Management of aortic disease in children with FBN1-related Marfan syndrome.

Marfan syndrome (MFS) is a hereditary connective tissue disorder with an estimated prevalence of 1:5000-1:10 000 individuals. It is a pleiotropic disease characterized by specific ocular, cardiovascular, and skeletal features. The most common cardiovascular complication is aortic root dilatation which untreated can lead to life-threatening aortic root dissection, mainly occurring in adult patients. Prompt diagnosis, appropriate follow-up, and timely treatment can prevent aortic events. Currently there are no specific recommendations for treatment of children with MFS, and management is greatly based on adult guidelines. Furthermore, due to the scarcity of studies including children, there is a lack of uniform treatment across different centres. This consensus document aims at bridging these gaps of knowledge. This work is a joint collaboration between the paediatric subgroup of the European Network of Vascular Diseases (VASCERN, Heritable Thoracic Aortic Disease Working Group) and the Association for European Paediatric and Congenital Cardiology (AEPC). A group of experts from 12 different centres and 8 different countries participated in this effort. This document reviews four main subjects, namely, (i) imaging of the aorta at diagnosis and follow-up, (ii) recommendations on medical treatment, (iii) recommendations on surgical treatment, and (iv) recommendations on sport participation.

Aortic Replacement for a Crawford II Thoracoabdominal Aneurysm With a Right-Sided Descending Aorta: A Case Report.

A 53-year-old woman was diagnosed with a Crawford II thoracoabdominal aortic aneurysm involving the right-sided descending aorta. The patient underwent aortic replacement via a thoracoabdominal approach. The right-sided descending thoracic aortic aneurysm was excluded. The patient had a favorable postoperative course. The excluded thoracic aneurysm had completely thrombosed without intercostal inflow. The right-sided descending aorta is a rare malformation. The exclusion technique was appropriate because there was no retrograde flow from the intercostal arteries and the Adamkiewicz artery originated from the lumbar region.

A Novel Heterozygous Intronic FBN1 Variant Contributes to Aberrant RNA Splicing in Marfan Syndrome.

BACKGROUND: Marfan syndrome (MFS) is a complex genetic systemic connective tissue disorder. It is well known that genetic factors play a critical role in the progression of MFS, with nearly all cases attributed to variants in the FBN1 gene. METHODS: We investigated a Chinese family with MFS spanning two generations. Whole exome sequencing, in silico analysis, minigene constructs, transfection, RT-PCR, and protein secondary structure analysis were used to analyze the genotype of the proband and his father. RESULTS: The main clinical manifestations of the proband and his father were subluxation of the left lens and high myopia with pectus deformity. Whole exome sequencing identified a novel single nucleotide variant (SNV) in the FBN1 gene at a non-canonical splice site, c.443-3C>G. This variant resulted in two abnormal mRNA transcripts, leading to a frameshift and an in-frame insertion. Further in vitro experiments indicated that the c.443-3C>G variant in FBN1 was pathogenic and functionally harmful. CONCLUSION: This research identified a novel intronic pathogenic FBN1: c.443-3C>G gene variant, which led to two different aberrant splicing effects. Further functional analysis expands the variant spectrum and provides a strong indication and sufficient basis for preimplantation genetic testing for monogenic disease (PGT-M).

Genetic analysis of a novel FBN1 mutation in a pediatric Marfan syndrome patient.

The aim of this study was to investigate a novel FBN1 gene mutation in a pediatric patient with Marfan syndrome (MFS) to provide a theoretical basis for genetic counseling. The subject was a 5-month-old male infant. With informed consent from the proband and his family, 2 mL of peripheral venous blood was collected from the patient, his father, mother, and sister. DNA was extracted using a DNA extraction kit with EDTA-K as an anticoagulant. The extracted DNA was subjected to minigene transcription and bioinformatics analysis. For minigene construction, wild-type and mutant minigenes were inserted into pcMINI and pcMINI-C vectors, respectively. Four recombinant vectors were transfected into the HeLa and 293T cell lines. After transfection for 48 hours, RNA was extracted from eight samples. DNA was also extracted from the family members' samples to construct a library. Target regions were captured using the SureSelect Human All Exon V6 (Agilent) kit and were sequenced with Illumina NovaSeq (sequencing read length 2×150 bp). Bioinformatic analysis identified the c.8226+5del mutation as a variant of uncertain clinical significance (VOUS). Literature and database reviews confirmed that this mutation had not been previously reported, identifying it as a novel mutation. The study identified a novel FBN1 mutation, c.8226+5del, that may be associated with clinical features such as low-set ears and distinctive facial characteristics in the proband. This mutation likely affects normal mRNA splicing, altering the structure and function of Exon 64 and potentially contributing to the development of autosomal dominant MFS.

Cardiovascular Management of Aortopathy in Children: A Scientific Statement From the American Heart Association.

Aortopathy encompasses a spectrum of conditions predisposing to dilation, aneurysm, dissection, or rupture of the aorta and other blood vessels. Aortopathy is diagnosed commonly in children, from infancy through adolescence, primarily affecting the thoracic aorta, with variable involvement of the peripheral vasculature. Pathogeneses include connective tissue disorders, smooth muscle contraction disorders, and congenital heart disease, including bicuspid aortic valve, among others. The American Heart Association has published guidelines for diagnosis and management of thoracic aortic disease. However, these guidelines are predominantly focused on adults and cannot be applied adeptly to growing children with emerging features, growth and developmental changes, including puberty, and different risk profiles compared with adults. Management to reduce risk of progressive aortic dilation and dissection or rupture in children is complex and involves genetic testing, cardiovascular imaging, medical therapy, lifestyle modifications, and surgical guidance that differ in many ways from adult management. Pediatric practice varies widely, likely because aortopathy is pathogenically heterogeneous, including genetic and nongenetic conditions, and there is limited published evidence to guide care in children. To optimize care and reduce variation in management, experts in pediatric aortopathy convened to generate this scientific statement regarding the cardiovascular care of children with aortopathy. Available evidence and expert consensus were combined to create this scientific statement. The most common causes of pediatric aortopathy are reviewed. This document provides a general framework for cardiovascular management of aortopathy in children, while allowing for modification based on the personal and familial characteristics of each child and family.

miRNA-Driven Regulation of Endothelial-to-Mesenchymal Transition Differs among Thoracic Aortic Aneurysms.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End-MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632-driven End-MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End-MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End-MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients' blood. Our findings definitively demonstrate that the End-MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

Complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.

Mutations in fibrillin 1 (FBN1) is the main cause of Marfan syndrome (MFS) with thoracic aortic aneurysm (TAA) as the main complication. Activation of the complement system plays a key role in the formation of thoracic and abdominal aortic aneurysms. However, the role of the complement system in MFS-associated aortic aneurysms remains unclear. In this study, we observed increased levels of complement C3a and C5a in the plasma of MFS patients and mouse, and the increased deposition of the activated complement system product C3b/iC3b was also observed in the elastic fiber rupture zone of 3-month-old MFS mice. The expression of C3a receptor (C3aR) was increased in MFS aortas, and recombinant C3a promoted the expression of cytokines in macrophages. The administration of a C3aR antagonist (C3aRA) attenuated the development of thoracic aortic aneurysms in MFS mice. The increased inflammation response and matrix metalloproteinases activities were also attenuated by C3aRA treatment in MFS mice. Therefore, these findings indicate that the complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.

Temporal Pattern Analysis of Ultrasound Surveillance Data in Vascular Connective Tissue Disorders.

BACKGROUND: Ehlers-Danlos syndrome (EDS), Marfan syndrome (MFS), and Loeys-Dietz syndrome (LDS) are connective tissue disorders frequently associated with vascular aneurysm formation, dissections, and subsequent major complications. Regular imaging surveillance is recommended for these conditions. However, no guidelines currently exist regarding imaging modality or surveillance intervals. METHODS: This retrospective single-center observational study analyzed clinical and imaging data of patients attending an outpatient clinic for vascular connective tissue disorders between August 2008 and January 2024. Imaging (1424 data points in total) and clinical data were extracted from electronic health records. Analysis primarily included a comparison of vessel diameter progression across imaging modalities, with an additional review of the clinical history of vascular events. RESULTS: In total, 19 patients with vascular connective tissue disorders (vCTDs) underwent consultations at our outpatient clinic. Nine (47.4%) patients experienced vascular events, while two (10.5%) passed away during the study period. Multimodal imaging surveillance revealed a tendency towards arterial diameter increase. Consistent ultrasound monitoring provided more reliable diameter progression data for the same arterial segment than a combination of imaging modalities. Temporal analysis indicated a tendency for the continuous growth of the abdominal aorta, the common and internal carotid artery, and the common femoral and popliteal artery. CONCLUSION: The study highlights the importance of standardized, modality-specific imaging protocols in monitoring patients with vCTDs. The variability in disease progression among these patients further complicates surveillance strategies, contemplating the need for individualized approaches. Further research and prospective multicenter studies are required to refine and improve monitoring protocols.

Double somatic mosaicism in Marfan syndrome.

Marfan syndrome (MFS) is a hereditary systemic connective tissue disorder with great clinical variability. It is caused by heterozygous pathogenic variants in the FBN1 gene. Cardinal manifestations involve the cardiovascular, ocular, and skeletal systems. Clinical diagnosis is based on the revised Ghent nosology. We present the case of a child with a Marfan systemic score of 9 whose genetic study revealed two pathogenic mosaic frameshift variants in the FBN1 gene. Mosaicism is very rare in patients diagnosed with MFS, and this is the first description of a patient with two pathogenic mosaic variants in the FBN1 gene. Both variants are present in cells derived from ectodermal (buccal swab) and mesodermal (leukocyte) tissues, suggesting a mutation prior to gastrulation. We propose a defective repair of the de novo variant in the complementary strand as the mechanism that led this individual to be a carrier of two different populations of mutant cells carrying adjacent variants.

Right ventricular function in marfan patients remains stable despite multiple cardiac interventions.

OBJECTIVES: Mitral valve regurgitation and left ventricular dysfunction are cardiovascular symptoms of Marfan syndrome. There is a paucity of information on tricuspid valve regurgitation and right ventricular function. In patients with Marfan syndrome, we looked at long-term changes in right ventricular function, tricuspid valve regurgitation, and freedom from tricuspid valve repair. METHODS: Retrospective-observational single-centre analysis on right ventricular function and tricuspid regurgitation in Marfan patients who underwent surgery with cardioplegic arrest between 1995 and 2020. Patients were followed-up from first operation until death, with echocardiographic changes analysed longitudinally. Composite end-point was TAPSE ≤ 16mm, severe tricuspid regurgitation, or tricuspid repair. RESULTS: The study included 135 patients who underwent 193 operations, 58 of those were reoperations in 40 patients. Median age at first operation was 35 years (IQR 26-46), median follow-up was 8.0 years (IQR 3.0-16.0), and median time-to-first-reoperation was 7.5 years (IQR 3.4-12.5). The composite end-point occurred in 81 observations in 40 patients, mostly as a recurrent event, after median 7.0 years (IQR 1.0-13.0). 10-year-cumulative-incidence for composite end-point was 22.0% (95% CI 15-31), and 9.0% (95% CI 4.4-16) for new-onset TAPSE ≤ 16mm, but no significant change in TAPSE was observed at 10 years. Tricuspid regurgitation was associated with increased risk of annual progression (P < 0.001), but not clinically relevant at 10 years. Actuarial 10-year-survival was 91.1%. CONCLUSIONS: In Marfan patients with a history of cardiac surgery and subsequent reoperations, the right-ventricular function remains stable. The incidence of severe tricuspid regurgitation and tricuspid repair remain low.

Impact of valve-sparing aortic root replacement on aortic fluid dynamics and biomechanics in patients with syndromic heritable thoracic aortic disease.

OBJECTIVES: Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms are poorly understood. This prospective, longitudinal study aims to assess the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients, and to examine whether they present altered haemodynamics or biomechanics prior to surgery compared to sHTAD patients with no indication for surgery (sHTAD-NSx) and healthy volunteers (HV). METHODS: Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two 4D flow CMR studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two age, sex and BSA matched cohorts of 40 HV and 16 sHTAD-NSx patients with available 4D flow CMR, were selected for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV) and aortic strain were analysed in the ascending (AscAo) and descending aorta (DescAo). RESULTS: All patients with sHTAD presented altered haemodynamics and increased aortic stiffness (p<0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm2/s in HV, p=0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p=0.002), and decreased WSS (0.36 vs 0.47N/m2 in HV, p=0.004) in the proximal DescAo. After VSARR, proximal DescAo in-plane rotational flow (p=0.010) and circumferential WSS increased (p=0.011), no longer differing from HV, but through-plane rotational flow, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3cm²/s, p=0.047). Most AscAo flow alterations were restored to physiological values after VSARR. CONCLUSIONS: In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk.

Comparison of long-term outcomes of the Bentall procedure between patients with and without Marfan syndrome.

The Bentall procedure, using a composite valve graft, has become one of the standard therapies for aortic root disease. Patients with Marfan syndrome are prone to aortic annular dilatation and dissection and often undergo aortic root replacement, including the Bentall procedure. Therefore, this study aimed to compare the long-term outcomes of the Bentall procedure between Japanese patients with and without Marfan syndrome. Data from 294 patients who underwent the Bentall procedure over 37 years were retrospectively analyzed. The study compared the data of patients with Marfan syndrome (n = 94) and those without it (n = 200). Patient characteristics, surgical techniques, and postoperative outcomes were evaluated. Statistical analyses were performed to identify risk factors associated with early mortality, late mortality, reoperation, and aortic root reoperation. The early mortality rate was 4.1%, with no significant difference between patients with and without Marfan syndrome. The long-term survival rates at 10, 20, and 30 years were 81.0%, 66.5%, and 49.1%, respectively, with no significant between-group differences. Aortic reoperations were more frequent in patients with Marfan syndrome; however, the number did not differ significantly between the groups. Risk factors for late mortality included diabetes and coronary reimplantation with an inclusion technique. Aortic dissection, Marfan syndrome, and smoking were risk factors for aortic reoperation. Late mortality after the Bentall procedure was comparable between Japanese patients with and without Marfan syndrome although aortic reoperation was significantly frequent in patients with Marfan syndrome. Continuous monitoring and management, including the prevention of aortic dissection and dilation of residual aorta, are crucial for patients with Marfan syndrome undergoing the Bentall procedure.

Assessing hip joint-related structure and patient-reported outcomes in people with Marfan syndrome.

OBJECTIVE: People with Marfan syndrome (MFS) have clinical symptoms of hip pain, but to date, there is limited knowledge about hip-related structural abnormalities in these patients. Therefore, the purpose of this cross-sectional study was to assess hip-related structural abnormalities and patient-reported outcomes (PRO) in a cohort of patients with MFS compared to healthy controls. METHODS: Nineteen individuals with MFS (17 females, 39.8±11.5 years) and 19 age, sex, and body mass index-matched healthy, asymptomatic individuals (17 females, 36.2±12.5 years) underwent radiographic imaging and unilateral hip MRI. The Scoring Osteoarthritis with MRI (SHOMRI) technique was used to assess hip-related morphological abnormalities between the MFS and control groups. All participants completed the Hip disability and Osteoarthritis Outcome Score (HOOS) to assess hip-related symptoms, pain, and function during activities of daily living (ADL) and quality of life (QOL). RESULTS: The MFS group exhibited higher lateral center edge angles (p < .001). Despite similar severity of femoral cartilage damage (p = 1.0), the MFS group exhibited a higher severity (p = 0.046) of acetabular cartilage degeneration (1.21±1.08) compared to the controls (0.53±1.02). There were no between-group differences in severity of labral pathology, subchondral cysts, or edema. Individuals with MFS also self-reported significantly lower HOOS symptoms (p = 0.003), pain (p = 0.014), ADL (p = 0.028), and QOL (p = 0.014) sub-scores, indicating worse hip-related PRO in MFS. CONCLUSION: Our study results suggest that individuals with MFS exhibit early signs of acetabular cartilage degeneration and poor hip-related clinical outcomes compared to healthy individuals. Future work should investigate the underlying biomechanical mechanisms associated with hip joint degeneration in the MFS population.

Mitral Valve Repair for Mitral Regurgitation in Patients With Marfan Syndrome.

BACKGROUND: There is concern about the durability of mitral valve repair (MVr) for mitral regurgitation (MR) in Marfan patients due to limited long-term data. Furthermore, a detailed time course of changes in cardiac function after MVr in Marfan patients has not been reported. We examined repair techniques, postoperative cardiac function, and outcomes of MVr in Marfan patients. METHODS AND RESULTS: We retrospectively reviewed 29 Marfan patients (mean [±SD] age 27.4±14.8 years) who underwent MVr at The University of Tokyo Hospital from 2010 to 2022. The mean follow-up period was 5.2±3.2 years. The causes of MR were isolated anterior leaflet prolapse in 25% of patients, isolated posterior leaflet prolapse in 11%, and bileaflet prolapse in 64%. Echocardiographic findings showed significant decreases in left ventricular (LV) diastolic and left atrial diameters 1 week after MVr. LV systolic diameter was significantly decreased 3 years after MVr, and LV ejection fraction initially declined before subsequently increasing. The in-hospital and 30-day mortality rates were 0%. At 5 years, the overall survival rate was 94% and the rate of freedom from MR was 84%. CONCLUSIONS: The mid- to long-term outcomes after MVr in Marfan patients were satisfactory, supporting the durability of MVr in these patients. Postoperative cardiac reverse remodeling occurred in a phased manner in Marfan patients, similar to that in patients with degenerative MR.

Management of a pregnant woman with Marfan syndrome and aortic root and aberrant right subclavian artery aneurysm: a case report.

Background: Marfan syndrome is a genetic connective tissue disorder that commonly affects the cardiovascular, skeletal, and ocular system. The increased risk of developing thoracic aortic aneurysms that can lead to aortic dissection and rupture is the main source of mortality in these patients. Pregnancy-induced changes can further increase the risk for aortic complications, especially in patients with an aortic root diameter > 45 mm. Case summary: The case of a 26-year-old female with Marfan syndrome who was lost to follow-up for five years and presented to our department being pregnant at 21 weeks is presented. Echocardiography and cardiovascular magnetic resonance (CMR) showed an aortic root diameter of 55 mm and a large aneurysm of an aberrant right subclavian artery. Following multidisciplinary team discussion, valve-sparing aortic root and ascending aortic replacement was performed at 22 weeks of gestation without any complications. During the remaining pregnancy, the patient had frequent clinical and CMR follow-up investigations showing a mild increased size of the subclavian aneurysm. Uncomplicated caesarean delivery was performed at 35 weeks of gestation, and the subclavian artery aneurysm was successfully treated by interventional embolization. Discussion: Although cardiovascular surgery in our patient during pregnancy was uncomplicated, the case illustrates that pre-pregnancy counselling in Marfan patients is recommended to reduce the risk for mother and child.

Comparative Analysis of Long-Term Outcomes in Thoracoabdominal Aortic Aneurysm Repair Between Marfan Syndrome and Non-Marfan Syndrome Patients.

OBJECTIVES: A consensus on the management of thoracoabdominal aortic aneurysms (TAAA) in patients with Marfan syndrome (MFS) has not yet been established. This study aimed to compare the long-term outcomes after open TAAA repair in patients with and without MFS. METHODS: This retrospective study encompassed 230 consecutive patients who underwent TAAA repair between 2012 and 2022, including a comparison of 69 MFS patients and 161 non-MFS patients. The primary endpoint was long-term mortality. The secondary endpoint was early composite adverse events, including early mortality, permanent stroke, permanent paraplegia, permanent renal failure, and reoperation. Univariable and multivariable logistic regression analyses were employed to assess the impact of MFS on early composite adverse events, while univariable and multivariable Cox proportional hazards models were constructed to evaluate the association between MFS and overall mortality. RESULTS: Compared with non-MFS patients, MFS patients were younger (31.9±8.5 vs 44.8±12.3 years; P<0.001), with less comorbid coronary artery disease (0 vs 8.1%; P=0.034), more frequently underwent Crawford extent III repair (56.5% vs 34.8%; P=0.002) and applied normothermic iliac perfusion (91.3% vs 81.4%; P=0.057). There was no significant difference in the rate of early composite adverse events between MFS and non-MFS groups (23.2% vs 14.3%; P=0.099), which was verified by multivariable logistic regression analyses with multiple models. Overall mortality was significantly lower in MFS group compared to non-MFS group (log-rank P=0.026), with 1-, 5- and 10-year cumulative mortality of 4.4% vs 8.7%, 8.1% vs 17.2% and 20.9% vs 36.4%, respectively. Multivariable Cox regression analyses across different models further confirmed MFS as a significant protective factor for overall mortality (Model1: HR 0.31, 95%CI 0.13-0.73, P=0.007; Model2: HR 0.32, 95%CI 0.13-0.75, P=0.009; Model3: HR 0.38, 95%CI 0.15-0.95, P=0.039). CONCLUSIONS: Despite varying risk profiles, MFS patients undergoing open TAAA repair can achieve comparable or even superior outcomes to non-MFS patients under tailored surgical strategies, meticulous perioperative care, and close follow-up surveillance, especially in the long term.

Generation of Marfan syndrome-specific induced pluripotent stem cells harboring FBN1 mutations.

Marfan syndrome (MFS) is a hereditary condition caused by mutations in the FBN1 gene. Genetic mutations in the FBN1 locus impact the function of the encoded protein, Fibrillin 1, a structural molecule forming microfibrils found in the connective tissue. MFS patients develop severe cardiovascular complications including thoracic aortic aneurysm and aortic dissection, which predispose them to an enhanced risk of premature death. Here, we generated two induced pluripotent stem cell (iPSC) lines harboring mutations in the FBN1 gene (p.C1942C>A and c.1954 T>C), directly derived from MFS patients. We have shown that both iPSC lines displayed expression of pluripotency markers, normal karyotype and ability of trilineage differentiation, representing a valuable tool for the identification of new therapeutic strategies for intervening in this disease.

Complicated type B aortic dissection in a pregnant woman with Marfan syndrome.

Marfan syndrome is a rare inherited connective tissue disorder that can result in significant morbidity and mortality. We report a case of a 29-year-old pregnant woman presenting with an acute type B aortic dissection. Owing to cardiopulmonary decompensation and intestinal malperfusion, she underwent an emergency cesarean section followed by left subclavian to carotid transposition and thoracic endovascular aortic repair that was complicated by a retrograde type A aortic dissection and was managed surgically. Molecular testing confirmed the diagnosis of Marfan syndrome. This case highlights that multidisciplinary and hybrid management of challenging cases of acute aortic syndromes can result in a favorable outcome.

Visual Outcomes in Ectopia Lentis in Marfan Syndrome: A Study of Four Surgical Techniques in Children and Adults.

Background/Objectives: To evaluate how the surgical technique and type of implanted intraocular lens influence the postoperative visual acuity and complications in ectopia lentis associated to Marfan syndrome patients. Materials and Methods: The medical records and videos of ectopia lentis surgeries in patients (children and adults) with Marfan syndrome, were retrospectively reviewed and compared. The study included 33 eyes that underwent four different intraocular lens implantation (IOL) techniques: IOL in conjunction with a simple capsular tension ring, IOL in conjunction with a Cionni modified capsular tension ring (m-CTR), two-point scleral IOL fixation and IOL with one haptic in the bag and one haptic sutured to the sclera. Results: Vision significantly improved from a mean preoperative visual acuity of 0.1122 to a mean postoperative visual acuity of 0.4539 in both age groups (p < 0.0001), with no difference in the primary outcome between children and adults. The most common surgical technique used in both age groups was IOL in conjunction with an m-CTR. There was only one major postoperative complication requiring additional surgery. Conclusions: Zonular weakness mainly influenced by age was the most important selection criterion for the surgical approach. Regardless of the technique employed, the postoperative visual acuity was improved in both adults and children.

Are aortic biomechanical properties early markers of dilatation in patients with Marfan syndrome? A systematic review and meta-analysis.

Although tissue stiffness is known to play an important role in aortic dilatation, the current guidelines for offering preventative surgery in patients with Marfan syndrome rely solely on the aortic diameter. In this systematic review and meta-analysis, we analyze and compare literature on in vivo aortic stiffness measures in Marfan patients. Our aim is to assess the potential of these measurements as early indicators of aortic dilatation. Following the PRISMA guidelines, we collected literature on diameter and three in vivo stiffness measures: Pulse wave velocity (PWV), ß -stiffness index (SI) and distensibility, at five different aortic locations in patients with Marfan syndrome. Results were reviewed and compared against each other. For meta-analysis, an augmented dataset was created by combining data from the literature. Regression with respect to age and statistical comparisons were performed. Thirty articles reporting data from 1925 patients with Marfan and 836 patients without Marfan were reviewed. PWV was found to be higher in Marfan, but only in dilated aortas. Distensibility was found to be lower even in non-dilated aortas, and its decrease was associated with higher chances of developing aortic dilatation. ß -SI was higher in Marfan patients and was positively correlated with the rate of aortic dilatation, emphasizing its role as a valuable indicator. In our meta-analysis, all stiffness measures showed a significant variation with age. Distensibility and ß -stiffness index were different in Marfan patients at all locations, and the difference was more pronounced after accounting for age-related variation. From the literature, ß -SI and distensibility emerge as the best predictors of future aortic dilatation. Our meta-analysis quantifies age-related changes in aortic stiffness and highlights the importance of accounting for age in comparing these measurements. Missing diameter values in the literature limited our analysis. Further investigation of criteria combining stiffness and diameter is recommended to better assist clinical decisions for prophylactic surgery.