AUGMENT-HF: Novel implantable device safe, effective in patients with advanced HF

CHICAGO — A novel implantable device was administered safely and associated with clinical benefit in patients with advanced HF, according to phase 2 trial data presented at the American Heart Association Scientific Sessions.

Researchers studied the safety and efficacy of an alginate hydrogel (Algisyl-LVR, LoneStar Heart Inc.) that is injected into the midwall of the left ventricle of patients with dilated LV, where it remains as a permanent implant intended to reduce LV wall stress and prevent or reverse the progression of HF.

Previous research has demonstrated the benefit of injecting biomaterials into diseased myocardia of animals and a phase 1 study of alginate hydrogel showed significant improvements in cardiac function and reverse LV remodeling at 3 months in patients with symptomatic HF undergoing CABG, Douglas L. Mann, MD, chief of the cardiovascular division, Lewin Chair and professor of medicine at Washington University School of Medicine and cardiologist-in-chief at Barnes Jewish Hospital, St. Louis, said during a presentation.

Douglas L. Mann

For the phase 2 AUGMENT-HF trial, Mann and colleagues randomly assigned 78 patients with advanced HF (mean age, 62.3 years; 85% men) to the alginate hydrogel implant or to remain on optimal medical therapy. All patients were symptomatic, had ejection fraction ≤35%, had peak oxygen level of 9 mL/min/kg to 14.5 mL/min/kg, had LV end-diameter diastolic index 30 mm/m² to 40 mm/m² and had LV wall thickness ≥8 mm.

The primary efficacy endpoint was peak maximum oxygen consumptionat 6 months. The primary safety endpoint was 30-day mortality.

Compared with those assigned the usual care, patients assigned the alginate hydrogel implant had higher peak maximum oxygen consumption (13.2 mL/min/kg vs. 12.4 mL/min/kg; P<.014) and a greater change in mean peak maximum oxygen consumption from baseline (0.8 mL/min/kg vs. –0.2 mL/min/kg; P<.014) at 6 months, according to Mann, a member of the Cardiology Today Editorial Board.

The implant group also had a greater improvement in 6-minute walk test (84.7 m vs. –15.4 m; P<.001) and a greater rate of improvement in NYHA class (P<.001) compared with controls at 6 months, he said.

There were three deaths in the implant group within 30 days of implantation (8.57%); the prespecified estimate was 5% with a 95% CI of 1.8 to 23.06, provided there were fewer than four deaths observed within 30 days, according to Mann. “Based upon the prespecified data analysis plan, the primary safety endpoint of AUGMENT-HF was met,” he said.

The implant group had more adverse events than the control group at 6 months (HR=3.41; 95% CI, 1.87-6.22), but that was to be expected given that the implant group underwent surgery and the control group did not, Mann said. He noted that the difference in serious adverse events was not statistically significant (HR=2.08; 95% CI, 0.94-4.6).

“The results of the AUGMENT-HF trial demonstrated that Algisyl can be administered safely in an advanced HF patient population, with an acceptable 30-day postoperative morbidity and mortality. Treatment with Algisyl provides and improvement in functional capacity and HF symptoms when compared to patients who are treated with optimal medical management alone,” Mann said, noting that future studies will assess long-term benefits. “This study provides proof of concept for LV reconstruction with Algisyl as a potential novel new therapy for patients with advanced HF.” – by Erik Swain

For more information:

Mann DL. CS.02: Off the Beaten Pathologies. Presented at: American Heart Association Scientific Sessions; Nov. 15-19, 2014; Chicago.

Disclosure: The study was funded by LoneStar Heart. Mann reports serving on scientific advisory boards for Eli Lilly, LoneStar Heart and Miragen Therapeutics, consulting for Bio Control Medical, Cardioxyl, Janssen Pharmaceuticals and Medtronic, and receiving grant support from the NIH.