Perinatal/Neonatal Case Presentation

Journal of Perinatology (2004) 24, 112–117. doi:10.1038/sj.jp.7211038 Published online 22 January 2004

Congenital Complete Heart Block: Fetal Management Protocol, Review of the Literature, and Report of the Smallest Successful Pacemaker Implantation

Mary T Donofrio MD, FAAP, FACC1, Scott D Gullquist MD, FAAP, FACC1, Inder D Mehta MD2 and William B Moskowitz MD, FAAP, FACC1

  1. 1Department of Pediatrics, Division of Pediatric Cardiology, Medical College of Virginia Hospital of Virginia Commonwealth University, Richmond, VA, USA
  2. 2Department of Surgery, Division of Pediatric Cardiothoracic Surgery, Medical College of Virginia Hospital of Virginia Commonwealth University, Richmond, VA, USA.

Correspondence: Mary T. Donofrio, MD, FAAP, FACC, Pediatric Echocardiography and Fetal Cardiology, Children's Heart Center, Medical College of Virginia Hospital of the Virginia Commonwealth University, Box 980342, Richmond, VA 23298, USA

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Abstract

Fetuses with complete heart block have an increased mortality with most deaths occurring in utero or during infancy. The cardiac evaluation of these fetuses is difficult since the ventricular rate is low and the heart is dilated. We have implemented a strategy that includes the biophysical profile, which assesses fetal well-being, in combination with the cardiovascular profile that assesses cardiac function and the circulation. We present two cases of fetal complete heart block in which early delivery was recommended due to worsening cardiovascular profile scores. Biophysical profile scores were normal. Both babies were successfully treated, despite having risk factors that predicted poor outcomes. We hypothesize that our management protocol initiated intervention before fetal compromise, hydrops, and myocardial damage occurred. We recommend an evaluation of heart function in addition to an assessment of fetal well-being in fetuses with complete heart block. Early delivery should be considered if there is evidence of distress and/or deteriorating cardiac function.

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INTRODUCTION

Autoimmune-associated congenital complete heart block (CHB) is a rare but important disease that can now be diagnosed in utero using fetal echocardiography. 1,2,3,4 The overall incidence of isolated CHB has been reported to be approximately 1:15,000 to 20,000 live births.5 Several reviews have shown that children diagnosed prenatally have an increased mortality compared to those diagnosed immediately after birth or later in childhood.1,2,3,4 Most of the deaths in CHB patients occur in early infancy; however, there have been in utero deaths reported. Fetuses and infants at risk include those with hydrops fetalis, those with low ventricular rates, and those born prematurely.1,2,3,4

The cardiac evaluation of the fetus with CHB can be challenging. Knowing when to initiate an early delivery can often be difficult since the ventricular rate is low and the heart is usually very dilated, even in those fetuses without compromise. At our institution, we have implemented a strategy that involves close fetal surveillance using the biophysical profile score (BPP), which assesses fetal well-being and is a marker for in utero asphyxia and acidosis,6,7 in combination with the cardiovascular profile score (CVP), which assesses cardiac function and the adequacy of the fetal circulation.8 We present two cases of isolated fetal CHB that were followed serially in utero using obstetrical ultrasound and fetal echocardiography. In both cases, early delivery was recommended due to worsening CVP scores. BPP scores were normal. Both babies were successfully treated with pacemaker implantation in the neonatal period, despite having risk factors that historically would have predicted poor outcomes. In addition, Case 1 is the smallest and most premature newborn to undergo pacemaker implantation successfully.

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CASE 1

A 30-year-old woman was referred for a fetal echocardiogram at 28 5/7 weeks gestation after routine Doppler interrogation of the heart revealed the rate to be 40 bpm. Ultrasound revealed no evidence of fetal distress. The estimated fetal weight was at the 25th percentile for gestational age. Maternal assessment revealed positive ANA and anti-Rho antibodies. Anti-La was negative. There were no symptoms of lupus or any connective tissue disease. Of note is that at a previous obstetrical visit 2 weeks prior to her presentation, the fetal heart rate was documented to be 150 bpm.

Fetal echocardiogram revealed normal visceral and atrial situs and normal cardiac anatomy, including outflow tracts and ductal and aortic arches. Foramen ovale and ductus arteriosus flow were right to left. Both ventricles were dilated (Figure 1) and there was qualitatively decreased systolic ventricular function given the degree of bradycardia and volume load. Interrogation of the rhythm by simultaneous M-mode of atrial and ventricular contraction revealed discordant atrioventricular conduction. The atrial rate was 125 bpm, and the ventricular rate was 44 bpm (Figure 2). There was mild systolic tricuspid regurgitation and a small circumferential pericardial effusion. Umbilical venous flow was abnormal and revealed pulsations during ventricular systole that were theorized to be due to the tricuspid regurgitation (Figure 3). No atrial pulsations were noted. A CVP score of 5 was assigned. The BPP score excluding heart rate was normal at 8 (2 for breathing, movement, tone, and amniotic fluid volume) (Table 1, Figure 4). The patient was admitted, and terbutaline was started and increased to a maximum dose of 5 mg q6 hours to increase fetal heart rate and improve cardiac function. Steroids were also given to accelerate fetal lung development.

Figure 1.
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Fetal echocardiogram at Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author weeks gestation. Note the dilation of the heart. LA=left atrium, LV=left ventricle, RA=right atrium, RV=right ventricle.

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Figure 2.
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M-mode identifying complete heart block with atrioventricular discordance. A=atrial contraction, V=ventricular contraction.

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Figure 3.
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Doppler interrogation of the umbilical vein. Note the venous pulsations. P=pulsations, UA=umbilical artery, UV=umbilical vein.

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Figure 4.
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Graphic representation of change in cardiovascular profile and biophysical profile scores for Case 1. BPP=biophysical profile, CVP=cardiovascular profile, squares=BPP score (normal=8), diamonds=CVP score (normal=10).

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Repeat fetal echocardiogram carried out the following morning revealed an increase in systolic ventricular function. The tricuspid regurgitation was decreased in severity and the pericardial effusion had not changed. The atrial rate was increased to 162 bpm, and the ventricular rate remained at 45 bpm. The CVP score, now 6, suggested that heart function remained diminished but at least had not worsened. The BPP again was normal (Table 1, Figure 4). The following day, still on terbutaline, the systolic function of the heart was less hyperdynamic, and the heart was more dilated. The tricuspid regurgitation had worsened, the pericardial effusion was increased, and there was a suggestion of new skin edema. Umbilical venous flow continued to reveal abnormal pulsations. A CVP score of 4 suggested worsening cardiac function. The BPP score continued to be normal (Table 1, Figure 4). In consultation with the neonatal, perinatal, and obstetrical services, the decision was made to deliver the baby despite the degree of prematurity.

At birth, Apgars were 6 at 1 minute and 7 at 5 minutes. The cord pH was 7.35. The weight was 1219 g. Physical examination revealed a premature infant in respiratory distress with notable grunting and retractions. The heart rate ranged between 40 and 55 bpm, the blood pressure was 48/28, the respiratory rate was 36, and the pulse oximetry reading was 94%. The lung examination revealed bilateral crackles. The cardiac examination was significant for an S3 gallop. Perfusion was mildly decreased. There were no clinical signs of hydrops fetalis. The baby was intubated and mechanical ventilation was initiated. Echocardiogram revealed a dilated heart, a small pericardial effusion, and hyperdynamic ventricular function with a fractional shortening (FS) of 52%. Dopamine at 15 mug/kg/minute and epinephrine at 0.08 mug/kg/minute were started. The heart rate increased up to a maximum of 70 bpm and perfusion improved. On day of life 6, an epicardial pacemaker set in the VVI mode programmed at 100 bpm was placed. Initially she did well, but on postoperative day 1 she was noted to be poorly perfused and cyanotic with a pulse oximetry reading of 70%. Echocardiogram revealed that the left ventricle was less dilated; however, the interventricular septal wall motion was paradoxical. There was decreased ventricular function with an FS of 21%. There was moderate tricuspid regurgitation that estimated a normal right ventricular pressure. The tricuspid regurgitation jet was directed across the foramen ovale and was the only source of right to left shunting. The pacemaker rate was increased to 120 bpm and dobutamine was started. Serial follow-up echocardiograms over the ensuing days revealed slow improvement in ventricular function and a decrease in tricuspid regurgitation. Dobutamine was discontinued and digoxin was started. By 4 weeks postpacemaker implantation, the FS had increased to 32% and interventricular wall motion was improved, but remained hypokinetic. There was no tricuspid regurgitation. At subsequent follow-up at 6 months of age, left and right ventricular chamber size and wall thicknesses had normalized. Ventricular function was normal with an FS of 32%. The digoxin was discontinued. At the 12-month evaluation, heart function again was normal.

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CASE 2

A 34-year-old woman was referred for fetal echocardiogram at 24 weeks gestation after routine Doppler interrogation of the heart revealed the rate to be 50 bpm. Obstetrical history was positive for a prior fetal demise after a planned early delivery for severe maternal HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Maternal evaluation for lupus was negative (ANA=1:80, antibody titers negative, and no clinical signs or symptoms of autoimmune disease). The family had one living child without medical problems. Ultrasound revealed no evidence of fetal distress or hydrops fetalis. The estimated fetal weight was at the 50th percentile for gestational age.

Fetal echocardiogram revealed normal visceral and atrial situs and normal cardiac anatomy including outflow tracts and ductal and aortic arches. Foramen ovale and ductus arteriosus flow were right to left. Both ventricles appeared dilated. There was hyperdynamic systolic ventricular function. Interrogation of the rhythm by M-mode revealed discordant atrioventricular conduction. The atrial rate was 140 bpm and the ventricular rate was 48 bpm. Umbilical venous flow was normal and there was no tricuspid regurgitation. The CVP and BPP scores were normal (Table 2, Figure 5).

Figure 5.
Figure 5 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Graphic representation of change in cardiovascular profile and biophysical profile scores for Case 2. BPP=biophysical profile, CVP=cardiovascular profile, squares=BPP score (normal=8), diamonds=CVP score (normal=10).

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Repeat evaluation at 27 weeks gestation revealed no change in the fetal or cardiac status. At 31 weeks, the heart appeared more dilated. Systolic ventricular function remained good, and there were no other new findings. At this point, the CVP score was 9. The BPP remained normal (Table 2, Figure 5). Owing to the change in the CVP score, more frequent fetal assessment was recommended. At 33 weeks gestation, new systolic tricuspid regurgitation was documented. The heart was even more dilated. Ventricular function was preserved. The CVP score of 8 suggested worsening cardiac function. The BPP continued to be normal (Table 2, Figure 5).

Obstetrical ultrasound at 35 weeks gestation revealed decreased fetal movement. There was no evidence of hydrops fetalis. Fetal echocardiogram revealed that the heart was more dilated. Ventricular function was good. The tricuspid regurgitation was still present and new mitral regurgitation had developed. Interrogation of the rhythm revealed a ventricular rate of 48 bpm. The CVP was worse at 7. The BPP, calculated also to be 7, was also decreased (Table 2, Figure 5). The decision was made to deliver the baby.

At birth, Apgars were 8 at 1 minute and 9 at 5 minutes. The physical examination was normal except for a heart rate that ranged between 40 and 60 bpm, and the presence of an S3 gallop. There was no evidence of fetal distress. Echocardiogram revealed a structurally normal heart. There was hyperdynamic systolic function with an FS of 48%. There was mild tricuspid and mitral regurgitation. On day of life 6, an epicardial pacemaker set in the VVI mode programmed at 100 bpm was placed. Postoperative echocardiogram revealed normal ventricular chamber size, biventricular hypertrophy, and hyperdynamic function with an FS of 57%. Dynamic right and left ventricular outflow gradients (both estimated at 20 mmHg) were identified and thought to be due to muscular hypertrophy. At 1- and 2-year follow-up, he has done well without any complications. His heart size and ventricular function are normal and there has been resolution of the ventricular hypertrophy, outflow obstruction, and tricuspid and mitral regurgitation.

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DISCUSSION

The two cases presented represent our recent experience with prenatally diagnosed autoimmune CHB. Both fetuses were followed serially in- utero using obstetrical ultrasound and fetal echocardiography, and the decision to deliver early rather than persist with the pregnancy was made using a strategy of close fetal surveillance using scores obtained from BPP and CVP assessment. In both cases, early delivery was recommended due to worsening CVP scores. Both babies were successfully treated with pacemaker implantation in the neonatal period, and have had normalization of their heart size and function. In addition, the fetus of Case 1 who weighed 1219 g, to our knowledge, is the smallest newborn to undergo pacemaker implantation successfully.

With the technologic advances in ultrasound, prenatal diagnosis of autoimmune CHB has become standard of care in most institutions. Recently, several centers have reported their experience in fetuses and babies diagnosed in utero versus at birth or later in life. In general, the mortality continues to be significant in children with CHB with the majority of the deaths occurring either in utero or during infancy. In a study by Jaeggi et al.,4 102 cases of CHB (29 diagnosed in utero) were identified. Of those diagnosed in utero, 45% died. Deaths occurring in utero were due to hydrops fetalis, endocardial fibroelastosis, placental infarction, and associated with a heart rate <50 bpm. Neonatal deaths were related to complications of prematurity (<32 weeks), hydrops fetalis, endocardial fibroelastosis, and arrhythmias. In a study using data from the National Neonatal Lupus Registry,1 113 children with CHB (85 diagnosed in utero) were studied. The mortality was 19%, with most deaths occurring in the neonatal period or in-utero. The only risk factor for death was delivery at <34 weeks gestation. Eronen et al.2 reported the results of 91 infants with CHB (83 diagnosed in utero). The mortality was 16%, with most deaths occurring in infancy. Only one death occurred in utero. Risk factors for poor outcome included hydrops fetalis, a low fetal and/or neonatal heart rate, low birth weight, male sex, and complications from prematurity or neonatal lupus. Finally, in a study of infants diagnosed in utero with CHB by Groves et al.,3 the mortality was 33% with nine of the deaths occurring in utero. Factors identified that suggested poor prognosis included hydrops fetalis, and a low (<55 bpm) or sudden rapid drop in the heart rate. According to the literature, the two cases reported are in the high-risk population of fetuses with this disease. Both were diagnosed in utero and had low heart rates. The fetus in Case 1 also had early signs of hydrops fetalis and a very premature delivery. Despite these risk factors, the outcomes were good. We hypothesize that our management strategy, which prompted the decision to deliver early before heart function deteriorated and severe hydrops fetalis developed, impacted on the natural history of the in utero disease process.

The dilated cardiomyopathy that occurs in fetuses and infants with CHB usually resolves after pacemaker implantation, however, persistent dilation with cardiac dysfunction or recurrence of a cardiomyopathy can occur, and is often associated with a poor outcome. In a study by Moak et al.,9 16 infants with CHB (12 diagnosed in utero) and a late-onset cardiomyopathy after pacemaker implantation were evaluated. Left ventricular function was normal soon after birth in 15. Heart failure developed before age 2 in 75%. Biopsies revealed hypertrophy, fibrosis, and/or myocyte degeneration. Four died and seven required heart transplant. No risk factors for poor outcome were identified. In another study,10 nine children with CHB (eight diagnosed in utero) and a dilated cardiomyopathy were compared to children with CHB who had normal heart function. The heart rate at birth for those who had a cardiomyopathy was lower than the normal group (mean of 43 versus 63 bpm). Risk factors identified included the presence of autoimmune antibodies in the child, increased heart size at presentation, and no improvement in ventricular function with pacemaker implantation. Finally, in a study by Nield et al.,11 13 infants with CHB and endocardial fibroelastosis diagnosed in utero or at birth were evaluated. Nine died and two underwent heart transplant. Immunohistochemistry performed in four patients, three diagnosed in utero, revealed deposition of IgG and IgM and/or T-cell infiltrates. These data suggest that permanent injury may occur in the hearts of these children and is likely due to an immune response. Why it occurs in some cases and not others is unknown. It may be that the injury due to the immune response in combination with the injury that occurs as a result of persistent in utero cardiac compromise leads to the permanent myocardial damage that is seen at birth. Our cases, despite being in the high-risk group for a persistent or recurrent cardiomyopathy, had normalization in heart size and function and have had no evidence of deterioration. We hypothesize that by following a protocol that assesses not only fetal well-being but also cardiac function and the fetal circulation, the permanent myocardial injury that can occur in these children might have been avoided.

We have developed a protocol of close fetal and cardiac surveillance for fetuses with CHB. A comprehensive evaluation that includes not only a standard assessment of fetal well-being but also a more specific assessment of cardiac function and the fetal circulation is utilized. The BPP, a 10-point fetal assessment protocol first described by Manning et al.,6 evaluates fetal breathing, movement, tone, reactivity, and amniotic fluid volume, and has been shown to correlate with fetal asphyxia, acidosis, and poor outcome. The heart rate component, which is the fetal "nonstress test", is an evaluation of fetal heart rate variability in the absence of uterine contractions. This component of the BPP is believed to be an indicator of fetal acidosis,7 and is likely the best marker for fetal distress due to poor perfusion. Unfortunately, for fetuses with CHB, ventricular heart rate variability cannot be utilized. This makes the BPP a less than ideal test to assess fetal well-being if it is used alone. We, therefore, have added the CVP to our comprehensive evaluation of CHB fetuses. The CVP, originally described by Huhta,8 is a 10-point assessment of cardiac function and the fetal circulation. The score deducts points for the presence of abnormal signs, in a manner similar to the BPP. The five categories evaluated include the presence of hydrops (-1 for ascites or pericardial/pleural effusion, -2 for skin edema), the presence of venous pulsations (-1 for ductus venosus pulsations, -2 for umbilical vein pulsations), umbilical artery Doppler evaluation (-1 for absent end-diasolic flow, -2 for reversed diastolic flow), the presence of cardiac enlargement (-1 for a cardiothoracic area of 35 to 50%, -2 for an area >50%), and an assessment of cardiac function (-1 for holosystolic tricuspid insufficiency or an FS <28%, -2 for mitral insufficiency or abnormal ventricular diastolic filling). Interrogation of the atrioventricular valves for regurgitation is an important component of the cardiac function assessment in the CVP. Used in conjunction with FS measurements, new tricuspid and/or mitral regurgitation has been shown to be a marker for cardiac decompensation. For the two cases reported, the deterioration in CVP indicated worsening cardiac function and prompted the decision for early delivery. Interestingly, the BPP remained relatively normal for the duration of both pregnancies. In Case 1 especially, we believe that early delivery before severe hydrops developed allowed us to manage the infant successfully, despite the degree of prematurity and cardiac involvement. In the literature, it is hydrops fetalis that is the most frequently implicated risk factor for poor outcome. We speculate that if the fetus had remained in utero, permanent cardiac injury, endocardial fibroelastosis, and a dilated cardiomyopathy may have occurred. Case 2, which was less severe, also likely benefited from the same strategy. Despite a low resting heart rate, and a slightly premature delivery, the infant was successfully treated with no evidence of any long-term cardiac complications.

In conclusion, we believe that close fetal surveillance is needed for fetuses diagnosed with autoimmune congenital CHB. In addition to the standard BPP, a comprehensive evaluation of heart function and the fetal circulation should be routinely performed. Delivery should be considered if there is evidence of fetal distress and/or deteriorating cardiac performance even in cases where there is prematurity. The aggressive strategy for the management of CHB fetuses that we have adopted was successful in the two cases presented. A multicenter prospective study with a large cohort of patients is needed to determine the best management strategy for fetuses with CHB.

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References

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