Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction

Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

Le remplacement valvulaire aortique chez le jeune adulte

Chez le jeune adulte, le substitut valvulaire aortique idéal demeure inconnu. La prothèse mécanique est durable. Cependant, elle requiert une anticoagulation à vie. De récentes études ont démontré un excès de mortalité à long terme chez les patients après un remplacement valvulaire aortique (RVA) mécanique. D’autres part, plusieurs patientes sont en âge de procréer lorsqu’une chirurgie est indiquée. La grossesse chez les patientes porteuses de RVA mécanique est à risque d’évènements thromboemboliques. Dans ce contexte, ces derniers sont mieux prévenus par la warfarine comparativement à l’héparine chez les patientes enceintes porteuses de prothèses mécaniques. Cependant, la warfarine est associée à des malformations fœtales. Les prothèses biologiques évitent l’anticoagulation. Par contre, la dégénérescence structurelle de la prothèse est plus rapide chez les patients jeunes, ce qui les expose à un haut risque de réintervention. L’objectif de ce mémoire est d’étudier les issues à long terme suivant un RVA chez le jeune adulte. Deux études ont été réalisées dans le cadre de ce travail. La première avait pour objectif de déterminer la survie et les complications à long terme dans une population de jeunes adultes ayant subi un RVA mécanique isolé. La survie de ce groupe de patient est inférieure à celle de la population générale québécoise appariée pour l’âge et le sexe. De plus, il existe un risque faible, mais constant à long terme de dysfonction de la prothèse et de réopération dans cette population. La deuxième étude a pour objectif de déterminer les complications cardiaques, maternelles et fœtales durant la grossesse chez des patientes porteuses de RVA mécanique ou biologique. Les résultats obtenus démontrent que la grossesse chez ces patientes est associée à un risque de complications maternelles et cardiaques significatives, et ce surtout chez les patientes porteuses d’une prothèse mécanique.

Predictores de cambio en la función ventricular izquierda posterior a implante valvular aórtico transcateter comparado con reemplazo valvular aórtico quirúrgico en el hospital universitario fundación Cardioinfantil instituto de cardiología – Bogotá

Objetivos: Identificar predictores de recuperación de la función ventricular izquierda y comparar los hallazgos ecocardiográficos en pacientes con estenosis aórtica crítica sometidos a reemplazo quirúrgico de la válvula aórtica (RVA) o implantación de válvula aórtica transcatéter (TAVI). Métodos: Cuarenta y cuatro pacientes tratados con RVA se compararon con 34 pacientes con TAVI, los datos ecocardiográficos fueron retrospectivamente obtenidos antes de la intervención y previo al alta. Resultados: Se analizaron retrospectivamente pacientes tratados en la FCI - IC desde 2009 - 2015 (n = 78 pacientes, con una media de edad 70,29 ± 11,63, EuroSCORE logístico 3,75 (3-8,55) en RVA y 20,4 (15 , 47-23,32) en TAVI. Ambos grupos mostraron una disminución en los gradientes de la válvula aórtica, más en pacientes de TAVI, con un gradiente transaórtico pico (24,5 vs 18,5, p = 0,001) y medio (14 vs 10, p = 0,002) En comparación con RVA, TAVI presentó un mayor número de pacientes con insuficiencia aórtica paravalvular (47,1% frente a 2,3% p = 0.000). En total, el 61,5% presentó mejoría precoz de la función ventricular, el predictor en severo compromiso de la función del ventrículo izquierdo fue un alto índice de masa ventricular izquierda. Conclusiones: La implantación transcatéter de válvula aórtica es una alternativa al reemplazo quirúrgico de la válvula aórtica en pacientes con estenosis aórtica y alto riesgo quirúrgico. La recuperación postoperatoria precoz de la función ventricular izquierda en pacientes con severo compromiso de la función ventricular estuvo asociada a alto índice de masa ventricular izquierda.

Análisis de supervivencia en pacientes con prótesis valvular biológica, Fundación Cardioinfantil-Instituto de Cardiología, Colombia, 2005-2013

Introducción: A partir de la década de los cincuenta el manejo de la enfermedad valvular presenta cambios significativos cuando se incorporan los reemplazos valvulares tanto mecánicos como biológicos dentro de las opciones de tratamiento quirúrgico (1). Las válvulas biológicas se desarrollaron como una alternativa que buscaba evitar los problemas relacionados con la anticoagulación y con la idea de utilizar un tejido que se comportara hemodinámicamente como el nativo. Este estudio está enfocado en establecer la sobrevida global y la libertad de reoperación de la válvula de los pacientes sometidos a reemplazo valvular aórtico y mitral biológicos en la Fundación Cardioinfantil - IC a 1, 3, 5 y 10 años. Materiales y métodos: Estudio de cohorte retrospectiva de supervivencia de pacientes sometidos a reemplazo valvular aórtico y/o mitral biológico intervenidos en la Fundación Cardioinfantil entre 2005 y 2013. Resultados: Se obtuvieron 919 pacientes incluidos en el análisis general y 876 (95,3%) pacientes con seguimiento efectivo para el análisis de sobrevida. La edad promedio fue 64años. La sobrevida a 1, 3, 5 y 10 años fue 95%,90%,85% y 69% respectivamente. El seguimiento efectivo para el desenlace reoperación fue del 55% y se encontró una libertad de reoperación del 99%, 96%, 93% y 81% a los 1, 3, 5 y 10 años. No hubo diferencias significativas entre la localización de la válvula ni en el tipo de válvula aortica empleada. Conclusiones: La sobrevida de los pacientes que son llevados a reemplazo valvular biológico en este estudio es comparable a grandes cohortes internacionales. La sobrevida de los pacientes llevados a reemplazo valvular con prótesis biológicas en posición mitral y aortica fue similar a 1, 3, 5 y 10 años.

1,4-Dioxane enhances properties and biocompatibility of polyanionic collagen for tissue engineering applications

Polyanionic collagen obtained from bovine pericardial tissue submitted to alkaline hydrolysis is an acellular matrix with strong potential in tissue engineering. However, increasing the carboxyl content reduces fibril formation and thermal stability compared to the native tissues. In the present work, we propose a chemical protocol based on the association of alkaline hydrolysis with 1,4-dioxane treatment to either attenuate or revert the drastic structural modifications promoted by alkaline treatments. For the characterization of the polyanionic membranes treated with 1,4-dioxane, we found that (1) scanning electron microscopy (SEM) shows a stronger reorientation and aggregation of collagen microfibrils; (2) histological evaluation reveals recovering of the alignment of collagen fibers and reassociation with elastic fibers; (3) differential scanning calorimetry (DSC) shows an increase in thermal stability; and (4) in biocompatibility assays there is a normal attachment, morphology and proliferation associated with high survival of the mouse fibroblast cell line NIH3T3 in reconstituted membranes, which behave as native membranes. Our conclusions reinforce the ability of 1,4-dioxane to enhance the properties of negatively charged polyanionic collagen associated with its potential use as biomaterials for grafting, cationic drug- or cell-delivery systems and for the coating of cardiovascular devices.

Extracellular matrix of porcine pericardium: Biochemistry and collagen architecture

Pericardial tissue has been used to construct bioprostheses employed in the repair of different kinds of injuries, mostly cardiac. However, calcification and mechanical failure have been the main causes of the limited durability of cardiac bioprostheses constructed with bovine pericardium. In the course of this work, a study was conducted on porcine fibrous pericardium, its microscopic structure and biochemical nature. The general morphology and architecture of collagen were studied under conventional light and polarized light microscopy. The biochemical study of the pericardial matrix was conducted according to the following procedures: swelling test, hydroxyproline and collagen dosage, quantification of amino acids in soluble collagen, component extraction of the extracellular matrix of the right and left ventral regions of pericardium with different molarities of guanidine chloride, protein and glycosaminoglycan (GAG) dosage, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and total GAG analysis. Microscopic analysis showed collagen fibers arranged in multidirectionally oriented layers forming a closely knit web, with a larger number of fibers obliquely oriented, initiating at the lower central region toward the upper left lateral relative to the heart. No qualitative differences were found between proteins extracted from the right and left regions. Likewise, no differences were found between fresh and frozen material. Protein dosages from left frontal and right frontal pericardium regions showed no significant differences. The quantities of extracted GAGs were too small for detection by the method used. Enzymatic digestion and electrophoretic analysis showed that the GAG found is possibly dermatan sulfate. The proteoglycan showed a running standard very similar to the small proteoglycan decorin.

Estudo in vivo do comportamento de bioprótese liofilizada: seguimento de 3 meses em carneiros jovens

OBJETIVO: Para melhorar as propriedades mecânicas e imunogênicas, o glutaraldeído é utilizado no tratamento do pericárdio bovino que é utilizado em biopróteses. A liofilização do pericárdio bovino tratado com glutaraldeído diminui os radicais aldeído, com provável redução do potencial para calcificação. O objetivo deste estudo é avaliar os efeitos da liofilização em biopróteses valvares de pericárdio bovino como mecanismo protetor na diminuição da disfunção estrutural valvar. MÉTODOS: Foi realizado o implante de biopróteses de pericárdio bovino tratado com glutaraldeído, liofilizadas ou não, em carneiros de 6 meses de idade, sendo os animais eutanasiados com 3 meses de seguimento. As biopróteses foram implantadas em posição pulmonar, com auxílio de circulação extracorpórea. Um grupo controle e outro grupo liofilizado foram avaliados quanto ao gradiente ventrículo direito/artéria pulmonar (VD/AP) no implante e explante; análise quantitativa de cálcio; inflamação; trombose e pannus. O nível de significância estabelecido foi de 5%. RESULTADOS: O gradiente médio VD/AP, no grupo controle, no implante, foi 2,04 ± 1,56 mmHg e, no grupo de liofilização, foi 6,61 ± 4,03 mmHg. No explante, esse gradiente aumentou para 7,71 ± 3,92 mmHg e 8,24 ± 6,2 mmHg, respectivamente, nos grupos controle e liofilização. O teor de cálcio médio, após 3 meses, nas biopróteses do grupo controle foi 21,6 ± 39,12 µg Ca+2/mg de peso seco, em comparação com um teor médio de 41,19 ± 46,85 µg Ca+2/mg de peso seco no grupo liofilizado (P = 0,662). CONCLUSÃO: A liofilização de próteses valvares com pericárdio bovino tratado com glutaraldeído não demonstrou diminuição da calcificação neste experimento.

Early hemodynamic and neurohormonal response after transcatheter aortic valve implantation

The conventional surgical aortic bioprostheses used for treatment of aortic stenosis (AS) are inherently stenotic in nature. The more favorable mechanical profile of the Medtronic CoreValve bioprosthesis may translate into a better hemodynamic and neurohormonal response.

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES Survival, stroke, and New York Heart Association functional class. RESULTS Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.

The Freedom SOLO bovine pericardial stentless valve

Abstract: The third-generation bovine pericardium Freedom SOLO (FS) stentless valve emerged in 2004 as a modified version of the Pericarbon Freedom stentless valve and as a very attractive alternative to stented bioprostheses. The design, choice of tissue, and anticalcification treatment fulfill most, if not all, requirements for an ideal valve substitute. The FS combines the single-suture, subcoronary implantation technique with the latest-generation bovine pericardial tissue and novel anticalcification treatment. The design allows imitation of the native healthy valve through unrestricted adaption to the patient's anatomy, reproducing a normal valve/root complex. However, despite hemodynamic performance superior to stented valves, we are approaching a critical observation period as superior durability, freedom from structural valve deterioration, and nonstructural failure has not been proven as expected. However, optimal performance and freedom from structural valve deterioration depend on correct sizing and perfect symmetric implantation, to ensure low leaflet stress. Any malpositioning can lead to tissue fatigue over time. Furthermore, the potential for better outcomes depends on optimal patient selection and observance of the limitations for the use of stentless valves, particularly for the FS. Clearly, stentless valve implantation techniques are less reproducible and standardized, and require surgeon-dependent experience and skill. Regardless of whether or not stentless valve durability surpasses third-generation stented bioprostheses, they will continue to play a role in the surgical repertoire. This review intends to help practitioners avoid pitfalls, observe limitations, and improve patient selection for optimal long-term outcome with the attractive FS stentless valve.

Clinical experience with the freedom SOLO stentless aortic valve in 277 consecutive patients.

BACKGROUND The Sorin Freedom SOLO (FS) bovine pericardial stentless valve prosthesis is designed for supraannular, subcoronary implantation. We report our experience and results with 277 consecutively implanted FS bioprostheses. METHODS 277 patients (mean age, 74.2 ± 7.3 years; 139 (50.2%) female) underwent aortic valve replacement (AVR) with the FS stentless bioprosthesis. The hemodynamic performance was investigated with transthoracic echocardiography at discharge, 6 months later, and yearly thereafter. Follow-up was 100% complete, with an average observation time of 2.6 ± 1.7 years and a total of 697.3 patient-years. RESULTS The overall 30-day mortality was 4.3%. The mortalities for isolated AVR and combined procedures were 1.9% and 7.3%, respectively. No causes of death were valve-related. Preoperative peak (74.2 ± 23.0 mm Hg) and mean (48.6 ± 16.3 mm Hg) gradients decreased to 15.6 ± 5.4 mm Hg and 8.8 ± 3.0 mm Hg postoperatively and remained unchanged for as long as 5 years. The postoperative mean effective orifice area (EOA) for valve sizes 19, 21, 23, 25, and 27 were 1.49 ± 0.32 cm(2), 1.67 ± 0.40 cm(2), 1.92 ± 0.38 cm(2), 2.01 ± 0.42 cm(2), and 2.13 ± 0.36 cm(2), respectively. Severe prosthesis-patient mismach (PPM) was completely absent, and moderate PPM occurred in 17 patients (6.1%). In isolated AVR, 0.8% of patients with preoperative sinus rhythm required a permanent pacemaker before hospital discharge. There was 100% freedom from structural valve deterioration, 99.6 % freedom from endocarditis and reoperation, and 97.3% freedom from thromboembolism at 5 years. CONCLUSIONS The FS stentless aortic valve is safe to implant, and it shows excellent hemodynamic performance and early and midterm results. Owing to the favorable EOA, the valve appears particularly attractive for patients at risk for PPM.

Expanding Indications of Transcatheter Heart Valve Interventions.

Transcatheter aortic valve replacement (TAVR) has been established as a less invasive alternative to open-heart surgery in inoperable or high-risk patients presenting with symptomatic severe aortic valve stenosis. The feasibility and efficacy of valve-in-valve implantation in degenerated surgical aortic bioprostheses have also been described and can currently be considered a valuable treatment option in patients deemed unsuitable for repeat cardiac surgery. However, the clinical use of TAVR devices is not limited to the treatment of the tricuspid stenotic aortic valve. Several additional indications including treatment of the bicuspid stenotic aortic valve, aortic regurgitation, and valve-in-valve or valve-in-ring implantation in the mitral or tricuspid position as well as treatment of pure mitral, tricuspid, or pulmonary regurgitation have been described. The purpose of the present review is to summarize the available evidence concerning the emerging off-label use of TAVR devices in current clinical practice. Case examples have been selected to highlight the main procedural steps of each particular intervention.

Mechanical versus biological aortic valve replacement strategies.

Aortic valve replacement (AVR) is the most frequently performed procedure in valve surgery. The controversy about the optimal choice of the prosthetic valve is as old as the technique itself. Currently there is no perfect valve substitute available. The main challenge is to choose between mechanical and biological prosthetic valves. Biological valves include pericardial (bovine, porcine or equine) and native porcine bioprostheses designed in stented or stentless versions. Homografts and pulmonary autografts are reserved for special indications and will not be discussed in detail in this review. We will focus on the decision making between artificial biological and mechanical prostheses, respectively. The first part of this article reviews guideline recommendations concerning the choice of aortic prostheses in different clinical situations while the second part is focused on novel strategies in the treatment of patients with aortic valve pathology.

Genetic engineering of vein grafts resistant to atherosclerosis.

Previously, researchers have speculated that genetic engineering can improve the long-term function of vascular grafts which are prone to atherosclerosis and occlusion. In this study, we demonstrated that an intraoperative gene therapy approach using antisense oligodeoxynucleotide blockage of medial smooth muscle cell proliferation can prevent the accelerated atherosclerosis that is responsible for autologous vein graft failure. Selective blockade of the expression of genes for two cell cycle regulatory proteins, proliferating cell nuclear antigen and cell division cycle 2 kinase, was achieved in the smooth muscle cells of rabbit jugular veins grafted into the carotid arteries. This alteration of gene expression successfully redirected vein graft biology away from neointimal hyperplasia and toward medial hypertrophy, yielding conduits that more closely resembled normal arteries. More importantly, these genetically engineered grafts proved resistant to diet-induced atherosclerosis. These findings establish the feasibility of developing genetically engineered bioprostheses that are resistant to failure and better suited to the long-term treatment of occlusive vascular disease.

Valves cardiaques par génie tissulaire - Simplification des essais et concept tubulaire

Les substituts valvulaires disponibles actuellement comportent encore plusieurs lacunes. La disponibilité restreinte des allogreffes, les risques de coagulation associés aux valves mécaniques et la durabilité limitée des bioprothèses en tissu animal sont toutes des problématiques que le génie tissulaire a le potentiel de surmonter. Avec la méthode d’auto-assemblage, le seul support des cellules consiste en leur propre matrice extracellulaire, permettant la fabrication d’un tissu entièrement libre de matériau exogène. Ce projet a été précédé par ceux des doctorantes Catherine Tremblay et Véronique Laterreur, ayant respectivement développé une méthode de fabrication de valves moulées par auto-assemblage et une nouvelle version de bioréacteur. Au cours de cette maîtrise, le nouveau bioréacteur a été adapté à une utilisation stérile avec des tissus vivants et la méthode de fabrication de valves moulées a été modifiée puis éprouvée avec la production de 4 prototypes. Ces derniers n’ont pas permis d’obtenir des performances satisfaisantes en bioréacteur, motivant la conception d’une nouvelle méthode. Plutôt que de tenter de répliquer la forme native des valves cardiaques, des études récentes ont suggéré une géométrie tubulaire. Cela permettrait une fabrication simplifiée, une implantation rapide, et un encombrement minimal en vue d’opérations percutanées. Cette approche minimaliste s’accorde bien avec la méthode d’auto-assemblage, qui a déjà été utilisée pour la production de vaisseaux de petits diamètres. Un total de 11 tubes ont été produits par l’enroulement de feuillets fibroblastiques auto-assemblés, puis ont été transférés sur des mandrins de diamètre inférieur, leur permettant de se contracter librement. La caractérisation de deux tubes contrôles a démontré que cette phase de précontraction était bénéfique pour les propriétés du tissu en plus de prévenir la contraction en bioréacteur. Les prototypes finaux pouvaient supporter un écoulement physiologique pulmonaire. Cette nouvelle méthode montre que le procédé d’auto-assemblage a le potentiel d’être utilisé pour fabriquer des valves cardiaques tubulaires.