Familial aggregation of Bicuspid Aortic Valve: is it useful a family screeninng?

Amelia Carro, Gisela Teixidó, Francesca Huguet, María Sanz, Antonio Barros, Artur Evangelista, David García-Dorado

Cardiovascular Diseases. Aortic Pathology

6th VHIR Scientific Session

29th-30th November 2012

Vall d’Hebron University Hospital

Most common congenital heart disease1 (0.5-1%; male predominance 3:1)

High morbility

-Valvular dysfunction /Infectious endocarditis

-Aortic complications

Familial or sporadic

Associated malformations

Introduction: Bicuspid aortic valve

Nistri et al. Am J Cardiol 2005;96(5):718-721

Type 1 Type 2 Antero-posterior Right-left

We aimed to test the usefulness of systematic echocardiographic screening of

first-degree relatives (FDR) of patients with a confirmed BAV

Proband: Family history + Physical exam + Transthoracic Echocardiogram

Familial screening:

Family history + Physical exam + Transthoracic Echocardiogram

Cascade strategy

Objectives and methods

60 BAV

Personal history Family history (pedigree)

Physcal exam Echocardiogram

Informed consent

69 (19,2%) Deceased

105 (29,3%) Refused

Not available

184 FDR

analysed

81 BAV

10 Refused 11 FDR not available

Recruitment phase

Personal history Physcal exam

Echocardiogram Informed consent

358 FDR

Baseline

carachteristics

Probands

N= 60

Male n (%) 45 (75)

Age (years) 49,6±15,5 (16-76)

HBP n (%) 27 (44.5)

AP configuration n (%) 43 (72.4)

Aortic dilatation n (%)

-SV≥37mm

-SV≥21mm/m2

-AA≥37mm

-AA≥21mm/m2

29 (48.3)

28 (46.6)

48 (80)

47 (78.3) HBP:high blood pressure; AP: antero-posterior; SV: sinus of Valsalva; AA: ascending aorta

358 FDR

11 AoV abnormalities

184 FDR

analysed

Probands FDR

N 60 184

Male n (%) 45 (75) 94 (55.1)

Age (years) 49,6±15,5 (16-76) 43.1±19.2 (8-91)

HBP n (%) 27 (44.5) 42 (22.8)

Diabetes n (%) 4 (6.6) 35 (19)

Dislipemia n (%) 22 (36.6) 35 (19)

Aortic Dilatation n (%)

-SV≥37mm

-SV≥21mm/m2

-AA≥37mm

-AA≥21mm/m2

29 (48.3)

28 (46.6)

48 (80)

47 (78.3)

26 (14.1)

22 (11.9)

26 (14.1)

24 (13)

FDR: first degree relatives; HBP:high blood pressure; SV: sinus of Valsalva; AA: ascending aorta; AoV: aortic valve

FDR prevalence: 5.9% Familial prevalence: 16.6%

Necessary Number of FDR to screen:13

Distributed in 10 families

Results (1)

60 BAV

FDR: first-degree relative; AP: Antero-posterior; RL: Rigth-left; M: male; F: female; AoR: aortic regurgitation; AoS: aortic stenosis

Results (2)

Relation to proband

Proband phenotype

FDR phenotype Age Gender Symptoms Valve function

1 Son AP

Quadricuspid 16 M No Normal

2 Son RL 10 M No Mild AoR

3 Son AP AP 31 M No Mild AoR

4 Son AP AP 22 M No Mild AoR

5 Son AP AP 10 M No Normal

6 Brother AP AP 57 M No Mild AoR

7 Sister AP AP 48 F No Mild AoR

8 Father RL Unreadable 61 M Dyspnea Severe AoR

9 Mother RL RL 56 F No Moderate AoR

10 Father RL RL 59 M No Mild AoR

11 Uncle AP Unreadable 90 M Dyspnea Moderate AoS + AoR

Male predominance 4:1 Antero-posterior 60%

Discussion

Sans Coma V. Cardiol Young 1993/Anat Rec 1996 Fernández B. JACC 2009

Padang R. Circulation Genetics 2012

VALVULOGENESIS

Predisposing genetic factor

eNOS protuberance,

absence of GATA5 Neural crest defect

Abnormal septation Normal septation

Disease progression and complications

Enviromental/epigenetic factors

Enviromental/epigenetic factors

Discussion

Valvulopatí

a Aortopatí

a

Malf

asociada

s

Calloway T. Am J Med Genet 2011 Sans Coma V. J Anat 2012

Conclusions

The prevalence of bicuspid aortic valve is higher in first-degree relatives of

affected patients than in the general population.

Echocardiographic screening of first-degree relatives is a useful approach for

identifying asymptomatic cases, and should therefore be offered to all first-degree

relatives of bicuspid aortic valve individuals.

Different patterns of aortic valve configuration within the same family reinforce

the complexity of inheritance and deserve furhter investigation.

THANK YOU VERY MUCH!