Valvulogenesis of a living, innervated pulmonary root induced by an acellular scaffold.

Heart valve disease is a major cause of mortality and morbidity worldwide with no effective medical therapy and no ideal valve substitute emulating the extremely sophisticated functions of a living heart valve. These functions influence survival and quality of life. This has stimulated extensive attempts at tissue engineering "living" heart valves. These attempts utilised combinations of allogeneic/ autologous cells and biological scaffolds with practical, regulatory, and ethical issues. In situ regeneration depends on scaffolds that attract, house and instruct cells and promote connective tissue formation. We describe a surgical, tissue-engineered, anatomically precise, novel off-the-shelf, acellular, synthetic scaffold inducing a rapid process of morphogenesis involving relevant cell types, extracellular matrix, regulatory elements including nerves and humoral components. This process relies on specific material characteristics, design and "morphodynamism".

Novel concepts and early results of repairing common arterial trunk.

OBJECTIVES: Common Arterial Trunk (CAT) continues to have a very poor prognosis globally. To address that, we have developed a novel technique targeting key concepts for the correction of all components of the anomaly, using autologous arterial tissue. This aims to enhance results, availability worldwide, and importantly to avoid the need for repeated reoperations. METHODS: From January 2019 to 4 January 2021, all patients with isolated CAT had repair of the defect using autologous arterial trunk tissue with direct right ventricle (RV) to pulmonary artery (PA) connection. Clinical outcomes, follow-up which included multi-slice computed tomography 3D segmentation and 4D cardiovascular magnetic resonance flow, are presented. RESULTS: Twenty patients were included in the study (median age 4.5 months). There were 2 hospital deaths due to systemic infection and pulmonary hypertensive crisis, respectively. Following discharge all patients remained asymptomatic with no signs of heart failure and improved pattern of growth (median follow-up: 8 months). Early postoperative 3D segmentation showed a conical shaped neo-right ventricular outflow chamber connecting the body of the RV to the main PA through a valveless ostium, and normal crossing of PA and neo-aorta. 4D cardiovascular magnetic resonance pattern of flow showed normal rapid laminar flow through the atrioventricular valves followed by a vortex towards the outflow tracts. There was laminar flow through the neo-aorta and neo-PA with velocity not exceeding 2.5 m/s. The PA regurgitant fraction was 25 ± 5% and was limited to early diastole. CONCLUSIONS: The initial results of utilizing the key concepts, using autologous arterial tissue for the repair of CAT, are encouraging, both clinically and by multimodality imaging.

Expanding Valve Repair in Rheumatic Heart Disease.

Rheumatic heart disease is a serious ailment with significant morbidity and mortality in endemic areas; yet, there is no agreement on indication, timing, and surgical modality for treating rheumatic valve affection. There is mounting evidence that rheumatic mitral valve repair is possible with good long-term results, less is the case with rheumatic aortic valve disease. We discuss the surgical approach for both valves emphasizing the role of multimodality imaging.

Biocompatibility and Application of Carbon Fibers in Heart Valve Tissue Engineering.

The success of tissue-engineered heart valves rely on a balance between polymer degradation, appropriate cell repopulation, and extracellular matrix (ECM) deposition, in order for the valves to continue their vital function. However, the process of remodeling is highly dynamic and species dependent. The carbon fibers have been well used in the construction industry for their high tensile strength and flexibility and, therefore, might be relevant to support tissue-engineered hearts valve during this transition in the mechanically demanding environment of the circulation. The aim of this study was to assess the suitability of the carbon fibers to be incorporated into tissue-engineered heart valves, with respect to optimizing their cellular interaction and mechanical flexibility during valve opening and closure. The morphology and surface oxidation of the carbon fibers were characterized by scanning electron microscopy (SEM). Their ability to interact with human adipose-derived stem cells (hADSCs) was assessed with respect to cell attachment and phenotypic changes. hADSCs attached and maintained their expression of stem cell markers with negligible differentiation to other lineages. Incorporation of the carbon fibers into a stand-alone tissue-engineered aortic root, comprised of jet-sprayed polycaprolactone aligned carbon fibers, had no negative effects on the opening and closure characteristics of the valve when simulated in a pulsatile bioreactor. In conclusion, the carbon fibers were found to be conducive to hADSC attachment and maintaining their phenotype. The carbon fibers were sufficiently flexible for full motion of valvular opening and closure. This study provides a proof-of-concept for the incorporation of the carbon fibers into tissue-engineered heart valves to continue their vital function during scaffold degradation.

A New Technique for Shaping the Aortic Sinuses and Conserving Dynamism in the Remodeling Operation.

BACKGROUND: Preserving dynamism and recreating the sinuses in the Dacron graft are thought to be important for optimizing results of aortic valve-conserving operations. METHODS: We describe a novel technique that preserves dynamism and recreates the sinotubular junction. In addition, it tailors 3 sinuses of defined longitudinal and transverse curvatures in a straight Dacron tube during the operation. The technique has been used in 6 patients with varied aortic root pathology. We performed preoperative and postoperative multimodality imaging using computerized image analysis as well as 3-dimensional models. RESULTS: There was no early or midterm death. Upon discharge, patients were clinically well, with echocardiographic evidence of minimal (3 patients) or mild (3 patients) aortic regurgitation. Computed tomography and cardiac magnetic resonance imaging with extensive image analysis of the aortic root size, shape, and function showed partial or complete normalization of these parameters. This included the shape and dynamism of the aortic annulus and the size and shape of the geometric (effective) orifice. The 4-dimensional magnetic resonance imaging pattern of flow in the sinuses and ascending aorta showed favorable vortices in the sinuses, right-handed helical flow, and marked diminution of energy loss in the ascending aorta. CONCLUSIONS: The novel technique described here is simple, practical, and cost-effective because it uses a widely available straight Dacron tube. The technique does not use rigid internal or external support. The early results are encouraging. Larger series with longer follow-up are required.

The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project: defining a healthy volunteer cohort.

The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities toward advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations, such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac magnetic resonance imaging (MRI), and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions. We identified 1262 variants in 27 cardiomyopathy genes of which 15.1% were not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.

Aortic root dynamism, geometry, and function after the remodeling operation: Clinical relevance.

OBJECTIVES: Valve-conserving operations for aneurysms of the ascending aorta and root offer many advantages, and their use is steadily increasing. Optimizing the results of these operations depends on providing the best conditions for normal function and durability of the new root. METHODS: Multimodality imaging including 2-dimensional echocardiography, multislice computed tomography, and cardiovascular magnetic resonance combined with image processing and computational fluid dynamics were used to define geometry, dynamism and aortic root function, before and after the remodeling operation. This was compared with 4 age-matched controls. RESULTS: The size and shape of the ascending aorta, aortic root, and its component parts showed considerable changes postoperatively, with preservation of dynamism. The postoperative size of the aortic annulus was reduced without the use of external bands or foreign material. Importantly, the elliptical shape of the annulus was maintained and changed during the cardiac cycle (Δ ellipticity index was 15% and 28% in patients 1 and 2, respectively). The "cyclic" area of the annulus changed in size (Δarea: 11.3% in patient 1 and 13.1% in patient 2). Functional analysis showed preserved reservoir function of the aortic root, and computational fluid dynamics demonstrated normalized pattern of flow in the ascending aorta, sinuses of Valsalva, and distal aorta. CONCLUSIONS: The remodeling operation results in near-normal geometry of the aortic root while maintaining dynamism of the aortic root and its components. This could have very important functional implications; the influence of these effects on both early- and long-term outcomes needs to be studied further.