ROADMAP: Long-term LVAD Implant in Ambulatory HF Shows Benefit, Also Risks

NICE, FRANCE — Functionally limited heart-failure patients who received a left ventricular assist device (LVAD) as destination therapy had significantly improved survival and functional status at 12 months when compared with similar patients treated with optimal medical therapy alone^[1].

While there were also improvements in health-related quality of life and a reduction in the severity of depression, the researchers did observe an increased risk of adverse events with LVAD therapy, including an increased risk of ischemic stroke.

"There were more adverse events in the LVAD arm, but these patients were sicker than the optimal-medical-therapy group," said lead investigator Dr Jerry Estep (Methodist DeBakey Heart and Vascular Center, Houston, TX). "With an observational study like this, when you're examining how patients are treated in a real-world case scenario, we noted that a greater percentage of patients receiving the LVAD up front had shortness of breath at rest, a greater percentage had worse quality of life, and [they also had] a higher severity of depression."

To heartwire from Medscape, Estep said a composite adverse event, one that included bleeding, infection of the LVAD driveline, pump thrombus, stroke, arrhythmias, and worsening heart failure was significantly higher in the 97 patients who received the LVAD (HeartMate 2, Thoratec) compared with the 103 patients who received medical therapy. He pointed out, though, that fewer patients in the LVAD arm had worsening heart failure.

"Overall, the adverse-event rate was less in the medical-management arm, yet despite this, patients supported by LVADs had a greater improvement in quality of life and a greater improvement in the severity of their depression," he said. "This is in the face of the adverse events. I think that positions us as heart-failure specialists to carefully weigh benefits vs risks in a patient population where LVADs haven't been widely adopted."

Mapping Out Risks and Benefits

The observational study, known as the ROADMAP trial, was presented this week here at the International Society for Heart and Lung Transplantation 2015 Scientific Sessions (ISHLT).

The study, which is reflective of an advanced HF cohort, included NYHA class 3 or 4 patients with a left ventricular ejection fraction (LVEF) <25%. In addition, the patients had been hospitalized at least once in the past year for HF and had a baseline 6-minute-walk test of at least 300 m. In the LVAD arm, a significantly larger percentage of patients had NYHA class 4 HF and were classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 4 at baseline. All patients met the US Food and Drug Administration (FDA) indications for LVAD destination therapy.

"Importantly, what distinguishes this advanced heart-failure cohort from end-stage, sicker patients is that they were not dependent on intravenous inotropic support," said Estep. "They were outpatients, they were ambulatory, but they had shortness of breath at rest or with minimal exertion. It's a patient population that largely hasn't been implanted with a permanent LVAD. There has been little adoption in this patient profile."

In total, 103 patients received guideline-optimized medical therapy and 97 received the LVAD as destination therapy. The primary end point—a composite end point that included survival at 12 months and an increase in the 6-minute-walk test of at least 75 m—occurred in 39% of patients treated with an LVAD and 21% of those who received optimal medical therapy (P=0.017).

Regarding secondary end points, as noted, there were significant improvements in quality of life and depression scores among those who received LVAD destination therapy. In addition, 68% of LVAD-treated patients had an improvement of at least 1 NYHA functional class compared with 20% of patients treated with medical therapy.

Adverse Events at 12 Months

Estep said that in this patient population, the purpose of an LVAD as destination therapy is ultimately to improve quality of life and functional capacity. For that reason, the researchers included survival combined with quality of life as an end point. That said, he noted that survival alone on original therapy was 64% in the optimal-medical-therapy arm and 80% in the LVAD arm at 12 months, a statistically significant difference.

"Patients who received an LVAD had a greater chance of living longer on original therapy, had an improvement in their 6-minute-walk distance, and felt better," said Estep.

On the whole, the ROADMAP investigators say the results of the trial are hypothesis-generating, given the observational nature of the study. A more accurate assessment of the risks and benefits of LVAD as destination therapy in this patient population will emerge with a randomized, controlled clinical trial testing the two treatment options.

ROADMAP was sponsored by Thoratec. Estep reports grant/research support and serving as a consultant to Thoratec.

Heartwire from Medscape © 2015  Medscape, LLC

Cite this: ROADMAP: Long-term LVAD Implant in Ambulatory HF Shows Benefit, Also Risks - Medscape - Apr 17, 2015.