Europace Advance Access originally published online on March 9, 2007
Europace 2007 9(4):228-232; doi:10.1093/europace/eum008
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PACING
Evolution of left ventricular function in paediatric patients with permanent right ventricular pacing for isolated congenital heart block: a medium term follow-up
Hungarian Institute of Cardiology, Haller u. 29, 1096-H, Budapest, Hungary
Manuscript submitted 27 November 2006. Accepted after revision 10 December 2006.
* Corresponding author. Tel: +36 30 2 187637; fax: +36 1 2157067. E-mail address: szili.torok{at}kardio.hu
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Abstract |
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Aims: We aimed to assess the evolution of left ventricular (LV) systolic function in children with right ventricular apical (RVA) pacing for isolated congenital heart block (ICHB) and to identify possible predictors of LV function deterioration. Right ventricular apical pacing can be detrimental to LV function in a significant number of adults. Effects in children are still controversial.
Methods and results Left ventricular shortening fraction (LV SF) and QRS duration were retrospectively assessed in 45 children with RVA pacing for ICHB: before pacemaker (PM) implantation, immediately after and then regularly during a follow-up of 58.69 ± 45.23 months. Patients were categorized as stable or deteriorators according to an arbitrarily chosen cut-off point of 
7% decrease in LV SF. Lupus status was unknown. Overall LV SF did not change significantly (41.42% ± 8.21 before pacing, 39.77% ± 7.03 immediately after PM implant, 37.43% ± 9.91 with chronic pacing, P = NS). Deteriorators (n = 13) had significantly higher baseline heart rate (57.5 ± 8.7 vs. 46.9 ± 10.5 bpm, P < 0.05) and baseline LV SF (46.17 ± 8.13 vs. 38.4 ± 6.4%; P < 0.05), a significantly higher proportion of them being implanted before 2 years of age: 8 of 13 (61.5%) vs. 5 of 25 (20%) in the stable group (P < 0.05). Deteriorators had a higher incidence of an initial epicardial lead and narrower native QRS.
Conclusion Permanent RVA pacing for ICHB does not necessarily affect LV function in children. The risk of deterioration of LV function seems to be higher in children with higher baseline heart rate and better baseline LV SF, especially with pacing at a younger age, a narrower native QRS and RVA epicardial pacing site.
Key Words: Congenital heart block, Permanent pacing, Children, LV systolic function
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Introduction |
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The estimated incidence of congenital heart block (CHB) in the general population is 1/11 000–1/22 000 live-born infants,1
,2 in 15–30% of the cases there is associated structural heart disease.3 Untreated isolated congenital heart block (ICHB) carries an unpredictable risk of sudden cardiac death and is also associated with heart failure morbidity.4 The natural course of chronically paced paediatric patients has been considered to be relatively benign, with a normal life expectancy.5
Permanent cardiac pacing in paediatric patients is traditionally performed at the right ventricle apex (RVA), mainly for the simplicity of the implantation and stability of the lead performance with either endocardial or epicardial approach. However, RVA pacing causes asynchronous left ventricular (LV) contraction due to bypassing of the normal conducting system and non-physiological activation sequence.6 This is associated with multiple short-term adverse effects of non-homogeneous LV wall strain such as paradoxical septal motion, altered LV systolic performance,7–9 elevated LV filling pressure,10 and altered coronary blood flow.11 Chronic RVA pacing can induce histopathological anomalies.12 These anomalies can be the substrate of pacing induced LV dysfunction reported in a significant number of patients.13–15 Although the clinical significance of pacing induced anomalies is still controversial, in paediatric patients there are data supporting LV adverse remodeling,16,17 possibly resulting in dilated cardiomyopathy (DCM) and heart failure.18–20 The aim of the present investigation was to asses the evolution of LV function in children paced for ICHB and to identify possible predictors of deterioration of LV function with chronic RVA pacing.
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Methods |
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Study patients
The study group consisted of 45 children (20 females) who underwent permanent RV pacemaker (PM) implantation between March 1989 and September 2004 for congenital heart block (CHB) in the absence of significant structural heart disease. The presence of any condition known to affect LV function was excluded from the study. The study group consisted of patients with ICHB (n = 33), CHB associated with long QT syndrome (n = 3), CHB and insignificant cardiac structural anomalies [small ostium secundum type atrial septal defect (n = 5), bicuspid aortic valve (n = 1), and mild pulmonary valve stenosis (n = 1)], or corrected congenital heart structural anomalies [surgically closed ventricular septal defect (n = 1) or patent ductus arteriosus (n = 1)]. Patients who were diagnosed as having myocarditis and/or DCM before or at the time of PM implantation, and the patients with signs of medically refractory heart failure who had not responded to pacing were excluded from the group. None of the mothers had clinical evidence of lupus erythematosus, but their antibody status was not assessed.
Clinical data
Demographic data including sex, age at PM implant, baseline heart rate, type of RV lead, (epicardial vs. endocardial), rate and mode of pacing (single vs. dual chamber, with or without rate response), and duration of pacing were collected. Complications and reimplantations (including changing the lead and/or pacing mode) were also recorded.
All available echocardiographic and ECG data prior and after PM implantation were obtained. Left ventricular function was evaluated by two-dimensional and M-mode echocardiography. Left ventricular end-diastolic diameter (LVEDD) and LV end-systolic diameter (LVESD) were measured. Left ventricular shortening fraction (LV SF) calculated as (LVEDD–LVESD)/LVEDD x 100 was used as a marker of LV function. Left ventricular SF (%) and QRS duration (ms) were measured before and immediately after PM implantation, and then regularly during the follow-up. Using the most recent echocardiographic study patients were divided into two groups according to an arbitrarily chosen cut-off point of a persistent 7% absolute decrease in LV SF, as deteriorator patients (D) with <7% decrease being the stable (S) group.
Statistical analysis
The measured values are expressed as mean ± SD. Data showing Gaussian distribution were compared using paired (data before and after PM implantation) and Student's t-tests (comparing data in the subgroups). Dichotomous variables were compared using 
2 test. Non-parametric data were compared using Wilcoxon test. To determine the variables independently associated with deterioration of LV systolic function after pacing multivariate analysis was performed for the following clinical values: age at the PM implantation, type of leads, baseline QRS duration, baseline LV SF, and baseline heart rate. The level of significance was set at P < 0.05.
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Results |
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Patient data
The mean duration of follow-up was 58.69 ± 45.23 months (range: 5–188.5 months) (Table 1). Pacing indications were severe bradycardia/pauses, syncope, LV dilation, and AV block associated with long QT syndrome. There were no significant complications related to the PM implantation. The mean age at the time of PM implantation was 47.67 ± 47.38 months (median 35.9, range 0–144). In 18 children (40%), pacing commenced under 2 years of age. Twenty five children (56%) received a single chamber PM. Pacing site was RVA in all the patients, and an epicardial lead was initially implanted in 19 patients (42%). At the time of the implant, patients with epicardial leads were significantly younger (12.8 ± 23 months vs. 75.5 ± 43 months) and they had a significantly narrower native and paced QRS than patients with endocardial leads (53.7 ± 11.5 vs. 69.5 ± 13.5 ms, respectively, 118 ± 21 vs. 143 ± 19 ms, P < 0.05). During the follow-up there was no significant difference in paced QRS duration between epicardial and endocardial leads (145 ± 20 vs. 155 ± 25 ms, P = NS).
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Evolution of the LV systolic function during follow-up
For the overall group, chronic RV pacing did not affect LV systolic function significantly (Figure 1 and Table 2).
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There were 13 patients (28.9%) in whom LV SF decreased by
7% (deteriorators) (Table 3). There was a trend for this group to be younger at the time of PM implant, significantly more patients in the deteriorator group being implanted before 2 years of age: 8 of 13 (61.5%) by comparison with 5 of 25 (20%) in the stable group (P < 0.05) (Figure 2). On univariate analysis, baseline heart rate and LV SF were significantly higher in deteriorators (57.5 ± 8.7 vs. 47.4 ± 10.4 bpm, respectively, 46.17 ± 8.13% vs. 38.4 ± 6.4%, P < 0.05). In this group, there was also a trend for epicardial lead implantation and a narrower native QRS. There was no significant difference in the pacing rate between subgroups, as well in PM type (single vs. dual chamber, rate responsive vs. fixed rate). On multivariate analysis a better baseline LV SF and a higher baseline heart rate were independently associated with LV systolic function deterioration.
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Progression to DCM
Only three patients (6.6%) developed DCM. One was diagnosed after 11 months of pacing, one after 25 months, and one after 9 years of pacing. Pacing was started at the age of first day of life, 20 months and 25 months, respectively. Initially, a single chamber system was implanted in all these patients. In one patient, cardiac resynchronization therapy was later introduced. None of the clinical and pacing data was associated with the development of DCM.
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Discussion |
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The major finding of this study is that RVA pacing in paediatric patients is not necessarily deleterious, although a significant number of them express a deterioration in LV systolic function, especially with early institution of pacing.
Evolution of LV function in paediatric patients with chronic RV pacing. Comparison with former studies: predictors
Isolated congenital heart block in the era of modern pacing has been considered to be a benign condition with excellent long-term prognosis.5 However, due to extremely long periods of pacing in patients stimulated from childhood or even the newborn period, concerns emerged regarding known negative effects of chronic RV apical pacing on LV function. Clinical data are still controversial, some supporting an overall negative effect12,16,17 while others denying it.21 Although the present study did not find a significant overall deleterious effect of RV apex pacing on systolic LV function, we found that a significant proportion (29%) of these patients had developed various degrees of LV function deterioration. Interestingly, this is in concordance with other observations on adult populations, including the magnitude.13,15 The predictive value of better pre-implant LV systolic function is somewhat unexpected and confirms recent adult data.15 On the other hand, younger age at the moment of the implant seems to be an important factor.3,18,19,20
Surprisingly, in this study higher baseline heart rate was predictive of deterioration of LV function with RVA pacing, opposite to other data.19 A possible explanation for this is that we excluded patients with signs of myocarditis and DCM as well as those with heart failure that was refractory to pacing. Those patients usually have lower escape rates, very likely due to a more diffuse myocardial and conducting tissue disease. Another explanation for this finding is that mean age at the PM implantation in the deteriorator group was lower, which can attenuate the known age-related effect of escape focus rate slowing.5 However, multivariate analysis showed that higher baseline heart rate in the deteriorator group is independent of younger age at the moment of PM implantation.
The increased use of epicardial leads in the deteriorator group seems to be related to significantly increased proportion of these patients receiving a PM before 2 years of age, pacing parameters of modern steroid-eluting epicardial leads being equivalent to those of endocardial leads in paediatric patients.22 Furthermore, there are data showing that the paced QRS depends on the presence of structural heart disease and widening above 120 ms is not observed in children under 4 years.23 Interestingly enough, in this patient population we did not observe significant differences between epicardial and endocardial lead implants in the paced QRS in the overall group. This can be partly explained by the fact that epicardial implants were performed at younger age in this study. The increased likelihood of a narrower native QRS duration in the deteriorator group is related to younger age at the implant, as supported by the fact that native QRS width increases with age.23,24
Dilated cardiomyopathy
In this study, we found a 6.6% incidence of DCM, which is concordant with previous data.18,19,25 The aetiology of late onset cardiomyopathy can be in utero autoimmune myocarditis.18,19 Isolated congenital heart block being only a part of a more diffuse process with different clinical expression due to genetic or environmental factors. One must consider also post-natal myocarditis as well as tachycardiomyopathy induced especially with early institution of pacing.
Possible mechanisms: adverse remodelling: the role of alternative pacing sites
There are data that chronic strain anomalies induced by RVA pacing translate not only into microscopic disarray but also in detrimental LV remodelling, with increased LV end-diastolic diameter and septal to posterior wall thickness ratio,17 eventually evolving to DCM. There is evidence that allowing intrinsic rhythm,26 changing the pacing site to LV apex,27 or upgrading to a biventricular system26 can improve LV systolic function. Pacing at the LV apex is also associated with resolution of perfusion defects induced by RV apical pacing,27 possibly by a more synchronous LV electrical activation pattern.28 Although there seems to be some agreement that LV apex is the optimal epicardial pacing site for CHB, data on optimal endocardial pacing site is less clear. There is an increasing trend for positioning the ventricular lead into septal positions in the RV, preferably in the RV outflow tract (RVOT),29 which is also advantageous if one considers that the heart of a child primarily grows in the long axis. However, there are at least four RV septal pacing positions,30 and, at least in adult populations, some of them seem not to be superior to RV apical pacing.31 Another important issue when alternative pacing sites are discussed is the diffuse nature of conducting tissue disease in CHB.
Study limitations
This study is limited due to its retrospective nature, which makes fixed time comparisons impossible. Furthermore, maternal antibody status was unknown which may underestimate autoimmune cardiomyopathy in the patients. Another potential limitation is the use of LV SF for the evaluation of LV systolic function which can underestimate the proportion of deteriorators by comparison with more sensitive methods like TDI or three-dimensional, especially in patients with asynchronous LV wall contraction. However, due to diffuse nature of pacing-induced LV anomalies LV SF can be considered reliable, especially in the context of limited inter-observer variability (all the echocardiographic studies were done only by three experienced operators). More importantly, we included in the deteriorator group only the patients with persistent decrease in LV SF. In addition, a 7% absolute decline in LV SF corresponds to a 15% decrease in LV ejection fraction (LV EF), which is a higher cut-off value than previously used in any of the available studies.13,15 An important aspect is that we eliminated the patients in whom primary or secondary myocardial diseases could blur the effect of pacing. There could be also an underestimation of the true proportion of deteriorators by the limited period of follow-up (shorter than 12 months for a few patients). Although in some studies LV systolic function was significantly affected by RVA pacing in only 18 months,32 most of the studies done on RVA pacing showed that the LV systolic function can already be affected at 6 months of follow-up.13,14,15
Conclusions
Right ventricular apical pacing for ICHB in paediatric patients is still a safe procedure, although it does affect LV systolic function in a significant proportion of children, warranting close follow-up not only for their pacing parameters but also for their LV function, especially in patients younger than 2 years of age, with good baseline LV function and higher baseline heart rate. Late onset cardiomyopathy associated with pacing is infrequent. Our data suggest that RVA epicardial lead implantation may not be optimal in these patients and an alternative site for the epicardial lead placement should be considered.
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