Abnormal Cardiac Magnetic Resonance-Derived Ascending Aortic Area Strain Demonstrates Altered Ventriculo-Vascular Function in Marfan Syndrome.

PURPOSE: There remains a need for improved imaging markers for risk stratification and treatment guidance in Marfan syndrome (MFS). After aortic root replacement (ARR), vascular remodeling and progressive aneurysm formation can occur due to alterations in up- and downstream wall biomechanics and hemodynamics. We aim to compare the ventriculo-vascular properties of patients with MFS with controls, and investigate the correlation between ascending aortic area strain and descending aortic area strain (DAAS) with other clinical variables. PATIENTS AND METHODS: Nineteen patients with MFS (47% males), including 6 with ARR were studied. In 26 studies, aortic area strain was measured using cross-sectional cardiac magnetic resonance images at the ascending and proximal descending aortic levels. Left atrial, left ventricular longitudinal, and left ventricle circumferential strain (left atrial longitudinal strain, left ventricular longitudinal strain, and left ventricular circumferential strain, respectively) were measured using cardiac magnetic resonance-feature tracking. RESULTS: Compared with healthy controls, patients with MFS had significantly impaired left ventricular longitudinal strain and left ventricular circumferential strain (-15.8 ± 4.7 vs -19.7 ± 4.8, P = 0.005, and -17.7 ± 4.0 vs -27.0 ± 4.1, P < 0.001). Left atrial longitudinal strain was comparable between patients with MFS and controls. AAAS was significantly reduced (19.0 [11.9, 23.7] vs 46.1 ± 11.3, P < 0.001), whereas DAAS was not significantly decreased. AAAS and DAAS were negatively correlated with age, whereas no significant associations were identified with left ventricle function indices. No significant differences were observed between the ventriculo-vascular properties of patients with MFS who underwent ARR and those who did not. CONCLUSION: Patients with MFS demonstrated impaired ventricular and vascular function compared with healthy controls. Further investigations are warranted to determine clinical utility of aortic stiffness indices for predicting primary and repeat aortic events.

Web-based survey investigating cardiovascular complications in hypermobile Ehlers-Danlos syndrome after COVID-19 infection and vaccination.

BACKGROUND: Hypermobile Ehlers-Danlos syndrome is a heritable connective tissue disorder associated with generalized joint hypermobility but also other multisystem comorbidities, many of which may be exacerbated during a viral illness or after a vaccination. We sought to determine whether individuals with hypermobile Ehlers Danlos syndrome report an increase in adverse events, including cardiovascular events, after COVID-19 illness or vaccination. METHODS: A cross-sectional web-based survey was made available from November 22, 2021, through March 15, 2022. 368 respondents primarily from the United States self-reported data including diagnosis. We used a Cox proportional hazards model with time varying indicators for COVID-19 illness or vaccination in the previous 30 days. RESULTS: We found a significantly increased rate of new abnormal heart rhythms reported in the 30 days following COVID-19 illness. No additional cardiovascular events were reported after COVID-19 illness. 2.5% of respondents with COVID-19 illness were hospitalized. We did not find a statistically significant increased rate of cardiovascular events in the 30 days following any COVID-19 vaccination dose. Post COVID-19 vaccination, 87.2% of hypermobile Ehlers-Danlos syndrome respondents endorsed an expected adverse event (EAE), and 3.1% reported an emergency department visit/hospitalization, of those who received at least one vaccine dose. Events possibly reflecting exacerbation of orthostasis/dysautonomia were common. CONCLUSION: Respondents did not report an increased rate of any cardiovascular events in the 30 days following COVID-19 vaccination; however, those with hypermobile Ehlers-Danlos syndrome experienced a high rate of expected adverse events after vaccination consistent with a high baseline prevalence of similar symptoms. No cardiovascular events other than new abnormal heart rhythms were reported at any point after a COVID-19 illness.

Cardiovascular and obstetrical outcomes among delivering patients with Marfan or Loeys-Dietz syndrome: a retrospective analysis by hospital delivery setting.

BACKGROUND: Pregnancy is a high-risk time for patients with Marfan syndrome or Loeys-Dietz syndrome because of the risk for cardiovascular complications, including the risk for aortic dissection. Little is known about the differences in obstetrical and cardiac outcomes based on delivery hospital setting (academic or academic-affiliated vs community medical centers). OBJECTIVE: This study aimed to evaluate the obstetrical and cardiac outcomes of patients with Marfan syndrome or Loeys-Dietz syndrome based on delivery hospital setting. STUDY DESIGN: This was a secondary analysis of a retrospective, observational cohort study of singleton pregnancies among patients with a diagnosis of Marfan syndrome or Loeys-Dietz syndrome from 1990 to 2016. Patients were identified through the Marfan Foundation, the Loeys-Dietz Syndrome Foundation, or the Cardiovascular Connective Tissue Clinic at Johns Hopkins Hospital. Data were obtained via self-reported obstetrical history and verified by review of medical records. Nonparametric analyses were performed using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: A total of 273 deliveries among patients with Marfan syndrome or Loeys-Dietz syndrome were included in this analysis (Table 1). More patients who had a known diagnosis before delivery of either Marfan syndrome or Loeys-Dietz syndrome delivered at an academic hospital as opposed to a community hospital (78.6% vs 59.9%; P=.001). Patients with Marfan syndrome or Loeys-Dietz syndrome who delivered at academic centers were more likely to have an operative vaginal delivery than those who delivered at community centers (23.7% vs 8.6%; P=.002). When the indications for cesarean delivery were assessed, connective tissue disease was the primary indication for the mode of delivery at community centers when compared with academic centers (55.6% vs 43.5%; P=.02). There were higher rates of cesarean delivery for arrest of labor and/or malpresentation at community hospitals than at academic centers (23.6% vs 5.3%; P=.01). There were no differences between groups in terms of the method of anesthesia used for delivery. Among those with a known diagnosis of Marfan syndrome or Loeys-Dietz syndrome before delivery, there were increased operative vaginal delivery rates at academic hospitals than at community hospitals (27.2% vs 15.1%; P=.03) (Table 2). More patients with an aortic root measuring ≥4 cm before or after pregnancy delivered at academic centers as opposed to community centers (33.0% vs 10.2%; P=.01), but there were no significant differences in the median size of the aortic root during pregnancy or during the postpartum assessment between delivery locations. Cardiovascular complications were rare; 8 patients who delivered at academic centers and 7 patients who delivered at community centers had an aortic dissection either in pregnancy or the postpartum period (P=.79). CONCLUSION: Patients with Marfan syndrome or Loeys-Dietz syndrome and more severe aortic phenotypes were more likely to deliver at academic hospitals. Those who delivered at academic hospitals had higher rates of operative vaginal delivery. Despite lower frequencies of aortic root diameter >4.0 cm, those who delivered at community hospitals had higher rates of cesarean delivery for the indication of Marfan syndrome or Loeys-Dietz syndrome. Optimal delivery management of these patients requires further prospective research.

The utilization of genetic counselors by patient support groups.

The theoretical benefits of collaboration between patient support groups and genetic counselors have been discussed in the literature. However, no study has quantified the rate or ways that support groups utilize genetic counselors. This study surveyed one person in a leadership role at genetic support organizations to determine how many of the organizations have a relationship with genetic counselors, their utilization of genetic counselors, and their satisfaction with that relationship. It was found that 64.8% of organizations had a relationship with genetic counselors. Relationships were more likely to exist when organizations had full-time workers, had a primary focus on research, or offered a number and variety of services to members. Ways in which organizations utilized genetic counselors included as speakers at conferences, answering patient inquiries, and serving on expert panels. These relationships were supported through funding, networking, and patients connecting the two parties. Overall, representatives from organizations that had a relationship of any sort with genetic counselors were more likely to indicate satisfaction with that relationship than dissatisfaction (χ2 (4, n = 89) = 45.053, p < 0.001). Even so, many respondents indicated that they wanted to continue to grow their relationship with genetic counselors but were hindered by the lack of funding or access to genetic counselors who could be engaged in their cause. Thus, while relationships and satisfaction with the relationship to genetic counselors were generally high, this study highlights access, outreach, and funding as areas of focus to improve utilization of genetic counselors in the support group sector.

Postnatal Progressive Craniosynostosis in Syndromic Conditions: Two Patients With Saethre-Chotzen Due to TWIST1 Gene Deletions and Review of the Literature.

Saethre-Chotzen syndrome (SCS) is a known craniosynostosis syndrome with a variable presentation of craniofacial and somatic involvement. Congenital coronal craniosynostosis is most commonly observed in SCS; however, progressive postnatal craniosynostosis of other sutures has been reported. The authors present 2 infants with progressive postnatal craniosynostosis and SCS caused by chromosome 7p deletions including the TWIST1 gene. The evolution of their clinical features and a literature review of patients with syndromic, postnatal progressive craniosynostosis illustrate the importance of longitudinal observation and management of these patients.

Vascular aneurysms in Ehlers-Danlos syndrome subtypes: A systematic review.

Aneurysmal lesions are commonly seen in Ehlers-Danlos Syndrome (EDS). To better identify the regional and vessel-specific spectrum of aneurysms in different subtypes of EDS, we performed a systematic review. We searched Medline for relevant studies from 1963 to April 2022. Studies providing a report of any EDS subtype by genetic diagnosis, histologic analysis, or clinical criteria were included. A total of 448 patients from 220 studies were included. 720 vessel-specific aneurysms were reported: 386 in the abdominopelvic area, 165 in the intracranial region, 98 in the thorax, 2 in the extremities, and 6 in the venous system. In 27 out of the 65 patients with ruptured aneurysms, the ruptured aneurysm was the initial presentation. Multiple aneurysms were present in 163 out of 249 patients who had been systematically evaluated for other locations of aneurysms. The head and neck and abdominopelvic regions are two potential foci for aneurysm formation in patients with EDS. The aneurysm development in EDS is not confined to arteries; the venous system and cardiac septa may also be affected. Many patients develop multiple aneurysms, either at the time of the initial presentation or throughout their lifetime and aneurysm formation or rupture may be the first presentation of EDS.

The mental health impact of aortic dissection.

Although the topics of surgical techniques and medical therapies have been widely studied in aortic dissection (AD), studies examining the short- and long-term impact of this event on mental health are largely lacking. Many of the studies have used the 36-Item Short Form Survey at variable time points after the event. However, AD as medical trauma has a complex impact on a person's identity. Its implications for emotional, mental, social, existential, and self-concept could be explored more robustly. This topic was identified as a topic of interest by the AD Collaborative. The AD Collaborative Mental Health Working Group was formed and performed a landscape review to summarize current literature surrounding quality of life research in those who have experienced AD, identify gaps in knowledge, and to outline future research questions.

Loeys-Dietz syndrome caused by 1q41 deletion including TGFB2 is associated with a neurodevelopmental phenotype.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that commonly results in a dilated aorta, aneurysms, joint laxity, craniosynostosis, and soft skin that bruises easily. Neurodevelopmental abnormalities are uncommon in LDS. Two previous reports present a total of four patients with LDS due to pure 1q41 deletions involving TGFB2 (Gaspar et al., American Journal of Medical Genetics Part A, 2017, 173, 2289-2292; Lindsay et al., Nature Genetics, 2012, 44, 922-927). The current report describes an additional five patients with similar deletions. Seven of the nine patients present with some degree of hypotonia and gross motor delay, and three of the nine present with speech delay and/or intellectual disability (ID). The smallest deletion common to all patients is a 785 kb locus that contains two genes: RRP15 and TGFB2. Previous studies report that TGFB2 knockout mice exhibit severe perinatal anomalies (Sanford et al., Development, 1997, 124, 2659-2670) and TGFB2 is expressed in the embryonic mouse hindbrain floor (Chleilat et al., Frontiers in Cellular Neuroscience, 2019, 13). The deletion of TGFB2 may be associated with a neurodevelopmental phenotype with incomplete penetrance and variable expression.

D-dimer in Marfan syndrome: effect of obstructive sleep apnea induced blood pressure surges.

Aortic dissection and rupture are the major causes of premature death in persons with Marfan syndrome (MFS), a rare genetic disorder featuring cardiovascular, skeletal, and ocular impairments. We and others have found that obstructive sleep apnea (OSA) confers significant vascular stress in this population and may accelerate aortic disease progression. We hypothesized that D-dimer, a diagnostic biomarker for several types of vascular injury that is also elevated in persons with MFS with aortic enlargement, may be sensitive to cardiovascular stresses caused by OSA. To test this concept, we recruited 16 persons with MFS without aortic dissection and randomized them to two nights of polysomnography, without (baseline) and with OSA treatment: continuous positive airway pressure (CPAP). In addition to scoring OSA by the apnea-hypopnea index (AHI), beat-by-beat systolic BP (SBP) and pulse-pressure (PP) fluctuations were quantified. Morning blood samples were also assayed for D-dimer levels. In this cohort (male:female, 10:6; age, 36 ± 13 yr; aortic diameter, 4 ± 1 cm), CPAP eliminated OSA (AHI: 20 ± 17 vs. 3 ± 2 events/h, P = 0.001) and decreased fluctuations in SBP (13 ± 4 vs. 9 ± 3 mmHg, P = 0.011) and PP (7 ± 2 vs. 5 ± 2 mmHg, P = 0.013). CPAP also reduced D-dimer levels from 1,108 ± 656 to 882 ± 532 ng/mL (P = 0.023). Linear regression revealed a positive association between the maximum PP during OSA and D-dimer in both the unadjusted (r = 0.523, P = 0.038) and a model adjusted for contemporaneous aortic root diameter (r = 0.733, P = 0.028). Our study revealed that overnight CPAP reduces D-dimer levels commensurate with the elimination of OSA and concomitant hemodynamic fluctuations. Morning D-dimer measurements together with OSA screening might serve as predictors of vascular injury in MFS.NEW & NOTEWORTHY What is New? Surges in blood pressure caused by obstructive sleep apnea during sleep increase vascular stress and D-dimer levels in Marfan syndrome. Elevations in D-dimer can be lowered with CPAP. What is Noteworthy? D-dimer levels might serve as a marker for determining the significance of obstructive sleep apnea in persons with Marfan syndrome. D-dimer or obstructive sleep apnea screening is a potential method to identify persons with Marfan syndrome at risk for adverse cardiovascular events.

Assessment of pleural pressure during sleep in Marfan syndrome.

STUDY OBJECTIVES: Patients with Marfan syndrome (MFS) have a high risk for aortic aneurysms. They are also susceptible to sleep-disordered breathing that may expose them to highly negative intrathoracic pressures known to increase aortic transmural pressure, which may accelerate aortic dilatation. Our objective was to quantify overnight intrathoracic pressure changes during sleep in snoring patients with MFS and the therapeutic effect of continuous positive airway pressure (CPAP). METHODS: We used a questionnaire to identify self-reported snoring patients with MFS. In these patients, we monitored intrathoracic pressure using esophageal pressure (Pes) during overnight baseline and CPAP sleep studies. We defined a peak-inspiratory Pes (Pespeak-insp) < - 5 cm H2O as greater than normal and examined the distribution of Pespeak-insp during baseline and CPAP studies. RESULTS: In our sample of 23 snorers with MFS, we found that 70% of sleep breaths exhibited Pespeak-insp < -5 cm H2O, with apnea/hypopneass accounting for only 12%, suggesting prevalent stable flow-limited breathing and snoring. In a subset (n = 12) with Pes monitoring during a CPAP night, CPAP lowered the mean proportion of breaths with Pespeak-insp < -5 cm H2O from 83.7% ± 14.9% to 3.6% ± 3.0% (P < .001). In addition, contemporaneous aortic root diameter was associated with the mean Pespeak-insp during inspiratory flow-limited breathing and apneas/hypopneas (ß = -0.05, r = .675, P = .033). CONCLUSIONS: The sleep state in MFS revealed prolonged exposure to exaggerated negative inspiratory Pes, which was reversible with CPAP. Since negative intrathoracic pressure can contribute to thoracic aortic stress and aortic dilatation, snoring may be a reversible risk factor for progression of aortic pathology in MFS. CITATION: Sowho M, Jun J, Sgambati F, et al. Assessment of pleural pressure during sleep in Marfan syndrome. J Clin Sleep Med. 2022;18(6):1583-1592.

Accurate assignment of disease liability to genetic variants using only population data.

PURPOSE: The growing size of public variant repositories prompted us to test the accuracy of pathogenicity prediction of DNA variants using population data alone. METHODS: Under the a priori assumption that the ratio of the prevalence of variants in healthy population vs that in affected populations form 2 distinct distributions (pathogenic and benign), we used a Bayesian method to assign probability to a variant belonging to either distribution. RESULTS: The approach, termed Bayesian prevalence ratio (BayPR), accurately parsed 300 of 313 expertly curated CFTR variants: 284 of 296 pathogenic/likely pathogenic variants in 1 distribution and 16 of 17 benign/likely benign variants in another. BayPR produced an area under the receiver operating characteristic curve of 0.99 for 103 functionally confirmed missense CFTR variants, which is equal to or exceeds 10 commonly used algorithms (area under the receiver operating characteristic curve range = 0.54-0.99). Application of BayPR to expertly curated variants in 8 genes associated with 7 Mendelian conditions led to the assignment of a disease-causing probability of ≥80% to 1350 of 1374 (98.3%) pathogenic/likely pathogenic variants and of ≤20% to 22 of 23 (95.7%) benign/likely benign variants. CONCLUSION: Irrespective of the variant type or functional effect, the BayPR approach provides probabilities of pathogenicity for DNA variants responsible for Mendelian disorders using only the variant counts in affected and unaffected population samples.

Predictors of low bone density and fracture risk in Loeys-Dietz syndrome.

PURPOSE: Loeys-Dietz syndrome (LDS) is a connective tissue disorder affecting multiple organ systems, including bone. METHODS: We defined the bone phenotype and clinical predictors of low bone density and fracture risk in 77 patients with LDS type 1 to type 5. RESULTS: Patients with LDS had dual-energy x-ray absorptiometry (DXA) Z-scores significantly < 0, and 50% of children and 9% of adults had Z-scores < -2. Sixty percent of patients had ≥1 fracture, and 24% of patients with spinal x-rays scans showed spinal compression fractures. Lower body mass index, asthma, male sex and eosinophilic gastrointestinal disease were correlated with lower DXA Z-scores. The count of 5 LDS-associated skeletal features (scoliosis, pes planus, arachnodactyly, spondylolisthesis, and camptodactyly) in patients with LDS was correlated with DXA Z-score. Adults with ≥1 skeletal features had DXA Z-scores significantly < 0, and children with >2 features had DXA Z-score significantly < -2. Bone turnover markers suggest accelerated bone resorption. Data from 5 patients treated with bisphosphonates suggest a beneficial effect. CONCLUSION: All LDS types are associated with reduced bone density and increased risk of fracture, which may be due to increased bone resorption. Clinical features can predict a subgroup of patients at highest risk of low bone density and fracture risk.

Association of sleep apnoea risk and aortic enlargement in Marfan syndrome.

BACKGROUND: Marfan syndrome (MFS) is a connective tissue disorder characterised by complex aortic pathology and a high prevalence of obstructive sleep apnoea (OSA). OSA produces intrathoracic transmural stresses that may accelerate aortic injury. The current study was designed to examine the associations between OSA risk and markers of aortic enlargement in MFS. METHOD: Consecutive patients with MFS were recruited at Johns Hopkins if they completed a STOP-BANG survey. Composite survey scores were categorised into those with low OSA risk (STOP-BANG <3) and high OSA risk (STOP-BANG ≥3). Participants' aortic data were collated to ascertain aortic root diameter, dilatation and prior aortic root replacement. Regression analyses were used to examine associations between OSA risk strata and these aortic parameters. RESULTS: Of the 89 participants studied, 28% had a high OSA risk and 32% had aortic grafts. Persons with high OSA risk had greater aortic root diameter (mm) (ß=4.13, SE=1.81, p=0.027) and aortic root dilatation (ß=2.80, SE=1.34, p=0.046) compared with those with low OSA risk . In addition, the odds of prior aortic root replacement was three times greater in those with high OSA risk compared with those with low OSA risk. CONCLUSION: In MFS, high OSA risk is associated with aortic enlargement and a threefold increased risk of having had prior aortic root replacement. These findings invite further exploration of the relationship between OSA and aortic disease in MFS, and studies to clarify whether targeted interventions for OSA might mitigate aortic disease progression in MFS. REGISTRATION NUMBER: IRB00157483.

Toward precision medicine in vascular connective tissue disorders.

Tremendous progress has been made in understanding the etiology, pathogenesis, and treatment of inherited vascular connective tissue disorders. While new insights regarding disease etiology and pathogenesis have informed patient counseling and care, there are numerous obstacles that need to be overcome in order to achieve the full promise of precision medicine. In this review, these issues will be discussed in the context of Marfan syndrome and Loeys-Dietz syndrome, with additional emphasis on the pioneering contributions made by Victor McKusick.

Recruitment, retention, and adherence in a clinical trial: The Pediatric Heart Network's Marfan Trial experience.

BACKGROUND/AIMS: The Pediatric Heart Network Marfan Trial was a randomized trial comparing atenolol versus losartan on aortic root dilation in 608 children and young adults with Marfan syndrome. Barriers to enrollment included a limited pool of eligible participants, restrictive entry criteria, and a diverse age range that required pediatric and adult expertise. Retention was complicated by a 3-year commitment to a complex study and medication regimen. The Network partnered with the Marfan Foundation, bridging the community with the research. The aims of this study are to report protocol and medication adherence and associated predictive factors, and to describe recruitment and retention strategies. METHODS: Recruitment, retention, and adherence to protocol activities related to the primary outcome were measured. Retention was measured by percentage of enrolled participants with 3-year outcome data. Protocol adherence was calculated by completion rates of study visits, ambulatory electrocardiography (Holter monitoring), and quarterly calls. Medication adherence was assessed by the number of tablets or the amount of liquid in bottles returned. Centers were ranked according to adherence (high, medium, and low tertiles). Recruitment, retention, and adherence questionnaires were completed by sites. Descriptive statistics summarized recruitment, retention, and adherence, as well as questionnaire results. Regression modeling assessed predictors of adherence. RESULTS: Completion rates for visits, Holter monitors, and quarterly calls were 99%, 94%, and 96%, respectively. Primary outcome data at 3 years were obtained for 88% of participants. The mean percentage of medication taken was estimated at 89%. Site and age were associated with all measures of adherence. Young adult and African American participants had lower levels of adherence. Higher adherence sites employed more strategies; had more staffing resources, less key staff turnover, and more collaboration with referring providers; utilized the Foundation's resources; and used a greater number of strategies to recruit, retain, and promote protocol and medication adherence. CONCLUSION: Overall adherence was excellent for this trial conducted within a National Institutes of Health-funded clinical trial network. Strategies specifically targeted to young adults and African Americans may have been beneficial. Many strategies employed by higher adherence sites are ones that any site could easily use, such as greeting families at non-study hospital visits, asking for family feedback, providing calendars for tracking schedules, and recommending apps for medication reminders. Additional key learnings include adherence differences by age, race, and site, the value of collaborative learning, and the importance of partnerships with patient advocacy groups. These lessons could shape recruitment, retention, and adherence to improve the quality of future complex trials involving rare conditions.

Safety and outcome of gastrostomy tube placement in patients with Loeys-Dietz syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS) is a systemic connective tissue disease (CTD) associated with a predisposition for intestinal inflammation, food allergy, and failure to thrive, often necessitating nutritional supplementation via gastrostomy tube. Poor wound healing has also been observed in in some patients with CTD, potentially increasing the risk of surgical interventions. We undertook to determine the safety and efficacy of gastrostomy tube placement in this population. METHODS: We performed a retrospective cohort study of 10 LDS patients who had a total of 12 gastrostomy tubes placed. RESULTS: No procedural complications occurred, although one patient developed buried bumper syndrome in the near post-procedural time period and one patient had a small abscess at a surgical stitch. Most patients exhibited improvements in growth, with a median immediate improvement in BMI Z-score of 0.2 per month following the institution of gastrostomy tube feedings. Those with uncontrolled inflammation due to inflammatory bowel disease or eosinophilic gastrointestinal disease showed the least benefit and in some cases failed to demonstrate significant weight gain despite nutritional supplementation. CONCLUSIONS: Gastrostomy tube placement (surgical or endoscopic) is a generally safe and a reasonable therapeutic option for patients with LDS despite their underlying CTD.

Sleep disordered breathing in Marfan syndrome: Value of standard screening questionnaires.

BACKGROUND: A high prevalence of sleep disordered breathing (SDB) has been reported in persons with Marfan syndrome (MFS), a single gene disorder of connective tissue resulting in premature death from aortic rupture. The burden of SDB and accompanying hemodynamic stress could warrant broad screening in this population. Our goal was to assess the utility of traditional SDB screening tools in our sample of persons with MFS. METHODS: Participants were recruited during an annual Marfan Foundation meeting and Marfan status confirmed using the Ghent criteria. Screening questionnaires were administered and SDB assessed by home sleep testing. We assessed accuracy of screening tools using receiver-operating characteristic curve analyses. RESULTS: The prevalence of moderate-severe SDB was 32% in our sample of 31 MFS participants. The Stop-Bang questionnaire had the highest positive predictive value (PPV) of 60% and the highest negative predictive value (NPV) of 100% using the high- and moderate-risk cut-offs, respectively, and the Berlin questionnaire had a PPV of 50% and an NPV of 92.3% at the high-risk cut-off. When those with mild SDB were included, the Stop-Bang and the Sleep Apnea Clinical Score (SACS) questionnaires demonstrated useful screening accuracies with PPVs of 94.7% and 92.9%, and NPVs of 63.6% and 47.1%, respectively, at the moderate-risk cut-offs. CONCLUSION: A survey of SDB in a sample of persons with MFS reveals not only a high burden of SDB but also that conventional screening instruments have utility if adapted appropriately. Future studies should validate the utility of these screening tools given concerns that SDB may contribute to progression of aortic pathology in MFS.