Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery.

BACKGROUND: Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA. METHODS: This was a randomized single-blind trial (GOT ICE [Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest]) of patients undergoing arch surgery with HCA plus antegrade cerebral perfusion at 4 US referral aortic centers (August 2016-December 2021). Patients were randomized to 1 of 3 hypothermia groups: DP, deep (≤20.0 °C); LM, low-moderate (20.1-24.0 °C); and HM, high-moderate (24.1-28.0 °C). The primary outcome was composite global cognitive change score between baseline and 4 weeks postoperatively. Analysis followed the intention-to-treat principle to evaluate if: (1) LM noninferior to DP on global cognitive change score; (2) DP superior to HM. The secondary outcomes were domain-specific cognitive change scores, neuroimaging findings, quality of life, and adverse events. RESULTS: A total of 308 patients consented; 282 met inclusion and were randomized. A total of 273 completed surgery, and 251 completed the 4-week follow-up (DP, 85 [34%]; LM, 80 [34%]; HM, 86 [34%]). Mean global cognitive change score from baseline to 4 weeks in the LM group was noninferior to the DP group; likewise, no significant difference was observed between DP and HM. Noninferiority of LM versus DP, and lack of difference between DP and HM, remained for domain-specific cognitive change scores, except structured verbal memory, with noninferiority of LM versus DP not established and structured verbal memory better preserved in DP versus HM (P = 0.036). There were no significant differences in structural or functional magnetic resonance imaging brain imaging between groups postoperatively. Regardless of temperature, patients who underwent HCA demonstrated significant reductions in cerebral gray matter volume, cortical thickness, and regional brain functional connectivity. Thirty-day in-hospital mortality, major morbidity, and quality of life were not different between groups. CONCLUSIONS: This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia on global cognitive change 4 weeks after surgery, although in secondary analysis, structured verbal memory was better preserved in the deep group. The verbal memory differences in the low- and high-moderate groups and structural and functional connectivity reductions from baseline merit further investigation and suggest opportunities to further optimize brain perfusion during HCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02834065.

2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

Myths and methodologies: Cardiopulmonary exercise testing for surgical risk stratification in patients with an abdominal aortic aneurysm; balancing risk over benefit.

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure-induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom-limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring 'myth' that AAA patients should be fearful of and avoid rigorous exercise. On the contrary, by appraising fundamental vascular mechanobiological forces associated with exercise, in conjunction with 'methodological' recommendations for risk mitigation specific to this patient population, we highlight that the benefits conferred by cardiopulmonary exercise testing and exercise training across the continuum of intensity far outweigh the short-term risks posed by potential AAA rupture.

Editor's Choice - Trends in Management and Outcomes of Type B Aortic Dissection: A Report From the International Registry of Aortic Dissection.

OBJECTIVE: To describe the trends in management and outcomes of patients with acute type B aortic dissection in the International Registry of Acute Aortic Dissection. METHODS: From 1996 - 2022, 3 908 patients were divided into similar sized quartiles (T1, T2, T3, and T4). In hospital outcomes were analysed for each quartile. Survival rates following admission were compared using Kaplan-Meier analyses with Mantel-Cox Log rank tests. RESULTS: Endovascular treatment increased from 19.1% in T1 to 37.2% in T4 (ptrend < .001). Correspondingly, medical therapy decreased from 65.7% in T1 to 54.0% in T4 (ptrend < .001), and open surgery from 14.8% in T1 to 7.0% in T4 (ptrend < .001). In hospital mortality decreased in the overall cohort from 10.7% in T1 to 6.1% in T4 (ptrend < .001), as well as in medically, endovascularly and surgically treated patients (ptrend = .017, .033, and .011, respectively). Overall post-admission survival at three years increased (T1: 74.8% vs. T4: 77.3%; p = .006). CONCLUSION: Considerable changes in the management of acute type B aortic dissection were observed over time, with a significant increase in the use of endovascular treatment and a corresponding reduction in open surgery and medical management. These changes were associated with a decreased overall in hospital and three year post-admission mortality rate among quartiles.

Uncomplicated Type B Aortic Dissection: Challenges in Diagnosis and Categorization.

BACKGROUND: Acute type B aortic dissection (TBAD) is a rare disease that is likely under-diagnosed in the UK. As a progressive, dynamic clinical entity, many patients initially diagnosed with uncomplicated TBAD deteriorate, developing end-organ malperfusion and aortic rupture (complicated TBAD). An evaluation of the binary approach to the diagnosis and categorisation of TBAD is needed. METHODS: A narrative review of the risk factors predisposing patients to progression from unTBAD to coTBAD was undertaken. RESULTS: Key high-risk features predispose the development of complicated TBAD, such as maximal aortic diameter > 40 mm and partial false lumen thrombosis. CONCLUSION: An appreciation of the factors that predispose to complicated TBAD would aid clinical decision-making surrounding TBAD.

The misnomer of uncomplicated type B aortic dissection.

BACKGROUND: Acute type B aortic dissection (TBAD) is a rare condition that can be divided into complicated (CoTBAD) and uncomplicated (UnCoTBAD) based on certain presenting clinical and radiological features, with UnCoTBAD constituting the majority of TBAD cases. The classification of TBAD directly affects the treatment pathway taken, however, there remains confusion as to exactly what differentiates complicated from uncomplicated TBAD. AIMS: The scope of this review is to delineate the literature defining the intervention parameters for UnCoTBAD. METHODS: A comprehensive literature search was conducted using multiple electronic databases including PubMed, Scopus, and EMBASE to collate and summarize all research evidence on intervention parameters and protocols for UnCoTBAD. RESULTS: A TBAD without evidence of malperfusion or rupture might be classified as uncomplicated but there remains a subgroup who might exhibit high-risk features. Two clinical features representative of "high risk" are refractory pain and persistent hypertension. First-line treatment for CoTBAD is TEVAR, and whilst this has also proven its safety and effectiveness in UnCoTBAD, it is still being managed conservatively. However, TBAD is a dynamic pathology and a significant proportion of UnCoTBADs can progress to become complicated, thus necessitating more complex intervention. While the "high-risk" UnCoTBAD do benefit the most from TEVAR, yet, the defining parameters are still debatable as this benefit can be extended to a wider UnCoTBAD population. CONCLUSION: Uncomplicated TBAD remains a misnomer as it is frequently representative of a complex ongoing disease process requiring very close monitoring in a critical care setting. A clear diagnostic pathway may improve decision making following a diagnosis of UnCoTBAD. Choice of treatment still predominantly depends on when an equilibrium might be reached where the risks of TEVAR outweigh the natural history of the dissection in both the short- and long-term.

Cardiothoracic surgery leadership and learning are indispensable to each other.

Cardiothoracic surgery is facing a multitude of challenges in leadership and training on the global scale, these being a complex and aging patient population, shortage of cardiac surgeons, diminishing student interest and trainee enthusiasm, increasingly challenging training obstacles and work-life imbalances, suboptimal job prospects, reports of discrimination and bullying and lack of diversity as well as gap between innovation and technology, clinical application, and training of future surgeons. The survival of cardiac surgery hinges on the leadership attracting and retaining young surgeons into the specialty. Mentoring, leading through example, recognizing the work-life imbalances, adapting to diverse and modern training models and embracing diversity with respect to gender and race, will ultimately be required to create and cultivate a nurturing environment of training and preparing future leaders. The vision for training future generations of cardiothoracic surgeons must rely heavily on strengthening the unity of the heart team. In doing so we can provide the best possible care for our patients and a most fulfilling career for the future generation of cardiac surgeons.

Perspectives of Surgeons from Atlanta, USA.

BACKGROUND: The COVID-19 pandemic in late 2019 quickly stretched health care system across the globe. Mortalities, shortages in health care system capacity, and lack of experience in similar circumstances required innovation in the way health care is delivered. Health care systems changed operating schedules, staff work pattern, and how patients are cared for. The effects of these changes reached patients, staff and training in different ways. METHODS: We searched the Pubmed and EMBASE for articles related to COVID-19. We also searched local emails and information provided to staff during the pandemic RESULTS: The COVID-19 pandemic affected organizations, patients, and staff. The organizations and staff had to adapt to the times to provide a safe and appropriate service to our patients. CONCLUSION: The pandemic challenged and changed the way we work as health care providers, and how we train the future surgeons. Changes in the system were effective.

Management of the aortic root in type A aortic dissection: A valve sparing approach.

BACKGROUND: Type A acute aortic dissection (TAAAD) is rapidly fatal without emergency repair. Surgical outcomes have improved over the years with improvements in technique and postoperative care. Classically, supracomissural aortic replacement has been the standard of care. However, reintervention rates, particularly on the aortic root in certain groups of patients, shifted the focus towards improving long-term results of surgical repair. With regard to the aortic root, root replacement has been the gold standard. However, the surgical community realized that valve replacement in itself is a disease, and valve sparing aortic root replacement (VSRR) took center stage in the care of these patients. METHODS: We searched the Pubmed and EMBASE databases for articles related to VSRR and composite valve conduit (CVC) root replacement, and the long-term results of these techniques in TAAAD. RESULTS: Supracomissural repair is limited by reintervention, and CVC results are affected by complications related to the prosthetic valve. Conversely, VSRR is associated with good short-term outcomes, improvement in quality of life, and it is durable. CONCLUSION: VSRR is a sound technique in TAAAD in experienced hands.

Bicuspid aortic valve sparing root replacement.

BACKGROUND AND AIM OF STUDY: Mid and long-term data regarding the durability of bicuspid aortic valve sparing root replacement is not completely understood. In this study, our institutional experience is reviewed regarding this procedure with special attention to the operative technique. METHODS: From 2004 to 2019, 1241 patients underwent aortic root replacement and of these 79 patients underwent bicuspid aortic valve sparing root replacement. Early and late outcomes along with echocardiographic data were reviewed. Univariate analysis was used to identify risk factors for mortality. RESULTS: Median age at operation was 43 (inner quartile range: 34.5-50.5) years, with 17% (14) being female. Median follow up time was 4 (inner quartile range: 1-8) years with 359 years of total follow up. Early mortality was 2.5% (2). Overall 10-year freedom from aortic valve intervention was 95.6%. Risk factor analysis did not demonstrate preoperative root diameter, aortic diameter, or aortic insufficiency to be risk factors for mortality. CONCLUSION: Bicuspid aortic valve sparing root replacement can be performed safely in the setting of aortic root pathology and valve insufficiency. With appropriate selection and excellent surgical technique, long-term durable valve function is observed without the need for repeat valve intervention.

A Novel Anisotropic Failure Criterion With Dispersed Fiber Orientations for Aortic Tissues.

Accurate failure criteria play a fundamental role in biomechanical analyses of aortic wall rupture and dissection. Experimental investigations have demonstrated a significant difference of aortic wall strengths in the circumferential and axial directions. Therefore, the isotropic von Mises stress and maximum principal stress, commonly used in computational analysis of the aortic wall, are inadequate for modeling of anisotropic failure properties. In this study, we propose a novel stress-based anisotropic failure criterion with dispersed fiber orientations. In the new failure criterion, the overall failure metric is computed by using angular integration (AI) of failure metrics in all directions. Affine rotations of fiber orientations due to finite deformation are taken into account in an anisotropic hyperelastic constitutive model. To examine fitting capability of the failure criterion, a set of off-axis uniaxial tension tests were performed on aortic tissues of four porcine individuals and 18 human ascending thoracic aortic aneurysm (ATAA) patients. The dispersed fiber failure criterion demonstrates a good fitting capability with the off-axis testing data. Under simulated biaxial stress conditions, the dispersed fiber failure criterion predicts a smaller failure envelope comparing to those predicted by the traditional anisotropic criteria without fiber dispersion, which highlights the potentially important role of fiber dispersion in the failure of the aortic wall. Our results suggest that the deformation-dependent fiber orientations need to be considered when wall strength determined from uniaxial tests are used for in vivo biomechanical analysis. More investigations are needed to determine biaxial failure properties of the aortic wall.

Time of day does not influence outcomes in acute type A aortic dissection: Results from the IRAD.

BACKGROUND: Type A acute aortic dissection (TAAAD) represents a surgical emergency requiring intervention regardless of time of day. Whether such a "evening effect" exists regarding outcomes for TAAAD has not been previously studied using a large registry data. METHODS: Patients with TAAAD were identified from the International Registry of Acute Aortic Dissections (1996-2019). Outcomes were compared between patients undergoing operative repair during the daytime (D), defined as 8 am-5 pm, versus the evening (N), defined as 5 pm-8 am. RESULTS: Four thousand one-hundrd and ninety-seven surgically treated patients with TAAAD were identified, with 1824 patients undergoing daytime surgery (43.5%) and 2373 patients undergoing evening surgery (56.5%). Daytime patients were more likely to have undergone prior cardiac surgery (13.2% vs. 9.5%; p < .001) and have had a prior aortic dissection (4.8% vs. 3.4%; p = .04). Evening patients were more likely to have been transferred from a referring hospital (70.8% vs. 75.0%; p = .003). Daytime patients were more likely to undergo aortic valve sparing root procedures (23.3% vs. 19.2%; p = .035); however, total arch replacement was performed with equal frequency (19.4% vs. 18.8%; p = .751). In-hospital mortality (D: 17.3% vs. N. 16.2%; p = .325) was similar between both groups. Subgroup analysis examining the effect of weekend presentation revealed no significant mortality difference. CONCLUSIONS: A majority of TAAAD patients underwent surgical repair at night. There were higher rates of postoperative tamponade in evening patients; however, mortality was similar. The expertise of cardiac-dedicated operative and critical care teams regardless of time of day as well as training paradigms may explain similar mortality outcomes in this high risk population.

The distance of the primary intimal tear from the left subclavian artery predicts aortic growth in uncomplicated type B aortic dissection.

OBJECTIVE: Controversy exists about the optimal treatment of acute uncomplicated type B aortic dissection (auTBAD). Optimal medical therapy (OMT) provides excellent short-term outcomes, but long-term results are poor. Ideally, auTBAD patients who will fail to respond to OMT in the chronic phase could be identified and undergo thoracic endovascular aortic repair. The purpose of this study was to identify radiographic predictors of auTBAD patients who will fail to respond to OMT. METHODS: A review of the Emory aortic database from 2000 to 2017 identified 320 auTBAD patients initially treated with OMT. From this cohort, 121 patients with two or more contrast-enhanced imaging scans were available for analysis. These patients were initially divided into groups based on growth of the thoracic aorta ≥10 mm or intervention due to aneurysmal growth: growth (n = 72) and no growth (n = 49). TeraRecon (Foster City, Calif) imaging software was used to analyze characteristics of the primary intimal tear (PIT), false lumen, and overall aortic size. Finally, Cox proportional hazards models were constructed to estimate hazard ratios and to identify predictors of OMT failure. RESULTS: The mean age of all patients was 54 ± 11 years, and 67% were male. Thirty-eight patients (53%) in the growth group underwent intervention. There were no differences between groups in age, hypertension, diabetes mellitus, tobacco abuse, or chronic obstructive pulmonary disease. The distance of the PIT from the left subclavian artery in patients with auTBAD was significantly shorter in the growth group (growth, 27 mm [9-66 mm]; no growth, 77 mm [26-142 mm]; P < .01). Multivariable Cox regression analysis identified the distance of the PIT from the left subclavian artery and a thoracic aortic diameter >45 mm as independent predictors of failure of OMT. Partial false lumen thrombosis was not a predictor of aortic growth. CONCLUSIONS: The distance of the PIT from the left subclavian artery is a predictor of aortic growth in auTBAD. Patients with a primary tear located in zone 3 of the proximal descending thoracic aorta should be monitored closely and may be considered for early thoracic endovascular aortic repair in the setting of auTBAD.

Bad company: supracristal VSD presenting with ruptured sinus of valsalva aneurysm. a case presentation with echocardiographic depiction and an analysis of contemporary literature.

Supracristal ventricular septal defect (SCVSD), a defect of the infundibular portion of the interventricular septum just below the right aortic cusp, occurs more frequently in Eastern Asian populations. SCVSD may be complicated by right sinus of Valsalva aneurysm (SoVA). We present the case of a 26-year-old male of Korean descent with a history of a childhood murmur who was referred to our institution for progressive heart failure symptoms. He was diagnosed with SCVSD and ruptured right SoVA based on history, physical exam, and echocardiography including three-dimensional transesophageal echocardiography with reconstructed surgical views. The patient underwent SCVSD closure, SoVA excision, and valve-sparing aortic root replacement. We reviewed the echocardiography literature regarding SCVSD and SoVA, and analyzed contemporary literature of SoVA and its relationship with SCVSD. We conclude that a higher prevalence of ruptured SoVA in Eastern Asians is likely related to a higher prevalence of underlying SCVSD in this population.

Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function.

Cyclooxygenase-2 (COX-2) expression is associated with poor prognosis across a range of human cancers, including breast cancer. The contribution of tumor cell-derived COX-2 to tumorigenesis has been examined in numerous studies; however, the role of stromal-derived COX-2 is ill-defined. Here, we examined how COX-2 in myeloid cells, an immune cell subset that includes macrophages, influences mammary tumor progression. In mice engineered to selectively lack myeloid cell COX-2 [myeloid-COX-2 knockout (KO) mice], spontaneous neu oncogene-induced tumor onset was delayed, tumor burden reduced, and tumor growth slowed compared with wild-type (WT). Similarly, growth of neu-transformed mammary tumor cells as orthotopic tumors in immune competent syngeneic myeloid-COX-2 KO host mice was reduced compared with WT. By flow cytometric analysis, orthotopic myeloid-COX-2 KO tumors had lower tumor-associated macrophage (TAM) infiltration consistent with impaired colony stimulating factor-1-dependent chemotaxis by COX-2 deficient macrophages in vitro. Further, in both spontaneous and orthotopic tumors, COX-2-deficient TAM displayed lower immunosuppressive M2 markers and this was coincident with less suppression of CD8(+) cytotoxic T lymphocytes (CTLs) in myeloid-COX-2 KO tumors. These studies suggest that reduced tumor growth in myeloid-COX-2 KO mice resulted from disruption of M2-like TAM function, thereby enhancing T-cell survival and immune surveillance. Antibody-mediated depletion of CD8(+), but not CD4(+) cells, restored tumor growth in myeloid-COX-2 KO to WT levels, indicating that CD8(+) CTLs are dominant antitumor effectors in myeloid-COX-2 KO mice. Our studies suggest that inhibition of myeloid cell COX-2 can potentiate CTL-mediated tumor cytotoxicity and may provide a novel therapeutic approach in breast cancer therapy.

Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion.

BACKGROUND: Platelet (PLT) and plasma transfusion remain the mainstay hemostatic therapy for perioperative bleeding. Several studies have indicated that acquired fibrinogen (FIB) deficiency can be the primary cause of bleeding after cardiac surgery. The aim of this study was to compare hematologic and transfusion profiles between the first-line FIB replacement and PLT transfusion in post-cardiac surgical bleeding. STUDY DESIGN AND METHODS: In this prospective, randomized, open-label study, 20 adult patients who underwent valve replacement or repair and fulfilled preset visual bleeding scale were randomized to 4 g of FIB or 1 unit of apheresis PLTs. Primary endpoints included hemostatic condition in the surgical field and 24-hour hemostatic product usage. Hematologic data, clinical outcome, and safety data were collected up to the 28th day postoperative visit. RESULTS: In patients who received the first-line FIB concentrate (n = 10), the visual bleeding scale improved after intervention, and the incidence of PLT transfusion and total plasma donor exposure were lower compared to the PLT group (n = 10). Postintervention FIB level was statistically higher (209 mg/dL vs. 165 mg/dL) in the FIB group than in the PLT group, but PLT count and prothrombin were lower. There were no statistical differences in the postoperative blood loss and red blood cell transfusion between two groups. CONCLUSIONS: Our preliminary data indicate that the primary FIB replacement may potentially reduce the incidence of PLT transfusion and the number of donor exposures. Plasma FIB level of 200 mg/dL is attainable with a single dose of 4 g, and this level seems to mitigate bleeding despite moderately decreased thrombin generation.

Reintervention after valve-sparing aortic root replacement: A comprehensive analysis of 781 David V procedures.

OBJECTIVE: Studies of reintervention after valve-sparing aortic root replacement (VSRR) are limited by sample size and failure to evaluate all types of reinterventions, including distal aorta and transcatheter interventions. In this report, reintervention after VSRR using a large patient cohort was comprehensively analyzed. METHODS: In a series involving 2 academic aortic centers, 781 consecutive patients from 2005 to 2020 undergoing David V VSRR for aortic aneurysm (91%) or dissection (9%) were included. Median age was 50 years, and 23% had a bicuspid aortic valve (AV). Median follow-up was 7.0 years. Open or transcatheter reintervention on the AV, proximal, or distal thoracic aorta was identified. Cumulative incidence was calculated, and subdistribution hazard models identified factors associated with reintervention. Time-dependent incidence of reintervention was plotted using risk-hazard functions. RESULTS: Sixty-eight reinterventions (57 open, 11 transcatheter) were performed. Reinterventions were divided by indication into degenerative AV (n = 26, including 1 transcatheter aortic valve replacement), endocarditis (n = 11), proximal aorta (n = 8), and distal aorta (n = 23, including 10 thoracic endovascular aortic repairs). Risk of reintervention for endocarditis peaked 1 to 3 years after VSRR, whereas other indications had stable, low rates of occurrence throughout the follow-up period. The cumulative incidence of reintervention was 12.5% whereas the cumulative incidence of AV reintervention was 7.0% at 10 years and was associated with residual postoperative aortic insufficiency. In-hospital mortality after reintervention was 3%. CONCLUSIONS: Reintervention rates after VSRR are relatively low in long-term follow-up and can be performed with acceptable operative risk. The majority of reinterventions are performed for indications other than AV degeneration, with the timing of reintervention varying by the specific clinical indication.

Open, endovascular or hybrid repair of aortic arch disease: narrative review of diverse strategies with diverse options.

OBJECTIVES: The management of aortic arch disease is complex. Open surgical management continues to evolve, and the introduction of endovascular repair is revolutionizing aortic arch surgery. Although these innovative techniques have generated the opportunity for better outcomes in select patients, they have also introduced confusion and uncertainty regarding best practices. METHODS: In New York, we developed a collaborative group, the New York Aortic Consortium, as a means of cross-linking knowledge and working together to better understand and treat aortic disease. In our meeting in May 2023, regional aortic experts and invited international experts discussed the contemporary management of aortic arch disease, differences in interpretation of the available literature and the integration of endovascular technology into disease management. We summarized the current state of aortic arch surgery in this review article. RESULTS: Approaches to aortic arch repair have evolved substantially, whether it be methods to reduce cerebral ischaemia, improve haemostasis, simplify future operations or expand options for high-risk patients with endovascular approaches. However, the transverse aortic arch remains challenging to repair. Among our collaborative group of cardiac/aortic surgeons, we discovered a wide disparity in our practice patterns and our management strategies of patients with aortic arch disease. CONCLUSIONS: It is important to build unique institutional expertise in the context of complex and evolving management of aortic arch disease with open surgery, endovascular repair and hybrid approaches, tailored to the risk profiles and anatomical specifics of individual patients.

Neurological event rates and associated risk factors in acute type B aortic dissections treated by thoracic aortic endovascular repair.

OBJECTIVES: Thoracic endovascular aortic repair is the method of choice in patients with complicated type B acute aortic dissection. However, thoracic endovascular aortic repair carries a risk of periprocedural neurological events including stroke and spinal cord ischemia. We aimed to look at procedure-related neurological complications within a large cohort of patients with type B acute aortic dissection treated by thoracic endovascular aortic repair. METHODS: Between 1996 and 2021, the International Registry of Acute Aortic Dissection collected data on 3783 patients with type B acute aortic dissection. For this analysis, 648 patients with type B acute aortic dissection treated by thoracic endovascular aortic repair were included (69.4% male, mean age 62.7 ± 13.4 years). Patients were excluded who presented with a preexisting neurologic deficit or received adjunctive procedures. Demographics, clinical symptoms, and outcomes were analyzed. The primary end point was the periprocedural incidence of neurological events (defined as stroke, spinal cord ischemia, transient neurological deficit, or coma). Predictors for perioperative neurological events and follow-up outcomes were considered as secondary end points. RESULTS: Periprocedure neurological events were noted in 72 patients (11.1%) and included strokes (n = 29, 4.6%), spinal cord ischemias (n = 21, 3.3%), transient neurological deficits (n = 16, 2.6%), or coma (n = 6, 1.0%). The group with neurological events had a significantly higher in-hospital mortality (20.8% vs 4.3%, P < .001). Patients with neurological events were more likely to be female (40.3% vs 29.3%, P = .077), and aortic rupture was more often cited as an indication for thoracic endovascular aortic repair (38.8% vs 16.5%, P < .001). In patients with neurological events, more stent grafts were used (2 vs 1 stent graft, P = .002). Multivariable logistic regression analysis showed that aortic rupture (odds ratio, 3.12, 95% confidence interval, 1.44-6.78, P = .004) and female sex (odds ratio, 1.984, 95% confidence interval, 1.031-3.817, P = .040) were significantly associated with perioperative neurological events. CONCLUSIONS: In this highly selected group from dedicated aortic centers, more than 1 in 10 patients with type B acute aortic dissection treated by thoracic endovascular aortic repair had neurological events, in particular women. Further research is needed to identify the causes and presentation of these events after thoracic endovascular aortic repair, especially among women.

Mammary carcinoma cell derived cyclooxygenase 2 suppresses tumor immune surveillance by enhancing intratumoral immune checkpoint activity.

INTRODUCTION: Systemic inhibition of the inflammatory enzyme cyclooxygenase (COX) 2 decreases the risk of breast cancer and its recurrence. However, the biology of COX-2 in the multicellular tumor microenvironment is poorly defined. METHODS: Mammary tumor onset and multiplicity were examined in ErbB2 transgenic mice that were deficient in mammary epithelial cell COX-2 (COX-2(MEC)KO) compared to wild type (WT) mice. Tumors were analyzed, by real time PCR, immune-staining and flow cytometry, for proliferation, apoptosis, angiogenesis and immune microenvironment. Lentiviral shRNA delivery was used to knock down (KD) COX-2 in ErbB2-transformed mouse breast cancer cells (COX-2KD), and growth as orthotopic tumors was examined in syngenic recipient mice, with or without depletion of CD8+ immune cells. RESULTS: Mammary tumor onset was delayed, and multiplicity halved, in COX-2(MEC)KO mice compared to WT. COX-2(MEC)KO tumors showed decreased expression of Ki67, a proliferation marker, as well as reduced VEGFA, its receptor VEGFR2, endothelial NOS and the vascular endothelial marker CD31, indicating reduced tumor vascularization. COX-2(MEC)KO tumors contained more CD4+ T helper (Th) cells and CD8+ cytotoxic immune cells (CTL) consistent with increased immune surveillance. The ratio of Th markers Tbet (Th1) to GATA3 (Th2) was higher, and levels of Retnla, a M2 macrophage marker, lower, in COX-2(MEC)KO tumor infiltrating leukocytes compared to WT, suggesting a prevalence of pro-immune Th1 over immune suppressive Th2 lymphocytes, and reduced macrophage polarization to the immune suppressive M2 phenotype. Enhanced immune surveillance in COX-2(MEC)KO tumors was coincident with increased intratumoral CXCL9, a T cell chemoattractant, and decreased expression of T lymphocyte co-inhibitory receptors CTLA4 and PD-1, as well as PD-L1, the ligand for PD-1. PD-L1 was also decreased in IFNγ-treated COX-2KD mouse mammary cancer cells in vitro and, compared to control cells, growth of COX-2KD cells as orthotopic tumors in immune competent mice was markedly suppressed. However, robust growth of COX-2KD tumor cells was evident when recipients were depleted of CD8+ cells. CONCLUSIONS: The data strongly support that, in addition to its angiogenic function, tumor cell COX-2 suppresses intratumoral cytotoxic CD8+ immune cell function, possibly through upregulation of immune checkpoints, thereby contributing to tumor immune escape. COX-2 inhibition may be clinically useful to augment breast cancer immunotherapy.