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Use of the mitral valve–tricuspid valve distance as a marker of fetal endocardial cushion defects
American Journal of Obstetrics and Gynecology (2004) 191, 1483e5
www.ajog.org
Use of the mitral valveetricuspid valve distance as a marker of fetal endocardial cushion defects Alan D. Bolnick, MD,a Carolyn M. Zelop, MD,a Beth Milewski, MD,a Elisa A. Gianferrari, MD,b Adam F. Borgida, MD,a James F. X. Egan, MDa,b Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Connecticut School of Medicine, Farmington, Conn,a and Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Saint Francis Hospital and Medical Center, Hartford, Connb
KEY WORDS Mitral valveetricuspid valve distance Endocardial cushion defect Echocardiography
Objective: The purpose of this study was to compare the mitral valveetricuspid valve distance in second-trimester fetuses with normal cardiac anatomy versus those fetuses with endocardial cushion defects. Study design: We identified fetuses between 16 and 24 weeks of gestation. The distance between the insertions of the medial leaflets of the mitral and tricuspid valves were obtained. Linear regression curves were generated. Results: The mean mitral valveetricuspid valve distance for 86 fetuses with normal cardiac anatomy was 2.02 mm, compared with 0.37 mm in 13 fetuses with endocardial cushion defects (P Z .0001). Linear regression curve correlating mitral valveetricuspid valve distance with gestational age showed a gradual slope (R2 Z 0.28; P ! .0001). With a mitral valveetricuspid valve distance !5th percentile as a marker for the diagnosis of endocardial cushion defect gave a sensitivity of 69.2%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 95.6%, and a false-positive rate of 0% (P Z .0001). Conclusion: The mitral valveetricuspid valve distance is useful clinically in the detection of endocardial cushion defects in second-trimester fetuses. Ó 2004 Elsevier Inc. All rights reserved.
Prenatal sonographic assessment of the 4-chamber cardiac view includes the evaluation of the normal distance or offset between the mitral valve and the more apically displaced tricuspid valve (Figure 1). Although the orientation of the atrioventricular valves usually is evaluated subjectively, more recently, investigators have sought to quantify the offset to establish gestational age norms (Figure 2). Vettraino et al1 showed the clinical usefulness of the exaggerated
Presented at the Twenty-Fourth Annual Meeting of the Society for Maternal-Fetal Medicine, February 2-7, 2004, New Orleans, La. Reprints will not be available from the authors. 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.05.042
mitral valveetricuspid valve distance (M-T D) in the prenatal diagnosis of Ebstein’s anomaly. Conversely, a narrowing of the atrioventricular offset would be suggestive of an endocardial cushion defect that occurs when a single multileaflet atrioventricular valve replaces separate mitral and tricuspid valves (Figure 3). An atrioventricular septal defect is a common cardiac condition that affects between 3.0% and 7.3% of infants with congenital heart disease.2-6 Allan2 examined 5 years of congenital heart disease at a large tertiary hospital and documented a !50% detection rate of fetal endocardial cushion defects. Similarly, Kirk et al4 examined their experience over a 5-year period and reported detection rates for atrioventricular septal defects of 63% to 87%.
1484
Figure 1 Apical 4-chamber view of the fetal heart. LV, Left ventricle; RV, right ventricle; LA, left atrium; RA, right atrium.
Figure 2 Detail of the M-T D in an apical 4-chamber view in a normal fetal heart. The number 1 is at the level of the superior portion of the septal leaflet insertion of the tricuspid valve. The number 2 is at the level of the inferior portion of the medial insertion of the mitral valve. The arrows delineate the M-T D. LV, Left ventricle; RV, right ventricle; LA, left atrium; RA, right atrium.
Therefore, we sought to compare the M-T D in second trimester fetuses with normal cardiac anatomy to those fetuses with antenatally diagnosed endocardial cushion defects.
Methods We performed a retrospective analysis of our ultrasound database from 1997 through 2003 for all fetuses who underwent an anatomic survey. We identified fetuses between 16 and 24 weeks of gestation for whom there were apical 4-chamber views at end diastole (Figure 1).
Bolnick et al
Figure 3 Apical view of a fetus with a partial endocardial cushion defect (primum atrial septal defect) shows the coplanar mitral and tricuspid valves. LV, Left ventricle; RV, right ventricle.
All ultrasound examinations were performed at our institution by a registered diagnostic medical sonographer who was supervised by Board Certified Perinatologists. Pediatric cardiologists verified suspected cases of endocardial cushion defects (Figure 3). Images were enlarged to measure electronically the distance between the insertion of the medial leaflets of the mitral and tricuspid valves for fetuses with normal cardiac anatomy and in a subset with endocardial cushion defects (Figures 2 and 4).7 A linear regression curve was generated for the M-T D in normal subjects by gestational age (Figure 5). The sensitivity, specificity, and positive and negative predictive values were determined with a M-T D !5th percentile of the expected M-T D as a marker for fetal endocardial cushion defects. Fisher exact and Student t test were used for statistical comparisons. Approval for the study was obtained from the Institutional Review Board at our hospital.
Results The mean M-T D for 86 fetuses with normal cardiac anatomy was 2.02 mm (95% CI, 1.86-2.18 mm) compared with 0.37 mm (95% CI, 0.033-0.7 mm) in 13 fetuses with endocardial cushion defects (P Z .0001). The linear regression curve that correlated M-T D with gestational age showed a gradual slope (R2 Z 0.28; P ! .0001; Figure 5). An M-T D !5th percentile was a marker for the diagnosis of endocardial cushion defects, from which we derived a sensitivity of 69.2%, a specificity of 100%,
Bolnick et al
1485
Figure 5 M-T D with mean and 5th and 95th percentiles. The dots represent the endocardial cushion defect cases.
Figure 4 Detail of the M-T D in a fetus with a partial endocardial cushion defect. The number 1 is at the level of the superior portion of the septal leaflet insertion of the tricuspid valve. The number 2 is at the level of the inferior portion of the medial insertion of the mitral valve. The arrow delineates the M-T D. LV, Left ventricle; RV, right ventricle.
a positive predictive value of 100%, a negative predictive value of 95.6%, and false-positive rate of 0% (P Z .0001).
Comment In this population-based study, the use of M-T D appears to be a clinically useful marker in the detection of endocardial cushion defects in second trimester fetuses. Prenatal echocardiography reveals that the septal insertion of the tricuspid valve is closer to the apex than that of the corresponding medial insertion of the mitral valve. Although this distance is usually assessed subjectively, our study demonstrates that the distance can be quantified throughout the second trimester in fetuses with normal cardiac anatomy. As reported by Vettraino et al,1 quantitative normograms for M-T D can be generated for fetuses with normal cardiac anatomy in the second and third trimester. On the basis of gestational norms, they demonstrated that an exaggerated M-T D could be used to diagnose Ebstein’s anomaly. Our study also demonstrates that a narrowing of the M-T D can signify the presence of an endocardial cushion defect. The use of our normative data may improve the prenatal detection of an endocardial cushion defect. Although our sample size was large, our study had several limitations. Because we relied on electronically
stored images, we may not have always measured the M-T D distance at the same point in the cardiac cycle. We did not assess intra- and interobserver reproducibility of the M-T D. In conclusion, our study confirms the previous reporting of a positive correlation between M-T Ds and gestational age. To our knowledge, this is the first study to assess the clinical usefulness of a narrowing of M-T D from expected normal gestational age variations. A M-T D that is O5th percentile is reassuring and diminishes the likelihood of an endocardial cushion defect. Conversely, those fetuses with a M-T D !5th percentile require further evaluation with echocardiography and consultation with pediatric cardiology. Further studies are required to evaluate prospectively the usefulness of M-T D as a noninvasive sonographic marker for congenital heart disease.
References 1. Vettraino IM, Huang R, Comstock CH. The normal offset of the tricuspid septal leaflet in the fetus. J Ultrasound Med 2002;21: 1099-104. 2. Allen L. Textbook of fetal cardiology. London: Greenwich Medical Media Limited; 2000. 3. Gembruch U, Knopfle G, Chatterjee M, et al. Prenatal diagnosis of atrioventricular canal malformations with up-to-date echocardiographic technology: report of 14 cases. Am Heart J 1991;121: 1489-97. 4. Kirk JS, Comstock CH, Lee W, Smith RS, Riggs TW, Weinhouse E. Sonographic screening to detect fetal cardiac anomalies: a 5-year experience with 111 abnormal cases. Obstet Gynecol 1997;89:227-32. 5. Pierpont ME, Markwald RR, Lin AE. Genetic aspects of atrioventricular septal defects. Am J Med Genet 2000;97:289-296. 6. Ugarte M, Enriquez de Salamanca F, Quero M. Endocardial cushion defects: an anatomical study of 54 specimens. Br Heart J 1976;38:674-82. 7. Gusseenhoven EJ, Stewart PA, Becker AE, Essed CE, Ligtvoet KM, Villeneurve VH. Offsetting of the septal tricuspid leaflet in normal hearts and in hearts with Ebstein’s anomaly: anatomic and echographic correlation. Am J Cardiol 1984;53:172-6.
www.ajog.org
Use of the mitral valveetricuspid valve distance as a marker of fetal endocardial cushion defects Alan D. Bolnick, MD,a Carolyn M. Zelop, MD,a Beth Milewski, MD,a Elisa A. Gianferrari, MD,b Adam F. Borgida, MD,a James F. X. Egan, MDa,b Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Connecticut School of Medicine, Farmington, Conn,a and Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Saint Francis Hospital and Medical Center, Hartford, Connb
KEY WORDS Mitral valveetricuspid valve distance Endocardial cushion defect Echocardiography
Objective: The purpose of this study was to compare the mitral valveetricuspid valve distance in second-trimester fetuses with normal cardiac anatomy versus those fetuses with endocardial cushion defects. Study design: We identified fetuses between 16 and 24 weeks of gestation. The distance between the insertions of the medial leaflets of the mitral and tricuspid valves were obtained. Linear regression curves were generated. Results: The mean mitral valveetricuspid valve distance for 86 fetuses with normal cardiac anatomy was 2.02 mm, compared with 0.37 mm in 13 fetuses with endocardial cushion defects (P Z .0001). Linear regression curve correlating mitral valveetricuspid valve distance with gestational age showed a gradual slope (R2 Z 0.28; P ! .0001). With a mitral valveetricuspid valve distance !5th percentile as a marker for the diagnosis of endocardial cushion defect gave a sensitivity of 69.2%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 95.6%, and a false-positive rate of 0% (P Z .0001). Conclusion: The mitral valveetricuspid valve distance is useful clinically in the detection of endocardial cushion defects in second-trimester fetuses. Ó 2004 Elsevier Inc. All rights reserved.
Prenatal sonographic assessment of the 4-chamber cardiac view includes the evaluation of the normal distance or offset between the mitral valve and the more apically displaced tricuspid valve (Figure 1). Although the orientation of the atrioventricular valves usually is evaluated subjectively, more recently, investigators have sought to quantify the offset to establish gestational age norms (Figure 2). Vettraino et al1 showed the clinical usefulness of the exaggerated
Presented at the Twenty-Fourth Annual Meeting of the Society for Maternal-Fetal Medicine, February 2-7, 2004, New Orleans, La. Reprints will not be available from the authors. 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.05.042
mitral valveetricuspid valve distance (M-T D) in the prenatal diagnosis of Ebstein’s anomaly. Conversely, a narrowing of the atrioventricular offset would be suggestive of an endocardial cushion defect that occurs when a single multileaflet atrioventricular valve replaces separate mitral and tricuspid valves (Figure 3). An atrioventricular septal defect is a common cardiac condition that affects between 3.0% and 7.3% of infants with congenital heart disease.2-6 Allan2 examined 5 years of congenital heart disease at a large tertiary hospital and documented a !50% detection rate of fetal endocardial cushion defects. Similarly, Kirk et al4 examined their experience over a 5-year period and reported detection rates for atrioventricular septal defects of 63% to 87%.
1484
Figure 1 Apical 4-chamber view of the fetal heart. LV, Left ventricle; RV, right ventricle; LA, left atrium; RA, right atrium.
Figure 2 Detail of the M-T D in an apical 4-chamber view in a normal fetal heart. The number 1 is at the level of the superior portion of the septal leaflet insertion of the tricuspid valve. The number 2 is at the level of the inferior portion of the medial insertion of the mitral valve. The arrows delineate the M-T D. LV, Left ventricle; RV, right ventricle; LA, left atrium; RA, right atrium.
Therefore, we sought to compare the M-T D in second trimester fetuses with normal cardiac anatomy to those fetuses with antenatally diagnosed endocardial cushion defects.
Methods We performed a retrospective analysis of our ultrasound database from 1997 through 2003 for all fetuses who underwent an anatomic survey. We identified fetuses between 16 and 24 weeks of gestation for whom there were apical 4-chamber views at end diastole (Figure 1).
Bolnick et al
Figure 3 Apical view of a fetus with a partial endocardial cushion defect (primum atrial septal defect) shows the coplanar mitral and tricuspid valves. LV, Left ventricle; RV, right ventricle.
All ultrasound examinations were performed at our institution by a registered diagnostic medical sonographer who was supervised by Board Certified Perinatologists. Pediatric cardiologists verified suspected cases of endocardial cushion defects (Figure 3). Images were enlarged to measure electronically the distance between the insertion of the medial leaflets of the mitral and tricuspid valves for fetuses with normal cardiac anatomy and in a subset with endocardial cushion defects (Figures 2 and 4).7 A linear regression curve was generated for the M-T D in normal subjects by gestational age (Figure 5). The sensitivity, specificity, and positive and negative predictive values were determined with a M-T D !5th percentile of the expected M-T D as a marker for fetal endocardial cushion defects. Fisher exact and Student t test were used for statistical comparisons. Approval for the study was obtained from the Institutional Review Board at our hospital.
Results The mean M-T D for 86 fetuses with normal cardiac anatomy was 2.02 mm (95% CI, 1.86-2.18 mm) compared with 0.37 mm (95% CI, 0.033-0.7 mm) in 13 fetuses with endocardial cushion defects (P Z .0001). The linear regression curve that correlated M-T D with gestational age showed a gradual slope (R2 Z 0.28; P ! .0001; Figure 5). An M-T D !5th percentile was a marker for the diagnosis of endocardial cushion defects, from which we derived a sensitivity of 69.2%, a specificity of 100%,
Bolnick et al
1485
Figure 5 M-T D with mean and 5th and 95th percentiles. The dots represent the endocardial cushion defect cases.
Figure 4 Detail of the M-T D in a fetus with a partial endocardial cushion defect. The number 1 is at the level of the superior portion of the septal leaflet insertion of the tricuspid valve. The number 2 is at the level of the inferior portion of the medial insertion of the mitral valve. The arrow delineates the M-T D. LV, Left ventricle; RV, right ventricle.
a positive predictive value of 100%, a negative predictive value of 95.6%, and false-positive rate of 0% (P Z .0001).
Comment In this population-based study, the use of M-T D appears to be a clinically useful marker in the detection of endocardial cushion defects in second trimester fetuses. Prenatal echocardiography reveals that the septal insertion of the tricuspid valve is closer to the apex than that of the corresponding medial insertion of the mitral valve. Although this distance is usually assessed subjectively, our study demonstrates that the distance can be quantified throughout the second trimester in fetuses with normal cardiac anatomy. As reported by Vettraino et al,1 quantitative normograms for M-T D can be generated for fetuses with normal cardiac anatomy in the second and third trimester. On the basis of gestational norms, they demonstrated that an exaggerated M-T D could be used to diagnose Ebstein’s anomaly. Our study also demonstrates that a narrowing of the M-T D can signify the presence of an endocardial cushion defect. The use of our normative data may improve the prenatal detection of an endocardial cushion defect. Although our sample size was large, our study had several limitations. Because we relied on electronically
stored images, we may not have always measured the M-T D distance at the same point in the cardiac cycle. We did not assess intra- and interobserver reproducibility of the M-T D. In conclusion, our study confirms the previous reporting of a positive correlation between M-T Ds and gestational age. To our knowledge, this is the first study to assess the clinical usefulness of a narrowing of M-T D from expected normal gestational age variations. A M-T D that is O5th percentile is reassuring and diminishes the likelihood of an endocardial cushion defect. Conversely, those fetuses with a M-T D !5th percentile require further evaluation with echocardiography and consultation with pediatric cardiology. Further studies are required to evaluate prospectively the usefulness of M-T D as a noninvasive sonographic marker for congenital heart disease.
References 1. Vettraino IM, Huang R, Comstock CH. The normal offset of the tricuspid septal leaflet in the fetus. J Ultrasound Med 2002;21: 1099-104. 2. Allen L. Textbook of fetal cardiology. London: Greenwich Medical Media Limited; 2000. 3. Gembruch U, Knopfle G, Chatterjee M, et al. Prenatal diagnosis of atrioventricular canal malformations with up-to-date echocardiographic technology: report of 14 cases. Am Heart J 1991;121: 1489-97. 4. Kirk JS, Comstock CH, Lee W, Smith RS, Riggs TW, Weinhouse E. Sonographic screening to detect fetal cardiac anomalies: a 5-year experience with 111 abnormal cases. Obstet Gynecol 1997;89:227-32. 5. Pierpont ME, Markwald RR, Lin AE. Genetic aspects of atrioventricular septal defects. Am J Med Genet 2000;97:289-296. 6. Ugarte M, Enriquez de Salamanca F, Quero M. Endocardial cushion defects: an anatomical study of 54 specimens. Br Heart J 1976;38:674-82. 7. Gusseenhoven EJ, Stewart PA, Becker AE, Essed CE, Ligtvoet KM, Villeneurve VH. Offsetting of the septal tricuspid leaflet in normal hearts and in hearts with Ebstein’s anomaly: anatomic and echographic correlation. Am J Cardiol 1984;53:172-6.