411193

et al.Journal of Diagnostic Medical Sonography

JDMXXX10.1177/8756479311411193Gomien

Original Articles

Echocardiographic Findings in Fetuses With Vascular Lesions or Malformations

Journal of Diagnostic Medical Sonography 27(4) 153157 The Author(s) 2011 Reprints and permission: http://www. sagepub.com/journalsPermissions.nav DOI: 10.1177/8756479311411193 http://jdm.sagepub.com

Susan Gomien, BS, RDMS1, Regina Keller, AS, RDMS, RDCS, RVT1, James F. Cnota, MD1, and Erik C. Michelfelder, MD1

Abstract Fetal vascular lesions or malformations such as sacrococcygeal teratomas, cervical teratomas, chorioangiomas, and vein of Galen aneurysms are associated with an increased risk of fetal death due to cardiac failure and hydrops. Large vascular lesions have the potential to result in increased cardiac output and volume overload on the fetal heart. As the heart compensates for the increasing blood flow, cardiovascular changes, demonstrable on fetal echocardiography, are likely to occur in the fetus. In the current era of fetal intervention and surgery, it is important to characterize these changes as a means of recognizing cardiac dysfunction and selecting patients for fetal intervention and management. This retrospective study characterizes the echocardiographic findings in fetuses with vascular lesions or malformations using 2D, color, and pulsed-wave Doppler imaging. Keywords fetal echocardiography, vascular lesions, volume overload, cardiac failure

Vascular fetal or placental masses, such as sacrococcygeal teratoma (SCT), cervical teratoma, chorioangiomas, or arteriovenous malformations, are rare but serious lesions that are associated with increased fetal morbidity and mortality.1 As the prenatal diagnosis of vascular lesions has become more common, attention has focused on therapies that may positively affect the outcome in these high-risk fetuses.24 Fetal hydrops, due to the sequela of high cardiac output failure, is a primary cause of death.3,5,6 However, characterization of the fetal cardiovascular derangements in these fetuses is not well described in the literature. Large vascular lesions would be expected to place a volume overload on the fetal heart. As the heart compensates for the increasing blood flow, cardiovascular changes would be anticipated in the fetus. These changes may include cardiac enlargement, increased combined cardiac output (CCO), atrioventricular valve regurgitation (AVVR), or signs of increasing central venous pressure, such as abnormal waveforms in the umbilical vein (UV) and ductus venosus (DV). Ascites and pleural and pericardial effusions may also develop.7,8 With advancing capabilities of fetal intervention, recognition of these changes may play an important role in the care of these patients, both in assessing fetal well-being and determining optimal timing of fetal interventional procedures.

The purpose of this study was to compare fetal cardiovascular findings between a cohort of fetuses with vascular lesions and a cohort of normal control fetuses.

Materials and Methods

This study involved a retrospective review of clinical records of all fetuses sent to our laboratory for fetal echocardiography from December 2004 through July 2009 with referral diagnoses of SCT, cervical teratoma, chorioangioma, or vein of Galen aneurysm. Any fetus found to have a structurally abnormal heart or cardiac arrhythmia was excluded from the study. All data collection and storage were done under approval of the institutional review board to ensure proper handling of protected health information under the Health Information Portability and Accountability Act. The review resulted in 28 affected fetuses on whom fetal echocardiograms

Cincinnati Childrens Hospital Medical Center, Cincinnati, OH, USA

Corresponding Author: Susan Gomien, BS, RDMS, Cincinnati Childrens Hospital Medical Center, MLC 2003, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA Email: susan.gomien@cchmc.org

154 were performed and compared with 18 normal control fetal echocardiograms. The mean gestational age of the affected fetuses at the time of scanning was 30 4.37 weeks, and the mean gestational age of the normal control fetuses at time of scanning was 25 6.14 weeks. All studies were scanned on either an Acuson Sequoia or S2000 (Siemens Medical Solutions USA, Malvern, Pennsylvania) using a 6C2 transducer, performed by one of three staff fetal sonographers or two pediatric cardiologists. Using standard 2D imaging, the cardiothoracic area ratio (CTR) was obtained by acquiring a four-chamber view of the fetal heart in a transverse plane of the fetal thorax. Using one image, the area of the heart and the area of the thoracic cavity were measured. Normal CTR is considered to be less than 35%. Color Doppler interrogation was used to demonstrate AVVR, if present, allowing for a qualitative assessment of severity. Our laboratory considers the width and length of the regurgitant jet and assigns a degree of trivial, mild, moderate, or severe. The CCO indexed to fetal weight was calculated by obtaining the aortic and pulmonic valve annulus diameter, velocity time integral (VTI), heart rate, and fetal weight. The aortic and pulmonic valve annuli are each obtained using a 2D image with the sound beam perpendicular to the valve annulus, with caliper placement from leaflet insertion to leaflet insertion. Often, the best views to obtain these measurements are in a long axis, showing the left ventricular outflow tract, and a short axis, showing the right ventricular outflow tract, respectively. The VTI for the aortic and pulmonic blood flow is obtained using pulsed Doppler at an angle as close to zero degrees as possible to the flow across each valve. Sweeping from the apical four-chamber to an apical five-chamber view will result in an accurate aortic waveform, whereas a sagittal view of the ductal arch will allow for an appropriate pulmonic waveform. Heart rate is obtained on each VTI waveform. Last, the estimated fetal weight of each fetus is calculated using the standard views and measurements associated with the Hadlock formula.9 To screen for evidence of elevated central venous pressure, pulsed-wave Doppler waveforms obtained from the ductus venosus and umbilical vein were evaluated. The ductus venosus was evaluated for abnormal flow pattern during atrial contraction, including absent or reversed end-diastolic flow. The umbilical vein was evaluated for pulsatility occurring during atrial contraction. The flow pattern in the umbilical artery was also routinely assessed (Figure 1). Finally, the presence or absence of ascites or pleural or pericardial effusion in the fetus was assessed. Statistical analysis of the information consisted of unpaired Student t test or nonparametric methods when appropriate for continuous variables. The relationship

Journal of Diagnostic Medical Sonography 27(4)

Figure 1. (A) Ductus venosus waveform. Image compares normal, continuous forward flow above baseline to abnormal, flow reversal below baseline (open arrow). (B) Umbilical cord waveform. Image compares normal continuous, nonpulsatile umbilical vein flow to abnormal pulsatile flow (open arrow). It is important to note that the timing of the pulsatility corresponds to atrial contraction (white arrow).

between CTR and CCO was assessed by simple regression analysis. Differences in the frequency of categorical variables were compared by chi-square analysis or Fisher exact test with Yates correction for small numbers, as appropriate. Statistical significance was assigned to P values <.05.

Results
Fetal echocardiograms performed on 28 fetuses with vascular lesions or malformation were reviewed and compared with 18 normal control fetuses. Study data are summarized in Table 1. The fetal vascular lesion group was studied at a later average gestational age and at a lower (although likely not clinically significant) average heart rate than control fetuses. Analysis of the data demonstrated a significantly higher CTR (0.39 0.10 vs 0.27 0.04, P = .0001; Figure 2) and significantly higher CCO (563 162 vs 442 153, P = .02; Figure 3) in the fetuses with vascular lesions or malformations. Regression analysis demonstrated a significant positive relationship between CTR and CCO (r = 0.68, P < .001; Figure 4). Eight of the 28 fetuses (29%) with vascular lesions had AVVR, whereas none of the normal fetuses had AVVR (2 = 6.2, P < .02). Waveform analysis of the UV and DV showed no abnormalities in the normal fetuses. Three of the fetuses with vascular lesions demonstrated one or more venous flow abnormalities, including pulsatility of the UV (3 of

Gomien et al.
Table 1. Comparison of Fetuses With Vascular Lesions vs Controls FVL (n = 28) Gestational age, wk, mean SD Heart rate, beats/ min, mean SD CTR, mean SD CCO, mL/min/kg, mean SD AVVR, No. (%) UV abnormality, No. (%) DV abnormality, No. (%) 30 4.37 138 8 0.39 0.10 563 162 8/28 (28.6) 3/28 (10.7) 1/28 (3.6) Control (n = 18) 24 6.14 144 8 0.27 0.04 442 153 0/18 (0) 0/18 (0) 0/18 (0) P Value <.01 <.01 <.01 .02 <.01 .61 .26
CT area ratio

155

0.7 0.6 0.5 0.4 0.3 0.2 0.1 0

r = 0.67, P < .0001

200

400 600 800 CCO (ml/min/kg)

1000

1200

Figure 4. Linear regression demonstrating relationship between cardiothoracic (CT) area ratio and combined cardiac output (CCO) in study cohort.

AVVR, atrioventricular valve regurgitation; CCO, combined cardiac output; CTR, cardiothoracic area ratio; DV, ductus venosus Doppler; FVL, fetal vascular lesion; UV, umbilical venous Doppler.

0.6 0.5 CT area ratio 0.4 0.3 0.2 0.1 0 Normal FVL

28; P = NS) and absent or end-diastolic flow in the DV (1 of 28; P = NS). Two of the fetuses with vascular lesions had absent end-diastolic flow in the umbilical artery. Ascites or pericardial or pleural effusion was noted in 5 of the 28 fetuses2 with frank hydropswith vascular lesions, whereas no fluid collections were found in the normal control group (P = NS).

Discussion
The differences between the fetal and postnatal cardiovascular systems have been well documented and understood for many years. These differences include myocardial characteristics, a parallel circulation, and specific vascular connections that close after birth.8 Using fetal echocardiography, the fetal circulation and cardiac output can be evaluated and compared with previously established normal values.10,11 In the setting of vascular lesions, the increased demand placed on the fetal cardiovascular system can result in high cardiac output and fetal hydrops, leading to heart failure in the fetus. Many cases of fetal demise due to high cardiac output associated with fetal hydrops in fetuses with vascular lesions have been documented.1,6,12 Available fetal therapies include minimally invasive amnioreduction, fetoscopic surgery, radiofrequency ablation, and open fetal surgery. Fetal interventions have been shown to improve the survival rate of fetuses with vascular lesions.4 Understanding the effect of increased load on the fetal heart in the setting of vascular lesions has been shown to be important for determining the timing of intervention.8 It has been determined that the most important information needed for evaluation of cardiac function in a fetus with hydrops includes CTR, venous Doppler waveform analysis, and presence of atrioventricular valve insufficiency. This cardiovascular profile can be useful in predicting the probability of developing

Figure 2. Comparison of cardiothoracic (CT) area ratio in normal control fetuses versus fetuses with vascular lesion or malformation (FVL). Error bars indicate 1 SD, P = .0001.

800 700 600 500 400 300 200 100 0

CCO (ml/min/kg)

Normal

FVL

Figure 3. Comparison of combined cardiac output (CCO, in mL/min/kg) in normal control fetuses versus fetuses with vascular lesion or malformation (FVL). Error bars indicate 1 SD, P = .02.

156 fetal hydrops7; therefore, accuracy of the measurements and Doppler acquisition is essential. Application of basic sonography physics principles will ensure the most appropriate, high-quality images and waveforms for analysis. For all images, the depth should be minimized and the sector width reduced as much as possible to obtain the highest possible frame rate. Previous descriptive studies8 have discussed the cardiac findings associated with fetuses having vascular lesions without comparison with a normal control group. Therefore, the aim of this study was to distinguish the CTR, AVVR, CCO, and venous Doppler waveform findings in 28 fetuses with vascular lesions or malformation, including sacrococcygeal teratomas, cervical teratomas, placental chorioangiomas, or vein of Galen malformations, to 18 normal control fetuses. Albeit a small cohort, the data collected during this study established a significantly elevated CTR and significantly higher CCO in the fetuses with vascular lesions or malformations compared with the normal control group (Figures 2 and 3). A significant positive relationship between CTR and CCO was also noted (Figure 4). This suggests that CTR may serve as a surrogate marker of elevated CCO when it is not technically feasible to accurately estimate CCO (e.g., because of poor imaging windows). Of the 28 fetuses with vascular lesions, 8 had AVVR, whereas none of the normal fetuses had AVVR. This underscores the notion that AVVR is an important marker of cardiovascular derangement in these fetuses and could play an important role in the routine fetal cardiac examination of the fetus with vascular masses/malformations. Waveform analysis of the UV and DV showed no abnormalities in the normal fetuses, but 4 of the fetuses with vascular lesions demonstrated abnormalities in these areas. Of the 28 fetuses with vascular lesions, 3 had pulsatility of the UV, and 1 had absent end-diastolic flow in the DV (Figure 1). Thus, the results of our investigation suggest that evidence of elevated central venous pressure, possibly a precursor to the development of hydrops, is present in a small but significant percentage of fetuses with vascular lesions. These data suggest that incorporation of venous Doppler flow analysis in the routine cardiac evaluation of these fetuses may also be useful in detecting cardiovascular functional derangements. The significance of the gestational age differences between the groups is unclear; however, we believe its role is likely trivial, as the functional cardiac findings are expected to be similar for both gestational age periods. Although the compared heart rate between the groups indicates a statistical difference, we do not believe that the difference in heart rate is of clinical significance. If anything, the slightly lower heart rate in the vascular lesion fetuses would account for an even larger stroke

Journal of Diagnostic Medical Sonography 27(4) volume (as an explanation for the observed increase in CCO) as CCO is calculated as the product of stroke volume and heart rate. Applying the cardiovascular profile score previously noted, we believe the most significant finding of this study is the increased CTR and AVVR. Fifteen of the 28 fetuses with vascular lesions had a CTR greater than 0.35, and 8 of these same fetuses also had AVVR. If an obstetric laboratory has difficulty incorporating the entire cardiovascular profile evaluation because of time constraints or other factors, at least obtaining the CTR and color Doppler evaluation for AVVR could prove helpful in determining which fetuses are at highest risk for increased cardiac output and heart failure. Those fetuses could then be referred to a pediatric cardiologist for a full functional assessment. Limitations of this study include a relatively small cohort size, slight variation of gestational age between the study and control groups, and the lack of postnatal follow-up information. Evaluation of postnatal outcomes, although potentially informative, fell outside of the aims of the current study. Furthermore, these data would be difficult to obtain, as we are a tertiary referral center for fetal therapy, and many of our patients come from a great geographic distance from our center and are likely to receive postnatal care at their local referring center.

Conclusion
On the basis of the findings of this study, along with the advancements in fetal therapies, we believe evaluation of cardiovascular changes in fetuses with vascular lesions could provide significant diagnostic information. Incorporation of these measurements and Doppler evaluations into the protocol when scanning fetuses with vascular lesions should be considered. Decisions on management and intervention may be influenced by the findings and could significantly affect the prognosis of the pregnancy. Given that the data in this study are supported by small numbers, a larger study would be needed to confirm these observations. Acknowledgment
We thank Meredith Kinsel-Ziter, RDCS, for her contribution to data collection during the timeframe of this study.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The author(s) received no financial support for the research and/or authorship of this article.

Gomien et al. References

1. Isaacs H Jr: Fetal hydrops associated with tumors. Am J Perinatol 2008;25(1):4368. 2. Fadler KM, Askin DF: Sacrococcygeal teratoma in the newborn: a case study of prenatal management and clinical intervention. Neonatal Netw 2008;27(3):185191. 3. Okada T, Sasaki F, Cho K, et al: Management and outcome in prenatally diagnosed sacrococcygeal teratomas. Pediatr Int 2008;50(4):576580. 4. Hedrick HL, Flake AW, Crombleholme TM, et al: Sacrococcygeal teratoma: prenatal assessment, fetal intervention, and outcome. J Pediatr Surg 2004;39(3):430438. 5. Silverman NH, Schmidt KG: Ventricular volume overload in the human fetus: observations from fetal echocardiography. J Am Soc Echocardiogr 1990;3(1):2029. 6. Langer JC, Harrison MR, Schmidt KG, et al: Fetal hydrops and death from sacrococcygeal teratoma: rationale for fetal surgery. Am J Obstet Gynecol 1989;160(5, pt 1): 11451150.

157
7. Huhta JC:Guidelines for the evaluation of heart failure in the fetus with or without hydrops. Pediatr Cardiol 2004;25(3):274286. 8. Rychik J:Fetal cardiovascular physiology. Pediatr Cardiol 2004;25(3):201209. 9. Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK: Estimation of fetal weight with the use of head, body, and femur measurements: a prospective study. Am J Obstet Gynecol 1985;151(3):333337. 10. Hecher K, Campbell S, Doyle P, Harrington K, Nicolaides K: Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation: arterial, intracardiac, and venous blood flow velocity studies. Circulation 1995;91(1):129138. 11. Mielke G, Benda N: Cardiac output and central distribution of blood flow in the human fetus. Circulation 2001; 103 (12):16621668. 12. Flake AW, Harrison MR, Adzick NS, Laberge JM, Warsof SL: Fetal sacrococcygeal teratoma. J Pediatr Surg 1986; 21(7):563566.