- Email: [email protected]
To the Editor—Response:
Letters to the Editor
1119
Lawrie TDV, eds. Comprehensive Electrocardiography, Volume 2. New York: Pergamon Press, 1989:1267–1329. 18. Coronel R, Opthof T, Plotnikov AN, Wilms-Schopman FJG, Shlapakova IN, Danilo P Jr, Sosunov EA, Anyukhovsky EP, Janse MJ, Rosen MR. Long-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient. Cardiovasc Res 2007;74:416 – 425. 19. Xia Y, Yuan S. In vivo validation of the T-peak to T-end interval: implications for the genesis of the T wave. Heart Rhythm 2007;4:349 –350.
Is there an upper common pathway in AVNRT? To the Editor: In their recent interesting article on atrioventricular nodal reentrant tachycardia (AVNRT), Otomo et al1 provide data on the “upper common pathway.” In early studies and sporadic case reports, ventriculoatrial block patterns and variable His– atrial conduction times have been interpreted as suggesting the presence of a common pathway with decremental conduction properties.2– 4 However, no histologic data supporting such a notion have ever been produced. Subsequent evidence, derived from high-resolution mapping in animal hearts5 as well as human electrophysiology6,7 and intraoperative8 studies, also has clearly argued against the notion of a separate entity connecting the AVNRT circuit with the atria. The majority of patients with slow–fast AVNRT have multiple heterogeneous sites of early atrial activation during the arrhythmia rather than a focal breakthrough site,6 whereas earliest retrograde activation may be recorded in both the right and left atria.9 It seems that, if anything, upper and perhaps even lower common pathways represent concepts for which, as Valderrábano stated in his thoughtful editorial commentary in the same issue of Heart Rhythm,10 “the mechanisms and relevance . . . remain speculative.” Perhaps now is the time to abandon this rather unsupported speculation? Demosthenes G. Katritsis, MD, PhD, FRCP [email protected] Department of Cardiology Athens Euroclinic Athens, Greece
References 1. Otomo K, Nagata Y, Uno K, Fujiwara H, Iesaka Y. Atypical atrioventricular nodal reentrant tachycardia with eccentric coronary sinus activation: electrophysiological characteristics and essential effects of left-sided ablation inside the coronary sinus. Heart Rhythm 2007;4:421– 432. 2. Miller JM, Rosenthal ME, Vassalo JA, Josephson ME. Atrioventricular nodal reentrant tachycardia: studies on upper and lower “common pathways.” Circulation 1987;75:930 –940. 3. Chinushi M, Aizawa Y, Ogawa Y, Fujita S, Kusano Y, Miyajima S, Shibata A. Successful slow pathway ablation in a patient with atrioventricular nodal reentrant tachycardia having a proximal common pathway. Pacing Clin Electrophysiol 1998;21:1316 –1318. 4. Guo HM, Nerheim P, Olshansky B. Irregular atrial activation during atrioventricular nodal re-entrant tachycardia: evidence of an upper common pathway. J Cardiovasc Electrophysiol 2003;14:309 –313. 5. Loh P, de Bakker JM, Hocini M, Thibault B, Hauer RN, Janse MJ. Reentrant pathway during ventricular echoes is confined to the atrioventricular node: high-resolution mapping and dissection of the triangle of Koch in isolated, perfused canine hearts. Circulation 1999;100:1346 –1353. 6. Anselme F, Hook B, Monahan K, Frederiks J, Callans D, Zardini M, Epstein LM, Zebede J, Josephson ME. Heterogeneity of retrograde fast-pathway con-
7.
8.
9.
10.
duction pattern in patients with atrioventricular nodal reentry tachycardia: observations by simultaneous multisite catheter mapping of Koch’s triangle. Circulation 1996;93:960 –968. McGuire MA, Lau K-C, Johnson DC, Richards DA, Uther JB, Ross DL. Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia. Evidence that a common pathway of nodal tissue is not present above the reentrant circuit. Circulation 1991;83:1232–1246. Keim S, Werner P, Jazayeri M, Akhtar M, Tchou P. Localization of the fast and slow pathways in atrioventricular nodal re-entrant tachycardia by intraoperative ice mapping. Circulation 1992;86:919 –925. Katritsis DG, Ellenbogen KA, Becker AE. Atrial activation during atrioventricular nodal reentrant tachycardia: studies on retrograde fast pathway conduction. Heart Rhythm 2006;3:993–1000. Valderrábano M. Atypical atrioventricular nodal reentry with eccentric atrial activation. Is the right target on the left? Heart Rhythm 2007;4:433– 434.
To the Editor—Response: We appreciate Dr. Katritsis’s interest in our article on atypical atrioventricular (AV) nodal reentrant tachycardia (AVNRT) with eccentric coronary sinus activation,1 which suggested the presence of an upper common pathway (UCP) in 4 (1%) of the 340 cases with all forms of AVNRT. In his letter to the editor, Dr. Katritsis points out that the concept of a UCP was only speculative and should be abandoned because data2– 6 in the literature argue against the presence of a UCP. Nevertheless, we still believe that, in at least some AVNRT cases, the tachycardia circuit would be subatrial and the concept of a UCP would be required to explain the unusual phenomena, including ventriculoatrial (VA) dissociation. Before discussing whether or not the tachycardia circuit of AVNRT was confined to the AV node (“subatrial”) and connected to the atrium via a UCP, it seems crucial to define the extent of the “AV node.” Previous morphologic studies of the AV node have demonstrated a superior dense network of nodal tissue (compact AV node), an inferior portion of the AV node into which atrial bands gradually merged (transitional cell zone), and superficial transitional cells along the anterior limbus of the fossa ovalis.7,8 This threedimensional reconstruction demonstrates that AV nodal tissue occupies the bulk of the triangle of Koch. Therefore, much of the disagreement on the role of the atrium in the genesis of the tachycardia circuit seems to be derived from the definition of the extent of the AV node, especially from the failure to recognize the transitional cell zone as a specialized tissue that is part of the AV node. As described in our previous9 as well as recent report1 on the UCP, the tachycardia circuit was considered to be subatrial and connected to the atrium via a functional UCP in at least some rare cases with atypical AVNRT. The electrophysiologic evidence for a subatrial reentrant circuit and UCP included VA dissociation during a tachycardia, Wenckebach, 2:1 VA block without any tachycardia interruption, and variations in the H-A interval and/or retrograde atrial activation sequence during a stable tachycardia cycle length. An intraatrial conduction block between the perinodal atrium within the tachycardia circuit and the rest of the atrium cannot be excluded as a possible mechanism for those unusual phenomena; however, an intraatrial Wenckebach or 2:1 conduction block would be an extremely rare phenomenon at a tachycardia cycle length as long as 350 –500 ms in patients without any organic heart disease. In
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our hypothesis, the UCP is a functional entity not insulated from the surrounding tissue and can be manifest only during a tachycardia; therefore, the failure of previous histologic studies to demonstrate a UCP would not necessarily mean the absence of a UCP. Furthermore, discrepancies between histologic and electrophysiologic characteristics of AV junctional tissue have been reported.10 Thus, it is possible that histologic evaluation cannot differentiate perinodal working atrial myocardium from AV nodal transitional tissue with electrophysiologic characteristics resembling those of AV nodal cells10 that form parts of the tachycardia circuit or UCP. The excellent experimental study by Loh et al2 demonstrated that a single AV nodal echo beat could occur without the participation of superior and inferior atrionodal connections in the rabbit heart; therefore, the reentrant circuit was subatrial. Other investigators3–5 do not support the concept of a UCP because the retrograde atrial activation pattern during the tachycardia was heterogeneous in the AVNRT cases; however, their results2–5 seem rather compatible with the concept of a subatrial reentrant circuit and UCP, if the UCP has multiple atrial connections. Examples of a UCP with multiple atrial connections are shown in Figure 3B of our recent article1 and in Figure 3 of our previous article.9 Finally, whether or not the concept of a subatrial reentrant circuit and UCP can be extrapolated to general AVNRT cases remains unclear because evidence for a subatrial reentrant circuit and UCP has been observed in as few as 1%–2%1,9 of general AVNRT cases. Thus, we believe that the concept of a subatrial reentrant circuit and UCP is compatible with previous data and is the best explanation for the unusual phenomena in selected AVNRT cases, although, as Valderrábano10 stated in his editorial commentary, “the mechanism and relevance . . . remain speculative.” Kiyoshi Otomo, MD [email protected] Yasutoshi Nagata, MD Kikuya Uno, MD, PhD Yoshito Iesaka, MD, PhD Division of Cardiology, Cardiovascular Center Tsuchiura Kyodo Hospital Tsuchiura, Japan
References 1. Otomo K, Nagata Y, Uno K, Fujiwara H, Iesaka Y. Atypical atrioventricular nodal reentrant tachycardia with eccentric coronary sinus activation: electrophysiological characteristics and essential effects of left-sided ablation inside the coronary sinus. Heart Rhythm 2007;4:421– 432. 2. Loh P, de Bakker JM, Hocini M, Thibault B, Hauer RN, Janse MJ. Reentrant pathway during ventricular echoes is confined to the atrioventricular node: high-resolution mapping and dissection of the triangle of Koch in isolated, perfused canine hearts. Circulation 1999;100:1346 –1353. 3. Anselme F, Hook B, Monahan K, Frederiks J, Callans D, Zardini M, Epstein LM, Zebede J, Josephson ME. Heterogeneity of retrograde fast-pathway conduction pattern in patients with atrioventricular nodal reentry tachycardia: observations by simultaneous multisite catheter mapping of Koch’s triangle. Circulation 1996;93:960 –968. 4. McGuire MA, Lau K-C, Johnson DC, Richards DA, Uther JB, Ross DL. Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia. Evidence that a common pathway of nodal tissue is not present above the reentrant circuit. Circulation 1991;83:1232–1246. 5. Katritsis DG, Ellenbogen KA, Becker AE. Atrial activation during atrioventricular nodal reentrant tachycardia: studies on retrograde fast pathway conduction. Heart Rhythm 2006;3:993–1000.
6. Keim S, Werner P, Jazayeri M, Akhtar M, Tchou P. Localization of the fast and slow pathways in atrioventricular nodal re-entrant tachycardia by intraoperative ice mapping. Circulation 1992;86:919 –925. 7. Anderson RH, Janse MJ, van Capelle FJ, Billette J, Becker AE, Durrer D. A combined morphological and electrophysiological study of the atrioventricular node of the rabbit heart. Circ Res 1974;35:909 –922. 8. Janse MJ. Propagation of atrial impulse through the atrioventricular node. In Touboul P, Waldo AL, eds. Atrial Arrhythmias: Current Concepts and Management. St. Louis: Mosby-Year Book, 1990:141–152. 9. Otomo K, Okamura H, Noda T, Satomi K, Shimizu W, Suyama K, Kurita T, Aihara N, Kamakura S. Unique electrophysiologic characteristics of atrioventricular nodal reentrant tachycardia with different ventriculoatrial block patterns: effects of slow pathway ablation and insights into the location of the reentrant circuit. Heart Rhythm 2006;3:544 –554. 10. McGuire MA, de Bakker JM, Vermeulen JT, Moorman AF, Loh P, Thibault B, Vermeulen JL, Becker AE, Janse MJ. Atrioventricular junctional tissue. Discrepancy between histological and electrophysiological characteristics. Circulation 1996;94:571–577. 11. Valderrábano M. Atypical atrioventricular nodal reentry with eccentric atrial activation. Is the right target on the left? Heart Rhythm 2007;4:433– 434.
To the Editor: We read with interest, and increasing surprise, the Creative Concepts article by Elizari et al1 published in the March 2007 issue of Heart Rhythm. We submit that the evidence on which the authors base their hypothesis is not sound. We know that cells migrating into the heart from the neural crest are crucially involved in the intricate morphogenesis of the outflow tract. However, we also know that, eventually, they make no material contribution to the myocardium of the outflow tract. Many of the cells subsequently disappear, as has been shown in unambiguous fashion by molecular lineage studies.2 Also questionable is whether, as claimed by Elizari et al,1 the myocardium clothing the pulmonary veins is populated by cells derived from the neural crest. In this situation, lineage studies also have failed to reveal any material contribution from the neural crest to the atrial myocardium. It is far more likely that the cells entering the venous pole from the neural crest form the autonomic nerves that are unequivocally related to the pulmonary veins. The musculature of the pulmonary veins themselves is derived from mediastinal myocardium.3 This myocardium is phenotypically different from the myocardium that gives rise to the definitive conduction tissues.4 In this respect, therefore, the reference made by Elizari et al to a postulated contribution from the neural crest to the specialized myocytes of the conduction system is particularly misleading. It is true that many investigators have suggested that the cells migrating from the neural crest do contribute materially to the conduction system.5 However, some of those who made such initial suggestions now admit that there is no evidence supporting this contention.6,7 With regard to the cells entering the arterial pole, it is indeed the case that they populate the ridges, or cushions, which initially divide the embryonic outflow tract, and that they enter the leaflets of the developing arterial valves. However, as far as we are aware, there is no evidence that the cells remain in the free-standing muscular infundibulum that supports the leaflets of the pulmonary valve. This is the structure that is derived by muscularization of the proximal
1119
Lawrie TDV, eds. Comprehensive Electrocardiography, Volume 2. New York: Pergamon Press, 1989:1267–1329. 18. Coronel R, Opthof T, Plotnikov AN, Wilms-Schopman FJG, Shlapakova IN, Danilo P Jr, Sosunov EA, Anyukhovsky EP, Janse MJ, Rosen MR. Long-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient. Cardiovasc Res 2007;74:416 – 425. 19. Xia Y, Yuan S. In vivo validation of the T-peak to T-end interval: implications for the genesis of the T wave. Heart Rhythm 2007;4:349 –350.
Is there an upper common pathway in AVNRT? To the Editor: In their recent interesting article on atrioventricular nodal reentrant tachycardia (AVNRT), Otomo et al1 provide data on the “upper common pathway.” In early studies and sporadic case reports, ventriculoatrial block patterns and variable His– atrial conduction times have been interpreted as suggesting the presence of a common pathway with decremental conduction properties.2– 4 However, no histologic data supporting such a notion have ever been produced. Subsequent evidence, derived from high-resolution mapping in animal hearts5 as well as human electrophysiology6,7 and intraoperative8 studies, also has clearly argued against the notion of a separate entity connecting the AVNRT circuit with the atria. The majority of patients with slow–fast AVNRT have multiple heterogeneous sites of early atrial activation during the arrhythmia rather than a focal breakthrough site,6 whereas earliest retrograde activation may be recorded in both the right and left atria.9 It seems that, if anything, upper and perhaps even lower common pathways represent concepts for which, as Valderrábano stated in his thoughtful editorial commentary in the same issue of Heart Rhythm,10 “the mechanisms and relevance . . . remain speculative.” Perhaps now is the time to abandon this rather unsupported speculation? Demosthenes G. Katritsis, MD, PhD, FRCP [email protected] Department of Cardiology Athens Euroclinic Athens, Greece
References 1. Otomo K, Nagata Y, Uno K, Fujiwara H, Iesaka Y. Atypical atrioventricular nodal reentrant tachycardia with eccentric coronary sinus activation: electrophysiological characteristics and essential effects of left-sided ablation inside the coronary sinus. Heart Rhythm 2007;4:421– 432. 2. Miller JM, Rosenthal ME, Vassalo JA, Josephson ME. Atrioventricular nodal reentrant tachycardia: studies on upper and lower “common pathways.” Circulation 1987;75:930 –940. 3. Chinushi M, Aizawa Y, Ogawa Y, Fujita S, Kusano Y, Miyajima S, Shibata A. Successful slow pathway ablation in a patient with atrioventricular nodal reentrant tachycardia having a proximal common pathway. Pacing Clin Electrophysiol 1998;21:1316 –1318. 4. Guo HM, Nerheim P, Olshansky B. Irregular atrial activation during atrioventricular nodal re-entrant tachycardia: evidence of an upper common pathway. J Cardiovasc Electrophysiol 2003;14:309 –313. 5. Loh P, de Bakker JM, Hocini M, Thibault B, Hauer RN, Janse MJ. Reentrant pathway during ventricular echoes is confined to the atrioventricular node: high-resolution mapping and dissection of the triangle of Koch in isolated, perfused canine hearts. Circulation 1999;100:1346 –1353. 6. Anselme F, Hook B, Monahan K, Frederiks J, Callans D, Zardini M, Epstein LM, Zebede J, Josephson ME. Heterogeneity of retrograde fast-pathway con-
7.
8.
9.
10.
duction pattern in patients with atrioventricular nodal reentry tachycardia: observations by simultaneous multisite catheter mapping of Koch’s triangle. Circulation 1996;93:960 –968. McGuire MA, Lau K-C, Johnson DC, Richards DA, Uther JB, Ross DL. Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia. Evidence that a common pathway of nodal tissue is not present above the reentrant circuit. Circulation 1991;83:1232–1246. Keim S, Werner P, Jazayeri M, Akhtar M, Tchou P. Localization of the fast and slow pathways in atrioventricular nodal re-entrant tachycardia by intraoperative ice mapping. Circulation 1992;86:919 –925. Katritsis DG, Ellenbogen KA, Becker AE. Atrial activation during atrioventricular nodal reentrant tachycardia: studies on retrograde fast pathway conduction. Heart Rhythm 2006;3:993–1000. Valderrábano M. Atypical atrioventricular nodal reentry with eccentric atrial activation. Is the right target on the left? Heart Rhythm 2007;4:433– 434.
To the Editor—Response: We appreciate Dr. Katritsis’s interest in our article on atypical atrioventricular (AV) nodal reentrant tachycardia (AVNRT) with eccentric coronary sinus activation,1 which suggested the presence of an upper common pathway (UCP) in 4 (1%) of the 340 cases with all forms of AVNRT. In his letter to the editor, Dr. Katritsis points out that the concept of a UCP was only speculative and should be abandoned because data2– 6 in the literature argue against the presence of a UCP. Nevertheless, we still believe that, in at least some AVNRT cases, the tachycardia circuit would be subatrial and the concept of a UCP would be required to explain the unusual phenomena, including ventriculoatrial (VA) dissociation. Before discussing whether or not the tachycardia circuit of AVNRT was confined to the AV node (“subatrial”) and connected to the atrium via a UCP, it seems crucial to define the extent of the “AV node.” Previous morphologic studies of the AV node have demonstrated a superior dense network of nodal tissue (compact AV node), an inferior portion of the AV node into which atrial bands gradually merged (transitional cell zone), and superficial transitional cells along the anterior limbus of the fossa ovalis.7,8 This threedimensional reconstruction demonstrates that AV nodal tissue occupies the bulk of the triangle of Koch. Therefore, much of the disagreement on the role of the atrium in the genesis of the tachycardia circuit seems to be derived from the definition of the extent of the AV node, especially from the failure to recognize the transitional cell zone as a specialized tissue that is part of the AV node. As described in our previous9 as well as recent report1 on the UCP, the tachycardia circuit was considered to be subatrial and connected to the atrium via a functional UCP in at least some rare cases with atypical AVNRT. The electrophysiologic evidence for a subatrial reentrant circuit and UCP included VA dissociation during a tachycardia, Wenckebach, 2:1 VA block without any tachycardia interruption, and variations in the H-A interval and/or retrograde atrial activation sequence during a stable tachycardia cycle length. An intraatrial conduction block between the perinodal atrium within the tachycardia circuit and the rest of the atrium cannot be excluded as a possible mechanism for those unusual phenomena; however, an intraatrial Wenckebach or 2:1 conduction block would be an extremely rare phenomenon at a tachycardia cycle length as long as 350 –500 ms in patients without any organic heart disease. In
1120
Heart Rhythm, Vol 4, No 8, August 2007
our hypothesis, the UCP is a functional entity not insulated from the surrounding tissue and can be manifest only during a tachycardia; therefore, the failure of previous histologic studies to demonstrate a UCP would not necessarily mean the absence of a UCP. Furthermore, discrepancies between histologic and electrophysiologic characteristics of AV junctional tissue have been reported.10 Thus, it is possible that histologic evaluation cannot differentiate perinodal working atrial myocardium from AV nodal transitional tissue with electrophysiologic characteristics resembling those of AV nodal cells10 that form parts of the tachycardia circuit or UCP. The excellent experimental study by Loh et al2 demonstrated that a single AV nodal echo beat could occur without the participation of superior and inferior atrionodal connections in the rabbit heart; therefore, the reentrant circuit was subatrial. Other investigators3–5 do not support the concept of a UCP because the retrograde atrial activation pattern during the tachycardia was heterogeneous in the AVNRT cases; however, their results2–5 seem rather compatible with the concept of a subatrial reentrant circuit and UCP, if the UCP has multiple atrial connections. Examples of a UCP with multiple atrial connections are shown in Figure 3B of our recent article1 and in Figure 3 of our previous article.9 Finally, whether or not the concept of a subatrial reentrant circuit and UCP can be extrapolated to general AVNRT cases remains unclear because evidence for a subatrial reentrant circuit and UCP has been observed in as few as 1%–2%1,9 of general AVNRT cases. Thus, we believe that the concept of a subatrial reentrant circuit and UCP is compatible with previous data and is the best explanation for the unusual phenomena in selected AVNRT cases, although, as Valderrábano10 stated in his editorial commentary, “the mechanism and relevance . . . remain speculative.” Kiyoshi Otomo, MD [email protected] Yasutoshi Nagata, MD Kikuya Uno, MD, PhD Yoshito Iesaka, MD, PhD Division of Cardiology, Cardiovascular Center Tsuchiura Kyodo Hospital Tsuchiura, Japan
References 1. Otomo K, Nagata Y, Uno K, Fujiwara H, Iesaka Y. Atypical atrioventricular nodal reentrant tachycardia with eccentric coronary sinus activation: electrophysiological characteristics and essential effects of left-sided ablation inside the coronary sinus. Heart Rhythm 2007;4:421– 432. 2. Loh P, de Bakker JM, Hocini M, Thibault B, Hauer RN, Janse MJ. Reentrant pathway during ventricular echoes is confined to the atrioventricular node: high-resolution mapping and dissection of the triangle of Koch in isolated, perfused canine hearts. Circulation 1999;100:1346 –1353. 3. Anselme F, Hook B, Monahan K, Frederiks J, Callans D, Zardini M, Epstein LM, Zebede J, Josephson ME. Heterogeneity of retrograde fast-pathway conduction pattern in patients with atrioventricular nodal reentry tachycardia: observations by simultaneous multisite catheter mapping of Koch’s triangle. Circulation 1996;93:960 –968. 4. McGuire MA, Lau K-C, Johnson DC, Richards DA, Uther JB, Ross DL. Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia. Evidence that a common pathway of nodal tissue is not present above the reentrant circuit. Circulation 1991;83:1232–1246. 5. Katritsis DG, Ellenbogen KA, Becker AE. Atrial activation during atrioventricular nodal reentrant tachycardia: studies on retrograde fast pathway conduction. Heart Rhythm 2006;3:993–1000.
6. Keim S, Werner P, Jazayeri M, Akhtar M, Tchou P. Localization of the fast and slow pathways in atrioventricular nodal re-entrant tachycardia by intraoperative ice mapping. Circulation 1992;86:919 –925. 7. Anderson RH, Janse MJ, van Capelle FJ, Billette J, Becker AE, Durrer D. A combined morphological and electrophysiological study of the atrioventricular node of the rabbit heart. Circ Res 1974;35:909 –922. 8. Janse MJ. Propagation of atrial impulse through the atrioventricular node. In Touboul P, Waldo AL, eds. Atrial Arrhythmias: Current Concepts and Management. St. Louis: Mosby-Year Book, 1990:141–152. 9. Otomo K, Okamura H, Noda T, Satomi K, Shimizu W, Suyama K, Kurita T, Aihara N, Kamakura S. Unique electrophysiologic characteristics of atrioventricular nodal reentrant tachycardia with different ventriculoatrial block patterns: effects of slow pathway ablation and insights into the location of the reentrant circuit. Heart Rhythm 2006;3:544 –554. 10. McGuire MA, de Bakker JM, Vermeulen JT, Moorman AF, Loh P, Thibault B, Vermeulen JL, Becker AE, Janse MJ. Atrioventricular junctional tissue. Discrepancy between histological and electrophysiological characteristics. Circulation 1996;94:571–577. 11. Valderrábano M. Atypical atrioventricular nodal reentry with eccentric atrial activation. Is the right target on the left? Heart Rhythm 2007;4:433– 434.
To the Editor: We read with interest, and increasing surprise, the Creative Concepts article by Elizari et al1 published in the March 2007 issue of Heart Rhythm. We submit that the evidence on which the authors base their hypothesis is not sound. We know that cells migrating into the heart from the neural crest are crucially involved in the intricate morphogenesis of the outflow tract. However, we also know that, eventually, they make no material contribution to the myocardium of the outflow tract. Many of the cells subsequently disappear, as has been shown in unambiguous fashion by molecular lineage studies.2 Also questionable is whether, as claimed by Elizari et al,1 the myocardium clothing the pulmonary veins is populated by cells derived from the neural crest. In this situation, lineage studies also have failed to reveal any material contribution from the neural crest to the atrial myocardium. It is far more likely that the cells entering the venous pole from the neural crest form the autonomic nerves that are unequivocally related to the pulmonary veins. The musculature of the pulmonary veins themselves is derived from mediastinal myocardium.3 This myocardium is phenotypically different from the myocardium that gives rise to the definitive conduction tissues.4 In this respect, therefore, the reference made by Elizari et al to a postulated contribution from the neural crest to the specialized myocytes of the conduction system is particularly misleading. It is true that many investigators have suggested that the cells migrating from the neural crest do contribute materially to the conduction system.5 However, some of those who made such initial suggestions now admit that there is no evidence supporting this contention.6,7 With regard to the cells entering the arterial pole, it is indeed the case that they populate the ridges, or cushions, which initially divide the embryonic outflow tract, and that they enter the leaflets of the developing arterial valves. However, as far as we are aware, there is no evidence that the cells remain in the free-standing muscular infundibulum that supports the leaflets of the pulmonary valve. This is the structure that is derived by muscularization of the proximal