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.

scholarly journals Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeffrey Aalders ◽  
Laurens Léger ◽  
Louis Van der Meeren ◽  
Natasja Van den Vreken ◽  
Andre G. Skirtach ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Myocardial Dysfunction ◽  
Electrode Array ◽  
Cyclic Strain ◽  
Culture Conditions ◽  
Pathogenic Variants ◽  
The Matrix ◽  
Heart Muscle Cells ◽  
Fibrillin 1 ◽  
Induced Pluripotent

Abstract Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by pathogenic variants in the fibrillin-1 (FBN1) gene. Myocardial dysfunction has been demonstrated in MFS patients and mouse models, but little is known about the intrinsic effect on the cardiomyocytes (CMs). In this study, both induced pluripotent stem cells derived from a MFS-patient and the line with the corrected FBN1 mutation were differentiated to CMs. Several functional analyses are performed on this model to study MFS related cardiomyopathy. Atomic force microscopy revealed that MFS CMs are stiffer compared to corrected CMs. The contraction amplitude of MFS CMs is decreased compared to corrected CMs. Under normal culture conditions, MFS CMs show a lower beat-to-beat variability compared to corrected CMs using multi electrode array. Isoproterenol-induced stress or cyclic strain demonstrates lack of support from the matrix in MFS CMs. This study reports the first cardiac cell culture model for MFS, revealing abnormalities in the behavior of MFS CMs that are related to matrix defects. Based on these results, we postulate that impaired support from the extracellular environment plays a key role in the improper functioning of CMs in MFS.

Marfan syndrome and the evolving spectrum of heritable thoracic aortic disease: Do we need genetics for clinical decisions?

VASA ◽  
2010 ◽  
Vol 39 (1) ◽  
pp. 17-32 ◽  
Author(s):  
von Kodolitsch ◽  
Rybczynski ◽  
Bernhardt ◽  
Mir ◽  
Treede ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Autosomal Dominant ◽  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Clinical Implications ◽  
Thoracic Aortic Disease ◽  
Gene Coding ◽  
Autosomal Dominant Fashion ◽  
Fibrillin 1 ◽  
Work Up

Marfan syndrome (MFS) is a disorder of the connective tissue that is inherited in an autosomal dominant fashion and that is classically caused by mutations in the gene coding for fibrillin-1, FBN1. The high mortality of untreated MFS results almost exclusively from aortic complications such as aortic dissection and rupture. However, more than half of patients with Marfan-like features do not have MFS, but have other diseases including inherited aortic aneurysms and dissections (TAAD). We elucidate the increasing spectrum of syndromes associated with Marfan-like features and discuss the clinical implications of these diseases. We performed a systematic review to tabulate all known inherited diseases and syndromes carrying a risk for thoracic aortic disease. We discuss evidence that different syndromes with different causative genes and mutations have different prognoses and profiles of cardiovascular manifestations. We conclude that future decisions for optimized management of patients with inherited TAAD require a comprehensive clinical and genetic work-up.

Aortic Aneurysm

2018 ◽  
Author(s):  
Christine E Lee ◽  
Leily Naraghi ◽  
Beatrice Hoffmann
Keyword(s):  
Aortic Aneurysm ◽  
Aortic Dissection ◽  
Intramural Hematoma ◽  
Aortic Disease ◽  
Magnetic Resonance Images ◽  
Aortic Aneurysms ◽  
High Morbidity ◽  
Aortic Diseases ◽  
Decision Algorithm ◽  
Type B Dissection

Aortic diseases are relatively rare but are associated with high morbidity and mortality. Emergency physicians (EPs) should consider aortic disease in all patients with pain in the torso, particularly those with other diverse or seemingly unconnected complaints. This review summarizes the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes for patients with abdominal aortic aneurysms (AAAs), thoracic aortic aneurysms (TAAs), and aortic dissection. Figures show a transverse image of an AAAs with a transmural hematoma, a three-dimensional computed tomographic angiogram (CTA) rendering of a thoracic aneurysm associated with a bicuspid aortic valve in the typical ascending aortic location, a chest x-ray film demonstrating prominent and blurred aortic knob due to TAA, acute aortic dissection subtypes, an electrocardiogram and transesophageal echocardiography of a patient with acute ascending aortic dissection, magnetic resonance images of a patient with dissection of the proximal descending aorta, CT representations of a type A dissection involving a dilated ascending aorta and a type B dissection involving the descending thoracic aorta, and a decision algorithm for evaluation and treatment of a suspected aortic dissection. Tables list normal aortic dimensions by CTA and echocardiography, average annual rate of expansion and rupture of AAA based on current diameter, and the etiology of TAA. Key words: AAA, aorta, aortic dissection, ascending aortic dissection, descending aortic dissection, intimal tear, intramural hematoma, thoracic aortic aneurysm

Genetics of vascular disease: Marfan syndrome and aortic disease

ESC CardioMed ◽  
2018 ◽  
pp. 713-715
Author(s):  
Dorien Schepers ◽  
Bart Loeys
Keyword(s):  
Extracellular Matrix ◽  
Marfan Syndrome ◽  
Transforming Growth Factor Beta ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Aortic Disease ◽  
Extracellular Matrix Protein ◽  
Genetic Defects ◽  
Fibrillin 1 ◽  
Growth Factor Beta

Marfan syndrome is an autosomal dominant, multisystemic disorder, presenting with skeletal, ocular, and cardiovascular symptoms. This connective tissue disease is caused by mutations in FBN1, encoding fibrillin-1, which is an important extracellular matrix protein. Marfan syndrome shows significant clinical overlap with Loeys–Dietz syndrome, which is caused by genetic defects in components of the transforming growth factor-beta pathway: TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, and SMAD3. Overlapping clinical features between Marfan syndrome and Loeys–Dietz syndrome include aortic root aneurysm, arachnodactyly, scoliosis, and pectus deformity.

SMAD3 pathogenic variants: risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium

2019 ◽  
Vol 56 (4) ◽  
pp. 252-260 ◽  
Author(s):  
Ellen M Hostetler ◽  
Ellen S Regalado ◽  
Dong-Chuan Guo ◽  
Nadine Hanna ◽  
Pauline Arnaud ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Cumulative Risk ◽  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Disease ◽  
Thoracic Aortic Aneurysms ◽  
Missense Variants ◽  
Variant Type ◽  
Pathogenic Variants ◽  
Reduced Penetrance

BackgroundPathogenic variants in SMAD3 cause thoracic aortic aneurysms and dissections, along with aneurysms and rupture of other arteries. Here, we examined differences in clinical presentation of aortic events (dissection or surgical repair of an aneurysm) with respect to age and variant type in an international cohort of individuals with SMAD3 variants.MethodsAortic status and events, vital status and clinical features were abstracted through retrospective review of medical records of 212 individuals with 51 unique SMAD3 variants, including haploinsufficiency (HI) and missense substitutions in the MH2 domain, as well as novel in-frame deletions and missense variants in the MH1 domain.ResultsAortic events were documented in 37% of cases, with dissections accounting for 70% of events. The median age at first aortic event was significantly lower in individuals with SMAD3 MH2 missense variants than those with HI variants (42years vs 49 years; p=0.003), but there was no difference in frequency of aortic events by variant type. The cumulative risk of an aortic event was 50% at 54 years of age. No aortic events in childhood were observed.ConclusionsSMAD3 pathogenic variants cause thoracic aortic aneurysms and dissections in the majority of individuals with variable age of onset and reduced penetrance. Of the covariates examined, the type of underlying SMAD3 variant was responsible for some of this variation. Later onset of aortic events and the absence of aortic events in children associated with SMAD3 variants support gene-specific management of this disorder.

Clinical outcomes in hybrid repair procedures for pathologies involving the aortic arch

Vascular ◽  
2014 ◽  
Vol 23 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Sebastian Zerwes ◽  
Giesbert Leissner ◽  
Yvonne Gosslau ◽  
Rudolf Jakob ◽  
Hans-Kees Bruijnen ◽  
...  
Keyword(s):  
Success Rate ◽  
Aortic Arch ◽  
Circulatory Arrest ◽  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Type I ◽  
Technical Success ◽  
Aortic Diseases ◽  
Promising Alternative ◽  
Technical Success Rate

Objective Fifty patients with complex aortic disease, who received hybrid treatment of the aortic arch with supra-aortic debranching and endovascular stent-graft repair, were evaluated in regard to events of primary (survival and technical success) and secondary (procedure-related complications) interest. Methods The single-center study was conducted over an eight-year period from December 2004 to December 2012. Treated medical conditions included 23 aortic aneurysms (46%), 21 aortic dissections (42%), and six penetrating aortic ulcers (12%). Procedures were divided into groups of elective, urgent, and emergent. Results Twenty-eight (56%) patients were operated electively, 15 (30%) urgently, and seven (14%) emergently. Sternotomy, cardiopulmonary bypass, and deep hypothermic circulatory arrest were required in 12 (24%) patients. The primary technical success rate was 86% and raised to 92% ( n = 46) of secondary technical success rate after therapy of three type I endoleaks. The 30-day mortality added up to 16.0%, and the mean time of survival was 49.3 months. In a total of eight (16%) patients, an endoleak occurred (five endoleaks type I, three endoleaks type II), while nine (18%) of patients suffered a perioperative stroke. Conclusions In severely ill patients with complex aortic diseases, hybrid therapy may offer a promising alternative to conventional open repair.

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 Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Tharmarajan Ramprasath ◽  
Young-Min Han ◽  
Donghong Zhang ◽  
Chang-Jiang Yu ◽  
Ming-Hui Zou
Keyword(s):  
Mammalian Cells ◽  
Inflammatory Process ◽  
Cell Types ◽  
Aortic Disease ◽  
Kynurenine Pathway ◽  
Aortic Aneurysms ◽  
Health Concern ◽  
High Morbidity ◽  
Aortic Diseases ◽  
And Migration

Aortic diseases are the primary public health concern. As asymptomatic diseases, abdominal aortic aneurysm (AAA) and atherosclerosis are associated with high morbidity and mortality. The inflammatory process constitutes an essential part of a pathogenic cascade of aortic diseases, including atherosclerosis and aortic aneurysms. Inflammation on various vascular beds, including endothelium, smooth muscle cell proliferation and migration, and inflammatory cell infiltration (monocytes, macrophages, neutrophils, etc.), play critical roles in the initiation and progression of aortic diseases. The tryptophan (Trp) metabolism or kynurenine pathway (KP) is the primary way of degrading Trp in most mammalian cells, disturbed by cytokines under various stress. KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), etc. Depends on the cell types, these metabolites can elicit both hyper- and anti-inflammatory effects. Accumulating evidence obtained from various animal disease models indicates that KP contributes to the inflammatory process during the development of vascular disease, notably atherosclerosis and aneurysm development. This review outlines current insights into how perturbed Trp metabolism instigates aortic inflammation and aortic disease phenotypes. We also briefly highlight how targeting Trp metabolic pathways should be considered for treating aortic diseases.

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