Deborah Brauser

May 02, 2016

WASHINGTON, DC — One-year results from the HeartMate 3 (Thoratec/St Jude Medical) left ventricular assist device (LVAD) CE Mark Trial continued to build upon its positive 6-month findings announced last fall, say investigators.

As previously reported, the nonrandomized study of 50 patients implanted with the HeartMate 3 met its prespecified primary end point of a 92% survival rate at 6 months, which led to European CE Mark approval in October 2015.

The newly announced findings showed an 80% survival rate at 1 year, when combining destination-therapy (DT) and bridge-to-transplant (BTT) data; and 74% of the participants remained on support[1]. There were no occurrences of pump thrombosis, malfunctions, or hemolysis.

In addition, both gastrointestinal (GI) bleeding and strokes were reduced by 50% between the 6-month and 1-year assessment points. There were four GI events during the first 6 months, but only two additional events occurred in the second 6 months. And six strokes of any type occurred during the first 6 months vs three additional strokes during the second.

Finally, the 6-minute walk test increased significantly from baseline, as did quality-of-life scores (both comparisons, P<0.0001).

"In this first-in-human experience with the HeartMate 3, survival remains high and similar to previously published data in a blended population," said lead investigator Dr Thomas Krabatsch (Deutsches Herzzentrum Berlin, Germany) at the International Society for Heart and Lung Transplantation (ISHLT) 2016 Scientific Sessions—where the study was the only "highlighted research" discussed at the event's opening plenary session.

"Most important, there continues to be no pump thrombosis at all with this device," added Krabatsch, referencing the adverse event that has plagued the HeartMate II LVAD.

Favorable Results, Small Sample Size

Official discussant Dr Daniel Goldstein (Montefiore Medical Center, New York City) told heartwire from Medscape that it's important to keep in mind that this was a small, single-arm study with new technology. "So you have to take the results with some degree of uncertainty. And that's why there's a need for a very large trial."

Speaking of that very thing, Goldstein will be one of the principal investigators for the upcoming MOMENTUM 3 trial of more than 1000 patients receiving the HeartMate II or HeartMate 3. "I think it will definitively answer the role of this device in the US and what it may be able to accomplish and improve over existing technologies," he said.

"Europeans have a very quick regulatory process, where after 6 months of data you can start these patients on this with commercial use. That's not so in the United States," noted Goldstein. "But I am very encouraged with the hemocompatibility part of these results because this pump was designed for that purpose."

When asked for comment, Dr Jeffrey Teuteberg (University of Pittsburgh Medical Center, PA) told heartwire that he was glad to see the high survival rate but agreed with Goldstein that "this was still a relatively small experience."

"It's hard to make huge judgments about the overall technology compared with everything else, but these results were very favorable," said Teuteberg.

"Front-Loaded" Adverse Events

The study, which included 10 centers in six countries, enrolled the participants between June and November 2014. All of the patients (90% men; mean age 59 years) were in NYHA class 3B or 4 or ACC/AHA stage D and had an LVEF <25%; 82% were in INTERMACS grade 3 or 4, 10% were in the more severe grade 2, and 8% were in grade 5 or 6.

In addition, 27 were BTT patients and the other 23 were DT patients. Only three of the patients had transplants by the end of 12 months.

Of the nine patients who had died within 1 year postimplant, causes were from stroke (n=3), multiorgan failure (n=2), sepsis (n=1), and suicide, circulatory failure, and cancer (n=1 in each of the latter three types).

Other adverse events reported included sepsis occurring in eight patients in the first 6 months and in two additional patients during the second 6 months; driveline infections in five and three, respectively; ischemic stroke in four and one; hemorrhagic stroke in two and two; and right heart failure in five and zero.

"Most of the adverse events were front-loaded, with the majority occurring in the first 30 days," reported Krabatsch. "It was encouraging to see that in the second half of the year, almost all of the event rates were lower than in the first half. And there's been no right heart failure requiring inotropes after the first 6 months."

Krabatsch added that four of the six total GI bleeding events that occurred by 1 year were in the DT patients. Outflow graft thrombosis did occur in one patient at day 209, which led to ischemic stroke and death.

On the other hand, 89% of the patients were in NYHA class 1 or 2 by 1 year after implant (P<0.0001 when compared with baseline data). And there was a 219-m median improvement in 6-minute walk test from baseline to 1 year.

Exciting but Challenging Times Ahead

Teuteberg, who was not involved with this research, agreed with Goldstein's earlier comments that European device approval isn't as stringent as it is in the US. "I think in Europe they're more looking for no harm, whereas the US looks for benefit and no harm. So the number of patients needed, as well as follow-up time, is just different. It's not necessarily better or worse, just different approaches from the regulatory agencies."

That said, "I was very glad to see all the zeros listed on the screen for instances of pump thrombosis in this study," said Teuteberg. If this new iteration in continuous-flow technology can continue to show this in bigger trials, "it's going to be a big win."

"I think it's an exciting time for mechanical support," added Goldstein. "These pumps are still relatively 'dumb.' They aren't smart pumps that give us blood-pressure monitoring or a lot of the other information we'd like to have. But I think that's the next step, along with continued miniaturization and complete removal of driveline technology to a sort of WiFi, wireless technology," he said.

For now, "there's some 'wait and see' and some potentially exciting things in the works, as well as some challenges," concluded Goldstein.

The study was originally funded by Thoratec, which was bought by St Jude Medical last year. It was announced last week that Abbott will be acquiring St Jude Medical. Krabatsch reported being a heart-failure-treatment advisory board member for St Jude Medical. Goldstein reported being one of the national principal investigators for the MOMENTUM 3 study, receiving funds from Thoratec/St Jude, and being on the medical advisory board for HeartWare. Teuteberg reported being on MOMENTUM's clinical-events committee "to review any adverse events," does advisory and speaking work with HeartWare, and has received support from Abiomed.

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