Genetics of valvular heart disease

Abstract

Valvular heart disease is associated with significant morbidity and mortality and often the result of congenital malformations. However, the prevalence is increasing in adults not only because of the growing aging population, but also because of improvements in the medical and surgical care of children with congenital heart valve defects. The success of the Human Genome Project and major advances in genetic technologies, in combination with our increased understanding of heart valve development, has led to the discovery of numerous genetic contributors to heart valve disease. These have been uncovered using a variety of approaches including the examination of familial valve disease and genome-wide association studies to investigate sporadic cases. This review will discuss these findings and their implications in the treatment of valvular heart disease.

Fig. 1

Cardiac valve development. A, At day 21 of gestation, the linear heart tube is formed and the primitive heart completes rightward looping by day 28 of human gestation. Significant remodeling of the inner curvature and growth of the ventricular chambers then occurs to result in the maturely developed heart with partitioned systemic (red) and pulmonary circulations (blue) by day 50. Regions of atrioventricular and outflow tract (OFT) cushion formation and development are shown in pink. LA left atrium, LV left ventricle, RA right atrium, RV right ventricle. B, Growth of the superior, inferior, and lateral endocardial cushions in the common atrioventricular canal is shown. Days of human gestation are noted. By day 35, the superior and inferior cushions have fused to divide to result in 2 atrioventricular openings. AV atrioventricular, EC endocardial cushions. C, Transverse section through the common outflow tract (truncus arteriosus) with 4 truncal swellings at day 35 of gestation. At day 42 of gestation, the common outflow tract has started to divide into the aorta (AO) and pulmonary artery (PA) and leaflet formation has begun. By day 49, the aorta and pulmonary artery are septated and each has 3 leaflets. Adapted from: Garg V. “Growth of the Normal Human Heart” In: Preedy VR, editor. Handbook of Growth and Growth Monitoring in Health and Disease. New York: Springer; 2011; and Garg V. “Insights into the Genetic Basis of Congenital Heart Disease”. Cell Mol Life Sci. 2006;63:1141–8 [4, 6]