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.

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.

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.

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.

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.

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.

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.

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.

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.

Aggressive Phenotype of Intravascular Lymphoma Relative to Other Malignant Intraabdominal Tumors Requiring Vascular Reconstruction.

BACKGROUND: Safe resection of intraabdominal and retroperitoneal malignancies with a goal of negative margins may require vascular surgical assistance with grafting of the aorta and/or vena cava. The current report reviews malignancies associated with major vascular reconstructions at a single tertiary referral center. METHODS: Adults with abdominal or retroperitoneal tumors involving the aorta, vena cava, or iliac arteries that underwent reconstruction with vascular grafts at the University of Michigan from 2010 to 2016 were reviewed retrospectively. The initial presentation, surgical management, and outcomes were analyzed. RESULTS: Twelve patients with tumors involving the abdominal aorta, vena cava, or iliac arteries underwent major vascular reconstruction in this seven-year study period. Tumor pathology included solid tumors (leiomyosarcoma [n = 7], germ cell tumor [n = 3], and intravascular lymphoma [n = 2]). Surgical treatment included grafting of the vena cava (n = 6), aorta (n = 3), iliac artery (n = 4), or both the aorta and vena cava (n = 1). Patients with intravascular lymphoma were identified incidentally during treatment of abdominal aortic aneurysm or on pathological analysis of thromboembolism from an aortic source. Other patients had planned resection. Follow-up ranged from 9 to 86 months (median: 28.9). There were no graft occlusions. Tumor metastasized or recurred in patients with sarcoma (n = 2; 28.6%), germ cell tumor (n = 1; 33.3%), and intravascular lymphoma (n = 2; 100%). Both patients with lymphoma had multiple anastomotic or tumor-embolic pseudoaneurysms for <14 months after vascular reconstruction. Both lymphoma patients died during follow-up. CONCLUSIONS: This single-center review suggests that sarcoma and germ cell tumors may be safely resected in conjunction with major vascular reconstruction in carefully selected patients. In comparison, intravascular lymphoma identified incidentally at the time of aortic reconstruction resulted in a more malignant course with pseudoaneurysm formation of anastomoses or native vessels, cancer recurrence, and 100% mortality. Aneurysm contents and emboli should be carefully reviewed perioperatively by pathologists.

Arterial reconstructions for chronic lower extremity ischemia in preadolescent and adolescent children.

OBJECTIVE: Chronic lower extremity ischemia in pediatric patients is uncommon. The intent of this study was to better define the arterial reconstructive options and their long-term durability in preadolescent and adolescent children having clinically relevant arterial occlusions affecting the lower extremity. METHODS: The medical records of 33 consecutive pediatric patients who underwent lower extremity revascularization for chronic ischemia at the University of Michigan from 1974 to 2016 were reviewed. Patients were categorized by age, clinical manifestation, surgical intervention undertaken, and outcomes. RESULTS: Operative treatments involved 26 preadolescent children (mean age, 6.1 years; range, 3-9 years) and 7 adolescent children (mean age, 13.9 years; range, 10-17 years). Occlusions were due to earlier injury related to catheter (14), cannula (2), or both catheter and cannula (14); penetrating trauma (2); and vasculitis (1). Preoperative manifestations included symptomatic extremity ischemia (25), growth retardation manifested by documented limb length discrepancies (21), and scoliosis (5). Primary arterial reconstructions were delayed after the precipitating vascular event an average of 5.3 and 11.2 years in the preadolescent and adolescent children, respectively. Primary procedures involved revascularizations of 36 extremities (in preadolescents and adolescents) including autologous vein (26/5), polyethylene terephthalate (Dacron; 1/0), and expanded polytetrafluoroethylene (0/3) bypasses and vein patch angioplasty (0/1). Vein grafts traversing the abdominal cavity (15) were wrapped with a synthetic mesh. Excluding one early graft occlusion, there were no major early postoperative complications after the primary procedures. Secondary operations followed 31% of the primary operations, being performed an average of 8.8 and 6.7 years later (in 8 preadolescent and 3 adolescent children, respectively) for late graft occlusions (6), graft stenoses (3), aneurysmal vein grafts (2), and anastomotic pseudoaneurysm (1). The unassisted primary graft patency rate was 69%, and the assisted secondary graft patency rate was 94%. Symptomatic ischemia resolved in all but two children. Mean postoperative ankle-brachial indices improved to 1.08 from 0.76 preoperatively. Among children having postoperative documentation of limb lengths, the limb length discrepancies became less (11), were unchanged (1), or progressed (3). Follow-up averaged 8.0 years. There was no operative mortality in this experience. CONCLUSIONS: Primary lower extremity arterial reconstructions in children with chronic lower extremity ischemia can be successfully undertaken with excellent results. Nevertheless, the potential for late primary graft failures, evident in nearly a third of this experience, mandates careful long-term follow-up and may necessitate secondary interventions to maintain satisfactory outcomes.

Arterial reconstructions for pediatric splanchnic artery occlusive disease.

OBJECTIVE: Pediatric splanchnic arterial occlusive disease is uncommon and a rare cause of clinically relevant intestinal ischemia. This study was undertaken to better define the clinical manifestations and appropriate treatment of celiac artery (CA) and superior mesenteric artery (SMA) occlusive disease in children. METHODS: Clinical courses of 30 consecutive children undergoing operations for splanchnic arterial occlusive disease at the University of Michigan from 1992 to 2017 were retrospectively analyzed. RESULTS: Vascular reconstructions were performed for splanchnic arterial disease in 18 boys and 12 girls, 1.5 to 16 years of age (mean, 7.5 ± 4.1 years). Isolated splanchnic arterial disease was uncommon (2 children), being more often associated with abdominal aortic coarctations (19 children) or ostial renal artery stenoses (25 children). Primary splanchnic arterial reconstructions (30) included aortic reimplantation of SMAs (15) or celiacomesenteric arteries (2), aortoceliac and aortomesenteric bypasses (7), reimplantation of the CA as a patch over the stenotic SMA orifice (3), and patch angioplasty of the CA (2) or SMA (1). There was no perioperative mortality. Two groups (I and II) were identified for study. Group I children (14) experienced symptomatic intestinal ischemia, manifested by various combinations of chronic postprandial abdominal discomfort (14), ischemia-related intestinal bleeding (2), or failure to thrive (4). Four children in group I became symptomatic after known CA and SMA occlusive disease was left untreated at the time they underwent earlier interventions for renovascular hypertension. Seven secondary redo interventions were undertaken for recurrent symptoms in six group I children. Only one major periprocedural complication occurred: segmental colon infarction. The assisted patency rate of reconstructed arteries in group I children was 93%, and intestinal ischemic symptoms resolved in every child. Group I follow-up from the most recent splanchnic arterial reconstruction averaged 4.3 years. Group II children (16) without manifestations of intestinal ischemia underwent prophylactic splanchnic arterial reconstructions in concert with combined aortic and renal artery procedures (11), isolated abdominal aortic reconstructions (3), or renal artery reconstructions alone (2). Group II children experienced no major perioperative morbidity and remained asymptomatic postoperatively, and none required secondary splanchnic artery interventions. Group II follow-up averaged 7.4 years. CONCLUSIONS: Pediatric splanchnic artery occlusive lesions are often associated with developmental aortic and renal artery occlusive disease. Carefully conducted therapeutic and prophylactic reconstructive procedures are appropriate in children having splanchnic arterial occlusive disease.

Impact of Left Subclavian Artery Revascularization before Thoracic Endovascular Aortic Repair on Postoperative Cerebrovascular Hemodynamics.

BACKGROUND: The impact of left subclavian artery (LSA) revascularization before thoracic endovascular aortic repair (TEVAR) on cerebrovascular flow is not well described. We studied bilateral vertebral and carotid artery flow characteristics before and after TEVAR to evaluate the hemodynamic effects of LSA revascularization. METHODS: Seventy-four patients with mixed etiologies (mean age 70.9 ± 10.5 years) underwent LSA revascularization and TEVAR (2006-2016) and had available preoperative and postoperative carotid duplex study available. Data from patient demographics, procedures, preoperative, and postoperative carotid duplex studies were gathered. Revascularization was by left common carotid artery (LCCA) to LSA bypass (n = 70, 94.6%) or LSA to LCCA transposition (n = 4, 5.4%). RESULTS: Duplex confirmation of antegrade left vertebral artery (LVA) flow decreased significantly after TEVAR with LSA revascularization (100.0% vs. 77.9%, P < 0.001). Incidence of retrograde LVA flow increased from 0.0% to 8.3% (P = 0.063). Postoperatively, LVA bidirectional flow was observed in 3 patients (4.4%). Flow directions in the right vertebral artery (RVA) did not change significantly. Peak systolic velocity (PSV) in the LVA decreased significantly after TEVAR from 55.1 ± 22.0 cm/s to 35.9 ± 26.3 cm/s (P < 0.001). In contrast, PSV increased in the RVA and the right internal carotid artery (ICA; 52.2 ± 21.7 cm/s to 63.2 ± 23.3 cm/s, P = 0.012 and 95.3 ± 46.8 cm/s to 102.8 ± 42.9 cm/s, P = 0.011). PSV did not change significantly in the left ICA. At mean follow-up of 36.6 ± 26.8 months, primary bypass patency was 100.0%. Postoperatively, one case of temporary spinal cord ischemia was seen (1.4%). Stroke rate was 6.9% (n = 5, 100.0% embolic), all without permanent disabilities. Stroke circulation distribution was 60.0% posterior, 20.0% anterior, and 20.0% mixed. Location of stroke was left sided (n = 2) or in both hemispheres (n = 3). There were no deaths at 30 days. Neurological events during follow-up included 3 new strokes. All-cause mortality rate during follow-up was 12.2% (n = 9). CONCLUSIONS: Adjunctive LSA revascularization in the setting of zone 2 TEVAR coverage is associated with hemodynamic vertebral artery changes. Future studies in larger sample sizes should evaluate whether these novel findings are an important determinant of postoperative neurologic events.

Pancreaticoduodenal and Gastroduodenal Artery Aneurysms Associated with Celiac Artery Occlusive Disease.

BACKGROUND: The purpose of this study is to better define the clinical relevance of aneurysms affecting collateral vessels in patients with celiac artery (CA) occlusive disease. METHODS: True pancreaticoduodenal artery (PDA) and gastroduodenal artery (GDA) aneurysms associated with CA stenoses or occlusions reported from 1970 to 2010 in the English literature and similar cases treated at the University of Michigan were reviewed. Clinical presentations and differing treatment modalities were documented and analyzed. RESULTS: One hundred twenty-five patients having CA occlusive disease exhibited true arterial aneurysms affecting the PDA (105 patients), GDA (10 patients), or both PDA and GDA and their branches (10 patients). Aneurysm size averaged 2.1 cm. Included were 110 patients culled from the literature and 15 treated by the authors. The mean age of patients in this series was 59 years and there was no gender predilection. Aneurysms were asymptomatic in 26%. Abdominal pain affected 54% of the patients, including all who experienced rupture. Rupture occurred in 48 patients of whom 15 were hemodynamically unstable, including 6 who died. Surgical interventions included endovascular embolization (39), aneurysmectomy alone (25), and aneurysmectomy with arterial reconstruction (20). Salutary outcomes occurred in 91% of the cases. Open surgical procedures have remained constant, but were equaled by endovascular interventions in 1996, with the latter having increased 3-fold in the past 15 years. CONCLUSIONS: PDA and GDA aneurysms associated with CA occlusive disease carry a high risk of nonfatal rupture, warranting early treatment. Endovascular and open interventions may be successfully undertaken with minimal risks in treating these uncommon aneurysms.

Natural History of Iatrogenic Pediatric Femoral Artery Injury.

BACKGROUND: Iatrogenic femoral artery trauma complicates the course of critically ill neonates and children. Complications from persistent arterial occlusion may include claudication and limb length discrepancies. Data supporting risk factors for such and need for revascularization are lacking. METHODS: Review of a prospectively maintained database at a tertiary institution of iatrogenic pediatric femoral artery injuries incurred between 2013 and 2014 was performed. Additional injuries were identified by review of pediatric arterial duplex performed between 2008 and 2013. Demographics, risk factors, and outcomes were queried. Data analysis utilized Fischer's exact t-test and logistic regression. RESULTS: Seventy-six patients were identified of which 68 presented with acute limb ischemia (ALI) and 8 with chronic iliofemoral arterial occlusion resulting in claudication (n = 6) or limb length discrepancy (n = 2). Mean weight at injury was 6.3 kg; mean age at injury was 49 weeks (50% aged <3 months). Mean follow-up was 14 months (out to 11 years). Six patients required surgery for ALI, and 6 required delayed operation for limb length discrepancy (n = 4) or for persistent external iliac artery (EIA) occlusion. Mean age at delayed revascularization was 6 years (range: 2-13 years). Vasopressor use, mechanism/location of injury, and concomitant venous thrombosis were not significantly correlated with need for operation; trends suggested that cardiac catheterization and EIA thrombosis may correlate with chronic disease. Increased age at injury was associated with need for operation. CONCLUSIONS: Although a majority of children with ALI may be successfully treated medically, 9% will require operation for ALI and 16% ultimately required revascularization during follow-up. Persistent iliofemoral arterial thrombosis is a likely risk factor for limb length discrepancy with growth; identifying risk factors for this and improved methods for surveillance requires ongoing investigation.

Surgical treatment of abdominal aortic aneurysms in infancy and early childhood.

OBJECTIVE: Pediatric abdominal aortic aneurysms (AAAs) are rare. The intent of this report was to review the presentation and surgical management of AAAs in infancy and early childhood. METHODS: The clinical courses of young children undergoing AAA surgery were subjected to a retrospective review and analysis. RESULTS: Eleven children, nine boys and two girls, ranging in age from 2 weeks to 6 years, underwent surgical treatment of AAA at the University of Michigan from 2002 to 2014. Aneurysms were supraceliac (2), suprarenal (2), pararenal (2), or infrarenal (5). Associated iliac aneurysms (3) affected two children. Concomitant stenoses affected the renal (14), superior mesenteric (4), and celiac (3) arteries. AAAs were attributed to developmental defects (7), including three arising immediately beyond aortic narrowings; infection after umbilical artery catheterization (2); tuberous sclerosis (1); and trauma (1). Primary operative interventions included aneurysmectomy with a thoracoabdominal bypass (4), open aneurysmorrhaphy (2), closed aneurysmorrhaphy (2), and aneurysmectomy with an infrarenal aortoaortic bypass (1) or an aortoiliac bypass (2). Perioperative death occurred in one child who had preoperative heart and renal failure. Aortic graft occlusion affected two children at 1 month and 3 years postoperatively. The remaining children incurred no aortic reconstruction-related morbidity. Follow-up among the 10 survivors averaged 4.9 years. CONCLUSIONS: Successful surgical treatment of AAAs in infants and young children requires careful execution of a diverse group of surgical techniques based on the etiology, the child's size and growth potential, and the aneurysm's location and coexisting branch involvement.

Pediatric nonaortic arterial aneurysms.

OBJECTIVE: Pediatric arterial aneurysms are extremely uncommon. Indications for intervention remain poorly defined and treatments vary. The impetus for this study was to better define the contemporary surgical management of pediatric nonaortic arterial aneurysms. METHODS: A retrospective analysis was conducted of 41 children with 61 aneurysms who underwent surgical treatment from 1983 to 2015 at the University of Michigan. Arteries affected included: renal (n = 26), femoral (n = 7), iliac (n = 7), superior mesenteric (n = 4), brachial (n = 3), carotid (n = 3), popliteal (n = 3), axillary (n = 2), celiac (n = 2), ulnar (n = 2), common hepatic (n = 1), and temporal (n = 1). Intracranial aneurysms and aortic aneurysms treated during the same time period were not included in this study. Primary outcomes analyzed were postoperative complications, mortality, and freedom from reintervention. RESULTS: The study included 27 boys and 14 girls, with a median age of 9.8 years (range, 2 months-18 years) and a weight of 31.0 kg (range, 3.8-71 kg). Multiple aneurysms existed in 14 children. Obvious factors that contributed to aneurysmal formation included: proximal juxta-aneurysmal stenoses (n = 14), trauma (n = 12), Kawasaki disease (n = 4), Ehlers-Danlos type IV syndrome (n = 1), and infection (n = 1). Preoperative diagnoses were established using arteriography (n = 23), magnetic resonance angiography (n = 6), computed tomographic arteriography (n = 5), or ultrasonography (n = 7), and confirmed during surgery. Indications for surgery included risk of expansion and rupture, potential thrombosis or embolization of aneurysmal thrombus, local soft tissue and nerve compression, and secondary hypertension in the case of renal artery aneurysms. Primary surgical techniques included: aneurysm resection with reanastomsis, reimplantation, or angioplastic closure (n = 16), interposition (n = 10) or bypass grafts (n = 2), ligation (n = 9), plication (n = 8), endovascular occlusion (n = 3), and nephrectomy (n = 4) in cases of unreconstructable renal aneurysmal disease. Later secondary operations were required to treat stenoses at the site of the original aneurysm repairs (n = 2) and new aneurysmal development (n = 1). Postoperative follow-up averaged 47 months (range, 1-349 months). No major perioperative morbidity and no mortality was encountered in this experience. CONCLUSIONS: Pediatric arterial aneurysms represent a complex disease that affects multiple vascular territories. Results of the current series suggest that individualized surgical treatment, ranging from simple ligations to major arterial reconstructions, was durable and can be undertaken with minimal risk.