Loeys-Dietz Research Articles

Utilization of percutaneous closure devices for large bore arterial access in patients with genetic aortopathy does not result in increased rates of access site complications

ObjectivePercutaneous closure devices for arterial sheaths of sufficient caliber to deliver aortic endografts have a published success rate of 90-95%. Despite this, they are frequently avoided in patients with genetic aortopathy due to concern for high failure rates and increased complications in the setting of compromised tissue integrity. This study aims to compare rates of access site complications following large bore percutaneous access among patients with and without confirmed genetic aortopathy. MethodsAll patients undergoing endovascular aortic procedures requiring large bore (≥9Fr) femoral sheath access between 2019-2023 were identified. The specific mutation, demographics, comorbidities, and operative details including maximum sheath size were recorded. Outcomes including unplanned femoral cutdown, access site complications and reinterventions were evaluated. These factors were then compared between patients with and without a laboratory confirmed mutation associated with genetic aortopathy. A supplemental analysis was then performed on all patients with genetic aortopathy from 2014-2023. ResultsAmong the 404 patients identified, 33 (8%) had confirmed genetic aortopathy. Among these, 7 patients (21%) had Marfan syndrome, 7 (21%) had Loeys-Dietz syndrome, and 3 (9%) had vascular Ehlers-Danlos. Also represented were ACTA2, PRKG1, FOXE3, and LOX mutations. The genetic aortopathy group was significantly younger (median genetic aortopathy: median 52 years; non-genetic aortopathy: 71 years; p<0.001). TEVAR was most frequent in the genetic aortopathy group (52%), followed by Zone II arch replacement with frozen elephant trunk (21%); the most frequent operation among the non-genetic aortopathy group was F/BEVAR(43%), followed by TEVAR (25%). Both groups had a median sheath size of 20 Fr; the patients with genetic aortopathy had higher rates of both prior open (genetic aortopathy: 27%; non-genetic aortopathy: 12%; p=0.015) and prior percutaneous ipsilateral access (genetic aortopathy: 58%; non-genetic aortopathy: 39%; p=0.041). Rates of unplanned cutdowns (genetic aortopathy: 0%; non-genetic aortopathy: 6%) and access site complications (genetic aortopathy: 0%; non-genetic aortopathy: 8%) did not significantly differ between groups (p=0.160 and p=0.096, respectively). In supplementary analysis, there was one patient with genetic aortopathy who required unplanned cutdown, yielding an overall technical success rate of 97% for percutaneous closure over a 10-year period. ConclusionsPercutaneous access is safe and effective in patients with confirmed genetic aortopathy with similar rates of unplanned cutdown as those in patients without genetic aortopathy. Given the high rates of staged, repeat aortic procedures in this patient population, percutaneous closure should be attempted to avoid an obligate femoral incision, thereby reducing the potential for wound complications and increasing the ease of future procedures.

Epilepsy in Loeys-Dietz Syndrome: The Rare Concurrence of a Connective Tissue and Neuronal Migration Disorder

We present a 7-year-old girl who presented to our emergency department in active status epilepticus. Seizures responded to standard antiepileptic medications; however, baseline work-up for seizure etiology remained unremarkable. Her new-onset seizures were further investigated via EEG and MRI brain, which revealed focal epileptiform discharges and periventricular nodular heterotopia, respectively. Concurrently, the clinical evaluation revealed extensive marfanoid features, and a personal history of eczema and asthma. Her family history was pertinent for aortic valve disease, asthma, and tall stature. Given the peculiar skeletal features, allergic propensities and coexistent weighty family history, a molecular genetic panel analysis for Marfan Syndrome and Loeys-Dietz Syndrome (LDS) were sought. Genetic testing revealed an underlying heterozygous variant in the TGFBR-1 gene; thereby confirming the presence of LDS. The child had responded well to single antiepileptic agent therapy and was discharged in good condition with regular outpatient cardiac and neurology follow-up. This is a unique case reported of a child with genetically diagnosed LDS concurring with an underlying neuronal migration disorder, manifesting in an acute, severe, and lifethreatening fashion.

Pregnancy and inherited aortopathies: insights from specialized care

Abstract Background Genetic counselling, pregnancy follow-up and delivery planning in women with aortopathy should be conducted by a multidisciplinary team in an expert centre. Purpose Our objective was to analyze the impact of pregnancy on aortopathy outcomes in a centre specialized in inherited cardiovascular conditions in the United Kingdom. Methods All women with aortopathy referred to our centre due to pregnancy between 2016 and 2023 were retrospectively analyzed. Demographic, clinical, obstetric, genetic, electrocardiographic, and multimodal imaging variables were collected. Results Between 2016 and 2023, 22 women with aortopathy were referred to our centre for pregnancy follow-up and delivery planning. Among them, 14 (63.6%) had Marfan syndrome (FBN1+), 4 (18.2%) family history of aortic dissection without known genetic mutations, 2 (9.1%) bicuspid aortic valve with aortic dilation and 2 (9.1%) Loeys-Dietz syndrome (SMAD3+). The average number of births per patient was 1.55. Among those with an identified mutation, 4 (25%) underwent preimplantation diagnosis. In total, there were 40 pregnancies resulting in 34 live births. 15 women (68.2%) had an aortic root dimension &amp;lt;40mm and 7 (31.8%) ≥40mm. There were 4 (26.7%) and 5 (71.4%) patients in each group under beta-blockers. Out of the total 40 pregnancies, there were 6 (15%) miscarriages, all in the first trimester, 2 (5%) cases of preeclampsia and 1 (2.5%) case of gestational diabetes. There were no statistically significant differences between these complications and the aortic root dimension (8 (20%) &amp;lt;40mm vs 1 (2.5%) ≥40mm; p = 0.160) or the absence or presence of treatment (3 (7.5%) vs 6 (15%); p = 0.769). Regarding delivery, 16 patients (72.7%) underwent vaginal delivery and 6 (27.3%) has a caesarean section. After delivery, there were 6 cases of major bleeding, 4 (10%) after vaginal delivery and 2 (5%) after caesarean (p=0.376). One patient had a subacute type A aortic dissection in the context of Marfan syndrome with an aortic root of 40mm before pregnancy. No significant differences were observed in the occurrence of these complications based on the aortic root dimension (5 (12.5%) &amp;lt;40mm vs 2 (5%) ≥40mm; p = 0.928) or the absence or presence of treatment (2 (5%) vs 5 (12.5%) respectively; p = 0.591). 100% of the patients survived pregnancy and the postpartum period. Conclusions Our findings underscore the complexity of managing aortopathy during pregnancy. This highlights the importance of a comprehensive risk assessment for precise pregnancy and delivery planning.

Identification of Genetic Variants Associated with Hereditary Thoracic Aortic Diseases (HTADs) Using Next Generation Sequencing (NGS) Technology and Genotype-Phenotype Correlations.

Hereditary thoracic aorta diseases (HTADs) are a heterogeneous group of rare disorders whose major manifestation is represented by aneurysm and/or dissection frequently located at the level of the ascending thoracic aorta. The diseases have an insidious evolution and can be encountered as an isolated manifestation or can also be associated with systemic, extra-aortic manifestations (syndromic HTADs). Along with the development of molecular testing technologies, important progress has been made in deciphering the heterogeneous etiology of HTADs. The aim of this study is to identify the genetic variants associated with a group of patients who presented clinical signs suggestive of a syndromic form of HTAD. Genetic testing based on next-generation sequencing (NGS) technology was performed using a gene panel (Illumina TruSight Cardio Sequencing Panel) or whole exome sequencing (WES). In the majority of cases (8/10), de novo mutations in the FBN1 gene were detected and correlated with the Marfan syndrome phenotype. In another case, a known mutation in the TGFBR2 gene associated with Loeys-Dietz syndrome was detected. Two other pathogenic heterozygous variants (one de novo and the other a known mutation) in the SLC2A10 gene (compound heterozygous genotype) were identified in a patient diagnosed with arterial tortuosity syndrome (ATORS). We presented the genotype-phenotype correlations, especially related to the clinical evolution, highlighting the particularities of each patient in a family context. We also emphasized the importance of genetic testing and patient monitoring to avoid acute aortic events.

Genetic variants in patients with multiple arterial aneurysms

PurposeThe aim of this study was to identify causal genetic variants in patients with multiple arterial aneurysms.MethodsFrom a total cohort of 3107 patients diagnosed with an arterial aneurysm from 2006 to 2016, patients with known hereditary connective tissue diseases, vasculitis, or other arterial pathologies (n = 918) were excluded. Of the remaining cohort (n = 2189), patients with at least 4 aneurysms at different arterial locations (n = 143) were included. Nine blood samples of respective patients were available and derived from the institutional vascular biomaterial bank, and analyzed by whole exome sequencing (WES). Possible candidate variants were selected based on in silico predictions: (I) Truncating variants or (II) Variants that were classified as likely pathogenic (SIFT score < 0.05 or PolyPhen score > 0.9) and with low (< 0.001) or unknown gnomAD allele frequency. The human genome databases GeneCards and MalaCards were used to correlate the variants with regard to possible associations with vascular diseases.ResultsA total of 24 variants in 23 different genes associated with vascular diseases were detected in the cohort. One patient with eight aneurysms was heterozygous for a variant in SMAD3, for which pathogenic variants are phenotypically associated with Loeys-Dietz syndrome 3. A heterozygous variant in TNXB was found in a patient with five aneurysms. Homozygous or compound heterozygous pathogenic variants in this gene are associated with Ehlers-Danlos syndrome (classical-like). Another patient with six aneurysms carried two heterozygous TET2 variants together with a heterozygous PPM1D variant. Pathogenic variants in these genes are associated with clonal hematopoiesis of indeterminate potential (CHIP), a known risk factor for cardiovascular disease.ConclusionAll nine patients in this study carried variants in genes associated with vascular diseases. Current knowledge of the specific variants is insufficient to classify them as pathogenic at the present time, underlining the need for a better understanding of the consequences of genetic variants. WES should be considered for patients with multiple arterial aneurysms to detect germline variants and to improve clinical management for the individual and family members.

A familial case of aortic dilatation with p.Tyr470Cys in TGFBR2 in which the phenotype included only vascular lesions.

Hereditary connective tissue diseases have different risks of aortic dissection depending on the causative gene. We report a family with no extravascular phenotype and a clinical diagnosis of familial thoracic aortic aneurysm and dissection, but genetic testing confirmed p.Tyr470Cys in TGFBR2, which is typically the responsible gene for Loeys-Dietz syndrome. Validation of the clinical diagnosis by genetic testing is warranted.

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.

Whole aorta imaging shows increased risk for thoracic aortic aneurysms and dilatations in relatives of abdominal aortic aneurysm patients

ObjectiveFor relatives of abdominal aortic aneurysm (AAA) patients, guidelines recommend abdominal imaging aimed at early detection and management of AAA, and do not include screening for thoracic aortic aneurysms (TAA). We aimed to investigate if TAA occur in undiagnosed relatives of AAA patients without a known genetic susceptibility for aneurysms, similar to families with identified genetic susceptibilities for aneurysms like in Marfan and Loeys-Dietz syndrome, where both AAA and TAA occur. MethodsRelatives of AAA patients were invited for non-contrast whole aorta CT screening. Systematic measurements of the CT scans were used to detect aneurysms and dilatations. Classification into familial and non-familial was based on reported family histories. In addition, aneurysm gene panel testing of AAA index cases was used for the classification of high vs unknown genetic risk (high genetic risk: familial aneurysm or a (likely) pathogenic variant (P/LP) in an aneurysm gene; unknown genetic risk: no family history or P/LP). ResultsWhole aorta imaging of 301 relatives of 115 abdominal aortic aneurysm index-patients with non-contrast CT scans showed a 28-fold increase in thoracic aortic aneurysms in relatives (1.7%, p<0.001 versus the age adjusted population) and a high frequency of thoracic dilatations in 18% of the relatives. Thoracic aneurysms and dilatations in relatives occurred even when index patients were unaware of familial aneurysms. AAA was increased in the relatives compared to the age adjusted population (8%, p<0.001). ConclusionsAn increased risk for thoracic aneurysms and dilatations was detected by whole aorta imaging of relatives of AAA index patients, even when index patients were unaware of familial aneurysms.These results indicate -still unknown- shared genetic susceptibilities for thoracic and abdominal aneurysms. Therefore, imaging of the whole aorta of relatives of all abdominal aneurysm patients, will improve early detection of aortic aneurysms in relatives of all AAA patients.

Successful Open Repair of a Thoracoabdominal Aortic Aneurysm After Multiple Failed Endovascular Treatments in a 22-Years-Old Individual With Loeys-Dietz Syndrome.

Loeys-Dietz syndrome is a rare genetically triggered disease characterized by aortic involvement, predisposing individuals to aneurysm and dissection at young age. Open repair is considered the treatment of choice despite the fact that it is associated with significant morbidity and mortality rates. On the other hand, endovascular treatment may be also considered an acceptable option in specific cases such as emergency or in patients unfit for open surgery or when landing zones are within surgical grafts. We report the case of a thoracoabdominal aortic aneurysm (TAAA) open surgical repair (OSR) in a 22-year-old male patient diagnosed with type 2 Loeys-Dietz syndrome, treated by means of a TAAA replacement with a 30-mm multi-branched "Coselli" aortic graft (Vascutek, Renfrewshire, Scotland, UK) after multiple previously interventions, including a thoracic endovascular aortic repair (TEVAR) and a custom made endograft for the visceral aorta.

Thoracoabdominal aortic replacement in a 6-year-old boy with Loeys-Dietz syndrome

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.

Open Surgical Repair in a Patient With Loeys-Dietz Syndrome and Extensive Vascular Compromise: A Case Report and Literature Review.

Loeys-Dietz syndrome (LDS) has been associated with multiple vascular abnormalities involving the entire arterial tree. However, limited reports regarding compromise in the aortoiliac and femoral bifurcation are available. Further, recommendations for optimal approach, thresholds for diameter at the time of surgery, and surveillance are also limited. We present a case of a 67-year-old male patient with LDS and aneurysmal aortoiliac and enlarging common femoral arteries aneurysms, who underwent open surgical repair. His past surgical history included multiple vascular interventions for lower extremity claudication and bilateral hip replacements. The right hip arthroplasty was previously removed due to infection. From the vascular standpoint, the patient underwent staged endovascular left hypogastric artery embolization and open aorto-bi-profunda bypass with a Rifampin-soaked Dacron graft. At 5-month follow-up, he remains asymptomatic with healed incisions and patent bypasses. This case highlights the challenges in managing peripheral aneurysms in LDS patients, emphasizing the need for tailored treatment strategies. While open repair is preferred, endovascular options may be considered in selected cases. Surveillance remains critical with annual cross-sectional imaging. Surgical planning is intricate due to comorbidities, anatomical complexities, and previous surgical infection. Surveillance of these patients must be strict as multiple vascular and non-vascular complications may arise. Therefore, collaborative decision-making is essential for optimal outcomes in this known high-risk population with connective tissue disorders.

The recognition of Loeys–Dietz syndrome as a differential diagnosis

The recognition of Loeys–Dietz syndrome as a differential diagnosis

Diagnosis and management of complex cardiovascular pathology in a patient with type III Loeys-Dietz Syndrome

Diagnosis and management of complex cardiovascular pathology in a patient with type III Loeys-Dietz Syndrome

Like Father like Daughter: Surgical Redo Thoracoabdominal Aneurysm Repairs in a Family With Loeys-Dietz Syndrome.

Loeys Dietz Syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from a mutation in the transforming growth factor beta receptor (TGFBR) family of genes. It is commonly associated with the development of aortic aneurysms and dissections. We report the successful open surgical management of thoracoabdominal aneurysms in a father and daughter with Loeys-Dietz Syndrome after failed endovascular repair. The daughter required stent graft explantation, while the stent graft remained in the father. These cases highlight the importance of early genetic testing of both patients and first-degree family members in those with a strong history of aortic disease, even when there is a lack of typical connective tissue disorder associated physical exam findings and open surgical index operations.

A nomoscore of four genes for predicting the rupture risk in abdominal aortic aneurysm patients with osteoarthritis

BackgroundAbdominal aortic aneurysm (AAA) represents one of the most life-threatening cardiovascular diseases and is increasingly becoming a significant global public health concern. The aneurysms-osteoarthritis syndrome (AOS) has gained recognition, as patients with this syndrome often exhibit early-stage osteoarthritis (OA) and have a substantially increased risk of rupture, even with mild dilation of the aneurysm. The aim of this study was to discover potential biomarkers that can predict the occurrence of AAA rupture in patients with OA. MethodsTwo gene expression profile datasets (GSE98278, GSE51588) and two single-cell RNA-seq datasets (GSE164678, GSE152583) were obtained from the GEO database. Functional enrichment analysis, PPI network construction, and machine learning algorithms, including LASSO, Random Forest, and SVM-RFE, were utilized to identify hub genes. In addition, a nomogram and ROC curves were generated to predict the risk of rupture in patients with AAA. Moreover, we analyzed the immune cell infiltration in the AAA tissue microenvironment by CIBERSORT and validated key gene expression in different macrophage subtypes through single-cell analysis. ResultsA total of 105 intersecting DEGs that showed consistent changes between rAAA and OA dataset were identified. From these DEGs, four hub genes (PAK1, FCGR1B, LOX and PDPN) were selected by machine learning. High predictive performance was observed for the nomogram based on these hub genes, with an AUC of 0.975 (95 % CI: 0.942–1.000). Abnormal immune cell infiltration was detected in rAAA and correlated significantly with the hub genes. Ruptured AAA cases exhibited higher nomoscore values and lower M2 macrophage infiltration compared to stable AAA. Validation in animal models (PPE+BAPN-induced rAAA) confirmed the significant role of these biomarkers in AAA pathology. ConclusionThe present study successfully identified four potential hub genes (PAK1, FCGR1B, LOX and PDPN) and developed a robust predictive nomogram to assess the risk of AAA rupture. The findings also shed light on the connection between hub genes and immune cell components in the microenvironment of rAAA. These findings support future research on key genes in AAA patients with OA, providing insights for novel management strategies for AAA.

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.

Temporal Pattern Analysis of Ultrasound Surveillance Data in Vascular Connective Tissue Disorders.

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. 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. 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. 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.

Engineered vascular grafts lend unique insight to pathophysiology of aortic aneurysms

Yang etal.1 generate tissue engineered blood vessels from hiPSC-derived smooth muscle cells harboring a mutation found in Loeys-Dietz syndrome. Invitro and invivo data from these vessels provide new insight into the molecular physiology of aortic aneurysms and may create a paradigm for understanding a suite of vascular diseases.

Impact of valve-sparing aortic root replacement on aortic fluid dynamics and biomechanics in patients with syndromic heritable thoracic aortic disease

Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms are poorly understood. This prospective, longitudinal study aims to assess the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients, and to examine whether they present altered haemodynamics or biomechanics prior to surgery compared to sHTAD patients with no indication for surgery (sHTAD-NSx) and healthy volunteers (HV). Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two 4D flow CMR studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two age, sex and BSA matched cohorts of 40 HV and 16 sHTAD-NSx patients with available 4D flow CMR, were selected for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV) and aortic strain were analysed in the ascending (AscAo) and descending aorta (DescAo). All patients with sHTAD presented altered haemodynamics and increased aortic stiffness (p<0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm2/s in HV, p=0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p=0.002), and decreased WSS (0.36 vs 0.47N/m2 in HV, p=0.004) in the proximal DescAo. After VSARR, proximal DescAo in-plane rotational flow (p=0.010) and circumferential WSS increased (p=0.011), no longer differing from HV, but through-plane rotational flow, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3cm²/s, p=0.047). Most AscAo flow alterations were restored to physiological values after VSARR. In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk.

Spontaneous Carotid Dissection as a Manifestation of Loeys–Dietz Syndrome Type 1 with Incomplete Penetrance

Spontaneous Carotid Dissection as a Manifestation of Loeys–Dietz Syndrome Type 1 with Incomplete Penetrance