6126Peripheral aneurysms in Marfan patients are common and are related to age and advanced aortic disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Mila ◽  
G Teixido Tura ◽  
C Granato ◽  
J Limeres ◽  
L Servato ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Ct Angiography ◽  
Marfan Syndrome ◽  
Aortic Surgery ◽  
Aortic Disease ◽  
Arterial System ◽  
Whole Body ◽  
Fbn1 Mutation ◽  
Peripheral Aneurysms

Abstract Background Peripheral aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their real prevalence in MFS is unknown. Furthermore, they are commonly seen in other genetic entities such as Loeys-Dietz syndrome. We aimed to investigate the prevalence of peripheral aneurysm in Marfan syndrome. Methods Patients with clinical criteria of Marfan syndrome and identified FBN1 mutation were evaluated. Only patients with either MRI or CT angiography assessing peripheral vessels were included in this study. MRI and CT angiography studies were retrospectively evaluated to detect the presence of peripheral aneurysms. Aortic dissection-related arterial dilations were excluded. Aortic events and those related to aneurysm complications were collected during follow-up. Results Two hundred and nine patients with Marfan and FBN1 mutation were evaluated. Of these 136 (65.1%) had undergone either MRA or CTA with peripheral artery study during follow-up. Mean age at the last follow-up visit was 42.4±14.1yrs; 54.4% were men, and mean follow-up 7.3±3.1 years. Sixty-six aneurysms were identified in 42 (30.9%) patients. The most common locations were the iliac arteries in 23. The rest were: renal (7), vertebral (5), splenic (5), coeliac (3), brachiocephalic (1), subclavian (3), carotid (3), axillary (2), internal mammary (3), femoral (2), hypogastric (3), bronchial (2), coronary (1), hepatic (1), lumbar (1), gastroduodenal (1) and popliteal (1). Twenty-six patients (61.9%) had more than one peripheral aneurysm, and only 4 required surgery. Patients with peripheral aneurysms were older (47.2±14.3yrs vs 40.2±13.6yrs, p=0.06) and more frequently men (69.0% vs 47.9% p=0.026). Although patients with peripheral aneurysms did not more frequently have aortic dissection (16.7% vs 17.0%, p=0.586), they did more frequently have aortic surgery (73.8% vs 47.9% p=0.05). Conclusions Peripheral aneurysms are present in one third of Marfan syndrome patients and are related to age and more advanced aortic disease. Systematic use of whole-body vascular assessment in Marfan patients can provide a comprehensive evaluation of the entire arterial system, identifying other sites of vascular involvement at risk of potential complications, and the subgroup of patients with more aggressive vascular disease expression.

scholarly journals Family history of aortic dissection is not a risk factor in Marfan syndrome with a FBN1 gene mutation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Tchitchinadze ◽  
O Milleron ◽  
L Eliahou ◽  
S Jadoui ◽  
N Ould Ouali ◽  
...  
Keyword(s):  
Risk Factor ◽  
Family History ◽  
Aortic Dissection ◽  
Gene Mutation ◽  
Marfan Syndrome ◽  
Aortic Surgery ◽  
Aortic Disease ◽  
Personal Risk ◽  
Fbn1 Gene ◽  
History Of

Abstract Background A history family of aortic dissection was considered as a risk factor for aortic dissection in patients with Marfan syndrome with a FBN1 mutation. Objectives Evaluate whether a family history of aortic dissection is a risk marker for dissection in this population Methods Retrospective study of patients coming to the reference centre between 1996 and 2018, carrying a FBN1 gene mutation. Pedigrees were obtained for each patient, and familial screening actively pursued. Patients with a family history of aortic dissection were compared with patients without family history of aortic dissection. Results 1700 patients (age 33.2 (±17) years, 51% women) with a FBN1 gene mutation were included. 145 (8,5%) patients underwent aortic dissection at a mean age of 37.9 (±11.4) years and 323 (19%) patients had been operated at 33.8 (±13.9) years. 481 patients had a family history of aortic dissection, including 38 who dissected themselves, and 88 who underwent surgery. 1219 had no family history of aortic dissection, including 107 who dissected themselves, and 235 who underwent surgery. Therefore, the personal risk for aortic dissection was similar in patients with and without a family history of aortic dissection (38/481, i.e. 7.9% vs 107/1219, i.e. 8.8%), as was the personal risk for prophylactic aortic surgery (88/481, i.e. 18.3% vs. 253/1219, i.e. 17.2%), and the risk for either aortic dissection or prophylactic aortic surgery (118/481, i.e. 24.5% vs. 328/1219, i.e. 26.9%). Conclusions In Marfan syndrome with a FBN1 gene mutation, a family history of aortic dissection is not a marker of aortic disease severity. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Cardiomyopathy in Genetic Aortic Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Laura Muiño-Mosquera ◽  
Julie De Backer
Keyword(s):  
Marfan Syndrome ◽  
Myocardial Dysfunction ◽  
Genetic Defect ◽  
Positive Family History ◽  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Aortic Diseases ◽  
Pathogenic Variants ◽  
Fibrillin 1

Genetic aortic diseases are a group of illnesses characterized by aortic aneurysms or dissection in the presence of an underlying genetic defect. They are part of the broader spectrum of heritable thoracic aortic disease, which also includes those cases of aortic aneurysm or dissection with a positive family history but in whom no genetic cause is identified. Aortic disease in these conditions is a major cause of mortality, justifying clinical and scientific emphasis on the aorta. Aortic valve disease and atrioventricular valve abnormalities are known as important additional manifestations that require careful follow-up and management. The archetype of genetic aortic disease is Marfan syndrome, caused by pathogenic variants in the Fibrillin-1 gene. Given the presence of fibrillin-1 microfibers in the myocardium, myocardial dysfunction and associated arrhythmia are conceivable and have been shown to contribute to morbidity and mortality in patients with Marfan syndrome. In this review, we will discuss data on myocardial disease from human studies as well as insights obtained from the study of mouse models of Marfan syndrome. We will elaborate on the various phenotypic presentations in childhood and in adults and on the topic of arrhythmia. We will also briefly discuss the limited data available on other genetic forms of aortic disease.

Aortic diseases

ESC CardioMed ◽  
2018 ◽  
pp. 2861-2863
Author(s):  
Bernard Iung
Keyword(s):  
Aortic Valve ◽  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Bicuspid Aortic Valve ◽  
Young Women ◽  
Beta Blockers ◽  
Aortic Aneurysms ◽  
Maximum Diameter ◽  
Aortic Diseases

Aortic diseases encountered in young women are mainly associated with syndromic diseases, which are often heritable, or bicuspid aortic valve. The most frequent syndromic disease is Marfan syndrome. In Marfan syndrome, the risk of aortic dissection is low during pregnancy when the maximum diameter of the ascending aorta is less than 45 mm. Dissection may affect the thoracic ascending or descending aorta. The risk of aortic dissection is low in bicuspid aortic valve when the aortic diameter is less than 50 mm. Beta blockers are recommended throughout pregnancy in Marfan syndrome and are often used in other causes of aortic aneurysms. Close echocardiographic follow-up is needed during pregnancy and after delivery.

Aortic diseases

ESC CardioMed ◽  
2018 ◽  
pp. 2861-2863
Author(s):  
Bernard Iung
Keyword(s):  
Aortic Valve ◽  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Bicuspid Aortic Valve ◽  
Young Women ◽  
Beta Blockers ◽  
Aortic Aneurysms ◽  
Maximum Diameter ◽  
Aortic Diseases

Aortic diseases encountered in young women are mainly associated with syndromic diseases, which are often heritable, or bicuspid aortic valve. The most frequent syndromic disease is Marfan syndrome. In Marfan syndrome, the risk of aortic dissection is low during pregnancy when the maximum diameter of the ascending aorta is less than 45 mm. Dissection may affect the thoracic ascending or descending aorta. The risk of aortic dissection is low in bicuspid aortic valve when the aortic diameter is less than 50 mm. Beta blockers are recommended throughout pregnancy in Marfan syndrome and are often used in other causes of aortic aneurysms. Close echocardiographic follow-up is needed during pregnancy and after delivery.

Endovascular abdominal aortic aneurysm repair in patients with Marfan syndrome

Vascular ◽  
2019 ◽  
Vol 28 (1) ◽  
pp. 48-52
Author(s):  
Allan Marc Conway ◽  
Khalil Qato ◽  
Gautam Anand ◽  
Laurie Mondry ◽  
Gary Giangola ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Open Repair ◽  
Aortic Surgery ◽  
Endovascular Aneurysm Repair ◽  
Aortic Aneurysms ◽  
Type I ◽  
Femoral Access ◽  
Abdominal Aortic ◽  
Aneurysm Repair

Objectives Marfan syndrome patients are at risk for aortic degeneration. Repair is traditionally performed with open surgery as this is deemed more durable. Endovascular aneurysm repair remains controversial. We report on the outcomes of Marfan syndrome patients with abdominal aortic aneurysms undergoing endovascular aneurysm repair. Methods The Vascular Quality Initiative registry identified 35,889 patients, including 29 with Marfan syndrome, treated with endovascular aneurysm repair from January 2003 to December 2017. Outcomes were analyzed per the Society for Vascular Surgery reporting standards. Results Median age was 70.0 years (IQR, 57.0–75.0), and 22 (75.9%) were male. Median aneurysm diameter was 5.3 cm (IQR, 4.9–6.3 cm), with an aortic neck length and diameter of 2.0 cm (IQR, 1.6–2.8 cm) and 2.5 cm (IQR, 2.2–2.8 cm), respectively. Twenty-one (72.4%) patients were asymptomatic, seven (24.1%) symptomatic, and one (3.4%) presented with rupture. Ten (34.5%) patients had prior aortic surgery. Six (20.7%) were unfit for open surgical repair. Length of stay was 2.0 days (IQR, 1.0–3.0 days). Percutaneous femoral access was performed in 15 (51.7%) patients with no complications. A type IA endoleak was present in one (3.4%), type IB in one (3.4%), and type II endoleak in two (6.9%) patients. There were no postoperative pulmonary, cardiac, or neurological complications. In-hospital mortality occurred in one (3.4%) patient who presented with a rupture and had been deemed unfit for open repair. A conversion to open repair was required. The patient expired on post-operative day 0. Early clinical success was achieved in 26 (89.7%) patients. Follow-up was available for 15 (51.7%) patients at a median time of 766 days (IQR, 653–937). There were no reinterventions or mortalities. Change in sac diameter was −0.6 cm (IQR, −1.1 to −0.2 cm), with no type I or III endoleaks. Discussion Endovascular aneurysm repair for patients with Marfan syndrome is feasible, and can be performed safely. Mid-term outcomes suggest this technique is durable. More robust long-term follow-up is needed.

scholarly journals Inhibition of HIPK2 Alleviates Thoracic Aortic Disease in Mice With Progressively Severe Marfan Syndrome

2021 ◽  
Author(s):  
Cristina I. Caescu ◽  
Jens Hansen ◽  
Brittany Crockett ◽  
Wenzhen Xiao ◽  
Pauline Arnaud ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Aortic Aneurysm ◽  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Thoracic Aortic Aneurysm ◽  
Acute Aortic Dissection ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Aortic Disease ◽  
Computational Analyses

Objective: Despite considerable research, the goal of finding nonsurgical remedies against thoracic aortic aneurysm and acute aortic dissection remains elusive. We sought to identify a novel aortic protein kinase that can be pharmacologically targeted to mitigate aneurysmal disease in a well-established mouse model of early-onset progressively severe Marfan syndrome (MFS). Approach and Results: Computational analyses of transcriptomic data derived from the ascending aorta of MFS mice predicted a probable association between thoracic aortic aneurysm and acute aortic dissection development and the multifunctional, stress-activated HIPK2 (homeodomain-interacting protein kinase 2). Consistent with this prediction, Hipk2 gene inactivation significantly extended the survival of MFS mice by slowing aneurysm growth and delaying transmural rupture. HIPK2 also ranked among the top predicted protein kinases in computational analyses of genes differentially expressed in the dilated aorta of 3 MFS patients, which strengthened the clinical relevance of the experimental finding. Additional in silico analyses of the human and mouse data sets identified the TGF (transforming growth factor)-β/Smad3 signaling pathway as a potential target of HIPK2 in the MFS aorta. Chronic treatment of MFS mice with an allosteric inhibitor of HIPK2-mediated stimulation of Smad3 signaling validated this prediction by mitigating thoracic aortic aneurysm and acute aortic dissection pathology and partially improving aortic material stiffness. Conclusions: HIPK2 is a previously unrecognized determinant of aneurysmal disease and an attractive new target for antithoracic aortic aneurysm and acute aortic dissection multidrug therapy.

Long-term follow-up in patients with aortic diseases

ESC CardioMed ◽  
2018 ◽  
pp. 2622-2624
Author(s):  
Udo Sechtem ◽  
Oliver Gaemperli
Keyword(s):  
Aortic Dissection ◽  
Chronic Phase ◽  
Aortic Disease ◽  
Treatment Goals ◽  
Aortic Diseases ◽  
Long Term Follow Up ◽  
Aortic Interventions ◽  
Immediate Surgery

Patients with aortic disease usually require life-long surveillance, regardless of the initial treatment strategy. This surveillance consists of clinical evaluation, reassessment of a patient’s medical therapies and treatment goals, and imaging of the aorta. This chapter addresses the chronic phase of aortic dissection, including patients discharged after aortic interventions. It also deals with the follow-up of patients in whom chronic aortic dissection or aneurysm is diagnosed incidentally and in whom there was no need for immediate surgery.

444Plasma levels of microfibrillar associated protein type 4 (MFAP4) are predictive for aortic dissection in patients with Marfan Syndrome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M M Van Andel ◽  
S Wanga ◽  
X Yin ◽  
P Skroblin ◽  
D R Koolbergen ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Elastic Fiber ◽  
Aortic Distensibility ◽  
High Plasma ◽  
Type B ◽  
Tgf Beta ◽  
Fibrillin 1 ◽  
Aortic Dissections

Abstract Aim Marfan syndrome is a disorder with mutations in the fibrillin-1 gene, leading to elastic fiber degradation and increased TGF-beta signaling. The life-threatening feature of Marfan is aneurysm formation with a risk of fatal aortic dissections. In a proteomics screen, we identified MFAP4, a protein involved in fibrillin-1 and elastic fiber formation, to be increased in the Marfan aorta. We aim to study the role of MFAP4 in Marfan aortic disease. Methods and results MFAP4 co-localizes in the aorta with elastin and collagen fibers. In vitro experiments show that MFAP4 expression is upregulated by TGF-beta, which could explain the increased MFAP4 protein levels in the Marfan aorta. In a substudy of 96 Marfan patients from the COMPARE trial, MFAP4 levels correlate with aortic root diameter (r=0.30, p=0.01). Patients previously enrolled in the COMPARE trial were retrospectively analyzed. Cardiovascular events, including aortic dissection, were assessed. Plasma samples were prospectively collected at time of inclusion in the study and analyzed retrospectively on MFAP4. In the 7 years of follow up, 5 Type B dissections occurred, all of them in patients in the upper tertile of plasma MFAP4. High plasma MFAP4 associates with poor dissection-free survival (Figure 1). Moreover, the aortic distensibility as measure for aortic stiffness and damage, was calculated throughout the aorta from available MRI images of these patients. Interestingly, in the descending thoracic aorta where type B dissections occur, the aortic distensibility is significantly lower (indicating decreased aortic elasticity) in Marfan patients with high plasma MFAP4, thus associating with aortic damage. Figure 1 Conclusion MFAP4, a protein involved in extracellular matrix assembly, is elevated in the Marfan aorta. High plasma MFAP4 seems to reflect aortic damage and predicted type B aortic dissections in up to 7 years follow up.

Maternal and fetal outcomes in pregnancies complicated by Marfan syndrome

Heart ◽  
2019 ◽  
Vol 105 (22) ◽  
pp. 1725-1731 ◽  
Author(s):  
Matthew Cauldwell ◽  
Philip J Steer ◽  
Stephanie L Curtis ◽  
Aarthi Mohan ◽  
Samuel Dockree ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Beta Blockers ◽  
Type B ◽  
Maternal Deaths ◽  
Type B Dissection ◽  
Maternal And Neonatal Outcomes ◽  
Preconception Counselling ◽  
Aortic Size

ObjectivesInformation to guide counselling and management for pregnancy in women with Marfan syndrome (MFS) is limited. We therefore conducted a UK multicentre study.MethodsRetrospective observational study of women with MFS delivering between January 1998 and March 2018 in 12 UK centres reporting data on maternal and neonatal outcomes.ResultsIn total, there were 258 pregnancies in 151 women with MFS (19 women had prior aortic root replacements), including 226 pregnancies ≥24 weeks (two sets of twins), 20 miscarriages and 12 pregnancy terminations. Excluding miscarriages and terminations, there were 221 live births in 139 women. Only 50% of women received preconception counselling. There were no deaths, but five women experienced aortic dissection (1.9%; one type A and four type B—one had a type B dissection at 12 weeks and subsequent termination of pregnancy). Five women required cardiac surgery postpartum. No predictors for aortic dissection could be identified. The babies of the 131 (65.8%) women taking beta-blockers were on average 316 g lighter (p<0.001). Caesarean section rates were high (50%), particularly in women with dilated aortic roots. In 55 women, echocardiographic aortic imaging was available prepregnancy and postpregnancy; there was a small but significant average increase in AoR size of 0.84 mm (Median follow-up 2.3 months)ConclusionThere were no maternal deaths, and the aortic dissection rate was 1.9% (mainly type B). There with no identifiable factors associated with aortic dissection in our cohort. Preconception counselling rates were low and need improvement. Aortic size measurements increased marginally following pregnancy.

Use of 3D Printing to Guide Creation of Fenestrations in Physician-Modified Stent-Grafts for Treatment of Thoracoabdominal Aortic Disease

2020 ◽  
Vol 27 (3) ◽  
pp. 385-393 ◽  
Author(s):  
Yuan-Hao Tong ◽  
Tong Yu ◽  
Min-Jie Zhou ◽  
Chen Liu ◽  
Min Zhou ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Stent Graft ◽  
Aortic Disease ◽  
Covered Stents ◽  
Stent Grafts ◽  
Aortic Stent Graft ◽  
Computed Tomography Images ◽  
Thoracoabdominal Aortic Disease ◽  
3D Printed

Purpose: To summarize the experience and outcomes of total endovascular repair of thoracoabdominal aortic disease using 3-dimensional (3D) printed models to guide on-site creation of fenestrations in aortic stent-grafts. Materials and Methods: From April 2018 to March 2019, 34 patients (mean age 58±14 years; 24 men) with thoracoabdominal aortic disease were treated in our department. Nineteen patients had thoracoabdominal aortic dissection and 15 had thoracoabdominal aortic aneurysm. Preoperatively, a 3D printed model of the aorta was made according to computed tomography images. In the operating room, the main aortic stent-graft was completely released in the 3D printed model, and the position of each fenestration or branch was marked on the stent-graft. The fenestrations were then made using an electric pen. Wires were sewn to the edge of the fenestrations using nonabsorbable sutures. After customization, the aortic stent-graft was reloaded into the delivery sheath and deployed. Results: The printing process took ~5 hours (1 hour for image reconstruction, 3 hours for printing, and 1 hour for postprocessing). The physician-modified stent-grafts had a total of 107 fenestrations secured by 102 bridging stent-grafts, including 73 covered stents and 29 bare stents. The average procedure time was 5.6±1.2 hours, including a mean 1.3 hours for stent-graft customization. No renal insufficiency or paraplegia occurred. Two branch arteries were lost during the operation. One patient (3%) died 1 week after surgery from a retrograde dissection rupture. One patient developed a minor cerebral infarction postoperatively. The mean follow-up time was 8.5 months. There was 1 endoleak from a fenestration (coil embolized) and 4 distal ruptures of the aortic dissection (3 treated and 1 observed). Conclusion: Three-dimensional printing can be used to guide creation of fenestrated stent-grafts for the treatment of thoracoabdominal aortic diseases involving crucial branches. This technique appears to be more accurate than the traditional measurement method, with short-term follow-up demonstrating the safety and reliability of the method. However, further research and development are needed.

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