To our knowledge, this is the first longitudinal study of atrial and ventricular heart rate and rhythm patterns in a sizable population of fetuses with AVB assessed by magnetocardiography. We found that 2° AVB, isolated 3° AVB, and 3° AVB associated with structural cardiac disease manifest distinctly different electrophysiological characteristics and that no transitions occurred between 2° and 3° AVB. Fetuses with 2° AVB showed complex, variable rhythm patterns associated with diverse forms of AV conduction and variable atrial rhythms. In fetuses with isolated 3° AVB, disease progression was reflected in the escape rhythm, which could deteriorate to a nonreactive pattern, often in association with intermittent QRS broadening and/or tachycardia. Junctional ectopic tachycardia and frequent ventricular ectopy were early predictors of more severe disease. Remarkably, all patients with isolated AVB are alive and well. In contrast, those with structural cardiac disease and 3° AVB showed nonreactive heart rate tracings, comparatively monotonous rhythm, and high postnatal mortality. This high mortality in association with structural heart disease has been previously reported (9
); the nonreactivity implies that the pacemaker is infranodal.
Junctional ectopic tachycardia and VT, which were present in 30% of 3° AVB subjects, were not generally identified before referral despite multiple echocardiograms, in part because of their brief and paroxysmal nature and also because these rhythms were not easily distinguished from intermittent conduction or various forms of ectopy. We speculate that VT, JET, and frequent ectopy may be characteristic of an acute stage of 3° AVB and that their prevalence may relate to the severity of the disease during the acute phase. Our findings suggest that when JET is observed in the fetus with or without AVB, the mother should be tested for SSA and SSB antibodies, as previously suggested by Dubin et al. (10
It is commonly believed that AVB associated with SSA antibodies occurs gradually and that the degree of block reflects disease severity, but this has not been systematically documented. Our data suggest that the preponderance of injury to the conduction system occurs early and very rapidly and/or that 2° and 3° fetal AVB may have different etiology. The 3° AVB fetuses were already in 3° AVB at presentation, generally before 30 weeks’ gestation. Although it is plausible that these fetuses had gradual progression from 1° to 3° AVB before recognition, our data suggest instead that the onset of 3° AVB was rapid and was often accompanied by frequent ectopy and JET. The 2° AVB fetuses presented at similar gestational ages, yet remained in 2° AVB throughout the study. In contrast, some previous studies have reported a substantial conversion rate from 2° to 3° fetal AVB (9
). We speculate that the presence of frequent ectopy and JET, which were common at early gestational ages, and isorhythmic AV dissociation, can lead to overestimation of 2° versus 3° fetal AVB and of conversion from 2° to 3° fetal AVB.
Fetuses with 2° AVB exhibited complex, changing rhythms such as intermittent pre-excitation, alternating high and low atrial rhythms, and variable AV conduction, including rhythm patterns suggestive of multiple AV nodal pathways and/or “supernormal” conduction. “Supernormal” conduction refers not to conduction that is more rapid than normal, but to conduction that is more rapid than expected, pertaining especially to situations when block is expected. It has been invoked previously to explain PR alternation in patients with impaired AV conduction (11
); however, conclusive evidence is generally difficult to obtain due to such alternative explanations as dual AV nodal pathways, concealed junctional extrasystoles, and “gap” phenomena (13
). In this study, the suggestion of “supernormal” conduction in association with PR alternation was supported by analysis of AV conduction curves. The marked PR prolongation during the “long” phase of the cycle strongly suggests the presence of a concealed, slow AV nodal pathway. The consistent conduction at extremely short RP interval during the “short” phase of the cycle, along with the fact that the pattern always terminated with block during the “long” phase, suggests that conduction during the “short” phase occurred through a concealed “supernormal” pathway.
We have previously shown that T-wave abnormalities (QT prolongation, T-wave alternans) (14
) and P-wave amplitude elevation (15
) are common in fetal bradycardia, including fetal AVB, and may be associated with suboptimal outcome and compensatory hypertrophy, respectively. In this study, the incidence and degree of QRS prolongation was modest; however, fetuses with wide escape rhythms, even when present intermittently, required neonatal pacing. PR prolongation in 2° AVB was also modest in most subjects, implying that detection of disease onset based on assessment of echocardiographic mechanical PR interval will require high measurement precision. Fetal magnetocardiography monitoring and other electrophysiological screening for pre-clinical features of antibody-mediated conduction disease such as atrial or ventricular hypertrophy, T-wave alternans, or QT prolongation before the onset of heart block may supplement the echocardiographic mechanical AV interval measurement in pregnant lupus or antibody-positive patients.
Owing to the ability of fMCG to assess atrial and ventricular FHR simultaneously, it could be seen that beat-to-beat FHR variability was abolished when the ventricular rate fell below about 56 beats/min, and it could be verified that the atrial reactivity remained normal despite the wide-ranging reactivity of the ventricular FHR. It was also observed that VSA caused a marked increase in beat-to-beat atrial FHR variability, which was evident even before the third trimester when beat-to-beat FHR variability normally is very low due to immaturity of the parasympathetic nervous system. This implies that arterial pulsations, which are the source of VSA, exert a rapid and strong influence on sinus rate, although their influence is evident only during heart block and/or AV dissociation.
The use of steroid therapy in fetal AVB associated with SSA antibodies remains controversial. Although we found no evidence that steroid therapy is effective in reversing AVB or nonreactivity, we believe that the improved long-term survival reported by Jaeggi et al. (16
) justifies the use of steroid therapy when acute inflammatory findings or poor prognostic indicators such as ventricular dysfunction or endocardial fibroelastosis, arrhythmias, severe QT prolongation, or T-wave alternans are present. A means by which the role of steroids in AVB could be elucidated would involve study of a large number of SSA-positive patients during sinus rhythm, using fMCG to seek the natural history of AVB and the causes of sudden demise. A limitation of the technique, however, is the very low signal amplitude before about 18 weeks’ gestation.