Incidence of Fetal Arrhythmia Before and During the COVID-19 Pandemic: A Single-Center Experience.

Fetal arrhythmias are rare and carry significant morbidity and mortality without appropriate treatment. Initial reports exist of fetal arrhythmia in the setting of maternal COVID-19 infection. Our study sought to evaluate incidence of fetal arrhythmia before and during the COVID-19 pandemic at our institution. This retrospective cohort study from a tertiary care fetal cardiac center utilized the institutional REDCap database to search fetal arrhythmia diagnostic codes. Medical records of mother-fetus dyads were reviewed and data were collected on diagnoses, gestational age, treatment regimen, and postnatal outcomes. Patients were divided into pre-COVID and peri-COVID segments. 8368 total pregnancies were evaluated during the 7.3 years of study period. Forty-five patients (0.5%) had a significant fetal arrhythmia and were included in this study: 19 (42%) in the pre-COVID-19 group and 26 (58%) in the peri-COVID-19 group. No patients had associated congenital heart disease. There was a notable increase in the incidence of fetal supraventricular tachycardia (SVT) (1.82 per 1000 vs 2.65 per 1000 pregnancies) and complete heart block (1.04 per 1000 vs 1.77 per 1000 pregnancies) but no apparent change in other tachyarrhythmias during the COVID era. The proportion of antibody-mediated complete heart block increased from 50 to 87.5%. There was also an increase in the percentage of SVT patients requiring postnatal treatment during COVID-19 (53.8% vs 62.5%). Our experience shows an increased incidence of some fetal arrhythmia diagnoses during the COVID-19 pandemic. Additional multi-center studies will be necessary to fully evaluate the increased burden of fetal arrhythmias during the COVID-19 era as well as to elucidate etiology.

Abnormal fetal heart rate patterns caused by pathophysiologic processes other than fetal acidemia.

Fetal acidemia is a common final pathway to fetal death, and in many cases, to fetal central nervous system injury. However, certain fetal pathophysiological processes are associated with significant category II or category III fetal heart rate changes before the development of or in the absence of fetal acidemia. The most frequent of these processes include fetal infection and/or inflammation, anemia, fetal congenital heart disease, and fetal central nervous system injury. In the presence of significant category II or category III fetal heart rate patterns, clinicians should consider the possibility of the aforementioned fetal processes depending on the clinical circumstances. The common characteristic of these pathophysiological processes is that their associated fetal heart rate patterns are linked to increased adverse neonatal outcomes despite the absence of acidemia at birth. Therefore, in these cases, the fetal heart rate patterns may provide more insight about the fetal condition and pathophysiology than the acid-base status at birth. In addition, as successful timing of intrapartum interventions on the basis of evolution of fetal heart rate patterns aims to prevent fetal acidemia, it may not be logical to continue to use the fetal acid-base status at birth as the gold standard outcome to determine the predictive ability of category II or III fetal heart rate patterns. A more reasonable approach may be to use the umbilical cord blood acid-base status at birth as the gold standard for determining the appropriateness of the timing of our interventions.

Abnormal Microscopic Findings in the Placenta Correlate With the Severity of Fetal Heart Failure.

BACKGROUND: This study investigated the association between placental pathology and fetal heart failure.Methods and Results: Singletons with a congenital heart defect (CHD) and/or arrhythmia (n=168) and gestational age-matched controls (n=52) were included in the study. The associations between macro- and microscopic abnormal findings of the placenta and the severity of fetal heart failure were evaluated using the cardiovascular profile (CVP) score. Nine features were microscopically identified and assessed in sections of the placenta: premature villi, edematous villi, fibrotic villi, chorioamnionitis, chorangiosis, fibrin deposition, subchorionic hematoma, infarcted villi, and nucleated red blood cells in villous vessels. Among singletons with CHD and/or arrhythmia, the final CVP score was ≥8 in 140 cases, 6 or 7 in 15 cases, and ≤5 in 13 cases. Microscopic analysis showed that the frequency and severity of premature and edematous villi and increased nucleated red blood cells in villous vessels were greater in cases of fetal heart failure. These microscopic findings were more common and severe in cases with a final CVP score ≤5 than in gestational age-matched controls. The prevalence of abnormal macroscopic findings of the placenta and umbilical cord was similar regardless of the severity of fetal heart failure. CONCLUSIONS: Premature and edematous villi and increased nucleated red blood cells in villous vessels were correlated with the severity of fetal heart failure in cases of CHD and/or arrhythmia.

Treatment, not delivery, of the late preterm and term fetus with supraventricular arrhythmia.

OBJECTIVE: While in-utero treatment of sustained fetal supraventricular arrhythmia (SVA) is standard practice in the previable and preterm fetus, data are limited on best practice for late preterm (34 + 0 to 36 + 6 weeks), early term (37 + 0 to 38 + 6 weeks) and term (> 39 weeks) fetuses with SVA. We reviewed the delivery and postnatal outcomes of fetuses at ≥ 35 weeks of gestation undergoing treatment rather than immediate delivery. METHODS: This was a retrospective case series of fetuses presenting at ≥ 35 weeks of gestation with sustained SVA and treated transplacentally at six institutions between 2012 and 2022. Data were collected on gestational age at presentation and delivery, SVA diagnosis (short ventriculoatrial (VA) tachycardia, long VA tachycardia or atrial flutter), type of antiarrhythmic medication used, interval between treatment and conversion to sinus rhythm and postnatal SVA recurrence. RESULTS: Overall, 37 fetuses presented at a median gestational age of 35.7 (range, 35.0-39.7) weeks with short VA tachycardia (n = 20), long VA tachycardia (n = 7) or atrial flutter (n = 10). Four (11%) fetuses were hydropic. In-utero treatment led to restoration of sinus rhythm in 35 (95%) fetuses at a median of 2 (range, 1-17) days; this included three of the four fetuses with hydrops. Antiarrhythmic medications included flecainide (n = 11), digoxin (n = 7), sotalol (n = 11) and dual therapy (n = 8). Neonates were liveborn at 36-41 weeks via spontaneous vaginal delivery (23/37 (62%)) or Cesarean delivery (14/37 (38%)). Cesarean delivery was indicated for fetal SVA in two fetuses, atrial ectopy or sinus bradycardia in three fetuses and obstetric reasons in nine fetuses that were in sinus rhythm at the time of delivery. Twenty-one (57%) cases were treated for recurrent SVA after birth. CONCLUSION: In-utero treatment of the near term and term (≥ 35-week) SVA fetus is highly successful even in the presence of hydrops, with the majority of cases delivered vaginally closer to term, thereby avoiding unnecessary Cesarean section. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal premature atrial contractions: natural course, risk factors and adverse outcomes.

OBJECTIVE: Fetal premature atrial contractions (PACs) are usually benign, but are associated with congenital heart defects (CHDs) and tachyarrhythmias, which in turn carry a risk of cardiac failure and fetal death. We aimed to explore the frequency of adverse outcomes and to identify risk factors for tachyarrhythmias in pregnancies complicated by fetal PACs. METHODS: Fetuses diagnosed with PACs at two academic centres in Amsterdam between 2007 and 2022 were included in this retrospective cohort study. Cases with congenital anomalies or a prior diagnosis of CHD or other arrhythmias were excluded. M-mode and Doppler tracings were reanalysed and the PACs frequency recorded. We explored the incidence of adverse outcomes defined as: underlying CHDs not identified during the 20 weeks fetal anomaly scan, tachyarrhythmias, other arrhythmias, administration of antiarrhythmic therapy and death. Risk factors for tachyarrhythmias were analysed using odds ratios (OR). RESULTS: In 24% of the referred cases, PACs resolved before confirmation at the fetal medicine unit (FMU). Of the 939 included cases with proven PACs, the total incidence of adverse outcome was 6.8% (64/939). CHDs were diagnosed in 14 cases (1.5%, 95%-CI 0.9-2.5%) of which eight prenatally and six postnatally. Compared to baseline, the incidence of CHD in the presence of fetal PACs was increased (OR 1.8, 95%-CI 1.0-3.3, p=0.034). Tachyarrhythmias occurred prenatally and/or postnatally in 32 cases (3.4%) of which eight (25.0%) showed signs of cardiac failure and in 23 (71.9%) antiarrhythmic therapy was required. None of the tachyarrhythmias led to fetal or neonatal death. Risk factors for a tachyarrhythmia were: PACs with short runs of supraventricular tachycardia (OR 99), blocked PACs (OR 30), PACs in bigeminy (OR 22), frequent PACs (1 per 5-10 beats) (OR 6.9), signs of cardiac failure (OR 14) and the presence of a foramen ovale aneurysm (OR 5.0). CONCLUSIONS: PACs are generally benign and resolve often spontaneously. However, fetuses with irregular heart rate should be referred for advanced ultrasonography, which should focus on the type of PACs and risk classification. When risk factors for tachyarrhythmias are identified, weekly heart rate monitoring is advised until the PACs resolve. In the absence of risk factors, standard obstetric care may be sufficient with additional instructions to report reduced fetal movements. Should tachyarrhythmias or cardiac failure develop, referral back to the FMU is then indicated. This article is protected by copyright. All rights reserved.

Fetal permanent junctional reciprocating tachycardia with dilated cardiomyopathy, normal heart rate and transient fetal hydrops; a case report.

Permanent junctional reciprocating tachycardia (PJRT) is a rare form of congenital arrhythmia occurring predominantly in infants and children. Prenatal presentation is frequently characterized by incessant tachycardia leading to dilated cardiomyopathy (DCM). Some patients can have a normal heart rate which leads to a delayed diagnosis. We report a case of a neonate who was presented prenatally with DCM, fetal hydrops, and no signs of fetal arrhythmia. Diagnosis of PJRT was established after delivery with characteristic electrocardiographic patterns. Successful conversion to sinus rhythm with digoxin and amiodarone was achieved three months later. At 16 months of age, both echocardiography and electrocardiography were normal.

Reducing the burden of surveillance in pregnant women with no history of fetal atrioventricular block using the negative predictive value of anti-Ro/SSA antibody titers.

BACKGROUND: The risk of fetal atrioventricular block in anti-Ro/SSA antibody-exposed pregnancies with no previous affected offspring is approximately 2%. A high antibody titer is necessary but not sufficient for atrioventricular block, and specific antibody titers do not predict risk. However, there are no data on the negative predictive value of antibody titer to identify pregnancies at low risk of fetal atrioventricular block, and may not require surveillance. OBJECTIVE: This study aimed to define anti-Ro52 and anti-Ro60 antibody thresholds for the identification of fetuses unlikely to develop atrioventricular block using clinically validated and research laboratory tests. STUDY DESIGN: This study performed a multicenter review of pregnant subjects who tested positive in their local commercial laboratories for anti-Ro/SSA antibodies at the University of Colorado Children's Hospital (2014-2021) and Phoenix Children's Hospital (2014-2021) and enrolled in the Research Registry for Neonatal Lupus (RRNL) at New York University Langone Medical Center (2002-2021). The subjects were referred on the basis of rheumatologic symptoms or history of atrioventricular block in a previous pregnancy and were retrospectively grouped on the basis of pregnancy outcome. Group 1 indicated no fetal atrioventricular block in current or past pregnancies; group 2 indicated fetal atrioventricular block in the current pregnancy; and group 3 indicated normal current pregnancy but with fetal atrioventricular block in a previous pregnancy. Maternal sera were analyzed for anti-Ro52 and anti-Ro60 antibodies using a clinically validated multiplex bead assay (Associated Regional and University Pathologists Laboratories, Salt Lake City, UT) and a research enzyme-linked immunosorbent immunoassay (New York University). This study calculated the negative predictive value separately for anti-Ro52 and anti-Ro60 antibodies and for the 2 combined using a logistic regression model and a parallel testing strategy. RESULTS: This study recruited 270 subjects (141 in group 1, 66 in group 2, and 63 in group 3). Of note, 89 subjects in group 1 had data on hydroxychloroquine treatment: anti-Ro/SSA antibody titers were no different between those treated (n=46) and untreated (n=43). Mean anti-Ro52 and anti-Ro60 titers were the lowest in group 1 and not different between groups 2 and 3. No case of fetal atrioventricular block developed among subjects with anti-Ro52 and anti-Ro60 titers of <110 arbitrary units per milliliter using the multiplex bead assay of the Associated Regional and University Pathologists Laboratories (n=141). No case of fetal atrioventricular block developed among subjects with research laboratory anti-Ro52 titers of <650 and anti-Ro60 of <4060 enzyme-linked immunosorbent immunoassay units (n=94). Using these 100% negative predictive value thresholds, more than 50% of the anti-Ro/SSA antibody pregnancies that ultimately had no fetal atrioventricular block could be excluded from surveillance based on clinical and research titers, respectively. CONCLUSION: Study data suggested that there is a clinical immunoassay level of maternal anti-Ro/SSA antibodies below which the pregnancy is at low risk of fetal atrioventricular block. This study speculated that prospectively applying these data may avert the costly serial echocardiograms currently recommended for all anti-Ro/SSA-antibody positive pregnancies and guide future management.

Implications of fetal premature atrial contractions: systematic review.

OBJECTIVE: Fetal heart-rate irregularities occur in 1-2% of pregnancies and are usually caused by premature atrial contractions (PAC). Although PAC are considered benign, they may be associated with cardiac defects and tachyarrhythmia. We aimed to determine the incidence of congenital heart defects (CHDs) and complications in fetuses with PAC. METHODS: This was a systematic review and meta-analysis conducted in accordance with the PRISMA statement for reporting items for systematic reviews and meta-analyses. MEDLINE and EMBASE were searched from 1990 to June 2021 to identify studies on fetuses with PAC. The primary outcome was CHD; secondary outcomes were complications using the endpoints supraventricular tachyarrhythmia (SVT), cardiac failure and intrauterine fetal demise. Meta-analysis of proportions was performed, subdivided into high-risk and low-risk populations based on reason for referral. Pooled incidences with 95% CIs were calculated. RESULTS: Of 2443 unique articles identified, 19 cohort studies including 2260 fetuses were included. The pooled incidence of CHD in fetuses with PAC was 2.8% (95% CI, 1.5-4.1%), when 0.6% is the incidence expected in the general population. The pooled incidence of CHD was 7.2% (95% CI, 3.5-10.9%) in the high-risk population and 0.9% (95% CI, 0.0-2.0%) in the low-risk population. SVT occurred in 1.4% (95% CI, 0.6-3.4%) of fetuses diagnosed with PAC. Cardiac failure was described in 16 fetuses (1.4% (95% CI, 0.5-3.5%)), of which eight were CHD-related. Intrauterine fetal demise occurred in four fetuses (0.9% (95% CI, 0.5-1.7%)) and was related to CHD in two cases. CONCLUSIONS: Our findings suggest that the risk of CHD in fetuses with PAC is 4-5 times higher than that in the general population. CHD was present more frequently in the high-risk population. Consequently, an advanced ultrasound examination to diagnose PAC correctly and exclude CHD is recommended. Complications of PAC are rare but can result in fetal demise, thus weekly fetal heart-rate monitoring remains advisable to enable early detection of SVT and to prevent cardiac failure. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Simple method to distinguish the type of fetal premature contraction using arterial Doppler time interval measurements.

AIM: The purpose of this study was to establish a simple method to distinguish premature ventricular contractions (PVC) from premature atrial contractions (PAC) using a fetal Doppler ultrasound arterial pulse waveform to measure time intervals between sinus node restarting. METHODS: We retrospectively identified 14 fetuses with premature contraction (8 with PAC, 6 with PVC). We measured two distinct parts of time intervals using an arterial pulsed-wave Doppler: the two consecutive waveforms just before the premature contraction (2-V interval) and two consecutive waveforms including the premature contraction (XV interval) to measure time intervals between sinus node restarting. We then evaluated the time difference between the 2-V and XV intervals in PVC compared to PAC. RESULTS: For PVC, the difference between the 2-V interval and the XV interval was significantly shorter than that for PAC. A cut-off point of 33 ms, where a difference ≤33 ms was clearly shown to be associated with a PVC and a difference more than 33 ms signified a PAC was demonstrated. CONCLUSION: The 2-V and XV interval measurements, used to measure time intervals between sinus node restarting, could easily distinguish PVC from PAC in utero. Therefore, this study could potentially be a feasible and effective method for obstetricians or sonographers to employ usefully.

Mothers with long QT syndrome are at increased risk for fetal death: findings from a multicenter international study.

BACKGROUND: Most fetal deaths are unexplained. Long QT syndrome is a genetic disorder of cardiac ion channels. Affected individuals, including fetuses, are predisposed to sudden death. We sought to determine the risk of fetal death in familial long QT syndrome, in which the mother or father carries the long QT syndrome genotype. In addition, we assessed whether risk differed if the long QT syndrome genotype was inherited from the mother or father. OBJECTIVE: This was a retrospective review of pregnancies in families with the 3 most common heterozygous pathogenic long QT syndrome genotypes in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3), which occur in approximately 1 in 2000 individuals. The purpose of our study was to compare pregnancy and birth outcomes in familial long QT syndrome with the normal population and between maternal and paternal carriers of the long QT syndrome genotype. We hypothesized that fetal death before (miscarriage) and after (stillbirths) 20 weeks gestation would be increased in familial long QT syndrome compared with the normal population and that the parent of origin would not affect birth outcomes. STUDY DESIGN: Our study was a multicenter observational case series of 148 pregnancies from 103 families (80 mothers, 23 fathers) with familial long QT syndrome (60 with LQT1, 29 with LQT2, 14 with LQT3) who were recruited from 11 international centers with expertise in hereditary heart rhythm diseases, pediatric and/or adult electrophysiology, and high-risk pregnancies. Clinical databases from these sites were reviewed for long QT syndrome that occurred in men or women of childbearing age (18-40 years). Pregnancy outcomes (livebirth, stillbirth, and miscarriage), birthweights, and gestational age at delivery were compared among long QT syndrome genotypes and between maternal vs paternal long QT syndrome-affected status with the use of logistic regression analysis. RESULTS: Most offspring (80%; 118/148) were liveborn at term; 66% of offspring (73/110) had long QT syndrome. Newborn infants of mothers with long QT syndrome were delivered earlier and, when the data were controlled for gestational age, weighed less than newborn infants of long QT syndrome fathers. Fetal arrhythmias were observed rarely, but stillbirths (fetal death at >20 weeks gestation) were 8 times more frequent in long QT syndrome (4% vs approximately 0.5%); miscarriages (fetal death at ≤20 weeks gestation) were 2 times that of the general population (16% vs 8%). The likelihood of fetal death was significantly greater with maternal vs paternal long QT syndrome (24.4% vs 3.4%; P=.036). Only 10% of all fetal deaths underwent postmortem long QT syndrome testing; 2 of 3 cases were positive for the family long QT syndrome genotype. CONCLUSION: This is the first report to demonstrate that mothers with long QT syndrome are at increased risk of fetal death and to uncover a previously unreported cause of stillbirth. Our results suggest that maternal effects of long QT syndrome channelopathy may cause placental or myometrial dysfunction that confers increased susceptibility to fetal death and growth restriction in newborn survivors, regardless of long QT syndrome status.

Prenatal detection of fetal heart disease at Jordan University Hospital: early experience in a developing country.

OBJECTIVE: To report on the first 5 years of establishment of fetal echocardiographic services at the Jordan University Hospital with emphasis on diagnosis and outcome. METHODS: A retrospective chart review was conducted on all fetal echocardiographic studies performed between January 2011 and December 2015. Data collected included maternal demographics, referral indications, fetal cardiac diagnosis, correlation to post-natal diagnosis, outcome of pregnancy including pre-mature delivery and perinatal mortality. Basic statistical analysis was performed including demographic analysis, and calculation of fetal echocardiographic sensitivity and specificity. RESULTS: A total of 208 fetuses underwent fetal echocardiographic evaluation at a mean gestational age of 26.5 (±5) weeks. The most common referral indication was a suspicion of CHD during the obstetric ultrasound (44.2%), followed by cardiac dysfunction (18.2%), and a family history of CHD (14.9%). Fetal echocardiography showed CHD in 71 fetuses (34%), heart failure in 26 (12.5%), arrhythmia in 9 (4.3%), and intracardiac masses in 2. In the remaining 100 fetuses (48%), fetal echocardiography showed normal evaluation. For detecting CHD, fetal echocardiography had a sensitivity and specificity of 91.7% and 95.4%, respectively. Perinatal mortality including termination of pregnancy, intrauterine fetal death, and neonatal mortality was highest in heart failure (77%), and was 41% for CHD. CONCLUSION: The fetal cardiac diagnostic services at the Jordan University Hospital have encouraging initial results with a relatively high sensitivity and specificity. The services further positively impacted the quality of counselling offered and facilitated pre- and post-natal management.

Hemodynamics in fetal arrhythmia.

Fetal arrhythmias are among the few conditions that can be managed in utero. However, accurate diagnosis is essential for appropriate management. Ultrasound-based imaging methods can be used to study fetal heart structure and function noninvasively and help to understand fetal cardiovascular pathophysiology, and they remain the mainstay of evaluating fetuses with arrhythmias in clinical settings. Hemodynamic evaluation using Doppler echocardiography allows the elucidation of the electrophysiological mechanism and helps to make an accurate diagnosis. It can also be used as a tool to understand fetal cardiac pathophysiology, for assessing fetal condition and monitoring the effect of antiarrhythmic treatment. This narrative review describes Doppler techniques that are useful for evaluating fetal cardiac rhythms to refine diagnosis and provides an overview of hemodynamic changes observed in different types of fetal arrhythmia.

Fetal arrhythmogenic right ventricular cardiomyopathy with double mutations in TMEM43.

We herein describe a fetal case of arrhythmogenic right ventricular cardiomyopathy (ARVC) with double mutations in transmembrane protein 43 (TMEM43). RV aneurysm and ventricular arrhythmia were detected during the fetal period. After birth, electrocardiogram showed frequent premature ventricular contractions (PVC) of left bundle branch block morphology and epsilon waves in the right-sided chest leads. Echocardiography also indicated RV aneurysm with regionally decreased systolic function. PVC disappeared after treatment with amiodarone and mexiletin. Mutations in TMEM43, which was recently identified as the causative gene of ARVC type 5, were also confirmed in the present patient and in the patient's mother, and they were therefore diagnosed with ARVC. The present case confirms that symptoms of ARVC can emerge during the fetal period. Pediatricians need to keep in mind the possibility of ARVC when they encounter patients with RV aneurysm and arrhythmia.

Decreased baseline variability on fetal heart rate pattern in a fetus with heterotaxy syndrome.

In a fetus with suspected heterotaxy syndrome, a decreased/absent baseline variability of fetal heart rate pattern developed at gestational week 36(+5) and continued for 5 days until birth at gestational week 37(+2), while repeat biophysical profile scorings with ultrasound were consistently unremarkable. This neonate weighing 2404 g with Apgar scores of 7 (1-min) and 8 (5-min) and umbilical arterial cord blood pH of 7.28 with base deficit of 3.9 mmol/L, showed a heart rate of 120 b.p.m. for 3 h after birth, but subsequently developed sinus bradycardia (84 b.p.m.) unresponsive to crying. Isoproterenol initiated 9 h after birth was effective in the increase of heart rate to 120 b.p.m. in this neonate. Brain magnetic resonance imaging at 16 days of age was unremarkable. The decreased/absent baseline variability of fetal heart rate pattern was speculated to have been caused by sinus node dysfunction, and not by reduced fetal oxygenation in this case.

Surveillance of fetal arrhythmias in the outpatient setting: current limitations and call for action.

Surveillance of fetal arrhythmias in the outpatient setting remains limited by lack of monitoring modalities. Despite technological advances made in the field of obstetrics, existing devices are not currently suitable to monitor fetal arrhythmias. In this report, the author describes the current and developing fetal heart rate monitoring technologies including the recent introduction of hand-held Doppler monitors for outpatient surveillance of fetal arrhythmias.

Hierarchical online contrastive anomaly detection for fetal arrhythmia diagnosis in ultrasound.

Arrhythmia is a major cardiac abnormality in fetuses. Therefore, early diagnosis of arrhythmia is clinically crucial. Pulsed-wave Doppler ultrasound is a commonly used diagnostic tool for fetal arrhythmia. Its key step for diagnosis involves identifying adjacent measurable cardiac cycles (MCCs). As cardiac activity is complex and the experience of sonographers is often varied, automation can improve user-independence and diagnostic-validity. However, arrhythmias pose several challenges for automation because of complex waveform variations, which can cause major localization bias and missed or false detection of MCCs. Filtering out non-MCC anomalies is difficult because of large intra-class and small inter-class variations between MCCs and non-MCCs caused by agnostic morphological waveform variations. Moreover, rare arrhythmia cases are insufficient for classification algorithms to adequately learn discriminative features. Using only normal cases for training, we propose a novel hierarchical online contrastive anomaly detection (HOCAD) framework for arrhythmia diagnosis during test time. The contribution of this study is three-fold. First, we develop a coarse-to-fine framework inspired by hierarchical diagnostic logic, which can refine localization and avoid missed detection of MCCs. Second, we propose an online learning-based contrastive anomaly detection with two new anomaly scores, which can adaptively filter out non-MCC anomalies on a single image during testing. With these complementary efforts, we precisely determine MCCs for correct measurements and diagnosis. Third, to the best of our knowledge, this is the first reported study investigating intelligent diagnosis of fetal arrhythmia on a large-scale and multi-center ultrasound dataset. Extensive experiments on 3850 cases, including 266 cases covering three typical types of arrhythmias, demonstrate the effectiveness of the proposed framework.

Diagnosis of fetal arrhythmia in echocardiography imaging using deep learning with cyclic loss.

Background: Fetal arrhythmias frequently co-occur with congenital heart disease in fetuses. The peaks observed in M-mode fetal echocardiograms serve as pivotal diagnostic markers for fetal arrhythmias. However, speckles, artifacts, and noise pose notable challenges for accurate image analysis. While current deep learning networks mainly overlook cardiac cyclic information, this study concentrated on the integration of such features, leveraging contextual constraints derived from cardiac cyclical features to improve diagnostic accuracy. Methods: This study proposed a novel deep learning architecture for diagnosing fetal arrhythmias. The architecture presented a loss function tailored to the cardiac cyclical information and formulated a diagnostic algorithm for classifying fetal arrhythmias. The training and validation processes utilized a dataset comprising 4440 patches gathered from 890 participants. Results: Incorporating cyclic loss significantly enhanced the performance of deep learning networks in predicting peak points for diagnosing fetal arrhythmia, resulting in improvements ranging from 7.11% to 14.81% in F1-score across different network combinations. Particularly noteworthy was the 18.2% improvement in the F1-score for the low-quality group. Additionally, the precision of diagnosing fetal arrhythmia across four categories exhibited improvement, with an average improvement rate of 20.6%. Conclusion: This study introduced a cyclic loss mechanism based on the cardiac cycle information. Comparative evaluations were conducted using baseline methods and state-of-the-art deep learning architectures with the fetal echocardiogram dataset. These evaluations demonstrated the proposed framework's superior accuracy in diagnosing fetal arrhythmias. It is also crucial to note that further external testing is essential to assess the model's generalizability and clinical value.

An intelligent quantification system for fetal heart rhythm assessment: A multicenter prospective study.

BACKGROUND: The motion relationship and time intervals of the pulsed-wave Doppler (PWD) spectrum are essential for diagnosing fetal arrhythmia. However, few technologies currently are available to automatically calculate fetal cardiac time intervals (CTIs). OBJECTIVE: The purpose of this study was to develop a fetal heart rhythm intelligent quantification system (HR-IQS) for the automatic extraction of CTIs and establish the normal reference range for fetal CTIs. METHODS: A total of 6498 PWD spectrums of 2630 fetuses over the junction between the left ventricular inflow and outflow tracts were recorded across 14 centers. E, A, and V waves were manually labeled by 3 experienced fetal cardiologists, with 17 CTIs extracted. Five-fold cross-validation was performed for training and testing of the deep learning model. Agreement between the manual and HR-IQS-based values was evaluated using the intraclass correlation coefficient and Spearman's rank correlation coefficient. The Jarque-Bera test was applied to evaluate the normality of CTIs' distributions, and the normal reference range of 17 CTIs was established with quantile regression. Arrhythmia subset was compared with the non-arrhythmia subset using the Mann-Whitney U test. RESULTS: Significant positive correlation (P <.001) and moderate-to-excellent consistency (P <.001) between the manual and HR-IQS automated measurements of CTIs was found. The distribution of CTIs was non-normal (P <.001). The normal range (2.5th to 97.5th percentiles) was successfully established for the 17 CTIs. CONCLUSIONS: Using our HR-IQS is feasible for the automated calculation of CTIs in practice and thus could provide a promising tool for the assessment of fetal rhythm and function.

Preventing and Treating Torsades de Pointes in the Mother, Fetus and Newborn in the Highest Risk Pregnancies with Inherited Arrhythmia Syndromes.

The number of women of childbearing age who have been diagnosed in childhood with ion channelopathy and effectively treated using beta blockers, cardiac sympathectomy, and life-saving cardiac pacemakers/defibrillators is increasing. Since many of these diseases are inherited as autosomal dominant, offspring have about a 50% risk of having the disease, though many will be only mildly impacted during fetal life. However, highly complex delivery room preparation is increasingly needed in pregnancies with inherited arrhythmia syndromes (IASs). However, specific Doppler techniques show meanwhile a better understanding of fetal electrophysiology. The advent of fetal magnetocardiography (FMCG) now allows the detection of fetal Torsades de Pointes (TdP) ventricular tachycardia and other LQT-associated arrhythmias (QTc prolongation, functional second AV block, T-wave alternans, sinus bradycardia, late-coupled ventricular ectopy and monomorphic VT) in susceptible fetuses during the second and third trimester. These types of arrhythmias can be due to either de novo or familial Long QT Syndrome (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), or other IAS. It is imperative that the multiple specialists involved in the antenatal, peripartum, and neonatal care of these women and their fetuses/infants have the optimal knowledge, training and equipment in order to care for these highly specialized pregnancies and deliveries. In this review, we outline the steps to recognize symptomatic LQTS in either the mother, fetus or both, along with suggestions for evaluation and management of the pregnancy, delivery, or post-partum period impacted by LQTS.

Systematic review of long QT syndrome identified during fetal life.

Fetal long QT syndrome (LQTS) may present with sinus bradycardia, functional 2:1 atrioventricular block (AVB), and ventricular arrhythmias (ventricular tachycardia [VT]/torsades de pointes [TdP]) and lead to fetal or postnatal death. We performed a systematic review and individual participant data meta-analysis of 83 studies reporting outcomes of 265 fetuses for which suspected LQTS was confirmed postnatally and determined risk of adverse perinatal and postnatal outcomes using logistic and stepwise logistic regression. A longer fetal QTc was more predictive of death than any other antenatal factor (receiver operating characteristic [ROC] area under the curve [AUC] 0.85; 95% confidence interval [CI] 0.66-1.00). Risk of death was significantly increased with fetal QTc >600 ms. Neither fetal heart rate nor heart rate z-score predicted death (ROC AUC 0.51; 95% CI 0.31-0.71; and ROC AUC 0.59; 95% CI 0.37-0.80, respectively). The combination of antenatal VT/TdP or functional 2:1 AVB and lack of family history of LQTS was also highly predictive of death (ROC AUC 0.82; 95% CI 0.76-0.88). Our data provide clinical screening tools to enable prediction and intervention for fetuses with LQTS at risk of death.