Biomechanical engineering analysis of neochordae length's impact on chordal forces in mitral repair.

OBJECTIVES: Artificial neochordae implantation is commonly used for mitral valve (MV) repair. However, neochordae length estimation can be difficult to perform. The objective was to assess the impact of neochordae length changes on MV haemodynamics and neochordal forces. METHODS: Porcine MVs (n = 6) were implanted in an ex vivo left heart simulator. MV prolapse (MVP) was generated by excising at least 2 native primary chordae supporting the P2 segments from each papillary muscle. Two neochordae anchored on each papillary muscle were placed with 1 tied to the native chord length (exact length) and the other tied with variable lengths from 2× to 0.5× of the native length (variable length). Haemodynamics, neochordal forces and echocardiography data were collected. RESULTS: Neochord implantation repair successfully eliminated mitral regurgitation with repaired regurgitant fractions of approximately 4% regardless of neochord length (P < 0.01). Leaflet coaptation height also significantly improved to a minimum height of 1.3 cm compared with that of MVP (0.9 ± 0.4 cm, P < 0.05). Peak and average forces on exact length neochordae increased as variable length neochordae lengths increased. Peak and average forces on the variable length neochordae increased with shortened lengths. Overall, chordal forces appeared to vary more drastically in variable length neochordae compared with exact length neochordae. CONCLUSIONS: MV regurgitation was eliminated with neochordal repair, regardless of the neochord length. However, chordal forces varied significantly with different neochord lengths, with a preferentially greater impact on the variable length neochord. Further validation studies may be performed before translating to clinical practices.

Neochordal Goldilocks: Analyzing the biomechanics of neochord length on papillary muscle forces suggests higher tolerance to shorter neochordae.

OBJECTIVE: Estimating neochord lengths during mitral valve repair is challenging, because approximation must be performed largely based on intuition and surgical experience. Little data exist on quantifying the effects of neochord length misestimation. We aimed to evaluate the impact of neochord length on papillary muscle forces and mitral valve hemodynamics, which is especially pertinent because increased forces have been linked to aberrant mitral valve biomechanics. METHODS: Porcine mitral valves (n = 8) were mounted in an ex vivo heart simulator, and papillary muscles were fixed to high-resolution strain gauges while hemodynamic data were recorded. We used an adjustable system to modulate neochord lengths. Optimal length was qualitatively verified by a single experienced operator, and neochordae were randomly lengthened or shortened in 1-mm increments up to ±5 mm from the optimal length. RESULTS: Optimal length neochordae resulted in the lowest peak composite papillary muscle forces (6.94 ± 0.29 N), significantly different from all lengths greater than ±1 mm. Both longer and shorter neochordae increased forces linearly according to difference from optimal length. Both peak papillary muscle forces and mitral regurgitation scaled more aggressively for longer versus shorter neochordae by factors of 1.6 and 6.9, respectively. CONCLUSIONS: Leveraging precision ex vivo heart simulation, we found that millimeter-level neochord length differences can result in significant differences in papillary muscle forces and mitral regurgitation, thereby altering valvular biomechanics. Differences in lengthened versus shortened neochordae scaling of forces and mitral regurgitation may indicate different levels of biomechanical tolerance toward longer and shorter neochordae. Our findings highlight the need for more thorough biomechanical understanding of neochordal mitral valve repair.

Biomechanics and clinical outcomes of various conduit configurations in valve sparing aortic root replacement.

Background: Several conduit configurations, such as straight graft (SG), Valsalva graft (VG), anticommissural plication (ACP), and the Stanford modification (SMOD) technique, have been described for the valve-sparing aortic root replacement (VSARR) procedure. Prior ex vivo studies have evaluated the impact of conduit configurations on root biomechanics, but the mock coronary artery circuits used could not replicate the physical properties of native coronary arteries. Moreover, the individual leaflet's biomechanics, including the fluttering phenomenon, were unclear. Methods: Porcine aortic roots with coronary arteries were explanted (n=5) and underwent VSARR using SG, VG, ACP, and SMOD for evaluation in an ex vivo left heart flow loop simulator. Additionally, 762 patients who underwent VSARR from 1993 through 2022 at our center were retrospectively reviewed. Analysis of variance was performed to evaluate differences between different conduit configurations, with post hoc Tukey's correction for pairwise testing. Results: SG demonstrated lower rapid leaflet opening velocity compared with VG (P=0.001) and SMOD (P=0.045) in the left coronary cusp (LCC), lower rapid leaflet closing velocity compared with VG (P=0.04) in the right coronary cusp (RCC), and lower relative opening force compared with ACP (P=0.04) in the RCC. The flutter frequency was lower in baseline compared with VG (P=0.02) and in VG compared with ACP (P=0.03) in the LCC. Left coronary artery mean flow was higher in SG compared with SMOD (P=0.02) and ACP (P=0.05). Clinically, operations using SG compared with sinus-containing graft was associated with shorter aortic cross-clamp and cardiopulmonary bypass time (P<0.001, <0.001). Conclusions: SG demonstrated hemodynamics and biomechanics most closely recapitulating those from the native root with significantly shorter intraoperative times compared with repair using sinus-containing graft. Future in vivo validation studies as well as correlation with comprehensive, comparative clinical study outcomes may provide additional invaluable insights regarding strategies to further enhance repair durability.

Ex vivo biomechanical analysis of the Ross procedure using the modified inclusion technique in a 3-dimensionally printed left heart simulator.

OBJECTIVE: The inclusion technique was developed to reinforce the pulmonary autograft to prevent dilation after the Ross procedure. Anticommissural plication (ACP), a modification technique, can reduce graft size and create neosinuses. The objective was to evaluate pulmonary valve biomechanics using the inclusion technique in the Ross procedure with and without ACP. METHODS: Seven porcine and 5 human pulmonary autografts were harvested from hearts obtained from a meat abattoir and from heart transplant recipients and donors, respectively. Five additional porcine autografts without reinforcement were used as controls. The Ross procedure was performed using the inclusion technique with a straight polyethylene terephthalate graft. The same specimens were tested both with and without ACP. Hemodynamic parameter data, echocardiography, and high-speed videography were collected via the ex vivo heart simulator. RESULTS: Porcine autograft regurgitation was significantly lower after the use of inclusion technique compared with controls (P < .01). ACP compared with non-ACP in both porcine and human pulmonary autografts was associated with lower leaflet rapid opening velocity (3.9 ± 2.4 cm/sec vs 5.9 ± 2.4 cm/sec; P = .03; 3.5 ± 0.9 cm/sec vs 4.4 ± 1.0 cm/sec; P = .01), rapid closing velocity (1.9 ± 1.6 cm/sec vs 3.1 ± 2.0 cm/sec; P = .01; 1.8 ± 0.7 cm/sec vs 2.2 ± 0.3 cm/sec; P = .13), relative rapid opening force (4.6 ± 3.0 vs 7.7 ± 5.2; P = .03; 3.0 ± 0.6 vs 4.0 ± 2.1; P = .30), and relative rapid closing force (2.5 ± 3.4 vs 5.9 ± 2.3; P = .17; 1.4 ± 1.3 vs 2.3 ± 0.6; P = .25). CONCLUSIONS: The Ross procedure using the inclusion technique demonstrated excellent hemodynamic parameter results. The ACP technique was associated with more favorable leaflet biomechanics. In vivo validation should be performed to allow direct translation to clinical practice.

Biomechanical evaluation of aortic regurgitation from cusp prolapse using an ex vivo 3D-printed commissure geometric alignment device.

BACKGROUND: Aortic regurgitation (AR) is one of the most common cardiac valvular diseases, and it is frequently caused by cusp prolapse. However, the precise relationship of commissure position and aortic cusp prolapse with AR is not fully understood. In this study, we developed a 3D-printed commissure geometric alignment device to investigate the effect of commissure height and inter-commissure angle on AR and aortic cusp prolapse. METHODS: Three porcine aortic valves were explanted from hearts obtained from a meat abattoir and were mounted in the commissure geometric alignment device. Nine commissure configurations were tested for each specimen, exploring independent and concurrent effects of commissure height and inter-commissure angle change on AR and aortic cusp prolapse. Each commissure configuration was tested in our 3D printed ex vivo left heart simulator. Hemodynamics data, echocardiography, and high-speed videography were obtained. RESULTS: AR due to aortic cusp prolapse was successfully generated using our commissure geometric alignment device. Mean aortic regurgitation fraction measured for the baseline, high commissure, low commissure, high commissure and wide inter-commissure angle, high commissure and narrow inter-commissure angle, low commissure and wide inter-commissure angle, low commissure and narrow inter-commissure angle, wide commissure, and narrow commissure configurations from all samples were 4.6 ± 1.4%, 9.7 ± 3.7%, 4.2 ± 0.5%, 11.7 ± 5.8%, 13.0 ± 8.5%, 4.8 ± 0.9%, 7.3 ± 1.7%, 5.1 ± 1.2%, and 7.1 ± 3.1%, respectively. CONCLUSIONS: AR was most prominent when commissure heights were changed from their native levels with concomitant reduced inter-commissure angle. Findings from this study provide important evidence demonstrating the relationship between commissure position and aortic cusp prolapse and may have a significant impact on patient outcomes after surgical repair of aortic valves.

A Novel Device for Intraoperative Direct Visualization of a Pressurized Root in Aortic Valve Repair.

PURPOSE: One major challenge in generating reproducible aortic valve (AV) repair results is the inability to assess AV morphology under physiologic pressure. A transparent intraoperative AV visualization device was designed and manufactured. DESCRIPTION: This device comprises an open proximal end, a cantilevered edge to allow attachment of the device to the aorta or graft, a distal viewing surface, and 2 side ports for fluid delivery and air removal. EVALUATION: The performance of the device was evaluated ex vivo using normal porcine AV in situ (n = 3), porcine AV after valve-sparing aortic root replacement (VSARR) (n = 3), porcine pulmonary valve in the Ross procedure (n = 3), and in 3 patients who underwent VSARR. AV morphology was clearly visualized using the device in all experiments. In human subjects, the use of this device successfully showed cusp prolapse after the initial VSARR and effectively guided additional cusp repair. CONCLUSIONS: This device successfully allows for direct visual assessment of the AV apparatus under physiologic pressure. The use of this device can potentially increase the adoptability of AV repair in clinical practice.

Biomechanical engineering analysis of an acute papillary muscle rupture disease model using an innovative 3D-printed left heart simulator.

OBJECTIVES: The severity of acute papillary muscle (PM) rupture varies according to the extent and site of the rupture. However, the haemodynamic effects of different rupture variations are still poorly understood. Using a novel ex vivo model, we sought to study acute PM rupture to improve clinical management. METHODS: Using porcine mitral valves (n = 32) mounted within an ex vivo left heart simulator, PM rupture was simulated. The mitral valve was divided into quadrants for analysis according to the PM heads. Acute PM rupture was simulated by incrementally cutting from 1/3 to the total number of chordae arising from 1 PM head of interest. Haemodynamic parameters were measured. RESULTS: Rupture >2/3 of the chordae from 1 given PM head or regurgitation fraction >60% led to markedly deteriorated haemodynamics. Rupture at the anterolateral PM had a stronger negative effect on haemodynamics than rupture at the posteromedial PM. Rupture occurring at the anterior head of the anterolateral PM led to more marked haemodynamic instability than rupture occurring at the other PM heads. CONCLUSIONS: The haemodynamic effects of acute PM rupture vary considerably according to the site and extent of the rupture. Rupture of ≤2/3 of chordae from 1 PM head or rupture at the posteromedial PM lead to less marked haemodynamics effects, suggesting a higher likelihood of tolerating surgery. Rupture at the anterolateral PM, specifically the anterior head, rupture of >2/3 of chordae from 1 PM head or regurgitation fraction >60% led to marked haemodynamic instability, suggesting the potential benefit from bridging strategies prior to surgery.

Artificial papillary muscle device for off-pump transapical mitral valve repair.

OBJECTIVE: New transapical minimally invasive artificial chordae implantation devices are a promising alternative to traditional open-heart repair, with the potential for decreased postoperative morbidity and reduced recovery time. However, these devices can place increased stress on the artificial chordae. We designed an artificial papillary muscle to alleviate artificial chordae stresses and thus increase repair durability. METHODS: The artificial papillary muscle device is a narrow elastic column with an inner core that can be implanted during the minimally invasive transapical procedure via the same ventricular incision site. The device was 3-dimensionally printed in biocompatible silicone for this study. To test efficacy, porcine mitral valves (n = 6) were mounted in a heart simulator, and isolated regurgitation was induced. Each valve was repaired with a polytetrafluoroethylene suture with apical anchoring followed by artificial papillary muscle anchoring. In each case, a high-resolution Fiber Bragg Grating sensor recorded forces on the suture. RESULTS: Hemodynamic data confirmed that both repairs-with and without the artificial papillary muscle device-were successful in eliminating mitral regurgitation. Both the peak artificial chordae force and the rate of change of force at the onset of systole were significantly lower with the device compared with apical anchoring without the device (P < .001 and P < .001, respectively). CONCLUSIONS: Our novel artificial papillary muscle could integrate with minimally invasive repairs to shorten the artificial chordae and behave as an elastic damper, thus reducing sharp increases in force. With our device, we have the potential to improve the durability of off-pump transapical mitral valve repair procedures.

Heart Valve Biomechanics: The Frontiers of Modeling Modalities and the Expansive Capabilities of Ex Vivo Heart Simulation.

The field of heart valve biomechanics is a rapidly expanding, highly clinically relevant area of research. While most valvular pathologies are rooted in biomechanical changes, the technologies for studying these pathologies and identifying treatments have largely been limited. Nonetheless, significant advancements are underway to better understand the biomechanics of heart valves, pathologies, and interventional therapeutics, and these advancements have largely been driven by crucial in silico, ex vivo, and in vivo modeling technologies. These modalities represent cutting-edge abilities for generating novel insights regarding native, disease, and repair physiologies, and each has unique advantages and limitations for advancing study in this field. In particular, novel ex vivo modeling technologies represent an especially promising class of translatable research that leverages the advantages from both in silico and in vivo modeling to provide deep quantitative and qualitative insights on valvular biomechanics. The frontiers of this work are being discovered by innovative research groups that have used creative, interdisciplinary approaches toward recapitulating in vivo physiology, changing the landscape of clinical understanding and practice for cardiovascular surgery and medicine.

Ex Vivo Analysis of a Porcine Bicuspid Aortic Valve and Aneurysm Disease Model.

We identified an extremely rare congenital porcine type 0 lateral bicuspid aortic valve from a fresh porcine heart. Using a 3-dimensionally printed ex vivo left heart simulator, we analyzed valvular hemodynamics at baseline, in an aortic aneurysm disease model, and after valve-sparing root replacement. We showed that bicuspid aortic valve regurgitation due to aortic aneurysm can be successfully repaired without significant hemodynamic impairment using the valve-sparing root replacement technique in an individualized approach. Our results provide direct hemodynamic evidence supporting the use of valve-sparing root replacement for patients with bicuspid aortic valve regurgitation.

A Novel Aortic Regurgitation Model from Cusp Prolapse with Hemodynamic Validation Using an Ex Vivo Left Heart Simulator.

Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mimics human aortic regurgitation (AR) from cusp prolapse is needed to accurately examine valve biomechanics. To simulate AR, four porcine aortic valves were explanted, and the commissure between the two largest leaflets was detached and re-implanted 5 mm lower to induce cusp prolapse. Four additional valves were tested in their native state as controls. All valves were tested in a heart simulator while hemodynamics, high-speed videography, and echocardiography data were collected. Our AR model successfully reproduced cusp prolapse with significant increase in regurgitant volume compared with that of the controls (23.2 ± 8.9 versus 2.8 ± 1.6 ml, p = 0.017). Hemodynamics data confirmed the simulation of physiologic disease conditions. Echocardiography and color flow mapping demonstrated the presence of mild to moderate eccentric regurgitation in our AR model. This novel AR model has enormous potential in the evaluation of valve biomechanics and surgical repair techniques. Graphical Abstract.

Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat.

Congenital urinary tract obstruction is the most important cause of renal insufficiency in infants and children, and angiotensin-converting enzyme (ACE) inhibitors attenuate the progression of renal disease in adults. ACE inhibitors are increasingly utilized in children with progressive renal disease. Because angiotensin is necessary for normal renal development, we examined the effects of ACE inhibition both during and immediately following the period of postnatal nephrogenesis in the neonatal rat subjected to sham operation or partial unilateral ureteral obstruction (UUO) under general anesthesia within the first 48 h of life. Rats in group I received enalapril 30 mg/kg body wt (or vehicle) daily for the first 10 days, while in group II, the 10 days of treatment began 10 days after surgery. Kidneys were harvested at day 21 and analyzed for apoptosis (TUNEL), interstitial macrophages (ED-1 immunohistochemistry), myofibroblasts (alpha-smooth muscle actin), and collagen (Sirius red). Partial UUO delayed glomerular maturation and increased ipsilateral renal macrophage infiltration, alpha-smooth muscle actin and Sirius red staining. In group I, enalapril increased myofibroblast accumulation in sham-operated kidneys, but not in obstructed kidneys. In contrast, in group II, enalapril further increased macrophage, myofibroblast, and collagen accumulation following partial UUO. The relative abundance of components of the kallikrein-kinin system, measured by Western blot, was not altered by partial UUO in the 14- and 28-day-old rat. Thus, in contrast to its salutary effects at later ages, ACE inhibition can worsen injury to the partially obstructed kidney during renal maturation even after the completion of nephrogenesis.