Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs

Although COVID-19 is primarily a respiratory disease, it may affect also the cardiovascular system. COVID-19 patients with cardiovascular disorder (CVD) develop a more severe disease course with a significantly higher mortality rate than non-CVD patients. A common denominator of CVD is the dysfunction of endothelial cells (ECs), increased vascular permeability, endothelial-to-mesenchymal transition, coagulation, and inflammation. It has been assumed that clinical complications in COVID-19 patients suffering from CVD are caused by SARS-CoV-2 infection of ECs through the angiotensin-converting enzyme 2 (ACE2) receptor and the cellular transmembrane protease serine 2 (TMPRSS2) and the consequent dysfunction of the infected vascular cells. Meanwhile, other factors associated with SARS-CoV-2 entry into the host cells have been described, including disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), the C-type lectin CD209L or heparan sulfate proteoglycans (HSPG). Here, we discuss the current data about the putative entry of SARS-CoV-2 into endothelial and smooth muscle cells. Furthermore, we highlight the potential role of long non-coding RNAs (lncRNAs) affecting vascular permeability in CVD, a process that might exacerbate disease in COVID-19 patients

Hospital Incidence, Treatment, and Outcome of 885 Patients with Thoracoabdominal Aortic Aneurysms Treated in Switzerland over 10 Years-A Secondary Analysis of Swiss DRG Data

Despite the development of fenestrated and branched endovascular aortic repair (f/bEVAR), the surgical management of thoraco-abdominal aortic aneurysms (TAAAs) remains a major challenge. The aim of this study was to analyse the hospital incidence and hospital mortality of patients treated for TAAAs in Switzerland. Secondary data analysis was performed using nationwide administrative discharge data from 2009-2018. Standardised incidence rates and adjusted mortality rates were calculated. A total of 885 cases were identified (83.2% nonruptured (nrTAAA), 16.8% ruptured (rTAAA)), where 69.3% were male. The hospital incidence rate for nrTAAA was 0.4 per 100,000 women and 0.9 per 100,000 men in 2009, which had doubled for both sexes by 2018. For rTAAA, there was no trend over the years. The most common procedure was f/bEVAR (44.2%), followed by OAR (39.5%), and 9.8% received a hybrid procedure. There was a significant increase in endovascular procedures over time. The all-cause mortality was 7.1% with nrTAAA and 55% with rTAAA. The mortality was lower for rTAAA when f/bEVAR or hybrid procedures were used. A ruptured aneurysm and higher comorbidity were associated with higher hospital mortality. This study demonstrates that the treatment approach has changed significantly over the observed period. The use of f/bEVAR nearly tripled in nrTAAA and doubled in rTAAA during this decade

Baroreceptors in the Aortic Arch and Their Potential Role in Aortic Dissection and Aneurysms

The arterial baroreflex is a key autonomic regulator of blood pressure whose dysfunction has been related to several cardiovascular diseases. Changes in blood pressure are sensed by specific mechanosensory proteins, called baroreceptors, particularly located in the outer layer of the carotid sinus and the inner curvature of the aortic arch. The signal is propagated along the afferent nerves to the central nervous system and serves as negative feedback of the heart rate. Despite extensive research, the precise molecular nature of baroreceptors remains elusive. Current knowledge assumes that baroreceptors are ion channels at the nerve endings within the outer layer of the arteries. However, the evidence is based mainly on animal experiments, and the specific types of mechanosensitive receptors responsible for the signal transduction are still unknown. Only a few studies have investigated mechanosensory transmission in the aortic arch. In addition, although aortic dissection, and particularly type A involving the aortic arch, is one of the most life-threatening cardiovascular disorders, there is no knowledge about the impact of aortic dissection on baroreceptor function. In this review, we aim not to highlight the regulation of the heart rate but what mechanical stimuli and what possible ion channels transfer the corresponding signal within the aortic arch, summarizing and updating the current knowledge about baroreceptors, specifically in the aortic arch, and the impact of aortic pathologies on their function

Long-Term Outcomes in Thoracic Endovascular Aortic Repair for Complicated Type B Aortic Dissection or Intramural Hematoma Depending on Proximal Landing Zone

Thoracic endovascular aortic repair (TEVAR) is the preferred treatment for complicated type B aortic dissection (TBAD) or intramural hematoma (IMH). This study aimed to investigate the association of the proximal landing zone and its morphology with long-term outcomes in patients with TBAD or IMH. A total of 94 patients who underwent TEVAR for TBAD or IMH between 10/2003 and 01/2020 were included. The cohort was divided according to the proximal landing in Ishimaru zone 2 or 3 and the presence of a healthy landing zone (HLZ; non-dissected or aneurysmatic, ≥2 cm length). Primary outcome was freedom from aortic reintervention. Secondary endpoints were freedom from aortic growth, stroke, spinal cord ischemia, retrograde dissection, proximal stent-graft induced new entry (pSINE), debranching failure, and mortality. Outcomes were assessed using Cox proportional hazard models with mortality as a competing risk. A proximal TEVAR landing in zone 2 was associated with higher rates of reinterventions compared to zone 3 (33% vs. 15%, p = 0.031), spinal cord ischemia (8% vs. 0%, p = 0.037), and pSINE (13% vs. 2%, p = 0.032). No difference was found for the other outcomes, including mortality. Landing in dissected segments was not associated with impaired results. Proximal TEVAR landing in zone 3 may be preferable with regard to long-term aortic reintervention in patients with TBAD or IMH

Prognostic model for survival of patients with abdominal aortic aneurysms treated with endovascular aneurysm repair.

The role of endovascular aneurysm repair (EVAR) in patients with asymptomatic abdominal aortic aneurysm (AAA) who are unfit for open surgical repair has been questioned. The impending risk of aneurysm rupture, the risk of elective repair, and the life expectancy must be balanced when considering elective AAA repair. This retrospective observational cohort study included all consecutive patients treated with standard EVAR for AAA at a referral centre between 2001 and 2020. A previously published predictive model for survival after EVAR in patients treated between 2001 and 2012 was temporally validated using patients treated at the same institution between 2013 and 2020 and updated using the overall cohort. 558 patients (91.2% males, mean age 74.9 years) were included. Older age, lower eGFR, and COPD were independent predictors for impaired survival. A risk score showed good discrimination between four risk groups (Harrel's C = 0.70). The 5-years survival probabilities were only 40% in "high-risk" patients, 68% in "moderate-to-high-risk" patients, 83% in "low-to-moderate-risk", and 89% in "low-risk" patients. Low-risk patients with a favourable life expectancy are likely to benefit from EVAR, while high-risk patients with a short life expectancy may not benefit from EVAR at the current diameter threshold

Inter-hospital transfer of patients with ruptured abdominal aortic aneurysm in Switzerland

Objectives: To analyse the association of inter-hospital transfer on hospital mortality in patients with ruptured abdominal aortic aneurysms (rAAA) in Switzerland. Design: Secondary data analysis of case-related hospital discharge data from the Swiss Federal Statistical Office for the years 2009-2018. All cases with rAAA as primary or secondary diagnosis were included. Cases with rAAA as a secondary diagnosis without surgical treatment and cases that had been transferred to another hospital without surgical treatment at the referring hospital were excluded. Methods: Logistic regression models for hospital mortality were constructed with age, sex, type of admission, van Walraven comorbidity score, type of treatment, insurance class, hospital level, and year of treatment as independent variables. Results: From 1 January 2009 to 31 December 2018, 1798 cases with rAAA were treated either surgically (62.5%) or palliatively (37.5%) in Switzerland. 72.9% of the cases were directly treated (surgically or palliative) at the hospital of first presentation, whereas 27.1% of all cases with rAAA were transferred between hospitals. The overall crude hospital mortality was 50.3%; in the surgically treated cohort it was 23.1%, in the palliative treated cohort it was 95.7%.Inter-hospital transfer was associated with better survival compared to patients directly admitted (OR 0.52, 95%-CI: 0.36-0.75, p<.001). Treatment in major hospitals was associated with a significantly higher mortality compared to treatment in university hospitals (OR 1.98, 1.41-2.79, p<.001). There was no evidence for an association of open repair with hospital mortality, OR 1.06, 0.77-1.48, p=.722, compared to endovascular repair. Conclusions: In a healthcare system such as Switzerland with a highly specialised rescue chain, transfer of haemodynamically stable patients with rAAA is probably safe. In this setting, a centralised medical care might outweigh the potential disadvantages of a limited delay due to patient transfer. Further studies are needed to address potential confounding factors such as hemodynamic and anatomical features. Keywords: "DRG"; "aortic aneurysm; "aortic rupture"; "patient transfer"; "secondary data analysis"; abdominal"

Relevance of Type II Endoleak After Endovascular Repair of Ruptured Abdominal Aortic Aneurysms: A Retrospective Single-Center Cohort Study

Introduction: Endovascular aortic repair (EVAR) is widely used as an alternative to open repair in elective and even in emergent cases of ruptured abdominal aortic aneurysm (rAAA). One of the most frequent complications after EVAR is type II endoleak (T2EL). In elective therapy, evidence-based therapeutic recommendations for T2EL are limited. Completely unclear is the role of T2EL after EVAR for rAAA (rEVAR). This study aims to investigate the significance of T2ELs after rEVAR. Patients and methods: This is a retrospective single-center data analysis of all patients who underwent rEVAR between January 2010 and December 2020 with primary T2EL. The outcome criteria were overall and T2EL-related mortality and reintervention rate as well as development of aneurysm diameter over follow-up (FU). Results: During the study period between January 2010 and December 2020, 35 (25%) out of 138 patients with rEVAR presented a primary postoperative T2EL (age 74±11 years, 34 males). At rupture, mean aneurysm diameter was 73±12 mm. Follow-up was 26 (0–172) months. The reintervention-free survival was 69% (95% confidence interval [CI]: 55%–86%) at 30 days, 58% (95% CI: 43%–78%) at 1 year, and 52% (95% CI: 36%–75%) at 3 years. In 40% (n=14), T2ELs resolved spontaneously within a median time of 3.4 (0.03–85.6) months. The overall and T2EL reintervention rates were 43% (n=15) and 9% (n=3), respectively. Within 30 days, 11 patients (31%) required reintervention, of which 2 were T2EL related. Aneurysm sac growth by ≥5 mm was seen in 3 patients (9%), and aneurysm shrinkage rate was significantly higher in sealed T2EL group (86% vs 5%, p<0.0001). The overall survival was 85% (95% CI: 74%–98%) at 30 days, 75% (95% CI: 61%–92%) at 1 year, and 67% (95% CI: 51%–87%) at 3 years. Six deaths were aneurysm related, while 1 was T2EL related within the first 30 days due to persistent hemorrhage. During FU, one more patient died due to a T2EL-related secondary rupture (T2EL-related mortality, 5.7%, n=2). Multivariable analysis revealed that arterial hypertension was associated with an increased risk for reintervention (hazard ratio [HR]: 27.8, 95% CI: 1.48–521, p=0.026) and age was associated with an increased risk for mortality (HR 1.14, 95% CI: 1.04–1.26, p=0.005). Conclusion: T2ELs after rEVAR showed a benign course in most cases. In the short term, the possibility of persistent bleeding should be considered. In the mid term, a consequent FU protocol is required to detect known late complications after EVAR at an early stage and to prevent secondary rupture and death

Chronische mesenteriale Ischämie

Die chronische mesenteriale Ischämie (CMI) ist definiert als eine insuffiziente Perfusion des Gastrointestinaltrakts, die länger als 3 Monate andauert. Die häufigste Ursache ist die Arteriosklerose. Typische Symptome sind postprandiale Schmerzen, Gewichtsverlust und Diarrhöen. Besteht eine CMI, besteht grundsätzlich die Indikation zur Revaskularisierung, wobei sowohl eine endovaskuläre (ER) als auch offen-operative Revaskularisierung (OR) zur Verfügung stehen und die A. mesenterica superior das primäre Zielgefäß sein sollte. Klarer Vorteil der ER ist die geringere Invasivität mit niedriger Morbidität und Verweildauer sowie dadurch bedingten geringeren Kosten. Nachteil ist die erhöhte Rezidiv- und Reinterventionsrate. OR bietet eine deutlich bessere Offenheitsrate mit jedoch initial erhöhter perioperativer Morbidität. Im Hinblick auf die Mortalität zeigte sich weder im kurz- noch längerfristigen Verlauf ein signifikanter Unterschied, wobei aussagekräftige prospektive randomisierte Studien mit vergleichbaren Langzeitdaten fehlen. Aktuell wird bei passender Anatomie prinzipiell ein primär endovaskuläres Vorgehen empfohlen. Nach Revaskularisierung sollten engmaschige Verlaufskontrollen zur frühzeitigen Erkennung möglicher Rezidivstenosen durchgeführt werden, um schwere Komplikationen wie die Entstehung einer lebensbedrohlichen akuten mesenterialen Ischämie zu verhindern

Hospital incidence and mortality of patients treated for abdominal aortic aneurysms in Switzerland - a secondary analysis of Swiss DRG statistics data

AIM OF THE STUDY To analyse hospital incidence and in-hospital mortality of patients treated for abdominal aortic aneurysms in Switzerland. METHODS Secondary data analysis of case-related hospital discharge data of the Swiss Federal Statistical Office for the years 2009-2018. Patients who were hospitalised and surgically treated for nonruptured abdominal aortic aneurysms or hospitalised and treated for ruptured abdominal aortic aneurysms were included in the analysis. Standardised annual incidences rates were calculated using the European standard population 2013. In-hospital all-cause mortality rates were calculated as raw values and standardised for age, sex, and the van Walraven comorbidity score. RESULTS A total of 10,728 cases were included in this study, of which 87.1% were male. Overall, 22.7% of the patients presented with a ruptured abdominal aortic aneurysm; 46% of these cases were surgically treated whereas 54% received conservative therapy. The age-standardised cumulative hospital incidences for treatment of nonruptured abdominal aortic aneurysms were 2.6 (95% confidence interval 2.5-2.8) and 19.7 (19.2-20.1) per 100,000 for women and men, respectively; for ruptured aneurysms it was 0.4 (0.3-2.4) per 100,000 in women, and 2.7 (2.6-2.9) in men. The annual incidence rates were stable in the decade observed. The adjusted mortality rates for treatment of nonruptured aneurysms decreased from 5.5% (2.6-11.2%) in 2009 to 1.4% (0.5-3.6%) in 2018 in women, and from 2.4% (1.3-4.5%) in 2009 to 0.6% (0.2-1.5%) in 2018 in men. The adjusted mortality rates for treatment of ruptured abdominal aortic aneurysms remained high without relevant improvements for either sex over time: for women 32.4% (24.1-42.1%), for men 19.7% (16.8-22.8%). CONCLUSIONS The hospital incidence rates for nonruptured and ruptured abdominal aortic aneurysms remained unchanged in the decade observed. Compared with Germany, there was no evidence for a decrease in the annual incidence rates for ruptured abdominal aortic aneurysms in Switzerland. Mortality rates in the elective setting were low and decreased in the last decade but remained high in patients treated for ruptured aneurysms. Efforts to reduce the incidence of ruptured abdominal aortic aneurysms are needed to reduce aneurysm-related mortality in Switzerland

Alterungsbedingte Gefäßveränderungen am Beispiel der Arteria carotis

Einer der Hauptrisikofaktoren für das Vorliegen einer Karotisstenose und des karotisbedingten Schlaganfalls ist das Lebensalter. Ziel dieses Übersichtsartikels ist die Darstellung des aktuellen Wissensstands über altersbedingte Veränderungen der Gefäße am Beispiel der Karotisstenose.Die Gefäßalterung (vaskuläre Seneszenz) als Abnahme struktureller und funktioneller Eigenschaften der Gefäßwand spielt sich auf verschiedenen Ebenen ab. Auf multizellulärer Ebene kommt es mit zunehmendem Alter hauptsächlich aufgrund von atherosklerotischen Veränderungen der Gefäßwand zu einer Zunahme von Gefäßvolumen und -durchmesser sowie der Intima-Media-Dicke. Auf zellulärer und extrazellulärer Ebene kommt es zur Abnahme von Elastinfasern, glatten Muskelzellen und der Gesamtzellularität sowie zur Zunahme der Lipid‑, Cholesterin- und Kalziumphosphatablagerungen und der Neovaskularisierung. Ursachen der Gefäßalterung auf molekularer Ebene sind insbesondere oxidativer Stress, chronische Entzündungsreaktion, mitochondriale Dysfunktion, epigenetische Veränderungen, Dysregulation der Expression nicht kodierender RNAs (ncRNAs) und die Zunahme der Seneszenz. Der altersbedingte Verlust der Heilungs- und Reparaturfähigkeit des Gewebes macht die Plaques vulnerabler und im Falle der A. carotis anfälliger für ischämische Schlaganfälle.Zunehmende Erkenntnisse über den Einfluss des Alterns auf die Epigenetik und der ncRNAs in atherosklerotischen Plaques kann zukünftig das individuelle Risiko von Patienten genauer quantifizieren und zur Entwicklung zielgerichteter Therapiestrategien beitragen. Weitere Studien sind auf diesem Gebiet jedoch notwendig, um das gesamte Ausmaß der Gefäßalterung und den damit einhergehenden Erkrankungen zu verstehen, damit diesen dann gezielt entgegenwirkt werden kann