Minneapolis, MN - A small study in acute decompensated heart-failure patients has shown that peripheral venovenous ultrafiltration (System 100 Fluid Removal System, CHF Solutions, Brooklyn Park, MN) results in greater weight loss and fluid removal at 24 hours than usual care [1]. A second study has also shown that peripheral ultrafiltration before intravenous (IV) diuretics is a safe and effective means to reduce hospital length of stay (LOS) and hospital readmissions [2].

Preliminary results from both studies were originally presented at the Heart Failure Society of America 2004 Annual Scientific Meeting and reported by heartwire at that time. The papers are now published in the December 6, 2005 issue of the Journal of the American College of Cardiology.

In the first study, known as the Randomized Controlled Trial of Ultrafiltration for Decompensated Congestive Heart Failure (RAPID-CHF), lead investigator Dr Bradley Bart (Minnesota Heart Failure Consortium, Minneapolis) and colleagues compared efficacy of ultrafiltration vs the best medical therapy in hospitalized CHF patients with fluid overload. The ultrafiltration device was associated with greater fluid removal, weight loss, and symptom relief compared with medical therapy alone, although the primary end point, weight loss, did not achieve statistical significance.

"One of the most exciting things about this treatment is that it affords us an opportunity to learn a little bit more about diuretics," Bart told heartwire. "In the past, we've never had an alternative. Everyone got diuretics so we never really had any sense of how someone might do if they were treated without diuretics. Ultrafiltration is something that represents an alternative approach to volume management. From the patient standpoint, the patients respond very positively to treatment, as the fluid is removed so quickly. They can see it and feel that progress is being made in their care."

Typically, ultrafiltration for CHF is reserved for patients with renal failure or those unresponsive to diuretics. Bart noted that in many of the heart-failure trials, the use of high doses of diuretics is associated with increased risks of mortality and sudden death. Diuretics are also difficult to use, he added, with a variable dose response in patients. Moreover, data from the Acute Decompensated Heart Failure National Registry (ADHERE) show that as many as one in five patients admitted to the hospital with acute heart failure are discharged with no weight loss, suggesting the drugs are ineffective in a large number of patients, said Bart.

In RAPID-CHF, a proof-of-concept study, 20 patients hospitalized with CHF were randomized to a single eight-hour ultrafiltration session in addition to usual care and 20 patients were randomized to usual care alone. At 24 hours, ultrafiltration resulted in significant fluid reductions and a trend toward greater weight reduction compared with usual care.

The study was conducted in various hospital settings on a standard cardiology floor (as opposed to an ICU unit). The device is small, portable, and less invasive, requiring only central IV access. As to why the study might have missed the primary end point, Bart pointed out that the usual-care patients were aggressively treated, resulting in a large diuretic effect. Had the weight loss seen in the ultrafiltration patients been compared with a historical control, the difference between the two patient groups would have been larger.

Bart told heartwire that he does not believe that every heart-failure patient should be treated with ultrafiltration therapy. One of the important questions that remain is how to select the patient who would benefit the most from this treatment, he said. Patients with fluid overload, some degree of renal insufficiency, and those refractory to diuretic therapy might make good candidates for ultrafiltration, he said.

In a second paper on ultrafiltration, Dr Maria Rosa Costanzo (Midwest Heart Foundation, Lombard, IL) and colleagues report data from a small 20-patient study designed to test whether the use of ultrafiltration before any IV diuretic in patients with decompensated HF and diuretic resistance could reestablish euvolemia and permit hospital discharge in three days or less without adverse events and prevent rehospitalization up to three months.

In this high-risk heart-failure population, investigators removed 8654 mL of fluid with the novel ultrafiltration device. Of the 20 patients, 12 were discharged in three days or less. Patients lost an average of 6 kg, with their weight remaining less than their pretreatment weight at 30 and 90 days. In addition to significantly decreasing hospital length of stay and readmission, investigators report significant reductions in neurohormonal activation and no significant changes in serum creatinine or electrolytes. There was no recurrent volume overload reported by three months and no reported hypotension.

Drs Robert Bourge and José Tallaj (University of Alabama, Birmingham), in an editorial accompanying the published studies, write, "From these two studies, we can conclude that UF [ultrafiltration] is probably safe and results in a fast and effective method of fluid and salt removal with a resultant improvement in the symptoms of congestion in patients with CHF and volume overload [3]."

They add that another important effect of ultrafiltration is a decrease in neurohormonal activity, manifested by declining levels of renin, norepinephrine, and aldosterone. Like Bart, the editorialists stressed that ultrafiltration is not a substitute for dialysis as the device is unable to remove waste products.

Bourge and Tallaj caution that while the device is a welcome addition to clinicians looking to reduce fluid overload and symptoms in CHF patients, large-scale, randomized studies are needed to evaluate potential adverse effects as well as the durability of the benefits. Such a study, a prospective randomized trial of ultrafiltration vs IV diuretics at 20 centers, known as the UNLOAD trial and led by Costanzo, has recently completed enrollment and is expected to be presented at the American College of Cardiology 2006 Scientific Sessions in Atlanta, GA.

As to who would ultimately use the technology in the management of fluid overload, Bart suspects that most cardiologists would be using the technology without nephrologists.

"In the past, the ultrafiltration has been done by dialysis nurses with the dialysis machine. There was no way you could get it done without the input of nephrology," said Bart. "With this new machine, you don't need a dialysis nurse, you don't need a dialysis machine, and you don't really need a nephrologist. Whenever you make changes like that some people are going to be concerned about the change, but I think these two studies that were published should alleviate some of those concerns. We didn't run into trouble with electrolytes or acute renal failure."