AUGMENT-HF: LV augmentation improves HF symptoms, functional capacity

NATIONAL HARBOR, Md. — A novel device for treatment of advanced HF administered in addition to optimal medical therapy improved symptoms, exercise time and performance and 6-minute walk test results compared with optimal care alone, researchers reported at the Heart Failure Society of America Annual Scientific Meeting.

In the prospective, multicenter AUGMENT-HF trial, researchers randomly assigned 78 patients with moderate-to-severe HF at a 1:1 ratio to optimal standard medical care alone (n = 38) or optimal medical therapy in addition to treatment with Algisyl (LoneStar Heart).

Algisyl consists of an alginate hydrogel injected as a permanent implant into the midwall of the left ventricle via limited thoracotomy and is intended to increase LV wall thickness, reduce wall stress and prevent or reverse HF progression, researcher Douglas L. Mann, MD, chief of cardiology at Washington University School of Medicine in St. Louis, said during a presentation.

Douglas L. Mann

Patients were enrolled from 15 centers throughout Europe and Australia. All patients had LV ejection fraction of 35% or lower, LV wall thickness of 8 mm or greater and peak VO₂ of 9 mL/min/kg to 14.5 mL/min/kg at baseline, and they exhibited persistent symptoms despite prior treatment with optimal medical and/or device therapy before enrollment.

The primary efficacy endpoint was peak VO₂ at 6 months, with secondary endpoints including HF symptoms, 6-minute walk test results and cardiac function during follow-up.

At 6 months, the Algisyl group had a greater adjusted mean peak VO₂ (13.5 mL/min/kg vs. 12.2 mL/min/kg; P = .014). Patients in the Algisyl group also exhibited a 1-minute improvement in total exercise time (P = .001) and a peak workload increase of 10.2 W (P < .001) compared with the optimal medical therapy group. Six-minute walk test results also improved in the Algisyl group, with a treatment effect on median walk distance of 141 m compared with the standard care group (P < .001).

Mann noted that significantly more patients in the Algisyl group had a NYHA class of I or II than in the optimal medical therapy group (84% vs. 26%; OR = 30.2; 95% CI, 5.7-160.5 for improvement by one class).

Three patients died within 30 days of follow-up, for a mortality rate of 8.57%, meeting the primary safety endpoint for the trial, Mann said. Incidence of total adverse events at up to 6 months was significantly higher in the Algisyl group (77% of patients vs. 45%; HR = 3.41; 95% CI, 1.87-6.22), with a trend toward significantly increased risk for serious events (40% vs. 26%; HR = 2.08; 95% CI, 0.94-4.6).

Major adverse cardiac events occurred at similar rates between the groups (27.5% of patients for Algisyl vs. 26.3% for standard medical therapy). However, Mann said, the Algisyl group had lower event rates if events occurring during index hospitalization were excluded (17.5% vs. 26.3%). In particular, incidence of worsening HF was lower in the Algysil group compared with the standard treatment group (10% of patients vs. 21.1%). Mann also noted that fewer patients in the Algisyl group required HF-related hospitalization during 12 months of follow-up.

“Algisyl injections can be administered safely in patients with advanced HF, with an acceptable 30-day postoperative morbidity and mortality,” he said. “We believe that this study provides proof of concept for LV restoration with Algisyl as a potential novel therapy for patients with advanced HF.” Mann added that long-term follow-up data for the cohort will be presented during the American Heart Association Scientific Sessions.

Reference:

Mann DL, et al. Late-Breaking Clinical Trials. Presented at: Heart Failure Society of America Annual Scientific Meeting; Sept. 26-29, 2015; National Harbor, Md.

Disclosure: Mann reports serving on scientific advisory boards for Lilly Corp., LoneStar Heart and Miragen Therapeutics, consulting for Bio Control Medical, Cardioxyl, Janssen and Medtronic and receiving grant support from the NIH.