ATLANTA — Peripheral ultrafiltration trounced aggressive intravenous diuretics—the long-standard, yet previously unchallenged, therapy for acute decompensated heart failure—in a major randomized trial presented at the annual meeting of the American College of Cardiology.

The novel mechanical ultrafiltration method safely produced greater weight and fluid loss than did loop diuretics. It also cut total rehospitalization days and emergency department visits by more than half during the 90 days after discharge, reported Dr. Maria Rosa Costanzo, principal investigator in the Ultrafiltration vs. IV Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure (UNLOAD) trial.

“We believe that the results of this trial are immediately applicable to a large proportion of patients admitted with decompensated heart failure,” said Dr. Costanzo, medical director at the Edward Hospital Center for Advanced Heart Failure, Naperville, Ill.

UNLOAD was a 28-center study involving 200 patients hospitalized for decompensated heart failure and volume overload. Patients were randomized to peripheral ultrafiltration or aggressive use of loop diuretics—the standard therapy—with the goals of getting them stabilized, feeling better, and out of the hospital as quickly as possible.

Patients in the ultrafiltration arm averaged a weight loss of 5.0 kg at 48 hours, with no adverse impact on renal function, compared with 3.1 kg with standard care. The mean net fluid loss of 4.6 L in the ultrafiltration group at 48 hours was also significantly greater than the 3.3 L in the standard care group.

But what really grabbed the attention of heart failure specialists in the audience was the difference in 90-day outcomes. That's because decompensated heart failure is the number one cause of hospital admission in the United States, with 90% of these hospitalizations resulting from volume overload—and health policy officials are desperate to reduce that enormous burden on resources.

Patients in the ultrafiltration group were rehospitalized for heart failure for a collective 123 days during the 3 months after discharge, compared with 330 days in the standard care group. The ultrafiltration group also fared markedly better in terms of other resource-utilization end points (see box).

Dr. Costanzo attributed the sustained benefits of ultrafiltration to three factors: It doesn't activate neurohormonal systems, as do loop diuretics; it is more efficient in that it removes proportionately more sodium per unit fluid removed; and it allows patients to take “a diuretic holiday,” as reflected in their lower dose of oral diuretics at discharge, compared with patients who had received loop diuretics.

The use of high-dose intravenous diuretics has been linked to increased short-term morbidity and mortality. Most physicians will be surprised to learn that the safety and efficacy of this long-standard therapy has never been tested in a randomized trial, she added.

Dr. Gregg C. Fonarow called the UNLOAD data “very impressive and something that I think should influence clinical practice now. The adverse consequences of high-dose loop diuretics have been underappreciated. Anything we can do to get fluid off while limiting the amount of loop diuretics needed is good from a physiologic standpoint,” he said in an interview.

UNLOAD sets the stage for a larger, more definitive outcomes study, added Dr. Fonarow, professor of medicine at the University of California, Los Angeles and director of the Ahmanson-UCLA Cardiomyopathy Center.

Ultrafiltration was accomplished using a Food and Drug Administration-approved device marketed by CHF Solutions Inc. Unlike older ultrafiltration methods, which never caught on because they required central venous access and intensive patient monitoring, the CHF Solutions device is easy to use, requires only peripheral venous access, and takes only 33 mL of blood extracorporeally at any given time. The device can remove up to 500 cc of fluid per hour, with most patients requiring one or two 8-hour treatment sessions.

The single-use filter costs about $800; however, that pales next to the potential cost savings through reduced rehospitalization, especially because Medicare won't reimburse for rehospitalization within 30 days, Dr. Costanzo observed.

However, results showed that the markedly greater fluid loss achieved with ultrafiltration did not translate into greater symptom relief. Dyspnea scores at 48 hours were similar in the two treatment arms. In fact, change in dyspnea score did not significantly correlate with weight loss at 48 hours. This challenges the traditional practice of using congestive symptoms to decide when to start and stop therapy in decompensated heart failure.

Indeed, the observation that symptoms of congestion aren't a sufficiently sensitive guide to fluid volume provides a further boost to ongoing efforts to develop implantable hemodynamic monitors for this clinical application.

Dr. Costanzo is on the medical advisory board of CHF Solutions, which sponsored UNLOAD.

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