Outcome in young patients with isolated complete atrioventricular block and permanent pacemaker treatment: A nationwide study of 127 patients

doi:10.1016/j.hrthm.2015.06.028

Heart Rhythm

Volume 12, Issue 11, November 2015, Pages 2278-2284

https://doi.org/10.1016/j.hrthm.2015.06.028 Get rights and content

Background

Subgroups of pacemaker (PM)–treated children with isolated complete atrioventricular block are at risk of developing left ventricular (LV) dysfunction.

Objectives

We aimed to compare the long-term outcome in anti-SSA-Ro/SSB-La antibody-exposed (AB+) and unexposed (AB−) patients and identify preimplantation variables associated with poor outcome.

Methods

In total, 127 PM-treated patients aged 0–17 years with isolated complete atrioventricular block were studied retrospectively.

Results

Sixty-three patients were diagnosed prenatally, of whom 92% were AB+. Before PM treatment, fractional shortening (FS) z-score was significantly lower in AB+ patients than in AB− patients (−0.14 ± 3.6 vs 2.03 ± 2.3). Before PM implantation, there were sex differences (male/female) in median time from diagnosis to PM implantation (0.2 years vs 1.0 years), median neonatal heart rate (50 beats/min vs 60 beats/min), left ventricular end-diastolic dimension (LVEDD) z-score (2.68 ± 1.41 vs 1.74 ± 1.40), and FS (−0.19 ± 3.38 vs 1.42 ± 2.98). The median age at PM implantation was 3.2 years, and median follow-up was 8.7 years. At follow-up, LVEDD and FS did not differ significantly between AB+ and AB− patients, but LVEDD was higher in patients diagnosed before 1 month of age. Nine patients (8%) developed LV dysfunction, and 4 died. LV dysfunction was associated with diagnosis before 1 month of age and abnormal LV function before PM implantation.

Conclusion

LV dysfunction at follow-up was seen only in cases diagnosed before 1 month, with abnormal echocardiography before PM implantation. Boys had a more compromised cardiac status and were paced at an earlier age than girls. Fetal AB exposure and male sex were related to abnormal LV function before PM therapy, but not at follow-up.

Introduction

Isolated congenital complete atrioventricular block (CAVB) is a rare disease that in the majority of cases is associated with exposure to maternal SSA/Ro and/or SSB/La autoantibodies, whereas isolated CAVB diagnosed later in life is usually not associated with exposure to maternal autoantibodies.¹ Indication for early pacemaker (PM) treatment is based on symptoms resulting from ventricular dysfunction and low heart rate, but also on electrocardiographic data. In spite of adequate timing of pacing in accordance with established guidelines, a subgroup of patients with CAVB will develop dilated cardiomyopathy (DCM).2, 3 Some studies suggest an association between right ventricular (RV) pacing and development of DCM.4, 5 Most studies are, however, small and do not differentiate between autoantibody-exposed (AB+) and unexposed (AB−) cases.

To address this knowledge gap, we performed a nationwide retrospective cohort study on PM-treated patients with isolated CAVB diagnosed before 15 years of age (1) to investigate if the long-term outcome after PM treatment was different in AB+ and AB− individuals with isolated CAVB and (2) to identify preimplantation factors associated with poor outcome.

Section snippets

Patient Selection

The strategy of identification and enrollment of patients has been described previously.⁶ Briefly, patients were identified by searching the following registers: (1) Swedish ICD and Pacemaker Registry, (2) Swedish National Patient Registry, (3) Swedish Cause of Death Registry, and (4) local clinical patient registries, as well as through a network of pediatricians, cardiologists, and rheumatologists at 6 university hospitals in Sweden. Identified patients were asked to participate, and written

Baseline Characteristics

Table 1 details the clinical characteristics. In total, 127 patients were followed for a median of 8.7 years, of whom 112 (88%) had mothers who were tested for the presence of SSA-Ro/SSB-La autoantibodies and 69 (62%) were AB+. Sixty-three patients (50%) were diagnosed in fetal life, and 92% of those tested were AB+ (Figure 1). The proportion of cases diagnosed before 1 month of age was significantly higher in AB+ cases than in AB− cases, often with CAVB already present at presentation (Table 1

Discussion

In this retrospective nationwide study, we describe the outcomes in the largest reported data set of young persons with isolated CAVB and PM treatment. The survival rate was 96% at follow-up after approximately 9 years of pacing. Overall, this outcome compares well with previous studies, with survival rates around 95% and similar duration of follow-up.2, 9

Nine patients (8%) developed LV dysfunction, a result similar to those of several previous studies,2, 4, 10, 11, 12, 13 but different from

Conclusion

Our study confirms previous results showing an excellent outcome of patients with isolated CAVB and PM treatment. In the subgroup developing LV dysfunction, early diagnosis and impaired cardiac status before PM treatment were risk factors of poor outcome. We also report on a sex difference in time from diagnosis to PM treatment as well as more impaired LVF values in males than in females before PM treatment—a new finding that needs to be further elucidated, preferably in a prospective setting.

Acknowledgments

We thank the following persons who contributed to data collection: Katarina Hanséus, PhD, Margareta Hellman, MD, and Ida Jeremiasen, MD, Skåne University Hospital, Lund; Anders Nygren, PhD, Mats Mellander, PhD, and Britt-Marie Ekman-Joelsson, PhD, Queen Silvia Children’s Hospital, Gothenburg; André Bachtiar, MD, Karlstad County Hospital Karlstad; Eva Fernlund, MD, Linköping University Hospital Linköping; Linda Lagnefeldt, RN, Elisabeth Zeffer, RN, and Anita Fredenson, Karolinska University

References (20)

E.T. Jaeggi et al.
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)
F.E. Udink ten Cate et al.
Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children
J Am Coll Cardiol
(2001)
J.P. Moak et al.
Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela
J Am Coll Cardiol
(2001)
S.D. Colan et al.
Developmental modulation of myocardial mechanics: age- and growth-related alterations in afterload and contractility
J Am Coll Cardiol
(1992)
E. Villain et al.
Presentation and prognosis of complete atrioventricular block in childhood, according to maternal antibody status
J Am Coll Cardiol.
(2006)
J.P. Buyon 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)
J.J. Kim et al.
Ventricular function and long-term pacing in children with congenital complete atrioventricular block
J Cardiovasc Electrophysiol
(2007)
R.A. Gebauer et al.
Predictors of left ventricular remodelling and failure in right ventricular pacing in the young
Eur Heart J
(2009)
S. Salomonsson et al.
A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block
Scand J Immunol
(2011)
C. Kampmann et al.
Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe
Heart
(2000)

There are more references available in the full text version of this article.

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Longitudinal echocardiographic parameters before and after pacemaker placement in congenital complete heart block
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Congenital complete heart block (CCHB) is seen in 1:15,000–1:20,000 live births, with risk of left ventricular (LV) dysfunction or dilated cardiomyopathy in 7%–23% of subjects.
The purpose of this study was to investigate serial changes in LV size and systolic function in paced CCHB subjects to examine the effect of time from pacemaker on echocardiographic parameters.
Single-center retrospective cohort analysis of paced CCHB subjects was performed. Echocardiographic data were collected before and after pacemaker placement. Linear mixed effect regression of left ventricular end-diastolic dimension (LVEDD) z-score, left ventricular shortening fraction (LVSF), and left ventricular ejection fraction (LVEF) was performed, with slopes compared before and after pacemaker placement.
Of 114 CCHB subjects, 52 had echocardiographic data before and after pacemaker placement. Median age at CCHB diagnosis was 0.6 [interquartile range 0.0–3.5] years; age at pacemaker placement 3.4 [0.5–9.0] years; and pacing duration 10.8 [5.2–13.7] years. Estimated LVEDD z-score was 1.4 at pacemaker placement and decreased –0.08 per year (95% confidence interval [CI] –0.12 to –0.04; P = .002) to 0.2 (95% CI –0.3 to +0.3) 15 years postplacement. Estimated LVSF decreased –1.1% per year (95% CI –1.7% to –0.6%; P <.001) from 6 months prepacemaker placement to 34% (95% CI 32%–37%) 4 years postplacement. There was no significant change in LVSF between 4 and 15 years postplacement. Estimated LVEF did not change significantly after pacemaker placement, with estimated LVEF 59% (95% CI 55%–62%) 15 years postplacement.
In 52 paced CCHB subjects, estimated LVEDD z-score decreased significantly after pacemaker placement, and estimated LVSF and LVEF remained within normal limits at 15 years postpacemaker placement.
A Not-So-Natural History of Nonsurgical Complete Atrioventricular Block in Children in the Current Era
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Incidence of morbidity and mortality in a cohort of congenital complete heart block patients followed over 40 years
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Citation Excerpt :
It is possible that a greater degree of myocardial inflammation in utero may increase the likelihood of fetal diagnosis of heart block and also increase the likelihood of presentation of heart failure and/or cardiomyopathy early in life. Although our study demonstrated a similar rate of survival (94%) and rates of heart failure and/or cardiomyopathy (12%) to previous studies, the composite outcome reached in 23% of subjects is higher than in several previously published studies.2,6-10 We attribute this difference to our composite definition of the primary outcome, combining LV systolic dysfunction, heart failure, cardiomyopathy, use of CRT, and mortality.
Congenital complete heart block (CCHB) is seen in 1:15,000–20,000 births and commonly requires pacemaker placement by young adulthood. There is limited understanding of cardiac morbidity and mortality.
The purpose of this study was to determine the long-term incidence of cardiac morbidity and mortality in subjects with CCHB and identify associated risk factors.
Retrospective cohort analysis of subjects with CCHB at Children’s Hospital of Philadelphia between 1976 and 2018 was performed. The primary outcome was a composite of death, left ventricular systolic dysfunction, heart failure, cardiomyopathy, or cardiac resynchronization therapy (CRT). Cox proportional hazard models assessed independent risk factors for the primary outcome and its components (death, heart failure and/or cardiomyopathy, CRT).
One-hundred fourteen subjects (58% female; median age at last visit 15.2 years) were included. Eighty-eight (77%) underwent pacemaker implantation (median age at placement 1.9 years; interquartile range [IQR] 0.1–8.0 years). Twenty-six subjects (23%) reached the primary outcome; 7 (6%) died and 14 (12%) were diagnosed with heart failure and/or cardiomyopathy. Median time from diagnosis to primary outcome was 3.1 years (IQR 0.0–10.8 years). There were no significant associations between age at diagnosis <1 year (hazard ratio [HR] 1.5; 95% confidence interval [CI] 0.6–3.9), fetal diagnosis (HR 2.3; 95% CI 0.96–5.6), or maternal antibody positivity (HR 2.4; 95% CI 0.9-6.6) and the primary outcome. Fetal diagnosis had a higher associated hazard of heart failure and/or cardiomyopathy (HR 4.5; 95% CI 1.3–15.0).
In 114 subjects with CCHB, 23% reached the composite outcome of cardiac morbidity and mortality, with no significant association between age at diagnosis, fetal diagnosis, and maternal antibody status with composite cardiac morbidity and mortality.
Editorial commentary: Live better electrically? Optimizing the timing and application of pacing in congenital heart block
2020, Trends in Cardiovascular Medicine
Congenital heart block: Pace earlier (Childhood) than later (Adulthood)
2020, Trends in Cardiovascular Medicine
Congenital complete heart block (CCHB) occurs in 2–5% of pregnancies with positive anti-Ro/SSA and/or anti-La/SSB antibodies, and has a recurrence rate of 12–25% in a subsequent pregnancy. After trans-placental passage, these autoantibodies attack and destroy the atrioventricular (AV) node in susceptible fetuses with the highest-risk period observed between 16 and 28 weeks’ gestational age. Many mothers are asymptomatic carriers, while <1/3 have a preexisting diagnosis of a rheumatic disease. The mortality of CCHB is predominant in utero and in the first months of life, reaching 15–30%. The diagnosis of CCHB can be confirmed by fetal echocardiography before birth and by electrocardiography after birth. Whether early in-utero detection and treatment might prevent or reverse this condition remains controversial. In addition to autoantibody-associated CCHB, there is also an isolated (absent structural heart disease) nonimmune early- or late-onset heart block detected later in childhood that may be associated with specific genetic markers or other pathogenic mechanisms. In isolated immune or non-immune CCHB, cardiac pacemakers are implanted in symptomatic patients, however, data on the natural history of CCHB in the adult life indicate that all patients, even if asymptomatic, should receive a pacemaker when first diagnosed. However, important issues have emerged in these patients wherein life-long conventional right ventricular apical pacing may produce left ventricular dysfunction (pacing-induced cardiomyopathy) necessitating a priori alternate site pacing or subsequent upgrading to biventricular pacing. All these issues are herein reviewed and two algorithms are proposed for diagnosis and management of CCHB in the fetus and in the older individual.
Predicting postpartum cardiac events in pregnant women with complete atrioventricular block
2019, Journal of Cardiology
Women with complete atrioventricular block (CAVB) can tolerate hemodynamic changes during pregnancy; however, the incidence of cardiac events in women with CAVB may increase after delivery. The aim of this study was to investigate predictive factors for postpartum cardiac events in pregnant women with CAVB.
Pregnant women with CAVB who received perinatal management at a tertiary cardiac center from 1981 to 2015 were retrospectively reviewed. Univariate and multivariate logistic analyses of postpartum cardiac events were performed. Postpartum cardiac event was defined as cardiopulmonary arrest, cardiac failure, or the need for permanent pacemaker implantation (p-PMI) within 3 months after delivery. A total of 63 pregnancies in 36 women with CAVB were included in this study; 25 had undergone p-PMI before pregnancy. Regardless of p-PMI status, women with CAVB had no further increases in heart rate during the second and third trimesters. No heart failure was found during pregnancy and delivery. Postpartum cardiac events occurred in 9 pregnancies (14.3%) in 8 women with CAVB; 3 had cardiac failure and p-PMI, 3 had cardiac failure, 2 required p-PMI, and 1 had cardiopulmonary arrest. Multivariate analysis showed that perinatal ventricular pause (odds ratio 11.60, 95% confidence interval 1.90–82.18, p < 0.01) and family history of CAVB (odds ratio 10.59, 95% confidence interval 1.36–90.56, p = 0.03) were associated with postpartum cardiac events.
All cardiac events occurred during the postpartum period among women with CAVB, and ventricular pause during the perinatal period and a family history of CAVB were predictors of postpartum cardiac events. Close follow-up should be considered during the postpartum period for women with high-risk CAVB.

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: This study was supported by grants from the Swedish Heart and Lung Foundation, Karolinska Institutet Research Foundations, Freemason’s in Stockholm Foundation for Children’s Welfare, Samariten Foundation, and Swedish ICD and Pacemaker Registry.

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Outcome in young patients with isolated complete atrioventricular block and permanent pacemaker treatment: A nationwide study of 127 patients

Background

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Patient Selection

Baseline Characteristics

Discussion

Conclusion

Acknowledgments

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol.

J Am Coll Cardiol

Ventricular function and long-term pacing in children with congenital complete atrioventricular block

J Cardiovasc Electrophysiol

Predictors of left ventricular remodelling and failure in right ventricular pacing in the young

Eur Heart J

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block

Scand J Immunol

Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe

Heart