Prenatal diagnosis of congenital left ventricular diverticulum

Congenital ventricular diverticulum (CVD) accounts for 0.05% of all cases of congenital heart malformation1. CVD is a form of extracardiac outpouching and is divided into apical and non-apical types according to location. Apical CVD has been described as a part of pentalogy of Cantrell, a group of congenital anomalies involving the median supraumbilical abdominal wall, lower sternum, anterior diaphragm, diaphragmatic pericardium and intracardiac anatomy2. Ventricular diverticula may derive from abnormal attachment of the heart tube to the yolk sac, eventually causing a portion of the ventricle to be drawn out as the yolk sac elements recede. Common types of intracardiac anomaly in pentalogy of Cantrell include ventricular septal defect, atrial septal defect and pulmonary stenosis or atresia. Here, we present a case of pentalogy of Cantrell in which the only intracardiac defect was apical left CVD. A 24-year-old pregnant woman was referred to our institution at 23 weeks of gestation because of suspected congenital heart disease. At 12 weeks, nuchal translucency thickness was 3.1 mm and the heart was located entirely within the chest. Echocardiography at 23 weeks showed that the fetal heart was positioned in the middle of the thorax, indicating mesocardia. Two-dimensional ultrasound imaging revealed a finger-like diverticulum that arose from the left ventricular apex and extended to the umbilicus through a partial interruption of the anterior diaphragm (Figure 1a). Color Doppler imaging of the cardiac diverticulum showed bidirectional arterial blood flow and revealed that its contraction was synchronized with the rest of the left ventricle (Figure 1b,c, Videoclip S1). The spatial relationship of the ventricular diverticulum and the umbilical vein was visualized clearly on four-dimensional (4D) color Doppler with spatiotemporal image correlation (STIC) and high-definition flow (HDflow) render mode (Voluson E10; GE Healthcare, Zipf, Austria) (Figure 1d, Videoclip S2). No other abnormalities were observed. Fetal karyotyping and chromosomal microarray analysis (Affymetrix 750K; Thermo Fisher Scientific, Santa Clara, CA, USA) were normal. A female neonate was delivered vaginally at 39 + 5 weeks of gestation weighing 3120 g. Medical records indicated that the neonate was referred to a cardiovascular hospital for heart surgery at 2 days postpartum. Physical examination noted that the neonate was well-developed with normal gross appearance. A subcutaneous pulsating mass that originated in the inferior portion of the sternum and extended along the abdominal midline to the umbilicus was noted upon palpation, and pulsations were synchronized with precordial activity. Echocardiography performed at 2 days postpartum showed a large, narrow-necked vascular structure with bidirectional flow originating in the left ventricular apex. Cleft of the lower sternum was observed on computed


Prenatal diagnosis of congenital left ventricular diverticulum
Congenital ventricular diverticulum (CVD) accounts for 0.05% of all cases of congenital heart malformation 1 . CVD is a form of extracardiac outpouching and is divided into apical and non-apical types according to location. Apical CVD has been described as a part of pentalogy of Cantrell, a group of congenital anomalies involving the median supraumbilical abdominal wall, lower sternum, anterior diaphragm, diaphragmatic pericardium and intracardiac anatomy 2 . Ventricular diverticula may derive from abnormal attachment of the heart tube to the yolk sac, eventually causing a portion of the ventricle to be drawn out as the yolk sac elements recede. Common types of intracardiac anomaly in pentalogy of Cantrell include ventricular septal defect, atrial septal defect and pulmonary stenosis or atresia. Here, we present a case of pentalogy of Cantrell in which the only intracardiac defect was apical left CVD.
A 24-year-old pregnant woman was referred to our institution at 23 weeks of gestation because of suspected congenital heart disease. At 12 weeks, nuchal translucency thickness was 3.1 mm and the heart was located entirely within the chest. Echocardiography at 23 weeks showed that the fetal heart was positioned in the middle of the thorax, indicating mesocardia. Two-dimensional ultrasound imaging revealed a finger-like diverticulum that arose from the left ventricular apex and extended to the umbilicus through a partial interruption of the anterior diaphragm ( Figure 1a). Color Doppler imaging of the cardiac diverticulum showed bidirectional arterial blood flow and revealed that its contraction was synchronized with the rest of the left ventricle (Figure 1b,c, Videoclip S1). The spatial relationship of the ventricular diverticulum and the umbilical vein was visualized clearly on four-dimensional (4D) color Doppler with spatiotemporal image correlation (STIC) and high-definition flow (HDflow) render mode (Voluson E10; GE Healthcare, Zipf, Austria) ( Figure 1d, Videoclip S2). No other abnormalities were observed. Fetal karyotyping and chromosomal microarray analysis (Affymetrix 750K; Thermo Fisher Scientific, Santa Clara, CA, USA) were normal.
A female neonate was delivered vaginally at 39 + 5 weeks of gestation weighing 3120 g. Medical records indicated that the neonate was referred to a cardiovascular hospital for heart surgery at 2 days postpartum. Physical examination noted that the neonate was well-developed with normal gross appearance. A subcutaneous pulsating mass that originated in the inferior portion of the sternum and extended along the abdominal midline to the umbilicus was noted upon palpation, and pulsations were synchronized with precordial activity. Echocardiography performed at 2 days postpartum showed a large, narrow-necked vascular structure with bidirectional flow originating in the left ventricular apex. Cleft of the lower sternum was observed on computed tomography at 3 days postpartum. Intraoperative findings were consistent with those on pre-and postnatal imaging, demonstrating a diverticulum anterior to the abdominal wall, covered only by a thin layer of skin and subcutaneous tissue. The thin serosal layer covering the diverticulum appeared to be an extension of the pericardium without an obvious pericardial defect. The diverticulum was ligated at its communication with the left ventricle. Histopathological analysis confirmed the presence of myocardial cells in the diverticulum (Figure 2). Whole-exome sequencing of the infant was performed after birth but no gene variation correlated with pentalogy of Cantrell was observed within the detection range.
A previous study reported that left ventricular diverticulum is related to pentalogy of Cantrell and almost always accompanies additional intracardiac defects 3 . Pentalogy of Cantrell is a rare, complex congenital abnormality resulting from developmental failure of the mesoderm and/or deficient ventral migration 4 . Developmental failure of the mesoderm results in diaphragmatic, pericardial and intracardiac defects, while deficient ventral migration of primordial structures results in defects of the sternum and epigastrium. With improvements in ultrasound technology, it is now possible to diagnose pentalogy of Cantrell and delineate severe heart abnormalities in the fetus as early as 12 weeks' gestation. Increased nuchal translucency thickness may also prompt early medical attention. The diagnosis of CVD can be made clinically based on the presence of a pulsatile epigastric mass with associated signs of cardiac defect and a displaced cardiac axis indicative of dextrocardia or mesocardia. Patients with CVD should be evaluated carefully for the presence of pentalogy of Cantrell. Lower sternal defects expose mediastinal structures to injury, increase the risk of respiratory disease and may lead to paradoxical respiratory movement 5 . Complications associated with CVD include rupture, thrombus formation and arrhythmia; thus, early assessment and surgical treatment are advisable. Fortunately, our case did not experience such complications pre-or postnatally.
In conclusion, we present a rare case of incomplete pentalogy of Cantrell in which CVD was the sole intracardiac defect. The long-term prognosis for fetuses with pentalogy of Cantrell depends on the severity of cardiac and other associated malformations. Prenatal diagnosis using clinical and imaging tools is important because early detection and surgical intervention may be lifesaving 6 . In our case, fetal echocardiography using 4D color Doppler with STIC and HDflow mode facilitated visualization of the spatial relationship between the left ventricular diverticulum and the umbilical vein. Prenatal counseling should be tailored for proper management of such cases.