Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/28/15 For personal use only.
Review
Tachyarrhythmias and catheter ablation in adult congenital heart disease Expert Rev. Cardiovasc. Ther. 12(6), 751–770 (2014)
Henry Chubb1,2, Steven E Williams1,3, Matthew Wright1,3, Eric Rosenthal2,3 and Mark O’Neill*1,3 1 Division of Imaging Sciences and Biomedical Engineering and Division of Cardiovascular Medicine, King’s College London, 4th Floor, North Wing, St Thomas’ Hospital, Westminster Bridge Road, London, UK 2 Department of Paediatric Cardiology, Evelina London Children’s Hospital, London, UK 3 Adult Congenital Heart Disease Group, Departments of Cardiology at Guy’s and St Thomas’ NHS Foundation Trust and Evelina London Children’s Hospital, London, UK *Author for correspondence: Tel.: +44 020 7188 4989 Fax: +44 020 7188 5442 [email protected]
informahealthcare.com
Advances in surgical technique have had an immense impact on longevity and quality of life in patients with congenital heart disease. However, an inevitable consequence of these surgical successes is the creation of a unique patient population whose anatomy, surgical history and haemodynamics result in the development of a challenging and complex arrhythmia substrate. Furthermore, this patient group remains susceptible to the arrhythmias seen in the general adult population. It is through a thorough appreciation of the cardiac structural defect, the surgical corrective approach, and haemodynamic impact that the most effective arrhythmia care can be delivered. Catheter ablation techniques offer a highly effective management option but require a meticulous attention to the real-time integration of anatomical and electrophysiological information to identify and eliminate the culprit arrhythmia substrate. This review describes the current approach to the interventional management of patients with tachyarrhythmias in the context of congenital heart disease. KEYWORDS: arrhythmia • congenital heart disease • electrophysiology • sudden death
Congenital heart defects occur in approximately 7.5 births per 1000 [1] and approximately 50% are severe enough to warrant intervention in childhood. Today, more than 85% of these patients survive into adulthood, with approximately 1 million patients living with congenital heart disease (CHD) in the USA [2], and at least a further 1.2 million in Europe [3]. Of these, more than 50% are adults. Among patients with CHD, arrhythmias in childhood are relatively rare, but the arrhythmia burden increases significantly with age. The onset of a new arrhythmia represents the result of an acute arrhythmia trigger after years of gradual development of the appropriate hemodynamic and electrophysiological substrate to sustain tachycardia. Fifty percent of adults living with repaired CHD can be expected to be admitted to hospital over any 5-year period, and of these 20% will be arrhythmia related [4], the leading single cause of morbidity and hospital admissions. While the full spectrum of brady- and tachyarrhythmias is encountered in the CHD population, this review focuses on tachyarrhythmias and the role of catheter ablation in their treatment.
10.1586/14779072.2014.914434
Arrhythmia burden Pathophysiological factors
The factors that precipitate rhythm abnormalities in patients with CHD can be broadly divided into two groups: those that are present at birth and those that evolve over time, including the consequences of treatment strategies and hemodynamic abnormalities. Genetics
To our knowledge, there is no evidence that any genetic abnormality directly associated with cardiac arrhythmia, such as those causing monogenic ion-channel disease (channelopathies), has been causally linked to structural heart disease [5]. However, there are rare cases where genetic mutations causing structural and rhythm abnormities have been established. The Tbx5 gene, linked to Holt–Oram syndrome, is involved in the maturation of the conduction system as well as the creation of an atrial septal defect (ASD) [6]. Genetic mutations associated with Wolff–Parkinson–White syndrome have also been identified [7,8]. With the advent of whole genome array comparative genomic hybridization, it seems likely that in
2014 Informa UK Ltd
ISSN 1477-9072
751
Review
Chubb, Williams, Wright, Rosenthal & O’Neill
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/28/15 For personal use only.
Table 1. The typical associated abnormalities of the conduction system with defined cardiac lesions. Sinoatrial node
AV node
AV bundle
His-Purkinje system
Absent right AV connection
Normal
Muscular floor of the RA, adjacent to an abnormally formed central fibrous body [25]
Penetrates fibrous body toward the left side of the septum
Long non-branching segment at posterior margin of VSD (if present)
Ebstein’s anomaly
Normal
Normal
Normal
Normal
Accessory pathways commonly occur (up to 40%)
DILV
Normal
Posteroinferior [36] or anterolateral [123]
Dependent upon relationship of LV and RV [123]
Long non-branching segment at posterior margin of VSD
Many variations in conduction system described
AVSD
Normal
Outside of triangle of Koch- inferior, anterior to os of coronary sinus
Passes along lower rim of the ventricular septum
Extensive non-branching bundle on the crest of the inlet part of the muscular septum
Left atrial isomerism
None or hypoplastic and located posteroinferiorly, distal to SVC
Complete AV block in 15% at birth
Interrupted in 10–20%
Usually normal, dependent upon septal anatomy
Mo¨nckeberg sling may exist between bundles
[124]
Notes
Some may have twin AVNs [25]
Right atrial isomerism
Often two: at junction of SVC and RA on each side [25]
Twin AVNs (anterior and posterior)
Often twin AV bundles
Dependent upon septal anatomy
Mo¨nckeberg sling may exist between bundles
Discordant AV connections
Normal
Atrial wall related to the anterolateral quadrant of the MV
Running through region of fibrous continuity between MV and posterior great artery
Long non-branching segment courses anterior to the outflow tract of the posterior great artery (anterior-superior to VSD if present)
Second, posterior, AVN may be present. Mo¨nckeberg sling may connect the two non-branching segments
AV: Atrioventricular; AVN: Atrioventricular node; AVSD: Atrioventriculoseptal defect; DILV: Double inlet left ventricle; MV: Mitral valve; RA: Right atrium; SVC: Superior vena cava; VSD: Ventricular septal defect.
the future genetic abnormalities will be identified in patients with CHD that predispose to arrhythmia over and above their peers with similar structural heart disease, and this may aid risk stratification. Conduction system
Abnormalities of the conduction system associated with CHD are well described. The embryonic cardiac conduction system is far broader than the definitive adult conduction system, and many factors are involved in the maturation and specialization process that continues well beyond birth. The Leiden University Group have published an detailed review of the development of the cardiac conduction system [6], and controversies remain regarding the processes involved. Many structural forms of CHD are associated with predictable conduction system abnormalities, but a degree of heterogeneity remains. The groups of lesions most commonly associated with abnormalities of the conduction system are those with malalignment of the septal structures, particularly 752
those with laterality disturbances. The typical distribution of the conduction system in those lesions is detailed in TABLE 1. An understanding of these malformations is important for the interventionalist not only in reducing complications of ablation therapy, but also in the elucidation of some tachyarrhythmia mechanisms. Consequences of treatment & hemodynamic status
Long-term suboptimal hemodynamic conditions and surgical scarring provide ideal substrate for arrhythmogenesis. Over time, volume overloaded atria exhibit electrical remodeling [9] and increased thickness [10], with extension of the scar regions [11]. The pathological findings regarding fibrosis within the volume and pressure overloaded atrium are mixed. Some groups have reported relatively little fibrosis [10], while others have documented significantly increased fibrosis, with increased myocyte diameter and longer inter-capillary distances [12]. These differences may reflect patient selection and, perhaps, a pathophysiological distinction: it may be the case Expert Rev. Cardiovasc. Ther. 12(6), (2014)
Tachyarrhythmias & catheter ablation in adult CHD
A
B
SVC
C
SVC RPA
RPA
Review
SVC RPA
SVC Right auricle used as a conduit to the RPA
Anastomosis of enlarged cardiac end of SVC to RP
RA closed
Gore-tex conduit
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/28/15 For personal use only.
RA ASD closed
Placement of baffle inside right atrium, forming a channel with a decreased diameter
RA
Tricuspid valve closed
RA
RA closed IVC
IVC IVC
Classical Fontan
Lateral tunnel (intra-atrial baffle)
Extra-cardiac conduit
Figure 1. The evolution of Fontan surgical techniques. Classical atriopulmonary connection (A) lateral tunnel (B) and extracardiac conduit (C). ASD: Atrial septal defect; IVC: Inferior vena cava; RA: Right atrium; RPA: Right pulmonary artery; SVC: Superior vena cava. Reproduced with permission from [16].
that fibrosis is not simply a cause but also an effect of atrial arrhythmia (AA). In contrast, the pressure and volume overloaded ventricles may often develop significant fibrosis [13]. However, there is no doubt that there is an evolving substrate for arrhythmias, not related simply to location of surgical scars, reflected in relatively low prevalence of arrhythmias in the early years, and high prevalence at older age. Changes in surgical technique have played a key role in the reduced prevalence of arrhythmias in CHD. The evolution of the Fontan technique from the classical Fontan, with a direct atriopulmonary connection, to the lateral tunnel and extracardiac conduit (FIGURE 1) has bought about a significant reduction in late arrhythmias from approximately 20 to 5% in 8 years [14–16]. This reflects particularly the reduction in right atrial dilation that occurred with the classical atriopulmonary (AP) Fontan procedure, and also smaller stepwise improvements in surgical techniques and medical management. Atrial switches are now exceptionally rare for patients with transposition of the great arteries with normal looping of the right ventricle (TGA), with a consequent significant reduction in AAs and sinoatrial node dysfunction. Parallel changes in the surgical approach to Tetralogy of Fallot (ToF) have also bought about a reduction in late arrhythmias, with reduced use of ventriculotomies and maintenance of a competent pulmonary valve (PV) where possible [17]. The advancement of catheter techniques has also served to reduce the surgical intervention rate and therefore the surgical scar burden. For example, in pulmonary atresia with intact ventricular septum, those patients who underwent radiofrequency (RF) perforation of the atretic PV, rather than a surgical valvotomy, have a vastly reduced prevalence of cardiac arrhythmias in long-term follow-up [18–20].
informahealthcare.com
Prevalence of arrhythmias
The prevalence of tachyarrhythmias in the congenital population has been studied by a variety of methods. By reviewing the records of 38,428 patients with CHD, Bouchardy et al. [21] identified 5812 patients (15.1%) with documented AAs. However, there is a marked increase in prevalence with advancing age, with >50% of patients with CHD (that reach adulthood) experiencing AAs by the age of 65 years, and this rises to 63% for those with severe CHD. A subsequent review also suggested that AAs are more common in rightsided lesions than left-sided (61 vs 54% lifetime risk, respectively) [22]. However, even this high figure may underrepresent the true prevalence, as a significant proportion of arrhythmias in the CHD population are asymptomatic. Czosek et al. [23] reviewed 589 Holter studies performed on 189 patients with TOF, dextro-transposition of the great arteries (d-TGA) (after an atrial switch) and single ventricle circulation. It is interesting to note that of 44 patients with symptoms during the recording, only on one occasion was it associated with a sustained arrhythmia (atrial flutter). In contrast, the arrhythmias that precipitated a change in management were generally asymptomatic. Rodriguez et al. [24] have also looked at the prevalence of arrhythmias as assessed by ambulatory monitoring, and 76% of the arrhythmias in their 140 patients with CHD over 18 years old were asymptomatic (arrhythmias occurred in 30%). The quoted prevalence of arrhythmias for each congenital lesion varies widely, depending upon diagnostic criteria, surgical era and length of follow-up (TABLE 2). Khairy et al. [25] have published an excellent review of arrhythmias according to specific cardiac lesions and recent retrospective studies have added to that knowledge base. The most common cardiac lesions 753
Review
Chubb, Williams, Wright, Rosenthal & O’Neill
Table 2. Quoted prevalence of arrhythmias in congenital heart disease.
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/28/15 For personal use only.
Intervention
Accessory pathway
IART
AF
Focal atrial
VT
Ref.
ASD
Highly dependent upon age and management strategy (see text)
[21,28,80]
VSD
Highly dependent upon age and management strategy (see text)
[21,27]
AVSD
Surgical repair
TOF
Surgical repair
7.6%
Review
Tachyarrhythmias and catheter ablation in adult congenital heart disease Expert Rev. Cardiovasc. Ther. 12(6), 751–770 (2014)
Henry Chubb1,2, Steven E Williams1,3, Matthew Wright1,3, Eric Rosenthal2,3 and Mark O’Neill*1,3 1 Division of Imaging Sciences and Biomedical Engineering and Division of Cardiovascular Medicine, King’s College London, 4th Floor, North Wing, St Thomas’ Hospital, Westminster Bridge Road, London, UK 2 Department of Paediatric Cardiology, Evelina London Children’s Hospital, London, UK 3 Adult Congenital Heart Disease Group, Departments of Cardiology at Guy’s and St Thomas’ NHS Foundation Trust and Evelina London Children’s Hospital, London, UK *Author for correspondence: Tel.: +44 020 7188 4989 Fax: +44 020 7188 5442 [email protected]
informahealthcare.com
Advances in surgical technique have had an immense impact on longevity and quality of life in patients with congenital heart disease. However, an inevitable consequence of these surgical successes is the creation of a unique patient population whose anatomy, surgical history and haemodynamics result in the development of a challenging and complex arrhythmia substrate. Furthermore, this patient group remains susceptible to the arrhythmias seen in the general adult population. It is through a thorough appreciation of the cardiac structural defect, the surgical corrective approach, and haemodynamic impact that the most effective arrhythmia care can be delivered. Catheter ablation techniques offer a highly effective management option but require a meticulous attention to the real-time integration of anatomical and electrophysiological information to identify and eliminate the culprit arrhythmia substrate. This review describes the current approach to the interventional management of patients with tachyarrhythmias in the context of congenital heart disease. KEYWORDS: arrhythmia • congenital heart disease • electrophysiology • sudden death
Congenital heart defects occur in approximately 7.5 births per 1000 [1] and approximately 50% are severe enough to warrant intervention in childhood. Today, more than 85% of these patients survive into adulthood, with approximately 1 million patients living with congenital heart disease (CHD) in the USA [2], and at least a further 1.2 million in Europe [3]. Of these, more than 50% are adults. Among patients with CHD, arrhythmias in childhood are relatively rare, but the arrhythmia burden increases significantly with age. The onset of a new arrhythmia represents the result of an acute arrhythmia trigger after years of gradual development of the appropriate hemodynamic and electrophysiological substrate to sustain tachycardia. Fifty percent of adults living with repaired CHD can be expected to be admitted to hospital over any 5-year period, and of these 20% will be arrhythmia related [4], the leading single cause of morbidity and hospital admissions. While the full spectrum of brady- and tachyarrhythmias is encountered in the CHD population, this review focuses on tachyarrhythmias and the role of catheter ablation in their treatment.
10.1586/14779072.2014.914434
Arrhythmia burden Pathophysiological factors
The factors that precipitate rhythm abnormalities in patients with CHD can be broadly divided into two groups: those that are present at birth and those that evolve over time, including the consequences of treatment strategies and hemodynamic abnormalities. Genetics
To our knowledge, there is no evidence that any genetic abnormality directly associated with cardiac arrhythmia, such as those causing monogenic ion-channel disease (channelopathies), has been causally linked to structural heart disease [5]. However, there are rare cases where genetic mutations causing structural and rhythm abnormities have been established. The Tbx5 gene, linked to Holt–Oram syndrome, is involved in the maturation of the conduction system as well as the creation of an atrial septal defect (ASD) [6]. Genetic mutations associated with Wolff–Parkinson–White syndrome have also been identified [7,8]. With the advent of whole genome array comparative genomic hybridization, it seems likely that in
2014 Informa UK Ltd
ISSN 1477-9072
751
Review
Chubb, Williams, Wright, Rosenthal & O’Neill
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/28/15 For personal use only.
Table 1. The typical associated abnormalities of the conduction system with defined cardiac lesions. Sinoatrial node
AV node
AV bundle
His-Purkinje system
Absent right AV connection
Normal
Muscular floor of the RA, adjacent to an abnormally formed central fibrous body [25]
Penetrates fibrous body toward the left side of the septum
Long non-branching segment at posterior margin of VSD (if present)
Ebstein’s anomaly
Normal
Normal
Normal
Normal
Accessory pathways commonly occur (up to 40%)
DILV
Normal
Posteroinferior [36] or anterolateral [123]
Dependent upon relationship of LV and RV [123]
Long non-branching segment at posterior margin of VSD
Many variations in conduction system described
AVSD
Normal
Outside of triangle of Koch- inferior, anterior to os of coronary sinus
Passes along lower rim of the ventricular septum
Extensive non-branching bundle on the crest of the inlet part of the muscular septum
Left atrial isomerism
None or hypoplastic and located posteroinferiorly, distal to SVC
Complete AV block in 15% at birth
Interrupted in 10–20%
Usually normal, dependent upon septal anatomy
Mo¨nckeberg sling may exist between bundles
[124]
Notes
Some may have twin AVNs [25]
Right atrial isomerism
Often two: at junction of SVC and RA on each side [25]
Twin AVNs (anterior and posterior)
Often twin AV bundles
Dependent upon septal anatomy
Mo¨nckeberg sling may exist between bundles
Discordant AV connections
Normal
Atrial wall related to the anterolateral quadrant of the MV
Running through region of fibrous continuity between MV and posterior great artery
Long non-branching segment courses anterior to the outflow tract of the posterior great artery (anterior-superior to VSD if present)
Second, posterior, AVN may be present. Mo¨nckeberg sling may connect the two non-branching segments
AV: Atrioventricular; AVN: Atrioventricular node; AVSD: Atrioventriculoseptal defect; DILV: Double inlet left ventricle; MV: Mitral valve; RA: Right atrium; SVC: Superior vena cava; VSD: Ventricular septal defect.
the future genetic abnormalities will be identified in patients with CHD that predispose to arrhythmia over and above their peers with similar structural heart disease, and this may aid risk stratification. Conduction system
Abnormalities of the conduction system associated with CHD are well described. The embryonic cardiac conduction system is far broader than the definitive adult conduction system, and many factors are involved in the maturation and specialization process that continues well beyond birth. The Leiden University Group have published an detailed review of the development of the cardiac conduction system [6], and controversies remain regarding the processes involved. Many structural forms of CHD are associated with predictable conduction system abnormalities, but a degree of heterogeneity remains. The groups of lesions most commonly associated with abnormalities of the conduction system are those with malalignment of the septal structures, particularly 752
those with laterality disturbances. The typical distribution of the conduction system in those lesions is detailed in TABLE 1. An understanding of these malformations is important for the interventionalist not only in reducing complications of ablation therapy, but also in the elucidation of some tachyarrhythmia mechanisms. Consequences of treatment & hemodynamic status
Long-term suboptimal hemodynamic conditions and surgical scarring provide ideal substrate for arrhythmogenesis. Over time, volume overloaded atria exhibit electrical remodeling [9] and increased thickness [10], with extension of the scar regions [11]. The pathological findings regarding fibrosis within the volume and pressure overloaded atrium are mixed. Some groups have reported relatively little fibrosis [10], while others have documented significantly increased fibrosis, with increased myocyte diameter and longer inter-capillary distances [12]. These differences may reflect patient selection and, perhaps, a pathophysiological distinction: it may be the case Expert Rev. Cardiovasc. Ther. 12(6), (2014)
Tachyarrhythmias & catheter ablation in adult CHD
A
B
SVC
C
SVC RPA
RPA
Review
SVC RPA
SVC Right auricle used as a conduit to the RPA
Anastomosis of enlarged cardiac end of SVC to RP
RA closed
Gore-tex conduit
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/28/15 For personal use only.
RA ASD closed
Placement of baffle inside right atrium, forming a channel with a decreased diameter
RA
Tricuspid valve closed
RA
RA closed IVC
IVC IVC
Classical Fontan
Lateral tunnel (intra-atrial baffle)
Extra-cardiac conduit
Figure 1. The evolution of Fontan surgical techniques. Classical atriopulmonary connection (A) lateral tunnel (B) and extracardiac conduit (C). ASD: Atrial septal defect; IVC: Inferior vena cava; RA: Right atrium; RPA: Right pulmonary artery; SVC: Superior vena cava. Reproduced with permission from [16].
that fibrosis is not simply a cause but also an effect of atrial arrhythmia (AA). In contrast, the pressure and volume overloaded ventricles may often develop significant fibrosis [13]. However, there is no doubt that there is an evolving substrate for arrhythmias, not related simply to location of surgical scars, reflected in relatively low prevalence of arrhythmias in the early years, and high prevalence at older age. Changes in surgical technique have played a key role in the reduced prevalence of arrhythmias in CHD. The evolution of the Fontan technique from the classical Fontan, with a direct atriopulmonary connection, to the lateral tunnel and extracardiac conduit (FIGURE 1) has bought about a significant reduction in late arrhythmias from approximately 20 to 5% in 8 years [14–16]. This reflects particularly the reduction in right atrial dilation that occurred with the classical atriopulmonary (AP) Fontan procedure, and also smaller stepwise improvements in surgical techniques and medical management. Atrial switches are now exceptionally rare for patients with transposition of the great arteries with normal looping of the right ventricle (TGA), with a consequent significant reduction in AAs and sinoatrial node dysfunction. Parallel changes in the surgical approach to Tetralogy of Fallot (ToF) have also bought about a reduction in late arrhythmias, with reduced use of ventriculotomies and maintenance of a competent pulmonary valve (PV) where possible [17]. The advancement of catheter techniques has also served to reduce the surgical intervention rate and therefore the surgical scar burden. For example, in pulmonary atresia with intact ventricular septum, those patients who underwent radiofrequency (RF) perforation of the atretic PV, rather than a surgical valvotomy, have a vastly reduced prevalence of cardiac arrhythmias in long-term follow-up [18–20].
informahealthcare.com
Prevalence of arrhythmias
The prevalence of tachyarrhythmias in the congenital population has been studied by a variety of methods. By reviewing the records of 38,428 patients with CHD, Bouchardy et al. [21] identified 5812 patients (15.1%) with documented AAs. However, there is a marked increase in prevalence with advancing age, with >50% of patients with CHD (that reach adulthood) experiencing AAs by the age of 65 years, and this rises to 63% for those with severe CHD. A subsequent review also suggested that AAs are more common in rightsided lesions than left-sided (61 vs 54% lifetime risk, respectively) [22]. However, even this high figure may underrepresent the true prevalence, as a significant proportion of arrhythmias in the CHD population are asymptomatic. Czosek et al. [23] reviewed 589 Holter studies performed on 189 patients with TOF, dextro-transposition of the great arteries (d-TGA) (after an atrial switch) and single ventricle circulation. It is interesting to note that of 44 patients with symptoms during the recording, only on one occasion was it associated with a sustained arrhythmia (atrial flutter). In contrast, the arrhythmias that precipitated a change in management were generally asymptomatic. Rodriguez et al. [24] have also looked at the prevalence of arrhythmias as assessed by ambulatory monitoring, and 76% of the arrhythmias in their 140 patients with CHD over 18 years old were asymptomatic (arrhythmias occurred in 30%). The quoted prevalence of arrhythmias for each congenital lesion varies widely, depending upon diagnostic criteria, surgical era and length of follow-up (TABLE 2). Khairy et al. [25] have published an excellent review of arrhythmias according to specific cardiac lesions and recent retrospective studies have added to that knowledge base. The most common cardiac lesions 753
Review
Chubb, Williams, Wright, Rosenthal & O’Neill
Table 2. Quoted prevalence of arrhythmias in congenital heart disease.
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/28/15 For personal use only.
Intervention
Accessory pathway
IART
AF
Focal atrial
VT
Ref.
ASD
Highly dependent upon age and management strategy (see text)
[21,28,80]
VSD
Highly dependent upon age and management strategy (see text)
[21,27]
AVSD
Surgical repair
TOF
Surgical repair
7.6%
