Fetal double outlet right ventricle without heterotaxy syndrome: Diagnostic spectrum, associated extracardiac pathology and clinical outcomes.

OBJECTIVES: To document the clinical spectrum and outcomes of fetal double outlet right ventricle (DORV) without heterotaxy in a recent diagnostic era. METHODS: Prenatal cases of DORV consecutively diagnosed from 2007 to 2018 were retrospectively identified. Clinical records, including details regarding genetic testing and pre and postnatal imaging were reviewed. RESULTS: DORV was diagnosed in 99 fetuses without heterotaxy. The most common anatomic subtype was subaortic ventricular septal defect (VSD) and normally related great arteries with (n = 45, 45%) or without (n = 13, 13%) pulmonary stenosis. The remainder had a subpulmonic VSD with transposed great arteries (n = 15, 15%), atrioventricular valve atresia (n = 24, 24%), or remote VSD (n = 2, 2%). A genetic diagnosis was found in 32 (34%) of 93 tested. Major extracardiac anomalies were found in 40 (40%), including 17/24 (71%) with and 22/69 (32%) without an abnormal karyotype, with VACTERL association in 9. Genetic and/or extracardiac pathology was identified in 37/58 (64%) with a subaortic VSD, 5/15 (33%) with a subpulmonic VSD, 9/24 (38%) of those with AV valve atresia and 2/2 (100%) with a remote VSD. A genetic abnormality was a significant predictor of fetal demise (9/37 vs 1/62 p < 0.01) or pregnancy termination (12/35 vs 9/64 p = 0.03). CONCLUSIONS: Fetal DORV is associated with a high rate of genetic abnormalities and extracardiac pathology. The presence of genetic abnormalities impacts prenatal outcomes and parental decision-making.

Prenatal diagnosis, associated findings and postnatal outcome of fetuses with double outlet right ventricle (DORV) in a single center.

Objective To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with double outlet right ventricle (DORV). Methods All cases of DORV diagnosed prenatally over a period of 8 years were retrospectively collected in a single tertiary referral center. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. Results Forty-six cases of DORV were diagnosed prenatally. The mean gestational age at first diagnosis was 21+4 weeks (range, 13-37). A correct prenatal diagnosis of DORV was made in 96.3% of the cases. If the relation of the great arteries, the position of the ventricular septal defect (VSD) and additional cardiac anomalies are taken into account, the prenatal diagnosis was correct in 92.6% of the cases. One case was postnatally classified as transposition of the great arteries with subpulmonary VSD and was excluded from further analysis. A total of 41 (91.1%) fetuses with DORV had major additional cardiac anomalies, 30 (66.7%) had extracardiac anomalies and 13 (28.9%) had chromosomal or syndromal anomalies. Due to their complex additional anomalies, five (11.1%) of our 45 fetuses had multiple malformations and were highly suspicious for non-chromosomal genetic syndromes, although molecular diagnosis could not be provided. Disorders of laterality occurred in 10 (22.2%) fetuses. There were 17 terminations of pregnancy (37.8%), two (4.4%) intrauterine and seven (15.6%) postnatal deaths. Nineteen of 22 (86.4%) live-born children with an intention to treat were alive at last follow-up. The mean follow-up among survivors was 32 months (range, 2-72). Of 21 children who had already undergone postnatal surgery, eight (38.1%) achieved biventricular repair and 13 (61.9%) received univentricular palliation. One recently born child is still waiting for surgery. All children predicted prenatally to need a single ventricle palliation, and all children predicted to achieve biventricular repair, ultimately received the predicted type of surgery. After surgery, 14 of 18 (77.8%) children were healthy without any impairment. Conclusion DORV is a rare and often complex cardiac anomaly that can be diagnosed prenatally with high precision. DORV is frequently associated with major additional anomalies, leading to a high intrauterine and postnatal loss rate due to terminations or declined postnatal therapy. Without additional anomalies, the prognosis is good, although approximately 60% of children will have single ventricle palliation.

Coronary artery anomalies on preoperative cardiac CT in children with tetralogy of Fallot or Fallot type of double outlet right ventricle: comparison with surgical findings.

Coronary artery anomalies on preoperative cardiac CT have not been systematically compared with surgical findings in a large cohort of tetralogy of Fallot and Fallot type of double outlet right ventricle. This study was conducted to evaluate incidence and diagnostic accuracy of preoperative cardiac CT for identifying detailed coronary artery anatomy in these patients. Coronary artery anatomy on preoperative cardiac CT exams in 318 children with tetralogy of Fallot or Fallot type of double outlet right ventricle were reviewed and compared with surgical findings. Incidences of total and surgically critical coronary artery anomalies, concordance rate between cardiac CT and surgical findings, and diagnostic accuracy of cardiac CT were assessed. In addition, the types of surgical modifications for surgically critical coronary artery anomalies were reviewed. The incidences of total and surgically critical coronary artery anomalies were 8.5% (27/318) and 5.0% (16/318), respectively. The concordance rate between cardiac CT and surgical findings was 95.0% (302/318). The diagnostic accuracy of cardiac CT was 96.9% (308/318). In surgically significant coronary artery anomalies, tailored and careful right ventriculotomy was done in 13 cases, placement of a right ventricle-pulmonary artery conduit in two, and unroofing of the right coronary artery in one. Preoperative cardiac CT may be useful in identifying coronary artery anatomy in children with tetralogy of Fallot or Fallot type of double outlet right ventricle.

Incidence and Mortality of Adults With Pulmonary Hypertension and Congenital Heart Disease.

Reports on pulmonary hypertension (PH) in the aging congenital heart disease (CHD) population are few and focused on arterial PH and patients with systemic-to-pulmonary shunts. Our objective was to estimate incidence and mortality of adult-onset PH in the CHD population. Using Danish nationwide registries, we identified all patients diagnosed with CHD from 1963 to 1974 and 1977 to 2012. Patients were matched 1:10 by birth year and gender with general population subjects. Between 1977 and 2013 adults >18 years of age were followed up until PH diagnosis, death, or emigration, whichever came first, using data from the Danish National Registry of Patients. We computed cumulative incidences of PH. Using Cox regression, we compared the mortality rate between CHD subjects with and without PH matched by gender and birth year. We identified 14,860 patients with CHD. At 70 years of age, their overall cumulative incidence of PH was 7.2% (8.3% in those with systemic-to-pulmonary shunts and 5.3% in those without) compared with 0.4% in the general population. The 1-, 5-, and 10-year mortality for adults with CHD and PH was 24%, 44%, and 52%, respectively. This represented a 4-fold (95% confidence interval 3.3 to 5.6) increase in mortality compared with adults with CHD without PH after adjusting for gender, birth year, CHD severity, and presence of extracardiac defects. In conclusion the incidence of PH was substantially increased in adults with CHD relative to the general population. Of note, the increased incidence was not limited to those with a history of systemic-to-pulmonary shunts. PH was associated with increased mortality.

The concept of double inlet-double outlet right ventricle: a distinct congenital heart disease.

The aim of this study was to estimate the incidence and to analyze the anatomy of double inlet-double outlet right ventricle complex and its associated cardiac anomalies in our autopsy series. Among the 1640 hearts with congenital heart disease of our Anatomical Collection, we reviewed the specimens with double inlet-double outlet right ventricle, according to the sequential-segmental analysis, identifying associated cardiac anomalies and examining lung histology to assess the presence of pulmonary vascular disease. We identified 14 hearts with double inlet-double outlet right ventricle (0.85%). Right atrial isomerism was observed in 10 hearts, situs solitus in 3 and left atrial isomerism in one. Regarding the mode of atrioventricular connection, all hearts but one had a common atrioventricular valve. Systemic or pulmonary venous abnormalities were noted in all patients with atrial isomerism. In nine patients a valvular or subvalvular pulmonary stenosis was present. Among the functionally "univentricular hearts", double inlet- double outlet right ventricle represents a peculiar entity, mostly in association with right atrial isomerism. Multiple cardiac anomalies are associated and may complicate surgical repair.

Laterality defects in the national birth defects prevention study (1998-2007): birth prevalence and descriptive epidemiology.

Little is known epidemiologically about laterality defects. Using data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007. We identified 517 nonsyndromic cases (378 heterotaxy, 73.1%; 139 situs inversus totalis [SIT], 26.9%) resulting in an estimated birth prevalence of 1.1 per 10,000 live births (95% confidence interval 1.0­1.2). Prevalence did not differ significantly across sites, over time, or by inclusion of pregnancy termination. Laterality defects were more common among preterm cases compared to term cases, and in children born to mothers who were non-white or younger than 20 years compared to white mothers or those age 25­29 years. The distribution of associated cardiac and extra-cardiac defects, excluding the expected heterotaxy anomalies, varied by type of laterality defect. Cases with heterotaxy were significantly more likely than those with SIT to have double outlet right ventricle, atrioventricular canal defects, pulmonary stenosis, non-tetralogy of Fallot pulmonary atresia with ventricular septal defect, totally and partially anomalous pulmonary venous return; also more likely to have orofacial clefts, esophageal atresia, bowel atresias, and omphalocele, though not reaching statistical significance. Relatively more common among cases with SIT were Dandy- Walker malformation, anotia/microtia, and limb deficiency. The similarity in the demographic characteristics of heterotaxy and SIT supports the hypothesis that they are part of a continuum of abnormal left-right axis patterning. These findings on laterality defects may help guide clinical care, future research, and prevention strategies.

Right ductus arteriosus: facts and theory.

OBJECTIVE: To report fetal right-sided persistent ductus arteriosus (RPDA) in association with right aortic arch (RAA). STUDY DESIGN: Extensive sonographic fetal anatomical scans were consecutively performed on 19,874 private, self-referred pregnant women who wanted early sonographic detection of fetal anomalies. RESULTS: Of 19,874 transvaginal (TVS) sonographic examinations 40 fetuses had right aortic arch (RAA) and four of them (10%) had RPDA. We also diagnosed seven cases of RPDA with involvement of the left aortic arch where a right-curving pattern ("L" shape) parallel to the right pulmonary artery was suggestive of Rt. DA with left aortic arch. Only one (9%) of the RPDA cases was associated with a cardiac anomaly (double outlet right ventricle). None of the other eight RPDA cases had any discernible anomalies, and all of the fetuses with RPDA had normal karyotypes. CONCLUSIONS: In 10% of the fetuses with right aortic arch the ductal arch was also on the right side. An unusual-looking DA may be a RPDA associated with the left aortic arch. In most cases, the RPDA is a normal variant not associated with other anomalies.

Prevalence of associated cardiovascular abnormalities in 500 patients with aortic coarctation referred for cardiovascular magnetic resonance imaging to a tertiary center.

Coarctation of the aorta (CoA) is a common congenital defect whose overall incidence is 5-8% of all congenital cardiac anomalies. Associated cardiac anomalies have been well described in previous studies examining specific subgroups of CoA patients, particularly infants and necropsy specimens. The majority of studies, conducted from the 1970s to 1980s, excluded older children, adolescents, and adults. Given the advent of improved surgical and interventional techniques, many CoA patients are surviving into adulthood. This study examined a population of 500 CoA patients in the authors' cardiovascular magnetic resonance imaging (MRI) database involving a population of CoA survivors 5-79 years of age. This was to give a new perspective on the prevalence of associated cardiovascular abnormalities including the bicuspid aortic valve, arch hypoplasia, intracardiac shunts, and subaortic stenosis. These associated abnormalities are less prevalent than in previous studies, reflecting a milder spectrum of CoA. Cardiovascular MRI with its multiplanar imaging capabilities and lack of ionizing radiation is safe and suitable for evaluation and follow-up assessment of CoA patients. Evaluation of CoA by MRI should not be confined to the arch, but should include the heart and mediastinal vessels to assess for the presence and severity of any expected or unexpected associated anomalies.

Double outlet right ventricle with giant pulmonary artery aneurysm and severe aortic coarctation: diagnosis with multislice CT.

Complex cardiovascular pathologies in the pediatric population are usually evaluated with echocardiography and catheter angiography as initial and advanced imaging of choice, respectively. Echocardiography may pose some difficulties in the diagnosis of complex cardiovascular pathologies. Due to short acquisition times, detailed imaging by the use of post-processing techniques, reduced radiation exposure compared to catheter angiography, and additional information obtained on lung parenchyma, multi-slice computed tomography (CT) is the advanced imaging method of choice in selected cases. The present report describes a 14-year-old symptomatic case with complex cardiovascular pathology, whose vascular architecture could be properly demonstrated by multi-slice CT.

Spectrum of congenital heart disease in Malta. An excess of lesions causing right ventricular outflow tract obstruction in a population-base study.

AIMS: To quantify birth prevalence and spectrum of congenital heart disease in the Island population of Malta, and compare these rates with previous studies. METHODS: All patients diagnosed as having congenital heart disease by echocardiography, cardiac catheterization, surgery or post-mortem by 1 year of age between 1990-1994 were included. There were 231 cases of live born congenital heart disease with a birth prevalence of 8.8/1000 live births. The commonest lesions were ventricular septal defect, pulmonary stenosis and tetralogy of Fallot. The rates of individual lesions were compared with two recent epidemiological studies with similar methodologies. RESULTS: Although the overall birth prevalence of congenital heart disease was similar in three studies, significantly higher rates of pulmonary stenosis, tetralogy of Fallot and double outlet right ventricle were found in Malta, all of which predispose to right ventricular outflow tract obstruction. In contrast, there were lower rates of lesions causing left ventricular outflow tract obstruction. A higher rate of ventricular septal defect was also found. The Maltese gene pool may contain an inherent predisposition towards lesions causing right ventricular outflow tract obstruction.

Ventricular function after anatomic repair in patients with atrioventricular discordance.

Since June 1989, 18 patients with atrioventricular discordant anomalies under 15 years of age underwent anatomic correction, or double switch operation, with 2 hospital deaths (11%). Ages ranged from 1 year 4 months to 12 years (mean 7.2 years) and body weights ranged from 7.1 to 32.5 kg (mean 20.1 kg) at operation. Visceral situs was solitus in 12 and inversus in 6. Ventriculoarterial connection was discordant in 4 and double-outlet in 14. All had associated congenital cardiac anomalies consisting of ventricular septal defect in 17, atrial septal defect in 9, pulmonary atresia in 10, pulmonary stenosis in 6, systemic tricuspid regurgitation in 9, mitral regurgitation in 6, bilateral superior venae cavae in 6, patent ductus arteriosus in 6, Wolff-Parkinson-White syndrome in 2, and congenital atrioventricular block in 1. Previous palliation had been performed 19 times in 11 patients including systemic-pulmonary shunts in 10 patients and pulmonary banding in 1 patient. Anatomic correction consisted in the Mustard procedure in 12 or the Senning procedure in 6 at the atrial level and in external conduit repair in 14, arterial switch operations in 3, or direct anastomosis between the pulmonary artery and right ventricle in 1 at the ventriculoarterial level. The arterial switch operation was indicated in patients with a normal pulmonary valve, and external conduit repair was indicated for patients with pulmonic stenosis or atresia. Anatomic right ventricular end-diastolic volume showed significant reduction from 122.2% +/- 46.3% of normal to 78.8% +/- 24.0%, mainly owing to unloading of the ventricle after the operation (p < 0.0003). Right ventricular ejection fraction remained unchanged (56% +/- 8% to 56% +/- 6%). Anatomic left ventricular end-diastolic volume and left ventricular ejection fraction remained unchanged before and after the operation: volume 134.6% +/- 50.0% of normal to 127.3% +/- 32.8% and ejection fraction from 61% +/- 8% to 56% +/- 8%. Cardiac index averaged 3.1 +/- 0.5 L/min per square meter after the operation. The double switch operation is best indicated in patients with atrioventricular discordance associated with systemic tricuspid regurgitation and/or with poor systemic right ventricular function.

Pathogenesis of various forms of double outlet right ventricle in mouse fetal trisomy 13.

The pathogenesis of double outlet right ventricle with or without pulmonary infundibular atresia in mouse fetal trisomy 13 was studied at the organ level using microdissection and scanning electron microscopy. Altogether, 394 karyotyped trisomic embryos were collected between 11 days and 16 hours of gestation (presence of a vaginal plug = day 1) and 15 days of gestation at intervals of 8 hours, and at 16 days of gestation. The hearts were perfusion-fixed, microdissected, and prepared to be observed in scanning electron microscope in the following standardized orientations: frontal, right or left profile, septal and parietal halves of the right ventricle and outflow tract (conotruncus). Comparison of 276 trisomic hearts with their normal counterparts described previously has shown that: the first pathognomonic feature is the abnormal anterior position of the proximal part of the parietal outflow tract ridge or of both ridges (at 12 days and 16 hours of gestation); the abnormal anterior fusion of these ridges ("coalescence") results in a mesenchymal mass behind which is deviated the pulmonary part of the outflow tract lumen; from 14 days and 16 hours of gestation on, this lumen is either obstructed, resulting in a supravalvar stenosis of the pulmonary trunk and subsequently evolving into double outlet right ventricle with pulmonary infundibular atresia; or, in a minority of cases, this lumen is not obstructed and the heart develops into double outlet right ventricle without pulmonary infundibular atresia. The pathogenesis of these malformations differs from most of the known hypotheses based on deductions from human malformed hearts, as well as from observations of the pathogenesis of similar outflow tract malformations, such as those found in the Keeshond dog or rats treated with trimethadione.

Transatrial repair of double-chambered right ventricle.

Seventeen consecutive patients with double-chambered right ventricles underwent intracardiac repair from February, 1985 through March, 1989. Nine patients had an associated ventricular septal defect. A transatrial approach to the repair was utilized in all patients. Early postoperative right ventricular-to-left ventricular pressure ratio was a mean of 0.29, range 0.21 to 0.37. There were no hospital or late deaths. We conclude that transatrial repair of a double-chambered right ventricle can be accomplished routinely with satisfactory results.