Influence of pregnancy on cardiac function and hemodynamics in women with Ebstein's anomaly.

INTRODUCTION: We examined the perinatal outcomes and right ventricular function before pregnancy, during pregnancy, and after delivery in women with Ebstein's anomaly. MATERIAL AND METHODS: We retrospectively investigated the clinical course and mode of delivery and monitored hemodynamic parameters throughout pregnancy in 17 women with Ebstein's anomaly who delivered at our institution during the period of 1995-2015. RESULTS: Eight women, including nine pregnancies, underwent elective cesarean section, and nine women, including 14 pregnancies, underwent vaginal delivery. Elective cesarean section was performed in cases with significant heart failure or arrhythmias and in the presence of more than two of the following: cardiothoracic ratio ≥60%, moderate or severe tricuspid valve regurgitation, tricuspid valve regurgitation pressure gradient ≥35 mmHg during pregnancy. The cardiothoracic ratio and tricuspid valve regurgitation pressure gradient significantly increased during pregnancy compared with prepregnancy values. The New York Heart Association classification deteriorated from class I to class II or III in five cases during pregnancy. CONCLUSIONS: Although pregnancy was relatively safe among women with Ebstein's anomaly, some women developed cyanosis, arrhythmia, and heart failure, leading to elective cesarean section. Monitoring clinical and hemodynamic changes throughout pregnancy is advised to minimize maternal cardiac risk and select the appropriate mode of delivery.

Pregnancy and delivery outcomes from patients with repaired anomalous origin of the left coronary artery from the pulmonary artery.

AIM: We investigated the clinical courses before and during pregnancy and after delivery in patients with repaired anomalous origin of the left coronary artery from the pulmonary artery to determine the impact of the hemodynamic changes and cardiac function on the selection of the appropriate mode of delivery. METHODS: Six patients who underwent coronary artery reimplantation delivered 10 infants. We scrutinized the patients' hemodynamic changes on echocardiographs and the plasma brain natriuretic peptide levels before and during pregnancy and after delivery, the perinatal outcomes and maternal and fetal events. RESULTS: All patients were asymptomatic and categorized as having New York Heart Association functional class I before pregnancy. In 8 of 10 pregnancies, vaginal deliveries were performed; two elective cesarean sections were performed because of symptomatic heart failure. The hemodynamic parameters were stable throughout pregnancy and postdelivery, and no maternal or fetal events occurred in the patients who underwent vaginal deliveries. One cesarean section patient developed significant heart failure during the late second and third trimesters, which was accompanied by hemodynamic changes, including increased brain natriuretic peptide levels, left ventricular diastolic dysfunction and worsening arrhythmias, and thrombosis and post-partum hemorrhage occurred postdelivery. The baby had intrauterine growth retardation and small for gestational age. None of the babies had congenital anomalies. CONCLUSION: Pregnancy was safe in most of the asymptomatic patients long after anomalous origin of the left coronary artery from the pulmonary artery was repaired. Symptomatic heart failure might occur during pregnancy in patients with persisting myocardial damage. Pregnancy and delivery should be carefully managed.

Clinical implications of eicosapentaenoic acid/arachidonic acid ratio (EPA/AA) in adult patients with congenital heart disease.

Recent studies showed that a low ratio between the levels of eicosapentaenoic acid and those of arachidonic acid (EPA/AA) is associated with higher incidence of coronary artery disease and poor prognosis of heart failure, arrhythmia, and cardiac sudden death. However, the clinical implications of EPA/AA in adult patients with congenital heart disease remain unclear. We aimed to assess the prognostic value of EPA/AA regarding cardiac events in adult patients with congenital heart disease. We measured the serum levels of eicosapentaenoic acid and arachidonic acid in 130 adult patients (median age, 31 years) stratified into two groups according to their EPA/AA (low, ≤0.22; high, >0.22). We prospectively analyzed the association between EPA/AA and incidence of cardiac events during a mean observation period of 15 months, expressed in terms of hazard ratio (HR) with 95% confidence interval (95% CI). In the subgroup of patients with biventricular circulation (2VC) (n = 76), we analyzed the same clinical endpoints. In our study population, EPA/AA was not associated with the incidence of arrhythmic events (HR, 1.52; 95% CI, 0.82-2.85; p = 0.19), but low EPA/AA was a predictor of heart failure hospitalization (HR, 2.83; 95% CI, 1.35-6.30; p < 0.01). Among patients with 2VC, an EPA/AA of ≤0.25 was associated with a significantly higher risk of arrhythmic events (HR, 2.55; 95% CI, 1.11-6.41; p = 0.03) and heart failure hospitalization (HR, 5.20; 95% CI, 1.78-18.1; p < 0.01). EPA/AA represents a useful predictor of cardiac events in adult patients with congenital heart disease.

Outcomes from anomalous origin of the left coronary artery from the pulmonary artery repair: Long-term complications in relation to residual myocardial abnormalities.

BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary artery irregularity. This study aimed to clarify the long-term postoperative outcomes in ALCAPA patients, and to compare the infantile and adult types. METHODS: We retrospectively analyzed the clinical data from 33 patients with ALCAPA who underwent surgical repairs after 1980. The patients were grouped based on whether presentation occurred before (infantile type: n=14) or after (adult type: n=19) 1 year of age. RESULTS: The mean follow-up duration was 16 years. Preoperatively, the infantile type had greater impairment of the left ventricle ejection fraction (LVEF) (45±15%) compared with the adult type (59±10%) (p<0.01). Coronary revascularization significantly improved the postoperative LVEF (67±5%) (p<0.01) in the patients with the infantile type. The postoperative LVEF did not change in the adult type. The mitral regurgitation (MR) severity improved postoperatively, but the between-group difference was not significant. Postoperatively, none of the patients with the infantile type and 37% of the patients with the adult type had left ventricular asynergy (p=0.01), and both groups showed postoperative perfusion defects (79% vs 95%, p=0.29). Compared with the infantile type, the adult type had a significant prognostic value for composite cardiovascular events that comprised cardiac death, arrhythmias, MR deterioration, and hospitalization as a consequence of heart failure (p=0.04). CONCLUSIONS: Most patients showed favorable clinical outcomes postoperatively, but myocardial damage remained long after surgery and cardiovascular events occurred postoperatively. Hence, meticulous long-term follow-up is warranted.

Long-term Outcomes after Truncus Arteriosus Repair: A Single-center Experience for More than 40 Years.

OBJECTIVES: This study aimed to analyze long-term survival and functional outcomes after truncus arteriosus repair in a single institution with more than 40 years of follow-up. METHODS: Medical records were analyzed retrospectively in 52 patients who underwent the Rastelli procedure for truncus arteriosus repair between 1974 and 2002. Thirty-five patients survived the initial repair. The median age at the initial operation was 2.8 months (range, 0.1-123 months) and the body weight was 3.9 kg (range, 1.6 to 15.0 kg). RESULTS: The median age at follow-up was 23.6 years (range, 12.4 to 44.5 years). The median follow-up duration was 23.4 years (range, 12.3 to 40.7 years). The actuarial survival rate was 97% at 10 years and 93% at both 20 years and 40 years after the initial operation. At follow-up, most patients were in New York Heart Association (NYHA) functional classes I (73%) and II (24%). Thirty-six percent of patients had full-time jobs, 40% were students, and 21% were unemployed. Most patients (97%) had undergone conduit reoperations. Freedom from reoperation for right ventricular (RV) outflow and pulmonary artery (PA) stenosis was 59% at 5 years, 28% at 10 years, and 3% at 20 years after the initial operation. Freedom from catheter interventions for RV outflow and PA stenosis was 59% at 5 years, 47% at 10 years, and 38% at 20 years after the initial operation. Freedom from truncal valve replacement was 88% at 5 years, 85% at 10 years, and 70% at 20 years after the initial operation. CONCLUSIONS: In this single-center retrospective study, with long-term follow-up after repair of truncus arteriosus, long-term survival and functional outcomes were acceptable, despite the requirement for reoperation and multiple catheter interventions for RV outflow and PA stenosis in almost all patients, and the frequent requirement for late truncal valve operations.

Assessment of mechanical dyssynchrony in fulminant myocarditis.

It is often difficult to assess ventricular synchrony in patients with fulminant myocarditis. We report a pediatric case of fulminant myocarditis where clinical course and changes in dyssynchrony were followed with speckle tracking echocardiography. Dyssynchrony of the left ventricle changed day by day. It was useful to assess the progression of ventricular damage and its recovery.

Estrogen-like activity and dual roles in cell signaling of an Agaricus blazei Murrill mycelia-dikaryon extract.

Agaricus blazei (A. blazei) Murrill mycelia-dikaryon has attracted the attention of scientists and clinicians worldwide owing to its potential for the treatment of cancer. However, little is known about its effect on other pathologies. This study sought to extend the potential medical usefulness of A. blazei for preventing vascular damage and to unravel its mechanism of action. The A. blazei extract showed estrogen-like activity in both gene expression profiling and a luciferase assay. Indeed, the extract inhibited oxidized low-density lipoprotein-stimulated activation of Erk1/2, Akt and p38 in HUVECs and macrophage-derived TIB-67 cells. Moreover, the extract enhanced transcription of the glutathione peroxidase 3 (GPX3), α-synuclein (SNCA) and endothelial nitrogen-oxide synthase (eNOS) genes. Furthermore, atherosclerotic lesions in rabbits were reduced by intake of A. blazei powder. Therefore, A. blazei may be useful for preventing atherosclerosis via dual roles in cell signaling, suppression of macrophage development and the recovery of endothelial cells from vascular damage.

Asynchronous contraction of the 2 ventricles caused by ventricular pacing after a Fontan-type operation in a patient with a biventricular heart.

We treated a 6-year-old boy who had polysplenia syndrome and tetralogy of Fallot with a small right ventricle (RV), an atrial septal defect, a hemiazygos connection, and bilateral superior vena cava. Because the RV was too small for a biventricular repair to be performed, the patient underwent a total cavopulmonary shunt operation although his heart was biventricular and a pacemaker (VVI) had been implanted for management of the sick sinus syndrome complicated by polysplenia syndrome. After the operation, marked asynchronous contraction was noted between the morphological right and left ventricles and was probably responsible for the low cardiac output noted in this patient. In order to clarify the significance of the asynchronous contraction, we determined the cause of the low cardiac output by studying the time course of the volume changes in the morphological right and left ventricles during a cardiac cycle by using angiograms. In addition, we studied the interventricular flow dynamics by using pulsed-Doppler echocardiography. After a Fontan-type operation is performed on patients with a biventricular heart, the 2 ventricles may not function in perfect coordination when they have to work as 1 unit. These patients are likely to develop cardiac dysfunction due to interventricular to-and-fro flow dynamics. Asynchronous contraction between the 2 ventricles caused by abnormal interventricular conduction impaired the cardiac performance in the present case.

Beta-blocker therapy for cardiac dysfunction in patients with muscular dystrophy.

BACKGROUND: In muscular dystrophy, cardiac function deteriorates with time and heart failure is one of the major causes of death. Although the combination of angiotensin-converting enzyme inhibitors (ACEI) and beta-blockers improves cardiac function in adults, little is known about the efficacy of those drugs in patients with muscular dystrophy. METHODS AND RESULTS: The effect of the beta-blocker, carvedilol, and/or ACEI on ventricular function in patients with muscular dystrophy was studied. Carvedilol and an ACEI were given to 13 patients (ACEI group; mean age 18 years, range 7-27 years), and an ACEI only to 15 patients (carvedilol group; mean age 15 years, range 8-29 years). Diagnoses included Duchenne muscular dystrophy (n=25), Fukuyama muscular dystrophy (n=2), and Emery-Dreifuss muscular dystrophy (n=1). Echocardiographic parameters of the left ventricle were measured during the 2-3 years of follow-up. In the carvedilol group, combination therapy of carvedilol and an ACEI for 2 years resulted in a significant increase in left ventricular fractional shortening (LVFS). In the ACEI group, there was no significant change in LVFS. Left ventricular end-diastolic dimension increased in the ACEI group, but not in the carvedilol group. CONCLUSION: Carvedilol plus an ACEI improves left ventricular systolic function in patients with muscular dystrophy.

Cardiac involvement in Fukuyama-type congenital muscular dystrophy.

BACKGROUND: Fukuyama-type congenital muscular dystrophy is an autosomal recessive disorder characterized by generalized skeletal muscle weakness and hypotonia from early infancy and by mental retardation. Little is known about cardiac involvement in patients with Fukuyama-type congenital muscular dystrophy. This study evaluated whether cardiac involvement exists in patients with Fukuyama-type congenital muscular dystrophy. METHODS AND RESULTS: We evaluated left ventricular function using M-mode and Doppler echocardiography in 34 patients with Fukuyama-type congenital muscular dystrophy. The age ranged from 6 months to 30 years (median: 6 years). A total of 64 recordings were analyzed. Left ventricular dimensions and parameters of systolic function measured included left ventricular end-diastolic dimension, left ventricular fractional shortening, left ventricular wall thickness, and the mean velocity of circumferential fiber shortening and end-systolic wall stress relationship. Left ventricular end-diastolic dimension z score >2 was observed in 2 patients (6%). Left ventricular fractional shortening <0.28 and/or reduced mean velocity of circumferential fiber shortening in the mean velocity of circumferential fiber shortening-end-systolic wall stress relationship were observed in 16 patients (47%). A significant correlation between age and left ventricular fractional shortening was observed, and left ventricular fractional shortening decreased with age. Of 12 patients >15 years of age, 10 (83%) showed decreased left ventricular systolic function. Left ventricular fractional shortening was normal in most patients <10 years of age, and it was reduced in most patients >15 years of age. Five patients died of heart failure or respiratory problems, and a histologic examination confirmed the presence of myocardial fibrosis. No patients showed increased left ventricular wall thickness or a conduction abnormality on electrocardiograms. CONCLUSION: Cardiac involvement exists in patients with Fukuyama-type congenital muscular dystrophy and becomes evident in older children in the second decade. A cardiac evaluation, including echocardiograms and subsequent follow-up, is important, especially in patients >10 years of age.

Targeted disruption of hesr2 results in atrioventricular valve anomalies that lead to heart dysfunction.

Genes involved in the Notch signaling pathway have been shown to be critical regulators of cardiovascular development. In vitro studies have revealed that the Notch signaling pathway directly regulates transcription of hairy and enhancer of split-related (hesr) genes, encoding basic helix-loop-helix transcription factors. To assess the functional role of hesr genes in cardiovascular development, we generated mice with a targeted disruption of the hesr2 gene and used echocardiography to analyze heart function of the mutant mice. In the early postnatal period, a majority of hesr2 homozygous mice die as a result of congestive heart failure accompanied by pronounced heart enlargement. Transthoracic echocardiography on 5-day-old homozygous mice revealed tricuspid and mitral valve regurgitation and a dilated left ventricular chamber with markedly diminished fractional shortening of the left ventricle. The hemodynamic anomalies were accompanied by morphological changes, such as dysplastic atrioventricular (AV) valves, a perimembranous ventricular septal defect, and a secundum atrial septal defect. AV valve regurgitations attributable to dysplasia of the AV valves were most likely responsible for the heart dysfunction in hesr2 homozygous mice. These observations indicate that the Notch signaling target hesr2 plays an important role in the formation and function of the AV valves. In addition, hesr2 activity may be important for proper development of cardiomyocytes, thereby assuring normal left ventricular contractility. Because of the unique spectrum of cardiac anomalies expressed by hesr2-null mice, they represent a useful model system for elucidating the genetic basis of heart dysfunction.