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BACKGROUND Pregnant women with a Fontan circulation have a high risk of obstetric complications, such as preterm delivery and small for gestational age (SGA), which may be affected by low blood flow to the placenta and hypoxia. This study investigated placental pathology in a Fontan circulation.Methods and Results:Eighteen pregnancies in 11 women with a Fontan circulation were reviewed. Pregnancy outcomes showed 9 miscarriages and 9 live births, with 4 preterm deliveries. Five neonates were SGA (

Chronic active Epstein-Barr virus (CAEBV) infection characterized by persistent infectious mononucleosis-like symptoms can lead to cardiovascular diseases. We encountered two pregnant women with CAEBV histories complicated with cardiovascular diseases. A 36-year-old woman with a history of myocardial infarction due to CAEBV and coronary artery bypass grafting became pregnant. Her left ventricular ejection fraction (LVEF) decreased, and cesarean section was performed at 36 weeks of gestation. Her LVEF recovered after delivery. A 32-year-old woman with a history of CAEBV and chronic hypertension was diagnosed with mild pulmonary arterial hypertension (PAH) after conception. She strongly desired to continue the pregnancy. She became complicated with severe superimposed preeclampsia at 31 weeks of gestation, and cesarean section was performed. Her PAH did not deteriorate during pregnancy or the postpartum period. Women treated for CAEBV, even with complete remission, require a preconception evaluation focused on the cardiovascular system and careful management of their pregnancy.

Serial changes of electrocardiograms (ECG) could be used to assess their clinical features in atrial septal defects (ASD) after transcatheter closure together with other clinical parameters. We retrospectively studied 100 ASD patients who underwent transcatheter closure. Complications of persistent atrial fibrillation occurred in five ASD patients, and they were excluded. We divided the other 95 patients according to PQ intervals before closure (normal

Background: The maternal circulatory system and hormone balance both change dynamically during pregnancy, delivery, and the postpartum period. Although atrial natriuretic peptides and brain natriuretic peptides produced in the heart control circulatory homeostasis through their common receptor, NPR1, the physiologic and pathophysiologic roles of endogenous atrial natriuretic peptide/brain natriuretic peptide in the perinatal period are not fully understood. Methods: To clarify the physiologic and pathophysiologic roles of the endogenous atrial natriuretic peptide/brain natriuretic peptide–NPR1 system during the perinatal period, the phenotype of female wild-type and conventional or tissue-specific Npr1-knockout mice during the perinatal period was examined, especially focusing on maternal heart weight, blood pressure, and cardiac function. Results: In wild-type mice, lactation but not pregnancy induced reversible cardiac hypertrophy accompanied by increases in fetal cardiac gene mRNAs and ERK1/2 (extracellular signaling-regulated kinase) phosphorylation. Npr1-knockout mice exhibited significantly higher plasma aldosterone level than did wild-type mice, severe cardiac hypertrophy accompanied by fibrosis, and left ventricular dysfunction in the lactation period. Npr1-knockout mice showed a high mortality rate over consecutive pregnancy–lactation cycles. In the hearts of Npr1-knockout mice during or after the lactation period, an increase in interleukin-6 mRNA expression, phosphorylation of signal transducer and activator of transcription 3, and activation of the calcineurin–nuclear factor of the activated T cells pathway were observed. Pharmacologic inhibition of the mineralocorticoid receptor or neuron-specific deletion of the mineralocorticoid receptor gene significantly ameliorated cardiac hypertrophy in lactating Npr1-knockout mice. Anti–interleukin-6 receptor antibody administration tended to reduce cardiac hypertrophy in lactating Npr1-knockout mice. Conclusions: These results suggest that the characteristics of lactation-induced cardiac hypertrophy in wild-type mice are different from exercise-induced cardiac hypertrophy, and that the endogenous atrial natriuretic peptide/brain natriuretic peptide–NPR1 system plays an important role in protecting the maternal heart from interleukin-6–induced inflammation and remodeling in the lactation period, a condition mimicking peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a specific cardiomyopathy in which heart failure develops due to reduced myocardial contraction during pregnancy or in the postpartum period in women without a previous history of heart disease. The epidemiology of PPCM has been reported in various countries and areas, and the incidence of PPCM differed among these reports. The incidence was highest (1 in 102 deliveries) in Nigeria and lowest (1 in 15,533 births) in Japan. The incidence was higher in African-Americans than in other races in several reports from the United States, and was also high in African countries and Haiti, indicating that the risk for PPCM is highest in the black race. However, the study design and definition of PPCM differ among studies, and these differences may influence the incidence. Moreover, the incidence of PPCM and the maternal mortality rate were well correlated. Since maternal mortality reflects the level of perinatal health care and hygiene, this finding suggests that the extent of perinatal care is partly related to the incidence of PPCM, which reflects heart failure and cardiomyopathy of unknown cause in women.

The frequency of newborns with congenital heart disease (CHD) is approximately 1% in the general population; however, the recurrence rate of CHD in mothers with CHD differs in ethnicity and reports. We therefore aimed to determine the prevalence of CHD among neonates born to mothers with CHD in our institute in Japan. We reviewed the medical charts of 803 neonates delivered by 529 women with CHD at the National Cerebral and Cardiovascular Center from 1982 to 2016. They included isolated ventricular septal defect (VSD,31.4%), isolated atrial septal defect (ASD, 23.3%), tetralogy of Fallot (TOF,10.6%). We defined CHD in neonates as being diagnosed within 1 month of birth. We estimated that the average rate of the CHD recurrence was 3.1%. The recurrence ratios in each maternal CHD were 8.6%, 7.1%, 6.2%, 4.8%, 3.6%, and 1.5% for PS, CoA, TOF, atrioventricular septal defect, VSD, and ASD, respectively. The rate of CHD in offsprings whose mothers have CHD was 3 times greater than that of mothers with healthy hearts. Almost half of neonates with CHD had the same phenotype as their mother in our series. Especially, PS and CoA were closely related to the type of maternal CHD.

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, Pregnancy

Arterial switch operation (ASO) for dextro-transposition of the great arteries (d-TGA) has gradually replaced the atrial switch operation and has become the standard operation. To date, the outcomes of pregnant women with d-TGA after this new operation have not been investigated. In this study, we investigated the impact of ASO on pregnant outcomes and mid-term prognosis in women with d-TGA and compared with the atrial switch operation through the literature review.There were 20 pregnancies in 10 women with d-TGA after ASO and 6 resulted in abortion. Among 14 successful pregnancies in 10 women, 11 pregnancies achieved the term delivery and 3 pregnancies, including 1 twin pregnancy, resulted in preterm labor. Maternal cardiovascular events occurred in 4 (heart failure and arrhythmias in 3 and arrhythmia in 1), and all were controllable with medications. Risk factors for the peripartum cardiac events were older age at ASO and delivery, and higher concentration of brain natriuretic peptide (BNP) at first trimester (p0.05). In 7-60 month-follow-up after delivery, no case showed deterioration of functional class and systemic ventricular function. According to the literature review, women after ASO demonstrated a better prognosis than those after the atrial switch operation.The majority of women with d-TGA after ASO tolerated pregnancy and delivery well. The older age at ASO, an elderly pregnancy, and higher BNP levels at the first trimester were possibly risk factors of peripartum cardiovascular events among the group. The literature reviews and this study may indicate the advantage of systemic left ventricle compared with systemic right ventricle in long-term outcomes after delivery.

Background: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. Methods: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN , and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated. Results: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [ P *]=1.2×10 –46 ). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P *=7.0×10 –8 ), DSP (odds ratio=14.9, P *=1.0×10 –8 ), and BAG3 (odds ratio=53.1, P *=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P =2.5×10 –4 ), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. Conclusions: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

Aim This study aimed to characterize the incidence and clinical significance of pregnancy-related aortic dissection using a large-scale survey in Japan. Methods A questionnaire requesting the detailed information included in the clinical charts of pregnancy-related aortic dissection cases (without any personally identifying information) was designed between 2013 and 2017 and administered to 407 perinatal centers in Japan. The response rate was 70.5%. Seventeen cases of pregnancy-related aortic dissection were identified. Results Maternal death due to aortic dissection was observed in nine patients (56.2%) while seven survived (43.8%). Dissection occurred during the postpartum period in 10 cases (62.5%), the third trimester in 4 (25.0%), labor in 1 (6.2%), and the second trimester in 1 (6.2%). The most common underlying diseases were: Marfan syndrome (25.0%), Loeys-Dietz syndrome (6.2%), hypertension (6.2%), and Takayasu aortitis (6.2%). Stanford type A aortic dissection was associated with maternal death during both pregnancy and the postpartum period. However, deceased patients showed lower rates of pre-diagnosed connective tissue disease than did survivors. Conclusions The mortality rate of aortic dissection that occurred during pregnancy or postnatal periods was more than 50%. Aortic dissection occurred more frequently in the postnatal period than during pregnancy, and less frequently in women previously diagnosed with connective tissue disease than in women without any medical history of aortic disorders. If symptoms suggestive of aortic dissection, such as severe back pain, are observed, even after the end of pregnancy, exhaustive diagnostic examinations should be carried out.

To clarify the association between anesthetic technique and maternal and neonatal outcomes in parturients with congenital heart disease (CHD).Retrospective, observational cohort study.An academic hospital.A total of 263 consecutive parturients with CHD who underwent cesarean section from 1994 to 2019.None.The authors compared postpartum cardiovascular events (composite of heart failure, pulmonary hypertension, arrhythmia, and thromboembolic complications) and neonatal outcomes (intubation and Apgar score7 at one or five minutes) by anesthetic technique. Among 263 cesarean sections, general anesthesia was performed in 47 (17.9%) parturients and neuraxial anesthesia in 214 (81.3%) parturients. Cardiovascular events were more common in the general anesthesia group (n = 7; 14.9%) than in the neuraxial anesthesia group (n = 17; 7.9%). Generalized linear mixed models assuming a binomial distribution (ie, mixed-effects logistic regression), with a random intercept for each modified World Health Organization classification for maternal cardiovascular risk, revealed that general anesthesia was not significantly associated with cardiovascular events (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.30-3.29). In addition, general anesthesia was associated with composite neonatal outcomes (Apgar score7 at one or five minutes or need for neonatal intubation; OR, 13.3; 95% CI, 5.52-32.0).Anesthetic technique is not significantly associated with postpartum composite cardiovascular events. General anesthesia is significantly associated with increased need for neonatal intubation and lower Apgar scores.

Objective To clarify the association between anaesthetic technique and maternal and neonatal outcomes in parturients with CHD. Design Retrospective observational cohort study. Setting Academic hospital. Population A total of 263 consecutive parturients with congenital heart disease (CHD) who underwent caesarean section. Methods Charts from 1994–2019 were reviewed. Main outcome measures We compared postpartum cardiovascular events (composite of heart failure, pulmonary hypertension, arrhythmia, and thromboembolic complications) and neonatal outcomes (intubation and Apgar score

Pregnancy with a mechanical heart valve (MHV) is high risk for valve thrombosis because pregnancy is a hyper-coagulation state. In addition, warfarin use during pregnancy is restricted due to its fetotoxicity, and postpartum bleeding may be increased with anticoagulation. In particular, placenta previa under anticoagulation may cause massive postpartum bleeding. The optimal anticoagulation for a pregnant woman with mitral and aortic double MHVs is not known. In addition, suitable techniques for control of bleeding in a case of placenta previa under anticoagulation are not known. Thus, a case of a pregnant woman with mitral and aortic double MHVs and placenta previa is presented. The case was managed without valve thrombosis through precise unfractionated heparin dose adjustment and frequent activated partial thromboplastin time monitoring, along with maintenance of antithrombin levels. Compression sutures were found to be effective for controlling bleeding from the attachment site of placenta previa even under anticoagulation.

Objective Cardiovascular disease increases the risk of maternal mortality. This study examined the risk factors for cardiovascular events in pregnant women with cardiovascular disease. Methods This was a case-control study conducted in 2 phases at Japanese maternal and fetal care centers. The primary survey, using an interviewer-administered questionnaire, investigated whether the institutions had managed pregnant women with cardiovascular disease from April 2014 to March 2016. From 424 individual facilities surveyed, 135 facilities were found to have experience in managing pregnant women. In the secondary survey, the 135 institutions were asked to complete a web-based questionnaire, which collected detailed clinical information about cases, including cardiovascular disease, cardiovascular events, maternal background, and the perinatal outcome. Results Information on 302 pregnant women with cardiovascular disease was collected. None of the 302 patients died. There were 25 women with cardiovascular events (cardiovascular event group) and 277 women without cardiovascular events (non-cardiovascular event group); the two groups were compared. No significant differences were found in the perinatal outcomes. Medication use before pregnancy was identified as a risk factor for cardiovascular events (adjusted odds ratio, 23.28; 95% confidence interval, 8.15-66.47; pI were risk factors for cardiovascular events in pregnant women with cardiovascular disease.

Background The number of pregnant women with dilated cardiomyopathy (DCM) is relatively small, and therefore their prognosis after pregnancy is unknown. This study aims to elucidate pregnancy outcomes among women with DCM, as well as the long-term prognosis after pregnancy. Methods Thirty-five pregnancies and deliveries in 30 women, diagnosed with DCM before pregnancy, were retrospectively analyzed. Results All women had a left ventricular ejection fraction (LVEF) over 30% and belonged to the New York Heart Association (NYHA) class I or II before pregnancy. The mean gestational age at delivery was 36 weeks with 15 (43%) preterm deliveries. Eight pregnancies (23%) were complicated by peripartum cardiac events including 1 ventricular arrhythmia, 6 heart failures, and 1 significant deterioration in LVEF requiring termination of pregnancy. NYHA class II, pre-pregnancy use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker/diuretics, elevated brain natriuretic peptide (BNP), and advanced diastolic dysfunction assessed by Doppler echocardiography were defined as risk factors for cardiac events. Although the more severe cases took beta-blockers during pregnancy, the rates of cardiac events and decreasing LVEF did not differ significantly between those taking beta-blockers and those who were not. Values of LVEF decreased by almost 10% after the average 4-year post-delivery follow-up period. The long-term event-free survival was considerably worse among women with peripartum cardiac events than in those without (p Conclusions DCM women with pre-pregnancy LVEF over 30% tolerated pregnancy, but the rate of preterm delivery was high. Peripartum cardiovascular events occurred more often in women with NYHA class II, as well as those who received medications before and during pregnancy and showed more elevated BNP and advanced diastolic dysfunction before pregnancy. Beta-blockers likely allowed similar outcomes for DCM patients with lower initial LVEFs. Close monitoring later in life is required, particularly among the women with peripartum cardiac events.

A 35-year-old woman was referred to our hospital for the management of acutely decompensated heart failure due to peripartum cardiomyopathy (PPCM). Generally, cardiac examinations are performed after the manifestation of heart failure in patients with PPCM. Thus, reports of serial cardiac examinations before the onset of PPCM are scarce. In this case, we were able to document the serial echocardiographic findings before the onset of life-threatening PPCM. We found that the left ventricular systolic function was preserved at 35 weeks of gestation but declined acutely after delivery at 38 weeks. Although speculative, these findings suggest that left ventricular dilation might precede the onset of PPCM.

AIM We sought to examine the safety and efficacy of a 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS), and to evaluate the changes in biomarkers of infection, anemia and cardiovascular conditions after LNG-IUS insertion in women with cardiovascular disease. METHODS We prospectively followed women with a cardiovascular disease in whom a 52-mg LNG-IUS was inserted between 2009 and 2015. The primary outcome was the frequency of cardiovascular and gynecologic side effects due to the LNG-IUS over the year after LNG-IUS insertion. The secondary outcomes were the changes in menstrual blood loss and biomarkers, e.g., white blood cell count and the levels of C-reactive protein, hemoglobin and brain natriuretic peptide. We also evaluated the 24-month continuation rate of LNG-IUS. RESULTS A total of 34 women were prospectively followed-up, including two women with pulmonary hypertension. No cardiovascular side effects were identified during the 1 year after LNG-IUS insertion, other than one case of mild vasovagal reaction at insertion. Neither the white blood cell count nor the C-reactive protein value increased after LNG-IUS insertion. The menstrual blood loss was decreased in most subjects and the median hemoglobin levels increased significantly within 1 year after insertion (P

Little is known about pregnancies of left ventricular noncompaction cardiomyopathy (LVNC), much less cases in which LVNC was definitively diagnosed prepregnancy. We report the cases of three pregnant Japanese women definitively diagnosed with LVNC prepregnancy. Case 1 presented LVNC with restrictive phenotype. Her pregnancy was terminated due to exacerbated pulmonary hypertension and low output status at 30 weeks' gestation. Case 2 presented isolated LVNC with nonsustained ventricle tachycardia. A cesarean section was performed at 36 weeks' gestation because of placenta previa. Case 3 presented dilated LVNC. Labor induction was performed because of decreased left ventricular ejection fraction, leading to a vaginal delivery at 37 weeks' gestation. In all cases, no thromboembolic event was identified during pregnancy; two patients received anticoagulants. We reviewed all English-literature cases of pregnant women definitively diagnosed with LVNC prepregnancy to analyze causes of adverse pregnancy outcomes and the necessity of anticoagulation. Four of the six pregnancies identified were terminated due to exacerbated cardiomyopathy phenotypes and not complications due to noncompaction itself, resulting in three cases' preterm deliveries. No thromboembolic event was identified by maintenance of the anticoagulation strategy determined prepregnancy. In pregnancies with LVNC, the possibility of a severe cardiac event and the indications for termination of the pregnancy can depend on the cardiomyopathy phenotypes, not noncompaction itself. Anticoagulation only because of the pregnancy itself may be redundant. In the management of LVNC during pregnancy, close monitoring of the condition of different phenotypes and reassessment of the necessity of anticoagulation can contribute to the pregnancy outcome.

Objective: We studied the effect and safety of epidural anesthesia during labor in pregnant women with cardiovascular disease. Materials and methods: In the pregnant women with cardiovascular disease, we compared maternal outcome and suppressive effect on blood pressure retrospectively between the epidural group (anesthetized epidurally during labor) and the no-epidural group (not anesthetized epidurally during labor). Results: A total of 277 patients were included in the analyses. Cardiovascular events decreased significantly in epidural group (P

Pregnancy with Marfan syndrome (MFS) presents challenges to the clinician because of the increased incidence of maternal cardiovascular complications, including acute aortic dissection (ADD) and the involvement of the fetus owing to the urgency of the need for surgery and the low likelihood of survival with premature delivery. Patient 1 was a 36-year-old pregnant Japanese woman with MFS who was referred at 16 gestational weeks with aortic root diameter 35.1 mm. Stanford type B AAD occurred on delivery without evident blood pressure changes. Patient 2 was a 31-year-old pregnant Japanese woman with MFS with aortic root diameter 28.3 mm at 20 gestational weeks after David procedure. Ultimately fatal Stanford type B AAD occurred on post-partum day 15. Both patients were treated with beta-blockers when AAD occurred. Although these two patients were initially considered to have relatively low risk according to previous reports and guidelines, AAD occurred. It is very important to provide information about these high pregnancy risks to women with MFS before conception, and to follow MFS pregnancies with great caution.

Background Pregnancy is one of the biggest concerns for women with long QT syndrome (LQTS). Objectives This study investigated pregnancy-related arrhythmic risk and the efficacy and safety of β-blocker therapy for lethal ventricular arrhythmias in pregnant women with LQTS (LQT-P) and their babies. Methods 136 pregnancies in 76 LQT-P (29±5 years old; 22 LQT1, 36 LQT2, one LQT3, and 17 genotype-unknown) were enrolled. We retrospectively analysed their clinical and electrophysiological characteristics and pregnancy outcomes in the presence (BB group: n=42) or absence of β-blocker therapy (non-BB group: n=94). Results All of the BB group had been diagnosed with LQTS with previous events, whereas 65% of the non-BB group had not been diagnosed at pregnancy. Pregnancy increased heart rate in the non-BB group; however, no significant difference was observed in QT and Tpeak-Tend intervals between the two groups. In the BB group, only two events occurred at postpartum, whereas 12 events occurred in the non-BB group during pregnancy (n=6) or postpartum period (n=6). The frequency of spontaneous abortion did not differ between the two groups. Fetal growth rate and proportion of infants with congenital malformation were similar between the two groups, but premature delivery and low birthweight infants were more common in those taking BB (OR 4.79, 95% CI 1.51 to 15.21 and OR 3.25, 95% CI 1.17 to 9.09, respectively). Conclusions Early diagnosis and β-blocker therapy for high-risk patients with LQTS are important for prevention of cardiac events during pregnancy and the postpartum period, and β-blocker therapy may be tolerated for babies in LQT-P cases.

Background Amlodipine is used for the treatment of hypertension, but reports on its use in early pregnancy are limited. Methods and Results In the present study, we recruited 231 women with chronic hypertension, including those who received amlodipine or other antihypertensives during early pregnancy, and investigated frequencies of morphologic abnormalities in their 231 offspring. Specifically, we evaluated 48 neonates exposed to amlodipine in the first trimester (amlodipine group, Group A), 54 neonates exposed to antihypertensives other than amlodipine (other antihypertensive group, Group O), and 129 neonates not exposed to antihypertensives (no‐antihypertensive group, Group N). The number of morphologic abnormalities of offspring in each group were 2 in Group A (4.2%; 95% CI , 0.51–14.25); 3 in Group O (5.6%; 95% CI , 1.16–15.39) and 6 in Group N (4.7%; 95% CI, 1.73–9.85). The odds ratio of the primary outcome comparing Group A and Group O was 0.74 (95% CI : 0.118–4.621) and Group A and Group N was 0.89 (95% CI : 0.174–4.575). Conclusions The odds of birth defects in Group A in the first trimester were not significantly different from those with or without other antihypertensives.

A 33-year-old woman at 17 weeks of gestation who had a single-chamber atrial pacemaker implanted ([figure 1A][1]) owing to sick sinus syndrome presented with a typical atrial flutter (AFL) ([figure 1B][1]) and decreased cardiac contractility. She had heart failure during a previous pregnancy because

Pregnancy with pulmonary arterial hypertension (PAH) has a significantly high risk of maternal death and women with PAH are basically advised to avoid pregnancy. Recently, several reports have described pregnant women with PAH who were treated with pulmonary vasodilators during pregnancy and delivered safely. However, the efficacy of this treatment during pregnancy is still not clear. Here we report on the short-term outcomes of three primiparous women with PAH who were prescribed pulmonary vasodilator therapy during their pregnancies. All women delivered preterm due to cardiac and/or obstetric reasons and were discharged without any complication. Pulmonary vasodilator therapy can be used safely during the pregnancies of PAH patients and may contribute to improved maternal and fetal prognoses.

Heparin anticoagulant therapy for thromboembolic disorders during pregnancy is problematic due to unexpected adverse bleeding. To avoid bleeding, we have used a less-intensive anticoagulation protocol of unfractionated heparin (UFH). The protocol had a therapeutic activated partial thromboplastin time (APTT) ratio of 1.5–2.0 with the control value, a UFH dose of ≤ 30,000 U/day, and an antithrombin (AT) activity target of ≥ 70%. In the present study, we evaluated this protocol using an anti-Xa assay. We collected UFH-treated plasma samples from ten consecutive pregnant Japanese patients with current or previous thromboembolic disorders. Seven patients remained in the therapeutic APTT ratio range (heparin-sensitive [HS] group). The other three patients had difficulty remaining within the therapeutic range (heparin-resistant [HR] group). In the HR group, two had AT deficiency and one had congenital absence of the inferior vena cava. Of the HS and HR samples, 73% and 31%, respectively, were within the therapeutic anti-Xa activity range 0.3–0.7 U/mL, indicating difficulty for the HR group to remain within the therapeutic range. Neither major bleeding nor symptomatic thromboembolic episodes occurred in either group. These findings suggest that the less-intensive anticoagulation protocol is permissive and may be beneficial in the HS group.

Peripartum cardiomyopathy (PPCM) is rare but life-threatening. We herein report the case of a 48-year-old woman with PPCM after oocyte donation and delivery of twins. Two weeks after delivery, she suffered from severe symptoms of heart failure [orthopnea, New York Heart Association (NYHA) class IV, pulmonary edema and a reduced left ventricular ejection fraction of 18%]. Although standard heart failure therapy was effective for diminishing the congestion, it was not sufficient to improve her symptoms or left ventricular systolic dysfunction. During admission, we added bromocriptine. A year later after the onset, she was in a good state with an improved left ventricular systolic function.

The effect of pregnancy on aortic root in women with repaired conotruncal anomalies (CTA) has not been clarified. This study examined aortic diameters during and after pregnancy in women with repaired CTA. A retrospective review of consecutive pregnant women with repaired CTA was performed for results of echocardiography from 1 year before pregnancy to 3 years after delivery and compared with findings from healthy pregnant volunteers. Participants comprised 42 subjects and 49 deliveries with repaired CTA (CTA group), and 47 healthy pregnant women (control group). Although no maternal aortic events were encountered, aortic diameters during pregnancy increased by 1.0 ± 2.2 mm (maximum, 7.0 mm) in the CTA group and 0.6 ± 1.3 mm (maximum, 3.4 mm) in the control group (p = 0.13). The CTA subgroup with increase in aortic diameter ≥ 3.5 mm during pregnancy showed no reversion to baseline diameter at follow-up > 6 months after delivery. Significant risk factors for increased aortic diameter and no reversal included pulmonary atresia, history of aortopulmonary shunt, older age at repair, and smaller left ventricular end-diastolic diameter pre-pregnancy. Women with repaired CTA tolerated pregnancy and delivery well. However, the aortic root progressively dilated during pregnancy and 1/4 of them, especially those with longstanding high aortic blood flow before repair, showed an increase of aortic root size of ≥ 3.5 mm during the peripartum period; this dilatation tended not to revert to the pre-pregnancy diameter. Therefore, serial measurement of the aortic root during pregnancy and after delivery is recommended in these women.

BACKGROUND The effects of β-adrenergic blockers on the fetus are not well understood. We analyzed the maternal and neonatal outcomes of β-adrenergic blocker treatment during pregnancy to identify the risk of fetal growth restriction (FGR). METHODS AND RESULTS We retrospectively reviewed 158 pregnancies in women with cardiovascular disease at a single center. Maternal and neonatal outcomes were analyzed in 3 categories: the carvedilol (α/β-adrenergic blocker; α/β group, n=13); β-adrenergic blocker (β group, n=45), and control groups (n=100). Maternal outcome was not significantly different between the groups. FGR occurred in 1 patient (7%) in the α/β group, in 12 (26%) in the β group, and in 3 (3%) in the control group; there was a significant difference between the incidence of FGR between the β group and control group (P

Aim Cesarean section is commonly selected in pregnancy with Moyamoya disease. We consider vaginal delivery with epidural anesthesia a viable alternative in such cases. Methods Mode of delivery and outcomes were examined in 27 pregnancies in 19 women with Moyamoya disease treated at the Department of Perinatology, National Cardiovascular Center, Japan, from 1983 to 2013. Of these 27 pregnancies, 20 were delivered vaginally with epidural anesthesia. The cerebral circulation, mode of delivery, maternal outcome (presence of symptoms due to Moyamoya disease intrapartum) and neonatal outcome (gestational week, birthweight, Apgar score at 5 min and pH of umbilical artery) were investigated. Results The cerebral circulation was judged to be good in all pregnancies. No symptoms due to Moyamoya disease intrapartum were seen in the vaginal delivery cases. Conclusion Our findings indicate that vaginal delivery is viable in pregnancy with Moyamoya disease and that unnecessary cesarean section may be avoided. These findings are limited by the retrospective nature of the study.

Aims The incidence of Takayasu arteritis during child-bearing years is relatively high. The management of pregnancies in patients with this disease is of great importance in clinical obstetrics. Here we analyzed pregnancies of women with Takayasu arteritis with and without complications. Material and Methods We retrospectively identified 27 pregnancies in 20 women with Takayasu arteritis seen between 1983 and 2005 at the National Cardiovascular Center, in Osaka, Japan. The incidences of obstetric events, steroid dose increase in pregnancy, and cardiovascular events were compared between group I (no complications), group II (one complication), and group III (two or more complications). Results None of the pregnancies showed Takayasu arteritis activity. The obstetric events were pre-eclampsia in four pregnancies (15%), fetal growth restriction in one (4%), and abruption in one (4%). Three pregnancies involved a steroids dose increase. There were no cardiovascular events. Eighty percent of the pregnancies that included an obstetric event also involved the mother's chronic hypertension. Conclusions Pregnant women without active Takayasu arteritis have a low risk of developing a cardiovascular event. For women with chronic hypertension, it might be important to note the development of pre-eclampsia, fetal growth restriction and abruption.

Background: There are few studies of pregnancy and delivery in patients with an implantable cardioverter-defibrillator (ICD). The purpose of this study was to investigate maternal and fetal outcome in these patients. Methods and Results: Six pregnant women with an ICD were retrospectively reviewed. All women underwent implantation of an ICD before pregnancy and delivered at the National Cerebral and Cardiovascular Center. The mean age at pregnancy and the mean follow-up period after ICD implantation were 28±3 years old and 5±3 years, respectively. There was no device-related complication during pregnancy. In 4 women, the number of tachyarrhythmias such as non-sustained ventricular tachycardia increased after the end of the second trimester of pregnancy and anti-arrhythmic medications were gradually increased. No patient received discharges or shocks from the ICD during pregnancy, however, and only one required anti-tachycardia pacing at 27 weeks’ gestation. Mean gestational age at delivery was 37±2 weeks and all deliveries were by cesarean section, including 5 as emergency deliveries due to a fetal indication. After delivery, 2 mothers had reduced cardiac function and 1 received an ICD shock for the first time. Conclusions: Pregnancy did not increase the risk of an ICD-related complication under appropriate management. Additional caution might be required in the postpartum period as well as during pregnancy and labor. (Circ J 2013; 77: 1166–1170)

Objectives Pregnancy can be well tolerated after the repair of aortic coarctation. However, a higher incidence of hypertensive disorders during these pregnancies was reported. We analyzed the perinatal changes in echocardiographic parameters in women with aortic coarctation and investigated the risk factors of gestational hypertension (GH). Methods We retrospectively identified 15 pregnancies in nine Japanese women with aortic coarctation between 1982 and 2015. We categorized the patients according to the presence/absence of GH as the group with GH(n=3) and that without GH(n=12). The echocardiographic parameters were compared between groups. Results Our analysis revealed that a pre-pregnancy Doppler-measured pressure gradient≥20mmHg and a left ventricular mass index≥95g/m 2 were significant risk factors for GH. The left ventricular end-diastolic diameters at the first and the third trimesters, the left ventricular end-systolic diameters at the first trimester, and the left ventricular ejection fraction at the third trimester were also significantly higher in the pregnancies with GH. All of these findings had been obtained before the patients' GH occurred. Conclusions Hypertrophy of the left ventricle with a lower ejection fraction and a high pressure gradient across the coarctation were risk factors for GH in the patients with aortic coarctation. Thus, serial measurements using echocardiography are important for predicting GH in women with aortic coarctation. However, further research investigating this finding with a larger sample size is needed.

Background and aims For patients with homozygous familial hypercholesterolemia (HoFH), atherogenic lipoprotein changes and increased stress on cardiovascular system during pregnancy may pose substantial risk for both the mother and her fetus. Although lipoprotein apheresis (LA) is reported as the most effective therapy to control LDL-C levels during pregnancy in HoFH patients, only case reports have been published, and there is no guidance for management. Methods We report twelve pregnancies and ten deliveries in seven patients with HoFH, and compare the clinical outcomes between patients who received LA during pregnancy and those who did not. Results One patient who refused LA during pregnancy died from acute myocardial infarction after delivery. Another patient whose adherence to LA was poor also died of myocardial infarction during pregnancy. One patient who initiated LA at the age of 18 had to discontinue LA due to severe symptoms of angina pectoris during pregnancy. Another had symptoms of nausea, hypotension, and bradycardia with increased levels of serum bradykinin during a dextran sulfate cellulose absorption-based LA procedure. Although two of the other three patients had already had coronary artery disease by the time of pregnancy, early initiation of LA from childhood and good adherence to it during pregnancy resulted in the delivery of healthy infants without adverse effects. Conclusions LA is essential for managing pregnancy safely in patients with HoFH. Increasing numbers of documented cases, including ours, will be helpful to guide future therapeutic decisions.

Peripartum cardiomyopathy (PPCM) is a rare, but life-threatening condition that occurs during the peripartum period in previously healthy women. Although its etiology remains unknown, potential risk factors include hypertensive disorders during pregnancy, such as preeclampsia, advanced maternal age, multiparity, multiple gestation, and African descent. Several cohort studies of PPCM revealed that the prevalence of these risk factors was quite similar. Clinically, approximately 40% of PPCM patients are complicated with hypertensive disorders during pregnancy. Because PPCM is a diagnosis of exclusion, heterogeneity is a common element in its pathogenesis. Recent genetic research has given us new aspects of the disease. PPCM and dilated cardiomyopathy (DCM) share genetic predisposition: 15% of PPCM patients were found to have genetic mutations that have been associated with DCM, and they showed a lower recovery rate. Other basic research using PPCM model mice suggests that predisposition genes related to both hypertensive and cardiac disorders via angiogenic imbalance may explain common elements of hypertensive disorders and PPCM. Furthermore, hypertensive disorders during pregnancy are now found to be a risk factor of not only PPCM, but also cardiomyopathy in the future. Understanding genetic variations allows us to stratify PPCM patients and to guide therapy. (Circ J 2016; 80: 1684-1688).

Background: Improved medical techniques have allowed most women with repaired tetralogy of Fallot (TOF) to reach childbearing age. The predictors of adverse events and the effects of pregnancy on cardiac function have not been clearly described in these patients. Methods and Results: In the present study we retrospectively reviewed 40 deliveries in 25 patients with repaired TOF. There were 23 patients in New York Heart Association (NYHA) class I, and 2 in classes II-III before pregnancy. The mean age at delivery was 29.1 years and the mean gestational period was 37.8 weeks. Seven pregnancies (17.5%) in 7 patients were complicated with cardiac events such as a decline in NYHA class and arrhythmia. History of ablation and the baseline cardiothoracic ratio on chest radiography were predictors of adverse events. Peak plasma brain natriuretic peptide (BNP) level after the second trimester was higher in patients with cardiac events. Left ventricular size and contraction did not change from before to after pregnancy, but the right ventricle was enlarged at 6 months after delivery. Conclusions: Many of the pregnancies in women with repaired TOF were successful. However, careful management is required for some patients and the BNP level may be a useful marker to identify these patients. Because the right heart tended to be enlarged in the late postpartum period, pregnancy may also affect the long-term prognosis of patients with repaired TOF. (Circ J 2012; 76: 957-963)

The goal of the study was to determine risk factors for maternal cardiac failure in pregnancy complicated with dilated cardiomyopathy (DCM). The subjects were 29 patients diagnosed with DCM before conception or during the first 7 months of pregnancy. DCM was defined as left ventricle end-diastolic dimension (LVDd)⩾48 mm and/or fractional shortening (%FS)⩽30% on echocardiography. Patients were followed until at least 1 year after delivery and were categorized into a poor prognosis group (n=6; death or end stage heart failure of New York Heart Association (NYHA) class III and IV) and a good prognosis group (n=23; all other cases). DCM was initially diagnosed during pregnancy in 6/6 and 8/23 patients in the poor and good prognosis groups, respectively (P

Background: Aortic dilatation and dissection are severe complications of pregnancy that may cause maternal death. The purpose of the present study was to investigate risk factors for aortic dilatation or dissection in pregnant Japanese women with Marfan syndrome. Methods and Results: A total of 28 patients with Marfan syndrome were investigated retrospectively during pregnancy and after delivery at 1 institution. These patients were divided into 2 groups: those who experienced aortic dilatation or dissection (group D, n=11) and those who did not (group ND, n=17). In group D, aortic dilatation or dissection occurred in 7 cases during pregnancy (2 in the 2nd trimester, 5 in the 3rd trimester) and 4 cases after birth. The 2 cases in the 2nd trimester involved aortic dilatation >60mm and those patients underwent hemiarch replacement and a David operation, respectively. Delivery by cesarean section (64% vs. 18%, P

Background: There has been no nationwide survey concerning peripartum cardiomyopathy (PPCM) among the Asian population, and clinical profiles of PPCM complicated with hypertensive disorders complicating pregnancy (HD) as the major risk factor of PPCM have not been characterized. Methods and Results: A retrospective, nationwide survey of PPCM in 2007 and 2008 all over Japan was performed and the clinical characteristics were compared between patients with and without HD. We obtained data for 102 patients. HD during pregnancy occurred in 42 patients (41%). Patients with HD were older than those without HD (33.8 vs. 31.9 years old, P

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

Background Percutaneous peripheral intervention (PPI) for superficial femoral artery (SFA) stenosis is associated with a high restenosis rate. Whether PPI improves the long-term outcome of patients with SFA occlusive disease remains to be determined. Methods and Results A review was done of 107 patients with SFA occlusive disease. Fifty-five patients received PPI for SFA (ie, PPI group) and 52 patients received conservative medical therapy (ie, control group). Clinical records were searched for adverse events (eg, death, limb amputation, re-hospitalization, new onset of coronary artery disease and cerebrovascular disease) for an average of 30.6±17.7 months. At follow-up, only 5 patients (9.1%) in the PPI group experienced improved limb symptoms compared with baseline, and 6 patients (10.9%) showed ischemic skin ulcer or gangrene. In addition, 2 of these 6 patients were unsuccessful PPI cases complicated with distal embolization and perforation. In the control group, 3 patients (5.8%) presented with improved limb symptoms, and an equal number of patients had worsening of symptoms. Although 2 patients showed ischemic skin ulcers at follow-up, both patients had these lesions at baseline. Adverse events were observed more frequently in the PPI group than the control group (69.1% vs 46.2%, p

Elevated vasoinhibin derived from prolactin and cathepsin D activities in sera of patients with preeclampsia

Background:The influence of the physiological circulatory changes during pregnancy on hypertrophic cardiomyopathy (HCM) is unclear. There have been no comprehensive studies of pregnant women with HCM in the Japanese population.Methods and Results:A total of 27 pregnancies (23 women with HCM) were retrospectively reviewed. A total of 18 cardiovascular events occurred in 13 of the 27 pregnancies (48%), and 13 of these events (76%) were related to arrhythmia. The cardiovascular events tended to occur in the early stage of pregnancy (≈30 gestational weeks) or postpartum. The events related to arrhythmia mainly occurred in the early stage of pregnancy or at approximately 30 gestational weeks. Four pregnancies were terminated because of cardiovascular events. Cardiovascular events occurred in 8 of 9 pregnancies in women on medication before pregnancy (88%), 7 of 10 pregnancies with high CARPREG score (70%), and in 9 of 12 pregnancies with high ZAHARA score (75%).Conclusions:Cardiovascular events occurred in more than half of the pregnant women complicated with HCM, and the arrhythmia is the most common cardiovascular event. Medication in the pre-pregnancy period, and CARPREG or ZAHARA score ≥1 were identified as risk factors of cardiac events during pregnancy or postpartum. (Circ J 2014; 78: 2501–2506)