Abdominal Aortic Endograft Implantation Immediately Induces Vascular Stiffness Gradients That May Promote Adverse Aortic Neck Dilatation: Results of A Porcine Ex Vivo Study.

PURPOSE: Endovascular aortic repair (EVAR) is the method of choice for most abdominal aortic aneurysm (AAA) patients requiring intervention. However, chronic aortic neck dilatation (AND) following EVAR progressively weakens the structural seal between vessel and endograft and compromises long-term results of the therapy. This experimental ex vivo study seeks to investigate mechanisms of AND. MATERIALS AND METHODS: Porcine abdominal aortas (n=20) were harvested from slaughterhouse pigs and connected to a mock circulation. A commercially available endograft was implanted (n=10) or aortas were left untreated as controls (n=10). Vascular circumferential strain was assessed via ultrasound in defined aortic segments as a parameter of aortic stiffness. Histology and aortic gene expression analysis were performed to investigate potential changes of aortic wall structure and molecular differences due to endograft implantation. RESULTS: We found that endograft implantation acutely induces a significant stiffness gradient directly at the interface between stented and unstented aortic segments under pulsatile pressure. Comparing stented aortas with unstented controls, we detected increased aortic expression levels of inflammatory cytokines (Il6 and Ccl2) and matrix metalloproteinases (Mmp2 and Mmp9) after 6 hours of pulsatile pressurization. This effect, however, was abolished when repeating the same experiment under 6 hours of static pressure. CONCLUSIONS: We identified endograft-induced aortic stiffness gradients as an early trigger of inflammatory aortic remodeling processes that might promote AND. These results highlight the importance of adequate endograft designs to minimize vascular stiffness gradients and forestall late complications, such as AND. CLINICAL IMPACT: AND may compromise the long-term results following endovascular aortic repair. However, the mechanisms behind the underlying detrimental aortic remodeling are still unclear. In this study we find that endograft-induced aortic stiffness gradients induce an inflammatory aortic remodeling response consistent with AND. This novel pathomechanistic insight may guide the design of new aortic endografts that minimize vascular stiffness gradients and forestall late complications such as AND.

Apoptotic Cell Death in Bicuspid-Aortic-Valve-Associated Aortopathy.

The bicuspid aortic valve (BAV) is the most common cardiovascular congenital abnormality and is frequently associated with proximal aortopathy. We analyzed the tissues of patients with bicuspid and tricuspid aortic valve (TAV) regarding the protein expression of the receptor for advanced glycation products (RAGE) and its ligands, the advanced glycation end products (AGE), as well as the S100 calcium-binding protein A6 (S100A6). Since S100A6 overexpression attenuates cardiomyocyte apoptosis, we investigated the diverse pathways of apoptosis and autophagic cell death in the human ascending aortic specimen of 57 and 49 patients with BAV and TAV morphology, respectively, to identify differences and explanations for the higher risk of patients with BAV for severe cardiovascular diseases. We found significantly increased levels of RAGE, AGE and S100A6 in the aortic tissue of bicuspid patients which may promote apoptosis via the upregulation of caspase-3 activity. Although increased caspase-3 activity was not detected in BAV patients, increased protein expression of the 48 kDa fragment of vimentin was detected. mTOR as a downstream protein of Akt was significantly higher in patients with BAV, whereas Bcl-2 was increased in patients with TAV, assuming a better protection against apoptosis. The autophagy-related proteins p62 and ERK1/2 were increased in patients with BAV, assuming that cells in bicuspid tissue are more likely to undergo apoptotic cell death leading to changes in the wall and finally to aortopathies. We provide first-hand evidence of increased apoptotic cell death in the aortic tissue of BAV patients which may thus provide an explanation for the increased risk of structural aortic wall deficiency possibly underlying aortic aneurysm formation or acute dissection.

The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months.

Non-surgical bleeding (NSB) remains the most critical complication in patients under left ventricular assist device (LVAD) support. It is well known that blood exposed to high shear stress results in platelet dysfunction. Compared to patients without NSB, decreased surface expression of platelet receptor GPIbα was observed in LVAD patients with NSB. In this study, we aimed to compare the expression level of glycoprotein (GP)Ib-IX-V platelet receptor complex in HeartMate 3 (HM 3) patients with and without bleeding complications to investigate the alterations of the platelet transcriptomic profile on platelet damage and increased bleeding risk. Blood samples were obtained from HM 3 patients with NSB (bleeder group, n = 27) and without NSB (non-bleeder group, n = 55). The bleeder group was further divided into patients with early NSB (bleeder ≤ 3 mo, n = 19) and patients with late NSB (bleeder > 3 mo, n = 8). The mRNA and protein expression of GPIbα, GPIX and GPV were quantified for each patient. Non-bleeder, bleeder ≤ 3 mo and bleeder > 3 mo were comparable regarding the mRNA expression of GPIbα, GPIX and GPV (p > 0.05). The protein analysis revealed a significantly reduced expression level of the main receptor subunit GPIbα in bleeders ≤ 3 mo (p = 0.04). We suggest that the observed reduction of platelet receptor GPIbα protein expression in patients who experienced their first bleeding event within 3 months after LVAD implantation may influence platelet physiology. The alterations of functional GPIbα potentially reduce the platelet adhesion capacities, which may lead to an impaired hemostatic process and the elevated propensity of bleeding in HM 3 patients.

Effects of fluids vs. vasopressors on spinal cord microperfusion in hemorrhagic shock induced ischemia/reperfusion.

OBJECTIVE: Spinal cord injury induced by ischemia/reperfusion is a devastating complication of aortic repair. Despite developments for prevention and treatment of spinal cord injury, incidence is still considerably high majorly impacting patient outcome. Microcirculation is paramount for tissue perfusion and oxygen supply and often dissociated from macrohemodynamic parameters used to guide resuscitation. Effects of fluids vs. vasopressors in the setting of hemodynamic resuscitation on spinal cord microperfusion are unknown. Aim of this study was to compare the effects of vasopressor and fluid resuscitation on spinal cord microperfusion in a translational acute pig model of hemorrhagic shock induced ischemia/reperfusion injury. METHODS: We designed this study as prospective randomized explorative large animal study. We induced hemorrhagic shock in 20 pigs as a model of global ischemia/reperfusion injury. We randomized animals to receive either fluid or vasopressor resuscitation. We measured spinal cord microperfusion using fluorescent microspheres as well as laser-Doppler probes. We monitored and analyzed macrohemodynamic parameters and cerebrospinal fluid pressure. RESULTS: Spinal cord microperfusion decreased following hemorrhagic shock induced ischemia/reperfusion injury. Both fluids and vasopressors sufficiently restored spinal cord microperfusion. There were no important changes between groups (percentage changes compared to baseline: fluids 14.0 (0.31-27.6) vs. vasopressors 24.3 (8.12-40.4), p = .340). However, cerebrospinal fluid pressure was higher in animals receiving fluid resuscitation (percentage changes compared to baseline: fluids 27.7 (12.6-42.8) vs. vasopressors -5.56 ((-19.8)-8.72), p = .003). Microcirculatory resuscitation was in line with improvements of macrohemodynamic parameters. CONCLUSIONS: Both, fluids and vasopressors, equally restored spinal cord microperfusion in a porcine acute model of hemorrhagic shock induced ischemia/reperfusion injury. However, significant differences in cerebrospinal fluid pressure following resuscitation were present. Future studies should evaluate these effects in perfusion disruption induced ischemia/reperfusion conditions of microcirculatory deterioration.

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation.

Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear. Thus, we compared the platelet receptor composition of patients with (bleeder group, n = 18) and without NSB (non-bleeder group, n = 18) prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and after bleeding complications in the post-implant period. Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Bleeders and non-bleeders were comparable regarding clinical characteristics, von Willebrand factor diagnostics and the aggregation capacity before and after LVAD implantation (p > 0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (33%; n = 6), epistaxis (22%; n = 4), hematuria or hematoma (17%; n = 3, respectively) and cerebral bleeding (11%; n = 2). Prior to LVAD implantation, a restricted surface expression of the platelet receptors P-selectin and GPIIb/IIIa was observed in the bleeder group (P-selectin: 7.2 ± 2.6%; GPIIb/IIIa: 26,900 ± 13,608 U) compared to non-bleeders (P-selectin: 12.4 ± 8.1%, p = 0.02; GPIIb/IIIa: 36,259 ± 9914 U; p = 0.02). We hypothesized that the reduced platelet receptor expression of P-selectin and GPIIb/IIIa prior to LVAD implantation may be linked to LVAD-related NSB.

Management of aortic root in type A dissection: Bentall approach.

BACKGROUND: We analyzed the results of the modified Bentall procedure in a high-risk group of patients presenting with acute type A aortic dissection (ATAAD). METHODS: ATAAD patients undergoing a modified Bentall between 1996 and 2018 (n = 314) were analyzed. Mechanical composite conduits were used in 45%, and biological ones using either a bioprosthesis implanted into an aortic graft (33%) or xeno-/homograft root conduits (22%) in the rest. Preoperative malperfusion was present in 34% of patients and cardiopulmonary resuscitation required in 9%. RESULTS: Concomitant arch procedures consisted of hemiarch in 56% and total arch/elephant trunk in 34%, while concomitant coronary artery surgery was required in 20%. The average cross-clamp and cardiopulmonary bypass times were 126 ± 43 and 210 ± 76 min, respectively, while the average circulatory arrest times were 29 ± 17 min. A total of 69 patients (22%) suffered permanent neurologic deficit, while myocardial infarction occurred in 18 cases (6%) and low cardiac output syndrome in 47 (15%). The in-hospital mortality rate was 17% due to intractable low cardiac output syndrome (n = 29), major brain injury (n = 16), multiorgan failure (n = 6), and sepsis (n = 2). The independent predictors of in-hospital mortality were critical preoperative state (odds ratio [OR], 5.6; p < .001), coronary malperfusion (OR, 3.6; p = .002), coronary artery disease (OR, 2.6; p = .033), and prior cerebrovascular accident (OR, 5.6; p = .002). CONCLUSIONS: The modified Bentall operation, along with necessary concomitant procedures, can be performed with good early results in high-risk ATAAD patients presenting.

Computed tomography improves the differentiation of infectious mediastinitis from normal postoperative changes after sternotomy in cardiac surgery.

OBJECTIVES: To identify CT parameters independently associated with infectious mediastinitis after cardiac surgery and to improve the discrimination of patients with acute infection from those with normal postoperative changes. METHODS: In this single-center, retrospective, observational cohort study, we evaluated thoracic CT scans of poststernotomy cardiac surgery patients. Inclusion criteria were clinically suspected mediastinitis, unclear CT signs (e.g., retrosternal mass), and subsequent deep revision surgery. Revision surgery and microbiological samples determined the mediastinitis status. Overall, 22 qualitative and quantitative CT imaging parameters were assessed and associated with infectious mediastinitis in univariate and multivariate regression models. Discriminative capacity and incremental value of the CT features to available clinical parameters were determined by AUC and likelihood-ratio tests, respectively. RESULTS: Overall 105 patients (82% men; 67.0 ± 10.3 years) underwent CT and deep revision surgery. Mediastinitis was confirmed in 83/105 (79%) patients. Among available clinical parameters, only C-reactive protein (CRP) was independently associated with infectious mediastinitis (multivariate odds ratio (OR) (per standard deviation) = 2.3; p < 0.001). In the CT, the presence of free gas, pleural effusions, and brachiocephalic lymph node size were independently associated with mediastinitis (multivariate ORs = 1.3-6.3; p < 0.001-0.039). Addition of these CT parameters to CRP increased the model fit significantly (X2 = 17.9; p < 0.001; AUC, 0.83 vs. 0.73). CONCLUSION: The presence of free gas, pleural effusions, and brachiocephalic lymph node size in CT is independently associated with infectious mediastinitis in poststernotomy patients with retrosternal mass. These imaging features may help to differentiate mediastinitis from normal postoperative changes beyond traditional clinical parameters such as CRP. KEY POINTS: • Presence of free gas, pleural effusions, and brachiocephalic lymph node size on CT are associated independently with infectious mediastinitis. • Combination of these CT parameters increases the discriminatory capacity of clinical parameters such as CRP.

Pre-Implant Immune Status is Associated with Infection Risk After Left Ventricular Assist Device Implantation.

Purpose: Infection is the most common complication after left ventricular assist device (LVAD) implantation. The immune status of LVAD patients is relevant for the incidence and severity of infection, but it is unknown if there is a predisposing immune status prior to LVAD implantation that contributes to an increased risk for infection in the post-implant period. We analyzed the pre-LVAD immune status in patients with infection within 3 months after LVAD implantation in comparison to infection-free patients. Patients and Methods: Fifty-four consecutive LVAD patients were included in this study. According to their infectious history in the first 3 months after LVAD implantation, these patients were grouped into an infection (n=23) and an infection-free group (n=31). Pre-LVAD blood samples were obtained for flow cytometric analysis of immunological parameters including B cells, subsets of T, dendritic and natural killer cells. Patient-specific, clinical and laboratory data were recorded. Results: Blood count analysis prior to LVAD implantation showed comparable counts of erythrocytes (p=0.19), platelets (p=0.33) and leukocytes (p=0.50) between patients with infection and infection-free patients in the post-implant period. Patients with infection in the first 3 months after LVAD implantation had lower concentrations of lymphocytes (p=0.02). Forty percent of the patients with infection showed more often pre-LVAD neutrophil-to-lymphocyte ratios (NLR) >7 than patients without infection in the first 3 months after LVAD implantation (14%, p=0.05). Patients with infection already had lower percentages of CD3+ T cells (p=0.03), CD19+ B cells (p<0.01), BDCA2+ pDCs (p=0.03) and BDCA4+ plasmacytoid DCs (pDCs) (p=0.05) prior to LVAD implantation than infection-free patients. Conclusion: Our results demonstrated that patients with infection in the early post-implant period showed lower concentrations of lymphocytes, especially of CD3+ T cells and CD19+ B cells, decreased percentages of BDCA2+ and BDCA4+ pDCs, and had more often NLRs >7 indicating moderate-to-severe inflammation. Thus, we identified specific immunological changes pre-LVAD that could help to identify patients at risk for infection in the early post-implant period.

Minimally invasive staged segmental artery coil embolization (MIS2ACE) for spinal cord protection.

Minimally invasive staged segmental artery coil embolization (MIS2ACE) is an emerging technology for priming of the paraspinous collateral network prior to open or endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Its safety and efficacy have been previously proven in various experimental settings and confirmed in numerous multicentric pilot studies for open and endovascular repair. MIS2ACE is safe and has the potential to decisively reduce the risk of postoperative paraplegia, the most devastating complication of open and endovascular TAAA repair, still affecting up to 20% of patients. Up to now, MIS2ACE has been clinically implemented with excellent results, and is currently being investigated in the international, multicenter, randomized controlled trial PAPAartis, funded by the German Research foundation, and the European Union. MIS2ACE can be performed under local anesthesia, enabling continuous monitoring of neurological function, and in case of clinical signs of imminent ischemia, preemptive interruption of the procedure. A thorough evaluation of preoperative computed tomography (CT) imaging for identification of open and accessible segmental arteries (SAs) is critical. Segmental artery occlusion can be achieved with either micro coils, or vascular plugs. A maximum number of seven SAs is currently recommended to be occluded in the same session, and a minimum interval of 5 days should be awaited between either two MIS2ACE sessions or between MIS2ACE and the final repair. Adjuvant side-effects of MIS2ACE are the reduction in segmental back-bleeding during open repair leading to harmful steal phenomenon and the reduction of the incidence of type II endoleaks in endovascular repair. Current contraindications for MIS2ACE are emergency cases, hostile anatomy, and a shaggy aorta. Other neuroprotective adjuncts such as cerebrospinal fluid (CSF) drainage, permissive hypertension, motor-evoked potentials (MEP)/somato-sensory evoked potentials (SSEP) and monitoring of paraspinous muscle oxygenation by near-infrared spectroscopy should also be applied independent of prior MIS2ACE procedure.

Rationale of the PAPAartis trial.

Surgical and interventional repair of thoracoabdominal aortic aneurysms improve survival significantly compared to the natural history of the disease. However, both strategies are associated with a substantial risk of spinal cord ischemia, which has been reported to occur-even in contemporary series by expert centers-in up to 12% of patients, depending on the extent of the disease. Following improved neurological outcomes after staged approaches in extensive clinical and long-term large animal studies, and the description of the "collateral network", the concept of "Minimally Invasive Staged Segmental Artery Coil Embolization" (MIS2ACE) was introduced by Etz et al. This concept of priming the collateral network in order to improve spinal cord blood supply showed promising experimental and early clinical outcomes, and consequently led to the initiation of the randomized controlled multicenter PAPAartis trial (Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging). This Keynote Lecture describes the background and rationale for this trial and gives an update on the current status.

Near-Infrared Spectroscopy for Spinal Cord Monitoring-A Roadmap to Translational Research in Aortic Medicine.

Extensive aortic aneurysms represent a unique challenge necessitating interdisciplinary efforts for safe and effective treatment. Despite various adjunctive neuroprotective strategies, ischemic spinal cord injury remains a devastating complication. This article describes the implementation of collateral network near-infrared spectroscopy as the first noninvasive spinal cord monitoring modality in the setting of extensive open and endovascular aortic repair, from early conceptualization to clinical utilization. Potential capabilities and remaining uncertainties based on current evidence are outlined and discussed.

Sex-Related Differences After Proximal Aortic Surgery: Outcome Analysis of 1773 Consecutive Patients.

BACKGROUND: Guidelines on the management of aortic aneurysm disease do not account for sex differences regarding surgical procedures on the proximal aorta, although faster aneurysm growth, increased rupture risk, and higher postoperative mortality have been found in women. We therefore analyzed outcome differences between men and women receiving operations on the proximal aorta. METHODS: A total of 1773 patients underwent nonemergency surgical procedures on the aortic valve (AV) and proximal aorta at our institution between 2000 and 2018. Of these, 772 patients (21.8% women) received a Bentall procedure, 349 (20.3% women) had AV-sparing root replacement, and 652 (31.1% women) underwent AV and supracommissural ascending aorta replacement. Primary outcomes were in-hospital mortality and midterm survival. RESULTS: When assessing sex-related differences within the entire group of patients that received an operation on the proximal aorta, women were found to be older, had a lower body mass index, and were smokers less often. Despite shorter procedural times, median ventilation times and intensive care unit length of stay were longer in women. In-house mortality was also higher in women (3.6% vs 0.9%, P < .001). Multivariable logistic regression revealed age (odds ratio [OR], 1.8; 95% CI, 1.4-2.3 per 5 years added; P < .001), female sex (OR, 2.6; 95% CI, 1.2-5.8; P = .02), and urgent surgery (OR, 3.1; 95% CI, 1.2-7.3; P = .01) as independent risk factors for in-house death. Midterm survival was lower for women in the entire cohort (P = .02) and particularly within the Bentall subgroup (P = .004). CONCLUSIONS: Female sex is an independent risk factor for operative mortality in patients undergoing proximal aortic surgery but is currently not addressed in guidelines. More research should focus on etiology and prevention of these worse outcomes in female patients.

Is perioperative fast-track management the future of proximal aortic repair?

OBJECTIVES: The Bentall procedure is the gold standard for patients with combined aortic root dilation and valve dysfunction. Over the past decade, fast-track (FT) perioperative anaesthetic management protocols have progressively evolved. We reviewed our results for selected patients undergoing Bentall surgery under an FT protocol. METHODS: We retrospectively analysed a consecutive cohort of patients who underwent elective Bentall procedures at our institution between 2000 and 2018. Complex aortic root repair (i.e. David and Ross procedure, redo surgery, major concomitant procedures, emergency repair for acute dissections) was excluded. Patients who underwent conventional perioperative treatment and those treated according to our institutional FT concept were compared following 1:1 propensity score matching. RESULTS: Of 772 patients who fit the in- and exclusion criteria, 565 were treated conventionally post-surgery, while 207 were treated using the FT protocol. Propensity score matching resulted in 197 pairs, with no differences in baseline characteristics after matching. In-house mortality, 30-day mortality and overall all-cause long-term mortality were comparable between the FT and the conventionally treated cohort. Postoperative anaesthetic care unit/intensive care unit length-of-stay (6.2 vs 20.6 h, P = 0.03) and postoperative ventilation times (158.9 vs 465.5 min, P < 0.001) were significantly shorter in the FT cohort. There were no differences in rates of postoperative adverse events. CONCLUSIONS: In centres with experienced anaesthesiologists, perioperative FT management is non-inferior to conventionally treated patients undergoing elective Bentall procedures without compromising patient safety.

The Feasibility of Less-Invasive Bentall Surgery: A Real-World Analysis.

OBJECTIVE: Minimally invasive approaches are being used increasingly in cardiac surgery and applied in a wider range of operations, including complex aortic procedures. The aim of this study was to examine the safety and feasibility of a partial upper sternotomy approach for isolated elective aortic root replacement (a modified Bentall procedure). METHODS: We performed a retrospective analysis of 768 consecutive patients who had undergone isolated Bentall surgery between January 2000 and January 2021 at our institution, with the exclusion of re-operations, endocarditis, acute aortic dissections, and root replacement with major concomitant procedures such as multi-valve or coronary bypass surgery. A total of 98 patients were operated on via partial sternotomy (PS) and were matched 2:1 to 196 patients operated on via full sternotomy (FS). RESULTS: The procedure time was 12 min longer in the PS group (205 min vs. 192.5 min in the FS group, p = 0.002), however, cardiopulmonary bypass and aortic cross-clamp times were comparable between groups. Eight PS-procedures were converted to full sternotomy, predominantly for bleeding complications (n = 6). Re-exploration for acute bleeding was necessary in 11% of the PS group and 4.1% of the FS group (p = 0.02). Five FS patients and none in the PS group required emergency coronary bypass grafting for postoperative coronary obstruction (p = 0.2). PS patients were hospitalized for a significantly shorter period (9.5 days vs. 10.5 days in the FS group, respectively). There were no significant differences regarding in-hospital (p = 0.4) and mid-term mortality (p = 0.73), as well as for other perioperative complications. CONCLUSIONS: Performing Bentall operations via partial upper sternotomy is associated with similar perfusion and cross-clamp times, as well as overall mortality, when compared to a full sternotomy approach. A low threshold for conversion to full sternotomy should be accepted if limited access proves insufficient for the handling of intraoperative complications, particularly bleeding.

Early Intraluminal Frozen Elephant Trunk Stent Graft Thrombosis After Aortic Arch Surgery.

BACKGROUND: Partial intraluminal thrombosis of the frozen elephant trunk (FET) stent graft is a poorly described but not infrequent complication after aortic arch surgery. This study aims to describe and analyze the occurrence of early FET stent graft thrombosis. METHODS: Retrospective single-center analysis including patients who underwent aortic arch replacement with FET technique between 2006 and 2020. Stent graft thrombosis was diagnosed through computed tomography scan. Several computed tomography scan parameters and clinical variables were analyzed as predictors of this event. RESULTS: A total of 125 patients were included for analysis. Among these, 21 (16.8%) patients developed early postoperative FET stent graft thrombosis. Mean volumetric size of the aorta was 12.2 ± 2.0 mL in patients with FET stent graft thrombosis and 10.1 ± 2.8 mL in patients without thrombosis (P < .01). Thrombosis occurred more frequently among patients requiring thoracic endovascular aortic repair completion (15 of 21 [71.4%] patients) than in patients with completely excluded aneurysms (6 of 21 [28.6%] patients) (P = .01). Mean stent-to-aneurysm diameter ratio was 0.8 ± 0.2 among patients with thrombosis and 1.0 ± 0.2 among patients without thrombosis (P < .01). Thrombosis was more frequently observed among patients with conservative management of postoperative bleeding (P = .04). Patients with early FET thrombosis had a nonsignificantly higher in-hospital all-cause mortality than patients without thrombosis (19.0% vs 8.7%; P = .3). CONCLUSIONS: Early postoperative intraluminal thrombosis is a frequent complication post FET surgery. Smaller stent graft sizes, larger or partially covered aneurysms, and major bleeding are associated with early thrombosis. Slight FET oversizing, prompt thoracic endovascular aortic repair completion, and early reintervention for major bleeding may prevent early thrombosis.

miR-132-3p and KLF7 as novel regulators of aortic stiffening-associated EndMT in type 2 diabetes mellitus.

BACKGROUND: The prevalence of diabetes mellitus has risen considerably and currently affects more than 422 million people worldwide. Cardiovascular diseases including myocardial infarction and heart failure represent the major cause of death in type 2 diabetes (T2D). Diabetes patients exhibit accelerated aortic stiffening which is an independent predictor of cardiovascular disease and mortality. We recently showed that aortic stiffness precedes hypertension in a mouse model of diabetes (db/db mice), making aortic stiffness an early contributor to cardiovascular disease development. Elucidating how aortic stiffening develops is a pressing need in order to halt the pathophysiological process at an early time point. METHODS: To assess EndMT occurrence, we performed co-immunofluorescence staining of an endothelial marker (CD31) with mesenchymal markers (α-SMA/S100A4) in aortic sections from db/db mice. Moreover, we performed qRT-PCR to analyze mRNA expression of EndMT transcription factors in aortic sections of db/db mice and diabetic patients. To identify the underlying mechanism by which EndMT contributes to aortic stiffening, we used aortas from db/db mice and diabetic patients in combination with high glucose-treated human umbilical vein endothelial cells (HUVECs) as an in vitro model of diabetes-associated EndMT. RESULTS: We demonstrate robust CD31/α-SMA and CD31/S100A4 co-localization in aortic sections of db/db mice which was almost absent in control mice. Moreover, we demonstrate a significant upregulation of EndMT transcription factors in aortic sections of db/db mice and diabetic patients. As underlying regulator, we identified miR-132-3p as the most significantly downregulated miR in the micronome of db/db mice and high glucose-treated HUVECs. Indeed, miR-132-3p was also significantly downregulated in aortic tissue from diabetic patients. We identified Kruppel-like factor 7 (KLF7) as a target of miR-132-3p and show a significant upregulation of KLF7 in aortic sections of db/db mice and diabetic patients as well as in high glucose-treated HUVECs. We further demonstrate that miR-132-3p overexpression and KLF7 downregulation ameliorates EndMT in high glucose-treated HUVECs. CONCLUSIONS: We demonstrate for the first time that EndMT contributes to aortic stiffening in T2D. We identified miR-132-3p and KLF7 as novel EndMT regulators in this context. Altogether, this gives us new insights in the development of aortic stiffening in T2D.

The Impact of Obesity on T and NK Cells after LVAD Implantation.

INTRODUCTION: Infections are a major problem after left ventricular assist device (LVAD) implantation that affects morbidity, mortality, and the quality of life. Obesity often increases the risk for infection. In the cohort of LVAD patients, it is unknown if obesity affects the immunological parameters involved in viral defense. Therefore, this study investigated whether overweight or obesity affects immunological parameters such as CD8+ T cells and natural killer (NK) cells. METHODS: Immune cell subsets of CD8+ T cells and NK cells were compared between normal-weight (BMI 18.5-24.9 kg/m2, n = 17), pre-obese (BMI 25.0-29.9 kg/m2, n = 24), and obese (BMI ≥30 kg/m2, n = 27) patients. Cell subsets and cytokine serum levels were quantified prior to LVAD implantation and at 3, 6, and 12 months after LVAD implantation. RESULTS: At the end of the first postoperative year, obese patients (31.8% ± 2.1%) had a lower proportion of CD8+ T cells than normal-weight patients (42.4% ± 4.1%; p = 0.04), and the percentage of CD8+ T cells was negatively correlated with BMI (p = 0.03; r = -0.329). The proportion of circulating NK cells increased after LVAD implantation patients in normal-weight (p = 0.01) and obese patients (p < 0.01). Patients with pre-obesity showed a delayed increase (p < 0.01) 12 months after LVAD implantation. Further, obese patients showed an increase in the percentage of CD57+ NK cells after 6 and 12 months (p = 0.01) of treatment, higher proportions of CD56bright NK cells (p = 0.01), and lower proportions of CD56dim/neg NK cells (p = 0.03) 3 months after LVAD implantation than normal-weight patients. The proportion of CD56bright NK cells positively correlated with BMI (p < 0.01, r = 0.403) 1 year after LVAD implantation. CONCLUSIONS: This study documented that obesity affects CD8+ T cells and subsets of NK cells in patients with LVAD in the first year after LVAD implantation. Lower proportions of CD8+ T cells and CD56dim/neg NK cells and higher proportion of CD56bright NK cells were detected in obese but not in pre-obese and normal-weight LVAD patients during the first year after LVAD implantation. The induced immunological imbalance and phenotypic changes of T and NK cells may influence viral and bacterial immunoreactivity.

Body mass index-dependent immunological profile changes after left ventricular assist device implantation.

Purpose: Infection is a common complication following left ventricular assist device (LVAD) implantation. Patients with obesity are particularly at risk due to their high percentage of adipose tissue and the resulting chronic inflammatory state and resulting immunological changes. This study investigated changes of immunological parameters in relation to body mass index (BMI) during the first year after LVAD implantation. Methods: Blood samples were obtained prior to LVAD implantation and at 3 (1st FU), 6 (2nd FU) and 12 mo (3rd FU) after LVAD implantation. Patients were divided into three groups (normal weight: BMI of 18.5-24.9 kg/m2; n=12; pre-obesity: 25.0-29.9 kg/m2; n=15; obesity: ≥ 30.0 kg/m2; n=17) based on their BMI at the time of LVAD implantation. Flow cytometric analyses for CD4+ and CD8+ T cells, regulatory T cells (Tregs), B cells as well as dendritic cells (DCs) were performed. Results: After LVAD implantation, obese patients (0.51 ± 0.20%) showed a higher proportion of overall DCs than normal-weight (0.28 ± 0.10%) and pre-obese patients (0.32 ± 0.11%, p<0.01) at 3rd FU. The proportion of BDCA3+ myeloid DCs was lower in obese patients (64.3 ± 26.5%) compared to normal-weight patients (82.7 ± 10.0%, pnormal-weight vs. obesity=0.05) at 2nd FU after LVAD implantation. The analysis of BDCA4+ plasmacytoid DCs revealed a reduced proportion in pre-obese (21.1 ± 9.8%, pnormal-weight vs. pre-obesity=0.01) and obese patients (23.7 ± 10.6%, pnormal-weight vs. obesity=0.05) compared to normal-weight patients (33.1 ± 8.2%) in the 1st FU. T cell analysis showed that CD4+ T cells of obese patients (62.4 ± 9.0%) significantly increased in comparison to pre-obese patients (52.7 ± 10.0%, ppre-obesity vs. obesity=0.05) and CD8+ T cells were lower in obese patients (31.8 ± 8.5%) than in normal-weight patients (42.4 ± 14.2%; pnormal-weight vs. obesity=0.04) at the 3rd FU. Furthermore, we observed significantly reduced proportions of Tregs in pre-obese patients compared to normal-weight and obese patients at 2nd FU (p=0.02) and 3rd FU (p=0.01) after LVAD implantation. Conclusion: This study reported changes of the innate and adaptive immune system of pre-obese and obese compared to normal-weight patients one year after LVAD implantation. DCs and their subsets, CD8+ T cells and Tregs were affected immune cell populations that indicate immunological changes which might increase the incidence of postoperative infection.

Ischemic Spinal Cord Injury-Experimental Evidence and Evolution of Protective Measures.

BACKGROUND: Paraplegia remains one of the most devastating complications of descending and thoracoabdominal aortic repair. The aim of this review is to outline the current state of art in the rapidly developing field of spinal cord injury research. METHODS: A review of PubMed and Web of Science databases was performed using the following terms and their combinations: spinal cord, injury, ischemia, ischemia-reperfusion, ischemic spinal cord injury, paraplegia, paraparesis. Articles published before July 2019 were screened and included if considered relevant. RESULTS: The review focuses on the topic of spinal cord injury and the developments concerning methods of monitoring, diagnosing, and preventing spinal cord injury. CONCLUSIONS: Translation of novel technologies from bench to bedside and into everyday clinical practice is challenging; however, each of the developing areas holds great promise in spinal cord injury prevention.

Iatrogenic Type A Aortic Dissection: Challenges and Frontiers-Contemporary Single Center Data and Clinical Perspective.

Iatrogenic aortic dissection (IAD) is a rare but devastating complication in cardiac surgery and related procedures. Due to its rarity, published data on emergency surgery following IAD are limited. Herein, we discuss IAD occurring intra- and postoperatively, including those occurring during transcatheter aortic valve replacement and cardiac catheterization, and present benchmark data from our consecutive, single-center experience. We demonstrate changes in patient characteristics, surgical approaches, and outcomes over a 23-year period.