Vascular Ehlers-Danlos Syndrome Research Articles

Headache disorders in patients with Ehlers-Danlos syndromes and hypermobility spectrum disorders

Extra-articular symptoms, including headaches, are frequently encountered in patients with Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders (HSD), and may be the presenting complaint. Migraine is reported in up to three quarters of patients with symptomatic joint hypermobility, have a higher headache frequency, and an earlier age of onset compared to the general population. Orthostatic headache is an important presentation, and should raise suspicion of an underlying spinal cerebrospinal fluid leak, dysautonomia, and craniocervical pathology, which are all associated with heritable connective tissue disorders (HCTD) including EDS. Any proposed invasive procedure should be scrupulously balanced against its potential risks, taking into account the type of EDS (e.g., vascular EDS) and its systemic manifestations. This is particularly pertinent when suspecting craniocervical instability since it remains a controversial diagnosis with a limited treatment evidence-base. This article reviews the commonly encountered headache disorders in patients with joint hypermobility-related conditions with a focus on EDS and HSD, describes their diverse presentations, and an overview of the recommended management strategies. It also emphasises the need for increased awareness of comorbid conditions in EDS and HSD among clinicians treating headaches to ensure a patient-tailored approach and facilitate a multidisciplinary approach in managing often complex cases.

A bizarre case of recurrent hemoptysis and pneumothorax in a young male

Vascular Ehlers–Danlos syndrome (vEDS) is a rare inherited disorder affecting approximately 1 in 150,000 individuals, caused by heterozygous mutations in the COL3A1 gene. Characterized by primary spontaneous pneumothorax and severe connective tissue fragility, vEDS remains poorly understood clinically, making diagnosis challenging. We present the case of a 20-year-old male with a history of mitral valve prolapse, recurrent hemoptysis, knee joint dislocations, and easy bruising. In February 2023, he was admitted to the emergency department following a seizure, syncope, and altered sensorium, which led to an extensive evaluation of his non-specific symptoms. Ultimately, he was diagnosed with vEDS.

Ballooning and Bursting of Barrels and Pipes: A Rare Case of Suspected Vascular Ehlers–Danlos Disease

Vascular Ehler–Danlos disease (vEDS), a rare subtype of a rare disease, is a life-threatening disease, with an increased risk for spontaneous vascular or visceral rupture. These patients have fatal complications ranging from vascular aneurysms, dissection, and rupture of systemic vessels to frequent thromboembolic events, the common causes of death in these individuals with a shortened life span. In the present case, a 28-year-old male with history of shoulder dislocations and spontaneous colon perforation presented to the primary care clinic with right lower extremity swelling and pain. His history includes presentation to the emergency department with left lower leg swelling with compartment syndrome one year prior. A CT angiogram of lower extremities and abdomen revealed acute arterial extravasation of the left posterior tibial artery, indicating a ruptured aneurysm along with aneurysms of the splenic artery and left common iliac artery. He was treated with a saphenous vein graft, but was associated with post-operative complications that necessitated below-knee amputation. CT angiogram of his right leg revealed occlusion of the anterior tibial and peroneal arteries with aneurysms, and, ultimately, he was referred to a tertiary care center for aneurysm embolization. This case report emphasizes the frequent vascular complications encountered in vascular EDS patients, and thus advocates for close and regular monitoring for early referral and surgical management of their vascular anomalies. Finally, genetic counseling and screening of asymptomatic family members should be routinely implemented in these patients.

Echocardiographic Assessment in Patients with Vascular Ehlers-Danlos Syndrome: Insights from an Unexplored Field.

Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol is a β1-adrenoceptor antagonist with partial β2 agonist activity that has been shown to reduce rates of vascular events in this setting, though the underlying mechanisms are not yet fully understood. Moreover, very few echocardiographic data are available in patients with vEDS. To perform a comprehensive echocardiographic assessment of a cohort of patients with vEDS with or without celiprolol therapy compared with healthy subjects. Twenty patients with genetically confirmed diagnosis of vEDS followed at our Institution (University Hospital of Brescia, Italy) were divided into two groups according to whether or not they were on celiprolol therapy at the maximum recommended dose (400mg daily) for at least 12 months. Both groups were compared to 10 healthy individuals matched for sex, age, body mass index (BMI), and office blood pressure (BP) values. Each participant underwent transthoracic echocardiography with tissue Doppler analysis (TDI) for a comprehensive evaluation of cardiac structure and function. Mean age was 35 years and mean BMI was 21.6 kg/m2. Female sex was prevalent (60%). Left ventricular (LV) internal diameter values tended to be lower in patients with untreated vEDS than in healthy controls (4.33 vs 4.74cm, respectively), though this difference was not statistically significant. Similar data were observed for LV mass index (56.9 vs 68.6 g/m2), stroke volume (56.6 vs 71.6 mL), and E/A ratio (1.26 vs 1.66), whereas an opposite trend was observed for e' lateral (13.2 vs 12.2cm/s). No statistically significant difference was found between groups in terms of other parameters of LV mass, systolic and diastolic function. A normal LV geometry was found in all the cases. Indices of mechano-energetic efficiency and ventricular-arterial coupling were also similar between groups. No patient presented with aortic root dilation, mitral valve prolapse, valve insufficiency of more than mild degree, or valve stenosis of any degree. Our study suggests that patients with vEDS have normal cardiac mass and geometry, as well as normal systolic and diastolic function. Celiprolol therapy does not seem to significantly influence such aspects. Compared with vascular imaging, less stringent follow-up with echocardiography seems reasonable in this setting. Future studies with prospective design should confirm these aspects.

A diagnosis of vascular ehlers-danlos syndrome in childhood: clinical and molecular features of 63 individuals

Abstract Background Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder characterised by generalised severe tissue friability and predominantly caused by pathogenic COL3A1 variants. Diagnosis of vEDS in childhood primarily occurs due to a positive family history and/or the occurrence of an early arterial or intestinal event. However, little has been reported on additional clinical characteristics and management in this population. Purpose This study aims to identify critical drivers of a childhood vEDS diagnosis in individuals diagnosed through a national EDS service. Methods 63 individuals (24 index, 31 females) with a clinical and genetic diagnosis of vEDS in childhood (< 18 years) were identified through a national EDS service, and childhood cardiovascular surveillance was conducted through joint inherited cardiovascular disease clinics. Results Diagnosis of vEDS in childhood occurred at a median age of 7 years (IQR 3-12) and was predominantly driven by positive family history of vEDS (55.5%). Clinical investigations were directly initiated by occurrence of a major clinical event in n=13 (20.6%), and a total of 17 major clinical events in childhood were recorded in 13 individuals. First events occurred at a median age of 11 years (IQR 0-13) and vascular events, though infrequent, occurred as early as the first year of life. In individuals who did not have a positive family history or major event, easy and/or excessive bruising was the most frequent cause for referral (60%). Conclusions This cohort provides further details of the clinical and genetic characteristics of children with vEDS and contributes new insight into drivers of vEDS diagnosis in childhood and the importance of long-term management, including paediatric cardiovascular surveillance.

Multiple Arterial Aneurysms Revealing a New Case of Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome (EDS) is a rare genetic disorder transmitted in an autosomal dominant mode. Its progression in young adults is marked by vascular, digestive, and obstetric complications. We report the case of a 24-year-old woman presenting with a mass in the right femoral triangle. Non-invasive imaging revealed multiple staged arterial aneurysms in the lower limbs. The diagnosis of vascular Ehlers-Danlos syndrome was established based on facial dysmorphia, acrogeria, and a history of right humeral aneurysm surgery. The patient underwent surgery for the right femoral aneurysm due to its significant size and risk of rupture, with simple monitoring for the other arterial aneurysms that were discovered incidentally. The postoperative course was uneventful with a favorable outcome.

Exercise, Sports Participation, and Quality of Life in Young Patients with Heritable Thoracic Aortic Disease.

Patients with heritable thoracic aortic disease (HTAD)are often restricted from sports and certain types of exercise. This study was designed to investigate the effect of lifetime exercise exposure and competitive sports participation on quality of life (QOL) in patients aged 15-35 with syndromic [Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers-Danlos syndrome (vEDS)] and non-syndromic heritable thoracic aortic disease (nsHTAD). This cross-sectional study employed questionnaires to assess lifetime exercise exposure and utilized the PedsQL QOL Inventory. We developed an Exercise Exposure Score (EES) to quantify lifetime exercise exposure. Questionnaires were completed via telephone with complimentary medical record review. Forty patients were enrolled. Mean age was 26 years. The diagnosis was MFS in 83%. Despite 88% of patients being restricted by their provider, 65% reported competitive sports participation and 93% reported recreational exercise. Participants with an EES greater than the median had significantly better total QOL scores compared to those below the median (78 vs 65, p = 0.03). There were significant positive correlations between current frequency of exercise and psychosocial QOL (slope = 3.9, 95% CI: (1.2, 6.6), p = 0.005), physical QOL (slope = 8.1, 95% CI: (4.1, 12), p < 0.001), and total QOL score (slope = 6.0, 95% CI: (3.1, 9.0), p < 0.001). We found no difference in aortic size or need for surgical intervention between those above and below the median EES, or between those who did and did not participate in competitive sports. Despite exercise restrictions, young HTAD patients are physically active. Increased lifetime exercise and current physical activity levels were associated with improved QOL in HTAD patients.

Hemoperitoneum Due to Dissection and Rupture of the Superior Mesenteric Artery in a Patient With COL3A1 Mutation.

Introduction: Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant disorder that results from mutations in the collagen type III gene. It is a risk factor for medium-sized artery aneurysms, dissections, and ruptures. We report a case of hemoperitoneum due to medial dissection and rupture of the superior mesenteric artery related to vEDS. Methods: A full body CT scan and full three cavity autopsy was performed in a 47-year-old man with a history of an intermittent abdominal cramping for one week rand complex past medical history that included a sigmoid bowel perforation at age 20, and previous popliteal artery pseudoaneurysm rupture. Histology and genetic testing were performed. Results: The postmortem computed tomography and autopsy showed a significant hemoperitoneum due to a ruptured dissection of the superior mesenteric artery and branches, and multiple splanchnic artery dissections with renal and small bowel infarctions. Genetic testing revealed a heterozygous COL3A1 gene variant associated with Ehlers-Danlos syndrome. Death was attributed to hemoperitoneum due to medial dissection and rupture of the superior mesenteric artery due to arteriopathy. Discussion: The relatively young age and medical history correlate with the autopsy findings and genetic testing towards the conclusion of an arteriopathy consistent with vEDS.

Pregnancy Outcomes in Women With Vascular EDS Provide High Mortality Rates.

Pregnancy Outcomes in Women With Vascular EDS Provide High Mortality Rates.

Bridging the Diagnostic Gap for Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders: Evidence of a Common Extracellular Matrix Fragmentation Pattern in Patient Plasma as a PotentialBiomarker.

Diagnosing hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD), common overlapping multisystemic conditions featuring symptomatic joint hypermobility, is challenging due to lack of established causes and diagnostic tools. Currently, the 2017 diagnostic criteria for hEDS are used, with non-qualifying cases classified as HSD, although the distinction remains debated. We previously showed extracellular matrix (ECM) disorganization in both hEDS and HSD dermal fibroblasts involving fibronectin (FN), type I collagen (COLLI), and tenascin (TN), with matrix metalloproteinase-generated fragments in conditioned media. Here, we investigated these fragments in patient plasma using Western blotting across diverse cohorts, including patients with hEDS, HSD, classical EDS (cEDS), vascular EDS (vEDS), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA), and healthy donors, uncovering distinctive patterns. Notably, hEDS/HSD displayed a shared FN and COLLI fragment signature, supporting their classification as a single disorder and prompting reconsideration of the hEDS criteria. Our results hold the promise for the first blood test for diagnosing hEDS/HSD, present insights into the pathomechanisms, and open the door for therapeutic trials focused on restoring ECM homeostasis using an objective marker. Additionally, our findings offer potential biomarkers also for OA, RA, and PsA, advancing diagnostic and therapeutic strategies in these prevalent joint diseases.

Surgical and irradiated case of early breast cancer in a patient with Ehlers–Danlos syndrome

BackgroundEhlers–Danlos syndrome (EDS) is a rare inherited connective tissue disease characterized by hyperextensibility of the skin and joints and tissue fragility of the skin and blood vessels, Vascular EDS is the most severe form of EDS, with abnormal arterial fragility. There have been no reports of breast cancer occurring in patients with vascular EDS. Here, we report here a very rare case of breast cancer in a patient with vascular EDS.Case presentationA 46-year-old woman with vascular EDS underwent partial left mastectomy and sentinel lymph node biopsy for left breast cancer (cStage 0) detected by medical examination. The final pathological diagnosis was invasive ductal carcinoma of the breast (pStage IA) [hormone receptor-positive, HER2 score 2 equivocal (FISH-positive), Ki-67LI 18%, luminal-HER2 type]. BluePrint was submitted as an aid in determining the postoperative treatment strategy, BluePrint Molecular Subtype HER2-type. However, the 10-year breast cancer mortality risk using Predict was low (5%). After consultation with the patient, the decision was made to administer postoperative radiation to the preserved breast along with hormone therapy only. There was no delay in postoperative wound healing, and the patient was free of metastatic recurrence for 9 months after surgery.ConclusionWe performed surgery, postoperative radiotherapy, and hormonal therapy in a breast cancer patient with vascular EDS without major complications.

Longitudinal echocardiography in pediatric patients with hypermobile Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos, Marfan and Loeys-Dietz syndromes have increased risk of aortic dilation and dissection. Previous early studies showed hypermobile Ehlers-Danlos syndrome (hEDS) may also have increased risk, with echocardiography screening recommended; subsequent studies have not confirmed the risk or recommended echocardiography. This pediatric-based study assessed aortic dilation prevalence in those with hEDS by serial echocardiographic examinations and assessed family history for aortic dissections. We retrospectively identified individuals with hEDS who had echocardiography studies from the electronic medical records at one pediatric center. Aortic root Z-scores >2.0 were found in 15/225 subjects (average age 12.9 years) on initial echocardiograms, with no Z-score >3.0. Subsequent studies (n = 68) found statistically significant decline in aortic root Z-scores. Repeat echocardiography in those with initial aortic root Z-score >2.0 (n = 10) demonstrated a decline in Z score <2.0 in seven. On final examination, 9/225 (4.0%) had a Z-score >2.0, not statistically different from the general population. No aortic dissection occurred in first- or second-degree relatives. In conclusion, aortic root dilation rate in hEDS is likely not different from the general population. We propose that in the absence of other cardiac findings or suspicion for another disorder, echocardiography is not required in hEDS.

Is Exon Skipping a Viable Therapeutic Approach for Vascular Ehlers-Danlos Syndrome with Mutations in COL3A1 Exon 10 or 15?

Vascular Ehlers-Danlos syndrome or Ehlers-Danlos syndrome type IV (vEDS) is a connective tissue disorder characterised by skin hyperextensibility, joint hypermobility and fatal vascular rupture caused by COL3A1 mutations that affect collagen III expression, homo-trimer assembly and secretion. Along with collagens I, II, V and XI, collagen III plays an important role in the extracellular matrix, particularly in the inner organs. To date, only symptomatic treatment for vEDS patients is available. Fibroblasts derived from vEDS patients carrying dominant negative and/or haploinsufficiency mutations in COL3A1 deposit reduced collagen III in the extracellular matrix. This study explored the potential of an antisense oligonucleotide (ASO)-mediated splice modulating strategy to bypass disease-causing COL3A1 mutations reported in the in-frame exons 10 and 15. Antisense oligonucleotides designed to redirect COL3A1 pre-mRNA processing and excise exons 10 or 15 were transfected into dermal fibroblasts derived from vEDS patients and a healthy control subject. Efficient exon 10 or 15 excision from the mature COL3A1 mRNA was achieved and intracellular collagen III expression was increased after treatment with ASOs; however, collagen III deposition into the extracellular matrix was reduced in patient cells. The region encoded by exon 10 includes a glycosylation site, and exon 15 encodes hydroxyproline and hydroxylysine-containing triplet repeats, predicted to be crucial for collagen III assembly. These results emphasize the importance of post-translational modification for collagen III homo-trimer assembly. In conclusion, while efficient skipping of target COL3A1 exons was achieved, the induced collagen III isoforms generated showed defects in extracellular matrix formation. While therapeutic ASO-mediated exon skipping is not indicated for the patients in this study, the observations are restricted to exons 10 and 15 and may not be applicable to other collagen III in-frame exons.

Current Evidence and Future Perspectives in the Medical Management of Vascular Ehlers-Danlos Syndrome: Focus on Vascular Prevention.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant connective tissue disease resulting from pathogenic variants in the collagen type III alpha 1 chain (COL3A1) gene, encoding type III procollagen. Patients with vEDS present with severe tissue fragility that can result in arterial aneurysm, dissection, or rupture, especially of medium-caliber vessels. Although early reports have indicated a very high mortality rate in affected patients, with an estimated median survival of around 50 years, recent times have seen a remarkable improvement in outcomes in this population. This shift could be related to greater awareness of the disease among patients and physicians, with improved management both in terms of follow-up and treatment of complications. Increasing use of drugs acting on the cardiovascular system may also have contributed to this improvement. In particular, celiprolol, a β1 cardio-selective blocker with a β2-agonist vasodilator effect, has been shown to reduce rates of vascular events in patients with vEDS. However, the evidence on the true benefits and possible mechanisms responsible for the protective effect of celiprolol in this specific setting remains limited. Drugs targeting the extracellular matrix organization and autophagy-lysosome pathways are currently under investigation and could play a role in the future. This narrative review aims to summarize current evidence and future perspectives on vEDS medical treatment, with a specific focus on vascular prevention.

Catastrophic CPR-Related Injuries in Vascular Ehlers-Danlos Syndrome: A Case Report and Review.

This article presents a case of severe CPR-related injuries leading to diagnosis of vascular Ehlers-Danlos syndrome. The subject is a 36-year-old female with a past medical history of a 10-mm aneurysm of the right internal carotid artery discovered on imaging 3 years prior to death. Major autopsy findings included subarachnoid hemorrhage in the base of the brain, bilateral hemothoraces, hemopericardium, laceration of the interatrial septum, laceration of the left pulmonary artery, and changes secondary to chronic alveolar hemorrhage in the lungs. The autopsy findings and subsequent unremarkable toxicology studies led to the suspicion of an underlying and clinically undiagnosed connective tissue disorder. Broad genetic exome testing revealed a mutation consistent with vascular Ehlers-Danlos syndrome. An overview of this disease, its diagnosis, and differential are further described herein, along with recommendations for forensic pathologists.

Novel Insights into the Aortic Mechanical Properties of Mice Modeling Hereditary Aortic Diseases.

Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models. We used two mouse models (Fbn1C1041G and Fbn1mgR ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of Efemp2 and three CRISPR/Cas9-engineered knock-in models (Ltbp1, Mfap4, and Timp1). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture. The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the Ltbp1, Mfap4, and Timp1 knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice. Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.

Generation of two iPSC lines from vascular Ehlers-Danlos Syndrome (vEDS) patients carrying a missense mutation in COL3A1 gene

Vascular Ehlers-Danlos Syndrome (vEDS) is an inherited connective tissue disorder caused by COL3A1 gene, mutations that encodes type III collagen, a crucial component of blood vessels. vEDS can be life-threatening as these patients can have severe internal bleeding due to arterial rupture. Here, we generated induced pluripotent stem cell (iPSC) lines from two vEDS patients carrying a missense mutation in the COL3A1 (c.226A > G, p.Asn76Asp) gene. These lines exhibited typical iPSC characteristics including morphology, expression of pluripotency markers, and could differentiate to all three germ layer. These iPSC lines can serve as valuable tools for elucidating the pathophysiology underlying vEDS.

National registry insights on genetic aortopathies and thoracic endovascular aortic interventions

ObjectiveThoracic endovascular aortic repair (TEVAR) in patients with genetic aortopathies (GA) is controversial, given concerns of durability. We describe characteristics and outcomes after TEVAR in patients with GA. MethodsAll patients undergoing TEVAR between 2010 and 2023 in the Vascular Quality Iniatitive were identified and categorized as having a GA or not. Demographics, baseline, and procedural characteristics were compared among groups. Multivariable logistic regression was used to evaluate the independent association of GA with postoperative outcomes. Kaplan-Meier methods and multivariable Cox regression analyses were used to evaluate 5-year survival and 2-year reinterventions. ResultsOf 19,340 patients, 304 (1.6%) had GA (87% Marfan syndrome, 9% Loeys-Dietz syndrome, and 4% vascular Ehlers-Danlos syndrome). Compared with patients without GA, patients with GA were younger (50 years [interquartile range, 37-72 years] vs 70 years [interquartile range, 61-77 years]), more often presented with acute dissection (28% vs 18%), postdissection aneurysm (48% vs 17%), had a symptomatic presentation (50% vs 39%), and were less likely to have degenerative aneurysms (18% vs 47%) or penetrating aortic ulcer (and intramural hematoma) (3% vs 13%) (all P < .001). Patients with GA were more likely to have prior repair of the ascending aorta/arch (open, 56% vs 11% [P < .001]; endovascular, 5.6% vs 2.1% [P = .017]) or the descending thoracic aorta (open, 12% vs 2% [P = .007]; endovascular, 8.2% vs 3.6% [P = .011]). No significant differences were found in prior abdominal suprarenal repairs; however, patients with GA had more prior open infrarenal repairs (5.3% vs 3.2%), but fewer prior endovascular infrarenal repairs (3.3% vs 5.5%) (all P < .05). After adjusting for demographics, comorbidities, and disease characteristics, patients with GA had similar odds of perioperative mortality (4.6% vs 7.0%; adjusted odds ratio [aOR], 1.1; 95% confidence interval [CI], 0.57-1.9; P = .75), any in-hospital complication (26% vs 23%; aOR, 1.24; 95% CI, 0.92-1.6; P = .14), or in-hospital reintervention (13% vs 8.3%; aOR, 1.25; 95% CI, 0.84-1.80; P = .25) compared with patients without GA. However, patients with GA had a higher likelihood of postoperative vasopressors (33% vs 27%; aOR, 1.44; 95% CI, 1.1-1.9; P = .006) and transfusion (25% vs 23%; aOR, 1.39; 95% CI, 1.03-1.9; P = .006). The 2-year reintervention rates were higher in patients with GA (25% vs 13%; adjusted hazard ratio, 1.99; 95% CI, 1.4-2.9; P < .001), but 5-year survival was similar (81% vs 74%; adjusted hazard ratio, 1.02; 95% CI, 0.70-1.50; P = .1). ConclusionsTEVAR for patients with GA seemed to be safe initially, with similar odds for in-hospital complications, in-hospital reinterventions, and perioperative mortality, as well as similar hazards for 5-year mortality compared with patients without GA. However, patients with GA had higher 2-year reintervention rates. Future studies should assess long-term durability after TEVAR compared with the recommended open repair to appropriately weigh the risks and benefits of endovascular treatment in patients with GA.

A Rare Case of Recurrent Hemopneumothorax

Abstract Hemopneumothorax is most commonly encountered following trauma. Spontaneous hemopneumothorax is rare. Causes of spontaneous hemopneumothorax include congenital cystic lung diseases, bleeding disorders, collagen vascular diseases such as rheumatoid arthritis, systemic lupus erythematosus, and complications of lung malignancies. Vascular Ehlers–Danlos syndrome (vEDS) is a life-threatening rare genetic disorder with a high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. This report is of a young male presenting with a history of recurrent hemopneumothorax. He was diagnosed with vEDS by identifying a COL3A1 gene mutation. This report emphasizes the importance of genetic studies when young patients present with unexplained and recurrent hemopneumothorax. Genetic counseling and close monitoring are imperative for the prevention of severe complications.

FIRST COMPREHENSIVE ECHOCARDIOGRAPHIC ASSESSMENT IN PATIENTS WITH VASCULAR EHLERS-DANLOS SYNDROME WITH OR WITHOUT CELIPROLOL THERAPY AT THE MAXIMUM RECOMMENDED DOSE

Objective: Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol is a beta1-adrenoceptor antagonist with partial beta2 agonist activity that has been shown to reduce rates of vascular events in this setting, though the underlying mechanisms are not yet fully understood. Moreover, few data on echocardiographic assessment are available in patients with vEDS. Design and method: Twenty patients with genetically confirmed diagnosis of vEDS followed at our Institution were divided into two groups (10 patients each) according to whether or not they were on celiprolol therapy at the maximum recommended dose (400 mg daily) for at least 12 months. Both groups were compared to 10 healthy individuals matched for sex, age, body mass index (BMI), and office blood pressure values. Each participant underwent transthoracic echocardiography with tissue Doppler analysis for a comprehensive evaluation of cardiac structure and function. Results: Mean age was 35 years and mean BMI was 21.6 kg/m2. Female sex was prevalent (60%). Left ventricular (LV) internal diameter values tended to be lower in patients with untreated vEDS than in healthy controls, though this difference was not statistically significant (4.33 vs 4.74 cm, respectively; p=0.053). Similar data were observed for LV mass index (56.9 vs 68.6 g/m2; p=0.093), stroke volume (56.6 vs 71.6 mL; p=0.068), and E/A ratio (1.26 vs 1.66; p=0.082), whereas an opposite trend was observed for e’ lateral (13.2 vs 12.2; p=0.096). No statistically significant difference was found between groups in terms of other parameters of LV mass, systolic and diastolic function. A normal LV geometry was found in all the cases. Indices of mechano-energetic efficiency and ventricular-arterial coupling were also similar between groups. No patient presented with aortic root dilation, mitral valve prolapse, valve insufficiency of more than mild degree, or valve stenosis of any degree. Conclusions: Our study suggests that patients with vEDS have normal cardiac mass and geometry, as well as normal systolic and diastolic function. Celiprolol therapy does not seem to significantly influence such aspects. Future studies on larger cohort of patients should confirm these aspects.