1 One Year Follow-Up Results from AUGMENT-HF: A Multicenter Randomized Controlled Clinical Trial of the Efficacy of Left Ventricular Augmentation with Algisyl-LVR in the Treatment of Heart Failure* Douglas L. Mann, Randall J. Lee, Andrew J.S. Coats, Gheorghe Neagoe, Dinu Dragomir, Enrico Pusineri, Massimo Piredda, Luca Bettari, Bridget-Anne Kirwan, Robert Dowling, Maurizio Volterrani, Scott D. Solomon, Hani N. Sabbah, Andy Hinson, Stefan D. Anker on behalf of the AUGMENT-HF Investigators Disclosures: Scientific Advisory Board - Lone Star Heart, miRagen therapeutics, Lilly Corporation Consultant Bio Control Medical, Cardioxyl, Medtronic Grant Support NIH * These data will be published online in European Journal of Heart Failure following this presentation 2 Therapeutic options are limited for patients with advanced heart failure who become refractory to conventional pharmacological therapies The injection of biomaterials into diseased myocardium has been shown to reduce myofiber stress, LV wall stress, restore LV geometry and improve LV function 1,2 Algisyl is a medical device that consists of an alginate hydrogel that is injected into the midwall of the LV, where it remains as a permanent implant that is intended to reduce LV wall stress and prevent or reverse the progression of HF Results of the AUGMENT-HF 6-month primary endpoint analysis were presented at this meeting in 2014 and published earlier this summer 3 Background 1 Sabbah HN, et. al., JACC Heart Fail. 2013;1(3): Lee RJ, et. al, Int J Cardiol Jul 2;199: Anker, SD, et. al. Eur Heart J Sep 7;36(34): 3 Modified (LVR)Dilated P x R = 2h P x R = 2h R R h Mechanism of Action of Algisyl h LV Restoration & Laplaces Law 4 Placement of Alginate Hydrogel via a Limited Thoracotomy LV Restoration with Algisyl Mean procedure duration 80.5 (24.9) minutes Mean number of implants 15.5 (2.0) Mean total volume of Alginate-hydrogel 4.6 (0.6) mL 5 AUGMENT-HF Study Design & Objectives Multicenter prospective randomized clinical trial 78 Patients with moderate to severe HF that had been treated with optimal medical and/or device therapy, randomized 1:1 40 patients randomized to Algisyl implant procedure + optimal standard medical therapy (SMT) 38 patients randomized to optimal standard medical therapy alone 15 centers in Australia, Italy, Romania, Netherlands & Germany Primary Efficacy Endpoint: peak VO 2 assessed by a blinded core lab at 6 months Secondary Endpoints: peak VO 2, 6MWT, Symptoms, QOL and measures of LV remodeling (echo) at 12, 18 and 24 months Safety: clinical outcomes (MACE) adjudicated by blinded CEC 6 Inclusion criteria Written informed consent ischemic or non-ischemic HF patients who are symptomatic despite optimal evidence-based therapies for HF LVEF 35% Peak VO 2 of mL/min/kg LVEDDi 30 to 40mm/m 2 (LVEDD/BSA) Stable, evidence-based therapy for heart failure Previously reported high compliance: diuretics (99%) Beta Blockers (95%), ARBs/ACE-enzyme inhibitors (89%) and MRAs (69% ) Exclusion criteria renal, hepatic, stroke and MI status LV wall thickness < 8 mm required for implant AUGMENT-HF Key Inclusion & Exclusion Criteria 7 AUGMENT-HF Baseline Demographics Patients Completing 1-year follow-up All Patients (n=73)* All (n=59)** Control (n=33) Algisyl (n=26) Age (years)62.6 9.0 Ischemic HF42 (58%)35 (59%)20 (61%)15 (58%) Non-ischemic HF31 (42%)24 (41%)13 (39%)11 (42%) NYHA Class III/IV81%79%76%81% LVEF (%) 25.5 5.0 Peak VO 2 (mL/min/kg) 12.2 1.8 6MWT distance (m) 293 95 Mitral regurgitation (51%)27 (46%)18 (55%)9 (35%) Hypertension43 (59%)37 (63%)20 (61%)17 (65%) Diabetes29 (40%)25 (42%)15 (46%)10 (39%) Previous PCI or CABG20 (27%)17 (29%)9 (27%)8 (31%) * Modified Intention-to-Treat (mITT) population; ** 1 patient assessed by telephone only 8 Peak VO 2 - Mean Change from Baseline Algisyl was superior to SMT at 12 months with a mean treatment effect of 2.10 mL/kg/min (CI 0.963.24). Algisyl patients completed the 1 year follow-up with a mean peak VO2 of 14.0 (3.1) mL/min/kg 9 Anaerobic Threshold Mean Change from Baseline AT is independent of patient motivation or effort. Algisyl was superior to SMT with a mean treatment effect of 2.34 mL/kg/min (CI 1.353.32) at 12 months (p