Third-Generation LVAD Shows Good Efficacy, Safety
Major Finding: Patients who received a HeartWare VAD as a bridge to transplant had a 92% rate of survival at 180 days after initial device placement, compared with the 90% rate in patients in a contemporaneous control group who received a commercially available VAD.
Data Source: The ADVANCE study, a prospective series of 140 patients with severe heart failure who received a HeartWare VAD as a bridge to transplant during August 2008–February 2010. The comparison group included 499 similar patients who received a commercially available LVAD in the United States during the same period.
Disclosures: ADVANCE was sponsored by HeartWare, the device developer. Dr. Aaronson said that he has received research support from HeartWare, Thoratec, and Terumo. Dr. Jessup is a consultant to Medtronic and a speaker on behalf of Boston Scientific, and has received research funding from Scios. Dr. Stevenson has been a consultant to Medtronic.
Mortality during the first 30 days following device placement ran 1.4% in the HeartWare group and 3.4% in the control patients. The 1.4% perioperative rate in the HeartWare recipients was "remarkable," Dr. Aaronson said, and was "comparable to the rate in patients electively receiving an aortic valve replacement."
The HeartWare recipients also showed statistically significant and clinically meaningful improvements in their quality of life. Their average scores on the Kansas City Cardiomyopathy Questionnaire for clinical summary and overall summary rose from a level consistent with severe heart failure at baseline to a level indicating mild heart failure 3 months after device placement. Their average EuroQol 5D self-rating showed an increase after 3 months that was comparable with "what is usually reported for heart transplant recipients," Dr. Aaronson said.
As Dr. Aaronson noted, much attention focused on adverse events. His analysis compared the rates seen in the 140 HeartWare VAD recipients vs. 281 patients who received the HeartMate II VAD in a multicenter study done during 2005-2008 that led to HeartMate II’s approval (J. Am. Coll. Cardiol. 2009;54:312-21). In the HeartWare series, bleeding at gastrointestinal sites occurred at a rate of 25% per patient-year, and bleeds requiring surgery occurred in 27% per patient-year. In the HeartMate II series, bleeds needing surgery occurred in 45% per patient-year, with no report on gastrointestinal bleeds. The 25% per patient-year gastrointestinal-bleeding rate in the HeartWare patients was "relatively low, about one-third the rate that’s been reported" by individual centers for patients who received the HeartMate II, he said.
"We need to know if there is a meaningful difference in the gastrointestinal bleeding, a key issue for all the nonpulsatile VADs," Dr. Jessup said.
Infection rates with the HeartWare VAD (39% per patient-year) also ran "substantially lower" than the 85% rate reported from the HeartMate II multicenter series. Ventricular arrhythmias also showed a substantial reduction with the HeartWare VAD (13% per patient-year vs. 40% per patient-year in the HeartMate II series).
Ischemic stroke rates with the HeartWare VAD ran 11% per patient-year, similar to the 9% rate seen in the multicenter HeartMate II series. Hemorrhagic stroke occurred at the same rate (5% per patient-year) with both devices. Half of the 10 ischemic strokes in the HeartWare VAD recipients occurred during the first 48 hours following device placement. "We believe they were surgically related; there is a clear learning curve" for placing the HeartWare VAD, Dr. Aaronson said. In addition, he noted that 8 of the 10 patients who had ischemic strokes later recovered to "moderate disability."
Another "key issue" that experience with the HeartWare VAD has so far not addressed is aortic valve insufficiency, Dr. Jessup said. "No one talks about it in these short-term trials, but you really see aortic insufficiency in destination-treatment trials. The longer you see patients [with LVADs], the more you see them developing hypertension and aortic insufficiency. Will there be a difference in the VADs for aortic insufficiency?"
The study was sponsored by HeartWare, the device developer. Dr. Aaronson said that he has received research support from HeartWare, Thoratec, and Terumo. Dr. Jessup is a consultant to Medtronic and a speaker on behalf of Boston Scientific, and has received research funding from Scios. Dr. Stevenson has been a consultant to Medtronic.
