Pediatric ECG-Based Deep Learning to Predict Left Ventricular Dysfunction and Remodeling.

BACKGROUND: Artificial intelligence-enhanced ECG analysis shows promise to detect ventricular dysfunction and remodeling in adult populations. However, its application to pediatric populations remains underexplored. METHODS: A convolutional neural network was trained on paired ECG-echocardiograms (≤2 days apart) from patients ≤18 years of age without major congenital heart disease to detect human expert-classified greater than mild left ventricular (LV) dysfunction, hypertrophy, and dilation (individually and as a composite outcome). Model performance was evaluated on single ECG-echocardiogram pairs per patient at Boston Children's Hospital and externally at Mount Sinai Hospital using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). RESULTS: The training cohort comprised 92 377 ECG-echocardiogram pairs (46 261 patients; median age, 8.2 years). Test groups included internal testing (12 631 patients; median age, 8.8 years; 4.6% composite outcomes), emergency department (2830 patients; median age, 7.7 years; 10.0% composite outcomes), and external validation (5088 patients; median age, 4.3 years; 6.1% composite outcomes) cohorts. Model performance was similar on internal test and emergency department cohorts, with model predictions of LV hypertrophy outperforming the pediatric cardiologist expert benchmark. Adding age and sex to the model added no benefit to model performance. When using quantitative outcome cutoffs, model performance was similar between internal testing (composite outcome: AUROC, 0.88, AUPRC, 0.43; LV dysfunction: AUROC, 0.92, AUPRC, 0.23; LV hypertrophy: AUROC, 0.88, AUPRC, 0.28; LV dilation: AUROC, 0.91, AUPRC, 0.47) and external validation (composite outcome: AUROC, 0.86, AUPRC, 0.39; LV dysfunction: AUROC, 0.94, AUPRC, 0.32; LV hypertrophy: AUROC, 0.84, AUPRC, 0.25; LV dilation: AUROC, 0.87, AUPRC, 0.33), with composite outcome negative predictive values of 99.0% and 99.2%, respectively. Saliency mapping highlighted ECG components that influenced model predictions (precordial QRS complexes for all outcomes; T waves for LV dysfunction). High-risk ECG features include lateral T-wave inversion (LV dysfunction), deep S waves in V1 and V2 and tall R waves in V6 (LV hypertrophy), and tall R waves in V4 through V6 (LV dilation). CONCLUSIONS: This externally validated algorithm shows promise to inexpensively screen for LV dysfunction and remodeling in children, which may facilitate improved access to care by democratizing the expertise of pediatric cardiologists.

Circulating Spike Protein Detected in Post-COVID-19 mRNA Vaccine Myocarditis.

BACKGROUND: Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail. METHODS: From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects. RESULTS: Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t test; P<0.0001). CONCLUSIONS: Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine-induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause.

Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

Insight into the Role of the Child Opportunity Index on Surgical Outcomes in Congenital Heart Disease.

OBJECTIVE: To use neighborhood-level Child Opportunity Index (COI) measures to investigate disparities in congenital heart surgery postoperative outcomes and identify potential targets for intervention. STUDY DESIGN: In this single-institution retrospective cohort study, children <18 years old who underwent cardiac surgery between 2010 and 2020 were included. Patient-level demographics and neighborhood-level COI were used as predictor variables. COI-a composite US census tract-based score measuring educational, health/environmental, and social/economic opportunities-was dichotomized as lower (<40th percentile) vs higher (≥40th percentile). Cumulative incidence of hospital discharge was compared between groups using death as a competing risk, adjusting for clinical characteristics associated with outcomes. Secondary outcomes included hospital readmission and death within 30 days. RESULTS: Among 6247 patients (55% male) with a median age of 0.8 years (IQR, 0.2-4.3), 26% had lower COI. Lower COI was associated with longer hospital lengths of stay (adjusted HR, 1.2; 95% CI, 1.1-1.2; P < .001) and an increased risk of death (adjusted OR, 2.0; 95% CI. 1.4-2.8; P < .001), but not hospital readmission (P = .6). At the neighborhood level, lacking health insurance coverage, food/housing insecurity, lower parental literacy and college attainment, and lower socioeconomic status were associated with longer hospital length of stay and increased risk of death. At the patient-level, public insurance (adjusted OR, 1.4; 95% CI, 1.0-2.0; P = .03) and caretaker Spanish language (adjusted OR 2.4; 95% CI, 1.2-4.3; P < .01) were associated with an increased risk of death. CONCLUSIONS: Lower COI is associated with longer length of stay and higher early postoperative mortality. Risk factors identified including Spanish language, food/housing insecurity, and parental literacy serve as potential intervention targets.

Retroflexed catheter course reduces the risk of right free wall accessory pathway recurrence.

INTRODUCTION: Accessory atrioventricular pathways (APs) may mediate atrioventricular reciprocating tachycardia and, in some cases, have the potential to conduct atrial tachycardia rapidly, which can be life threatening. While catheter ablation can be curative, ablation of right free wall APs is associated with a high rate of recurrence, likely secondary to reduced catheter stability along the right free wall atrioventricular groove. We sought to identify characteristics associated with a lower rate of recurrence and hypothesized ablation lesions placed on the ventricular side of the atrioventricular groove using a retroflexed catheter approach would decrease rates of recurrence. METHODS AND RESULTS: Retrospective chart review of patients who underwent catheter ablation of a right free wall AP from January 1, 2008 through June 1, 2021 with >2 months follow up. Cox proportional hazards regression was used to identify relationships between predictor variables and AP recurrence. We identified 95 patients who underwent ablation of 98 right free wall APs. Median age was 13.1 years and median weight at ablation was 52.3 kg. Overall, 23/98 (23%) APs recurred. Use of a retroflexed catheter course approaching the atrioventricular groove from the ventricular aspect was associated with reduced risk of AP recurrence with (univariable hazard ratio of 0.10 [95% confidence interval: 0.01-0.78]), which remained significant in multiple two variable Cox proportional hazards models. CONCLUSION: Use of a retroflexed catheter course is associated with a reduced likelihood of AP recurrence. This approach results in improved catheter stability and should be considered for ablation of right free wall APs.

Medical cardioversion of atrial fibrillation and flutter with class IC antiarrhythmic drugs in young patients with and without congenital heart disease.

INTRODUCTION: The use of flecainide and propafenone for medical cardioversion of atrial fibrillation (AF) and atrial flutter/intra-atrial reentrant tachycardia (IART) is well-described in adults without congenital heart disease (CHD). Data are sparse regarding their use for the same purpose in adults with CHD and in adolescent patients with anatomically normal hearts and we sought to describe the use of class IC drugs in this population and identify factors associated with decreased likelihood of success. METHODS: Single center retrospective cohort study of patients who received oral flecainide or propafenone for medical cardioversion of AF or IART from 2000 to 2022. The unit of analysis was each episode of AF/IART. We performed a time-to-sinus rhythm analysis using a Cox proportional hazards model clustering on the patient to identify factors associated with increased likelihood of success. RESULTS: We identified 45 episodes involving 41 patients. As only episodes of AF were successfully cardioverted with medical therapy, episodes of IART were excluded from our analyses. Use of flecainide was the only factor associated with increased likelihood of success. There was a statistically insignificant trend toward decreased likelihood of success in patients with CHD. CONCLUSIONS: Flecainide was more effective than propafenone. We did not detect a difference in rate of conversion to sinus rhythm between patients with and without CHD and were likely underpowered to do so, however, there was a trend toward decreased likelihood of success in patients with CHD. That said, medical therapy was effective in >50% of patients with CHD with AF.

Ventricular dyssynchrony late after the Fontan operation is associated with decreased survival.

BACKGROUND: Ventricular dyssynchrony and its relationship to clinical outcomes is not well characterized in patients following Fontan palliation. METHODS: Single-center retrospective analysis of cardiac magnetic resonance (CMR) imaging of patients with a Fontan circulation and an age-matched healthy comparison cohort as controls. Feature tracking was performed on all slices of a ventricular short-axis cine stack. Circumferential and radial strain, strain rate, and displacement were measured; and multiple dyssynchrony metrics were calculated based on timing of these measurements (including standard deviation of time-to-peak, maximum opposing wall delay, and maximum base-to-apex delay). Primary endpoint was a composite measure including time to death, heart transplant or heart transplant listing (D/HTx). RESULTS: A total of 503 cases (15 y; IQR 10, 21) and 42 controls (16 y; IQR 11, 20) were analyzed. Compared to controls, Fontan patients had increased dyssynchrony metrics, longer QRS duration, larger ventricular volumes, and worse systolic function. Dyssynchrony metrics were higher in patients with right ventricular (RV) or mixed morphology compared to those with LV morphology. At median follow-up of 4.3 years, 11% had D/HTx. Multiple risk factors for D/HTx were identified, including RV morphology, ventricular dilation, dysfunction, QRS prolongation, and dyssynchrony. Ventricular dilation and RV morphology were independently associated with D/HTx. CONCLUSIONS: Compared to control LVs, single right and mixed morphology ventricles in the Fontan circulation exhibit a higher degree of mechanical dyssynchrony as evaluated by CMR-FT. Dyssynchrony indices correlate with ventricular size and function and are associated with death or need for heart transplantation. These data add to the growing understanding regarding factors that can be used to risk-stratify patients with the Fontan circulation.

MIS-C across three SARS-CoV-2 variants: Changes in COVID-19 testing and clinical characteristics in a cohort of U.S. children.

As new variants of SARS-Co-V 2 have emerged over time and Omicron sub-variants have become dominant, the severity of illness from COVID-19 has declined despite greater transmissibility. There are fewer data on how the history, diagnosis, and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) have changed with evolution in SARS-CoV-2 variants. We conducted a retrospective cohort study of patients hospitalized with MIS-C between April 2020 and July 2022 in a tertiary referral center. Patients were sorted into Alpha, Delta, and Omicron variant cohorts by date of admission and using national and regional data on variant prevalence. Among 108 patients with MIS-C, significantly more patients had a documented history of COVID-19 in the two months before MIS-C during Omicron (74%) than during Alpha (42%) (p = 0.03). Platelet count and absolute lymphocyte count were lowest during Omicron, without significant differences in other laboratory tests. However, markers of clinical severity, including percentage with ICU admission, length of ICU stay, use of inotropes, or left ventricular dysfunction, did not differ across variants. This study is limited by its small, single-center case series design and by classification of patients into era of variant by admission date rather than genomic testing of SARS- CoV-2 samples.     Conclusion: Antecedent COVID-19 was more often documented in the Omicron than Alpha or Delta eras, but clinical severity of MIS-C was similar across variant eras. What is Known: • There has been a decrease in incidence of MIS-C in children despite widespread infection with new variants of COVID-19. • Data has varied on if the severity of MIS-C has changed over time across different variant infections. What is New: • MIS-C patients were significantly more likely to report a known prior infection with SARS-CoV-2 during Omicron than during Alpha. • There was no difference in severity of MIS-C between the Alpha, Delta, and Omicron cohorts in our patient population.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with substantial cardiovascular implications. Although infection with SARS-CoV-2 is usually mild in children, some children later develop a severe inflammatory disease that can have manifestations similar to toxic shock syndrome or Kawasaki disease. This syndrome has been defined by the US Centers for Disease Control and Prevention as multisystem inflammatory syndrome in children. Although the prevalence is unknown, >600 cases have been reported in the literature. Multisystem inflammatory syndrome in children appears to be more common in Black and Hispanic children in the United States. Multisystem inflammatory syndrome in children typically occurs a few weeks after acute infection and the putative etiology is a dysregulated inflammatory response to SARS-CoV-2 infection. Persistent fever and gastrointestinal symptoms are the most common symptoms. Cardiac manifestations are common, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, and conduction abnormalities. Severe cases can present as vasodilatory or cardiogenic shock requiring fluid resuscitation, inotropic support, and in the most severe cases, mechanical ventilation and extracorporeal membrane oxygenation. Empirical treatments have aimed at reversing the inflammatory response using immunomodulatory medications. Intravenous immunoglobulin, steroids, and other immunomodulatory agents have been used frequently. Most patients recover within days to a couple of weeks and mortality is rare, although the medium- and long-term sequelae, particularly cardiovascular complications, are not yet known. This review describes the published data on multisystem inflammatory syndrome in children, focusing on cardiac complications, and provides clinical considerations for cardiac evaluation and follow-up.

The NHLBI Study on Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC): Design and Objectives.

BACKGROUND: The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. METHODS: This multicenter observational cohort study will enroll at least 600 patients <21 years old who meet the Centers for Disease Control and Prevention case definition of MIS-C across multiple North American centers over 2 years. The study will collect detailed hospital and follow-up data for up to 5 years, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF) <45% during the acute illness. The primary outcomes are the worst LVEF and the highest coronary artery z-score of the left anterior descending or right coronary artery. Other outcomes include occurrence and course of non-cardiac organ dysfunction, inflammation, and major medical events. Independent adjudication of cases will classify participants as definite, possible, or not MIS-C. Analysis of the outcomes will include descriptive statistics and regression analysis with stratification by definite or possible MIS-C. The MUSIC study will provide phenotypic data to support basic and translational research studies. CONCLUSION: The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

Follow-up cardiac magnetic resonance in children with vaccine-associated myocarditis.

Myocarditis is a rare complication of the COVID-19 mRNA vaccine. We previously reported a case series of 15 adolescents with vaccine-associated myocarditis, 87% of whom had abnormalities on initial cardiac magnetic resonance (CMR), including late gadolinium enhancement (LGE) in 80%. We performed follow-up CMRs to determine the trajectory of myocardial recovery and better understand the natural history of vaccine-associated myocarditis. Case series of patients age < 19 years admitted to Boston Children's Hospital with acute vaccine-associated myocarditis following the BNT162b2 vaccine who had abnormal CMR at the time of initial presentation, and underwent follow-up testing. CMR assessment included left ventricular (LV) ejection fraction, T2-weighted myocardial imaging, LV global native T1, LV global T2, extracellular volume (ECV), and late gadolinium enhancement (LGE). Ten patients (9 male, median age 15 years) with vaccine-associated myocarditis underwent follow-up CMR at a median of 92 days (range 76-119) after hospital discharge. LGE was persistent in 80% of patients, though improved from prior in all cases. Two patients (20%) had abnormal LV global T1 at presentation, which normalized on follow-up. ECV decreased between acute presentation and follow-up in 6/10 patients; it remained elevated at follow-up in 1 patient and borderline in 3 patients. CONCLUSION: CMR performed ~3 months after admission for COVID-19 vaccine-associated myocarditis showed improvement of LGE in all patients, but persistent in the majority. Follow-up CMR 6-12 months after acute episode should be considered to better understand the long-term cardiac risks. WHAT IS KNOWN: • Myocarditis is a rare side effect of COVID-19 mRNA vaccine. •Late gadolinium enhancement is present on most cardiac magnetic resonance at the time of acute presentation. WHAT IS NEW: •Late gadolinium enhancement improved on all repeat cardiac magnetic resonance at 3-month follow-up. •Most patients still had a small amount of late gadolinium enhancement, the clinical significance of which is yet to be determined.

Deep Learning-Based Approach to Automatically Assess Coronary Distensibility Following Kawasaki Disease.

Kawasaki disease is an acute vasculitis affecting children, which can lead to coronary artery (CA) aneurysms. Optical coherence tomography (OCT) has identified CA wall damage in KD patients, but it is unclear if these findings correlate with any distensibility changes in the CA and how these changes evolve over time. This paper seeks to establish the link between OCT findings and vessel distensibility with a novel deep learning coronary artery segmentation system and use the segmentation framework to automatically analyze the temporal evolution of coronary stiffness over many years. 27 KD patients underwent catheterization with coronary angiography of the left coronary artery (LCA), followed by OCT of proximal and distal segments of the LCA. Changes in the CA caliber over the cardiac cycle were measured automatically and compared against OCT findings suggestive of KD-related vascular damage. In addition, 34 KD patients with regressed or persistent CA aneurysms were followed with serial CA angiography over an average of 14.5 years. Distensibility changes were calculated using a deep learning coronary artery segmentation framework and evaluated longitudinally. Distensibility in the coronary arteries after KD negatively correlated with increasing severity of OCT findings of KD-related vessel damage. KD patients have a significant increase in CA wall stiffness at 1 year after diagnosis, which then plateaus subsequently, compared to controls. Also, patients with persistent CA aneurysms have a statistically significant increase in wall stiffness over time in comparison to those with regressed CA aneurysms. Distensibility changes in the CA of KD patients calculated using our automated deep learning approach correlates with the severity of OCT findings of KD-related CA damage. This decreased distensibility peaks at 1 year in KD patients when following longitudinally and is more severe in those with persistent CA aneurysms.

Rapid ascending aorta stiffening in bicuspid aortic valve on serial cardiovascular magnetic resonance evaluation: comparison with connective tissue disorders.

BACKGROUND: Aortic stiffness has been shown to be abnormal in patients with bicuspid aortic valve (BAV), and is considered a component of the aortopathy associated with this condition. Progressive aortic stiffening associated with aging has been previously described in normal adults. However, it is not known if aging related aortic stiffening occurs at the same rate in BAV patients. We determined the longitudinal rate of decline in segmental distensibility in BAV patients using serial cardiovascular magnetic resonance (CMR) studies, and compared to previously published results from a group of patients with connective tissue disorders (CTD). METHODS: A retrospective review of CMR and clinical data on children and adults with BAV (n = 49, 73% male; 23 ± 11 years) with at least two CMRs (total 98 examinations) over a median follow-up of 4.1 years (range 1-9 years) was performed to measure aortic distensibility at the ascending (AAo) and descending aorta (DAo). Longitudinal changes in aortic stiffness were assessed using linear mixed-effects modeling. The comparison group of CTD patients had a similar age and gender profile (n = 50, 64% male; 20.6 ± 12 years). RESULTS: Compared to CTD patients, BAV patients had a more distensible AAo early in life but showed a steeper decline in distensibility on serial examinations [mean 10-year decline in AAo distensibility (× 10-3 mmHg-1) 2.4 in BAV vs 1.3 in CTD, p = 0.005]. In contrast, the DAo was more distensible in BAV patients throughout the age spectrum, and DAo distensibility declined with aging at a rate similar to CTD patients [mean 10 year decline in DAo distensibility (× 10-3 mmHg-1) 0.3 in BAV vs 0.4 in CTD, p = 0.58]. CONCLUSIONS: On serial CMR measurements, AAo distensibility declined at significantly steeper rate in BAV patients compared to a comparison group with CTDs, while DAo distensibility declined at similar rates in both groups. These findings offer new mechanistic insights into the differing pathogenesis of the aortopathy seen in BAV and CTD patients.

Coagulation profiles and viscoelastic testing in multisystem inflammatory syndrome in children.

OBJECTIVE: To characterize viscoelastic testing profiles of children with multisystem inflammatory syndrome in children (MIS-C). METHODS: This single-center retrospective review included 30 patients diagnosed with MIS-C from March 1 to September 1, 2020. Thromboelastography (TEG) with platelet mapping was performed in 19 (63%) patients and compared to age- and sex-matched controls prior to cardiac surgery. Relationships between TEG parameters and inflammatory markers were assessed using correlation. RESULTS: Patients with MIS-C had abnormal TEG results compared to controls, including decreased kinetic (K) time (1.1 vs. 1.7 minutes, p < .01), increased alpha angle (75.0° vs. 65.7°, p < .01), increased maximum amplitude (70.8 vs. 58.3 mm, p < .01), and decreased lysis in 30 minutes (Ly30) (1.1% vs. 3.7%, p = .03); consistent with increased clot formation rate and strength, and reduced fibrinolysis. TEG maximum amplitude was moderately correlated with erythrocyte sedimentation rate (ESR) (r = 0.60, p = .02), initial platelet count (r = 0.67, p < .01), and peak platelet count (r = 0.51, p = .03). TEG alpha angle was moderately correlated with peak platelet count (r = 0.54, p = .02). Seventeen (57%) patients received aspirin (ASA) and anticoagulation, five (17%) received only ASA, and three (10%) received only anticoagulation. No patients had a symptomatic thrombotic event. Six (20%) patients had a bleeding event, none of which was major. CONCLUSIONS: Patients with MIS-C had evidence of hypercoagulability on TEG. Increased ESR and platelets were associated with higher clot strength. Patients were prophylactically treated with ASA or anticoagulation with no symptomatic thrombosis or major bleeding. Further multicenter study is required to characterize the rate of thrombosis and optimal thromboprophylaxis algorithm in this patient population.

Cardiac manifestations in SARS-CoV-2-associated multisystem inflammatory syndrome in children: a comprehensive review and proposed clinical approach.

Initial reports on COVID-19 described children as largely spared from severe manifestations, with only 2-6% of children requiring intensive care treatment. However, since mid-April 2020, clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID-19 have been reported. This condition was named as SARS-Cov-2-associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease. Here, we present a narrative review of cases reported in literature and we discuss the clinical acute and follow-up management of these patients. Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes. Elevated inflammatory markers and evidence of cytokine storm were frequently observed. A subset of these patients also presented with hypotension and shock (20-100%) from either acute myocardial dysfunction or systemic hyperinflammation/vasodilation. Coronary artery dilation or aneurysms have been described in 6-24%, and arrhythmias in 7-60%. Cardiac support, immunomodulation, and anticoagulation are the key aspects for the management of the acute phase. Long-term structured follow-up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations.Conclusion: Multisystem inflammatory syndrome is a novel syndrome related to SARS-CoV-2 infection. Evidence is still scarce but rapidly emerging in the literature. Cardiac manifestations are frequent, including myocardial and coronary involvement, and need to be carefully identified and monitored over time. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2. What is New: • Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock. • Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias. • Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation. • Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.

Variation in the management of Kawasaki disease in Australia and New Zealand: A survey of paediatricians.

AIM: This study aimed to describe the current management practices for Kawasaki disease (KD) in Australia and New Zealand. METHODS: We performed a secondary analysis on the Australian and New Zealand responses to a large international survey of clinicians' perspectives on KD diagnosis and management. RESULTS: There was general consensus among Australian and New Zealand clinicians regarding the indications for intravenous immunoglobulin and aspirin in the management of acute KD. There was less consensus on the dose of these agents, the definition and management of treatment-resistant KD and the approach to long-term thromboprophylaxis. CONCLUSION: Most clinicians use intravenous immunoglobulin for primary treatment of KD. There is variation regarding other aspects of KD diagnosis and important management issues. Future studies should confirm whether this reported variation occurs in real-world practice and assess potential impacts on patient outcome.

Value of provocative electrophysiology testing in the management of pediatric patients after congenital heart surgery.

OBJECTIVE: To determine the impact of provocative electrophysiology testing in postoperative congenital heart disease (CHD) patients on the management of supraventricular tachycardia (SVT) and clinical outcomes. METHODS: This is a retrospective study including patients <18 years of age with surgery for CHD who had postoperative SVT between 2006 and 2017. Postoperative outcomes were compared between patients with and without postoperative electrophysiology testing using the Wilcoxon rank sum test, Fisher's exact test, Kaplan-Meier method with the log-rank test, and Cox proportional hazard model. RESULTS: From 341 patients who had SVT after surgery for CHD, 65 (19%) had postoperative electrophysiology testing. There was no significant difference in baseline patient characteristics or surgical complexity between patients with and without electrophysiology testing. Patients with inducible SVT on electrophysiology testing were more likely to have recurrence of SVT prior to hospital discharge with an odds ratio 4.0 (95% confidence interval 1.3, 12.0). Patients who underwent postoperative electrophysiology testing had shorter intensive care unit (12 [6, 20] vs 16 [9, 32] days, HR 2.1 [95% CI 1.6, 2.8], P < .001) and hospital (25 [13, 38] vs 31 [18, 54] days, HR 1.8 [95% CI 1.4, 2.4], P < .001) length of stay. CONCLUSION: Postoperative electrophysiology testing was associated with improved postoperative outcomes, likely related to the ability to predict recurrence of arrhythmia and tailored antiarrhythmic management.

Echocardiographic Parameters During and Beyond Onset of Kawasaki Disease Correlate with Onset Serum N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP).

The N-terminal proBNP (NT-proBNP), produced by cardiomyocytes, has several reported utilities and associations in acute Kawasaki disease (KD). The objective of this study is to examine the relationship between serum values of NT-proBNP at time of KD diagnosis with cardiac systolic, diastolic function and electrocardiographic changes, at onset of the disease and during the first year of follow-up. KD was diagnosed in 127 children between March 2007 and July 2014, mean diagnostic age 3.5 ± 2.9 years. Coronary artery maximum z score was 2.6 ± 2.8 (range - 0.6 to + 18.9), with giant aneurysm in 5/122 (4.1%). Age-adjusted NT-proBNP was 2.6 ± 1.6 z score, 78/122 (63.9%) > 2.0. There was a crescendo correlation between onset NT-proBNP z score and C-Reactive protein (CRP) serum levels (slope + 0.49, p < 0.001). There was a crescendo correlation between NT-proBNP z score and indexed left ventricular (LV) mass (slope + 1.86, p = 0.02), LV diastolic function parameter E/e' ratio (slope + 0.31, p = 0.04) and a decrescendo correlation with age-adjusted LV shortening fraction (SF) (- 0.63, p = 0.02). Lower SF z score, higher left ventricular mass index and E/e' ratio were associated with higher NT-proBNP z score, but without correlation with CRP levels. Within 2-3 months from the onset of the disease, there was a resolution of the systolic dysfunction. Electrocardiographic parameter changes were associated with decreased LV shortening fraction but not with NT-proBNP. KD patients with elevated NT-proBNP at onset have sub-clinical myocardial involvement and might benefit from follow-up and continued evaluation, even in the absence of coronary artery involvement.

Impact of Socioeconomic Status on Outcomes of Patients with Kawasaki Disease.

OBJECTIVE: To evaluate the association of neighborhood socioeconomic status (SES) with time to intravenous immunoglobulin treatment, length of stay (LOS), and coronary artery aneurysms (CAAs) in patients with Kawasaki disease. STUDY DESIGN: We examined the relationship of SES in 915 patients treated at a large academic center between 2000 and 2017. Neighborhood SES was measured using a US census-based score derived from 6 measures related to income, education, and occupation. Linear and logistic regression were used to examine the association of SES with number of days of fever at time of treatment, LOS, and CAA. RESULTS: Patients in the lowest SES quartile were treated later than patients with greater SES (7 [IQR 5, 9] vs 6 [IQR 5, 8] days, P = .01). Patients in the lowest SES quartile were more likely to be treated after 10 days of illness, with an OR 1.9 (95% CI 1.3-2.8). In multivariable analysis, SES remained an independent predictor of the number of days of fever at time of treatment (P = .01). Patients in the lowest SES quartile had longer LOS than patients with greater SES (3 [IQR 2, 5] vs 3 [IQR 2, 4], P = .007). In subgroup analysis of white children, those in the lowest SES quartile vs quartiles 2-4 were more likely to develop large/giant CAA 17 (12%) vs 30 (6%), P = .03. CONCLUSIONS: Lower SES is associated with delayed treatment, prolonged LOS, and increased risk of large/giant CAA. Novel approaches to diagnosis and education are needed for children living in low-SES neighborhoods.