The Maastricht Acquisition Platform for Studying Mechanisms of Cell-Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease.

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5-5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold of <55 mm. Moreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue-cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell-matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.

The evolution of arch surgery: Frozen elephant trunk or conventional elephant trunk?

Treatment of aortic arch aneurysms and dissections require highly complex surgical procedures with devastating complications and mortality rates. Currently, repair of the complete arch until the proximal descending thoracic aorta consists of a two-stage procedure, called elephant trunk (ET) technique, or a single stage a single-stage technique referred to as frozen elephant trunk (FET). There is conflicting evidence about the perioperative results of ET in comparison with FET. We carried out a meta-analysis to investigate possible differences in perioperative and early (up to 30 days) outcomes of ET vs. FET, particularly for mortality, spinal cord injury (SCI), stroke, and renal failure. We also performed a meta-regression to explore the effects of age and sex as possible cofactors. Twenty-one studies containing data from interventions conducted between 1997 and 2019 and published between 2008 and 2021 with 3153 patients (68.5% male) were included. ET was applied to 1,693 patients (53.7%) and FET to 1460 (46.3%). Overall mortality after ET was 250/1693 (14.8%) and after FET 116/1460 (7.9%). Relative risk (RR) and 95% confidence interval (CI) were 1.37 [1.04 to 1.81], p = 0.027. There was no significant effect of age and sex. SCI occurrence after the second stage of ET was 45/1693 (2.7%) and after FET 70/1,460 patients (4.8%) RR 0.53 [0.35 to 0.81], p = 0.004. Age and sex were not associated with the risk of SCI. No significant differences were observed between ET and FET in the incidence of stroke and renal failure. Our results indicate that ET is associated with higher early mortality but lower incidence of SCI compared to FET. When studies published in the last 5 years were analyzed, no significant differences in mortality or SCI were found between ET and FET. This difference is attributed to a decrease in mortality after ET, as the mortality after FET did not change significantly over time.

Aortic root replacement in severe left ventricular dysfunction: The added value of beating-heart surgery.

There are limits to the use of cardioplegic arrest during complex cardiac surgical procedures, especially in patients with severe left ventricular dysfunction. In the current report, we graphically present the detailed surgical strategy and technique for beating-heart aortic root replacement with concomitant coronary bypass grafting, for patients otherwise deemed inoperable. With support of cardiopulmonary bypass (CPB), beating-heart bypass surgery is realized, after which the bypass grafts can selectively be connected to the CPB, preserving coronary flow. Then, on the beating and perfused heart, a complex procedure such as aortic root replacement can be performed, without jeopardizing postoperative cardiac function. However, several important caveats and remarks regarding the use of beating-heart surgery should be considered, including: coronary perfusion verification and maintenance, temperature management, and prevention of air embolisms. By use of this strategy, risks associated with cardioplegic arrest are minimized, while it circumvents the potential need for long-term postoperative extracorporeal membrane oxygenation.

Postsurgical Thrombotic Microangiopathy and Deregulated Complement.

Postsurgical thrombotic microangiopathy (TMA) is a complication associated with significant morbidity and mortality. Still, the pathophysiological underlying mechanism of postsurgical TMA, a diagnosis often overlooked in postoperative patients with acute kidney injury and thrombocytopenia, is largely unknown. Here, we report the case of a 56-year-old male that developed anuric acute kidney injury, Coombs-negative hemolysis, and thrombocytopenia after surgical aortic arch replacement. Massive ex vivo complement activation on the endothelium, a rare complement gene variant in C2, at-risk haplotype MCPggaac, and excellent response to therapeutic complement inhibition, points to the pivotal role of complement in the pathophysiology of disease. Moreover, the importance of a multidisciplinary team approach in (postsurgical) thrombocytopenia is emphasized.

Editor's Choice - Extending Aortic Replacement Beyond the Proximal Arch in Acute Type A Aortic Dissection: A Meta-Analysis of Short Term Outcomes and Long Term Actuarial Survival.

OBJECTIVE: The extent of aortic replacement during surgery for acute type A aortic dissection (ATAAD) is an important matter of debate. This meta-analysis aimed to evaluate the short and long term outcomes of a proximal aortic repair (PAR) vs. total arch replacement (TAR) in the treatment of ATAAD. DATA SOURCES: A systematic search of PubMed and Embase was performed. Studies comparing PAR to TAR for ATAAD were included. REVIEW METHODS: The primary outcomes were early death and long term actuarial survival at one, five, and 10 years. Random effects models in conjunction with relative risks (RRs) were used for meta-analyses. RESULTS: Nineteen studies were included, comprising 5 744 patients (proximal: n = 4 208; total arch: n = 1 536). PAR was associated with reduced early mortality (10.8% [95% confidence interval (CI) 8.4 - 13.7] vs. 14.0% [95% CI 10.4 - 18.7]; RR 0.73 [95% CI 0.63 - 0.85]) and reduced post-operative renal failure (10.4% [95% CI 7.2 - 14.8] vs. 11.1% [95% CI 6.7 - 17.5]; RR 0.77 [95% CI 0.66 - 0.90]), but there was no difference in stroke (8.0% [95% CI 5.9 - 10.7] vs. 7.3% [95% CI 4.6 - 11.3]; RR 0.87 [95% CI 0.69 - 1.10]). No statistically significant difference was found for survival after one year (83.2% [95% CI 77.5 - 87.7] vs. 78.6% [95% CI 69.7 - 85.5]; RR 1.05 [95% CI 0.99 - 1.11]), which persisted after five years (75.4% [95% CI 71.2 - 79.2] vs. 74.5% [95% CI 64.7 - 82.3]; RR 1.02 [95% CI 0.91 - 1.14]). After 10 years, there was a significant survival benefit for patients who underwent TAR (64.7% [95% CI 61.1 - 68.1] vs. 72.4% [95% CI 67.5 - 76.7]; RR 0.91 [95% CI 0.84 - 0.99]). CONCLUSION: PAR appears to lead to an improved early mortality rate and a reduced complication rate. In the current meta-analysis, the suggestion of an improved 10 year survival benefit of TAR was found, which should be interpreted in the context of potential confounders such as age at presentation, comorbidities, and haemodynamic stability. In any case, PAR seems to be intuitive in older patients with limited dissections, and in those presenting in less stable conditions.

Nicotine promotes vascular calcification via intracellular Ca2+-mediated, Nox5-induced oxidative stress, and extracellular vesicle release in vascular smooth muscle cells.

AIMS: Smokers are at increased risk of cardiovascular events. However, the exact mechanisms through which smoking influences cardiovascular disease resulting in accelerated atherosclerosis and vascular calcification are unknown. The aim of this study was to investigate effects of nicotine on initiation of vascular smooth muscle cell (VSMC) calcification and to elucidate underlying mechanisms. METHODS AND RESULTS: We assessed vascular calcification of 62 carotid lesions of both smoking and non-smoking patients using ex vivo micro-computed tomography (µCT) scanning. Calcification was present more often in carotid plaques of smokers (n = 22 of 30, 73.3%) compared to non-smokers (n = 11 of 32, 34.3%; P < 0.001), confirming higher atherosclerotic burden. The difference was particularly profound for microcalcifications, which was 17-fold higher in smokers compared to non-smokers. In vitro, nicotine-induced human primary VSMC calcification, and increased osteogenic gene expression (Runx2, Osx, BSP, and OPN) and extracellular vesicle (EV) secretion. The pro-calcifying effects of nicotine were mediated by Ca2+-dependent Nox5. SiRNA knock-down of Nox5 inhibited nicotine-induced EV release and calcification. Moreover, pre-treatment of hVSMCs with vitamin K2 ameliorated nicotine-induced intracellular oxidative stress, EV secretion, and calcification. Using nicotinic acetylcholine receptor (nAChR) blockers α-bungarotoxin and hexamethonium bromide, we found that the effects of nicotine on intracellular Ca2+ and oxidative stress were mediated by α7 and α3 nAChR. Finally, we showed that Nox5 expression was higher in carotid arteries of smokers and correlated with calcification levels in these vessels. CONCLUSION: In this study, we provide evidence that nicotine induces Nox5-mediated pro-calcific processes as novel mechanism of increased atherosclerotic calcification. We identified that activation of α7 and α3 nAChR by nicotine increases intracellular Ca2+ and initiates calcification of hVSMCs through increased Nox5 activity, leading to oxidative stress-mediated EV release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease.

Intra-Operative Video-Based Measurement of Biaxial Strains of the Ascending Thoracic Aorta.

Local biaxial deformation measurements are essential for the in-depth investigation of tissue properties and remodeling of the ascending thoracic aorta, particularly in aneurysm formation. Current clinical imaging modalities pose limitations around the resolution and tracking of anatomical markers. We evaluated a new intra-operative video-based method to assess local biaxial strains of the ascending thoracic aorta. In 30 patients undergoing open-chest surgery, we obtained repeated biaxial strain measurements, at low- and high-pressure conditions. Precision was very acceptable, with coefficients of variation for biaxial strains remaining below 20%. With our four-marker arrangement, we were able to detect significant local differences in the longitudinal strain as well as in circumferential strain. Overall, the magnitude of strains we obtained (range: 0.02-0.05) was in line with previous reports using other modalities. The proposed method enables the assessment of local aortic biaxial strains and may enable new, clinically informed mechanistic studies using biomechanical modeling as well as mechanobiological profiling.

Hybrid stenting with silicone Y stents and metallic stents in the management of severe malignant airway stenosis and fistulas.

BACKGROUND: Airway stenting is frequently used in the palliative treatment of patients with advanced tumor-induced airway stenosis and fistulas. However, there is paucity of studies regarding the use of airway stents in restoring patency. The aim of the study was to assess the efficacy and safety of hybrid silicon Y stents and covered self-expanding metal stents (SEMS) and in reestablishing patency in airway stenoses and fistulas. METHODS: This retrospective study included 31 patients between January 2016 to December 2019 with inoperable complex malignant airway stenoses and fistulas, managed with Silicone Y stents, and covered SEMS. The clinical details, clinical outcomes and complications up to 6 months were extracted from medical records. The improvement of performance was assessed based on modified British Medical Research Council (mMRC) dyspnea scores (t=6.892, P<0.001), Karnofsky Performance Scores (KPS) (t=-11.653, P<0.001), and performance status (PS) (t=3.503, P<0.001). RESULT: A total of 31 silicon Y stents and 35 covered SEMSs were inserted. Of the 31 patients (M:F 20:11; age: 54.64±9.57), 25/31 (80.6%) experienced immediate relief of symptoms following stent placement. Patients' mMRC dyspnea scores, KPS, and PS showed significant improvement following stenting. The mean duration of stent placement was 146.3±47.7 days, and 17/31 (55%) patients were alive at 6 months. No major complications related to hybrid stenting were observed during the follow-up period. CONCLUSIONS: Hybrid stenting is a feasible and safe palliative treatment for malignant airway stenosis and fistulas to improve quality of life and can be performed without major complications.

Veno-Arterial Extracorporeal Life Support in Heart Transplant and Ventricle Assist Device Centres. Meta-analysis.

AIMS: Because reported mortality on veno-arterial (V-A) extracorporeal life support (ECLS) substantially varies between centres, the aim of the current analysis was to assess the outcomes between units performing heart transplantation and/or implanting ventricular assist device (HTx/VAD) vs. non-HTx/VAD units in patients undergoing V-A ECLS for cardiogenic shock. METHODS AND RESULTS: Systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed using PubMed/MEDLINE databases until 30 November 2019. Articles reporting in-hospital/30-day mortality and centre's HTx/VAD status were included. In-hospital outcomes and long-term survival were analysed in subgroup meta-analysis. A total of 174 studies enrolling n = 13 308 patients were included with 20 series performed in non-HTx/VAD centres (1016 patients, 7.8%). Majority of patients underwent V-A ECLS for post-cardiotomy shock (44.2%) and acute myocardial infarction (20.7%). Estimated overall in-hospital mortality was 57.2% (54.9-59.4%). Mortality rates were higher in non-HTx/VAD [65.5% (59.8-70.8%)] as compared with HTx/VAD centres [55.8% (53.3-58.2%)], P < 0.001. Estimated late survival was 61.8% (55.7-67.9%) without differences between non-HTx/VAD and HTx/VAD centres: 66.5% (30.3-1.02%) vs. 61.7% (55.5-67.8%), respectively (P = 0.797). No differences were seen with respect to ECLS duration, limb complications, and reoperations for bleeding, kidney injury, and sepsis. Yet, weaning rates were higher in HTx/VAD vs. non-HTx/VAD centres: 58.7% (56.2-61.1%) vs. 48.9% (42.0-55.9%), P = 0.010. Estimated rate of bridge to heart transplant was 6.6% (5.2-8.3%) with numerical, yet not statistically significant, difference between non-HTx/VAD [2.7% (0.8-8.3%)] as compared with HTx/VAD [6.7% (5.3-8.6%)] (P = 0.131). CONCLUSIONS: Survival after V-A ECLS differed according to centre's HTx/VAD status. Potentially different risk profiles of patients must be taken account for before definite conclusions are drawn.

Extracorporeal Life Support in Hemorrhagic Conditions: A Systematic Review.

Extracorporeal life support (ECLS) is indicated in refractory acute respiratory or cardiac failure. According to the need for anticoagulation, bleeding conditions (e.g., in trauma, pulmonary bleeding) have been considered a contraindication for the use of ECLS. However, there is increasing evidence for improved outcomes after ECLS support in hemorrhagic patients based on the benefits of hemodynamic support outweighing the increased risk of bleeding. We conducted a systematic literature search according to the PRISMA guidelines and reviewed publications describing ECLS support in hemorrhagic conditions. Seventy-four case reports, four case series, seven retrospective database observational studies, and one preliminary result of an ongoing study were reviewed. In total, 181 patients were identified in total of 86 manuscripts. The reports included patients suffering from bleeding caused by pulmonary hemorrhage (n = 53), trauma (n = 96), postpulmonary endarterectomy (n = 13), tracheal bleeding (n = 1), postpartum or cesarean delivery (n = 11), and intracranial hemorrhage (n = 7). Lower targeted titration of heparin infusion, heparin-free ECLS until coagulation is normalized, clamping of the endotracheal tube, and other ad hoc possibilities represent potential beneficial maneuvers in such conditions. Once the patient is cannulated and circulation restored, bleeding control surgery is performed for stabilization if indicated. The use of ECLS for temporary circulatory or respiratory support in critical patients with refractory hemorrhagic shock appears feasible considering tailored ECMO management strategies. Further investigation is needed to better elucidate the patient selection and ECLS management approaches.

Evaluating the diagnostic accuracy of maximal aortic diameter, length and volume for prediction of aortic dissection.

OBJECTIVE: Management of thoracic aortic aneurysms (TAAs) comprises regular diameter follow-up until the indication criterion for prophylactic surgery is reached. However, this approach is unable to predict the majority of acute type A aortic dissections (ATAADs). The current study aims to evaluate the diagnostic accuracy of ascending aortic diameter, length and volume for occurrence of ATAAD. METHODS: This two-centre observational cohort study retrospectively screened 477 consecutive patients who presented with ATAAD between 2009 and 2018. Of those, 25 (5.2%) underwent CT angiography (CTA) within 2 years before dissection onset. Aortic diameter, length and volume of these patients ('pre-ATAAD') were compared with those of TAA controls (n=75). Receiver operating curve analysis was performed to evaluate the predictive accuracy of the three different measurements. RESULTS: 96% of patients with pre-ATAAD did not meet the surgical diameter threshold of 55 mm before dissection onset. Maximal aortic diameters (45 (40-49) mm vs 46 (44-49) mm, p=0.075) and volume (126 (95-157) cm3 vs 124 (102-136) cm3, p=0.909) were comparable between patients with pre-ATAAD and TAA controls. Conversely, ascending aortic length (84±9 mm vs 90±16 mm, p=0.031) was significantly larger in patients with pre-ATAAD. All three parameters had an area under the curve of >0.800. At the 55 mm cut-off point, the maximal diameter yielded a positive predictive value (PPV) of 20%. While maintaining same specificity levels, measurements of aortic volume and length showed superior diagnostic accuracy (PPV 55% and 70%, respectively). CONCLUSION: Measurements of aortic volume and length have superior diagnostic accuracy compared with the maximal diameter and could improve the timely identification of patients at risk for ATAAD.

The impact of Centre's heart transplant status and volume on in-hospital outcomes following extracorporeal membrane oxygenation for refractory post-cardiotomy cardiogenic shock: a meta-analysis.

BACKGROUND: Postcardiotomy cardiogenic shock (PCS) that is refractory to inotropic support remains a major concern in cardiac surgery and is almost universally fatal unless treated with mechanical support. While reported mortality rates on ECMO vary from center to center, aim of the current report is assess if the outcomes differ between centres according to volume and heart transplantation status. METHODS: A systematic search was performed according to PRISMA statement using PubMed/Medline databases between 2010 and 2018. Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and heart transplantation status of the centre. Paediatric and congenital heart surgery-related studies along with those conducted in the setting of veno-venous ECMO for respiratory distress syndrome were excluded. Differences were assessed by means of subgroup meta-analysis and meta-regression. RESULTS: Fifty-four studies enrolling N = 4421 ECMO patients were included. Of those, 6 series were performed in non-HTx centres (204 pts.;4.6%). Overall 30-day survival (95% Confidence Intervals) was 35.3% (32.5-38.2%) and did not statistically differ between non-HTx: 33.3% (26.8-40.4%) and HTx centres: 35.7% (32.7-38.8%); Pinteraction = 0.531. There was no impact of centre volume on survival as well: ßcoef = 0.0006; P = 0.833. No statistical differences were seen between HTx and non-HTx with respect to ECMO duration, limb complications, reoperations for bleeding, kidney injury and sepsis. There were however significantly less neurological complications in the HTx as compared to non-HTx centres: 11.9% vs 19.5% respectively; P = 0.009; an inverse relationship was seen for neurologic complications in centres performing more ECMOs annually ßcoef = - 0.0066; P = 0.031. Weaning rates and bridging to HTx and/or VADs were higher in HTx facilities. CONCLUSIONS: There was no apparent difference in survival after ECMO implantation for refractory PCS according to centre's ECMO volume and transplantation status. Potentially different risk profiles of patients in these centres must be taken account for before definite conclusions are drawn.

Pulmonary artery cannulation to enhance extracorporeal membrane oxygenation management in acute cardiac failure.

OBJECTIVES: Pulmonary artery (PA) cannulation during peripheral venoarterial extracorporeal membrane oxygenation (ECMO) has been shown to be effective either for indirect left ventricular (LV) unloading or to allow right ventricular (RV) bypass with associated gas-exchange support in case of acute RV with respiratory failure. This case series reports the results of such peculiar ECMO configurations with PA cannulation in different clinical conditions. METHODS: All consecutive patients receiving PA cannulation (direct or percutaneous) from January 2015 to September 2018 in 3 institutions were retrospectively reviewed. Isolated LV unloading or RV support, as well as dynamic support including initial drainage followed by perfusion through the PA cannula, was used as part of the ECMO configuration according to the type of patient and the patient's haemodynamic/functional needs. RESULTS: Fifteen patients (8 men, age range 45-73 years, EuroSCORE log range 14.45-91.60%) affected by acute LV, RV or biventricular failure of various aetiologies, were supported by this ECMO mode. Percutaneous PA cannulation was performed in 10 patients and direct PA cannulation, in 5 cases. Dynamic ECMO management (initially draining and then perfusing through the PA cannula) was carried out in 6 patients. Mean ECMO duration was 9.1 days (range 6-17 days). One patient exhibited pericardial fluid during the implant of a PA cannula (no lesion found when the chest was opened), and weaning from temporary circulatory support was achieved in 14 patients (1 who received a transplant). Three patients (20%) died in-hospital, and 12 patients were successfully discharged without major complications. CONCLUSIONS: Effective indirect LV unloading in peripheral venoarterial ECMO as well as isolated RV support can be achieved by PA cannulation. Such an ECMO configuration may allow the counteraction of common venoarterial ECMO shortcomings or allow dynamic/adjustable management of ECMO according to specific ventricular dysfunction and haemodynamic needs. Percutaneous PA cannulation was shown to be safe and feasible without major complications. Additional investigation is needed to confirm the safety and efficacy of such an ECMO configuration and management in a larger patient population.

Baseline surgical status and short-term mortality after extracorporeal membrane oxygenation for post-cardiotomy shock: a meta-analysis.

OBJECTIVE: While reported mortality rates on post-cardiotomy extracorporeal membrane oxygenation vary from center to center, impact of baseline surgical status (elective/urgent/emergency/salvage) on mortality is still unknown. METHODS: A systematic search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using PubMed/Medline databases until March 2018 using the keywords "postcardiotomy," "cardiogenic shock," "extracorporeal membrane oxygenation," and "extracorporeal life support." Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and baseline surgical status. The correlations between mortality and percentage of elective/urgent/emergency cases were investigated. Inference analysis of baseline status and extracorporeal membrane oxygenation complications was conducted as well. RESULTS: Twenty-two studies (conducted between 1993 and 2017) enrolling N = 2,235 post-cardiotomy extracorporeal membrane oxygenation patients were found. Patients were mostly of non-emergency status (65.2%). Overall in-hospital/30-day mortality event rate (95% confidence intervals) was 66.7% (63.3-69.9%). There were no differences in in-hospital/30-day mortality with respect to baseline surgical status in the subgroup analysis (test for subgroup differences; p = 0.406). Similarly, no differences between mortality in studies enrolling <50 versus ⩾50% of emergency/salvage cases was found: respective event rates were 66.9% (63.1-70.4%) versus 64.4% (57.3-70.8%); p = 0.525. Yet, there was a significant positive association between increasing percentage of emergency/salvage cases and rates of neurological complications (p < 0.001), limb complications (p < 0.001), and bleeding (p = 0.051). Incidence of brain death (p = 0.099) and sepsis (p = 0.134) was increased as well. CONCLUSION: Other factors than baseline surgical status may, to a higher degree, influence the mortality in patients treated with extracorporeal membrane oxygenation for post-cardiotomy cardiogenic shock. Baseline status, however, strongly influences the complication occurrence while on extracorporeal membrane oxygenation.

Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation.

Aortic aneurysm is a vascular disease whereby the ECM (extracellular matrix) of a blood vessel degenerates, leading to dilation and eventually vessel wall rupture. Recently, it was shown that calcification of the vessel wall is involved in both the initiation and progression of aneurysms. Changes in aortic wall structure that lead to aneurysm formation and vascular calcification are actively mediated by vascular smooth muscle cells. Vascular smooth muscle cells in a healthy vessel wall are termed contractile as they maintain vascular tone and remain quiescent. However, in pathological conditions they can dedifferentiate into a synthetic phenotype, whereby they secrete extracellular vesicles, proliferate, and migrate to repair injury. This process is called phenotypic switching and is often the first step in vascular pathology. Additionally, healthy vascular smooth muscle cells synthesize VKDPs (vitamin K-dependent proteins), which are involved in inhibition of vascular calcification. The metabolism of these proteins is known to be disrupted in vascular pathologies. In this review, we summarize the current literature on vascular smooth muscle cell phenotypic switching and vascular calcification in relation to aneurysm. Moreover, we address the role of vitamin K and VKDPs that are involved in vascular calcification and aneurysm. Visual Overview- An online visual overview is available for this article.

Aorto-atrial fistula formation and therapy.

Aorta-atrial fistulas (AAF) are a rare but complex pathological condition. These fistulas are characterised by aberrant blood flow between the aorta and either atrium. In the present manuscript, we present a comprehensive overview of the clinical characteristics, formation and treatment of this condition. A literature review was conducted using PubMed. Aorta-Atrial Fistula was used as the primary search term. The clinical presentation of AAF encompasses a wide range of signs and symptoms of heart failure including dyspnoea, chest pain, palpitations, fatigue, weakness coughing or oedema. Causes of fistulas can be congenital or acquired, whilst diagnosis is normally achieved via echocardiography or MRI. Due to the low incidence of AAF, no clinical trials have been performed in AAF patients and treatment strategies are based on expert opinion and consensus amongst the treating physicians. Uncorrected AAF may continue to impose a risk of progression to overt heart failure. The repair of an AAF can either be surgical or percutaneous. AAF is a relatively rare but very serious condition. Clinicians should consider the possibility of AAF, when a new continuous cardiac murmur occurs, especially in patients with a history of cardiac surgery or with signs of heart failure. Closure of the AAF fistula tract is generally recommended. Further studies are required to define optimal therapeutic strategies, but these are hindered by the rarity of the occurrence of this disorder.

Aorto-atrial fistula formation and closure: a systematic review.

Blood flow between the aorta and atrium is a rare but complex pathological condition, also known as aorto-atrial fistula (AAF). The exact incidence of this condition is unknown, as are the major precipitating factors and best treatment options. We carried out a systematic review of the available case report literature reporting AAF. We systematically reviewed literature on AAF formation and closure. Separate Medline (PubMed), EMBASE, and Cochrane database queries were performed. The following MESH headings were used: atrium, ventricle, fistula, cardiac, shunts, aortic, aorto-atrial tunnels and coronary cameral fistula. All papers were considered for analysis irrespective of their quality, or the journal in which they were published. Fistula formation from the ascending aorta to the atria occurred more often in the right atrium compared to the left. Endocarditis was the major cause of AAF formation, whilst congenital causes were responsible for nearly 12%. In a number of cases fistula formation occurred secondary to cardiac surgery, whilst chest traumas were a relatively rare cause of AAF. Correction via an open surgical approach occurred in 73.5% of cases, whilst percutaneous intervention was utilised in 10% of patients. In 74.3% of all studied cases the fistula repair was successful and patients survived the procedures. In 14.7% of the cases patients did not survive. Similar outcomes were observed between percutaneous and surgical interventions. Data from larger populations with AAF is lacking, meaning that specific data regarding incidence and prevalence does currently not exist.

Modified Gott shunt to avoid left ventricular overload and cerebral hypoperfusion during distal aortic arch surgery.

We present a simple solution to address-at the same time-the issue of spinal perfusion, overload on the left ventricle, and brain perfusion during complex distal arch and descending aortic surgery. It is a modification of a passive Gott shunt that includes an extra 10-mm tube interposed between the side port of the ascending aorta cannula and the left subclavian artery. This technique may represent an extra option for surgeons during complex aortic surgery to maintain satisfactory distal perfusion, to reduce the cardiac load, and to provide adequate perfusion to the brain.

Minimally invasive management of central ECMO after ascending aortic surgery.

A small percentage of ascending aortic surgical procedures require temporary mechanical circulatory support, of which veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is the most established technique. We present a surgical technique for minimally invasive central V-A ECMO management, avoiding resternotomy or ventricular compression, while maintaining antegrade blood flow and permitting sternal closure following ascending aortic surgery.