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

The overall goal of the following experiment is to use patient specific mathematical models to quantify the effects on myofiber stress after injection therapy using an alginate hydrogel alge cell LVR, this is achieved by first identifying the left ventricular free wall halfway between the apex and base for implantation of the hydrogel. As a second step inject 0.3 ccs of the hydrogel slowly in one uninterrupted motion at 10 to 19 sites along the mid ventricular level. This thickens the left ventricular free wall.

Next, a patient specific mathematical model of the left ventricle is constructed using MRI images from before and after injection. In order to quantify the effects of the hydrogel injection therapy on myofiber stress results show ventricular myofiber stress is reduced over time by the addition of the Alger CIL LVR hydrogel. The main advantage of this technique over existing methods such as Laplace's Law for estimating ventricular wall stress, is we can take into account the fiber structure of the left ventricular wall and make predictions of stress components in the local muscle fiber direction.

Demonstrating the procedure will be Dr.Swan Lee, a postdoctoral scholar here in the Department of Surgery. To begin this procedure, access the heart through standard sternotomy. During the procedure, the heart should remain beating and no cardiopulmonary bypass is required.

Once access to the heart has been created, identify the free wall of the left ventricle at the mid ventricular level, which is halfway between the apex and base of the heart. Next, mark the location for intra myocardial injections of algin hydrogel. Using a surgical marker, make as many as 10 to 19 markings along a single line, one centimeter apart, starting at the interseptal groove and ending at the postero septal groove At the mid ventricular level right before use, mix the alge cell LVR together by combining a sterile solution of sodium alginate at 2%weight per volume in 6%mannitol with sterile calcium alginate that is suspended as insoluble particles.

Also in 4.6%Mannitol pass the solutions back and forth between two syringes five times to mix the alternate hydrogel. Once the hydrogel is thoroughly mixed, angle the tip of the syringe. In order to make it easier to inject the mixture in the intra myocardial space, two minutes after the initial mixing of the gel, insert the needle at a 45 degree angle and inject 0.3 ccs of the mixture at a rate of 0.1 cc per second.

If the needle becomes clogged at any time, remove and replace the needle. Continue to inject the mixture into each location on the wall of the left ventricle that was previously mapped. Each syringe contains enough hydrogel solution for use at four to five implant sites.

As many as five hydrogel preparations may be needed depending on the size of the left ventricle. To begin the digitization of the left ventricle for analysis, first, obtain the short and long axis MRIs containing images of the left ventricle using freely available software, nevus lab and its contour segmentation object library. Digitize the endocardial surface and epicardial surface of the left ventricle, contour the endocardial and epicardial boundaries found in the short axis and long axis views of the MRIs containing the left ventricle.

The points of the epicardium and endocardium are then automatically generated in 3D space. Then import the 3D points into commercially available software called rapid form using a function called insert import. Finally output the surfaces as initial graphics, exchange specifications or iiss surfaces.

The next step in this process is to import the iiss surfaces into commercially available software called true grid in order to create a finite element mesh of the left ventricle. Using the true grid software fill the space between the endocardial and epicardial surface with an eight node tri linear brick element. In general, a mesh containing about 3000 elements with three elements through the wall.

Thickness is sufficient to model the left ventricle to quantify left ventricular stress using the finite element method with ls, Dyna import the input deck as a K file from Truegrid into closer and in-house. Software available upon request closer will automatically assign the prescribed myofiber direction in each element as a vector. Next, write the boundary conditions and assign the myocardial material model to the elements imported from truegrid.

First, impose nodal displacement at the left ventricle base with the keyword SPC in Sina. The nodes in the epicardial basal ring are fixed and the rest of the nodes at the LV base are constrained to move only on the basal plane. Next, assign a constitutive law or stress train relationship to all the elements using the keyword mat with material identity.

1 28 in Elaina then impose pressure as boundary conditions with the keyword load underscore segments on the elemental surfaces. Defining the endocardial surface. Also define a pressure time load curve using the keyword define underscore curve to simulate the end of diastole.

Prescribe a pressure that increases rapidly with time to a prescribed end diastolic pressure of 20 millimeters.Mercury. The pressure is kept constant at the end. Diastolic pressure and sufficient time is then allowed for the left ventricle to reach steady state.

Next, simulate the end of systole by prescribing a pressure that increases rapidly with time from the end diastolic state until a prescribed end systolic pressure of 125 millimeters. Mercury is achieved. The pressure is kept constant at the systolic pressure and sufficient time is then allowed for the left ventricle to reach steady state.

Then import the completed input deck into the commercial finite element solver LS dyna in order to compute the ventricular wall stresses and the left ventricle cavity volume At end of diastole and at end of systole, finally adjust the material parameters reflecting the passive stiffness and the contractility of the myocardium. Continue adjusting until the computed LV cavity volume matches. The MRI measured volume at end of diastole and end of systole shown here are the baseline and six month post-op MRIs of a patient's heart who underwent algi cell LVR injection treatment.

The arrows indicate the locations of the patient's left ventricle and chose a dramatic reduction in the overall left ventricle size systolic and diastolic stresses calculated. Using this model provide a means to quantitatively measure ventricular improvement, non-invasively over time six months post-injection. This subject has seen both a thickening of the ventricular wall as well as a dramatic decrease in wall stress as indicated by the blue color.

After watching this video, you should have a good idea of how algi cell LVR injection therapy is carried out and how left ventricular MyFi stress distributions are calculated in vivo using patient specific mathematical modeling.