Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies.

OBJECTIVE: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). METHODS: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. RESULTS: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. CONCLUSION: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms.

Impact of Pediatric Obesity on Diurnal Blood Pressure Assessment and Cardiovascular Risk Markers.

Background: The prevalence of hypertension is increasing particularly among obese children and adolescents. Obese children and adolescents with hypertension are likely to remain hypertensive as they reach adulthood and hypertension is linked to an increased risk for cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has become one of the most important tools in diagnosing hypertension in children and adolescents and circadian patterns of blood pressure may be important disease-risk predictors. Methods: A retrospective chart review was conducted in patients aged 6-21 years who underwent 24-h ABPM at Kentucky Children's Hospital (KCH) from August 2012 through June 2017. Exclusion criteria included conditions that could affect blood pressure including chronic kidney disease and other renal abnormalities, congenital heart disease, cancer, and thyroid disease. Subjects were categorized by body mass index into normal (below 85th percentile), overweight (85th-95th percentile), stage I obesity (95th-119th percentile), stage II obesity (120th-139th) and stage III obesity (>140th). Non-dipping was defined as a nocturnal BP reduction of <10%. Results: Two hundred and sixty-three patients (156 male patients) were included in the analysis, of whom 70 were normal weight, 33 overweight, 55 stage I obesity, 53 stage II, and 52 stage III obesity. Although there was no significant difference between normal weight and obese groups for prevalence of hypertension, there was a greater prevalence of SBP non-dipping in obese patients as BMI increased (p = 0.008). Furthermore, non-dippers had a significantly elevated LVMI as well as abnormal lab values for uric acid, blood lipid panel, creatinine, and TSH (p < 0.05). Conclusions: These findings demonstrate that obese children and adolescents constitute a large proportion of hypertensive children and adolescents and the severity of pediatric obesity is associated with nocturnal BP non-dipping. Additionally, obesity in children is linked to several cardiovascular risk factors including left ventricular hypertrophy, dyslipidemia, and elevated uric acid levels. Further studies utilizing ABPM measures on risk stratification in this very high-risk population are warranted.

Objective Assessment of Physiologic Alterations Associated With Hemodynamically Significant Patent Ductus Arteriosus in Extremely Premature Neonates.

Delay in closure of ductus arteriosus in postnatal life may lead to serious consequences and complications in an extremely premature neonate secondary to hemodynamic alterations in regional blood flow pattern in various organs. Despite the widespread recognition amongst neonatologists to identify a hemodynamically significant patent ductus arteriosus (hsPDA) early in the postnatal course, there is lack of consensus in its definition and thus the threshold to initiate treatment. Echocardiographic assessment of PDA shunt size and volume combined with neonatologists' impression of clinical significance is most frequently used to determine the need for treatment of PDA. Common clinical signs of hsPDA utilized as surrogate for decreased tissue perfusion may lag behind early echocardiographic signs. Although echocardiogram allows direct assessment of PDA shunt and hemodynamic alterations in the heart, it is limited by dependence on pediatric cardiologist availability, interobserver variation and isolated time point assessment. Electrical cardiometry (EC) is a non-invasive continuous real time measurement of cardiac output by applying changes in thoracic electrical impedance. EC has been validated in preterm newborns by concomitant transthoracic echocardiogram assessments and may be beneficial in studying changes in cardiac output in premature newborns with hsPDA. Alterations in perfusion index derived from continuous pulse oximetry monitoring has been used to study changes in cardiac performance and tissue perfusion in infants with PDA. Near infrared spectroscopy (NIRS) has been used to objectively and continuously assess variations in renal, mesenteric, and cerebral oxygen saturation and thus perfusion changes due to diastolic vascular steal from hsPDA in preterm neonates. Doppler ultrasound studies measuring resistive indices in cerebral circulation indicate disturbance in cerebral perfusion secondary to ductal steal. With recent trends of change in practice toward less intervention in care of preterm newborn, treatment strategy needs to be targeted for select preterm population most vulnerable to adverse hemodynamic effects of PDA. Integration of these novel ways of hemodynamic and tissue perfusion assessment in routine clinical care may help mitigate the challenges in defining and targeting treatment of hsPDA thereby improving outcomes in extremely premature neonates.

Effect of In utero Non-steroidal anti-inflammatory drug therapy for severe ebstein anomaly or tricuspid valve dysplasia (NSAID therapy for fetal ebstein anomaly)

Abstract: Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) are rare congenital malformations associated with nearly 50% mortality when diagnosed in utero. The diseases often produce severe tricuspid regurgitation (TR) in the fetus and in some cases, pulmonary regurgitation (PR) and circular shunting ensue. Since the ductus arteriosus (DA) plays a critical role in the circular shunt and may be constricted by transplacental non-steroidal anti-inflammatory drugs (NSAIDs), we sought to assess the effect of NSAIDs on fetuses with EA/TVD. We reviewed mothers of singleton fetuses with EA/TVD and PR, indicative of circular shunting, who were offered NSAIDs at multiple centers from 2010-2018. Initial dosing consisted of indomethacin, followed by ibuprofen in most cases. Twenty-one patients at 10 centers were offered therapy 4 at a median gestational age (GA) of 30.0 weeks (range: 20.9-34.9). Most (15/21=71%) mothers received NSAIDs, and 12/15 (80%) achieved DA constriction after a median of 2.0 days (1.0-6.0). All fetuses with DA constriction had improved PR; 92% had improved Doppler patterns. Median GA at pregnancy outcome was 36.1 weeks (30.7-39.0) in fetuses with DA constriction vs. 33 weeks (23.3-37.3) in fetuses who did not receive NSAIDs or achieve DA constriction (p=0.040). Eleven of 12 patients (92%) with DA constriction survived to live-birth, whereas 4/9 patients (44%) who did not receive NSAIDs or achieve DA constriction survived (p=0.046). In conclusion, our findings demonstrate the proof of concept that NSAIDs mitigate circular shunt physiology by DA constriction and improve PR among fetuses with severe EA/TVD. Although the early results are encouraging, further investigation is necessary to determine safety and efficacy.

Effect of In Utero Non-Steroidal Anti-Inflammatory Drug Therapy for Severe Ebstein Anomaly or Tricuspid Valve Dysplasia (NSAID Therapy for Fetal Ebstein anomaly).

Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) are rare congenital malformations associated with nearly 50% mortality when diagnosed in utero. The diseases often produce severe tricuspid regurgitation (TR) in the fetus and in some cases, pulmonary regurgitation (PR) and circular shunting ensue. Since the ductus arteriosus (DA) plays a critical role in the circular shunt and may be constricted by transplacental nonsteroidal anti-inflammatory drugs (NSAIDs), we sought to assess the effect of NSAIDs on fetuses with EA/TVD. We reviewed mothers of singleton fetuses with EA/TVD and PR, indicative of circular shunting, who were offered NSAIDs at multiple centers from 2010 to 2018. Initial dosing consisted of indomethacin, followed by ibuprofen in most cases. Twenty-one patients at 10 centers were offered therapy at a median gestational age (GA) of 30.0 weeks (range: 20.9 to 34.9). Most (15/21 = 71%) mothers received NSAIDs, and 12 of 15 (80%) achieved DA constriction after a median of 2.0 days (1.0 to 6.0). All fetuses with DA constriction had improved PR; 92% had improved Doppler patterns. Median GA at pregnancy outcome (live-birth or fetal demise) was 36.1 weeks (30.7 to 39.0) in fetuses with DA constriction versus 33 weeks (23.3 to 37.3) in fetuses who did not receive NSAIDs or achieve DA constriction (p = 0.040). Eleven of 12 patients (92%) with DA constriction survived to live-birth, whereas 4 of 9 patients (44%) who did not receive NSAIDs or achieve DA constriction survived (p = 0.046). In conclusion, our findings demonstrate the proof of concept that NSAIDs mitigate circular shunt physiology by DA constriction and improve PR among fetuses with severe EA/TVD. Although the early results are encouraging, further investigation is necessary to determine safety and efficacy.

Relationship between perfusion index and patent ductus arteriosus in preterm infants.

BACKGROUND: Perfusion index (PI) is a noninvasive measure of perfusion. ΔPI (difference between pre- and postductal PI) may identify hemodynamically significant PDA. However, studies are limited to brief and intermittent ΔPI sampling. Our objective is to assess the value of continuous high resolution ΔPI monitoring in the diagnosis of PDA. METHODS: Continuous ΔPI monitoring in preterm infants was prospectively performed using two high-resolution pulse oximeters. Perfusion Index measures (ΔPI mean and variability, pre- and postductal PI) were analyzed over a 4-h period prior to echocardiography. A cardiologist blinded to the results evaluated for PDA on echocardiography. Linear mixed regression models were utilized for analyses. RESULTS: We obtained 31 echocardiography observations. Mean ΔPI (-0.23 vs. 0.16; P < 0.05), mean pre-PI (0.86 vs. 1.26; P < 0.05), and ΔPI variability (0.39 vs. 0.61; P = 0.05) were lower in infants with PDA compared to infants without PDA at the time of echocardiography. CONCLUSION: Mean ΔPI, ΔPI variability, and mean pre-PI measured 4 h prior to echocardiography detect PDA in preterm infants. PI is dynamic and should be assessed continuously. Perfusion index is a promising bedside measurement to identify PDA in preterm infants.

Impact of gestational age on neonatal hearing screening in vaginally-born late-preterm and early-term infants.

BACKGROUND: Late-preterm and early-term (LP-ET) infants, defined herein as 35(0)-37(6) weeks' gestation, often fail on 1st otoacoustic emissions (OAE) test. HYPOTHESIS: LP-ET infants fail more than term infants (38(0)-42 weeks' gestation) on the 1st OAE test. Aim : To evaluate the effect of gestational age on the 1st OAE test. METHODS: We studied 1,572 vaginally-delivered (VD) infants ≥35 weeks' gestation (1.1.2011-30.9.2011). Perinatal and neonatal variables and results of OAE tests were recorded. RESULTS: LP-ET infants, compared to full-term infants, had a significantly 2-fold higher need for repeated hearing tests: 80.2 versus 43.3 tests/1,000 neonates, respectively (p = 0.026). Univariate analysis showed that late prematurity and age at 1st OAE were significantly associated with failure on 1st OAE. At age 24-42 h, failure on 1st OAE was 2-fold higher in the LP-ET infants than in full-term infants: 9.4 versus 4.7% (p = 0.02). Risk for failure on 1st OAE was age-dependent: 9-fold higher when 1st OAE was performed at 24-42 h of age (5.3%) versus 0.6% after age 42 h. Multivariate analysis showed that variables that were independently significantly associated with failure on 1st OAE included late prematurity (OR 2.0 (1.1-3.7)) and age at 1st OAE (OR 9.2 (1.2-70.7)). CONCLUSIONS: Compared to term infants, VD LP-ET infants had 2-fold higher rates of failure on 1st OAE (up to 42 h of life) and needed repeated hearing tests. Failure rates after 42 h become negligible in both groups. In VD LP-ET infants, 1st OAE is better performed after 42 h of age.

Implanted defibrillators in young hypertrophic cardiomyopathy patients: a multicenter study.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, with an annual risk of sudden cardiac death (SCD) estimated at 1 %. Limited data are available regarding both the risk of SCD in the young HCM population and the use of implantable cardioverter-defibrillators (ICDs). This retrospective study included all patients with HCM who underwent ICD implantation for primary or secondary prevention of SCD before the age of 30 years at five institutions between 1995 and 2009. There were 99 devices implanted in 73 patients. Appropriate shocks occurred for 11 % of all the patients. None of the previously identified conventional risk factors for SCD in HCM patients were associated with increased risk of appropriate shocks in the young study cohort. During a median follow-up period of 2.4 years, inappropriate shocks occurred for 22 % of the patients. Older age at implant was associated with a decreased risk of inappropriate shock. Those who underwent implantation in the earlier decade had a higher incidence of inappropriate shocks. Late complications including lead fracture or dislodgement, generator malfunction, and infection occurred for 32 % of the patients. Three patients died (4 %), one of whom had an arrhythmic sudden death. A greater proportion of primary prevention implantations was performed for patients from the latter decade. Over time, ICD use in young HCM patients has become increasingly primary prevention oriented. Shock rates mirror those reported in adult series, and there is a substantial incidence of device complications.

Junctional ectopic tachycardia after congenital heart surgery in the current surgical era.

To determine the incidence of postoperative junctional ectopic tachycardia (JET) in a modern cohort of pediatric patients, evaluate possible risk factors for JET, and examine the effects of JET on postoperative morbidity and mortality. JET is common after congenital heart surgery. JET-related mortality has been a rare event at our center, which is different from previous reports. We reviewed records for pediatric patients who had postoperative arrhythmias between January 2006 and June 2010 at a large tertiary-care children's hospital. We performed a matched case-control study to identify risk factors for JET and a matched-cohort study to compare outcomes between patients and controls. Whenever possible, each JET case was randomly matched to two controls on the basis of lesion, repair, and surgical period. We identified 54 patients with JET (incidence = 1.4 %). After multivariate logistic regression analysis, low operative weight, cardiopulmonary bypass (CPB) duration >100 min, and immediate postoperative serum lactic acid level >20 mg/dl were associated with increased odds of developing JET. Patients with JET had longer mechanical ventilation time, cardiac intensive care unit (CICU) stay, and hospital stay. There was only one death in JET group (1.8 %) with no significant difference compared with the control group. JET remains a relatively common postoperative arrhythmia, but it is less frequent than previously reported. JET occurs more commonly in smaller patients with longer CPB runs and significant postoperative lactic acidosis levels. Mortality associated with JET is lower than historically reported, but morbidity remains high.

Clinical spectrum in a family with tropomyosin-mediated hypertrophic cardiomyopathy and sudden death in childhood.

This report demonstrates variable clinical courses in several members of a family with tropomyosin-mediated hypertrophic cardiomyopathy (HCM) (L185R mutation). The index case was an 8-year-old girl who died from sudden cardiac death and was diagnosed with HCM on autopsy. Her father had minimal hypertrophy but had an implantable cardioverter defibrillator placed prophylactically with no appropriate shocks. Two brothers progressed from normal phenotype to HCM on follow-up, the younger with significant hypertrophy and the older with mild hypertrophy. They both had malignant arrhythmia courses with VF, which was terminated by ICD shock. In conclusion, family members with same genotype can have significantly variable phenotypes.

Successful transcatheter cryoablation in infants with drug-resistant supraventricular tachycardia: a case series.

PURPOSE: Drug-resistant supraventricular tachycardia can cause hemodynamic instability, especially in infants. There are no case-series reports of transcatheter cryoablation treatment for infants with drug-resistant supraventricular tachycardia. Our purpose is to report our experience with transcatheter cryoablation in three infants with drug-resistant supraventricular tachycardia. METHODS: We reviewed clinical and electrophysiologic data from infants who underwent cryothermal ablation for drug-resistant supraventricular tachycardia (SVT) at our institution. RESULTS: Three patients (age 10-42 days) underwent transcatheter cryothermal ablation over a 1-year period. None had arrhythmia suppression on medical management, and all had hemodynamic instability from persistent SVT episodes. Cryothermal mapping (-30 C) localized the suspected foci. All foci were adjacent to the AV node. Cryoablation lesions were delivered at and around mapped foci. In one patient, cryothermal energy application eliminated the SVT but resulted in transient right bundle branch block that resolved later. Two patients had hemodynamically insignificant episodes of SVT in the immediate post-ablation period that resolved with standard antiarrhythmic treatment. One died of sepsis but remained SVT free for 10 days after the procedure without antiarrhythmic medications. Neither of the two surviving patients had SVT recurrence at 6-month follow-up off medications. CONCLUSIONS: In our series, transcatheter cryoablation was an effective treatment for drug-resistant SVT in infants. We encountered some early nonsustained post-procedure SVT; however, such episodes did not predict procedural failure.