Biomechanical Identification of High-Risk Patients Requiring Permanent Pacemaker After Transcatheter Aortic Valve Replacement

BackgroundCardiac conduction disturbance requiring new permanent pacemaker implantation (PPI) is an important complication of TAVR that has been associated with increased mortality. It is extremely challenging to optimize the valve size alone to prevent a complete atrioventricular block (AVB).MethodsIn this study, we randomly took 48 patients who underwent TAVR and had been followed for at least 2 years to assess the risk of AVB. CT images of 48 patients with TAVR were analyzed using three-dimensional (3D) anatomical models of the aortic valve apparatus. The stresses were formulated according to loading force and tissue properties. Support vector regression (SVR) was used to model the relationship between AVB risk and biomechanical stresses. To avoid AVB, overlapping regions on the prosthetic valve where AV bundle passes will be removed as cylindrical sector with the angle θ. Thus, the optimization of the valve shape will be predicted with the joint optimization of the θ and valve size R.ResultsThe average AVB risk prediction accuracy was 83.33% in the range from 0.8–0.85 with 95% CI for all cases; specifically, 85.71% for Group A (no AVB), and 80.0% for Group B (undergoing AVB after the TAVR).ConclusionsThis model can estimate the optimal valve size and shape to avoid the risk of AVB after TAVR. This optimization may eliminate the excessive stresses to keep the normal function of both AV bundle and valve leaflets, leading to a favorable clinical outcome. The combination of biomechanical properties and machine learning method substantially improved prediction of surgical results.

P2275Left-sided deviation and fibrous-fatty infiltration of the right bundle branch in the elderly: implication for transcatheter aortic valve implantation (TAVI) procedure

Introduction Permanent and irreversible damage to the conduction tissue is one of the most common complications of TAVI. Detailed knowledge of the anatomy of the atrioventricular (AV) bundle is crucial to minimize the potential for injury to the His bundle branch block or complete AV block. Purpose Preexisting anatomic location and damage of the right bundle branch (RBB) may have important unrecognized clinical implications. Methods The myocardial arrangement and the presence of fibrous and fatty tissue infiltration of the AV conduction axis and right bundle branch were examined by dissection techniques and histological sections in 57 structurally normal human heart specimens (48 males, 77±7 years). Results The AV conduction axis enters the AV component of the membranous septum and is encircled by the fibrous tissue of the central fibrous body. The AV bundle is divided in a non-branching portion and a branching portion. After a short distance of the non-branching component along the septal crest, the RBB arises at the end of the branching portion of the conduction axis and is located superficially in the muscular ventricular septum. The RBB takes off from the bundle at the level of origin of the superior fascicle of the left bundle, passing then through the thickness of the ventricular septum to emerge beneath the medial papillary muscle of the tricuspid valve. In 22 hearts (49%) in which we found to have a relatively left-sided deviation of the AV bundle in relation to the interventricular membranous septum the RBB runs intramyocardial along the muscular interventricular septum. In the remaining 51% of the hearts the RBB runs subendocardially in the crest of the interventricular muscular septum. We found connective tissue and fatty infiltration along the right bundle branch in 23 hearts (40%) from its origin to its distal part. A significant correlation was found between age and the presence of RBB fibrosis (85% of hearts from individuals with age >80 years). These 2 conditions may make the RBB very vulnerable to self-expanding aortic valves during or after TAVI (figure). RBB and its critical region Conclusions The presence of an intramyocardial location of the RBB with a lef-sided deviation and the fibro-fatty infiltration found in the mayority of senescent hearts are relevant anatomic determinants that may increase the risk of complete AV block following a TAVI procedure.

Outcomes of Vascularized Bone Allotransplantation with Surgically Induced Autogenous Angiogenesis in a Large Animal Model: Bone Healing, Remodeling, and Material Properties

Background Bone vascularized composite allotransplantation (VCA) is a possible alternative for the treatment of large bone defects. Clinical application of VCAs is limited by the need for life-long immunosuppression (IS). We report an alternative method to maintain bone allotransplant viability in a large animal model without the need for life-long IS by using autogenous vessel implantation. Methods Fourteen bone only VCAs were transplanted in a porcine tibia defect model with short-term IS. Two groups were used to evaluate the effect of the implantation of an autogenous arteriovenous (AV)-bundle, therefore the only difference between the groups was the patency of the AV-bundle. We radiographically evaluated bone healing and allogenic pedicle patency. AV-bundle patency and union were evaluated with micro-CT. Bone remodeling was assessed with histomorphometry and material properties were evaluated with axial compression testing and cyclic reference point indentation. Results Two subjects did not reach the final time point. Twelve tibiae healed proximally, and nine at the distal transplant–bone interface. Bone allotransplants showed their viability in the first 4 to 6 weeks by significant periosteal bridging arising from the transplant and maintained pedicle patency. Bone material properties were not affected by the implantation of an AV-bundle when compared with ligated AV-bundle controls, but diminished compared with normal bone. Significantly higher bone formation rates resulted from the implantation of a patent AV-bundle. Conclusion New periosteal bone formation and subsequent bone healing result from blood flow through the microsurgically repaired nutrient blood supply, demonstrated by maintained allogenic pedicle patency. The implantation of a patent autogenous AV-bundle has no adverse effect on material properties, but a positive effect on bone remodeling of endosteal surfaces despite thrombosis of the allogenic pedicle. Bone material properties change after transplantation compared with normal bone, although 20-weeks survival time is relatively short for the final evaluation of bone material properties.

An Intrinsic Angiogenesis Approach and Varying Bioceramic Scaffold Architecture Affect Blood Vessel Formation in Bone Tissue Engineering In Vivo

Early establishment of angiogenesis is critical for bone tissue engineering. Recently, a technique was introduced, which is based on the idea of using axial vascularization of the host tissues in engineered grafts, namely the “intrinsic angiogenesis chamber” technique, which utilizes an artery and a vein to construct an AV-Bundle. The aim of this study was to evaluate the effect of varying scaffold architecture of calcium alkali orthophosphate scaffolds (CAOP), resulting from two different fabrication procedures, namely 3D printing (RP) or a Schwarzwalder-Somers replica technique (SSM), on angiogenesis in vivo when combining a microvascular technique with bioceramic scaffolds colonized with stem cells for bone tissue engineering. 32 adult female Wistar rats, in which critical size segmental discontinuity defects 6 mm in length were created in the left femur, were divided into 4 groups, group 1 received a RP scaffold colonized with rat stem cells after 7d of dynamic cell culture and an AV-Bundle (AVB), group 2 a SSM scaffold with rat stem cells after 7d of dynamic cell culture and an AVB, group 3 a RP control scaffold (without cells and AVB), group 4 a SSM control scaffold (without cells and AVB). After 3 and 6 months, angiomicro-CT after perfusion with a contrast agent, image reconstruction, histomorphometric and immunohistochemical analysis utilizing antibodies to collagen IV, vWF and CD-31 were performed. At 6 months, a statistically significant higher blood vessel volume%, blood vessel surface/volume, blood vessel thickness, blood vessel density and blood vessel linear density was observed with RP scaffolds with cells and AVB than with the other groups. At 6 mths, RP with cells and AVB displayed the highest expression of collagen IV (score 2.75), CD31 (score 2.75) and vWF (score 2.6), which is indicative of highly dense blood vessels. Both angio-CT and immunohistochemical analysis demonstrated that AVB is an efficient technique for achieving scaffold vascularization in critical size segmental defects after 3 and 6 months of implantation.

Enhancement of VEGF on Axial Vascularization of Nano-HA/Collagen/PLA Composites: A Histomorphometric Study on Rabbits

The aim of this study was to investigate whether the nanohydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLA) composite is suitable to be compounded with VEGF to enhance the axial vascularization in vivo. Thirty rabbits were divided into 2 groups of 15 animals each. In control group, a nHAC/PLA scaffold slice was vascularized axially by an inserted ligated femoral arteriovenous (AV) bundle in the animal. In experimental group, a slice compounded with VEGF gel was applied. The rabbits were sacrificed at 2 weeks, 6 weeks, and 10 weeks after surgery; the specimens of scaffold slices underwent histomorphometric examination; analysis of the microvessel density (MVD) of both groups was done. The combination with VEGF (Group B) did not enhance the vascularization in early phase (2 and 6 weeks,P>0.05) but worked in later phase (10 weeks,P<0.05). The data of the experiment demonstrated the suitability of the nHAC/PLA composite as carrier for the growth factor VEGF, enabling its sustained release in bioactive form with enough binding efficacy.

Axial Vascularization of Nano-HA/Collagen/PLA Composites by Arteriovenous Bundle

In previous studies, nano-hydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLA) composites have been prepared and confirmed to repair small sized bone defects. However, they are restricted to repair a large defect without sufficient oxygen and nutrition for cell survival. The result of this study confirmed that nHAC/PLA composites could be axially vascularized by being implanted intramuscularly with arteriovenous (AV) bundle (Group A) in the groins of rabbits. The combination with autologous bone marrow (Group B) could not enhance it the vascularization in early phase (2 weeks,P>0.05), but it could enhance in middle and later phases (6 and 10 weeks,P<0.01). It meant that nHAC/PLA could be prefabricated as a vascularized bone substitute for grafting.

Abstract 635: The Proximal AV Bundle in the Human Heart and Related Morbidity

INTRODUCTION: The proximal AV bundle (PAVB) has been shown to be the only input to the AV node (AVN) in the canine heart in anatomoelectrical reports over the past 20 years. The anatomic studies utilized photographic correlations of epi- and endocardial aspects of whole hearts through blocking, and serial histologic parallel, perpendicular and transverse plane Goldner Trichrome stained sections of the flattened heart; Karnovsky’s fixative at pH 7.2 and sucrose buffer rinses; direct 3D and stereotaxic analysis. Electrical studies, under direct observation of in-vitro superfused hearts, delineated unique wire, catheter, and micropipet electrode potentials via high K, transections, Lucifer Yellow iontophoresis and photoablations during spontaneous and paced SA node rhythms and with simultaneous SA node, atrionodal bundles, PAVB, AVN and distal AV bundle recordings. HYPOTHESIS: The PAVB exists in the human heart. METHODS AND RESULTS: Explanted normal human hearts, deemed unsuitable for transplantation, processed as above with transverse sections, revealed that the AVN (Figs. A–C ) is joined by the PAVB at a 90-degree angle (Figs. B, C ). These “normal” hearts from older patients (57– 80 yr) had atrophic or absent atrial myocardium. In Figure C , most of the right medial atrial wall myocardium, but not the left atrium (LA), had been replaced by fat. CONCLUSIONS: PAVB is the only AVN input in the human heart. As in the canine heart, PAVB also runs away from the annulus and is apposed to LA. Knowledge of the PAVB should be helpful in decreasing morbidity associated with clinical procedures. Care must be taken in ablating the fast superior atrionodal bundle pathway input to the PAVB. Figures A and B are from the same 60 yr and C is from a 71 yr old heart. AVN (A) is apposed to the left ventricular outflow tract (LVOFT and dotted line) along with the PAVB ( B and C ). But as seen in C , PAVB assumes a position apposed to LA, And, as in the dog heart, thereafter (not shown here) PAVB is completely apposed to LA.

The AV junction region of the heart: a comprehensive study correlating gross anatomy and direct three-dimensional analysis. Part II. Morphology and cytoarchitecture

This “Part II morphology and cytoarchitecture” study is based on paraffin-embedded specimens in which the extracellular and intracellular matrix are preserved; single parallel, perpendicular, and transverse serial sections of the entire atrioventricular (AV) junction region (AVJR) and their correlation with photographs of the tissue blocks. As in Part I, the same major new findings are: 1) a coronary sinus fossa is formed by the superoposterior right medial atria wall (MAW), the left atrium, and the coronary sinus roof; 2) the posterior MAW forms two myocardial bridges and is isolated from the sinus venarum by the floor of the inferior vena cava; 3) the tendon of Todaro terminates in the superior lip of the coronary sinus ostium; 4) only ordinary myocardium contacts the annulus fibrosus, and there is little to no collagen separating its myofibers and tissues; 5) the ventricular septum shoulder is humped shaped, completely overlaid by annular myocardium, and joined by struts of papillary muscle; 6) the membranous septum joining the ventricular septum shoulder to the crista supraventricularis forms part of the aortic valve sinus walls; and 7) myocardium of the atrionodal bundles is aggregated into numerous small fascicles encased by collagen and is outside of the MAW as are the other specialized tissues. The proximal AV bundle and medial atrionodal bundle are aligned to the medial leg of Koch's triangle and the tendon of Todaro. These data show, therefore, that the AVJR contains two overlapping atrial circuits. In the MAW, acivation of the posterior region is delayed because of the two myocardial bridges. Puncture of the AVJR can produce communication with an extracardiac space, posteriorly and medially, and with the aorta, anteriorly.

Morphology and electrophysiology of the mammalian atrioventricular node

The AV node of those mammalian species in which it has been thoroughly investigated (rabbit, ferret, and humans) consists of various cell types: transitional cells, midnodal (or typical nodal cells), lower nodal cells, and cells of the AV bundle. There are at least two inputs to the AV node, a posterior one via the crista terminalis and an anterior one via the interatrial septum, where atrial fibers gradually merge with transitional cells. The role of a possible third input from the left atrium has not been investigated. Since the transition from atrial fibers to nodal fibers is gradual, it is very difficult to define the "beginning" of the AV node, and gross measurements of AV nodal length may be misleading. Histologically, the "end" of the AV node is equally difficult to define. At the site where macroscopically the AV node ends, at the point where the AV bundle penetrates into the membranous septum, typical nodal cells intermingle with His bundle cells. A conspicuous feature, found in all species studied, is the paucity of junctional complexes, most marked in the midnodal area. The functional counterpart of this is an increased coupling resistance between nodal cells. An electrophysiological classification of the AV nodal area, based on transmembrane action potential characteristics during various imposed atrial rhythms (rapid pacing, trains of premature impulses), into AN (including ANCO and ANL), N, and NH zones has been described by various authors for the rabbit heart. In those studies in which activation patterns, transmembrane potential characteristics, and histology have been compared, a good correlation has been found between AN and transitional cells, N cells and the area where transitional cells and cells of the beginning of the AV bundle merge with midnodal cells, and NH cells and cells of the AV bundle. Dead-end pathways correspond to the posterior extension of the bundle of lower nodal cells and to anterior overlay fibers. During propagation of a normal sinus beat, activation of the AN zone accounts for at least 25% of conduction time from atrium to His bundle, the small N zone being the main source of AV nodal delay. Cycle length-dependent conduction delay is localized in the N zone. Conduction block of premature atrial impulses can occur both in the N zone and in the AN zone, depending on the degree of prematurity. Several factors determining AV nodal conduction delay have been identified.(ABSTRACT TRUNCATED AT 400 WORDS)