International Journal of Cardiology 174 (2014) 1–6
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Review
Visualizing anatomical evidences on atrioventricular conduction system for TAVI Tomokazu Kawashima ⁎, Fumi Sato Department of Anatomy, School of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan
a r t i c l e
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Article history: Received 4 November 2013 Received in revised form 28 February 2014 Accepted 1 April 2014 Available online 12 April 2014 Keywords: Transcatheter aortic valve implantation Atrioventricular conduction system Clinical anatomy New conduction abnormalities Aortic stenosis
a b s t r a c t Visualizing the anatomy of the atrioventricular (AV) conduction axis substantiates that there is remarkable interindividual variation at the macro- and microscopic levels, and that the atrioventricular bundle and left bundle branch are located more anteriorly, distally, and cranially and much closer to the aortic root complex than previously thought. The AV conduction system may therefore be compromised during implantation of a transcatheter aortic valve prosthesis, which may account for the relatively high incidence of new cardiac conduction abnormalities when conventional prosthetic valves are used. The design of the newer JenaValve® may afford advantages over more conventional valves by avoiding the high-risk implantation area and the potential for coronary ostia obstruction. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Transcatheter aortic valve implantation (TAVI) is an effective means of treating patients with severe aortic stenosis in whom surgical aortic valve replacement (SAVR) is contraindicated as a consequence of high surgical risk. Nevertheless, higher grade atrioventricular (AV) block requiring permanent pacemaker implantation (PPI) is more common after TAVI (12–44%) than SAVR (3–8%) [1–9]. Recent retrospective studies have reported that the incidence of new conduction abnormalities after implantation of the CoreValve® (Medtronic CV, Luxembourg) is in the range of 9–44% [1,2,5,6,10–17], and 0–12% after implantation of the Edwards SAPIEN® (Edwards Lifesciences Corporation, Irvine, CA, USA) valve [6,14,15,18–23]. As the popularity of TAVI grows, the avoidance of new conduction abnormalities has emerged as a pressing problem. Most reports of new conduction abnormalities after TAVI have examined and identified a variety of contributing and predictive factors based on a conventional understanding of the anatomy of the cardiac conduction system. Several have sought to explain the causes of new conduction abnormalities using histological findings combined with actual cardiac photographs upon which a schematic of what is generally understood to represent the AV conduction system has been superimposed [6,8,10,17]. Importantly, however, the clinical importance of substantial inter-individual anatomic variation, and the function of newly identified areas of specialized myocardium in the paranodal area and the AV rings are still not ⁎ Corresponding author. Tel.: +81 3 3762 4151; fax: +81 3 5493 5411. E-mail address: [email protected] (T. Kawashima).
http://dx.doi.org/10.1016/j.ijcard.2014.04.003 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
completely understood [24–27]. Presently, technical difficulties can make some of the most important structures of the conduction system hard to visualize at a macroscopic level, although a non-branching atrioventricular bundle (AVB) may be evident within the solid central fibrous body. It has a whitish colour; the direction of the fibres in the branching AVB can be differentiated from surrounding cardiac myocytes; and continuous structures can be found within the AV conduction axis. In this brief review paper, we describe the current understanding of the extent and importance of inter-individual variation in the AV conduction system, how it may influence outcome after TAVI and a strategy for the design of transcatheter aortic valves that would reduce the incidence of new conduction abnormalities after implantation. 2. Implications of variant AVB position for implantable valve width It is well recognized that a disorder of the conduction system more distal than the atrioventricular node (AVN) results in a higher grade AV block. Therefore, a better understanding of variations in the position of the AVB is likely to help predict and potentially prevent new post-procedural conduction abnormalities. The triangle of Koch, which is defined by the tendon of Todaro, the attachment of the tricuspid valve, and the ostium of the coronary sinus, is often used as an anatomical landmark for the position of the AVN, whereas the lower border of the membranous septum (MS) is considered to be a landmark for the position of the AVB. However, the actual position of the AVB is generally adjacent to the infra-anterior border of the MS, covered by a roof of ventricular muscle and ascending
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Fig. 1. Positional variation of the atrioventricular conduction axis. a | Typical positions of the compact atrioventricular node in the triangle of Koch, which is defined by the tendon of Todaro (purple dots), the tricuspid valve (blue dots) and the ostium of the coronary sinus, and the atrioventricular bundle in the infra-anterior border of the membranous septum. Right chamber view in the corrected anatomical position. b–c | Positional variation of the atrioventricular bundle within the ventricular septum just below the membranous septum. The atrioventricular bundle positioned in the right and left halves of the ventricular septum, respectively. Sections through the centre of the membranous septum. d–f | The exposed atrioventricular bundle before (d) and after (e) dissection, and histological findings (f), respectively (modification after Kawashima T and Sasaki H. Gross anatomy of the human cardiac conduction system with comparative morphological and developmental implications for human application. Ann Anat 193(1), 1–12 (2011)). Abbreviations: AVB, atrioventricular bundle; AVN, atrioventricular node; CS, coronary sinus; LV, left ventricle; MS, membranous septum; RA, right atrium; RBB, right bundle branch; RC, right coronary cusp; RV, right ventricle; TT, tendon of Todaro; TV, tricuspid valve; VS, ventricular septum.
obliquely from the infra-posterior to supra-anterior directions (Fig. 1a). It can be challenging to identify the AVB as it transits the MS and enters the ventricular septum. Roughly speaking, the AVB courses within the right half of the ventricular septum in approximately 50% of cases (Fig. 1a–b) and in the left half in approximately 30% (Fig. 1c), and was found to arise from the ventricular septum and course on to the MS just under the endocardium in 26 out of 115 elderly hearts (22.6%, Fig. 1d–e). Based on the close proximity of the AVB to the aortic root complex, complete AV block requiring PPI can easily be anticipated if a calcified valve is crushed and/or insertion of the valve prosthesis exerts pressure on the surrounding tissues. Evidence of variant AVB position, especially if a branching AVB lies superficially within the left half of the ventricular septum (Fig. 1c), and exposure of the distal AVB (Fig. 1d–e), should be recognized as risk factors for a complete AV block after TAVI. New conduction disorders cannot yet be predicted before TAVI in clinical practice as current imaging techniques do not allow the position of the AVB to be visualized. An alternative approach is to recognize that the anatomical evidence of a variable AVB position might explain the association between use of wider prosthetic valves in a small annulus and the development of a new conduction abnormality. Although the implanted TAVI does not always injure the AV conduction system, an unpredictable AVB position could be one of the triggers of post-procedural complete AV block and prolonged QRS duration on the electrocardiogram [12,17]. Therefore, we suggest that in the absence of the ability to identify the position of the AVB, the width of the valve prosthesis must be selected
with care to avoid new conduction abnormalities, especially if the aortic valve is severely calcified. 3. Implications of the attitudinally corrected position of the branching AVB and left bundle branch for choice of valve height The morphology and position of the branching AVB and left bundle branch (LBB) are also directly associated with new conduction abnormalities after TAVI [6,10,17]. The branching AVB is a distal part of the AVB, a continuation of the non-branching or penetrating AVB, and divides into the right bundle branch (RBB) and LBB. Considering the development and structure of the MS, it is reasonable to assume that the entire width of the LBB lies within the MS. Generally speaking, the branching AVB is positioned in the anterior one-half to two-thirds of the infra-anterior border of the MS, and therefore the LBB courses into the left ventricle very soon after branching from the narrow origin of the AVB (Fig. 2). However, the position at which the LBB emerges from the deep ventricular septum and enters the superficial portion just under the endocardium also varies individually, and depends on the depth and position of the AVB within the ventricular septum (Fig. 1). In contrast, the anatomical position and characteristics of the LBB can also explain the occurrence of new left bundle branch block (LBBB) after TAVI. The frequency of new LBBB appears to be higher after CoreValve implantation (29–83%) [10,14,28–30] than Edwards SAPIEN implantation (6–18%) [18,20,31,32], which may be further influenced by any inflammation caused by the stent containing the valve prosthesis [30].
T. Kawashima, F. Sato / International Journal of Cardiology 174 (2014) 1–6
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Fig. 2. Morphology and positions of the atrioventricular bundle, bundle branches and membranous septum. a | The atrioventricular conduction axis viewed from the right chamber. b | The left bundle branch originating from the branching atrioventricular bundle in the anterior two-thirds of the membranous septum viewed from the left chamber. c | Section sites and macroscopic superimposition of the left bundle branch. d–h | Topographical changes of the atrioventricular conduction axis and its relationship with the membranous septum. Abbreviations: AVB, atrioventricular bundle; LBB, left bundle branch; LBBa, anterior radiation of left bundle branch; LBBp, posterior radiation of left bundle branch; LV, left ventricle; MS, membranous septum; NC, non-coronary cusp; RA, right atrium; RBB, right bundle branch; RC, right coronary cusp; RFT, right fibrous trigone; RV, right ventricle; STJ, sinotubular junction; TV, tricuspid valve; VAJ, ventriculoarterial junction; VS, ventricular septum.
The anatomical relationship between the basal ring (BR) and infraanterior border of the MS, which corresponds to the position of the branching AVB, may also be important (Fig. 3d–f). We found that the anterior half of the MS is positioned cranially to the BR in 78.1% of cases. The clinical incidence of complete AV block requiring PPI has been reported to be less frequent, in the region of 12–44% [1–9]. The difference may be explained by the occasional need to crush or press the calcified aortic valve leaflets against the distal AVB or MS. Moreover, we also demonstrated that the distal portion of the branching AVB was mostly contained within the aortic root complex, and the distal branching AVB lay up to 5 mm below the BR in all cases. Approximately one-third to one-half of the SAPIEN valve should sit below the most basal leaflet attachment (BR) to permit effective sealing [33], whereas the CoreValve prosthesis should be positioned approximately 4 mm (range 0–12 mm) below the BR [34]. The close proximity of the branching AVB to the valve implantation site may make it difficult to avoid a new conduction disorder after TAVI with the two most commonly used valves, regardless of their heights. The expectation that the shorter Edwards SAPIEN valve should be less likely to cause post-procedural LBBB and complete AV block after TAVI than the taller CoreValve in patients with pre-implantation RBBB appears to be reflected by the results of outcome studies [8,10,12,32]. It is important to identify the implantation area that carries the greatest risk of complete AV block after TAVI to inform current clinical practice and guide the design of new prostheses. 4. High-risk implantation area and the optimal design of the TAVI valve The position of the MS between the right coronary and non-coronary leaflets is also subject to inter-individual variation (Fig. 3a–c), although it is most frequently located on the side of the right coronary cusp. It is
perhaps not fully appreciated that the AVB is prone to injury if it lies near the non-coronary cusp [35]; the AVB and LBB emerge superficially approximately 6 mm below the non-coronary sinus just below the MS [28,34], while the LBB emerges at the junction between the noncoronary aspect of the MS and the right fibrous trigone (RFT, Fig. 4a) [8,17]. As shown in Fig. 2a–c, a non-branching or penetrating AVB running within the RFT is relatively longer and merges with the branching AVB at the anterior (right coronary) half to two-thirds of the base of the MS (Fig. 4b). Furthermore, the anterior MS basement line gradually impinges upon the BR in 78.1% of cases (identified by the red-dashed area of the LBB in Fig. 4b). This suggests that a distal branching AVB may be easily crushed or injured during TAVI, causing complete AV block and LBBB. Although all the specimens examined in our study were from Japanese subjects, we believe that it can be inferred that the area at greatest risk of injury during TAVI is the side of the MS adjacent to the right coronary cusp, not the non-coronary side as previously thought. Detailed inspection of the anatomy of the AV conduction system clearly shows that the position of the branching bundle is more anterior, distal and cranial than is generally recognized (indicated by the yellow arrows in Fig. 4b). It is anticipated that the design of newer transcatheter valves will reduce the incidence of new conduction abnormalities after TAVI, with clinical outcomes reported in large multicentre series, registries and trials [30,36]. The material from which the stent is manufactured is also likely to be important. The nitinol frame of the CoreValve might exert a higher pressure on the ventricular septum than the stainless steel or cobalt chromium frame of the Edwards SAPIEN valve [30]. Our findings suggest that the larger mesh stent of the third-generation Edwards SAPIEN XT® (Fig. 4d) may also afford advantages over second-generation valves (Fig. 4c). Outcomes after transapical implantation of the newer JenaValve®, which has a relatively smaller amount of stent material and a double-layer system of three
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Fig. 3. Positional variations of the membranous septum and branching atrioventricular bundle. a–c | Variation of the membranous septum indicated by an asterisk on the sides of the: (a) right cusp, (b) intermediate and (c) left cusp of the membranous septum. d–e | Structures of the aortic root: (d) aortic valve complex and (e) its opened structures. f | The area of the infra-anterior border of the membranous septum which corresponds to the position of the atrioventricular bundle, from the most basal points of the right coronary and non-coronary leaflets on the basal ring. Red and blue lines show the atrioventricular bundle within and outside the aortic root complex, respectively. The most distal atrioventricular bundles are visible on this section of the aortic root. Abbreviations: BR, basal ring; LC, left coronary cusp; LV, left ventricle; NC, non-coronary cusp; RC, right coronary cusp; STJ, sinotubular junction; VAJ, ventriculoarterial junction.
adjustable anchoring clips in two rows (Fig. 4e: JenaValve Technology, Munich, Germany) [37], also appear promising. The ability to adjust the distances between the clips under 3D computed tomography or magnetic resonance imaging guidance allows the operator to avoid traumatizing the high-risk area in which the AV conduction system may lie (Fig. 4f) [38–42]. Furthermore, some new generation transcatheter aortic valve systems, the JenaValve, Symetis Acurate™ (Symetis Inc., Switzerland) valve, and Engager™ Aortic Valve prosthesis (Medtronic, Inc., Minneapolis, MN, USA), are designed for subcoronary implantation and they might be an advantage with regard to avoiding coronary obstruction and paravalvular leakage [43,44]. Therefore, the design of the JenaValve is less likely to impinge on the AV conduction system, potentially reducing the incidence of new conduction disorders after TAVI, in addition to the prevention of coronary occlusion in patients such as Asians with shorter distance between the annulus and coronary ostia. Although further clinical trials are necessary, early reports suggest that post-procedural PPI has only been necessary in 9% of cases [44].
5. Conclusions We have identified that inter-individual variability in the position of the branching AVB and LBB is a likely anatomical cause of new conduction abnormalities after TAVI: more anterior, distal and cranial positions pose a higher risk than previously recognized. Current imaging techniques are not capable of determining the positions of these structures. The design of the JenaValve is less likely to impinge on the AV conduction system, potentially reducing the incidence of new conduction disorders after TAVI, in addition to the prevention of coronary occlusion in patients with shorter distance between the annulus and coronary ostia.
Author contributions T. Kawashima researched and wrote the article, and reviewed/edited the manuscript. F. Sato substantially contributed to the discussion of its content, and reviewed/edited the manuscript.
T. Kawashima, F. Sato / International Journal of Cardiology 174 (2014) 1–6
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Fig. 4. Variability in the position of the atrioventricular conduction system and recent advances in the design of transcatheter valves. a| Recent recognition of the left bundle branch position (modification after Khawaja, M. Z. et al. Permanent pacemaker insertion after CoreValve® transcatheter aortic valve implantation: incidence and contributing factors (the UK CoreValve Collaborative). Circulation 123(9), 951–960 (2011)). b| Position of the left bundle branch according to our findings. The branching AVB and origin of the LBB are closer to the right cusp side and lie more distally and cranially (indicated by the yellow arrows) than previously thought. c | The second-generation Edwards valve, Edwards SAPIEN® (Edwards Lifesciences Corporation, Irvine, CA, USA). ©2013 Edwards Lifesciences Corporation. All rights reserved. d | The third-generation Edwards SAPIEN XT® has larger mesh windows. ©2013 Edwards Lifesciences Corporation. All rights reserved. e | The JenaValve® (JenaValve Technology, Munich, Germany). ©2011 JenaValve Technology. All rights reserved. f | The JenaValve offers the ability to adjust the position of space between the anchoring clips in the high-risk area around the right coronary side of membranous septum. Abbreviations: BR, basal ring; LBB, left bundle branch; LC, left coronary sinus; LFT, left fibrous trigone; MS, membranous septum; MV, mitral valve; NC, non-coronary sinus; RC, right coronary sinus; RFT, right fibrous trigone; STJ, sinotubular junction; VAJ, ventriculoarterial junction; VS, ventricular septum.
Acknowledgements This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (No. 23791579) and a project research grant of Toho University School of Medicine (No. 23-29). This study complies with the Declaration of Helsinki and Ethics Committee of our university (No. 23011). The authors thank Mr. Makoto Sakai (Toho University, Tokyo, Japan) for his technical help.
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Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Review
Visualizing anatomical evidences on atrioventricular conduction system for TAVI Tomokazu Kawashima ⁎, Fumi Sato Department of Anatomy, School of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan
a r t i c l e
i n f o
Article history: Received 4 November 2013 Received in revised form 28 February 2014 Accepted 1 April 2014 Available online 12 April 2014 Keywords: Transcatheter aortic valve implantation Atrioventricular conduction system Clinical anatomy New conduction abnormalities Aortic stenosis
a b s t r a c t Visualizing the anatomy of the atrioventricular (AV) conduction axis substantiates that there is remarkable interindividual variation at the macro- and microscopic levels, and that the atrioventricular bundle and left bundle branch are located more anteriorly, distally, and cranially and much closer to the aortic root complex than previously thought. The AV conduction system may therefore be compromised during implantation of a transcatheter aortic valve prosthesis, which may account for the relatively high incidence of new cardiac conduction abnormalities when conventional prosthetic valves are used. The design of the newer JenaValve® may afford advantages over more conventional valves by avoiding the high-risk implantation area and the potential for coronary ostia obstruction. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Transcatheter aortic valve implantation (TAVI) is an effective means of treating patients with severe aortic stenosis in whom surgical aortic valve replacement (SAVR) is contraindicated as a consequence of high surgical risk. Nevertheless, higher grade atrioventricular (AV) block requiring permanent pacemaker implantation (PPI) is more common after TAVI (12–44%) than SAVR (3–8%) [1–9]. Recent retrospective studies have reported that the incidence of new conduction abnormalities after implantation of the CoreValve® (Medtronic CV, Luxembourg) is in the range of 9–44% [1,2,5,6,10–17], and 0–12% after implantation of the Edwards SAPIEN® (Edwards Lifesciences Corporation, Irvine, CA, USA) valve [6,14,15,18–23]. As the popularity of TAVI grows, the avoidance of new conduction abnormalities has emerged as a pressing problem. Most reports of new conduction abnormalities after TAVI have examined and identified a variety of contributing and predictive factors based on a conventional understanding of the anatomy of the cardiac conduction system. Several have sought to explain the causes of new conduction abnormalities using histological findings combined with actual cardiac photographs upon which a schematic of what is generally understood to represent the AV conduction system has been superimposed [6,8,10,17]. Importantly, however, the clinical importance of substantial inter-individual anatomic variation, and the function of newly identified areas of specialized myocardium in the paranodal area and the AV rings are still not ⁎ Corresponding author. Tel.: +81 3 3762 4151; fax: +81 3 5493 5411. E-mail address: [email protected] (T. Kawashima).
http://dx.doi.org/10.1016/j.ijcard.2014.04.003 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
completely understood [24–27]. Presently, technical difficulties can make some of the most important structures of the conduction system hard to visualize at a macroscopic level, although a non-branching atrioventricular bundle (AVB) may be evident within the solid central fibrous body. It has a whitish colour; the direction of the fibres in the branching AVB can be differentiated from surrounding cardiac myocytes; and continuous structures can be found within the AV conduction axis. In this brief review paper, we describe the current understanding of the extent and importance of inter-individual variation in the AV conduction system, how it may influence outcome after TAVI and a strategy for the design of transcatheter aortic valves that would reduce the incidence of new conduction abnormalities after implantation. 2. Implications of variant AVB position for implantable valve width It is well recognized that a disorder of the conduction system more distal than the atrioventricular node (AVN) results in a higher grade AV block. Therefore, a better understanding of variations in the position of the AVB is likely to help predict and potentially prevent new post-procedural conduction abnormalities. The triangle of Koch, which is defined by the tendon of Todaro, the attachment of the tricuspid valve, and the ostium of the coronary sinus, is often used as an anatomical landmark for the position of the AVN, whereas the lower border of the membranous septum (MS) is considered to be a landmark for the position of the AVB. However, the actual position of the AVB is generally adjacent to the infra-anterior border of the MS, covered by a roof of ventricular muscle and ascending
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Fig. 1. Positional variation of the atrioventricular conduction axis. a | Typical positions of the compact atrioventricular node in the triangle of Koch, which is defined by the tendon of Todaro (purple dots), the tricuspid valve (blue dots) and the ostium of the coronary sinus, and the atrioventricular bundle in the infra-anterior border of the membranous septum. Right chamber view in the corrected anatomical position. b–c | Positional variation of the atrioventricular bundle within the ventricular septum just below the membranous septum. The atrioventricular bundle positioned in the right and left halves of the ventricular septum, respectively. Sections through the centre of the membranous septum. d–f | The exposed atrioventricular bundle before (d) and after (e) dissection, and histological findings (f), respectively (modification after Kawashima T and Sasaki H. Gross anatomy of the human cardiac conduction system with comparative morphological and developmental implications for human application. Ann Anat 193(1), 1–12 (2011)). Abbreviations: AVB, atrioventricular bundle; AVN, atrioventricular node; CS, coronary sinus; LV, left ventricle; MS, membranous septum; RA, right atrium; RBB, right bundle branch; RC, right coronary cusp; RV, right ventricle; TT, tendon of Todaro; TV, tricuspid valve; VS, ventricular septum.
obliquely from the infra-posterior to supra-anterior directions (Fig. 1a). It can be challenging to identify the AVB as it transits the MS and enters the ventricular septum. Roughly speaking, the AVB courses within the right half of the ventricular septum in approximately 50% of cases (Fig. 1a–b) and in the left half in approximately 30% (Fig. 1c), and was found to arise from the ventricular septum and course on to the MS just under the endocardium in 26 out of 115 elderly hearts (22.6%, Fig. 1d–e). Based on the close proximity of the AVB to the aortic root complex, complete AV block requiring PPI can easily be anticipated if a calcified valve is crushed and/or insertion of the valve prosthesis exerts pressure on the surrounding tissues. Evidence of variant AVB position, especially if a branching AVB lies superficially within the left half of the ventricular septum (Fig. 1c), and exposure of the distal AVB (Fig. 1d–e), should be recognized as risk factors for a complete AV block after TAVI. New conduction disorders cannot yet be predicted before TAVI in clinical practice as current imaging techniques do not allow the position of the AVB to be visualized. An alternative approach is to recognize that the anatomical evidence of a variable AVB position might explain the association between use of wider prosthetic valves in a small annulus and the development of a new conduction abnormality. Although the implanted TAVI does not always injure the AV conduction system, an unpredictable AVB position could be one of the triggers of post-procedural complete AV block and prolonged QRS duration on the electrocardiogram [12,17]. Therefore, we suggest that in the absence of the ability to identify the position of the AVB, the width of the valve prosthesis must be selected
with care to avoid new conduction abnormalities, especially if the aortic valve is severely calcified. 3. Implications of the attitudinally corrected position of the branching AVB and left bundle branch for choice of valve height The morphology and position of the branching AVB and left bundle branch (LBB) are also directly associated with new conduction abnormalities after TAVI [6,10,17]. The branching AVB is a distal part of the AVB, a continuation of the non-branching or penetrating AVB, and divides into the right bundle branch (RBB) and LBB. Considering the development and structure of the MS, it is reasonable to assume that the entire width of the LBB lies within the MS. Generally speaking, the branching AVB is positioned in the anterior one-half to two-thirds of the infra-anterior border of the MS, and therefore the LBB courses into the left ventricle very soon after branching from the narrow origin of the AVB (Fig. 2). However, the position at which the LBB emerges from the deep ventricular septum and enters the superficial portion just under the endocardium also varies individually, and depends on the depth and position of the AVB within the ventricular septum (Fig. 1). In contrast, the anatomical position and characteristics of the LBB can also explain the occurrence of new left bundle branch block (LBBB) after TAVI. The frequency of new LBBB appears to be higher after CoreValve implantation (29–83%) [10,14,28–30] than Edwards SAPIEN implantation (6–18%) [18,20,31,32], which may be further influenced by any inflammation caused by the stent containing the valve prosthesis [30].
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Fig. 2. Morphology and positions of the atrioventricular bundle, bundle branches and membranous septum. a | The atrioventricular conduction axis viewed from the right chamber. b | The left bundle branch originating from the branching atrioventricular bundle in the anterior two-thirds of the membranous septum viewed from the left chamber. c | Section sites and macroscopic superimposition of the left bundle branch. d–h | Topographical changes of the atrioventricular conduction axis and its relationship with the membranous septum. Abbreviations: AVB, atrioventricular bundle; LBB, left bundle branch; LBBa, anterior radiation of left bundle branch; LBBp, posterior radiation of left bundle branch; LV, left ventricle; MS, membranous septum; NC, non-coronary cusp; RA, right atrium; RBB, right bundle branch; RC, right coronary cusp; RFT, right fibrous trigone; RV, right ventricle; STJ, sinotubular junction; TV, tricuspid valve; VAJ, ventriculoarterial junction; VS, ventricular septum.
The anatomical relationship between the basal ring (BR) and infraanterior border of the MS, which corresponds to the position of the branching AVB, may also be important (Fig. 3d–f). We found that the anterior half of the MS is positioned cranially to the BR in 78.1% of cases. The clinical incidence of complete AV block requiring PPI has been reported to be less frequent, in the region of 12–44% [1–9]. The difference may be explained by the occasional need to crush or press the calcified aortic valve leaflets against the distal AVB or MS. Moreover, we also demonstrated that the distal portion of the branching AVB was mostly contained within the aortic root complex, and the distal branching AVB lay up to 5 mm below the BR in all cases. Approximately one-third to one-half of the SAPIEN valve should sit below the most basal leaflet attachment (BR) to permit effective sealing [33], whereas the CoreValve prosthesis should be positioned approximately 4 mm (range 0–12 mm) below the BR [34]. The close proximity of the branching AVB to the valve implantation site may make it difficult to avoid a new conduction disorder after TAVI with the two most commonly used valves, regardless of their heights. The expectation that the shorter Edwards SAPIEN valve should be less likely to cause post-procedural LBBB and complete AV block after TAVI than the taller CoreValve in patients with pre-implantation RBBB appears to be reflected by the results of outcome studies [8,10,12,32]. It is important to identify the implantation area that carries the greatest risk of complete AV block after TAVI to inform current clinical practice and guide the design of new prostheses. 4. High-risk implantation area and the optimal design of the TAVI valve The position of the MS between the right coronary and non-coronary leaflets is also subject to inter-individual variation (Fig. 3a–c), although it is most frequently located on the side of the right coronary cusp. It is
perhaps not fully appreciated that the AVB is prone to injury if it lies near the non-coronary cusp [35]; the AVB and LBB emerge superficially approximately 6 mm below the non-coronary sinus just below the MS [28,34], while the LBB emerges at the junction between the noncoronary aspect of the MS and the right fibrous trigone (RFT, Fig. 4a) [8,17]. As shown in Fig. 2a–c, a non-branching or penetrating AVB running within the RFT is relatively longer and merges with the branching AVB at the anterior (right coronary) half to two-thirds of the base of the MS (Fig. 4b). Furthermore, the anterior MS basement line gradually impinges upon the BR in 78.1% of cases (identified by the red-dashed area of the LBB in Fig. 4b). This suggests that a distal branching AVB may be easily crushed or injured during TAVI, causing complete AV block and LBBB. Although all the specimens examined in our study were from Japanese subjects, we believe that it can be inferred that the area at greatest risk of injury during TAVI is the side of the MS adjacent to the right coronary cusp, not the non-coronary side as previously thought. Detailed inspection of the anatomy of the AV conduction system clearly shows that the position of the branching bundle is more anterior, distal and cranial than is generally recognized (indicated by the yellow arrows in Fig. 4b). It is anticipated that the design of newer transcatheter valves will reduce the incidence of new conduction abnormalities after TAVI, with clinical outcomes reported in large multicentre series, registries and trials [30,36]. The material from which the stent is manufactured is also likely to be important. The nitinol frame of the CoreValve might exert a higher pressure on the ventricular septum than the stainless steel or cobalt chromium frame of the Edwards SAPIEN valve [30]. Our findings suggest that the larger mesh stent of the third-generation Edwards SAPIEN XT® (Fig. 4d) may also afford advantages over second-generation valves (Fig. 4c). Outcomes after transapical implantation of the newer JenaValve®, which has a relatively smaller amount of stent material and a double-layer system of three
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Fig. 3. Positional variations of the membranous septum and branching atrioventricular bundle. a–c | Variation of the membranous septum indicated by an asterisk on the sides of the: (a) right cusp, (b) intermediate and (c) left cusp of the membranous septum. d–e | Structures of the aortic root: (d) aortic valve complex and (e) its opened structures. f | The area of the infra-anterior border of the membranous septum which corresponds to the position of the atrioventricular bundle, from the most basal points of the right coronary and non-coronary leaflets on the basal ring. Red and blue lines show the atrioventricular bundle within and outside the aortic root complex, respectively. The most distal atrioventricular bundles are visible on this section of the aortic root. Abbreviations: BR, basal ring; LC, left coronary cusp; LV, left ventricle; NC, non-coronary cusp; RC, right coronary cusp; STJ, sinotubular junction; VAJ, ventriculoarterial junction.
adjustable anchoring clips in two rows (Fig. 4e: JenaValve Technology, Munich, Germany) [37], also appear promising. The ability to adjust the distances between the clips under 3D computed tomography or magnetic resonance imaging guidance allows the operator to avoid traumatizing the high-risk area in which the AV conduction system may lie (Fig. 4f) [38–42]. Furthermore, some new generation transcatheter aortic valve systems, the JenaValve, Symetis Acurate™ (Symetis Inc., Switzerland) valve, and Engager™ Aortic Valve prosthesis (Medtronic, Inc., Minneapolis, MN, USA), are designed for subcoronary implantation and they might be an advantage with regard to avoiding coronary obstruction and paravalvular leakage [43,44]. Therefore, the design of the JenaValve is less likely to impinge on the AV conduction system, potentially reducing the incidence of new conduction disorders after TAVI, in addition to the prevention of coronary occlusion in patients such as Asians with shorter distance between the annulus and coronary ostia. Although further clinical trials are necessary, early reports suggest that post-procedural PPI has only been necessary in 9% of cases [44].
5. Conclusions We have identified that inter-individual variability in the position of the branching AVB and LBB is a likely anatomical cause of new conduction abnormalities after TAVI: more anterior, distal and cranial positions pose a higher risk than previously recognized. Current imaging techniques are not capable of determining the positions of these structures. The design of the JenaValve is less likely to impinge on the AV conduction system, potentially reducing the incidence of new conduction disorders after TAVI, in addition to the prevention of coronary occlusion in patients with shorter distance between the annulus and coronary ostia.
Author contributions T. Kawashima researched and wrote the article, and reviewed/edited the manuscript. F. Sato substantially contributed to the discussion of its content, and reviewed/edited the manuscript.
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Fig. 4. Variability in the position of the atrioventricular conduction system and recent advances in the design of transcatheter valves. a| Recent recognition of the left bundle branch position (modification after Khawaja, M. Z. et al. Permanent pacemaker insertion after CoreValve® transcatheter aortic valve implantation: incidence and contributing factors (the UK CoreValve Collaborative). Circulation 123(9), 951–960 (2011)). b| Position of the left bundle branch according to our findings. The branching AVB and origin of the LBB are closer to the right cusp side and lie more distally and cranially (indicated by the yellow arrows) than previously thought. c | The second-generation Edwards valve, Edwards SAPIEN® (Edwards Lifesciences Corporation, Irvine, CA, USA). ©2013 Edwards Lifesciences Corporation. All rights reserved. d | The third-generation Edwards SAPIEN XT® has larger mesh windows. ©2013 Edwards Lifesciences Corporation. All rights reserved. e | The JenaValve® (JenaValve Technology, Munich, Germany). ©2011 JenaValve Technology. All rights reserved. f | The JenaValve offers the ability to adjust the position of space between the anchoring clips in the high-risk area around the right coronary side of membranous septum. Abbreviations: BR, basal ring; LBB, left bundle branch; LC, left coronary sinus; LFT, left fibrous trigone; MS, membranous septum; MV, mitral valve; NC, non-coronary sinus; RC, right coronary sinus; RFT, right fibrous trigone; STJ, sinotubular junction; VAJ, ventriculoarterial junction; VS, ventricular septum.
Acknowledgements This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (No. 23791579) and a project research grant of Toho University School of Medicine (No. 23-29). This study complies with the Declaration of Helsinki and Ethics Committee of our university (No. 23011). The authors thank Mr. Makoto Sakai (Toho University, Tokyo, Japan) for his technical help.
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