ABSTRACT
BACKGROUND: Cervical arterial tortuosity is associated with adverse outcomes in Loeys-Dietz syndrome and other heritable aortopathies. METHODS AND RESULTS: A method to assess tortuosity based on curvature of the vessel centerline in 3-dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys-Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow-up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow-up). Logistic regression was performed to assess the likelihood of clinical end point according to baseline carotid tortuosity. Total absolute curvature at baseline was 11.13±5.76 and was relatively unchanged at 8 to 10 years (fold change: 0.026±0.298, P=1.00), whereas tortuosity index at baseline was 0.262±0.131, with greater variability at 8 to 10 years (fold change: 0.302±0.656, P=0.818). Baseline total absolute curvature correlated with aortic root diameter (r=0.456, P=0.004) and was independently associated with aortic events during the 4-year follow-up (adjusted odds ratio [OR], 2.64 [95% CI, 1.02-6.85]). Baseline tortuosity index correlated with age (r=0.532, P<0.001) and was not associated with events (adjusted OR, 1.88 [95% CI, 0.79-4.51]). Finally, baseline total absolute curvature had good discrimination of 4-year outcomes (area under the curve=0.724, P=0.014), which may be prognostic or predictive. CONCLUSIONS: Here we introduce cervical carotid tortuosity as a promising quantitative biomarker with validated, standardized characteristics. Specifically, we recommend the adoption of a curvature-based measure, total absolute curvature, for early detection or monitoring of disease progression in Loeys-Dietz syndrome.
Subject(s)
Carotid Arteries , Computed Tomography Angiography , Loeys-Dietz Syndrome , Magnetic Resonance Angiography , Humans , Female , Male , Risk Assessment , Adult , Loeys-Dietz Syndrome/genetics , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/diagnosis , Loeys-Dietz Syndrome/diagnostic imaging , Middle Aged , Carotid Arteries/diagnostic imaging , Carotid Arteries/pathology , Risk Factors , Young Adult , Predictive Value of Tests , Aortic Dissection/diagnostic imaging , Aortic Dissection/diagnosis , Aortic Dissection/surgery , Vascular Malformations/diagnostic imaging , Vascular Malformations/diagnosis , Imaging, Three-Dimensional , Reproducibility of Results , Skin Diseases, Genetic/genetics , Skin Diseases, Genetic/diagnostic imaging , Skin Diseases, Genetic/diagnosisABSTRACT
Loeys-Dietz syndrome (LDS) is an autosomal-dominant connective tissue disorder associated with mutations in the transforming growth factor ß receptor. It is characterized by distinctive craniofacial changes, skeletal features, and cardiovascular complications. We present a case of a 24-year-old male with development delay and a one-year history of progressively worsening dyspnea on moderate exertion and orthopnea. Echocardiography revealed right atrial and right ventricle dilation, right ventricle hypertrophy, atrial septal defect, and aneurysmal dilation of the pulmonary artery trunk. This case underscores the importance of early detection and comprehensive imaging in patients suspected of having LDS, particularly considering the potential for atypical vascular manifestations.
Subject(s)
Delayed Diagnosis , Echocardiography , Heart Septal Defects, Atrial , Loeys-Dietz Syndrome , Pulmonary Artery , Humans , Male , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/diagnosis , Heart Septal Defects, Atrial/complications , Heart Septal Defects, Atrial/diagnosis , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/abnormalities , Young Adult , Echocardiography/methods , Dilatation, Pathologic , Diagnosis, DifferentialABSTRACT
Haemifacial microsomia is an asymmetrical congenital tissue malformation developed from the first and second branchial arches with or without multi-system involvement. Alternatively recognised as Goldenhar syndrome or oculoauriculovertebral spectrum (OAVS), it is an aetiologically heterogeneous group of disorders showing dominant trends in inheritable form.We present a case of a boy in early childhood with concomitant craniofacial features of craniofacial microsomia with Loeys-Dietz syndrome. He had a unilateral hypoplastic face, asymmetrical ear malformations and multiple preauricular tags with epibulbar dermoid (features suggestive of Goldenhar syndrome). On detailed clinical evaluation, he met Beighton's criteria and was diagnosed with arterial tortuosity. Further molecular testing confirmed the diagnosis of Loeys-Dietz syndrome type II.Loeys-Dietz syndrome is characterised by aortic root enlargement or type A dissection with or without other vascular malformations and facial midline defects. Molecular testing is required to establish the diagnosis because of overlapping features with other connective tissue disorders.
Subject(s)
Connective Tissue Diseases , Goldenhar Syndrome , Loeys-Dietz Syndrome , Skin Diseases, Genetic , Male , Humans , Child, Preschool , Goldenhar Syndrome/diagnosis , Loeys-Dietz Syndrome/complications , Ear, External/abnormalities , Connective Tissue Diseases/complications , Skin Diseases, Genetic/complicationsABSTRACT
Children with Marfan (MFS) and Loeys-Dietz syndrome (LDS) report limitations in physical activities, sports, school, leisure, and work participation in daily life. This observational, cross-sectional, multicenter study explores associations between physical fitness and cardiovascular parameters, systemic manifestations, fatigue, and pain in children with MFS and LDS. Forty-two participants, aged 6-18 years (mean (SD) 11.5(3.7)), diagnosed with MFS (n = 36) or LDS (n = 6), were enrolled. Physical fitness was evaluated using the Fitkids Treadmill Test's time to exhaustion (TTE) outcome measure. Cardiovascular parameters (e.g., echocardiographic parameters, aortic surgery, cardiovascular medication) and systemic manifestations (systemic score of the revised Ghent criteria) were collected. Pain was obtained by visual analog scale. Fatigue was evaluated by PROMIS® Fatigue-10a-Pediatric-v2.0-short-form and PROMIS® Fatigue-10a-Parent-Proxy-v2.0-short-form. Multivariate linear regression analyses explored associations between physical fitness (dependent variable) and independent variables that emerged from the univariate linear regression analyses (criterion p < .05). The total group (MFS and LDS) and the MFS subgroup scored below norms on physical fitness TTE Z-score (mean (SD) -3.1 (2.9); -3.0 (3.0), respectively). Univariate analyses showed associations between TTE Z-score aortic surgery, fatigue, and pain (criterion p < .05). Multivariate analyses showed an association between physical fitness and pediatric self-reported fatigue that explained 48%; 49%, respectively, of TTE Z-score variance (F (1,18) = 18.6, p ≤ .001, r2 = .48; F (1,15) = 16,3, p = .01, r2 = .49, respectively). Conclusions: Physical fitness is low in children with MFS or LDS and associated with self-reported fatigue. Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with MFS and LDS. What is Known: ⢠Marfan and Loeys-Dietz syndrome are heritable connective tissue disorders and share cardiovascular and systemic manifestations. ⢠Children with Marfan and Loeys-Dietz syndrome report increased levels of disability, fatigue and pain, as well as reduced levels of physical activity, overall health and health-related quality of life. What is New: ⢠Physical fitness is low in children with Marfan and Loeys-Dietz syndrome and associated with self-reported fatigue. ⢠Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with Marfan and Loeys-Dietz syndrome.
Subject(s)
Fatigue , Loeys-Dietz Syndrome , Marfan Syndrome , Pain , Physical Fitness , Humans , Loeys-Dietz Syndrome/physiopathology , Loeys-Dietz Syndrome/complications , Adolescent , Marfan Syndrome/physiopathology , Marfan Syndrome/complications , Child , Male , Cross-Sectional Studies , Female , Physical Fitness/physiology , Fatigue/etiology , Fatigue/physiopathology , Pain/etiology , Pain/physiopathology , Exercise TestABSTRACT
Thoracic aortic disease (TAD) poses substantial risks during pregnancy, particularly for women with genetic conditions such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome. This review examines the epidemiology, risk assessment, and management of TAD in pregnancy. Preconception counseling is vital considering the hereditary nature of TAD and potential pregnancy-related complications. Genetic testing and imaging surveillance aid in risk assessment. Medical management, including beta-blockade and strict blood pressure control, is essential throughout pregnancy. Surgical interventions may be necessary in certain cases. A multidisciplinary approach involving cardiologists, obstetricians, cardiac surgeons, anesthesiologists, and other specialists with expertise in cardio-obstetrics is essential for optimal outcomes. Patient education and shared decision-making play vital roles in navigating the complexities of TAD in pregnancy and improving maternal and neonatal outcomes.
Subject(s)
Aortic Diseases , Loeys-Dietz Syndrome , Marfan Syndrome , Pregnancy , Infant, Newborn , Humans , Female , Aorta , Loeys-Dietz Syndrome/complications , Marfan Syndrome/diagnosis , Marfan Syndrome/epidemiology , Marfan Syndrome/therapy , Risk AssessmentABSTRACT
OBJECTIVES: The aim of this study was to report on mid-term outcomes after endovascular aortic repair (EVAR) in patients with Marfan (MFS) or Loeys-Dietz (LDS) syndrome. METHODS: We analysed data from 2 European centres of patients with MFS and LDS undergoing EVAR. Patients were analysed based on (i) timing of the procedure (planned versus emergency procedure) and (ii) the nature of the landing zone (safe versus non-safe). The primary end-point was freedom from reintervention. Secondary end-points were freedom from stroke, bleeding and death. RESULTS: A population of 419 patients with MFS (n = 352) or LDS (n = 67) was analysed for the purpose of this study. Thirty-nine patients (9%) underwent EVAR. Indications for thoracic endovascular aortic repair or EVAR were aortic dissection in 13 (33%) patients, aortic aneurysm in 22 (57%) patients and others (intercostal patch aneurysm, penetrating atherosclerotic ulcer, pseudoaneurysm, kinking of frozen elephant trunk (FET)) in 4 (10%) patients. Thoracic endovascular repair was performed in 34 patients, and abdominal endovascular aortic repair was performed in 5 patients. Mean age at 1st thoracic endovascular aortic repair/EVAR was 48.5 ± 15.4 years. Mean follow-up after 1st thoracic endovascular aortic repair/EVAR was 5.9 ± 4.4 years. There was no statistically significant difference in the rate of reinterventions between patients with non-safe landing zone and the patients with safe proximal landing zone (P = 0.609). Furthermore, there was no increased probability for reintervention after planned endovascular intervention compared to emergency procedures (P = 0.916). Mean time to reintervention, either open surgical or endovascular, after planned endovascular intervention was in median 3.9 years (95% confidence interval 2.0-5.9 years) and 2.0 years (95% confidence interval -1.1 to 5.1 years) (P = 0.23) after emergency procedures. CONCLUSIONS: EVAR in patients with MFS and LDS and a safe landing zone is feasible and safe. Endovascular treatment is a viable option when employed by a multi-disciplinary aortic team even if the landing zone is in native tissue.
Subject(s)
Aortic Aneurysm, Thoracic , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Loeys-Dietz Syndrome , Marfan Syndrome , Humans , Adult , Middle Aged , Loeys-Dietz Syndrome/surgery , Loeys-Dietz Syndrome/complications , Endovascular Aneurysm Repair , Marfan Syndrome/complications , Marfan Syndrome/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/methods , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Treatment Outcome , Retrospective Studies , Aortic Aneurysm, Thoracic/surgery , Postoperative Complications/epidemiology , Postoperative Complications/surgeryABSTRACT
OBJECTIVE: Loeys-Dietz syndrome (LDS) is a rare, autosomal dominant connective tissue disorder which can aggressively affect the aortic vasculature. Limited information is available regarding its impact on pregnancy and postpartum outcomes. CASE REPORT: A pregnant 38-year-old nulliparous woman with mild aortic regurgitation and family history of aortic aneurysms presented with an aortic root measuring 49 mm. Despite concerns of an underlying connective tissue disorder, a definitive diagnosis was not reached. She delivered under strict blood pressure control, developed intractable uterine atony, and underwent uterine artery embolization. On the second postpartum day, aortic dissection was incidentally diagnosed, and aortic root replacement surgery was performed. Genetic testing revealed a novel in-frame SMAD3 deletion [NM_005902.4: c.703_708del, (p.Ile235_Ser236del)], leading to a diagnosis of LDS type 3. CONCLUSION: This case highlights the high postpartum aortic dissection risk in women with LDS, emphasizing the importance of early diagnosis in pregnant women with few clinical symptoms.
Subject(s)
Aortic Dissection , Connective Tissue Diseases , Loeys-Dietz Syndrome , Humans , Female , Pregnancy , Adult , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/diagnosis , Loeys-Dietz Syndrome/genetics , Postpartum Period , Aortic Dissection/diagnosis , Aortic Dissection/genetics , Smad3 Protein/geneticsABSTRACT
Loeys-Dietz syndrome (LDS) is an autosomal dominant heritable disorder due to pathogenic variants in one of several genes involved in TGF-ß (transforming growth factor-beta) signalling. LDS is associated with aortic aneurysm and dissection. LDS may also lead to extra-aortic aneurysms, the majority of which occur in the head and neck vasculature. Visceral aneurysms are uncommon, and no cases of distal superior mesenteric artery (SMA) branch aneurysms in patients with LDS have been reported. Three related females with TGFBR1-related LDS developed distal SMA branch artery aneurysms involving the ileocolic and jejunal arteries. Endovascular or surgical intervention was performed in each. The presence and severity of arterial, craniofacial, and cutaneous features of LDS in these patients are variable. TGFBR1-related LDS may rarely lead to SMA branch artery aneurysms that can develop later in life. Surgical and endovascular procedures can successfully treat these aneurysms, but data to guide size thresholds and optimal treatment strategies are lacking.
Subject(s)
Endovascular Procedures , Loeys-Dietz Syndrome , Female , Humans , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/genetics , Receptor, Transforming Growth Factor-beta Type I/genetics , Dissection , Mesenteric Artery, SuperiorABSTRACT
Loeys-Dietz syndrome (LDS) is an autosomal connective tissue disorder commonly presenting with hypertelorism, bifid uvula, aortic aneurysms, and arterial tortuosity. The aim of the present study was to investigate differences in tortuosity index (TI) between genotypes of LDS, possible progression over time and its use as an adjunctive prognostic tool alongside aortic dimensions to aid timely surgical planning in pediatric patients. A retrospective observational study of pediatric LDS patients referred to our center (November 2012-February 2021) was conducted. Using magnetic resonance angiography (MRA) with 3D maximum intensity projection volume-rendered angiogram, arterial TI was measured. Twenty three patients had genetically confirmed LDS with at least one head and neck MRA and 19 had no less than one follow-up MRA available. All patients presented arterial tortuosity. Patients with TGFBR2 variants had greater values of TI compared to patients with TGFB2 variants (p = 0.041). For patients who did not undergo surgery (n = 18), z-scores at the level of the sinus of Valsalva showed a significant correlation with vertebral TI (rs = 0.547). There was one death during follow-up. This study demonstrates that patients with LDS and TGFBR2 variants have greater values of TI than patients with TGFB2 variants and that greatest values of TI are associated with increased aortic root z-scores. Furthermore, as TI decreases over time, less frequent neuroimaging follow-up can be considered. Nevertheless, additional studies are needed to better define more accurate risk stratification and long-term surveillance in these patients.
Subject(s)
Arteries/abnormalities , Joint Instability , Loeys-Dietz Syndrome , Skin Diseases, Genetic , Vascular Malformations , Child , Humans , Receptor, Transforming Growth Factor-beta Type II/genetics , Loeys-Dietz Syndrome/diagnosis , Loeys-Dietz Syndrome/genetics , Loeys-Dietz Syndrome/complications , Skin Diseases, Genetic/complications , Aorta/pathologySubject(s)
Loeys-Dietz Syndrome , Mutation, Missense , Receptor, Transforming Growth Factor-beta Type I , Humans , Receptor, Transforming Growth Factor-beta Type I/genetics , Loeys-Dietz Syndrome/genetics , Loeys-Dietz Syndrome/pathology , Loeys-Dietz Syndrome/complications , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Female , MaleABSTRACT
BACKGROUND: Iatrogenic aortic dissection during cardiac surgery is a rare but critical complication. At present, no strategies have been developed to prevent it. We herein report a case of intraoperative aortic dissection during aortic root replacement in an older patient with Loeys-Dietz syndrome type III who had no family history of aortic disease. CASE PRESENTATION: A 60-year-old man was admitted to the hospital for Stanford type B acute aortic dissection and given conservative treatment. He was found to have aortic root dilatation and severe aortic regurgitation. Thus, elective Bentall procedure was performed. Postoperative computed tomography showed new Stanford type A aortic dissection that may have developed due to aortic cannulation during surgery. The patient was given conservative treatment and successfully discharged to home at postoperative day 34. Although he had no family history of aortic disease, a genetic test revealed an unreported SMAD3 frameshift mutation (c.742_749dup, p. Gln252ThrfsTer7), and the patient was diagnosed with Loeys-Dietz syndrome type III. CONCLUSION: In patients with connective tissue disorder, aortic manipulations may become the cause of critical complications. Avoiding the use of invasive techniques, such as cannulation and cross-clamping, and implementing treatment strategies, such as perfusion from other sites than the aorta and open distal anastomosis, can prevent these complications, and may be useful treatment modalities. The possibility of connective tissue disease should be considered even if the patient is older and has no family history of aortic disease.
Subject(s)
Aortic Dissection , Loeys-Dietz Syndrome , Male , Humans , Middle Aged , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/genetics , Loeys-Dietz Syndrome/surgery , Aortic Valve , Aorta , Aortic Dissection/etiology , Aortic Dissection/surgery , Iatrogenic DiseaseABSTRACT
Hereditary connective tissue disorders are a broad group of congenital disorders that are characterized by a pathological weakness of the connective tissue as a result of an incorrect genesis, leading to multisystem complaints. We describe a 14-year-old patient with the hereditary connective tissue disorder Loeys-Dietz syndrome who was admitted to a child psychiatric crisis unit because of depressive and anxiety symptoms. A systematic literature search was carried out to analyze the prevalence of depressive and anxiety symptoms in individuals with hereditary connective tissue disorders Loeys-Dietz syndrome, Ehlers-Danlos syndrome and Marfan syndrome, to identify a possible association between these disorders and explanations for this. We conclude that there is an increased incidence of depression and anxiety symptoms in which pain, fatigue, social support and functioning, quality of life and functional limitations seem to play a role. There is a need for further research to determine exactly which factors contribute and how these can be targeted in prevention and treatment.
Subject(s)
Connective Tissue Diseases , Ehlers-Danlos Syndrome , Loeys-Dietz Syndrome , Adolescent , Humans , Anxiety , Connective Tissue , Connective Tissue Diseases/complications , Connective Tissue Diseases/diagnosis , Ehlers-Danlos Syndrome/complications , Ehlers-Danlos Syndrome/diagnosis , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/diagnosis , Quality of LifeABSTRACT
Loeys-Dietz syndrome (LDS) is a connective tissue disease related to ß-transforming growth factor mutations, which causes aneurysms formation, vascular tortuosity and skeletal manifestations. The prognosis is very poor, and mortality occurs at the age of 27 in patients without surgical treatment. Despite being diagnosed in childhood, is not usual surgical aortic replacement in children. We report a case of 12 years old child with LDS and multiple aneurysms in thoracic aorta, undergoing complete aortic arch replacement and our proposal for the anesthetic management, due to surgical complexity and implications in pediatric population.
El síndrome de Loeys-Dietz (SDL) es una enfermedad del tejido conectivo debida a mutaciones del factor de crecimiento transformador beta que provocan formación de aneurismas, malformaciones vasculares y esqueléticas. Tiene mal pronóstico y el fallecimiento sobreviene de media a los 27 años sin tratamiento quirúrgico. A pesar de diagnosticarse en la infancia, es infrecuente la cirugía en niños. Presentamos el caso de una niña de 12 años con SDL y aneurisma múltiple en aorta torácica, programada para recambio completo de arco aórtico, proponiendo estrategias para el manejo anestésico, dada la complejidad y las implicaciones de esta cirugía en la población pediátrica.
Subject(s)
Anesthetics , Loeys-Dietz Syndrome , Child , Humans , Aorta, Thoracic/surgery , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/genetics , Loeys-Dietz Syndrome/surgery , MutationABSTRACT
We report the case of a 36-year-old European female patient presenting with a sinus valsalva aneurysm of 47 mm with moderate aortic regurgitation. Additionally, an aneurysm of the brachiocephalic trunk and multiple aneurysms of the right internal mammary artery were identified. Previous medical history included Loeys-Dietz syndrome (LDS) Type RII due to a TGF-beta receptor mutation, and beta thalassemia minor with a baseline hemoglobin of 9,3 g/dL on admission.Reconstruction of the aortic root and hemiarch replacement was performed in circulatory arrest under moderate hypothermia. During surgery, hypothermia was required as part of the cerebral protection strategy. We aim to highlight special considerations and discuss the effects of cooling, rewarming and the use of cardiopulmonary bypass (CPB) during extensive surgery in a patient with LDS and beta thalassemia minor.
Subject(s)
Aortic Valve Insufficiency , Hypothermia , Loeys-Dietz Syndrome , beta-Thalassemia , Humans , Female , Adult , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/surgery , beta-Thalassemia/complications , AortaABSTRACT
We herein report the 10-year surgical course of a 27-year-old woman who underwent two surgeries after being diagnosed with Loeys-Dietz syndrome. As described in previous cases, this patient developed ectopic arterial enlargement. We followed her temporal changes over a 10-year period, including the changes in computed tomography, pathology, and surgery.
Subject(s)
Loeys-Dietz Syndrome , Humans , Female , Adult , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/diagnosis , Loeys-Dietz Syndrome/surgery , Follow-Up Studies , Arteries/pathology , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: Patients with Loeys-Dietz syndrome demonstrate a heightened risk of distal thoracic aortic events after valve-sparing aortic root replacement. This study assesses the clinical risks and hemodynamic consequences of a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome and characterizes smooth muscle cell phenotype in Loeys-Dietz syndrome aneurysmal and normal-sized downstream aorta. METHODS: Patients with genetically confirmed Loeys-Dietz syndrome (n = 8) underwent prophylactic aortic arch replacement during valve-sparing aortic root replacement. Four-dimensional flow magnetic resonance imaging studies were performed in 4 patients with Loeys-Dietz syndrome (valve-sparing aortic root replacement + arch) and compared with patients with contemporary Marfan syndrome (valve-sparing aortic root replacement only, n = 5) and control patients (without aortopathy, n = 5). Aortic tissues from 4 patients with Loeys-Dietz syndrome and 2 organ donors were processed for anatomically segmented single-cell RNA sequencing and histologic assessment. RESULTS: Patients with Loeys-Dietz syndrome valve-sparing aortic root replacement + arch had no deaths, major morbidity, or aortic events in a median of 2 years follow-up. Four-dimensional magnetic resonance imaging demonstrated altered flow parameters in patients with postoperative aortopathy relative to controls, but no clear deleterious changes due to arch replacement. Integrated analysis of aortic single-cell RNA sequencing data (>49,000 cells) identified a continuum of abnormal smooth muscle cell phenotypic modulation in Loeys-Dietz syndrome defined by reduced contractility and enriched extracellular matrix synthesis, adhesion receptors, and transforming growth factor-beta signaling. These modulated smooth muscle cells populated the Loeys-Dietz syndrome tunica media with gradually reduced density from the overtly aneurysmal root to the nondilated arch. CONCLUSIONS: Patients with Loeys-Dietz syndrome demonstrated excellent surgical outcomes without overt downstream flow or shear stress disturbances after concomitant valve-sparing aortic root replacement + arch operations. Abnormal smooth muscle cell-mediated aortic remodeling occurs within the normal diameter, clinically at-risk Loeys-Dietz syndrome arch segment. These initial clinical and pathophysiologic findings support concomitant arch replacement in Loeys-Dietz syndrome.
Subject(s)
Loeys-Dietz Syndrome , Marfan Syndrome , Humans , Loeys-Dietz Syndrome/complications , Loeys-Dietz Syndrome/diagnostic imaging , Loeys-Dietz Syndrome/surgery , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aorta/surgery , Marfan Syndrome/pathology , Vascular Surgical Procedures/methodsABSTRACT
Importance: Endovascular treatment is not recommended for aortic pathologies in patients with connective tissue diseases (CTDs) other than in redo operations and as bridging procedures in emergencies. However, recent developments in endovascular technology may challenge this dogma. Objective: To assess the midterm outcomes of endovascular aortic repair in patients with CTD. Design, Setting, and Participants: For this descriptive retrospective study, data on demographics, interventions, and short-term and midterm outcomes were collected from 18 aortic centers in Europe, Asia, North America, and New Zealand. Patients with CTD who had undergone endovascular aortic repair from 2005 to 2020 were included. Data were analyzed from December 2021 to November 2022. Exposure: All principal endovascular aortic repairs, including redo surgery and complex repairs of the aortic arch and visceral aorta. Main Outcomes and Measures: Short-term and midterm survival, rates of secondary procedures, and conversion to open repair. Results: In total, 171 patients were included: 142 with Marfan syndrome, 17 with Loeys-Dietz syndrome, and 12 with vascular Ehlers-Danlos syndrome (vEDS). Median (IQR) age was 49.9 years (37.9-59.0), and 107 patients (62.6%) were male. One hundred fifty-two (88.9%) were treated for aortic dissections and 19 (11.1%) for degenerative aneurysms. One hundred thirty-six patients (79.5%) had undergone open aortic surgery before the index endovascular repair. In 74 patients (43.3%), arch and/or visceral branches were included in the repair. Primary technical success was achieved in 168 patients (98.2%), and 30-day mortality was 2.9% (5 patients). Survival at 1 and 5 years was 96.2% and 80.6% for Marfan syndrome, 93.8% and 85.2% for Loeys-Dietz syndrome, and 75.0% and 43.8% for vEDS, respectively. After a median (IQR) follow-up of 4.7 years (1.9-9.2), 91 patients (53.2%) had undergone secondary procedures, of which 14 (8.2%) were open conversions. Conclusions and Relevance: This study found that endovascular aortic interventions, including redo procedures and complex repairs of the aortic arch and visceral aorta, in patients with CTD had a high rate of early technical success, low perioperative mortality, and a midterm survival rate comparable with reports of open aortic surgery in patients with CTD. The rate of secondary procedures was high, but few patients required conversion to open repair. Improvements in devices and techniques, as well as ongoing follow-up, may result in endovascular treatment for patients with CTD being included in guideline recommendations.
Subject(s)
Aortic Aneurysm, Thoracic , Connective Tissue Diseases , Ehlers-Danlos Syndrome, Type IV , Endovascular Procedures , Loeys-Dietz Syndrome , Marfan Syndrome , Humans , Male , Middle Aged , Female , Marfan Syndrome/complications , Marfan Syndrome/surgery , Loeys-Dietz Syndrome/complications , Retrospective Studies , Treatment Outcome , Endovascular Procedures/methods , Connective Tissue Diseases/complications , Connective Tissue Diseases/surgery , AortaABSTRACT
OBJECTIVE: To investigate bone fragility in patients with hereditary connective tissue disorders (HCTD), including Ehlers-Danlos syndrome (EDS), Marfan's syndrome (MFS) and Loeys-Dietz syndrome (LDS). METHODS: From inception to June 2022, potentially eligible studies were identified in the Medline and EMBASE databases using search strategy that included terms for "HCTD", "Fracture" and "Osteoporosis". Eligible studies must consist of a group of patients with HCTD and report prevalence/incidence of fracture/osteoporosis in their participants, with or without comparison with healthy individuals. Point estimates with standard errors were obtained from each study and combined using the generic inverse variance method. RESULTS: Among the 4206 articles identified, 19 studies were included. The pooled prevalence of fracture in EDS, MFS, and LDS were 44% (95% confidence interval [CI], 25% to 65%, I2 88%), 17% (95% CI, 11% to 26%, I2 68%), 69% (95% CI, 47% to 85%, I2 83%), respectively. The pooled prevalence of osteoporosis in EDS was 17% (95% CI, 8% to 34%, I2 96%). EDS was associated with fracture [pooled odds ratio {OR} 4.90 (95% CI, 1.49 - 16.08, I2 86%)], but not osteoporosis [pooled OR 1.34 (95% CI, 0.28 - 6.36, I2 87%). One study reported a 5% (95% CI, 3% to 8%) prevalence of osteoporosis in MFS, which was associated with fracture [incidence rate ratio 1.35 (95% CI, 1.18 - 1.55)] and osteoporosis [subhazard ratio 3.97 (95% CI, 2.53 - 6.25)]. CONCLUSION: EDS was associated with fracture, which could be independent of osteoporosis status. MFS had a milder degree of increased risk of fracture and osteoporosis. Despite no data from cohort studies, there was a significantly higher rate of fracture in LDS.