Potential Role of Mechanical Stress in the Etiology of Pediatric Heart Disease: Septal Shear Stress in Subaortic Stenosis

• Published in: Journal of the American College of Cardiology 1997-07, Vol.30 (1), p.247-254
• Main Authors: Cape, Edward G, VanAuker, Michael D, Sigfússon, Gunnlaugur, Tacy, Theresa A, del Nido, Pedro J
• Format: Article
• Language: English
• Subjects: Adolescent; Aortic Valve Stenosis - etiology; Aortic Valve Stenosis - genetics; Aortic Valve Stenosis - pathology; Biological and medical sciences; Cardiology. Vascular system; Cell Division; Child; Child, Preschool; Confounding Factors (Epidemiology); Endocardial and cardiac valvular diseases; Heart; Heart Septum - pathology; Heart Septum - physiopathology; Humans; Medical sciences; Models, Cardiovascular; Stress, Mechanical
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(97)00048-X

Objectives. The objective of this study was to show elevations in septal shear stress in response to morphologic abnormalities that have been associated with discrete subaortic stenosis (SAS) in children. Combined with the published data, this critical connection supports a four-stage etiology of SAS that is advanced in this report. Background. Subaortic stenosis constitutes up to 20% of left ventricular outflow obstruction in children and frequently requires surgical removal, and the lesions may reappear unpredictably after the operation. The etiology of SAS is unknown. This study proposes a four-stage etiology for SAS that I) combines morphologic abnormalities, II) elevation of septal shear stress, III) genetic predisposition and IV) cellular proliferation in response to shear stress. Methods. Morphologic structures of a left ventricular outflow tract were modeled based on measurements in patients with and without SAS. Septal shear stress was studied in response to changes in aortoseptal angle (AoSA) (120° to 150°), outflow tract convergence angle (45°, 22.5° and 0°), 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. Variations in AoSA produced marked elevations in septal shear stress (from 103 dynes/cm2for 150° angle to 150 dynes/cm2for 120° angle for baseline conditions). This effect was not dependent on the convergence angle in the outflow tract (150 to 132 dynes/cm2over full range of angles including extreme case of 0°). A VSD enhanced this effect (150 to 220 dynes/cm2at steep angle of 120° 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, with a reduction of the distance between the VSD and the aortic annulus causing further increases in septal shear stress (220 and 266 dynes/cm2for distances of 6 and 2 mm from the annulus, respectively). Conclusions. Small changes in AoSA produce important changes in septal shear stress. The levels of stress increase are consistent with cellular flow studies showing stimulation of growth factors and cellular proliferation. Steepened AoSA may be a risk factor for the development of SAS. Evidence exists for all four stages of the proposed etiology of SAS. (J Am Coll Cardiol 1997;30:247–54)