Complex Valve Repair

https://www.ahajournals.org/doi/10.1161/circ.144.suppl_1.13734

https://link.springer.com/article/10.1007/s10439-023-03178-1

Single ventricle physiology (SVP) is used to describe any congenital heart lesion that is unable to support independent pulmonary and systemic circulations. Current treatment strategies rely on a series of palliation surgeries that culminate in the Fontan physiology, which relies on the single functioning ventricle to provide systemic circulation while passively routing venous return through the pulmonary circulation. Despite significant reductions in early mortality, the presence of atrioventricular valve (AVV) regurgitation is a key predictor of heart failure in these patients. We sought to evaluate the biomechanical changes associated with the AVV in SVP physiologies. Found that the tricuspid anterior leaflet experienced elevated maximum force, average force, and maximum yank compared to the posterior and septal leaflets. Between physiologies, maximum yank was greatest in the Norwood physiology relative to the Glenn, Fontan, and Late Fontan physiologies. These contrasting trends suggest that long- and short-term mechanics of AVV failure in single ventricle differ and that AVV interventions should account for asymmetries in force profiles between leaflets and physiologies.

https://www.sciencedirect.com/science/article/pii/S1043067922002738#fig0006

Tricuspid valve regurgitation in single ventricle disease remains a significant challenge and is associated with increased mortality and Fontan failure. Two key etiologies of valve regurgitation are annular dilation and leaflet tethering (LT). We sought to understand the relative contributions of annular dilation and leaflet tethering on leaflet forces in single ventricle physiology. Control models were secured to a size-matched hypoplastic left heart syndrome (HLHS)-type annulus and compared to: (1) normal tricuspid valves secured to a size-matched saddle-shaped annulus, (2) HLHS-type annulus with LT, (3) HLHS-type annulus with annular dilation (dilation valves), or (4) a combined disease model with both dilation and tethering (disease valves). We report that the anterior leaflet experiences the highest forces in the normal tricuspid annulus under single ventricle physiology conditions. Annular dilation resulted in an increase in forces on the septal leaflet and LT resulted in an increase in forces across all 3 leaflets. Annular dilation and LT combined resulted in the largest increase in leaflet forces across all 3 leaflets.

https://journals.sagepub.com/doi/full/10.1177/21501351211070288

Aortic stenosis accounts for approximately 5% of all congenital heart disease.1 For moderate and severe forms of stenosis, surgical intervention is required, and valve replacement is often necessary. The options for aortic valve replacement (mechanical, bioprosthetic, homograft, pulmonary autograft) each have their attendant risks and benefits. Of these, only the Ross procedure, which involves the use of a pulmonary autograft to create a neo-aortic pulmonary root, allows for growth potential and is therefore of special interest in congenital heart surgery. Many previous studies have demonstrated long-term durability with the pulmonary autograft with low incidence of failure and revision. However, despite the success of the Ross procedure, there are significant concerns that the pulmonary autograft experiences root dilatation over time, causing aneurysm formation and valvular regurgitation.This study uses novel techniques to combine ex vivo simulation and tissue analysis to further investigate the biomechanics of the Ross procedure. Neo-aortic pulmonary roots demonstrated equivalence in valve function and distensibility but did experience changes in biomechanical properties and morphology. These changes may contribute to long-term complications associated with the Ross procedure.

https://learningcenter.sts.org/content/science-and-innovation-congenital-heart-surgery

Another popularized technique in recent years for the treatment of aortic stenosis is the construction of a neo-valve using a patient’s pericardium. Ozaki et al. have advocated for the utilization of a patient’s pericardium to create a neo-leaflet using glutaraldehyde as a tanning agent to increase the tensile strength and durability of this biomaterial. The Ozaki procedure as reported in the literature utilizes pericardium that has been tanned for 10 min in glutaraldehyde. However, the optimal duration of pericardial tanning time for the Ozaki procedure has not been determined. A 10-min tanning time results in neo-leaflets with tensile strain and tensile stress properties most similar to native aortic valve leaflets. The autologous pericardium tanned with glutaraldehyde for 10 min resulted in the lowest valve regurgitation, lowest pressure gradient, and highest leaflet velocities in ex vivo simulations. Substantial improvements indicate the potential for optimizing the valve function and durability, marking a significant step toward enhancing aortic valve reconstruction techniques. Further research endeavors, particularly in clinical settings, are essential to validate and translate these findings into tangible clinical benefits.

https://www.aats.org/resources/biomechanical-assessment-of-no-9943

Objective is to compare the impact of no-cut tricuspidization and bicuspidization repairs on valve performance in a diseased quadricuspid truncal valve model. A Type C quadricuspid valve disease model (two symmetric dominant and two symmetric diminutive leaflets) was created in explanted porcine aortic roots. Three types of repairs-tricuspidization (sewing two diminutive leaflets together), symmetric bicuspidization (diminutive-dominant, diminutive-dominant), and asymmetric bicuspidization (diminutive-diminutive, dominant-dominant)-were completed without cutting or adding leaflet material. Repair of diseased Type C quadricuspid valve without cutting of leaflet material is feasible. Tricuspidization repair is associated with lower transvalvular gradient, reduced regurgitation fraction, and higher orifice area compared to bicuspidization techniques.

Popularized by Schäfers and colleagues approximately 2 decades ago, bicuspidization repair remains an important tool in the cardiac surgeon's armamentarium for congenital aortic valve disease. Originally reserved for the unicuspid aortic valve—the technique has been successfully adapted to bicuspid, tricuspid, and even quadricuspid aortic valve pathology. Bicuspidization repair is applied to severe congenital aortic valve lesions and recently increasingly recognized as an effective and durable surgical approach. The consequences of changes in leaflet geometry in this repair, however, are relatively unstudied. Our initial work sought to design the optimal gross morphology associated with surgical bicuspidization with computational simulations based on the hypothesis that modifications to the free edge length cause or relieve stenosis.

Model bicuspid valves were constructed with varying free edge lengths and gross morphology. Fluid-structure interaction simulations were conducted in a single patient-specific model geometry. The models were evaluated for primary targets of stenosis and regurgitation. Secondary targets were assessed and included qualitative hemodynamics, geometric height, effective height, orifice area, and billow. Stenosis decreased with increasing free edge length and was pronounced with free edge length less than or equal to 1.3 times the annular diameter d. With free edge length 1.5d or greater, no stenosis occurred. All models were free of regurgitation. Substantial billow occurred with free edge length 1.7d or greater.

https://www.sciencedirect.com/science/article/pii/S0022522324000096

Based on results from the initial study, 3 representative groups (FELAD 1.2, 1.57, 1.8) in addition to a diseased unicuspid control model were replicated in explanted juvenile porcine aortic roots. Free-edge lengths were modified within the same root using a bovine pericardial patch (St Jude Medical Pericardial Patch with EnCap Technology) and run on a validated univentricular pulse duplicator. At each stage (control, FELAD 1.2, 1.57, 1.8), these valves were run under physiological parameters. Measured outcomes included mean transvalvular gradient, regurgitation fraction, and orifice area. As expected, Free-edge length significantly impacts valve performance after bicuspidization repair for congenital aortic valve disease. Compared with FELAD of 1.2 and 1.8, sizing to a ratio of 1.57 can significantly improve stenosis by optimizing orifice area. Although the impact of free-edge length on regurgitation fraction is less striking, sizing to FELAD 1.57 is still associated with superior performance.

https://www.aats.org/resources/a-novel-approach-for-aortic-va-7040, https://www.sciencedirect.com/science/article/pii/S2666273624002560).

Next, we turned to investigate the effect of graft sizing on valve performance in valve-sparing aortic root replacement for bicuspid aortic valves. The merits of valve-sparing aortic root replacement in a preserved bicuspid valve are well accepted, yet the operation’s ideal parameters remain unknown. In addition to a diseased control model, 3 representative groups—free-edge length to aortic/graft diameter (FELAD) ratio <1.3, 1.5 to 1.64, and >1.7—were replicated in explanted porcine aortic roots using straight grafts sized respective to the native free-edge length. For a symmetric bicuspid aortic valve, performance after valve-sparing aortic root replacement shows a bimodal distribution across graft size similarly to our previous results. The ex vivo study reports that free-edge length-to-graft diameter ratio values beyond 1.5-1.64 in either direction lead to significant stenosis and that regurgitation may persist for values below this range.

https://www.aats.org/resources/effect-of-graft-sizing-in-valv-7713, https://www.sciencedirect.com/science/article/pii/S2666250724001603)

Our current work applies an in-vitro and computational approach to systematically study the effects of changes in leaflet height in symmetric bicuspidization repair.

https://www.aats.org/resources/simulation-guided-design-of-le-10025

Health Enabling Advancements through Regenerative Tissue Printing (HEART) is an ambitious ARPA-H funded initiative aiming to bioprint a full scale, fully functional human heart into a living pig. The project is led by BASE faculty member, Dr. Mark Skylar-Scott of the Department of Bioengineering, with close collaborations from several co-PIs, including the Ma Lab.

Our current efforts are focused on the design, optimization, and testing of all four cardiac valves using computational and ex vivo simulation, and in large animal in vivo models. We are creating protocols for the juvenile and adult ectopic and heterotopic heart transplantation porcine models which will be conducted in a future phase of the project.

https://news.stanford.edu/stories/2023/09/moonshot-effort-aims-bioprint-human-heart-implant-pig

https://arpa-h.gov/news-and-events/arpa-h-award-takes-step-address-organ-transplant-shortages

In an effort to expand access to this technology, a second protocol for valve fabrication using the Printess system, which is a “a low-cost, open-source 3D printer for multimaterial and high-throughput direct ink writing of soft and living materials”, is also ongoing.

https://onlinelibrary.wiley.com/doi/full/10.1002/adma.202414971