PATHOPHYSIOLOGY AND NATURAL HISTORY CONGENITAL HEART DISEASE Arrested rotation of the outflow tract may explain double-outlet right ventricle

In a previous study the possibility that tetralogy of Fallot and transposition of the great arteries may arise as a result of embryonic arrests in the normal rotation of the junction of the outflow tract and the great arteries was investigated. The results suggested that the development of other transposition complexes such as double-outlet right ventricle might also be related to arrests in this process of rotation. To further study this question 20 normal hearts and 15 hearts with double-outlet right ventricle obtained at autopsy were studied. The angle of the aortic-to-pulmonary valve axis relative to the inferior surface of the heart, as viewed from apex to base, was measured from postmortem radiographs. For normal hearts the mean angle was 81 4(SE) degrees. For 13 of the 15 hearts with double-outlet right ventricle the mean angle was 4 + 7(SE) degrees. Two hearts with doubleoutlet right ventricle showed markedly divergent aortic-to-pulmonary valve angles, with a mean of 228 + 1 1 (SE) degrees, and were therefore grouped separately. Although direct comparison of hearts and embryos is difficult because of the differences in methods of determining angles, the valve positions in normal hearts was most similar to Carnegie stage 19, as found in an earlier study. The majority of the hearts with double-outlet right ventricle resembled stage 16 embryos. The results of this study, as well as those of the earlier studies, support the hypothesis that a spectrum of cardiac anomalies with anomalous origin of great vessels arises as arrests in the normal rotation of the semilunar valve region during embryogenesis. Circulation 77, No. 6, 1258-1265, 1988. IN A STUDY using three-dimensional computerized reconstructions of serially sectioned human embryos it was possible to show quantitatively that the junction of the outflow tract and the great arteries undergoes a rapid rotation between Carnegie stages 15 and 19.1 This finding led to an examination of the possibility that an arrest in the rotation of the outflow tract may result in certain cardiac malformations such as tetralogy of Fallot and transposition of the great arteries.2 It was shown that the positions of the semilunar valves in hearts with transposition of the great arteries resembled those in stage 15, whereas the semilunar valve positions in hearts with tetralogy of Fallot resembled those in stage 18. The semilunar valve positions in normal hearts were found to be most similar to those in stage 19, a period when normal cardiogenesis is largely complete. 6̀ These results suggested that these anomalies arise as arrests in the normal rotation of the semilunar valve axis. The results also suggested that other transposition complexes, such as double-outlet right ventricle, might also be caused by arrests in the rotation of the semilunar valve axis. The present study was undertaken to further study this question. Materials and methods Since the term double-outlet right ventricle was first used in 1957 by Witham, a variety of workers have defined the term differently. Although the definition that deemphasizes the importance of aortic-mitral discontinuity, proposed separately by Anderson8 and Lev9 10 and their colleagues, may be more useful from a clinical perspective, the more rigid criteria set forth by Neufield et al."1-13 and Van Praagh et al.`4 were used in this study. Thus, the hearts with double-outlet right ventricle in this study had both great vessels taking origin from the right ventricle and no fibrous continuity between semilunar and atrioventricular valves. Fifteen hearts with double-outlet right ventricle as defined above were examined. Thirteen of these were obtained from patients undergoing autopsy at The Johns Hopkins Hospital between 1948 and 1984. The remaining two hearts were from outside hospitals. Cases with asplenia or polysplenia syndrome were excluded from this study. Two hearts with mitral atresia and a single, morphologically right ventricle were, however, included. Twenty normal hearts were also examined. Usually the hearts had been distended in 3.7% formaldehyde solution before dissection. Two thin metal probes were inserted across each semilunar valve ring so as to form a cross with the center of the cross coinciding with the center of each valve. Stereoscopic radiographs of the hearts were then prepared. The centers of the aortic and pulmonary valves were located on the radiograph and CIRCULATION From the Autopsy Pathology Division of the Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore. Address for correspondence: Dr. Grover M. Hutchins, Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21205. Received Oct. 15, 1987; revision accepted Feb. 25, 1988. 1258 by gest on A ril 4, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-CONGENITAL HEART DISEASE a line from the aortic valve to the pulmonary valve was drawn. A line parallel to the inferior aspect of the atrioventricular groove was then drawn so as to intersect the aortic-pulmonary line. Viewing the heart in an apical-to-basal direction, the angle of the aortic-pulmonary line was then determined with use of the line parallel to the inferior surface of the heart as the zero line. Additional information about each case was obtained by reviewing the autopsy records.