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.

De Novo Balanced Translocations Disrupting the FBN1 Gene Diagnosed by Genome Sequencing: An Uncommon Cause of Marfan Syndrome Modifying Genetic Counseling.

Marfan syndrome (MFS) is a well-characterized rare genetic connective tissue disorder. The features of MFS are primarily skeletal, ocular, and cardiovascular and are mainly caused by single-nucleotide variants (SNVs) in the FBN1 gene (MIM#134797) located on chromosome 15q21.1.

Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium.

Background: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

Methods And Results: MAD was determined by direct measurement of echocardiographic images.

Online Personal Training in Patients With Marfan Syndrome: A Randomized Controlled Study of Its Impact on Quality of Life and Physical Capacity.

Background: Marfan syndrome (MFS) is a genetic disorder affecting the vascular and musculoskeletal systems. Limited knowledge exists regarding the exercise benefits for this population. This study aimed to explore the impact of a structured exercise program on the quality of life (QoL) and physical capabilities of patients with MFS.

Management of aortic disease in children with FBN1-related Marfan syndrome.

Marfan syndrome (MFS) is a hereditary connective tissue disorder with an estimated prevalence of 1:5000-1:10 000 individuals. It is a pleiotropic disease characterized by specific ocular, cardiovascular, and skeletal features. The most common cardiovascular complication is aortic root dilatation which untreated can lead to life-threatening aortic root dissection, mainly occurring in adult patients.

Rationale and design of the PACIFIC-PRESERVED (PhenomApping, ClassIFication and Innovation for Cardiac dysfunction in patients with heart failure and PRESERVED left ventricular ejection fraction) study.

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that is poorly defined, reflecting an incomplete understanding of its pathophysiology.

Aim: To redefine the phenotypic spectrum of HFpEF.

Methods: The PACIFIC-PRESERVED study is a prospective multicentre cohort study designed to perform multidimensional deep phenotyping of patients diagnosed with HFpEF (left ventricular ejection fraction≥50%), patients with heart failure with reduced ejection fraction (left ventricular ejection fraction≤40%) and subjects without overt heart failure (3:2:1 ratio).

Pathogenic variants affecting the TB5 domain of the fibrillin-1 protein: not only in geleophysic/acromicric dysplasias but also in Marfan syndrome.

Background: Marfan syndrome (MFS) is a multisystem disease with a unique combination of skeletal, cardiovascular and ocular features. Geleophysic/acromicric dysplasias (GPHYSD/ACMICD), characterised by short stature and extremities, are described as 'the mirror image' of MFS. The numerous pathogenic variants identified in MFS are located all along the gene and lead to the same final pathogenic sequence.

Multicentre medicoeconomic evaluation of cardiac magnetic resonance imaging for predicting coronary artery disease in left ventricular dysfunction: The CAMAREC study design.

Background: Cardiac magnetic resonance imaging may provide a non-invasive alternative to coronary angiography for differentiating between ischaemic and non-ischaemic cardiomyopathy in cases of unexplained reduced left ventricular ejection fraction.

Aim: The CAMAREC study aims to evaluate the diagnostic accuracy of cardiac magnetic resonance imaging in predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, using coronary angiography as the gold standard for comparison.

Methods: CAMAREC is a prospective cohort study of 406 patients in 10 centres with newly diagnosed, unexplained left ventricular ejection fraction ≤ 45%.

Primary Non-Aortic Lesions Are Not Rare in Marfan Syndrome and Are Associated with Aortic Dissection Independently of Age.

Purpose: The study sought to estimate the prevalence of primary non-aortic lesions (PNAL) unrelated to extension of aortic dissection (AD) in a cohort of patients with Marfan syndrome (MFS).

Methods: Adult patients presenting with pathogenic FBN1 mutations and an available pan-aortic contrast-enhanced CTA in eight French MFS clinics from April to October 2018 were included. Clinical and radiological data, particularly the presence of aortic lesions and PNAL (including aneurysm and ectasia), were retrospectively analyzed.

Multimodality imaging in thoracic aortic diseases: a clinical consensus statement from the European Association of Cardiovascular Imaging and the European Society of Cardiology working group on aorta and peripheral vascular diseases.

Imaging techniques play a pivotal role in the diagnosis, follow-up, and management of aortic diseases. Multimodality imaging provides complementary and essential information for this evaluation. Echocardiography, computed tomography, cardiovascular magnetic resonance, and nuclear imaging each have strengths and limitations in the assessment of the aorta.

HTAD patient pathway: Strategy for diagnostic work-up of patients and families with (suspected) heritable thoracic aortic diseases (HTAD). A statement from the HTAD working group of VASCERN.

Heritable thoracic aortic diseases (HTAD) are rare pathologies associated with thoracic aortic aneurysms and dissection, which can be syndromic or non-syndromic. They may result from genetic defects. Associated genes identified to date are classified into those encoding components of the (a) extracellular matrix (b) TGFβ pathway and (c) smooth muscle contractile mechanism.

Smooth Muscle Cell Relaxation Worsens Aortic Dilatation and Clinical Presentation in a BAPN/Angiotensin II-Induced Aortic Dissection Model in Rats.

Introduction: Beta-aminopropionitrile (BAPN) administration is a chemically induced model for preclinical aortic pathologies research. Angiotensin II (AngII) has been widely used to promotes aortic dissections in mice. Here, we provide insight on a modified aortic dissection model in rats.

Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials.

Background: Angiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments.

Methods: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021.

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.

Prognosis of Adults With Isolated Left Ventricular Non-Compaction: Results of a Prospective Multicentric Study.

Background: Whether left ventricular non-compaction (LVNC) bears a different prognosis than dilated cardiomyopathy (DCM) is still a matter of debate.

Methods: From a multicenter French prospective registry, we compared the outcomes of 98 patients with LVNC and 65 with DCM. The primary endpoint combined cardiovascular death, heart transplantation, and hospitalization for cardiovascular events.

Arrhythmia and impaired myocardial function in heritable thoracic aortic disease: An international retrospective cohort study.

Background: Heritable thoracic aortic diseases (HTAD), typically entailing aortic complications, can be caused by pathogenic variants or likely pathogenic variants (PV/LPVs) in several genes, including fibrillin1 (FBN1), Actin Alpha2 (ACTA2) and genes encoding components of the transforming growth factor (TGF)-β signaling pathway. In addition to aortic complications, non-aortic cardiac disease such as impaired myocardial function and/or arrhythmia have been increasingly reported, mainly in Marfan syndrome with underlying FBN1 PV/LPVs and are acknowledged as additional causes of morbidity and mortality. The prevalence of these manifestations in the various HTAD entities is largely unknown.

Non-Dissecting Distal Aortic and Peripheral Arterial Aneurysms in Patients With Marfan Syndrome.

Background: In Marfan syndrome (MFS), an aortic or peripheral arterial dilatation is usually the consequence of aortic dissection. Non-dissecting distal aortic and peripheral aneurysms (DAPA) are barely described. We sought to determine the incidence and prognostic impact of non-dissecting DAPA, requiring a surgical repair in a large population of patients with MFS.

Is physical activity a future therapy for patients with Marfan syndrome?

Introduction: The international recommendations tend to avoid physical activity (PA) for patients with Marfan syndrome (MFS). However, exceptions have recently been made in the most recent recommendations for these patients, suggesting benefits from doing PA at low intensity only. Furthermore, there is no evidence that moderate aerobic or weight training can worsen the disease symptoms and increase mortality of MFS patients.