Severe cardiac conduction disease associated with titin gene mutation.

Heart block is rare in pediatrics with many possible causes. An association between complete heart block (CHB) and pathogenic titin (TTN) mutations have not been previously described. We report a 9-year-old female with history of leukodystrophy and family history of atrial fibrillation who presented with syncope and conduction abnormalities, including CHB. She underwent pacemaker implantation and genetic testing demonstrated a pathogenic TTN mutation likely responsible for her cardiac findings. Our case suggests an association between TTN mutations and conduction disease and emphasizes broadening gene testing in assessing these patients, especially when a family history is present.

Cardiovascular Follow-up of Patients Treated for MIS-C.

OBJECTIVES: To assess the prevalence of residual cardiovascular pathology by cardiac MRI (CMR), ambulatory rhythm monitoring, and cardiopulmonary exercise testing (CPET) in patients ∼6 months after multisystem inflammatory disease in children (MIS-C). METHODS: Patients seen for MIS-C follow-up were referred for CMR, ambulatory rhythm monitoring, and CPET ∼6 months after illness. Patients were included if they had ≥1 follow-up study performed by the time of data collection. MIS-C was diagnosed on the basis of the Centers for Disease Control and Prevention criteria. Myocardial injury during acute illness was defined as serum Troponin-I level >0.05 ng/mL or diminished left ventricular systolic function on echocardiogram. RESULTS: Sixty-nine of 153 patients seen for MIS-C follow-up had ≥1 follow-up cardiac study between October 2020-June 2022. Thirty-seven (54%) had evidence of myocardial injury during acute illness. Of these, 12 of 26 (46%) had ≥1 abnormality on CMR, 4 of 33 (12%) had abnormal ambulatory rhythm monitor results, and 18 of 22 (82%) had reduced functional capacity on CPET. Of the 37 patients without apparent myocardial injury, 11 of 21 (52%) had ≥1 abnormality on CMR, 1 of 24 (4%) had an abnormal ambulatory rhythm monitor result, and 11 of 15 (73%) had reduced functional capacity on CPET. The prevalence of abnormal findings was not statistically significantly different between groups. CONCLUSIONS: The high prevalence of abnormal findings on follow-up cardiac studies and lack of significant difference between patients with and without apparent myocardial injury during hospitalization suggests that all patients treated for MIS-C warrant cardiology follow-up.

Ectopic Atrial Tachycardia in Infants Following Congenital Heart Disease Surgery.

Although ectopic atrial tachycardia (EAT) is common following surgery for congenital heart disease (CHD), there are limited data regarding this arrhythmia. This study assessed risk factors and outcomes for patients less than one year of age with post-operative EAT. This was a retrospective analysis of infants undergoing CHD surgery from 2007 to 2020. Patients and surgeries with EAT were compared to controls without EAT. Out of 5372 infant CHD surgeries, EAT developed in 129 (2.5%). Compared to controls, the EAT cohort was younger (median 7 vs 85 days, p < 0.01), weighed less at time of surgery (3.3 vs 4.2 kg, p < 0.01), and was more likely to have DiGeorge syndrome (7.7% vs 3.0%, p < 0.01). Multivariate analysis revealed total anomalous venous connection (TAPVC) repair (odds ratio [OR] 2.8; 95% confidence interval 1.5-5.2), DiGeorge syndrome (OR 2.4; 1.1-5.2), Society of Thoracic Surgeons-European Association for Cardio-Thoracic surgery (STAT) category ≥ 4 (OR 2.1; 1.0-4.4), and longer cardiopulmonary bypass times (OR 1.1; 1.0-1.2) as independent risk factors for EAT. The onset of EAT occurred a median of 9 days (IQR 5-14 days) after CHD surgery. Antiarrhythmic treatment was initiated in 109/129 patients (84%) with propranolol (71%) and amiodarone (24%) the most commonly used medications. Although 15 (11.6%) patients did not survive to hospital discharge, EAT was not directly implicated in any deaths. EAT occurred after 2.5% of infant CHD surgeries. In addition to TAPVC repair, longer and more complex surgeries were associated with an increased the risk for the development of post-operative EAT.

Third Trimester Fetal Heart Rates in Antibody-Mediated Complete Heart Block Predict Need for Neonatal Pacemaker Placement.

Congenital complete heart block (CCHB) affects 1 in 20,000 newborns. This study evaluates fetal and neonatal risk factors predictive of neonatal pacemaker placement in antibody-mediated complete heart block. The Children's Hospital Los Angeles institutional fetal, pacemaker, and medical record databases were queried for confirmed SSA/SSB cases of CCHB between January 2004 and July 2019. Cases excluded were those with a diagnosis beyond the neonatal period, diagnosis of a channelopathy, or if maternal antibody status was unknown. We recorded the gestational age (GA), birth weight (BW), fetal heart rates (FHRs) of the last echocardiogram before delivery, specific neonatal ECG and echocardiogram findings, age at pacemaker placement, and mortality. Of 43 neonates identified with CCHB, 27 had confirmed maternal antibody exposure. Variables associated with neonatal pacemaker implantation were FHRs < 50 bpm (p = 0.005), neonatal heart rates < 52 bpm (p = 0.015), and neonatal left ventricular fractional shortening (FS) percentages < 34% (p = 0.03). On multivariate analysis, FHR remained significant (p = 0.03) and demonstrated an increased risk of neonatal pacemaker placement by an odds ratio of 12.5 (95% CI 1.3-116, p = 0.05). The median GA at which the FHR was obtained was 34 weeks (IQR 26-35 weeks). Neonatal pacemaker placement was highly associated with a FHR < 50 bpm, neonatal HR < 52 bpm, and neonatal FS < 34%. FHRs at 34 weeks GA (IQR 26-35 weeks) correlated well with postnatal heart rates and were predictive of neonatal pacemaker placement.

Difficulties with invasive risk stratification performed under anesthesia in pediatric Wolff-Parkinson-White Syndrome.

BACKGROUND: Children with Wolff-Parkinson-White Syndrome (WPW) are at risk for sudden death. The gold standard for risk stratification in this population is the shortest pre-excited RR interval during atrial fibrillation (SPERRI). OBJECTIVE: The purpose of this study was to determine how closely measurements made in the electrophysiology laboratory in patients with WPW compared to SPERRI obtained during an episode of clinical pre-excited atrial fibrillation (Clinical-SPERRI). METHODS: This was a subgroup analysis of a multicenter study of children with WPW. Subjects in our study (N = 49) were included if they had Clinical-SPERRI measured in addition to 1 or more of 3 surrogate measurements: SPERRI obtained during electrophysiological study (EP-SPERRI), accessory pathway effective refractory period (APERP), or shortest pre-excited paced cycle length with 1:1 conduction (SPPCL). RESULTS: Seventy percent of electrophysiological measurements were made with patients under general anesthesia. Clinical-SPERRI moderately correlated with EP-SPERRI (r = 0.495; P = .012). However, 24% of our patients with Clinical-SPERRI ≤250 ms would have been misclassified as having a low-risk pathway based on EP-SPERRI >250 ms. Clinical-SPERRI did not correlate with APERP or SPPCL (r < 0.3; P >.1). Mean EP-SPERRI, APERP, and SPPCL all were greater than Clinical-SPERRI. CONCLUSION: Electrophysiology laboratory measurements of pathway characteristics made with patients under general anesthesia do not correlate well with Clinical-SPERRI. Of APERP, SPPCL, and EP-SPERRI, only EP-SPERRI had moderate correlation with Clinical-SPERRI. This study questions the predictive ability of invasive risk stratification with patients under general anesthesia, given that 24% of patients with high-risk Clinical-SPERRI (≤250 ms) had EP-SPERRI that may be considered low risk (>250 ms).

Life-Threatening Event Risk in Children With Wolff-Parkinson-White Syndrome: A Multicenter International Study.

OBJECTIVES: This study sought to characterize risk in children with Wolff-Parkinson-White (WPW) syndrome by comparing those who had experienced a life-threatening event (LTE) with a control population. BACKGROUND: Children with WPW syndrome are at risk of sudden death. METHODS: This retrospective multicenter pediatric study identified 912 subjects ≤21 years of age with WPW syndrome, using electrophysiology (EPS) studies. Case subjects had a history of LTE: sudden death, aborted sudden death, or atrial fibrillation (shortest pre-excited RR interval in atrial fibrillation [SPERRI] of ≤250 ms or with hemodynamic compromise); whereas subjects did not. We compared clinical and EPS data between cases and subjects. RESULTS: Case subjects (n = 96) were older and less likely than subjects (n = 816) to have symptoms or documented tachycardia. Mean age at LTE was 14.1 ± 3.9 years of age. The LTE was the sentinel symptom in 65%, consisting of rapidly conducted pre-excited atrial fibrillation (49%), aborted sudden death (45%), and sudden death (6%). Three risk components were considered at EPS: SPERRI, accessory pathway effective refractory period (APERP), and shortest paced cycle length with pre-excitation during atrial pacing (SPPCL), and all were shorter in cases than in control subjects. In multivariate analysis, risk factors for LTE included male sex, Ebstein malformation, rapid anterograde conduction (APERP, SPERRI, or SPPCL ≤250 ms), multiple pathways, and inducible atrial fibrillation. Of case subjects, 60 of 86 (69%) had ≥2 EPS risk stratification components performed; 22 of 60 (37%) did not have EPS-determined high-risk characteristics, and 15 of 60 (25%) had neither concerning pathway characteristics nor inducible atrioventricular reciprocating tachycardia. CONCLUSIONS: Young patients may experience LTE from WPW syndrome without prior symptoms or markers of high-risk on EPS.