Loeys-Dietz Research Articles

Open surgical replacement of the descending thoracic and thoracoabdominal aorta in patients with confirmed Marfan and Loeys-Dietz syndromes: A 20-year single-centre experience.

A relatively small proportion of patients with heritable thoracic aortic disease require open surgical replacement of the distal thoracic aorta. We reviewed the outcome in patients with Marfan and Loeys-Dietz syndromes treated in an aortic centre in the United Kingdom. We performed a single-centre retrospective study of consecutive patients treated between October 1999 and December 2019. The primary end point was 30-day mortality. Secondary end points were Kaplan-Meier estimates of medium-term survival and freedom from distal reintervention. Data are presented as median (interquartile range). A total of 58 patients [33 men; 51 with Marfan syndrome; median age 41 years (35-48); median aneurysm diameter 60 mm (55-74)] underwent open descending (n = 21) or thoracoabdominal aortic replacement (n = 37). All repairs were performed using cardiopulmonary bypass with hypothermic circulatory arrest in 31 patients. The 30-day mortality was 5.2% (n = 3, including 2 patients ≥ 60 years with significant comorbidity). Major non-fatal complications included early reoperation (n = 7), tracheostomy (n = 9), temporary renal replacement therapy (n = 3), permanent spinal cord deficit (n = 2) and permanent stroke (n = 1). Median follow-up was 81 months (48-127). Estimated (±standard error) 5-year survival was 85% ±5%. Seven patients had distal aortic reintervention with no deaths or spinal cord deficit: estimated 5-year freedom from distal reintervention was 94% ±3%. There was no difference in survival or freedom from distal reintervention comparing: elective vs. non-elective; type of heritable thoracic aortic disease; DeBakey type; or extent of surgical repair. Descending thoracic and thoracoabdominal aortic replacement in patients with heritable thoracic aortic disease can be performed with low perioperative morbidity and mortality, satisfactory long-term survival and low requirement for distal reintervention.

EP118: Connective tissue disorders not otherwise specified: Defining the problem

Connective tissue disorders (CTDs) such as Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers-Danlos syndrome (vEDS), and related disorders have clinical and molecular diagnostic criteria, known risks for aortic dilation and dissection, and guidelines for cardiac surveillance and management. Some patients, however, do not meet diagnostic criteria for a well characterized genetic CTD but possess physical signs and symptoms consistent with connective tissue involvement. For this population of patients with CTD not otherwise specified (CTD-NOS), few data exist about cardiac risk or other morbidity.

Latent TGFβ-binding proteins 1 and 3 protect the larval zebrafish outflow tract from aneurysmal dilatation.

ABSTRACTAortic root aneurysm is a common cause of morbidity and mortality in Loeys-Dietz and Marfan syndromes, where perturbations in transforming growth factor beta (TGFβ) signaling play a causal or contributory role, respectively. Despite the advantages of cross-species disease modeling, animal models of aortic root aneurysm are largely restricted to genetically engineered mice. Here, we report that zebrafish devoid of the genes encoding latent-transforming growth factor beta-binding protein 1 and 3 (ltbp1 and ltbp3, respectively) develop rapid and severe aneurysm of the outflow tract (OFT), the aortic root equivalent. Similar to syndromic aneurysm tissue, the distended OFTs display evidence for paradoxical hyperactivated TGFβ signaling. RNA-sequencing revealed significant overlap between the molecular signatures of disease tissue from mutant zebrafish and a mouse model of Marfan syndrome. Moreover, chemical inhibition of TGFβ signaling in wild-type animals phenocopied mutants but chemical activation did not, demonstrating that TGFβ signaling is protective against aneurysm. Human relevance is supported by recent studies implicating genetic lesions in LTBP3 and, potentially, LTBP1 as heritable causes of aortic root aneurysm. Ultimately, our data demonstrate that zebrafish can now be leveraged to interrogate thoracic aneurysmal disease and identify novel lead compounds through small-molecule suppressor screens.This article has an associated First Person interview with the first author of the paper.

Long-term durability of a reimplantationvalve-sparing aortic root replacement can be expected in both Marfan syndrome and Loeys-Dietz syndrome.

The goal of this study was to evaluate the surgical outcomes of a valve-sparing root replacement using the reimplantation technique for annuloaortic ectasia in patients with Marfan syndrome (MFS) and in those with Loeys-Dietz syndrome (LDS). We reviewed 103 patients with MSF with mutations in the fibrillin-1 gene and 28 patients with LDS with mutations in the transforming growth factor-beta receptor and 2, SMAD3 and transforming growth factor beta-2 from 1988 to 2020. Forty-four (42.7%) patients with MFS [26 men, 31 (7.6) years] and 10 (35.7%) patients with Loeys-Dietz syndrome (LDS) [7 men, 22 (standard deviation: 8.6) years] who had no aortic dissection and underwent valve-sparing root replacement were included. The preoperative sinus diameter [46 (45-50.5) mm in those with MFS vs 48 (47-50) mm in those with LDS, p = 0.420] and the percentage of aortic insufficiency > grade 2+ [31.8% (10/44) in patients with MFS vs 10.0% (1/10) in those with LDS, p = 0.667] revealed no significant differences between the 2 groups. The cumulative incidences of aortic insufficiency greater than grade 1 (p = 0.588) and aortic valve reoperation (p = 0.310) were comparable between the 2 groups. Patients with LDS had a higher tendency towards aortic dissection after the initial operation (p = 0.061) and a significantly higher cumulative incidence of aortic reoperation (p = 0.003) versus those with MFS. Patients with MFS and those with LDS showed similar cumulative incidences of recurrent aortic valve insufficiency and aortic valve reoperation. Those with LDS revealed a higher cumulative incidence of aortic reoperation and a greater tendency towards aortic dissection after the initial operation compared with those with MFS.

Thoracoabdominal aortic aneurysm in connective tissue disorder patients.

Connective tissue disorders (CTDs) are a group of genetically triggered diseases in which the primary defect involves collagen and elastin protein assembly with potential vascular degenerations such as thoracoabdominal aortic aneurysm (TAAA) and dissection. These most commonly include Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, and familial thoracic aortic aneurysm and dissection. Open surgical repair represents the standard approach in this specific group of patients. Extensive aortic replacements are generally performed in order to reduce long-term complications caused by the progressive dilatation of the remnant aortic segments. In the last decades, endovascular interventions have emerged as a valid alternative in patients affected by degenerative TAAA. However, in patients with CTD, this approach presents higher rates of reinterventions and postoperative complications with a disputable long-term durability, and it is nowadays performed for very selective indications such as severe comorbidities and urgent/emergent settings. Despite a deeper knowledge of the pathophysiological mechanisms involved in CTD, improvements in medical therapy, and a multidisciplinary approach fully involved in the management of these usually frailer patients, this specific group still represents a challenge. Further dedicated studies addressing mid-term and long-term outcomes in this selected population are needed.

Mitral valve prolapse but no mitral annular disjunction is related to mitral regurgitation progression in patients with Marfan syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Mitral annular disjunction (MAD) is a structural abnormality of the mitral annular fibrosus characterized by a separation between the atrial wall-mitral valve junction, and the left ventricular attachment (1,2). It has been associated with mitral valve prolapse (MVP). Limited data is available regarding the impact of the presence of MVP on the evolution of mitral regurgitation in these syndromic entities. Purpose To evaluate the prevalence of MAD, PMV, and the combination of both in patients with syndromic hereditary thoracic aortic disease (HTAD) including Marfan (MFS), Loeys-Dietz (LDS), and vascular Ehlers-Danlos syndromes (vEDS), and its relationship with mitral regurgitation (MR) severity and the need for mitral surgery at the follow-up. Methods Adult patients with syndromic HTAD seen at our specialized unit were retrospectively included. The presence of MAD, MVP, and significant MR at the first echocardiogram were evaluated. Electronic medical records were reviewed to register the need for mitral surgery. The last echocardiogram available was also assessed to evaluate MR progression. Results A total of 295 patients were included (235 MFS, 42 LDS, and 18 vEDS). The mean age at baseline was 39.0+-14.4 and 52.9% were female. MAD was present in 87 (37.0%) of MFS, 6 (14.3 %) of LDS and was not present in vEDS (p< 0.001). MVP was found in 105 (44.7%) of MFS, 6 (14.3%) of LDS and 0 in vEDS (p< 0.001). In MFS, MAD was significantly associated with MVP (p= <0.001) (Table 1). Concretely, 73 (31.1%) of the MFS patients had the concurrence of MAD and MVP and 14 (6.0%) of patients had isolated MAD (Table 2). At baseline, significant MR was observed in 30 (12.8%) of the MFS and in 18 (24.7%) of patients with concurrent MAD and MVP. Interestingly, significant MR was absent in patients with isolated MAD (Figure 1). MVP (OR 16.85 CI 4.43 – 64.07) but not MAD (p = 0.607), was associated with significant MR in the multivariate analysis. A second echocardiogram was available in 220 patients at > = 1 year (mean 4.1 +- 1.4 years). Overall, 25 (11.4%) presented significant progression of MR, 0 in the isolated MAD group, 13 (19.4%) in the MAD/MVP group and 6 (20.0%) of the isolated MVP (p = 0.007). After a mean clinical follow-up of 7.5 +- 3.2yrs, 10 patients required mitral surgery (6 prostheses, 4 valvuloplasties). After adjustment for the presence of MVP and time of follow-up, MAD was not associated with progression of MR (p= 0.529) but MVP was (OR 5.2 IC 1.70 - 15.93). Similarly, MVP (OR 5.6 CI 1.23 - 25.86) but not MAD (P= 0.096) was associated with the need for mitral surgery ., Conclusions The prevalence of MAD in syndromic HTAD is high, especially in Marfan syndrome, and absent in vEDS. In this retrospective observational study, the presence of MVP but not MAD was associated with mitral regurgitation evolution and the need for mitral surgery. Abstract Table 1 Abstract Figure 1

Targeted IL-4Rα blockade ameliorates refractory allergic eosinophilic inflammation in a patient with dysregulated TGF-β signaling due to ERBIN deficiency

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that possesses immune stimulatory and inhibitory functions, influences T-lymphocyte differentiation, and promotes cell proliferation and wound healing.1 This TGF-β signaling activates the transcription factor SMAD3, which increases interleukin-4 (IL-4) receptor expression associated with type 2–skewed immune responses (Figure 1). Dysregulated TGF-β signaling has been implicated in human syndromes with coexistent connective tissue abnormalities and atopy (eg, Ehlers-Danlos syndrome, Loeys-Dietz syndrome).

Spontaneous coronary artery dissection is infrequent in individuals with heritable thoracic aortic disease despite partially shared genetic susceptibility.

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N= 9), including COL3A1 (N= 3), FBN1 (N=2), TGFBR2 (N= 2), TGFBR1 (N= 1), and PRKG1 (N= 1). Individuals with SCAD had an increased frequency of iliac artery dissection (25.0% vs. 5.1%, p= 0.047). The prevalence of SCAD among individuals with TAD is low. The identification of pathogenic variants in genes previously described in individuals with SCAD, particularly those underlying vascular Ehlers-Danlos, Marfan syndrome, and Loeys-Dietz syndrome, is consistent with prior reports from clinical SCAD series. Further research is needed to identify specific genetic influences on SCAD risk.

Neurovascular abnormalities in patients with Loeys-Dietz syndrome type III

The aim of this article is to describe neurovascular findings in patients with Loeys Dietz syndrome type III and their possible clinical impact. Loeys Dietz syndrome type III, caused by pathogenic SMAD3 variants, is an autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. Neurovascular abnormalities have been described in other heritable aortic syndromes, however, reliable data in Loeys Dietz syndrome type III is missing.In our tertiary center, all adult patients with confirmed Loeys Dietz syndrome type III are followed in a standardized aorta outpatient clinic including Computed Tomography Angiography (CTA) of the head and neck region at baseline and (tri) yearly during follow-up. We performed an analysis of the neurovascular imaging findings and clinical follow-up. The primary outcome was a combined endpoint of mortality, dissection, cerebral vascular event and intervention. In addition, tortuosity and vascular growth were assessed. In total 26 patients (mean age 38.4 years, 38.5% males) underwent 102 (mean 3.9 (1-8) per patient) neurovascular Computed Tomography Angiography scans between 2010 and 2021. In 84.6% some form of neurovascular abnormality was found. The abnormalities at baseline were aneurysm (26.9%) dissection flap (7.7%), arterial tortuosity (61.5%), arterial coiling (23.1%) and arterial kinking (3.8%). During follow up (mean 8.85 (1-11) years) one patient suffered from sudden death and one patient needed a neuro-radiological intervention. No cerebral bleeding or stroke occurred.In conclusion, neurovascular imaging in Loeys Dietz syndrome type III patients revealed abnormalities such as aneurysm, tortuosity, coiling and kinking in the vast majority of patients, but clinical events were rare. Neurovascular screening and follow up is advised in all Loeys Dietz syndrome type III patients.

Impact of genotype on the progression of aortic disease in patients with Marfan syndrome and Loeys-Dietz syndrome

Marfan and Loeys-Dietz syndromes are connective tissue disorders characterized by high clinical variability. The major morbidity and mortality in both syndromes relate to the dilatation of the aorta predisposing to aortic tear. We investigated the putative relationship between the genotype, aortic growth speed and the occurrence of severe cardio vascular events (prophylactic surgery of the aortic root, aortic dissection or related death). We have performed a retrospective study of 102 patients with pathogenic variants in FBN1, TGFβR1 and R2 and SMAD3 genes followed at a Marfan reference center in France. The average age at the start of the study was 13.8 years and data were collected over 5 years. The FBN1 variants were classified as haploinsufficient (HI) or dominant negative (DN). Aortic diameters and aortic dilatation at the level of the Valsalva sinuses were assessed by echocardiography. No overall aortic growth difference was found between Marfan and Loeys-Dietz syndrome (1,14 vs. 1,11 mm/year, P = 0,74), neither between HI and DN groups (1,12 vs. 1,01 mm/year, P = 0,36). However, patients with a SMAD 3 mutation seem to have lower aortic growth than those in the TGFβ group (0,91 vs. 1,34 mm/year, P = 0,36). No difference concerning Valsalva sinus Z score evolution was found between these groups. We didn’t find any differences concerning the occurrence of cardio vascular events between Marfan and Loeys Dietz syndrome and their genetics subgroups. Aortic growth in men was significantly faster than in women (1,23 vs. 0,91 mm/year, P = 0,005). Marfan syndrome and Loeys-Dietz, as well as their genetics subgroups should be monitored similarly for the development of aortic root aneurysm. Like other phenotypic characteristics of these syndromes, the cardio vascular manifestations present a high variability among patients and a correlation genotype/phenotype is not informative for patient care. A possible exception is the TGFβ group, which may grow faster.

Connective tissue disease type mediates branch patency of grafts in open thoracoabdominal aortic reconstruction.

Despite a shared degenerative vascular phenotype, Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and other genetically distinct connective tissue diseases (CTDs) have unique extravascular pathologies that impact the outcomes of aortic replacement. The aim of our study was to investigate the association of CTD genotype with postoperative outcomes and branch patency following open thoracoabdominal aortic replacement in a large institutional cohort. All patients undergoing open branched thoracoabdominal aortic replacement at a single academic center from 2006 to 2020 were included and classified as CTD or non-CTD based on the presence of genotypic documentation. Outcomes were compared using analysis of variance and χ2 testing for continuous and discrete variables, respectively. Kaplan-Meier curves were utilized to examine patency of graft branches over time. Overall, 172 patients were included, with a mean follow-up of 30.5± 34.9months. CTD was present in 45 patients (26%); specifically, 32 had MFS, five had LDS, and eight had another CTD. Patients with CTDs had more extent II thoracoabdominal aneurysms (40% vs 15%), more reconstructed branches (3.5 vs 1.8), more frequently reconstructed visceral branches (86.7% vs 22.7%), and higher intraoperative blood loss (13.3 vs 6.8L; all P< .05) compared with non-CTD patients. Patients with MFS were more frequently systemically anticoagulated preoperatively (50% vs 5%) and demonstrated higher rates of postoperative deep vein thrombosis/pulmonary embolism compared with non-CTD patients (9%vs 2%; both P< .05). Five-year renal branch patency was decreased among all patients compared with visceral branches (87.3% vs 95.6%; P= .05), but there were no individual branch patency differences between patients with and without CTDs (P= .086). Overall branch patency at 1 and 5years was significantly higher in patients with MFS than in non-CTD patients (98.9% vs 89.1% at 5years); there were no significant patency differences between non-CTD patients and any other CTD subgroup, mostly due to early patency loss. Open thoracoabdominal reconstruction in patients with CTD is technically challenging and associated with increased transfusion and postoperative thromboembolic events when compared with non-CTD patients. Technical outcomes of the procedure are excellent and are differentially associated with genotype, with patients with MFS experiencing significantly improved branch patency over both non-CTD patients and patients with other CTDs, a finding which has multifactorial drivers.

Endovascular therapy for patients with heritable thoracic aortic disease.

Patients with genetic or heritable aortic conditions and thoracic aortic aneurysm syndrome often develop cardiovascular abnormalities originating at the aortic root and affecting the entire thoracoabdominal aorta. Although thoracic endovascular aortic repair (TEVAR) is usually avoided in these patients, TEVAR may be worthwhile for those at high risk for surgical complications and in certain emergency circumstances. We explored indications for TEVAR in patients with suspected or confirmed genetic or heritable aortic conditions and investigated early and mid-term outcomes. Our institutional aortic surgery database was queried for patients with suspected or confirmed Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, Turner syndrome, neurofibromatosis, or familial aortic aneurysm and dissection who underwent TEVAR between February 1, 2002 and October 31, 2020. We extracted operative details and in-hospital, follow-up, and survival data. Thirty-seven patients who underwent 40 endovascular interventions met the inclusion criteria; 25 previously underwent ascending aorta or aortic root surgery, and 21 previously underwent open thoracoabdominal surgery. Postoperative complications included respiratory failure (24.3%), cardiac complications (16.2%), renal failure (13.5%), tracheostomy (8.1%), and spinal cord ischemia (paraplegia/paraparesis) (8.1%). Follow-up ranged from 1.3 to 8.5 years (median: 3.6 years), with 15 deaths overall (three early/in-hospital). Thirteen patients (35.1%) had 22 repeat interventions (open and endovascular) post-TEVAR; five had the endograft removed. Despite consensus that thoracic aneurysms in patients with genetic or heritable aortic conditions should be treated with conventional open surgery, the outcomes from our study suggest that TEVAR might be suitable in emergency settings or for patients in this population who are not candidates for open surgery, who are at high risk for reintervention, or who have a previously implanted Dacron graft. Nonetheless, lifelong surveillance is important for these patients after TEVAR to monitor for new dissection at distal or proximal landing zones, as repeat interventions are frequent.

Histopathological Features of Monogenic Inflammatory Bowel Disease: Subanalysis of Systematic Review.

Histopathological Features of Monogenic Inflammatory Bowel Disease: Subanalysis of Systematic Review.

A Turkish Family with Loeys-dietz Syndrome and a Report of a Homozygous Patient with SMAD3 Pathogenic Variation

A Turkish Family with Loeys-dietz Syndrome and a Report of a Homozygous Patient with SMAD3 Pathogenic Variation

Multiple anesthesia experiences for two Loeys-Dietz syndrome (LDS) patients in the same family

Multiple anesthesia experiences for two Loeys-Dietz syndrome (LDS) patients in the same family

Increased intracranial arterial tortuosity is associated with worse cardiovascular outcome in patients with Loeys-Dietz syndrome

The aim of our study was to evaluate the association between intracranial arterial tortuosity and cardiovascular outcome in patients with Loeys-Dietz syndrome (LDS). We performed a retrospective analysis of all patients with genetically confirmed LDS who underwent at least one brain MRA at our institution (n = 32); demographic and clinical features were evaluated in relation to the tortuosity of intracranial arteries as measured by tortuosity index (TI), which was calculated using the formula: [(centerline length) / (straight-line length)-1] × 100. Receiver operating characteristic curve analysis for intracranial TI and the binary end point of aortic surgery showed vertebrobasilar TI (VBTI) to be the best classifier among the examined arterial segments (AUC = 0.822). Patients with higher VBTI showed a greater incidence of aortic surgery (p < 0.001) and underwent more surgical and endovascular procedures (p = 0.006), with a higher rate of operations (p = 0.002). Kaplan-Meier analysis showed a significantly longer surgery-free survival in patients with lower arterial tortuosity (p < 0.001). At multivariate analysis, higher VBTI was associated with an increased risk of surgery (p < 0.001), which was independent of gene mutation and patient age. Increased VBTI is a marker of adverse cardiovascular outcome in patients with LDS, which can be easily measured on brain MRA, and may be useful in the management of this heterogeneous patient population.

Clinical and Genetic Findings in a Series of Eight Families with Arthrogryposis

The term “arthrogryposis” is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an impairment of embryofetal neuromuscular function and development. The causes of arthrogryposis are multiple, and in newborns, it is difficult to predict the molecular defect as well as the clinical evolution just based on clinical findings. We studied a consecutive series of 13 participants who had amyoplasia, distal arthrogryposis (DA), or syndromic forms of arthrogryposis with normal intellectual development and other motor abilities. The underlying pathogenic variants were identified in 11 out of 13 participants. Correlating the genotype with the clinical features indicated that prenatal findings were specific for DA; this was helpful to identify familial cases, but features were non-specific for the involved gene. Perinatal clinical findings were similar among the participants, except for amyoplasia. Dilatation of the aortic root led to the diagnosis of Loeys–Dietz syndrome (LDS) in one case. The phenotype of DA type 5D (DA5D) and Escobar syndrome became more characteristic at later ages due to more pronounced pterygia. Follow-up indicated that DA type 1 (DA1)/DA type 2B (DA2B) spectrum and LDS had a more favorable course than the other forms. Hand clenching and talipes equinovarus/rocker bottom foot showed an improvement in all participants, and adducted thumb resolved in all forms except in amyoplasia. The combination of clinical evaluation with Next Generation Sequencing (NGS) analysis in the newborn may allow for an early diagnosis and, particularly in the DAs, suggests a favorable prognosis.

Loeys-Dietz and Shprintzen-Goldberg syndromes: analysis of TGF-β-opathies with craniofacial manifestations using an innovative multimodality method

BackgroundElevated transforming growth factor-beta (TGF-β) signalling has been implicated in the pathogenesis of Loeys-Dietz syndrome (LDS) and Shprintzen-Goldberg syndrome (SGS). In this study, we provide a qualitative and quantitative analysis...

Safety and Effectiveness of TEVAR in Native Proximal Landing Zone 2 for Chronic Type B Aortic Dissection in Patients With Genetic Aortic Syndrome

Objectives The aim of this study is to report the safety and effectiveness of thoracic endovascular aortic repair (TEVAR) in a native proximal landing zone (PLZ) 2 for chronic type B aortic dissection (TBAD) patients with genetic aortic syndrome (GAS). Methods A retrospective review of a single center database to identify patients with GAS treated with TEVAR in native PLZ 2 for chronic TBAD and thoracic false lumen aneurysm between February 2012 and February 2018 was undertaken. Results In total, 31 patients with GAS (24 Marfan syndrome [MFS], 5 Loeys-Dietz syndrome [LDS], and 2 vascular Ehlers-Danlos syndrome [vEDS]) were treated by endovascular repair. Nineteen patients were treated by TEVAR as index procedures with 8 patients (5 females, mean age = 55, range = 36–79 years old) receiving TEVAR in native PLZ 2. Left subclavian artery (LSA) perfusion was preserved in all 8 patients: by left common carotid artery-LSA bypass in 6 patients, chimney stenting of the LSA in 1 patient, and partial coverage of LSA ostium in 1 patient. Technical success was achieved in all patients (100%). There was no 30 day mortality (0%). The 30 day morbidity (0%) was free from major complications. The median follow-up was 40 months (range = 7–79). One patient died due to non-aortic-related cause. Native PLZ 2 was free from complications in MFS patients (5/8). Two patients with LDS developed type Ia endoleak with aneurysmal progression. One patient was treated by proximal extension with a double inner branched arch stent-graft landing in the replaced ascending aorta. The other one was treated with frozen elephant trunk. Conclusion Thoracic endovascular aortic repair in native PLZ 2 was safe and effective with no early or midterm PLZ complications in patients with MFS with chronic TBAD in this limited series. Native PLZ 2 is not safe in patients with LDS and should only be used in emergencies as a bridging to open repair.

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

PurposeLoeys–Dietz syndrome (LDS) is a connective tissue disorder affecting multiple organ systems, including bone. MethodsWe defined the bone phenotype and clinical predictors of low bone density and fracture risk in 77 patients with LDS type 1 to type 5. ResultsPatients 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. ConclusionAll 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.