Heart failure (HF) is a worldwide epidemic that contributes considerably to the overall cost of health care in developed nations. The number of people afflicted with this complex disease is increasing at an alarming pace—a trend that is likely to continue for many years to come. Over 1 million Americans suffer a myocardial infarction (MI) each year and many experience post-MI left ventricular (LV) remodeling, which manifests as progressive changes in LV structure and function. Post-MI LV remodeling is responsible for nearly 70% of all HF cases. Reduction of LV wall stress is considered a cornerstone in the treatment of HF. There are currently no reliable means to directly measure wall stresses in the intact LV. Thus, we rely on FE models, using LS-DYNA, to predict these stresses, knowing that the predictions cannot be validated directly, albeit we can validate deformations. To make our work more accessible to other researchers we are willing to help convert our models to freely available FE software like Continuity (http://www.continuity.ucsd.edu/) and FEBio (https://febio.org/).

A novel promising therapy for HF using intramyocardial injections of alginate to de-stress the heart based on a “micro-LVAD” (LV assist device) mechanism of action was designed computationally, validated pre-clinically, and then validated clinically in the AUGMENT-HF international prospective multi-center trial. The overall goal of our proposed research is to optimize a therapy for HF that involves percutaneous injection of an alginate hydrogel (Algisyl) in the failing myocardium.

We developed a novel percutaneous large animal (swine) model of ischemic HF. By preconditioning coronary arteries using balloon inflation prior to placing embolism coils two weeks apart, we reduced swine mortality to 10% and generated a realistic model of ischemic cardiomyopathy in large coronary arteries similar to those in patients. Treatment of HF with Algisyl, even without coronary artery bypass grafting (CABG), resulted in sustained improvement of LV contractile function with reduced LV volume. Our method for automatically optimizing intramyocardial injections for treating HF strongly suggests LV contractile function will be further improved if stiffer implants are placed in chronically infarcted LV regions. Additionally, our method for simulating the progression of HF8 strongly suggests that delivering Algisyl in the borderzone of acutely infarcted LV regions can prevent HF progression.

Our studies support the exciting concept that the injection of inert material into the LV free-wall (with or without CABG) is an effective strategy for inducing LV reverse remodeling that improves LV function and results in decreased myofiber stress. Moreover, if this therapy can be delivered percutaneously rather than via the currently used open-heart procedure, this therapy may become revolutionary for HF treatment. A minimally invasive procedure would be in the best interest of this patient population (i.e., one that cannot tolerate general anesthesia and surgery) and it would be significantly more cost effective than surgery.

We have developed a novel suction-based catheter device that accurately and precisely delivers the material into the LV subendocardium and prevents any potential embolization of the Algisyl in the ventricle. Our catheter device latches onto the endocardium using a suction cup to ensure injections at the needed sites. This innovation makes it possible to inject material endocardially into the heart wall percutaneously (including the interventricular septum) through a femoral artery access. Furthermore, this approach allows us to test a pre-emptive or preventative strategy for treating acute MI so that ischemic HF does not develop.