Impact of Genetic Diagnosis on Clinical Management of Patients With Congenital Heart Disease

Abstract

The first Blalock-Taussig shunt surgery in 1945 changed major congenital heart disease (CHD) from a universally lethal condition into a survivable one.1 In the 50 years that followed, rapid progress in anatomic diagnosis via echocardiography and dramatic improvement in surgical and catheterization techniques resulted in survival to adulthood and greatly improved quality of life for many individuals with CHD. Despite this, continuing progress in caring for individuals with the most complex forms of CHD has become incremental. One of the particularly frustrating aspects of managing patients with very complex CHD is that the outcomes are highly variable, even when accounting for surgical skill and anatomic complexity. In this issue of Circulation , Nakhleh et al2 show that a subset of patients with CHD and heterotaxy have airway ciliary dysfunction that may account for increased morbidity and mortality independently of the complexity of the CHD. This finding highlights a critical point that will surely affect patient care in the years to come; improving our understanding of the genetic origin of CHD is likely to affect response to therapy. The hope is that individualized therapy for CHD based on the underlying genetics will contribute to the next major improvement in outcome. Article see p 2232 Heterotaxy is defined as any arrangement of organs across the body's left-right axis that differs from complete situs solitus and complete situs inversus. CHD is one of the hallmarks of heterotaxy and is characterized by a wide range of highly complex cardiac anatomy,3,4 including but not limited to anomalous systemic and pulmonary venous return, complex atrioventricular canal, functionally single ventricle, and a range of abnormalities of the outflow tract (Table). Thus, the cardiac lesions associated with heterotaxy represent a significant surgical challenge; however, the surgical outcome in heterotaxy patients remains significantly …