Pathogenic FBN1 Genetic Variation and Aortic Dissection in Patients With Marfan Syndrome.

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 pathogenic variant who visited our reference center at least twice were included, provided they had not undergone aortic surgery or had an aortic dissection before their first visit.

Marfan Sartan: a randomized, double-blind, placebo-controlled trial.

Aims: To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS).

Methods And Results: A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when <50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age >10 years old, and receiving standard therapy.

Comparative assessment of ascending aortic aneurysms in Marfan patients using ECG-gated computerized tomographic angiography versus trans-thoracic echocardiography.

Background: Contrast-enhanced computed tomography (CT) is routinely used as a complementary technique to trans-thoracic echocardiography (TTE) for assessing thoracic aortic aneurysms (TAA). However different measures can be obtained on CT and there are no recommendations on which to use. The objective was to determine which CT measurements most closely match reference TTE measurements in Marfan patients with TAA.

The clinical presentation of Marfan syndrome is modulated by expression of wild-type FBN1 allele.

Marfan syndrome is an autosomal dominant disorder mainly caused by mutations within FBN1 gene. The disease displays large variability in age of onset or severity and very poor phenotype/genotype correlations have been demonstrated. We investigated the hypothesis that phenotype severity could be related to the variable expression level of fibrillin-1 (FBN1) synthesized from the wild-type (WT) allele.

Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

Background: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined.

Methods: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases.

Aortic dilatation patterns and rates in adults with bicuspid aortic valves: a comparative study with Marfan syndrome and degenerative aortopathy.

Background: Bicuspid aortic valve (BAV) is related to aortic dilatation, but patterns/rates are conflicting with no comparison among aneurysms of different aetiology. We sought to define ascending aorta dilatation patterns/progression rates in BAV versus other aortopathies (Marfan syndrome (MFS), degenerative aortopathy (DA)).

Design And Setting: Retrospective, observational study.

Pregnancy outcomes among women with Marfan syndrome.

Objective: To determine cardiac and obstetric outcomes among women with Marfan syndrome (MS) whose pregnancies were managed in accordance with the French national guidelines.

Methods: A descriptive analysis was conducted for a prospective cohort of 18 women with MS who gave birth in the maternity unit of Bichat-Claude Bernard Hospital, Paris, France, between January 1, 1998, and May 31, 2011. The study hospital was the national referral center for MS and related diseases.

Long-term efficacy of percutaneous mitral commissurotomy for restenosis after previous mitral commissurotomy.

Objective: We analysed long-term results of percutaneous mitral commissurotomy (PMC) performed because of mitral restenosis after previous commissurotomy.

Design: Follow-up of a prospective cohort.

Setting: Tertiary university hospital.

Reinterventions after percutaneous mitral commissurotomy during long-term follow-up, up to 20 years: the role of repeat percutaneous mitral commissurotomy.

Aims: We analysed reinterventions performed during long-term follow-up after percutaneous mitral commissurotomy (PMC) with a particular focus on freedom from mitral surgery and late results of repeat PMC.

Methods And Results: In 912 patients who had good immediate results of PMC (valve area ≥1.5 cm² with mitral regurgitation ≤2/4), we analysed survival without reintervention (surgery or repeat PMC) and survival without surgery alone, with a follow-up up to 20 years.

TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome.

A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.

Feasibility and outcomes of transcatheter aortic valve implantation in high-risk patients with stenotic bicuspid aortic valves.

Little is known about transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve stenosis, which usually represents a contraindication. The aim of this study was to assess the feasibility and the results of TAVI in this patient subset. Of 316 high-risk patients with severe aortic stenosis who underwent TAVI from January 2009 to January 2012, 15 (5%) had documented bicuspid aortic valves.

Late results of percutaneous mitral commissurotomy up to 20 years: development and validation of a risk score predicting late functional results from a series of 912 patients.

Background: Long-term follow-up after percutaneous mitral commissurotomy enables predictive factors of late results to be identified.

Methods And Results: Late results of percutaneous mitral commissurotomy were assessed in 1024 consecutive patients. Good immediate results, defined as valve area ≥1.

Surgical management of patients with Marfan syndrome: evolution throughout the years.

Aim: To evaluate the evolution of surgical management in a large population of patients with Marfan syndrome.

Methods: This is a retrospective study of patients fulfilling the Ghent criteria for Marfan syndrome, who visited the Centre de référence national pour le syndrome de Marfan et apparentés and underwent a surgical event before or during follow-up in the centre.

Results: One thousand and ninety-seven patients with Marfan syndrome, according to international criteria, came to the clinic between 1996 and 2010.

Respective effects of early cerebral and abdominal magnetic resonance imaging on clinical decisions in infective endocarditis.

Aims: Extracardiac complications of endocarditis influence diagnosis, therapeutic plans, and prognosis. The aim of this study was to assess how early combined cerebral and abdominal magnetic resonance imaging (MRI) affects the diagnosis and management of adults with endocarditis.

Methods And Results: In a single-centre prospective study, 58 patients with endocarditis underwent systematic cerebral and abdominal MRI within 7 days following admission.

Aortic event rate in the Marfan population: a cohort study.

Background: Optimal management, including timing of surgery, remains debated in Marfan syndrome because of a lack of data on aortic risk associated with this disease.

Methods And Results: We used our database to evaluate aortic risk associated with standardized care. Patients who fulfilled the international criteria, had not had previous aortic surgery or dissection, and came to our center at least twice were included.

Mitral regurgitation in patients referred for transcatheter aortic valve implantation using the Edwards Sapien prosthesis: mechanisms and early postprocedural changes.

Background: Transcatheter aortic valve implantation (TAVI) is an alternative to conventional surgery in high-risk patients with severe aortic stenosis (AS), but data regarding mitral regurgitation (MR) characteristics and changes after TAVI are sparse.

Methods: A total of 254 patients with severe AS referred for TAVI were prospectively enrolled. Comprehensive echocardiography was performed at baseline and at 7 days and 1 month in patients who underwent TAVI.

Comparison of semiquantitative and quantitative assessment of severity of aortic regurgitation: clinical implications.

Background: Recent studies have emphasized the importance of quantitative assessment of the degree of aortic regurgitation (AR). However, semiquantitative methods have remained mainly used despite their unclear diagnostic value. The aim of this study was to define the sensitivity and specificity of semiquantitative methods compared with the proximal isovelocity surface area method as a reference for the diagnostic of severe AR.

Real-time 3D transoesophageal measurement of the mitral valve area in patients with mitral stenosis.

Aims: Planimetry measured by two-dimensional transthoracic echocardiography (TTE, MVA2D) is the reference method for the evaluation of the severity of mitral stenosis (MS) but requires experienced operators and good echocardiographic windows. Real-time three-dimensional transoesophageal echocardiography (3D-TEE, MVA3D) may overcome these limitations but its accuracy has never been evaluated.

Methods And Results: We prospectively enrolled 80 patients (58±15 years, 86% female) referred for MS evaluation who underwent, within 1 week, a clinically indicated TTE and TEE.

Reappraisal of percutaneous aortic balloon valvuloplasty as a preliminary treatment strategy in the transcatheter aortic valve implantation era.

Aims: To assess the results of percutaneous aortic balloon valvuloplasty (PABV) as a potential bridge to further intervention in patients referred for transcatheter aortic valve implantation (TAVI).

Methods And Results: Two hundred and fifty-three patients referred for TAVI were studied: 41 (16%) were considered transiently unsuitable for either aortic valve replacement (AVR) or TAVI and underwent PABV as a bridge to intervention. In the others, primary TAVI or AVR was performed in 140 cases, and medical therapy alone in 72.

Early hemodynamic changes versus peak values: what is more useful to predict occurrence of dyspnea during stress echocardiography in patients with asymptomatic mitral stenosis?

Background: In asymptomatic mitral stenosis (MS), the usefulness of peak exercise Doppler echocardiography (DE) values is acknowledged, but the role of values recorded during the first stage of DE remains unclear.

Methods: DE was analyzed in 48 asymptomatic patients with significant MS and revealed dyspnea in 22 patients (46%).

Results: MS severity and rest and peak systolic pulmonary artery pressures (SPAPs) were not different between patients who did and did not develop dyspnea.

Dissection in Marfan syndrome: the importance of the descending aorta.

Aims: To better characterize patients with Marfan syndrome who have survived an acute aortic dissection and to estimate the risks of events in the descending aorta. Up until now, this portion of the aorta has not been well studied but is gaining importance due to improved patient survival.

Methods And Results: We report a retrospective cohort of 100 Marfan patients who survived an aortic dissection.

Usefulness of left atrial volume versus diameter to assess thromboembolic risk in mitral stenosis.

In patients with mitral stenosis (MS) in sinus rhythm (SR), guidelines recommend anticoagulation if the left atrium is enlarged based on diameter measurements. We sought to compare the association of left atrial (LA) diameter and LA volume with markers of thromboembolic risk (peak LA appendage emptying velocity [LAAv] and LA spontaneous contrast density) measured during transesophageal echocardiography in 152 patients with moderate to severe MS. High thromboembolic risk was defined by a peak LAAv < 25 cm/s and/or dense spontaneous contrast.