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.

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.

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.

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.

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.

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.

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.

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.

Clinical review of obstructive primary cardiac tumors in childhood.

OBJECTIVES: This study aims to examine the long-term outcomes of conservative management compared with surgical resection for obstructive and nonobstructive primary cardiac tumors in children. DESIGN: A 20-year retrospective review of primary cardiac tumors seen in the right ventricular outflow tract (RVOT) and left ventricular outflow tract (LVOT) in children at The Hospital for Sick Children, Toronto, Canada. Student's t-tests and Fisher's exact chi-square were used to compare outcomes between the conservatively managed vs. surgical resection groups and the obstructive vs. nonobstructive tumor groups. RESULTS: Between 1990 and 2010, we identified 130 children with intracardiac tumors among 52 937 (2.5 per 1000 children, 95th confidence interval: 2.1-2.9 per 1000). Thirty-six children (28%) had at least one cardiac tumor in the RVOT (n = 13) or LVOT (n = 23). Of those, 14 children had peak outflow gradients of >20 mm Hg at the diagnostic echocardiogram (median age at diagnosis: 4 days, range 0 days-6 months; mean follow-up: 7.8 ± 4.5 years). Rhabdomyoma was the most common tumor 27/36 (75%). Twelve (33%) patients underwent surgical repair vs. 24 patients who were observed only. There was no difference in survival. Patients who had surgery tended to be sicker (intubated at diagnosis 4/12, 33% vs. 1/23, 4%, P = .04). There were no deaths in either group. One child required reoperation for severe aortic insufficiency, and only one child in the observation group had residual obstruction at most recent follow-up. CONCLUSIONS: Primary cardiac tumors in childhood obstructing the RVOT or LVOT are uncommon findings after birth and may be managed nonsurgically in most cases.

Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

BACKGROUND: Congenital heart block (CHB) is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV) block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene) in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation). Using human fetal hearts (20-22 wks gestation), our immunoprecipitation (IP), Western blot analysis and immunofluorescence (IF) staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I). Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved) of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN) cells. CONCLUSIONS/SIGNIFICANCE: Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

Diagnosis and management of fetal heart failure.

Congestive fetal heart failure, defined as inability of the heart to deliver adequate blood flow to organs such as the brain, liver, and kidneys, is a common final outcome of many intrauterine disease states that may lead to fetal demise. Advances in fetal medicine during the past 3 decades now provide the diagnostic tools to detect and also treat conditions that may lead to fetal heart failure. Fetal echocardiographic findings depend on severity of diastolic and systolic dysfunction of both ventricles. At an advanced stage, findings include cardiomegaly; valvar regurgitation; venous congestion; fetal edema and effusions; oligohydramnios; and preferential shunting of blood flow to the brain, heart, and adrenals in the distressed fetus. A useful diagnostic tool to quantify severity of heart failure is the cardiovascular profile score, which is a composite score based on 5 different echocardiographic parameters. To predict outcomes, the score should be interpreted in the context of the underlying disease, as different causes of intrauterine heart failure may have highly variable outcomes. Low fetal cardiac output may result from a myocardial disease (cardiomyopathy, myocarditis, ischemia), abnormal loading conditions (arterial hypertension, obstructive structural heart disease, atrioventricular malformations, twin-to-twin transfusion), arrhythmia, or external cardiac compression (pleural and/or pericardial effusions, cardiac tumours). Treatment options are available for several of these conditions.

Fetal stenting of the atrial septum: technique and initial results in cardiac lesions with left atrial hypertension.

BACKGROUND: Hypoplastic left heart syndrome with a highly restrictive or intact atrial septum (HLHS-RAS) has a very high mortality. Fetal left atrial (LA) hypertension results in abnormal lung development with lymphangiectasia and pulmonary vein muscularization. We report our initial experience with percutaneous ultrasound-guided stenting of the fetal atrial septum to decompress the LA. METHODS: Retrospective review of fetuses with HLHS-RAS or a variant that underwent active perinatal management from 2000 to 2012. RESULTS: Ten fetuses were identified. Two died in utero (33, 29 weeks). Four required the urgent creation of an atrial communication immediately after birth but died subsequently (5-54 days). Four fetuses (28-36 weeks) underwent percutaneous stenting of the atrial septum, with ultrasound guidance and intravenous maternal sedation. Elevated LA pressure, pulmonary vein dilation and MRI estimated pulmonary perfusion all improved after stenting. Three of four stented fetuses were delivered vaginally. Atrial septectomy was performed within 48 h of delivery to ensure complete LA decompression, rather than for hypoxemia. Intraoperative lung biopsy demonstrated muscularized pulmonary veins and lymphangiectasia in all four. Two fetuses developed stent stenosis in utero and died after birth, from pulmonary hypertension and sepsis respectively. Two are alive, representing an improved outcome over our previous experience (p=0.03). CONCLUSION: Fetal atrial septal stenting is feasible without maternal complications and allows vaginal delivery of a more stable neonate. Fetal LA decompression ameliorates rather than reverses lung injury, and is one component of an approach that may improve survival in HLHS-RAS.

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.

Influence of RV restrictive physiology on LV diastolic function in children after tetralogy of Fallot repair.

BACKGROUND: Restrictive right ventricular (RV) physiology is a common finding after tetralogy of Fallot repair. Via diastolic ventricular interaction, RV filling characteristics may influence left ventricular (LV) filling. The aim of this study was to analyze the effect of RV diastolic physiology on LV diastolic properties. METHODS: This was a retrospective study including 112 pediatric patients after tetralogy of Fallot repair who underwent full echocardiographic evaluations. Restrictive RV physiology was defined as the presence of end-diastolic forward flow in the main pulmonary artery as detected in at least three consecutive cardiac cycles. RV and LV diastolic function was assessed by analyzing mitral or tricuspid inflow patterns, pulmonary venous flow traces, and pulsed tissue Doppler velocities at the tricuspid and mitral annuli. RESULTS: The mean age at the time of study was 12.9 ± 3.2 years. Restrictive RV physiology was identified in 58 of 112 patients (52%). Patients with RV restriction had larger right atrial and RV dimensions, as well as increased left atrial length and left atrial indexed volume compared with nonrestrictive patients. No differences were found in LV dimensions. Although parameters reflecting early LV diastolic filling (mitral E velocity, lateral annular E' velocity, isovolumetric relaxation time, and E/E' ratio) were not different between the restrictive and nonrestrictive patients, those reflecting late filling were different, with a significantly higher pulmonary venous A-wave reversal velocity and duration in the restrictive group (P < .001). Also, the difference between pulmonary venous A-wave reversal and mitral valve A-wave duration was higher in the restrictive group (P = .0007). CONCLUSIONS: End-diastolic forward flow in the main pulmonary artery is associated with larger RV dimensions in pediatric patients with postoperative tetralogy of Fallot. The presence of end-diastolic forward flow was not associated with other differences in RV diastolic parameters but with more pronounced pulmonary venous reversals and larger left atrial size. This indicates that ventricular diastolic interaction affects LV filling pressures.

Interaction between myocardial and vascular changes in obese children: a pilot study.

BACKGROUND: Changes in vascular and myocardial structure and function have been demonstrated in obese children, but limited data are available on how these changes are related. The aims of this study were to investigate vascular and myocardial changes in obese children with lipid abnormalities and to study the interactions between vascular and myocardial parameters. METHODS: A cross-sectional, prospective observational study was conducted. Twenty-one obese and 27 normal-weight controls aged 14 ± 2 years participated. Cardiac assessment included geometric parameters and myocardial deformation (strain and strain rate) analysis by color tissue Doppler and speckle-tracking echocardiography. Vascular assessment included carotid intima-media thickness, flow-mediated dilatation, pulse-wave velocity, and other stiffness measures of the aorta and carotid artery, as well as noninvasive estimation of arterial elastance and left ventricular (LV) end-systolic elastance. RESULTS: Obese children compared with controls had lower color tissue Doppler-derived LV systolic radial strain values (45 ± 11% vs 56 ± 12%, P = .002), lower speckle-tracking echocardiography-derived LV systolic longitudinal strain values (-18 ± 2% vs -21 ± 2%, P < .001), and lower speckle-tracking echocardiography-derived LV early diastolic strain rate values (1.7 ± 0.3 vs 2.5 ± 0.4, P < .001). Carotid intima-media thickness was increased, pulse-wave velocity was faster, and arterial distension coefficients were lower in obese children. The ratio of arterial elastance to LV end-systolic elastance (a marker of ventricular-arterial coupling) was lower in obese children than controls (0.73 ± 0.32 vs 0.47 ± 0.15, P = .003). Changes in vascular parameters were correlated with changes in longitudinal myocardial deformation parameters. CONCLUSIONS: Obese children with lipid abnormalities have reduced systolic and diastolic LV deformation characteristics, early vessel wall changes, and increased arterial stiffness. Abnormal ventricular-vascular interaction is suggested by these data and warrants further investigation.

Persistent fetal sinus bradycardia associated with maternal anti-SSA/Ro and anti-SSB/La antibodies.

OBJECTIVE: To study the clinical course and outcome of fetal sinus bradycardia (SB) due to maternal antibody-induced sinus node dysfunction. METHODS: We reviewed the maternal, prenatal, and postnatal findings of fetuses with SB associated with elevated maternal anti-SSA/Ro and anti-SSB/La antibodies. RESULTS: Of the 6 cases diagnosed prenatally, 3 had isolated SB persisting after birth and had a good prognosis. Three fetuses with SB and severe myocardial involvement (congenital complete heart block and/or endocardial fibroelastosis) succumbed in utero in spite of treatment. Postmortem histopathology in 1 fetus showed inflammatory destruction of the sinus and atrioventricular nodes. SB was detected incidentally in a 7-year-old girl. She had intermittent heart block with progressive sinus arrest requiring permanent pacemaker. CONCLUSION: Fetal SB associated with maternal autoantibodies may persist in childhood, with a good prognosis in the absence of widespread cardiac involvement.

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.