麻豆传媒

CHICAGO -- The "bridge to transplant" for patients awaiting a new heart may add another lane -- an experimental left ventricular assist device (LVAD) that appears to be as effective as already-approved LVADs used in patients with advanced heart failure awaiting transplant, researchers here reported.

Moreover, 92% of the patients treated with the HeartWare HVAD were alive with the device in place at 180 days, which is the "highest survival ever reported ever at 180 days [in LVAD bridge-to-transplant], said Keith Aaronson, MD, MS, of the University of Michigan.

Aaronson reported the results of the ADVANCE-BTT study at a late-breaking clinical trials presentation at the American Heart Association meeting.

The survival at one year was 91% in the HeartWare arm -- versus 86% in the control group.

One hundred and forty patients all awaiting heart transplants were included in the intention to treat analysis. The average age of patients was 53 and all had NYHA Class IV heart failure at baseline. Of those, 137 were treated according to protocol. Patients were treated at 30 participating U.S. centers.

The primary outcome of the ADVANCE-BTT study was the success rate at 180 days post-implant, with success defined as survival on the originally implanted device, transplant, or explant for ventricular recovery (patients must have survived 60 days post-explant).

The survival rate was compared with a control group comprised of 499 bridge to transplant patients treated with already approved LVADs, notably the HeartMate-2 device made by Thoratec.

"The treatment group success rate was 92% versus 90% in the control group (P <0.001 for noninferiority), Aaronson said.

But 10 of the HeartWare patients had ischemic strokes and seven patients had transient ischemic attacks -- a rate that was slightly higher than controls -- although there was no difference in hemorrhagic strokes.

Magdi Yacoub, MD, FRS, of Imperial College in London, said the stroke rate needed further study; "however, in defense of device, the strokes were mostly early -- in first 48 hours -- and many of them, up to 84%, were recoverable. This is a really important point. And it may well also be important to assess the anticoagulant therapy in this group."

Asked about the strokes, Aaronson told 麻豆传媒 that half of the 10 ischemic strokes had indeed occurred within the first 48 hours, and he said anticoagulation was problematic.

Although there was a recommendation for perioperative heparin, "the heparinization rate varied widely among centers." He said the standard anticoagulation regimen was "warfarin and aspirin and there was a recommendation for an INR of 2 to 3, but the average INR was 2."

Yacoub, who was not involved in the study, noted that LVAD technology has evolved rapidly, often creating expectations that fail to match actual results. That was the case, he said, with the ADVANCE-BTT study -- even though FDA requires only that a device demonstrate noninferiority to existing devices.

HeartWare "is an extremely attractive new device with a lot of potential because it is small and simple to insert," Yacoub said.

Unlike other devices, the HeartWare is inserted directly into the pericardium and does not require a pump pocket. It pumps up to 10 L/min of flow and uses an impeller -- a nonpulsatile -- design.

As a result, "with this third generation device, we had hoped this to translate to a clinical benefit", Yacoub said.

But that was not the case, although "there was less infection ... less infection related to a variety of causes, almost certainly due to the lack of extensive dissection ... and there may be less bleeding," Yacoub commented. Those results were encouraging, but not spectacular.

Seven patients also underwent device replacements, "including three devices that were removed due to low INR thrombosis," ADVANCE investigator Aaronson said in an interview.

Aaronson also cautioned that the study had a number of limitations, including the lack of randomization, so that "relevant baseline characteristics may differ between groups."

Moreover, comparing outcomes in the clinical trial treatment arm to data from a national registry was problematic because confirming the registry data -- from the Interagency Registry for Mechanical Assisted Circulatory Support (INTERMACS), which includes 3,187 patient outcomes -- was at difficult at best, Aaronson added.

In a subset of patients (n=79), the ADVANCE investigators also compared quality of life and functional measures at baseline to the same markers at 180 days, significant improvements (P <0.001) -- including a near doubling of the six-minute walk distance from 124 meters (almost 407 feet) to 237 meters (777.5 feet).

Comment