Heritability of aortic valve stenosis and bicuspid enrichment in families with aortic valve stenosis. (15th July 2022)

• Record Type: Journal Article
• Authors: Boureau, Anne-Sophie; Karakachoff, Matilde; Le Scouarnec, Solena; Capoulade, Romain; Cueff, Caroline; de Decker, Laure; Senage, Thomas; Verhoye, Jean-Philippe; Baufreton, Christophe; Roussel, Jean-Christian; Dina, Christian; Probst, Vincent; Schott, Jean-Jacques; Le Tourneau, Thierry
• Is Part Of: International journal of cardiology. Volume 359(2022)
• Page Start: 91
• Page End: 98
• Publication Date: 2022-07-15
• Subjects: Bicuspid aortic valve -- Calcific aortic valve stenosis -- Genetics -- Heritability; AVR Aortic valve replacement -- BAV Bicuspid aortic valve -- CAVS Calcific aortic valve stenosis -- CI Confidence Interval -- EAE/ASE European Association of Echocardiography and the American Society of Echocardiography guidelines -- IQR Inter Quartile Range -- PR Prevalence ratio -- SOLAR Sequential Oligogenic Linkage Analysis Routines -- TAV Tricuspid aortic valve -- TTE Trans-thoracic Doppler-echocardiography; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2022.04.022
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: Although a familial component of calcific aortic valve stenosis (CAVS) has been described, its heritability remains unknown. Hence, we aim to assess the heritability of CAVS and the prevalence of bicuspid aortic valve among CAVS families. Methods: Probands were recruited following aortic valve replacement (AVR) for severe CAVS on either tricuspid (TAV) or bicuspid aortic valve (BAV). After screening, relatives underwent a Doppler-echocardiography to assess the aortic valve morphology as well as the presence and severity of CAVS. Families were classified in two types according to proband's aortic valve phenotype: TAV or BAV families. Control families were recruited and screened for the presence of BAV. Results: Among the 2371 relatives from 138 CAVS families (pedigree cohort), heritability of CAVS was significant (h 2 = 0.47, p < 0.0001), in TAV (h 2 = 0.49, p < 0.0001) and BAV families (h 2 = 0.50, p < 0.0001). The prevalence of BAV in 790 relatives (phenotype cohort) was significantly increased in both TAV and BAV families compared to control families with a prevalence ratio of 2.6 ([95%CI:1.4–5.9]; p = 0.005) and 4.6 ([95%CI:2.4–13.4]; p < 0.0001), respectively. At least one relative had a BAV in 22.2% of tricuspid CAVS families. Conclusions: Our study confirms the heritability of CAVS in both TAV and BAV families, suggesting a genetic background of this frequent valvular disease. In addition, BAV enrichment in TAV families suggests an interplay between tricuspid CAVS and BAV. Overall results support the need to improve phenotyping (i.e. BAV, TAV, risk factors) in CAVS families in order to enhance the identification of rare and causal genetic variants of CAVS. Clinical Trials Identifier: NCT02890407. Highlights: Heritability of CAVS was significant, reinforcing the hypothesis of a genetic background The enrichment of BAV phenotype in relatives of tricuspid CAVS was significant. The results support the need to improve phenotyping in CAVS families to enhance the identification of genetic variants of CAVS. The clinicians should be aware of the heritability of CAVS for questioning patients about familial history of CAVS.