Comparative Study of Male and Female Patients Undergoing Frozen Elephant Trunk Total Arch Replacement.

BACKGROUND: Our aim was to investigate outcomes and long-term survival in male and female patients after frozen elephant trunk (FET) total arch replacement. METHODS: Between March 2013 and January 2023, 362 patients underwent aortic arch replacement via the FET technique. We compared patient characteristics and intra- and postoperative data between male and female patients. RESULTS: Male patients were significantly younger (p = 0.012) but revealed a higher incidence of coronary artery disease (p = 0.008) and preoperative dialysis (p = 0.017). More male patients presented with type A aortic dissections (p = 0.042) while more female patients had aortic aneurysms (p = 0.025). The aortic root was replaced in significantly more male patients (p = 0.013), resulting in significantly longer cardiopulmonary bypass duration (p < 0.001) and operative times (p < 0.001). There were no statistically significant differences in postoperative outcome parameters including in-hospital mortality (p = 0.346). However, new in-stent thrombus formation was significantly more frequent in female patients (p = 0.002). Age in years (odds ratio (OR): 1.026, p = 0.049), an acute pathology (OR: 1.941, p = 0.031) and preoperative dialyses (OR: 3.499, p = 0.010) were predictive for long-term mortality in our Cox regression model, sex (p = 0.466) was not. There was no statistical difference in overall survival (log rank: p = 0.425). CONCLUSIONS: Female patients are older but reveal fewer cardiovascular risk factors; aneurysms are more common in female than male patients. As female patients undergo concomitant surgical procedures less often, their operative times are shorter. While survival and outcomes were similar, female patients suffered from postoperative new in-stent thrombus formation significantly more often.

Training in Aortic Arch Surgery as a Blueprint for a Structured Educational Team Approach: A Review.

Background and objectives: The treatment of pathologies of the aortic arch is a complex field of cardiovascular surgery that has witnessed enormous progress recently. Such treatment is mainly performed in high-volume centres, and surgeons gain great experience in mastering potential difficulties even under emergency circumstances, thereby ensuring the effective therapy of more complex pathologies with lower complication rates. As the numbers of patients rise, so does the need for well-trained surgeons in aortic arch surgery. But how is it possible to learn surgical procedures in a responsible way that, in addition to surgical techniques, also places particular demands on the overall surgical management such as perfusion strategy and neuro-protection? This is why a good training programme teaching young surgeons without increasing the risk for patients is indispensable. Our intention was to highlight the most challenging aspects of aortic arch surgery teaching and how young surgeons can master them. Materials and Methods: We analysed the literature to find out which methods are most suitable for such teaching goals and what result they reveal when serving as teaching procedures. Results: Several studies were found comparing the surgical outcome of young trainees with that of specialists. It was found that the results were comparable whether the procedure was performed by a specialist or by a trainee assisted by the specialist. Conclusions: We thus came to the conclusion that even for such a complex type of intervention, the responsible training of young surgeons by experienced specialists is possible. However, it requires a clear strategy and team approach to ensure a safe outcome for the patient.

Similarities, differences and unmet needs regarding prosthetic materials in aortic arch replacement using the frozen elephant trunk technique: a review.

The constant improvement of operative techniques offers the possibility of treating an increasing number of patients with complex acute and chronic thoracic aortic pathologies involving the aortic arch. Reliable and durable prosthetic material forms the platform for these approaches. Besides the most important properties like impermeability for blood, infection and thrombotic resistance, there are also properties which are not seen at first glance but can nevertheless play a key role in the healing process and long-term results, such as endothelialization and immunostimulation. To ensure the best possible properties of the graft, different variables of the grafts are continuously developed. Beside the choice of material and the weaving technique, Dacron sealing with gelatin is in clinical use for many years but is still being discussed. Collecting clinical experiences with sealed and unsealed grafts in aortic arch replacement led to the conclusion that blood loss through the prosthesis, especially in the early phase after the implantation of the graft, is lowered by gelatin sealing. Furthermore, binding of antimicrobiotic and antithrombotic agents to the collagen are promising approaches to a better prevention of these dreaded complications. More research examining the healing process of the prosthesis is needed in order to find out more about the influence of the prosthesis sealing.

Acute, Chronic, and Treated Aortic Diseases Present Distinguishable Serum Proteome Fingerprints with Protein Profiles That Correlate with Disease Severity.

Aortic diseases are a rare but potentially life-threatening condition. We present a serum proteomic study for a spectrum of aortic diseases including thoracic aortic aneurysms (n = 11), chronic dissections (n = 9), acute aortic dissections (n = 11), and surgically treated dissections (n = 19) as well as healthy controls (n = 10) and patients of coronary heart disease (n = 10) to represent non-aortic cardiovascular disease. In total, we identified and quantified 425 proteins across all 70 samples. The different aortic diseases represented distinguishable proteome profiles. We identified protein clusters that positively or negatively correlate with disease severity, including increase of cytosolic tissue leakage proteins and decrease of components of the coagulation and complement system. Further, we identified a serum proteome fingerprint of acute aortic dissections, consisting, among others, of enriched inflammatory markers such as C-reactive protein and members of the S100 protein family. The study underlines the applicability of serum proteomics for the investigation of aortic diseases and highlights the possibility to establish disease-specific prognostic markers.

Downstream thoracic endovascular aortic repair following the frozen elephant trunk procedure.

The frozen elephant trunk technique has become a well-established treatment option for patients presenting all thoracic aortic pathologies including acute and chronic dissection, aortic aneurysms and even penetrating aortic ulcers involving the aortic arch and descending aorta. Nevertheless, there is a significant incidence of and risk for distal aortic reinterventions after the frozen elephant trunk. Indications mainly include a planned staged approach, diameter progression of downstream aortic segments and the development of distal stent-graft induced new entries (dSINEs). Endovascular stent-graft extension through conventional thoracic endovascular aortic repair (TEVAR) is a relatively simple and safe method to address any pathologies in the remaining descending thoracic aorta up to the level of the coeliac trunk. In fact, the frozen elephant trunk stent-graft provides an ideal proximal landing zone for any endovascular stent-graft extension. Postoperative outcomes are very promising with very low reported in-hospital mortality and morbidity. In case this 2-staged-approach fails to stabilize the remaining aorta, a 3-step procedure, namely open thoracoabdominal aortic replacement, is simplified because the anastomosis site has moved distally. Follow-up of all patients, following frozen elephant trunk implantation or distal stent-graft extension, is mandatory, ideally in an outpatient clinic dedicated to the aorta in order to identify disease progression or to detect any complications as soon as possible.

Distal Aortic Failure Following the Frozen Elephant Trunk Procedure for Aortic Dissection.

Background: Aim of this study was to report and to identify risk factors for distal aortic failure following aortic arch replacement via the frozen elephant trunk (FET) procedure. Methods: One hundred eighty-six consecutive patients underwent the FET procedure for acute and chronic aortic dissection. Our cohort was divided into patients with and without distal aortic failure. Distal aortic failure was defined as: (I) distal aortic reintervention, (II) aortic diameter dilatation to ≥ 6 cm or > 5 mm growth within 6 months, (III) development of a distal stent-graft-induced new entry (dSINE) and/or (IV) aortic-related death. Preoperative, intraoperative, postoperative and aortic morphological data were analyzed. Results: Distal aortic failure occurred in 88 (47.3%) patients. Forty-six (24.7%) required a distal reintervention, aortic diameter dilatation was observed in 9 (4.8%) patients, a dSINE occurred in 22 (11.8%) patients and 11 (6.4%) suffered an aortic-related death. We found no difference in the number of communications between true and false lumen (p = 0.25) but there were significantly more communications between Ishimaru zone 6-8 in the distal aortic failure group (p = 0.01). The volume of the thoracic descending aorta measured preoperatively and postoperatively within 36 months afterward was significantly larger in patients suffering distal aortic failure (p < 0.001; p = 0.011). Acute aortic dissection (SHR 2.111; p = 0.007), preoperative maximum descending aortic diameter (SHR 1.029; p = 0.018) and preoperative maximum aortic diameter at the level of the diaphragm (SHR 1.041; p = 0.012) were identified as risk factors for distal aortic failure. Conclusion: The incidence and risk of distal aortic failure following the FET procedure is high. Especially those patients with more acute and more extensive aortic dissections or larger preoperative descending aortic diameters carry a substantially higher risk of developing distal aortic failure. The prospective of the FET technique as a single-step treatment for aortic dissection seems low and follow-up in dedicated aortic centers is therefore paramount.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on the care of patients with acute and chronic aortic conditions.

OBJECTIVES: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on acute and elective thoracic and abdominal aortic procedures. METHODS: Forty departments shared their data on acute and elective thoracic and abdominal aortic procedures between January and May 2020 and January and May 2019 in Europe, Asia and the USA. Admission rates as well as delay from onset of symptoms to referral were compared. RESULTS: No differences in the number of acute thoracic and abdominal aortic procedures were observed between 2020 and the reference period in 2019 [incidence rates ratio (IRR): 0.96, confidence interval (CI) 0.89-1.04; P = 0.39]. Also, no difference in the time interval from acute onset of symptoms to referral was recorded (<12 h 32% vs > 12 h 68% in 2020, < 12 h 34% vs > 12 h 66% in 2019 P = 0.29). Conversely, a decline of 35% in elective procedures was seen (IRR: 0.81, CI 0.76-0.87; P < 0.001) with substantial differences between countries and the most pronounced decline in Italy (-40%, P < 0.001). Interestingly, in Switzerland, an increase in the number of elective cases was observed (+35%, P = 0.02). CONCLUSIONS: There was no change in the number of acute thoracic and abdominal aortic cases and procedures during the initial wave of the COVID-19 pandemic, whereas the case load of elective operations and procedures decreased significantly. Patients with acute aortic syndromes presented despite COVID-19 and were managed according to current guidelines. Further analysis is required to prove that deferral of elective cases had no impact on premature mortality.

Matrix Metalloproteinase-2 Isoforms Differ within the Aortic Wall of Ascending Aortic Aneurysms Associated with Bicuspid Aortic Valve.

The pathogenesis of ascending thoracic aortic aneurysm (aTAA) is thought to differ between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV), and one of the causes is different hemodynamics. Influenced by hemodynamics, the tissue levels of proteins associated with aTAA might differ between aTAAs with BAV and TAV and between different localities within the aortic wall. We therefore analyzed aTAA tissue levels of MMP-2 (matrix metalloproteinase-2) isoforms (Pro-MMP-2, active MMP-2, and total MMP-2) and tissue levels of MMP-14, TIMP-2 (tissue inhibitor of metalloproteinase-2), MMP-9, and TIMP-1 in 19 patients with BAV and 23 patients with TAV via gelatin zymography and enzyme-linked immunosorbent assay (ELISA), respectively. TAV and BAV groups' protein levels did not differ significantly. Whereas the TAV group exhibited no significant differences in protein levels between the aneurysm's anterior and posterior parts, the BAV group revealed significantly higher levels of Pro-MMP-2, total MMP-2, and TIMP-2 in the aneurysm's posterior parts (mean Pro-MMP-2 200.52 arbitrary units (AU) versus 161.12 AU, p=0.007; mean total MMP-2 235.22 AU versus 193.68 AU, p=0.002; mean TIMP-2 26.90 ng/ml versus 25.36 ng/ml, p=0.009), whereas the other proteins did not differ significantly within the aortic wall. Thus, MMPs are distributed more heterogeneously within the aortic wall of aTAAs associated with BAV than in those associated with TAV, which is a new aspect for understanding the underlying pathogenesis. This heterogeneous protein level distribution might be attributable to differences in the underlying pathogenesis, especially hemodynamics. This result is important for further studies as it will be essential to specify the location of samples to ensure data comparability regarding the main goals of understanding the pathogenesis of aTAA, optimizing treatments, and establishing a screening method for its potentially deadly complications.

A potential key mechanism in ascending aortic aneurysm development: Detection of a linear relationship between MMP-14/TIMP-2 ratio and active MMP-2.

OBJECTIVES: Elevated matrix metalloproteinase-2 (MMP-2) tissue levels have been associated with ascending thoracic aortic aneurysm (aTAA). As MMP-2 activation is controlled by interactions among matrix metalloproteinase-14 (MMP-14), a tissue inhibitor of metalloproteinases-2 (TIMP-2) and Pro-MMP-2 in cell culture, this activation process might also play a role in aTAA. METHODS: Via gelatin zymography we analyzed tissue levels of MMP-2 isoforms (Pro-MMP-2, active MMP-2, total MMP-2) and via enzyme-linked immunosorbent assay (ELISA,) MMP-14,TIMP-2 and total MMP-2 tissue levels in N = 42 patients with aTAA. As controls, MMP-14 and TIMP-2 aortic tissue levels in N = 9 patients undergoing coronary artery bypass surgery were measured via ELISA, and levels of MMP-2 isoforms in N = 11 patients via gelatin zymography. RESULTS: Active MMP-2 was significantly higher in aTAA than in controls. Patients with aTAA exhibited significantly lower Pro-MMP-2 and TIMP-2 levels. Total MMP-2 and MMP-14 did not differ significantly between groups. Regression analysis revealed a linear relationship between TIMP-2 and the MMP-14/TIMP-2 ratio, as well as active MMP-2 in aTAA. Aneurysmatic tissue can be accurately distinguished from control aortic tissue (AUC = 1) by analyzing the active MMP-2/Pro-MMP-2 ratio with a cutoff value of 0.11, whereas MMP-14 and TIMP-2 roles are negligible in ROC analysis. CONCLUSION: A larger amount of MMP-2 is activated in aTAA than in control aortic tissue-a factor that seems to be a central process in aneurysm development. When active MMP-2 exceeds 10% compared to Pro-MMP-2, we conclude that it originates from aneurysmatic tissue, which we regard as a starting point for further studies of aTAA biomarkers. The tissue's MMP-14/TIMP-2 ratio may regulate the degree of Pro-MMP-2 activation as a determining factor, while the enzymatic activities of MMP-14 and TIMP-2 do not seem to play a key role in aneurysm development.

Characterization of serum matrix metalloproteinase 2/9 levels in patients with ascending aortic aneurysms.

OBJECTIVES: The objectives of this study were to identify interrelations between matrix metalloproteinase-2 (MMP2)/MMP9 levels and clinical variables in patients with aortic root/ascending aortic aneurysms and to describe comorbidities as possible biasing factors in the widely discussed correlation of serum MMP levels and aortic diameter. METHODS: Serum MMP9 and MMP2 levels were quantified in 32 consecutive patients with ascending aortic and/or aortic root aneurysms (>45 mm) at the Heart Center University of Freiburg from May 2013 to January 2014. The influence of comorbidities and medication on serum MMP2 and MMP9 levels was studied. We took into account ascending aortic diameter (aAD), aortic valve configuration, hypertension, age and hyperlipidaemia as factors possibly altering serum MMP levels. The relation between serum MMP levels and aAD was examined by a correlation test based on ranks. RESULTS: Serum MMP2 levels and aAD correlated positively. Correlation was increased in patients without hyperlipidaemia (Spearman's ρ = 0.62, P = 0.008 in patients without hyperlipidaemia; ρ = 0.409, P = 0.020 in all patients). Serum MMP9 levels did not correlate with aAD and showed greater variation. Serum MMP9 levels were significantly associated with hyperlipidaemia (P = 0.037). CONCLUSIONS: The distinct correlation patterns in patients with and without hyperlipidaemia have to be considered when defining the potential of MMP2 as a biomarker in future studies. The relation between MMP9 and hyperlipidaemia has to be further investigated.

MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms.

OBJECTIVE: The need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress. METHODS: Serum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography. 24 patients had ascending aortic aneurysms, 10 of them also had aortic root aneurysms. Three patients had normally functioning valves, 12 had regurgitation alone, eight had regurgitation and stenosis and one had only stenosis. Patients had bicuspid and tricuspid aortic valves (9/15). Serum samples were taken preoperatively, and the aortic wall specimen collected during surgical aortic repair. RESULTS: Pro-MMP-2 was identified in all serum and tissue samples. Pro-MMP-2 was detected in all tissue and serum samples from patients with ascending aortic/aortic root aneurysms, irrespective of valve morphology or other clinical parameters and in serum from healthy controls. We also identified active MMP-2 in all tissue samples from patients with ascending aortic/aortic root aneurysms. None of the analyzed serum samples revealed signals relatable to active MMP-2. No correlation between aortic tissue total MMP-2 or tissue pro-MMP-2 or tissue active MMP-2 and serum MMP-2 was found and tissue MMP-2/pro-MMP-2/active MMP-2 did not correlate with aortic diameter. This evidence shows that pro-MMP-2 is the predominant MMP-2 species in serum of patients and healthy individuals and in aneurysmatic aortic tissue, irrespective of aortic valve configuration. Active MMP-2 species are either not released into systemic circulation or not detectable in serum. There is no reliable connection between aortic tissue-and serum MMP-2 isoforms, nor any indication that pro-MMP-2 functions as a common marker of high aortic wall stress.