Brain in Congenital Heart Disease Across the Lifespan: The Cumulative Burden of Injury

Abstract

The number of patients surviving with congenital heart disease (CHD) has soared over the last 3 decades. Adults constitute the fastest-growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has been focused largely on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes mellitus, and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. Against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions.

Keywords: congenital abnormalities; heart diseases.

Figure 1

Prevalence of congenital heart disease across the lifespan. Reprinted with permission from Mazor Dray E, Marelli AJ. Adult Congenital Heart Disease: Scope of the Problem. Cardiol Clin. 2015;33(4):503–512.

Figure 2

Neurocognitive impairment across the lifespan.

Figure 3

Illustration of the inverse relation between circulatory arrest and psychomotor development index in infants at one-year post the neonatal arterial switch operation for complete transposition of the great arteries. Reprinted with permission from Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KC, Barnes PD, Holmes GL, Hickey PR, Strand RD, Walsh AZ, Helmers SL, Constantinou JE, Carrazana EJ, Mayer JE, Hanley FL, Castaneda AR, Ware JH, Newburger JW. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. The New England Journal of Medicine. 1995;332:549–555.

Figure 4

Gradient between congenital heart disease severity and prevalence of neurodevelopmental impairment. Reprinted with permission from Wernovsky G. Current insights regarding neurological and developmental abnormalities in children and young adults with complex congenital cardiac disease. Cardiol Young 2006; 16 (Suppl 1): 92–104.

Figure 5

Vascular risk factors and midlife cognition. Reprinted with permission from Jefferson AL. Vascular risk factors and midlife cognition: Rethinking the exposure window. Circulation. 2014;129:1548–1550

Figure 6

Unifying hypothesis for the continuum of neurocognitive disease in the lifespan of congenital heart disease patients. Inspired from Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and dementia: How to move forward? Neurology. 2009;72:368–374.