Preclinical Assessment of Cardiac Valve Substitutes: Current Status and Considerations for Engineered Tissue Heart Valves

Zhang, Benjamin L.; Bianco, Richard W.; Schoen, Frederick J.

doi:10.3389/fcvm.2019.00072

Cited by 50 publications

(31 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three key functional parameters, i.e., EOA, pressure gradient, and peak jet velocity, were calculated to assess the hydrodynamic performances of BHV. All three parameters are important indicators for the clinical assessment of aortic valve stenosis severity 28,[59][60][61] . Although the baseline hydrodynamic performances of unimplanted BHV in pulse simulators have been repeatedly reported [62][63][64] , to the best of our knowledge, we are the first to evaluate the hydrodynamic performances of BHV following in vitro incubations that simulate AGE formation observed in clinical explants.…”

Section: Discussionmentioning

confidence: 99%

“…The pressure was adjusted via the Systemic Mean Pressure Control knob. All BHVs were subjected to physiological conditions for the aortic position as per ISO-5840 28 and FDA Replacement Heart Valve Guidance (heart rate at 70 BPM; temperature at 37°C; flow rate at 5L/min; Systolic and diastolic pressures at 110/80 ± 5 mmHg; mean pressure at 95 ± 5 mmHg; systolic duration at 35 ± 5%). Flow, ventricle pressure, and aortic pressure were measured using a transonic sensor (Transonic Systems, Ithaca, NY, USA) and pressure sensors (BDC Laboratories), respectively 29 .…”

Section: Patient Population (Supplementalmentioning

confidence: 99%

See 1 more Smart Citation

Glycation and Serum Albumin Infiltration Contribute to the Structural Degeneration of Bioprosthetic Heart Valves

Frasca

Xue

Kossar

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Bioprosthetic heart valves (BHV) are widely used to treat heart valve disease but are fundamentally limited by structural valve degeneration (SVD). Non-calcific mechanisms of SVD entirely account for approximately 30% of SVD cases and contribute to calcific SVD but remain understudied. Glycation mechanisms have not been previously associated with SVD, despite being established as degenerative in collagenous native tissues. Objectives:To determine whether blood component infiltration-based glycation and concomitant human serum albumin (HSA) deposition contribute mechanistically to SVD.Methods: Immunohistochemistry (IHC) was used to identify advanced glycation end-products (AGEs) and serum albumin accumulation in 45 aortic valve BHV explanted due to SVD, glutaraldehyde-treated bovine pericardium (BP) incubated in vitro in glyoxal and HSA, and rat subcutaneous BP implants. Structural impacts of glycation-related mechanisms were evaluated by second harmonic generation (SHG) collagen imaging. Hydrodynamic effects of valve glycation and concomitant HSA exposure were studied with an ISO-5840-compliant pulse duplicator system using surgical grade BHV.Results: All 45 clinical explants and in vitro-incubated BP demonstrated accumulated AGE and HSA compared to un-implanted, un-exposed BHV. SHG revealed instigation of collagen malalignment similar to that in SVD explants by glycation and HSA infiltration. Rat subdermal explants also showed AGE and serum albumin accumulation. Pulse duplication demonstrated significantly reduced orifice area and increased pressure gradient and peak fluid velocity following glyoxal and HSA incubations. Conclusions:Glycation and concomitant HSA infiltration occur in clinical BHV and contribute to structural and functional degeneration of leaflet tissue, thus representing novel, interacting mechanisms of BHV SVD.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Patient Population (Supplementalmentioning

confidence: 99%

Glycation and Serum Albumin Infiltration Contribute to the Structural Degeneration of Bioprosthetic Heart Valves

Frasca

Xue

Kossar

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Heart valve prosthesis are designated as high-risk medical devices, requiring rigorous in-vitro and in-vivo safety, efficacy and/or performance studies 24 . The use of standardized animal models for preclinical testing is thereby essential to provide invaluable information on the device safety.…”

Section: Discussionmentioning

confidence: 99%

Computed Tomography-based evaluation of porcine cardiac dimensions to assist in pre-study planning and optimized model selection for pre-clinical research

Lipiski¹,

Eberhard²,

Fleischmann³

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Hatem Alkadhi 2 & nikola cesarovic 1,7 the pig (Sus Scrofa Domestica) is an accepted model for preclinical evaluation of prosthetic heart valves and trans-catheter implantation techniques. Understanding porcine cardiac dimensions through threedimensional computed tomography (ct), increases preclinical study success, leading to higher cost efficiency and to the observance of the obligation to the 3 R principles. Cardiac CT images of twentyfour Swiss large white pigs were segmented; aortic root, mitral valve, pulmonary trunk, tricuspid valve, as well as the aorto-mitral angle and left atrial height were analyzed. Correlation coefficient (r) was calculated in relation to body weight. In Swiss large white pigs, valvular dimensions, length of the pulmonary artery and ascending aorta as well as left atrial height correlate with body weight. Coronary ostia heights and aorto-mitral angle size can be neglected in animal size selection; no changes were found for either of the two parameters with increasing body weight.

show abstract

“…The development of a tissue engineered heart valve (TEHV) created from an individual’s own cells with the ability to grow, repair, and remodel offers a potential solution to this problem. Significant progress has been made including the performance of the first clinical trials evaluating the safety of this technology [ 150 , 151 , 152 ]. Unfortunately, the preliminary results of these trials have demonstrated some significant valve-related complications that have prevented their widespread use, most notably leaflet retraction which leads to regurgitation.…”

Section: Ecm and Therapeuticsmentioning

confidence: 99%

Biology and Biomechanics of the Heart Valve Extracellular Matrix

Kodigepalli

Thatcher

West

et al. 2020

JCDD

Self Cite

View full text Add to dashboard Cite

Heart valves are dynamic structures that, in the average human, open and close over 100,000 times per day, and 3 × 109 times per lifetime to maintain unidirectional blood flow. Efficient, coordinated movement of the valve structures during the cardiac cycle is mediated by the intricate and sophisticated network of extracellular matrix (ECM) components that provide the necessary biomechanical properties to meet these mechanical demands. Organized in layers that accommodate passive functional movements of the valve leaflets, heart valve ECM is synthesized during embryonic development, and remodeled and maintained by resident cells throughout life. The failure of ECM organization compromises biomechanical function, and may lead to obstruction or leaking, which if left untreated can lead to heart failure. At present, effective treatment for heart valve dysfunction is limited and frequently ends with surgical repair or replacement, which comes with insuperable complications for many high-risk patients including aged and pediatric populations. Therefore, there is a critical need to fully appreciate the pathobiology of biomechanical valve failure in order to develop better, alternative therapies. To date, the majority of studies have focused on delineating valve disease mechanisms at the cellular level, namely the interstitial and endothelial lineages. However, less focus has been on the ECM, shown previously in other systems, to be a promising mechanism-inspired therapeutic target. Here, we highlight and review the biology and biomechanical contributions of key components of the heart valve ECM. Furthermore, we discuss how human diseases, including connective tissue disorders lead to aberrations in the abundance, organization and quality of these matrix proteins, resulting in instability of the valve infrastructure and gross functional impairment.

show abstract

Preclinical Assessment of Cardiac Valve Substitutes: Current Status and Considerations for Engineered Tissue Heart Valves

Cited by 50 publications

References 56 publications

Glycation and Serum Albumin Infiltration Contribute to the Structural Degeneration of Bioprosthetic Heart Valves

Glycation and Serum Albumin Infiltration Contribute to the Structural Degeneration of Bioprosthetic Heart Valves

Computed Tomography-based evaluation of porcine cardiac dimensions to assist in pre-study planning and optimized model selection for pre-clinical research

Biology and Biomechanics of the Heart Valve Extracellular Matrix

Contact Info

Product

Resources

About