EDITORIAL
Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp
Fetal Bradycardia Associated With Congenital Heart Defects – Is There a Clinicohistological Correlation? – Kazuhiro Takahashi, MD, PhD
T
he study by Miyoshi et al1 published in this issue of the Journal adds a new piece to the puzzle of fetal bradycardia associated with congenital heart defects (CHD). They reviewed the outcome of 29 fetuses with CHD associated with fetal bradycardia over a 6-year period and investigated potential outcome predictors in those populations. Prognosis is still poor and that there are different clinical manifestations, such as outcome and escape rhythm rate, among the CHDs: congenitally corrected transposition of the great arteries (CCTGA) and heterotaxy (polysplenia) in fetal congenital heart block (CHB). Are the differences in outcomes attributable to different histopathologies of fetal bradycardia between the populations?
Article p 854 From an electrophysiological viewpoint, the site of the block theoretically may be different in these CHDs. Generally, ECG data on the QRS width and the configuration of conducted beats and/or escape beats are of value in localizing the site of the block. Although a narrow QRS complex is most compatible with an atrioventricular (AV) nodal or intra-His problem, a wide QRS complex is most compatible with an infra-His problem. In CHB, the rate of the escape rhythm provides some information about the site of the block. Precise identification of the site of the block based on the ECG (escape rhythm rate and QRS width) may not be possible because considerable overlap is observed.2 However, presumed localization of a conduction disturbance may be possible and aid the clinician in planning the therapeutic approach. CHB can occur with CHDs or in otherwise normal hearts. When occurring in a structurally normal heart, the pattern of the cardiac conduction system can take 1 of 3 anatomic forms: atrial-axis discontinuity, nodal-ventricular discontinuity, or intraventricular discontinuity (Figure).3 The association between CHB and maternal connective tissue disease is well documented and a previous study has shown the lack of an AV node or nodal-ventricular discontinuity.4 CHB associated with CHDs is most frequently observed in the anomaly of CCTGA, isomerism of the atrial appendages (heterotaxy), and with some AV septal defects.5 In other words, the derangements in AV conduction are related to malalignment of the ventricular septum.
Figure. In histologic terms, congenitally complete heart block can take any of the 3 patterns illustrated here. (Reproduced with permission from Anderson RH, et al.3)
The opinions expressed in this article are not necessarily those of the editors or of the Japanese Circulation Society. Received February 17, 2015; accepted February 17, 2015; released online February 27, 2015 Department of Pediatric Cardiology, Okinawa Children’s Medical Center, Okinawa, Japan Mailing address: Kazuhiro Takahashi, MD, PhD, Department of Pediatric Cardiology, Okinawa Children’s Medical Center, 118-1 Arakawa, Haebaru, Okinawa 901-1193, Japan. E-mail: [email protected] ISSN-1346-9843 doi: 10.1253/circj.CJ-15-0191 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected] Circulation Journal Vol.79, April 2015
762
TAKAHASHI K
Table. Histopathology of Congenital Heart Block Etiology Autoimmune
Block level
Histopathology
Atrial-axis discontinuity
AV node is replaced by fibrous or fatty tissue
CCTGA
Supra-Hisian, proximal to the His bundle bifurcation
Fibrosis and disruption of the proximal nonbifurcating His bundle
Isomerism
Between the AV node and the conduction axis
CHD
AV, atrioventricular; CCTGA, congenitally corrected transposition of the great arteries; CHD, congenital heart disease.
CCTGA The histopathology of CHB is summarized in Table. The anomalous AV node and His bundle are generally anterior, and the long penetrating bundle is somewhat tenuous or vulnerable to fibrosis with advancing age.6,7 Histologic investigation has disclosed that fibrosis and disruption in an elongated non-branching His bundle, together with fibrosis, occurs at the junction with the anterior node in situs solitus with L-loop CCTGA (without pulmonary atresia).8–10 Electrophysiologic observations are consistent with the histological studies of CCTGA.11 Heterotaxy (Polysplenia) Heterotaxy patients with CHB may have a discontinuity between the AV node and His-Purkinje system,12 either because of an initial lack of fusion between the AV nodal tissue and the His bundle or a secondary interruption of the AV conduction axis.13 However, we currently do not have sufficient histological evidence of the infra-Hisian conduction system in heterotaxy syndrome. CHD patients have a conduction axis (His-Purkinje system) abnormality that includes sling-like tissues. In particular, patients with heterotaxy syndrome may have a tendency to such abnormalities. Notably, an association of sick sinus syndrome (SSS) with CHDs is high in the present study. The incidence of SSS was 14/20 (70%) in polysplenia, 1/2 (50%) in asplenia, 1/4 (25%) in CCTGA, and 0/3 (0%) in critical pulmonary stenosis. Hypoplasia or absence of the sinus node results in sinus bradycardia in polysplenia syndrome. Namely, AV block in polysplenia syndrome is associated with the absence of the sinus node. On the other hand, sinus node(s) are generally present in asplenia. The pathology of AV block in heterotaxy may be different even between polysplenia and asplenia. However, we do not have sufficient evidence to confirm this either histologically or electrophysiologically thus far. The present information may be helpful in the challenging management of fetal bradycardia in association with CHDs.14 Acknowledgments
Disclosures The author has no potential conflicts of interest to disclose.
References 1. Miyoshi T, Maeno Y, Sago H, Inamura N, Yasukouchi S, Kawataki M, et al. Fetal bradyarrhythmia associated with congenital heart defects: Nationwide survey in Japan. Circ J 2015; 79: 854 – 861. 2. Josephson ME. Atrioventricular conduction. In: Clinical cardiac electrophysiology techniques and interpretations, 4th edn. Lippincott Williams & Wilkins, 2008; 93 – 113. 3. Anderson RH, Ho SY. The morphologic substrates for pediatric arrhythmias. Cardiol Young 1991; 1: 159 – 176. 4. Ho SY, Esscher E, Anderson RH, Michaëlsson M. Anatomy of congenital complete heart block and relation to maternal anti-Ro antibodies. Am J Cardiol 1986; 58: 291 – 294. 5. Ho SY. Clinical pathology of the cardiac conduction system. Novartis Found Symp 2003; 250: 210 – 221, discussion 221 – 226, 276 – 279. 6. Anderson RH, Becker AE, Arnold R, Wilkinson JL. The conducting tissues in congenitally corrected transposition. Circulation 1974; 50: 911 – 923. 7. Warnes CA. Transposition of the great arteries. Circulation 2006; 114: 2699 – 2709. 8. Anderson RH, Becker AE, Arnold R, Wilkinson JL. The conducting tissues in congenitally corrected transposition. Circulation 1974; 50: 911 – 923. 9. Bharati S, McCue CM, Tingelstad JB, Mantakas M, Shiel F, Lev M. Lack of connection between the atria and the peripheral conduction system in a case of corrected transposition with congenital atrioventricular block. Am J Cardiol 1978; 42: 147 – 153. 10. Daliento L, Corrado D, Buja G, John N, Nava A, Thiene G. Rhythm and conduction disturbances in isolated, congenitally corrected transposition of the great arteries. Am J Cardiol 1986; 58: 314 – 318. 11. Foster JR, Damato AN, Kline LE, Akhtar M, Ruskin JN. Congenitally corrected transposition of the great vessels: Localization of the site of complete atrioventricular block using His bundle electrograms. Am J Cardiol 1976; 38: 383 – 387. 12. Garcia OL, Metha AV, Pickoff AS, Tamer DF, Ferrer PL, Wolff GS, et al. Left isomerism and complete atrioventricular block: A report of six cases. Am J Cardiol 1981; 48: 1103 – 1107. 13. Ho SY, Fagg N, Anderson RH, Cook A, Allan L. Disposition of the atrioventricular conduction tissues in the heart with isomerism of the atrial appendages: Its relation to congenital complete heart block. J Am Coll Cardiol 1992; 20: 904 – 910. 14. Suzuki T, Nishigaki K. Pacing therapy in pediatric and congenital heart disease patients. Circ J 2014; 78: 2848 – 2850.
The invaluable advice given by Dr H. Kurosawa on the histological perspectives is greatly appreciated.
Circulation Journal Vol.79, April 2015
Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp
Fetal Bradycardia Associated With Congenital Heart Defects – Is There a Clinicohistological Correlation? – Kazuhiro Takahashi, MD, PhD
T
he study by Miyoshi et al1 published in this issue of the Journal adds a new piece to the puzzle of fetal bradycardia associated with congenital heart defects (CHD). They reviewed the outcome of 29 fetuses with CHD associated with fetal bradycardia over a 6-year period and investigated potential outcome predictors in those populations. Prognosis is still poor and that there are different clinical manifestations, such as outcome and escape rhythm rate, among the CHDs: congenitally corrected transposition of the great arteries (CCTGA) and heterotaxy (polysplenia) in fetal congenital heart block (CHB). Are the differences in outcomes attributable to different histopathologies of fetal bradycardia between the populations?
Article p 854 From an electrophysiological viewpoint, the site of the block theoretically may be different in these CHDs. Generally, ECG data on the QRS width and the configuration of conducted beats and/or escape beats are of value in localizing the site of the block. Although a narrow QRS complex is most compatible with an atrioventricular (AV) nodal or intra-His problem, a wide QRS complex is most compatible with an infra-His problem. In CHB, the rate of the escape rhythm provides some information about the site of the block. Precise identification of the site of the block based on the ECG (escape rhythm rate and QRS width) may not be possible because considerable overlap is observed.2 However, presumed localization of a conduction disturbance may be possible and aid the clinician in planning the therapeutic approach. CHB can occur with CHDs or in otherwise normal hearts. When occurring in a structurally normal heart, the pattern of the cardiac conduction system can take 1 of 3 anatomic forms: atrial-axis discontinuity, nodal-ventricular discontinuity, or intraventricular discontinuity (Figure).3 The association between CHB and maternal connective tissue disease is well documented and a previous study has shown the lack of an AV node or nodal-ventricular discontinuity.4 CHB associated with CHDs is most frequently observed in the anomaly of CCTGA, isomerism of the atrial appendages (heterotaxy), and with some AV septal defects.5 In other words, the derangements in AV conduction are related to malalignment of the ventricular septum.
Figure. In histologic terms, congenitally complete heart block can take any of the 3 patterns illustrated here. (Reproduced with permission from Anderson RH, et al.3)
The opinions expressed in this article are not necessarily those of the editors or of the Japanese Circulation Society. Received February 17, 2015; accepted February 17, 2015; released online February 27, 2015 Department of Pediatric Cardiology, Okinawa Children’s Medical Center, Okinawa, Japan Mailing address: Kazuhiro Takahashi, MD, PhD, Department of Pediatric Cardiology, Okinawa Children’s Medical Center, 118-1 Arakawa, Haebaru, Okinawa 901-1193, Japan. E-mail: [email protected] ISSN-1346-9843 doi: 10.1253/circj.CJ-15-0191 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected] Circulation Journal Vol.79, April 2015
762
TAKAHASHI K
Table. Histopathology of Congenital Heart Block Etiology Autoimmune
Block level
Histopathology
Atrial-axis discontinuity
AV node is replaced by fibrous or fatty tissue
CCTGA
Supra-Hisian, proximal to the His bundle bifurcation
Fibrosis and disruption of the proximal nonbifurcating His bundle
Isomerism
Between the AV node and the conduction axis
CHD
AV, atrioventricular; CCTGA, congenitally corrected transposition of the great arteries; CHD, congenital heart disease.
CCTGA The histopathology of CHB is summarized in Table. The anomalous AV node and His bundle are generally anterior, and the long penetrating bundle is somewhat tenuous or vulnerable to fibrosis with advancing age.6,7 Histologic investigation has disclosed that fibrosis and disruption in an elongated non-branching His bundle, together with fibrosis, occurs at the junction with the anterior node in situs solitus with L-loop CCTGA (without pulmonary atresia).8–10 Electrophysiologic observations are consistent with the histological studies of CCTGA.11 Heterotaxy (Polysplenia) Heterotaxy patients with CHB may have a discontinuity between the AV node and His-Purkinje system,12 either because of an initial lack of fusion between the AV nodal tissue and the His bundle or a secondary interruption of the AV conduction axis.13 However, we currently do not have sufficient histological evidence of the infra-Hisian conduction system in heterotaxy syndrome. CHD patients have a conduction axis (His-Purkinje system) abnormality that includes sling-like tissues. In particular, patients with heterotaxy syndrome may have a tendency to such abnormalities. Notably, an association of sick sinus syndrome (SSS) with CHDs is high in the present study. The incidence of SSS was 14/20 (70%) in polysplenia, 1/2 (50%) in asplenia, 1/4 (25%) in CCTGA, and 0/3 (0%) in critical pulmonary stenosis. Hypoplasia or absence of the sinus node results in sinus bradycardia in polysplenia syndrome. Namely, AV block in polysplenia syndrome is associated with the absence of the sinus node. On the other hand, sinus node(s) are generally present in asplenia. The pathology of AV block in heterotaxy may be different even between polysplenia and asplenia. However, we do not have sufficient evidence to confirm this either histologically or electrophysiologically thus far. The present information may be helpful in the challenging management of fetal bradycardia in association with CHDs.14 Acknowledgments
Disclosures The author has no potential conflicts of interest to disclose.
References 1. Miyoshi T, Maeno Y, Sago H, Inamura N, Yasukouchi S, Kawataki M, et al. Fetal bradyarrhythmia associated with congenital heart defects: Nationwide survey in Japan. Circ J 2015; 79: 854 – 861. 2. Josephson ME. Atrioventricular conduction. In: Clinical cardiac electrophysiology techniques and interpretations, 4th edn. Lippincott Williams & Wilkins, 2008; 93 – 113. 3. Anderson RH, Ho SY. The morphologic substrates for pediatric arrhythmias. Cardiol Young 1991; 1: 159 – 176. 4. Ho SY, Esscher E, Anderson RH, Michaëlsson M. Anatomy of congenital complete heart block and relation to maternal anti-Ro antibodies. Am J Cardiol 1986; 58: 291 – 294. 5. Ho SY. Clinical pathology of the cardiac conduction system. Novartis Found Symp 2003; 250: 210 – 221, discussion 221 – 226, 276 – 279. 6. Anderson RH, Becker AE, Arnold R, Wilkinson JL. The conducting tissues in congenitally corrected transposition. Circulation 1974; 50: 911 – 923. 7. Warnes CA. Transposition of the great arteries. Circulation 2006; 114: 2699 – 2709. 8. Anderson RH, Becker AE, Arnold R, Wilkinson JL. The conducting tissues in congenitally corrected transposition. Circulation 1974; 50: 911 – 923. 9. Bharati S, McCue CM, Tingelstad JB, Mantakas M, Shiel F, Lev M. Lack of connection between the atria and the peripheral conduction system in a case of corrected transposition with congenital atrioventricular block. Am J Cardiol 1978; 42: 147 – 153. 10. Daliento L, Corrado D, Buja G, John N, Nava A, Thiene G. Rhythm and conduction disturbances in isolated, congenitally corrected transposition of the great arteries. Am J Cardiol 1986; 58: 314 – 318. 11. Foster JR, Damato AN, Kline LE, Akhtar M, Ruskin JN. Congenitally corrected transposition of the great vessels: Localization of the site of complete atrioventricular block using His bundle electrograms. Am J Cardiol 1976; 38: 383 – 387. 12. Garcia OL, Metha AV, Pickoff AS, Tamer DF, Ferrer PL, Wolff GS, et al. Left isomerism and complete atrioventricular block: A report of six cases. Am J Cardiol 1981; 48: 1103 – 1107. 13. Ho SY, Fagg N, Anderson RH, Cook A, Allan L. Disposition of the atrioventricular conduction tissues in the heart with isomerism of the atrial appendages: Its relation to congenital complete heart block. J Am Coll Cardiol 1992; 20: 904 – 910. 14. Suzuki T, Nishigaki K. Pacing therapy in pediatric and congenital heart disease patients. Circ J 2014; 78: 2848 – 2850.
The invaluable advice given by Dr H. Kurosawa on the histological perspectives is greatly appreciated.
Circulation Journal Vol.79, April 2015
