Natural history of visceral branch artery dissections and the influence of concurrent aortic dissection on overall and intervention-free survival.

OBJECTIVE: Visceral branch artery dissection (VBAD) is uncommon and may occur with or without an associated aortic dissection (AD). We hypothesized that isolated VBAD would have a more benign clinical course than those with concurrent AD and compared survival outcomes stratified based on aortic involvement. METHODS: VBAD over a 5-year period were identified using International Classification of Diseases codes. Data related to patient demographics, comorbid conditions, clinical presentation, management (including procedural interventions), and survival were obtained from medical records. Anatomic imaging studies were reviewed to characterize anatomy, including the presence or absence of concurrent AD. Overall survival and intervention-free survival were evaluated using Kaplan-Meier and Cox proportional hazards models. RESULTS: A total of 299 VBAD were identified, 174 of which were isolated VBAD and 125 were associated with concurrent AD. Seventy-one percent of patients were men, 77% were White, and 85% were non-Hispanic. The mean age was 61.1 ± 14.4 years. The mean follow-up was 53.2 ± 50.0 months. The estimated overall survival was 88.2% and the estimated overall intervention-free survival was 55.6% at 12 months. Isolated VBAD had better overall survival than those with concurrent AD (69.2% vs 32.4%; P < .001). Concurrent AD was also associated with inferior intervention-free survival (57.5% vs 7.3%; P < .001). Acute presentation was associated with decreased intervention-free survival (86.1% vs 13.4%; P < .001). Acute presentation was also associated with decreased overall survival in patients with isolated VBAD (60.8% vs 80.0% at 180 months; P < .001) and inferior intervention-free survival (48.4% vs 69.5% at 180 months; P < .001) in the subgroup of patients with isolated VBAD. Multivariable Cox models identified that age (hazard ratio [HR]: 1.05, standard deviation [SD]: 0.02; P = .001) was associated with inferior survival and renal dissections (HR: 3.08, SD: 0.99; P = .001) or mesenteric and renal dissections (HR: 3.39, SD: 1.44; P = .004) were associated with inferior intervention-free survival. CONCLUSIONS: Isolated VBAD has superior overall and intervention-free survival to those associated with concurrent AD. The absence vs presence of aortic involvement is useful for risk stratification and may support tailored approaches to the frequency of imaging surveillance.

Superior mesenteric aneurysm associated with median arcuate ligament syndrome and a single celiacomesenteric trunk.

Median arcuate ligament syndrome (MALS) is known to promote arterial collateral circulation development from mesenteric vessel compression and can lead to the development of visceral aneurysms. These aneurysms are often diagnosed at the time of rupture and pose a significant morality risk without appropriate intervention. A celiacomesenteric trunk is a rare anatomic variant in which the celiac artery and superior mesenteric artery share a common origin and has been postulated as a risk factor for developing MALS. In this report, we present a novel case of MALS in a patient with a celiacomesenteric trunk and a superior mesenteric artery aneurysm.

Tandem use of gastroesophageal resuscitative occlusion of the aorta followed by resuscitative endovascular balloon occlusion of the aorta in a lethal liver laceration model.

BACKGROUND: Gastroesophageal resuscitative occlusion of the aorta (GROA) has been shown effective in creating zone II aortic occlusion capable of temporarily improving survival in animal models of lethal noncompressible torso hemorrhage. In this study, tandem application of GROA transitioning to resuscitative endovascular balloon occlusion of the aorta (REBOA) is explored to demonstrate feasibility as a potential point-of-injury bridge to more advanced care, using a swine model of lethal abdominal hemorrhage. METHODS: Swine (n = 19) were anesthetized, instrumented, and subjected to a combination of controlled and uncontrolled hemorrhage from a grade-V liver laceration. Animals were designated as intervention (n = 9; GROA to REBOA) or control (n = 10), for 60 minutes. Following intervention, devices were deactivated, and animals received blood and crystalloid resuscitation. Animals were monitored for 4 hours. RESULTS: Injury resulted in onset of class IV shock in all animals with a mean arterial pressure (SD) of 24.5 (4.11) mm Hg at the start of intervention. Nine of 10 controls died during the intervention period with a median (interquartile) survival time of 8.5 (9.25) minutes. All animals receiving the intervention survived both the 60-minute intervention period demonstrating a significant survival improvement ( p = 0.0007). Transition from GROA to REBOA was successful in all animals with a transition time ranging from 30 to 90 seconds. Mean arterial pressure significantly improved in animals receiving GROA to REBOA for the duration of intervention, regardless of the method of aortic occlusion, with a range of 70.9 (16.04) mm Hg to 101.1 (15.3) mm Hg. Additional hemodynamics, metrics of shock, and oxygenation remained stable during intervention. CONCLUSION: Less invasive technologies such as GROA may present an opportunity to control noncompressible torso hemorrhage more rapidly, with a subsequent transition to more advanced care such as REBOA.

Stroke Following Thoracic Endovascular Aortic Repair: Determinants, Short and Long Term Impact.

We performed a contemporary assessment of clinical and radiographic factors of stroke after thoracic endovascular aortic repair (TEVAR). Patients undergoing TEVAR from 2006 to 2017 were identified. We assessed clinical and radiographic data, including preoperative head and neck computed tomography, Doppler ultrasonography, and intraoperative angiography. Our primary outcome was stroke after TEVAR. Four hundred seventy-nine patients underwent TEVAR, mean age 68.1 ± 19.5 years, 52.6% male. Indications for TEVAR included aneurysms (n = 238, 49.7%) or dissections (n = 152, 31.7%). Ishimaru landing zones were Zone 2 (n = 225, 47.0%), Zone 3 (n = 151, 31.5%), or Zone 4 (n = 103, 21.5%). Stroke occurred in 3.8% (n = 18) of patients, with 1.9% (8) major events (modified Rankin Scale >3). Pathophysiology was predominantly embolic (n = 14), and occurred in posterior (n = 6), anterior (n = 6), or combined circulation (n = 4), and in the left hemisphere (n = 10) or bilateral (n = 6). Univariate analysis suggested use of lumbar drain (33.3% versus 57.2%, P = 0.04), inability to revascularize the left subclavian artery (16.7% vs 5.2%, P = 0.04) and number of implanted components (2.5 ± 1.2 vs 2.0 ± 0.97, P = 0.03) were associated with stroke. Multivariable analysis identified number of implanted components (OR 1.7, 95%CI 1.17-2.67 P = 0.00) and inability to revascularize the left subclavian artery as independent predictors of stroke. Stroke was associated with a higher perioperative mortality (27.8% vs 3.9%, P < 0.01). Stroke after TEVAR is primarily embolic in nature and related to both anatomic and procedural factors. This may have important implications for device development in the era of endovascular arch repair.

Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture.

BACKGROUND: The risk of arterial diseases may be elevated among family members of individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the risk of arterial diseases in families of individuals with FMD. METHODS: Family histories for 73 probands with FMD were obtained, which included an analysis of 463 total first-degree relatives focusing on FMD and related arterial disorders. A polygenic risk score for FMD (PRSFMD) was constructed from prior genome-wide association findings of 584 FMD cases and 7139 controls and evaluated for association with an abdominal aortic aneurysm (AAA) in a cohort of 9693 AAA cases and 294 049 controls. A previously published PRSAAA was also assessed among the FMD cases and controls. RESULTS: Of all first degree relatives of probands, 9.3% were diagnosed with FMD, aneurysms, and dissections. Aneurysmal disease occurred in 60.5% of affected relatives and 5.6% of all relatives. Among 227 female first-degree relatives of probands, 4.8% (11) had FMD, representing a relative risk (RR)FMD of 1.5 ([95% CI, 0.75-2.8]; P=0.19) compared with the estimated population prevalence of 3.3%, though not of statistical significance. Of all fathers of FMD probands, 11% had AAAs resulting in a RRAAA of 2.3 ([95% CI, 1.12-4.6]; P=0.014) compared with population estimates. The PRSFMD was found to be associated with an AAA (odds ratio, 1.03 [95% CI, 1.01-1.05]; P=2.6×10-3), and the PRSAAA was found to be associated with FMD (odds ratio, 1.53 [95% CI, 1.2-1.9]; P=9.0×10-5) as well. CONCLUSIONS: FMD and AAAs seem to be sex-dimorphic manifestations of a heritable arterial disease with a partially shared complex genetic architecture. Excess risk of having an AAA according to a family history of FMD may justify screening in family members of individuals having FMD.

Results of the North American Complex Abdominal Aortic Debranching (NACAAD) Registry.

BACKGROUND: Hybrid debranching repair of pararenal and thoracoabdominal aortic aneurysms was initially designed as a better alternative to standard open repair, addressing the limitations of endovascular repair involving the visceral aorta. We reviewed the collective outcomes of hybrid debranching repairs using extra-anatomic, open surgical debranching of the renal-mesenteric arteries, followed by endovascular aortic stenting. METHODS: Data from patients who underwent hybrid repair in 14 North American institutions during 10 years were retrospectively reviewed. Society of Vascular Surgery scores were used to assess comorbidity risk. Early and late outcomes, including mortality, morbidity, reintervention, and patency were analyzed. RESULTS: A total of 208 patients (118 male; mean age, 71±8 years old) were treated by hybrid repair with extraanatomic reconstruction of 657 renal and mesenteric arteries (mean 3.2 vessels/patient). Mean aneurysm diameter was 6.6±1.3 cm. Thoracoabdominal aortic aneurysms were identified in 163 (78%) patients and pararenal aneurysms in 45 (22%). A single-stage repair was performed in 92 (44%) patients. The iliac arteries were the most common source of inflow (n=132; 63%), and most (n=150; 72%) had 3 or more bypasses. There were 30 (14%) early deaths, ranging widely across sites (0%-21%). A Society of Vascular Surgery comorbidity score >15 was the primary predictor of early mortality (P<0.01), whereas mortality was 3% in a score ≤9. Early complications occurred in 140 (73%) patients and included respiratory complications in 45 patients (22%) and spinal cord ischemia in 22 (11%), of whom 10 (45%) fully recovered. At 5 years, survival was 61±5%, primary graft patency was 90±2%, and secondary patency was 93±2%. The most significant predictor of late mortality was renal insufficiency (P<0.0001). CONCLUSIONS: Mortality after hybrid repair and visceral debranching is highly variable by center, but strongly affected by preoperative comorbidities and the centers' experience with the technique. With excellent graft patency at 5 years, the outcomes of hybrid repair done at centers of excellence and in carefully selected patients may be comparable (or better) than traditional open or even totally endovascular approaches. However, in patients already considered as high-risk for surgery, it may not offer better outcomes.

Histologic and morphologic character of pediatric abdominal aortic developmental coarctation and hypoplasia.

OBJECTIVES: Abdominal aortic coarctation and hypoplasia are uncommon diseases, recognized most often in pediatric-aged individuals. Comprehensive studies regarding the pathologic spectrum of these aortopathies are nonexistent. This investigation was undertaken to better define the histologic and morphologic character of abdominal aortic narrowings affecting children and assess its potential relevance to contemporary clinical practice. METHODS: Aortic specimens obtained during open operations in children being treated for symptomatic, noninflammatory abdominal aortic narrowings at the University of Michigan were subjected to histologic study after hematoxylin and eosin, Movat, Verhoeff Van Gieson, and Masson's trichrome preparations. Microscopic findings were correlated with the anatomic aortic images. In addition, a detailed review was completed of all prior reports in the English literature that included images depicting the histologic character of noninflammatory abdominal aortic narrowings in children. RESULTS: Among a series of 67 pediatric-aged individuals undergoing open surgical interventions for abdominal aortic narrowings, eight children ranging in age from 9 months to 18 years, had adequate aortic tissue available for study. The loci of the specimens paralleled the anatomic sites of segmental coarctations observed in the entire series, with involvement of the suprarenal abdominal aorta (n = 3), intrarenal aorta (n = 2), and infrarenal aorta (n = 1). Diffusely hypoplastic abdominal aortas (n = 2) included one case of a de facto aortic duplication, represented by a channel that paralleled the narrow native aorta and gave origin to celiac artery branches, as well as the superior mesenteric and renal arteries. Concentric or eccentric intimal fibroplasia was observed in every aorta, often with internal elastic fragmentation and duplication (n = 4). Media abnormalities included elastic tissue disorganization (n = 3) and focal medial fibrosis (n = 1). Organizing luminal thrombus occurred in two infants. Coexistent ostial stenoses of the celiac, superior mesenteric, or renal arteries were observed in all but the only child who had an infrarenal aortic coarctation. Neurofibromatosis type 1 affected one child whose histologic findings were indistinguishable from those of the other children. A review of prior published histologic images of abdominal aortic coarctation and hypoplasia affecting children from other centers revealed a total of 14 separate reports, each limited to single case photomicrographs, of which 11 exhibited intimal fibroplasia. CONCLUSIONS: Intimal fibroplasia is a common accompaniment of developmental abdominal aortic coarctation and hypoplasia. It is posited that intimal fibroplasia, which is likely progressive in instances of abnormal shear stresses in these diminutive vessels, may contribute to less salutary outcomes after endovascular and certain open reconstructions of pediatric abdominal aortic narrowings.

Gastroesophageal resuscitative occlusion of the aorta prolongs survival in a lethal liver laceration model.

BACKGROUND: Noncompressible torso hemorrhage management remains a challenge especially in the prehospital setting. We evaluated a device designed to occlude the aorta from the stomach (gastroesophageal resuscitative occlusion of the aorta [GROA]) for its ability to stop hemorrhage and improve survival in a swine model of lethal liver laceration and compared its performance to resuscitative endovascular balloon occlusion of the aorta (REBOA) and controls. METHODS: Swine (n = 24) were surgically instrumented and a 30% controlled arterial hemorrhage over 20 minutes was followed by liver laceration. Animals received either GROA, REBOA, or control (no treatment) for 60 minutes. Following intervention, devices were deactivated, and animals received whole blood and crystalloid resuscitation. Animals were monitored for an additional 4 hours. RESULTS: The liver laceration resulted in the onset of class IV shock. Mean arterial blood pressure (MAP) (standard deviation) decreased from 84.5 mm Hg (11.69 mm Hg) to 27.1 mm Hg (5.65 mm Hg) at the start of the intervention. Seven of eight control animals died from injury prior to the end of the intervention period with a median survival (interquartile) time of 10.5 minutes (12 minutes). All GROA and REBOA animals survived the duration of the intervention period (60 minutes) with median survival times of 86 minutes (232 minutes) and 79 minutes (199 minutes) after resuscitation, respectively. The GROA and REBOA animals experienced a significant improvement in survival compared with controls (p = 0.01). Resuscitative endovascular balloon occlusion of the aorta resulted in higher MAP at the end of intervention 114.6 mm Hg (22.9 mm Hg) compared with GROA 88.2 mm Hg (18.72 mm Hg) (p = 0.024), as well as increased lactate compared with GROA 13.2 meq·L-1 (1.56 meq·L-1) versus 10.5 meq·L-1 (1.89 meq·L-1) (p = 0.028). Histological examination of the gastric mucosa in surviving animals revealed mild ischemic injury from both GROA and REBOA. CONCLUSION: The GROA and REBOA devices were both effective at temporarily stanching lethal noncompressible torso hemorrhage of the abdomen and prolonging survival.

Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aortic root or ascending/descending aorta. TAA is a heritable disease that can be potentially life threatening. While 10%-20% of TAA cases are caused by rare, pathogenic variants in single genes, the origin of the majority of TAA cases remains unknown. A previous study implicated common variants in FBN1 with TAA disease risk. Here, we report a genome-wide scan of 1,351 TAA-affected individuals and 18,295 control individuals from the Cardiovascular Health Improvement Project and Michigan Genomics Initiative at the University of Michigan. We identified a genome-wide significant association with TAA for variants within the third intron of TCF7L2 following replication with meta-analysis of four additional independent cohorts. Common variants in this locus are the strongest known genetic risk factor for type 2 diabetes. Although evidence indicates the presence of different causal variants for TAA and type 2 diabetes at this locus, we observed an opposite direction of effect. The genetic association for TAA colocalizes with an aortic eQTL of TCF7L2, suggesting a functional relationship. These analyses predict an association of higher expression of TCF7L2 with TAA disease risk. In vitro, we show that upregulation of TCF7L2 is associated with BCL2 repression promoting vascular smooth muscle cell apoptosis, a key driver of TAA disease.

Vascular Deformation Mapping of Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a complex disease that requires regular imaging surveillance to monitor for aneurysm stability. Current imaging surveillance techniques use maximum diameter, often assessed by computed tomography angiography (CTA), to assess risk of rupture and determine candidacy for operative repair. However, maximum diameter measurements can be variable, do not reliably predict rupture risk and future AAA growth, and may be an oversimplification of complex AAA anatomy. Vascular deformation mapping (VDM) is a recently described technique that uses deformable image registration to quantify three-dimensional changes in aortic wall geometry, which has been previously used to quantify three-dimensional (3D) growth in thoracic aortic aneurysms, but the feasibility of the VDM technique for measuring 3D growth in AAA has not yet been studied. Seven patients with infra-renal AAAs were identified and VDM was used to identify three-dimensional maps of AAA growth. In the present study, we demonstrate that VDM is able to successfully identify and quantify 3D growth (and the lack thereof) in AAAs that is not apparent from maximum diameter. Furthermore, VDM can be used to quantify growth of the excluded aneurysm sac after endovascular aneurysm repair (EVAR). VDM may be a useful adjunct for surgical planning and appears to be a sensitive modality for detecting regional growth of AAAs.

T-Minus 10 Days: The Role of an Academic Medical Institution in Field Hospital Planning.

Alternate care sites (ACS) are locations that can be converted to provide either in-patient and/or out-patient health care services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities. In March through May of 2020, Michigan Medicine (MM), the affiliated health system of the University of Michigan, planned a 500 bed ACS at an off-site location. Termed the Michigan Medicine Field Hospital (MMFH), this ACS was intended to be a step-down care facility for low-acuity COVID-19 positive MM patients who could be transitioned from the hospital setting and safely cared for prior to discharge home, while also allowing increased bed capacity in the remaining MM hospitals for additional critical patient care. The planning was organized into six units: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. The purpose of this report is to describe the development and planning of an ACS within the MM academic medical center (AMC) to discuss anticipated barriers to success and to suggest guidance for health systems in future planning.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): Zone I Balloon Occlusion Time Affects Spinal Cord Injury in the Nonhuman Primate Model.

OBJECTIVES: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has been used clinically to limit torso bleeding and restore central perfusion. The objective of this study was to determine the sequelae of prolonged REBOA in a nonhuman primate animal model. SUMMARY BACKGROUND DATA: Prolonged duration of REBOA is associated with adverse clinical outcomes. Threshold occlusion values tied to relative risk have yet to be determined. METHODS: Juvenile baboons were subjected to 40% to 55% total blood volume hemorrhage to achieve profound hypotension and shock. Zone I REBOA was performed for 60 minutes to assess acute injury and survival at 4 hours (group 1; n = 7). Post-REBOA 10-day survival and complications were then compared between 60 minutes (group 2; n = 8) and 30 minutes (group 3; n = 6) REBOA animals. RESULTS: Overall survival was 20/21 (95%). IL-6 and IL-8 were elevated at 1 and 4 hours in group 1 (P = 0.005; P = 0.001). Comparing 60-minute REBOA with 30-minute REBOA, there was (1) hypertension compared with normotension (P = 0.005), (2) increased base deficit (P = 0.003), (3) elevated Troponin I (P = 0.04), and histological evidence of kidney injury (P = 0.004). In addition, group 2 demonstrated paralysis with histopathologic changes of spinal cord ischemia (SCI) in 4/8 (50%), with no SCI in group 3 (P = 0.033). CONCLUSIONS: REBOA limits mortality in the primate model of severe hemorrhagic shock. However, unopposed balloon inflation in the distal thoracic aorta for 60 minutes results in high rates of spinal cord ischemia, an effect mitigated by limiting balloon inflation to 30 minutes.

Fenestrated repair improves perioperative outcomes but lacks a hospital volume association for complex abdominal aortic aneurysms.

BACKGROUND: Complex abdominal aortic aneurysms (AAAs) have traditionally been treated with an open surgical repair (OSR). During the past decade, fenestrated endovascular aneurysm repair (FEVAR) has emerged as a viable option. Hospital procedural volume to outcome relationship for OSR of complex AAAs has been well established, but the impact of procedural volume on FEVAR outcomes remains undefined. This study investigated the outcomes of OSR and FEVAR for the treatment of complex AAAs and examined the hospital volume-outcome relationship for these procedures. METHODS: A retrospective review of a statewide vascular surgery registry was queried for all patients between 2012 and 2018 who underwent elective repair of a juxtarenal/pararenal AAA with FEVAR or OSR. The primary outcomes were 30-day mortality, myocardial infarction, and new dialysis. Secondary end points included postoperative pneumonia, renal dysfunction (creatine concentration increase of >2 mg/dL from preoperative baseline), major bleeding, early procedural complications, length of stay, and need for reintervention. To evaluate procedural volume-outcomes relationship, hospitals were stratified into low- and high-volume aortic centers based on a FEVAR annual procedural volume. To account for baseline differences, we calculated propensity scores and employed inverse probability of treatment weighting in comparing outcomes between treatment groups. RESULTS: A total of 589 patients underwent FEVAR (n = 186) or OSR (n = 403) for a complex AAA. After adjustment, OSR was associated with higher rates of 30-day mortality (10.7% vs 2.9%; P < .001) and need for dialysis (11.3% vs 1.8; P < .001). Postoperative pneumonia (6.8% vs 0.3%; P < .001) and need for transfusion (39.4% vs 10.4%; P < .001) were also significantly higher in the OSR cohort. The median length of stay for OSR and FEVAR was 9 days and 3 days, respectively. For those who underwent FEVAR, endoleaks were present in 12.1% of patients at 30 days and 6.1% of patients at 1 year, with the majority being type II. With a median follow-up period of 331 days (229-378 days), 1% of FEVAR patients required a secondary procedure, and there were no FEVAR conversions to an open aortic repair. Hospitals were divided into low- and high-volume aortic centers based on their annual FEVAR volume of complex AAAs. After adjustment, hospital FEVAR procedural volume was not associated with 30-day mortality or myocardial infarction. CONCLUSIONS: FEVAR was associated with lower perioperative morbidity and mortality compared with OSR for the management of complex AAAs. Procedural FEVAR volume outcome analysis suggests limited differences in 30-day morbidity, although long-term durability warrants further research.

Histologic and morphologic character of pediatric renal artery occlusive disease.

OBJECTIVE: The pathologic nature of pediatric renal artery occlusive lesions causing renovascular hypertension has been the subject of numerous anecdotal reports. This study was undertaken to define the character of childhood renal artery stenoses. A better understanding of this disease is particularly germane, given its unknown etiology and the limited success of certain contemporary treatment options. METHODS: Renal artery specimens obtained during open operations in children being treated for renovascular hypertension from 2004 to 2016 were studied. Excluded from study were arteries subjected to earlier open or endovascular operations. Histologic preparations employing hematoxylin-eosin, Movat, Masson trichrome, and Verhoeff-van Gieson stains allowed characterization of the intima, media, and adventitial tissues. External and luminal diameters were measured. Microscopic data were correlated with preoperative arteriographic images. The histologic and morphologic findings were assessed in regard to coexistent nonrenal arterial and aortic lesions as well as known syndromic diseases. RESULTS: Thirty-three stenotic renal arteries from 28 children were subjected to examination. Stenoses involved the proximal-ostial renal arteries (24), central renal arteries (7), and distal segmental renal arteries (2). Ostial stenoses commonly exhibited preocclusive concentric hyperplasia of intimal tissues, frequent internal elastic lamina disruptions, and diminutive and discontinuous media. Central and distal renal stenoses most often exhibited lesser intimal cellular hyperplasia and more noticeable fibrodysplasia of the media and adventitia. The mean external and luminal diameters of the renal arteries having ostial stenoses were smaller than the expected renal artery size for a given age. Abdominal aortic coarctation or hypoplastic aortas occurred in 14 children. Neurofibromatosis type 1 affected four children with ostial renal artery disease and one child with midrenal artery disease, but there were no distinguishing features unique to their stenoses. CONCLUSIONS: Pediatric renal artery stenotic disease affects exceedingly small arteries. Ostial lesions frequently exhibit extensive luminal encroachments characterized by cellular hyperplasia of intimal tissues and scant medial smooth muscle. Central and distal renal arterial stenoses were characterized most often by extensive fibrodysplasia of the media and adventitia. The early success and durability of catheter-based angioplasty may be compromised by the cellular abnormalities of pediatric renal artery occlusive disease observed in this investigation.

Gastroesophageal resuscitative occlusion of the aorta: Physiologic tolerance in a swine model of hemorrhagic shock.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been shown to be effective for management of noncompressible torso hemorrhage. However, this technique requires arterial cannulation, which can be time-consuming and not amendable to placement in austere environments. We present a novel, less invasive aortic occlusion device and technique designated gastroesophageal resuscitative occlusion of the aorta (GROA). In this study, we aimed to characterize the physiological tolerance and hemodynamic effects of a prototype GROA device in a model of severe hemorrhagic shock and resuscitation and compare with REBOA. METHODS: Swine (N = 47) were surgically instrumented for data collection. A 35% controlled arterial hemorrhage was followed by randomizing animals to 30-minute, 60-minute, or 90-minute interventions of GROA, REBOA, or control. Following intervention, devices were deactivated, and animals received whole blood and crystalloid resuscitation. Animals were monitored for an additional 4 hours. RESULTS: All animals except one GROA 90-minute application survived the duration of their intervention periods. Survival through resuscitation phase in GROA, REBOA, and control groups was similar in the 30-minute and 60-minute groups. The 90-minute occlusion groups exhibited deleterious effects upon device deactivation and reperfusion with two GROA animals surviving and no REBOA animals surviving. Mean (SD) arterial pressure in GROA and REBOA animals increased across all groups to 98 (31.50) mm Hg and 122 (24.79) mm Hg, respectively, following intervention. Lactate was elevated across all GROA and REBOA groups relative to controls during intervention but cleared by 4 hours in the 30-minute and 60-minute groups. Postmortem histological examination of the gastric mucosa revealed mild to moderate inflammation across all GROA groups. CONCLUSION: In this study, the hemodynamic effects and physiological tolerance of GROA was similar to REBOA. The GROA device was capable of achieving high zone II full aortic occlusion and may be able to serve as an effective method of aortic impingement.

A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia.

OBJECTIVE: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections (P=0.005). CONCLUSIONS: COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.

Surgical management of pediatric renin-mediated hypertension secondary to renal artery occlusive disease and abdominal aortic coarctation.

BACKGROUND: Renovascular hypertension (RVH) associated with renal artery and abdominal aortic narrowings is the third most common cause of pediatric hypertension. Untreated children may experience major cardiopulmonary complications, stroke, renal failure, and death. The impetus of this study was to describe the increasingly complex surgical practice for such patients with an emphasis on anatomic phenotype and contemporary outcomes after surgical management as a means of identifying those factors responsible for persistent or recurrent hypertension necessitating reoperation. METHODS: A retrospective analysis was performed of consecutive pediatric patients with RVH undergoing open surgical procedures at the University of Michigan from 1991 to 2017. Anatomic phenotype and patient risk factors were analyzed to predict outcomes of blood pressure control and the need for secondary operations using ordered and binomial logistic multinomial regression models, respectively. RESULTS: There were 169 children (76 girls, 93 boys) who underwent primary index operations at a median age of 8.3 years; 31 children (18%) had neurofibromatosis type 1, 76 (45%) had abdominal aortic coarctations, and 28 (17%) had a single functioning kidney. Before treatment at the University of Michigan, 51 children experienced failed previous open operations (15) or endovascular interventions (36) for RVH at other institutions. Primary surgical interventions (342) included main renal artery (136) and segmental renal artery (10) aortic reimplantation, renal artery bypass (55), segmental renal artery embolization (10), renal artery patch angioplasty (8), resection with reanastomosis (4), and partial or total nephrectomy (25). Non-renal artery procedures included patch aortoplasty (32), aortoaortic bypass (32), and splanchnic arterial revascularization (30). Nine patients required reoperation in the early postoperative period. During a mean follow-up of 49 months, secondary interventions were required in 35 children (21%), including both open surgical (37) and endovascular (14) interventions. Remedial intervention to preserve primary renal artery patency or a nephrectomy if such was impossible was required in 22 children (13%). The remaining secondary procedures were performed to treat previously untreated disease that became clinically evident during follow-up. Age at operation and abdominal aortic coarctation were independent predictors for reoperation. The overall experience revealed hypertension to be cured in 74 children (44%), improved in 78 (46%), and unchanged in 17 (10%). Children undergoing remedial operations were less likely (33%) to be cured of hypertension. There was no perioperative death or renal insufficiency requiring dialysis after either primary or secondary interventions. CONCLUSIONS: Contemporary surgical treatment of pediatric RVH provides a sustainable overall benefit to 90% of children. Interventions in the very young (<3 years) and concurrent abdominal aortic coarctation increase the likelihood of reoperation. Patients undergoing remedial surgery after earlier operative failures are less likely to be cured of hypertension. Judicious postoperative surveillance is imperative in children surgically treated for RVH.

Volume Standards for Open Abdominal Aortic Aneurysm Repair Are Not Associated With Improved Clinical Outcomes.

BACKGROUND: Volume-outcome relationships exist for many complex surgical procedures, prompting institutions to adopt surgical volume standards for credentialing. The current Leapfrog Group Hospital volume standard for open abdominal aortic aneurysm repair (OAR) is 15 per year. However, this is primarily based on data from the 1990s and may not be appropriate given the dramatic decline in OAR. We sought to quantify the proportion of hospitals meeting volume standards, the difference in perioperative outcomes between low-volume and high-volume hospitals, and the potential travel burden of volume credentialing on patients. METHODS: We identified Medicare beneficiaries for individuals aged ≥65 years undergoing OAR in 2013-2014. Hospital "all-payer" annual volume was estimated based on the national proportion of patients undergoing OAR covered by Medicare in the Vascular Quality Initiative. Hospital annual OAR volume was characterized as <5/year, 5-9/year, 10-14/year, and ≥15/year (high volume). Adjusted rates of postoperative morbidity, reoperation, failure to rescue, and mortality in 2014 were compared across volume cohorts. Distance between patients' home zip code and high-volume hospitals was calculated. RESULTS: A total of 21,191 OARs were performed at 1,445 hospitals between 2013 and 2014. The average hospital OAR annual volume was 7.8 (standard deviation [SD] ± 9.3) with a median of 4.5. Among the 1,445 hospitals, only 190 (13.1%) performed ≥15 OARs per year whereas 756 hospitals (53.3%) performed <5 per year. Among patients who underwent OAR in 2014, 5,395 (53.3%) received care at a hospital that performed <15 per year. There was no difference in complication, reoperation, or failure to rescue rates between high-volume and low-volume hospitals. Mortality did not significantly differ among OAR volume cohorts. Hospitals performing <5 OARs per year had a mortality rate of 5.7% compared with 5.6% at high-volume hospitals (P = 0.817). One-quarter of patients who received care at a low-volume hospital would have had to travel more than 60 miles to reach a high-volume hospital. CONCLUSIONS: By conservative estimates, only 13% of hospitals performing OAR meet current volume standards. Triaging all patients to high-volume hospitals would require shifting over 5,000 patients annually with no associated improvement in perioperative outcomes. Implementation of the current OAR hospital volume standard may significantly burden patients and hospitals without improving surgical outcomes.

Computational analysis of renal artery flow characteristics by modeling aortoplasty and aortic bypass interventions for abdominal aortic coarctation.

OBJECTIVE: Suprarenal abdominal aortic coarctation (SAAC) alters flow and pressure patterns to the kidneys and is often associated with severe angiotensin-mediated hypertension refractory to drug therapy. SAAC is most often treated by a thoracoabdominal bypass (TAB) or patch aortoplasty (PA). It is currently unclear what effect these interventions have on renal flow and pressure waveforms. This study, using retrospective data from a patient with SAAC subjected to a TAB, undertook computational modeling to analyze aortorenal blood flow preoperatively as well as postoperatively after a variety of TAB and PA interventions. METHODS: Patient-specific anatomic models were constructed from preoperative computed tomography angiograms of a 9-year-old child with an isolated SAAC. Fluid-structure interaction (FSI) simulations of hemodynamics were performed to analyze preoperative renal flow and pressure waveforms. A parametric study was then performed to examine the hemodynamic impact of different bypass diameters and patch oversizing. RESULTS: Preoperative FSI results documented diastole-dominated renal perfusion with considerable high-frequency disturbances in blood flow and pressure. The postoperative TAB right and left kidney volumes increased by 58% and 79%, respectively, reflecting the increased renal artery blood flows calculated by the FSI analysis. Postoperative increases in systolic flow accompanied decreases in high-frequency disturbances, aortic pressure, and collateral flow after all surgical interventions. In general, lesser degrees of high-frequency disturbances followed PA interventions. High-frequency disturbances were eliminated with the 0% PA in contrast to the 30% and 50% PA oversizing and TAB interventions, in which these flow disturbances remained. CONCLUSIONS: Both TAB and PA dramatically improved renal artery flow and pressure waveforms, although disturbed renal waveforms remained in many of the surgical scenarios. Importantly, only the 0% PA oversizing scenario eliminated all high-frequency disturbances, resulting in nearly normal aortorenal blood flow. The study also establishes the relevance of patient-specific computational modeling in planning interventions for the midaortic syndrome.

Computed tomography correlation of skeletal landmarks and vascular anatomy in civilian adult trauma patients: Implications for resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a valuable resuscitative adjunct in a variety of clinical settings. In resource-limited or emergency environments, REBOA may be required with delayed or absent image-guidance or verification. Catheter insertion lengths may be informed by making computed tomography (CT) correlations of skeletal landmarks with vascular lengths. METHODS: Between 2000 and 2015 at a single civilian tertiary care center, 2,247 trauma patients with CT imaging were identified, yielding 1,789 patients with adequate contrast opacification of the arterial system in the chest, abdomen, and pelvis. Individual scans were analyzed using MATLAB software, with custom high-throughput image processing algorithms applied to correlate centerline vascular anatomy with musculoskeletal landmarks. Data were analyzed using R version 3.3. RESULTS: The median centerline distance from the skin access to the aortic bifurcation was longer by 0.3 cm on the right than on the left side. Median aortic zone I length was 21.6 (interquartile range, 20.3-22.9) cm, while zone III was 8.7 (7.8-9.5) cm. Torso extent (TE) correlation to zone I was much higher than that for zone III (R2, 0.58 vs. 0.26 (right) and 0.58 vs. 0.27 (left); p < 0.001). Assuming a 4-cm balloon length, optimal fixed insertion length would be 48 cm and 28 cm for zones I and III (error, 0.4% vs. 33.3%), respectively, although out of zone placements can be reduced if adjusted for TE (error, 0% vs. 26.4%). CONCLUSION: Computed tomography morphometry suggests that a fixed REBOA catheter insertion length of 48 cm for zone I and 28 cm for zone III is optimal (on average, for average-height individuals), with improved accuracy by formulaic adjustments for TE. High residual error for zone III placement may require redesign of existing catheter balloon lengths or consideration of the relative risk associated with placing the balloon catheter too low or too high. LEVEL OF EVIDENCE: Prognostic/epidemiological, level III.