Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR

Abstract

Injection of Algisyl-LVR, a treatment under clinical development, is intended to treat patients with dilated cardiomyopathy. This treatment was recently used for the first time in patients who had symptomatic heart failure. In all patients, cardiac function of the left ventricle (LV) improved significantly, as manifested by consistent reduction of the LV volume and wall stress. Here we describe this novel treatment procedure and the methods used to quantify its effects on LV wall stress and function.Algisyl-LVR is a biopolymer gel consisting of Na + -Alginate and Ca 2+ -Alginate. The treatment procedure was carried out by mixing these two components and then combining them into one syringe for intramyocardial injections. This mixture was injected at 10 to 19 locations mid-way between the base and apex of the LV free wall in patients.Magnetic resonance imaging (MRI), together with mathematical modeling, was used to quantify the effects of this treatment in patients before treatment and at various time points during recovery. The epicardial and endocardial surfaces were first digitized from the MR images to reconstruct the LV geometry at end-systole and at end-diastole. Left ventricular cavity volumes were then measured from these reconstructed surfaces.Mathematical models of the LV were created from these MRI-reconstructed surfaces to calculate regional myofiber stress. Each LV model was constructed so that 1) it deforms according to a previously validated stress-strain relationship of the myocardium, and 2) the predicted LV cavity volume from these models matches the corresponding MRI-measured volume at end-diastole and end-systole. Diastolic filling was simulated by loading the LV endocardial surface with a prescribed end-diastolic pressure. Systolic contraction was simulated by concurrently loading the endocardial surface with a prescribed end-systolic pressure and adding active contraction in the myofiber direction. Regional myofiber stress at end-diastole and end-systole was computed from the deformed LV based on the stress-strain relationship.

Efficacy of intramyocardial injection of Algisyl-LVR for the treatment of ischemic heart failure in swine

“…Regional myofiber stress was computed using a validated mathematical model, as described elsewhere in detail [26] and shown in a video [27], except for the following differences. First, the in-vivo LV geometries of the mathematical (finite element) models were based on echocardiography (the .stl-files described above) instead of MRI.…”

“…Experiments in large [16–18] and small [19–21] animals, clinical evaluations in humans [22–24], as well as computational models [25–27] have all suggested that injection of biomaterials can limit LV remodeling post MI and improve LV function. Unlike other surgical approaches that modify the size of the dilated ventricle, myocardial injection with biopolymers decreases wall stress and improves regional and global LV function [28].…”

Effect of intra-myocardial Algisyl-LVR™ injectates on fibre structure in porcine heart failure

“…The separate material components are mixed immediately before use and then combined in one syringe for delivery as direct intramyocardial injections (Lee et al, 2013b). The polymer forms solid inclusions inside the myocardial wall and achieves its final material stiffness of 3–5 kPa.…”

Biomaterial‐Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives

“…In 2013, the results from the phase I/II clinical trial pilot study for the treatment were published (NCT00847964). (26) In the trial, three patients who were also undergoing revascularisation were treated. The trial was unblinded, non-randomised and had no control.…”