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Keywords:

  • congenital heart disease;
  • fetal echocardiography;
  • pulmonary atresia with intact ventricular septum (PAIVS);
  • tricuspid regurgitation;
  • ventriculocoronary connections (VCC)

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Objective

Pulmonary atresia with intact ventricular septum (PAIVS) is a rare cardiac malformation with a broad spectrum of anatomical manifestations, varying from types suitable for biventricular repair to those with diminutive right ventricle and primitive ventriculocoronary connections (VCC), more suitable for single-ventricle palliation or heart transplantation. We sought to test whether tricuspid regurgitation is an easily detectable prenatal criterion with which to identify PAIVS patients at lower risk of needing postnatal single-ventricle palliation.

Method

We identified retrospectively patients with both fetal diagnosis and postnatal confirmation of PAIVS who were seen at Bambino Gesù Hospital between January 2000 and December 2006. Tricuspid valve/mitral valve (TV/MV) ratio, presence and severity of tricuspid regurgitation and direct visualization of VCC were evaluated by echocardiography both pre- and postnatally.

Results

We identified 22 patients with a prenatal diagnosis of PAIVS. Four pregnancies were terminated and one fetus was lost to follow-up, leaving 17 patients for the analysis. Based on postnatal cardiac catheterization and/or echocardiography we divided our population in two groups: Group 1 included 10 patients with VCC; Group 2 included seven patients without VCC. At fetal echocardiography, tricuspid regurgitation was absent in all ten Group 1 patients and present in all seven Group 2 patients. VCC were seen directly in 6/10 Group 1 patients and in no Group 2 patients. A cut-off value of 0.56 for the TV/MV ratio was highly predictive of VCC during fetal life, with a sensitivity of 100% and a specificity of 90%.

Conclusions

The absence of tricuspid regurgitation in fetuses affected by PAIVS is a strong prenatal echocardiographic predictor of VCC, as is a TV/MV ratio < 0.56. Fetuses presenting with tricuspid regurgitation and relatively large right ventricle are at lower risk of needing single-ventricle palliation postnatally. This information could be helpful for appropriate prenatal counseling and postnatal decision-making. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Pulmonary atresia with intact ventricular septum (PAIVS) is a severe cardiac malformation characterized by variable right ventricular (RV) development, imperforate pulmonary valve, and possibly abnormal connections between the RV and the coronary arteries, known as ‘ventriculocoronary connections’ (VCC). Severe anomalies of the coronary arteries can result in an RV-dependent coronary circulation (RV-to-coronary fistulas with proximal stenoses/atresia of the right and/or left coronary arteries). The embryogenesis of PAIVS is unknown, but sustained RV hypertension during cardiac morphogenesis is thought to be responsible for persistence of sinusoids during fetal life. Genetically determined intrinsic alterations in the morphology of the RV myocardium could also be related to the presence of sinusoidal connections in PAIVS. Patients with an RV-dependent coronary circulation have a major portion of their left ventricular myocardium dependent on high-pressure blood flow from the RV and are at risk of ischemia or infarction if the RV is decompressed. Even in the setting of VCC without proximal stenoses or dual coronary supply, there is the theoretical potential for run-off of coronary flow into the RV that could lead to underperfusion of the myocardium.

The prognosis and management of PAIVS depend upon: 1) the severity of RV hypoplasia; 2) the morphology, diameter and function of the tricuspid valve (TV); and 3) the dependency of the myocardial perfusion on VCC. These three factors largely determine the type of repair (biventricular or 1 1/2-ventricular strategies, single-ventricle palliation or heart transplantation) that is suitable, as well as the long-term outcome1–7. However, while accurate description of the degree of RV hypoplasia, the anatomy of the TV and the presence of VCC is possible in the fetus8, 9, prenatal identification of RV-dependent coronary circulation is not achieved consistently10. VCC are typically found when the RV and TV are severely hypoplastic, with hypertrophy of the RV walls. Such a small ventricle has insufficient diastolic volume to sustain significant tricuspid insufficiency. In contrast, VCC are rare in PAIVS patients with a relatively large ventricle capable of supporting more significant tricuspid regurgitation11. We hypothesized that the absence or paucity of tricuspid regurgitation together with RV hypoplasia could be easily detectable indicators of VCC during prenatal life.

The objective of this study, therefore, was to test whether tricuspid regurgitation is an easily detectable prenatal criterion with which to identify PAIVS patients at lower risk of needing postnatal single-ventricle palliation.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Patient population

We identified retrospectively all fetuses with a prenatal diagnosis of PAIVS made between January 2000 and December 2006 at Bambino Gesù Hospital in Rome. Fetal and postnatal echocardiograms were reviewed, as were catheterization and surgical reports. Data ascertained included the prenatal diagnosis, the presence of VCC on angiography or postnatal echocardiography, observations at surgery of the size of the RV and TV and the presence of VCC. We also recorded the pre- and postnatal echocardiographic measurements of the TV, MV and TV/MV ratio. Classification of patients as having VCC (Group 1) or not having VCC (Group 2) was based on postnatal cardiac catheterization reports and/or echocardiograms.

Cardiac catheterization

In our institution, RV angiography is not always performed before surgical intervention in cases of PAIVS. The finding of abnormal coronary arterial flow pattern with Doppler echocardiography indicates the need for angiographic definition of coronary arterial anatomy before undertaking RV decompression. Conversely, patients with a larger RV and no coronary artery abnormality detected by color Doppler do not routinely undergo cardiac catheterization prior to RV decompression.

Fetal echocardiography

Two-dimensional ultrasound imaging and color Doppler flow imaging was performed systematically in all fetuses. The aortic root and RV myocardium were visualized using color Doppler with a low velocity scale setting (≤ 32 cm/s) to identify coronary flow. The diameters of the mitral valve (MV) and TV were measured in the four-chamber view between the hinge points of the TV and MV leaflets, immediately before closure of the atrioventricular valves, and were expressed as a ratio (TV/MV ratio). The presence and severity of tricuspid regurgitation was assessed in multiple views with color Doppler flow mapping and was graded semiquantitatively as absent (0), mild (1), moderate (2) or severe (3) based on the extension of the jet into the right atrium12. Scanning with color flow mapping allowed direct visualization of VCC as systolic high-velocity anterograde flow (i.e. from the RV into the coronary circulation) and diastolic low-velocity retrograde flow on the surface of the RV or within the RV myocardium13 (Figures 1 and 2).

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Figure 1. Ultrasound images in a fetus with pulmonary atresia with intact ventricular septum and diminutive right ventricle. Color Doppler (b) identified ventriculocoronary connections (arrow) as turbulent low-velocity flow in the small right ventricular cavity and into the hypertrophic right ventricular wall. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

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thumbnail image

Figure 2. Pulsed Doppler pattern of right coronary artery in the presence of ventriculocoronary connections. Note the competition of flow from the right ventricle to the aorta in systole and from the aortic root to the right ventricle in diastole.

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Statistical analysis

We evaluated the association between the prenatal echocardiographic findings and the presence of VCC using the chi-square test for discrete variables and Student's t-test for continuous variables. We also tested the diagnostic accuracy of each of the echocardiographic measures in predicting the presence of VCC, estimating sensitivity, specificity, predictive values and likelihood ratios. A receiver–operating characteristics (ROC) curve for TV/MV ratio was used to identify the cut-off value with the best diagnostic performance. Finally, a Pearson's correlation table was used to compare pre- and postnatal echocardiographic measures. P≤0.05 was considered statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

We identified 22 fetuses with PAIVS examined during the study period. Of these, 17 patients had both fetal diagnosis and postnatal confirmation of PAIVS and were included in the analysis (four pregnancies were terminated before 25 weeks' gestation according to the Italian legal limit for termination of pregnancy in the presence of fetal malformation (before neonatal viability) and one patient was lost to follow-up after 33 weeks). The mean ± SD gestational age at first diagnosis for the original 22 fetuses was 26.9 ± 5.28 weeks and for the 17 fetuses included in the study it was 28.2 ± 4.23 weeks. There was one case of dichorionic diamniotic pregnancy (Group 1). Among the 17 patients analyzed, VCC were confirmed postnatally in 10 (Group 1), and VCC were not present in seven (Group 2). One fetus in Group 1 had associated hypoplasia of the pulmonary arteries and multiple aortopulmonary collaterals seen at fetal ultrasound examination and subsequently confirmed by angiography after delivery. The remaining 16 patients had adequate native pulmonary arteries and no aortopulmonary collaterals.

Of the 10 patients in Group 1 (with VCC) none had tricuspid regurgitation at fetal echocardiography. It was possible to recognize VCC directly by color flow mapping in only six of these fetuses prenatally, partly because of a poor acoustic window in four cases.

Of the seven patients in Group 2, Grade 2–3 tricuspid regurgitation was present in all cases; in most cases, this was the primary reason for referral to our tertiary center for the fetal echocardiography. In these patients, no VCC were identified at fetal echocardiography or at postnatal echocardiography and/or cardiac catheterization.

Cardiac catheterization

In Group 1, RV angiography was performed in nine patients: in two before modified Blalock-Taussig (BT) shunt and in seven before bidirectional cavopulmonary anastomosis. We identified three patients having RV-dependent coronary circulation, while the remaining patient of Group 1 (with echocardiographic identification of VCC) died after a BT shunt. In Group 2, cardiac catheterization was performed in only two patients and showed no VCC.

Absence of tricuspid regurgitation had a sensitivity and specificity of 100%, while direct visualization of VCC alone during fetal life was less sensitive (60%), for detection of coronary abnormalities. There was a statistically significant difference (P < 0.001) in both TV diameter and TV/MV ratio between the two groups (Figure 3). On ROC curve analysis, with a cut-off value of 0.56, the TV/MV ratio was 100% sensitive and 90% specific in detecting VCC. The correlation between fetal and postnatal TV/MV ratio was excellent (r = 0.934; P < 0.001).

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Figure 3. Box plot of the median and interquartile range of the tricuspid valve/mitral valve (TV/MV) ratio in Groups 1 and 2 at 28.2 ± 4.23 weeks; there was a statistically significant difference (P < 0.001) in TV/MV ratio between the two groups. Whiskers show the extreme values.

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Outcomes

The average follow-up was 27.8 months. All fetuses were delivered by Cesarean section; in one case an emergency Cesarean section was performed at 36 weeks because of atrial flutter. Cesarean sections were planned because of the absence of an obstetrics unit in our pediatric tertiary center and the need for an intensive care unit to treat the ductus-dependent pulmonary circulation in these patients. Transitory supraventricular tachycardia occurred in utero in the affected fetus of the twin pregnancy. The mean ± SD gestational age at delivery was 37 ± 2 weeks. Patient characteristics and outcomes are summarized in Table 1.

Table 1. Morphological features and outcome in 17 patients with pulmonary atresia with intact ventricular septum
PrenatallyPostnatally
Degree of tricuspid regurgitation*Direct view of VCCTV/MV ratioTV/MV ratioConfirmation of sinusoidsInterventionPostoperative course
  • *

    Tricuspid regurgitation was graded based on the extension of the jet into the right atrium12. +, yes; −, no; BT, Blalock-Taussig; MV, mitral valve; TV, tricuspid valve; VCC, ventriculocoronary connections.

0+0.570.54+BT shunt; bidirectional Glenn; extracardiac FontanSurvived
0+0.450.50+BT shuntDied
00.480.55+BT shunt; bidirectional Glenn; extracardiac FontanSurvived
0+0.450.52+BT shunt; bidirectional Glenn; extracardiac FontanSurvived
00.470.50+BT shunt; bidirectional Glenn; extracardiac FontanSurvived
00.520.44+BT shunt and atrioseptectomy; bidirectional Glenn; extracardiac FontanSurvived
00.470.54+BT shunt and atrioseptectomy; bidirectional GlennSurvived
0+0.480.54+BT shunt; bidirectional GlennSurvived
0+0.560.66+BT shunt and outflow patchSurvived
0+0.430.44+Died before intervention
2–31.251.16BT shunt and outflow patchSurvived
1–20.570.68BT shunt and outflow patch; bidirectional GlennSurvived
30.750.83Died before intervention
311.07BT shunt and outflow patchSurvived
1–20.70.73BT shunt and outflow patchSurvived
2–30.90.83BT shunt and outflow patchSurvived
31.120.85BT shunt and outflow patchDied

Among the ten patients in Group 1, eight were staged toward Fontan operation without RV decompression, one of whom died. One patient underwent patch plasty of the RV outflow, with BT shunt. The patient with hypoplasic pulmonary arteries with multiple aortopulmonary collaterals was delivered at 34 weeks, with a birth weight of 1 kg, and died in the intensive care unit before surgery.

Among the seven patients in Group 2, six patients underwent patch plasty of the RV outflow with BT shunt, one of whom died due to intractable cyanosis. The other patient died before surgery due to progressive acidosis from birth complications.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

We found that the absence of TV regurgitation and a fetal TV/MV ratio < 0.56 are highly predictive of VCC in fetuses affected by PAIVS. The absence of tricuspid regurgitation is easily detectable during fetal ultrasound and is even more reliable at predicting VCC than is direct visualization of VCC themselves. Conversely, the presence of tricuspid regurgitation can identify fetuses at lower risk of needing single-ventricle palliation postnatally.

Although other investigators9, 14 have suggested that fetal and postnatal TV Z-score and rate of TV growth can predict postnatal outcome in cases of PAIVS, we chose to study the TV/MV ratio as a more reproducible and readily obtainable fetal predictor of VCC and possibly outcome15. The TV/MV ratio has been used postnatally as a predictor of biventricular repair according to the degree of RV development. Use of a ratio avoids the need for age-specific normal data. Our study was limited by the small number of patients; this was because of the rarity of the disease. However, despite the small sample size, the results we obtained are important and could help with both pre- and postnatal counseling and management.

PAIVS is a heterogeneous disease, and not all institutions base their initial management strategy on the presence of RV-dependent coronary circulation. In our series, there was no difference in early postoperative mortality between the two groups. It is well known that, among patients with PAIVS, outcomes are worse in those with an RV-dependent coronary circulation than they are in those without. Intermediate follow-up of patients with RV-dependent coronary circulation demonstrated a 5-year survival of 83%, with the surviving patients at ongoing risk of ischemia7. Longer follow-up is needed in this group to assess the rise in hazard function5, 16, 17.

In our population, PAIVS manifested more commonly as diminutive RV and VCC than it did as relatively large RV and normal coronary circulation. This differs from previous reports about postnatal populations4. It might be speculated that the reason for this difference could be a higher rate of termination of pregnancy in fetuses with PAIVS and significant tricuspid regurgitation; because tricuspid regurgitation is easily detectable during routine obstetric sonography, these patients might come to the attention of the examiner more frequently. Although the difference might also reflect sampling bias in a tertiary center such as ours, there are data supporting the fact that fetal echocardiography can modify the postnatal patient population of PAIVS18.

In conclusion, the absence of tricuspid regurgitation in fetuses affected by PAIVS is a strong prenatal echocardiographic predictor of VCC, as is a TV/MV ratio < 0.56. Fetuses presenting with tricuspid regurgitation and larger RV are at lower risk of needing single-ventricle palliation postnatally. This information could be helpful for appropriate prenatal counseling and for postnatal decision-making.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  • 1
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