Intra-myocardial alginate hydrogel injection acts as a left ventricular mid-wall constraint in swine.

Autor: Sack KL; Division of Adult Cardiothoracic Surgery, Department of Surgery, University of California at San Francisco, Box 0118, UC Hall Room U-158, San Francisco, CA, United States; Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa., Aliotta E; Department of Radiological Sciences, University of California, Los Angeles, California, USA., Choy JS; California Medical Innovations Institute, Inc., San Diego, California, USA., Ennis DB; Department of Radiological Sciences, University of California, Los Angeles, California, USA., Davies NH; Cardiovascular Research Unit, Department of Surgery, University of Cape Town, Cape Town, South Africa., Franz T; Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa; Bioengineering Science Research Group, Engineering Sciences, Faculty of Engineering and the Environment, University of Southampton, Southampton, UK., Kassab GS; California Medical Innovations Institute, Inc., San Diego, California, USA., Guccione JM; Division of Adult Cardiothoracic Surgery, Department of Surgery, University of California at San Francisco, Box 0118, UC Hall Room U-158, San Francisco, CA, United States. Electronic address: julius.guccione@ucsf.edu.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2020 Jul 15; Vol. 111, pp. 170-180. Date of Electronic Publication: 2020 May 16.
DOI: 10.1016/j.actbio.2020.04.033
Abstrakt: Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge about the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To identify the mechanism of action, we examined previously unobtainable measurements of cardiac function from in vivo, ex vivo, and in silico states of clinically relevant heart failure (HF) in large animals. High-resolution ex vivo magnetic resonance imaging and histological data were used along with state-of-the-art subject-specific computational model simulations. Ex vivo data were incorporated in detailed geometric computational models for swine hearts in health (n = 5), ischemic HF (n = 5), and ischemic HF treated with alginate hydrogel injection therapy (n = 5). Hydrogel injection therapy mitigated elongation of sarcomere lengths (1.68 ± 0.10μm [treated] vs. 1.78 ± 0.15μm [untreated], p<0.001). Systolic contractility in treated animals improved substantially (ejection fraction = 43.9 ± 2.8% [treated] vs. 34.7 ± 2.7% [untreated], p<0.01). The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as an LV mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated HF controls without causing negative secondary outcomes to cardiac function. STATEMENT OF SIGNIFICANCE: Heart failure is considered a growing epidemic and hence an important health problem in the US and worldwide. Its high prevalence (5.8 million and 23 million, respectively) is expected to increase by 25% in the US alone by 2030. Heart failure is associated with high morbidity and mortality, has a 5-year mortality rate of 50%, and contributes considerably to the overall cost of health care ($53.1 billion in the US by 2030). Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge concerning the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To understand the mechanism of action, we combined high-resolution ex vivo magnetic resonance imaging and histological data in swine with state-of-the-art subject-specific computational model simulations. The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as a left ventricular mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated heart failure controls without causing negative secondary outcomes to cardiac function. Moreover, if the hydrogel can be delivered percutaneously rather than via the currently used open-chest procedure, this therapy may become routine for heart failure 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.
(Copyright © 2020. Published by Elsevier Ltd.)
Databáze: MEDLINE
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