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A new appraisal of the management of acute aortic dissection is timely because of recent developments in diagnostic strategies (including biomarkers and imaging), endograft design, and surgical treatment, which have led to a better understanding of the epidemiology, risk factors, and molecular nature of aortic dissection. Although open surgery is the main treatment for proximal aortic repair, use of endovascular management is now established for complicated distal dissection and distal arch repair, and has recently been discussed as a pre-emptive measure to avoid late complications by inducing aortic remodelling.

Background and objectivesIn personalised external aortic root support (PEARS), a custom-made, macroporous mesh is used to stabilise a dilated aortic root and prevent dissection, primarily in patients with genetically driven aortopathies. Data are needed on the safety and postoperative incidence of aortic events.MethodsWe present a multicentre cohort study evaluating the first 200 consecutive patients (median age 33 years) undergoing surgery with an intention to perform PEARS for aortic root dilatation in 23 centres between 2004 and 2019. Perioperative outcomes were collected prospectively while clinical follow-up was retrieved retrospectively. Median follow-up was 21.2 months.ResultsThe main indication was Marfan syndrome (73.5%) and the most frequent concomitant procedure was mitral valve repair (10%). An intervention for myocardial ischaemia or coronary injury was needed in 11 patients, 1 case resulting in perioperative death. No ascending aortic dissections were observed in 596 documented postoperative patient years. Late reoperation was performed in 3 patients for operator failure to achieve complete mesh coverage. Among patients with at least mild aortic regurgitation (AR) preoperatively, 68% had no or trivial AR at follow-up.ConclusionsThis study represents the clinical history of the first 200 patients to undergo PEARS. To date, aortic dissection has not been observed in the restrained part of the aorta, yet long-term follow-up is needed to confirm the potential of PEARS to prevent dissection. While operative mortality is low, the reported coronary complications reflect the learning curve of aortic root surgery in patients with connective tissue disease. PEARS may stabilise or reduce aortic regurgitation.

Vascular inflammation contributes to cardiovascular diseases such as aortic aneurysm and dissection. However, the precise inflammatory pathways involved have not been clearly defined. We have shown here that subcutaneous infusion of Ang II, a vasopressor known to promote vascular inflammation, into older C57BL/6J mice induced aortic production of the proinflammatory cytokine IL-6 and the monocyte chemoattractant MCP-1. Production of these factors occurred predominantly in the tunica adventitia, along with macrophage recruitment, adventitial expansion, and development of thoracic and suprarenal aortic dissections. In contrast, a reduced incidence of dissections was observed after Ang II infusion into mice lacking either IL-6 or the MCP-1 receptor CCR2. Further analysis revealed that Ang II induced CCR2+CD14hiCD11bhiF4/80- macrophage accumulation selectively in aortic dissections and not in aortas from Il6-/- mice. Adoptive transfer of Ccr2+/+ monocytes into Ccr2-/- mice resulted in selective monocyte uptake into the ascending and suprarenal aorta in regions of enhanced ROS stress, with restoration of IL-6 secretion and increased incidence of dissection. In vitro, coculture of monocytes and aortic adventitial fibroblasts produced MCP-1- and IL-6-enriched conditioned medium that promoted differentiation of monocytes into macrophages, induced CD14 and CD11b upregulation, and induced MCP-1 and MMP-9 expression. These results suggest that leukocyte-fibroblast interactions in the aortic adventitia potentiate IL-6 production, inducing local monocyte recruitment and activation, thereby promoting MCP-1 secretion, vascular inflammation, ECM remodeling, and aortic destabilization.

BackgroundWomen with Turner syndrome (TS) are at increased risk of aortic dissection, which is related to ascending aortic diameter. However, the relation between aortic diameter and outcome is not well determined. This study evaluates the prevalence of aortic dilatation, the growth rate of the aorta and the risk of aortic complications in adults with TS.MethodsSingle centre, retrospective study of all women with TS followed with a strict protocol in an outpatient TS clinic. Aortic diameters were analysed using advanced imaging. The primary outcome was a combined endpoint of aortic-related mortality, aortic dissection and preventive aortic surgery. The secondary endpoint was aortic growth and prevalence of aortic dilatation, defined as an aortic size index >20 mm/m2 at baseline.ResultsAt least one cardiac MR/CT was available in 268 women with TS, having median age of 28.7 (IQR: 21.3–39.7) years. Aortic dilatation was present in 22%. Linear regression identified independent factors associated with larger aortic diameters: age (coefficient=0.23; p<0.001), hypertension (coefficient=2.7; p<0.001), bicuspid aortic valve (coefficient=3.3; p<0.001), 45XO karyotype (coefficient=1.7; p=0.002), weight (coefficient=0.075; p<0.001) and growth hormone treatment (coefficient=1.4; p=0.044). During follow-up (6.8±3.2 years), five women (2%) reached the primary endpoint (two dissections, three aortic surgery). Women withmore than one scan (n=171; 1015 patient-years follow-up), the median aortic growth was 0.20 (IQR: 0.00–0.44) mm/year. In multivariate analysis, aortic growth was not associated with baseline aortic diameter or other variables.ConclusionsAortic dilatation is common and known associations were confirmed in large adult TS cohort However, aortic dissection, related mortality and preventive aortic surgery are rare. Growth hormone treatment in childhood was associated with aortic dimensions.

The clinical manifestations of coronavirus disease 2019 (COVID-19) are non-specific and multi-inflammatory. They vary from mild to severe manifestations that can be life-threatening. The association of SARS-CoV-2 infection and pseudoaneurysm formation or rupture of an already existing aneurysm is still unexplored. Several mechanisms may be involved, including the direct destruction to the artery by the viral infection or through the release of the inflammatory cytokines. We are presenting a case of a 13-year-old girl with a ruptured cerebral pseudoaneurysm of the left middle cerebral artery (M2 segment) with severe intracerebral hemorrhage as the earliest manifestation of COVID-19 infection.

Bicuspid aortic valve is the most common congenital heart defect in adults. Dilatation of the proximal aorta, or bicuspid aortopathy, is present in approximately half these patients and can lead to complications, including aneurysm formation and aortic dissection. Bicuspid aortic valve is the most common congenital heart defect in adults, affecting 1.3% of the population worldwide, and is responsible for more deaths and complications than the combined effects of all the other congenital heart defects. 1 , 2 Although aortic stenosis and regurgitation are the most common complications of a bicuspid aortic valve, dilatation of any or all segments of the proximal aorta from the aortic root to the aortic arch, called bicuspid aortopathy, is also present in approximately 50% of affected persons. 1 – 4 Accumulating evidence suggests that the pattern of aortic dilatation in persons with a bicuspid aortic valve . . .

Vascular Ehlers-Danlos syndrome is a rare severe disease that causes arterial dissections and ruptures that can lead to early death. No preventive treatment has yet been validated. Our aim was to assess the ability of celiprolol, a β1-adrenoceptor antagonist with a β2-adrenoceptor agonist action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome. Our study was a multicentre, randomised, open trial with blinded assessment of clinical events in eight centres in France and one in Belgium. Patients with clinical vascular Ehlers-Danlos syndrome were randomly assigned to 5 years of treatment with celiprolol or to no treatment. Randomisation was done from a centralised, previously established list of sealed envelopes with stratification by patients' age (≤32 years or >32 years). 33 patients were positive for mutation of collagen 3A1 (COL3A1). Celiprolol was administered twice daily and uptitrated every 6 months by steps of 100 mg to a maximum of 400 mg per day. The primary endpoints were arterial events (rupture or dissection, fatal or not). This study is registered with ClinicalTrials.gov, number NCT00190411. 53 patients were randomly assigned to celiprolol (25 patients) or control groups (28). Mean duration of follow-up was 47 (SD 5) months, with the trial stopped early for treatment benefit. The primary endpoints were reached by five (20%) in the celiprolol group and by 14 (50%) controls (hazard ratio [HR] 0·36; 95% CI 0·15–0·88; p=0·040). Adverse events were severe fatigue in one patient after starting 100 mg celiprolol and mild fatigue in two patients related to dose uptitration. We suggest that celiprolol might be the treatment of choice for physicians aiming to prevent major complications in patients with vascular Ehlers-Danlos syndrome. Whether patients with similar clinical presentations and no mutation are also protected remains to be established. French Ministry of Health, Programme Hospitalier de Recherche Clinique 2001.

Aortic dissection and intramural haematoma comprise an aortopathy involving separation of the aortic wall. Underlying mechanisms of the condition remain unclear. Here we show that granulocyte macrophage colony-stimulating factor (GM-CSF) is a triggering molecule for this condition. Transcription factor Krüppel-like factor 6 (KLF6)-myeloid-specific conditional deficient mice exhibit this aortic phenotype when subjected to aortic inflammation. Mechanistically, KLF6 downregulates expression and secretion of GM-CSF. Administration of neutralizing antibody against GM-CSF prevents the condition in these mice. Conversely, administration of GM-CSF in combination with aortic inflammation to wild-type mice is sufficient to induce the phenotype, suggesting the general nature of effects. Moreover, patients with this condition show highly increased circulating levels of GM-CSF, which is also locally expressed in the dissected aorta. GM-CSF is therefore a key regulatory molecule causative of this aortopathy, and modulation of this cytokine might be an exploitable treatment strategy for the condition. Aortic dissection and intramural haematoma are caused by separation of the aortic wall via an unknown mechanism. Here the authors show that the inflammatory cytokine, granulocyte macrophage colony-stimulating factor, is a central regulatory molecule causative of these conditions in mice and humans.

OBJECTIVES The aim of this study was to analyse outcomes of downstream thoracic endovascular aortic repair (TEVAR) following the frozen elephant trunk (FET) procedure. METHODS Sixty-six patients underwent downstream TEVAR following the FET procedure to treat thoracic aortic dissections (n = 42, 64%), aneurysms (n = 19, 29%) or penetrating aortic ulcers involving the aortic arch (n = 5, 8%). Patient and outcome characteristics were analysed. RESULTS Downstream TEVAR was performed 7 [interquartile range: 2–18] months after the FET procedure in 39 male (59%) and 27 female (41%) patients aged 68 [interquartile range: 56, 75] years, including 11 patients (17%) with a connective tissue disease. Before TEVAR, cerebrospinal fluid drainage was put in place in 61 patients (92%). Patients were treated with 1 stent graft (n = 28, 42%), 2 stent grafts (n = 37, 56%) or 3 stent grafts (n = 1, 2%). The femoral artery was accessed through surgical cut-down (n = 15, 23%) or percutaneously (n = 49, 74%). One patient (2%) developed a temporary spinal cord injury that resolved spontaneously. No case of permanent spinal cord injury, stroke or death was observed. After 12 [interquartile range: 2–23] months, 15 patients required an additional aortic reintervention (endovascular: n = 6; surgical: n = 9). CONCLUSIONS Downstream TEVAR following the FET procedure is associated with excellent clinical outcomes. We thus maintain that staging thoracic aortic repair—FET and secondary TEVAR—is a very successful and safe strategy. Certain patients might need a tertiary procedure to fix their entire aortic pathology; therefore, they will require long-term continuous follow-up, ideally in a dedicated aortic clinic.

Sporadic aortic aneurysm and dissections (AADs) are common vascular diseases that carry a high mortality rate. ADAMTS-4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase involved in inflammation and matrix degradation. We previously showed ADAMTS-4 levels were increased in human sporadic descending thoracic AAD (TAAD) samples. Here, we provide evidence that ADAMTS-4 contributes to aortic destruction and sporadic AAD development. In a mouse model of sporadic AAD induced by a high-fat diet and angiotensin II infusion, ADAMTS-4 deficiency ( Adamts-4−/− ) significantly reduced challenge-induced aortic diameter enlargement, aneurysm formation, dissection and aortic rupture. Aortas in Adamts-4−/− mice showed reduced elastic fibre destruction, versican degradation, macrophage infiltration, and apoptosis. Interestingly, ADAMTS-4 was directly involved in smooth muscle cell (SMC) apoptosis. Under stress, ADAMTS-4 translocated to the nucleus in SMCs, especially in apoptotic SMCs. ADAMTS-4 directly cleaved and degraded poly ADP ribose polymerase-1 (a key molecule in DNA repair and cell survival), leading to SMC apoptosis. Finally, we showed significant ADAMTS-4 expression in aortic tissues from patients with sporadic ascending TAAD, particularly in SMCs. Our findings indicate that ADAMTS-4 induces SMC apoptosis, degrades versican, promotes inflammatory cell infiltration, and thus contributes to sporadic AAD development.