Prenatal uptake of valproic acid (VPA) was associated with increased risk of fetal cardiac anomalies and autism spectrum disorder (ASD), but uptake of VPA is considered the only effective treatment for epilepsy and other neurological disorders. Up until now, little is known about the effect of VPA on maternal – fetal heart rate (HR) coupling patterns; therefore, this study aims at studying such patterns in mice on embryonic day 15.5 (E15.5). At E12.5, 8 mothers were injected with VPA (VPA group) and another 8 mothers were injected with saline (control group). At E15.5, electrocardiogram (ECG) records of 15 minutes were collected from the 16 mothers and 25 fetuses. A maximum of 5-minutes and a minimum of 1-minute were selected from the ECG data for analysis. Mean RR intervals and coupling ratios and their occurrence percentages were calculated per 1minute. 1-minute analysis was done for periods with no arrhythmia and clear R peaks. The total number of 1-minute segments that were analyzed was 56 for the saline group and 54 for the VPA group. The correlation analysis between the 1:3 and 2:6 coupling ratios and RR intervals revealed that the ratios were significantly correlated in the saline group, whereas no significant correlations were observed in the VPA group. The results further revealed that fetal RR intervals are strongly correlated with maternal RR intervals in the saline group, but the same correlation is different in the VPA group. The presented results imply that maintaining certain coupling patterns are important for proper fetal cardiac development and maternal uptake of VPA may affect maternal-fetal HRs interactions.
Risk stratification of ventricular arrhythmias is vital to the optimal management in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect isolated late activation (ILA) by overcoming the limitations of conventional noninvasive predictors of ventricular tachyarrhythmias, including epsilon waves, late potential (LP), and right ventricular ejection fraction (RVEF), in ARVC patients.Methods and Results:We evaluated ILA on MCG, defined as discrete activations re-emerging after the decay of main RV activation (%magnitude >5%), and conventional noninvasive predictors of ventricular tachyarrhythmias (epsilon waves, LP, and RVEF) in 40 patients with ARVC. ILA was noted in 24 (60%) patients. Most ILAs were found in RV lateral or inferior areas (17/24, 71%). We defined "delayed ILA" as ILA in which the conduction delay exceeded its median (50 ms). During a median follow-up of 42.5 months, major arrhythmic events (MAEs: 1 sudden cardiac death, 3 sustained ventricular tachycardias, and 4 appropriate implantable cardioverter defibrillator discharges) occurred more frequently in patients with delayed ILA (6/12) than in those without (2/28; log-rank: P=0.004). Cox regression analysis identified delayed ILA as the only independent predictor of MAEs (hazard ratio 7.63, 95% confidence interval 1.72-52.6, P=0.007), and other noninvasive parameters were not significant predictors.MCG is useful to identify ARVC patients at high risk of future lethal ventricular arrhythmias.
This study aims to investigate the associations of maternal-fetal demographic information (age, gestational age, and body mass index (BMI)) and heart rate variability with their cardiac coupling mechanisms during pregnancy. Coupling was determined from one-minute maternal-fetal electrocardio-graphy (ECG) signals in 172 pregnant women using phase coherence (λ) calculations. Accordingly, variables such as gestational age, maternal BMI, and maternal-fetal heart rate were found significant (p-value < 0.05) in discriminating between [1:2], [2:3], and [3:5] coupling scenarios. The results suggest the importance of maternal-fetal parameters and ECG recordings in the assessment of fetal well-being during pregnancy. Clinical Relevance-The maternal psychophysiological states are highly correlated with the fetal cardiac system. Accurate characterization of this correlation leads to better clinical assessment protocols and treatment plans to prevent many stillbirth cases
Introduction Autism spectrum disorder (ASD) is considered a significant behavioral problem that is characterized by impairment in social interaction and communication. It is believed that some cases of ASD originate in the intrauterine maternal environment. Therefore, we hypothesized that there might be qualitative changes in the interaction between the mother and fetus in ASD during the prenatal period, hence, we investigated the similarity patterns between maternal and fetal heart rate (HR). Methods In this study, we first demonstrate the presence and formation of similarities between maternal and fetal RR interval (RRI) collected from typical developmental mice at different embryonic days (EDs), ED13.5, ED15.5, ED17.5, and ED18.5. The similarities were quantified by means of cross-correlation (CC) and magnitude-squared coherence (MSC) analyses. Correlation analysis between the CC coefficients and EDs and between MSC coefficients and EDs showed that the same coefficients increase with EDs, suggesting that similarities between maternal and fetal RRI are associated with typical fetal development. Next, because maternal and fetal similarities were indicative of development, a comparison analysis between the autism mouse model (injected with valproic acid (VPA)), and the control group (injected with saline) was performed for ED15.5 and ED18.5. Results The results of the comparison showed that the CC and MSC coefficients of VPA fetuses were significantly lower than that of the control group. The lower coefficients in VPA-treated mice suggest that they could be one of the features of ASD symptoms. The findings of this study can assist in identifying potential ASD causes during the prenatal period.
Background: Several studies have demonstrated the importance of mechanoelectrical interaction in patients with surgically corrected tetralogy of Fallot. However, the significance of atrioventricular conduction disturbance, that is PR interval prolongation, on adverse cardiac events in those patients remains to be elucidated. Methods: We examined electrocardiograms at baseline and their temporal change in a total of 176 patients with repaired tetralogy of Fallot (49% men; median age, 17.4 years). Then, we evaluated their correlation with right ventricular volume and function measured by cardiac magnetic resonance and the significance as a risk factor of adverse cardiac events: lethal ventricular arrhythmias, atrial arrhythmias, heart failure hospitalization, complete atrioventricular block (AVB), and all-cause death. Results: First-degree AVB was noted in 25 patients (14%). During a median follow-up of 10.0 (5.0–14.2) years, there was a progressive prolongation of PR interval (2.00±3.99 ms/y). Importantly, there were significant correlations between PR interval prolongation and right ventricular enlargement or right ventricular dysfunction. In contrast, in patients who underwent pulmonary valve replacement (n=23), significant shortening of PR interval by pulmonary valve replacement was noted (204±32 versus 176±34 ms; P =0.007). Cox regression analysis showed that first-degree AVB was an independent risk factor for lethal ventricular arrhythmias (hazard ratio, 5.479; 95% CI, 1.181–25.42; P =0.030) and complete AVB (hazard ratio, 27.67; 95% CI, 4.152–184.3; P <0.001) and had a tendency for heart failure hospitalization (hazard ratio, 3.301; 95% CI, 0.864–11.80; P =0.069). In addition, PR interval prolongation >2 ms/y was also a significant risk factor for lethal ventricular arrhythmias, regardless of the presence or absence of first-degree AVB at enrollment (hazard ratio, 24.18; 95% CI, 2.080–281.1; P =0.011). Conclusions: These results indicate that progressive atrioventricular conduction disturbance is correlated with right ventricular enlargement and could be a useful predictor for increased risk of lethal ventricular arrhythmias in patients with repaired tetralogy of Fallot.
Erythropoietin (Epo) is an important regulator of erythropoiesis and stimulates the proliferation of early erythroid precursors as well as the differentiation of late erythroid precursors of the erythroid lineage. However, recent studies have indicated that Epo also has angiogenic properties and plays an important role in the oestrogen-dependent cyclical angiogenesis within the mouse uterus. It was therefore postulated that Epo may be an important angiogenic factor in endometriosis. In order to address this hypothesis the concentration of Epo in peritoneal fluid (PF) was determined in patients with or without endometriosis. PF was collected from patients with endometriosis (n = 42) or without endometriosis (n = 18). Detectable concentrations of Epo were found in all PF samples analysed. The concentration of Epo in PF from patients with endometriosis was significantly higher than that in the control group (13.1 +/- 1.2 mIU/ml versus 7.2 +/- 0.7 mIU/ml, mean +/- SE respectively, P < 0.01). Furthermore, in patients with endometriosis the Epo concentrations in PF from patients with stage I disease (n = 17, 16.6 +/- 3.0 mIU/ml) were significantly higher than those with stage II (n = 8, 10.7 +/- 1.2 mIU/ml, P < 0.03), III (n = 13, 8.4 +/- 1.0 mIU/ml, P < 0.01), IV disease (n = 7, 7.5 +/- 1.0 mIU/ml, P < 0.01). These data suggest that Epo may play a role in the pathogenesis of endometriosis particularly in the initiation of the disease.
