S. Hamed Alavi

The Effects of Transcatheter Valve Crimping on Pericardial Leaflets

BACKGROUND Transcatheter aortic valve replacement has emerged as a promising therapy for treatment of severe aortic stenosis. Although it has been shown that these valves can be safely delivered and implanted, studies of valve longevity are lacking because of the infancy of the technology. Particularly, the effects of stent crimping on the valves leaflets have not yet been sufficiently investigated. In this study, we have characterized the effects of crimping on pericardial leaflets in time and through the depth of the tissue. METHODS To test the structural changes at the surface and deep layers of bovine pericardial leaflets, scanning electron microscopy and second-harmonic generation microscopy were used. An uncrimped tissue sample was imaged, followed by imaging a segment of tissue after crimping in a stented transcatheter valve, immediately after, at 20 minutes, and 60 minutes after crimping. The crimping experiment was performed for multiple crimping sizes (ie, 14F, 16F, and 18F). We defined a damage index that quantifies the level of leaflet structural changes as a result of crimping. RESULTS Based on the calculated damage indices and analyses of the raw images, it was determined that crimping does measurable damage to the leaflet tissue that persists with time. CONCLUSIONS Significant tissue damage was observed at the surface layers of the leaflets. In the deeper tissue layers, damage was substantial for 14F crimping; however, it became less significant but still visible for larger collapse profiles. Crimping may induce substantial structural damage to pericardial leaflets that does not improve with time.

Emerging Trends in Heart Valve Engineering: Part I. Solutions for Future

As the first section of a multi-part review series, this section provides an overview of the ongoing research and development aimed at fabricating novel heart valve replacements beyond what is currently available for patients. Here we discuss heart valve replacement options that involve a biological component or process for creation, either in vitro or in vivo (tissue-engineered heart valves), and heart valves that are fabricated from polymeric material that are considered permanent inert materials that may suffice for adults where growth is not required. Polymeric materials provide opportunities for cost-effective heart valves that can be more easily manufactured and can be easily integrated with artificial heart and ventricular assist device technologies. Tissue engineered heart valves show promise as a regenerative patient specific model that could be the future of all valve replacement. Because tissue-engineered heart valves depend on cells for their creation, understanding how cells sense and respond to chemical and physical stimuli in their microenvironment is critical and therefore, is also reviewed.

Inflammatory Response Assessment of a Hybrid Tissue-Engineered Heart Valve Leaflet

Despite substantial research in the past few decades, only slight progress has been made toward developing biocompatible, tissue-engineered scaffolds for heart valve leaflets that can withstand the dynamic pressure inside the heart. Recent progress on the development of hybrid scaffolds, which are composed of a thin metal mesh enclosed by multi-layered tissue, appear to be promising for heart valve engineering. This approach retains all the advantages of biological scaffolds while developing a strong extracellular matrix backbone to withstand dynamic loading. This study aims to test the inflammatory response of hybrid tissue-engineered leaflets based on characterizing the activation of macrophage cells cultured on the surfaces of the tissue construct. The results indicate that integration of biological layers around a metal mesh core—regardless of its type—may reduce the evoked inflammatory responses by THP-1 monocyte-like cells. This observation implies that masking a metal implant within a tissue construct prior to implantation can hide it from the immune system and may improve the implant’s biocompatibility.

Emerging Trends in Heart Valve Engineering: Part IV. Computational Modeling and Experimental Studies

In this final portion of an extensive review of heart valve engineering, we focus on the computational methods and experimental studies related to heart valves. The discussion begins with a thorough review of computational modeling and the governing equations of fluid and structural interaction. We then move onto multiscale and disease specific modeling. Finally, advanced methods related to in vitro testing of the heart valves are reviewed. This section of the review series is intended to illustrate application of computational methods and experimental studies and their interrelation for studying heart valves.

On the Mechanics of Transcatheter Aortic Valve Replacement.

Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic heart valve technology. TAVs are truly transformational as they bring the benefit of heart valve replacement to patients that would otherwise not be operated on. Nevertheless, like any new device technology, the high expectations are dampened with growing concerns arising from frequent complications that develop in patients, indicating that the technology is far from being mature. Some of the most common complications that plague current TAV devices include malpositioning, crimp-induced leaflet damage, paravalvular leak, thrombosis, conduction abnormalities and prosthesis-patient mismatch. In this article, we provide an in-depth review of the current state-of-the-art pertaining the mechanics of TAVs while highlighting various studies guiding clinicians, regulatory agencies, and next-generation device designers.

A Hybrid Tissue-Engineered Heart Valve.

PURPOSE This study describes the efforts to develop and test the first hybrid tissue-engineered heart valve whose leaflets are composed of an extra-thin superelastic Nitinol mesh tightly enclosed by uniform tissue layers composed of multiple cell types. DESCRIPTION The trileaflet Nitinol mesh scaffolds underwent three-dimensional cell culture with smooth muscle and fibroblast/myofibroblast cells enclosing the mesh, which were finally covered by an endothelial cell layer. EVALUATION Quantitative and qualitative assays were performed to analyze the microstructure of the tissues. A tissue composition almost similar to that of natural heart valve leaflets was observed. The function of the valves and their Nitinol scaffolds were tested in a heart flow simulator that confirmed the trileaflet valves open and close robustly under physiologic flow conditions with an effective orifice area of 75%. The tissue-metal attachment of the leaflets once exposed to physiologic flow rates was tested and approved. CONCLUSIONS Our preliminary results indicate that the novel hybrid approach with nondegradable scaffold for engineering heart valves is viable and may address the issues associated with current tissue-engineered valves developed with degradable scaffolds.

Emerging Trends in Heart Valve Engineering: Part III. Novel Technologies for Mitral Valve Repair and Replacement

In this portion of an extensive review of heart valve engineering, we focus on the current and emerging technologies and techniques to repair or replace the mitral valve. We begin with a discussion of the currently available mechanical and bioprosthetic mitral valves followed by the rationale and limitations of current surgical mitral annuloplasty methods; a discussion of the technique of neo-chordae fabrication and implantation; a review the procedures and clinical results for catheter-based mitral leaflet repair; a highlight of the motivation for and limitations of catheter-based annular reduction therapies; and introduce the early generation devices for catheter-based mitral valve replacement.

A Tri-Leaflet Nitinol Mesh Scaffold for Engineering Heart Valves

The epidemiology of valvular heart disease has significantly changed in the past few decades with aging as one of the main contributing factors. The available options for replacement of diseased valves are currently limited to mechanical and bioprosthetic valves, while the tissue engineered ones that are under study are currently far from clinical approval. The main problem with the tissue engineered heart valves is their progressive deterioration that leads to regurgitation and/or leaflet thickening a few months after implantation. The use of bioresorbable scaffolds is speculated to be one factor affecting these valves’ failure. We have previously developed a non-degradable superelastic nitinol mesh scaffold concept that can be used for heart valve tissue engineering applications. It is hypothesized that the use of a non-degradable superelastic nitinol mesh may increase the durability of tissue engineered heart valves, avoid their shrinkage, and accordingly prevent regurgitation. The current work aims to study the effects of the design features on mechanical characteristics of this valve scaffold to attain proper function prior to in vivo implantation.