Influenza vaccination during pregnancy and risk of selected major structural congenital heart defects, National Birth Defects Prevention Study 2006-2011.

BACKGROUND: Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs. METHODS: We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011. For defects with ≥5 exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; and maternal age at delivery, race/ethnicity, low folate intake, and smoking and alcohol use during B1P3. RESULTS: Overall, 124 (4.2%) simple CHD case mothers and 197 (4.0%) control mothers reported influenza vaccination from 1 month before through the third pregnancy month. The aOR for any simple CHD was 0.97 (95% CI: 0.76-1.23). Adjusted ORs for specific simple CHDs ranged from 0.62 for hypoplastic left heart syndrome to 2.34 for total anomalous pulmonary venous return (TAPVR). All adjusted CIs included the null except for TAPVR. CONCLUSIONS: Although we cannot fully exclude that exposure misclassification may have masked risks for some CHDs, findings add to existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. The TAPVR result may be due to chance, but it may help inform future studies.

Total anomalous pulmonary venous connection with another major congenital cardiac defect in biventricular hearts.

BACKGROUND: The association of total anomalous pulmonary venous connection (TAPVC) with major congenital cardiac anomalies is rare. This coexistence has an impact on the diagnosis and management strategies. The objective of this single centre study was to analyse the outcomes of such association in bi-ventricular hearts. METHODS: This is a single-centre retrospective review of all patients who underwent repair for TAPVC associated with major congenital cardiac anomalies in bi-ventricular hearts from February 2015 to March 2020. Data were obtained from the hospital database. The primary aim was to assess the surgical outcomes. In addition, we described the incidence, pathophysiology, morphology and surgical strategies in this cohort of patients. RESULTS: Out of a total of 274 patients who underwent repair for TAPVC during the study period, 16 (5.8%) patients had one or more major associated cardiac defect anomalies. The major associated lesions were ventricular septal defects (9), tetralogy of Fallot (2), transposition of the great arteries (1), aorto-pulmonary window (1), partial atrioventricular canal defect (1), pulmonary stenosis (1) and severe tricuspid valve regurgitation due to flail chord (1). The mean follow-up period is 32 ± 13 months. There were two deaths in the post-operative period and no deaths in the follow-up period. CONCLUSION: The incidence of major associated cardiovascular defects with TAPVC in bi-ventricular morphology is 5.8%. The presence of a major associated lesion with TAPVC significantly alters the pathophysiology and clinical presentation with an impact on diagnosis and treatment.

Isomerism of the atrial appendages: morphology and terminology.

BACKGROUND: Our aim is to identify the pathognomonic anatomical markers and the best terminology to describe the cardiac malformations associated with absent or multiple spleens, which are known as asplenia or polysplenia syndromes or isomerism. MATERIALS AND METHODS: We have reviewed 65 hearts with isomerism of atrial appendages of the Anatomical Collections of Congenital Heart Disease, Institute of Pathological Anatomy of the University of Padua consisting of 1800 specimens. All the hearts were classified according to sequential segmental classification. RESULTS: The incidence of isomerism was 3.6%. Of the total, 45 hearts with isomerism of right atrial appendages showed bilateral trilobed lungs, short bronchi, and absent spleen. The atrioventricular junction was univentricular in 49% of cases with a common atrioventricular valve in 91%. Pulmonary atresia and double outlet right ventricle were present in 40% and 47% of cases, respectively. Total anomalous pulmonary venous drainage and absent coronary sinus were always present. In 20 hearts with isomerism of left atrial appendages, bilateral bilobed lungs with long bilateral bronchi and multiple spleens were always found. The biventricular atrioventricular connection was present in 65% with a common valve in 30% of the hearts. The ventriculoarterial connection was concordant in 45% of cases, and aortic atresia and pulmonary atresia were both noted in 15% of each. An anomalous symmetric pulmonary venous drainage was observed in 65% of the hearts and interruption of inferior vena cava was found in 75% of cases. CONCLUSIONS: We believe that the appropriate terminology is based on the symmetrical morphology of the atrial appendages. The absence of the coronary sinus and the total anomalous pulmonary venous drainage are the markers of isomerism of the right atrial appendages. Symmetric pulmonary venous drainage and interruption of inferior vena cava are the markers of isomerism of left atrial appendages. In recent years, thanks to the improvement of clinical diagnosis and of surgical techniques these patients have the possibility to survive to adult age.

Maternal Obesity as a Risk Factor for the Development of Total Anomalous Pulmonary Venous Connection in Their Offspring.

The incidence of total anomalous pulmonary venous connection (TAPVC) in the Caucasian population is 2.5/100,000 live births (LB), and the incidence in the Hispanic population is 19.8/100,000 LB. Without knowing the exact etiology for the development of congenital heart disease, our objective was to determine the maternal factors associated with the development of TAPVC. METHODS: 55 mother-child binomials with isolated TAPVC (group I) and 152 healthy mother-child binomials (group II) were included. Both groups had no maternal history of addiction, pre-eclampsia, or type 1, 2 or gestational diabetes mellitus. Complete clinical histories were obtained for the women in both groups and perinatal and birth data were recorded. In addition, genealogies across three generations were constructed to determine affected first- or second-degree relatives with complex congenital heart disease. RESULTS: Among the maternal characteristics analyzed, women in group I had a higher number of pregnancies before gestation of the index case (p = <0.05), and the Body Mass Index (BMI) before pregnancy was higher compared to Group II (p < 0.05), with an adjusted risk of OR = 3.6 (p = 0.011). The family history showed a higher prevalence in the group of patients with TAPVC compared to healthy children (p < 0.05). CONCLUSION: Maternal obesity before pregnancy is a risk factor for the development of CATVP in children in the Mexican population.

Left circumflex coronary artery from the pulmonary artery in scimitar syndrome.

BACKGROUND: Scimitar syndrome is a rare combination of cardiopulmonary abnormalities found in 1-3 per 1000 live births. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is only found in 1 in 250-400 congenital heart disease patients. OBJECTIVE: We aimed to investigate the incidence of left circumflex ALCAPA within our referral center's cohort of scimitar syndrome patients. MATERIALS AND METHODS: A review of medical records, cardiac imaging and operative notes from all patients diagnosed with scimitar syndrome at our center between 1992 and 2016 was undertaken and all imaging reviewed. RESULTS: Fifty-four patients with scimitar syndrome and imaging were identified. Of these, 3 patients (1 male and 2 female) with ALCAPA were identified, representing an incidence of 5.5% (95% confidence interval [CI] 0-11.67%). In all three cases, the anomalous coronary arising from the pulmonary artery was the left circumflex coronary artery (LCx) and the point of origin was close to the pulmonary arterial bifurcation. CONCLUSION: We hypothesize that the prevalence of LCx-ALCAPA, in the setting of scimitar syndrome, may be greater than previously thought. We suggest that any patient with scimitar syndrome, especially with evidence of ischaemia, should be investigated for ALCAPA. Given its noninvasive nature and simultaneous imaging of the lungs, we suggest that cardiovascular CT is the most appropriate first-line investigation for these patients.

Scimitar Syndrome in Children and Adults: Natural History, Outcomes, and Risk Analysis.

BACKGROUND: Scimitar syndrome involves congenital anomalous pulmonary venous return to the inferior vena cava. Optimal management remains controversial. We describe the natural history of disease, nonsurgical and surgical outcomes, and risk factors for poor outcomes at our institution. METHODS: Patients with anomalous pulmonary venous return to the inferior vena cava documented on echocardiography at our institution between January 1994 and January 2015 were reviewed retrospectively. The study protocol IRB-AAAO1805 was approved. RESULTS: Forty-seven patients were identified, including 20 infants with significant associated congenital heart defects (42.6%, including 7 with single ventricle physiology), and 10 infants (21.3%) and 16 noninfants (34.0%) with isolated scimitar syndrome. Median follow-up was 3.55 years. Noninfants exhibited lower incidences of right pulmonary artery hypoplasia (p < 0.001), aortopulmonary collaterals (p = 0.004), and scimitar vein obstruction at the caval confluence (p = 0.032). Eighteen patients (38.3%) underwent surgical repair for scimitar syndrome. Overall mortality after baffle repair or scimitar vein reimplantation was 37.5% (3 of 8) for infants and 0% (0 of 6) for noninfants (p = 0.209). Overall mortality for medically managed infants was 46.7% (7 of 15) compared with 0% (0 of 8) for noninfants (p = 0.052). Multivariable analyses identified infantile onset as an independent risk factor for stenosis or obstruction after repair (hazard ratio 9.34, p = 0.048), and single ventricle physiology as an independent risk factor for mortality among unrepaired patients (hazard ratio 29.8, p = 0.004). CONCLUSIONS: The severity of scimitar syndrome depends on presenting age and associated congenital heart disease. Nonsurgical and surgical outcomes are suboptimal for infantile disease, which is a risk factor for stenosis after repair. Single ventricle physiology is associated with poor prognosis.

The natural history and surgical outcome of patients with scimitar syndrome: a multi-centre European study.

Aims: Treatment decisions in patients with scimitar syndrome (SS) are often challenging, especially in patients with isolated SS who are often asymptomatic and who might be diagnosed accidentally. We queried a large multi-institutional registry of SS patients to evaluate the natural history of this condition and to determine the efficacy of surgical treatment in terms of survival and clinical status. Methods and results: We collected data on 485 SS patients from 51 institutions; 279 (57%) patients were treated surgically (STPs) and 206 (43%) were clinically monitored (CMPs). Median age at last follow-up was 11.6 years (interquartile range 4-22 years). Overall survival probability at 30 years of age was 88% [85-92% confidence intervals (CI)] and was lower in patients with associated congenital heart disease (CHD) (P < 0.001) and pulmonary hypertension (P < 0.001). Most patients were asymptomatic at last follow-up (279/451, 62%); STPs were more frequently asymptomatic than CMPs (73% vs. 47%, P < 0.001), with fewer cardiac [odds ratio (OR) 0.42, 95% CI 0.22-0.82] and respiratory symptoms (OR 0.08, 95% CI 0.02-0.28). Many STPs (63/254, 25%) had stenosis/occlusion of the scimitar drainage, and this was associated with a younger age at surgery (OR 0.4, CI 0.21-0.78). Conclusion: Patients with SS have a high overall survival. Survival probability was lower in patients with associated CHDs and in patients with pulmonary hypertension. Surgical treatment of SS is beneficial in reducing symptoms, however, given the significant risk of post-operative scimitar drainage stenosis/occlusion, it should be tailored to a comprehensive haemodynamic evaluation and to the patient's age.

Bodily isomerism is an independent risk factor for pulmonary hypertension in adults with congenital heart disease.

INTRODUCTION: Bodily isomerism, or heterotaxy is a unique entity on which there is mirror imagery in various organ systems, leading to a deviation from the normal lateral arrangements of the viscera. Adults with such isomerism and associated congenital malformations of the heart are now reaching adulthood and developing long-term complications. This study investigates the prevalence and characteristics of pulmonary hypertension in adults with isomerism. METHODS: The 2012 iteration of the Nationwide Inpatient Sample was utilized and patients were identified as having or not having bodily isomerism and having or not having pulmonary hypertension. Univariate analysis utilizing Chi-square tabulation was done to assess characteristics associated with pulmonary hypertension. Next, a multivariate analysis was done on all patients to identify predictors of pulmonary hypertension followed by a multivariate analysis of patients with only isomerism to identify predictors of pulmonary hypertension specific to this subset. RESULTS: A total of 6,907,109 admissions were included in the analysis. Of these, 861 had isomerism (0.01%). Of those with isomerism, 5.6% were found to have pulmonary hypertension. When all patients were included in the multivariate analysis, isomerism was found to be an independent risk factor for pulmonary hypertension with an odds ratio of approximately 1.79. When only patients with isomerism were included in the multivariate analysis, advanced age, obesity, and history of anomalous pulmonary venous connection were independent risk factors of pulmonary hypertension. CONCLUSION: Pulmonary hypertension is more common in those with isomerism, with isomerism being an independent risk factor for pulmonary hypertension. The prevalence of pulmonary hypertension is 5.6% in the setting of isomerism. Independent risk factors for pulmonary hypertension in patients with isomerism include age, obesity, and history of anomalous pulmonary venous connection.

An increased incidence of total anomalous pulmonary venous connection among Hispanics in southern Nevada.

OBJECTIVE: Ethnicity may influence the occurrence of specific cardiac malformations. DESIGN: We retrospectively analyzed the occurrence of isolated total anomalous pulmonary venous connection in the Hispanic and non-Hispanic populations of Southern Nevada over a 10-year period from 2003 to 2013. RESULTS: The mean cases per 100,000 live births among Hispanics was 19.8 (99% confidence interval 5.9-33.7) and among non-Hispanics was 2.5 (99% confidence interval 0.4-4.6), P = 0.007. CONCLUSIONS: We found a significantly higher incidence of isolated total anomalous pulmonary venous connection in Hispanics vs. non-Hispanics.

Partial anomalous pulmonary venous return is common in Turner syndrome.

BACKGROUND: Cardiovascular disease affects >50% of Turner syndrome (TS) patients. With newer imaging modalities, this prevalence increases and the spectrum of recognized anomalies broadens. OBJECTIVE: To determine the prevalence and hemodynamic significance of partial anomalous pulmonary venous return (PAPVR) in adolescents and young adults with TS using transthoracic echocardiogram (TTE) and cardiac magnetic resonance (CMR), and to study the association with phenotype. METHODS: The records of 39 young TS patients who had received TTE and CMR were reviewed. RESULTS: PAPVR was diagnosed in seven (18%) patients; six were newly diagnosed by CMR after normal TTE. In one subject, PAPVR was associated with right ventricular enlargement and a pulmonic blood flow (Qp) to systemic blood flow (Qs) ratio of 1.9:1.0, necessitating surgical repair. In other subjects with and without PAPVR, Qp:Qs and the right ventricle to left ventricle end-diastolic volume ratio were statistically different. Other clinical features were not predictive of PAPVR. CONCLUSIONS: The prevalence of PAPVR is high in TS, and it may be hemodynamically significant. Diagnosis by TTE can be difficult. Appropriate screening and management are indicated.

[Scimitar syndrome in infancy]. / Síndrome de la cimitarra en edad pediátrica.

OBJECTIVE: To expose our 26 year experience in clinical management, interventional catheterization and surgical treatment of patients younger than 18 years with scimitar syndrome at the National Cardiology Institute. MATERIAL AND METHODS: We reviewed retrospectively all patients with scimitar syndrome in infancy between 1984 and 2010. Patients were divided in two groups: younger an older than one year at the time of the diagnosis. Medical records were analized, as well as chest radiography, electrocardiogram, echocardiogram and helicoidal tomography. All therapeutic procedures performed and their outcomes were analized. RESULTS: We studied 22 patients with scimitar syndrome, 20 of them with associated congenital heart disease. Congestive heart failure (p > or = 0.0001) and severe pulmonary hypertension (p > or = 0.002) were more frequent in patients younger than one year. We documented dextroposition and right lung hypoplasia in 14 patients, and aorto-pulmonary collateral arteries in 15 of them. Pulmonary hypertension was an important mortality risk factor (p > or = 0.007). CONCLUSIONS: Congestive heart failure and pulmonary hypertension are more frequent in patients younger than one year, and the former is a mortality risk factor. It is important to suspect this congenital heart disease in infants with dextroposition and congestive heart failure in order to provide an opportune treatment.

Partial anomalous pulmonary venous connection and pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Isolated partial anomalous pulmonary venous connection (PAPVC) has been implicated as a cause of pulmonary arterial hypertension (PAH); however this condition is often overlooked in the diagnostic work up of patients with PH. We studied the prevalence of PAH both in patients with isolated PAPVC or associated with other congenital heart diseases (CHD) such as atrial septal defect (ASD). We also aimed to identify factors related to the presence of PAH in these patients. METHODS: We retrospectively analyzed data from the Adult CHD database at the Cleveland Clinic, U.S.A. between October 2005-2010. We included all patients diagnosed with PAPVC with or without other CHD. We excluded all patients with previous corrective surgeries. RESULTS: We identified 14 (2.5%) patients with PAPVC. Group I included patients with PAPVC (with or without patent foramen ovale (PFO)). Group II included patients with PAPVC associated with other CHD. PAH was seen in six (6/14, 42.8%) patients, two (2/7, 28.5%) in group I and four (4/7, 57.1%) in group II (P = 0.3). The mean pulmonary artery pressure in all patients (n = 14) was 29.5 ± 13.8 mm Hg. group I had a mean PAP of 23.6 ± 6.6 mm Hg as compared to 33.7 ± 16.5 mm Hg for group II (P = 0.34). The two patients in group I with PAH had either two anomalous pulmonary veins or a condition (sickle cell disease) that could potentially explain the haemodynamic findings. CONCLUSIONS: Patients with PAPVC (with or without PFO) in the absence of other CHD had normal pulmonary arterial pressure (PAP) unless they have two pulmonary veins with anomalous return or associated conditions known to cause PAH.

Total anomalous pulmonary venous connection: impact of prenatal diagnosis.

OBJECTIVES: To investigate whether prenatal screening is effective in the detection of total anomalous pulmonary venous connection (TAPVC) and to identify common prenatal features. METHODS: This was a retrospective collaborative study involving 19 pediatric cardiac centers in the UK, Ireland and Sweden. Cases with TAPVC born between January 1, 1998 and December 31, 2004, and prenatally diagnosed cases whose estimated dates of delivery were within this time frame, were identified. Cases with functionally univentricular circulation or atrial isomerism were excluded. All available data and stored images were reviewed. RESULTS: Four-hundred and twenty-four cases with TAPVC were identified prenatally or postnatally, of whom eight (1.9%) had a prenatal diagnosis of TAPVC. Median gestational age at fetal diagnosis was 26 + 6 (range, 22 + 4 to 32 + 0) weeks. Six further fetuses with TAPVC had an abnormality diagnosed on prenatal ultrasound, but not the TAPVC. This included other congenital heart defects (four cases) and isolated pleural effusion (two cases). Seventeen (4.0%) of the 422 liveborn infants had a first-degree relative with congenital heart disease; and six of 17 had a sibling with TAPVC. Two died in utero. Of the liveborn infants diagnosed prenatally with TAPVC, none required urgent intervention for pulmonary venous obstruction and all were alive and well at a median of 2.3 (range, 1.0-7.0) years after surgical repair. CONCLUSION: Prenatal diagnosis of TAPVC is infrequent using current screening methods. Where there is a family history of TAPVC, specialized fetal echocardiography at 20 and 28 weeks' gestation may be indicated.

Scimitar syndrome: a complex form of anomalous pulmonary venous return.

Scimitar syndrome, or pulmonary venolobar syndrome, is a rare congenital anomaly, in which all the right pulmonary veins drain into the inferior vena cava. In this study, we review the diagnostic features, clinical management, and surgical strategy in the Scimitar syndrome and discuss the significance of new generation diagnostic imaging methods for this rare anomaly.

Atypical mycobacterial infection in sequestrated lung in an infant presenting with chronic pneumonitis and recurrent wheezing.

An infant was referred to us for persistent cough and recurrent wheezing. Chest X-ray showed an abnormal shadow in the right lower lobe. A volumetric contrast-enhanced computerized tomography (CT) scan of the chest revealed an abnormal blood vessel extending from the descending aorta to the right lower lobe and anomalous venous drainage from the right lower lobe into inferior vena cava. Angiography confirmed the CT scan findings. Pulmonary sequestration associated with scimitar syndrome was subsequently diagnosed. Patient underwent right lower lobectomy and right inferior pulmonary vein was anastomosed into the left atrium. Pathological examination after surgery revealed epitheloid granuloma in the sequestrated lung parenchyma and mycobacteria in the draining lymph nodes. This is a rare case of pulmonary sequestration associated with scimitar syndrome and complicated by mycobacterial infection.

Scimitar syndrome: incidence, treatment, and prognosis.

This study is based on a database of 16 years; we sought to define the incidence and outcome of scimitar syndrome. Of 8,771 patients, 5 (0.057%) with scimitar syndrome were identified and constituted the study population. Follow-up ranged from 1 to 16 years (median: 10 years). Diagnosis was assured by computed tomography in four patients and by cardiac catheterization in one. Two patients presented with respiratory distress soon after birth and required early pneumonectomy in one case and coil embolization of the abnormal feeding arteries to the right lower lung followed by surgical rerouting of the abnormal pulmonary vein and repair of the atrial septal defect in the other case. The former was supported by ventilator therapy for 3 years after pneumonectomy, but was finally weaned from the ventilator. Among the other three, two had repeated pneumonia that resolved after rerouting of the abnormal right pulmonary vein and cardiac repair. The asymptomatic child did not receive any intervention. In spite of the abnormal orientation of the airways, none of the four patients with detailed computed tomography imaging showed any significant compression of the airways. All five patients were doing well as of the last follow-up. In conclusion, scimitar syndrome is a very rare disease in this Asian country and the varied symptoms, such as tachypnea and repeated infection, could be improved after interventions.

The "horseshoe" lung: six new cases.

Six cases of horseshoe lung have been found in a group of 147 scimitar syndrome cases collected in a cooperative multicenter study. These cases were associated either with the severe infantile or with the benign adult form of the scimitar syndrome. The aim of this paper is to describe the clinical and imaging signs as well as the prognosis of 6 new cases of horseshoe lung in association with scimitar syndrome. The authors conclude (1) that the diagnosis of horseshoe lung may be strongly suspected on standard chest radiographs and confirmed by thoracic CT scan; (2) that the prognosis of scimitar syndrome does not seem to be worse when associated with horseshoe lung.

The "adult" form of the scimitar syndrome.

One hundred twenty-two cases of the adult form of the scimitar syndrome were collected from different cardiologic centers. The clinical, radiographic and hemodynamic findings are described. The scimitar syndrome is defined as an anomalous right pulmonary venous drainage, partial or complete, to the inferior vena cava. Additional characteristics of this syndrome such as hypoplasia and abnormalities of the vascular supply to the right lung, dextrocardia and abnormalities of the bronchial segmentation are common; bronchiectases are rare. The left to right shunt was less than 50% in 100 of the 122 patients. The pulmonary arterial pressures were normal in 94 patients and slightly elevated in 28. A follow-up study of these patients showed that, without surgical correction, they lead a normal life. An awareness of this syndrome may avoid unnecessary invasive diagnostic procedures and surgical treatment for most patients.