Algisyl-LVR™ with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart

Abstract

Background: Left ventricular (LV) wall stress reduction is a cornerstone in treating heart failure. Large animal models and computer simulations indicate that adding non-contractile material to the damaged LV wall can potentially reduce myofiber stress. We sought to quantify the effects of a novel implantable hydrogel (Algisyl-LVR™) treatment in combination with coronary artery bypass grafting (i.e. Algisyl-LVR™+CABG) on both LV function and wall stress in heart failure patients.

Methods and results: Magnetic resonance images obtained before treatment (n=3), and at 3 months (n=3) and 6 months (n=2) afterwards were used to reconstruct the LV geometry. Cardiac function was quantified using end-diastolic volume (EDV), end-systolic volume (ESV), regional wall thickness, sphericity index and regional myofiber stress computed using validated mathematical modeling. The LV became more ellipsoidal after treatment, and both EDV and ESV decreased substantially 3 months after treatment in all patients; EDV decreased from 264 ± 91 ml to 146 ± 86 ml and ESV decreased from 184 ± 85 ml to 86 ± 76 ml. Ejection fraction increased from 32 ± 8% to 47 ± 18% during that period. Volumetric-averaged wall thickness increased in all patients, from 1.06 ± 0.21 cm (baseline) to 1.3 ± 0.26 cm (3 months). These changes were accompanied by about a 35% decrease in myofiber stress at end-of-diastole and at end-of-systole. Post-treatment myofiber stress became more uniform in the LV.

Conclusions: These results support the novel concept that Algisyl-LVR™+CABG treatment leads to decreased myofiber stress, restored LV geometry and improved function.

Keywords: Congestive heart failure; Coronary artery bypass grafting; Dilated cardiomyopathy; Left ventricular wall stress; Magnetic resonance imaging; Mathematical modeling.

Fig. 1

Schematic of Algisyl-LVR™ injection in the left ventricle. (A) Short-axis view of the mid-ventricle, half way between the apex and base. (B) Algisyl-LVR™ (0.3 cc each) injected at 10 to 15 locations at the mid-ventricle free wall (excluding the septum).

Fig. 2

Long-axis view of the MRI in 3 patients at (a) end-systole and at (b) end-diastole.

Fig. 3

Effects of injection on left ventricle (LV) regional wall thickness. (a) LV average wall thickness at different time points. Cross-shaded: Patient 1, diagonally-shaded: Patient 2, dot-shaded: Patient 3 and plain-shaded: average. Average is shown with standard deviation. (b) Long-axis view of magnetic resonance image (MRI) at baseline (left) and at 6 months (right) from Patient 1 at end-of-systole. (c) Top: cross-section view of LV at baseline (left) and 6 months (right). Bottom: measured regional LV wall thickness based on the MRI-reconstructed LV of Patient 1. Thickness (cm) is indicated by the color shown on LV endocardium.

Fig. 4

Global LV performance indicator. (a) End-diastolic volume, (b) End-systolic volume, (c) Ejection fraction, (d) Sphericity index at baseline, 3 and 6 months post-treatment. Cross-shaded: Patient 1, diagonally-shaded: Patient 2, dot-shaded: Patient 3 and plain-shaded: average. Average is shown with standard deviation.

Fig. 5

Effects of treatment on myofiber stress. (a) Volumetric-averaged end-diastolic stress. (b) Volumetric-averaged end-systolic stress. (c) Peak end-systolic stress. (d) End-systolic regional myofiber stress distribution of Patient 1 LV at baseline (left) and 6 months after surgery (right). LV epicardium is displayed in white.