The Evolution of Aortic Aneurysm Repair: Past Lessons and Future Directions

The history and evolution of aortic aneurysm repair demonstrates an important paradigm within surgery, namely the importance of surgical pioneers and innovators who have\ud strived to achieve technical excellence and improve patient care. It also highlights the wider evolution of surgery from traditional open operative techniques to the modern minimally invasive procedures. The following chapter discusses the surgical innovators and the techniques they have described that have enabled the repair of both thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA).\ud Aortic aneurysms represent a significant health risk particularly for the elderly population. AAA is the 14th-leading cause of death for the 60- to 85-year–old age group in the United States (10.8 deaths per 100,000 population). TAA by contrast is less frequent with an incidence of 10.4 per 100,000. Both AAA and TAA are known to increase in prevalence with advancing age and have an increased prevalence in males. The risk of aneurysm rupture increases with increasing aneurysm diameter over 5.5-6.0 cm and is the primary indication for the repair of both TAA and AAA.Therefore surgery to repair both AAA and TAA is either pre-emptive to prevent rupture or emergent to repair a rupture. Repair of TAA and AAA by either open or minimally invasive techniques significantly reduces the risk of rupture and improves patient mortality. The establishment of these techniques has required the development of procedures from embryonic thoughts in the minds of the surgeons of antiquity through to the utilisation of ever increasing modern technologies

Computational fluid dynamics modelling in cardiovascular medicine

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length-And time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, populationaveraged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education-And service-related challenges

Contrast-enhanced ultrasound: clinical applications in patients with atherosclerosis

Contrast-enhanced ultrasound (CEUS) is increasingly being used to evaluate patients with known or suspected atherosclerosis. The administration of a microbubble contrast agent in conjunction with ultrasound results in an improved image quality and provides information that cannot be assessed with standard B-mode ultrasound. CEUS is a high-resolution, noninvasive imaging modality, which is safe and may benefit patients with coronary, carotid, or aortic atherosclerosis. CEUS allows a reliable assessment of endocardial borders, left ventricular function, intracardiac thrombus and myocardial perfusion. CEUS results in an improved detection of carotid atherosclerosis, and allows assessment of high-risk plaque characteristics including intraplaque vascularization, and ulceration. CEUS provides real-time bedside information in patients with a suspected or known abdominal aortic aneurysm or aortic dissection. The absence of ionizing radiation and safety of the contrast agent allow repetitive imaging which is particularly useful in the follow-up of patients after endovascular aneurysm repair. New developments in CEUS-based molecular imaging will improve the understanding of the pathophysiology of atherosclerosis and may in the future allow to image and directly treat cardiovascular diseases (theragnostic CEUS). Familiarity with the strengths and limitations of CEUS may have a major impact on the management of patients with atherosclerosis

Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis

Background: Vascular elasticity is crucial for maintaining hemodynamics. Molecular mechanisms involved in human elastogenesis are incompletely understood. We describe a syndrome of lethal arteriopathy associated with a novel, identical mutation in the fibulin 4 gene (FBLN4) in a unique cohort of infants from South India. Methods: Clinical characteristics, cardiovascular findings, outcomes and molecular genetics of twenty-two infants from a distinct population subgroup, presenting with characteristic arterial dilatation and tortuosity during the period August 2004 to June 2011 were studied. Results: Patients (11 males, 11 females) presented at median age of 1.5 months, belonging to unrelated families from identical ethno-geographical background; eight had a history of consanguinity. Cardiovascular features included aneurysmal dilatation, elongation, tortuosity and narrowing of the aorta, pulmonary artery and their branches. The phenotype included a variable combination of cutis laxa (52%), long philtrum-thin vermillion (90%), micrognathia (43%), hypertelorism (57%), prominent eyes (43%), sagging cheeks (43%), long slender digits (48%), and visible arterial pulsations (38%). Genetic studies revealed an identical c.608A > C (p. Asp203Ala) mutation in exon 7 of the FBLN4 gene in all 22 patients, homozygous in 21, and compound heterozygous in one patient with a p. Arg227Cys mutation in the same conserved cbEGF sequence. Homozygosity was lethal (17/21 died, median age 4 months). Isthmic hypoplasia (n = 9) correlated with early death (<= 4 months). Conclusions: A lethal, genetic disorder characterized by severe deformation of elastic arteries, was linked to novel mutations in the FBLN4 gene. While describing a hitherto unreported syndrome in this population subgroup, this study emphasizes the critical role of fibulin-4 in human elastogenesis

Focal Spot, Winter 2005/2006

https://digitalcommons.wustl.edu/focal_spot_archives/1101/thumbnail.jp

Wall Tension Regulates the Abundance of miR-133a in the Thoracic Aorta

A reduction in microRNA (miR)-133a is associated with dilation of the thoracic aorta (TA). Since wall tension increases with vessel diameter, this study tested the hypothesis that elevated mechanical tension induces the loss of miR-133a in the TA. Elevated tension (1.5g, 3hrs) applied to murine TA ex vivo reduced miR-133a (0.31±0.17 vs 1.00±0.25 fold; p\u3c0.05 vs normotension (0.7g)). Cyclic stretch (12%, 1Hz, 3hrs) reduced miR-133a in TA fibroblasts (0.21±0.02 vs 1.00±0.27 fold; p\u3c0.05 vs static control), with no change in smooth muscle cells. Neither transcription of miR-133a nor mRNA/protein levels of three microRNA-specific exoribonucleases were altered with stretching of the fibroblasts. However, stretch induced exosome secretion of miR-133a. Two in vivo models of hypertension were utilized to determine the effect of elevated wall tension on miR-133a in the TA: Angiotensin-II infusion (1.44mg/kg/day, 28 days) and a spontaneous hypertensive mouse line (BPH2). In both models, blood pressures were elevated and miR-133a was decreased in the TA compared to normotensive mice (0.69±0.06 and 0.52±0.04 vs 1.00±0.13 fold respectively; p\u3c0.05 for both). Plasma miR-133a was elevated in the BPH2 mice (3.39±0.77 vs 1.00±0.41 fold; p\u3c0.05 vs normotensive). Plasma miR-133a was also elevated in hypertensive human subjects (1.55±0.26 vs 1.00±0.18 fold, p\u3c0.05 vs normotensive). These findings demonstrate that the reduction in miR-133a levels that occurred with increased mechanical stretch of the TA was likely driven by exosome secretion from TA fibroblasts, and may provide a novel target for detrimental remodeling of the vasculature in the setting of hypertension

Open-Source Telemedicine Platform for Wireless Medical Video Communication

An m-health system for real-time wireless communication of medical video based on open-source software is presented. The objective is to deliver a low-cost telemedicine platform which will allow for reliable remote diagnosis m-health applications such as emergency incidents, mass population screening, and medical education purposes. The performance of the proposed system is demonstrated using five atherosclerotic plaque ultrasound videos. The videos are encoded at the clinically acquired resolution, in addition to lower, QCIF, and CIF resolutions, at different bitrates, and four different encoding structures. Commercially available wireless local area network (WLAN) and 3.5G high-speed packet access (HSPA) wireless channels are used to validate the developed platform. Objective video quality assessment is based on PSNR ratings, following calibration using the variable frame delay (VFD) algorithm that removes temporal mismatch between original and received videos. Clinical evaluation is based on atherosclerotic plaque ultrasound video assessment protocol. Experimental results show that adequate diagnostic quality wireless medical video communications are realized using the designed telemedicine platform. HSPA cellular networks provide for ultrasound video transmission at the acquired resolution, while VFD algorithm utilization bridges objective and subjective ratings

Experiment and Animal Models of AAA

Introduction: The incidence of abdominal aortic aneurysms has been increasing throughout the world. The etiology and pathophysiology of this disease are very complicated and complex and include biomechanical aspects as well as biological processes. The effect of these mechanisms is the degradation of the aortic wall, which leads to its dilation and rupture. The possibilities for studying such complex pathophysiology in humans are very limited. That is why we use various mathematical models and a number of different animal models of aneurysm. Methods: A summary of the basic characteristics, findings and examples of using the most widely used animal models of abdominal aortic aneurysm. Information has been obtained from our own experience with laboratory animals and from studies published and available on the Pubmed Internet database. The following search terms were used: aneurysm, aorta, animal model and experiment. Conclusion: Animal models of aortic aneurysms are a usable and useful tool in the study of AAA etiopathogenesis. They also serve as a means to find novel therapeutic pathways. Each model, like any animal species, is different and has its own limitations, advantages and disadvantages, which we should always consider during their use and while interpreting the results