Ultrafiltration Flops for Acute Cardiorenal Syndrome

LOS ANGELES – Mechanical venovenous ultrafiltration proved inferior to drug therapy in diuretic-responsive patients hospitalized with acute decompensated heart failure and cardiorenal syndrome in a major multicenter randomized trial.

In the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), weight loss due to elimination of excess fluid was similar at 96 hours in the two treatment arms. However, renal function was significantly worse in the ultrafiltration group at that time point, and it remained so even 60 days from baseline, Dr. Bradley A. Bart reported at the annual scientific sessions of the American Heart Association.

Moreover, the combined rate of the secondary end point comprising death or serious adverse events at 6 months was 72% in the ultrafiltration group, compared with 57% in patients treated with a standardized pharmacologic regimen, for an adjusted 50% increased risk in the ultrafiltration group. Serious adverse events included kidney failure, bleeding complications, and problems due to intravenous catheters.

"Neither group was adequately decongested at the time of hospital discharge. This is a challenging group of patients to treat. The 60-day event rates are very high, and better therapies are needed in the future," said Dr. Bart of the Hennepin County Medical Center, Minneapolis.

Acute cardiorenal syndrome occurs in up to one-third of patients with acute decompensated heart failure. The CARRESS-HF trial randomized 188 affected patients who were diuretic responsive to a stepped pharmacologic care algorithm or to ultrafiltration at a rate of 200 mL/hr using the commercially available Aquadex System 100 device manufactured by CHF Solutions.

Both treatment groups lost about 12 pounds through 96 hours. However, while mean serum creatinine was unchanged from baseline in the drug therapy group, it climbed by 0.25 mg/dL in the ultrafiltration group.

Discussant Dr. Milton Packer agreed with the investigators’ conclusion that the study data offer no support for the use of mechanical ultrafiltration in patients who are responsive to diuretics.

"I still think there’s a role for ultrafiltration in patients who are diuretic unresponsive," added Dr. Packer, professor and chairman of the department of clinical sciences at the University of Texas Southwestern Medical Center, Dallas.

He called CARRESS-HF "a really terrific study and an important one." Ultrafiltration can be programmed to pull fluid off of patients more rapidly than is possible with drug therapy. Had mechanical ultrafiltration performed better than well-managed drug therapy in CARRESS-HF, the message to physicians would have been that they shouldn’t spend much time fiddling with diuretic therapy in such patients, but should instead turn to ultrafiltration much earlier during the hospitalization, even in diuretic-responsive patients.

"What is striking about this study is that the difference in renal function was present not only during the ultrafiltration but afterward. That’s something that, frankly speaking, gives us pause. It may be worthwhile in someone who’s diuretic unresponsive; it’s not worthwhile in someone who is diuretic responsive," according to Dr. Packer.

Simultaneous with Dr. Bart’s presentation of the CARRESS-HF results at the AHA conference, the study findings were published online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1210357]).

In an accompanying editorial, Dr. W.H. Wilson Tang of the Cleveland Clinic called the outcomes in CARRESS-HF "overall dismal," with more than one-third of patients dying or being readmitted for acute decompensated heart failure within 60 days, regardless of their treatment arm. But that’s representative of what happens in everyday clinical practice when acute cardiorenal syndrome occurs (N. Engl. J. Med. 2012 [doi:10.1056/NEJMe1212881]).

It’s unclear why serum creatinine rose further and stayed high in the ultrafiltration-treated patients. Dr. Tang speculated that it might be because the mechanical device drew off fluid so rapidly that kidney perfusion was decreased.

"We may even have to confront the possibility that the pressure to reduce hospital length of stay with a strategy of initial aggressive diuresis in patients with acute decompensated heart failure may actually result in an increased incidence of the acute cardiorenal syndrome and cause unwanted consequences. Perhaps slow and steady may ultimately win the race after all," according to Dr. Tang.

CARRESS-HF was sponsored by the National Heart, Lung, and Blood Institute and carried out by the Heart Failure Clinical Research Network. Dr. Bart, Dr. Packer, and Dr. Tang reported having no relevant financial disclosures.

LOS ANGELES – Mechanical venovenous ultrafiltration proved inferior to drug therapy in diuretic-responsive patients hospitalized with acute decompensated heart failure and cardiorenal syndrome in a major multicenter randomized trial.

In the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), weight loss due to elimination of excess fluid was similar at 96 hours in the two treatment arms. However, renal function was significantly worse in the ultrafiltration group at that time point, and it remained so even 60 days from baseline, Dr. Bradley A. Bart reported at the annual scientific sessions of the American Heart Association.

Moreover, the combined rate of the secondary end point comprising death or serious adverse events at 6 months was 72% in the ultrafiltration group, compared with 57% in patients treated with a standardized pharmacologic regimen, for an adjusted 50% increased risk in the ultrafiltration group. Serious adverse events included kidney failure, bleeding complications, and problems due to intravenous catheters.

"Neither group was adequately decongested at the time of hospital discharge. This is a challenging group of patients to treat. The 60-day event rates are very high, and better therapies are needed in the future," said Dr. Bart of the Hennepin County Medical Center, Minneapolis.

Acute cardiorenal syndrome occurs in up to one-third of patients with acute decompensated heart failure. The CARRESS-HF trial randomized 188 affected patients who were diuretic responsive to a stepped pharmacologic care algorithm or to ultrafiltration at a rate of 200 mL/hr using the commercially available Aquadex System 100 device manufactured by CHF Solutions.

Both treatment groups lost about 12 pounds through 96 hours. However, while mean serum creatinine was unchanged from baseline in the drug therapy group, it climbed by 0.25 mg/dL in the ultrafiltration group.

Discussant Dr. Milton Packer agreed with the investigators’ conclusion that the study data offer no support for the use of mechanical ultrafiltration in patients who are responsive to diuretics.

"I still think there’s a role for ultrafiltration in patients who are diuretic unresponsive," added Dr. Packer, professor and chairman of the department of clinical sciences at the University of Texas Southwestern Medical Center, Dallas.

He called CARRESS-HF "a really terrific study and an important one." Ultrafiltration can be programmed to pull fluid off of patients more rapidly than is possible with drug therapy. Had mechanical ultrafiltration performed better than well-managed drug therapy in CARRESS-HF, the message to physicians would have been that they shouldn’t spend much time fiddling with diuretic therapy in such patients, but should instead turn to ultrafiltration much earlier during the hospitalization, even in diuretic-responsive patients.

"What is striking about this study is that the difference in renal function was present not only during the ultrafiltration but afterward. That’s something that, frankly speaking, gives us pause. It may be worthwhile in someone who’s diuretic unresponsive; it’s not worthwhile in someone who is diuretic responsive," according to Dr. Packer.

Simultaneous with Dr. Bart’s presentation of the CARRESS-HF results at the AHA conference, the study findings were published online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1210357]).

In an accompanying editorial, Dr. W.H. Wilson Tang of the Cleveland Clinic called the outcomes in CARRESS-HF "overall dismal," with more than one-third of patients dying or being readmitted for acute decompensated heart failure within 60 days, regardless of their treatment arm. But that’s representative of what happens in everyday clinical practice when acute cardiorenal syndrome occurs (N. Engl. J. Med. 2012 [doi:10.1056/NEJMe1212881]).

It’s unclear why serum creatinine rose further and stayed high in the ultrafiltration-treated patients. Dr. Tang speculated that it might be because the mechanical device drew off fluid so rapidly that kidney perfusion was decreased.

"We may even have to confront the possibility that the pressure to reduce hospital length of stay with a strategy of initial aggressive diuresis in patients with acute decompensated heart failure may actually result in an increased incidence of the acute cardiorenal syndrome and cause unwanted consequences. Perhaps slow and steady may ultimately win the race after all," according to Dr. Tang.

CARRESS-HF was sponsored by the National Heart, Lung, and Blood Institute and carried out by the Heart Failure Clinical Research Network. Dr. Bart, Dr. Packer, and Dr. Tang reported having no relevant financial disclosures.

LOS ANGELES – Mechanical venovenous ultrafiltration proved inferior to drug therapy in diuretic-responsive patients hospitalized with acute decompensated heart failure and cardiorenal syndrome in a major multicenter randomized trial.

In the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), weight loss due to elimination of excess fluid was similar at 96 hours in the two treatment arms. However, renal function was significantly worse in the ultrafiltration group at that time point, and it remained so even 60 days from baseline, Dr. Bradley A. Bart reported at the annual scientific sessions of the American Heart Association.

Moreover, the combined rate of the secondary end point comprising death or serious adverse events at 6 months was 72% in the ultrafiltration group, compared with 57% in patients treated with a standardized pharmacologic regimen, for an adjusted 50% increased risk in the ultrafiltration group. Serious adverse events included kidney failure, bleeding complications, and problems due to intravenous catheters.

"Neither group was adequately decongested at the time of hospital discharge. This is a challenging group of patients to treat. The 60-day event rates are very high, and better therapies are needed in the future," said Dr. Bart of the Hennepin County Medical Center, Minneapolis.

Acute cardiorenal syndrome occurs in up to one-third of patients with acute decompensated heart failure. The CARRESS-HF trial randomized 188 affected patients who were diuretic responsive to a stepped pharmacologic care algorithm or to ultrafiltration at a rate of 200 mL/hr using the commercially available Aquadex System 100 device manufactured by CHF Solutions.

Both treatment groups lost about 12 pounds through 96 hours. However, while mean serum creatinine was unchanged from baseline in the drug therapy group, it climbed by 0.25 mg/dL in the ultrafiltration group.

Discussant Dr. Milton Packer agreed with the investigators’ conclusion that the study data offer no support for the use of mechanical ultrafiltration in patients who are responsive to diuretics.

"I still think there’s a role for ultrafiltration in patients who are diuretic unresponsive," added Dr. Packer, professor and chairman of the department of clinical sciences at the University of Texas Southwestern Medical Center, Dallas.

He called CARRESS-HF "a really terrific study and an important one." Ultrafiltration can be programmed to pull fluid off of patients more rapidly than is possible with drug therapy. Had mechanical ultrafiltration performed better than well-managed drug therapy in CARRESS-HF, the message to physicians would have been that they shouldn’t spend much time fiddling with diuretic therapy in such patients, but should instead turn to ultrafiltration much earlier during the hospitalization, even in diuretic-responsive patients.

"What is striking about this study is that the difference in renal function was present not only during the ultrafiltration but afterward. That’s something that, frankly speaking, gives us pause. It may be worthwhile in someone who’s diuretic unresponsive; it’s not worthwhile in someone who is diuretic responsive," according to Dr. Packer.

Simultaneous with Dr. Bart’s presentation of the CARRESS-HF results at the AHA conference, the study findings were published online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1210357]).

In an accompanying editorial, Dr. W.H. Wilson Tang of the Cleveland Clinic called the outcomes in CARRESS-HF "overall dismal," with more than one-third of patients dying or being readmitted for acute decompensated heart failure within 60 days, regardless of their treatment arm. But that’s representative of what happens in everyday clinical practice when acute cardiorenal syndrome occurs (N. Engl. J. Med. 2012 [doi:10.1056/NEJMe1212881]).

It’s unclear why serum creatinine rose further and stayed high in the ultrafiltration-treated patients. Dr. Tang speculated that it might be because the mechanical device drew off fluid so rapidly that kidney perfusion was decreased.

"We may even have to confront the possibility that the pressure to reduce hospital length of stay with a strategy of initial aggressive diuresis in patients with acute decompensated heart failure may actually result in an increased incidence of the acute cardiorenal syndrome and cause unwanted consequences. Perhaps slow and steady may ultimately win the race after all," according to Dr. Tang.

CARRESS-HF was sponsored by the National Heart, Lung, and Blood Institute and carried out by the Heart Failure Clinical Research Network. Dr. Bart, Dr. Packer, and Dr. Tang reported having no relevant financial disclosures.