Practice Patterns and Barriers to Vascular Genetic Testing Among Vascular Surgeons.

INTRODUCTION: Engaging patients living with or at risk of aortic dissection via the Aortic Dissection Collaborative, physician education in vascular genetics was identified as a research priority. We surveyed vascular surgeons to characterize practice patterns, motivations, and barriers regarding aortopathy genetic testing. METHODS: An anonymous 27-question survey was distributed on social media platforms between November and December 2022. Domains included demographics, vascular genetic education, testing attitudes and utilization, and experience in treating patients with genetic vascular aortopathies. The analysis included summary statistics and unpaired t-test to compare responses by interest in incorporating testing and practice type. RESULTS: A total of 171 vascular surgeons from 15 countries responded to the survey (23% trainees). Over half received vascular genetics education during training (59%), and most (86%) were interested in incorporating genetic testing into their practice. Academic surgeons were more likely to have cared for a patient with a known genetic aortopathy over the past year than surgeons in hospital-based and private practices (83% vs. 56% vs. 27%; P < 0.01), to have ever made a referral to a medical geneticist (78% vs. 51% vs. 9%; P < 0.01), and have access to genetic counselors or geneticists (66% vs. 46% vs. 0%; P < 0.01). Barriers to genetic testing were rated as more significant by surgeons in nonacademic practices, with top barriers being insurance coverage of testing, cost of genetic testing, and access to genetic counselors. Evidence-based professional society guidelines were the strongest rated motivating factor for testing incorporation among respondents. CONCLUSIONS: Vascular surgeon attitudes are not major barriers to incorporating genetic testing for patients with aortopathies; however, practical challenges regarding genetic testing and counseling are barriers to implementation especially for vascular surgeons in nonacademic practices. Future efforts should focus on evidence-based society guidelines, continuing medical education to increase adoption, and facilitating access to genetic counseling.

Complicated and Uncomplicated Isolated Abdominal Aortic Dissections Demonstrate Different Patient Characteristics and Outcomes.

BACKGROUND: Isolated abdominal aortic dissection (IAAD) is a rare entity with poorly defined risk factors and wide variation in management. We set forth to compare patient characteristics, management, and outcomes of uncomplicated isolated abdominal aortic dissection (uIAAD) versus high risk and complicated isolated abdominal aortic dissection (hrcIAAD) to investigate whether these categories can be utilized to guide IAAD management and provide risk stratification for intervention. METHODS: Retrospective chart review was performed to identify all patients with spontaneous IAAD at a tertiary health care system between 1996 and 2022. Demographics, comorbidities, factors relating to initial presentation including imaging findings, and dissection outcomes including long-term all-cause mortality and aortic-related mortality from time of dissection to final available record were abstracted. IAAD demonstrating rupture or malperfusion were designated as complicated, those with aortic diameter greater than 4 cm on presentation or refractory pain were designated as high risk, and the remainder was designated as uIAAD. All variables were compared between hrcIAAD and uIAAD using Fisher's exact test, unpaired t-test, and Mann-Whitney U-test as appropriate. RESULTS: Over the study period, 74 patients presented with spontaneous IAAD (mean age 60 ± 16 years, 61% male) with postdissection follow-up records to an average of 6.8 ± 5.8 years. Of these, 76% presented with uIAAD versus 24% with hrcIAAD. hrcIAAD was diagnosed at a significantly younger age on average than uIAAD (52 ± 14 vs. 62 ± 16 years, P = 0.02), was less likely to present with concomitant hyperlipidemia (0% vs. 41%, P < 0.01), coronary artery disease (6% vs. 47%, P < 0.01), and prior smoking history (39% vs. 72%). hrcIAAD was more likely to present in patients with a genetic aortopathy (27% vs. 7%, P = 0.03). Hypertension was not significantly different between groups. Patients with hrcIAAD were significantly more likely to present with extension into iliac arteries compared to uIAAD (61% vs. 18%, P < 0.01). A much higher proportion of hrcIAAD required hospitalization compared to uIAAD (83% vs. 30%, P < 0.01) and operative intervention (67% vs. 7%, P < 0.01). While there was no significant difference in all-cause mortality between groups, there was a significant difference between aortic-related mortality which only occurred in those with hrcIAAD (28% vs. 0%, P < 0.01). CONCLUSIONS: Comparison of long-term outcomes suggests that hrcIAAD is associated with increased hospitalization and need for operative intervention compared to uIAAD. Significant differences in atherosclerotic risk factors and proportions of connective tissue disease history between patients who present with hrcIAAD and uIAAD suggest that differences in underlying etiology are largely responsible for whether IAAD progresses towards rupture or has a more benign course and should be considered in risk stratification to guide more specific and targeted management of IAAD.

Iliac artery dissection and rupture in a patient with classic Ehlers-Danlos syndrome due to COL5A1 null variant.

This is a case of a 46-year-old woman who presented with right common iliac artery dissection preceded by a left common iliac artery dissection and rupture 6 years earlier. Both iliac arteries required repair. Based on her presentation, she met the clinical diagnostic criteria for vascular Ehlers-Danlos syndrome; however, the genetic workup demonstrated that she had classic Ehlers-Danlos syndrome due to a null variant in COL5A1, which is rarely associated with arteriopathy.

Impact of COVID-19 on patients undergoing scheduled procedures for chronic venous disease.

OBJECTIVE: The COVID-19 pandemic has drastically altered the medical landscape. Various strategies have been employed to preserve hospital beds, personal protective equipment, and other resources to accommodate the surges of COVID-19 positive patients, hospital overcapacities, and staffing shortages. This has had a dramatic effect on vascular surgical practice. The objective of this study is to analyze the impact of the COVID-19 pandemic on surgical delays and adverse outcomes for patients with chronic venous disease scheduled to undergo elective operations. METHODS: The Vascular Surgery COVID-19 Collaborative (VASCC) was founded in March 2020 to evaluate the outcomes of patients with vascular disease whose operations were delayed. Modules were developed by vascular surgeon working groups and tested before implementation. A data analysis of outcomes of patients with chronic venous disease whose surgeries were postponed during the COVID-19 pandemic from March 2020 through February 2021 was performed for this study. RESULTS: A total of 150 patients from 12 institutions in the United States were included in the study. Indications for venous intervention were: 85.3% varicose veins, 10.7% varicose veins with venous ulceration, and 4.0% lipodermatosclerosis. One hundred two surgeries had successfully been completed at the time of data entry. The average length of the delay was 91 days, with a median of 78 days. Delays for venous ulceration procedures ranged from 38 to 208 days. No patients required an emergent intervention due to their venous disease, and no patients experienced major adverse events following their delayed surgeries. CONCLUSIONS: Interventions may be safely delayed for patients with venous disease requiring elective surgical intervention during the COVID-19 pandemic. This finding supports the American College of Surgeons' recommendations for the management of elective vascular surgical procedures. Office-based labs may be safe locations for continued treatment when resources are limited. Although the interventions can be safely postponed, the negative impact on quality of life warrants further investigation.

Open repair of a ruptured abdominal aorta with an aortoiliac vein fistula in a 7-month-old infant and review of the literature.

Ruptured abdominal aortic aneurysms are extremely rare in the pediatric population. In this video case report, we describe the successful repair of a ruptured abdominal aortic aneurysm in a 7-month-old female infant.

Obstetric considerations for aortopathy in pregnancy.

Aortic dissection (AD) associated with pregnancy can have catastrophic consequences for the mother and/or fetus. AD occurs in 4-5 per 1,000,000 pregnancies and, despite its rarity, is the third most frequent maternal cardiovascular cause of death. AD associated with pregnancy is most likely to occur in the third trimester or postpartum period. In individuals with genetic aortopathy, pregnancy is considered a high-risk time for AD. There are management strategies in the preconception, antepartum, delivery and postpartum periods to optimize patient care. A multi-disciplinary team that includes capability to perform cardiovascular surgery is critical. Imaging modalities including maternal echocardiogram and magnetic resonance imaging can be safely performed in pregnancy for surveillance of the aortic size. Computed tomography (CT) scan is reserved for scenarios where there is a high index of suspicion for AD in a pregnant person to limit fetal exposure to radiation. After counseling about the potential risks of a pregnancy, the decision to pursue pregnancy is ultimately at the discretion of the individual. The duty of the cardio-obstetric team is to ensure that the patient and their family understand the risks of a pregnancy and the plan of care.

Prevalence and outcomes of select rare vascular conditions in females: A descriptive review.

Rare vascular conditions frequently pose a diagnostic and therapeutic dilemma for health care providers. Several of these conditions have distinct relevance to females populations but, due to their infrequency, there has been little reported on the outcomes of rare vascular conditions specifically in females populations. We performed a literature review of a selection of three rare vascular conditions known to either disproportionately affect females (median arcuate ligament syndrome and fibromuscular dysplasia) or have unique manifestations in females populations (vascular Ehlers-Danlos syndrome). We performed a descriptive review of the literature focused on these three vascular conditions and identified aspects of the current available research describing sex-based differences in prevalence, any pathophysiology explaining the observed sex-based differences, and the contribution of sex to outcomes for each disease process. In addition, considerations for pregnant females with respect to each rare vascular disease process are discussed.

Natural history of the distal aorta following elective root replacement in patients with Marfan syndrome.

OBJECTIVE: It is unclear if the addition of a prophylactic arch operation is beneficial at the time of root replacement in patients with Marfan syndrome (MFS). This project aims to understand the fate of the distal aorta following elective root replacement in patients with MFS. METHODS: Between 2000 and 2019, 124 adult patients with MFS were identified as having undergone elective aortic root replacement with a clamped distal aortic anastomosis during their lifetime. Serial axial imaging was analyzed. The primary outcome was a composite of subsequent type B aortic dissection (TBAD), aneurysmal degeneration (>4 cm), and aortic reintervention. Secondary outcomes included subsequent TBAD and mortality. RESULTS: Mean age at root replacement was 33.3 years. Median follow-up was 11.3 years. Thirty-one patients (25%) experienced the primary outcome, with no survival difference (P = .9). The crossclamp and aortic cannulation sites were stable (growth rate, 0.33 mm/year), and 2 patients (1.6%) required reintervention there. Twenty-three patients (19.8%) experienced subsequent TBAD. Patients with TBAD had a higher rate of distal degeneration (P < .001), but no significant change in survival (P = .2). Preoperative hypertension (odds ratio, 3.96; P < .05) and younger age at root replacement (odds ratio, 1.05; P < .05) increased the risk of TBAD, based on regression analysis. CONCLUSIONS: The distal aorta (including the clamp and cannulation site) overall appears stable in patients with MFS following elective root replacement without prophylactic arch operation. Development of TBAD seems to be the primary driver of distal degeneration. Factors associated with TBAD development included hypertension, underscoring the importance of strict blood pressure control in these patients.

A multidisciplinary multistage complete mega aorta replacement and utilization of extracorporeal membrane oxygenation in thoracoabdominal aneurysm repair.

A 49-year-old woman underwent a 11-month multistage complete replacement of a mega aorta. Replacement stages included ascending aorta and arch replacement in conjunction with a frozen elephant trunk thoracic endovascular aortic repair, extension of thoracic endovascular aortic repair to zone 5, and open repair of the thoracoabdominal aneurysm with the use of venoarterial extracorporeal membrane oxygenation for circulatory support. This case illustrates the complexity of repairing a mega aorta, the multidisciplinary care and staging needed for repair, and the use of peripheral venoarterial extracorporeal membrane oxygenation for circulatory perfusion during thoracoabdominal aneurysm repair.

Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome.

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P=0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P=0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.

Operative repair of right intrathoracic subclavian artery aneurysms in patients with genetic arteriopathy.

True intrathoracic subclavian artery aneurysms (SCAAs) are rare and have various etiologies. Right intrathoracic SCAAs pose specific anatomic challenges to repair. We present three different operative approaches, open, endovascular, and hybrid repair, for the repair of a right intrathoracic SCAA in three patients with genetic arteriopathy: Marfan syndrome, vascular Ehlers-Danlos syndrome, and unspecified Ehlers-Danlos syndrome, respectively. These cases demonstrate an individualized operative approach based on the genetic diagnosis for each patient presenting with a right intrathoracic SCAA.

Emergency vascular surgical care in populations with unique physiologic characteristics: Pediatric, pregnant, and frail populations.

Vascular surgical emergencies are common in vascular surgical care and require complex decision making and multidisciplinary care. They are especially challenging when they occur in patients with unique physiological characteristics, such as pediatric, pregnant, and frail patients. Among the pediatric and pregnant population, vascular emergencies are rare. This rarity challenges accurate and timely diagnosis of the vascular emergency. This landscape review summarizes these three unique populations' epidemiology and emergency vascular considerations. Understanding the epidemiology is the foundation for accurate diagnosis and subsequent management. Considering each population's unique characteristics is crucial to the emergent vascular surgical interventions decision making. Collaborative and multidisciplinary care is vital in gaining expertise in managing these special populations and achieving optimal patient outcomes.

A systematic review supporting the Society for Vascular Surgery guidelines on the management of heritable aortopathies.

BACKGROUND: To support the development of clinical practice guidelines on the management of patients with genetic aortopathies and arteriopathies, a writing committee from the Society for Vascular Surgery has commissioned this systematic review. METHODS: We conducted a systematic review and searched multiple databases for studies addressing six questions identified by the Society for Vascular Surgery guideline committee about evaluating and managing patients with genetic aortopathies and arteriopathies. Studies were selected and appraised by pairs of independent reviewers. RESULTS: We included 12 studies in this systematic review. We did not identify studies about the long-term outcomes of endovascular repair for aortic aneurysm in patients with heritable aortopathy or about new aortic events in pregnant women with a history of aortic dissection (AD) or aneurysm. A small case series demonstrated a 100% survival rate and 100% aortic intervention-free survival at 15 months (range, 7-28 months) after endograft repair for type B AD. A positive genetic diagnosis was discovered in 36% of patients with aortic aneurysms and dissections who had no risk factors for hereditary aortopathies, and these patients had a mortality rate of 11% at a median follow-up duration of 5 months. Black patients had lower 30-day mortality than White patients (5.6% vs 9.0%, respectively), but they had a higher overall aortic reintervention rate at 30 days after AD repair (47% vs 27%, respectively). Aortic reinterventions owing to aneurysmal expansion and endoleak at 30 days were higher in Black patients than White patients. The certainty of evidence was judged to be very low across all the outcomes evaluated in this systematic review. CONCLUSIONS: The available evidence suggests high survival after thoracic endovascular aortic repair for type B AD in young patients with heritable aortopathies, but with limited long-term follow-up. Genetic testing in patients with acute aortic aneurysms and dissections had a high yield. It was positive for most patients with risk factors for hereditary aortopathies and in more than one-third for all other patients, and was associated with new aortic events within 15 years.

Endovascular repair of a common iliac artery aneurysm with an iliac branch device in a patient with vascular Ehlers-Danlos syndrome due to a null COL3A1 variant.

Endovascular repair is avoided in patients with connective tissues disorders due to concerns for stent graft migration and endoleaks. We describe a successful endovascular repair of a common iliac artery aneurysm with a bifurcated aortoiliac stent graft and iliac branch endoprosthesis in a patient with Vascular Ehlers-Danlos syndrome (VEDS) due to a null COL3A1 variant. This case demonstrates that the VEDS genotype is associated with tissue integrity, specifically, individuals with VEDS due to null/haploinsufficiency variants, and adds to our understanding of endovascular repair in this population.

Open repair of abdominal aortic aneurysms in patients with vascular Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos syndrome (VEDS) is rare, affecting an estimated 1 per 50,000 individuals, and is associated with abdominal aortic aneurysms (AAAs), among other arteriopathies. We present three patients with genetically confirmed VEDS who underwent successful open AAA surgical repair and demonstrate that elective open AAA repair with careful tissue manipulation is safe and feasible for patients with VEDS. These cases also demonstrate that the VEDS genotype is associated with the aortic tissue quality (genotype-surgical phenotype correlation), with the most friable tissue encountered in the patient with a large amino acid substitution and the least friable tissue in the patient with a null (haploinsufficiency) variant.

Splenic artery pathology presentation, operative interventions, and outcomes in 88 patients with vascular Ehlers-Danlos syndrome.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (VEDS) is rare and associated with arteriopathies. The aim of this study is to investigate the presentation, operative interventions, and outcomes of splenic arterial pathology in a population of more than 1500 individuals with genetically confirmed VEDS due to pathogenic COL3A1 variants. METHODS: Cross-sectional analysis of 1547 individuals was performed. The data were assembled by harmonizing data from three overlapping cohorts with genetically confirmed VEDS: the VEDS Collaborative Natural History Study (N = 242), a single-center cohort (N = 75), and the University of Washington Collagen Diagnostic Lab cohort (N = 1231). Duplicates were identified and removed. Patients were selected for analysis if they had splenic artery aneurysm (SAA), pseudoaneurysm, dissection, thrombosis, or rupture. Demographics, COL3A1 variants, interventions, and outcomes were analyzed. Comparisons by splenic artery rupture were made. RESULTS: A total of 88 patients presented between 1992 and 2021 with splenic artery pathology (5.7% of the cohort; mean age at diagnosis, 37 ± 11.1 years; 50% male). One-third were diagnosed with VEDS prior to the splenic artery pathology diagnosis, and 17% were diagnosed post-mortem. Most had a positive family history (61%). Most had COL3A1 variants associated with minimal normal collagen production (71.6%). Median follow up was 8.5 years (interquartile range, 0.9-14.7 years). Initial presentation was rupture in 47% of the cases. Splenic artery rupture overall was 51% (n = 45), including four cases of splenic rupture. There were no major differences in VEDS-related manifestations or COL3A1 variant type by rupture status. SAA was noted in 39% of the cases. Only 12 patients had splenic artery diameter documented in 12 cases with a median diameter of 12 mm (interquartile range, 10.3-19.3 mm). A total of 34 patients (38.6%) underwent 40 splenic arterial interventions: 21 open surgical, 18 embolization, and one unknown procedure. More than one splenic artery intervention was performed in five cases (14.7%). Open repair complications included arteriovenous fistula (n = 1), intestinal or pancreatic injury (n = 1 each), and four intraoperative deaths. There were no deaths or access site complications related to splenic artery embolization. Four patients (23.5%) developed a new SAA in the remaining splenic artery post embolization. All-cause mortality was 35% (n = 31), including 22 related to a ruptured splenic artery. CONCLUSIONS: Splenic arteriopathy in VEDS is associated with variants that affect the structure and secretion of type III collagen and frequently present with rupture. Rupture and open repair are associated with high morbidity and mortality, whereas embolization is associated with favorable outcomes. Suggest repair considerations at SAA diameter of 15 mm. Long-term follow-up is indicated as secondary splenic arteriopathy can occur.

Beta-Blocker Use during Pregnancy Correlates with Less Aortic Root Dilatation in Patients with Marfan's Syndrome.

BACKGROUND: Pregnant patients with Marfan's syndrome (MFS) are at an increased risk for adverse aortic outcomes. While beta-blockers are used to slow aortic root dilatation in nonpregnant MFS patients, the benefit of such therapy in pregnant MFS patients remains controversial. The purpose of this study was to investigate the effect of beta-blockers on aortic root dilatation during pregnancy in MFS patients. METHODS: This was a longitudinal single-center retrospective cohort study of females with MFS who completed a pregnancy between 2004 and 2020. Clinical, fetal, and echocardiographic data were compared in patients on- versus off-beta-blockers during pregnancy. RESULTS: A total of 20 pregnancies completed by 19 patients were evaluated. Beta-blocker therapy was initiated or continued in 13 (65%) of the 20 pregnancies. Pregnancies on-beta-blocker therapy experienced less aortic growth compared with those off-beta-blockers (0.10 [interquartile range, IQR: 0.10-0.20] vs. 0.30 cm [IQR: 0.25-0.35]; p = 0.03). Using univariate linear regression, maximum systolic blood pressures (SBP), increase in SBP, and absence of beta-blocker use in pregnancy were found to be significantly associated with greater increase in aortic diameter during pregnancy. There were no differences in rates of fetal growth restriction between pregnancies on- versus off-beta-blockers. CONCLUSION: This is the first study that we are aware of to evaluate changes in aortic dimensions in MFS pregnancies stratified by beta-blocker use. Beta-blocker therapy was found to be associated with less aortic root growth during pregnancy in MFS patients.