Response to Letters Regarding Article, “Perinatal Outcome of Fetal Atrioventricular Block: One-Hundred Sixteen Cases From a Single Institution”
We wish to thank Marijon for his comments on our recent article.1 We were also surprised with our results, which showed that in fetuses with normal cardiac anatomy, fetal, neonatal, and late death were not related to the presence or absence of anti-RO (SS-A) antibodies (29 positive anti-RO and 9 negative anti-RO of 38 surviving; P>0.05). Although our data showed no significant differences between the 2 groups in terms of fetal, neonatal, or late deaths, we agree that the finding of maternal autoantibodies is of great importance not only because they are mainly related to the genesis of the heart block (72% in our series) but also because they are related to the late outcome of maternal autoimmune diseases and dilated cardiomyopathy (DCM). Of course, these 2 entities differ completely in terms of pathophysiology and may also do so in terms of prognosis. Moreover, we do not have a ready explanation for the great differences in the incidence of DCM between our series and the series described by Villain et al.2 Although the title of this long-term study was “Perinatal Outcome of Fetal Av Block,” we have not focused only on this period and all patients were carefully followed up using the classically accepted diagnostic criteria for DCM3 and by physicians with expertise in pediatric cardiology. Our incidence of DCM was 6% (2/32 neonatal survivors of seropositive mothers), similar to those of other studies,4,5 and we are therefore sure that there has not been any kind of underestimation of DCM in this series.
We also wish to thank Jaeggi et al for their comments about our recent article.1 Of course, not all forms of isolated atrioventricular (AV) block have the same risks or outcome, and we think this article supports this idea, seeing that it presents many different aspects of this complex disorder:
First, we included all cases of AV block diagnosed by the first fetal echocardiogram, not to “improve survival estimates by 7%,” but because our intention was to show the natural history of this disease by not having any interruption in the isolated group. Even excluding cases that showed spontaneous regression of the AV block (all seronegative), page 1272 still showed that the 32 seropositive untreated fetuses had live birth and 1-year survival rates of 93% (95% confidence interval, 85 to 100) and 90% (95% confidence interval, 80 to 100), respectively. Moreover, after >20 years working with fetal echocardiography, we can affirm that minimal differences in the interatrial interval could occur in 2:1 AV block, and we should not celebrate when this aspect is present and immediately counsel the parents that everything will work itself out. When we perform the first fetal echocardiogram, we know neither the antibody status of the mother nor the “functional nature” of the heart block, and it is necessary to exercise caution before predicting a happy ending. We agree that Figure 3B shows some shadows that resemble atrial wall movement differing in time, but Figure 3A clearly shows that the intervals between atrial contractions were the same. Our diagnostic criteria are to consider 2:1 AV block when the time interval between atrial contractions is fixed, knowing that rapid periods of minimal difference can sometimes occur. These periods should not be considered to “neutralize” the periods of 2:1 AV block because the 2 phenomena may exist simultaneously. Thus, the patients presented in Table 2 were in accordance with the diagnostic criteria for 2:1 AV block, and we did not have any doubt about the differential diagnosis of premature blocked atrial contractions.
Secondly, in Table 1 of their article, Jaeggi et al6 show 4 cases of seronegative mothers, 2 treated with dexamethasone. Including seronegative patients in an article that asserts the importance of the use of routine transplacental immunosuppressive treatment to improve outcome of seropositive complete AV block is a contradiction, and seems as if Jaeggi et al (and not Lopes et al) are considering that “all forms of isolated AV block have the same risks, treatment, and outcome.”
Thirdly, we still have serious doubts that the standardized approach of Jaeggi et al6 does, in fact, account for the improved outcome. As requested by the letter from Jaeggi and colleagues, we compared our 36 cases with proven exposure to maternal anti-Ro antibodies at the time of AV block diagnosis with the data from the study by Jaeggi et al.6 The odds ratio of staying alive after the neonatal period for those who received treatment with dexamethasone was 0.78 (95% confidence interval, 0.14 to 4.35). Besides, 32 seropositive untreated fetuses had live birth and 1-year survival rates of 93% and 90%, respectively, which is quite different from 77% and 46%.6 We therefore believe that steroids and β-stimulation should be reserved for fetuses that are compromised, and further investigations should be addressed prospectively in a large-scale randomized study to clarify patient selection for this kind of treatment.
Lopes LM, Tavares GMP, Damiano AP, Lopes MAB, Aiello VD, Schultz R, Zugaib M. Perinatal outcome of fetal atrioventricular block: one-hundred-sixteen cases from a single institution. Circulation. 2008; 118: 1268–1275.
Daubeney PEF, Nugent AW, Chondros P, Carlin JB, Colan SD, Cheung M, Davis AM, Chow CW, Weintraub RG. Clinical features and outcomes of childhood dilated cardiomyopathy: results from a national population-based study. Circulation. 2006; 114: 2671–2678.
Udink ten Cate FE, Breur JM, Cohen MI, Boramanand N, Kapusta L, Crosson JE, Brenner JI, Lubbers LJ, Friedman AH, Vetter VL, Meijboom EJ. Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children. J Am Coll Cardiol. 2001; 37: 1129–1134.
Moak JP, Barron KS, Hougen TJ, Wiles HB, Balaji S, Sreeram N, Cohen MH, Nordenberg A, Van Hare GF, Friedman RA, Perez M, Cecchin F, Schneider DS, Nehgme RA, Buyon JP. Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela. J Am Coll Cardiol. 2001; 37: 238–242.
Jaeggi ET, Fouron JC, Silverman ED, Ryan G, Smallhorn J, Hornberger LK. Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation. 2004; 110: 1542–1548.