Genetic and epigenetic regulation of abdominal aortic aneurysms

Abdominal aortic aneurysms (AAAs) are focal dilations of the aorta that develop from degenerative changes in the media and adventitia of the vessel. Ruptured AAAs have a mortality of up to 85%, thus it is important to identify patients with AAA at increased risk for rupture who would benefit from increased surveillance and/or surgical repair. Although the exact genetic and epigenetic mechanisms regulating AAA formation are not completely understood, Mendelian cases of AAA, which result from pathologic variants in a single gene, have helped provide a basic understanding of AAA pathophysiology. More recently, genome wide associated studies (GWAS) have identified additional variants, termed single nucleotide polymorphisms, in humans that may be associated with AAAs. While some variants may be associated with AAAs and play causal roles in aneurysm pathogenesis, it should be emphasized that the majority of SNPs do not actually cause disease. In addition to GWAS, other studies have uncovered epigenetic causes of disease that regulate expression of genes known to be important in AAA pathogenesis. This review describes many of these genetic and epigenetic contributors of AAAs, which altogether provide a deeper insight into AAA pathogenesis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155527/1/cge13705.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155527/2/cge13705_am.pd

Emergent stent-graft treatment for rupture

It is not too surprising, given the lower prevalence of thoracic aortic aneurysms (TAA) as compared with abdominal aortic aneurysms (AAA), that development of endovascular devices for thoracic disease has lagged behind progress in the infrarenal area. Recently, published reports of decreased mortality associated with endovascular device implantation for ruptured AAAs have highlighted its potential advantage in emergent situations. The first reported use of an endovascular stent graft to treat a ruptured TAA was reported by Semba et al in 1997. Although the use of endovascular therapy to treat ruptured AAAs is gaining wider acceptance, its use in thoracic pathologies has been slow to develop in the United States, even though 20% of TAAs and nearly 50% of thoracic dissections present with rupture in the EUROSTAR registry. This may be a factor of relatively limited dissemination of technology. Examination of clinical trial enrollment shows that 10 sites in the United States account for approximately 50% of the cumulative implantations

Case Series on Double-Barrel Stenting for the Renal Arteries Associated With Fenestrated Repair (FEVAR) of Complex Anatomy Aortic Aneurysms

The double-barrel stenting (DBS) is a technique in which 2 parallel stents are simultaneously deployed through the same reinforced fenestration, into 2 adjacent target vessels. Prior reports describe the application of this technique for the treatment of superior mesenteric artery dissection with aneurysmal degeneration, coronary artery bifurcations, aortic arch branches, and intracranial aneurysms. The DBS technique is particularly useful in the context of fenestrated repair (FEVAR) of complex anatomy aortic aneurysms when the origin of visceral arteries branch off the aorta very close to each other or present early branches. We herein describe a case series including 7 patients who underwent a FEVAR procedure for thoracoabdominal and juxtarenal aortic aneurysms in which the presence of accessory renal arteries (ARA) or early renal branches was the reason for the application of this technique. Technical success was 100% and all stents were patent in the last follow-up CT scan (follow-up range: 1.8-62.8 months). There was only 1 small endoleak from indetermined source potentially related to the DBS, but the aneurysm sac decreased in size during follow-up and no secondary intervention was needed. Therefore, the DBS technique is a viable option for the incorporation of ARA or early renal branches to a fenestrated repair of aortic aneurysms with complex anatomy

Burden of Substance Abuse-Related Admissions to the Medical ICU

Background Admissions to the ICU related to alcohol, prescription drugs, and illicit drugs are shown to be widespread and costly. In 1993, a study revealed 28% of ICU admissions at Johns Hopkins Hospital were related to substance abuse and accrued 39% of costs. Since then, health-care expenditures have increased, and substance abuse treatment admissions have risen. We conducted a study to provide updated data on ICU utilization and costs related to licit and illicit abuse at a large county hospital in Indianapolis, Indiana. Methods All admissions to the medical ICU at Eskenazi Hospital from March to October 2017 were reviewed. Demographics, reason for admission, relation to substance abuse and specific substance, ICU and hospital length of stay, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, mortality, insurance status, and hospital charges were collected based on chart review. Results A total of 611 admissions generated $74,587,280.35 in charges. A total of 25.7% of admissions related to substance abuse accounted for 23.1% of total charges. Illicit drugs were 13% of total admissions, generating 11% of charges. Alcohol-related admissions were 9.5% of total admissions, generating 7.6% of charges. Prescription drugs were 2.9% of admissions, generating 4.2% of charges. Of the substance abuse admissions, patients were generally men and 40 to 64 years of age, with longer ICU stay, higher APACHE II scores, and higher mortality. Conclusions Substance abuse admissions make up almost a one-quarter of resources used by our ICU. Patients tend to be younger and sicker with a higher risk of death. Identifying and accurately describing the landscape of this current health crisis will help us take appropriate action in the future

Management of a thoracic endograft infection through an ascending to descending extra-anatomic aortic bypass and endograft explantation

A 52-year-old man presented 33 months after thoracic aortic endovascular repair with hemoptysis and was found to have an aortobronchial fistula secondary to a mycotic aneurysm. The endograft infection was managed in a two-stage fashion. During the initial stage, the patient underwent an ascending-to-descending thoracic aortic bypass. Neither cardiopulmonary bypass, hypothermic circulatory arrest, nor aortic cross-clamping were used. During the same hospitalization, the patient underwent successful endograft explantation through a left thoracotomy. Imaging at 6 months demonstrated no anastomotic concerns and resolution of residual pulmonary inflammation. Thoracic aortic endograft infections necessitating endograft removal can potentially be successfully and safely managed without the need for cardiopulmonary bypass, hypothermic circulatory arrest, or interruption of aortic blood flow

Aortoesophageal fistula after thoracic endovascular aortic repair and transthoracic embolization

Endografts are more commonly being used to treat thoracic aortic aneurysms and other vascular lesions. Endoleaks are a potential complication of this treatment modality and can be associated with aneurysmal sac expansion and rupture. This case report presents a patient who developed a type IA endoleak after endograft repair of a descending thoracic aneurysm. The endoleak was successfully treated through computed tomographic-guided transthoracic embolization, although the patient experienced lower extremity paraparesis postprocedurally. The patient’s endovascular repair was complicated by the development of an aortoesophageal fistula and endograft infection necessitating operative débridement and endograft explantation

“Off-the-shelf” devices for complex aortic aneurysm repair

BACKGROUND: Fenestrated devices currently require a 3- to 4-week manufacturing period before implantation; as such, there have been efforts to develop "off-the-shelf" (OTS) devices to reduce the time before definitive treatment can be accomplished. We examined all patients treated for complex aortic problems at our institution during the past 12 months to evaluate the suitability and early outcomes of the OTS devices vs commercially available endovascular options. METHODS: Between July 2012 and September 2013, patients undergoing aortic aneurysm repair were extracted from a prospectively managed aortic database. Two OTS devices, the Cook (Bloomington, Ind) p-Branch and the Endologix (Irvine, Calif) Ventana device, were being evaluated through clinical trials during this time frame. The custom Cook Zenith fenestrated endovascular (ZFEN) device was also available and approved by the U.S. Food and Drug Administration (FDA) during the study period. RESULTS: Of 224 aortic aneurysms treated at our institution during this period, there were a total of 85 patients with type IV thoracoabdominal aneurysms including juxtarenal aneurysms. Only 23 patients (27%) met anatomic criteria for OTS devices, with 16 patients having these investigational devices implanted. The major exclusion criterion for the p-Branch device was renal axial or circumferential position; the limiting factor for Ventana was infrasuperior mesenteric artery neck length restriction. Five of the patients who would have fit criteria for an OTS device had an FDA-approved (ZFEN) device implanted instead, and two patients opted for open repair as a result of follow-up requirements. An additional 25 patients received custom-designed (ZFEN) devices (n = 30; 35%), whereas 37 (44%) others did not meet criteria for any available endovascular device and were repaired with alternative management strategies. The mean age and maximal aortic diameter of the two cohorts (OTS and ZFEN) were 71.8 years and 72.7 years (P = NS) and 61.3 mm and 58.5 mm (P = NS), respectively. Technical success was 100%, with an overall 30-day mortality of 2.1% (n = 1, ZFEN). Major complications occurred in eight patients (17%; two OTS, six ZFEN). CONCLUSIONS: Whereas OTS device strategies will reduce the waiting times for patients with complex aortic aneurysmal disease, a significant number will still require custom-made device repair until additional device designs become available. Early experience with OTS devices does not demonstrate any significant renal risks; however, the treatment numbers are low and should be interpreted with caution until larger confirmatory studies are published. Further studies comparing the outcomes of these techniques are required to establish the best approach to handle endovascular repair of complex aortic aneurysm

“Off-the-shelf” devices for complex aortic aneurysm repair

BACKGROUND: Fenestrated devices currently require a 3- to 4-week manufacturing period before implantation; as such, there have been efforts to develop "off-the-shelf" (OTS) devices to reduce the time before definitive treatment can be accomplished. We examined all patients treated for complex aortic problems at our institution during the past 12 months to evaluate the suitability and early outcomes of the OTS devices vs commercially available endovascular options. METHODS: Between July 2012 and September 2013, patients undergoing aortic aneurysm repair were extracted from a prospectively managed aortic database. Two OTS devices, the Cook (Bloomington, Ind) p-Branch and the Endologix (Irvine, Calif) Ventana device, were being evaluated through clinical trials during this time frame. The custom Cook Zenith fenestrated endovascular (ZFEN) device was also available and approved by the U.S. Food and Drug Administration (FDA) during the study period. RESULTS: Of 224 aortic aneurysms treated at our institution during this period, there were a total of 85 patients with type IV thoracoabdominal aneurysms including juxtarenal aneurysms. Only 23 patients (27%) met anatomic criteria for OTS devices, with 16 patients having these investigational devices implanted. The major exclusion criterion for the p-Branch device was renal axial or circumferential position; the limiting factor for Ventana was infrasuperior mesenteric artery neck length restriction. Five of the patients who would have fit criteria for an OTS device had an FDA-approved (ZFEN) device implanted instead, and two patients opted for open repair as a result of follow-up requirements. An additional 25 patients received custom-designed (ZFEN) devices (n = 30; 35%), whereas 37 (44%) others did not meet criteria for any available endovascular device and were repaired with alternative management strategies. The mean age and maximal aortic diameter of the two cohorts (OTS and ZFEN) were 71.8 years and 72.7 years (P = NS) and 61.3 mm and 58.5 mm (P = NS), respectively. Technical success was 100%, with an overall 30-day mortality of 2.1% (n = 1, ZFEN). Major complications occurred in eight patients (17%; two OTS, six ZFEN). CONCLUSIONS: Whereas OTS device strategies will reduce the waiting times for patients with complex aortic aneurysmal disease, a significant number will still require custom-made device repair until additional device designs become available. Early experience with OTS devices does not demonstrate any significant renal risks; however, the treatment numbers are low and should be interpreted with caution until larger confirmatory studies are published. Further studies comparing the outcomes of these techniques are required to establish the best approach to handle endovascular repair of complex aortic aneurysm

Rare Case of Abdominal Aortic and Multiple Visceral Aneurysms in a Pediatric Patient With PIK3CA Mutation and Vasculitis

Abdominal aortic aneurysms (AAA) are most commonly observed in elderly male patients and are particularly rare in children. Among the pediatric population, they are usually diagnosed in the context of connective tissue disorders, genetic mutations, or vasculitis. The same is true of visceral arteries aneurysms. This case report describes the staged management of an 11-year-old patient presenting PIK3CA mutation and a 5.8 cm infrarenal AAA associated with bilateral common iliac arteries and multiple visceral aneurysms, the largest observed in the superior mesenteric artery (SMA = 3.2 cm). After careful evaluation, decision was made to first approach the most life-threatening lesion (the infrarenal AAA due to the large diameter) and the remaining aneurysms in secondary procedures, with special attention to the SMA aneurysm. The patient underwent a staged repair, with the first phase consisting of an aortobi-iliac graft with the distal anastomosis made at the left common iliac artery and right external iliac artery. The right hypogastric artery was ligated. The second procedure consisted of SMA aneurysm repair with a plication technique, as 7 branches were visualized coming off the aneurysm sac. Postoperative pathology analysis of the aortic and SMA aneurysms sac revealed vasculitis with a mixed inflammatory pattern and a COL3A1 gene heterozygote variant. He is currently in his 18th month after the last surgical intervention, receiving immunomodulatory therapy, with a planned follow-up by the interdisciplinary team to monitor the medications’ side effects and the diameter of the remaining visceral aneurysms

Coverage of the left subclavian artery during thoracic endovascular aortic repair

BackgroundThoracic aortic stent grafts require proximal and distal landing zones of adequate length to effectively exclude thoracic aortic lesions. The origins of the left subclavian artery and other aortic arch branch vessels often impose limitations on the proximal landing zone, thereby disallowing endovascular repair of more proximal thoracic lesions.MethodsBetween October 2000 and November 2005, 112 patients received stent grafts to treat lesions involving the thoracic aorta. The proximal aspect of the stent graft partially or totally occluded the origin of at least one great vessel in 28 patients (25%). The proximal attachment site was in zone 0 in one patient (3.6%), zone 1 in three patients (10.7%), and zone 2 in 24 patients (85.7%). Patients with proximal implantation in zones 0 or 1 underwent debranching procedures of the supra-aortic vessels before stent graft repair. In one patient who underwent zone 1 deployment, the left subclavian artery was revascularized before stent graft deployment. Among patients who underwent zone 2 deployment with partial or complete occlusion of the left subclavian artery, none underwent prior revascularization. Patients were assessed postoperatively and at follow-up for development of neurologic symptoms as well as symptoms of left upper extremity claudication or ischemia.ResultsMean follow-up was 7.3 months. Among the 24 patients with zone 2 implantation, 10 (42%) had partial left subclavian artery coverage at the time of their primary procedure. A total of 19 patients experienced complete cessation of antegrade flow through the origin of the left subclavian artery without revascularization at the time of the initial endograft repair as a result of a secondary procedure or as a consequence of left subclavian artery thrombosis. Left upper extremity symptoms developed in three (15.8%) patients that did not warrant intervention, and rest pain developed in one (5.3%), which was treated with the deployment of a left subclavian artery stent. Two primary (type IA and type III) endoleaks (7.1%) and one secondary endoleak (type IA) (3.6%) were observed in patients who underwent zone 2 deployment. Three cerebrovascular accidents were observed. Thoracic aortic lesions were successfully excluded in all patients who underwent supra-aortic debranching procedures.ConclusionIntentional coverage of the origin of the left subclavian artery to obtain an adequate proximal landing zone during endovascular repair of thoracic aortic lesions is well tolerated and may be managed expectantly, with some exceptions