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Graft infections are associated with severe morbidity and mortality. The widespread use of the frozen elephant technique increases the incidence of complex aortic patients to suffer from graft infections. Surgery of these patients is challenging. Removal of the stent graft portion of the frozen elephant technique prosthesis via sternotomy carries the risk of irreparable damage to the descending aorta. There is currently no single-stage surgical strategy that allows for the removal of all infected material apart from a hemi-clamshell approach. This approach is technically demanding and associated with significant morbidity and mortality. This results in conservative treatment in a substantial number of patients. Pericardial tube grafts have shown to be an excellent option in treating graft infections in various aortic segments with promising results concerning freedom of re-infection and survival. We report a single-stage, trans-sternal approach to remove all infected materials and simultaneously treat the descending aorta to prevent aortic catastrophe in 2 consecutive cases.

Objective To determine the outcome of Stanford type B aortic dissection in patients with Marfan syndrome and to evaluate aortic diameters at time of dissection as well as the impact of previous aortic root replacement. Methods Analysis of all patients with Marfan syndrome fulfilling Ghent criteria seen at this institution since 1995 until 2022. Results Thirty-six (19%) out of 188 patients with Marfan syndrome suffered from Stanford type B aortic dissection during the study period. Mean aortic diameter at time of dissection was 39.0 mm (95% CI: 35.6-42.3). Mean pre-dissection diameter (available in 25% of patients) was 32.1 mm (95% CI: 28.0-36.3) and mean expansion was 19% (95% CI: 11.9-26.2). There was no correlation between age and diameter at time of dissection ( Conclusions Stanford type B dissection in patients with Marfan syndrome occurs far below accepted thresholds for intervention. Risk for type B dissection is present throughout lifetime and two third of patients need an intervention after dissection. There is no difference in freedom from type B dissection between a Bentall procedure and a valve-sparing root replacement.

OBJECTIVES The prevalence and aetiology of acute aortic dissection type A (AADA) in patients ≤30 years is unknown. The aims of this clinical study were to determine the prevalence and potential aetiology of AADA in surgically treated patients ≤30 years and to evaluate the respective postoperative outcomes in this selective group of patients in a large multicentre study. METHODS Retrospective data collection was performed at 16 participating international aortic institutions. All patients ≤30 years at the time of dissection onset were included. The postoperative results were analysed with regard to connective tissue disease (CTD). RESULTS The overall prevalence of AADA ≤30 years was 1.8% (139 out of 7914 patients), including 51 (36.7%) patients who were retrospectively diagnosed with CTD. Cumulative postoperative mortality was 8.6%, 2.2% and 1.4%. Actuarial survival was 80% at 10 years postoperatively. Non-CTD patients (n = 88) had a significantly higher incidence of arterial hypertension (46.6% vs 9.8%; P CONCLUSIONS The prevalence of AADA in surgically treated patients ≤30 years is

Large thoracic and thoraco-abdominal aneurysms may compress adjacent mediastinal structures. We present a case of a large thoraco-abdominal aneurysm compressing the left atrium and leading to functional mitral valve stenosis after total aortic arch repair, requiring urgent open thoraco-abdominal aneurysm repair.

OBJECTIVES Thoracic endovascular aortic repair is the treatment of choice in complicated acute type B aortic dissection. How to infer predissection aortic diameter is not well understood. Our aim was to delineate changes in descending aortic geometry due to dissection. METHODS Five tertiary centres reviewed their acute aortic dissection type B databases containing 802 patients. All patients who had undergone computed tomography angiography less than 2 years before and immediately after aortic dissection onset were included. We compared the aortic geometry before and after the dissection onset. RESULTS Altogether 25 patients were included [median age 60 (first quartile 52, third quartile 72) years; 60% men]. In all except 1 patient, the maximum descending aortic diameter was less than 45 mm before aortic dissection onset. The largest increase in diameter induced by the dissection was observed in the proximal descending aorta 28.2 (25.1, 32.1) vs 34.6 (31.3, 39.1) mm (+6.4 mm; +23%; P < 0.001). The thoracic descending aortic length increased after the dissection onset [253.3 (229.3, 271.9) vs 261.3 (247.9, 285.4) mm; P = 0.003]. The predissection aortic diameter of the proximal thoracic descending aorta was 7.9 (5.2, 10.7) mm larger ( P < 0.001) than the post-dissection area-derived true-lumen diameter and 2.5 (1.3, 6.1) mm larger than the maximum true-lumen diameter ( P < 0.001). CONCLUSIONS Type B aortic dissection increases the diameter, length and volume of the descending thoracic aorta. The predissection aortic diameter most closely resembles the post-dissection maximum diameter of the true lumen.

Transforming growth factor–β (TGFβ) signaling drives aneurysm progression in multiple disorders, including Marfan syndrome (MFS), and therapies that inhibit this signaling cascade are in clinical trials. TGFβ can stimulate multiple intracellular signaling pathways, but it is unclear which of these pathways drives aortic disease and, when inhibited, which result in disease amelioration. Here we show that extracellular signal–regulated kinase (ERK) 1 and 2 and Smad2 are activated in a mouse model of MFS, and both are inhibited by therapies directed against TGFβ. Whereas selective inhibition of ERK1/2 activation ameliorated aortic growth, Smad4 deficiency exacerbated aortic disease and caused premature death in MFS mice. Smad4-deficient MFS mice uniquely showed activation of Jun N-terminal kinase–1 (JNK1), and a JNK antagonist ameliorated aortic growth in MFS mice that lacked or retained full Smad4 expression. Thus, noncanonical (Smad-independent) TGFβ signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease.

ObjectivesThis study aimed at developing a murine model of surgically induced acute aortic dissection type A for investigation of the formation and progression of acute aortic dissection and to test whether this system could be used for biomarker discovery.MethodsAdult fibrillin-1 deficient, Fbn1C1039G/+ mice and wild-type mice were anesthetized, ventilated, and the ascending aorta exposed via hemisternotomy. We hypothesized that acute aortic dissectiion could be induced either by injecting autologous blood into the aortic wall or by injury to the wall with aortic clamping. Echocardiography was done preoperatively, and serum samples were collected before and 30 minutes after the operation and analyzed by enzyme-linked immunosorbent assay.ResultsEchocardiography revealed larger aortic root diameters in Fbn1C1039G/+ compared with wild-type mice (P = .001). Histologic examination showed that aortic clamp injury but not injection of blood leads to large intimal tears, disruption of aortic wall structures, and localized dissection of the aortic media in Fbn1C1039G/+ mice. Acute aortic dissection developed in 4 of 5 Fbn1C1039G/+ mice versus 0 of 5 wild-type mice after aortic clamping (P < .01). Elastin staining showed higher elastic fiber fragmentation and disarray in Fbn1C1039G/+ compared with wild-type mice. Enzyme-linked immunosorbent assay analysis revealed elevated circulating transforming growth factor β1 concentrations after induction of acute aortic dissection in Fbn1C1039G/+ mice (P = .02, 150 ± 61 ng/mL vs 456 ± 97 ng/mL), but not in wild-type or sham-operated mice.ConclusionsAortic clamp injury can induce AAD in Fbn1C1039G/+, but not in wild-type mice. This murine model of surgically induced acute aortic dissection is highly reproducible and nonlethal in the short term. Using this system, we revealed that circulating transforming growth factor β1 is a promising biomarker for acute aortic dissection.

Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents. DOI: http://dx.doi.org/10.7554/eLife.08648.001, eLife digest Marfan syndrome is a disorder that affects the body's connective tissues, which maintain the structure of the body and support organs and other tissues. People with Marfan syndrome have connective tissues that can stretch more than those of other people, which put them at increased risk of a life-threatening tear in their aorta (the main artery in the body), muscle weakness and other problems. A cell communication pathway called TGFβ signaling is involved in cell growth and many other important processes. TGFβ signaling is more active in patients with Marfan syndrome due to mutations in a gene called FBN1. Drugs that block TGFβ signaling—which are also used to treat high blood pressure—can reduce the symptoms of the disorder. Unfortunately, not all people with Marfan disease can tolerate these drugs and other medications called calcium channel blockers, which also lower blood pressure, are often used as an alternative. It is thought that calcium channel blockers help reduce stress on blood vessels, but there is little data to show whether these drugs are safe and helpful for patients with Marfan syndrome. Now, Doyle, Doyle et al. studied the effect of two different calcium channel blockers on mice that have a mutation in Fbn1—the mouse equivalent of FBN1—that is similar to those found in humans with Marfan syndrome. The experiments show that the aortas of these mice grew more quickly and were more likely to tear when compared to mice that did not receive these drugs. Many of these aortic tears were fatal. The calcium channel blockers increased the activity of two signaling molecules that are regulated by TGFβ signaling. Treating the Marfan mice with other drugs that lower the activity of these signaling molecules protected the aorta, even if they were also treated with the calcium channel blockers. Doyle, Doyle et al. examined a registry of human patients. This revealed preliminary evidence that aortic tears and aortic repair surgery were more common in patients with Marfan syndrome who had received calcium channel blockers than patients who had been treated with other drugs. Together, these findings suggest that it may be dangerous to treat patients with Marfan syndrome with calcium channel blockers. Additional work will be needed to confirm this risk, to find out if it extends to other similar conditions, and to explore the therapeutic potential of drugs that target the two enzymes. DOI: http://dx.doi.org/10.7554/eLife.08648.002

Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remains unknown. We show that loss of AT2 expression accelerates the aberrant growth and rupture of the aorta in a mouse model of Marfan syndrome (MFS). The selective AT1 receptor blocker (ARB) losartan abrogated aneurysm progression in the mice; full protection required intact AT2 signaling. The angiotensin-converting enzyme inhibitor (ACEi) enalapril, which limits signaling through both receptors, was less effective. Both drugs attenuated canonical transforming growth factor–β (TGFβ) signaling in the aorta, but losartan uniquely inhibited TGFβ-mediated activation of extracellular signal–regulated kinase (ERK), by allowing continued signaling through AT2. These data highlight the protective nature of AT2 signaling and potentially inform the choice of therapies in MFS and related disorders.

Background— Marfan syndrome (MFS) is caused by mutations in the fibrillin-1 gene and dysregulation of transforming growth factor-β (TGF-β). Recent evidence suggests that losartan, an angiotensin II type 1 blocker that blunts TGF-β activation, may be an effective treatment for MFS. We hypothesized that dysregulation of TGF-β might be mirrored in circulating TGF-β concentrations. Methods and Results— Serum obtained from MFS mutant mice ( Fbn1 C1039G /+ ) treated with losartan was analyzed for circulating TGF-β1 concentrations and compared with those from placebo-treated and wild-type mice. Aortic root size was measured by echocardiography. Data were validated in patients with MFS and healthy individuals. In mice, circulating total TGF-β1 concentrations increased with age and were elevated in older untreated Fbn1 C1039G /+ mice compared with wild-type mice ( P =0.01; n=16; mean±SEM, 115±8 ng/mL versus n=17; mean±SEM, 92±4 ng/mL). Losartan-treated Fbn1 C1039G /+ mice had lower total TGF-β1 concentrations compared with age-matched Fbn1 C1039G /+ mice treated with placebo ( P =0.01; n=18; 90±5 ng/mL), and circulating total TGF-β1 levels were indistinguishable from those of age-matched wild-type mice ( P =0.8). Correlation was observed between circulating TGF-β1 levels and aortic root diameters in Fbn1 C1039G /+ and wild-type mice ( P =0.002). In humans, circulating total TGF-β1 concentrations were elevated in patients with MFS compared with control individuals ( P P ≤0.05). Conclusions— Circulating TGF-β1 concentrations are elevated in MFS and decrease after administration of losartan, β-blocker therapy, or both and therefore might serve as a prognostic and therapeutic marker in MFS.

Objectives: Acute aortic dissection type A is the main cause of mortality in patients with Marfan Syndrome (MFS). The aim of this study was to develop a procedure to surgically induce an acute aortic dissection type A in a mouse model of MFS, and to discover a diagnostic biomarker of the aortic lesion. Methods: Ten fibrillin-1 deficient (Fbn1C1039G/+) and ten wild-type (WT) mice at 8 months of age were intubated, ventilated and the aorta exposed via hemisternotomy. We hypothesized that an aortic dissection type A could be induced by performing an aortic clamp injury. Serum samples were collected before and after induction (30 min) of the aortic lesion from the right femoral vein. Total (acid activated) TGF-beta 1 concentrations were measured by ELISA. Echo measurements of the aortic root were obtained from a parasternal long axis view in all mice. Results: Transthoracic echocardiography of the aortic root performed prior to surgery showed significantly larger diameters in Fbn1C1039G/+ mice compared to WT (p Conclusions: We present a reproducible and in the short-term non-lethal mouse model of a surgically induced acute aortic dissection type A in MFS. TGF-beta 1 serum concentrations after inducing the aortic lesion significantly increased in Fbn1C1039G/+ mice but not in WT and Sham operated mice. TGF-beta 1 is a promising diagnostic biomarker for an acute aortic dissection type A in MFS.

Acute dissection and rupture of aortic aneurysms comprise for 1-2% of all deaths in developed countries. Dilation of the aorta is caused by several different mechanisms including inherited disorders of connective tissue. Recent reports estimate that 20% of patients presenting with thoracic aortic disease do have an underlying genetic basis of disease.