Detection of fetal right coronary artery–right ventricle fistula with pulmonary valve atresia using HDlive Flow with spatiotemporal image correlation

Introduction

Coronary artery fistula (CAF) is a rare congenital cardiovascular anomaly, which refers to the abnormal connection between the coronary artery and the ventricle or great vessels (1); it accounts for about 0.3% of congenital heart defects (2). In this study, we employed HDlive Flow with spatiotemporal image correlation (STIC) to detect fetal right coronary artery–right ventricle fistula with pulmonary valve atresia.

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was provided by the participating pregnant mothers for publication of this article and accompanying images and videos. A copy of the written consent is available for review by the editorial office of this journal.

During a routine ultrasound examination of a 35-year-old pregnant woman [gravida 2, para 1 (G2P1)], E10 (GE Healthcare, Milwaukee, WI, USA) ultrasound systems were used with the obstetric preset. Fetal echocardiography revealed structural abnormalities of the fetal heart at 22 weeks of gestation, including enlarged left and right coronary arteries (LCA/RCA 3.0 mm/2.1 mm) with blood flow filling (Figure 1A, Video 1). The diameter of the right ventricle of the fetus was 5.6 mm, and the ratio of the right ventricle to the left ventricle was 0.66. Right ventricular blood flowed into the aorta via the RCA through the open intracardiac trabecular space. Radiant flow demonstrated the RCA expansion (Figure 1B, Videos 2,3). The LCA ran along the interventricular septum to the apex of the heart and issued two branches, one of which was about 2.6 mm wide and joined into the RCA along the intramyocardial trabecular spaces. The other branch was 2.3 mm wide and supplied the left ventricular wall (Figure 1C). Four-dimensional (4D) color Doppler ultrasound with STIC and Hdlive Flow render mode clearly showed the fistula from the LCA merging into the RCA along the intramyocardial trabecular spaces (Figure 1D). On multi-section scanning, no obvious opening and closing annulus echo were detected at the pulmonary valve annulus. A membranous strong echo floating was detected, but not any forward blood flow signal in the main pulmonary artery. The reverse flow bundle was detected from the arterial duct. After prenatal diagnosis counseling, the pregnant woman and her family members induced labor at 23 weeks of gestation due to poor fetal prognosis. Autopsy was not performed.

Figure 1 Case 1 prenatal image of CAF. (A) 2D ultrasound shows dilated LCA/RCA. (B) Radiant flow demonstrating the RCA expansion. White arrows indicate RCA. (C) Color Doppler ultrasound shows blood flow from the LCA merging into the RCA along the intramyocardial trabecular spaces. (D) 4D color Doppler ultrasound with STIC and HDlive Flow render mode demonstrating the fistula from the LCA merging into the RCA along the intramyocardial trabecular spaces. LCA, left coronary artery; RCA, right coronary artery; CAF, coronary artery fistula; STIC, spatiotemporal image correlation; 2D, two-dimensional; 4D, four-dimensional.

During a routine ultrasound examination of a 30-year-old pregnant woman (G2P1), fetal echocardiography revealed structural abnormalities of fetal heart at 24 weeks of gestation. An examination was performed using a Voluson E10 ultrasound system (GE Healthcare). The diameter of the right ventricle of the fetus was small 3.2 mm, and the ratio of the right ventricle to the left ventricle was 0.24 (Figure 2A). The internal diameter of the LCA/RCA (1.9 mm/2.5 mm) widened. Color Doppler imaging demonstrated blood flow from the LCA merging into the RCA through the intramyocardial trabecular spaces (Figure 2B). Doppler spectroscopy showed a diastolic flow pattern and increased flow velocities in the dilated coronary arteries (Figure 2C). Using 4D color Doppler ultrasound with HDlive Flow with STIC, blood was shown to be flowing from the LCA through the trabecular space and ultimately into the RCA before emptying into the right ventricle (Figure 2D). During multi-planar scanning, the pulmonary valve annulus failed to demonstrate any discernible annular echoes corresponding to the opening and closing phases. Although a membranous strong echo floating was detected, there were no forward blood flow signals in the main pulmonary artery. No tricuspid valve opening and closing were observed in the four-chamber view. Although a strip-like strong echo was detected, color Doppler ultrasound showed no forward flow signal from right atrium to right ventricle was detected on both sides of the strong echo. The reverse flow bundle was detected in the arterial duct. The pregnant woman opted to proceed with the pregnancy and delivered a male neonate at 39 weeks by cesarean section at the request of the mother, weighing 2,512 g, with Apgar scores of 8-8-9 at 1, 5, and 10 min, respectively. Postpartum echocardiography showed the following characteristics: color Doppler examination visualized the blood flow associated with CAF (Figure 3A). Two-dimensional (2D) ultrasound revealed dilation of the LCA and RCA (Figure 3B). Color Doppler ultrasound illustrated fistulous connections, with the LCA communicating with the intramyocardial trabecular spaces and the RCA directly connecting into the right ventricle (Figure 3C,3D). The findings from transthoracic echocardiography and coronary angiography performed 20 days after birth were consistent with the prenatal ultrasonography results (Figure 3E).

Figure 2 Case 2 prenatal image of CAF. (A) 2D ultrasound revealed dysplasia of the fetal right ventricle. (B) Color Doppler ultrasound shows blood flow from the LCA merging into the RCA along the intramyocardial trabecular spaces. The white arrows indicate the blood flow pathways visualized by color Doppler ultrasound. (C) The Doppler spectrum demonstrates the diastolic flow pattern within dilated coronary arteries, as characterized by the spectral Doppler technique. (D) 4D color Doppler ultrasound with STIC and HDlive Flow render mode demonstrating blood flow from the LCA merging into the RCA along the intramyocardial trabecular spaces. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; LCA, left coronary artery; RCA, right coronary artery; CAF, coronary artery fistula; STIC, spatiotemporal image correlation; 2D, two-dimensional; 4D, four-dimensional.

Figure 3 Case 2 postpartum image of CAF. (A) Color Doppler examination shows the blood flow of CAF. (B) 2D ultrasound shows dilated LCA/RCA. (C) Color Doppler ultrasound demonstrating the fistula from the LCA into the intramyocardial trabecular spaces. (D) Color Doppler ultrasound demonstrating the fistula from the RCA into the right ventricle. (E) Computed tomography angiogram demonstrating the blood flowed from the LCA through the trabecular space and ultimately into the RCA before emptying into the right ventricle. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; CAF, coronary artery fistula; AO, aorta; LCA, left coronary artery; RCA, right coronary artery.

Discussion

The pathogenesis of CAF remains unclear, although it appears to be a cardiac muscle development disorder that occurs during fetal development. This condition leads to the persistence of intracardiac trabeculae, which are structures formed between endothelial cells and vascular lacunae (3). The majority of CAFs diagnosed prenatally originate from the RCA, traverse the right ventricle, and may present singly or in conjunction with other cardiovascular anomalies (4). In theory, a fistula can potentially form between a coronary artery and any neighboring cardiac chamber or major artery.

In this study, an expansion of the LCA/RCA was detected in the fetus reported in the first case. A collateral branch issuing from the LCA was observed connecting to the RCA along the open intracardiac trabecular space of the lateral wall of the right ventricle, eventually converging on the right ventricle. No accounts detailing this particular coronary fistula have been previously documented. Color Doppler imaging demonstrated that the blood flow from the LCA traveled along the lateral myocardial wall of the left ventricle, reaching the left ventricular apex, and subsequently branching out to the right ventricle and RCA, ultimately merging into the right ventricle. The incidence of this particular CAF is infrequent prior to parturition. In the case of pulmonary atresia with right ventricular dysplasia, due to insufficient blood supply to the right ventricle, the pressure of the coronary artery system rises to maintain myocardial metabolism, which causes an increase in coronary blood flow and dilation of the coronary arteries; whereas the pressure of the left heart system increases when it is responsible for the systemic circulation and the coronary arterial supply, which results in the shunting of blood from the left ventricle to the right ventricle through the coronary arterial collateral system, which in turn results in an abnormal increase in coronary blood flow and causes further dilation of coronary arteries. At the same time, the increased level of vascular endothelial growth factor (VEGF) in the ischemic state of the fetal myocardium contributes to the proliferation and expansion of coronary artery endothelial cells, especially in the case of right ventricular dysplasia, where the increased secretion of VEGF and other growth factors leads to a more pronounced dilation of the coronary arteries.

CAF is typically diagnosed postnatally, when clinical manifestations become evident. The paucity of fetal coronary artery visualization may be attributed to its minute size during the fetal period, rendering its challenging in early diagnosis. The examination process is further influenced by other factors, including the condition of the maternal abdominal wall, fetal movement, position, and gestational age. This study reports two cases of fetal right coronary artery–right ventricle fistula, accompanied by pulmonary valve atresia and right ventricular dysplasia. Pulmonary valve atresia results in a complete obstruction of the right ventricular outflow tract, preventing the right ventricle from pumping blood into the pulmonary artery. This obstruction leads to increased pressure within the right ventricle, but due to the lack of effective blood flow, the right ventricle may experience restricted development and gradual shrinkage. Consequently, both the systolic and diastolic functions of the right ventricle may become significantly impaired. In the context of pulmonary valve atresia, the right ventricle may progressively develop myocardial fibrosis due to obstructed blood flow and myocardial ischemia. The presence of a CAF could further reduce blood supply to the right ventricle, exacerbating the degree of myocardial ischemia, which may in turn promote the occurrence of fibrosis. In cases of fetal right ventricular dysplasia accompanied by pulmonary atresia, the sole route for fetal blood to reach the right ventricle is through the opening of the right ventricular wall sinus, which is subsequently cleared by the expansion of the coronary artery into the aorta. Thus, upon detection of fetal right ventricular hypoplasia during an ultrasound examination, it is imperative to entertain the possibility of a CAF to preclude a potential misdiagnosis.

In the past, most CAF cases were diagnosed primarily through 2D ultrasound and color Doppler imaging, whereas a limited number of cases were identified using 4D ultrasound (5,6). In this study, we utilized HDlive Flow combined with STIC technology to enhance the prenatal diagnosis of small fetal arterial and venous anomalies. HDlive Flow offers high-resolution imaging of blood flow, which is particularly valuable for detecting subtle vascular abnormalities in the small and intricate fetal circulatory system. Traditional 2D ultrasound often struggles to identify small, hidden vascular irregularities, but HDlive Flow allows for clearer visualization of blood vessels, enabling clinicians to detect conditions such as arterial stenosis, venous dilation, or malformed vessels that might otherwise go unnoticed.

STIC provides three-dimensional (3D) imaging by correlating spatial and temporal data, which significantly improves the ability to assess the structure and function of fetal vessels (7). By generating detailed 3D representations of the fetal vascular system, STIC technology helps to identify abnormalities such as abnormal vessel branching, flow disturbances, and other subtle structural anomalies that could be indicative of underlying developmental issues (8). The combination of these technologies offers a comprehensive, non-invasive approach to early diagnosis, particularly for small vascular anomalies that are difficult to assess with conventional imaging methods. Studies have shown that the integration of HDlive Flow and STIC can improve diagnostic accuracy, reduce the risk of missed diagnoses, and provide valuable insights into the fetal blood flow dynamics (9-11). Early detection of such anomalies is crucial for timely intervention and management, potentially reducing the risk of fetal distress or complications later in pregnancy. This approach represents a significant advancement in prenatal care, providing clinicians with more precise tools for assessing fetal health and optimizing outcomes. Utilizing prenatal ultrasound in conjunction with HDlive Flow with STIC facilitates the visualization of the intricate relationship between blood vessels encircling the fistula of CAF, thereby enhancing the accuracy of diagnosing CAF during prenatal stages. In the current investigation, two cases underwent routine 2D ultrasound and color Doppler ultrasound assessments, revealing dilated LCA/RCA. Upon integrating these findings with HDlive Flow with STIC, the distinctive anatomical location of the expanded coronary arteries was visualized in a 3D and intuitive manner. Multiple sections were scanned to trace the course of the CAF, thereby corroborating the diagnosis of a right coronary artery–right ventricle fistula. Precisely distinguishing CAF from the following conditions is vital: (I) ventricular septal defect, which refers to a disruption in the continuity of the ventricular septum. STIC-HDlive flow technology aids in the detection of atypical blood flow signals connecting the two ventricles; (II) coronary sinus dilation: color Doppler imaging and pulsed-wave Doppler can differentiate between coronary sinus dilation. The coronary sinus exhibits a low-velocity flow spectrum, whereas the fistula displays a high-speed turbulent signal (12).

In summary, 2D ultrasound and color Doppler imaging combined with HDlive Flow with STIC can accurately diagnose CAF and evaluate the basic development of the fetal heart, which can provide an important reference value for early intervention and treatment after delivery.

Acknowledgments

None.

Footnote

Funding: This study was supported by the Natural Science Foundation of Gansu Province (grant No. 23JRRA1391).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2214/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was provided by the participating pregnant mothers for publication of this article and accompanying images and videos. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Pisesky A, Nield LE, Rosenthal J, Jaeggi ET, Hornberger LK. Comparison of Pre- and Postnatally Diagnosed Coronary Artery Fistulae: Echocardiographic Features and Clinical Outcomes. J Am Soc Echocardiogr 2022;35:1322-35. [Crossref] [PubMed]
2. Al-Hijji M, El Sabbagh A, El Hajj S, AlKhouli M, El Sabawi B, Cabalka A, Miranda WR, Holmes DR, Rihal CS. Coronary Artery Fistulas: Indications, Techniques, Outcomes, and Complications of Transcatheter Fistula Closure. JACC Cardiovasc Interv 2021;14:1393-406. [Crossref] [PubMed]
3. Vaidyanathan B, Verma R, Kappanayil M, Kumar RK. Prenatal Diagnosis of a Large Left Coronary Artery to Right Ventricle Fistula With 3-Dimensional/4-Dimensional Spatiotemporal Image Correlation Rendering Followed by Successful Neonatal Transcatheter Closure. Circ Cardiovasc Imaging 2022;15:e014247. [Crossref] [PubMed]
4. Zeng S, Zhou Q, Tian L, Zhou J, Zhang M, Cao D. Isolated Coronary Artery Fistula in Fetal Heart: Case Reports and Literature Review. Fetal Pediatr Pathol 2016;35:348-52. [Crossref] [PubMed]
5. Li TG, Ma B, Nie F, Peng MJ. An unusual case of prenatal diagnosis of right coronary artery to right ventricle fistula with HD-flow render mode and spatiotemporal image correlation (STIC). Echocardiography 2020;37:1105-8. [Crossref] [PubMed]
6. Tekesin I, Uhlemann F. Prenatal diagnosis of coronary artery fistula using 2D and 3D/4D ultrasound. Ultrasound Obstet Gynecol 2018;51:274-5. [Crossref] [PubMed]
7. Karmegaraj B. Three- and Four-Dimensional Imaging of Ductus Arteriosus in Fetuses With Pulmonary Atresia and Aortic Arch Abnormalities. J Ultrasound Med 2024;43:609-16. [Crossref] [PubMed]
8. Li TG, Ma B, Yao LG. An unusual case of prenatal diagnosis of isolated subaortic left brachiocephalic vein with HDlive flow and spatiotemporal image correlation(STIC). Echocardiography 2022;39:122-4. [Crossref] [PubMed]
9. Tie HX, Ma B, Zhang DC, Li TG. Prenatal diagnosis of fetal inferior vena cava malformation using HDlive flow combined with spatiotemporal image correlation. Echocardiography 2022;39:685-90. [Crossref] [PubMed]
10. Ma B, Wang Y, Li T. Prenatal diagnosis of fetal retroesophageal left brachiocephalic vein with HDlive-Dlow render mode and spatiotemporal image correlation. Circ J 2021;85:80. [Crossref] [PubMed]
11. Ma B, Wu L, Zhang W. Rare vascular ring of right aortic arch and aberrant left subclavian artery in association with bilateral ductus arteriosus. Ultrasound Obstet Gynecol 2020;55:135-7. [Crossref] [PubMed]
12. Cui C, Liang W, Fan T, Liu L. Prenatal diagnosis of a right coronary artery to right atrial fistula with a giant coronary artery aneurysm: A case report. J Clin Ultrasound 2020;48:489-92. [Crossref] [PubMed]