Impact of thoracic endovascular aortic repair timing on aortic remodeling in acute type B aortic intramural hematoma.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) is increasingly utilized in the management of acute type B aortic intramural hematoma (TBIMH). Optimal timing for intervention has not been described. The aim of this study was to evaluate TEVAR timing on postoperative aortic remodeling. METHODS: A retrospective chart review was performed on patients who underwent TEVAR for TBIMH from January 2008 to September 2018. Imaging was reviewed pre- and postoperatively. Primary data points included true lumen diameter (TLD) and total aortic diameter (TAD) at the site of maximal pathology. Primary endpoint was aortic remodeling evidenced by a TAD/TLD ratio closest to 1.0. Secondary outcome was occurrence of aortic-related adverse events and mortality (AREM): aortic rupture, aortic-related death, progression to dissection, or need for aortic reintervention within 12 months. Patients undergoing emergent TEVAR (within 24 hours, 'eTEVAR') were compared with the remainder - delayed TEVAR ('dTEVAR'). RESULTS: We analyzed 71 patients that underwent TEVAR for TBIMH; 25 underwent emergent TEVAR and 46 patients underwent dTEVAR (median, 5.5 days; range, 2-120 days). There were no differences in demographics and comorbidities, and patients did not differ in presenting IMH thickness (12.6 ± 3.1 vs 11.3 ± 4.1 mm; P = .186) nor presenting TAD/TLD ratio (1.535 ± 0.471 vs 1.525 ± 0.397; P = .928) for eTEVAR and dTEVAR groups, respectively. eTEVAR patients had larger average presenting maximal descending aortic diameter (45.8 ± 14.3 vs 38.2 ± 7.5 mm; P = .018) and higher incidence of penetrating aortic ulcer on presenting computed tomography angiography (52.0% vs 21.7%; P = .033). Thirty-day mortality was 2 of 25 (8.0%) for eTEVAR and 2 of 45 (4.4%) for dTEVAR (P = .602). Postoperative aortic remodeling was more complete in the dTEVAR group (1.23 ± 0.12 vs 1.33 ± 0.15; P = .004). Case-control matching (controlling for presenting descending aortic diameter and penetrating aortic ulcer) on 30 patients still showed better aortic remodeling in the dTEVAR group (1.125 ± 0.100 vs 1.348 ± 0.42; P < .001). The incidence of AREM was higher in the eTEVAR (6/25; 24.0%) group compared with the dTEVAR group (2/46; 4.3%). At 12 months, freedom from AREM was higher in the dTEVAR group (95.7% vs 76.0%; P = .011). Postoperative TAD/TLD ratio was the best predictor for late aortic-related adverse events (area under the receiver operator characteristic = 0.825; P = .003). CONCLUSIONS: TEVAR for acute TBIMH within 24 hours of admission is associated with lower aortic remodeling and higher occurrence of late AREM. Delaying TEVAR when clinically possible could improve aortic remodeling and aortic-related outcomes.

Therapeutic window for obtaining favorable remodeling after thoracic endovascular aortic repair of type B aortic dissection.

OBJECTIVE: The purpose of the present study was to determine the most appropriate timing for thoracic endovascular aortic repair (TEVAR) of type B aortic dissection (TBAD) in terms of remodeling of the aorta. METHODS: A total of 41 patients who had undergone TEVAR for the treatment of aortic dissection were included in the present study. The patients were divided into two groups: those who had undergone TEVAR in the acute or subacute phase (group A) and those who had undergone TEVAR in the chronic phase (group B). The indications for TEVAR as the treatment of TBAD were the presence of aortic rupture or malperfusion of the aortic branches, a maximum aortic diameter of ≥40 mm on the initial diagnostic computed tomography scan, and/or expansion of the aorta of ≥5 mm within 3 months for acute and subacute TBAD. The indication was a maximum aortic diameter of ≥50 mm or expansion of the aorta of ≥5 mm within 1 year for chronic TBAD. The diameters of the aorta, true lumen, and false lumen were measured at the level of the most dilated part of the descending aorta (level M) and at the diaphragm (level D) on the computed tomography scan obtained before TEVAR and at the 2-year follow-up examination. RESULTS: The median interval between TEVAR and the onset of TBAD was 0.2 month (interquartile range, 0.03-0.7 month) in group A (n = 21) and 32 months (interquartile range, 4.7-35.2 months) in group B (n = 20). Except for the aortic diameter at level D in group B, favorable remodeling was obtained at both levels in both groups. The diameter change ratio of the aorta at level D was significantly greater in group A than in group B (P = .02). Receiver operating characteristic curve analysis of the interval for a significant decrease in the aortic diameter at level D yielded 4.2 months as the optimal threshold for performing TEVAR (area under the curve, 0.859; 95% confidence interval, 0.7-1.0). CONCLUSIONS: TEVAR for TBAD will result in favorable outcomes, irrespective of the timing of the procedure. However, it might be more effective to perform TEVAR within 4.2 months of the onset of TBAD, provided that the TEVAR procedure can be performed safely.

A systematic review of spinal cord ischemia prevention and management after open and endovascular aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) is one of the most devastating complications after descending thoracic aortic (DTA) and thoracoabdominal aortic (TAA) repairs. Patients who develop SCI have a poor prognosis, with mortality rates reaching 75% within the first year after surgery. Many factors have been shown to increase the risk of this complication, including the extent of TAA repair, length of aortic and collateral network coverage, embolization, and reduced spinal cord perfusion pressure. As a result, a variety of treatment strategies have been developed. We aimed to provide an up-to-date review of SCI rates with associated treatment algorithms from open and endovascular DTA and TAA repair. METHODS: Using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, a literature review with the MeSH (medical subject headings) terms "spinal cord ischemia," "spinal cord ischemia prevention and mitigation strategies," "spinal cord ischemia rates," and "spinal cord infarction" was performed in the Cochrane and PubMed databases to find all peer-reviewed studies of DTA and TAA repair with SCI complications reported. The search was limited to 2012 to 2021 and English-language reports. MeSH subheadings, including diagnosis, complications, physiopathology, surgery, mortality, and therapy, were used to further restrict the included studies. Studies were excluded if they were not of humans, had not pertained to SCI after DTA or TAA operative repair, and if the study had primarily discussed neuromonitoring techniques. Additionally, studies with <40 patients or limited information regarding SCI protection strategies were excluded. Each study was individually reviewed by two of us (S.L. and A.D.) to assess the type and extent of aortic pathology, operative technique, SCI protection or mitigation strategies, rates of overall and permanent SCI symptoms, associations with SCI on multivariate analysis, and mortality. RESULTS: Of the 450 studies returned by the MeSH search strategy, 41 met the inclusion criteria and were included in the final analysis. For the endovascular DTA repair patients, the overall SCI rates ranged from 0% to 10.6%, with permanent SCI symptoms ranging from 0% to 5.1%. The rate of overall SCI after endovascular and open TAA repair was 0% to 35%. The permanent SCI symptom rate was reported by only one study of open repair at 1.1%. The permanent SCI symptom rate after endovascular TAA repair was 2% to 20.5%. CONCLUSIONS: The present review has provided an up-to-date review of the current rates of SCI and the prevention and mitigation strategies used during DTA and TAA repair. We found that a multimodal approach, including a bundled institutional protocol, staging of multiple repairs, preservation of the collateral blood flow network, augmented spinal cord perfusion, selective cerebrospinal fluid drainage, and distal aortic perfusion during open TAA repairs, appears to be important in reducing the risk of SCI.

Effect of Anastomosis Angles on Retrograde Perfusion and Hemodynamics of Hybrid Treatment for Thoracoabdominal Aortic Aneurysm.

BACKGROUND: Hemodynamic effects on the retrograde visceral reconstruction (RVR) for thoracoabdominal aortic aneurysms treatment by anastomotic angle remains unclear. This study aims to qualitatively and quantitatively investigate the effects of different anastomotic angles on hemodynamics and patency. METHODS: Three RVR models with 45°, 60° and 90° anastomotic angles were reconstructed respectively by manipulating apostoperative patient-specific model. The manipulated models of the RVRs were numerically simulated and analyzed in terms of hemodynamics including theinstant and cumulative patency, flow pattern and indicators based on wall shear stress (WSS). RESULTS: Although a smaller anastomotic angle may decrease the patency rate of common iliac arteries, it can improve the visceral perfusion during a cardiac cycle. More importantly, RVR with the smallest anastomotic angle experienced a minimal low time-averaged wall shear stress, high oscillatory shear index and relative residence time in the anastomosis region, whereas the largest anastomotic angle can introduce more unfavorable WSS in the graft trunk. Furthermore, a spiral flow pattern was observed in the proximal graft trunk of all three models, where no high-risk shear distribution was detected in this region. CONCLUSION: A smaller anastomotic angle may have more benefits of hemodynamic environment in RVR, especially the WSS distribution and flow pattern in the graft trunk. We may also suggest that additional stents or an extended cuff for the graft can be used to induce spiral flow intentionally, which can further improve local hemodynamic environment and long-term prognosis.

Incidence of spinal cord ischemia according to the patency of reimplanted segmental arteries during thoracoabdominal aortic replacement.

BACKGROUND: This study aimed to investigate the impact of segmental artery reimplantation and its patency on spinal cord ischemia (SCI) in thoracoabdominal aorta replacement. METHODS: For 193 patients who underwent early postoperative computed tomographic (CT) angiography after thoracoabdominal aorta replacement, the technique of segmental artery reimplantation, their patency, and postoperative SCI were retrospectively investigated. RESULTS: The early patency rate of reimplanted segmental artery was 83.3% (210 of 252), as 13 were taken down intraoperatively and 42 were not visualized in the postoperative CT angiography. The patency rate differed according to the reimplantation technique: 93.6% (131/140) for en bloc patch, 95.6% (43/45) for small individual patch, and 53.7% (36/67) for graft interposition. SCI occurred in 13 (6.3%) patients, 4 of whom (2.0%) remained paraplegic permanently. SCI was significantly more frequent (P=0.044) in the patients in whom segmental artery reimplantation was not successful (take-down or occlusion, 6/37=16.2%) than in those who had all segmental arteries sacrificed intentionally (2/64=3.1%) and those who showed patency of all reimplanted segmental arteries (5/92=5.4%). Especially, there was no permanent paraplegia in the last group. Failure of intended segmental artery reimplantation was a significant risk factor of postoperative SCI in logistic regression analysis (P=0.012; odds ratio 4.65, 95% confidence interval 1.41-15.36). CONCLUSIONS: During thoracoabdominal aorta replacement, attention should be paid to the segmental artery reimplantation technique, which affects the risk of occlusion or intraoperative take-down and thereby may have impact on postoperative SCI.

TNFα induces endothelial dysfunction in rheumatoid arthritis via LOX-1 and arginase 2: reversal by monoclonal TNFα antibodies.

AIMS: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints and blood vessels. Despite low levels of low-density lipoprotein cholesterol (LDL-C), RA patients exhibit endothelial dysfunction and are at increased risk of death from cardiovascular complications, but the molecular mechanism of action is unknown. We aimed in the present study to identify the molecular mechanism of endothelial dysfunction in a mouse model of RA and in patients with RA. METHODS AND RESULTS: Endothelium-dependent relaxations to acetylcholine were reduced in aortae of two tumour necrosis factor alpha (TNFα) transgenic mouse lines with either mild (Tg3647) or severe (Tg197) forms of RA in a time- and severity-dependent fashion as assessed by organ chamber myograph. In Tg197, TNFα plasma levels were associated with severe endothelial dysfunction. LOX-1 receptor was markedly up-regulated leading to increased vascular oxLDL uptake and NFκB-mediated enhanced Arg2 expression via direct binding to its promoter resulting in reduced NO bioavailability and vascular cGMP levels as shown by ELISA and chromatin immunoprecipitation. Anti-TNFα treatment with infliximab normalized endothelial function together with LOX-1 and Arg2 serum levels in mice. In RA patients, soluble LOX-1 serum levels were also markedly increased and closely related to serum levels of C-reactive protein. Similarly, ARG2 serum levels were increased. Similarly, anti-TNFα treatment restored LOX-1 and ARG2 serum levels in RA patients. CONCLUSIONS: Increased TNFα levels not only contribute to RA, but also to endothelial dysfunction by increasing vascular oxLDL content and activation of the LOX-1/NFκB/Arg2 pathway leading to reduced NO bioavailability and decreased cGMP levels. Anti-TNFα treatment improved both articular symptoms and endothelial function by reducing LOX-1, vascular oxLDL, and Arg2 levels.

Outcomes of thoracic endovascular aortic repair in patients with concomitant blunt thoracic aortic injury and traumatic brain injury from the Aortic Trauma Foundation global registry.

BACKGROUND: Traumatic brain injury (TBI) and blunt thoracic aortic injury (BTAI) are the top two leading causes of death after blunt force trauma. Patients presenting with concomitant BTAI and TBI pose a specific challenge with respect to management strategy, because the optimal hemodynamic parameters are conflicting between the two pathologies. Early thoracic endovascular aortic repair (TEVAR) is often performed, even for minimal aortic injuries, to allow for the higher blood pressure parameters required for TBI management. However, the optimal timing of TEVAR for the treatment of BTAI in patients with concomitant TBI remains an active matter of controversy. METHODS: The Aortic Trauma Foundation international prospective multicenter registry was used to identify all patients who had undergone TEVAR for BTAI in the setting of TBI from 2015 to 2020. The primary outcomes included delayed ischemic or hemorrhagic stroke, in-hospital mortality, and aortic-related mortality. The outcomes were examined among patients who had undergone TEVAR at emergent (<6 vs ≥6 hours) or urgent (<24 vs ≥24 hours) intervals. RESULTS: A total of 100 patients (median age, 43 years; 79% men; median injury severity score, 41) with BTAI (Society for Vascular Surgery BTAI grade 1, 3%; grade 2, 10%; grade 3, 78%; grade 4, 9%) and concomitant TBI who had undergone TEVAR were identified. Emergent repair was performed for 51 patients (51%). Comparing emergent repair (<6 hours) to urgent repair (≥6 hours), no difference was found in delayed cerebral ischemic events (2.0% vs 4.1%; P = .614), in-hospital mortality (15.7% vs 22.4%; P = .389), or aortic-related mortality (2.0% vs 2.0%; P = .996) and no patient had experienced delayed hemorrhagic stroke. Likewise, repairs conducted in an urgent (<24 hours) setting showed no differences compared with those completed in an emergent (≥24 hours) setting regarding delayed ischemic stroke (2.6% vs 4.3%; P = .548), in-hospital mortality (18.2% vs 21.7%; P = .764), or aortic-related mortality (1.3% vs 4.3%; P = .654), and no patient had experienced delayed hemorrhagic stroke. CONCLUSIONS: In contrast to prior retrospective efforts, results from the Aortic Trauma Foundation international prospective multicenter registry have demonstrated that neither emergent nor urgent TEVAR for patients with concomitant BTAI and TBI was associated with delayed stroke, in-hospital mortality, or aortic-related mortality. In these patients, the timing of TEVAR did not have an effect on the outcomes. Therefore, the decision to intervene should be guided by individual patient factors rather than surgical timing.

A single baroreceptor unit consists of multiple sensors.

Arterial baroreceptors (BRs) play a vital role in the regulation of the cardiopulmonary system. What is known about how these sensors operate at the subcellular level is limited, however. Until recently, one afferent axon was considered to be connected to a single baroreceptor (one-sensor theory). However, in the lung, a single airway mechanosensory unit is now known to house many sensors (multiple-sensor theory). Here we tested the hypothesis that multiple-sensor theory also operates in BR units, using both morphological and electrophysiological approaches in rabbit aortic arch (in whole mount) labeled with Na+/K+-ATPase, as well as myelin basic protein antibodies, and examined microscopically. Sensory structures presented in compact clusters, similar to bunches of grapes. Sensory terminals, like those in the airways, formed leaf-like or knob-like expansions. That is, a single myelinated axon connected with multiple sensors forming a network. We also recorded single-unit activities from aortic baroreceptors in the depressor nerve in anesthetized rabbits and examined the unit response to a bolus intravenous injection of phenylephrine. Unit activity increased progressively as blood pressure (BP) increased. Five of eleven units abruptly changed their discharge pattern to a lower activity level after BP attained a plateau for a minute or two (when BP was maintained at the high level). These findings clearly show that the high discharge baroreceptor deactivates after over-excitation and unit activity falls to a low discharge sensor. In conclusion, our morphological and physiological data support the hypothesis that multiple-sensory theory can be applied to BR units.

Vena cava presents endothelial dysfunction prior to thoracic aorta in heart failure: the pivotal role of nNOS uncoupling/oxidative stress.

Arterial endothelial dysfunction has been extensively studied in heart failure (HF). However, little is known about the adjustments shown by the venous system in this condition. Considering that inferior vena cava (VC) tone could influence cardiac performance and HF prognosis, the aim of the present study was to assess the VC and thoracic aorta (TA) endothelial function of HF-post-myocardial infarction (MI) rats, comparing both endothelial responses and signaling pathways developed. Vascular reactivity of TA and VC from HF post-MI and sham operated (SO) rats was assessed with a wire myograph, 4 weeks after coronary artery occlusion surgery. Nitric oxide (NO), H2O2 production and oxidative stress were evaluated in situ with fluorescent probes, while protein expression and dimer/monomer ratio was assessed by Western blot. VC from HF rats presented endothelial dysfunction, while TA exhibited higher acetylcholine (ACh)-induced vasodilation when compared with vessels from SO rats. TA exhibited increased ACh-induced NO production due to a higher coupling of endothelial and neuronal NO synthases isoforms (eNOS, nNOS), and enhanced expression of antioxidant enzymes. These adjustments, however, were absent in VC of HF post-MI rats, which exhibited uncoupled nNOS, oxidative stress and higher H2O2 bioavailability. Altogether, the present study suggests a differential regulation of endothelial function between VC and TA of HF post-MI rats, most likely due to nNOS uncoupling and compromised antioxidant defense.

Abnormalities in lysine degradation are involved in early cardiomyocyte hypertrophy development in pressure-overloaded rats.

BACKGROUND: Cardiomyocyte metabolism changes before cardiac remodeling, but its role in early cardiac hypertrophy detection remains unclear. This study investigated early changes in plasma metabolomics in a pressure-overload cardiac hypertrophy model induced by transverse aortic constriction (TAC). METHODS: The TAC model was constructed by partly ligating the aortic arch. Twelve Sprague-Dawley rats were randomly divided into the TAC group (n = 6) and sham group (n = 6). Three weeks after surgery, cardiac echocardiography was performed to assess cardiac remodeling and function. Hematoxylin/eosin (HE), Masson, and wheat germ agglutinin (WGA) stains were used to observe pathological changes. Plasma metabolites were detected by UPLC-QTOFMS and Q-TOFMS. Specific metabolites were screened by orthogonal partial least squares discriminant analysis (OPLS-DA). Metabolic pathways were characterized by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the predictive value of the screened metabolites was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: Three weeks after surgery, the TAC and sham groups had similar left heart function and interventricular septum and diastolic left ventricular posterior wall thicknesses. However, on pathological examination, the cross-sectional area of cardiomyocytes and myocardial fibrosis severity were significantly elevated in TAC rats. OPLS-DA showed different metabolic patterns between the TAC and sham groups. Based on the criteria VIP > 1 and P < 0.05, 13 metabolites were screened out. KEGG analysis identified disrupted lysine degradation through the related metabolites 5-aminopentanoic acid, N6-acetyl-L-lysine, and L-lysine, with areas under the ROC curve (AUCs) of 0.917, 0.889, and 0.806, respectively, for predicting compensated cardiomyocyte hypertrophy. CONCLUSION: Disruption of lysine degradation might be involved in early cardiac hypertrophy development, and related metabolites might be potential predictive and interventional targets for subclinical cardiomyocyte hypertrophy.

Biomechanical Analysis of Cadaveric Thoracic Aorta Zones: The Isthmus is the Weakest Region.

BACKGROUND: The thoracic aorta is a site of multiple pathological processes, such as aneurysms and dissections. When considering the development of endovascular devices, this vessel has been extensively manipulated because of aortic diseases, as well as to serve as a route for procedures involving the head and neck vessels. Therefore, the aim of the present study was to obtain biomechanical experimental information about the strength and deformability of this vessel. MATERIALS AND METHODS: Thirty-one thoracic aorta specimens were harvested during the autopsy procedure. They were carefully dissected and transversally sectioned according to Criado's aortic arch map landing zones (0 to 4). The supra-aortic trunks were removed, and the aortic rings were opened in their convexity, which resulted in flat tissue segments. Four millimeter-wide strips were prepared from each zone after which they were attached to a clip system connected to the INSTRON SPEC 2200 device, which was responsible for pulling the fragment up to its rupture during the uniaxial tension test. The INSPEC software was used to coordinate the test, and data management was conducted via the SERIES IX software. The biomechanical variables that were measured included failure stress, failure tension, and failure strain. RESULTS: When comparing the five segments from all 31 aortas, three different strength levels were observed. Zones 0 and 1 exhibited the highest failure stress and failure tension values, followed by Zones 2 and 4. Zone 3 (aortic isthmus) was the weakest segment that was tested when compared to the stress and tension of Zones 0 and 1 (P < 0.001), the stress and tension of Zone 2 (P = 0.005 and P = 0.002, respectively) and the stress and tension of Zone 4 (P = 0.023 and P = 0.006, respectively). Among donors > 65 years-old, women presented significantly weaker descending aortas than men in regards to stress (P = 0.049) and tension (P = 0.014). Among male donors, the elderly donors presented significantly stiffer aortic walls and weaker ascending (P = 0.029 for stress) and descending (P = 0.004 for stress; P = 0.031 for tension) aortas than younger men. CONCLUSIONS: Uniaxial tensile strength tests revealed that the thoracic aorta is a very heterogeneous vessel. Isthmus frailty may add to the understanding of the pathophysiology of some aortic diseases that commonly compromise this region. The lower strength that was verifiedin some aortic segments from elderly donors may contribute to the genesis of some thoracic aorta diseases among that group of donors. These data can contribute to the development of new endovascular devices that are specifically designed for this vessel.

Population-Based Risk Factors for Ascending, Arch, Descending, and Abdominal Aortic Dilations for 60-74-Year-Old Individuals.

BACKGROUND: Aortic dilations (ectasias and aneurysms) may occur on any segment of the aorta. Pathogenesis varies between locations, suggesting that etiology and risk factors may differ. Despite this discrepancy, guidelines recommend screening of the whole aorta if 1 segmental dilation is discovered. OBJECTIVES: The purpose of this study was to determine the most dominant predictors for dilations at the ascending, arch, descending, and abdominal part of the aorta, and to establish comprehensive risk factor profiles for each aortic segment. METHODS: Individuals aged 60-74 years were randomly selected to participate in DANCAVAS I+II (Danish Cardiovascular Multicenter Screening Trials). Participants underwent cardiovascular risk assessments, including blood samples, blood pressure readings, medical records, and noncontrast computed tomography scans. Adjusted odds ratios for potential risk factors of dilations were estimated by multivariate logistic analyses. RESULTS: The study population consisted of 14,989 participants (14,235 men, 754 women) with an average age of 68 ± 4 years. The highest adjusted odd ratios for having any aortic dilation were observed when coexisting aortic dilations were present. Other noteworthy predictors included coexisting iliac dilations, hypertension, increasing body surface area, male sex, familial disposition, and atrial fibrillation, which were present in various combinations for the different aortic parts. Smoking and acute myocardial infarction were inversely associated with ascending and abdominal dilations. Diabetes was a shared protective factor. CONCLUSIONS: Risk factors differ for aortic dilations between locations. The most dominant predictor for having a dilation at any aortic segment is the presence of an aortic dilation elsewhere. This supports current guidelines when recommending a full screening of the aorta if a focal aortic dilation is discovered.

Conditioned Medium from Mesenchymal Stem Cells Alleviates Endothelial Dysfunction of Vascular Grafts Submitted to Ischemia/Reperfusion Injury in 15-Month-Old Rats.

In patients undergoing coronary artery bypass grafting (CABG), ischemia/reperfusion injury (IRI) is the main contributor to organ dysfunction. Aging-induced vascular damage may be further aggravated during CABG. Favorable effects of conditioned medium (CM) from mesenchymal stem cells (MSCs) have been suggested against IRI. We hypothesized that adding CM to saline protects vascular grafts from IRI in rats. We found that CM contains 28 factors involved in apoptosis, inflammation, and oxidative stress. Thoracic aortic rings from 15-month-old rats were explanted and immediately mounted in organ bath chambers (aged group) or underwent 24 h of cold ischemic preservation in saline-supplemented either with vehicle (aged-IR group) or CM (aged-IR+CM group), prior to mounting. Three-month-old rats were used as referent young animals. Aging was associated with an increase in intima-to-media thickness, an increase in collagen content, higher caspase-12 mRNA levels, and immunoreactivity compared to young rats. Impaired endothelium-dependent vasorelaxation to acetylcholine in the aged-IR group compared to the aged-aorta was improved by CM (aged 61 ± 2% vs. aged-IR 38 ± 2% vs. aged-IR+CM 50 ± 3%, p < 0.05). In the aged-IR group, the already high mRNA levels of caspase-12 were decreased by CM. CM alleviates endothelial dysfunction following IRI in 15-month-old rats. The protective effect may be related to the inhibition of caspase-12 expression.

Association of hemodynamic factors and progressive aortic dilatation following type A aortic dissection surgical repair.

Type A aortic dissection (TAAD) involves the ascending aorta or the arch. Acute TAAD usually requires urgent replacement of the ascending aorta. However, a subset of these patients develops aortic rupture due to further dilatation of the residual dissected aorta. There is currently no reliable means to predict the risk of dilatation following TAAD repair. In this study, we performed a comprehensive morphological and hemodynamic analysis for patients with and without progressive aortic dilatation following surgical replacement of the ascending aorta. Patient-specific models of repaired TAAD were reconstructed from post-surgery computed tomography images for detailed computational fluid dynamic analysis. Geometric and hemodynamic parameters were evaluated and compared between patients with stable aortic diameters (N = 9) and those with aortic dilatation (N = 8). Our results showed that the number of re-entry tears and true/false lumen pressure difference were significantly different between the two groups. Patients with progressive aortic dilatation had higher luminal pressure difference (6.7 [4.6, 10.9] vs. 0.9 [0.5, 2.3] mmHg; P = 0.001) and fewer re-entry tears (1.5 [1, 2.8] vs. 5 [3.3, 7.5]; P = 0.02) compared to patients with stable aortic diameters, suggesting that these factors may serve as potential predictors of aneurysmal dilatation following surgical repair of TAAD.

Anticoagulation and antiplatelet medications do not affect aortic remodeling after thoracic endovascular aortic repair for type B aortic dissection.

OBJECTIVE: There is a lack of evidence regarding the effect of anticoagulation and antiplatelet medications on aortic remodeling for aortic dissection after endovascular repair. We investigated whether anticoagulation and antiplatelet medications affect aortic remodeling after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: Records of the Vascular Quality Initiative TEVAR registry (2012-2020) were reviewed. Procedures performed for TBAD were included. Aortic reintervention, false lumen thrombosis of the treated aorta, and all-cause mortality at follow-up were compared between patients treated with and without anticoagulation medications. A secondary analysis was performed to assess the effect of antiplatelet therapy in patients not on anticoagulation. Cox proportional hazards models were used to estimate the effect of anticoagulation and antiplatelet therapies on outcomes. RESULTS: A total of 1210 patients (mean age, 60.7 ± 12.2 years; 825 males [68%]) were identified with a mean follow-up of 21.2 ± 15.7 months (range, 1-94 months). One hundred sixty-six patients (14%) were on anticoagulation medications at discharge and at follow-up. Patients on anticoagulation were more likely to be older (mean age, 65.5 vs 60 years; P < .001) and Caucasian (69% vs 55%; P = .003), with higher proportions of coronary artery disease (10% vs 3%; P < .001), congestive heart failure (10% vs 2%; P < .001), and chronic obstructive pulmonary disease (15% vs 9%; P = .017). There were no differences in the mean preoperative thoracic aortic diameter or the number of endografts used. At 18 months, the rates of aortic reinterventions (8% vs 9%; log-rank P = .873), complete false lumen thrombosis (52% vs 45%; P = .175), and mortality (2.5% vs 2.7%; P = .209) were similar in patients with and without anticoagulation, respectively. Controlling for covariates with the Cox regression method, anticoagulation use was not independently associated with a decreased rates of complete false lumen thrombosis (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.5-1.1; P = .132), increased need for aortic reinterventions (HR, 1.02; 95% CI, 0.62-1.68; P = .934), and mortality (HR, 1.25; 95% CI, 0.64-2.47; P = .514). On a secondary analysis, antiplatelet medications did not affect the rates of aortic reintervention, complete false lumen thrombosis, and mortality. CONCLUSIONS: Anticoagulation and antiplatelet medications do not appear to negatively influence the midterm endpoints of aortic reintervention or death in patients undergoing TEVAR for TBAD. Moreover, it did not impair complete false lumen thrombosis. Anticoagulation and antiplatelet medications do not adversely affect aortic remodeling and survival in this population at midterm.

Aortic Neck Dilatation Following Thoracic Endovascular Aortic Repair.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) has become a mainstay of treatment for a variety of thoracic aortic pathologies. Expansion of the proximal aortic neck after endovascular repair of abdominal aortic aneurysms has been demonstrated; however, dilatation of the proximal aortic neck after TEVAR has not been well described. We sought to describe remodeling of the proximal neck following TEVAR. METHODS: This is a retrospective, single institution review of patients who underwent TEVAR for thoracic aortic aneurysm (TAA) and dissection with aneurysmal degeneration from 2010 to 2019. Postoperative computed tomography scans were reviewed and aortic diameter was measured in orthogonal planes using 3-dimensional centerline reconstruction software. The primary outcome was change in aortic diameter at the proximal aortic neck as compared to the initial postoperative computed tomography scan. Clinical and operative data were analyzed to identify factors associated with significant neck dilatation. RESULTS: Of 87 patients who underwent TEVAR during the study period, 30 met inclusion criteria. Median follow up was 20.5 months. Median age was 67 years, and 15 patients (50%) were female. The proximal aortic neck experienced an overall increase over time in aortic diameter. Five mm distal to the graft showed the greatest rate of expansion, with a median increase of 1.3, 2.9, and 6.2 mm at one year, two years, and three years, respectively. When comparing patients who had mean expansion at this location of >2.0 mm/year to patients who did not, a higher percentage had dissection pathology (81.8% vs. 31.6%, P = 0.008), had graft placement at aortic landing zone 2 (36.4% vs. 5.3%, P = 0.028), and were smokers (100% vs. 52.6%, P = 0.006). Higher percent oversizing was shown to be associated with significant aortic neck dilatation for true aneurysms only. CONCLUSIONS: Aortic neck dilatation occurs over time for the majority of patients following TEVAR with the distal neck experiencing the highest rate of expansion. Dissection pathology, aortic landing zone 2, and smoking were found to be associated with a higher rate of neck dilatation.

Drag Forces after Thoracic Endovascular Aortic Repair. General Review of the Literature.

BACKGROUND: Despite the great evolution of endograft devices for thoracic endovascular aortic repair (TEVAR), threatening related complication such as graft migration and endoleaks still occur during follow up. The Drag Forces (DF), that is the displacement forces that play a role in graft migration and endoleaks caused by the blood flow against the thoracic graft, can be studied by means of Computational Fluid Dynamics (CFD). METHOD: A general review of papers found in current literature was performed. CFD studies available on the topic of thoracic aortic diseases and DF were analyzed. All anatomic, hemodynamics or graft related factors which could have an impact on DF were reported. RESULTS: Different factors deeply influence DF magnitude in the different site of the Ishimaru's zones classification: angulation, tortuosity and length of the landing zone, graft diameter, length and deployment position, blood pressure, pulse waveform, blood viscosity and patient heart rate have been related to the magnitude of DF. Moreover, also the three-dimensional orientation of DF is emerging as a fundamental issue from CFD studies. DF can be divided in sideways and upward components. The former, even of higher magnitude in zone 0, maintain always an orthogonal orientation and does not change in any type of aortic arch; the latter result strictly related to the anatomic complexity of the aortic arch with values up to four times higher in zone 3. CONCLUSION: Different DF magnitude and orientation could explain how TEVAR have higher rate of migration and endoleaks when we face with more complex aortic anatomies. All these aspects should be foreseen during the planning of TEVAR procedure. In this field, collaboration between physicians and engineers is crucial, as both parts have a primary role in understanding and describing hidden aspects involved in TEVAR procedures.

Retrograde inferior vena caval perfusion for total aortic arch replacement surgery: a randomized pilot study.

OBJECTIVES: Antegrade cerebral perfusion (ACP) under moderate hypothermic circulatory arrest is used during total aortic arch replacement surgery (TARS) in patients with acute type A aortic dissection, but it is associated with high mortality and morbidity. We hypothesized that combining ACP with retrograde inferior vena caval perfusion (RIVP) improves outcomes. METHODS: This pilot study was prospective, randomized, controlled and assessor-blinded. Patients scheduled for TARS were randomly treated with either ACP or RIVP + ACP. The primary outcome was a composite of mortality and major complications including paraplegia, postoperative renal failure, severe liver dysfunction, and gastrointestinal complications. Secondary outcomes included neurological complications, length of intubation and requirement of blood products. RESULTS: A total of 76 patients were recruited (n = 38 per group). Primary outcome occurred in 23 patients (61%) in the ACP group and 16 (42%) in the RIVP + ACP group (OR: 0.60, 95% CI: 0.21-1.62; p = 0.31). There was a lower incidence of transient neurological deficits in the RIVP + ACP group (26% vs. 58%, OR: 0.26; 95% CI: 0.10-0.67,p = 0.006;). The RIVP + ACP group underwent shorter intubation (25 vs 47 h, p = 0.022) and required fewer blood products (red cells, 3.8 units vs 6.5 units, p = 0.047; platelet: 2.0 units vs 2.0 units, p = 0.023) compared with the ACP group. CONCLUSIONS: RIVP + ACP may be associated with lower incidence of transient neurological deficits, shorter intubation and less blood transfusion requirement than ACP alone during TARS. Multi-center, randomized trials with larger samples are required to determine whether RIVP + ACP is associated with lower rates of mortality and major complications. TRIAL REGISTRATION: Pilot study of a RCT registered in clinicaltrials.gov (NCT03607786), Registered 30 July, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03607786 .