Transcatheter endomyocardial alginate-hydrogel injection for treatment of heart failure

Abstract

Abstract Background and Aim Intramyocardial injection of alginate-hydrogel, an emerging and promising strategy for patients with advanced heart failure (HF), is limited by the paucity of commercially available intramyocardial delivery methods. This study investigates the feasibility and safety of a novel X-DROP catheter injection system (Figure 1) for delivery of the alginate-hydrogel to pre-defined target areas in the treatment of HF with reduced ejection fraction. Methods and results Prior to the First-in-man, we demonstrated that transcatheter endo-myocardial alginate-hydrogel implantation (TEAi) was successfully and precisely performed with the X-DROP catheter system under TEE and fluoroscopy guidance in a healthy porcine model (Figure 2). Acute animal results (n = 15) showed no mortality, perforation, and sustained ventricular arrhythmias. Gross examination revealed the retention of the alginate-hydrogel in the pre-defined endocardial area at six months post-procedure (n = 4, Figure 2). The histological assessment showed that alginate-hydrogel was encapsulated by multiple layers of fibrosis without causing damage to the nearby myocardium. Expanding from the animal result, we conducted a first-in-human trial to evaluate the TEAi in patients with heart failure. Ten patients with NYHA class III-IV were enrolled, and all patients were successfully treated with TEAi without the device or procedure-related complications. At the 30-day follow-up, there were no serious adverse device events. One death occurred at a 3-month follow-up. The mean LVEF evaluated by MRI improved from 17.7±3.82 % at baseline to 24.94±11.15 % at 6 months post-procedure (p = 0.046). Also, ESV (297.50±67.85 vs 264.79±101.41, p = 0.029), EDV (359.5±71.92 vs 341.56±67.85, p = 0.105), six minutes walking test (339.7±37.6 m vs 370.4±64.8 m, p = 0.184), NYHA functional class (30% Class III and 70% Class IV vs 100% Class II), and KCCQ score (49.7±3.91 vs 79.0±8.1) were improved at 6-month follow-up. Holter monitor data showed no sustained ventricular arrhythmia during the TEAi or follow-up. Conclusions Our results established the safety and feasibility of TEAi using a novel platform, the X-DROP system and paved the way for the clinical application of intramyocardial injection of alginate-hydrogel in patients with HF.Figure 1Figure 2