Management Of Thoracic Aortic Aneurysms Research Articles

Clinical Interpretation of Genetic Variants in the Evaluation and Management of Thoracic Aortic Aneurysm and Dissection

BackgroundWe aimed to elucidate clinical implications of genetic variant interpretation in assessing disease severity and progression in thoracic aortic aneurysm and dissection (TAAD) patients. MethodsConsecutive TAAD patients with aortic root and/or ascending aortic aneurysms seen between 2011 and 2020 were included. Serial echocardiography, family history of TAAD, and management information were retrospectively collected and analyzed. Patients were classified into gene-positive (Gen-P), variants of uncertain significance, and gene-negative (Gen-N) groups. ResultsA total of 407 patients were included: mean age 53.7 ± 15.4 years, 64.4% men, and 38% with reported family history of TAAD. Thirty-seven (9.1%) were Gen-P; 147 (36.1%) had a variant of uncertain significance. The maximal aneurysm diameter was 4.78 mm larger in Gen-P than the other groups (P < .001). In 162 unoperated TAAD patients with serial echocardiographic measurements, aneurysms enlarged at a significantly higher rate in the Gen-P (1.36 mm/year, 95% CI: 0.77-1.95) than variants of uncertain significance and Gen-N groups (0.83 mm/year vs 0.89 mm/year, respectively; P < .001). Aneurysms were 20% more likely to require surgical intervention for every millimeter increase in diameter. When considered on an individual basis, the highest growth rates were found in the variants of uncertain significance group. ConclusionsWhile aneurysms linked to variants of uncertain significance demonstrate average growth rates comparable to those in Gen-N, close follow-up and genetic counseling in the variants of uncertain significance group are recommended for assessment of pathogenicity on a case-by-case basis. Early familial gene testing in TAAD is important to develop individualized preventive and therapeutic criteria.

Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection.

Thoracic aortic aneurysms (TAAs) are a major cause of death owing to weaker blood vessel walls and higher rupture rates in affected individuals. Vascular smooth muscle cells (VSMCs) are the predominant cell type within the aortic wall and their dysregulation may contribute to TAA progression. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, is involved in several pathological processes; however, the biological functions and mechanisms underlying VSMC phenotype transition and vascular intimal hyperplasia remain unclear. The present study aimed to determine the involvement of EZH2 in mediating VSMC function in the development of TAAs. The expression of EZH2 was revealed to be elevated in patients with thoracic aortic dissection and TAA mouse model through western blotting and reverse transcription-quantitative PCR experiments. Subsequently, a mouse model was established using β-aminopropionitrile. In vitro, EdU labeling, Transwell assay, wound healing assay and hematoxylin-eosin staining revealed that knocking down the Ezh2 gene could reduce the proliferation, invasion, migration, and calcification of mouse primary aortic smooth muscle cells. Flow cytometry analysis found that EZH2 deficiency increased cell apoptosis. Depletion of Ezh2 in mouse primary aortic VSMCs promoted the transformation of VSMCs from a synthetic to a contractile phenotype. Using RNA-sequencing analysis, it was demonstrated that Ezh2 regulated a group of genes, including integrin β3 (Itgb3), which are critically involved in the extracellular matrix signaling pathway. qChIP found Ezh2 occupies the Itgb3 promoter, thereby suppressing the expression of Itgb3. Ezh2 promotes the invasion and calcification of VSMCs, and this promoting effect is partially reversed by co-knocking down Itgb3. In conclusion, the present study identified a previously unrecognized EZH2-ITGB3 regulatory axis and thus provides novel mechanistic insights into the pathophysiological function of EZH2. EZH2 may thus serve as a potential target for the management of TAAs.

Thoracic Aortic Aneurysmal Disease: Comprehensive Recommendations for the Primary Care Physician

Thoracic aortic aneurysm (TAA) is a commonly encountered disease that is defined as aortic dilation with an increase in diameter of at least 50% greater than the expected age- and sex-adjusted size. Thoracic aortic aneurysms are described by their size, location, morphology, and cause. Primary care clinicians and other noncardiologists are often the first point of contact for patients with TAA. This review is intended to provide them with basic information on the differential diagnosis, diagnostic evaluation, and medical and surgical management of TAAs. Management decisions depend on having as precise a diagnosis as possible. Fortunately, this can often be achieved with a stepwise diagnostic approach that incorporates imaging and targeted genetic testing. Our review includes recommendations. In this review, we discuss these issues at a basic level and include recommendations for patients considering pregnancy.

How Important are Genetics in the Management of Thoracic Aortic Aneurysms and Acute Aortic Syndromes? What do we Know Today?

How Important are Genetics in the Management of Thoracic Aortic Aneurysms and Acute Aortic Syndromes? What do we Know Today?

4D segmentation of the thoracic aorta from 4D flow MRI using deep learning

Background4D flow MRI allows the analysis of hemodynamic changes in the aorta caused by pathologies such as thoracic aortic aneurysms (TAA). For personalized management of TAA, new biomarkers are required to analyze the effect of fluid structure iteration which can be obtained from 4D flow MRI. However, the generation of these biomarkers requires prior 4D segmentation of the aorta. ObjectiveTo develop an automatic deep learning model to segment the aorta in 4D from 4D flow MRI. MethodsSegmentation is addressed with a U-Net based segmentation model that treats each 4D flow MRI frame as an independent sample. Performance is measured with respect to Dice score (DS) and Hausdorff distance (HD). In addition, the maximum and minimum surface areas at the level of the ascending aorta are measured and compared with those obtained from cine-MRI. ResultsThe segmentation performance was 0.90 ± 0.02 for the DS and the mean HD was 9.58 ± 4.36 mm. A correlation coefficient of r = 0.85 was obtained for the maximum surface and r = 0.86 for the minimum surface between the 4D flow MRI and cine-MRI. ConclusionThe proposed automatic approach of 4D aortic segmentation from 4D flow MRI seems to be accurate enough to contribute to the wider use of this imaging technique in the analysis of pathologies such as TAA.

TEVAR Triumphant in the Battle

This population based cohort study demonstrated that the management of thoracic aortic aneurysms (TAA) in England has dramatically changed with the endovascular revolution in the last two decades.1 Using a national administrative dataset based on the International Statistical Classification of Diseases and Related Health Problems (ICD-9/ICD-10), Hanna et al. report a mean increase in hospitalisations for TAA of 6.4% per annum from 5.95 per 100 000 in 1998 to 14.36 per 100 000 in 2020 (p < .001).

Awake intubation for thoracic aortic aneurysm causing esophageal stenosis with food residues and compression of the pulmonary artery and left bronchi: a case report

BackgroundAnesthetic management of thoracic aortic aneurysms (TAAs) is sometimes difficult due to fatal complications, including hypovolemic shock secondary to aneurysm rupture. We report the successful management of an impending rupture of a TAA with associated esophageal stenosis and compression of the pulmonary artery and left bronchi.Case presentationAn 83-year-old woman, diagnosed with an impending rupture of the ascending TAA, was scheduled to undergo emergency total aortic arch replacement. Computed tomography showed esophageal stenosis with significant amounts of food residues in the thoracic esophagus and compression of the pulmonary artery and bronchi. We performed awake intubation and superior laryngeal nerve block with light sedation to prevent aspiration and aneurysmal rupture, respectively. General anesthesia was induced immediately after the intubation. No intraoperative complications occurred.ConclusionsPerforming awake intubation with a superior laryngeal nerve block and sedation may prevent aspiration of food residues and hemodynamic changes that may lead to rupture.

Surveillance for moderate-sized thoracic aortic aneurysms: Equality is the goal.

Comprehensive clinical and imaging-based surveillance represents a fundamental aspect in the management of thoracic aortic aneurysms (TAAs), affording the opportunity to identify intermediate-sized TAAs before the onset of worrying symptoms or devastating acute aortic dissection/rupture. Currently, size-based indices are favored as the major determinants driving patient selection for surgery, as supported by aortic guidelines, although it is recognized that smaller subthreshold TAAs may still confer substantial risks. Prophylactic aortic surgery can be offered within set timeframes at dedicated aortic centers with excellent outcomes, to mitigate the threat of acute aortic complications associated with a repeatedly deferred intervention. In this commentary, we discuss a recent article from the Journal of Cardiac Surgery that highlights important socioeconomic disparities in TAA surveillance and follow-up.

Thoracic Aortic Aneurysm: A Clinical Review.

Thoracic aortic aneurysms are common. Most thoracic aortic aneurysms are degenerative. However, some are associated with connective tissue disorders, bicuspid aortic valves, or familial/genetic predisposition. Most are asymptomatic, discovered incidentally on imaging. Aortic diameter is the best predictor of the natural history and risk of complications. Treating hypertension and smoking cessation can slow their growth. Surveillance imaging and referral for prophylactic aortic repair based on absolute aneurysm diameter is the primary means to decrease mortality from thoracic aortic aneurysm. We provide a practical evidence-based summary of the pathophysiology, risk factors, associated genetic syndromes, and clinical management of thoracic aortic aneurysms.

Efficacy and cost-effectiveness of cell saver usage in the repair of thoracic aortic aneurysms and dissections.

A substantial amount of blood loss occurs during the open repair of aortic aneurysms or dissections. The aim of the present study is to determine the efficacy and cost-effectiveness of cell saver devices in blood conservation during the open repair of thoracic aortic pathologies. The present study prospectively collected the data pertaining to 25 patients who underwent surgical management of thoracic aortic aneurysms or dissections using a cell saver (Group 1, n = 25). The volume and cost of transfusion and postoperative outcomes were compared with the second group of patients who underwent surgery without the use of cell savers in the previous year (Group 2, n = 25); the data pertaining to the same were retrospectively collected from the hospital records. The patient characteristics and categorical variables were compared using the x2 test and Fisher's exact test. Transfusion volume and costs were compared using the independent samples t-test and Mann-Whitney U test. The patients in both the groups displayed similar characteristics and risk factors. The total volume of allogenic red blood cell (p < 0.001) and total blood product (p = 0.01) transfusions were significantly lower in Group 1. The cost of red blood cell (p < 0.001) and total transfusions (p = 0.03) were lower in Group 1. The two groups displayed similar in-hospital morbidity and mortality rates. There was a significant association between the use of cell savers and the decreased need for red blood cell and total blood product transfusions. Considering the cost of the cell saver set, transfusion costs in the two groups were comparable.

Aortic Stiffness, Central Blood Pressure, and Pulsatile Arterial Load Predict Future Thoracic Aortic Aneurysm Expansion.

Thoracic aortic aneurysm is a disease associated with high morbidity and mortality. Clinically useful strategies for medical management of thoracic aortic aneurysm are critically needed. To address this need, we sought to determine the role of aortic stiffness and pulsatile arterial load on future aneurysm expansion. One hundred five consecutive, unoperated subjects with thoracic aortic aneurysm were recruited and prospectively followed. By combining arterial tonometry with echocardiography, we estimated measures of aortic stiffness, central blood pressure, steady, and pulsatile arterial load at baseline. Aneurysm size was measured at baseline and follow-up with imaging; growth was calculated in mm/y. Stepwise multivariable linear regression assessed associations of arterial stiffness and load measures with aneurysm growth after adjusting for potential confounders. Mean±SD age, baseline aneurysm size, and follow-up time were 62.6±11.4 years, 46.24±3.84 mm, and 2.92±1.01 years, respectively. Aneurysm growth rate was 0.43±0.37 mm/y. After correcting for multiple comparisons, higher central systolic (β±SE: 0.026±0.009, P=0.007), and pulse pressures (β±SE: 0.032±0.009, P=0.0002), carotid-femoral pulse wave velocity (β±SE: 0.032±0.011, P=0.005), amplitudes of the forward (β±SE: 0.044±0.012, P=0.0003) and reflected (β±SE: 0.060±0.020, P=0.003) pressure waves, and lower total arterial compliance (β±SE: -0.086±0.032, P=0.009) were independently associated with future aneurysm growth. Measures of aortic stiffness and pulsatile hemodynamics are independently associated with future thoracic aortic aneurysm growth and provide novel insights into disease activity. Our findings highlight the role of central hemodynamic assessment to tailor novel risk assessment and therapeutic strategies to patients with thoracic aortic aneurysm.

ESTIMATED AORTIC PULSE WAVE VELOCITY PREDICTS FUTURE THORACIC AORTIC ANEURYSM EXPANSION: RESULTS FROM A PROSPECTIVE COHORT STUDY WITH SEX-SPECIFIC ANALYSES

Thoracic aortic aneurysm (TAA) is a disease of increasing prevalence and associated with high morbidity and mortality. As such, novel, clinically useful strategies for risk assessment and medical management of TAA are critically needed. We have previously shown that aortic stiffness (measured by carotid-femoral pulse wave velocity, cfPWV) independently predicts future TAA growth. Since aortic pulse wave velocity can be mathematically estimated based on age and blood pressure (e-PWV), obviating the need for equipment and increasing clinical applicability, we sought to determine the predictive role of e-PWV on future TAA expansion.

The anaesthetic management of patients with thoracic ascending aortic aneurysms: A review.

Thoracic aortic aneurysms present significant challenges to clinicians, especially due to their complex nature and an evolving understanding of the safest and most effective ways to manage this condition in the perioperative setting. Thoracic aortic aneurysms have a prevalence rate of 1.3-8.9% in men and 1.0-2.2% in women, and they are estimated to affect more than five per 100,000 person-years. This is notable because the complications of thoracic aortic aneurysms can be catastrophic. The current understanding of the optimal intraoperative management of thoracic aortic aneurysms is changing, as more evidence becomes available regarding lung protective ventilation and its role in enhancing patient safety and wellbeing. This review strives to provide a brief historical understanding of thoracic aortic aneurysms and highlight some of the key discoveries and advances in the management of this condition. This review then describes an overview of the general anaesthetic principles associated with thoracic aortic aneurysms, including ventilatory modalities and how these impact a patient's physiology and intraoperative haemodynamics. A brief discussion on one-lung ventilation is then provided, drawing from current literature in the field, to describe the most up-to-date management of thoracic aortic aneurysms.

MEASURES OF AORTIC STIFFNESS, CENTRAL BLOOD PRESSURE AND PULSATILE ARTERIAL LOAD PREDICT FUTURE ANEURYSM EXPANSION

Thoracic aortic aneurysm (TAA) is a disease of increasing prevalence and associated with high morbidity and mortality. As such, novel, clinically useful stcArategies for risk assessment and medical management of TAA are critically needed. To address this need, we sought to determine the predictive role of aortic stiffness and pulsatile arterial load (which reflect the aorta’s health and function) on future TAA expansion. One hundred and six consecutive, unoperated subjects with TAA were recruited. By combining arterial tonometry with echocardiography using validated methods, we estimated measures of aortic stiffness, central blood pressure (BP), steady and pulsatile arterial load at baseline. Measures of aortic stiffness, central BP and pulsatile arterial load correlate directly with aortic health and function, while measures of steady arterial load reflect resistive load from peripheral arteries instead. Aneurysm size was measured at baseline and follow-up with imaging and indexed to height. TAA growth was calculated in (mm/m)/year. Stepwise multivariable linear regression assessed associations of baseline arterial stiffness and load measures, in separate models, with aneurysm growth. Variables considered in the models were: age, sex, BSA, mean arterial pressure, baseline aneurysm size, aneurysm etiology and location, follow-up time, concordant/discordant nature of the imaging modalities and history of hypertension, diabetes and smoking. Interaction terms for age, sex, and aneurysm etiology with each hemodynamic measure were tested in the models. Seventy five percent of subjects were men. Mean±SD age, baseline aneurysm size and follow-up time were 62.8±11.4 years, 46.5±3.9 mm and 2.3±0.9 years, respectively. Aneurysm growth rate was 0.34±0.36 mm/year in men and 0.73±0.84 mm/year in women (P=0.040). Results of the linear regression models are summarized in the Table. Measures of aortic stiffness, central BP and pulsatile arterial load independently predicted future aneurysm expansion. Conversely, brachial BP and steady arterial load did not. None of the interaction terms were significant, suggesting that results are equally applicable to all ages, both sexes, and all TAA etiologies. Potential applications of our findings are summarized in the Figure. Measures of aortic function, including aortic stiffness and pulsatile hemodynamics, independently predict future TAA growth and provide novel insights into disease activity. Moreover, some of the hemodynamic measures were superior to baseline aneurysm size (which is the standard for clinical assessment) in the prediction of future aneurysm expansion. Our findings demonstrate a potential role for non-invasive hemodynamic assessment as a means to better predict TAA disease activity and refine risk stratification in patients with TAA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Aortoesophageal fistula postthoracic endovascular aortic repair

Thoracic endovascular aortic repair (TEVAR) is one of the choices for management of thoracic aortic aneurysms.[1] However, the complications of this procedure remain undetermined.[1] We present a 91 years male with a fatal post TEVAR aortoesophageal pseudoaneurysm leak and fistula to draw attention for such complication and its primary symptoms that may provide immediate treatment.

Advanced Techniques in Thoracic Endovascular Aortic Repair: Chimneys/Periscopes, Fenestrated Endografts, and Branched Devices

Thoracic endovascular aortic repair (TEVAR) is a rapidly growing and improving technique for the management of thoracic aortic aneurysms, dissections, and traumatic aortic injury. These disease processes were previously treated exclusively by surgery, but TEVAR has substantially improved patient outcomes including reduced mortality, reduced paraplegia rate, and shorter hospital and/or intensive care unit stay compared to open surgery. TEVAR was initially isolated to the descending thoracic aorta, but the advent of advanced techniques has extended the scope to well beyond the left subclavian artery and into Zone 0. Recent techniques include chimney grafts, periscope grafts, in situ fenestrations, and physician modified grafts. In addition, commercial branched aortic devices are currently on trial and will likely vastly extend the off-the-shelf capabilities of TEVAR for aortic arch disease. This paper reviews the data, concepts, and technical aspects of current advanced TEVAR techniques, as well as ongoing clinical trials for thoracic branched aortic devices.

How can genetic diagnosis inform the decision of when to operate?

Genetic discovery for heritable thoracic aortic disease (HTAD) has been progressing at a brisk pace. Surgical management of thoracic aortic aneurysms and dissections has become more personalized, with genetic factors increasingly informing the decision of when to operate on patients. An improved understanding of genotype-phenotype correlations in patients with HTAD will ultimately lead to gene- and mutation-specific recommendations for surgical repair. Until more robust data from larger cohorts can inform our decisions, patients with HTAD should be seen by an aortic specialist for a tailored approach to elective surgical repair.

Open versus Endovascular Repair of Arch and Descending Thoracic Aneurysms: A Retrospective Comparison

Thoracic aortic aneurysms (TAAs) contribute significant mortality if left untreated, but surgical repair has historically carried substantial risks. We sought to observe trends and outcomes of open and endovascular thoracic endovascular aneurysm repair thoracic aortic repairs, so conducted a retrospective review of all patients who presented for management of TAAs from 2003 to 2013 at 2 hospitals in Sydney, Australia. A total of 179 patients presented with TAAs over the study period, including 5 ruptures. Fifty-two were treated nonoperatively, with 127 surgically repaired. Operative duration was significantly shorter in endovascular than open repair of arch (193±108 vs. 396±98min, P=0.0001) and descending aneurysms (242±116 vs. 422.5±161min, P=0.003). There were no differences in mortality or complication rates (including paraplegia), duration of hospital or intensive care unit stay, or transfusion requirements between endovascular and open TAA repairs. Apart from reduced surgical duration, this study revealed no benefits of endovascular over open TAA repair. Overall morbidity and mortality were low, even in elderly patients.

Multidisciplinary Aortopathy Clinics Should Now Be the Standard of Care in Canada

Thoracic aortic aneurysm is often undiagnosed and has a very poor prognosis when presented with acute aortic dissection. Early diagnosis, expert medical management, and elective aortic surgery are the cornerstones of improvement of long-term survival in thoracic aortic disease (TAD). International guidelines now recommend the acute and long-term management of patients with TAD to occur within multidisciplinary aortopathy clinics under the care of professionals with specific training and experience. Multidisciplinary “heart teams” are recognized to be more focused on patient-centric care, to facilitate faster clinical decision times with increased adherence to guideline-directed therapy, and to improve knowledge translation and physician and patient satisfaction. The range of differential diagnoses for TAD has expanded rapidly over the past decade. Diagnosis of an index case with a syndromic or nonsyndromic familial TAD allows for preventative care. Effective family screening can save lives by allowing for elective management of thoracic aortic aneurysm rather than emergent care of acute aortic complications. Expert cardiac imaging with access to the full range of required imaging modalities is central to all clinical management decisions. Medical and surgical management of TAD is now provided as personalized care according to patient- and disease-specific factors. Special considerations apply to pregnancy management for women with TAD. Multidisciplinary aortopathy clinics should now be the standard of care for the management of TAD in Canada and we should implement best practice guidelines. With the already established and emerging clinics, the stage is now set to build a Canadian Aortopathy Clinics Trials network.

Arterial hypertension and aortic root dilatation: an unsolved mystery

Introduction: Acute and chronic aortic syndromes are associated with substantial morbidity and mortality. Silent risk factors such as arterial hypertension and aortic root dilatation can increase the likelihood of aortic dissection or rupture. The relationship between arterial hypertension and the dimensions of the aortic root dimension is a topic of active debate. Materials and methods: We reviewed the literature on the physiopathology, diagnosis, natural history, and management of thoracic aortic aneurysms. Results: Biological variables influencing the size of the aorta include age, sex, body surface area, pressure values, and stroke volume. Pathologic enlargement of the thoracic aorta can be caused by genetic, degenerative, inflammatory, traumatic, or toxic factors. Studies investigating the correlation between aortic dimensions and arterial pressures (diastolic, systolic, or pulse) have produced discordant results. Discussion: Classically, emphasis has been placed on the importance of hypertension-related degeneration of the medial layer of the aortic wall, which leads to dilatation of the thoracic aorta, reduced aortic wall compliance, and increased pulse pressures. However, there are no published data that demonstrate unequivocally the existence of a pathogenetic correlation between arterial hypertension and aortic root dilatation. Furthermore, there is no evidence that antihypertensive therapy is effective in the management of nonsyndromic forms of aortic root dilatation. An interesting branch of research focuses on the importance of genetic predisposition in the pathogenesis of thoracic aortic aneurysms. Different genetic backgrounds could explain differences in the behaviour of aortic walls exposed to the same hemodynamic stress. Further study is needed to evaluate these focal physiopathological aspects.