A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial)

Abstract

Aims: AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel.

Methods: Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety.

Results: Enrolled patients were 63 ± 10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26 ± 5% and a mean peak VO2 of 12.2 ± 1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months-treatment effect vs.

Control: +1.24 mL/kg/min (95% confidence interval 0.26-2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001).

Conclusion: Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial.

Trial registration number: NCT01311791.

Keywords: Advanced chronic heart failure; Alginate-hydrogel; Exercise capacity; Safety; Symptoms.

Figure 1

Algisyl-LVR implantation. Standardization of the placement of the implants at the mid-ventricular level identified as the halfway point between the left ventricular base (defined as the atrioventricular groove) and apex (A). The implants are equally spaced in the mid-myocardium starting at the antero-septal groove and ending at the postero-septal groove (B). Note: alginate-hydrogel (LoneStar Heart, Inc., Laguna Hills, CA, USA) is a proprietary calcium-alginate-hydrogel that consists of two components: an Na⁺-alginate component supplied as a sterile aqueous solution with 4.6% mannitol and a Ca²⁺-alginate component consisting of water insoluble particles suspended in a sterile 4.6% mannitol solution. These two components are mixed immediately before use, and then combined in one syringe for delivery as intra-myocardial injections. Alginate-hydrogel is administered during a surgical procedure. A left thoracotomy is performed to expose the heart and the pericardium. The left ventricular free wall was identified and the injection sites marked with a surgical marker. In total, 10–19 intra-myocardial injections were made on the beating heart, circumferentially, at the left ventricular mid-ventricular level halfway between the left ventricular apex and base starting at the antero-septal groove and ending at the postero-septal groove. Left ventricular wall thickness must not have been <8 mm at the locations where the alginate-hydrogel was to be injected. The total number of injections administered for an individual patient depended on the size of the heart (amount of space available on the LV-free wall). All injections were made along or within ∼1 cm of a single mid-ventricular line, being careful to avoid any visible coronary vasculature. Standardization of the placement of the implants was performed via the identification of standard anatomical features (atrioventricular groove and apex). Injections of 0.3 mL of alginate-hydrogel were separated by ∼0.5–1 cm and made at the mid-wall depth of the myocardium.

Figure 2

(A) Peak VO₂ at 6 months: mean change (from baseline). (B) Peak watts at 6 months: mean change (from baseline). (C) Maximum exercise time at 6 months: mean change (from baseline). Control, standard medical therapy; SE, standard error; P-value, (adjusted) mean product effect.

Figure 3

Six-minute walk test distance at 6 months. Control, standard medical therapy; 6MWT, 6-min walk test.

Figure 4

New York Heart Association functional class at 6 months. Control, standard medical therapy; n, number of available values.

Figure A1

Consort diagram.