Clinical application of four-dimensional flow cardiovascular magnetic resonance in Marfan syndrome: A systematic review and meta-analysis.

This study aims to fill this gap by assessing the application of 4D flow CMR in MFS through a systematic review and meta-analysis. We conducted a comprehensive search of databases from their inception to May 1, 2023. Eligibility criteria were established based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), with studies scoring above five deemed high quality. Meta-analyses were performed using Stata 15.1 software. Nine studies were analyzed. Findings indicate MFS patients had increased vortex flow in the descending aorta (DAo), larger aortic root diameter (ARD) and Z-scores, lower inner wall shear stress (WSS) in the proximal descending aorta (pDAo), reduced in-plane rotational flow (IRF) in the aortic arch and proximal descending aorta (pDAo), and increased pulse wave velocity (PWV) in the ascending aorta (AAo) and DAo compared to healthy subjects. No significant difference in systolic flow reversal ratio was observed. Sensitivity analysis showed no heterogeneity and Egger's test revealed no publication bias. This meta-analysis underscores the effectiveness of 4D flow CMR in detecting MFS, particularly through indicators such as vortex flow, WSS, IRF, ARD, and PWV. The findings provide insights into diagnosing cardiovascular diseases and predicting cardiovascular events in MFS patients. Further case-control studies are needed to establish measurement standards and explore potential indicators for improved diagnosis and treatment of MFS.

Thoracic aorta diameters in Marfan patients: Intraindividual comparison of 3D modified relaxation-enhanced angiography without contrast and triggering (REACT) with transthoracic echocardiography.

OBJECTIVE: To compare the measurement of aortic diameters using a novel flow-independent MR-Angiography (3D modified Relaxation-Enhanced Angiography without Contrast and Triggering (modified REACT)) and transthoracic echocardiography (TTE) in Marfan syndrome (MFS) patients. MATERIAL AND METHODS: This retrospective, single-center analysis included 46 examinations of 32 MFS patients (mean age 37.5 ± 11.3 years, 17 women, no prior aortic surgery) who received TTE and 3D modified REACT (ECG- and respiratory-triggering, Compressed SENSE factor 9 for acceleration of image acquisition) of the thoracic aorta. Aortic diameters (sinus of Valsalva (SV), sinotubular junction (STJ), and ascending aorta (AoA)) were independently measured by two cardiologists in TTE (leading-edge) and two radiologists in modified REACT (inner-edge, using multiplanar reconstruction). Intraclass correlation coefficient, Bland-Altman analyses, and Pearson's correlation (r) were used to assess agreement between observers and methods. RESULTS: Interobserver correlation at the SV, STJ, and AoA were excellent for both, TTE (ICC = 0.95-0.98) and modified REACT (ICC = 0.99-1.00). There was no significant difference between TTE and modified REACT for diameters measured at the SV (39.24 ± 3.24 mm vs. 39.63 ± 3.76 mm; p = 0.26; r = 0.78) and the STJ (35.16 ± 4.47 mm vs. 35.37 ± 4.74 mm; p = 0.552; r = 0.87). AoA diameters determined by TTE were larger than in modified REACT (34.29 ± 5.31 mm vs. 30.65 ± 5.64 mm; p < 0.01; r = 0.74). The mean scan time of modified REACT was 05:06 min ± 02:47 min, depending on the patient's breathing frequency and heart rate. CONCLUSIONS: Both TTE and modified REACT showed a strong correlation for all aortic levels; however, at the AoA, diameters were larger using TTE, mostly due to the limited field of view of the latter with measurements being closer to the aortic valve. Given the excellent interobserver correlation and the strong agreement with TTE, modified REACT represents an attractive method to depict the thoracic aorta in MFS patients.

Marfan Syndrome beyond Aortic Root-Phenotyping Using Cardiovascular Magnetic Resonance Imaging and Clinical Implications.

Marfan syndrome (MFS) is an inherited autosomal-dominant connective tissue disorder with multiorgan involvement including musculoskeletal, respiratory, cardiovascular, ocular, and skin manifestations. Life expectancy in patients with MFS is primarily determined by the degree of cardiovascular involvement. Aortic disease is the major cardiovascular manifestation of MFS. However, non-aortic cardiac diseases, such as impaired myocardial function and arrhythmia, have been increasingly acknowledged as additional causes of morbidity and mortality. We present two cases demonstrating the phenotypical variation in patients with MFS and how CMR (Cardiovascular Magnetic Resonance) could serve as a "one stop shop" to retrieveS all the necessary information regarding aortic/vascular pathology as well as any potential underlying arrhythmogenic substrate or cardiomyopathic process.

Assessment of aortic diameter in Marfan patients: intraindividual comparison of 3D-Dixon and 2D-SSFP magnetic resonance imaging.

OBJECTIVES: To compare the accuracy and precision of 3D-Dixon and 2D-SSFP MR-imaging for assessment of aortic diameter in Marfan patients. METHODS: This prospective single-center study investigated respiratory-gated 3D-Dixon and breath-hold 2D-SSFP non-contrast MR-imaging at 3 T in 47 Marfan patients (36.0 ± 13.2 years, 28♀,19♂). Two radiologists performed individual diameter measurements at five levels of the thoracic aorta and evaluated image quality on a four-grade scale (1 = poor, 4 = excellent) and artifacts (1 = severe, 4 = none). Aortic root diameters acquired by echocardiography served as a reference standard. Intraclass correlation coefficient, Bland-Altman analyses, F-test, t-test, and regression analyses were used to assess agreement between observers and methods. RESULTS: Greatest aortic diameters were observed at the level of the sinuses of Valsalva (SOV) for 3D-Dixon (38.2 ± 6.8 mm) and 2D-SSFP (38.3 ± 7.1 mm) (p = 0.53). Intra- and interobserver correlation of diameter measurements was excellent at all aortic levels for both 3D-Dixon (r = 0.94-0.99 and r = 0.94-0.98) and 2D-SSFP (r = 0.96-1.00 and r = 0.95-0.99). 3D-Dixon-derived and 2D-SSFP-derived diameter measurements at the level of the SOV revealed a strong correlation with echocardiographic measurements (r = 0.92, p < 0.001 and r = 0.93, p < 0.001, respectively). The estimated mean image quality at the level of SOV was higher for 2D-SSFP compared to that for 3D-Dixon (3.3 (95%-CI: 3.1-3.5) vs. 2.9 (95%-CI: 2.7-3.1)) (p < 0.001). Imaging artifacts were less at all aortic levels for 3D-Dixon compared to 2D-SSFP (3.4-3.8 vs. 2.8-3.1) (all p < 0.002). CONCLUSION: Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP MR-imaging provide accurate and precise aortic diameter measurements. We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations of the aortic root. KEY POINTS: • Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP imaging provide accurate and precise aortic diameter measurements in patients suffering from Marfan syndrome. • Imaging artifacts are stronger in 2D-SFFP imaging than in 3D-Dixon imaging. • We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations.

Discrepancy of echocardiography and computed tomography in initial assessment and 2-year follow-up for monitoring Marfan syndrome and related disorders.

Patients with Marfan syndrome and related disorders are at risk for aortic dissection and aortic rupture and therefore require appropriate monitoring. Computed tomography (CT) and transthoracic echocardiography (TTE) are routinely used for initial diagnosis and follow-up. The purpose of this study is to compare whole-heart CT and TTE aortic measurement for initial work-up, 2-year follow-up, and detection of progressive aortic enlargement. This retrospective study included 95 patients diagnosed with Marfan syndrome or a related disorder. All patients underwent initial work-up including aortic diameter measurement using both electrocardiography-triggered whole-heart CT and TTE. Forty-two of these patients did not undergo aortic repair after initial work-up and were monitored by follow-up imaging within 2 years. Differences between the two methods for measuring aortic diameters were compared using Bland-Altman plots. The acceptable clinical limit of agreement (acLOA) for initial work-up, follow-up, and progression within 2 years was predefined as < ± 2 mm. Bland-Altman analysis revealed a small bias of 0.2 mm with wide limits of agreement (LOA) from + 6.3 to - 5.9 mm for the aortic sinus and a relevant bias of - 1.6 mm with wide LOA from + 5.6 to - 8.9 mm for the ascending aorta. Follow-up imaging yielded a small bias of 0.5 mm with a wide LOA from + 6.7 to - 5.8 mm for the aortic sinus and a relevant bias of 1.1 mm with wide LOA from + 8.1 to - 10.2 mm for the ascending aorta. Progressive aortic enlargement at follow-up was detected in 57% of patients using CT and 40% of patients using TTE. Measurement differences outside the acLOA were most frequently observed for the ascending aorta. Whole-heart CT and TTE measurements show good correlation, but the frequency of measurement differences outside the acLOA is high. TTE systematically overestimates aortic diameters. Therefore, whole-heart CT may be preferred for aortic monitoring of patients with Marfan syndrome and related disorders. TTE remains an indispensable imaging tool that provides additional information not available with CT.

Evaluating the sagittal spinal and pelvic parameters in Marfan syndrome patients affected by scoliosis.

INTRODUCTION: Spinal deformities present a common finding in patients affected with Marfan syndrome (MFS). More specifically, sagittal spine imbalances reflect the typical finding of such deformities. Observing spino-pelvic radiographs, we focused on eliciting any correlation between the pelvic incidence (PI), sacral slope (SS) and thoracolumbar kyphosis measurements, and categorising them according to a sagittal spinal classification system. MATERIALS AND METHODS: One hundred seventy patient records were found over a 6 year period, and further refined to incorporate a total of 44 patients. 25 males and 19 females with an average age of 20 years at imaging. Electronic and hard copies of radiographs were used and measurements were made with virtual Cobb meters, rulers and protractors. RESULTS: The mean PI was significantly different between type-I (46°) and type-II spines (35°) (p = 0.04), and the values for each class were as follows: type IA-53°, type IB-44°, type IC-36°, type IIA-42°, and type IIB-34°. Type II spines had a lower PI compared to type IA spines (p = 0.037) and to that of an unaffected population. Statistically significant differences were noted in SS between groups (t test; p < 0.001), and ANOVA demonstrated that the largest differences between spinal classes were found in SS. CONCLUSION: In our study, PI values were much higher in type I compared to type II spines. Type II spines had PI values as expected, however, had higher than expected SS values. SS followed a down trending pattern across all spinal classes. Type IIA spines had a much greater preponderance for male patients. Overall, we wish to highlight in particular that type II spines were associated with a much lower PI and SS, and report these differences in pelvic morphology and sagittal spine patterns seen in MFS patients. The pelvic tilt and sacral slope parameters observed in our Type II spines may further reflect and characterize the deformity.

Determine Cumulative Radiation Dose and Lifetime Cancer Risk in Marfan Syndrome Patients Who Underwent Computed Tomography Angiography of the Aorta in Northeast Thailand: A 5-Year Retrospective Cohort Study.

OBJECTIVE: To evaluate computed tomography angiography (CTA) data focusing on radiation dose parameters in Thais with Marfan syndrome (MFS) and estimate the distribution of cumulative radiation exposure from CTA surveillance and the risk of cancers. METHODS: Between 1st January 2015 and 31st December 2020, we retrospectively evaluated the cumulative CTA radiation doses of MFS patients who underwent CTA at Khon Kaen University Hospital, a leading teaching hospital and advanced tertiary care institution in northeastern Thailand. We utilized the Radiation Risk Assessment Tool (RadRAT) established at the National Cancer Institute in Bethesda, Maryland, to evaluate the risk of cancer-related CTA radiation. RESULTS: The study recruited 29 adult MFS patients who had CTA of the aorta during a 5-year study period with 89 CTA studies. The mean cumulative CTDI vol is 21.5 ± 14.68 mGy, mean cumulative DLP is 682.2 ± 466.7 mGy.cm, the mean baseline future risk for all cancer is 26,134 ± 7601 per 100,000, and the excess lifetime risk for all cancer is 2080.3 ± 1330 per 100,000. The excess lifetime risk of radiation-induced cancer associated with the CTA surveillance study is significantly lower than the risk of aortic dissection or rupture and lower than the baseline future cancer risk. CONCLUSIONS: We attempted to quantify the radiation-induced cancer risk from CTA surveillance imaging performed for MFS patients in this study, with all patients receiving a low-risk cumulative radiation dose (less than 1 Gy) and all patients having a low excessive lifetime risk of cancer as a result of CTA. The risk-benefit decision must be made at the point of care, and it entails balancing the benefits of surveillance imaging in anticipating rupture and providing practical, safe treatment, therefore avoiding morbidity and mortality.

Age and sex dependency of thoracic aortopathy in a mouse model of Marfan syndrome.

Thoracic aortic aneurysm is one of the manifestations of Marfan syndrome (MFS) that is known to affect men more severely than women. However, the incidence of MFS is similar between men and women. The aim of this study is to show that during pathological aortic dilation, sex-dependent severity of thoracic aortopathy in a mouse model of MFS translates into sex-dependent alterations in cells and matrix of the ascending aorta, consequently affecting aortic biomechanics. Fibrillin-1 C1041G/+ (Het) mice were used as a mouse model of MFS. Ultrasound measurements from 3 to 12 mo showed increased aortic diameter in Het aorta, with larger percentage increase in diameter for males compared with females. Immunohistochemistry showed decreased contractile smooth muscle cells in Het aortic wall compared with healthy aorta, which was accompanied by decreased contractility measured by wire myography. Elastin autofluorescence, second-harmonic generation microscopy of collagen fibers, and passive biomechanical assessments using myography showed more severe damage to elastin fibers, increased medial fibrosis, and increased stiffness of the aortic wall in MFS males but not females. Male and female Het mice showed increased expression of Sca-1-positive adventitial progenitor cells versus controls at young ages. In agreement with clinical data, Het mice demonstrate sex-dependent severity of thoracic aortopathy. It was also shown that aging exacerbates the disease state especially for males. Our findings suggest that female mice are protected from progression of aortic dilation at early ages, leading to a lag in aneurysm growth.NEW & NOTEWORTHY Male Fbn1C1041G/+ mice show more severe thoracic aortic changes compared with females, especially at 12 mo of age. Up to 6 mo of age, Sca-1+ smooth muscle progenitor cells are more abundant in the adventitia of both male and female Fbn1 Het mice compared with wild types (WTs). Male and female Het mice show similar patterns of expression of Sca-1+ cells at early ages.

Aortic flow dynamics and stiffness in Loeys-Dietz syndrome patients: a comparison with healthy volunteers and Marfan syndrome patients.

AIMS: To assess aortic flow and stiffness in patients with Loeys-Dietz syndrome (LDS) by 4D flow and cine cardiovascular magnetic resonance (CMR) and compare the results with those of healthy volunteers (HV) and Marfan syndrome (MFS) patients. METHODS AND RESULTS: Twenty-one LDS and 44 MFS patients with no previous aortic dissection or surgery and 35 HV underwent non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), and aortic diameters were obtained at 20 planes from the ascending (AAo) to the proximal descending aorta (DAo). IRF and SFRR were also quantified for aortic regions (proximal and distal AAo, arch and proximal DAo). Peak-systolic wall shear stress (WSS) maps were also estimated. Aortic stiffness was quantified using pulse wave velocity (PWV) and proximal AAo longitudinal strain. Compared to HV, LDS patients had lower rotational flow at the distal AAo (P = 0.002), arch (P = 0.002), and proximal DAo (P < 0.001) even after adjustment for age, stroke volume, and local diameter. LDS patients had higher SFRR in the proximal DAo compared to both HV (P = 0.024) and MFS patients (P = 0.015), even after adjustment for age and local diameter. Axial and circumferential WSS in LDS patients were lower than in HV. AAo circumferential WSS was lower in LDS compared to MFS patients. AAo and DAo PWV and proximal AAo longitudinal strain revealed stiffer aortas in LDS patients compared to HV (P = 0.007, 0.005, and 0.029, respectively) but no differences vs. MFS patients. CONCLUSION: Greater aortic stiffness as well as impaired IRF and WSS were present in LDS patients compared to HV. Conversely, similar aortic stiffness and overlapping aortic flow features were found in Loeys-Dietz and Marfan patients.

Peri-vascular adipose tissue attenuation on chest computed tomography in patients with Marfan Syndrome: a case series.

BACKGROUND AND AIM OF THE WORK: Marfan Syndrome is a genetic disorder that determines histopathological alterations of the aortic vascular wall leading to increased inflammatory component. The peri-vascular adipose tissue attenuation is a method able to capture localized vascular inflammation by mapping spatial changes of perivascular tissue attenuation on computed tomography. METHODS: We measured peri-vascular adipose tissue attenuation around the ascending aorta in three consecutive subjects with confirmed genetic diagnosis of Marfan Syndrome. All subjects received the genetic diagnosis of fibrillin-1 gene mutation as part of the family screening of patients with known Marfan Syndrome. Chest computed tomography was performed in such asymptomatic subjects after genetic confirmation of Marfan Syndrome. None of these subjects showed aortic aneurysms or suffered from chronic inflammatory/infectious disease. RESULTS: In the three subjects identified with Marfan Syndrome the value of aortic peri-vascular adipose tissue attenuation measured at chest computed tomography was higher than normal and the volume of aortic peri-vascular adipose tissue was lower. CONCLUSION: These preliminary observations suggest that peri-vascular adipose tissue attenuation is unexpectedly high in patients with Marfan Syndrome, notwithstanding the normal aortic diameter at the time of computed tomography. Whether this observation may find a clinical use in suspected Marfan Syndrome or in predicting aortic complications in Marfan Syndrome is worth to be assessed in prospective studies.

Intracranial Aneurysms in Patients with Marfan Syndrome: A Multicenter Propensity-Matched Analysis.

OBJECTIVE: We sought to identify risk factors for intracranial aneurysms (IAs) in Marfan syndrome (MFS) patients and to describe their characteristics. METHODS: Patients with confirmed MFS and vessel-dedicated brain imaging from January 1, 1980-December 1, 2020 were categorized according to the presence (IA) or absence (NIA) of IAs. Unmatched logistic regression analysis and propensity score matching were used for comparison. RESULTS: We included 159 patients, of whom 18 (11.3%) patients had radiographic diagnosis of IAs. Three patients (16.7%) had multiple lesions for a total of 24 IAs. One patient (5.5%) had de novo IA formation. Four patients (22.2%) underwent treatment: Two (11.1%) had open surgical clipping for ruptured aneurysms, and two (11.1%) patients had endovascular embolization for growth. In the unmatched analysis, current tobacco smoker status (odds ratio [OR]: 4.20; confidence interval [CI]: 1.11-15.6; P = 0.027) and history of coronary artery disease (CAD) (OR: 5.79; CI 1.76-20.2; P = 0.004) increased the odds for IA. Propensity score matching yielded 18 IA and 18 NIA patients matched for age, gender, race, prior stroke, and family history of aneurysms. History of CAD (IA = 11 [61.1%] vs. NIA = 4 (22.2%), P = 0.043) and current smoker status (IA = 6 [33.3%] vs. NIA = 0 (0%), P < 0.01) were significantly higher in the IA cohort. Body mass index (P = 0.622), diabetes (P = 0.180), hypertension (P = 0.732), prior stroke (P = 1.00), family history (P = 0.732), alcohol (P = 0.314), recreational drugs (P = 1.00), and other aneurysms (P = 0.585) were not statistically significant. CONCLUSIONS: Prevalence of IAs in our series of MFS patients was 11.3%, and de novo formation was 5.5%. MFS patients with a history of CAD and current smoker status had an increased risk of IA. Neurovascular radiographic screening should be considered in all patients with MFS, particularly in patients who smoke or have a history of heart disease.

Posterior trans-mediastinal lung herniation in a postoperative Marfan's patient.

Thoracic hernias are defined as the protrusion of contents either into or outside of the thoracic cavity. These hernias can be acquired or congenital and occur in varying locations. Acquired thoracic hernias typically develop after surgery or trauma. The most common form is intercostal herniation due to thoracotomy. Trans-mediastinal herniation of the lung is even less common, typically seen in patients with sequestration, scimitar syndrome, or pneumonectomy, and, when present, commonly occurs across the anterior mediastinum. Here, we present to our knowledge the first known case of posterior trans-mediastinal lung herniation diagnosed on CT after thoracoabdominal aneurysm repair in a patient with Marfan's disease, highlighting the importance of evaluating for rare anatomic complications in the post-operative setting. (1).

Predictive Physical Manifestations for Progression of Scoliosis in Marfan Syndrome.

STUDY DESIGN: A retrospective study of the prospective cohort. OBJECTIVE: To demonstrate the accurate distribution of the severity of scoliosis in patients with Marfan syndrome, and to identify the predictive physical features for progression of scoliosis in Marfan syndrome. SUMMARY OF BACKGROUND DATA: To date, no study has unveiled the risk factors for the progression of scoliosis in Marfan syndrome. METHODS: We retrospectively obtained data from a prospective cohort of the Marfan syndrome clinic at our institute. We enrolled patients whose whole spine radiographs in the standing position were evaluated at the age of 15 or above, from January 2014 to March 2020. The collected variables were physical manifestations defined as in the systemic score of the revised Ghent nosology. We classified the degree of scoliosis into four categories: "not apparent," "mild" (10° ≤ Cobb < 25°), "moderate" (25° ≤ Cobb < 40°), and "severe" (40° ≤ Cobb or surgery conducted). To identify the risk factors for progression of scoliosis in Marfan syndrome, we conducted univariate and multivariate association analyses between severe scoliosis and each physical manifestation. RESULTS: We identified 131 eligible patients (61 men and 70 women) with a mean age of 31.2 years. Scoliosis with a Cobb angle of ≥10° was identified in 116 patients (88.5%). Moderate scoliosis was identified in 33 patients (25.2%) and severe scoliosis in 53 patients (40.5%). The prevalence of each physical manifestation was equivalent to that reported in previous studies. Multivariate logistic regression analysis revealed that female sex (odds ratio, 3.27) and positive wrist sign (4.45) were predictive factors for progression of scoliosis into severe state in patients with Marfan syndrome. CONCLUSIONS: The present study demonstrated the accurate distribution of the severity of scoliosis and identified the predictive factors for progression of scoliosis in patients with Marfan syndrome.Level of Evidence: 3.

Artificial intelligence-based analysis of body composition in Marfan: skeletal muscle density and psoas muscle index predict aortic enlargement.

BACKGROUND: Patients with Marfan syndrome are at risk for aortic enlargement and are routinely monitored by computed tomography (CT) imaging. The purpose of this study is to analyse body composition using artificial intelligence (AI)-based tissue segmentation in patients with Marfan syndrome in order to identify possible predictors of progressive aortic enlargement. METHODS: In this study, the body composition of 25 patients aged ≤50 years with Marfan syndrome and no prior aortic repair was analysed at the third lumbar vertebra (L3) level from a retrospective dataset using an AI-based software tool (Visage Imaging). All patients underwent electrocardiography-triggered CT of the aorta twice within 2 years for suspected progression of aortic disease, suspected dissection, and/or pre-operative evaluation. Progression of aortic enlargement was defined as an increase in diameter at the aortic sinus or the ascending aorta of at least 2 mm. Patients meeting this definition were assigned to the 'progressive aortic enlargement' group (proAE group) and patients with stable diameters to the 'stable aortic enlargement' group (staAE group). Statistical analysis was performed using the Mann-Whitney U test. Two possible body composition predictors of aortic enlargement-skeletal muscle density (SMD) and psoas muscle index (PMI)-were analysed further using multivariant logistic regression analysis. Aortic enlargement was defined as the dependent variant, whereas PMI, SMD, age, sex, body mass index (BMI), beta blocker medication, and time interval between CT scans were defined as independent variants. RESULTS: There were 13 patients in the proAE group and 12 patients in the staAE group. AI-based automated analysis of body composition at L3 revealed a significantly increased SMD measured in Hounsfield units (HUs) in patients with aortic enlargement (proAE group: 50.0 ± 8.6 HU vs. staAE group: 39.0 ± 15.0 HU; P = 0.03). PMI also trended towards higher values in the proAE group (proAE group: 6.8 ± 2.3 vs. staAE group: 5.6 ± 1.3; P = 0.19). Multivariate logistic regression revealed significant prediction of aortic enlargement for SMD (P = 0.05) and PMI (P = 0.04). CONCLUSIONS: Artificial intelligence-based analysis of body composition at L3 in Marfan patients is feasible and easily available from CT angiography. Analysis of body composition at L3 revealed significantly higher SMD in patients with progressive aortic enlargement. PMI and SMD significantly predicted aortic enlargement in these patients. Using body composition as a predictor of progressive aortic enlargement may contribute information for risk stratification regarding follow-up intervals and the need for aortic repair.

Aortic Branch Aneurysms and Vascular Risk in Patients With Marfan Syndrome.

BACKGROUND: Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown. OBJECTIVES: The goal of this study was to assess the prevalence of aortic branch aneurysms in MFS and their relationship with aortic prognosis. METHODS: MFS patients with a pathogenic FBN1 genetic variant and at least one magnetic resonance or computed tomography angiography study assessing aortic branches were included. Aortic events and those related to aneurysm complications were recorded during follow-up. RESULTS: A total of 104 aneurysms were detected in 50 (26.7%) of the 187 patients with MFS (mean age 37.9 ± 14.4 years; 54% male) included in this study, with the iliac artery being the most common location (45 aneurysms). Thirty-one patients (62%) had >1 peripheral aneurysm, and surgery was performed in 5 (4.8%). Patients with aneurysms were older (41.9 ± 12.7 years vs. 36.7 ± 14.8 years; p = 0.040) and had more dilated aortic root (42.2 ± 6.4 mm vs. 38.8 ± 8.0 mm; p = 0.044) and dyslipidemia (31.0% vs. 9.7%; p = 0.001). In a subgroup of 95 patients with no previous aortic surgery or dissection followed up for 3.3 ± 2.6 years, the presence of arterial aneurysms was associated with a greater need for aortic surgery (hazard ratio: 3.4; 95% confidence interval: 1.1 to 10.3; p = 0.028) in a multivariable Cox analysis adjusted for age and aortic diameter. CONCLUSIONS: Aortic branch aneurysms are present in one-quarter of patients with MFS and are related to age and aortic dilation, and they independently predict the need for aortic surgery. The systematic use of whole-body vascular assessment is recommended to identify other sites of vascular involvement at risk for complications and to define the subgroup of patients with more aggressive aortic disease.

Intraindividual comparison of 1.5 T and 3 T non-contrast MR angiography for monitoring of aortic root diameters in Marfan patients.

BACKGROUND: Reproducible aortic diameter measurements are crucial for assessment of aortic growth and aneurysm formation in patients with Marfan syndrome. The objective of this study was to perform an intraindividual comparison of aortic measurements at 1.5 T and 3 T using non-contrast magnetic resonance angiography (MRA) in pre-surgical and post-surgical Marfan patients. METHODS: Forty consecutive Marfan patients were retrospectively evaluated by ECG-gated 2D balanced steady-state free precession (bSSFP) MRA at 1.5 T and 3 T after 363 ± 58 days. 24 patients were before and 16 patients after aortic root surgery. Two readers independently measured aortic diameters at seven aortic levels and rated the image quality/image artifacts (1 = poor/severe, 4 = excellent/none). Contrast-to-noise ratio (CNR) and signal intensity slopes between aortic lumen and vessel walls were semiautomatically determined. RESULTS: In pre-surgical Marfan patients, interobserver agreement of aortic root diameter measurements was significantly higher at 3 T compared to 1.5 T (p < 0.05). In post-surgical Marfan patients, image quality and artifacts were significantly worse at 3 T compared to 1.5 T (p < 0.05). CNR was higher at 3 T compared to 1.5 T at all aortic levels. Significantly steeper slopes of signal intensity curves were observed at 3 T at all aortic levels (p < 0.001). CONCLUSIONS: In pre-surgical Marfan patients, non-contrast MRA provides higher reproducibility of aortic diameter measurements at 3 T compared to 1.5 T. In post-surgical Marfan patients, metallic implants result in significantly worse imaging artifacts and reduced image quality at 3 T compared to 1.5 T. Therefore, we propose to monitor the thoracic aorta with non-contrast MRA at 3 T in pre-surgical Marfan patients and at 1.5 T in post-surgical Marfan patients.

Left atrial strain in the assessment of diastolic function: providing new insights into primary myocardial dysfunction in Marfan syndrome.

Previous studies using conventional echocardiographic measurements have reported subclinical left ventricular (LV) diastolic abnormalities in patients with Marfan syndrome (MFS). Left atrial (LA) strain allows an accurate categorization of LV diastolic dysfunction. We aimed to characterize LV myocardial performance in a cohort of MFS patients using STE-derived measurements (LV and LA strain) along with conventional echocardiographic parameters. We studied 127 adult patients with MFS (no prior cardiac surgery or significant valvular regurgitation) and 38 healthy controls. We performed detailed echocardiograms and selected left atrial reservoir strain (LASr) as a surrogate of impaired relaxation. Additionally, we searched for possible determinants of LASr in patients with MFS, with a special focus on the elastic properties of the aorta. In spite of lower E-wave, septal and lateral e' velocities and average E/e' ratio in MFS patients, all participants had normal diastolic function according to current guidelines. MFS patients exhibited reduced LV global longitudinal strain (19.3 ± 2.6 vs 21.6 ± 2.1%, p < 0.001) and reduced LASr (32.9 ± 8.5 vs 43.3 ± 7.8%, p < 0.001) compared to controls. In the MFS cohort, we found weak significant (p < 0.05) correlations between LASr and certain parameters: E/A ratio (R = 0.258), E wave (R = 0.226), aortic distensibility (R = 0.222), stiffness index (R = - 0.216), LV ejection fraction (R = 0.214), lateral e' (R = 0.210), LV end-systolic volume index (R = - 0.210), LV global longitudinal strain (R = 0.201), septal e' (R = 0.185). After multivariate analysis, only LV end-systolic volume index and E/A ratio maintained a weak independent association with LASr (R = - 0.220; p = 0.017 and R = 0.199; p = 0.046, respectively). In conclusion, LASr is reduced in patients with MFS, which may represent an early stage of LV diastolic dysfunction. LASr is not determined by the elastic properties of the aorta, suggesting that impaired myocardial relaxation is a primary condition in MFS.

Marfan syndrome in children: correlation between musculoskeletal features and cardiac Z-score.

We investigated the correlation between the musculoskeletal features and the cardiovascular anomalies in pediatric patients affected by Marfan syndrome, in order to identify possible orthopedic deformities that could be a warning sign for severe aortic dilatation. Moreover, we analyzed the role of the orthopedic aspects in the early diagnosis of the disease in a pediatric population. Seventy-two patients from 3 to 14 years of age, underwent interdisciplinary evaluation that included an orthopedic and cardiological examination. At the orthopedic examination, we analyzed the musculoskeletal features included in the systemic score of the revised Ghent criteria. Cardiological evaluation included a transthoracic echocardiography with definition of the cardiac Z-score, which is an index that evaluates aortic diameter. A statistical analysis was performed. We identified a statistically significant correlation between the presence of pectus excavatum and cardiac Z-score ≥3 (P = 0.022). Clinically, this data means that pectus excavatum is frequently observed in patients with larger aortic root diameter. On the contrary, no statistically significant correlation was found between the other investigated musculoskeletal features and a pathological Z-score. In the pediatric population, the diagnosis of Marfan syndrome remains difficult because many clinical manifestations are age-dependent and the Ghent criteria, usually used for adults, are not reliable in children. Our results show that the presence of pectus excavatum could help in the early identification of patients at greater risk of developing possibly fatal aortic disease. However, it is always indicated to screen all patients with Marfan syndrome for cardiac abnormalities, even in absence of pectus excavatum.

Increase in dural ectasia size in scoliosis patients with Marfan syndrome.

Increased dural ectasia and vertebral thinning in the lumbosacral spine are common in Marfan syndrome. Dural ectasia is unchanged in middle-aged patients, who have stopped growing. Therefore, evaluation from childhood to adulthood is mandatory. Sixteen patients [four men and 12 women; mean age:17.7 (8.6-33.5) years] with dural ectasia at final follow-up [mean follow-up: 10.4 (5.0-16.7) years] were enrolled. Dural sac diameter (DD)/vertebral diameter (VD) were measured on MRI or CT images of midline sagittal slices at the level of dural ectasia between L5 and S3. The widest part of the dural sac was evaluated with Fattori grading: grade 0, normal; 1, mild; 2, moderate; and 3, severe dural ectasia. At final follow-up, dural ectasia was observed at L5 in 3, S1 in 9, S2 in 14, and S3 in 11 patients. Respective changes in DD/VD from primary to final follow-up were L5: 21.7-24.2 mm/29.1-27.9 mm; S1: 17.0-18.6 mm/21.0-19.5 mm; S2: 15.5-19.6 mm (P < 0.01)/9.6-7.5 mm; and S3: 15.6-17.9 mm (P < 0.05)/6.2-3.3 mm (P < 0.05). Four patients had grade 0 dural ectasia, seven had grade 1, two had grade 2, and three had grade 3. Grade was increased in nine patients with juvenile to young adult patients but did not with adults. During follow-up, dural ectasia size changed in the juvenile to young adult patients with Marfan syndrome, particularly at the S2-S3 level in our series.