Publications by authors named "Hans-Henning Eckstein"

221 Publications

Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease.

Prog Cardiovasc Dis 2022 May 20. Epub 2022 May 20.

Department of Neurology, Center for Vascular Neurology and Intensive Care, University of Regensburg, Regensburg, Germany.

International guidelines strongly recommend statins alone or in combination with other lipid-lowering agents to lower low-density lipoprotein cholesterol (LDL-C) levels for patients with asymptomatic/symptomatic carotid stenosis (AsxCS/SCS). Lowering LDL-C levels is associated with significant reductions in transient ischemic attack, stroke, cardiovascular (CV) event and death rates. The aim of this multi-disciplinary overview is to summarize the benefits and risks associated with lowering LDL-C with statins or non-statin medications for Asx/SCS patients. The cerebrovascular and CV beneficial effects associated with statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and other non-statin lipid-lowering agents (e.g. fibrates, ezetimibe) are reviewed. The use of statins and PCSK9 inhibitors is associated with several beneficial effects for Asx/SCS patients, including carotid plaque stabilization and reduction of stroke rates. Ezetimibe and fibrates are associated with smaller reductions in stroke rates. The side-effects resulting from statin and PCSK9 inhibitor use are also highlighted. The benefits associated with lowering LDL-C with statins or non-statin lipid lowering agents (e.g. PCSK9 inhibitors) outweigh the risks and potential side-effects. Irrespective of their LDL-C levels, all Asx/SCS patients should receive high-dose statin treatment±ezetimibe or PCSK9 inhibitors for reduction not only of LDL-C levels, but also of stroke, cardiovascular mortality and coronary event rates.
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http://dx.doi.org/10.1016/j.pcad.2022.05.003DOI Listing
May 2022

Neuroimmune cardiovascular interfaces control atherosclerosis.

Nature 2022 05 27;605(7908):152-159. Epub 2022 Apr 27.

II. Medizinische Klinik und Poliklinik, Technische Universität München, Klinikum rechts der Isar, Munich, Germany.

Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes. As plaques lack innervation, the effects of neuronal control on atherosclerosis remain unclear. However, the immune system responds to plaques by forming leukocyte infiltrates in the outer connective tissue coat of arteries (the adventitia). Here, because the peripheral nervous system uses the adventitia as its principal conduit to reach distant targets, we postulated that the peripheral nervous system may directly interact with diseased arteries. Unexpectedly, widespread neuroimmune cardiovascular interfaces (NICIs) arose in mouse and human atherosclerosis-diseased adventitia segments showed expanded axon networks, including growth cones at axon endings near immune cells and media smooth muscle cells. Mouse NICIs established a structural artery-brain circuit (ABC): abdominal adventitia nociceptive afferents entered the central nervous system through spinal cord T-T dorsal root ganglia and were traced to higher brain regions, including the parabrachial and central amygdala neurons; and sympathetic efferent neurons projected from medullary and hypothalamic neurons to the adventitia through spinal intermediolateral neurons and both coeliac and sympathetic chain ganglia. Moreover, ABC peripheral nervous system components were activated: splenic sympathetic and coeliac vagus nerve activities increased in parallel to disease progression, whereas coeliac ganglionectomy led to the disintegration of adventitial NICIs, reduced disease progression and enhanced plaque stability. Thus, the peripheral nervous system uses NICIs to assemble a structural ABC, and therapeutic intervention in the ABC attenuates atherosclerosis.
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http://dx.doi.org/10.1038/s41586-022-04673-6DOI Listing
May 2022

Utilization and Regional Differences of In-Patient Services for Peripheral Arterial Disease and Acute Limb Ischemia in Germany: Secondary Analysis of Nationwide DRG Data.

J Clin Med 2022 Apr 11;11(8). Epub 2022 Apr 11.

Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.

Background: Peripheral arterial disease (PAD) and acute limb ischemia (ALI) pose an increasing strain on health care systems. The objective of this study was to describe the German health care landscape and to assess hospital utilization with respect to PAD and ALI.

Methods: Secondary data analysis of diagnosis-related group statistics data (2009-2018) provided by the German Federal Statistical Office. Inclusion of cases encoded by the International Classification of Diseases (ICD-10) codes for PAD and arterial embolism or thrombosis. Construction of line diagrams and choropleth maps to assess temporal trends and regional distributions.

Results: A total of 2,589,511 cases (median age 72 years, 63% male) were included, of which 2,110,925 underwent surgical or interventional therapy. Overall amputation rate was 17%, with the highest rates of minor (28%) and major amputations (15%) in patients with tissue loss. In-hospital mortality (overall 4.1%) increased in accordance to Fontaine stages and was the highest in patients suffering arterial embolism or thrombosis (10%). Between 2009 and 2018, the annual number of PAD cases with tissue loss (Fontaine stage IV) increased from 97,092 to 111,268, whereby associated hospital utilization decreased from 2.2 million to 2.0 million hospital days. Hospital incidence and hospital utilization showed a clustering with the highest numbers in eastern Germany, while major amputation rate and mortality were highest in northern parts of Germany.

Conclusions: Increased use of endovascular techniques was observed, while hospital utilization to treat PAD with tissue loss has decreased. This is despite an increased hospital incidence. Addressing socioeconomic inequalities and a more homogeneous distribution of dedicated vascular units might be advantageous in reducing the burden of disease associated with PAD and ALI.
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http://dx.doi.org/10.3390/jcm11082116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025059PMC
April 2022

Determination of the influence of weather and air constituents on aortic aneurysm ruptures.

Heliyon 2022 Apr 9;8(4):e09263. Epub 2022 Apr 9.

Regional Climate Change and Health, Faculty of Medicine, University of Augsburg, Universitätsstraße 2, 86159 Augsburg, Germany.

In this article, we present a method to determine the influence of meteorology and air pollutants on ruptured aortic aneurysm (rAA). In contrast to previous studies, our work takes into account highly resolved seasonal relationships, a time-lagged effect relationship of up to two weeks, and furthermore, potential confounding influences between the meteorological and air-hygienic variables are considered and eliminated using a cross-over procedure. We demonstrate the application of the method using the cities of Augsburg and Munich in southern Germany as examples, where a total of 152 rAA can be analyzed for the years 2010-2019. With the help of a Wilcoxon rank-sum test and the analysis of the atmospheric circulation, typical weather situations could be identified that have an influence on the occurrence of rAA in the southern German region. These are a rainy northwest wind-type in spring, humid weather in summer and warm southwest wind-type weather in autumn and winter.
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http://dx.doi.org/10.1016/j.heliyon.2022.e09263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018152PMC
April 2022

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Angiology 2022 Apr 12:33197221081914. Epub 2022 Apr 12.

Department of Surgery, 121343University of Nicosia Medical School, Nicosia, Cyprus.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.
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http://dx.doi.org/10.1177/00033197221081914DOI Listing
April 2022

One-year outcomes after transcarotid artery revascularization (TCAR) in the ROADSTER 2 trial.

J Vasc Surg 2022 Apr 2. Epub 2022 Apr 2.

Oklahoma Heart Hospital, Oklahoma City, OK.

Objectives: Transcarotid artery revascularization (TCAR) is a carotid stenting technique that utilizes reversal of cerebral arterial flow to confer cerebral protection. Although carotid endarterectomy (CEA) remains the standard for treatment of symptomatic and asymptomatic carotid stenosis, the search for the optimal minimally invasive option for the high-risk surgical patient continues. The goal of the current study is to evaluate the 1-year safety and efficacy of TCAR in a prospective clinical trial.

Methods: ROADSTER 2 is a prospective, open-label, single-arm, multicenter, post-approval registry for patients undergoing TCAR. All patients were considered high risk for CEA and underwent independent neurological assessments preoperatively, postoperatively, and had long-term clinical follow-up. The primary end point was incidence of ipsilateral stroke after treatment with the ENROUTE Transcarotid Stent System. Secondary end points included individual/composite rates of stroke, death, and perioperative myocardial infarction.

Results: Between June 2016 and November 2018, 155 patients at 21 centers in the United States and one in the European Union were enrolled and represented a subset of the overall trial. Asymptomatic (n = 119; 77%) and symptomatic patients (n = 36; 23%) with high-risk anatomic (ie, high lesion, restenosis, radiation injury; 43%), physiologic (32%), or combined factors (25%) were enrolled. No patient suffered a perioperative myocardial infarction or stroke. Over the year, no patient had an ipsilateral stroke, but four patients died (2.6%), all from non-neurological causes. Additionally, a technical success rate of 98.7% with a low cranial nerve deficit rate of 1.3% was achieved.

Conclusions: In patients with high risk factors, TCAR yields high technical success with a low stroke and death rate at 1 year. Further comparative studies with CEA are warranted.
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http://dx.doi.org/10.1016/j.jvs.2022.03.872DOI Listing
April 2022

[Important recommendations of the German-Austrian S3 guidelines on management of extracranial carotid artery stenosis].

Chirurg 2022 May 22;93(5):476-484. Epub 2022 Mar 22.

Klinik und Poliklinik für Vaskuläre und Endovaskuläre Chirurgie, Klinikum rechts der Isar der Technischen Universität München (TUM), München, Deutschland.

Background: Lesions of the extracranial carotid artery are the cause of 10-15 % of all cases of cerebral ischemia. The aims of the updated S3 guidelines are evidence-based and consensus-based recommendations for action on comprehensive care of patients with extracranial carotid stenosis in Germany and Austria.

Methods: A systematic literature search (1990-2019) and methodical assessment of existing guidelines and systematic reviews were carried out. Consensus answers to 37 key questions with evidence-based recommendations.

Results: The prevalence of extracranial carotid stenosis is approximately 4% and increases after the age of 65 years. The most important examination method is duplex sonography. Randomized controlled studies (RCT) have shown that carotid endarterectomy (CEA) of an asymptomatic 60-99% carotid artery stenosis reduces the absolute risk of stroke (absolute risk reduction, ARR) within 5 years in comparison to drug treatment alone by 4.1%. Due to an improved pharmaceutical prevention of arteriosclerosis, the S3 guidelines recommend a prophylactic CEA of a 60-99% stenosis only for patients without an increased surgical risk. Additionally, one or more clinical or imaging results should be present, which indicate an increased risk of carotid-related stroke in the follow-up. For medium-grade (50-69 %) and high-grade (70-99 %) symptomatic stenoses the ARRs after 5 years are 4.6% and 15.6%, respectively. Systematic reviews of RCTs have shown that CEA is associated with a ca. 50% lower periprocedural risk of stroke compared to carotid artery stenting (CAS). There are no differences in the long-term course. The CEA is recommended for high-grade asymptomatic, medium-grade and high-grade symptomatic carotid stenosis as a standard procedure, alternatively CAS can be considered. For both procedures the periprocedural stroke rate/mortality during hospitalization should be a maximum of 2% (asymptomatic stenosis) or 4% (symptomatic stenosis).

Conclusion: Both CEA and CAS necessitate a critical evaluation of the indications and strict quality criteria. Future studies should evaluate even better selection criteria for an individual, optimal, conservative, operative or endovascular treatment.
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http://dx.doi.org/10.1007/s00104-022-01622-xDOI Listing
May 2022

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

J Thorac Cardiovasc Surg 2022 Feb 10. Epub 2022 Feb 10.

Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jtcvs.2022.02.007DOI Listing
February 2022

Changes in Endocan and Dermatan Sulfate Are Associated with Biomechanical Properties of Abdominal Aortic Wall during Aneurysm Expansion and Rupture.

Thromb Haemost 2022 Feb 15. Epub 2022 Feb 15.

Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Background And Aims:  The study aimed to assess the potential of proteoglycans (PGs) and collagens as serological biomarkers in the abdominal aortic aneurysm (AAA). Furthermore, we investigated the underlying mechano-biological interactions and signaling pathways.

Methods:  Tissue and serum samples from patients with ruptured AAA (rAAA;  = 29), elective AAA (eAAA;  = 78), and healthy individuals ( = 8) were evaluated by histology, immunohistochemistry, and enzyme-linked immunosorbent assay, and mechanical properties were assessed by tensile tests. Regulatory pathways were determined by membrane-based sandwich immunoassay.

Results:  In AAA samples, collagen type I and III (Col1 and Col3), chondroitin sulfate, and dermatan sulfate (DS) were significantly increased compared with controls (3.0-, 3.2-, 1.3-, and 53-fold;  < 0.01). Col1 and endocan were also elevated in the serum of AAA patients (3.6- and 6.0-fold;  < 0.01), while DS was significantly decreased (2.5-fold;  < 0.01). Histological scoring showed increased total PGs and focal accumulation in rAAA compared with eAAA. Tissue β-stiffness was higher in rAAA compared with eAAA (2.0-fold,  = 0.02). Serum Col1 correlated with maximum tensile force and failure tension ( = 0.448 and 0.333;  < 0.01, and  = 0.02), tissue endocan correlated with α-stiffness ( = 0.340;  < 0.01). Signaling pathways in AAA were associated with extracellular matrix synthesis and vascular smooth muscle cell proliferation. In particular, Src family kinases and platelet-derived growth factor- and epidermal growth factor-related proteins seem to be involved.

Conclusion:  Our findings reveal a structural association between collagen and PGs and their response to changes in mechanical loads in AAA. Particularly Col1 and endocan reflect the mechano-biological conditions of the aortic wall also in the patient's serum and might serve for AAA risk stratification.
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http://dx.doi.org/10.1055/a-1772-0574DOI Listing
February 2022

Can We Still Teach Open Repair of Abdominal Aortic Aneurysm in The Endovascular Era? Single-Center Analysis on The Evolution of Procedural Characteristics Over 15 Years.

J Surg Educ 2022 Jul-Aug;79(4):885-895. Epub 2022 Feb 9.

Department for Vascular and Endovascular Surgery, Technical University Munich, Munich, Germany; Department for Vascular Medicine, Thoracic and Vascular Surgery, Medical Faculty Carl Gustav Carus and University Hospital, Technical University Dresden, Dresden, Germany. Electronic address:

Objective: In many vascular centers an endovascular first policy for the treatment of abdominal aortic aneurysms (AAA) has resulted in endovascular aortic repair (EVAR) outnumbering open aortic repair (OAR). The declining routine in OAR raises the question whether this might influence procedural outcomes and diminish surgical expertise for current and future vascular surgeons. We aimed to analyze OAR outcomes, AAA morphology and procedural details over the past 15 years while an endovascular first approach was successively implemented.

Particicpants And Design: All patients operated for (i)ntact infra-/juxtarenal AAA between January 1, 2005 and December 31, 2019 were identified. Outcome parameters were length of stay (hospital/ICU), in-hospital mortality and medical/surgical complications. Operative details were clamping zone, access and graft configuration. AAA anatomy including neck and iliac parameters was analyzed with Endosize©. Logistic regression, uni- and multivariate analysis were applied.

Results: 293 patients received elective OAR for iAAA. Baseline characteristics (age, sex, hypertension, smoking, occlusive disease, coronary disease, hyperlipidemia, diabetes, renal insufficiency and obesity) did not change over time. The number of OAR dropped significantly (-0.5 cases/year p = 0.02). The procedure time (2005-2007: 192.2 ± 87.5min to 2017-2019: 235.6 ± 88.2min; p = 0.0001) and the length of stay (2005-2007: 12.0 ± 7.9 to 2017-2019: 17.0 ± 23.1; p = 0.03) increased significantly, whereas the in-hospital mortality, length of ICU stay and complication rates didn't, nor did AAA anatomy. Upon multivariate analysis, annual number of OAR and any additional anastomosis significantly influenced procedure time, trainee involvement, for example, did not. Hospital length-of-stay depended on patient age (p = 0.002), complication rates (p < 0.0001) and procedure time (p = 0.006).

Conclusion: Mortality and complication rates for OAR have remained low and constant. With the increase of EVAR, the absolute number of OARs has decreased significantly. However, the total procedure time has increased and depends significantly on the annual number of OARs in total and per surgeon. This might influence outcome parameters and should be implanted in future surgical education.
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http://dx.doi.org/10.1016/j.jsurg.2022.01.010DOI Listing
June 2022

Learning curve and proficiency metrics for transcarotid artery revascularization.

J Vasc Surg 2022 Jun 19;75(6):1966-1976.e1. Epub 2022 Jan 19.

Department of Medicine, University of Maryland, Baltimore, Md.

Background: When introduced to a new procedure, physicians improve their performance and reduce their procedural adverse event rates rapidly during the initial cases and then improvement slows, signaling that proficiency has been achieved. Determining when they have acquired proficiency has important implications for procedural innovation, education, credentialing, and patient safety. We analyzed the worldwide experience with transcarotid artery revascularization (TCAR), a hybrid approach to carotid revascularization, to identify the (1) procedural performance measures associated with clinical and technical adverse events; (2) target levels of performance measures that minimize adverse event rates; and (3) number of TCAR cases needed to achieve the target levels for the performance measures.

Methods: The patient, lesion, and physician characteristics were collected for each TCAR procedure performed by each physician worldwide in an international quality assurance database. Four procedural performance measures were recorded for each procedure: flow-reversal time, fluoroscopy time, contrast volume, and total skin-to-skin time. Composite clinical adverse events (ie, transient ischemic attack, stroke, myocardial infarction, death) and composite technical adverse events (ie, aborted procedure, conversion to surgery, bleeding, dissection, cranial nerve injury, device failure), occurring within 24 hours were also recorded. Correlations between each performance measure and the clinical and technical adverse event rates were computed. The inflection points in the performance measures were identified at which no further improvements occurred in the adverse event rates. Finally, the minimum number of TCAR cases required to achieve the target performance measure levels was computed.

Results: A total of 18,240 procedures performed by 1273 physicians were analyzed. Of the 18,240 patients, 34.9% were women and 62.5% were asymptomatic. The flow-reversal time correlated with clinical adverse events adjusted for age, sex, and symptomatic status (R = 0.91; P < .0001) and adjusted technical adverse events (R = 0.86; P < .0001). The skin-to-skin time correlated with adjusted technical adverse events (R = 0.92; P < .0001). A reduction in flow-reversal times to <13.1 minutes and the skin-to-skin time to <81 minutes did not translate into further improvements in the adverse event rates. A minimum of 26 TCAR cases was required to achieve the target flow-reversal time, and a minimum of 15 cases was required to achieve the target skin-to-skin time.

Conclusions: The flow-reversal time and skin-to-skin time are appropriate performance measures for establishing the level of expertise of physicians as they acquire skills to perform TCAR. A target time of ≤13.1 minutes for flow-reversal and 81 minutes for skin-to-skin time minimized the adverse event rates. Familiarity with the steps involved in performing TCAR was achieved after ≥15 cases, and minimizing clinical adverse events occurred after ≥26 cases.
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http://dx.doi.org/10.1016/j.jvs.2021.12.073DOI Listing
June 2022

Pleural effusion: a potential surrogate marker for higher-risk patients with acute type B aortic dissections.

Eur J Cardiothorac Surg 2022 03;61(4):816-825

Department for Vascular and Endovascular Surgery, Munich Aortic Center (MAC), Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany.

Objectives: Pleural effusions (PEffs) are known to occur in type B acute aortic dissection (TBAAD). We investigated the relationship between pleural effusion and the development of early or late complications following TBAAD.

Methods: The incidence of PEff (defined as at least an obliteration of the costophrenic angle in a frontal projection) diagnosed on their initial chest X-ray in patients with TBAAD enrolled in the International Registry of Acute Aortic Dissection was examined. We analysed in-hospital outcomes and long-term survival separately for patients with and without PEffs (PEff+ versus PEff-, respectively).

Results: Included were 1252 patients with TBAAD, of whom 224 (17.9%) had PEff. Compared with patients without PEff in the initial chest X-ray, these were significantly older [mean age 67 (SD: 14.7) vs 63.4 (SD: 14.2) years, P = 0.001] and more often female (42.4% vs 34.2%, P = 0.021) and had more comorbidities (known aortic aneurysm, chronic obstructive pulmonary disease, chronic renal failure, diabetes, congestive heart failure or mitral valve disease). PEff was associated with higher in-hospital mortality (16.1% vs 9.1%, P = 0.002) and increased rates of neurological complications (16.6% vs 11.1%, P = 0.029), acute renal failure (27.2% vs 19.7%, P = 0.017) and hypotension (17.4% vs 9.6%, P = 0.001). In addition, patients with PEff underwent aortic repair more frequently (44.6% vs 32.5%, P < 0.001). In the long-term patients with PEff showed lower 5-year post-discharge survival (67.6% vs 77.6%, P = 0.004). Multivariable analysis with propensity-matched data showed that PEff was not an independent risk factor for in-hospital mortality (odds ratio 1.9, 95% CI 0.8-4.4, P = 0.141).

Conclusions: Patients with TBAAD and evidence of PEff showed a higher in-hospital mortality, are more likely to develop additional in-hospital complications and have a decreased likelihood of survival during follow-up. However, according to propensity-matched analysis, PEff remained not as an independent predictor of worse outcome but might serve as an early surrogate marker to identify higher-risk patients.
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http://dx.doi.org/10.1093/ejcts/ezab540DOI Listing
March 2022

Emerging evidence suggests that patients with high-grade asymptomatic carotid stenosis should be revascularized.

J Vasc Surg 2022 01;75(1S):23S-25S

Section of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH.

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http://dx.doi.org/10.1016/j.jvs.2021.06.002DOI Listing
January 2022

Optimal management of asymptomatic carotid stenosis in 2021: the jury is still out. An international, multispecialty, expert review and position statement.

Int Angiol 2022 Apr 16;41(2):158-169. Epub 2021 Dec 16.

Department of Clinical Research, University of Poitiers, CHU de Poitiers, Poitiers, France.

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients <75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.
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http://dx.doi.org/10.23736/S0392-9590.21.04825-2DOI Listing
April 2022

Concomitantly discovered visceral artery aneurysms do rarely grow during cancer therapy.

Clin Anat 2022 Apr 2;35(3):296-304. Epub 2021 Dec 2.

Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.

Visceral artery aneurysms (VAA) are a rare entity of arterial aneurysms with the imminent threat of rupture. The impact of cancer and chemotherapy on the growth of VAAs is unknown. A retrospective dual center cohort study of patients with concomitant VAA and different types of cancer was conducted and the impact of various chemotherapeutic agents on VAA growth was studied by sequential CT analysis. For comparison, a non-cancer all comer cohort with VAAs and no cancer was studied to compare different growth rates. The primary endpoint was aneurysm progress or regression >1.75 mm. Chi-square test, Fisher's exact test and Mann-Whitney test was used for statistical comparison. In the 17-year-period from January 2003 to March 2020, 59 patients with 30 splenic artery aneurysms, 14 celiac trunk aneurysms, 11 renal artery aneurysms and 4 other VAA and additional malignancy were identified. 20% of patients suffered from prostate cancer, the rest were heterogeneous. The most prevalent chemotherapies were alkylating agents (23%), antimetabolites (14%) and mitose inhibitors (10%). Eight patients had relevant growth of their VAA and one patient showed diameter regression (average growth rate 0.1 ± 0.5 mm/year). Twenty-nine patients with 14 splenic, 11 RAAs (seven right) and 4 celiac trunk aneurysms were available in the non-cancer comparison cohort (average growth rate 0.5 ± 0.9 mm/year, p = 0.058). However, the growth rate of patients receiving operative treatment for relevant VAA growth was significantly higher (p = 0.004). VAAs grow rarely, and rather slow. Cancer and/or chemotherapy do not significantly influence the annual growth rate. Additional control examinations seem unnecessary.
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http://dx.doi.org/10.1002/ca.23813DOI Listing
April 2022

Translating mouse models of abdominal aortic aneurysm to the translational needs of vascular surgery.

JVS Vasc Sci 2021 3;2:219-234. Epub 2021 Mar 3.

Department for Vascular and Endovascular Surgery, Technical University Munich, Munich, Germany.

Introduction: Abdominal aortic aneurysm (AAA) is a condition that has considerable socioeconomic impact and an eventual rupture is associated with high mortality and morbidity. Despite decades of research, surgical repair remains the treatment of choice and no medical therapy is currently available. Animal models and, in particular, murine models, of AAA are a vital tool for experimental in vivo research. However, each of the different models has individual limitations and provide only partial mimicry of human disease. This narrative review addresses the translational potential of the available mouse models, highlighting unanswered questions from a clinical perspective. It is based on a thorough presentation of the available literature and more than a decade of personal experience, with most of the available models in experimental and translational AAA research.

Results: From all the models published, only the four inducible models, namely the angiotensin II model (AngII), the porcine pancreatic elastase perfusion model (PPE), the external periadventitial elastase application (ePPE), and the CaCl model have been widely used by different independent research groups. Although the angiotensin II model provides features of dissection and aneurysm formation, the PPE model shows reliable features of human AAA, especially beyond day 7 after induction, but remains technically challenging. The translational value of ePPE as a model and the combination with β-aminopropionitrile to induce rupture and intraluminal thrombus formation is promising, but warrants further mechanistic insights. Finally, the external CaCl application is known to produce inflammatory vascular wall thickening. Unmet translational research questions include the origin of AAA development, monitoring aneurysm growth, gender issues, and novel surgical therapies as well as novel nonsurgical therapies.

Conclusion: New imaging techniques, experimental therapeutic alternatives, and endovascular treatment options provide a plethora of research topics to strengthen the individual features of currently available mouse models, creating the possibility of shedding new light on translational research questions.
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http://dx.doi.org/10.1016/j.jvssci.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577080PMC
March 2021

Proximal false lumen thrombosis is associated with low false lumen pressure and fewer complications in type B aortic dissection.

J Vasc Surg 2022 04 3;75(4):1181-1190.e5. Epub 2021 Nov 3.

Vascular Engineering Laboratory, Harry Perkins Institute of Medical Research, Queen Elizabeth II Medical Centre, Nedlands, Western Australia; UWA Centre for Medical Research, The University of Western Australia, Perth, Western Australia; School of Engineering, The University of Western Australia, Perth, Western Australia; Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Australian Research Council Centre for Personalised Therapeutics Technologies, Australian Capital Territory, Australia. Electronic address:

Background: Improved risk stratification is a key priority for type B aortic dissection (TBAD). Partial false lumen thrombus morphology is an emerging predictor of complications. However, partial thrombosis is poorly defined, and its evaluation in clinical studies has been inconsistent. Thus, we aimed to characterize the hemodynamic pressure in TBAD and determine how the pressure relates to the false lumen thrombus morphology and clinical events.

Methods: The retrospective admission computed tomography angiograms of 69 patients with acute TBAD were used to construct three-dimensional computational models for simulation of cyclical blood flow and calculation of pressure. The patients were categorized by the false lumen thrombus morphology as minimal, extensive, proximal or distal thrombosis. Linear regression analysis was used to compare the luminal pressure difference between the true and false lumen for each morphology group. The effect of morphology classification on the incidence of acute complications within 14 days was studied using logistic regression adjusted for clinical parameters. A survival analysis for adverse aortic events at 1 year was also performed using Cox regression.

Results: Of the 69 patients, 44 had experienced acute complications and 45 had had an adverse aortic event at 1 year. The mean ± standard deviation age was 62.6 ± 12.6 years, and 75.4% were men. Compared with the patients with minimal thrombosis, those with proximal thrombosis had a reduced false lumen pressure by 10.1 mm Hg (95% confidence interval [CI], 4.3-15.9 mm Hg; P = .001). The patients who had not experienced an acute complication had had a reduced relative false lumen pressure (-6.35 mm Hg vs -0.62 mm Hg; P = .03). Proximal thrombosis was associated with fewer acute complications (odds ratio, 0.17; 95% CI, 0.04-0.60; P = .01) and 1-year adverse aortic events (hazard ratio, 0.36; 95% CI, 0.16-0.80; P = .01).

Conclusions: We found that proximal false lumen thrombosis was a marker of reduced false lumen pressure. This might explain how proximal false lumen thrombosis appears to be protective of acute complications (eg, refractory hypertension or pain, aortic rupture, visceral or limb malperfusion, acute expansion) and adverse aortic events within the first year.
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http://dx.doi.org/10.1016/j.jvs.2021.10.035DOI Listing
April 2022

A systematic review and meta-analysis on early mortality after abdominal aortic aneurysm repair in females in urgent and elective settings.

J Vasc Surg 2022 03 3;75(3):1082-1088.e6. Epub 2021 Nov 3.

Vascular Surgery Department, Larissa University Hospital, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Objective: Females represent a group of patients with higher mortality after abdominal aortic aneurysm (AAA), endovascular (EVAR), or open surgical (OSR), repair. This systematic review aimed to evaluate the 30-day mortality after AAA repair in females, comparing both EVAR and OSR, in elective and urgent settings.

Methods: The protocol of the review was registered to the PROSPERO database (CRD42021242686). A search of the English literature was conducted, using PubMed, EMBASE, and CENTRAL databases, from inception to March 5, 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). Only studies reporting on 30-day mortality of AAA repair, in urgent and elective settings, comparing EVAR and OSR, in the female population were eligible. Patients were stratified according to the need for elective or urgent repair. Symptomatic and ruptured cases were included into the urgent group. Individual studies were assessed for risk of bias using the (Risk Of Bias In Non-randomised Studies - of Interventions) ROBINS-I tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence. The primary outcome was 30-day mortality after AAA repair in the female population, comparing EVAR and OSR. The outcomes were summarized as odds ratio, along with their 95% confidence intervals (CIs), through a paired meta-analysis.

Results: Eight studies reported data on 30-day mortality following AAA repair. A total of 56,982 females (22,995 EVAR vs 33,987 OSR) were included. A significantly reduced total 30-day mortality rate was recorded among females that underwent EVAR compared with OSR (odds ratio [OR], 0.25; 95% CI, 0.23-0.27; P < .001; Ι = 86%). In addition, a reduced 30-day mortality was found in females that underwent elective EVAR compared with OSR (OR, 0.37; 95% CI, 0.33-0.41; P < .001; Ι = 48%). Despite the fact that OSR was more frequently offered in the urgent setting (OR, 0.21; 95% CI, 0.19-0.23; P < .001; Ι = 84%), EVAR was associated with a reduced 30-day mortality (OR, 0.48; 95% CI, 0.40-0.57; P < .001; Ι = 0%).

Conclusions: In females, EVAR is associated with lower 30-day mortality in both elective and urgent AAA repair, although it appears as less likely to be offered in the setting of urgent AAA repair.
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http://dx.doi.org/10.1016/j.jvs.2021.10.040DOI Listing
March 2022

Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

J Stroke Cerebrovasc Dis 2022 Jan 1;31(1):106182. Epub 2021 Nov 1.

Department of Clinical Research, University of Poitiers, CHU de Poitiers, Poitiers, France.

Objectives: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic.

Materials And Methods: A literature review was performed with a focus on data from recent studies.

Results: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses.

Conclusions: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106182DOI Listing
January 2022

Successful implementation of best medical treatment for patients with asymptomatic carotid artery stenosis within a randomized controlled trial (SPACE-2).

Neurol Res Pract 2021 Oct 19;3(1):62. Epub 2021 Oct 19.

Department of Neurology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.

Background: Asymptomatic carotid artery stenosis (ACS) can be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or best medical treatment (BMT) only. For all treatment options, optimization of vascular risk factors such as arterial hypertension, hyperlipidemia, smoking, obesity, and insufficient physical activity is essential. Data on adherence to BMT and lifestyle modification in patients with ACS are sparse. The subject of this investigation is the implementation and quality of risk factor adjustment in the context of a randomized controlled trial.

Methods: A total of 513 patients in the prematurely terminated, randomized, controlled, multicenter SPACE-2 trial (ISRCTN 78592017) were analyzed within one year after randomization into 3 groups (CEA, CAS, and BMT only) for implementation of prespecified BMT recommendations and lifestyle modifications. Measurement time points were the screening visit and visits after one month (D30), 6 months (M6), and one year (A1). Differences between groups and follow-up visits (FUVs) relative to the screening visit were investigated.

Findings: For all FUVs, a significant increase in statin medication (91% at A1; p < 0.0001) was demonstrated to be associated with a significant decrease (p < 0.01) in cholesterol levels (median 167 mg/dl at A1) and LDL cholesterol levels (median 93 mg/dl at A1). The lowest cholesterol levels were achieved by patients in the BMT group. Seventy-eight percent of all patients reached predefined target cholesterol levels (< 200 mg/dl), with significantly better rates in the BMT group (p = 0.036 at D30). Furthermore, a significant decrease in arterial blood pressure at all FUVs (p < 0.05) was associated with a significant increase in antihypertensive medication (96% at A1, p < 0.0001). However, only 28% of patients achieved the predefined treatment goal of a systolic blood pressure of ≤ 130 mmHg. Forty-two of a total of 100 smokers at the screening visit quit smoking within one year, resulting in a significant increase in nonsmokers at all FUVs (p < 0.0001). Recommended HbA1c levels (< 7%) were achieved in 82% without significant changes after one year. Only 7% of obese (BMI > 25) patients achieved sufficient weight reduction after one year without significant changes at all FUVs (median BMI 27 at A1; p = 0.1201). The BMT group showed significantly (p = 0.024) higher rates of adequate physical activity than the intervention groups. Furthermore, after one year, the BMT group showed a comparatively significantly better implementation of risk factor modification (77%; p = 0.027) according to the treating physician.

Interpretation: SPACE-2 demonstrated sustained improvement in the noninterventional management of vascular risk factors in patients treated in a clinical trial by general practitioners, internists and neurologists. The best implemented treatment targets were a reduction in cholesterol and HbA1c levels. In this context, a significant increase in statin use was demonstrated. Blood pressure control missed its target but was significantly reduced by intensification of antihypertensive medication. Patients on BMT only had better adjusted lipid parameters and were more physically active. However, all groups failed to achieve sufficient weight reduction. Due to insufficient patient recruitment, the results must be interpreted cautiously.

Trial Registration: ISRCTN Registry, ISRCTN78592017, Registered 16 June 2007, https://www.isrctn.com/search?q=78592017 .
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http://dx.doi.org/10.1186/s42466-021-00153-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524978PMC
October 2021

Long Noncoding RNA Controls Advanced Atherosclerotic Lesion Formation and Plaque Destabilization.

Circulation 2021 11 14;144(19):1567-1583. Epub 2021 Oct 14.

Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, Germany (F.F., J. Pauli, H.W., N.G., S.B., S.M., Z.W., W.K., H.-H.E., V.P., L. Maegdefessel).

Background: Long noncoding RNAs (lncRNAs) are important regulators of biological processes involved in vascular tissue homeostasis and disease development. The present study assessed the functional contribution of the lncRNA myocardial infarction-associated transcript () to atherosclerosis and carotid artery disease.

Methods: We profiled differences in RNA transcript expression in patients with advanced carotid artery atherosclerotic lesions from the Biobank of Karolinska Endarterectomies. The lncRNA was identified as the most upregulated noncoding RNA transcript in carotid plaques compared with nonatherosclerotic control arteries, which was confirmed by quantitative real-time polymerase chain reaction and in situ hybridization.

Results: Experimental knockdown of , using site-specific antisense oligonucleotides (LNA-GapmeRs) not only markedly decreased proliferation and migration rates of cultured human carotid artery smooth muscle cells (SMCs) but also increased their apoptosis. mechanistically regulated SMC proliferation through the EGR1 (Early Growth Response 1)-ELK1 (ETS Transcription Factor ELK1)-ERK (Extracellular Signal-Regulated Kinase) pathway. is further involved in SMC phenotypic transition to proinflammatory macrophage-like cells through binding to the promoter region of and enhancing its transcription. Studies using and mice, and Yucatan mini-pigs, as well, confirmed the regulatory role of this lncRNA in SMC de- and transdifferentiation and advanced atherosclerotic lesion formation.

Conclusions: The lncRNA is a novel regulator of cellular processes in advanced atherosclerosis that controls proliferation, apoptosis, and phenotypic transition of SMCs, and the proinflammatory properties of macrophages, as well.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570347PMC
November 2021

Intraoperative completion studies in carotid endarterectomy: systematic review and meta-analysis of techniques and outcomes.

Ann Transl Med 2021 Jul;9(14):1201

Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Background: Declining perioperative stroke and death rates over the past 3 decades have been paralleled by an increasing use of intraoperative completion studies (ICS) following carotid endarterectomy (CEA). Techniques applied include angiography, intraoperative duplex ultrasound (IDUS), flowmetry, and angioscopy. This systematic review and meta-analysis is aiming on providing an overview of techniques and corresponding outcomes.

Methods: A PubMed based systematic literature review comprising the years 1980 through 2020 was performed using predefined keywords to identify articles on different ICS techniques. Pooled analyses and meta-analyses estimating risk ratios (RR) and 95% confidence intervals (CI) were performed to compare outcomes of different ICS modes to nonapplication of any ICS. I values were assessed to quantify study heterogeneities.

Results: Identification of 34 studies including patients undergoing CEA with angiography (n=53,218), IDUS (n=20,030), flowmetry (n=16,812), and angioscopy (n=2,291). Corresponding rates of perioperative stroke were 1.5%, 1.8%, 3.6%, and 1.5%, perioperative stroke or death occurred in 1.7%, 1.9%, 2.2%, and 2.0%. Intraoperative surgical revision rates were 6.2%, 5.9%, and 7.9% after CEA with angiography, IDUS, and angioscopy, respectively. Compared to nonapplication of any ICS, the pooled analysis revealed angiography to be significantly associated with lower rates of stroke (RR 0.47; 95% CI, 0.36-0.62; P<0.0001) and stroke or death (RR 0.76; 95% CI, 0.70-0.83; P<0.0001). IDUS was significantly associated with lower rates of stroke (RR 0.56; 95% CI, 0.43-0.73; P<0.0001) and stroke or death (RR 0.83; 95% CI, 0.74-0.93; P=0.0018), whereas angioscopy showed a significant association with a lower stroke rate (RR 0.48; 95% CI, 0.033-0.68; P=0.0001), but no effect on the combined stroke or death rate. Angioscopy was associated with a higher intraoperative revision rate compared to angiography (RR 1.29; 95% CI, 1.07-1.54; P=0.006). The meta-analyses confirmed lower perioperative stroke or death rates for angiography (RR 0.83; 95% CI, 0.76-0.91) and IDUS (RR 0.86; 95% CI, 0.76-0.98) compared to non-application of any ICS, whereas flowmetry showed no significant association.

Conclusions: This study represents the first systematic literature review and meta-analysis on usage of ICSs in CEA. Data strongly indicate a significant beneficial effect of angiography, IDUS, and angioscopy on perioperative CEA outcomes. Any carotid surgeon should consider implementation of ICSs in his routine armamentarium.
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http://dx.doi.org/10.21037/atm-20-2931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350645PMC
July 2021

European Stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis.

Eur Stroke J 2021 Jun 18;6(2). Epub 2021 Jun 18.

Department for Vascular and Endovascular Surgery, University Hospital, Technical University of Munich (TUM), Munich, Germany.

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. The aim of this guideline is to analyse the evidence pertaining to medical, surgical and endovascular treatment of patients with carotid stenosis. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Based on moderate quality evidence, we recommend carotid endarterectomy (CEA) in patients with ≥60-99% asymptomatic carotid stenosis considered to be at increased risk of stroke on best medical treatment (BMT) alone. We also recommend CEA for patients with ≥70-99% symptomatic stenosis, and we suggest CEA for patients with 50-69% symptomatic stenosis. Based on high quality evidence, we recommend CEA should be performed early, ideally within two weeks of the last retinal or cerebral ischaemic event in patients with ≥50-99% symptomatic stenosis. Based on low quality evidence, carotid artery stenting (CAS) may be considered in patients < 70 years old with symptomatic ≥50-99% carotid stenosis. Several randomised trials supporting these recommendations were started decades ago, and BMT, CEA and CAS have evolved since. The results of another large trial comparing outcomes after CAS versus CEA in patients with asymptomatic stenosis are anticipated in the near future. Further trials are needed to reassess the benefits of carotid revascularisation in combination with modern BMT in subgroups of patients with carotid stenosis.
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http://dx.doi.org/10.1177/23969873211026990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370086PMC
June 2021

European Stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis.

Eur Stroke J 2021 Jun 11;6(2):I-XLVII. Epub 2021 May 11.

Department for Vascular and Endovascular Surgery, University Hospital, Technical University of Munich (TUM), Munich, Germany.

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. The aim of this guideline is to analyse the evidence pertaining to medical, surgical and endovascular treatment of patients with carotid stenosis. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Based on moderate quality evidence, we recommend carotid endarterectomy (CEA) in patients with ≥60-99% asymptomatic carotid stenosis considered to be at increased risk of stroke on best medical treatment (BMT) alone. We also recommend CEA for patients with ≥70-99% symptomatic stenosis, and we suggest CEA for patients with 50-69% symptomatic stenosis. Based on high quality evidence, we recommend CEA should be performed early, ideally within two weeks of the last retinal or cerebral ischaemic event in patients with ≥50-99% symptomatic stenosis. Based on low quality evidence, carotid artery stenting (CAS) may be considered in patients < 70 years old with symptomatic ≥50-99% carotid stenosis. Several randomised trials supporting these recommendations were started decades ago, and BMT, CEA and CAS have evolved since. The results of another large trial comparing outcomes after CAS versus CEA in patients with asymptomatic stenosis are anticipated in the near future. Further trials are needed to reassess the benefits of carotid revascularisation in combination with modern BMT in subgroups of patients with carotid stenosis.
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http://dx.doi.org/10.1177/23969873211012121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370069PMC
June 2021

Multispectral optoacoustic tomography of lipid and hemoglobin contrast in human carotid atherosclerosis.

Photoacoustics 2021 Sep 9;23:100283. Epub 2021 Jul 9.

Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), Technical University of Munich, Munich, Germany.

Several imaging techniques aim at identifying features of carotid plaque instability but come with limitations, such as the use of contrast agents, long examination times and poor portability. Multispectral optoacoustic tomography (MSOT) employs light and sound to resolve lipid and hemoglobin content, both features associated with plaque instability, in a label-free, fast and highly portable way. Herein, 5 patients with carotid atherosclerosis, 5 healthy volunteers and 2 excised plaques, were scanned with handheld MSOT. Spectral unmixing allowed visualization of lipid and hemoglobin content within three ROIs: whole arterial cross-section, plaque and arterial lumen. Calculation of the fat-blood-ratio (FBR) value within the ROIs enabled the differentiation between patients and healthy volunteers (P = 0.001) and between plaque and lumen in patients (P = 0.04). Our results introduce MSOT as a tool for molecular imaging of human carotid atherosclerosis and open new possibilities for research and clinical assessment of carotid plaques.
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http://dx.doi.org/10.1016/j.pacs.2021.100283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340302PMC
September 2021

Management of patients with asymptomatic carotid stenosis may need to be individualized: a multidisciplinary call for action. Republication of J Stroke 2021;23:202-212.

Int Angiol 2021 Dec 27;40(6):487-496. Epub 2021 Jul 27.

School of Medicine, Department of Neurology and Stroke Program, University of Maryland, Baltimore, MD, USA.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery Guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g. silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.
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http://dx.doi.org/10.23736/S0392-9590.21.04751-9DOI Listing
December 2021

Contralateral Stenosis and Echolucent Plaque Morphology are Associated with Elevated Stroke Risk in Patients Treated with Asymptomatic Carotid Artery Stenosis within a Controlled Clinical Trial (SPACE-2).

J Stroke Cerebrovasc Dis 2021 Sep 24;30(9):105940. Epub 2021 Jul 24.

Department of Neurology, University Hospital of Heidelberg, Heidelberg, Germany. Electronic address:

Background: Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS.

Methods: The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed.

Results: Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50% vs. 20%; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70% vs. 20%; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS.

Conclusion: In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105940DOI Listing
September 2021
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