[Genetic aspects of valvulopathies]. / Aspects Génétiques des Valvulopathies.

Valvular dystrophies due to myxoid degeneration are common and potentially serious cardiac pathologies. They constitute a heterogeneous group of which the most usual is idiopathic mitral valvular prolapse (Barlow's disease). The majority of mitral valvular prolapses are sporadic, but there are several familial forms. Transmission is usually autosomal dominant with incomplete penetrance and variable expression. The first chromosomal location to be identified was on the 16p11-13 chromosome. Since then, two other loci have been identified on the 11p15.4 and 13q31-32 chromosomes. Our team has recently identified the first gene responsible for myxoid valvulopathy linked to the X chromosome, from a large family of 318 members. This is the gene that codes for filamin A, which is a cytoskeleton protein. The frequency of mutations in this gene is still unknown, but out of 7 families in which transmission was compatible with X-linked transmission, mutations were discovered in 4 of the families. Thanks to a genetic epidemiological approach, we have also demonstrated that there are familial forms of aortic stenosis, which are probably common. Identification of the genes implicated in these common forms of valvular pathology is important, as it will allow a better understanding of the pathophysiology of these valvular disorders and could lead to better therapeutic management in the future.

Predictors of Health-Related Quality of Life Decline after Transcatheter Aortic Valve Replacement in Older Patients with Severe Aortic Stenosis.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) has been shown to improve survival and quality of life in patients with severe aortic stenosis. However, one-third of patients have poor outcome as death, functional decline or quality of life (QoL) decline. The aim of this study was to determine cardiac and geriatric predictors of physical and mental QoL decline 6 months after a TAVI procedure in patients aged 75 and older. METHODS: Between January 2013 and June 2014, we did a prospective and multicenter study including patients ≥ 75 years old referred for TAVI. The primary outcome was the measure of QoL, assessed by the Short Form 36 survey (SF-36), before and 6 months after the intervention. Association between QoL decline and baseline characteristics including cardiac and geriatric factors was analysed by logistic regression models. RESULTS: Mean age of the 150 patients studied was 83.7 years old and 56% were men. The primary end point, mean SF-36 physical summary score, significantly improved between baseline and 6-month (33.6 vs. 36.4, p=0.003) whereas mental component score significantly decreased (48.2 vs. 36.4, p-value<0.001). However, patients with presence of depressive symptoms before the intervention had mental QoL improvement at six months (OR 0.04 [0.01-0.19], p-value<0.001) and no significant geriatric predictors were associated with physical QoL decline. CONCLUSION: The mental QoL significantly decreased and patients with preoperative depressive symptoms had mental QoL improvement at six months. Researches are needed to confirm that mental QoL of patients with depressive symptoms can be improved by TAVI.

Determinants in treatment decision-making in older patients with symptomatic severe aortic stenosis.

BACKGROUND: Three treatment options are available for patients with aortic stenosis: surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI) and medical treatment (MT). However, little is known about how Heart Team treatment decisions are made under routine conditions. The aim of this study was to identify the cardiac and geriatric components associated with treatment decision-making in older patients with symptomatic severe aortic stenosis. METHODS: Between 2011 and 2013, 337 consecutive patients ≥75 years old referred for pre-operative evaluation in Nantes University Hospital had a comprehensive cardiac and geriatric assessment. In this observational retrospective study, relationships between treatment decision-making and cardiac or geriatric components were evaluated through multivariable models. RESULTS: Surgical aortic valve replacement was proposed to 108 patients, TAVI to 131 and medical treatment to 98 patients. Mean age was 83±4 years and 51% were women. Geriatric components associated with treatment decision-making between SAVR vs. TAVI were age (p<0.001, OR=0.790), comorbidity score (p=0.027, OR=0.86), functional status (p<0.001, OR=1.46), and gait speed (p<0.001, OR=0.23). Cardiac components associated with decision-making between SAVR vs. TAVI were history of previous cardiac surgery (p<0.001, OR=0.09), left ventricular ejection fraction <50% (p<0.001, OR=0.14), coronary artery disease requiring revascularization (p=0.019, OR=0.4). Between TAVI vs. medical treatment, only history of previous cardiac surgery and presence of another severe valve disease were significant. CONCLUSION: Comorbidities, functional status and physical performance, were significantly associated with the consensual treatment decision-making, independently of cardiac components in older patients with symptomatic severe aortic stenosis.