Clinical Presentation and Therapy of Anomalies of the Situs.

Situs abnormalities may occur in many and most often more complex congenital cardiac malformations. These conditions are collectively referred to as heterotaxy syndromes, derived from the Greek words "heteros" meaning different and "taxos" meaning orientation or arrangement. Clinically, heterotaxy spectrum encompasses defects in the left-right laterality and arrangement of visceral organs. "Situs" is derived from Latin and is the place where something exists or originates. In human anatomy, situs can be solitus (derived from Latin, meaning "normal"), inversus, or ambiguus. Heterotaxy syndrome represents an intermediate arrangement of internal organs between situs solitus and situs inversus, also known as "situs ambiguous." Situs ambiguus describes an abnormal distribution of major visceral organs within the chest and abdomen. The determination of situs as normal, inversus, or ambiguus is primarily based on the location of unpaired organs such as the spleen, liver, stomach, and intestines. Diagnosis is made by clinical examination, echocardiography, a chest X-ray (position of the heart, stomach, and liver), and ultrasound of the abdominal organs. Situs is considered solitus if the left atrium, spleen, stomach, and the trilobed lung are on the left side and the liver and bilobed lung are on the right side. Situs ambiguus is present if the location of unpaired structures is random or indeterminate even after detailed and appropriate imaging. Situs inversus results when the arrangement of the thoracic and abdominal organs is mirrored. Individuals with situs inversus or situs solitus do not experience fatal dysfunction of their organ systems, as general anatomy and morphology of the abdominothoracic organ-vessel systems are conserved.

Investigation of the genetic and clinical features of laterality disorders in prenatal diagnosis: discovery of a novel compound heterozygous mutation in the DNAH11 gene.

BACKGROUND: Left-right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left-right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. METHODS: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). RESULTS: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. CONCLUSION: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.

Ultrasound and computed tomography angiography diagnosis of fetal right atrial isomerism with cardiac total anomalous pulmonary venous connection and intestinal malrotation: a case report and literature review.

Right atrial isomerism is a rare and severe isomerism. It is frequently associated with complex congenital heart disease and various extracardiac anomalies. Imaging diagnosis of right atrial isomerism is a challenge. Multisystem and complex anomalies in a 24-week-old fetus were diagnosed with prenatal ultrasound, postnatal computed tomography angiography (CTA), and autopsy. The ultrasound detected most major cardiovascular anomalies including right atrial isomerism and total anomalous pulmonary venous connection. The CTA further detected thoracic and abdominal malformations such as bilateral morphologically right bronchus, diaphragmatic hernia, asplenia, midline liver, and intestinal malrotation. The autopsy confirmed both ultrasound and CTA findings with additional findings, namely, bilateral trilobed lungs and bilateral morphological right auricles. Prenatal ultrasound and postnatal CTA can be complementary to each other in detecting multi-system complex anomalies. Their combined use can be useful for prenatal counseling and postpartum management.

A rare combination: a single common pulmonary vein with polysplenia syndrome.

A single common pulmonary vein is a rare anomaly, mostly occurring with asplenia. We wanted to report our case because it co-exists with polysplenia and ciliary dyskinesia.A baby girl about 2 months old with respiratory arrest was admitted to the emergency room of our hospital. She responded to pulmonary resuscitation. We ascertained from her medical history that she had been hospitalised twice because of recurrent lung infections. After the initial check and treatment, we applied imaging modalities to detect underlying problems of recurrent lung infection. Echocardiographic evaluation was suboptimal because of the widespread pulmonary infiltration. Still, we noticed a single common pulmonary vein without obstruction at the junction of the left atrium. Subsequently, a chest CT scan with contrast was performed. It revealed a single common pulmonary vein entering the left atrium with a single orifice, atrial septal defect, two lobes in both lungs, hepatic veins draining directly into the right atrium, and polysplenia. When the flow of a single common pulmonary vein goes directly to the right atrium through the defect, it may cause right heart dilatation as it did in our case. Therefore, patients may need to undergo surgery at an earlier age.

Long-Term Surgical Outcomes of Patients With Isomeric Right and Left Atrial Appendages.

Objectives: To compare the long-term outcomes of biventricular, univentricular, and so-called one-and-one-half ventricular repairs in patients with left and right isomerism. Methods: Surgical correction was undertaken, between 2000 and 2021, in 198 patients with right, and 233 with left isomerism. Results: The median age at operation was 24 days (interquartile range [IQR]: 18-45) and 60 days (IQR: 29-360) for those with right and left isomerism, respectively. Multidetector computed-tomographic angiocardiography demonstrated more than half of those with right isomerism had superior caval venous abnormalities, and one-third had a functionally univentricular heart. Almost four-fifths of those with left isomerism had an interrupted inferior caval vein, and one-third had complete atrioventricular septal defect. Biventricular repair was achieved in two-thirds of those with left isomerism, but under one-quarter with right isomerism (P < .001). Hazard regression for mortality revealed odds for prematurity at 5.5, pulmonary atresia at 2.81, atrioventricular septal defect with a common valvar orifice at 2.28, parachute mitral valve at 3.73, interrupted inferior caval vein at 0.53, and functionally univentricular heart with a totally anomalous pulmonary venous connection at 3.77. At a median follow-up of 124 months, the probability of survival was 87% for those with left, and 77% for those with right isomerism (P = .006). Conclusions: Multimodality imaging characterizes and delineates the relevant anatomical details, facilitating surgical management of individuals with isomeric atrial appendages. Continuing higher mortality despite surgical intervention in those with right isomerism points to the need for the reassessment of strategies for management.

A Prospective Management Strategy for Heterotaxy Syndrome with Intestinal Rotation Abnormalities: Imaging Does Not Predict Need for Surgery.

PURPOSE: Heterotaxy syndrome (HS) affects right-left anatomical development in 3% of children with congenital heart disease. Commonly, these patients have intestinal rotation abnormalities (IRA) that differ from typical malrotation. In this prospective study, we examine the development of a management pathway, imaging findings, and clinical course of patients with HS and IRA. METHODS: After literature review, a multispecialty focus group designed a pathway for HS. Participants from a single institution were prospectively enrolled from 2016 to 2019. They underwent an abdominal ultrasound and UGI, however timing was variable based on symptoms. Symptomatic IRA was defined as feeding intolerance, bilious or non-bilious vomiting, bloating, severe reflux, and intermittent pain or abdominal distention. Screening for symptoms occurred every three months for the first two years and then annually. RESULTS: 18 participants were followed for a median of 5.0 years. Three clinical categories were identified: 1) asymptomatic, not requiring intestinal surgery, 72.2%, 2) symptomatic with feeding intolerance or failure to thrive requiring gastrostomy placement and diagnostic laparoscopy with Ladd procedure, 16.7%, and 3) symptomatic requiring urgent exploration for suspicion of volvulus, 11.1%. Need for surgery did not necessarily correlate with US and/or UGI findings. CONCLUSIONS: In children with HS and IRA, postnatal imaging did not inform the need for intestinal surgery. Although rare, volvulus or other forms of proximal obstruction can be anticipated, and symptomatic patients should be offered surgical intervention. A multidisciplinary care pathway for patients with HS and IRA can coordinate care and help counsel families on the likelihood of needing intestinal surgery for IRA. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Prospective Cohort Study.

Intra-abdominal haemorrhaging after cardiac catheterisation: the importance of recognising vascular anomalies in heterotaxy syndrome.

A 2-month-old boy with a single ventricle underwent cardiac catheterisation. Inferior vena cava angiography at the end of the examination revealed local stenosis, flexion, and connection to the right hepatic vein. Six hours after catheterisation, he went into haemorrhagic shock. CT revealed contrast extravasation into the liver with ascites. A precise diagnosis of vascular anomalies is mandatory, especially in patients with heterotaxy syndrome.

Computed tomography and magnetic resonance imaging of congenital thoracic systemic venous anomalies.

We present the imaging findings of thoracic systemic venous anomalies diagnosed by computed tomography and magnetic resonance imaging. Persistent left superior vena cava is the commonest anomaly of the thoracic systemic veins encountered either incidentally as an isolated finding or associated with congenital heart disease. Inferior vena cava (IVC) interruption with azygos continuation is the second most common anomaly, which may also be isolated or be associated with left isomerism syndrome. The article will also discuss other rarer systemic venous anomalies including retroaortic brachiocephalic vein and IVC drainage into the left atrium. Finally, the impact of pre-procedure reporting of thoracic systemic venous anomalies on the choice of intervention and patient outcome will be addressed.

A puzzling CHD: a late diagnosis of left atrial isomerism.

We present a case of a 41-year-old patient with an unknown complex cardiac anatomy, who was previously submitted to two cardiac surgeries. Using multimodality imaging, a retrospective diagnosis was established, revealing a heterotaxy syndrome (left isomerism).

Predicting Cardiac Anatomy, Physiology, and Surgical Management Based on Fetal Echocardiography in Heterotaxy Syndrome.

OBJECTIVE: Heterotaxy syndrome (HS) is often associated with complex congenital heart disease (CHD). While fetal echocardiography (FE) permits accurate prenatal identification of most CHD, the high level of disease complexity in HS may pose challenges in predicting postnatal findings and outcomes. This study aimed to define the accuracy of FE in predicting postnatal anatomy, physiology, and surgical management of CHD in the setting of HS. STUDY DESIGN: Retrospective single-center cohort study including all patients with a prenatal diagnosis of HS from 2003 to 2018. Anatomic diagnoses from FE reports were compared with postnatal echocardiogram, catheterization, and operative reports. Prenatal predictions were compared with postnatal outcomes with a focus on ductal dependence, time to first intervention (immediate, neonatal period, 1-6 months, or older than 6 months), and surgical approach (single or biventricular). RESULTS: There were 102 pregnancies with fetal HS resulting in 21 terminations, 5 fetal losses, and 76 live births. Of the live births, 55 had significant CHD and available postnatal data for review. Among this group, survival to 1 year was 62% and was no different comparing single versus biventricular surgical approach. FE diagnostic accuracy varied by anatomic feature and was the lowest for diagnosis of venous anatomy. Determination of postnatal care was most accurate for predicting single versus biventricular surgical approach (91%), followed by ductal dependence (75%). Accuracy for predicting time to first intervention was the lowest at 69%. The most common reason for an incorrect prediction was difficulty in assessing the severity of pulmonary stenosis. CONCLUSION: FE permits accurate predictions regarding surgical approach. Characterizing systemic and pulmonary veins is challenging, as is predicting ductal dependence and time to first intervention. These data suggest that despite the high diagnostic accuracy of CHD in HS, a circumspect approach may be reasonable with regard to predicting some anatomic details and postnatal management decisions. KEY POINTS: · In HS, FE was most accurate for intracardiac anatomy.. · Diagnostic accuracy of venous anatomy was less reliable.. · Predicting surgical approach (single ventricle vs. biventricular) was highly accurate.. · Predicting ductal dependence and time-to-intervention were more challenging in some instances..

HETEROTAXY SYNDROME IN COVID-19 PATIENT WITH PULMONARY EMBOLISM AND AORTIC ANEURYSM: A RARE ACCIDENTAL COMBINATION (RADIOLOGICAL ASSESSMENT). / GETEROTAKSIIa, TROMBOEMBOLIIa LEGENEVOÏ ARTERIÏ TA ANEVRYZMA AORTY: RIDKISNE VYPADKOVE POIeDNANNIa (RADIOLOGIChNA OTsINKA).

With limited time for analysing computed tomography (CT) data in medical emergencies, radiologists and clinicians are not always aware of congenital pathologies, especially in asymptomatic cases. We present a case report of heterotaxy syndrome detected incidentally in a 62-year-old female with massive pulmonary embolism, local saccular aneurysm of the aortic arch and COVID-19. The presented case describes an unusual combination of life-threatening conditions and congenital anomalies. Using the CT angiography, we reported the preserved topography and morphology of the heart chambers. The superior and inferior venae cavae were located on the left, draining into a significantly dilated coronary sinus. Disordered abdominal organ arrangement included midline liver, right-sided stomach, the central location of the short pancreas, malrotation of the intestine, polysplenia, and atypical rise of visceral branches of the abdominal aorta. A comprehensive assessment of CT images promoted verification of undiagnosed congenital anomalies. Prompt recognition of heterotaxy syndrome in life-threatening conditions significantly impacts treatment tactics and should be the course of diagnostic and cautious interventions to reduce further complications.

A case of ventricular noncompaction associated with heterotaxy and atrioventricular block diagnosed at 15 weeks of gestation using superb microvascular imaging.

We present a case of fetal atrioventricular block, heterotaxy, and ventricular noncompaction observed longitudinally from the first to early second trimesters using B-mode and Doppler imaging, including superb microvascular imaging. At 12 weeks of gestation, the atrial and ventricular rates were 133 and 67 beats/min, respectively, and dextrocardia was noted. At 15 weeks of gestation, detailed sonography revealed ventricular septal defect, interruption of the inferior vena cava, dilated azygos vein, and double-outlet right ventricle. In addition, superb microvascular imaging revealed irregular contours in the anatomical left ventricular wall, indicating prominent trabeculations of the ventricle, which were characteristic findings of ventricular noncompaction. At 21 weeks of gestation, intrauterine fetal death occurred, and the autopsy revealed complex congenital heart disease, including ventricular noncompaction.

Polysplenia syndrome in adulthood: a case report.

Polysplenia syndrome mainly described in pediatrics; rarely and incidentally in adulthood. Most patients had their diagnosis done during childhood due to the frequent association to cardiac anomalies that speak for themselves earlier in life. Multiple spleens, cardiac defect and vascular malformation of the inferior vena cava with azygos or hemiazygos continuation are the most frequent observed malformations. Our patient was one this rarest adulthood incidental diagnosis, who presented in the emergency department for nephritic colic, and while imaging for this, multiples spleens and other visceral malformations were diagnosed. Hopefully, cardiac ultrasound hadn't showed any cardiac malformation and the patient was discharged aware of this condition. Through this publication we report the possible incidental diagnosis of polysplenia condition and highlight the fact that people with such important malformation can lead a normal life, and only awareness should be given for future surgeries, instrumental treatment or else.

Prenatal diagnosis of hepatic interruption of the inferior vena cava with azygos/hemiazygos continuation without structural heart defects: A case series.

OBJECTIVES: To describe fetal spectrum and echocardiographic characteristics of interrupted inferior vena cava (IIVC) with azygos/hemiazygous continuation without other structural heart defects and to evaluate its association with visceral heterotaxy and isomerism, extracardiac and genetic anomalies, and to review neonatal outcome. METHODS: This was a retrospective study of 14 fetuses with a confirmed diagnosis of IIVC with normal intracardiac anatomy. The following variables were collected; indication for referral, gestational age at diagnosis; associated isomerism and visceral heterotaxy, heart rhythm, genetic and extracardiac abnormalities, and fetal/neonatal outcome. RESULTS: Among 36 fetuses with IIVC, 14 cases (38.8%) had normal intracardiac anatomy. These IIVC cases correspond to 0.19% (14/7250) of all fetal cardiac examinations, and to 1.5% (14/922) of all cardiac abnormalities. Six patients had visceral abnormalities. Atrial appendage morphology was clearly depicted in three fetuses, both appendages were left. One fetus had bradyarrhythmia revealing atrial ectopic rhythm. Six fetuses did not have any concomitant cardiac or visceral abnormalities, therefore regarded as isolated. All babies were delivered at term with a good prognosis. CONCLUSION: Our study has shown that almost half of the IIVC cases without intracardiac structural anomalies displayed other findings of isomerism while the other half was isolated benign vascular variant. Therefore, prenatal diagnosis of IIVC should prompt a comprehensive evaluation for cardiac, situs, and visceral anomalies. The outcome is favorable.

Diffuse hepatocellular carcinoma secondary to cardiac cirrhosis in heterotaxy syndrome.

Heterotaxy syndrome is a rare congenital defect of left-right laterality of major visceral organs, often categorised by the presence of symmetric left or right atrial heart chambers with a single effective ventricle. Known as left or right atrial isomerism, these conditions may present with a distinct pattern of extracardiac anomalies. Heterotaxy is often palliated with the Fontan procedure and is suggested to be subject to similar long-term sequelae of congestive hepatopathy and ischaemia, increasing the risk for hepatocellular carcinoma. Few works document primary, localised hepatocellular carcinoma in patients with heterotaxy syndrome. We present a case of diffuse, multifocal metastatic hepatocellular carcinoma in a young patient with left atrial isomerism and dextrocardia. We also review suggested guidelines of surveillance for liver disease and hepatocellular carcinoma in this patient population.

Heterotaxy syndrome: Prenatal diagnosis, concomitant malformations and outcomes.

OBJECTIVE: The aim of this study is to define cardiac and extracardiac malformations in fetuses with heterotaxy syndrome and to determine perinatal and childhood prognosis. METHODS: In this retrospective study, fetuses diagnosed with heterotaxy syndrome on antenatal ultrasonography in a tertiary center between January 2014 and January 2021 were analyzed. Fetuses with heterotaxy syndrome were grouped as right atrial isomerism (RAI) and left atrial isomerism (LAI). RESULTS: A total of 62 fetuses, 32 (51.6%) with RAI and 30 (48.4%) with LAI, were included in the study. Extracardiac anomaly was detected in 25% of fetuses with RAI and 44% of fetuses with LAI (p = 0.13). Patients with univentricular repair had a higher childhood mortality than patients with biventricular repair (p = 0.031). The presence of conotruncal anomaly was an independent factor affecting mortality (HR = 5.09, CI 95% 1.09-23.71, p = 0.039). CONCLUSION: Hydrops fetalis, univentricular physiology and conotruncal anomalies are associated with poor outcomes in heterotaxy syndrome. The severity of the cardiac malformation is the main determinant of the outcomes. The presence of extracardiac malformations is associated with increased morbidity and mortality.

Pulmonary Versus Systemic Outflow Obstruction in Functionally Univentricular Hearts with Isomerism: An Observation.

Our objective was to review our experience with isomerism associated with univentricular hearts and evaluate the prevalence of pulmonary versus systemic outflow obstruction. We identified those prenatally or postnatally diagnosed, between September 2004 and October 2021, with right and left isomerism and a functionally univentricular heart. We identified 62, 51 prenatally and 11 postnatally. Of the 62, 61 had prenatal care for an 84% (51/61) prenatal detection rate. Of the 62, 36 (58%) had right isomerism. Of the 51 prenatally diagnosed, 36 were live-born, 13 had fetal demise, and two underwent elective termination. Of the total 62, 43 had pulmonary outflow obstruction, 14 had systemic outflow obstruction, three had no outflow obstruction, and two had a common arterial trunk. However, between September 2004 and December 2019, 41 of 52 (79%) had pulmonary outflow obstruction, and between January 2000 and October 2021, 2 of 10 (20%) had pulmonary outflow obstruction (p = 001). We noted a statistically significant temporal change in the prevalence of pulmonary versus systemic outflow obstruction in those with isomeric situs and a functionally univentricular heart. Further, prenatal diagnosis exceeded 80% in the general population of Nevada.