Search

Connective tissue disorders such as Marfan- and Loeys-Dietz syndrome (LDS) can lead to aortic aneurysms and aortic dissections in children. Patients with LDS often necessitating multiple aortic surgeries throughout their lives to extend their lifespan. A boy with LDS underwent Bentall procedure at the age of three for aortic aneurysm. At the age of six, this boy was referred to the hospital again due to severe abdominal pain. Computed tomographic angiography (CTA)indicates aortic dissection (DeBakey Type III, Stanford Type B). After a multidisciplinary team discussion, a successful thoracoabdominal aortic replacement was performed. [ABSTRACT FROM AUTHOR]

Aortopathy encompasses a spectrum of conditions predisposing to dilation, aneurysm, dissection, or rupture of the aorta and other blood vessels. Aortopathy is diagnosed commonly in children, from infancy through adolescence, primarily affecting the thoracic aorta, with variable involvement of the peripheral vasculature. Pathogeneses include connective tissue disorders, smooth muscle contraction disorders, and congenital heart disease, including bicuspid aortic valve, among others. The American Heart Association has published guidelines for diagnosis and management of thoracic aortic disease. However, these guidelines are predominantly focused on adults and cannot be applied adeptly to growing children with emerging features, growth and developmental changes, including puberty, and different risk profiles compared with adults. Management to reduce risk of progressive aortic dilation and dissection or rupture in children is complex and involves genetic testing, cardiovascular imaging, medical therapy, lifestyle modifications, and surgical guidance that differ in many ways from adult management. Pediatric practice varies widely, likely because aortopathy is pathogenically heterogeneous, including genetic and nongenetic conditions, and there is limited published evidence to guide care in children. To optimize care and reduce variation in management, experts in pediatric aortopathy convened to generate this scientific statement regarding the cardiovascular care of children with aortopathy. Available evidence and expert consensus were combined to create this scientific statement. The most common causes of pediatric aortopathy are reviewed. This document provides a general framework for cardiovascular management of aortopathy in children, while allowing for modification based on the personal and familial characteristics of each child and family. [ABSTRACT FROM AUTHOR]

Background: Ehlers–Danlos syndrome (EDS), Marfan syndrome (MFS), and Loeys–Dietz syndrome (LDS) are connective tissue disorders frequently associated with vascular aneurysm formation, dissections, and subsequent major complications. Regular imaging surveillance is recommended for these conditions. However, no guidelines currently exist regarding imaging modality or surveillance intervals. Methods: This retrospective single-center observational study analyzed clinical and imaging data of patients attending an outpatient clinic for vascular connective tissue disorders between August 2008 and January 2024. Imaging (1424 data points in total) and clinical data were extracted from electronic health records. Analysis primarily included a comparison of vessel diameter progression across imaging modalities, with an additional review of the clinical history of vascular events. Results: In total, 19 patients with vascular connective tissue disorders (vCTDs) underwent consultations at our outpatient clinic. Nine (47.4%) patients experienced vascular events, while two (10.5%) passed away during the study period. Multimodal imaging surveillance revealed a tendency towards arterial diameter increase. Consistent ultrasound monitoring provided more reliable diameter progression data for the same arterial segment than a combination of imaging modalities. Temporal analysis indicated a tendency for the continuous growth of the abdominal aorta, the common and internal carotid artery, and the common femoral and popliteal artery. Conclusion: The study highlights the importance of standardized, modality-specific imaging protocols in monitoring patients with vCTDs. The variability in disease progression among these patients further complicates surveillance strategies, contemplating the need for individualized approaches. Further research and prospective multicenter studies are required to refine and improve monitoring protocols. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Genetic variants associated with hereditary TAAD may contribute to nonsyndromic TAAD. We present the case of a 72‐year‐old man with nonsyndromic TAAD undergoing prophylactic surgery after a gene panel test revealed a pathogenic variant in TGFBR1, but the indication for genetic testing in such elderly‐onset cases still warrants further discussion. Hereditary thoracic aortic aneurysm and dissection (TAAD) is a serious clinical condition resulting in a fatal outcome. Recently, variants in causative genes for syndromic hereditary TAAD, such as Marfan syndrome and Loeys–Dietz syndrome (LDS), have been reported to predispose to the development of nonsyndromic TAAD; however, genetic testing for patients with elderly‐onset nonsyndromic TAAD warrants further discussion. We present a 72‐year‐old nonsyndromic Japanese man with moderate‐sized aortic annulus ectasia (AAE) with moderate aortic regurgitation and ascending to distal arch aortic dilatation (maximum diameter: 46 mm). He had been treated for hypertension and dyslipidemia for 7 years, and his eldest son had AAE at 33 years old and type A aortic dissection at 43 years old. Surgical repair was considered a treatment option because the patient potentially had a nonsyndromic hereditary aortic disease, and genetic panel testing for TAAD identified a pathogenic missense variant in TGFBR1 (c.934G > A, p.[Gly312Ser]), previously reported in patients with LDS type 1. He was diagnosed with nonsyndromic TGFBR1‐related aortopathy and underwent prophylactic surgery using a modified Bentall operation and total arch replacement with open stent graft implantation. Genetic testing was useful in guiding the treatment strategy, but further analysis is warranted to establish the clinical value in the treatment plan for patients with elderly‐onset nonsyndromic TAAD. [ABSTRACT FROM AUTHOR]

Objective: In heritable aortic diseases, different vascular involvement may occur with potential variable implications in aortic dilation/dissection risk. This study aimed to analyze the aortic anatomy of individuals with Marfan syndrome and Loeys-Dietz syndrome to identify possible morphological differences. Methods: Computed tomography and magnetic resonance imaging of the thoracoabdominal aorta from the proximal supra-aortic vessels to the femoral bifurcation level of 114 patients with Marfan and Loeys-Dietz syndromes and 20 matched control subjects were examined. Aortic diameters, areas, length, and tortuosity were measured in different aortic segments using specific vessel analysis software. Results: Patients with Marfan syndrome showed a higher prevalence of ascending aorta and aortic root dilation (P = .011), larger and longer aortic roots (P = .013) with pear-shaped phenotype, larger isthmus/descending aorta diameter ratio (P = .015), and larger suprarenal aorta and iliac arteries. Patients with Loeys-Dietz syndrome showed longer indexed segments and a significantly longer arch (P = .006) with type 2/3 arch prevalence (P = .097). Measurement ratios analysis provided cut-off values (aortic root to ascending aorta length/aortic root diameter, aortic root/sinotubular junction, aortic root/ascending aorta diameter) differentiating patients with Marfan syndrome from patients with Loeys-Dietz syndrome, even in the early stage of the disease. Conclusions: Both syndromes show peculiar anatomic patterns at different aortic levels irrespective of aortic dilation and disease severity. These features may represent the expression of different genetic mutations on aortic development, with a potential impact on prognosis and possibly contributing to better management of the diseases. The systematic adoption of whole body imaging with magnetic resonance or computed tomography should always be considered, because they allow a complete vascular assessment with practical indicators of differential diagnosis.

OBJECTIVE: To describe our experience in the cardiovascular characteristics and clinical evolution of patients with MS, ED and LD. MATERIALS AND METHODS: Patient records from the last 10 years were reviewed in a cross-sectional, observational and retrospective study. The diagnosis was made with family history and Ghent clinical criteria. Cardiac characteristics, treatment and clinical criteria. Cardiac characteristics, treatment and clinical behavior were analyzed. Percentages and frequencies are made. RESULTS: Thirty patients with SM, 18 with ED and 3 with LD (51 patients) were studied. The male gender predominated and the age ranged between 1 and 17 years of age. Patients with SM had 50% of family history, with LD 66% and with ED 44%. Cardiovascular alterations occurred in patients with MS in 73%, the most frequent being dilation of the aortic root. 66.6% patients with LD had vascular disease. Treatment was based on losartan and propranolol. None were managed with cardiovascular surgery. Follow-up ranged from 6 months to 9 years. The majority had no cardiovascular symptoms. None died. CONCLUSIONS: In patients with SM and LD, cardiovascular disease is common in children and adolescents. It is advisable to continue cardiovascular monitoring and early treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Key Clinical Message Genetic variants associated with hereditary TAAD may contribute to nonsyndromic TAAD. We present the case of a 72‐year‐old man with nonsyndromic TAAD undergoing prophylactic surgery after a gene panel test revealed a pathogenic variant in TGFBR1, but the indication for genetic testing in such elderly‐onset cases still warrants further discussion. Abstract Hereditary thoracic aortic aneurysm and dissection (TAAD) is a serious clinical condition resulting in a fatal outcome. Recently, variants in causative genes for syndromic hereditary TAAD, such as Marfan syndrome and Loeys–Dietz syndrome (LDS), have been reported to predispose to the development of nonsyndromic TAAD; however, genetic testing for patients with elderly‐onset nonsyndromic TAAD warrants further discussion. We present a 72‐year‐old nonsyndromic Japanese man with moderate‐sized aortic annulus ectasia (AAE) with moderate aortic regurgitation and ascending to distal arch aortic dilatation (maximum diameter: 46 mm). He had been treated for hypertension and dyslipidemia for 7 years, and his eldest son had AAE at 33 years old and type A aortic dissection at 43 years old. Surgical repair was considered a treatment option because the patient potentially had a nonsyndromic hereditary aortic disease, and genetic panel testing for TAAD identified a pathogenic missense variant in TGFBR1 (c.934G > A, p.[Gly312Ser]), previously reported in patients with LDS type 1. He was diagnosed with nonsyndromic TGFBR1‐related aortopathy and underwent prophylactic surgery using a modified Bentall operation and total arch replacement with open stent graft implantation. Genetic testing was useful in guiding the treatment strategy, but further analysis is warranted to establish the clinical value in the treatment plan for patients with elderly‐onset nonsyndromic TAAD.

BackgroundThis study aimed to investigate the influence of early diagnosis (ED) on surgical outcomes in patients definitively diagnosed with Loeys-Dietz syndrome (LDS).MethodsA retrospective review was conducted on 38 patients with LDS who underwent aortic surgery at our institution between January 1995 and June 2022. The primary endpoint was freedom from aortic reoperation.ResultsAmong the patients, the median age at the initial surgery was 33 (range: 39–44) years, and 23 (60.5%) patients were male. Twenty-one (55.3%; aortic dissection or rupture (n = 2) and aneurysm (n = 19)) patients were diagnosed with LDS before the initial surgery (ED group). Meanwhile, the remaining 17 (44.7%; aortic dissection or rupture (n = 13) and aneurysm (n = 4)) patients were after surgery [delayed diagnosis (DD) group]. The ED group had significantly lower rates of emergency surgery and concomitant arch procedure (P

A 16-year-old girl with Loeys-Dietz syndrome presented with an acute, complicated type B aortic dissection (AD) with mesenteric and right renal malperfusion owing to a dynamic obstruction. The anatomy of her AD and her genetic aortography were suboptimal for thoracic endovascular aortic repair. Given the concern for anticipated late aortic degeneration and the need for open aortic repair, she underwent successful transfemoral endovascular septal fenestration with stenting of the fenestration into the superior mesenteric artery and additional stenting of the right renal artery. Her renal failure and mesenteric angina resolved, and she was discharged home. Endovascular fenestration provides an elegant solution for AD-associated dynamic malperfusion of aortic branch vessels without compromising future open aortic repairs.

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.

Patients with heritable connective tissue disorders (HCTDs), represented by Marfan syndrome, can develop fatal aortic and/or arterial complications before age 50. Therefore, accurate diagnosis, appropriate medical treatment, and early prophylactic surgical treatment of aortic and arterial lesions are essential to improve prognosis. Patients with HCTDs generally present with specific physical features due to connective tissue abnormalities, while some patients with heritable thoracic aortic diseases (HTADs) have few distinctive physical characteristics. The development of genetic testing has made it possible to provide accurate diagnoses for patients with HCTDs/HTADs. This review provides an overview of the diagnosis and treatment of HCTDs/HTADs, including current evidence on cardiovascular interventions for this population. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Loeys‐Dietz syndrome (LDS) is an autosomal‐dominant connective tissue disorder associated with mutations in the transforming growth factor β 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Background: Ehlers–Danlos syndrome (EDS), Marfan syndrome (MFS), and Loeys–Dietz syndrome (LDS) are connective tissue disorders frequently associated with vascular aneurysm formation, dissections, and subsequent major complications. Regular imaging surveillance is recommended for these conditions. However, no guidelines currently exist regarding imaging modality or surveillance intervals. Methods: This retrospective single-center observational study analyzed clinical and imaging data of patients attending an outpatient clinic for vascular connective tissue disorders between August 2008 and January 2024. Imaging (1424 data points in total) and clinical data were extracted from electronic health records. Analysis primarily included a comparison of vessel diameter progression across imaging modalities, with an additional review of the clinical history of vascular events. Results: In total, 19 patients with vascular connective tissue disorders (vCTDs) underwent consultations at our outpatient clinic. Nine (47.4%) patients experienced vascular events, while two (10.5%) passed away during the study period. Multimodal imaging surveillance revealed a tendency towards arterial diameter increase. Consistent ultrasound monitoring provided more reliable diameter progression data for the same arterial segment than a combination of imaging modalities. Temporal analysis indicated a tendency for the continuous growth of the abdominal aorta, the common and internal carotid artery, and the common femoral and popliteal artery. Conclusion: The study highlights the importance of standardized, modality-specific imaging protocols in monitoring patients with vCTDs. The variability in disease progression among these patients further complicates surveillance strategies, contemplating the need for individualized approaches. Further research and prospective multicenter studies are required to refine and improve monitoring protocols.

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease. [ABSTRACT FROM AUTHOR]

Loeys-Dietz syndrome is a hereditary connective-tissue disorder first reported in 2005. It is caused by genetic defects in the transforming growth factor-beta (TGF-β) signaling pathway. TGF-β signaling plays an important role in connective-tissue development, differentiation, and homeostasis. Dysregulation of TGF-β signaling causes various defects in the skull, face, skeletal system, skin, and blood vessels. Symptoms of Loeys-Dietz syndrome include scoliosis, spider finger, joint laxity, club foot, hypertelorism, and cleft palate. In addition, aortic aneurysm, aortic dissection, bleeding tendency, delayed wound healing, allergic disease, and autoimmune disease have been reported. Here, we describe an 11-year-old male with type 1 diabetes mellitus who had frequent epistaxis and easy bruising from an early age, along with skin and joint hyperextension, atrophic scars, and long limbs. He was suspected of having a hereditary connective-tissue disorder and was diagnosed with Loeys-Dietz syndrome type 1 by next-generation sequencing. Similar to Marfan syndrome and Ehlers-Danlos syndrome, this disease has a high risk of aortic aneurysm and aortic dissection. In addition, because aortic dissection can occur at a young age, early diagnosis and periodic examination and treatment for cardiovascular diseases are necessary.

Objective: Genetic aortopathy, if left untreated, leads to aortic catastrophe in most affected individuals. We sought to determine the genetic mutation patterns and detection rates in patients with aortopathy and their families with a systematic screening protocol. Methods: In 2016 to 2020, patients with aortic dissection or root aneurysm (Z score ≥2) and their first-degree relatives were enrolled in a prospective registry at a tertiary referral center. The individuals underwent systematic single- or multi-gene panel testing depending on clinical presentations. Results: Among 575 enrolled individuals (mean age, 46.6 ± 14.5 years; 203 women), 346 (60.2%) underwent genetic testing. Rates of relevant gene mutations identified were 39.4% (91/231), 27.1% (54/199) and 72.4% (n = 105) in aneurysm, dissection, and family screening groups, respectively (P

Abstract 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.

Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder. Vessel tortuosity and aneurysms throughout the vasculature are unique to LDS. Aortic root enlargement is ubiquitous, with most patients undergoing root replacement at some point in their lifetime. Multiple vascular procedures are required to prolong life expectancy. We describe a staged hybrid approach to a 17-year-old patient with LDS presenting with ascending aorta, arch, and bilateral subclavian artery aneurysms and prominent tortuosity. Transposition of the left vertebral and subclavian arteries onto the common carotid artery was performed. Total aortic arch replacement with frozen elephant trunk extension into the descending thoracic aorta was performed as a second stage. Bilateral subclavian artery aneurysms were excluded with the use of a four-branched graft.

Streptococcus agalactiae is known to cause invasive infections in risk groups such as pregnant women, newborns, and immunosuppressed patients but it is uncommon in older children. We describe a case of recurrent infective endocarditis due to S. agalactiae in an 11-year-old boy with Loeys-Dietz syndrome who was successfully treated with long-term antimicrobial therapy for one year. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The prevalence and aetiology of acute aortic dissection type A (AADA) in patients ≤30 years is unknown. The aims of this clinical study were to determine the prevalence and potential aetiology of AADA in surgically treated patients ≤30 years and to evaluate the respective postoperative outcomes in this selective group of patients in a large multicentre study. METHODS Retrospective data collection was performed at 16 participating international aortic institutions. All patients ≤30 years at the time of dissection onset were included. The postoperative results were analysed with regard to connective tissue disease (CTD). RESULTS The overall prevalence of AADA ≤30 years was 1.8% (139 out of 7914 patients), including 51 (36.7%) patients who were retrospectively diagnosed with CTD. Cumulative postoperative mortality was 8.6%, 2.2% and 1.4%. Actuarial survival was 80% at 10 years postoperatively. Non-CTD patients (n  = 88) had a significantly higher incidence of arterial hypertension (46.6% vs 9.8%; P  < 0.001) while AADA affected the aortic root (P  < 0.001) and arch (P  = 0.029) significantly more often in the CTD group. A positive family history of aortic disease was present in 9.4% of the study cohort (n  = 13). CONCLUSIONS The prevalence of AADA in surgically treated patients ≤30 years is <2% with CTD and arterial hypertension as the 2 most prevalent triggers of AADA. Open surgery may be performed with good early results and excellent mid- to long-term outcomes. [ABSTRACT FROM AUTHOR]

An aberrant subclavian artery (ASA) (or lusoria) is the most common congenital anomaly of the aortic arch (0.5%-2.2%; female-to-male ratio 2:1 to 3:1). ASA can become aneurysmal and result in dissection, involving Kommerell's diverticulum when present and the aorta. Data of its significance in genetic arteriopathies are not available. The purpose of this study was to assess the prevalence and complications of ASA in gene-positive and -negative nonatherosclerotic arteriopathies. The series includes 1,418 consecutive patients with gene-positive (n = 854) and gene-negative arteriopathies (n = 564) diagnosed as part of institutional work-up for nonatherosclerotic syndromic and nonsyndromic arteriopathies. Comprehensive evaluation includes genetic counseling, next-generation sequencing multigene testing, cardiovascular and multidisciplinary assessment, and whole-body computed tomography angiography. ASA was found in 34 of 1,418 cases (2.4%), with a similar prevalence in gene-positive (n = 21 of 854, 2.5%) and gene-negative (n = 13 of 564, 2.3%) arteriopathies. Of the former 21 patients, 14 had Marfan syndrome, 5 had Loeys-Dietz syndrome, 1 had type-IV Ehlers-Danlos syndrome, and 1 had periventricular heterotopia type 1. ASA did not segregate with genetic defects. Dissection occurred in 5 of 21 patients with genetic arteriopathies (23.8%; 2 Marfan syndrome and 3 Loeys-Dietz syndrome), all with associated Kommerell's diverticulum. No dissections occurred in gene-negative patients. At baseline, none of the 5 patients with ASA dissection fulfilled criteria for elective repair according to guidelines. The risk of complications of ASA is higher in patients with genetic arteriopathies and is difficult to predict. In these diseases, imaging of the supra-aortic trunks should enter baseline investigations. Determination of precise indications for repair can prevent unexpected acute events such as those described. [Display omitted] [ABSTRACT FROM AUTHOR]

Loeys–Dietz syndrome (LDS) is an autosomal‐dominant connective‐tissue disorder with vascular and musculoskeletal abnormalities similar to Marfan syndrome. However, unlike Marfan, retinal detachment (RD) is rarely reported, and screening protocols do not currently feature ophthalmic assessment or RD counseling. We report a 5‐generation family affected by LDS, where RD occurred in six eyes of four individuals. The proband was an 84‐year‐old male recently diagnosed with type‐V LDS (TGFβ3 pathogenic variant c.899G>A, p.(Arg300Gln)). Further investigation was undertaken into the family's medical history. The proband experienced bilateral rhegmatogenous RD at age 60, requiring emergency surgical repair. Other notable ophthalmic features include unusual keratometry, abnormal biometry, and severe hayfever requiring long‐term sodium cromoglycate treatment. The proband's sister, father, and uncle had also experienced RDs, all prior to LDS diagnosis. This series demonstrates that RD risk may be significant in LDS, and on occasion the presenting clinical feature. We suggest ophthalmic examination should be added to the initial assessment LDS patients, and patients informed of the early warning symptoms of retinal detachment. As in Marfan syndrome, LDS patients may exhibit cornea plana and abnormal corneal topography, producing atypical biometry. They may also present with allergic conjunctivitis, and awareness of these signs might facilitate earlier diagnosis. [ABSTRACT FROM AUTHOR]

Background: Vascular Ehlers-Danlos (vEDS) and Loeys-Dietz syndromes (LDS) are hereditary disorders of connective tissue having severe vascular complications (HDCTv) which lead to an increased risk of premature death. Little is known about the impact of the disease in patient’s daily life. Method: Sixteen HDCTv patients (vEDS = 9 and LDS = 7), 16 age and sex-matched hypermobile Ehlers-Danlos syndrome patients (hEDS) and 18 healthy subjects (HS), responded to self-questionnaires assessing psychosocial adjustment, quality of life (QoL), anxiety, depression, pain, fatigue and sleep problems. Patients with HDCTv were also interviewed in order to explore qualitatively their experience with the disease. Results: Compared with HS, patients with HDCTv scored significantly higher on anxiety, depression, fatigue, sleep problems, and lower on QoL. Most HDCTv patients (93.8%) have optimal psychosocial adjustment. In addition, HDCTv patients scored higher on QoL and psychosocial adjustment, but lower in pain, fatigue, sleep problems, and depressive symptoms than hEDS patients. Four main themes were identified in qualitative analyses: living with HDCTv, knowledge/ ignorance of the disease, health behaviors/self-care and coping strategies. Conclusion: Our results suggest that despite the negative impact of HDCTv on the patients’ daily lives, overall, they present an optimal disease adjustment which points to appropriate coping strategies. More research in psychosocial aspects of people with these rare diseases are needed to confirm these results and better understand their needs. [ABSTRACT FROM AUTHOR]

Background: While representing a significant improvement, the introduction of next‐generation sequencing in genetic diagnosis also prompted new challenges. Despite widely recognized consensus guidelines for the interpretation of sequence variants, many variants remain unclassified or are discordantly interpreted. In heritable thoracic aortic aneurysms with dissection (HTAAD), most cases are caused by a heterozygous, private missense mutation, possibly contributing to the relatively common reports of variants with uncertain significance in this group. Segregation analysis necessitates advanced likelihood‐based methods typically inaccessible to non‐experts and is hampered by reduced penetrance, possible phenocopies, and non‐availability of DNA from deceased relatives. Methods: In this report, challenges in variant interpretation and the use of segregation analyses were illustrated in two families with a suspected HTAAD disorder. The R package segregatr, a novel implementation of full‐likelihood Bayes factor (FLB), was performed to explore the cosegregation of the variants in these families. Conclusion: Using the R package segregatr, cosegregation in the reported families concluded with strong and supporting evidence for pathogenicity. Surveillance of families in a multidisciplinary team enabling systematic phenotype description for standardized segregation analysis with a robust calculation method may be imperative for reliable variant interpretation in HTAAD. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Herz-, Thorax- und Gefaesschirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The commercial availability of the iliac branch endoprosthesis (IBE) has permitted endovascular repair of iliac artery aneurysms with the preservation of pelvic circulation. However, the device instructions for use require certain anatomic criteria that can limit deployment in ≤30% of patients. Moreover, branched endovascular treatment of common iliac artery aneurysms with IBE in patients with connective tissue disorders such as Loeys-Dietz syndrome has not been described. In the present report, we have described our technique of alternative endograft aortoiliac reconstruction to overcome anatomic barriers to IBE placement in a patient with a giant common iliac artery aneurysm in the setting of a rare pathogenic variant in the SMAD3 gene.

Ascending aortic aneurysm is very rare in children, and is usually seen in patients with underlying connective tissue disorders such as Marfans and Ehler–Danlos syndrome. Loeys–Dietz syndrome (LDS) is less commonly seen as a cause of ascending aortic aneurysms in children. In this case report, we describe pediatric Bentall procedure, which we successfully performed to a child with LDS (Type I) with giant ascending aortic enlargement and significant aortic regurgitation.

Loeys-Dietz syndrome is a genetic disorder that predisposes patients to aortic aneurysms. If left untreated, the natural history of the associated aortopathy often culminates in fatal aortic dissection. We describe the case of a 21-year-old man who was diagnosed with Loeys-Dietz syndrome after 2 family members died of aortic dissection. This case highlights the importance of increased physician awareness of this syndrome, which can play a crucial role in preventing premature sudden cardiac death caused by aortic catastrophe.

Abstract Background Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, especially aortic dilatations and arterial tortuosity, craniofacial and skeletal features, joint laxity or contractures, skin abnormalities, hypotonia and motor delay. Its diagnosis is established by the identification of a pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3 genes. In newborns and toddlers, vascular complications such as aneurism rupture, aortic dissection, and intracerebral incidents, can occur already in the weeks of life. To avoid these events, it is crucial to precociously identify this condition and to start an apunderwent a surgical procedurepropriate treatment which, depending on the severity of the vascular involvement, might be medical or surgical. Case presentation We report two cases of Loeys-Dietz syndrome precociously diagnosed. The first describes a male, born at 38 + 1 weeks of gestation, with hypotonia, joint hypermobility, arachnodactyly, and fingers joint contractures, as well as senile appearance and facial dysmorphisms. In the suspect of a connective tissue disorder, an echocardiography was performed and revealed an aortic root dilatation of 13 mm (Z score + 3). A trio based Whole Exome Sequencing found a novel de novo variant in the TGFBR2 gene. Despite the onset of a low-dose angiotensin receptor blocker therapy, the aneurysm progressed. The second case describes a female, born at 41 + 3 weeks of gestation. During the neonatal examination a cleft palate was noticed, as well as minor dysmorphisms. Since the family history was suspicious for connective tissue disorders, a genetic panel was performed and identified a pathogenetic variant in TGFB3 gene. In this case, the echocardiography revealed no abnormalities. Conclusions In addition to our cases, we identified 14 subjects with neonatal LDS in the medical literature. All of them had aortic involvement. Skeletal and face abnormalities, including eyes and palate malformations, were also highly frequent. Overall, 10 subjects required medical therapy to avoid aneurysm progression, and 8 patients underwent surgical procedures. Benefits of an early diagnosis of LDS are various and imply a potential modification of the natural history of the disease with early interventions on its complications.

Background Differences in the clinical course of heritable thoracic aortic disease based on the disease‐causing gene have not been fully evaluated. To clarify the clinical relevance of causative genes in heritable thoracic aortic disease, we assessed the clinical course of patients categorized based on genetic diagnosis. Methods and Results We investigated cardiovascular events and mortality in 518 genetically diagnosed patients in 4 groups: Group 1, FBN1 (n=344); Group 2, TGFBR1, TGFBR2, SMAD3, or TGFB2 (n=74); Group 3, COL3A1 (n=60); and Group 4, ACTA2 or MYH11 (n=40). The median age at the first cardiovascular event ranged from 30.0 to 35.5 years (P=0.36). Patients with gene variants related to transforming growth factor‐β signaling had a significantly higher rate of subsequent events than those with FBN1 variants (adjusted hazard ratio, 2.33 [95% CI, 1.60–3.38]; P

A 60-year-old man with Loeys-Dietz syndrome (LDS) underwent surgery for multiple left deep femoral artery aneurysms (DFAAs). An intraoperative graft replacement was performed from the common femoral artery to the distal DFAAs; the superficial femoral artery was sutured to the graft. DFAAs in association with LDS and the occurrence of multiple DFAAs are rare. To the best of our knowledge, no studies have reported their coexistence. Graft replacement was decided as the optimal treatment for our patient. However, treatment should be considered on a patient-by-patient basis. Therefore, a lower limb arterial examination should accompany the screening of patients with LDS.

BackgroundVascular Ehlers-Danlos (vEDS) and Loeys-Dietz syndromes (LDS) are hereditary disorders of connective tissue having severe vascular complications (HDCTv) which lead to an increased risk of premature death. Little is known about the impact of the disease in patient’s daily life.MethodSixteen HDCTv patients (vEDS = 9 and LDS = 7), 16 age and sex-matched hypermobile Ehlers-Danlos syndrome patients (hEDS) and 18 healthy subjects (HS), responded to self-questionnaires assessing psychosocial adjustment, quality of life (QoL), anxiety, depression, pain, fatigue and sleep problems. Patients with HDCTv were also interviewed in order to explore qualitatively their experience with the disease.ResultsCompared with HS, patients with HDCTv scored significantly higher on anxiety, depression, fatigue, sleep problems, and lower on QoL. Most HDCTv patients (93.8%) have optimal psychosocial adjustment. In addition, HDCTv patients scored higher on QoL and psychosocial adjustment, but lower in pain, fatigue, sleep problems, and depressive symptoms than hEDS patients. Four main themes were identified in qualitative analyses: living with HDCTv, knowledge/ignorance of the disease, health behaviors/self-care and coping strategies.ConclusionOur results suggest that despite the negative impact of HDCTv on the patients’ daily lives, overall, they present an optimal disease adjustment which points to appropriate coping strategies. More research in psychosocial aspects of people with these rare diseases are needed to confirm these results and better understand their needs.

Abstract Background While representing a significant improvement, the introduction of next‐generation sequencing in genetic diagnosis also prompted new challenges. Despite widely recognized consensus guidelines for the interpretation of sequence variants, many variants remain unclassified or are discordantly interpreted. In heritable thoracic aortic aneurysms with dissection (HTAAD), most cases are caused by a heterozygous, private missense mutation, possibly contributing to the relatively common reports of variants with uncertain significance in this group. Segregation analysis necessitates advanced likelihood‐based methods typically inaccessible to non‐experts and is hampered by reduced penetrance, possible phenocopies, and non‐availability of DNA from deceased relatives. Methods In this report, challenges in variant interpretation and the use of segregation analyses were illustrated in two families with a suspected HTAAD disorder. The R package segregatr, a novel implementation of full‐likelihood Bayes factor (FLB), was performed to explore the cosegregation of the variants in these families. Conclusion Using the R package segregatr, cosegregation in the reported families concluded with strong and supporting evidence for pathogenicity. Surveillance of families in a multidisciplinary team enabling systematic phenotype description for standardized segregation analysis with a robust calculation method may be imperative for reliable variant interpretation in HTAAD.

Aim: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes).Methods: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease. [ABSTRACT FROM AUTHOR]