POTENTIAL ROLE OF MECHANICAL-STRESS IN THE ETIOLOGY OF PEDIATRIC HEART-DISEASE - SEPTAL SHEAR-STRESS IN SUBAORTIC STENOSIS

Objectives. The objective of this study was to shaw elevations in sept al shear stress in response to morphologic abnormalities that have bee n associated with discrete subaortic stenosis (SAS) in children. Combi ned with the published data, this critical connection supports a four- stage etiology of SAS that is advanced in this report. Background. Sub aortic stenosis constitutes up to 20% of left ventricular outflow obst ruction in children and frequently requires surgical removal, and the lesions may reappear unpredictably after the operation. The etiology o f SAS is unknown. This study proposes a four-stage etiology for SAS th at I) combines morphologic abnormalities, II) elevation of septal shea r stress, III) genetic predisposition and IV) cellular proliferation i n response to shear stress. Methods. Morphologic structures of a left ventricular outflow tract were modeled based on measurements in patien ts with and without SAS. Septal shear stress was studied in response t o changes in aortoseptal angle (AoSA) (120 degrees to 150 degrees), ou tflow tract convergence angle (45 degrees, 22.5 degrees and 0 degrees) , presence/location of a ventricular septal defect (VSD) (3-mm VSD; 2 and 6 mm from annulus) and shunt velocity (3 and 5 m/s). Results. Vari ations in AoSA produced marked elevations in septal shear stress (from 103 dynes/cm(2) for 150 degrees angle to 150 dynes/cm(2) for 120 degr ees angle for baseline conditions). This effect was not dependent on t he convergence angle in the outflow tract (150 to 132 dynes/cm(2) over full range of angles including extreme case of 0 degrees). A VSD enha nced this effect (150 to 220 dynes/cm(2) at steep angle of 120 degrees and 3 m/s shunt velocity), consistent with the high incidence of VSDs in patients with SAS. The position of the VSD was also important, wit h a reduction of the distance between the VSD and the aortic annulus c ausing further increases in septal shear stress (220 and 266 dynes/cm( 2) for distances of 6 and 2 mm from the annulus, respectively). Conclu sions. Small changes in AoSA produce important changes in septal shear stress. The levels of stress increase are consistent with cellular fl ow studies-showing stimulation of growth factors and cellular prolifer ation. Steepened AoSA may be a risk factor for the development of SAS. Evidence exists for all four stages of the proposed etiology of SAS. (C) 1997 by the American College of Cardiology.