Antenatal antiarrhythmic treatment for fetal tachyarrhythmias: a study protocol for a prospective multicentre trial

Introduction Several retrospective or single-centrestudies demonstrated the efficacy of transplacentaltreatment of fetal tachyarrhythmias. Our retrospectivenationwide survey showed that the fetal therapy willbe successful at an overall rate of 90%. For fetuseswith hydrops, the treatment success rate will be 80%.However, standard protocol has not been established.The objective of this study is to evaluate the efficacy andsafety of the protocol-defined transplacental treatment offetal tachyarrhythmias. Participant recruitment began inOctober 2010.Methods and analysis The current study is a multicentre,single-arm interventional study. A total of 50 fetuseswill be enrolled from 15 Japanese institutions. Theprotocol-defined transplacental treatment is performed forsingletons with sustained fetal tachyarrhythmia ≥180 bpm,with a diagnosis of supraventricular tachycardia or atrialflutter. Digoxin, sotalol, flecainide or a combination is usedfor transplacental treatment. The primary endpoint isdisappearance of fetal tachyarrhythmias. The secondaryendpoints are fetal death related to tachyarrhythmia,proportion of preterm birth, rate of caesarean sectionattributable to fetal arrhythmia, improvement in fetalhydrops, neonatal arrhythmia, neonatal central nervoussystem disorders and neonatal survival. Maternal, fetal andneonatal adverse events are evaluated at 1 month afterbirth. Growth and development are also evaluated at 18and 36 months of corrected age.Ethics and dissemination The Institutional Review Boardof the National Cerebral and Cardiovascular Center ofJapan has approved this study. Our findings will be widelydisseminated through conference presentations and peerreviewedpublications

Plasma natriuretic peptide levels in fetuses with congenital heart defect and arrhythmia: a single-center prospective study

application/pdf内容の要旨・審査結果の要旨 / 三重大学大学院医学系研究科 生命医科学専攻 臨床医学系講座 産科婦人科学分

Plasma natriuretic peptide levels in fetuses with congenital heart defect and arrhythmia: a single-center prospective study

application/pdfObjectives:Diagnosing fetal heart failure remains challenging because it is difficult to know how well the fetal myocardium will perform as loading conditions change. In adult cardiology, natriuretic peptides (NPs) are established marker of heart failure. However, the number of studies investigating NP levels in fetuses is quite limited. The aim of this study was to evaluate the significance of plasma NP levels in the assessment of heart failure in fetuses with congenital heart defect (CHD) and arrhythmia. Methods:This was a prospective observational study at a tertiary pediatric cardiac center. A total of 129 singletons with CHD, arrhythmia, or both and 127 controls from 2012 to 2015 were analyzed. Umbilical cord plasma atrial NP, brain NP and N-terminal pro-brain NP levels at birth were compared with ultrasonography findings indicating fetal heart failure such as a cardiovascular profile (CVP) score and morphological characteristics. Results:Fetuses with CHD, arrhythmia, or both had higher NP levels than controls (P<0.01). NP levels of fetuses with CHD, arrhythmia, or both were inversely correlated with CVP score (P for trend <0.01). No differences were found in NP levels between fetuses with CHD or arrhythmia and a CVP score of ≥8 versus controls. Multivariate analysis showed that a CVP score of ≤5, tachy- or bradyarrhythmia at birth, preterm birth, and umbilical artery pH <7.15 are independently associated with high NP levels (P<0.01). Among fetuses with a CVP score of ≤7, abnormal venous Doppler sonography findings were significantly more common and more severe in fetuses with tachy- or bradyarrhythmia than those with CHDs, and fetuses with tachy- or bradyarrhythmia had higher NP levels than those with CHDs (P=0.01). Fetuses with right heart defect and moderate or severe tricuspid valve regurgitation had significantly higher NP levels than fetuses with other types of CHD (P<0.01). Conclusions:Plasma NP levels in fetuses with CHD, arrhythmia, or both are correlated with the severity of fetal heart failure. Elevated NP levels are mainly attributed to increases in central venous pressure secondary to arrhythmia or atrioventricular valve regurgitation due to a CHD, rather than the morphological abnormality itself.本文 / Department of Perinatology and Gynecology35

Markedly reduced ventricular arrhythmia during the peripartum period in a pregnant woman with Andersen-Tawil syndrome

Andersen-Tawil syndrome (ATS), also known as long QT syndrome type 7, is a rare autosomal dominant disease caused by a KCNJ2 mutation. The characteristic triad of ATS is periodic paralysis, dysmorphic features, and ventricular arrhythmia. We describe a case of a woman with Andersen-Tawil syndrome and a history of syncope whose pregnancy was complicated with frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT). Her PVCs and NSVT were significantly decreased during the peripartum period, especially during labor. We treated her with beta-blockers throughout her pregnancy, and she experienced no complications. Although the mechanism underlying the decreased PVCs and NSVT in pregnancy has not been elucidated, women with ATS may have less arrhythmic event risk during pregnancy

Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.

OBJECTIVES:Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model. METHODS:Pregnant C57BL/6 (B6) mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs) from B6-Green Fluorescence Protein (B6GFP) transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP. RESULTS:Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37). Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5) mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay. CONCLUSIONS:In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein

Magnesium sulfate-induced blocked premature atrial contractions resulting in fetal bradyarrhythmia

Here, we present a rare case of fetal bradyarrhythmia following magnesium sulfate therapy for preterm labor. After we switched treatment from ritodrine hydrochloride to magnesium sulfate at 25 weeks' gestation, the fetal heart rate dropped from 150 bpm to 80–100 bpm. Fetal echocardiography and magnetocardiography indicated bigeminy and trigeminy of blocked premature atrial contractions. It is well known that magnesium sulfate decreases the baseline and variability of fetal heart rate. Studies have reported a substantial decrease of 2–15 bpm in the baseline fetal heart rate, and magnesium has various effects on fetal heart rate patterns with a lower baseline fetal heart rate within the normal range of 110–160 bpm. This is the first report of magnesium sulfate-induced fetal bradyarrhythmia by prolongation of the refractory period of the atrioventricular node in the case of blocked premature atrial contractions. Clinicians should consider fetal bradyarrhythmia when the baseline fetal heart rate drops to <100 bpm after magnesium sulfate administration

Maternal and fetal outcomes in pregnancy complicated with Eisenmenger syndrome

Objective: The goal of the study was to clarify the risk factors for pregnancy complicated with Eisenmenger syndrome (ES). Materials and methods: A retrospective study was performed in 15 patients with ES who were managed throughout pregnancy at one institution from 1982 to 2013. Cases associated with congenital heart diseases other than atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) were excluded. Results: The congenital heart diseases in ES included ASD (n = 3), VSD (n = 9), and PDA (n = 3). Ten women chose termination and 5 continued with their pregnancies. In the 5 continuation cases (PDA 1, VSD 4), worsening of cyanosis, exertional fatigue and dyspnea appeared between 25 and 30 weeks gestation and cesarean section was performed at 30 (28–33) weeks. LVEF, PaO2, and SpO2 decreased and heart rate increased significantly from before pregnancy to 25–30 weeks gestation. From before to during the pregnancy, there were no significant changes in mean PABP or pulmonary vascular resistance (PVR) in four cases with data (582–592, 885 to 868, 1280 to 1291, 1476–1522 dyn × s/cm2). PVR at conception had a negative relationship with delivery weeks. NYHA classes before, during and 1 year after pregnancy were II, III and II. In one recent case, epoprostenol and tadalafil were administered during pregnancy. Conclusions: Pregnancy with ES has a high risk due to hypooxygenation, cyanosis, and cardiac failure, which can appear as common complications as early as the 2nd trimester. Early interventions with meticulous care are required for these complications during pregnancy and delivery. Keywords: Cardiac failure, Cyanosis, Eisenmenger syndrome, Pregnanc