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.

Mechanics of the dicrotic notch: An acceleration hypothesis.

The dicrotic notch is a prominent and distinctive feature of the pressure waveform in the central arteries. It is universally used to demarcate the end of systole and the beginning of diastole in these arteries. Despite its importance clinically, no physical mechanism for the formation of the dicrotic notch has been demonstrated convincingly. We first explore a mechanism based on the reflection of a backward wavefront from the aortic valve at the time of closure. This hypothesis is rejected on the basis of experimental evidence from measurements made in dogs. A new hypothesis is presented involving the acceleration of the aortic valve apparatus at the time of valve closure. This hypothesis is supported by new calculations of the acceleration of the aortic valve apparatus during the cardiac cycle based on computed tomography scans in man.

Revival and modification of the Mustard operation.

OBJECTIVE: The neonatal arterial switch operation is currently the procedure of choice for patients with transposition of the great arteries. However, a large number of patients present too late for the arterial switch operation and are best managed with the atrial switch operation. METHODS: We have used the Mustard operation in its original form or following a new modification designed to enhance the atrial functions and filling of the left ventricle in an attempt to improve long-term results. RESULTS: Between July 2013 and November 2018, a total of 101 patients underwent the Mustard operation, 86 with the new modification. The median age at operation was 16 months (6 months to 27 years). A total of 75 patients (74.3%) were male. Median preoperative oxygen saturation was 71%. There were no early deaths and there were 3 late deaths during a median follow-up period of 24.2 months (all in patients with large ventricular septal defect and established pulmonary vascular disease). At the latest follow-up, all patients were in stable sinus rhythm. There were no baffle leaks. Seven patients had asymptomatic narrowing of the superior baffle, and 1 patient required balloon dilatation. Follow-up is 100% complete and includes computed tomography and magnetic resonance imaging at regular intervals (75 patients to date). Computerized analysis of representative subsets showed enhanced rate and pattern of filling of the left ventricle in the modified operation compared with the classic operation. CONCLUSIONS: The use of the Mustard operation, particularly the modified technique should play an important role in treating late-presenting patients with transposition of the great arteries. Improving the pattern of filling of the left ventricle could enhance the long-term results of the Mustard operation.

Characterization of size, shape and pattern of flow in the neo-aorta and pulmonary artery in a patient following an innovative technique of repair for truncus arteriosus.

Background. Truncus arteriosus (TA) caries a very poor prognosis. In the absence of early correction, only 12 percent of patients born with this anomaly survive beyond one year. There is no agreement about the best method of surgical correction of this anomaly. We have devised an innovative valveless technique using autologous arterial tissue to repair TA. Objectives. Characterizing the size, shape and pattern of flow in the neo-aorta and pulmonary artery, in a patient following the new technique. Patient and Methods. Cardiac MRI and multislice CT imaging, followed by offline computerized image analysis was used in a patient aged 3 months, within 3 weeks of operating. Results. The size, shape and topology of the neo-aorta and pulmonary artery, approximated that present in normal hearts. The pattern of flow in the reconstructed vessels was laminar, throughout the cardiac cycle with minor acceleration during systole. The pulmonary regurgitation resulting from the absence of a valve occurred during late diastole, and was well tolerated. The size of the right ventricle diminished considerably following operation, and the right ventricular ejection fraction was supernormal. Conclusion. This early study in one patient provides new unique data of the size, shape, topology and pattern of flow in the neo-aorta and pulmonary artery, which appear to approximate normality. The long-term results of this promising operation need to be studied.

Progression of arterial toursosity syndrome to multiple aneurysms: Role of defining aortic flow and biomechanics.

Arterial tortuosity syndrome (ATS) is a rare aortopathy characterized by multiple areas of tortuosity, stenosis and aneurysms in large and mid-sized arteries. The management of this syndrome is challenging because its complexity and variability in presentation and progression require a thorough understanding of the biological and biomechanical changes that occur in the arterial system. Here we describe, for the first time, the progression of this disease diagnosed in a 3-year old girl and the use of modern imaging modalities including cardiac magnetic resonance (CMR) 4D Flow, 3D modeling, and computational fluid dynamic simulation to characterize the complex aortic flow and its biomechanics. The integration of these modalities with the clinical evaluation will help in our understanding of this disease and provide patient-specific management.

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.

Current state of the art and future of myectomy.

Surgical relief of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) requires more than septal myectomy. The procedure is currently the gold standard for all symptomatic HCM patients except those with comorbidities. The operation requires an individualized approach to restore the sophisticated functions of the left ventricular outflow tract (LVOT) without injury to the surrounding vital structures. The procedure should be tailored to deal with all the varied components of the obstruction including fibrous trigones, accessory tissues, and papillary muscle fusion. Preoperative multimodality imaging and numerical modeling combined with intraoperative transesophageal echocardiography (TEE) are essential to define existing anomalies as well as assess the adequacy of the repair. The mitral valve can be conserved in virtually all patients. The operation can be conducted with very low mortality and morbidity with predictable good outcomes both in the short and long term. Nevertheless, surgical relief of LVOTO is still grossly underused.

Spatial Orientation and Morphology of the Pulmonary Artery: Relevance to Optimising Design and Positioning of a Continuous Pressure Monitoring Device.

Personalised treatment of heart disease requires an understanding of the patient-specific characteristics, which can vary over time. A newly developed implantable surface acoustic wave pressure sensor, capable of continuous monitoring of the left ventricle filling pressure, is a novel device for personalised management of patients with heart disease. However, a one-size-fits-all approach to device sizing will affect its positioning within the pulmonary artery and its relationship to the interrogating device on the chest wall on a patient-specific level. In this paper, we analyse the spatial orientation and morphology of the pulmonary artery and its main branches in patients who could benefit from the device and normal controls. The results could optimise the design of the sensor, its stent, and importantly its placement, ensuring long-term monitoring in patient groups.

Utility of 4D Flow mapping in Eisenmenger syndrome with pulmonary atresia.

Management of patients with Eisenmenger syndrome with pulmonary atresia is challenging because of the complexity of the structure-function relationship of the components of the syndrome. Multi-modality imaging including cardiac magnetic resonance (CMR) 4D Flow offers unprecedented opportunities to unravel, at least in part, some of these components, and thus help in the management of these patients. In this study, we describe the use of these integrated methods with particular reference to CMR 4D Flow in a patient with Eisenmenger syndrome and pulmonary atresia and outline both the utility and the limitations. A comprehensive cardiac magnetic resonance (CMR) 4D Flow analysis was performed preoperatively and postoperatively, during peak systole, late systole, early diastole, and late diastole. The focus of the present study was to investigate the pattern of flow and dynamic changes at different levels of the aorta, as well as in the duct and the pulmonary arteries. Preoperatively, a right-handed helix and a vortex were observed in the dilated ascending aorta, and the duct flow was mainly dependent on reverse, upstream flow from the descending aorta, distal to the duct, during diastole, denoting low pulmonary vascular capacitance. Following repair, the flow in the ascending aorta and the descending aorta changed markedly. These changes included both timing and intensity of the right-handed helix, as well as the vortex in the ascending aorta. The significance of the observed changes in flow pattern and their influence on wall structure and function are discussed. Our study demonstrates the extremely powerful potential of CMR 4D Flow in the management of complex congenital anomalies.

Experimental validation of a tissue-joining implant providing flexible adaptation to the thickness of the stomach wall.

Endoscopy is gradually replacing open surgery in the gastrointestinal tract. Therefore, novel medical devices and instrumentation are required, such as flexible miniaturized mechanisms for tissue joining and manipulation. In this paper, an absorbable implant for the purpose of long-term tissue fixation is presented. An experimental validation of the implant design and functionality is introduced. The implant achieves tissue penetration and provides flexible adaptation according to the thickness of two stomach walls. This mechanism is easy as it is based on push-pull principle using unidirectional forces. The shape optimization of each implant part occurs by varying design-influencing factors. The load transmission on postmortem porcine tissue was measured in the frame of the experimental setup. The feasibility of the implant was tested, and the forces needed for the intended application quantified. The implant successfully achieves tissue penetration, load transmission, adjustment, and fixation. It is a new alternative to conventional tissue-joining mechanisms.