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Congenital Complete Heart Block: Single Tertiary Centre Experience
ORIGINAL ARTICLE
Original Article
Congenital Complete Heart Block: Single Tertiary Centre Experience夽 Jennifer Yan a , Suraj K. Varma b , Atul Malhotra a,c and Samuel Menahem b,c,∗ b
a Monash Newborn, Melbourne, Australia Monash Heart, Monash Medical Centre, Melbourne, Australia c Monash University, Melbourne, Australia
Background: Congenital complete heart block (CCHB) is an uncommon although important and potentially serious condition contributing to neonatal morbidity and mortality. Aims: To study the characteristics and outcomes of infants born with CCHB at a single tertiary centre. Methods: A retrospective review of all infants with CCHB over the last 20 years was carried out to determine the outcomes, and the indications and timing of pacemaker insertion. Results: Fifteen live born infants (10 male, 5 female) with CCHB were identified. Their mean (and SD) gestation and birth weight were 37 (3.3) weeks and 3100 (448) grams respectively. Maternal systemic lupus erythematosus (SLE) antibodies were present in eight (53%) pregnancies and two infants had congenitally corrected transposition of the great arteries (cCTGA). The median heart rate/minute at birth was 60 (range 40–80). Thirteen (87%) patients to date required a pacemaker. The median age of insertion of a pacemaker device was six months (range 2 days–16 years). All patients were paced epicardially – six initially with a single chamber and five with a dual chamber pacemaker. At the time of generator change, dual chamber pacemakers were used. The median life of an implanted pacemaker was six years (3–10 years). Except for a patient with cCTGA who has undergone a double switch procedure, all the patients had good systemic ventricular function. There was one death in the group unrelated to CCHB. Conclusions: CCHB is a uncommon but potentially serious condition in infancy. While a significant number of infants need a pacemaker, the overall outcome of infants with CCHB in our experience is good. (Heart, Lung and Circulation 2012;21:666–670) © 2012 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Keywords. Heart block; Congenital; Pacemaker
Introduction
C
ongenital complete heart block is a rare but potentially serious condition with an estimated incidence of 1 in 20,000 live births. Untreated, it is associated with a significant morbidity and mortality up to 10% [1]. Neonatal lupus is implicated in the majority (60–95%) of cases and is thought to be secondary to the transplacental transmission of maternal anti-Ro and anti-La antibodies [2–4]. In addition, a proportion of cases occur in association with structural heart disease, including congenitally corrected transposition of the great arteries, and left atrial isomerism with polysplenia and an atrioventricular Received 18 April 2012; received in revised form 20 May 2012; accepted 22 May 2012; available online 29 June 2012 夽
Presented in part to the Cardiac Society of Australia and New Zealand, August 2010. ∗ Corresponding author at: Fetal Cardiac Unit, Monash Medical Centre, 246, Clayton Road, Clayton, Melbourne, Victoria 3168, Australia. Tel.: +61 3 9594 6666; fax: +61 3 9576 1352. E-mail address: [email protected] (S. Menahem).
septal defect. Ultimately all patients with CCHB require permanent cardiac pacing [5]. Indications and timing for pacing have varied. However, it is recognised that early pacing may be required for infants with CCHB and associated structural heart disease. It may also benefit patients who are symptomatic or have specific electrocardiographic and echocardiographic parameters that have been associated with poorer prognostic outcome. Over the last 20 years, experience with, and the technical capabilities of cardiac pacemakers (smaller units, longer battery life and the time interval to reintervention) have significantly improved, with the indications for pacemaker therapy expanding. Nevertheless the timing of the insertion of the pacemaker is often delayed till there is a clear indication because of the subsequent need for lead and/or generator changes, etc. There is a currently a paucity of published Australasian data regarding the management of CCHB. We present a series of infants with CCHB managed at our centre. We reviewed the indications, timing and type of pacemaker used and compared our results with the published outcomes.
© 2012 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2012.05.784
VVIR DDDR
– DDDR DDDR VVIR
VVIR VVIR VVIR – DDDR VVIR
Epicardial Epicardial Epicardial – Epicardial Venous Epicardial – Epicardial Epicardial Epicardial Epicardial Epicardial Epicardial Epicardial 10.13 3.63 0.07 – 71.77 35.37 2.07 – 5.80 199.40 9.83 0.30 4.67 1.00 40.10 Dilated LV Poor growth Bradycardia No pacing Dyspnoea on exertion Dyspnoea on exertion LV dysfunction No pacing Lethargy Syncope Tiredness Hypotension CTGA-RV dysfunction CTGA-RV dysfunction Bradycardia 47 70 70 – – 45 60 64 –
Heart Rate at Birth
38 37 36 35 37 37 36 40 40 37 38 26 39 39 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Birth Wt (g) Gestational Age at Birth S.No.
Table 1. Summary of Patient Characteristics.
Fifteen live born infants (10 male, 5 female) with CCHB were identified. Their mean (and SD) gestation and birth weight were 37 (3.3) weeks and 3100 (448) grams respectively. Auto-antibodies directed against SS-A/Ro and SS-B/La ribonucleoproteins were present in mothers of 8 (53%) infants. Two patients had corrected transposition of the great arteries (cCTGA). The median heart rate at birth was 60 bpm (range 40–80). Thirteen (87%) patients to date have had a pacemaker inserted; the indications including bradycardia, poor exercise capacity and/or ventricular dysfunction (Table 1). The mean total follow-up duration was 10 years and follow-up duration since pacemaker insertion was 8.6 years in the series. The median age of pacemaker insertion was six months (range 2 days–16 years). All except one patient were paced initially by epicardial leads. Seven were initially paced using a single chamber and six with a dual chamber pacemaker. At the time of generator change, only a dual chamber pacemaker was inserted. The median life of an implanted pacemaker was six years (2.7–14 years). Good ventricular function was maintained in patients with isolated CCHB (without cCTGA). There was one death in the case series, of a premature infant with neonatal lupus whose mother was known to have SLE having previously had multiple miscarriages. CCHB was antenatally diagnosed at 19 weeks gestation. Delivery was prompted by a poor biophysical profile at 26 weeks gestation with reversal of umbilical artery Doppler end diastolic flows indicating compromised foetal circulation. She was born extremely premature (26/40 weeks’ gestation) with an extremely low birth weight (550 g) and suffered the full gamut of complications of the very premature infant. She died at 16 months
Indication for Pacing
Results
50 52 40 60 50
Age at Pacemaker Insertion (months)
Lead Placement
Pacing Mode
A retrospective review of all patients with CCHB at our institution was undertaken over the 20 year period from 1991 to 2010. All neonatal admissions coded for CCHB were included. The electronic records of patients referred to cardiology for ambulatory ECG monitoring and pacemaker checks were also reviewed. The review qualified as a quality assurance project approved by the hospital’s ethics committee. All cases fulfilled the criteria defined by Yater: a slow heart known to have been present from birth or from a very early age, the absence of a history of diphtheria or myocarditis which might cause heart block, no evidence of ischaemic heart disease or cardiomyopathy, and no previous cardiac surgery[6]. Demographic data were collected and included the gestational age and heart rate at birth, birth weight, autoantibody positivity and the presence of structural heart disease. The indications for a pacemaker insertion, the age of pacemaker insertion, electrocardiographic and echocardiographic parameters, method of lead placement, pacing mode, pacemaker and/or lead replacement were also reviewed as well as the outcomes highlighting any morbidity and mortality.
3105 2484 3080 2458 2803 3067 2660 3490 3450 – – 550 3776 3732 3100
Longevity (Time to 2nd Pacemaker) (years)
Patients & Methods
667
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6.24 – – – 6.07 14.29 10.24 – 5.99 – 7.08 – 2.72 – –
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of age from complications of severe chronic lung disease and pulmonary hypertension. She was initially externally paced on day 2. At 4 months she had a permanent single chamber pacemaker inserted. There were no complications or concerns with the function of either pacemaker.
Discussion The paper reviews a case series of CCHB from an Australian tertiary centre. The pathogenesis of one of the commonest causes of CCHB, namely neonatal lupus has become better understood over recent times. It is believed that transplacental transmission of maternal anti-Ro and anti-La antibodies has the potential to cause damage to the foetal cardiac conduction tissue at around 18–24 weeks gestation, leading to autoimmune mediated inflammation, fibrosis and heart block [7]. However, other factors must also be involved, as neonatal disease occurs in only 1–2% of cases where mothers are known antibody positive [8]. Anti-Ro/La is not currently screened for in pregnancy. In a known anti-Ro/La positive mother, heightened antenatal surveillance for early detection and the monitoring of the foetal heart rate is possible. In our case series, neonatal lupus was implicated in just over half the cases, a much lower rate as compared to those in the literature where lupus is implicated in a greater percentage. In one study, anti-Ro antibodies were detected in maternal sera in up to 98% of affected children [9]. The lower rates found in our study may reflect an incomplete retrospective data-set as our mothers were not universally tested. The other association with CCHB is congenital heart disease and in this series, two patients with associated structural heart disease had cCTGA, treated with pulmonary artery banding ± double switch procedure. They received early pacing at one and four months via DDDR (dual chamber physiologic pacing) and VVIR (single chamber rate responsive) respectively. Both had evidence of systemic right ventricular dysfunction on echocardiography. When associated with CCTGA, CCHB occurs secondary to abnormal development of the conducting system. Where normally the AV node is a posterior structure, in cCTGA both anterior and posterior AV nodal structures have been shown to exist, with the anterior node joining the bundle of His [10]. In fact, patients with cCTGA have an elevated lifetime risk of developing CCHB (up to 2% per year in one study) [11,12]. Development of CCHB was also more likely in the presence of an intact ventricular septum [11]. It is generally accepted that most patients with CCHB will eventually need pacing. The optimal timing of pacemaker insertion is unclear. The importance of early pacing is well established in symptomatic infants, and infants with CCHB and associated structural heart disease. For example, a low heart rate and prolonged QTc interval have indicated an unfavourable prognosis [5,13]. The benefit of pacing in these individuals is the elimination of the bradycardia, a potential trigger for ventricular tachyarrthymia or prolonged pauses [14]. In the asymptomatic patient, the need for and timing of pacemaker insertion is less clear. There are clinical and echocardiographic parameters, which have been identified as poor prognostic
Heart, Lung and Circulation 2012;21:666–670
markers such as increasing exercise intolerance, left ventricular enlargement with or without reduced function. In the absence of these indications, some still recommend pacing for all patients. CCHB detected in utero may be associated with high foetal and neonatal mortality and therefore the need for early postnatal intervention. However the mortality rates in early life may be high despite early pacing. Early diagnosis may be suspected by measuring the prolongation of PR interval on foetal echocardiography and monitoring for cardiac decompensation. Severe cases in utero may result in hydrops foetalis, endocardial fibroelastosis, pericardial effusion and foetal death [4,15,16]. In a study by Eronen et al. of 91 CCHB patients in Finland, there was a 16% overall mortality, of which 73% died within the first 12 months despite more than half (53%) receiving early pacing as a newborn. One in four of those affected by foetal hydrops died within three months of age. Cumulative probability of survival at 10 years old was 82%. Poor prognosis was associated with foetal hydrops, low foetal and neonatal heart rate, and neonatal problems attributable to prematurity or neonatal lupus [16]. The majority of patients with CCHB receive a pacemaker at some point during their lifetime, regardless of the age of diagnosis. In Jaeggi’s study of 102 patients, only 11% of neonatal and 12% of childhood cases did not require pacing by age 20 [4]. Our own data reports similar percentages with two patients (13%) who have not required pacing at the time of writing. Over the last 20 years, experience with, and the technical capabilities of cardiac pacemakers has significantly advanced, and indications for pacemaker therapy have been extended. Movement from single to dual-chamber pacing preference has occurred, limited in neonates by technical difficulty and atrial lead complications but with the advantages of sinus node responsiveness and haemodynamic benefits of physiologic atrioventricular synchrony [17]. The key benefit of pacing is of course in achieving an adequate ventricular rate; addition of atrioventricular and biventricular synchrony afford incremental benefits to short-term haemodynamic function above this, and appear to be important in long term outcomes. In a study by Breuer evaluating the effects of pacing in 149 CCHB patients, institution of pacemaker therapy was associated with a decrease in heart size and normalisation of shortening fraction in most patients, with no difference in outcome between VVI/DDD modes of pacing [18]. This is in contrast to the findings of others such as Karpawich et al. who compared VVI/DDD pacing and showed that although both pacing modes allowed increases in ventricular rate with exercise, VVI mode was associated with ectopy and greater risk for sudden death. At rest, patients in DDD mode also had comparatively slower resting sinus rates and better stroke volume, shortening fraction and cardiac output [19]. In our experience, both VVI and DDD pacemaker modes were met with good outcome. In light of the growing body of evidence for haemodynamic benefit from preservation of atrioventricular synchrony, dual chamber pacemakers were exclusively used at generator change, at which time age and size limitations are also less acute. In infants and
very young children, our preference tends towards VVI single chamber rate responsive pacing. This preference is due to concern that often the atrial lead, asked to pick up extremely low voltages, may fail to sense properly after a few weeks. Pacemaker generator longevity in this series was excellent: median interval to next pacemaker insertion was comparable if not favourable to other reports in the literature – 6 years (range 2.7–14.3 years) compared to 4.3 years (range 1.7–7.1 years) and 5.5 ± 3.4 years (range 1.7–7.1 years) for mean interval to first lead revision [17]. Mortality data in this study was much more favourable compared to the existing literature. In our series there was one death not attributable to CCHB. Overall mortality rates are generally reported between 10–15%, 5–8% in isolated congenital heart block and 29–40% in those with associated structural heart disease [1,16,20]. Reports from individual studies vary. One study reported high mortality rates with 15% mortality in isolated CCHB and 86% mortality in structural associated CCHB within the neonatal period [21]. Another study of 60 patients had a 15% cardiac attributable mortality rate, despite 67% pacemaker implantation in a population of autoantibody (i.e. not structural) associated CCHB [22]. In contrast, in Balmer’s study of 32 children, 81% were paced with one death from likely ventricular electrode exit block (3% mortality) [23]. The likelihood that this difference in outcome is primarily due to a difference in experience is low. This raises the question of whether the difference in outcome is due to presence of a different spectrum of disease seen within our Australasian series. Certainly it seems the reports of CCHB from South East Asia tend to run at slower heart rates [24]. The median heart rate among our cases was 60 bpm, at which rate these infants seem to cope quite well. Though guidelines suggest pacing below a heart rate of 55 bpm, usually a HR 50–55 bpm seems to be tolerated satisfactorily. A HR around 45 bpm may lead to symptoms, while a HR of 40 bpm or less needs pacing. In addition, contributing to the low mortality was the low number of cases with structural heart disease, which usually carry a higher mortality.
Conclusions CCHB is a rare but potentially serious condition in infancy, with a significant morbidity and mortality as described in the current literature. This is the first reported single centre series on the outcomes and experience of CCHB from Australia. While the occasional patient required early pacemaker insertion, the majority had a pacemaker inserted in late infancy or early childhood, the indications being ventricular dilatation, decreasing exercise tolerance or intermittent profound bradycardia. There was no mortality attributable to CCHB from our series. One death occurred in a patient with multiple co-morbidities and complications of extreme prematurity and low birth weight. Our figures are extremely favourable compared to previously described mortality rates of 10–15%. Initial implantation of a single chamber VVIR appeared satisfactory though all subsequently had a dual chamber DDD on
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669
reimplantation. The battery life statistics were better than that reported elsewhere. In our experience, CCHB has a good outcome. We postulate this may reflect a different spectrum of disease seen in Australia.
Acknowledgements Pacemaker implantation was carried out at the Royal Children’s Hospital, Melbourne or Monash Medical Centre, Clayton.
References [1] Michaelsson M, Engle MA. Congenital complete heart block: an international study of the natural history. Cardiovasc Clin 1972;4(3):85–101. [2] Johansen AS, Herlin T. Neonatal lupus syndrome. Association with complete congenital atrioventricular block. Ugeskr Laeger 1998;160(17):2521–5. [3] Ross BA. Congenital complete atrioventricular block. Pediatr Clin North Am 1990;37(1):69–78. [4] Jaeggi ET, Hamilton RM, Silverman ED, Zamora SA, Hornberger LK. Outcome of children with fetal: neonatal or childhood diagnosis of isolated congenital atrioventricular block. A single institution’s experience of 30 years. J Am Coll Cardiol 2002;39(1):130–7. [5] Michaelsson MA, Jonzon A, Riesenfeld T. Isolated congenital complete atrioventricular block in adult life. A prospective study. Circulation 1995;92(3):442–9. [6] Yater W. Congenital heart block: review of the literature; report of a case with incomplete heterotaxy; the electrocardiogram in dextrocardia. Am J Dis Child 1929;38(1):112–36. [7] Miranda-Carús ME, Askanase AD, Clancy RM, Di Donato F, Chou TM, Libera MR, et al. Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages. J Immunol 2000;165(9):5345–51. [8] Brucato A, Cimaz R, Caporali R, Ramoni V, Buyon J. Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies. Clin Rev Allergy Immunol 2011;40(1):27–41. [9] Smeenk RJ. Immunological aspects of congenital atrioventricular block. Pacing Clin Electrophysiol 1997;20(8 Pt 2):2093–7. [10] Chow LT, Cook AC, Ho SY, Leung MP, Anderson RH. Isolated congenitally complete heart block attributable to combined nodoventricular and intraventricular discontinuity. Hum Pathol 1998;29(7):729–36. [11] Huhta JC, Maloney JD, Ritter DG, Ilstrup DM, Feldt RH. Complete atrioventricular block in patients with atrioventricular discordance. Circulation 1983;67(6):1374–7. [12] Lundstrom U, Bull C, Wyse RK, Somerville J. The natural and unnatural history of congenitally corrected transposition. Am J Cardiol 1990;65(18):1222–9. [13] Groves AM, Allan LD, Rosenthal E. Outcome of isolated congenital complete heart block diagnosed in utero. Heart 1996;75(2):190–4. [14] Friedman RA. Congenital AV block. Pace me now or pace me later? Circulation 1995;92(3):283–5. [15] Buyon JP, Hiebert R, Copel J, Craft J, Friedman D, Katholi M, et al. Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol 1998;31(7):1658–66.
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[16] Eronen M, Sirèn MK, Ekblad H, Tikanoja T, Julkunen H, Paavilainen T. Short- and long-term outcome of children with congenital complete heart block diagnosed in utero or as a newborn. Pediatrics 2000;106(1 Pt 1):86–91. [17] Kelle AM, Backer CL, Tsao S, Stewart RD, Franklin WH, Deal BJ, et al. Dual-chamber epicardial pacing in neonates with congenital heart block. J Thorac Cardiovasc Surg 2007;134(5):1188–92. [18] Breur JM, Udink Ten Cate FE, Kapusta L, Cohen MI, Crosson JE, Boramanand N, et al. Pacemaker therapy in isolated congenital complete atrioventricular block. Pacing Clin Electrophysiol 2002;25(12):1685–91. [19] Karpawich PP, Perry BL, Farooki ZQ, Clapp SK, Jackson WL, Cicalese CA, et al. Pacing in children and young adults with nonsurgical atrioventricular block: comparison of single-rate ventricular and dual-chamber modes. Am Heart J 1987;113(2 Pt 1):316–21. [20] Pinsky WW, Gillette PC, Garson Jr A, McNamara DG. Diagnosis: management, and long-term results of patients
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[21]
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with congenital complete atrioventricular block. Pediatrics 1982;69(6):728–33. Schmidt KG, Ulmer HE, Silverman NH, Kleinman CS, Copel JA. Perinatal outcome of fetal complete atrioventricular block: a multicenter experience. J Am Coll Cardiol 1991;17(6):1360–6. Waltuck J, Buyon JP. Autoantibody-associated congenital heart block: outcome in mothers and children. Ann Intern Med 1994;120(7):544–51. Balmer C, Fasnacht M, Rahn M, Molinari L, Bauersfeld U. Long-term follow up of children with congenital complete atrioventricular block and the impact of pacemaker therapy. Europace 2002;4(4):345–9. Khongphatthanayothin A, Chotivitayatarakorn P, Benjacholamas V, Muangmingsuk S, Lertsupcharoen P, Thisyakorn C. Complete heart block in children at King Chulalongkorn Memorial Hospital. J Med Assoc Thai 2001;84(Suppl. 1):S111–7.
Original Article
Congenital Complete Heart Block: Single Tertiary Centre Experience夽 Jennifer Yan a , Suraj K. Varma b , Atul Malhotra a,c and Samuel Menahem b,c,∗ b
a Monash Newborn, Melbourne, Australia Monash Heart, Monash Medical Centre, Melbourne, Australia c Monash University, Melbourne, Australia
Background: Congenital complete heart block (CCHB) is an uncommon although important and potentially serious condition contributing to neonatal morbidity and mortality. Aims: To study the characteristics and outcomes of infants born with CCHB at a single tertiary centre. Methods: A retrospective review of all infants with CCHB over the last 20 years was carried out to determine the outcomes, and the indications and timing of pacemaker insertion. Results: Fifteen live born infants (10 male, 5 female) with CCHB were identified. Their mean (and SD) gestation and birth weight were 37 (3.3) weeks and 3100 (448) grams respectively. Maternal systemic lupus erythematosus (SLE) antibodies were present in eight (53%) pregnancies and two infants had congenitally corrected transposition of the great arteries (cCTGA). The median heart rate/minute at birth was 60 (range 40–80). Thirteen (87%) patients to date required a pacemaker. The median age of insertion of a pacemaker device was six months (range 2 days–16 years). All patients were paced epicardially – six initially with a single chamber and five with a dual chamber pacemaker. At the time of generator change, dual chamber pacemakers were used. The median life of an implanted pacemaker was six years (3–10 years). Except for a patient with cCTGA who has undergone a double switch procedure, all the patients had good systemic ventricular function. There was one death in the group unrelated to CCHB. Conclusions: CCHB is a uncommon but potentially serious condition in infancy. While a significant number of infants need a pacemaker, the overall outcome of infants with CCHB in our experience is good. (Heart, Lung and Circulation 2012;21:666–670) © 2012 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Keywords. Heart block; Congenital; Pacemaker
Introduction
C
ongenital complete heart block is a rare but potentially serious condition with an estimated incidence of 1 in 20,000 live births. Untreated, it is associated with a significant morbidity and mortality up to 10% [1]. Neonatal lupus is implicated in the majority (60–95%) of cases and is thought to be secondary to the transplacental transmission of maternal anti-Ro and anti-La antibodies [2–4]. In addition, a proportion of cases occur in association with structural heart disease, including congenitally corrected transposition of the great arteries, and left atrial isomerism with polysplenia and an atrioventricular Received 18 April 2012; received in revised form 20 May 2012; accepted 22 May 2012; available online 29 June 2012 夽
Presented in part to the Cardiac Society of Australia and New Zealand, August 2010. ∗ Corresponding author at: Fetal Cardiac Unit, Monash Medical Centre, 246, Clayton Road, Clayton, Melbourne, Victoria 3168, Australia. Tel.: +61 3 9594 6666; fax: +61 3 9576 1352. E-mail address: [email protected] (S. Menahem).
septal defect. Ultimately all patients with CCHB require permanent cardiac pacing [5]. Indications and timing for pacing have varied. However, it is recognised that early pacing may be required for infants with CCHB and associated structural heart disease. It may also benefit patients who are symptomatic or have specific electrocardiographic and echocardiographic parameters that have been associated with poorer prognostic outcome. Over the last 20 years, experience with, and the technical capabilities of cardiac pacemakers (smaller units, longer battery life and the time interval to reintervention) have significantly improved, with the indications for pacemaker therapy expanding. Nevertheless the timing of the insertion of the pacemaker is often delayed till there is a clear indication because of the subsequent need for lead and/or generator changes, etc. There is a currently a paucity of published Australasian data regarding the management of CCHB. We present a series of infants with CCHB managed at our centre. We reviewed the indications, timing and type of pacemaker used and compared our results with the published outcomes.
© 2012 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2012.05.784
VVIR DDDR
– DDDR DDDR VVIR
VVIR VVIR VVIR – DDDR VVIR
Epicardial Epicardial Epicardial – Epicardial Venous Epicardial – Epicardial Epicardial Epicardial Epicardial Epicardial Epicardial Epicardial 10.13 3.63 0.07 – 71.77 35.37 2.07 – 5.80 199.40 9.83 0.30 4.67 1.00 40.10 Dilated LV Poor growth Bradycardia No pacing Dyspnoea on exertion Dyspnoea on exertion LV dysfunction No pacing Lethargy Syncope Tiredness Hypotension CTGA-RV dysfunction CTGA-RV dysfunction Bradycardia 47 70 70 – – 45 60 64 –
Heart Rate at Birth
38 37 36 35 37 37 36 40 40 37 38 26 39 39 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Birth Wt (g) Gestational Age at Birth S.No.
Table 1. Summary of Patient Characteristics.
Fifteen live born infants (10 male, 5 female) with CCHB were identified. Their mean (and SD) gestation and birth weight were 37 (3.3) weeks and 3100 (448) grams respectively. Auto-antibodies directed against SS-A/Ro and SS-B/La ribonucleoproteins were present in mothers of 8 (53%) infants. Two patients had corrected transposition of the great arteries (cCTGA). The median heart rate at birth was 60 bpm (range 40–80). Thirteen (87%) patients to date have had a pacemaker inserted; the indications including bradycardia, poor exercise capacity and/or ventricular dysfunction (Table 1). The mean total follow-up duration was 10 years and follow-up duration since pacemaker insertion was 8.6 years in the series. The median age of pacemaker insertion was six months (range 2 days–16 years). All except one patient were paced initially by epicardial leads. Seven were initially paced using a single chamber and six with a dual chamber pacemaker. At the time of generator change, only a dual chamber pacemaker was inserted. The median life of an implanted pacemaker was six years (2.7–14 years). Good ventricular function was maintained in patients with isolated CCHB (without cCTGA). There was one death in the case series, of a premature infant with neonatal lupus whose mother was known to have SLE having previously had multiple miscarriages. CCHB was antenatally diagnosed at 19 weeks gestation. Delivery was prompted by a poor biophysical profile at 26 weeks gestation with reversal of umbilical artery Doppler end diastolic flows indicating compromised foetal circulation. She was born extremely premature (26/40 weeks’ gestation) with an extremely low birth weight (550 g) and suffered the full gamut of complications of the very premature infant. She died at 16 months
Indication for Pacing
Results
50 52 40 60 50
Age at Pacemaker Insertion (months)
Lead Placement
Pacing Mode
A retrospective review of all patients with CCHB at our institution was undertaken over the 20 year period from 1991 to 2010. All neonatal admissions coded for CCHB were included. The electronic records of patients referred to cardiology for ambulatory ECG monitoring and pacemaker checks were also reviewed. The review qualified as a quality assurance project approved by the hospital’s ethics committee. All cases fulfilled the criteria defined by Yater: a slow heart known to have been present from birth or from a very early age, the absence of a history of diphtheria or myocarditis which might cause heart block, no evidence of ischaemic heart disease or cardiomyopathy, and no previous cardiac surgery[6]. Demographic data were collected and included the gestational age and heart rate at birth, birth weight, autoantibody positivity and the presence of structural heart disease. The indications for a pacemaker insertion, the age of pacemaker insertion, electrocardiographic and echocardiographic parameters, method of lead placement, pacing mode, pacemaker and/or lead replacement were also reviewed as well as the outcomes highlighting any morbidity and mortality.
3105 2484 3080 2458 2803 3067 2660 3490 3450 – – 550 3776 3732 3100
Longevity (Time to 2nd Pacemaker) (years)
Patients & Methods
667
ORIGINAL ARTICLE
Yan et al. Complete heart block
6.24 – – – 6.07 14.29 10.24 – 5.99 – 7.08 – 2.72 – –
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of age from complications of severe chronic lung disease and pulmonary hypertension. She was initially externally paced on day 2. At 4 months she had a permanent single chamber pacemaker inserted. There were no complications or concerns with the function of either pacemaker.
Discussion The paper reviews a case series of CCHB from an Australian tertiary centre. The pathogenesis of one of the commonest causes of CCHB, namely neonatal lupus has become better understood over recent times. It is believed that transplacental transmission of maternal anti-Ro and anti-La antibodies has the potential to cause damage to the foetal cardiac conduction tissue at around 18–24 weeks gestation, leading to autoimmune mediated inflammation, fibrosis and heart block [7]. However, other factors must also be involved, as neonatal disease occurs in only 1–2% of cases where mothers are known antibody positive [8]. Anti-Ro/La is not currently screened for in pregnancy. In a known anti-Ro/La positive mother, heightened antenatal surveillance for early detection and the monitoring of the foetal heart rate is possible. In our case series, neonatal lupus was implicated in just over half the cases, a much lower rate as compared to those in the literature where lupus is implicated in a greater percentage. In one study, anti-Ro antibodies were detected in maternal sera in up to 98% of affected children [9]. The lower rates found in our study may reflect an incomplete retrospective data-set as our mothers were not universally tested. The other association with CCHB is congenital heart disease and in this series, two patients with associated structural heart disease had cCTGA, treated with pulmonary artery banding ± double switch procedure. They received early pacing at one and four months via DDDR (dual chamber physiologic pacing) and VVIR (single chamber rate responsive) respectively. Both had evidence of systemic right ventricular dysfunction on echocardiography. When associated with CCTGA, CCHB occurs secondary to abnormal development of the conducting system. Where normally the AV node is a posterior structure, in cCTGA both anterior and posterior AV nodal structures have been shown to exist, with the anterior node joining the bundle of His [10]. In fact, patients with cCTGA have an elevated lifetime risk of developing CCHB (up to 2% per year in one study) [11,12]. Development of CCHB was also more likely in the presence of an intact ventricular septum [11]. It is generally accepted that most patients with CCHB will eventually need pacing. The optimal timing of pacemaker insertion is unclear. The importance of early pacing is well established in symptomatic infants, and infants with CCHB and associated structural heart disease. For example, a low heart rate and prolonged QTc interval have indicated an unfavourable prognosis [5,13]. The benefit of pacing in these individuals is the elimination of the bradycardia, a potential trigger for ventricular tachyarrthymia or prolonged pauses [14]. In the asymptomatic patient, the need for and timing of pacemaker insertion is less clear. There are clinical and echocardiographic parameters, which have been identified as poor prognostic
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markers such as increasing exercise intolerance, left ventricular enlargement with or without reduced function. In the absence of these indications, some still recommend pacing for all patients. CCHB detected in utero may be associated with high foetal and neonatal mortality and therefore the need for early postnatal intervention. However the mortality rates in early life may be high despite early pacing. Early diagnosis may be suspected by measuring the prolongation of PR interval on foetal echocardiography and monitoring for cardiac decompensation. Severe cases in utero may result in hydrops foetalis, endocardial fibroelastosis, pericardial effusion and foetal death [4,15,16]. In a study by Eronen et al. of 91 CCHB patients in Finland, there was a 16% overall mortality, of which 73% died within the first 12 months despite more than half (53%) receiving early pacing as a newborn. One in four of those affected by foetal hydrops died within three months of age. Cumulative probability of survival at 10 years old was 82%. Poor prognosis was associated with foetal hydrops, low foetal and neonatal heart rate, and neonatal problems attributable to prematurity or neonatal lupus [16]. The majority of patients with CCHB receive a pacemaker at some point during their lifetime, regardless of the age of diagnosis. In Jaeggi’s study of 102 patients, only 11% of neonatal and 12% of childhood cases did not require pacing by age 20 [4]. Our own data reports similar percentages with two patients (13%) who have not required pacing at the time of writing. Over the last 20 years, experience with, and the technical capabilities of cardiac pacemakers has significantly advanced, and indications for pacemaker therapy have been extended. Movement from single to dual-chamber pacing preference has occurred, limited in neonates by technical difficulty and atrial lead complications but with the advantages of sinus node responsiveness and haemodynamic benefits of physiologic atrioventricular synchrony [17]. The key benefit of pacing is of course in achieving an adequate ventricular rate; addition of atrioventricular and biventricular synchrony afford incremental benefits to short-term haemodynamic function above this, and appear to be important in long term outcomes. In a study by Breuer evaluating the effects of pacing in 149 CCHB patients, institution of pacemaker therapy was associated with a decrease in heart size and normalisation of shortening fraction in most patients, with no difference in outcome between VVI/DDD modes of pacing [18]. This is in contrast to the findings of others such as Karpawich et al. who compared VVI/DDD pacing and showed that although both pacing modes allowed increases in ventricular rate with exercise, VVI mode was associated with ectopy and greater risk for sudden death. At rest, patients in DDD mode also had comparatively slower resting sinus rates and better stroke volume, shortening fraction and cardiac output [19]. In our experience, both VVI and DDD pacemaker modes were met with good outcome. In light of the growing body of evidence for haemodynamic benefit from preservation of atrioventricular synchrony, dual chamber pacemakers were exclusively used at generator change, at which time age and size limitations are also less acute. In infants and
very young children, our preference tends towards VVI single chamber rate responsive pacing. This preference is due to concern that often the atrial lead, asked to pick up extremely low voltages, may fail to sense properly after a few weeks. Pacemaker generator longevity in this series was excellent: median interval to next pacemaker insertion was comparable if not favourable to other reports in the literature – 6 years (range 2.7–14.3 years) compared to 4.3 years (range 1.7–7.1 years) and 5.5 ± 3.4 years (range 1.7–7.1 years) for mean interval to first lead revision [17]. Mortality data in this study was much more favourable compared to the existing literature. In our series there was one death not attributable to CCHB. Overall mortality rates are generally reported between 10–15%, 5–8% in isolated congenital heart block and 29–40% in those with associated structural heart disease [1,16,20]. Reports from individual studies vary. One study reported high mortality rates with 15% mortality in isolated CCHB and 86% mortality in structural associated CCHB within the neonatal period [21]. Another study of 60 patients had a 15% cardiac attributable mortality rate, despite 67% pacemaker implantation in a population of autoantibody (i.e. not structural) associated CCHB [22]. In contrast, in Balmer’s study of 32 children, 81% were paced with one death from likely ventricular electrode exit block (3% mortality) [23]. The likelihood that this difference in outcome is primarily due to a difference in experience is low. This raises the question of whether the difference in outcome is due to presence of a different spectrum of disease seen within our Australasian series. Certainly it seems the reports of CCHB from South East Asia tend to run at slower heart rates [24]. The median heart rate among our cases was 60 bpm, at which rate these infants seem to cope quite well. Though guidelines suggest pacing below a heart rate of 55 bpm, usually a HR 50–55 bpm seems to be tolerated satisfactorily. A HR around 45 bpm may lead to symptoms, while a HR of 40 bpm or less needs pacing. In addition, contributing to the low mortality was the low number of cases with structural heart disease, which usually carry a higher mortality.
Conclusions CCHB is a rare but potentially serious condition in infancy, with a significant morbidity and mortality as described in the current literature. This is the first reported single centre series on the outcomes and experience of CCHB from Australia. While the occasional patient required early pacemaker insertion, the majority had a pacemaker inserted in late infancy or early childhood, the indications being ventricular dilatation, decreasing exercise tolerance or intermittent profound bradycardia. There was no mortality attributable to CCHB from our series. One death occurred in a patient with multiple co-morbidities and complications of extreme prematurity and low birth weight. Our figures are extremely favourable compared to previously described mortality rates of 10–15%. Initial implantation of a single chamber VVIR appeared satisfactory though all subsequently had a dual chamber DDD on
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reimplantation. The battery life statistics were better than that reported elsewhere. In our experience, CCHB has a good outcome. We postulate this may reflect a different spectrum of disease seen in Australia.
Acknowledgements Pacemaker implantation was carried out at the Royal Children’s Hospital, Melbourne or Monash Medical Centre, Clayton.
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