- Email: [email protected]
Suitability of cardiac resynchronisation therapy in patients with Fontan circulation and congenitally corrected transposition of the great arteries
Suitability of cardiac resynchronisation therapy in patients with Fontan circulation and congenitally corrected transposition of the great arteries P. Demetriades, A. Bell, C. Gubran, H. Marshall, J. de Bono, L. Hudsmith PII: DOI: Reference:
S0167-5273(17)32672-4 doi:10.1016/j.ijcard.2017.08.066 IJCA 25396
To appear in:
International Journal of Cardiology
Received date: Revised date: Accepted date:
4 May 2017 18 August 2017 29 August 2017
Please cite this article as: Demetriades P, Bell A, Gubran C, Marshall H, de Bono J, Hudsmith L, Suitability of cardiac resynchronisation therapy in patients with Fontan circulation and congenitally corrected transposition of the great arteries, International Journal of Cardiology (2017), doi:10.1016/j.ijcard.2017.08.066
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Suitability of Cardiac Resynchronisation Therapy in Patients with Fontan Circulation
IP
T
and Congenitally Corrected Transposition of the Great Arteries
SC R
Authors:
Demetriades P1, Bell A2, Gubran C1, Marshall H1, de Bono J1, Hudsmith L1
NU
1. Department of Adult Congenital Heart Disease, Birmingham, United Kingdom 2. University of Birmingham Medical School, Birmingham, United Kingdom
MA
All above authors take responsibility for all aspects of the reliability and freedom from
D
bias of the data presented and their discussed interpretation
TE
Corresponding Author
CE P
Name: Dr Polyvios Demetriades
Email: [email protected]
AC
Postal address: Cardiology Department, Queen Elizabeth Hospital, Mindelsohn Way Edgbaston, Birmingham, B15 2GW (Cardiology secretaries: 0121 371 4494) Grant support This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors Conflicts of interest The authors report no relationships that could be construed as a conflict of interest
ACCEPTED MANUSCRIPT Key Words Cardiac resynchronisation therapy, Adult Congenital Heart Disease, Fontan
IP
T
circulation, Congenitally Corrected Transposition of Great Arteries, Heart failure
SC R
Abbreviations
CRT: cardiac resynchronisation therapy; LV: left ventricle; RV: right ventricle; ACHD: adult congenital heart disease; ccTGA: congenitally corrected transposition of the
York
Heart
Association;
PACES/
MA
New
NU
great arteries; SSV: single systemic ventricle; SRV: systemic right ventricle; NYHA: HRS:
Paediatric
And
Congenital
Electrophysiology Society and Heart Rhythm Society; RBBB: right bundle branch
AC
CE P
TE
Cavopulmonary Connection
D
block; LBBB: left bundle branch block; AP: atriopulmonary; TCPC: Total
ACCEPTED MANUSCRIPT Abstract Background
IP
T
Cardiac resynchronisation therapy (CRT) is a well-recognised treatment in systolic heart failure. There is limited evidence in congenital patients with univentricular hearts or systemic
SC R
right ventricles. In 2014 PACES /HRS published a consensus statement recommending CRT if ventricular ejection fraction (EF) ≤35%, QRS duration ≥150ms (with RBBB in systemic
NU
RV), NYHA II-IV and ventricular dilatation. The incidence of patients meeting these criteria in whom CRT is possible is not known.
MA
Methods
Retrospective analysis of 203 patients with a uninventricular Fontan circulation and 55
TE
D
patients with ccTGA under specialist ACHD care. Results
CE P
Univentricular functional data was available for 194 (96%), 10 (5%) having EF ≤ 35%. QRS duration was available for 190 (94%) and was ≥150ms in five (3%). EF data was available
AC
for 54 (98%) ccTGA patients, and was ≤35% in 6 (11%). QRS duration was ≥150ms in 13 (26%). Only four patients fulfilled recommendations and two received CRT. Conclusions
Only a small proportion of patients with single ventricles or ccTGA meet the criteria for CRT. In many of these patients there are significant anatomical barriers to CRT which limit its use in this population. The decision to implant CRT in complex ACHD requires discussion in a combined ACHD electrophysiology surgical multidisciplinary meeting and close collaboration with patients.
ACCEPTED MANUSCRIPT Introduction Cardiac resynchronisation therapy (CRT) is a well-recognised treatment for patients with
T
systolic heart failure1, helping restore atrioventricular, inter- and intra-ventricular synchrony2,
IP
improving left ventricular (LV) function, reducing mitral regurgitation and inducing LV reverse
SC R
remodelling3 as well as improvement in symptoms and exercise capacity in dilated and ischaemic cardiomyopathy4.
NU
There is some evidence to support the role of CRT5 in adult congenital heart disease (ACHD) population: two discrete groups that may benefit from CRT are congenitally
MA
corrected transposition of the great arteries (ccTGA) with systemic right ventricle (SRV) and Fontan circulation with a single systemic ventricle (SSV)6.
D
ccTGA is characterised by the combination of atrioventricular and ventriculoarterial
TE
discordance leading to a systemic RV which differs structurally, functionally and physiologically to a systemic LV7. Patients can start to develop RV dysfunction, systemic
CE P
atrioventricular valve regurgitation, atrio-ventricular conduction abnormalities, arrhythmias and heart failure symptoms by the third decade.
AC
The Fontan circulation follows surgical procedures designed to overcome the absence of two distinct ventricular chambers, resulting in a single functioning ventricle8. The “failing Fontan” will lead to progressive functional decline, arrhythmias and multi-organ dysfunction. It is unclear how many patients with this anatomy would respond to resynchronisation in these populations. In 2006, Diller et al showed that up to 4-9% of patients with a systemic RV may be potential candidates for CRT translated from non-congenital trials9. The efficacy of CRT may vary depending on the precise structure and function of each circulation. Some small studies in children have shown promising reverse ventricular remodelling with CRT10,11; a small retrospective study showed both NYHA and EF improvement in a univentricular paediatric population but with limited long term effects12.
ACCEPTED MANUSCRIPT In 2014, Paediatric And Congenital Electrophysiology Society (PACES) and Heart Rhythm Society (HRS) expert consensus statement6 recommended CRT in SRV patients with ejection fraction <35% and RV dilatation, NYHA II-IV, RBBB, QRS duration (QRSd) >150ms
IP
T
in non-paced and NYHA I-IV and >40% V-pacing in paced and in univentricular patients with ventricular EF of ≤35%, with QRSd ≥150ms in a LBBB or RBBB morphology (spontaneous
SC R
or paced), ventricular dilatation and NYHA II-IV symptoms [IIa, C].
It is not clear what proportion of patients with a systemic right ventricle or univentricular heart
NU
would meet these criteria for CRT and in how many of these it is technically possible.
MA
We performed a retrospective review of a large quaternary ACHD centre to identify the incidence of patients meeting the HRS/PACES criteria for resynchronization in ccTGA
AC
CE P
TE
D
patients and univentricular patients with complex anatomy.
ACCEPTED MANUSCRIPT Methods We identified patients from the ACHD database at the University Hospitals Birmingham, UK.
T
Patients with transplanted hearts or who had undergone double switch operations were
IP
excluded. Retrospective review of clinical data regarding the ejection fraction, QRSd and
AC
CE P
TE
D
MA
NU
to identify which patients would qualify for CRT.
SC R
NYHA status at latest clinic review, compared with current PACES / HRS recommendations
ACCEPTED MANUSCRIPT Results Fontan Patients (single systemic ventricle):
T
We identified 203 Fontan patients of which 8 were excluded (heart transplant). Mean age
IP
was 22 ± 3.5 years (median 21 years, range 19-68 years) and 99 patients (49%) were
SC R
female (Table 1). Most were atriopulmonary (AP) Fontan (n=95, 47%) followed by extracardiac Total Cavopulmonary Connection (TCPC) n=76 (38%).
NU
Functional data was available for 194 (96%): 84 magnetic resonance imaging (CMR) and 110 transthoracic echocardiogram (TTE) with most patients (n=111, 58%) having normal
MA
univentricular function (EF ≥55%) whereas 73 (37%) had mild/moderately impaired function (EF 36-54%). Ten patients (5%) had severe systolic dysfunction with EF ≤ 35%.
D
QRSd was available for 190 (94%): ≤120ms in 163 patients (86%) and 121-149ms in 22
TE
patients (11%). Only five patients (3%) had QRSd ≥150ms; three of these were paced.
CE P
Only two patients (1%) from our univentricular heart population had EF ≤35%, QRSd ≥150ms and NYHA II-IV, thus fulfilling current indications for CRT. Neither patient had received device therapy. One patient was NYHA IV, tricuspid atresia with an AP Fontan and
AC
subsequent conversion to TCPC. The second patient (NYHA II) had right atrial isomerism with pulmonary atresia and an unfenestrated TCPC. In both patients CRT could only be achieved through a surgical approach and the risks of this were considered by the multidisciplinary team to outweigh the potential benefits. ccTGA patients (systemic right ventricle): 55 patients were identified with ccTGA, mean age 44 ± 16 (median=41 years, range=18-81 years) (Table 1), 29 (53%) female. Associated congenital heart defects included ventricular septal defect (n=22, 40%) and pulmonary stenosis (n=18, 33%). Most patients were NYHA Class I (n=38, 68%) and only one patient (2%) NYHA Class IV.
ACCEPTED MANUSCRIPT Systemic right ventricular functional data was available for 54 patients (98% TTE). Function was normal in 18 patients (33%) and mild / moderately impaired in 30 patients (56%). Six
T
patients (11%) had severely impaired SRV function.
IP
ECG data was available for 50 patients (90%). QRS was paced in 15 patients. QRSd was
SC R
≤120ms in 25 (50%), 121-149ms in 12 (24%) and ≥q150ms in 13 patients (26%). Only two patients (4%) from the ccTGA population fulfilled the PACES/HRS guidelines for CRT and had already had devices implanted: a patient (NYHA IV) with ccTGA, pulmonary
NU
stenosis, VSD and congenital complete heart block, VSD closure and left ventricular to
AC
CE P
TE
D
MA
pulmonary artery homograft and one with ccTGA and previous pulmonary artery banding.
ACCEPTED MANUSCRIPT Discussion Experience with CRT in ACHD is limited: the majority of evidence is extracted from the
T
pediatric cohort or combined cohorts in retrospective surveys which have shown significant
IP
improvements in NYHA, ventricular function and QRSd in a number of patients12,13,14,15.
SC R
Janousek et al16 and Jauvert et al17 reported clinical improvement and reduced QRSd in all patients with CRT in SRV. However, Cecchin et al12 and Dubin et al 200513 demonstrated a
NU
higher non-responder rate. Sakaguchi et al18 also reported an improvement in NYHA but no improvement in ventricular volumes in systemic RV patients with CRT.
MA
In 2017, Koyak Z et al19 published a large retrospective study of 48 ACHD patients that had undergone CRT implantation. They included 11 SRV patients; two showed improvement in
D
EF and four in NYHA. Response to CRT in the SRV population was considerably lower
TE
compared to other types of congenital heart disease.
CE P
Only three studies have reported CRT response in single ventricles in a total of 22 patients (paediatric and adult) with variable responses: 15 patients demonstrated clinical improvement with seven non-responders, demonstrating the heterogeneity of this
AC
population12,13,14.
In the light of such studies HRS/PACES produced guidelines specifically for adult congenital heart disease patients. It is unknown how many patients with an SRV or SSV would meet these criteria. In 2006, Diller et al9 showed 4.1% of ccTGA patients met the original noncongenital guidelines for CRT implantation which is similar to our findings of 4% of ccTGA with the new guidelines. Our study is the first to look at the impact of new congenital specific guidelines for CRT. We show that only a small proportion of patients with an SRV (4%) or an SSV (1%) meet the new criteria for recommending CRT. However, this number does represent a third of all patients with ccTGA and severely impaired left ventricular function.
ACCEPTED MANUSCRIPT Whilst resynchronisation is relatively straightforward in patients with ccTGA, access is much more difficult in patients following surgery for a univentricular heart. The coronary sinus may be accessible in some patients with a single ventricle; however, in the majority, cardiac
IP
T
resynchronisation can only be achieved through a lead in the systemic circulation or via a surgical or hybrid approach. Although two patients met the current guidelines for CRT with
SC R
univentricular hearts, in both patients the risks of such a procedure were felt to outweigh the potential benefits.
NU
In conclusion, we have shown that only a small proportion of adult patients with a systemic right ventricle or univentricular heart meet the updated HRC/PACES guidelines for CRT in
MA
congenital heart disease and that CRT is often unfeasible even when they do. However, CRT remains an important tool particularly for patients with a systemic RV who have a
AC
CE P
TE
D
severely impaired ejection fraction.
ACCEPTED MANUSCRIPT Acknowledgments None declared
IP
T
References
SC R
1. Abraham WT, Hayes LD. Cardiac resynchronisation therapy for heart failure. Circulation. 2003;108:2596-2603
NU
2. Auricchio A, Ding J, Spinelli JC et al. Cardiac resynchronisation therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay. J Am Coll Cardiol. 2002;39(7):1163-1169
MA
3. Verhaert D, Grimm RA, Puntawangkoon C et al. Long-Term reverse remodelling with cardiac resynchronisation therapy: results of extended echocardiographic follow-up. J Am Col Cardiol. 2010;55(17):1788-1795 4. Cleland JG, Daubert JC, Erdmann E et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49
TE
D
5. Khairy P, Fournier A, Thibault T, Dubuc M, Therien J, Vobecky SJ. Cardiac resynchronisation therapy in congenital heart disease. Inter J Cardiol. 2006;109(2):160-168
CE P
6. Khairy P, Van Hare GF, Balaji S et al. PACES/HRS Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease. Can J Cardiol. 2014;30(10):1-63 7. Hornung TS, Calder L. Congenitally Corrected Transposition of the Great Arteries. Heart. 2010;96:1154-1161
AC
8. Deal JB, Jacobs ML. Management of the failing Fontan circulation. Heart. 2012;98:10981104 9. Diller GP, Okonko D, Uebing A, Ho SY, Gatzoulis MA. Cardiac resynchronization therapy for adult congenital heart disease patients with a systemic right ventricle: analysis of feasibility and review of early experience. Europace. 2006;8(4):267-72 10. Van Beek E, Backx A, Singh S. Cardiac resynchronization as therapy for congestive cardiac failure in children dependent on chronic cardiac pacing. Cardiol Young. 2006;16:187189 11. Moak JP, Hasbani K, Ramwell C et al. Dilated cardiomyopathy following right ventricular pacing for AV block in young patients: resolution after upgrading to biventricular pacing systems. J Cardiovasc Electrophysiol. 2006;17:1068–1071 12. Cecchin F, Frangini PA, Brown D et al. Cardiac resynchronization therapy (and multisite pacing) in paediatrics and congenital heart disease: five years’ experience in a single institution. J Cardiovasc Electr. 2009,20(1):58-65
ACCEPTED MANUSCRIPT 13. Dubin AM, Janousek J, Rhee E, Strieper MJ, Cecchin F, Law IH et al. Resynchronization therapy in pediatric and congenital heart disease patients: an international multicenter study. J Am Coll Cardiol 2005;46:2277–83.
SC R
IP
T
14. Janousek J, Gebauer RA, Abdul-Khaliq H et al. Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates. Heart 2009;95:1165 – 1171. 15. Motonaga KS, Dubin AM. Cardiac resynchronization therapy for pediatric patients with heart failure and congenital heart disease. Circulation. 2014;129:1879-1891
NU
16. Janousek J, Tomek V, Chaloupecky VA, et al. Cardiac resynchronization therapy: a novel adjunct to the treatment and prevention of systemic right ventricular failure. J Am Coll Cardiol 2004;44:1927–31
D
MA
17. Jauvert G, Rousseau-Paziaud J, Villain E, Iserin L, Hidden-Lucet F, Ladouceur M, Sidi D. Effects of cardiac resynchronization therapy on echocardiographic indices, functional capacity, and clinical outcomes of patients with a systemic right ventricle. Europace. 2009;11:184–190.
TE
18. Sakaguchi H, Miyazaki A, Yamada O et al. Cardiac resynchronization therapy for various systemic ventricular morphologies in patients with congenital heart disease. Circ J. 2015;79(3):649-55
AC
CE P
19. Koyak Z, de Groot JR, Krimly A et al. Cardiac resynchronisation therapy in adults with congenital heart disease. Europace. 2017 Jan 20. pii: euw386
ACCEPTED MANUSCRIPT
Table 1. Demographics, NYHA status, ejection fraction and QRS duration of univentricular
T
(n=203) and systemic right ventricular (n=55) heart patients
n=203
Mean age ± SD
22 ± 3.5 21
NU
Median age
SC R
Demographics
Age range
41
99 (49)
29 (53)
n=203 (%)
n=55 (%)
108 (53)
38 (68)
62 (31)
8 (15)
27 (13)
8 (15)
6 (3)
1 (2)
n=194 (%)
n=54 (%)
111 (58)
18 (33)
35-55%
73 (37)
30 (56)
<35%
10 (5)
6 (11)
n=190 (%)
n=50 (%)
<120 ms
163 (86)
25 (50)
120-149 ms
22 (11)
12 (24)
5 (3)
13 (26)
TE
Class I
44 ± 16
18-81
D
NYHA status
n=55
19-68
MA
Female gender (%)
Systemic RV
IP
Univentricular
Class II
CE P
Class III Class IV
>55%
AC
Ejection fraction (n)
QRS duration
>150 ms
S0167-5273(17)32672-4 doi:10.1016/j.ijcard.2017.08.066 IJCA 25396
To appear in:
International Journal of Cardiology
Received date: Revised date: Accepted date:
4 May 2017 18 August 2017 29 August 2017
Please cite this article as: Demetriades P, Bell A, Gubran C, Marshall H, de Bono J, Hudsmith L, Suitability of cardiac resynchronisation therapy in patients with Fontan circulation and congenitally corrected transposition of the great arteries, International Journal of Cardiology (2017), doi:10.1016/j.ijcard.2017.08.066
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Suitability of Cardiac Resynchronisation Therapy in Patients with Fontan Circulation
IP
T
and Congenitally Corrected Transposition of the Great Arteries
SC R
Authors:
Demetriades P1, Bell A2, Gubran C1, Marshall H1, de Bono J1, Hudsmith L1
NU
1. Department of Adult Congenital Heart Disease, Birmingham, United Kingdom 2. University of Birmingham Medical School, Birmingham, United Kingdom
MA
All above authors take responsibility for all aspects of the reliability and freedom from
D
bias of the data presented and their discussed interpretation
TE
Corresponding Author
CE P
Name: Dr Polyvios Demetriades
Email: [email protected]
AC
Postal address: Cardiology Department, Queen Elizabeth Hospital, Mindelsohn Way Edgbaston, Birmingham, B15 2GW (Cardiology secretaries: 0121 371 4494) Grant support This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors Conflicts of interest The authors report no relationships that could be construed as a conflict of interest
ACCEPTED MANUSCRIPT Key Words Cardiac resynchronisation therapy, Adult Congenital Heart Disease, Fontan
IP
T
circulation, Congenitally Corrected Transposition of Great Arteries, Heart failure
SC R
Abbreviations
CRT: cardiac resynchronisation therapy; LV: left ventricle; RV: right ventricle; ACHD: adult congenital heart disease; ccTGA: congenitally corrected transposition of the
York
Heart
Association;
PACES/
MA
New
NU
great arteries; SSV: single systemic ventricle; SRV: systemic right ventricle; NYHA: HRS:
Paediatric
And
Congenital
Electrophysiology Society and Heart Rhythm Society; RBBB: right bundle branch
AC
CE P
TE
Cavopulmonary Connection
D
block; LBBB: left bundle branch block; AP: atriopulmonary; TCPC: Total
ACCEPTED MANUSCRIPT Abstract Background
IP
T
Cardiac resynchronisation therapy (CRT) is a well-recognised treatment in systolic heart failure. There is limited evidence in congenital patients with univentricular hearts or systemic
SC R
right ventricles. In 2014 PACES /HRS published a consensus statement recommending CRT if ventricular ejection fraction (EF) ≤35%, QRS duration ≥150ms (with RBBB in systemic
NU
RV), NYHA II-IV and ventricular dilatation. The incidence of patients meeting these criteria in whom CRT is possible is not known.
MA
Methods
Retrospective analysis of 203 patients with a uninventricular Fontan circulation and 55
TE
D
patients with ccTGA under specialist ACHD care. Results
CE P
Univentricular functional data was available for 194 (96%), 10 (5%) having EF ≤ 35%. QRS duration was available for 190 (94%) and was ≥150ms in five (3%). EF data was available
AC
for 54 (98%) ccTGA patients, and was ≤35% in 6 (11%). QRS duration was ≥150ms in 13 (26%). Only four patients fulfilled recommendations and two received CRT. Conclusions
Only a small proportion of patients with single ventricles or ccTGA meet the criteria for CRT. In many of these patients there are significant anatomical barriers to CRT which limit its use in this population. The decision to implant CRT in complex ACHD requires discussion in a combined ACHD electrophysiology surgical multidisciplinary meeting and close collaboration with patients.
ACCEPTED MANUSCRIPT Introduction Cardiac resynchronisation therapy (CRT) is a well-recognised treatment for patients with
T
systolic heart failure1, helping restore atrioventricular, inter- and intra-ventricular synchrony2,
IP
improving left ventricular (LV) function, reducing mitral regurgitation and inducing LV reverse
SC R
remodelling3 as well as improvement in symptoms and exercise capacity in dilated and ischaemic cardiomyopathy4.
NU
There is some evidence to support the role of CRT5 in adult congenital heart disease (ACHD) population: two discrete groups that may benefit from CRT are congenitally
MA
corrected transposition of the great arteries (ccTGA) with systemic right ventricle (SRV) and Fontan circulation with a single systemic ventricle (SSV)6.
D
ccTGA is characterised by the combination of atrioventricular and ventriculoarterial
TE
discordance leading to a systemic RV which differs structurally, functionally and physiologically to a systemic LV7. Patients can start to develop RV dysfunction, systemic
CE P
atrioventricular valve regurgitation, atrio-ventricular conduction abnormalities, arrhythmias and heart failure symptoms by the third decade.
AC
The Fontan circulation follows surgical procedures designed to overcome the absence of two distinct ventricular chambers, resulting in a single functioning ventricle8. The “failing Fontan” will lead to progressive functional decline, arrhythmias and multi-organ dysfunction. It is unclear how many patients with this anatomy would respond to resynchronisation in these populations. In 2006, Diller et al showed that up to 4-9% of patients with a systemic RV may be potential candidates for CRT translated from non-congenital trials9. The efficacy of CRT may vary depending on the precise structure and function of each circulation. Some small studies in children have shown promising reverse ventricular remodelling with CRT10,11; a small retrospective study showed both NYHA and EF improvement in a univentricular paediatric population but with limited long term effects12.
ACCEPTED MANUSCRIPT In 2014, Paediatric And Congenital Electrophysiology Society (PACES) and Heart Rhythm Society (HRS) expert consensus statement6 recommended CRT in SRV patients with ejection fraction <35% and RV dilatation, NYHA II-IV, RBBB, QRS duration (QRSd) >150ms
IP
T
in non-paced and NYHA I-IV and >40% V-pacing in paced and in univentricular patients with ventricular EF of ≤35%, with QRSd ≥150ms in a LBBB or RBBB morphology (spontaneous
SC R
or paced), ventricular dilatation and NYHA II-IV symptoms [IIa, C].
It is not clear what proportion of patients with a systemic right ventricle or univentricular heart
NU
would meet these criteria for CRT and in how many of these it is technically possible.
MA
We performed a retrospective review of a large quaternary ACHD centre to identify the incidence of patients meeting the HRS/PACES criteria for resynchronization in ccTGA
AC
CE P
TE
D
patients and univentricular patients with complex anatomy.
ACCEPTED MANUSCRIPT Methods We identified patients from the ACHD database at the University Hospitals Birmingham, UK.
T
Patients with transplanted hearts or who had undergone double switch operations were
IP
excluded. Retrospective review of clinical data regarding the ejection fraction, QRSd and
AC
CE P
TE
D
MA
NU
to identify which patients would qualify for CRT.
SC R
NYHA status at latest clinic review, compared with current PACES / HRS recommendations
ACCEPTED MANUSCRIPT Results Fontan Patients (single systemic ventricle):
T
We identified 203 Fontan patients of which 8 were excluded (heart transplant). Mean age
IP
was 22 ± 3.5 years (median 21 years, range 19-68 years) and 99 patients (49%) were
SC R
female (Table 1). Most were atriopulmonary (AP) Fontan (n=95, 47%) followed by extracardiac Total Cavopulmonary Connection (TCPC) n=76 (38%).
NU
Functional data was available for 194 (96%): 84 magnetic resonance imaging (CMR) and 110 transthoracic echocardiogram (TTE) with most patients (n=111, 58%) having normal
MA
univentricular function (EF ≥55%) whereas 73 (37%) had mild/moderately impaired function (EF 36-54%). Ten patients (5%) had severe systolic dysfunction with EF ≤ 35%.
D
QRSd was available for 190 (94%): ≤120ms in 163 patients (86%) and 121-149ms in 22
TE
patients (11%). Only five patients (3%) had QRSd ≥150ms; three of these were paced.
CE P
Only two patients (1%) from our univentricular heart population had EF ≤35%, QRSd ≥150ms and NYHA II-IV, thus fulfilling current indications for CRT. Neither patient had received device therapy. One patient was NYHA IV, tricuspid atresia with an AP Fontan and
AC
subsequent conversion to TCPC. The second patient (NYHA II) had right atrial isomerism with pulmonary atresia and an unfenestrated TCPC. In both patients CRT could only be achieved through a surgical approach and the risks of this were considered by the multidisciplinary team to outweigh the potential benefits. ccTGA patients (systemic right ventricle): 55 patients were identified with ccTGA, mean age 44 ± 16 (median=41 years, range=18-81 years) (Table 1), 29 (53%) female. Associated congenital heart defects included ventricular septal defect (n=22, 40%) and pulmonary stenosis (n=18, 33%). Most patients were NYHA Class I (n=38, 68%) and only one patient (2%) NYHA Class IV.
ACCEPTED MANUSCRIPT Systemic right ventricular functional data was available for 54 patients (98% TTE). Function was normal in 18 patients (33%) and mild / moderately impaired in 30 patients (56%). Six
T
patients (11%) had severely impaired SRV function.
IP
ECG data was available for 50 patients (90%). QRS was paced in 15 patients. QRSd was
SC R
≤120ms in 25 (50%), 121-149ms in 12 (24%) and ≥q150ms in 13 patients (26%). Only two patients (4%) from the ccTGA population fulfilled the PACES/HRS guidelines for CRT and had already had devices implanted: a patient (NYHA IV) with ccTGA, pulmonary
NU
stenosis, VSD and congenital complete heart block, VSD closure and left ventricular to
AC
CE P
TE
D
MA
pulmonary artery homograft and one with ccTGA and previous pulmonary artery banding.
ACCEPTED MANUSCRIPT Discussion Experience with CRT in ACHD is limited: the majority of evidence is extracted from the
T
pediatric cohort or combined cohorts in retrospective surveys which have shown significant
IP
improvements in NYHA, ventricular function and QRSd in a number of patients12,13,14,15.
SC R
Janousek et al16 and Jauvert et al17 reported clinical improvement and reduced QRSd in all patients with CRT in SRV. However, Cecchin et al12 and Dubin et al 200513 demonstrated a
NU
higher non-responder rate. Sakaguchi et al18 also reported an improvement in NYHA but no improvement in ventricular volumes in systemic RV patients with CRT.
MA
In 2017, Koyak Z et al19 published a large retrospective study of 48 ACHD patients that had undergone CRT implantation. They included 11 SRV patients; two showed improvement in
D
EF and four in NYHA. Response to CRT in the SRV population was considerably lower
TE
compared to other types of congenital heart disease.
CE P
Only three studies have reported CRT response in single ventricles in a total of 22 patients (paediatric and adult) with variable responses: 15 patients demonstrated clinical improvement with seven non-responders, demonstrating the heterogeneity of this
AC
population12,13,14.
In the light of such studies HRS/PACES produced guidelines specifically for adult congenital heart disease patients. It is unknown how many patients with an SRV or SSV would meet these criteria. In 2006, Diller et al9 showed 4.1% of ccTGA patients met the original noncongenital guidelines for CRT implantation which is similar to our findings of 4% of ccTGA with the new guidelines. Our study is the first to look at the impact of new congenital specific guidelines for CRT. We show that only a small proportion of patients with an SRV (4%) or an SSV (1%) meet the new criteria for recommending CRT. However, this number does represent a third of all patients with ccTGA and severely impaired left ventricular function.
ACCEPTED MANUSCRIPT Whilst resynchronisation is relatively straightforward in patients with ccTGA, access is much more difficult in patients following surgery for a univentricular heart. The coronary sinus may be accessible in some patients with a single ventricle; however, in the majority, cardiac
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resynchronisation can only be achieved through a lead in the systemic circulation or via a surgical or hybrid approach. Although two patients met the current guidelines for CRT with
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univentricular hearts, in both patients the risks of such a procedure were felt to outweigh the potential benefits.
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In conclusion, we have shown that only a small proportion of adult patients with a systemic right ventricle or univentricular heart meet the updated HRC/PACES guidelines for CRT in
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congenital heart disease and that CRT is often unfeasible even when they do. However, CRT remains an important tool particularly for patients with a systemic RV who have a
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severely impaired ejection fraction.
ACCEPTED MANUSCRIPT Acknowledgments None declared
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References
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8. Deal JB, Jacobs ML. Management of the failing Fontan circulation. Heart. 2012;98:10981104 9. Diller GP, Okonko D, Uebing A, Ho SY, Gatzoulis MA. Cardiac resynchronization therapy for adult congenital heart disease patients with a systemic right ventricle: analysis of feasibility and review of early experience. Europace. 2006;8(4):267-72 10. Van Beek E, Backx A, Singh S. Cardiac resynchronization as therapy for congestive cardiac failure in children dependent on chronic cardiac pacing. Cardiol Young. 2006;16:187189 11. Moak JP, Hasbani K, Ramwell C et al. Dilated cardiomyopathy following right ventricular pacing for AV block in young patients: resolution after upgrading to biventricular pacing systems. J Cardiovasc Electrophysiol. 2006;17:1068–1071 12. Cecchin F, Frangini PA, Brown D et al. Cardiac resynchronization therapy (and multisite pacing) in paediatrics and congenital heart disease: five years’ experience in a single institution. J Cardiovasc Electr. 2009,20(1):58-65
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18. Sakaguchi H, Miyazaki A, Yamada O et al. Cardiac resynchronization therapy for various systemic ventricular morphologies in patients with congenital heart disease. Circ J. 2015;79(3):649-55
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Table 1. Demographics, NYHA status, ejection fraction and QRS duration of univentricular
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(n=203) and systemic right ventricular (n=55) heart patients
n=203
Mean age ± SD
22 ± 3.5 21
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Median age
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Demographics
Age range
41
99 (49)
29 (53)
n=203 (%)
n=55 (%)
108 (53)
38 (68)
62 (31)
8 (15)
27 (13)
8 (15)
6 (3)
1 (2)
n=194 (%)
n=54 (%)
111 (58)
18 (33)
35-55%
73 (37)
30 (56)
<35%
10 (5)
6 (11)
n=190 (%)
n=50 (%)
<120 ms
163 (86)
25 (50)
120-149 ms
22 (11)
12 (24)
5 (3)
13 (26)
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Class I
44 ± 16
18-81
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NYHA status
n=55
19-68
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Female gender (%)
Systemic RV
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Univentricular
Class II
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Class III Class IV
>55%
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Ejection fraction (n)
QRS duration
>150 ms