Guillaume Jondeau

Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine) · Service de Cardiologie

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 (HTAD) gene in in a cross-sectional analysis of 2014-2023 dat...

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 FBN1 pathogenic variants identified in MFS are located all al...

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 imag...

Background: Marfan syndrome (MFS) is a rare genetic disorder affecting the vascular and musculoskeletal systems. Exercise is classically contraindicated and there are no data on the limitations associated with the syndrome and the benefits of training in this population. This study aimed to characterise the quality of life (QoL) and physical capaci...

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 t...

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...

Background: Heart failure (HF) registries include rich data on patient inclusion characteristics, but follow-up information is often incomplete. Medicoadministrative databases may provide less clinical information than registries, e.g. on left ventricular ejection fraction (LVEF), but long-term data are exhaustive and reliable. The combination of...

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. The effect of smooth muscle cell (SMC) relaxation with vas...

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 musc...

Background Timely diagnosis of patients with Heritable Thoracic Aortic Diseases (HTAD) is essential to avoid (often fatal) aortic dissection. Experts of the HTAD rare disease working group of the European Reference Network of Rare Vascular diseases (vascern) aimed to propose a pathway to: (1) improve patient care by diminishing time to diagnosis; (...

Background Mitral valve (MV) pathology, including prolapse and regurgitation, is a well-known cardiovascular manifestation associated with the genes that predispose to Heritable Thoracic Aortic Disease (HTAD). The extent to which there are differences in prevalence, presentation and severity of MV pathology as a function of the underlying genetic c...

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 met...

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 dissecti...

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, an...

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 aor...

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 p...

Background Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients. Methods In this randomised,...

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 tra...

This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant...

Established since 2017 and co-funded by the European commission, VASCERN is the European Reference Network aiming at improving and homogenizing care of patients with rare multisystemic vascular diseases throughout Europe. It gathers 31 expert teams from 26 highly specialized multidisciplinary HCPs, plus 7 Affiliated Partner centers, from 16 EU Memb...

Background The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) was launched in 2017 and involves, to date, 35 highly specialised multidisciplinary expert centres (from the 30 full Healthcare Provider members) coming from 11 countries and more than 70 patient organizations from 16 countries. The eHealth Working Group (WG...

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 arte...

Background Bicuspid Aortic Valve (BAV) is associated with an asymmetrical (not circular) aortic root, resulting in variability in the aortic root diameter measurements obtained using different techniques. The objective of this study was to describe the aortic root asymmetry, including its orientation in the thorax, in relation to the various phenot...

Background Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS) and related heritable thoracic aortic diseases (HTAD) are well-known for their aortic complications. Myocardial dysfunction and arrhythmia are less known in this setting but have been increasingly reported as additional causes of morbidity and mortality. Related to the rarity of the disor...

Marfan syndrome (MFS) is an autosomal hereditary pathology affecting 1:5000 peoples. Alteration of the fibrillin 1 gene (FBN1) results in haplo-insufficiency of the FBN1 protein mainly altering the vascular system. International recommendations have gradually allowed MFS patients to perform training programs because of its potential benefits. Howev...

Conflict of interest statementConflict of interest: E. Vidal-Petiot reports personal fees and non-financial support from Servier, outside the submitted work. A. Cohen-Solal has received grants or honoraria from Novartis, Servier, Daiichi Sankyo, Vifor, Menarini and Cardiorentis, outside of the submitted work. J. Frija-Masson reports non-financial s...

Objective Despite considerable research, the goal of finding nonsurgical remedies against thoracic aortic aneurysm and acute aortic dissection remains elusive. We sought to identify a novel aortic protein kinase that can be pharmacologically targeted to mitigate aneurysmal disease in a well-established mouse model of early-onset progressively sever...

Background Few data exist concerning genotype–phenotype relationships in left ventricular noncompaction (LVNC). Methods and Results From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype–phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of...

Purpose Marfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype–phenotype correlations have been found in proband studies only. Methods In 1,575 consecutive MFS probands and relatives from t...

Purpose Individuals with mosaic pathogenic variants in the FBN1 gene are mainly described in the course of familial screening. In the literature, almost all these mosaic individuals are asymptomatic. In this study, we report the experience of our team on more than 5,000 Marfan syndrome (MFS) probands. Methods Next-generation sequencing (NGS) captu...

Background Cardiovascular disease is the leading cause of death during pregnancy with thoracic aortic dissection being one of the main causes. Thoracic aortic disease is commonly related to hereditary disorders and congenital heart malformations such as bicuspid aortic valve (BAV). Pregnancy is considered a high risk period in women with underlying...

Marfan syndrome and related disorders. Marfan syndrome is an autosomal dominant disease, affecting about 1/5000 persons. It includes aortic wall fragility responsible for aortic root dilatation and risk of dissection, mitral valve prolapse, ophthalmological features (ectopia lentis, flat cornea, myopia), skeletal features (excessive height, arachno...

Backgrounds: Coronary angiography(CA) is usually performed in patients with reduced left ventricular ejection fraction(LVEF) to SEARCH: ischemic cardiomyopathy. Our aim was to examine the agreement between CA and cardiovascular magnetic resonance(CMR) among a cohort of patients with unexplained reduced LVEF, and estimate what would have been the c...

Objectif Évaluer le coût de la prise en charge médicale de certaines pathologies rares à partir des bases du système national des données de santé (SNDS) et estimer le surcoût spécifique lié à la maladie. Méthode L’étude était fondée sur l’exploitation des données du SNDS en ciblant cinq pathologies rares identifiables à partir de codes diagnostic...

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease with often unrecognized inherited forms. We sought to identify novel pathogenic variants associated with autosomal dominant inheritance of TAAD. We analyzed exome sequencing data from 35 French TAAD families and performed next-generation sequencing capture panel of genes i...

Aims: The aim of this study was to evaluate the effect of the creation of a left-to-right interatrial shunt on pulmonary haemodynamics in rats with heart failure with preserved ejection fraction (HFPEF). Methods and results: An interatrial communication (IAC) was created in 11 healthy rats (Lewis rats) and 11 rats which developed HFPEF (36-week-...

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with considerable inter- and intra-familial clinical variability. The contribution of inherited modifiers to variability has not been quantified. We analyzed the distribution of 23 clinical features in 1306 well-phenotyped MFS patients carrying FBN1 mutations. We found strong...

(Abstracted from Eur Heart J 2019;40:3848–3855) The World Health Organization recognizes that the reduction of maternal mortality worldwide is a critical goal. Currently, 1% to 4% of pregnant women have maternal heart disease, which has translated into 15% of maternal deaths.

Purpose Marfanoid habitus (MH) combined with intellectual disability (ID) (MHID) is a clinically and genetically heterogeneous presentation. The combination of array CGH and targeted sequencing of genes responsible for Marfan or Lujan–Fryns syndrome explain no more than 20% of subjects. Methods To further decipher the genetic basis of MHID, we per...

SKI pathogenic variations are associated with Shprintzen–Goldberg Syndrome (SGS), a rare systemic connective tissue disorder characterized by craniofacial, skeletal and cardiovascular features. So far, the clinical description, including intellectual disability, has been relatively homogeneous, and the known pathogenic variations were located in tw...

Background: Pathogenic SMAD3 variants are responsible for a cardiovascular phenotype, mainly thoracic aortic aneurysms and dissections. Precocious identification of the vascular risk such as aortic dilatation in mutated patients has a major impact in terms of management, particularly to avoid dissection and sudden death. These vascular damages are...

Background: Aortic risk has not been evaluated in patients with Marfan syndrome and documented pathogenic variants in the FBN1 gene. Objectives: This study sought to describe aortic risk in a population with Marfan syndrome with pathogenic variants in the FBN1 gene as a function of aortic root diameter. Methods: Patients carrying an FBN1 patho...

Objective: Regional and global longitudinal strain (RLS-GLS) are considered reliable indexes of myocardial viability in chronic ischemic patients and prediction of left ventricular (LV) functional recovery after acute myocardial infarction (MI) with preserved left ventricular ejection fraction (LVEF). We tested in the present study whether RLS and...

Objectives: In Marfan syndrome (MFS) patients, endovascular repair carries a risk of aortic wall injury, which may result in retrograde aortic dissection, dilatation, or false aneurysm at the landing zones. It was hypothesised that potentially these complications may be avoided using modified practices. This study aimed to describe experience of a...

The ACTA2 gene encodes for smooth muscle specific α-actin, a critical component of the contractile apparatus of the vascular smooth muscle cell. Pathogenic variants in the ACTA2 gene are the most frequently encountered genetic cause of non-syndromic hereditary thoracic aortic disease (HTAD). Although thoracic aortic aneurysm and/or dissection is th...

Background: Little is known about the incidence of cardiovascular events (CVEs) and their associated risk markers in children with Marfan syndrome (MFS). Aims: To assess the incidence of CVEs and determine risk markers in a cohort diagnosed with Marfan syndrome during childhood and followed for several years. Methods: From a French multicentre...

Purpose of review: Although the majority of thoracic aortic aneurysms and dissections (TAD) in the overall population are mainly related to arterial hypertension and atherosclerosis, Heritable Thoracic Aortic Disease (HTAD) are increasingly recognized, especially in younger individuals. As fatal events in the setting of HTAD are preventable with t...

Thanks to a better knowledge of the genetic causes of many diseases and an improvement in genetic testing techniques, genetics has gained an important role in the multidisciplinary approach to diagnosis and management of congenital heart disease and aortic pathology. With the introduction of strategies for precision medicine, it is expected that th...

Marfan syndrome (MFS) is associated with mutations in fibrillin-1 that predispose afflicted individuals to progressive thoracic aortic aneurysm (TAA) leading to dissection and rupture of the vessel wall. Here we combined computational and experimental approaches to identify and test FDA-approved drugs that may slow or even halt aneurysm progression...

Aortic valve surgery in non-elderly patients represents a very challenging patient population. The younger the patient is at the point of aortic valve intervention, the longer their anticipated life expectancy will be, with longer exposure to valve-related complications and risk for re-operation. Although the latest international guidelines recomme...

Introduction Left ventricular non-compaction (LVNC) is a rare cardiomyopathy that may be of genetic origin, however few data are available about the global yield of mutation screening, the spectrum of genes and allelic variations. Purpose The aim of this prospective study was to better characterize the allelic and genetic spectrum of isolated LVNC...

Aims: Reducing maternal mortality is a World Health Organization (WHO) global health goal. Although maternal deaths due to haemorrhage and infection are declining, those related to heart disease are increasing and are now the most important cause in western countries. The aim is to define contemporary diagnosis-specific outcomes in pregnant women...

Objective: Failure of thoracic endovascular aortic repair (TEVAR) in chronic aortic dissections can be partially explained by retrograde false lumen (FL) flow through distal re-entry tears. After implantation of a thoracic stent graft, FL thrombosis occurs in less than 50% of the cases. The objectives of this study were to describe the feasibility...

Background: Both bicuspid aortic valve (BAV) and Marfan syndrome have been associated with aortic dissection risk, but it is unknown whether the presence of BAV is associated with an increased aortic risk in patients with an FBN1 gene mutation. We evaluated aortic diameters, aortic valve function, and aortic shape in Marfan syndrome patients with...

Marfan syndrome (MFS) is a rare connective tissue disorder mainly due to mutations in the FBN1 gene. Great phenotypic variability is notable for age of onset, the presence and absence, and the number and the severity of the symptoms. Our team showed that FBN1 gene expression level was a good surrogate endpoint for severity of some MFS clinical feat...

Heritable thoracic aortic aneurysms and dissections (hTAAD) are life-threatening complications of well-known syndromic diseases or underdiagnosed nonsyndromic heritable forms (nshTAAD). Both have an autosomal dominant transmission and are genetically heterogeneous. Our objective was to describe the relevance of molecular diagnosis in these patients...

Background Pathogenic variants in SMAD3 cause thoracic aortic aneurysms and dissections, along with aneurysms and rupture of other arteries. Here, we examined differences in clinical presentation of aortic events (dissection or surgical repair of an aneurysm) with respect to age and variant type in an international cohort of individuals with SMAD3...

Introduction Currently, 2D TTE is used in routine practice for the follow-up of ascending aorta aneurism (AAA). When the maximal aortic diameter reaches the surgical threshold, ECG-gated computerized tomographic angiography (CT) is used to confirm the diameter. No study has evaluated ascending aortic diameter measurement with 3D trans-thoracic echo...

Background Outcome of acute heart failure (AHF) patients according to the final destination after emergency department (ED) has been poorly studied with contradictory results. Purpose To compare long-term outcomes after an episode of acute heart failure (AHF) in patients according to their destinations after ED. Methods OFICA (Observatoire Franca...

Objectives Dural ectasia is a major criterion for Marfan syndrome (MFS) diagnosis. However, its definition remains fuzzy with studies on small sample size reporting different criteria to differentiate between Marfan and controls. Methods All MFS patients with a mutation in the Fibrillin-1 gene who underwent a complete CT scan in our center were in...

In recent years, simple renal cysts have been associated with an increased risk of aortic aneurysms. There is little data regarding aortic dilation in patients with autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to compare Sinuses of Valsalva (SoV) and tubular ascending aorta diameters in ADPKD patients with matched...

Introduction Sur des modèles animaux d’hibernation, lorsque la FEVG est significativement diminuée, on retrouve systématiquement des plages de nécrose histologique. Notre hypothèse est qu’une zone de nécrose est toujours visible sur l’IRM en cas de FEVG ≤ 45 % si l’origine est ischémique. Une étude pilote rétrospective semble confirmer cette affirm...

Left ventricular non‐compaction (LVNC) is a cardiomyopathy that may be of genetic origin; however, few data are available about the yield of mutation, the spectrum of genes and allelic variations. The aim of this study was to better characterize the genetic spectrum of isolated LVNC in a prospective cohort of 95 unrelated adult patients through the...

Aims Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with sh...

Objectives: Current national registries are lacking detailed pathology-driven analysis and long-term patients outcomes. The Heart Valve Society (HVS) aortic valve (AV) repair research network started the Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (AVIATOR) to evaluate long-term patient outcomes of AV repair and...

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that displays a great clinical variability. Previous work in our laboratory showed that fibrillin-1 (FBN1) messenger RNA (mRNA) expression is a surrogate endpoint for MFS severity. Therefore, an expression quantitative trait loci (eQTL) analysis was performed to identify tran...

Marfan syndrome (MFS) is a rare autosomal dominant connective tissue disorder related to variants in the FBN1 gene. Prognosis is related to aortic risk of dissection following aneurysm. MFS clinical variability is notable, for age of onset as well as severity and number of clinical manifestations. To identify genetic modifiers, we combined genome-w...

Introduction: Natural history of patients with TGFBR1 or TGFBR2 mutations is not well known Hypothesis: Physical features may indicate high risk patients Methods: Data were collected on 403 patients with either TGFBR1 or TGFBR2 mutations. We compared the phenotypic features of patients with and without aortic dissection. Results: Patients with aort...