A deep learning framework for noninvasive fetal ECG signal extraction.

Introduction: The availability of proactive techniques for health monitoring is essential to reducing fetal mortality and avoiding complications in fetal wellbeing. In harsh circumstances such as pandemics, earthquakes, and low-resource settings, the incompetence of many healthcare systems worldwide in providing essential services, especially for pregnant women, is critical. Being able to continuously monitor the fetus in hospitals and homes in a direct and fast manner is very important in such conditions. Methods: Monitoring the health of the baby can potentially be accomplished through the computation of vital bio-signal measures using a clear fetal electrocardiogram (ECG) signal. The aim of this study is to develop a framework to detect and identify the R-peaks of the fetal ECG directly from a 12 channel abdominal composite signal. Thus, signals were recorded noninvasively from 70 pregnant (healthy and with health conditions) women with no records of fetal abnormalities. The proposed model employs a recurrent neural network architecture to robustly detect the fetal ECG R-peaks. Results: To test the proposed framework, we performed both subject-dependent (5-fold cross-validation) and independent (leave-one-subject-out) tests. The proposed framework achieved average accuracy values of 94.2% and 88.8%, respectively. More specifically, the leave-one-subject-out test accuracy was 86.7% during the challenging period of vernix caseosa layer formation. Furthermore, we computed the fetal heart rate from the detected R-peaks, and the demonstrated results highlight the robustness of the proposed framework. Discussion: This work has the potential to cater to the critical industry of maternal and fetal healthcare as well as advance related applications.

Three-dimensional cardiac magnetic resonance allows the identification of slow-conducting anatomical isthmuses in tetralogy of Fallot.

BACKGROUND AND AIMS: Patients with repaired tetralogy of Fallot remain at risk of life-threatening ventricular tachycardia related to slow-conducting anatomical isthmuses (SCAIs). Preventive ablation of SCAI identified by invasive electroanatomical mapping is increasingly performed. This study aimed to non-invasively identify SCAI using 3D late gadolinium enhancement cardiac magnetic resonance (3D-LGE-CMR). METHODS: Consecutive tetralogy of Fallot patients who underwent right ventricular electroanatomical mapping (RV-EAM) and 3D-LGE-CMR were included. High signal intensity threshold for abnormal myocardium was determined based on direct comparison of bipolar voltages and signal intensity by co-registration of RV-EAM with 3D-LGE-CMR. The diagnostic performance of 3D-LGE-CMR to non-invasively identify SCAI was determined, validated in a second cohort, and compared with the discriminative ability of proposed risk scores. RESULTS: The derivation cohort consisted of 48 (34 ± 16 years) and the validation cohort of 53 patients (36 ± 18 years). In the derivation cohort, 78 of 107 anatomical isthmuses (AIs) identified by EAM were normal-conducting AI, 22 were SCAI, and 7 blocked AI. High signal intensity threshold was 42% of the maximal signal intensity. The sensitivity and specificity of 3D-LGE-CMR for identifying SCAI or blocked AI were 100% and 90%, respectively. In the validation cohort, 85 of 124 AIs were normal-conducting AI, 36 were SCAI, and 3 blocked AI. The sensitivity and specificity of 3D-LGE-CMR were 95% and 91%, respectively. All risk scores showed an at best modest performance to identify SCAI (area under the curve ≤ .68). CONCLUSIONS: 3D late gadolinium enhancement cardiac magnetic resonance can identify SCAI with excellent accuracy and may refine non-invasive risk stratification and patient selection for invasive EAM in tetralogy of Fallot.

Mechanosensing regulates tissue repair program in macrophages.

Tissue-resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a noncanonical, integrin-independent mechanism analogous to amoeboid migration. We find that these cytoskeletal dynamics also integrate biochemical signaling by colony-stimulating factor 1 and ultimately regulate chromatin accessibility to control the mechanosensitive gene expression program. This study identifies an "amoeboid" mode of ECM mechanosensing through which macrophages may regulate tissue repair and fibrosis.

Efficacy of Cefiderocol, a Novel Siderophore Cephalosporin, against Multidrug Resistant Acinetobacter baumannii Clinical Isolates in Japan.

Multidrug-resistant Acinetobacter baumannii (MDRAB) is an important pathogen that causes nosocomial infections and is resistant to almost all antibiotics, including carbapenems. Cefiderocol is a novel siderophore cephalosporin active against a broad spectrum of gram-negative bacteria. However, the susceptibility of MDRAB to cefiderocol has not yet been reported in Japan. In this study, we measured the minimum inhibitory concentrations (MICs) of antibiotics including cefiderocol against MDRAB clinical isolates collected during a nosocomial outbreak between 2009 and 2010 at the Teikyo University Hospital in Japan. We found that all 10 MDRAB clinical isolates tested were susceptible to cefiderocol, with an MIC range of 0.12 to 1 µg/mL. All the isolates also exhibited resistance to ampicillin-sulbactam and an intermediate resistance to colistin, whereas nine of them were susceptible to tigecycline. DNA sequencing revealed that all strains harbored an OXA-51-like carbapenemase, a major cause of carbapenem resistance in A. baumannii in Japan. In conclusion, this study showed that the cefiderocol susceptibility of MDRAB clinical isolates in Japan was equivalent to that to colistin or tigecycline, and thus cefiderocol is a potential treatment option for MDRAB infections.

Evaluation of Statistical Approaches in Developing a Predictive Model of Severe COVID-19 during Early Phase of Pandemic with Limited Data Resources.

As evidence of risk factors for severe cases of coronavirus disease 2019 (COVID-19) was uncertain in early phases of the pandemic, the development of an efficient predictive model for severe cases to triage high-risk individuals represented an urgent yet challenging issue. It is crucial to select appropriate statistical models when available data and evidence are limited. This study was conducted to assess the accuracy of different statistical models in predicting severe cases using demographic data from patients with COVID-19 prior to the emergence of consequential variants. We analyzed data from 929 consecutive patients diagnosed with COVID-19 prior to March 2021, including their age, sex, body mass index, and past medical histories, and compared areas under the receiver operating characteristic curve (ROC AUC) between different statistical models. The random forest (RF) model, deep learning (DL) models with not too many neurons, and naïve Bayes model exhibited AUC measures of > 0.70 with the validation datasets. The naïve Bayes model performed the best with the AUC measures of > 0.80. The accuracies in RF were more robust with narrower distribution of AUC measures compared to those in DL. The benefit of performing feature selection with a training dataset before building models was seen in some models, but not in all models. In summary, the naïve Bayes and RF models exhibited ideal predictive performance even with limited available data. The benefit of performing feature selection before building models with limited data resources depended on machine learning methods and parameters.

Mapping and Ablation of Ventricular Tachycardia in Inherited Left Ventricular Cardiomyopathies.

Advances in the field of human genetics have led to an accumulating understanding of the genetic basis of distinct nonischemic cardiomyopathies associated with ventricular tachycardias (VTs) and sudden cardiac death. To date, there is an increasing proportion of patients with inherited cardiomyopathies requiring catheter ablation for VTs. This review provides an overview of disease-causing gene mutations frequently encountered and relevant for clinical electrophysiologists. Available data on VT ablation in patients with an inherited etiology and a phenotype of a nondilated left ventricular cardiomyopathy, dilated cardiomyopathy, or hypertrophic cardiomyopathy are summarized. VTs amenable to catheter ablation are related to nonischemic fibrosis. Recent insights into genotype-phenotype relations of subtype and location of fibrosis have important implications for treatment planning. Current strategies to delineate nonischemic fibrosis and related arrhythmogenic substrates using multimodal imaging, image integration, and electroanatomical mapping are provided. The ablation approach depends on substrate location and extension. Related procedural aspects including patient-tailored (enhanced) ablation strategies and outcomes are outlined. Challenging substrates for VT and the underlying inherited etiologies with a high risk for rapid progressive heart failure contribute to poor outcomes after catheter ablation. Electroanatomical data obtained during ablation may allow the identification of patients at particular risk who need to be considered for early work-up for left ventricular assist device implantation or heart transplantation.

Investigating the association of maternal heart rate variability with fetal birth weight.

Maternal heart rate (HR) was reported to affect birth weight and birth outcomes. Low birth weight constitutes a major health problem, and it is estimated that around 15% to 20% of births worldwide are low weight. In our previous study, we discussed the presence of similarities between maternal and fetal HRs, therefore, here, we propose to develop a parameter based on maternal and fetal HR variability (HRV) to divide data into two patterns to investigate the association of fetal birth weight with maternal HR and HRV. The parameter was derived from non-invasive records of maternal and fetal electrocardiograms (ECGs) that were collected from 78 subjects (age: 22 - 44 years old, gestational age (GA): 19 - 40 weeks). The HRV parameter was calculated by first evaluating the standard deviation (SD) of the number of R peaks occurring per 2 seconds (snRpp2s). Then, the difference between maternal and fetal snRpp2s (dmf) was calculated. The correlation between our derived parameter [dmf] with GA revealed a significant correlation that suggested the dmf's association with fetal development. The association analysis results between birthweight with maternal HR and HRV per pattern showed that significant negative correlations exist between them in one pattern. Still, the same correlations were not observed in the other pattern. This study's findings emphasise maternal health's role in fetal development assessment. In addition, this study highlights the importance of developing novel factors for properly assessing fetal development and birth outcomes.

Prediction of fetal RR intervals from maternal factors using machine learning models.

Previous literature has highlighted the importance of maternal behavior during the prenatal period for the upbringing of healthy adults. During pregnancy, fetal health assessments are mainly carried out non-invasively by monitoring fetal growth and heart rate (HR) or RR interval (RRI). Despite this, research entailing prediction of fHRs from mHRs is scarce mainly due to the difficulty in non-invasive measurements of fetal electrocardiogram (fECG). Also, so far, it is unknown how mHRs are associated with fHR over the short term. In this study, we used two machine learning models, support vector regression (SVR) and random forest (RF), for predicting average fetal RRI (fRRI). The predicted fRRI values were compared with actual fRRI values calculated from non-invasive fECG. fRRI was predicted from 13 maternal features that consisted of age, weight, and non-invasive ECG-derived parameters that included HR variability (HRV) and R wave amplitude variability. 156 records were used for training the models and the results showed that the SVR model outperformed the RF model with a root mean square error (RMSE) of 29 ms and an average error percentage (< 5%). Correlation analysis between predicted and actual fRRI values showed that the Spearman coefficient for the SVR and RF models were 0.31 (P < 0.001) and 0.19 (P < 0.05), respectively. The SVR model was further used to predict fRRI of 14 subjects who were not included in the training. The latter prediction results showed that individual error percentages were (≤ 5%) except in 3 subjects. The results of this study show that maternal factors can be potentially used for the assessment of fetal well-being based on fetal HR or RRI.

GM-CSF receptor/SYK/JNK/FOXO1/CD11c signaling promotes atherosclerosis.

Atherosclerosis complicates chronic inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus, suggesting that a shared physiological pathway regulates inflammatory responses in these diseases wherein spleen tyrosine kinase (SYK) is involved. We aimed to identify a shared therapeutic target for atherosclerosis and inflammatory diseases. We used Syk-knockout atherosclerosis-prone mice to determine whether SYK is involved in atherosclerosis via the inflammatory response and elucidate the mechanism of SYK signaling. The Syk-knockout mice showed reduced atherosclerosis in vivo, and macrophages derived from this strain showed ameliorated cell migration in vitro. CD11c expression decreased on Syk-knockout monocytes and macrophages; it was upregulated by forkhead box protein O1 (FOXO1) after stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF), and c-Jun amino-terminal kinase (JNK) mediated SYK signaling to FOXO1. Furthermore, FOXO1 inhibitor treatment mitigated atherosclerosis in mice. Thus, GM-CSF receptor/SYK/JNK/FOXO1/CD11c signaling in monocytes and macrophages and FOXO1 could be therapeutic targets for atherosclerosis and inflammatory diseases.

The R″ wave in V1 and the negative terminal QRS vector in aVF combine to a novel 12-lead ECG algorithm to identify slow conducting anatomical isthmus 3 in patients with tetralogy of Fallot.

AIMS: Patients with repaired tetralogy of Fallot (rTOF) have an increased risk of ventricular tachycardia (VT), with slow conducting anatomical isthmus (SCAI) 3 as dominant VT substrate. In patients with right bundle branch block (RBBB), SCAI 3 leads to local activation delay with a shift of terminal RV activation towards the lateral RV outflow tract which may be detected by terminal QRS vector changes on sinus rhythm electrocardiogram (ECG). METHODS AND RESULTS: Consecutive rTOF patients aged ≥16 years with RBBB who underwent electroanatomical mapping at our institution between 2017-2022 and 2010-2016 comprised the derivation and validation cohort, respectively. Forty-six patients were included in the derivation cohort (aged 40±15 years, QRS duration 165±23 ms). Among patients with SCAI 3 (n = 31, 67%), 17 (55%) had an R″ in V1, 18 (58%) had a negative terminal QRS portion (NTP) ≥80 ms in aVF, and 12 (39%) had both ECG characteristics, compared to only 1 (7%), 1 (7%), and 0 patient without SCAI, respectively.Combining R″ in V1 and/or NTP ≥80 ms in aVF into a diagnostic algorithm resulted in a sensitivity of 74% and specificity of 87% in detecting SCAI 3. The inter-observer agreement for the diagnostic algorithm was 0.875. In the validation cohort [n = 33, 18 (55%) with SCAI 3], the diagnostic algorithm had a sensitivity of 83% and specificity of 80% for identifying SCAI 3. CONCLUSION: A sinus rhythm ECG-based algorithm including R″ in V1 and/or NTP ≥80 ms in aVF can identify rTOF patients with a SCAI 3 and may contribute to non-invasive risk stratification for VT.

Staphylococcus haemolyticus attenuates the antibacterial effect of teicoplanin via aggregates and biofilms.

OBJECTIVES: This study aimed to determine the inhibitory and bactericidal effects of teicoplanin (TEC) on TEC-susceptible Staphylococcus haemolyticus isolated from a patient with cancer in whom infection persisted despite TEC therapy. We also focused on the biofilm-forming ability of the isolate in vitro. METHODS: S. haemolyticus clinical isolate (strain 1369A) and its control strain, ATCC 29970 were cultured in Luria-Bertani (LB) broth with TEC. The inhibitory and bactericidal effects of TEC on planktonic, adherent, biofilm-dispersed, and biofilm-embedded cells of these strains were analyzed by using a biofilm formation/viability assay kit. The expression of biofilm-related genes was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Biofilm formation was determined by using scanning electron microscopy (SEM). RESULTS: The clinical isolate of S. haemolyticus had enhanced ability to bacterial growth, adherence, aggregation, and biofilm formation, thus the inhibitory and bactericidal effects of TEC on planktonic, adherent, biofilm-dispersed, and biofilm-embedded cells of the isolate were attenuated. Additionally, TEC induced cell aggregation, biofilm formation, and some biofilm-related gene expression of the isolate. CONCLUSION: The clinical isolate of S. haemolyticus is resistant to TEC treatment due to cell aggregation and biofilm formation.

Volume-Weighted Unipolar Voltage Predicts Heart Failure Mortality in Patients With Dilated Cardiomyopathy and Ventricular Arrhythmias.

BACKGROUND: Patients with dilated cardiomyopathy (DCM) who are undergoing catheter ablation of ventricular arrhythmias (VAs) are at risk of rapidly progressive heart failure (HF). Endocardial voltages decrease with loss of viable myocardium. Global left ventricular (LV) voltage as a surrogate for the amount of remaining viable myocardium may predict prognosis. OBJECTIVES: This study evaluated whether the newly proposed parameter volume-weighted (vw) unipolar voltage (UV) can predict HF-related adverse outcomes (HFOs), including death, heart transplantation, or ventricular assist device implantation, in DCM. METHODS: In consecutive patients with DCM referred for VA ablation, vwUV was calculated by mathematically integrating UV over the left ventricle, divided by the endocardial LV surface area and wall thickness. Patients were followed for HFOs. RESULTS: A total of 103 patients (57 ± 14 years of age; left ventricular ejection fraction [LVEF], 39% ± 13%) were included. Median vwUV was 9.75 (IQR: 7.27-12.29). During a median follow-up of 24 months (IQR: 8-47 months), 25 patients (24%) died, and 16 had HFOs 7 months (IQR: 1-18 months) after ablation. Patients with HFOs had significantly lower LVEF (29% ± 10% vs 41% ± 12%), vw bipolar voltage (BV) (3.00 [IQR: 2.47-3.53] vs 5.00 [IQR: 4.12-5.73]), and vwUV (5.94 [IQR: 5.28-6.55] vs 10.37 [IQR: 8.82-12.81]; all P < 0.001), than patients without HFOs. In Cox regression analysis and goodness-of-fit tests, vwUV was the strongest and independent predictor for HFOs (HR: 3.68; CI: 2.09-6.45; likelihood ratio chi-square, 33.05; P < 0.001). CONCLUSIONS: The novel parameter vwUV, as a surrogate for the amount of viable myocardium, identifies patients with DCM with VA who are at high risk for HF progression and mortality.

Pleomorphic Ventricular Tachycardia in Dilated Cardiomyopathy Predicts Ventricular Tachycardia Recurrence After Ablation Independent From Cardiac Function: Comparison With Patients With Ischemic Heart Disease.

BACKGROUND: In dilated cardiomyopathy (DCM), outcome after catheter ablation of ventricular tachycardia (VT) is modest, compared with ischemic heart disease (IHD). Pleomorphic VT (PL-VT) has been associated with fibrotic remodeling and end-stage heart failure in IHD. The prognostic role of PL-VT in DCM is unknown. METHODS: Consecutive IHD (2009-2016) or DCM (2008-2018) patients undergoing ablation for monomorphic VT were included. PL-VT was defined as ≥1 spontaneous change of the 12-lead VT-morphology during the same induced VT episode. Patients were followed for VT recurrence and mortality. RESULTS: A total of 247 patients (86% men; 63±13 years; IHD n=152; DCM n=95) underwent ablation for monomorphic VT. PL-VT was observed in 22 and 29 patients with IHD and DCM, respectively (14% versus 31%, P=0.003). In IHD, PL-VT was associated with lower LVEF (28±9% versus 34±12%, P=0.02) and only observed in those with LVEF<40%. In contrast, in DCM, PL-VT was not related to LVEF and induced in 27% of patients with LVEF>40%. During a median follow-up of 30 months, 79 (32%) patients died (IHD 48; DCM 31; P=0.88) and 120 (49%) had VT recurrence (IHD 59; DCM 61; P<0.001). PL-VT was associated with mortality in IHD but not in DCM. In IHD, VT recurrence was independently associated with LVEF, number of induced VTs, and procedural noncomplete success. Of note, in DCM, PL-VT (HR, 2.62 [95% CI, 1.47-4.69]), pathogenic mutation (HR, 2.13 [95% CI, 1.16-3.91]), and anteroseptal VT substrate (HR, 1.75 [95% CI, 1.00-3.07]) independently predicted VT recurrence. CONCLUSIONS: In IHD, PL-VT was associated with low LVEF and mortality. In DCM, PL-VT was not associated with mortality but a predictor of VT recurrence independent from LVEF. PL-VT in DCM may indicate a specific arrhythmic substrate difficult to control by current ablation techniques.

Correlation between maternal and fetal heart rate increases with fetal mouse age in typical development and is disturbed in autism mouse model treated with valproic acid.

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.

Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, "VasSF," based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj). Apolipoprotein A-2 (ApoA2) has been identified as one of VasSF's target molecules. METHODS: Here, we tested the potential of anti-apolipoprotein A-2 antibodies (anti-ApoA2) as a new therapeutic drug against KD by examining its effect on a mouse model, in which KD was induced via Candida albicans water-soluble fraction (CAWS). CAWS (2 mg/mouse) was injected intraperitoneally into C57BL/6NCrSlc mice for five consecutive days. The incidence and histological severity of vasculitis in CAWS-induced coronary arteritis in mice administered anti-ApoA2 was examined. The following experimental groups were tested: solvent (only PBS (-) injection); anti-ApoA2 antibodies at dosages of 0.05 mg, 0.1 mg, and 0.5 mg/kg/day; human IgG at 0.1 mg/kg/day. RESULTS: The group treated with anti-ApoA2 0.5 mg/kg/day showed a lower incidence of panvasculitis induced by CAWS, less inflammation of the coronary arteries and aortic roots, and lower levels of serum IL-6, M-CSF, and MIP-1α and 32 cytokines/chemokines compared with those in the solvent group. CONCLUSIONS: The anti-ApoA2 treatment suppressed the development of coronary arteritis in an animal KD model and anti-ApoA2 shows potential as an effective therapeutic candidate for the treatment of KD vasculitis. The use of specific antibodies that display higher vasculitis-suppressing effects, such as anti-ApoA2, may attenuate KD as well as other infectious diseases, with less severe adverse side effects than treatment with IVIg.

Similarities between maternal and fetal RR interval tachograms and their association with fetal development.

An association between maternal and fetal heart rate (HR) has been reported but, so far, little is known about its physiological implication and importance relative to fetal development. Associations between both HRs were investigated previously by performing beat-by-beat coupling analysis and correlation analysis between average maternal and fetal HRs. However, studies reporting on the presence of similarities between maternal and fetal HRs or RR intervals (RRIs) over the short term (e.g., 5-min) at different gestational ages (GAs) are scarce. Here, we demonstrate the presence of similarities in the variations exhibited by maternal and fetal RRl tachograms (RRITs). To quantify the same similarities, a cross-correlation (CC) analysis between resampled maternal and fetal RRITs was conducted; RRITs were obtained from non-invasive electrocardiogram (ECG). The degree of similarity between maternal and fetal RRITs (bmfRRITs) was quantified by calculating four CC coefficients. CC analysis was performed for a total of 330 segments (two 5-min segments from 158 subjects and one 5-min from 14 subjects). To investigate the association of the similarity bmfRRITs with fetal development, the linear correlation between the calculated CC coefficients and GA was calculated. The results from the latter analysis showed that similarities bmfRRITs are common occurrences, they can be negative or positive, and they increase with GA suggesting the presence of a regulation that is associated with proper fetal development. To get an insight into the physiological mechanisms involved in the similarity bmfRRITs, the association of the same similarity with maternal and fetal HR variability (HRV) was investigated by comparing the means of two groups in which one of them had higher CC values compared to the other. The two groups were created by using the data from the 158 subjects where fetal RRI (fRRI) calculation from two 5-min ECG segments was feasible. The results of the comparison showed that the maternal very low frequency (VLF) HRV parameter is potentially associated with the similarity bmfRRITs implying that maternal hormones could be linked to the regulations involved in the similarity bmfRRITs. Our findings in this study reinforce the role of the maternal intrauterine environment on fetal development.

Ventricular Tachycardia Ablation in Adult Congenital Heart Disease.

Patients with congenital heart disease (CHD) are at risk for late ventricular tachycardia (VT) and sudden cardiac death. Slow conducting anatomical isthmuses, bordered by unexcitable tissue created by valve annuli, ventricular incisions, and prosthetic material are the dominant substrate for macroreentrant monomorphic VTs in repaired CHD. These well-defined substrates allow for catheter or surgical transection with clear endpoints. This review elaborates on VT substrates in various CHD, and evolving mapping and ablation approaches. Because most research is conducted in patients with repaired tetralogy of Fallot, this malformation will serve as a paradigm.

Ventricular Arrhythmia Substrate Distribution and Its Relation to Sympathetic Innervation in Nonischemic Cardiomyopathy Patients.

BACKGROUND: Nonischemic cardiomyopathy patients referred for catheter ablation of ventricular arrhythmias (VAs) typically have either inferolateral (ILS) or anteroseptal (ASS) VA substrate locations, with poorer outcomes for ASS. Sympathetic denervation is an important determinant of arrhythmogenicity. Its relation to nonischemic fibrosis in general and to the different VA substrates is unknown. OBJECTIVES: This study sought to evaluate the association between VA substrates, myocardial fibrosis, and sympathetic denervation. METHODS: Thirty-five patients from the Leiden Nonischemic Cardiomyopathy Study, who underwent electroanatomic voltage mapping and iodine-123 metaiodobenzylguanidine imaging between 2011 and 2018 were included. Late gadolinium-enhanced cardiac magnetic resonance data were collected when available. The relation between global cardiac sympathetic innervation and area-weighted unipolar voltage (UV) as a surrogate for diffuse fibrosis was evaluated. For regional analysis, patients were categorized as ASS or ILS. The distribution of low UV, sympathetic denervation, and late gadolinium enhancement (LGE) scar were compared using the 17-segment model. RESULTS: Median area-weighted UV was 12.3 mV in patients with normal sympathetic innervation and 8.7 mV in patients with sympathetic denervation. Global sympathetic denervation correlated with diffuse myocardial fibrosis (R = 0.53; P = 0.02). ILS (n = 13) matched with low UV, sympathetic denervation, and LGE scar in all patients, whereas ASS (n = 11) matched with low UV in all patients, with LGE scar in 63% (P = 0.20), but with sympathetic denervation in only 27% of patients (P = 0.0002). CONCLUSIONS: Global cardiac sympathetic denervation is related to fibrosis in nonischemic cardiomyopathy patients with VA. The mismatch between regional fibrosis and preserved innervation for ASS may contribute to a VA substrate difficult to control by catheter ablation.

Deep learning identifies cardiac coupling between mother and fetus during gestation.

In the last two decades, stillbirth has caused around 2 million fetal deaths worldwide. Although current ultrasound tools are reliably used for the assessment of fetal growth during pregnancy, it still raises safety issues on the fetus, requires skilled providers, and has economic concerns in less developed countries. Here, we propose deep coherence, a novel artificial intelligence (AI) approach that relies on 1 min non-invasive electrocardiography (ECG) to explain the association between maternal and fetal heartbeats during pregnancy. We validated the performance of this approach using a trained deep learning tool on a total of 941 one minute maternal-fetal R-peaks segments collected from 172 pregnant women (20-40 weeks). The high accuracy achieved by the tool (90%) in identifying coupling scenarios demonstrated the potential of using AI as a monitoring tool for frequent evaluation of fetal development. The interpretability of deep learning was significant in explaining synchronization mechanisms between the maternal and fetal heartbeats. This study could potentially pave the way toward the integration of automated deep learning tools in clinical practice to provide timely and continuous fetal monitoring while reducing triage, side-effects, and costs associated with current clinical devices.

Model-based estimation of QT intervals of mouse fetal electrocardiogram.

BACKGROUND: Abnormal prolongation in the QT interval or long QT syndrome (LQTS) is associated with several cardiac complications such as sudden infant death syndrome (SIDS). LQTS is believed to be linked to genetic mutations which can be understood by using animal models, such as mice models. Nevertheless, the research related to fetal QT interval in mice is still limited because of challenges associated with T wave measurements in fetal electrocardiogram (fECG). Reliable measurement of T waves is essential for estimating their end timings for QT interval assessment. RESULTS: A mathematical model was used to estimate QT intervals. Estimated QT intervals were validated with Q-aortic closure (Q-Ac) intervals of Doppler ultrasound (DUS) and comparison between both showed good agreement with a correlation coefficient higher than 0.88 (r > 0.88, P < 0.05). CONCLUSION: Model-based estimation of QT intervals can help in better understanding of QT intervals in fetal mice.