Fetal cardiac and neonatal cerebral hemodynamics and oxygen metabolism in transposition of the great arteries.

OBJECTIVES: Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA-IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA-IVS, those with TGA-VSD and age-matched controls. METHODS: Cardiac hemodynamics were assessed in TGA-IVS and TGA-VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante- and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO2 ) and an index of microvascular cerebral blood flow (CBFi ), along with peripheral arterial oxygen saturation (SpO2 ), in TGA-IVS and TGA-VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO2i ). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age-matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable. RESULTS: LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA-IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA-VSD fetuses. Compared with controls, DAF was decreased in TGA-IVS fetuses throughout pregnancy and in TGA-VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA-IVS and TGA-VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA-IVS group than in the TGA-VSD group. In addition, UA-PI was lower at GA2 and CPR higher at GA3 in TGA-VSD fetuses compared with TGA-IVS fetuses. Within 3 days after birth, SpO2 and SO2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO2i were higher. Preoperative SpO2 was also lower in TGA-VSD neonates than in those with TGA-IVS. From preoperative to predischarge periods, SpO2 and OEF increased in both TGA groups, but CBFi and CMRO2i increased only in the TGA-VSD group. During the predischarge period, SO2 was higher in TGA-IVS than in TGA-VSD neonates, while CBFi was lower. CONCLUSIONS: Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA-IVS, fetuses with TGA-VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA-VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA-VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Cardiac hemodynamics in fetuses with transposition of the great arteries and intact ventricular septum from diagnosis to end of pregnancy: longitudinal follow-up.

OBJECTIVES: Little is known about cardiac hemodynamics in the fetus with transposition of the great arteries and intact ventricular septum (TGA-IVS). Better understanding of the fetal physiology in TGA-IVS would help to provide insights into specific clinical complications observed after birth, in particular neonatal hypoxia and pulmonary hypertension. The aim of this study was to assess cardiac hemodynamics in fetuses with TGA-IVS by performing systematic longitudinal echocardiographic follow-up from diagnosis to delivery. METHODS: This was a longitudinal retrospective study of fetuses referred between 2010 and 2018 to the Sainte-Justine University Hospital Centre. Complete assessment of cardiac hemodynamics was performed in fetuses with TGA-IVS at 18-22, 28-32 and 35-38 weeks' gestation, which were compared with normal fetuses matched for gestational age. The maximum diameter of the foramen ovale was measured using two-dimensional echocardiography under the guidance of color Doppler echocardiography. Fetal cardiac hemodynamics were analyzed according to postnatal preductal transcutaneous oxygen saturation (TcSO2 ) < 65% or ≥ 65%, as a neonatal outcome, in fetuses with TGA-IVS. RESULTS: In total, 59 fetuses with TGA-IVS and 160 normal fetuses were included. Global cardiac output was significantly higher in fetuses with TGA-IVS than in controls, mainly owing to higher global pulmonary output, while global systemic cardiac output did not differ between TGA-IVS fetuses and controls throughout pregnancy. Aortic flow (right ventricular output in fetuses with TGA-IVS, left ventricular output in controls) was significantly higher in fetuses with TGA-IVS than in normal fetuses. Ductal flow was significantly lower in fetuses with TGA-IVS at every timepoint, and this difference increased considerably after 28-32 weeks. In parallel, the diameter of the foramen ovale was significantly smaller in fetuses with TGA-IVS at 28-32 and 35-38 weeks, with a stagnation in growth after 28 weeks, compared with continuous growth in normal fetuses. Most of these cardiac hemodynamic anomalies in fetuses with TGA-IVS were already present at 18-22 weeks, and the differences became greater at 28-32 weeks' gestation. TGA-IVS neonates with TcSO2 < 65% had lower fetal left ventricular output, higher diastolic ductal retrograde flow and smaller foramen ovale at 28-32 weeks, compared with fetal values in those with postnatal TcSO2 ≥ 65%. CONCLUSIONS: Compared with normal fetuses, those with TGA-IVS undergo a complex redistribution of blood flow during the second half of pregnancy, with higher global pulmonary flow, lower ductal flow (with negative diastolic flow at the end of pregnancy) and a smaller foramen ovale. In addition, fetal cardiac hemodynamic anomalies observed at 28-32 weeks' gestation were associated with lower postnatal TcSO2 . These observations may provide a better understanding of premature closure of the foramen ovale and postnatal hypoxia that are specific to TGA-IVS physiology. © 2019 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal diagnosis and prognosis of accelerated idioventricular rhythm.

OBJECTIVES: As postnatal identification of accelerated idioventricular rhythm (AIVR) relies on specific electrocardiographic patterns, prenatal diagnosis of this condition is challenging and its true incidence is unknown. The objectives of this study were to evaluate the performance of prenatal ultrasonography in identifying intrauterine cardiocirculatory events linked to specific electrocardiographic signs of postnatal AIVR, including left or right ventricular origin, and to assess the prenatal prognosis of this arrhythmia. METHODS: We reviewed Doppler tracings from the superior vena cava/ascending aorta (SVC/Ao), ductus venosus (DV), ductus arteriosus (DA) and aortic isthmus (AoI), as well as simultaneous M-mode recordings of septal and left ventricular wall motions of fetuses diagnosed with AIVR from January 2004 to December 2014. RESULTS: Three cases of AIVR were identified among 27 912 fetuses. SVC/Ao Doppler flow recordings revealed atrioventricular dissociation (ventricular rates within 20% of atrial rates) in all three fetuses and episodes of isorhythmic atrioventricular dissociation in one, while M-mode confirmed normal left ventricular shortening fraction in all cases. Fusion beats were observed on AoI tracing in one fetus, while simultaneous recordings of AoI and DA revealed signs of right bundle branch block in one case and left bundle branch block in the other two. On DV Doppler recordings, retrograde a-waves in the presence of simultaneous atrial and ventricular contractions were observed in all three fetuses, leading to an increase in central venous pressure in all and hydrops fetalis in two cases without evidence of ventricular dysfunction. CONCLUSIONS: Echocardiographic criteria required for postnatal diagnosis of AIVR can be documented in utero using specific ultrasonographic approaches. During fetal life, AIVR may not be a benign entity. Hydrops fetalis is frequently associated with AIVR because of increase in central venous pressure related to simultaneous atrioventricular contractions; thus, the ultrasonographic investigation protocol of fetuses with unexplained hydrops fetalis should aim at ruling out AIVR and include Doppler flow recordings in SVC/Ao, DV, AoI, DA and umbilical vein. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Tetralogy of Fallot: Preoperative assessment with MR and CT imaging.

Tetralogy of Fallot has a broad anatomical spectrum. In mild forms of the condition the obstruction is only located in the right ventricular infundibulum, whereas in severe forms the pulmonary valve is atretic, the pulmonary arteries are absent and the lung is supplied by aorto-pulmonary collateral arteries. Surgical management differs from conventional surgery in the former situation, whereas in the latter it is complex and requires reconstruction of the pulmonary arteries (unifocalization) carried out in more than one stage and with a high morbidity rate. The key factors to establish before corrective surgery are the levels and degree of obstruction of the right ventricular outflow tract, the development of the pulmonary arteries and the presence of collateral arteries. The main role of magnetic resonance imaging along with that of computed tomography angiography are discussed and illustrated.

Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia.

Anthracyclines are efficient chemotherapy agents. However, their use is limited by anthracycline-induced cardiotoxicity (CT). We investigated the influence of polymorphisms in doxorubicin metabolic and functional pathways on late-onset CT as estimated by echocardiography in 251 childhood acute lymphoblastic leukemia (cALL) patients. Association analyses revealed a modulating effect of two variants: A-1629 T in ABCC5, an ATP-binding cassette transporter, and G894T in the NOS3 endothelial nitric oxide synthase gene. Individuals with the ABCC5 TT-1629 genotype had an average of 8-12% reduction of ejection (EF) and shortening fractions (SF; EF: P<0.0001, and SF: P=0.001, respectively). A protective effect of the NOS3 TT894 genotype on EF was seen in high-risk patients (P=0.02), especially in those who did not receive dexrazoxane (P=0.002). Analysis of an additional cohort of 44 cALL patients replicated the ABCC5 association but was underpowered for NOS3. In summary, we identified two biomarkers that may contribute to cALL anthracycline CT risk stratification.

Sildenafil for the Treatment of Pulmonary Arterial Hypertension in Infants with Bronchopulmonary Dysplasia.

Sildenafil, a phosphodiesterase-5 inhibitor, is a controversial treatment option for pulmonary arterial hypertension (PAH), a significant complication of bronchopulmonary dysplasia (BPD). The objective of this study was to evaluate the use of sildenafil in infants with PAH secondary to BPD. This was a retrospective review of medical records of all premature infants with PAH associated with BPD treated with sildenafil between January 2009 and May 2013 in a level 3 neonatal intensive care unit. The primary outcomes were clinical response (20 % decreases in respiratory support score or oxygen requirements) and echocardiographic response (20 % decrease in tricuspid regurgitation gradient or change of at least 1° of septal flattening). Twenty-three infants were included in the study. Significant echocardiographic and clinical responses were, respectively, observed in 71 and 35 % of cases. Most clinical responses were observed in the first 48 h of treatment, and the median time to an echocardiographic response was of 19 days. The median dose of sildenafil used was 4.4 mg/kg/day, with a median time to reach the maximum dose of 9 days. Transient hypotension was the primary reported side effect, and it was observed in 44 % of our study population. Sildenafil treatment in patients with PAH secondary to BPD was associated with an echocardiographic improvement in the majority of patients, whereas clinical improvement was observed in a minority of patients. Many infants presented with transient hypotension during the course of the treatment. Further prospective studies are required to better assess safety and efficacy of this treatment in this population.

Impact of prenatal diagnosis of transposition of the great arteries on obstetric and early postnatal management.

OBJECTIVES: A growing percentage of cases of transposition of the great arteries (TGA) are being diagnosed prenatally. A decrease in the percentage of spontaneous deliveries has been reported, but the rate of cesarean section (c-section) in this population has never been studied. Our goal was to determine whether prenatal diagnosis affects delivery and immediate neonatal management of TGA neonates. STUDY DESIGN: A series of 121 TGA arterial switch candidates were included over a 6-year period. Variables on delivery, clinical status at ICU admission, arrival time and atrial septostomy were recorded retrospectively. Comparisons between the two groups were made by Student's t or Chi-squared test. RESULTS: A cohort of 121 patients was enrolled (48 prenatal and 73 postnatal diagnoses). Induced delivery and c-section were more frequent in the prenatal (54.1% and 31%) than in the postnatal diagnosis group (19.4% and 8%; p<0.0002 and p<0.001, respectively). The mean interval between birth and ICU admission was 2h 30 min in the prenatal compared to 26 h in the postnatal diagnosis group (p<0.001). Arrival times were similar in both groups. Atrial septostomy by umbilical route was more often feasible in the prenatal (81%) than in the postnatal diagnosis group (51%; p<0.001), with a higher rate of failure in the latter. CONCLUSION: Prenatal awareness of TGA was associated with a higher percentage of induced deliveries and a major increase in the rate of c-section, without any impact on the newborn except easier umbilical atrial septostomy and earlier ICU admission.

Relevance of measuring diastolic time intervals in the ductus venosus during the early stages of twin-twin transfusion syndrome.

OBJECTIVE: To determine if the discrete myocardial diastolic dysfunction documented previously in the recipient twin during the early stages of twin-twin transfusion syndrome (TTTS) has any repercussion on flow velocities through the ductus venosus (DV) and to investigate if this could allow early differentiation between TTTS and selective intrauterine growth restriction (IUGR). METHODS: Two groups of monochorionic twin pregnancies with growth discordance between twins were reviewed retrospectively. Group I was composed of fetuses in Stages I and II of TTTS; laser or amnioreduction was not performed in any instance. Group II twin pairs each included one fetus with IUGR due to placental circulatory insufficiency. Intertwin differences (smaller minus larger fetus) were analyzed for myocardial performance index of the right ventricle (MPI-RV) and for time variables in the DV. RESULTS: There were 38 pairs of monochorionic twins (24 TTTS and 14 IUGR) in this study. In the TTTS group, the donors had a significantly lower MPI-RV (0.419 +/- 0.18 vs. 0.596 +/- 0.17, F(1,19df) = 24.017, P < 0.001), a significantly longer total ventricular filling time (150.9 +/- 25.6 ms vs. 124.0 +/- 22.6 ms; F(1,21df) = 19.631, P < 0.001) and a significantly longer early filling time (118.9 +/- 22.9 ms vs. 92.6 +/- 18.9 ms, F(1,21df) = 28.419, P < 0.001) than had the recipient. None of these three differences was present in the IUGR group. Probability studies revealed that cut-off values of 12.75 for intertwin differences in total filling time and 8.5 for intertwin differences in early filling time had sensitivities of 71% and 92%, respectively. The false-positive rates were 23% and 15%, respectively, for the early diagnosis of TTTS. CONCLUSION: In monochorionic twin pregnancies, shortening of the ventricular filling time in the recipient twin indicates diastolic myocardial dysfunction occurring early in the pathophysiology of TTTS. This early interwin difference in myocardial function is not found in pregnancies with IUGR in one twin due to placental circulatory insufficiency, allowing early differentiation between TTTS and selective IUGR.

[Long QT syndrome in children: analysis of the Lyon series]. / Syndrome du QT long congénital chez l'enfant. Analyse de la série lyonnaise.

Congenital long QT syndrome is a rare and serious disorder in children. In addition to the clinical and electrocardiographical diagnostic criteria, molecular biochemistry has identified six genes which are implicated in this pathology. Our study involved a retrospective analysis of 23 patients aged less than 21 with congenital long QT syndrome, followed up for an average of two years. Genotypes were obtained for all of the patients. There were unfortunately two deaths, one of which had a mutation in the SCN5A gene. The other patient had a double mutation of the SCN5A and KCNE2 genes. Symptomatic patients had QT and QTc intervals noticeably longer than the asymptomatic patients, although this difference was not shown to be significant. LQT3 patients as well as those with a double mutation were affected more severely because two of the three LQT3 patients and one of the two patients with a double mutation suffered a cardiac arrest. Three patients in our study showed no mutation. Nevertheless, two of them suffered a severe cardiac event. This confirms the limits of genetic diagnosis, which could be envisaged in all cases. All of the clinical and ECG data should be combined with the genetic analysis in order to confirm the diagnosis.

Early intertwin differences in myocardial performance during the twin-to-twin transfusion syndrome.

BACKGROUND: In the twin-to-twin transfusion syndrome (TTTS), pressure rather than volume overload is increasingly considered as a key factor in the pathogenesis of the cardiomyopathy of the recipient twin. If this is the case, cardiac dysfunction should be among the first signs observed with TTTS. The objective of this study was to determine whether intertwin differences in myocardial function are modified early in the course of TTTS and whether they can help to differentiate this condition from intrauterine growth restriction (IUGR). METHODS AND RESULTS: Eight variables were analyzed on the first fetal echocardiography on 21 pairs of twins with TTTS and 11 with IUGR. No difference was found between the 2 groups for the cardiothoracic ratio, pulsatility indices in the umbilical and middle cerebral arteries, and peak velocity of the middle cerebral artery. Significant difference was found for ventricular septal thickness, but with no association with the conditions under study. With TTTS, left ventricular shortening fraction was consistently greater in the donor twins, and myocardial performance indices (MPIs) were elevated in the recipient twins. This increase in MPI was caused by a lengthening of the isovolumic periods compared with those of the donor twin: left ventricular and right ventricular isovolumic periods 0.105+/-0.047 and 0.097+/-0.026 seconds, respectively, for the recipient twins versus 0.0561+/-0.46 and 0.065+/-0.03 seconds, respectively, for the donor twins (P<0.001). These changes in the isovolumic periods were mainly due to significant prolongation of isovolumic relaxation times. A change in left ventricular MPI > or =0.09 combined with a change in right ventricular MPI > or =0.05 would identify a TTTS with a sensitivity of 75% and a false-positive rate of 9%. CONCLUSIONS: The observed diastolic function impairment goes along with the pressure-overload pathogenic concept proposed in TTTS. Assessment of intertwin difference in MPI is a valuable tool for early differential diagnosis between TTTS and isolated IUGR.

[Genetics and congenital heart diseases]. / Génétique et cardiopathies congénitales.

We describe in this article the recent data on the genetics of congenital heart defects (CHD) organised by type of CHD although each predisposing genetic factor is associated with a whole variety of CHD types. The recent progress resulting from animal models, molecular cytogenetics and CHD familial cases studies allow a better understanding of the determinism of CHD. This lead in term to improved counselling of parents of affected children and of CHD adults who would like to become parents. Nevertheless, more progress is needed to reach a better accuracy in prediction.

Reference values for an index of fetal aortic isthmus blood flow during the second half of pregnancy.

OBJECTIVE: During fetal life, the parallel position of the two cardiac ventricles confers a special status to the aortic isthmus. Flow through the isthmus reflects the balance between the performances of the two ventricles and their respective peripheral impedances. This study proposes a fetal aortic isthmus flow velocity index and its reference values defined on the basis of gestational age (GA). METHODS: Video recordings of 111 normal fetuses from 18 to 39 weeks of gestation were retrospectively reviewed. An isthmus flow velocity index (IFI) was calculated as follows: IFI = (systolic + diastolic)/systolic velocity integrals. GA-specific reference ranges of IFI were constructed. RESULTS: An IFI of 1.33 +/- 0.03 was found at 18 weeks. This value decreased slightly but steadily with GA to reach 1.23 +/- 0.16 at 39 weeks. This change is mainly related to a decrease in diastolic velocity integrals. CONCLUSION: The proposed IFI provides information on the direction and, indirectly, on the volume of blood flow through the fetal aortic isthmus.

[Dobutamine echocardiography in children after heart transplantation]. / Echocardiographie sous perfusion de dobutamine chez l'enfant après transplantation cardiaque.

Coronary disease of the transplanted heart is the principal cause limiting long-term survival of patients and grafts. In view of the invasive nature of coronary angiography, dobutamine echocardiography has been proposed as a non-invasive diagnostic method for this disease. The aim of this study was to determine the feasibility and reliability of this investigation in transplanted children. Twenty-one echoes were performed with dobutamine infusions in 17 patients transplanted at 10 months to 16.9 years of age (average 8.4 years), and followed up 1.1 to 10.1 years (average 4.4 years): 4 were on antihypertensive drugs but none were treated by betablockers. Dobutamine echocardiography was performed according to the standard protocol used in adults. The maximal level was attained in all cases. No major side effects were observed. The maximal heart rate attained 57 to 89% of the theoretical maximal rate, an increase of 44 to 184% compared with the basal heart rate. The maximal systolic blood pressure rose to 120 to 194 mmHg, an increase of 8 to 109% compared with resting values. The contractility scores and segmental contractile index were normal in 18 cases, abnormal at the maximal level in 2 cases (hypokinesia of segments 8 and 9 and akinesia of segments 10 and 16 with an index of 1.2), abnormal at the lowest levels (hypokinesia of segment 7 with an index of 1.1) and maximal level (hypokinesia of segments 1 and 7 with an index of 1.2) in one case. These results were concordant with coronary angiography performed within 2 to 8 days of echocardiography, and considered as the diagnostic investigation of reference (sensitivity 75%, specificity 100%, positive predictive value 100% and negative predictive value 93%). The authors conclude that dobutamine echocardiography is a non-invasive method easily performed with low risk in transplanted children but its diagnostic performance in coronary disease of the transplanted heart should be confirmed in larger studies.