Sex Differences in Cardiovascular Disease-Related Hospitalization and Mortality in Japan　- Analysis of Health Records From a Nationwide Claim-Based Database, the Japanese Registry of All Cardiac and Vascular Disease (JROAD).

BACKGROUND: The prevalence of cardiovascular disease (CVD) is rising in Japan with its aging population, but there is a lack of epidemiological data on sex differences in CVD, including acute coronary syndrome (ACS), acute heart failure (AHF), and acute aortic disease. METHODS AND RESULTS: This retrospective study analyzed data from 1,349,017 patients (January 2012-December 2020) using the Japanese Registry Of All Cardiac and Vascular Diseases database. ACS patients were youngest on average (70.5±12.9 years) and had the lowest female proportion (28.9%). AHF patients had the oldest mean age (79.7±12.0 years) and the highest proportion of females (48.0%). Acute aortic disease had the highest in-hospital mortality (26.1%), followed by AHF (11.5%) and ACS (8.9%). Sex-based mortality differences were notable in acute aortic disease, with higher male mortality in Stanford Type A acute aortic dissection (AAD) with surgery (males: 14.2% vs. females: 10.4%, P<0.001) and similar rates in Type B AAD (males: 6.2% vs. females: 7.9%, P=0.52). Aging was a universal risk factor for in-hospital mortality. Female sex was a risk factor for ACS and acute aortic disease but not for AHF or Types A and B AAD. CONCLUSIONS: Sex-based disparities in the CVD-related hospitalization and mortality within the Japanese national population have been highlighted for the first time, indicating the importance of sex-specific strategies in the management and understanding of these conditions.

National Survey Identifying the Factors Affecting the Career Development of Cardiologists in Japan.

BACKGROUND: Equality in training opportunities, studying abroad, and satisfaction with work are not well investigated among Japanese cardiologists.Methods and Results: We studied cardiologists' career development using a questionnaire that was emailed to 14,798 cardiologists belonging to the Japanese Circulation Society (JCS) in September 2022. Feelings regarding equality in training opportunities, preferences for studying abroad, and satisfaction with work were evaluated with regard to cardiologists' age, sex, and other confounding factors. Survey responses were obtained from 2,566 cardiologists (17.3%). The mean (±SD) age of female (n=624) and male (n=1,942) cardiologists who responded to the survey was 45.6±9.5 and 50.0±10.6 years, respectively. Inequality in training opportunities was felt more by female than male cardiologists (44.1% vs. 33.9%) and by younger (<45 years old) than older (≥45 years old) (42.0% vs. 32.8%). Female cardiologists were less likely to prefer studying abroad (53.7% vs. 59.9%) and less satisfied with their work (71.3% vs. 80.8%) than male cardiologists. Increased feelings of inequality and lower work satisfaction were investigated among cardiologists who were young, had family care duties, and had no mentors. In the subanalysis, significant regional differences were found in cardiologists' career development in Japan. CONCLUSIONS: Female and younger cardiologists felt greater inequality in career development than male and older cardiologists. A diverse workplace may prompt equality in training opportunities and work satisfaction for both female and male cardiologists.

Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy.

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.

Deficiency of Cardiac Natriuretic Peptide Signaling Promotes Peripartum Cardiomyopathy-Like Remodeling in the Mouse Heart.

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.

Clinicopathologic Study of Placentas From Women With a Fontan Circulation.

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 (<5th percentile). Eight placentas from live births in 7 women were available for the study. Five placentas had low weight placenta for gestational age, and 7 grossly showed a chronic subchorionic hematoma. Histological examination revealed all placentas had some form of histological hypoxic lesions: maternal vascular malperfusion in 7, fetal vascular malperfusion in 1, and other hypoxia-related lesions in 8. Quantitative analyses, including immunohistochemistry (CD31, CD68, and hypoxia inducible factor-1α antibodies) and Masson's trichrome staining, were also performed and compared with 5 control placentas. Capillary density and the area of fibrosis were significantly greater in placentas from women with a Fontan circulation than in control placentas. CONCLUSIONS: Placentas in a Fontan circulation were characterized by a high frequency of low placental weight, chronic subchorionic hematoma, and constant histological hypoxic changes, which could reflect altered maternal cardiac conditions and lead to poor pregnancy outcomes.

Anesthesia for Cesarean Section and Postpartum Cardiovascular Events in Congenital Heart Disease: A Retrospective Cohort Study.

OBJECTIVE: To clarify the association between anesthetic technique and maternal and neonatal outcomes in parturients with congenital heart disease (CHD). DESIGN: Retrospective, observational cohort study. SETTING: An academic hospital. PARTICIPANTS: A total of 263 consecutive parturients with CHD who underwent cesarean section from 1994 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors compared postpartum cardiovascular events (composite of heart failure, pulmonary hypertension, arrhythmia, and thromboembolic complications) and neonatal outcomes (intubation and Apgar score <7 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 score <7 at one or five minutes or need for neonatal intubation; OR, 13.3; 95% CI, 5.52-32.0). CONCLUSION: 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.

Two cases of pregnancy after achieving complete remission of chronic active Epstein-Barr virus infection.

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.

Cardiovascular disease among pregnant women after anticancer therapy.

Recent advances in cancer therapies have enabled many women diagnosed with malignancies during childhood and adolescence to survive longer and therefore to reach an age where they wish to conceive. When providing cancer treatment such as anticancer drugs and radiotherapy, attention is often paid to preserving future fertility, but little is known about maternal pregnancy risks, and in particular cardiovascular complications. Recent studies have shown that cardiovascular diseases such as cardiomyopathy, heart failure, and arrhythmias often occur during and soon after anticancer therapy. This has led to the emergence of the specialized field of "onco-cardiology" or "cardio-oncology," in which oncologists and cardiologists collaborate, as well as the publication of multiple clinical practice guidelines. The interdisciplinary onco-cardiology team plays an important role in further improving the prognosis of cancer survivors. The current recommendation for women after anticancer therapy who wish to conceive is to undergo cardiovascular screening, regardless of whether there is a history of cardiovascular complications or not, in order to provide preconception counseling. Pregnancies in cancer-survivors, who experience cardiovascular complications, should be managed perinatally by a multidisciplinary team including obstetricians and cardiologists. Absence of cardiovascular disease on screening does not preclude the possibility that new cardiac dysfunction may occur during the perinatal period, especially in women with a history of high-dose anthracycline drug administration and/or radiation therapy. In such high-risk cases, follow-up of cardiac function throughout the perinatal period is required.

Aortic dissection during pregnancy and puerperium: A Japanese nationwide survey.

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.

Elaborate evaluation of serial changes in electrocardiograms of atrial septal defects after transcatheter closure for a better understanding of the recovery process.

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: < 200 ms, n = 51; prolonged: ≥ 200 ms, n = 44) to evaluate their clinical characteristics and parameters such as echocardiography, chest X-rays, and brain natriuretic protein (BNP) levels. Individuals in the prolonged PQ group were significantly older, had higher incidences of paroxysmal atrial fibrillation (PAF) and heart failure (HF) treated with more ß-blockers and diuretics, and with a higher tendency of NYHA functional classification and BNP levels than the normal PQ group. The prolonged PQ group also had a significantly higher incidence of complete right bundle branch block, wider QRS intervals, and larger cardiothoracic ratios in chest X-rays accompanied by larger right atrial-areas and larger left atrial dimensions in echocardiograms. Furthermore, the prolonged PQ intervals with less PQ interval shortening after transcatheter closure revealed that the patients were the oldest at the time of closures and showed less structural normalization of the right heart and left atrium after ASD closure. PAF and HF also occurred more frequently in this subgroup. These results suggested that the ASD patients with prolonged PQ intervals with less PQ shortening were accompanied by more advanced clinical conditions. Together with other clinical parameters, detailed analyses of ECG and their changes after closure could elucidate the clinical characteristics and status of ASD patients with transcatheter closure and were useful for predicting structural normalization after transcatheter closure.

Appropriate delivery method for cardiac disease pregnancy based on noninvasive cardiac monitoring.

Background There are numerous significant physiological changes occurring in circulation during labor. To detect these rapid hemodynamic changes, invasive and intermittent measurement techniques are not reliable. To suggest a suitable delivery method for pregnancy with cardiac disease, this study analyzed how each delivery method influences cardiac function using a noninvasive and continuous measurement technique. Methods A prospective study was accomplished at the National Cerebral and Cardiovascular Center in Japan from October 1, 2014, to November 30, 2018. The classification of the healthy heart pregnant women was according to the delivery method: vaginal delivery (VD) without epidural anesthesia, VD with epidural anesthesia, and caesarean section (CS). The hemodynamic parameters cardiac index (CI), stroke volume index (SI), and heart rate (HR) were evaluated regularly throughout delivery by noninvasive electrical cardiometry monitor. Results Ten cases were examined for each group. CI and HR were significantly increased before VD, while the increase in CI and HR was mild in the epidural group in comparison to the nonepidural group. SI was increased toward the delivery in the epidural group, and it was constant in the nonepidural group. However, there was no alteration in the level of outcomes of the two groups. In CS, SI increased and HR decreased before delivery. After delivery, SI continued to increase, while HR did not change but CI increased. Conclusion In VD, the increase in venous circulation according to the autotransfusion is managed by increasing HR. By epidural anesthesia, the increase in HR was suppressed and SI was increased. However, as epidural anesthesia increases the vascular capacity, the level of SI outcome was comparable. In CS, the HR was decreased because of the spinal anesthesia and the SI was increased because of many factors like hydration. As there are many factors to control in CS, VD with epidural anesthesia will be the first preference for most cardiac patients.

Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.

Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

Peripartum Management of Pregnant Women With Congenital Heart Disease.

BACKGROUND: The average maternal age at delivery, and thus the associated maternal risk are increasing including in women with congenital heart disease (CHD). A comprehensive management approach is therefore required for pregnant women with CHD. The present study aimed to investigate the factors determining peripartum safety in women with CHD.Methods and Results:We retrospectively collected multicenter data for 217 pregnant women with CHD (age at delivery: 31.4±5.6 years; NYHA classifications I and II: 88.9% and 7.4%, respectively). CHD severity was classified according to the American College of Cardiology/American Heart Association guidelines as simple (n=116), moderate complexity (n=69), or great complexity (n=32). Cardiovascular (CV) events (heart failure: n=24, arrhythmia: n=9) occurred in 30 women during the peripartum period. Moderate or great complexity CHD was associated with more CV events during gestation than simple CHD. CV events occurred earlier in women with moderate or great complexity compared with simple CHD. Number of deliveries (multiparity), NYHA functional class, and severity of CHD were predictors of CV events. CONCLUSIONS: This study identified not only the severity of CHD according to the ACC/AHA and NYHA classifications, but also the number of deliveries, as important predictive factors of CV events in women with CHD. This information should be made available to women with CHD and medical personnel to promote safe deliveries.

Safety and efficacy of a 52-mg levonorgestrel-releasing intrauterine system in women with cardiovascular disease.

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 < 0.001 and P = 0.002). Moreover, brain natriuretic peptide levels tended to decrease in correspondence with the hemoglobin elevation (P = 0.074). The 24-month LNG-IUS continuation rate was 97% (95% confidence interval 85-100). CONCLUSION: No clinically significant cardiovascular event was identified during the 1 year after 52-mg LNG-IUS insertion among women with cardiovascular disease. The 52-mg LNG-IUS may have specific favorable effects by decreasing the risk of iron deficiency anemia in these women.

Impact of Pregnancy on Aortic Root in Women with Repaired Conotruncal Anomalies.

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.

Recurrent Congenital Heart Diseases Among Neonates Born to Mothers with Congenital Heart Diseases.

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.

Worldwide Incidence of Peripartum Cardiomyopathy and Overall Maternal Mortality.

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.

Cardiomyopathy Phenotypes and Pregnancy Outcomes with Left Ventricular Noncompaction Cardiomyopathy.

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.

Utility of Fluid Assessment Based on the Intrathoracic Impedance Monitoring in a Peripartum Woman with Heart Disease.

Recently, implantable cardioverter-defibrillators (ICD) have become capable of monitoring intrathoracic impedance to detect an increased fluid volume and heart failure. Pregnancy is a well-known cause of an increased body fluid volume; however, it is not clear whether the measurement of intrathoracic impedance by ICD is clinically useful for precisely detecting heart failure in pregnant women. We herein report the case of a 39-year-old woman with an ICD that had been implanted after an event of ventricular fibrillation due to severe aortic regurgitation with a bicuspid aortic valve. Elevated right ventricular pressure and brain natriuretic peptide levels were detected at 37 weeks of gestation and postpartum. At the same time, the ICD's stored fluid index gradually increased and exceeded the threshold on the 10th day after delivery. She was treated with diuretics and recovered from postpartum heart failure. The physiological volume changed in the perinatal period, but we were still able to detect heart failure by ICD. Intrathoracic impedance monitoring is effective in the perinatal field.