Rationale – Heart failure is a healthcare epidemic to which coronary heart disease contributes significantly, and for which there is limited number of therapeutic options. Progressive thinning and dilation of the left ventricle (LV) increases wall stress and myocardial oxygen consumption. Injectable biopolymers implanted in the myocardial wall have been proposed to increase wall thickness and to reduce chamber volume, and hence, decrease wall stress and improve cardiac function. Objective – The purpose of this study was to evaluate the efficacy of a biopolymer (Algisyl-LVR) to reverse or prevent LV remodeling in a swine model of ischemic heart failure (IHF). Methods and Results – IHF was induced in 11 swine by occluding the marginal obtuse branches of the left circumflex artery. Algisyl-LVR was injected 8 weeks after into the LV myocardial free wall in 5 of the 12 animals. The animals were followed up for 8 additional weeks. Echocardiographic examinations were made every two weeks. Within 8 weeks of treatment, the ejection fraction increased from 30.5%±7.7% to 42.4%±3.5% (treated group) vs. 37.3%±3.8% to 34.3%±2.9% (control), p<0.01. Stroke volume increased from 18.5±9.3 mL to 41.3±13.3 mL (treated group) vs. 25.4±2.3 mL to 31.4±5.3 mL (control), p<0.05. Wall thickness in end-diastole of the infarcted region changed from 0.69±0.06 cm to 0.81±0.13 cm (treated group) vs. 0.73±0.09 cm to 0.68±0.11 cm (control), p<0.05. Sphericity index remained almost unchanged after treatment, 0.57±0.05 to 0.56±0.07 (treated group) vs. 0.67±0.08 to 0.69±0.11 (control), although differences were found at the end of the study between both groups (p<0.001). End-systolic myofiber stress changed from 28.4±9.6 kPa to 17.3±6.1 kPa (treated group) vs. 25.5±7.1 kPa to 28.4±5.8 kPa (control), p<0.05. Conclusions – Algisyl-LVR is an effective strategy that serves as a micro-LV assist device to reduce stress and hence prevent or reverse maladaptive cardiac remodeling and myocardial dysfunction caused by IHF in swine.
|Choy JS, Leng S, Acevedo-Bolton G, Shaul S, Guo X, Zhong L, Guccione JM, Kassab GS. Efficacy of Intramyocardial Injection of Algisyl-LVR for the treatment of Ischemic Heart Failure in Swine. (Under Review in Circulation Research) (2017)|
|Sack KL, Aliotta E, Choy JS, Franz T, Ennis DB, Kassab GS, Guccione JM. Intra-Myocardium Alginate Biomaterial Injection Preserves Tissue Structure in the Porcine Heart. (under review in JACC: Basic to Translational Science) (2017)|
Using Diffusion Tensor MRI in ex-vivo Porcine hearts, we find that the injection of Algisyl does not significantly affect myofiber orientation or tissue structure.