Left ventricular pacing in neonates and infants with isolated congenital complete or advanced atrioventricular block: short- and medium-term outcome

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1 Europace (2015) 17, doi: /europace/euu180 CLINICAL RESEARCH Cardiac electrophysiology Left ventricular pacing in neonates and infants with isolated congenital complete or advanced atrioventricular block: short- and medium-term outcome Massimo Stefano Silvetti 1 *, Duccio Di Carlo 2, Antonio Ammirati 1, Silvia Placidi 1, Corrado Di Mambro 1, Lucilla Ravà 3, and Fabrizio Drago 1 1 Arrhythmia Unit and Syncope Unit, Department of Paediatric Cardiology, Bambino Gesù Children s Hospital, IRCCS, Via Torre di Palidoro 1, Palidoro-Rome, Italy; 2 Cardiac Surgery Unit, Bambino Gesù Children s Hospital, IRCCS, Rome, Italy; and 3 Epidemiology Unit, Bambino Gesù Children s Hospital, IRCCS, Rome, Italy Received 9 September 2013; accepted after revision 10 June 2014; online publish-ahead-of-print 12 August 2014 Aims Right ventricular (RV) pacing may induce left ventricular (LV) dysfunction: neonates and infants with isolated congenital complete/advanced atrioventricular block (CCAVB) are at high risk of developing RV pacing-induced LV dyssynchrony, remodelling, and dysfunction. We prospectively investigated whether LV pacing results in normal LV function and good clinical status in the short/medium term.... Methods In this single-centre, prospective study, 10 consecutive patients with CCAVB (median age 4 months, range: ) and results underwent pacemaker implantation (4 VVIR, 6 DDD) using epicardial leads (on the LV apex in 8, on the LV free wall in 2). Data were collected at implantation and at 1- and 12-month follow-up. Echocardiographic evaluation included two-dimensional/three-dimensional assessment of LV dimensions, function (ejection fraction, EF), and ventricular synchrony (interventricular and intraventricular dyssynchrony). Prior to pacemaker implantation, EF was normal in six patients, 50% in two, 40% in two. All patients showed good clinical status and normal LV dimensions at follow-up. Patients with LV dilatation and impaired EF at implantation showed LV reverse remodelling and enhanced LV function. Normal LV function and synchrony were observed in most patients (one patient with EF 53% and three patients with mild dyssynchrony at 12-month follow-up). Paced QRS complex tended to be wider than native QRS complexes (P ¼ 0.07); QTc duration of paced complexes was within normal limits or only slightly prolonged, without significant differences compared with QTc interval of native complexes.... Conclusion At short- and medium-term follow-up, LV pacing results in satisfactory LV electromechanical function and synchrony in neonates and infants with CCAVB Keywords Children Cardiac pacing Alternative pacing sites Congenital atrioventricular block Heart failure Introduction Permanent cardiac pacing in children 1 and infants 2 4 with isolated congenital complete or advanced atrioventricular block (CCAVB) is technically challenging because of age, body size, somatic growth, and the expected long duration of pacing. 5 Although conventional right ventricular (RV) pacing is generally well tolerated, it may induce ventricular dyssynchrony 6,7 predisposing to left ventricular (LV) remodelling and dysfunction in 6 13% of children Neonates and infants with CCAVB are at high risk of developing RV pacing-induced LV dyssynchrony, remodelling, and dysfunction. Pacing-induced dilated cardiomyopathy (DCM) has been reported to occur early in up to 32% of these patients. 12 Therefore, alternative pacing sites have been proposed. Epicardial LV pacing, either from the apex or free wall, has been shown to preserve ventricular function and synchrony. 11,13 16 We prospectively investigated whether LV * Corresponding author. Tel: ; fax address: silvetti@opbg.net Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oup.com.

2 604 M.S. Silvetti et al. What s new? This is the first prospective study of neonates and infants with congenital complete/advanced atrioventricular block undergoing left ventricular (LV) pacing. At 12-month follow-up, the clinical status was good in all patients, with normal LV function and synchrony in most patients. Patients with LV dilatation and dysfunction at implantation showed reverse remodelling of LV dimensions and function. QTc duration of paced QRS complexes was within normal limits or only slightly prolonged and there were no significant differences compared with QTc intervals of native QRS complexes (narrower QRS). pacing results in normal function and good clinical status in the short and medium term. Methods All consecutive neonates and infants referred to the Arrhythmia Unit of Bambino Gesù Children s Hospital (Rome, Italy) for CCAVB requiring pacemaker implantation between 2010 and 2012 were enroled in this single-centre, prospective study. The following data were recorded: demographics, including age and size of patients, surgical procedure, characteristics of the pacing system implanted, electrocardiographic and echocardiographic findings at implantation and during follow-up, occurrence of complications, and the clinical status at the most recent follow-up. The study complies with the Declaration of Helsinki. The research protocol was approved by the locally appointed ethics committee. Informed consent was obtained from the guardians of all patients. Implant procedure, pacemakers, and leads All patients routinely underwent electrocardiogram (ECG) and echocardiography prior to implantation. The surgical technique used for implantation of the pacing system at our centre has already been described. 2,17 Briefly, a midline sternotomy is performed and the pacing leads are sewn to the epicardial surface of the heart. The epicardial leads are tunnelled to the abdomen, and the pacemaker is placed in a pocket created beneath the posterior fascia of the rectus abdominis. The indications for pacing were in accordance with the guidelines of the European Society of Cardiology. 18 The site of lead implantation wasthe LV apex(beyond left anterior descending coronary artery, at a minimum distance of 5 mm) in eight patients and the LV free wall towards the apex in two. Leads were steroid-eluting, either unipolar (Medtronic 4965, five atrial and six ventricular) or bipolar (Medtronic 4968, one atrial and four ventricular), directly affixed and sutured to the epicardium. In bipolar leads, the location of the stimulating electrode (cathode) was considered as the site of implantation. Six dual-chamber (DDD) and four single-chamber (VVIR) pacemakers were implanted. At implantation, the lower and upper pacing rates were 80 (60 110) and 190 ( ) b.p.m., respectively. In patients with VVIR pacemakers, the lower and upper pacing rates were 100 (75 110) and 160 ( ) b.p.m., respectively. In patients with DDD pacemakers, the lower and upper pacing rates were 80 (60 90) and 185 ( ) b.p.m., respectively. The sensed atrioventricular delay, set at 105 (60 120) ms, was optimized using Doppler echocardiography, and adapted to increases in heart rate with a minimum value of 60 (50 80) ms. Follow-up All patients were followed up with clinical evaluation and telemetric pacemaker interrogation at 1, 3, and 6 months after implantation, and every 6 months thereafter. A standard 12-lead ECG was recorded at 1 and 12 months. Parameters evaluated included heart rhythm, atrial and ventricular rate, QRS duration, and QT duration. QRS and QT duration were measured manually from standard ECG recorded at a paper speed of 25 mm/s; QT duration was measured by two independent readers; the QT interval was calculated by the tangent method. 19 If calculations differed between readers, the average value was used. The QTc interval was calculated according to Bazett s formula. QTc dispersion (QTcd) was also measured. Echocardiographic evaluation was performed routinely prior to pacemaker implantation, and at 1- and 12-month follow-up. Standard M-mode, two-dimensional, and Doppler measurements were obtained, including LV dimensions (expressed as absolute values and weight-related Z scores), LV fractional shortening (FS, normal value, n.v.: 28%, subnormal:,28%, depressed:,25%), interventricular dyssynchrony [interventricular mechanical delay (IVMD), as the time from QRS onset to aortic flow onset minus QRS onset to pulmonary flow onset, n.v.,40 ms], and LV dyssynchrony [septal to posterior wall motion delay (SPWMD), n.v.,130 ms]. Three-dimensional echocardiographic data were acquired for measurement of LV volumes and function [ejection fraction (EF), n.v.: 55%, subnormal:,55%, depressed:,45%] and the systolic dyssynchrony index (SDI, n.v.:,5.5, mild: 5.5, moderate: 11, severe LV systolic dyssynchrony: 15.5). 20,21 The assessment of interventricular and intraventricular dyssynchrony was not performed routinely prior to pacemaker implantation. All post-implant echocardiographic studies were performed by a single expert cardiologist blinded to the pacing site. Statistical analysis Continuous variables are expressed as median and range, and categorical variables as absolute numbers and percentages. Mean + standard deviation of QRS duration is reported merely for comparison with other measurements reported in the literature. Friedman test was used for assessing correlations of repeated measures (pre-implantation, 1 and 12 months post-implantation), and Kendall s coefficient of concordance was calculated. The non-parametric Spearman s correlation coefficient was calculated to assess correlations between values of SDI, EF, and QRS duration. Comparison with historical data on RV pacing in neonates and infants 12 was performed using the two-sample Wilcoxon rank-sum (Mann Whitney) test. A P value of,0.05 was considered statistically significant. All statistical analyses were conducted using StataSE 12.0 (StataCorp.). Results Between 2010 and 2012, 10 patients (8 female) with CCAVB underwent pacemaker implantation using epicardial ventricular leads placed in the LV. Autoantibodies (anti-ssa/ro and anti-ssb/ La) were detected in five out of nine patients (one patient was not investigated). All patients were in good clinical status before the implant procedure, except one who had congestive heart failure requiring temporary intravenous inotropic support.

3 Left ventricular pacing in infants 605 Age at implantation was 4 months (range: 3 days to 16 months), body weight was 6.0 (2.4 10) kg, and height was 60 (46 80) cm. Patients undergoing single-chamber pacemaker implantation were younger, but without statistical significance (median age 3 months, range: 3 days to 6 months vs. median age 10 months, range: 3 days to 15 months, P ¼ 0.2), and had a significantly lower body weight than patients receiving a dual-chamber pacemaker (2.8 kg, range: kg, vs. 8.4 kg, range: 3 10 kg, P ¼ 0.03). Differences in lower and upper pacing rates between VVIR and DDD modes were not significant. Electrocardiographic and echocardiographic data at implantation Electrocardiographic data and echocardiographic findings are summarized in Table 1. The interobserver difference in QTc measurement was 1% (0 7%). Sinus tachycardia was detected on standard 12-lead ECG in three patients (175, 180, and 200 b.p.m.). The native QRS complex was narrow in all but two patients (110 ms), and QTc prolongation was observed in four patients (480, 500, 500, and 520 ms). Doppler echocardiographic examination revealed mild LV dilatation in three patients (Z scores ). Left ventricular FS was normal in seven patients, 27% in one patient, and,25% in two patients; EF was 55% in six patients, 50% in two patients, and 40% in two patients. Complications There were no intraoperative complications. One case of mediastinitis occurred 4 days after implantation. The patient was treated with systemic antibiotics and mediastinal irrigation with complete recovery. No other early or late (.3 months) post-operative complications were recorded. Follow-up The amount of ventricular pacing was 99.5% (95 100%). All patients were in good clinical status at the follow-up visits without the need for drug treatment. None of them developed either signs of congestive heart failure or DCM. All patients showed normal growth: at 1-month follow-up, weight was 6.2 ( ) kg and height was 63 (50 81) cm; at 12-month follow-up, weight was 9.9 ( ) kg and height was 82 (69 90) cm. Electrocardiographic data and echocardiographic findings Electrocardiographic data and echocardiographic findings at followup are summarized in Table 2. Sinus rate showed a tendency towards a reduction [145 ( ) b.p.m. before pacemaker implantation, 133 ( ) b.p.m. at 1-month follow-up, and 116 (98 142) b.p.m. at 12-month followup; P ¼ 0.2, Kendall s coefficient ¼ 0.47]. The ECG (Figure 1) showed mild prolongation of the paced QRS complex [90 (80 110) ms] as compared with the native QRS complex [60 (50 110) ms, P ¼ 0.07, Kendall s coefficient ¼ 0.57]. The mean + standard deviation of QRS duration was ms. QTc intervals of paced QRS complexes were at the upper limit of normal or only slightly prolonged [450 ( ) and 440 ( ) ms at 1- and 12-month follow-ups, respectively] but not significantly longer than in the native QRS complex [435 ( ) ms, P ¼ 0.2, Kendall s coefficient ¼ 0.43]. QTc dispersion was within normal limits [40 (20 80), 40 (20 50), and 40 (30 60) ms at implantation, and 1- and 12-month follow-ups, respectively; P ¼ 0.7]. At the echocardiographic examinations, LV end-diastolic diameter showed a small but significant increase (24 30 mm, P ¼ 0.018, Kendall s coefficient ¼ 0.73) and LV end-systolic diameter showed a marginally significant increase (14 16 mm, P ¼ 0.059, Kendall s coefficient ¼ 0.60). However, Z scores during follow-up were normal, with a trend towards a reduction after pacemaker implantation. Left ventricular volumes were within normal limits: LV enddiastolic and end-systolic volumes were 14 (5 19) and 6 (2 9) ml at implantation, 17 (5 20) and 7 (2 9) ml at 1-month follow-up, and 15 (11 22) and 6 (4 9) ml at 12-month follow-up, respectively Table 1 Patients pre-implantation data Patient Age Weight Heart rate Sinus rate QRS QTc LVEDD Z LVESD FS Pacing (years) (kg) (b.p.m.) (b.p.m.) (ms) (ms) (mm) score (mm) (%) site LVA LVA LVA LVFW LVA LVA LVFW LVA LVA LVA Median // b.p.m., beats per minute; FS, fractional shortening; LVA, left ventricular apex; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end systolic diameter; LVFW, left ventricular free wall.

4 606 M.S. Silvetti et al. Table 2 Patients data at 1 and 12 months Patient Heart rate (b.p.m.) Sinus rate (b.p.m.) QRS (ms) QTc (ms) LVEDD (ms) Z score LVESD (ms) FS (%)... Follow-up 1 month Median Follow-up 12 months Median Kendall s coefficient P The correlations between repeated measurements (pre-implantation, 1 12 months) were performed by Friedman test (see text for further details). b.p.m., beats per minute; FS, fractional shortening; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end systolic diameter; NA, not available. (P ¼ 0.09 and P ¼ 0.10). Left ventricular function improved, with FS increasing from 43 to 46% (P ¼ 0.054, Kendall s coefficient ¼ 0.61) and EF from 55 to 59% (P ¼ 0.4, Kendall s coefficient ¼ 0.35) (Table 2 and Figure 2). In patients with impaired LV function prior to pacemaker implantation, EF increased during follow-up. In two patients with the highest pre-implantation EF values, a slight reduction in EF was observed (from 61 to 55% and from 62 to 53%). Two patients showed an EF of 53% at 1- and 12-month follow-ups, respectively. In the remaining patients, EF was within the normal range (Figure 2). The assessment of interventricular and intraventricular dyssynchrony revealed normal IVMD values in all but one patient (Figure 3) and normal SPWMD values in all but three patients (Figure 4). Systolic dyssynchrony index could not be evaluated in three patients at 1-month follow-up because of restlessness. At 12-month follow-up, SDI was within normal limits in all but three patients who showed mild dyssynchrony (range: ) (Figure 5). Spearman s correlation coefficient revealed an inverse correlation between EF and SDI (20.4, P ¼ 0.3), and EF and QRS duration (20.2, P ¼ 0.6); the relationship between QRS duration and SDI was (P ¼ 0.9). In comparison with historical data on RV pacing, 12 there were no significant differences in age, EF, heart rate, and sinus rate at implantation, as well as in the upper pacing rate, whereas a nearly significant difference was found in the lower pacing rate. The only significant difference was the duration of paced QRS complexes, being shorter with LV pacing than with RV pacing [90 (80 110) vs. 130 ( ) ms, P ¼ ] (Table 3). Discussion Single-centre retrospective studies have consistently shown that LV pacing is safe and effective in preserving LV synchrony and function. 11,13,16,22 Alargeretrospectivemulticentresurvey 23 andamulticentre cross-sectional echocardiographic evaluation of retrospectively collected data 24 have both demonstrated that the pacing site is the most important determinant of LV function in children with CCAVB: LV function was shown to be significantly improved after chronic LV pacing (LV apex/lateral free wall) compared with chronic RV pacing, especially if the RV free wall was the pacing site, regardless of the pacing mode (DDD or VVIR). 23,24 In addition, in an experimental study, LV apical and septal pacing was found to maintain LV contractility, relaxation, and efficiency compared with RV pacing. 25 To the best of our knowledge, this is the first prospective study of neonates and infants with CCAVB undergoing pacemaker implantation

5 Left ventricular pacing in infants 607 A B Figure 1 Electrocardiogram. (A) VVIR pacing (Patient 7, pacing site: LV free wall); (B) DDD pacing (Patient 8, pacing site: LV apex).

6 608 M.S. Silvetti et al. 70 Ejection fraction SPWMD EF, % ms Pre-impl. 1 month 12 months pt.1 pt.2 pt.3 pt.4 pt.5 pt.6 pt.7 pt.8 pt.9 pt Figure 2 Changes in LV EF. pt., patient; pre-impl., before pacemaker implantation. Median (range): pre-impl. 55% (36 62%); 1 month 58% (53 60%); 12 months 59% (53 66%). Kendall s coefficient 0.35, P ¼ 0.4. See text for further details month 12 months pt.1 pt.2 pt.3 pt.4 pt.5 pt.6 pt.7 pt.8 pt.9 pt IVMD Figure 4 Changes in septal to posterior wall motion delay (SPWMD). ms, milliseconds, pt., patient. Median (range): 1 month, 120 ms ( ms); 12 months 102 ms ( ms). Kendall s coefficient 0.44, P ¼ 0.5. See text for further details SDI ms % month 12 months pt.1 pt.2 pt.3 pt.4 pt.5 pt.6 pt.7 pt.8 pt.9 pt Figure 3 Changes in IVMD. ms, milliseconds, pt., patient. Median (range): 1 month, 16 ms (5 53 ms); 12 months, 13 ms (3 35 ms). Kendall s coefficient 0.79, P ¼ 0.1. See text for further details. 0 1 month 12 months pt.1 pt.2 pt.3 pt.4 pt.5 pt.6 pt.7 pt.8 pt.9 pt.10 with epicardial leads placed in the LV. Despite the small sample size that makes relevance and reliability of correlations questionable and the relatively short follow-up, data obtained prospectively from this peculiar patient subset seem to provide valuable information. Figure 5 Changes in the SDI. pt., patient. Median (range): 1 month, 6.6% ( ms); 12 months, 4.9% ( ). Kendall s coefficient 0.38, P ¼ 0.6. See text for further details.

7 Left ventricular pacing in infants 609 Table 3 Comparison of LV and RV pacing LV pacing RV pacing 12 P value (current data)... Age at implantation 0.4 ( ) 0.1 ( ) 0.1 (years) Heart rate (b.p.m.) 60 (42 80) 59 (40 86) 0.6 Sinus rate (b.p.m.) 145 ( ) 140 ( ) 0.9 Pre-implantation 55 (36 62) 58 (52 68) 0.5 EF (%) Lower pacing rate 80 (60 110) 95 (70 135) (b.p.m.) Upper pacing rate 160 ( ) 180 ( ) 0.5 (b.p.m.) Paced QRS duration (ms) 90 (80 110) 130 ( ) The comparison was performed by two-sample Wilcoxon rank-sum (Mann Whitney) test. See text for further details. b.p.m., beats per minute; LV, left ventricular; RV, right ventricular. The clinical outcome was favourable after 1 year of pacing at physiological rates. At last follow-up examination, all infants showed good growth and haemodynamic status, no signs of heart failure, normal LV dimensions, adequate LV function and synchrony. Notably, EF was improved in patients with impaired pre-implant LV function and was normal in most patients. Interventricular mechanical delay and SPWMD values were overall within normal limits. At 12-month follow-up, the SDI values were normal in 70% of patients, and only mild dyssynchrony was observed in the remaining 30%. In adult patients, the SDI proved useful in assessing global LV systolic dyssynchrony, showing an inverse correlation with EF and a direct correlation with QRS duration. 26 An inverse relationship between SDI and EF was also found in our study, though not reaching statistical significance. Our findings show a reverse LV remodelling in patients with LV dilatation and dysfunction prior to pacemaker implantation, as reported in children with a de novo biventricular implantation. 27 Moreover, IVMD and SPWMD values were positive, meaning that the pulmonary valve opens before the aortic valve and the posterior wall does not contract before the septum, as in the normal sequence. In one of the largest studies on pacing sites in children, LV pacing resulted in short or negative IVMD and SPWMD. The authors found minimal interventricular and intraventricular dyssynchrony with LV apical and free wall pacing, while a reversed intra-lv dyssynchrony occurred with pacing towards the LV base. 24 While IVMD in the present study approaches the range shownbyjanouseket al., 24 SPWMD is considerably higher and consistently positive. This discrepancy of SPWMD can be related to the different populations examined: we collected a homogeneous group of patients, neonates, and infants with lower age at implantation ( vs years 24 )treatedbythesamesurgicalteamand largely paced from the LV apex (or from LV free wall towards the apex). These data show that in very young patients with small ventricular mass, LV apex pacing produces a sequence of activation close to normal sequence due to the homogeneous spread of activation from the apex towards the base, as expected in the absence of delay of activation between septum and left free wall. This activation might change with growth and the increase of ventricular dimension and mass: SPWMD show a trend towards a reduction after 1 year of pacing (Figure 4). More patients and longer follow-up could better explain these findings. Although this study did not aim to compare RV and LV pacing in neonates and infants, the absence of pacing-induced DCM is an interesting finding. In our previous experience in neonates and infants with normal ventricular function at implantation, 12 32% of patients who had undergone conventional epicardial RV pacing developed DCM early after pacemaker implantation (median time to DCM occurrence: 4 months), suggesting that DCM may be due to electromechanical dyssynchrony induced by high-rate RV pacing. A prolonged QT interval and/or a broad QRS escape rhythm at implantation seemed to be risk factors for DCM. These ECG features (QRS and QT duration) may be signs of myocardial damage, more severe electrical disease, and pre-implantation dyssynchrony. A subclinical myocardial damage may occur as a result of a higher pre-load at the lower heart rate pre-pacing, and EF can remain within the normal range because of the increased pre-load. The comparison with these historical data, 12 although not ideal, reveals that the two study populations do not significantly differ in terms of age, EF, heart rate, and sinus rate at implantation. The most relevant difference is the duration of the paced QRS complex, significantly shorter with LV pacing (Table 3) than with RV pacing. Most notably, although in adult patients the QRS complex is usually longer with LV pacing than with RV pacing, in our little patients LV pacing did not result in wide QRS complexes (Figure 1). In addition, in our study, the mean QRS duration in infants ( ms) seemed to be shorter than that reported in other older paediatric cohorts ( and ms 11 ). The wider QRS in older children and in adults may be the effect of an age-related increase in myocardial mass or the consequence of an underlying structural heart disease. It has been suggested that QRS duration may not be related to LV function, as it reflects the total electric activation time but not the sequence of activation. 16,24 However, an inverse correlation between LV fractional area change and paced QRS duration was demonstrated. 7 A trend towards an inverse relationship between EF and QRS was also evidenced in our study, with a lack of statistical significance that may simply be a reflection of inadequate sample size. It may therefore be assumed that a narrower paced QRS seems beneficial. In the present study, the higher sinus rate prior to implantation may suggest the presence of subclinical myocardial damage. At follow-up, an increase in heart rate (by pacing) and a reduction in atrial rate were observed. These features demonstrate the beneficial effect of pacing without the occurrence (or worsening) of sinus tachycardia induced by subclinical heart failure. Furthermore, pacing rates were high enough to cause LV dysfunction in the presence of significant dyssynchrony. It has been demonstrated that the use of Bazett s formula results in the most rate-dependent behaviour of paced QTc interval leading to longer QTc. 28 Therefore, despite the pacing rate used in our study and the wider paced QRS complex, at 12-month follow-up QTc intervals were normal or slightly prolonged 29 and not significantly longer than QTc intervals at implantation. This may be another sign of electromechanical reverse remodelling induced by LV pacing.

8 610 M.S. Silvetti et al. Limitations This study was not intended to compare different pacing sites. The comparison with our previous work 12 was performed merely to underline the good clinical and instrumental outcome in a population that, in our experience, seemed to be more prone to develop the worst effects of dyssynchronous pacing. Certainly, the lack of a prospective control group (either non-paced or paced at more conventional sites) makes a true comparison impossible, limiting the relevance of our analysis. In 10 patients, the relevance and reliability of correlations are questionable. However, despite the small sample size and the relatively short follow-up to obtain homogeneous data, some patients are now entering their third year of follow-up with a favourable clinical outcome. A direct comparison of echocardiographic data before and after pacing could not be made because the dyssynchrony assessment was not performed prior to implantation but only at different times of follow-up. Conclusions In a small cohort of neonates and infants with CCAVB undergoing permanent pacing early in their life, LV pacing resulted in (i) good clinical status in all patients and normal LV function in all but one patient (EF 53%); (ii) normal values of IVMD, SPWMD, and SDI in most patients; (iii) a reverse remodelling of LV dimensions and function in patients with LV dilatation and impaired EF at implantation; (iv) QTc duration within normal limits or only slightly prolonged as compared with native complexes, most likely as a sign of electromechanical reverse remodelling. These findings provide additional clinical, ECG, and echocardiographic data contributing to improve our knowledge of pacing physiology in small children with CCAVB. 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