An association between congenital complete atrioventricular block (cCAVB) and aortic dilation during childhood has recently been reported. We sought to further explore this relation with particular emphasis on the natural history of aortic abnormalities over time. The relation of maternal anti-Ro/La antibody status to the aortic size of children affected with cCAVB was also assessed. The patients were evaluated longitudinally with serial echocardiography. During a 15-year period, 62 patients at our institution were diagnosed with cCAVB, of whom 40% were exposed to maternal autoimmune antibodies and 35% were not. The antibody status in the remaining patients was unknown. The patients underwent 9.3 ± 6.5 echocardiograms during the follow-up period. Dilation of the ascending aorta, defined as a z score >2.0, was present on the initial echocardiogram in all patients exposed to maternal antibodies and persisted during long-term follow-up in 96% of these patients. In contrast, 5% and 10% of patients without exposure to maternal autoimmune antibodies had aortic dilation on the initial and follow-up studies, respectively (p <0.001 and p <0.001, respectively). In conclusion, patients with autoimmune-mediated cCAVB merit periodic echocardiographic monitoring into adulthood to assess persistent or progressive aortic dilation and its attendant complications.
It has recently been recognized that some infants with congenital complete atrioventricular block (cCAVB) have dilation of the ascending aorta. Whether this dilation occurs secondary to the increase in stroke volume accompanying the reduced heart rate or whether aortic dilation occurs as an associated primary defect is not known. We sought to assess the frequency of aortic dilation in patients with isolated cCAVB, to determine the clinical correlates of aortic dilation in this population, including maternal antibody status, and to describe the natural history of aortic dilation in affected patients.
Methods
The present study was reviewed by our institutional review board and granted a waiver of informed consent. The pediatric cardiology databases were reviewed, and all patients who were diagnosed with isolated congenital heart block during fetal life or childhood (age <18 years) from May 1985 to December 2009 were identified.
The diagnosis of cCAVB was determined by the clinical history at the initial evaluation and was made in accordance with the cardiac, rather than the rheumatologic, definition of the disorder. The cardiac definition restricts isolated cCAVB to a relatively young age even if it extends beyond the first month of life.
The following clinical data were then abstracted from the medical records of the identified patients: gestational age at diagnosis, gestational age at birth, birth weight, maternal anti-Ro and anti-La antibody status, presence or absence of maternal rheumatologic disorders, age at initial postpartum echocardiogram, heart rate at the initial echocardiogram, age at pacemaker implantation, follow-up duration, age at last echocardiogram, and clinical status. All patients were assigned to 1 of 3 categories according to their maternal antibody status: anti-Ro/La positive, anti-Ro/La negative, or unknown.
All patients underwent echocardiography at diagnosis, before pacemaker placement, and throughout the follow-up period. All studies were completed by a qualified echocardiographic sonographer and reviewed by a board-certified pediatric cardiologist. For the purposes of the present study, all echocardiograms were independently examined by 2 study investigators, and the echocardiographic measurements were recorded off-line. The echocardiographic measurements included the aortic diameters obtained from the parasternal long-axis view in systole and diastole, using the inner-edge to inner-edge technique, and measured at the level of the sinuses of Valsalva and ascending aorta. The ascending aortic measurement was obtained at the widest point of ascending aortic dilation in accordance with the recommendations set forth by the American Society of Echocardiography. For each location, 3 measurements were obtained and averaged. The individual z scores were then calculated for each aortic systolic measurement to compare differences in body size-adjusted aortic measurements between study groups and within groups over time. The left ventricular end-diastolic diameter, and shortening fraction were recorded from the parasternal views. The ratio of the ascending aortic diameter to the sinus of Valsalva diameter was calculated on each study using the measurements obtained and compared to normal values to determine whether aortic dilation differentially affected any portion of the aorta studied.
The subjects were excluded for the following reasons: no appropriate echocardiographic images at diagnosis, no recorded height or weight, preventing assessment of z scores, the presence of hemodynamically important structural heart disease (all defects other than a patent foramen ovale or small atrial septal defect), and the presence of other diagnoses associated with aortic dilation (i.e., bicuspid aortic valve, Turner syndrome, Marfan syndrome, or Loeys Dietz syndrome).
Summary statistics were calculated and reported as the median and 25th and 75th interquartiles. The Statistical Package for Social Sciences, version 14, for Windows (SPSS, Chicago, Illinois) was used. Continuous data were compared using the Wilcoxon rank sign test, Mann-Whitney U test, and Kruskal-Wallis test, as indicated. Categorical data were compared using chi-square tests. A trend for age at diagnosis was assessed using the chi-square for trend test. Statistical significance was defined as a p value of <0.05.
Results
A total of 57 patients met the inclusion criteria. Of the 57 patients, 14 with cCAVB were excluded from additional analysis for the following reasons: echocardiographic images obtained at diagnosis or on ≥1 follow-up echocardiogram were inadequate to measure all aortic diameters (n = 8), absent documentation of height or weight at the echocardiographic study (n = 3), and the presence of structural cardiac defects (n = 3). No patient had potentially confounding diagnoses associated with aortopathy.
Select demographic and clinical features are listed in Table 1 . Of the 57 patients, 23 (40%) were born to women with documented anti-Ro/La antibodies and 20 (35%) were born to women who were antibody negative. The mothers of the remaining 14 patients (25%) had an unknown antibody status, and these patients were excluded from additional analysis. Most of the antibody-positive group had been diagnosed prenatally or immediately after birth; thus, their small body size is reflective of their younger age. In contrast, most of the antibody-negative patients were diagnosed postnatally. The duration of clinical follow-up for the 2 groups was similar ( Table 1 ). Of the entire patient cohort, 20% had reached adulthood (age >18 years) at their last assessment.
| Variable | Anti-Ro/La Positive (n = 23) | Anti-Ro/La Negative (n = 20) | p Value |
|---|---|---|---|
| Male | 9 (39%) | 13 (65%) | 0.09 |
| Age at diagnosis (days) | <0.001 | ||
| Median | 0 | 858 | |
| Interquartile range | 37, 1,944 | ||
| Diagnosis period | <0.001 | ||
| Prenatal | 10 (44%) | 0 | |
| At birth | 10 (44%) | 4 (20%) | |
| >1 Day of life | 3 (13%) | 16 (80%) | |
| Heart rate (beats/min) at presentation | 0.14 | ||
| Median | 66 | 56 | |
| Interquartile range | 54, 83 | 46, 80 | |
| Age at pacemaker placement (years) | <0.001 | ||
| Median | 0 | 6.3 | |
| Interquartile range | 0, 0.6 | 3, 10.3 | |
| Duration of follow-up (years) | 0.17 | ||
| Median | 8.2 | 11.5 | |
| Interquartile range | 5.6, 12.4 | 6.5, 18.5 | |
| Interval between first and last echocardiogram (years) | 0.86 | ||
| Median | 4.8 | 4.1 | |
| Interquartile range | 2.1, 10.5 | 1.4, 12.7 | |
| Death/transplant | 2 (9%) | 0 | 0.18 |
Of the entire patient cohort of 43 patients, 33 (77%) required pacemaker placement at a median age of 1.1 years (interquartile range 0 to 6.6). Antibody status was not related to the need for pacemaker implantation (70% of antibody-positive patients vs 80% of antibody-negative patients, p = 0.43). When studying the entire cohort of patients, no relation was found between the initial ascending aortic z score and the heart rate at the first echocardiogram (r = 0.07, p = 0.7). Given that the age at diagnosis varied significantly between those with and without antibody exposure, the patients who were antibody positive were also analyzed separately. Within this group of patients, no relation was also found between the indexed ascending aortic diameter and heart rate at diagnosis (r = −0.003, p = 0.9) or at long-term follow-up (r = 0.2, p = 0.3).
No cardiac deaths occurred in this patient series; however, 1 patient from the antibody-positive cohort died from trauma. One patient in the antibody-positive group required cardiac transplantation at 2 years of age for congestive heart failure secondary to progressive decrease in left ventricular function in the setting of a dilated cardiomyopathy present from birth. Two others in this group had stable asymptomatic dilated cardiomyopathy. These 3 patients did not differ from the rest of the antibody-positive cohort with respect to the ascending aortic z score at diagnosis (5.4 ± 2.7 vs 4.7 ± 2.4, p = 0.6) or at long-term follow-up (4.1 ± 0.9 vs 4.2 ± 2.9, p = 0.9). All remaining patients were free of cardiac symptoms with normal ventricular function at long-term follow-up.
The entire cohort of patients with cCAVB, irrespective of antibody status, underwent serial echocardiography with a mean number of echocardiograms per patient of 9.2 ± 6.5. Of the 575 echocardiograms performed, 402 (70%) were available for review. Of those reviewed, adequate imaging of the ascending aorta, defined as a demonstration of ≥2 cm above the sinotubular junction, was obtained for only 66% of the studies.
The initial echocardiographic findings for the maternal antibody positive and negative groups are reported in Table 2 . In those patients with autoimmune-mediated cCAVB, 6 (26%) had dilation at the level of the sinuses of Valsalva, and all had dilation of the ascending aorta ( Table 2 ). In contrast, dilation of the sinuses of Valsalva was not seen in any patient whose mother tested negative for anti-Ro/La antibodies. The median ascending aortic z scores in the antibody-positive group were significantly greater than in the antibody-negative group ( Table 2 ). In contrast to the normal configuration of the ascending aorta, the ratio of the ascending aorta to sinuses of Valsalva was abnormal (i.e., >1) on the initial echocardiogram in 87% of the maternal antibody-positive patients reflective of isolated or disproportionate ascending aortic dilation in the vast majority of these patients. Patients with a documented absence of exposure to maternal anti-Ro/La antibodies were significantly more likely to have a normal configuration of the aortic root, with the largest aortic diameter obtained at the sinuses of Valsalva ( Table 2 ). Despite the presence of 3 patients with dilated cardiomyopathy in the antibody-positive group, the overall left ventricular size and function was normal in both groups of patients ( Table 2 ). No patient had greater than trivial aortic insufficiency, despite significant aortic dilation.
