Diagnosis and Management of Fetal Arrhythmias in the Current Era.

Diagnosis and management of fetal arrhythmias have changed over the past 40-50 years since propranolol was first used to treat fetal tachycardia in 1975 and when first attempts were made at in utero pacing for complete heart block in 1986. Ongoing clinical trials, including the FAST therapy trial for fetal tachycardia and the STOP-BLOQ trial for anti-Ro-mediated fetal heart block, are working to improve diagnosis and management of fetal arrhythmias for both mother and fetus. We are also learning more about how "silent arrhythmias", like long QT syndrome and other inherited channelopathies, may be identified by recognizing "subtle" abnormalities in fetal heart rate, and while echocardiography yet remains the primary tool for diagnosing fetal arrhythmias, research efforts continue to advance the clinical envelope for fetal electrocardiography and fetal magnetocardiography. Pharmacologic management of fetal arrhythmias remains one of the most successful achievements of fetal intervention. Patience, vigilance, and multidisciplinary collaboration are key to successful diagnosis and treatment.

Low Baseline Fetal Heart Rate Leads to Diagnosis of Long QT Syndrome Type 1.

A low baseline fetal heart rate at 20 weeks' gestation was detected in a fetus without cardiac structural anomalies. Fetal echocardiography and magnetocardiography were used to diagnose congenital long QT syndrome. It was confirmed in the neonate, and the same pathogenic variant in KCNQ1 was subsequently identified in the mother.

Fetal Congenital Complete Heart Block: A Rare Case with an Extremely Low Ventricular Rate and Review of Current Management Strategies.

Congenital complete heart block (CCHB) is associated with high intrauterine and post-natal mortality. Prenatal detection and management, as well as appropriate delivery planning, may improve the outcomes in CCHB. We describe a rare case of CCHB that initially presented with fetal ascites and high-grade second-degree heart block noted on fetal echocardiography. The mother was noted to be positive for anti-SSA antibodies, and treatment with maternal steroids was started in an effort to reverse the fetal cardiac conduction abnormality. However, the fetal cardiac rhythm progressed to complete heart block by the follow up evaluation and the fetus had a continual declination of heart rate throughout the pregnancy to a low fetal heart rate of 25 beats per minute (bpm). This case demonstrates the lowest fetal ventricular rate documented in the literature and illustrates a severe presentation of a rare disease process. An overview of the existing knowledge related to etiology, prenatal evaluation with fetal echocardiography and fetal magnetocardiography, prenatal management, and delivery planning in fetuses with prenatally detected CCHB is included.

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.

Ferrite Shield to Enhance the Performance of Optically Pumped Magnetometers for Fetal Magnetocardiography.

Fetal magnetocardiography (fMCG) has proven to be an important tool for the prenatal monitoring of electrical cardiac activity; however, the high cost of superconducting quantum instrumentation (SQUID) poses a limitation for the dissemination of fMCG as a routine clinical technique. Recently, optically pumped magnetometers (OPMs) operating within person-sized, cylindrical shields have made fMCG more practical, but environmental magnetic interference entering through the shield opening substantially degrades the quality of fMCG signals. The goal of this study was to further attenuate these interferences by placing the OPM array within a small ferrite shield. FMCG recordings were made with and without the ferrite shield in ten subjects inside a person-sized, three-layer mu-metal cylindrical shield. Although the fetal signal was slightly attenuated, the environmental interference was reduced substantially, and maternal interference was also diminished. This increased the signal-to-noise ratio significantly and improved the resolution of the smaller waveform components. The performance improvement was highest in the axial direction and compensated for a major weakness of open-ended, person-sized shields. The ferrite shield is especially beneficial for the deployment of triaxial OPM sensors, which require effective shielding in all directions.

2023 HRS expert consensus statement on the management of arrhythmias during pregnancy.

This international multidisciplinary expert consensus statement is intended to provide comprehensive guidance that can be referenced at the point of care to cardiac electrophysiologists, cardiologists, and other health care professionals, on the management of cardiac arrhythmias in pregnant patients and in fetuses. This document covers general concepts related to arrhythmias, including both brady- and tachyarrhythmias, in both the patient and the fetus during pregnancy. Recommendations are provided for optimal approaches to diagnosis and evaluation of arrhythmias; selection of invasive and noninvasive options for treatment of arrhythmias; and disease- and patient-specific considerations when risk stratifying, diagnosing, and treating arrhythmias in pregnant patients and fetuses. Gaps in knowledge and new directions for future research are also identified.

Fetal Arrhythmia Diagnosis and Pharmacologic Management.

One of the most successful achievements of fetal intervention is the pharmacologic management of fetal arrhythmias. This management usually takes place during the second or third trimester. While most arrhythmias in the fetus are benign, both tachy- and bradyarrhythmias can lead to fetal hydrops or cardiac dysfunction and require treatment under certain conditions. This review will highlight precise diagnosis by fetal echocardiography and magnetocardiography, the 2 primary means of diagnosing fetuses with arrhythmia. Additionally, transient or hidden arrhythmias such as bundle branch block, QT prolongation, and torsades de pointes, which can lead to cardiomyopathy and sudden unexplained death in the fetus, may also need pharmacologic treatment. The review will address the types of drug therapies; current knowledge of drug usage, efficacy, and precautions; and the transition to neonatal treatments when indicated. Finally, we will highlight new assessments, including the role of the nurse in the care of fetal arrhythmias. The prognosis for the human fetus with arrhythmias continues to improve as we expand our ability to provide intensive care unit-like monitoring, to better understand drug treatments, to optimize subsequent pregnancy monitoring, to effectively predict timing for delivery, and to follow up these conditions into the neonatal period and into childhood. Coordinated initiatives that facilitate clinical fetal research are needed to address gaps in knowledge and to facilitate fetal drug and device development.

Contribution of Fetal Magnetocardiography to Diagnosis, Risk Assessment, and Treatment of Fetal Arrhythmia.

Background Fetal echocardiography has been the mainstay of fetal arrhythmia diagnosis; however, fetal magnetocardiography (fMCG) has recently become clinically available. We sought to determine to what extent fMCG contributed to the precision and accuracy of fetal arrhythmia diagnosis and risk assessment, and in turn, how this altered pregnancy management. Methods and Results We reviewed fMCG tracings and medical records of 215 pregnancies referred to the Biomagnetism Laboratory, UW-Madison, over the last 10 years, because of fetal arrhythmia or risk of arrhythmia. We compared referral diagnosis and treatment with fMCG diagnosis using a rating scale and restricted our review to the 144 subjects from the tachycardia, bradycardia/AV block, and familial long QT syndrome categories. Additional fMCG findings beyond those of the referring echocardiogram, or an alternative diagnosis were seen in 117/144 (81%), and 81 (56%) were critical changes. Eight (5.5%) had resolution of arrhythmia before fMCG. At least moderate changes in management were seen in 109/144 (76%) fetuses, of which 35/144 (24%) were major. The most diverse fMCG presentation was long QT syndrome, present in all 3 referral categories. Four of 5 stillbirths were seen with long QT syndrome. Nine fetuses showed torsades de pointes ventricular tachycardia, of which only 2 were recognized before fMCG. Conclusions FMCG has a significant impact on prenatal diagnosis and management of arrhythmias or familial arrhythmia risk, which cannot be fully met by existing technology. The combination of fMCG and fetal echocardiography in fetal care centers will be needed in the future to optimize care.

Fetal Unguarded Mitral Valve Orifice, Aortic Atresia, and Severe Left Heart Enlargement.

Unguarded mitral valve orifice is a rare disease with only 7 described cases in the literature. We describe the first known case of unguarded mitral valve orifice with normal segmental cardiac anatomy, severe left ventricular dilatation and dysfunction, aortic atresia, and atrial flutter. (Level of Difficulty: Advanced.).

Genotype Predicts Outcomes in Fetuses and Neonates With Severe Congenital Long QT Syndrome.

OBJECTIVES: This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs). BACKGROUND: LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown. METHODS: A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death. RESULTS: A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001). CONCLUSIONS: In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.

Dynamics of the use of magnetocardiography in the study of the cardiac conduction system of the chick embryo.

INTRODUCTION: Human fetal magnetocardiography (fMCG) has been done for several decades to evaluate fetal arrhythmias using a superconducting quantum interference device (SQUID) magnetometer, but there is little work in embryonic/fetal animal models. This study uses an optically-pumped magnetometer (OPM) to obtain an fMCG in the chick embryo. METHODS: White Leghorn chick embryos were examined from incubation Day #10-19. Different examination chambers were tested to optimize embryonic thermal stability and magnetic signal acquisition. All examinations were done with magnetic shielding. The OPM sensors were placed next to the egg shell. The embryo's position was localized by transilluminating the intact egg or ultrasound imaging the egg with an open air cell to optimize sensor placement. The raw data for each embryo was postprocessed to obtain a fMCG composite waveform. RESULTS: fMCG's were obtained in embryos from Day #12 to 19. The best success with intact eggs was obtained using five sensors; one at the bottom and four around the lower perimeter of the egg at 90° intervals with the egg oriented vertically and the air cell up. Using ultrasound imaging with the air cell open only two sensors were necessary, one at the bottom and one laterally next to the embryo. fMCGs were analyzed for heart rate and rhythm, each portion of the PQRST waveform, and the PR interval, QRS complex, RR interval, and QT interval. CONCLUSIONS: This study validates the chick embryo as an animal model to study in a longitudinal and noninvasive fashion the fetal cardiac conduction system by using OPM magnetocardiography.

Noninvasive Fetal Electrocardiography in the Diagnosis of Long QT Syndrome: A Case Series.

INTRODUCTION: Early detection and monitoring for malignant arrhythmias is fundamental to prenatal care in long QT syndrome (LQTS). Recently, we studied the feasibility of isolating the fetal electrocardiogram (fECG) and measuring electrocardiographic intervals with a noninvasive fECG device using blind source separation with reference signal. Our aim was to evaluate the ability of fECG to diagnose LQTS. CASE PRESENTATIONS: We identified 3 cases of clinically suspected LQTS based on fetal echocardiogram (2 had sinus bradycardia, 1 had second-degree atrioventricular block with negative maternal anti-SSA/SSB antibody titers). With institutional review board approval, these patients were prospectively enrolled for fECG acquisition. Offline post-processing generated fECG waveforms and calculated QT intervals. Case 1 and 3 had a maternal history of LQTS. Two of the three fetuses with suspected LQTS had confirmed LQTS by postnatal ECG and genetic testing. FECG was able to identify a prolonged corrected QT interval in both cases. One of these also had fetal magnetocardiography (fMCG), which yielded similar findings to the fECG. The third fetus had a normal fECG; fMCG and postnatal ECG were also normal. CONCLUSIONS: In 3 cases, fECG findings corroborated the diagnosis of LQTS. Noninvasive fECG may offer a novel method for fECG that is portable and more clinically accessible.