Extracardiac Doppler indices predict perinatal mortality in fetuses with Ebstein anomaly and tricuspid valve dysplasia.

OBJECTIVES: Ebstein anomaly and tricuspid valve dysplasia (EA/TVD) carry high perinatal mortality. Past studies have focused on cardiac predictors of mortality; we sought to describe the fetal echo (FE) extracardiac Dopplers in this cohort and determine their association with perinatal mortality. METHOD: Fetuses with EA/TVD at 23 centers from 2005-2011 were included for retrospective study. Doppler pattern and velocity of the umbilical artery (UA), umbilical vein (UV), ductus venosus (DV), and middle cerebral artery (MCA) were collected. Bivariate and multivariate analyzes were performed. The primary outcome measure was perinatal mortality, defined as fetal demise or neonatal death. RESULTS: Of 190 cases that met eligibility criteria, alterations were seen in 50% of UA, 16% of UV, 48% of DV, and 8% of MCA Doppler indices on the last FE (median 27.4 weeks). Independent predictors of perinatal mortality included abnormal UA Doppler pattern of absence or reversed end diastolic flow (OR 9.7) and UV velocity z score <1 (OR 2.5), in addition to diagnosis <32 weeks (OR 4.2) and tricuspid valve (TV) annulus z score ≥6 (OR 5.3). CONCLUSION: Abnormal UA Doppler pattern and decreased UV velocity are independent predictors of perinatal mortality in EA/TVD fetuses and should be used to refine mortality risk and guide perinatal management.

Outcomes and Predictors of Perinatal Mortality in Fetuses With Ebstein Anomaly or Tricuspid Valve Dysplasia in the Current Era: A Multicenter Study.

BACKGROUND: Ebstein anomaly and tricuspid valve dysplasia are rare congenital tricuspid valve malformations associated with high perinatal mortality. The literature consists of small, single-center case series spanning several decades. We performed a multicenter study to assess the outcomes and factors associated with mortality after fetal diagnosis in the current era. METHODS AND RESULTS: Fetuses diagnosed with Ebstein anomaly and tricuspid valve dysplasia from 2005 to 2011 were included from 23 centers. The primary outcome was perinatal mortality, defined as fetal demise or death before neonatal discharge. Of 243 fetuses diagnosed at a mean gestational age of 27±6 weeks, there were 11 lost to follow-up (5%), 15 terminations (6%), and 41 demises (17%). In the live-born cohort of 176 live-born patients, 56 (32%) died before discharge, yielding an overall perinatal mortality of 45%. Independent predictors of mortality at the time of diagnosis were gestational age <32 weeks (odds ratio, 8.6; 95% confidence interval, 3.5-21.0; P<0.001), tricuspid valve annulus diameter z-score (odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P<0.001), pulmonary regurgitation (odds ratio, 2.9; 95% confidence interval, 1.4-6.2; P<0.001), and a pericardial effusion (odds ratio, 2.5; 95% confidence interval, 1.1-6.0; P=0.04). Nonsurvivors were more likely to have pulmonary regurgitation at any gestational age (61% versus 34%; P<0.001), and lower gestational age and weight at birth (35 versus 37 weeks; 2.5 versus 3.0 kg; both P<0.001). CONCLUSION: In this large, contemporary series of fetuses with Ebstein anomaly and tricuspid valve dysplasia, perinatal mortality remained high. Fetuses with pulmonary regurgitation, indicating circular shunt physiology, are a high-risk cohort and may benefit from more innovative therapeutic approaches to improve survival.

Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus.

The etiology of idiopathic dilated cardiomyopathy (iDCM) remains unknown. Immune therapies have improved outcome in fetuses with DCM born to mothers with autoimmune disease (aDCM). The purpose of this retrospective study was to compare the myocardial B and T cell profiles in fetuses and neonates with idiopathic DCM (iDCM) versus autoimmune-mediated DCM (aDCM) and to describe the normal cell maturation within the human fetal myocardium. Of 60 fetal autopsy cases identified from institutional databases, 10 had aDCM (18-38 weeks), 12 iDCM (19-37 weeks) and 38 had normal hearts (11-40 weeks). Paraffin-embedded myocardium sections were stained for all lymphocyte (CD45), B cells (CD20, CD79a), T cells (CD3, CD4, CD7, CD8) and monocyte (CD68) surface markers. Two independent, blinded cell counts were performed. Normal hearts expressed all B and T cell markers in a bimodal fashion, with peaks at 22 and 37 weeks of gestation. The aDCM cohort was most distinct from normal hearts, with less overall T cell markers [EST -9.1 (2.6) cells/mm(2), p = 0.001], CD4 [EST -2.0 (0.6), p = 0.001], CD3 [EST -3.9 (1.0), p < 0.001], CD7 [EST -3.0 (1.1), p = 0.01] overall B cell markers [EST -4.9 (1.8), p = 0.01] and CD79a counts [EST -2.3 (0.9), p = 0.01]. The iDCM group had less overall B cell markers [EST -4.0 (1.8), p = 0.03] and CD79a [EST -1.7 (0.9), p = 0.05], but no difference in T cell markers. Autoimmune-mediated DCM fetuses have less B and T cell markers, whereas iDCM fetuses have less B cell markers compared with normal fetal hearts. The fetal immune system may play a role in the normal development of the heart and evolution of dilated cardiomyopathy.

A unique foetal case of left ventricular non-compaction associated with arrhythmia, structural cardiac anomalies, and agenesis of the ductus venosus.

A 21-week gestational age foetus was diagnosed with left ventricular non-compaction, Ebstein's anomaly, sinus bradycardia, first-degree heart block, and agenesis of the ductus venosus. The prognosis was guarded given the constellation of findings, and the foetus was monitored closely. Despite a potentially poor outcome, the foetus survived. Prognosis in foetally diagnosed left ventricular non-compaction is usually poor; however, rarely, foetuses can survive postnatally.

The impact of not having a ductus arteriosus on clinical outcomes in foetuses diagnosed with tetralogy of Fallot.

BACKGROUND: Foetuses with simple tetralogy of Fallot almost universally have a patent ductus arteriosus. Two recently identified cases had an absent patent ductus arteriosus, requiring emergent intervention at birth. The objective of this study was to determine whether foetuses diagnosed with tetralogy of Fallot and no patent ductus arteriosus have poorer outcomes compared with those with tetralogy of Fallot+patent ductus arteriosus. METHODS: All foetal cases of tetralogy of Fallot between January, 2000 and 2012 were retrospectively identified from The Hospital for Sick Children (Toronto, Canada) database. Cases - tetralogy of Fallot+no patent ductus arteriosus confirmed on postnatal echo - and controls - tetralogy of Fallot+patent ductus arteriosus, matched for gestational age - were identified from prenatal records, and both clinical and echocardiographic data were reviewed. Optimal outcome was defined as valve-sparing repair with no residual lesions. Student's t-tests and Fisher's exact χ2 were used to compare groups. RESULTS: n=115 foetuses were diagnosed with tetralogy of Fallot: 11 (9%) had no patent ductus arteriosus, and were matched to 22 controls - mean gestational age at diagnosis 23.2±4.2 weeks, 23.4±6.6 weeks, respectively. Cases had a higher proportion of right aortic arches (64% versus 14%, p<0.001). Foetal and postnatal echocardiographic data did not reveal significant differences in branch pulmonary artery sizes, pulmonary valve sizes, or ventricular function. No differences were identified for cyanosis at birth (2/10 versus 7/20, p=0.67), or catheter intervention (5/10 versus 4/22, p=0.12). Optimal outcome rates were similar between cases and controls (4/11 (36%) versus 5/21 (24%), p=0.68). CONCLUSIONS: The patent ductus arteriosus does not appear to have an impact on clinical outcome in foetuses with tetralogy of Fallot.

Factors associated with in utero demise of fetuses that have underlying cardiac pathologies.

Factors associated with in utero fetal demise (IUFD) of fetuses that have underlying cardiac pathologies are largely unknown. This case-control study aimed to define the prevalence of IUFD in fetuses with a diagnosis of cardiac pathologies and to identify prenatal predictors of IUFD. Between January 2004 and December 2010, 74 IUFD cases [4.6 %; 95 % confidence interval (CI) 3.7-5.8 %] were identified from 1,584 cases with a diagnosis of structural or functional cardiac lesions in the Hospital for Sick Children database. The cases were divided into right-sided (N = 28), left-sided (N = 23), great artery (N = 8), and miscellaneous (N = 15) groups. The control subjects (1:1 ratio) were fetuses that had cardiac pathology diagnosed within 48 h of the IUFD case. Multivariable regression models were used to determine echocardiographic predictors of IUFD. The prevalence of IUFD was greatest in hypertrophic cardiomyopathy (8/16, 50 %) and Ebstein's anomaly/tricuspid dysplasia (4/15, 27 %) and lowest in transposition of the great arteries (2/85, 1 %). The findings showed IUFD to be associated with hydrops in 17 (23 %) of the 74 cases and arrhythmia in 11 (15 %) of the 74 cases. The factors identified by univariable logistic regression analyses were right ventricular dysfunction [odds ratio (OR) 2.7; p = 0.001], left ventricular dysfunction (OR 1.8; p = 0.007), umbilical vein pulsations (OR 10.9; p = 0.002), and abnormal ductus venosus flow (OR 3.3; p = 0.01). The factors associated with IUFD in multivariable logistic regression models were cardiomegaly (OR 5.6; p = 0.01), hydrops (OR 29.5; p = 0.001), pericardial effusion (OR 4.1; p = 0.06), and extracardiac abnormalities (OR 7.2; p < 0.001). The prevalence of IUFD is greatest in conditions affecting the ventricular myocardium. The onset of IUFD appears to be related initially to right ventricular dysfunction. Closer surveillance is recommended for lesions at risk of IUFD.

Foetal echocardiographic assessment of borderline small left ventricles can predict the need for postnatal intervention.

BACKGROUND: We sought to prospectively determine foetal echocardiographic factors associated with neonatal interventions in borderline hypoplastic left ventricles. METHODS: Foetuses were included who had a left ventricle that was 2-4 standard deviations below normal for length or diameter and had forward flow across the mitral and aortic valves. Factors associated with an intervention in the first month of life or no need for intervention were sought using univariate and multivariate logistic regression models. RESULTS: From 2005 to 2008, 47 foetuses meeting the criteria had an additional diagnosis (+foetal coarctation/+transverse arch hypoplasia): atrioventricular septal defect 7 (+2/+0), double outlet right ventricle 2 (+0/+0), Shone's complex 19 (+9/+4), and ventricular disproportion 19 (+13/+11; 4 both). There were seven pregnancies terminated, three foetal demises, and five had compassionate care. There were 32 livebirths that either had a biventricular repair (n = 20, n = 2 dead), univentricular palliation (n = 2, both alive), or no intervention (n = 9). Overall survival of livebirths to 6 months of age was 79%. Factors associated with early intervention on first foetal echocardiogram were: obstructed or retrograde arch flow (p = 0.08, odds ratio 3.3), coarctation (p = 0.05, odds ratio 11.4), and left ventricle outflow obstruction (p = 0.05, odds ratio 12.5). Neonatal factors included: Shone's diagnosis (p = 0.02, odds ratio 4.9), bicuspid aortic valve (p = 0.005, odds ratio 11.7), and larger tricuspid valve z-score (p = 0.05, odds ratio 3.6). A neonatal factor associated with no intervention was a larger mitral valve z-score (mean 23.8 versus 24.2 intervention group, p = 0.04, odds ratio 2.8). DISCUSSION: The need for early intervention in foetuses with borderline hypoplastic left ventricle can be predicted by foetal echocardiography.

Comparison of transplacental treatment of fetal supraventricular tachyarrhythmias with digoxin, flecainide, and sotalol: results of a nonrandomized multicenter study.

BACKGROUND: Fetal tachyarrhythmia may result in low cardiac output and death. Consequently, antiarrhythmic treatment is offered in most affected pregnancies. We compared 3 drugs commonly used to control supraventricular tachycardia (SVT) and atrial flutter (AF). METHODS AND RESULTS: We reviewed 159 consecutive referrals with fetal SVT (n=114) and AF (n=45). Of these, 75 fetuses with SVT and 36 with AF were treated nonrandomly with transplacental flecainide (n=35), sotalol (n=52), or digoxin (n=24) as a first-line agent. Prenatal treatment failure was associated with an incessant versus intermittent arrhythmia pattern (n=85; hazard ratio [HR]=3.1; P<0.001) and, for SVT, with fetal hydrops (n=28; HR=1.8; P=0.04). Atrial flutter had a lower rate of conversion to sinus rhythm before delivery than SVT (HR=2.0; P=0.005). Cardioversion at 5 and 10 days occurred in 50% and 63% of treated SVT cases, respectively, but in only 25% and 41% of treated AF cases. Sotalol was associated with higher rates of prenatal AF termination than digoxin (HR=5.4; P=0.05) or flecainide (HR=7.4; P=0.03). If incessant AF/SVT persisted to day 5 (n=45), median ventricular rates declined more with flecainide (-22%) and digoxin (-13%) than with sotalol (-5%; P<0.001). Flecainide (HR=2.1; P=0.02) and digoxin (HR=2.9; P=0.01) were also associated with a higher rate of conversion of fetal SVT to a normal rhythm over time. No serious drug-related adverse events were observed, but arrhythmia-related mortality was 5%. CONCLUSION: Flecainide and digoxin were superior to sotalol in converting SVT to a normal rhythm and in slowing both AF and SVT to better-tolerated ventricular rates and therefore might be considered first to treat significant fetal tachyarrhythmia.

Comparison of Pre- and Postnatally Diagnosed Coronary Artery Fistulae: Echocardiographic Features and Clinical Outcomes.

BACKGROUND: Coronary artery fistulae (CAFs) are abnormal connections of a coronary artery to a cardiac chamber or vessel. There is a paucity of data regarding clinical outcomes, especially when detected prenatally. METHODS: This was a multicenter retrospective cohort study of all CAF cases from 2002 to 2016. Clinical characteristics and outcomes were compared between the prenatal and postnatal cohorts. A scoping literature review of prenatal CAFs was completed. RESULTS: CAFs were diagnosed prenatally in 12 (median, 23 weeks' gestation; interquartile range, 17-36 weeks' gestation) and postnatally in 94 (median, 2.8 years; interquartile range, 0-15 years) cases. Structural heart defects were present in five (42%) prenatal and 19 (20%) postnatal cases (P = .011) and genetic conditions in five (42%) and 14 (15%), respectively (P = .001). CAFs were considered large in 12 (100%) prenatal versus 14 (15%) postnatal cases (P < .001). The CAF distribution was similar between cohorts: 39 (67%) from the left and 19 (33%) from the right coronary artery, with the most common exit sites being the main pulmonary artery 54 (51%), right ventricle 30 (28%), and right atrium 12 (11%). Of prenatal cases, all large at presentation, none progressed, six (50%) resolved by birth, and one (8%) underwent elective neonatal ligation. Of postnatal cases, one presented in cardiogenic shock, and no other case had ventricular dysfunction, arrhythmias, or ischemic changes. Nine (10%) with large shunts underwent intervention (seven percutaneous, two surgical), of whom three were symptomatic. Two (17%) prenatal and two (2%) postnatal cases had coronary abnormalities, two with normal results on stress perfusion imaging. Postnatal death occurred in two (17%) prenatal and four (4%) postnatal cases (P = .05). Of the total 36 prenatal cases reported in the literature, including the 12 cases in the present series, 10 (28%) had clinical symptoms at birth, including three (8%) with cardiogenic shock, and 19 (53%) underwent intervention. CONCLUSIONS: Prenatally and postnatally encountered CAFs are associated with a good prognosis for most, with many not requiring intervention. Although half of the prenatal CAFs resolved prenatally, given the risk for cardiogenic shock at birth and heart failure in early infancy, appropriate perinatal planning and postnatal surveillance is warranted.

The myocardium of fetuses with endocardial fibroelastosis contains fewer B and T lymphocytes than normal control myocardium.

The observation that endocardial fibroelastosis (EFE) can result from an immune response to maternal autoantibody deposition in the fetal myocardium raises the possibility that the fetal immune system may contribute to the pathogenesis of idiopathic EFE and dilated cardiomyopathy (DCM). This study sought to characterize myocardial immune cell presence in fetuses and neonates with idiopathic EFE + DCM, in those with EFE + structural heart disease, and in normal control subjects. Paraffin tissue sections from fetuses identified from the pathology database were stained for B cell, T cell, macrophage, and general hematopoietic cell surface markers. Of the 14 fetuses included in the study, 5 had EFE + DCM, 4 had EFE + structural heart disease, and 5 were normal control fetuses. The EFE + DCM group had fewer B cells than the control group (0.15 vs. 0.44 cells/mm(2); p = 0.005). The EFE + heart disease group had both fewer B cells (0.18 vs. 0.44 cells/mm(2); p = 0.08) and T cells (0.29 vs. 0.80 cells/mm(2); p = 0.04) than the control group. The CD4/CD8 ratio was similar in the EFE + DCM and EFE + heart disease groups (1.0 vs. 0.9; p = 0.17) but higher in the EFE + DCM group than in the control group (0.9 vs. 0.3; p = 0.03). The myocardium of fetuses with EFE contains fewer B and T lymphocytes than normal control fetuses.

Impact of prenatal diagnosis and anatomical subtype on outcome in double outlet right ventricle.

BACKGROUND: We sought to investigate the influence of prenatal diagnosis and risk factors for adverse outcomes in double outlet right ventricle (DORV) not associated with heterotaxy. METHODS: Patients with a pre or postnatal diagnosis of DORV from 2000 to 2007 were identified and classified into 3 subgroups: subaortic ventricular septal defect (VSD) and normal great artery (GA) arrangement (=VSD type), tetralogy of Fallot type, and transposition of the GA type (=TGA type). Patients with heterotaxy, atrioventricular septal defect, valve atresia, and ventricular hypoplasia were excluded. Complex postnatal care was defined as prematurity, need for prostaglandins, surgical repair <2 months, or univentricular palliation. Risk factors for complex postnatal care and demise were sought in multivariable logistic regression models. One hundred fort-five patients were included (93 prenatal, 52 postnatal). RESULTS: There were 24 pregnancy terminations and 7 in utero deaths. Fetal demise was associated with abnormal karyotype (odds ratio [OR] 1.9, P = .01), any tricuspid valve regurgitation (OR 10.6, P = .01), and hydrops (OR 23.8, P = .02). Of 114 liveborn patients, 23 were tetralogy-type, 67 VSD-type, and 24 TGA-type patients. Postnatal survival of liveborn patients at 1 year was similar in pre- versus postnatally diagnosed patients (84% vs 85%). Abnormal GA relationship (OR 2.9, P = .02), subpulmonary VSD (OR 6.0, P = .001), unobstructed pulmonary blood flow at birth (OR 2.8, P = .05), and aortic coarctation (OR 9.0, P = .007) were associated with suboptimal postsurgical outcomes. CONCLUSION: Double outlet right ventricle, even without heterotaxy, is associated with complex postnatal care and high risk of early demise. Morphologic subtype, irrespective of pre- or postnatal diagnosis, is a major determinant of outcome.

Fetal cardiac tumors: a single-center experience of 40 cases.

OBJECTIVE: To determine the natural history and outcome of fetal cardiac tumors. METHODS: This was a retrospective cohort study of all prenatally detected cases of cardiac tumors at a tertiary cardiac care center. RESULTS: Forty fetuses were identified to have one or several cardiac tumors in association with fetal hydrops (18%), ventricular obstruction (30%) and/or arrhythmia (13%). Of 33 cases with rhabdomyoma, three patients elected to terminate the pregnancy, four offspring died at birth and 26 (79%) survived. On follow-up, 95% of all live-born cases with rhabdomyomas were free of cardiac symptoms but 88% had tuberous sclerosis. All three fetuses with teratoma presented with hydrops and none of them survived. In contrast, all three fetuses with cardiac fibroma are alive and have a biventricular physiology. One fetus with a large atrial hemangioendothelioma died in early infancy. Fetal or neonatal death was associated with an earlier cardiac anomaly diagnosis, earlier delivery, larger tumor size and fetal hydrops at presentation. CONCLUSIONS: The outcome of fetal cardiac tumors was predicted by the etiology and size of the cardiac mass and the presence of hydrops. Although most cardiac rhabdomyomas have a relatively benign perinatal course, the long-term prognosis is determined by the neurological manifestations associated with tuberous sclerosis.

Risk Factors for Mortality and Circulatory Outcome Among Neonates Prenatally Diagnosed With Ebstein Anomaly or Tricuspid Valve Dysplasia: A Multicenter Study.

Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia, we found that one third of live-born patients died before hospital discharge. We sought to further describe postnatal management strategies and to define risk factors for neonatal mortality and circulatory outcome at discharge. Methods and Results This 23-center, retrospective study from 2005 to 2011 included 243 fetuses with Ebstein anomaly or tricuspid valve dysplasia. Among live-born patients, clinical and echocardiographic factors were evaluated for association with neonatal mortality and palliated versus biventricular circulation at discharge. Of 176 live-born patients, 7 received comfort care, 11 died <24 hours after birth, and 4 had insufficient data. Among 154 remaining patients, 38 (25%) did not survive to discharge. Nearly half (46%) underwent intervention. Mortality differed by procedure; no deaths occurred in patients who underwent right ventricular exclusion. At discharge, 56% of the cohort had a biventricular circulation (13% following intervention) and 19% were palliated. Lower tricuspid regurgitation jet velocity (odds ratio [OR], 2.3 [1.1-5.0], 95% CI, per m/s; P=0.025) and lack of antegrade flow across the pulmonary valve (OR, 4.5 [1.3-14.2]; P=0.015) were associated with neonatal mortality by multivariable logistic regression. These variables, along with smaller pulmonary valve dimension, were also associated with a palliated outcome. Conclusions Among neonates with Ebstein anomaly or tricuspid valve dysplasia diagnosed in utero, a variety of management strategies were used across centers, with poor outcomes overall. High-risk patients with low tricuspid regurgitation jet velocity and no antegrade pulmonary blood flow should be considered for right ventricular exclusion to optimize their chance of survival.

Improving Prenatal Diagnosis of Coarctation of the Aorta.

BACKGROUND: The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta. METHODS: A single-centre retrospective cohort study (2005-2015) of 107 fetuses diagnosed with suspected coarctation of the aorta in the setting of an apex-forming left ventricle and antegrade flow across the mitral and aortic valves. RESULTS: Median gestational age at diagnosis was 32 weeks (interquartile range, 23-35 weeks). Fifty-six (52%) did not require any neonatal intervention, 51 patients (48%) underwent a biventricular repair. In univariable analysis, an increase in ascending aorta (AAo) peak Doppler flow velocity (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.05-1.91] per 20 cm/s; P = 0.03) was associated with intervention. No intervention was associated with larger isthmus size (OR, 0.23; P < 0.001), transverse arch diameter (OR, 0.23; P < 0.001), and aortic (OR, 0.72; P = 0.02), mitral (OR, 0.58; P = 0.001), and AAo (OR, 0.53; P < 0.001) z-scores. In multivariable analysis, higher peak AAo Doppler (OR, 2.51 [95% CI, 1.54-4.58] per 20 cm/s; P = 0.001) and younger gestational age at diagnosis (OR, 0.81 [95% CI, 0.70-0.93] per week; P = 0.005) were associated with intervention, whereas a higher AAo z-score (OR, 0.65 [95% CI, 0.43-0.94] per z; P = 0.029) and transverse arch dimension (OR, 0.44 [95% CI, 0.18-0.97]; P = 0.05) decreased the risk of intervention. CONCLUSIONS: In prenatally suspected coarctation, the variables associated with intervention comprised smaller AAo and transverse arch size, earlier gestational age at diagnosis, and the additional finding of a higher peak AAo Doppler.

Diagnosis and management of fetal bradyarrhythmias.

Complete atrioventricular block (CAVB) is the most common cause of persistent fetal bradycardia. In the presence of a structurally normal heart, it develops primarily in anti-Ro and anti-La positive antibody pregnancies after 20 weeks of gestation. There is a significant risk of perinatal demise, particularly in association with fetal hydrops, poor ventricular function, and heart rates < 55 beats/min. Transplacental treatment strategies are aimed at preventing or modulating these risk factors. Maternal administration of dexamethasone to mitigate or prevent concomitant myocardial inflammation, in combination with beta-stimulation for persistent fetal bradycardia < 55 beats/min to increase fetal cardiac output, has resulted in significantly improved fetal and neonatal outcomes without reversing CAVB.

Outcome after prenatal diagnosis of tricuspid atresia: a multicenter experience.

BACKGROUND: The outcome of prenatally diagnosed tricuspid atresia (TA) is undefined. We sought to characterize clinical and echocardiographic features of fetal TA and to determine factors associated with mortality. METHODS AND RESULTS: All fetuses with TA (n = 88) seen at 3 tertiary care institutions from 1990 to 2005 were reviewed. There were 58 liveborn infants (median gestational age 38 weeks, range 24-40 weeks), 4 in utero demises, 25 terminations of pregnancy, and 1 mother lost to follow-up. Obstruction was present at the pulmonary valve in 27 (45%), aortic valve in 6 (10%), and aortic arch in 15 (25%). Three neonates received compassionate care, 1 died with multiple extracardiac anomalies, 2 were lost to follow-up, and 52 liveborns were actively managed with Blalock-Taussig shunt (23), Norwood palliation (14), pulmonary artery band (10), bidirectional cavopulmonary connection (3), atrial septostomy (1), and right outflow stent (1). Of those actively managed, there were 7 (14%) of 52 who died. Kaplan-Meier estimates of survival were 91% at 1 month, 87% at 6 months, and 83% at 1 year with no subsequent deaths for 13 years. By multivariate analysis, 2 independent factors were associated with an increase in time-related mortality in the actively managed group: presence of chromosomal anomaly or syndrome (P = .005) and use of extracorporeal membrane oxygenation (P = .002). CONCLUSIONS: This is the largest study describing TA in fetus. Compared with published observations of TA diagnosed postnatally, antenatal diagnosis of TA appears to have similar short-term survival in pregnancies surviving to birth.

Determinants of outcome in fetal pulmonary valve stenosis or atresia with intact ventricular septum.

Pulmonary valve stenosis or atresia with intact ventricular septum represents a spectrum of severity. This study aimed to identify ultrasound markers of biventricular versus non-biventricular outcome. The fetal echocardiograms of 41 fetuses diagnosed with pulmonary stenosis or atresia and right ventricular (RV)/left ventricular (LV) length ratios >0.4 from 17 to 31 weeks of gestation were reviewed. Of 27 live-born patients with intention to treat, 8 had non-biventricular outcomes and 19 had biventricular circulation. At the time of diagnosis, poor RV function, flow reversal in the arterial duct, the degree of tricuspid valve (TV) regurgitation, and inferior vena cava Doppler flow pattern did not differ between the 2 outcome groups. However, RV sinusoids, the RV/LV length ratio, the TV/mitral valve ratio, and TV inflow duration were significantly different. Cut-off values derived from receiver-operating characteristic curves yielding the best sensitivity and specificity for a non-biventricular outcome were TV/mitral valve ratio <0.7, RV/LV length ratio <0.6, TV inflow duration <31.5% of cardiac cycle length, and the presence of RV sinusoids. If 3 of these 4 criteria were fulfilled, this predicted a non-biventricular outcome with sensitivity of 100% and specificity of 75%. In conclusion, in fetuses < or =31 weeks of gestation with pulmonary stenosis or atresia and intact ventricular septum, progression to a non-biventricular outcome can be predicted by a 4-criterion scoring system. The criteria may be useful in selecting fetuses for prenatal catheter intervention to prevent progressive RV hypoplasia.

Concurrent maternal and fetal tachyarrhythmia in pregnancy.

The occurrence of a maternal and fetal tachyarrhythmia together in pregnancy is exceedingly rare. We report a case of a persistent fetal atrial ectopic tachycardia occurring in conjunction with a maternal atrial tachycardia with left ventricular systolic dysfunction. Amiodarone was effective in treating both maternal and fetal arrhythmias.

Clinical features, management, and outcome of children with fetal and postnatal diagnoses of isomerism syndromes.

BACKGROUND: Isomerism is associated with a complex spectrum of anomalies. There is paucity of data on prenatally detected cases. METHODS AND RESULTS: Between January 1990 and February 2004, 83 of 166 cases (50%) had a prenatal diagnosis of left isomerism (LAI; 52 of 97) or right isomerism (RAI; 31 of 69) at our institution. The spectrum of anomalies, management, and outcomes was compared for fetal and postnatal diagnoses of LAI and RAI. RAI more often than LAI was associated with AV septal defect (90% versus 56%; P<0.0001), pulmonary outflow obstruction (91% versus 37%; P<0.0001), total anomalous pulmonary venous drainage (73% versus 13%; P<0.0001), and abnormal VA connections (68% versus 33%; P<0.0001), whereas inferior vena cava interruption (3% versus 93%; P<0.0001), complete AV block (0% versus 13%; P=0.004), aortic obstruction (6% versus 33%; P<0.0001), and extracardiac defects (5% versus 25%; P=0.006) were less common. The spectrum of lesions was comparable for fetal and postnatal cases, except for AV block (fetal, 25%; postnatal, 0%; P=0.0002) and AV septal defect (fetal, 67%; postnatal, 42%; P=0.023) in LAI. Fetal demise was due mainly to pregnancy termination (LAI, 42%; RAI, 45%). Survival of actively managed children with LAI was significantly better than for those with RAI (P<0.0001) but did not differ with regard to fetal versus postnatal diagnosis. Most LAI cases required no intervention or underwent successful biventricular cardiac surgery (65%), unlike RAI cases (13%; P<0.0001). CONCLUSIONS: Prenatal diagnosis did not affect overall survival despite facilitated care. The prognosis of RAI was worse compared with LAI because of more complex associated cardiac defects and the inability to perform successful surgical procedures.

Contemporary Outcomes and Factors Associated With Mortality After a Fetal or Neonatal Diagnosis of Ebstein Anomaly and Tricuspid Valve Disease.

BACKGROUND: Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) are rare anomalies and data on outcomes after a fetal or neonatal EA/TVD diagnosis are conflicting. METHODS: To examine the outcome and identify markers predictive of mortality, we reviewed our single-centre experience from 2000-2014. Variables were analyzed separately for cases diagnosed in utero without pregnancy termination and for all live-born patients. RESULTS: Of 47 fetal cases, 8 (17%) died in utero and 10 (21%) as neonates. Independent predictors associated with fetal demise included severe tricuspid regurgitation with a Doppler gradient < 40 mm Hg (odds ratio, 1.22 per mm Hg deduction; P = 0.003) and pulmonary regurgitation (odds ratio, 11.4; P = 0.03) at the baseline examination. A novel prognostic score (range, 0-10) combining the severity of 5 echocardiographic findings was independently associated with overall mortality (hazard ratio [HR], 1.39 per point increase; P = 0.01). Survival rates of 66 live births at 1 month, 1 year, and 5 years were 86%, 82%, and 80% respectively, and 75%, 60%, and 55% remained free from surgery at the same points in time. Factors associated with postnatal death in multivariate analysis included a younger gestational age at birth (HR per week, 1.59; P < 0.001), tricuspid annulus diameter (HR per z-score increase, 1.76; P = 0.004), and no pulmonary forward flow (HR, 4.63; P = 0.03). CONCLUSIONS: Our experience with fetal and neonatal EA/TVD shows better survival rates than previously reported. Mortality after a fetal diagnosis was significantly associated with hemodynamic changes indicative of a circular shunt, including pulmonary and tricuspid regurgitation severe enough to cause diastolic umbilical arterial flow reversal.