a systematic review. Am J Cardiovasc Drugs. 2013; 13(5):365-373.
34. Wertman BM, Gura V, Schwarz ER. Ultrafiltration for the management of acute decompensated heart failure. J Card Fail. 2008; 14(9):754-759.
35. Wobbe B, Wagner J, Szabo DK, et al. Ultrafiltration is better than diuretic therapy for volume-overloaded acute heart failure patients: a meta-analysis. Heart Fail Rev. 2021; 26(3):577-585.
36. Yancy CW. Climbing the mountain of acute decompensated heart failure: the EVEREST trials. JAMA. 2007; 297(12):1374-1376.
37. Zhi Q, Liang JC. Diuretics and ultrafiltration in acute heart failure syndrome. Int Heart J. 2013; 54(6): 390-394.

Government Agency, Medical Society, and other Authoritative Publications:

1. Dickstein K, Cohen-Solal A, Filippatos G, et al.: Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology (ESC). 2010 Focused update of ESC Guidelines on device therapy in heart failure. 2010. Eur J Heart Fail. 2010; 31:2677-2687.
2. Flynn K. Brief overview: Ultrafiltration for decompensated heart failure. Boston, MA: Technology Assessment Program (VATAP), Office of Patient Care Services, Veterans Health Administration; January 2011.
3. Heidenreich P, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the management of heart failure: A report of the American College of Cardiology/ American Heart Association Joint Committee on Clinical Practice Guidelines. 2022; 145(18):e895-e1032.
4. Hunt SA, Abraham WT, Chin MH, et al. 2009 Focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2009; 119(14):e391- e479. Available at: http://circ.ahajournals.org/content/119/14/e391.full.pdf. Accessed on December 6, 2023.
5. Jessup M, Abraham WT, Casey DE, et al. writing on behalf of the 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult Writing Committee. 2009 Focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2009; 119(14):1977-2016. Available at: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.109.192064. Accessed on December 6, 2023.
6. McDonagh T, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC): Develop with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2021 42:3599-3726.
7. McDonagh T, Metra M, Adamo M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Society of Cardiology (ESC): Develop with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal 2023; 44(37):3627-3639.
8. McMurray JJ, Adamopoulos S, Anker SD, et al.: European Society of Cardiology (ESC). Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the ESC. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012; 33(14):1787-1847. Available at: http://www.escardio.org/static_file/Escardio/Guidelines/publications/HFGuidelines-Heart-Failure-Web-Tables.pdf. Accessed on December 6, 2023.
9. Pan I, McGregor M. Efficacy, safety and cost of ultrafiltration for the management of acute decompensated heart failure. Report No 47. Montreal, QC: Technology Assessment Unit of the McGill University Health Centre (MUHC); May 31, 2010. Available at:  http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?AccessionNumber=32010001378. Accessed on December 6, 2023.
10. U.S. Food and Drug Administration 510(k) Premarket Notification Database. Aquadex FlexFlow^™ System Summary of Safety and Effectiveness. No. K062922. Rockville, MD: FDA. December 13, 2006. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf6/K062922.pdf. Accessed on December 6, 2023.
11. U.S. Food and Drug Administration 510(k) Premarket Notification Database. Aquadex FlexFlow^™ System Summary of Safety and Effectiveness. No. K070512. Rockville, MD: FDA. April 27, 2007. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf7/K070512.pdf. Accessed on December 6, 2023.
12. U.S. Food and Drug Administration 510(k) Premarket Notification Database. Aquadex FlexFlow^™  System 2.0. Summary of Safety and Effectiveness. No. K192756. Silver Spring, MD: FDA. February 24, 2020. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf19/K192756.pdf. Accessed on December 6, 2023.
13. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 128(16):e240-e327.

1.  Clinical information about heart failure from the Cleveland Clinic Journal of Medicine. Updated May 01, 2019. Available at: http://my.clevelandclinic.org/health/articles/heart-failure. Accessed on December 6, 2023.

Aquadex FlexFlow System
Aquapheresis
Heart Failure
PRISMA^™ Continuous Fluid Management System
Ultrafiltration

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