Complete atrioventricular block diagnosed prenatally: anything new on the block?

In this issue of Ultrasound in Obstetrics and Gynecology there are two articles describing separate series of experiences with congenital heart block (CHB)1, 2. As this topic is not new on the horizon of fetal echocardiographic diagnosis of CHB, why are we seeing two fairly large series being published simultaneously? The answer probably lies in the now ready accessibility of improved ultrasound technology. This, and the collaboration of multiple centers, makes the acquisition of case series easier and quicker. It is now clear that there are basically two flavors of CHB diagnosed in utero: that which is associated with underlying structural heart disease, and the form of CHB that is associated with autoimmune antibodies. CHB associated with structural heart disease generally takes the form of left-sided isomerism or congenitally corrected transposition of the great arteries (cc-TGA). This particular type of CHB presents early in gestation, is associated with a very high risk of mortality, has no effective therapy, and highlights the importance of good prenatal counseling of the family. Not discussed in the accompanying articles is the potential role of improving technology of fetal pacing nor the usefulness of early recognition with high-definition fetal echocardiography with Doppler techniques in an attempt to diagnose first-degree block by PR interval prolongation3. The CHB that is associated with autoimmune antibodies, known as neonatal lupus, accounts for about half of the fetal diagnoses of CHB and has a much more favorable prognosis. Autoimmune-associated CHB occurs in about 1 : 15 000 live births but has a much higher prevalence of 1 : 50 births in antibody-positive women. Although the prognosis for autoantibody-associated CHB is better than that with structural heart disease4, there is still an approximately 20% mortality rate in this disease and most of the survivors (about 67%) require pacemakers5. There is a rate of late cardiomyopathy of approximately 10%. In the case of autoimmune-related CHB, various therapies have been tried including maternal dexamethasone, beta-agonists, fetal pacing and plasmapheresis. Except for the possible benefit of dexamethasone for the treatment of hydrops per se, no therapy has been proven to work in this disease. This fact calls for the initiation of an international, multicenter trial to search for treatments. An exciting suggestion is the use of prophylactic maternal intravenous gammaglobulin to prevent the onset of this serious disease. The Berg article1 is a retrospective review of all the cases of second- or third-degree fetal heart block gathered from three centers. Out of a total of 60 fetuses, 32 had complex congenital heart disease, of which 31 were left isomerism and one was a cc-TGA. There were only two survivors. In contrast, 20 fetuses had fetal heart block with maternal antibodies and no structural heart disease, and of this group there were 16 survivors. Finally, there was a small group of eight patients with CHB in the absence of maternal antibodies in addition to the absence of structural heart disease. There were only three survivors from this group. The authors were able to show that predictors of non-survival included the presence of hydrops and of structural heart disease. In the autoimmune antibody group, an enlarged fetal heart was a sign associated with hydrops and poor survival. In fact, in the cases in which the cardiothoracic circumference ratio exceeded 0.61 the fetuses all died. In the Berg article1 all 60 cases of CHB were detected prenatally, a tribute to fine fetal diagnostic skills. This group reports two cases of antibody-positive isolated CHB that reverted to either first-degree block or normal rhythm at birth. The patient with complete heart block reverting to normal sinus rhythm and persisting on follow up until the age of 13 years would be the first case in the literature to exhibit such a cure. It is also curious that digoxin was used occasionally in these cases as it is often withheld in the presence of bradycardia. Dexamethasone use in such pregnancies seemed to have no effect, as is supported in the literature. It is notable that sympathomimetic use was employed regardless of ventricular rate and seemed to have no effect. The Jaeggi article2 looks at the prenatal diagnosis of complete atrioventricular block and focuses on those cases that are associated with structural heart disease. The researchers combined the experience from two medical centers in a retrospective evaluation between 1990 and 2002 and compared this with reviews of the literature, including their own prior series. Jaeggi's group describes a total of 59 consecutive cases of fetal congenital atrioventricular block. Of these fetuses, 24 (41%) had underlying major congenital heart disease: 18 cases of left isomerism, three cases of cc-TGA, two cases of atrioventricular septal defect, and one case of a complex total anomalous pulmonary venous return. Conversely, they had 35 cases of isolated CHB that were previously reported by their group. Among the 24 cases of CHB with structural heart disease it can be concluded that these cases were detected earlier than the cases of autoimmune disease, and were more likely to be associated with hydrops, especially if the heart rate was under 60 bpm. The structural cases had a higher rate of termination of pregnancy and a lower rate of being offered prenatal therapy. Of the 16 structural CHB cases with continued pregnancies, three were offered treatment with beta-inotropes, but all the fetuses died. It is curious that the ventricular heart rates were comparable between the structural group and the autoimmune group but the structural group had a lower atrial rate, probably associated with anomalies of the sinoatrial node. The autoimmune group was less likely to have hydrops but more likely to have endocardial fibroelastosis. The structural heart block group had an overall 18% survival rate as compared to the isolated autoimmune heart block group with a 75% survival rate at 1 year. Of the four neonatal survivors of structural heart disease-associated heart block, all had a fetal heart rate above 60 bpm, and three of the four were able to undergo biventricular repair. The presence of two relatively similar series of prenatal diagnosis of atrioventricular block allows the knowledge gained from the two series to be combined. In the Berg series1, 32/60 fetuses with heart block had structural disease; in the Jaeggi series2, 24/59 patients had structural heart disease. The structural heart disease generally took the form of the very high-risk left isomerism, as well as the lower-risk cc-TGA. We learned that structural heart disease is associated with an extremely poor prognosis in fetuses with CHB. The structural lesions led to an earlier diagnosis of heart block, there was an absence of effective therapy, and a higher risk of fetal loss. The presence of cardiac enlargement is a predictor of hydrops and fetal demise. This information is not unique in the literature, but it does contrast quite well with the better outcome seen in cases of autoimmune-associated CHB without structural heart disease when there is usually an 80% survival. We are also taught that the ventricular rate itself in the presence of fetal heart block is not predictive of outcome, and that the use of sympathomimetics is generally not useful. What might be learned from the comparison of these two studies is that one might consider that structural heart disease-associated CHB holds a dismal prognosis and that the families are best served by knowledgeable prenatal counseling. Conversely, in the presence of autoimmune CHB without structural fetal heart disease the prognosis is much better, and therefore one would offer frequent serial echocardiography to these affected cases, with the use of Doppler mechanical PR interval detection of the earliest signs of heart block in subsequent pregnancies at risk. In the future it is hoped that prospective drug trials may be able to discover a preventive therapy for the autoantibody-associated cases at risk.