Marfan Syndrome Group Research Articles

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

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. 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). 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. 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.

Comparative analysis of long-term outcomes in thoracoabdominal aortic aneurysm repair between Marfan syndrome patients and non–Marfan syndrome patients

BackgroundA consensus on the management of thoracoabdominal aortic aneurysm (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. MethodsThis retrospective study examined 230 consecutive patients who underwent TAAA repair between 2012 and 2022, including of 69 MFS patients and 161 non-MFS patients. The primary endpoint was long-term mortality. The secondary endpoint was a composite of early adverse events, including early mortality, permanent stroke, permanent paraplegia, permanent renal failure, and reoperation. Univariable and multivariable logistic regression analyses were used to assess the impact of MFS on early composite adverse events, and univariable and multivariable Cox proportional hazards models were constructed to evaluate the association between MFS and overall mortality. ResultsCompared with non-MFS patients, MFS patients were younger (mean, 31.9 ± 8.5 years vs 44.8 ± 12.3 years; P < .001), had less comorbid coronary artery disease (0 vs 8.1%; P = .034), more frequently underwent Crawford extent III repair (56.5% vs 34.8%; P = .002) and applied normothermic iliac perfusion (91.3% vs 81.4%; P = .057). There was no significant difference in the rate of early composite adverse events between the MFS and non-MFS groups (23.2% vs 14.3%; P = .099), which was verified by multivariable logistic regression analyses with multiple models. Overall mortality was significantly lower in the MFS group compared to the non-MFS group (P = .026, log-rank test), with 1-, 5-, and 10-year cumulative mortality of 4.4% versus 8.7%, 8.1% versus 17.2%, and 20.9% versus 36.4%, respectively. Multivariable Cox regression analyses across different models further confirmed MFS as a significant protective factor for overall mortality (model 1: hazard ratio [HR], 0.31; 95% confidence interval [CI] 0.13-0.73; P = .007; model 2: HR, 0.32, 95% CI, 0.13-0.75; P = .009; model 3: HR, 0.38; 95% CI, 0.15-0.95; P = .039). ConclusionsDespite varying risk profiles, MFS patients undergoing open TAAA repair can achieve comparable or even superior outcomes to non-MFS patients with tailored surgical strategies, meticulous perioperative care, and close follow-up surveillance, especially in the long term.

Anterior scleral thickness in Marfan syndrome: A quantitative analysis.

To investigate the anterior scleral thickness (AST) in patients with Marfan syndrome (MFS). A prospective, cross-sectional study was conducted at the Department of Ophthalmology, Ghent University Hospital, Ghent, including patients with a genetically confirmed clinical diagnosis of MFS and age-, gender- and axial length-matched controls. Subjects with known corneal, conjunctival or scleral pathology and a history of ocular surgery, including pars plana vitrectomy, recent contact lens use or high-grade astigmatism were excluded. Subjects underwent non-cycloplegic autorefraction, Scheimpflug-based corneal tomography, axial length measurement and spectral-domain optical coherence tomography (OCT). AST was manually measured at 1 mm (AST1), 2 mm (AST2) and 3 mm (AST3) from the scleral spur, temporally and nasally. A total of 56 subjects (28 subjects in the MFS group and 28 matched subjects in the control group) were included in this study. In patients with MFS, AST was significantly reduced compared to matched controls, both overall and at every analysed measuring point in the nasal and temporal areas (p < 0.001). Central corneal thickness (CCT) and mean keratometry (Kmean) values were significantly lower in patients with MFS (p < 0.05). A positive correlation was found between nasal AST and CCT in patients with MFS. No correlation was found between AST and Kmean or between AST and axial length. In patients with MFS with ectopia lentis, compared to those without, temporal AST3 was significantly lower (p < 0.05). AST was significantly lower in patients with MFS harbouring a variant predicted to cause haploinsufficiency compared to those with a variant expected to lead to a dominant negative effect for both nasal and temporal measurements. Based on anterior segment OCT measurements, AST of patients with MFS is significantly lower compared to matched controls.

Health-related quality of life in children and adolescents with Marfan syndrome or related disorders: a controlled cross-sectional study

BackgroundThis cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome (MFS) or related disorders and to evaluate the factors associated with HRQoL in this population. Sixty-three children with MFS and 124 age- and sex-matched healthy children were recruited. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) generic questionnaire. The correlation between HRQoL scores and the different continuous parameters (age, body mass index, disease severity, systemic score, aortic sinus diameter, and aerobic physical capacity) was evaluated using Pearson’s or Spearman’s coefficient. A multiple linear regression analysis was performed on the two health summary self-reported PedsQL™ scores (physical and psychosocial) to identify the factors associated with HRQoL in the MFS group.ResultsExcept for emotional functioning, all other domains of HRQoL (psychosocial and physical health, social and school functions) were significantly lower in children with MFS compared to matched healthy children. In the MFS group, the physical health summary score was significantly lower in female than in male patients (self-report: absolute difference [95%CI] = -8.7 [-17.0; -0.47], P = 0.04; proxy-report: absolute difference [95%CI] = -8.6 [-17.3; 0.02], P = 0.05) and also negatively correlated with the systemic score (self-report: R = -0.24, P = 0.06; proxy-report: R = -0.29, P = 0.03) and with the height Z-score (proxy-report: R = -0.29, P = 0.03). There was no significant difference in the physical health summary scores between the different genetic subgroups. In the subgroup of 27 patients who performed a cardiopulmonary exercise test, self- and proxy-reported physical health summary scores were highly correlated with their aerobic physical capacity assessed by peak oxygen consumption (VO2max) and ventilatory anaerobic threshold (VAT). In the multivariate analysis, the most important independent predictors of decreased physical health were increased height, decreased body mass index, decreased VAT and use of prophylactic therapy.ConclusionsThis study reports an impaired HRQoL in children and adolescents with MFS or related conditions, in comparison with matched healthy children. Educational and rehabilitation programs must be developed and evaluated to improve exercise capacity and HRQoL in these patients.Trial registrationClinicalTrials.gov, NCT03236571. Registered 28 July 2017.

Quality of life in young patients with acute type a aortic dissection in China: comparison with Marfan syndrome and non-Marfan syndrome

BackgroundThere is a paucity of Chinese studies evaluating the quality of life (QoL) in young acute type A aortic dissection (AAAD) patients with Marfan syndrome.MethodsYoung adult AAAD patients (younger than 45 years old) underwent surgical treatment at our institution from January 2017 to December 2020 were consecutive enrolled. The hospital survivors completed 1 year of follow up. Patients were divided into two groups according to the presence or absence of Marfan syndrome (MFS). A 1:1 propensity score matching (PSM) with a caliper 0.2 was conducted to balance potential bias in baseline. The follow-up data were analyzed primarily for change in quality of life and anxiety status.ResultsAfter PSM, 32 comparable pairs were matched. The baseline data were comparable and postoperative complications were similar between groups. In terms of SF-36 scale, the role physical, bodily pain, role emotional and mental health subscales were no significantly improved in MFS patients over time. At 1 year after discharged, the subscale of mental health and bodily pain were significantly lower in the MFS group than in the non-MFS group. In terms of HADS assessments, the level of anxiety in MFS patients was significantly higher than in non-MFS patients at 1 year after discharged.ConclusionsThe QoL in young AAAD patients with MFS is lower than those without MFS after surgery. This may be associated with the uncontrollable persistent chronic pain and the uncertainty and concerns for the disease’s progression.

Reduced volume and altered composition of paraspinal muscles in Marfan syndrome: A retrospective cohort study.

Retrospective cohort study. Spinal deformities in patients with Marfan syndrome (MFS) are distinct from those in patients with idiopathic scoliosis (IS). It is more prone to progression and more likely to present with sagittal malalignment than IS. However, the etiology of this characteristic spinal deformity in MFS remains unclear. This study aimed to determine the spinal musculature characteristics in patients with MFS on the hypothesis that the paraspinal muscles of patients with MFS would be qualitatively or quantitatively different from those of patients with IS. Seventeen consecutive patients with MFS aged 25 years or younger undergoing surgery for scoliosis in our hospital were compared with age- and sex-matched patients with IS undergoing surgery for scoliosis. The body size-adjusted relative cross-sectional area (rCSA), fatty infiltration ratio (FI%), and relative functional cross-sectional area (rFCSA) of the psoas muscles (PM) and paravertebral muscles (PVM) at L3/4 and L4/5 were measured using preoperative T2-weighted magnetic resonance imaging. Functional CSA was defined as total CSA minus the fatty infiltration area of each muscle and rFCSA was calculated as the body size-adjusted functional CSA. The rCSA of the PM at L3/4 and L4/5 was significantly smaller in the MFS group than in the IS group (L3/4, P = .021; L4/5, P = .002). The FI% of the PM at L4/5 was significantly higher in the MFS group (P = .044). Consequently, the rFCSA of the PM at L3/4 and L4/5 and the rFCSA of the PVM at L3/4 in the MFS group were significantly smaller than those in the IS group (PM at L3/4, P = .021; PM at L4/5, P = .001; PVM at L3/4, P = .025). Compared with patients with IS, patients with MFS exhibited significantly decreased body-size-adjusted CSA of the PM and reduced body-size-adjusted functional CSA of the PVM and PM. These findings may partially explain the characteristics of distinctive spinal deformities in patients with MFS.

Nanoscale Structural Comparison of Fibrillin-1 Microfibrils Isolated from Marfan and Non-Marfan Syndrome Human Aorta.

Fibrillin-1 microfibrils are essential elements of the extracellular matrix serving as a scaffold for the deposition of elastin and endowing connective tissues with tensile strength and elasticity. Mutations in the fibrillin-1 gene (FBN1) are linked to Marfan syndrome (MFS), a systemic connective tissue disorder that, besides other heterogeneous symptoms, usually manifests in life-threatening aortic complications. The aortic involvement may be explained by a dysregulation of microfibrillar function and, conceivably, alterations in the microfibrils' supramolecular structure. Here, we present a nanoscale structural characterization of fibrillin-1 microfibrils isolated from two human aortic samples with different FBN1 gene mutations by using atomic force microscopy, and their comparison with microfibrillar assemblies purified from four non-MFS human aortic samples. Fibrillin-1 microfibrils displayed a characteristic "beads-on-a-string" appearance. The microfibrillar assemblies were investigated for bead geometry (height, length, and width), interbead region height, and periodicity. MFS fibrillin-1 microfibrils had a slightly higher mean bead height, but the bead length and width, as well as the interbead height, were significantly smaller in the MFS group. The mean periodicity varied around 50-52 nm among samples. The data suggest an overall thinner and presumably more frail structure for the MFS fibrillin-1 microfibrils, which may play a role in the development of MFS-related aortic symptomatology.

Morphometric Assessment of the Ciliary Body in Patients With Marfan Syndrome and Ectopia Lentis: A Quantitative Study Using Ultrasound Biomicroscopy

To explore the biometric characteristics of the ciliary body in patients with Marfan syndrome (MFS) and ectopia lentis (EL). Cross-sectional study. Seventy-two consecutive patients with MFS and EL and 72 nondiseased control subjects were recruited. Ciliary body biometric parameters such as ciliary muscle cross-sectional area at 2000 µm from the scleral spur (CMA2000), ciliary muscle thickness at 1000 µm from the scleral spur (CMT1000), and maximum ciliary body thickness (CBTmax) were measured from multiple directions with ultrasound biomicroscopy (UBM). The relationship between ciliary body parameters and other ocular characteristics was also evaluated. Average CMA2000, CMT1000, and CBTmax were 0.692 ± 0.015 mm2, 0.405 ± 0.010 mm, and 0.855 ± 0.023 mm in eyes of patients with MFS, respectively, and were significantly smaller than these values in control subjects (all P < .001). The prevalence of ciliary body thinning was 22.2% in the MFS group vs 0 in the control group (P < .001); eyes with more severe EL had smaller CMA2000 (P=.050), thinner CMT1000 (P=.022), and shorter CBTmax (P=.015). Patients with microspherophakia (MSP) had even smaller CMA2000 (P=.033) and CMT1000 (P=.044) than those without MSP. The most common subluxation direction was in the superonasal quadrant (n=25; 39.7%), which probably correlates with the thinnest CMT1000 in the inferotemporal quadrant (P=.005). Patients with MFS and EL had thinner ciliary muscles, shorter ciliary processes, and a higher prevalence of ciliary body thinning, especially those with MSP. Both the extent and direction of subluxation were associated with ciliary body biometry.</ABSTRACT>.

Thoracic aortopathy in Marfan syndrome overlaps with mechanisms seen in bicuspid aortic valve disease.

Thoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine. This study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals. Bicuspid aortic valve (BAV; n = 36), TAV (n = 23), and MFS (n = 8) patients were included. Ascending aortic wall specimen were studied for general histologic features, apoptosis, markers of cardiovascular ageing, expression of synthetic and contractile vascular smooth muscle cells (VSMC), and fibrillin-1 expression. The MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima (p < 0.0005), a lower expression of contractile VSMCs (p < 0.05), more elastic fiber thinning (p < 0.001), lack of inflammation (p < 0.001), and a decreased progerin expression (p < 0.05) as compared to the TAV. Other features of cardiovascular ageing differed between the BAV and MFS. Dilated BAV patients demonstrated less medial degeneration (p < 0.0001), VSMC nuclei loss (p < 0.0001), apoptosis of the vessel wall (p < 0.03), and elastic fiber fragmentation and disorganization (p < 0.001), as compared to the MFS and dilated TAV. This study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions.

Quantitative analysis of choriocapillaris flow deficits and choroidal thickness in children with Marfan syndrome

PurposeTo evaluate the characteristics and associated factors of choroidal thickness (ChT) and choriocapillaris flow deficit percentage (CC FD%) in children with Marfan syndrome (MFS).MethodsThis is a cross-sectional study. The ChT...

Comprehensive Characterization of Arterial and Cardiac Function in Marfan Syndrome—Can Biomarkers Help Improve Outcome?

Background: Marfan Syndrome (MFS) has been associated with increased aortic stiffness and left ventricular dysfunction. The latter may be due to the underlying genotype and/or secondary to aortic stiffening (vascular-ventricular interaction). The aim of this study was to characterize arterial and cardiac function in MFS using a multimodal approach. Methods: Prospective observational study of MFS patients and healthy controls. Methods included echocardiography, ascending aortic distensibility, common carotid intima media thickness [cIMT], parameters of wave reflection, carotid-femoral pulse wave velocity [cfPWV]), reactive hyperemia index [RHI], and biomarker analysis (Olink, CVII panel). Results: We included 20 patients with MFS and 67 controls. Ascending aortic distensibility, cIMT and RHI were decreased, while all parameters of arterial wave reflection, stiffness and BNP levels were increased in the MFS group. Both systolic and diastolic function were impaired relative to controls. Within the MFS group, no significant correlation between arterial and cardiac function was identified. However, cfPWV correlated significantly with indexed left ventricular mass and volume in MFS. Bran natriuretic peptide (BNP) was the only biomarker significantly elevated in MFS following correction for age and sex. Conclusions: MFS patients have generally increased aortic stiffness, endothelial dysfunction and BNP levels while cIMT is decreased, supporting that the mechanism of general stiffening is different from acquired vascular disease. CfPWV is associated with cardiac size, blood pressure and BNP in MFS patients. These may be early markers of disease progression that are suitable for monitoring pharmacological treatment effects in MFS patients.

CHARACTERISTICS OF THE FOVEAL MICROVASCULATURE IN CHILDREN WITH MARFAN SYNDROME: An Optical Coherence Tomography Angiography Study.

To investigate the characteristics of foveal microvasculature in children with Marfan syndrome (MFS). Ninety eyes from 45 MFS patients and 76 eyes from 38 healthy individuals of age-matched, sex-matched, and axial length-matched were enrolled. Characteristics of the superficial capillary plexus including the vessel density, perfusion density, and foveal avascular zone were analyzed by optical coherence tomography angiography. The vessel density and the circularity index of the foveal avascular zone were significantly decreased in the MFS group compared with the controls (P = 0.017 and P = 0.004 respectively). In MFS group, the central vessel density (P = 0.003) and perfusion density (P = 0.001) were negatively correlated with the best-corrected visual acuity. The foveal avascular zone area was correlated with the aortic diameters (P = 0.001) and the paratemporal perfusion density was correlated with the ejection fraction (P = 0.003). Moreover, the paratemporal perfusion density and the circularity index of foveal avascular zone were found to be correlated with the aortic Z-score (P < 0.001 and P = 0.003 respectively). Retinal microvascular decrease and its correlation with best-corrected visual acuity and cardiac functions were observed in the MFS group. The optical coherence tomography angiography may help to characterize the underlying pathophysiology features of MFS and enable early detection and prevention of vascular changes in MFS.

Photophobia and disability glare in adult patients with Marfan syndrome: a case-control study.

The aim of the present study was to investigate photophobia and disability glare in adult patients with Marfan syndrome (MFS). In this case-control study, 44 patients with MFS (87 eyes) were compared to 44 controls (88 eyes), who were matched for age and sex. The subjects were asked to grade their photophobia and glare using 10-cm visual analogue scales (VAS), which were marked with 'never' at zero and 'always' at 10 -cm. In addition, disability glare was measured with C-Quant straylight meter. The patients with MFS had significantly higher VAS scores than the controls in four out of seven statements related to photophobia and glare. When including cataract, spherical equivalent, iris colour, axial length and corneal curvature, three of the seven statements were still significantly different between the two groups. The mean straylight values were 1.29 ± 0.03 log(s) in the MFS group and 1.01 ± 0.03 log(s) in the control group (p < 0.001, mixed model). These differences remained significant after adjusting for cataract, spherical equivalent, iris colour, axial length and corneal curvature. Patients with MFS reported more photophobia and had a higher straylight value than the control group. Awareness of these findings of more photophobia and glare in the MFS patients is important when counselling and treating these patients.

The differences in surgical long-term outcomes between Marfan syndrome and Loeys-Dietz syndrome.

The aim of this study was to disclose the differences of surgical outcomes between Marfan syndrome with mutations in fibrillin-1 gene and Loeys-Dietz syndrome with mutations in transforming growth factor-beta receptor 1 and 2. We reviewed 368 patients aged less than 50years who underwent surgery for thoracic aortic diseases between 1988 and 2019, and enrolled 99 patients with Marfan syndrome (26.9%; 57 men, 33±7.5years) and 24 patients with Loeys-Dietz syndrome (6.5%; 13 men, 28±11years). Freedom from all causes of mortality was similar between the 2 groups (P=.40, log-rank). The cumulative incidence of reintervention was significantly lower in the Marfan syndrome group than in the Loeys-Dietz syndrome group (P=.016, Gray). The cumulative incidence of first aortic arch reoperation for aortic arch aneurysm was significantly lower in the Marfan syndrome group than in the Loeys-Dietz syndrome group (P<.001, Gray). The cumulative incidence of first aortic root reoperation for aortic root aneurysm (P=.57, Gray) and first descending aorta reoperation for descending aortic aneurysm (P=.76, Gray) was similar between the 2 groups. The cumulative incidence of aortic dissection after initial surgery was significantly lower in Marfan syndrome than in Loeys-Dietz syndrome (P=.0059, Gray). Loeys-Dietz syndrome with mutations in transforming growth factor-beta receptor 1 and 2 revealed higher rates of reoperation, and more specifically the arch reoperation was higher in those with Loeys-Dietz syndrome than those with Marfan syndrome. Aggressive arch surgery in the initial operation on the proximal aorta is recommendable in Loeys-Dietz syndrome to avoid additional aortic events. In Marfan syndrome, this is controversial in patients without dissection because of a low possibility to expand.

Comparison of Evolution of Aortic Root Dilation and Ghent Criteria in Preadolescents and Adolescents with and without Marfan Syndrome

To determine whether the Ghent Criteria (2010) can be reliably used in evaluating preadolescents and adolescents for Marfan syndrome by comparing aortic growth, systemic scores, and anthropometric features in individuals with and without Marfan syndrome. A retrospective chart review was completed for patients less than 15years of age referred for Marfan syndrome. Comparisons were made between the first and last visit. Paired t tests were used to compare Ghent systemic scores. Wilcoxon rank-sum test were used to compare age, aortic root z scores, height z scores, and body mass index z scores. Recursive partitioning was used to identify combinations of factors to distinguish Marfan syndrome. In total, 53 individuals met inclusion criteria (29 Marfan syndrome and 24 non-Marfan syndrome). Ghent systemic score increased in the Marfan syndrome group and declined in the non-Marfan syndrome. The non-Marfan syndrome group did not develop progressive aortic root dilation with age. Individuals with Marfan syndrome had higher median height z scores than non-Marfan syndrome, with no difference in median body mass index z score between groups. A combination of aortic root z score above 0.95 and Ghent systemic score above 3 was highly indicative of a Marfan syndrome diagnosis in children less than 15years of age. The Ghent criteria (2010) can be used to reliably exclude a diagnosis of Marfan syndrome in individuals less than 15years of age. Genetic testing should be used as an aide in confirming or excluding the diagnosis of Marfan syndrome in individuals with an aortic root z score above 0.95 in combination with a Ghent systemic score above 3 at initial visit.

Increased visceral arterial tortuosity in Marfan syndrome

BackgroundClinical evidence suggests that the currently recommended approach to estimate the risk of aortic dissection in Marfan syndrome (MFS) is not reliable enough. Therefore, we investigated the possible role of visceral arterial tortuosity in the risk stratification.Methods and resultsSplenic and renal arteries of 37 MFS patients and 74 age and gender matched control subjects were segmented using CT angiography imaging. To measure tortuosity, distance metric (DM), sum of angles metric (SOAM), inflection count metric (ICM), and the ratio of ICM and SOAM (ICM/SOAM) were calculated. DM of the splenic, right and left renal artery was significantly higher in MFS patients than in controls (2.44 [1.92-2.80] vs. 1.75 [1.57-2.18] p < 0.001; 1.16 [1.10-1.28] vs. 1.11 [1.07-1.15] p = 0.011; 1.40 [1.29-1.70] vs. 1.13 [1.09-1.23] p < 0.001, respectively). A similar tendency for ICM and an opposite tendency for SOAM were observed. ICM/SOAM was significantly higher in the MFS group compared to controls in case of all three arteries (73.35 [62.26-93.63] vs. 50.91 [43.19-65.62] p < 0.001; 26.52 [20.69-30.24] vs. 19.95 [16.47-22.95] p < 0.001; 22.81 [18.64-30.96] vs. 18.38 [15.29-21.46] p < 0.001, respectively). MFS patients who underwent aortic root replacement had increased right and left renal DM and ICM/SOAM compared to MFS patients without surgery.ConclusionTo our knowledge this is the first demonstration of increased arterial tortuosity in MFS on visceral arteries. Visceral arterial tortuosity, dominated by curves of lower frequency but higher amplitude according to the observed opposite tendency between the DM and SOAM metrics, could be a possible new predictor of serious manifestations of MFS.

Classifying Ectopia Lentis in Marfan Syndrome into Five Grades of Increasing Severity.

Purpose: To describe a five-grade classification of ectopia lentis in Marfan syndrome (MFS) and to evaluate the positive predictive value of the early grades of ectopia lentis. Methods: We prospectively included MFS patients and their healthy relatives. The anterior segment examination was classified into grades 0 to 5, and we studied the sensitivity, specificity, and positive predictive value of ectopia lentis in this classification. Results: Seventy-four MFS patients and thirty-six healthy controls were examined. In the MFS group, grades 1, 2, 3, and 4 were present in 15, 24, 17, and 7 patients, respectively, whereas 11 patients in this group did not present ectopia lentis. In the control group, grades 0 and 1 were observed in 30 and 6 individuals, respectively. Sensitivity to ectopia lentis of at least grade 2 was 64.9%, with 100% specificity, whereas sensitivity to ectopia lentis of at least grade 1 was 85.1%, with 83.3% specificity. The positive predictive value of ectopia lentis that was greater than or equal to grade 2 was 100%, whereas that of ectopia lentis greater than or equal to grade 1 was 91.3%. Conclusions: High positive predictive values s were found to be associated with grades 2 and higher of the five-grade classification of ectopia lentis. This classification should help to harmonize clinical practices for this major feature of MFS.

P1448 Thoracic aorta and circulating transforming growth factor-b in marfan syndrome and marfanoid habitus

Abstract Purpose Current understanding of the pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MS) focuses upon abnormal activity of the transforming growth factor beta (TGF-β) signalling pathway. Circulating TGF-β predicts cardiovascular events in patients with MS and is elevated in the entire spectrum of aortic syndromes. Marfanoid habitus (MH) patients not meeting the MS criteria (TAA, ectopia lentis, family history), but share the same skeletal features and are the part of the Marfan continuum. Our aim was to evaluate the possible role of elevated TGF-β level in the aortic dilatation at mid-term follow-up in Marfanoid habitus patients. Methods 33 consecutive patients with a presumptive clinical diagnosis of Marfan syndrome were referred to Almazov centre and enrolled in our observational, prospective, single-center study. Nine of them (mean age 27.9 ± 9.3) fulfilled diagnosis of MS according to revised Ghent criteria. 24 subjects (mean age 21.8 ± 3.4) with skeletal features of Marfanoid habitus have had no major findings of MS. Proximal aortic segments were visualized in the parasternal long-axis and suprasternal views. Concentration of TGF-β1 and TGF-β2 in serum was determined using a test system Human Platinum ELISA. End points analyzed during 5 years of follow-up were mortality, aortic-related events, and aortic dimension changes. Results During 122 person-years of the follow-up (median 5.1 years) no deaths or aortic-related events occurred in Marfanoid habitus patients. TGF-β1 and TGF-β2 serum levels were elevated in patients with Marfanoid habitus (14.2 ± 27.6 and 2.1 ± 1.7 ng/ml, respectively) but were lower than in MS group (44.6 ± 47.3 ng/ml, p = 0.03 and 2.7 ± 1.7 ng/ml, p = 0.39, respectively). A high TGF-β1 serum level (cutoff &amp;gt;14.75 ng/ml, provided by the manufacturer of our TGF-β assay) was detected in 44% and TGF-β2 (&amp;gt;2.0 ng/ml) in majority patients (67%) of the MS group. In Marfanoid habitus group we found a high TGF-β1 serum level only in 4 (17%) patients and TGF-β2 in 9 (38%) patients. Aortic diameter at the sinuses of Valsalva and Z-score were significantly lower in Marfanoid habitus group (29.2 ± 2.8 mm and 1.56 ± 0.93) than in MS patients (43.1 ± 15.1 mm, p = 0.0007 and 6.86 ± 5.83, p = 0.004) at the beginning of study and significantly increased during the follow-up (31.3 ± 2.9 mm and 1,69 ± 0,15, p &amp;lt; 0.001 for both). There was no correlation between TGF-β level and aortic dimensions in patients with MS and marfanoid habitus. Conclusion In young adults with Marfanoid habitus and the current absence of ascending aortic aneurysm we found the increased TGF-β level and aortic root enlargement during the follow-up. High TGF-β serum level may contribute to the excessive progression of aortic dilatation later over mid-to-late aging and requires further investigation to establish its role in the aortic aneurysm pathogenesis.

Early and Midterm Results of Thoracoabdominal Aortic Aneurysm Repair in Patients with Marfan Syndrome

Objective To evaluate the early and midterm results of surgical repair of thoracoabdominal aortic aneurysm(TAAA)in patients with Marfan syndrome(MFS). Methods The clinical data of patients with MFS undergoing TAAA repair in Fuwai Hospital between January 2009 and December 2017 were retrospectively analyzed.These patients were divided into two groups:MFS group(n=58)and non-MFS group(n=98).The baseline data,early postoperative results,and midterm follow-up outcomes were compared between these two groups. Results MFS patients were significantly younger(32 years old vs. 45 years old,t=9.603,P=0.000)and more frequently had a history of aortic aneurysm or dissection(19% vs. 0,χ 2=19.996,P=0.000)than non-MFS patients.However,the proportions of males and smokers were significantly lower when compared with non-MFS patients(55.2% vs. 80.6%,χ 2=11.489,P=0.001;13.8% vs. 46.9%,χ 2=17.686,P=0.001).There was no significant difference in proportion of emergency operation,prophylactic cerebrospinal fluid drainage,operation time,intra-operative circulation management,and intra-operative blood transfusion(all P>0.05).The 30-day mortality rate was significantly lower in MFS group than in non-MFS group(0 vs. 9.2%, [Formula: see text]=5.034,P=0.025). Conclusions For patients with MFS,TAAA repair provides lower 30-day mortality and comparative middle-term survival.However,the re-intervention rate is higher among MFS patients,highlighting the importance of close follow-up.

Clinical Significance of Electrocardiograph Abnormalities: Analysis on Electrocardiographs of 75 Marfan Cases Complicated with Aortic Disease

Purpose: Marfan syndrome (MFS) is one of the most common hereditary connective tissue disorders, with various adverse manifestations ranging from typical ocular, cardiovascular, and musculoskeletal abnormalities to manifestations involving the lungs, skin, and central nervous system. In patients with MFS, the most lethal manifestations are aortic lesion presenting as aortic insufficiency, thoracic and abdominal aortic dilatation, aneurysm, and dissection. Clinically, these patients often present with various types of arrhythmias and abnormal electrocardiographs (EKGs); however, there have been few studies of MFS-associated arrhythmias either in China or abroad. This investigation aims to elucidate the association between Marfan-associated aortic lesions and accompanying arrhythmia characteristics. Methods: From September 2016 to January 2018, 75 consecutive patients diagnosed with MFS and aortic disease manifestation were enrolled in the study (MFS group). During the same time period, 76 consecutive nonMFS patients with aortic disease were enrolled as positive controls (dissection group) and 100 consecutive healthy patients were enrolled during routine health checkups as negative controls (checkup group). EKG characteristics between the three groups were analyzed. Results: Compared to the checkup group, both the MFS group and dissection group showed more EKG abnormalities (P 0.05), the MFS group showed a significantly higher occurrence of sinus bradycardia and first-degree atrioventricular block (P