Aortic and arterial manifestations and clinical features in -related heritable thoracic aortic disease: results from the Montalcino Aortic Consortium.

Background: Pathogenic variants in may lead to a syndromic genetic aortopathy. Heritable thoracic aortic disease (HTAD) and arterial events may occur in -related disease but there are limited outcomes data on vascular events in this condition.

Methods: Clinical data, phenotypical features and aortic outcomes in individuals with pathogenic/likely pathogenic (P/LP) variants enrolled in the Montalcino Aortic Consortium registry were reviewed.

Facilitating return of actionable genetic research results from a biobank repository: Participant uptake and utilization of digital interventions.

Research participants report interest in receiving genetic research results. How best to return results remains unclear. In this randomized pilot study, we sought to assess the feasibility of returning actionable research results through a two-step process including a patient-centered digital intervention as compared with a genetic counselor (GC) in the Penn Medicine biobank.

Acute Aortic Dissection: Observational Lessons Learned From 11 000 Patients.

Background: Over the past 25 years, diagnosis and therapy for acute aortic dissection (AAD) have evolved. We aimed to study the effects of these iterative changes in care.

Methods: Patients with nontraumatic AAD enrolled in the International Registry of Acute Aortic Dissection (61 centers; 15 countries) were divided into time-based tertiles (groups) from 1996 to 2022.

Comparative Risks of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease.

Background: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

Objectives: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

Methods: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, and location of recruitment.

Early Mortality in Type A Acute Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection.

Importance: Early data revealed a mortality rate of 1% to 2% per hour for type A acute aortic dissection (TAAAD) during the initial 48 hours. Despite advances in diagnostic testing and treatment, this mortality rate continues to be cited because of a lack of contemporary data characterizing early mortality and the effect of timely surgery.

Objective: To examine early mortality rates for patients with TAAAD in the contemporary era.

Development and performance of a hereditary hemorrhagic telangiectasia-specific quality-of-life instrument.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by arteriovenous malformations and telangiectasia, with primary clinical manifestations of epistaxis and gastrointestinal bleeding and resultant anemia. HHT negatively affects health-related quality of life (HR-QoL); however, existing tools to measure HR-QoL are not HHT specific. Our objective was to develop an HHT-specific HR-QoL (HHT-QoL) instrument and evaluate its performance in a cross-sectional survey of individuals with HHT.

Cardiovascular Outcomes in Aortopathy: GenTAC Registry of Genetically Triggered Aortic Aneurysms and Related Conditions.

Background: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.

Objectives: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.

Methods: The GenTAC study had a retrospective/prospective design.

Location of Aortic Enlargement and Risk of Type A Dissection at Smaller Diameters.

Background: Previous work has demonstrated that more than one-half of acute type A aortic dissections (ATADs) occur at a maximal aortic diameter (MAD) of <5.5 cm. However, no analysis has investigated whether ATAD risk at smaller MADs is more common with modest dilation of the aortic root (AR) or supracoronary ascending aorta (AA) in patients without genetically triggered aortopathy.

Digital vascular lesions detected by transillumination.

Abnormalities of the capillaries of the digits in hereditary hemorrhagic telangiectasia can be detected by shining through a narrow beam of light through the dorsal side and visualizing the vasculature on the palmar side, a procedure termed transillumination. This study was performed to determine if this method can detect digital vascular abnormalities in aortopathies and arteriopathies. Transillumination was performed in patients with Marfan syndrome (MFS), thoracic aortic aneurysm and dissection (TAAD), vascular Ehlers-Danlos syndrome (vEDS), bicuspid aortic valve with aortopathy, and arteriopathies without aortopathy.

Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant, age-related but highly penetrant condition with substantial intrafamilial and interfamilial variability. MFS is caused by pathogenetic variants in FBN1, which encodes fibrillin-1, a major structural component of the extracellular matrix that provides support to connective tissues, particularly in arteries, the pericondrium and structures in the eye. Up to 25% of individuals with MFS have de novo variants.

Expanding the phenotypic spectrum of Mendelian connective tissue disorders to include prominent kidney phenotypes.

Heritable connective tissue disorders are a group of diseases, each rare, characterized by various combinations of skin, joint, musculoskeletal, organ, and vascular involvement. Although kidney abnormalities have been reported in some connective tissue disorders, they are rarely a presenting feature. Here we present three patients with prominent kidney phenotypes who were found by whole exome sequencing to have variants in established connective tissue genes associated with Loeys-Dietz syndrome and congenital contractural arachnodactyly.

Arachnodactyly represented in art.

Arachnodactyly, a term used since 1902 to describe abnormally long (spider-like) fingers, is a pathologic feature of several heritable conditions, notably the Marfan syndrome and congenital contractural arachnodactyly. A number of prominent artists, dating from the 16th to the 20th centuries, have depicted subjects with unusually long fingers, sometime associated with elongation of the body, neck and head. El Greco incorporated this style in many paintings.

Uncertainty in Genomics Impacts Precision Medicine.

As exacting as genetic and genomic testing have become, health professionals continue to encounter uncertainty in their applications to medical practice. As examining the human genome at more refined levels increases, so is the likelihood of encountering uncertainty about the meaning of the information. The history of this concept informs how we might confront and deal with uncertainty, and what the future might hold.

Clinical Features and Outcomes of Pregnancy-Related Acute Aortic Dissection.

Importance: Women with aortopathy conditions are at risk for pregnancy-related aortic dissection, and these conditions may not be recognized until after the aortic dissection occurs.

Objective: To examine the clinical characteristics, imaging features, and outcomes in women with pregnancy-related acute aortic dissection.

Design, Setting, And Participants: A cohort study, comprising data from the International Registry of Acute Aortic Dissection (IRAD) (February 1, 1998, to February 28, 2018).

Cerebrovascular Malformations in a Pediatric Hereditary Hemorrhagic Telangiectasia Cohort.

Background: We determined the frequency of cerebrovascular malformations in a pediatric cohort with hereditary hemorrhagic telangiectasia.

Methods: Retrospective cohort study of 54 children diagnosed with hereditary hemorrhagic telangiectasia at a tertiary care center. All neuroimaging was reviewed to assess for number and types of cerebrovascular malformations and for intracerebral hemorrhage and arterial ischemic stroke.

Features of Marfan syndrome not listed in the Ghent nosology - the dark side of the disease.

: The revised Ghent nosology presents the classical features of Marfan syndrome. However, behind its familiar face, Marfan syndrome hides less well-known features.: The German Marfan Organization listed unusual symptoms and clinical experts reviewed the literature on clinical features of Marfan syndrome not listed in the Ghent nosology.

Postembolotherapy Pulmonary Arteriovenous Malformation Follow-Up: A Role for Graded Transthoracic Contrast Echocardiography Prior to High-Resolution Chest CT Scan.

Background: High-resolution chest CT (HRCT) scan is recommended after pulmonary arteriovenous malformation (PAVM) embolotherapy to assess for PAVM persistence and untreated PAVM growth. Graded transthoracic contrast echocardiography (TTCE) predicts the need for embolotherapy in PAVM screening. This study sought to determine whether postembolotherapy graded TTCE can similarly predict the need for repeat embolotherapy.

Open Thoracoabdominal Aortic Repair in Patients With Heritable Aortic Disease in the GenTAC Registry.

Background: Although patients with various types of heritable aortopathy often require distal aortic repair, data are limited regarding the most extensive operations-open thoracoabdominal aortic aneurysm (TAAA) repairs. The objective of this multicenter registry study was to characterize TAAA repairs in a large cohort of patients with different heritable aortic diseases.

Methods: From the 3699 patients enrolled at 8 participating centers in the Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) Registry, we identified 155 open TAAA repairs in 142 unique patients.

Carnival: A Graph-Based Data Integration and Query Tool to Support Patient Cohort Generation for Clinical Research.

Clinical research studies often leverage various heterogeneous data sources including patient electronic health record, online survey, and genomic data. We introduce a graph-based, data integration and query tool called Carnival. We demonstrate its powerful ability to unify data from these disparate data sources to create datasets for two studies: prevalence and incidence case/control matches for coronary artery disease and controls for Marfan syndrome.

Lack of Growth of Small (≤2 mm Feeding Artery) Untreated Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia.

Purpose: To assess pulmonary arteriovenous malformation (PAVM) growth among patients with untreated PAVMs using imaging from long-term follow-up per hereditary hemorrhagic telangiectasia international guidelines.

Materials And Methods: Analysis included 88 untreated PAVMs from 21 patients (6 male;15 female; mean age at presentation 47 y; range, 12-68 y). Two CT studies with the longest interval between were evaluated (mean 8.