Left ventricular (LV) pacing in newborns and infants: Echo assessment of LV systolic function and synchrony at 5‐year follow‐up

Small retrospective studies reported that left ventricular (LV) pacing is likely to preserve LV function in children with isolated congenital complete atrioventricular block (CCAVB). The aim of this study was to prospectively evaluate LV contractility and synchrony in a cohort of neonates/infants at pacemaker implantation and follow‐up.

in our previous prospective study on LV pacing in a small cohort of patients. 10 On this ground, in the present study, we report the outcome of a larger group of neonates and infants with CCAVB treated with LV epicardial pacing through a longer follow-up period.

METHODS
Between 2010 and 2018, all consecutive neonates and infants referred to the Cardiac Arrhythmias Unit of Bambino Gesù Children's Hospital (Rome) for CCAVB requiring pacemaker implantation were enrolled in this single-center, prospective study. The study population included patients with CCAVB without other congenital heart defects. The following data were recorded: demographic characteristics, including age and size of patients, pacing system implanted, electrocardiographic and echocardiographic findings at implantation and during follow-up, and 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 echocardiogram evaluation before implantation.
The surgical technique used for pacing system implantation at our Center was already described. 10 Briefly, a midline sternotomy or a sub-  In patients with DDD pacemakers, the sensed atrioventricular delay was optimized using Doppler echocardiography for mitral flow mea-surements (median: 100; 25th-75th centiles: 80-120 ms), and adapted to increases in heart rate (shortest 60, 50-90 ms).

Follow-up
All patients were followed up at 1 and 6 months after implantation with clinical evaluation and telemetric pacemaker interrogation. Thereafter, the same evaluation was repeated every 6 months.
During in-hospital controls, a standard 12-lead ECG was recorded.

Pacemaker implantation and follow-up
Data at implantation are reported in Table 1 (Table 2). However, EF improved in all patients with low EF, reaching normal values. GLS was within normal limits in all patients. Figure 1 shows GLS measurements in two patients, one with LVA pacing and one with LVFW pacing. The presence of autoantibodies had no effect on LV systolic function.

DISCUSSION
In the last few years, alternative pacing sites in pediatric pacing have been more commonly used, either with endocardial pacing in the right ventricle 18,19 or with epicardial pacing in the LV. Retrospective studies in children have consistently shown that LV pacing is safe and effective in preserving LV synchrony and function. [8][9][20][21][22] In 2015, our group published the first prospective study on this issue, 10  LV pacing from LV apex (preferred site) or from the low free wall (used in three cases at the beginning of this experience) seems to produce a sequence of activation close to normal, probably due to the homogeneous spread of activation from the apex/low lateral wall toward the base, as expected in absence of delay of activation between septum and left free wall. 10 Moreover, in the small group of patients with reduced EF before pacemaker implantation, EF increased and normalized after LV pacing. Consequently, a positive functional effect of LV pacing can be predicted in infants or small children with CCAVB and impaired LV function. In addition, the effect on LV function is independent from pacing mode used, VVIR or DDD. A simple VVIR pacemaker is generally enough to preserve heart rate and LV function in low-birthweight infants with CCAVB and structurally normal heart. 25

LIMITATIONS
The limitations of this study are as follows: the single-center study, the relatively small number of patients (common to most pediatric studies), and the follow-up not longer than 5 years. Moreover, echo-derived measurements have been used as sole criteria of ventricular function.
Indeed, echo measurements can be biased and subjective to individual interpretation. EF is not a perfect index of contractility, as it is influenced by LV loads and volumes. 23 Then, volumes and strain measurements were registered 24 to better assess contractility. The automated quantification of myocardial strain reduces the measurement errors, the interobserver variability, and intraobserver variability and improves accuracy and reproducibility of this method. It can be questioned that no patient underwent direct hemodynamic contractility measurements. However, the hemodynamic assessment is an invasive test that in this cohort was not necessary due to the good clinical status of patients and possible procedural risks. Cardiac magnetic resonance is another effective noninvasive functional tool, but it is not allowed with epicardial leads.

CONCLUSIONS
In a cohort of neonates and infants with CCAVB, LV pacing demonstrated at 5-year follow-up: 1. to be effective in maintaining good clinical status; 2. to preserve LV systolic function and synchrony; 3. that high DDD pacing rates did not show deleterious effects on LV function; and 4. to increase EF in patients with impaired LV function before pacemaker implantation.
These findings provide additional pacing and electrocardiographic and echocardiographic data that may improve our knowledge of pacing physiology in small children with CCAVB.

AUTHOR CONTRIBUTIONS
Massimo Stefano Silvetti and Fabrizio Drago were associated with concept/design, data analysis/interpretation, drafting article, critical revision of article, and approval of article. Giulia Muzi, Marta Unolt, Carolina D'Anna, and Corrado Di Mambro assisted in data collection, data analysis/interpretation, drafting article, critical revision of article, and approval of article. Fabio Anselmo Saputo was associated with data collection, data analysis/interpretation, and approval of article. Sonia Albanese and Antonio Ammirati assisted in data collection, data anal-ysis/interpretation, critical revision of article, and approval of article.
Lucilla Ravà was associated with data analysis/interpretation, statistics, critical revision of article, and approval of article.