Race-based outcomes of thoracic aortic aneurysms and dissections in the Global Registry for Endovascular Aortic Treatment.

OBJECTIVE: This study characterizes racial differences in presentation, as well as short- and long-term outcomes after endovascular treatment of thoracic aortic aneurysm (TAA) and type B aortic dissection (TBAD). METHODS: We queried the Gore Global Registry for Endovascular Aortic Treatment for thoracic endovascular aortic repairs (TEVARs) performed between 2010 and 2016 and followed through 2022. Pathologies represented were descending TAA, complicated TBAD, and uncomplicated TBAD. Using standard statistical tests, we compared overall and pathology-specific demographics, procedural factors, and outcomes among Black and White patients undergoing TEVAR. RESULTS: We identified 438 TEVAR cases, including 236 descending TAA, 121 complicated TBAD, and 74 uncomplicated TBAD. Overall, Black patients were younger and had a higher incidence of renal insufficiency (P = .001), whereas White patients had more chronic obstructive pulmonary disease (P = .003) and cardiac arrhythmias (P = .037). In patients treated for descending TAA, Black patients had increased device- and procedure-related complications (34.3% vs 17.4%; P = .014), conversion to open repair (2.9% vs 0%; P = .011) and type II endoleak (5.7% vs 1.0%; P = .040), but no differences in mortality, length of hospital stay, or major adverse cardiovascular events. Whereas outcomes of TEVAR for uncomplicated TBAD were comparable, Black patients more frequently presented with complicated TBAD than White patients (Black, 40.5% vs White, 24.8%; P = .008) and had subsequently greater reintervention rates (28.1% vs 12.4%; P = .012), all-cause mortality (hazard ratio, 4.28; 95% confidence interval, 1.74-10.5; P = .002) and aortic-related mortality (hazard ratio, 16.7; 95% confidence interval, 1.49-186; P = .022). CONCLUSIONS: Despite increased device- and procedure-related complications, similar short- and long-term outcomes are achieved in Black and White patients undergoing TEVAR for descending TAA and uncomplicated TBAD. However, Black patients are more likely to present with, require reintervention for, and suffer mortality from complicated TBAD.

The Transcriptomics of the Human Vein Transformation After Arteriovenous Fistula Anastomosis Uncovers Layer-Specific Remodeling and Hallmarks of Maturation Failure.

Introduction: The molecular transformation of the human preaccess vein after arteriovenous fistula (AVF) creation is poorly understood. This limits our ability to design efficacious therapies to improve maturation outcomes. Methods: Bulk RNA sequencing (RNA-seq) followed by paired bioinformatic analyses and validation assays were performed in 76 longitudinal vascular biopsies (veins and AVFs) from 38 patients with stage 5 chronic kidney disease or end-stage kidney disease undergoing surgeries for 2-stage AVF creation (19 matured, 19 failed). Results: A total of 3637 transcripts were differentially expressed between veins and AVFs independent of maturation outcomes, with 80% upregulated in fistulas. The postoperative transcriptome demonstrated transcriptional activation of basement membrane and interstitial extracellular matrix (ECM) components, including preexisting and novel collagens, proteoglycans, hemostasis factors, and angiogenesis regulators. A postoperative intramural cytokine storm involved >80 chemokines, interleukins, and growth factors. Postoperative changes in ECM expression were differentially distributed in the AVF wall, with proteoglycans and fibrillar collagens predominantly found in the intima and media, respectively. Interestingly, upregulated matrisome genes were enough to make a crude separation of AVFs that failed from those with successful maturation. We identified 102 differentially expressed genes (DEGs) in association with AVF maturation failure, including upregulation of network collagen VIII in medial smooth muscle cells (SMCs) and downregulation of endothelial-predominant transcripts and ECM regulators. Conclusion: This work delineates the molecular changes that characterize venous remodeling after AVF creation and those relevant to maturation failure. We provide an essential framework to streamline translational models and our search for antistenotic therapies.

Vein morphometry in end-stage kidney disease: Teasing out the contribution of age, comorbidities, and vintage to chronic wall remodeling.

Background: Chronic kidney disease (CKD) is a highly comorbid condition with significant effects on vascular health and remodeling. Upper extremity veins are important in end-stage kidney disease (ESKD) due to their potential use to create vascular accesses. However, unlike arteries, the contribution of CKD-associated factors to the chronic remodeling of veins has been barely studied. Methods: We measured morphometric parameters in 315 upper extremity veins, 131 (85% basilic) from stage 5 CKD/ESKD patients and 184 (89% basilic) from non-CKD organ donors. Associations of demographic and clinical characteristics with intimal hyperplasia (IH) and medial fibrosis were evaluated using multivariate regression models. Results: The study cohort included 33% females, 30% blacks, 32% Hispanics, and 37% whites. Over 60% had hypertension, and 25% had diabetes independent of CKD status. Among kidney disease participants, 26% had stage 5 CKD, while 22 and 52% had ESKD with and without history of a previous arteriovenous fistula/graft (AVF/AVG), respectively. Intimal hyperplasia was associated with older age (ß = 0.13 per year, confidence interval [CI] = 0.002-0.26), dialysis vintage > 12 months (ß = 0.22, CI = 0.09-0.35), and previous AVF/AVG creation (ß = 0.19, CI = 0.06-0.32). Upper quartile values of IH were significantly associated with diabetes (odds ratio [OR] = 2.02, CI = 1.08-3.80), which demonstrated an additive effect with previous AVF/AVG history and longer vintage in exacerbating IH. Medial fibrosis also increased as a function of age (ß = 0.17, CI = 0.04-0.30) and among patients with diabetes (ß = 0.15, CI = 0.03-0.28). Age was the predominant factor predicting upper quartile values of fibrosis (OR = 1.03 per year, CI = 1.01-1.05) independent of other comorbidities. Conclusion: Age and diabetes are the most important risk factors for chronic development of venous IH and fibrosis independent of CKD status. Among kidney disease patients, longer dialysis vintage, and history of a previous AVF/AVG are strong predictors of IH.

Extracorporeal membrane oxygenation (ECMO): Can we do it ourselves?

Extracorporeal membrane oxygenation (ECMO) is a selectively available therapeutic option, generally available in a large-size referral healthcare system. In a single-center experience of the use of venovenous ECMO for COVID-19 ARDS in a medium-size healthcare system during the pandemic, West et al. in their study have convincingly demonstrated that ECMO can become a broadly available therapeutic option without compromising quality.

Radial Long Sheath Angioplasty for Proximal Severe Flow-Limiting Radial Artery Spasm Using the Dotter Technique.

BACKGROUND: Although studies have continued to demonstrate the advantages of transradial access (TRA) for neurointervention, radial artery spasm (RAS) has remained a frequent cause of TRA failure. Dotter and Judkins initially described a technique to dilate areas of peripheral vascular stenosis by advancing sequentially larger catheters across the lesion over a guidewire. We have presented our institutional experience with the use of a modified Dotter technique with long radial sheaths to dilate areas of proximal flow-limiting RAS. In the present study, we reviewed the use of the Dotter technique for alleviating RAS in patients undergoing TRA for neurointervention. METHODS: We performed a retrospective review of all patients undergoing TRA for neurointervention at our institution from 2018 to 2020 to identify patients with proximal flow-limiting RAS. For the identified patients, a modified Dotter technique had been used to dilate the stenosis. The demographic and periprocedural data were assessed to identify any adverse outcomes. RESULTS: Four patients with severe proximal flow-limiting RAS were identified. In each case, a hydrophilic long radial sheath and vascular dilator were sequentially advanced through the stenosis. In all cases, repeat angiography demonstrated improvement of the spasm, and the final radial angiograms demonstrated persistent improvement in caliber and regularity of the vessel. Each procedure was also completed via TRA with no periprocedural complications. CONCLUSIONS: Our modified Dotter technique was effective in bypassing areas of severe proximal flow-limiting RAS, obviating the need for access site conversion. Additional studies are warranted to understand the implication of the angioplasty-like effects seen within the radial artery after removal of the long radial sheaths.

The Genetic Basis of Adaptation following Plastic Changes in Coloration in a Novel Environment.

Phenotypic plasticity has been hypothesized to precede and facilitate adaptation to novel environments [1-8], but examples of plasticity preceding adaptation in wild populations are rare (but see [9, 10]). We studied a population of side-blotched lizards, Uta stansburiana, living on a lava flow that formed 22,500 years ago [11] to understand the origin of their novel melanic phenotype that makes them cryptic on the black lava. We found that lizards living on and off of the lava flow exhibited phenotypic plasticity in coloration but also appeared to have heritable differences in pigmentation. We sequenced the exomes of 104 individuals and identified two known regulators of melanin production, PREP and PRKAR1A, which had markedly increased levels of divergence between lizards living on and off the lava flow. The derived variants in PREP and PRKAR1A were only found in the lava population and were associated with increased pigmentation levels in an experimental cohort of hatchling lizards. Simulations suggest that the derived variants in the PREP and PRKAR1A genes arose recently and were under strong positive selection in the lava population. Overall, our results suggest that ancestral plasticity for coloration facilitated initial survival in the lava environment and was followed by genetic changes that modified the phenotype in the direction of the induced plastic response, possibly through de novo mutations. These observations provide a detailed example supporting the hypothesis that plasticity aids in the initial colonization of a novel habitat, with natural selection subsequently refining the phenotype with genetic adaptations to the new environment. VIDEO ABSTRACT.