Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Variants on Short- and Mid-term Cardiac Outcomes in Multisystem Inflammatory Syndrome in Children.

Cardiac outcomes of 131 children with multisystem inflammatory syndrome (MIS-C) were examined. The majority of the cohort was male (66.4%) and half were Black (49.6%). Cardiac involvement was evident in 25% of the cohort at diagnosis. Favorable short- and mid-term outcomes were documented on follow-up, irrespective of the severe acute respiratory syndrome coronavirus 2 variants causing the infection.

Examination of Adverse Reactions After COVID-19 Vaccination Among Patients With a History of Multisystem Inflammatory Syndrome in Children.

Importance: Data are limited regarding adverse reactions after COVID-19 vaccination in patients with a history of multisystem inflammatory syndrome in children (MIS-C). The lack of vaccine safety data in this unique population may cause hesitancy and concern for many families and health care professionals. Objective: To describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C. Design, Setting, and Participants: In this multicenter cross-sectional study including 22 North American centers participating in a National Heart, Lung, and Blood Institute, National Institutes of Health-sponsored study, Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC), patients with a prior diagnosis of MIS-C who were eligible for COVID-19 vaccination (age ≥5 years; ≥90 days after MIS-C diagnosis) were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions. Exposures: COVID-19 vaccination after MIS-C diagnosis. Main Outcomes and Measures: The main outcome was adverse reactions following COVID-19 vaccination. Comparisons were made using the Wilcoxon rank sum test for continuous variables and the χ2 or Fisher exact test for categorical variables. Results: Of 385 vaccine-eligible patients who were surveyed, 185 (48.1%) received at least 1 vaccine dose; 136 of the vaccinated patients (73.5%) were male, and the median age was 12.2 years (IQR, 9.5-14.7 years). Among vaccinated patients, 1 (0.5%) identified as American Indian/Alaska Native, non-Hispanic; 9 (4.9%) as Asian, non-Hispanic; 45 (24.3%) as Black, non-Hispanic; 59 (31.9%) as Hispanic or Latino; 53 (28.6%) as White, non-Hispanic; 2 (1.1%) as multiracial, non-Hispanic; and 2 (1.1%) as other, non-Hispanic; 14 (7.6%) had unknown or undeclared race and ethnicity. The median time from MIS-C diagnosis to first vaccine dose was 9.0 months (IQR, 5.1-11.9 months); 31 patients (16.8%) received 1 dose, 142 (76.8%) received 2 doses, and 12 (6.5%) received 3 doses. Almost all patients received the BNT162b2 vaccine (347 of 351 vaccine doses [98.9%]). Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness (62 patients [33.5%]) and/or fatigue (32 [17.3%]). In 32 patients (17.3%), adverse reactions were treated with medications, most commonly acetaminophen (21 patients [11.4%]) or ibuprofen (11 [5.9%]). Four patients (2.2%) sought medical evaluation, but none required testing or hospitalization. There were no patients with any serious adverse events, including myocarditis or recurrence of MIS-C. Conclusions and Relevance: In this cross-sectional study of patients with a history of MIS-C, no serious adverse events were reported after COVID-19 vaccination. These findings suggest that the safety profile of COVID-19 vaccination administered at least 90 days following MIS-C diagnosis appears to be similar to that in the general population.

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.

Orthostatic intolerance in post-concussion patients.

Orthostatic intolerance (OI) following pediatric concussion is not well understood. Assessing the prevalence of concussion-related OI and how it compares to non-concussion-related OI will improve care for patients suffering with these symptoms. OBJECTIVE: We set out to describe concussion-related OI in adolescence, with particular emphasis on time to recovery and differences from non-concussion-related OI (including male vs. female prevalence). Retrospective chart reviews were completed on post-concussion patients endorsing symptoms of OI. The patients' sex, sport history, previous concussions, time since injury, and recovery time were analyzed and compared between males and females as well as against general OI statistics. Thirty-nine pediatric patients, representing 8.7% of all new patients referred to a specialized concussion clinic over a 13-month interval, were included in the chart review. Mean age of onset was 15.0 ± 2.5 years and 18 (46%) were males. The median times from evaluation to symptom resolution were 120 days. Of 18 patients who completed head-up tilt table testing, 17 (94%) had orthostatic tachycardic response (>40 bpm heart rate increment). Post-concussive OI differs from other orthostatic intolerance etiologies, lacking a strong female predominance and exhibiting a shorter time course to recovery compared to other etiologies of OI (but longer recovery time compared to concussion patients in general). Clinical orthostatic vital signs may not be sensitive for diagnosing orthostatic intolerance in athletes, likely due to higher vagal tone and more efficient skeletal muscle pump.

Noisy Breathing in an Infant: A Case Report.

The diagnosis of vascular rings is challenging and may be delayed as symptoms overlap with more common conditions associated with childhood. Underlying genetic associations of this condition remain largely undiscovered. In this report, we present a patient with a double aortic arch and highlight the importance of diagnostic imaging. We also engage in a review of the important genetic considerations.

"Treat-to-close": Non-repairable ASD-PAH in the adult: Results from the North American ASD-PAH (NAAP) Multicenter Registry.

BACKGROUND: Adults presenting with an unrepaired atrial septal defect and pulmonary arterial hypertension (ASD-PAH) are typically classified as "correctable" or "non-correctable". The use of directed PAH medical therapy in non-correctable ASD-PAH leading to favorable closure candidacy, repair status and long-term follow-up is not well studied. We therefore sought to characterize response to PAH targeted therapy in 'non-correctable' ASD-PAH. METHODS AND RESULTS: Nine North American tertiary care centers submitted retrospective data from adults with unrepaired ASD-PAH that did not meet recommendations for repair at initial presentation (1996-2017). Sixty-nine patients (women 51(74%), 40 ±â€¯15 years, mean pulmonary artery pressure (mPA) 51 ±â€¯13 mm Hg, pulmonary vascular resistance (PVR) 8.7 ±â€¯4.9 Wood units, Qp:Qs 1.6 ±â€¯0.4) were enrolled. All patients were prescribed PAH targeted therapy and late shunt repair occurred in 19(28%) (Women 15(29%) vs. Men 4(22%), p = 0.6). At late follow-up (4.4 ±â€¯2.9 years) 6-minute walk test distance (6MWTD) was significantly better in the group that underwent repair (486 ±â€¯89 m vs. 375 ±â€¯139 m, p < 0.05). Transthoracic echo showed significant improvement in right ventricular (RV) function (severe dysfunction in repaired 8(40%) vs. unrepaired groups 35(69%), p < 0.05). Divergent survival curves suggest that with larger studies and more follow-up, differences in survival between repaired and unrepaired groups may be important. (repaired: 17(94%) vs. unrepaired: 32(81%), p = 0.18). CONCLUSIONS: This is the first and largest multicenter study evaluating the "treat-to-close" approach in non-correctable ASD-PAH. Our new data supports further study of this strategy in patients who have reversibility of PAH in response to targeted therapy. We demonstrate that in the carefully selected patient with non-correctable ASD-PAH, successful shunt repair is possible if post-therapy PVR is ≤6.5 Wood units. Patients who underwent repair had improved RV function following PAH targeted therapy. Divergent survival curves suggest that with further study, defect repair may affect medium-term to late survival.

Frontiers in Fontan failure: Innovation and improving outcomes: A conference summary.

The initial "Frontiers in Fontan Failure" conference in 2015 in Atlanta, GA, provided an opportunity for experts in the field of pediatric cardiology and adult congenital heart disease to focus on the etiology, physiology, and potential interventions for patients with "Failing Fontan" physiology. Four types of "Fontan Failure" were described and then published by Dr Book et al. The acknowledgment that even Dr Fontan himself realized that the Fontan procedure "imposed a gradually declining functional capacity and premature late death after an initial period of often excellent palliation." The purpose of the second "Frontiers in Fontan Failure" was to further the discussion regarding new data and technologies as well as novel interventions. The 2017 "Frontiers in Fontan Failure: Innovation and Improving Outcomes" was sponsored by Children's Healthcare of Atlanta, Sibley Heart Center Cardiology, and Emory University School of Medicine. Future directions in the management of Fontan failure include further investigations into the risk of sudden cardiac death and how to properly prevent it, achievable interventions in modifying the Fontan physiology to treat or prevent late complications, and improved and refined algorithms in Fontan surveillance. Finally, further research into the interventional treatment of lymphatic-related complications hold the promise of marked improvement in the quality of life of advanced Fontan failure patients and as such should be encouraged and contributed to.

Pediatric dysautonomia: Much-maligned, often overmedicated, but not as complex as you think.

Dysautonomia is an increasingly recognized yet still poorly understood disease within the field of pediatrics. Symptoms, including dizziness, headaches, fatigue, joint pain, anxiety, and intolerance of heat or cold, are often significant and difficult to sort, especially in terms of their relation to each other. This often leads to referral to multiple subspecialists, who then proceed to treat seemingly familiar symptoms in kind. In the authors' experience, this leads to more frustration on the part of the patients and their physicians when symptom improvement does not follow (or can even worsen). On the other hand, by understanding the pathophysiology, treatment success is possible by directing therapies toward the root causes and just as importantly, enlisting the patient in a daily treatment plan. In the text that follows, we hope to convey these viewpoints by highlighting an involved case, discussing the pathophysiology, outlining the usual evaluation, and finally describing our approach to treatment.

Four new cases of pediatric thoracic aortic aneurysm (TAA) with review of the molecular genetic basis, utilizing the newly published consensus nomenclature.

The majority of thoracic aortic aneurysms (TAA) in the pediatric population are due to post repair etiology (iatrogenic). Although rare, underlying inheritable disease and congenital cardiac anomalies represent the most common non-iatrogenic cause of TAA among patients in this age group (1-21 years of age). Herein, we present a case series of 9aortic aneurysms with varying underlying etiology. We discuss the molecular genetic basis of these syndromes in conjunction with the radiological findings and histological description utilizing the newly published consensus criteria article.

"Frontiers in Fontan failure: A summary of conference proceedings".

"Frontiers in Fontan Failure" was the title of a 2015 conference sponsored by Children's Healthcare of Atlanta and Emory University School of Medicine. In what is hoped to be the first of many such gatherings, speakers and attendees gathered to discuss the problem of long-term clinical deterioration in these patients. Specific focuses included properly defining the problem and then discussing different treatment strategies, both medical and surgical. The health of the liver after Fontan palliation was a particular point of emphasis, as were quality of life and future directions.

Catheter-measured Hemodynamics of Adult Fontan Circulation: Associations with Adverse Event and End-organ Dysfunctions.

BACKGROUND: In heart failure, a high systemic vascular resistance index (SVRI), high central venous pressure (CVP), and low cardiac index (CI) predict poor outcomes. Conversely, late hemodynamic manifestations of failing Fontan circulation and associations with end-organ dysfunction are not well understood. METHODS: A retrospective review of right-heart catheterization data of adult Fontan patients between 2002 and 2014 was conducted. Relationships between hemodynamic variables and serious adverse events (death or heart transplant) were examined using the Cox proportional hazard analysis. Correlations between the hemodynamic measurements and signs of end-organ dysfunction (MELD-XI, Child-Pugh, VAST score, estimated glomerular filtration rate [eGFR]) were analyzed. RESULTS: Sixty post-Fontan patients (85% systemic left ventricle, 40% atriopulmonary Fontan, mean age of 28 years, and mean time since Fontan operation of 21.9 years) were included. At baseline, those with an event were statistically younger, had lower transcutaneous oxygen saturations, were more likely to have an atriopulmonary Fontan, and were more likely to have a pacemaker. Eighteen experienced a cardiovascularly significant event. Using univariate analysis to compare the event and nonevent groups, mean CI was 2.8 ± 0.9 vs. 2.4 ± 0.5 L/min/m2 (P = .004), and CVP was 18.6 ± 6.5 vs. 16.1 ± 4.3 mmHg (P = .03). However, the statistical significances did not persist in the multivariate model. Higher CVP and pulmonary capillary wedge pressure (PCWP) were associated with higher MELD-XI and Child-Pugh scores, and the VAST score was only associated with PCWP. CONCLUSIONS: Symptomatic adult Fontan patients who experienced an event manifested with a higher CI and CVP, although the multivariate Cox proportional hazard analysis did not yield any significant associations. The presences of hepatic dysfunction and portal venous outflow obstruction were associated with a higher CVP and PCWP. Renal dysfunction was prevalent but no statistically significant association between the hemodynamic measurements was identified, although trends toward a higher CVP and transpulmonary gradient were identified.

Risk Assessment and Management of the Mother with Cardiovascular Disease.

Chronic medical conditions account for most nonobstetrical pregnancy-related maternal complications. Preconception counseling of women with cardiovascular disease can be aided by an understanding of cardiovascular physiology in pregnancy and risk scores to guide management.

Tissue Doppler Imaging-derived Diastolic Function Assessment in Children With Sickle Cell Disease and Its Relation With Ferritin.

Diastolic dysfunction has been shown to occur earlier than systolic dysfunction in iron overload states in adult patients with sickle cell disease (SCD). Tissue Doppler imaging (TDI)-derived E/E' has emerged as a noninvasive marker of diastolic function. We sought to determine diastolic function in children with SCD and study its relation with iron overload. A retrospective review of medical records of 225 pediatric patients with SCD who received an echocardiogram between January 2008 and December 2012 was performed. Echocardiographic measures including M-mode, spectral Doppler, and TDI-derived E/E' were compared with previously published data in healthy children. The left ventricular end-diastolic and end-systolic dimensions were significantly higher in SCD (P<0.0001) and the shortening fraction was similar (P=0.66). E/E' ratio was significantly higher in SCD at the mitral annulus, septum, and tricuspid annulus. In 54% of subjects, the septal E/E' was >8, indicating elevated left ventricular filling pressure. However, there was no significant correlation between ferritin level and E/E' ratios. Pediatric patients with SCD have a high prevalence of elevated estimated left ventricular filling pressure, but this does not correlate with ferritin levels.

Elevated tricuspid regurgitant velocity as a marker for pulmonary hypertension in children with sickle cell disease: less prevalent and predictive than previously thought?

Although elevated tricuspid regurgitant velocity (TRV), an echocardiographic marker for pulmonary hypertension, has previously been tied to mortality in adult patients with sickle cell disease, recent data demonstrated that it correlates poorly with catheterization findings. We describe the largest echocardiographic evaluation of pediatric patients with sickle cell disease to date, specifically the results of a protocol whereby a TRV≥250 cm/s prompted further evaluation. We investigated if elevated TRV would independently identify patients at risk for increased morbidity. A clinical echocardiographic database containing 630 patients with sickle cell disease was retrospectively reviewed; 120 patients (19%) met inclusion criteria and were compared 1:1 to randomly selected age-matched controls from the same database. By multivariate analysis, the elevated TRV cohort did not differ from controls in likelihood of acute chest episodes, hospitalization, or stroke. The study cohort's mean TRV in fact decreased to 242±33 cm/s at follow-up without a discernible and comprehensive intervention to explain the improvement. Three patients had catheterization-proven pulmonary hypertension. In conclusion, elevated TRV in children with sickle cell disease is less prevalent than previously thought and is not independently associated with increased short-term morbidity.

Severe aortopathy due to fibulin-4 deficiency: molecular insights, surgical strategy, and a review of the literature.

UNLABELLED: Mutations in the EFEMP2 (alias FBLN4) gene, which encodes the extracellular matrix protein fibulin-4, lead to severe aortopathy with aneurysm formation and vascular tortuosity. The disease phenotype, termed autosomal recessive cutis laxa type 1B (ARCL 1B), is rare among heritable connective tissue diseases but becomes more likely when noting family consanguinity and loose, inelastic skin in the patient. Our patient presented with an intercurrent illness exacerbating upper airway obstruction due to compression from a large aortic aneurysm. Genetic testing eventually revealed the causative mutation. She was initially treated with an angiotensin II receptor blocker and beta-blocker and eventually underwent total thoracic aortic replacement via a two-stage elephant trunk-type procedure. She recovered well and is currently asymptomatic but will require lifetime follow-up due to residual vascular tortuosity and aneurysm risk. CONCLUSION: Better understanding of the importance of transforming growth factor beta signaling in the pathophysiology of aortopathies such as ARCL 1B has led to targeted medical therapies. Specific surgical techniques can lead to optimal outcomes in these patients.

Hemodynamic phenotype of the failing Fontan in an adult population.

Fontan failure can occur even with normal systolic ventricular function and often in the context of significant liver disease. We hypothesized that Fontan failure is hemodynamically distinct from traditional heart failure and characterized by low systemic vascular resistance (SVR) index and preserved cardiac index. Twenty-seven symptomatic adult Fontan (SAF) patients who underwent catheterization from 2001 to 2011 constituted our study group. Fifty-four predominantly asymptomatic pediatric Fontan (PF) patients who underwent catheterization during the same period were randomly selected to perform a control:case cohort analysis. Clinical comparisons were made between the 2 groups. The adults were more symptomatic than the PF cohort (New York Heart Association classes I and II or III and IV: 48% or 52% [SAF] vs 94% or 6% [PF], respectively, p <0.01). SAF versus PF mean catheterization findings were central venous pressure 18 ± 6 versus 14 ± 3 mm Hg (p <0.01), SVR index 1,680 ± 368 versus 1,960 ± 550 dyn s/cm(5)/m(2) (p = 0.02), and cardiac index 2.7 ± 0.8 versus 2.8 ± 0.7 L/min/m(2) (p = 0.25). By imaging, the SAF cohort demonstrated a greater incidence of abnormal liver texture changes (96% vs 75%, p = 0.04) and nodularity (77% vs 42%, p = 0.02). In conclusion, adult patients with failing Fontan circulation had a lower SVR index and similar cardiac index compared with the pediatric cohort. Liver disease in the adults was more advanced. Our data suggest that Fontan failure is a distinct circulatory derangement with hemodynamic features similar to portal hypertension, albeit with limited ability to augment cardiac output.

Features of portal hypertension are associated with major adverse events in Fontan patients: the VAST study.

BACKGROUND: Chronic congestive hepatopathy is known to cause hepatic fibrosis and portal hypertension in patients post-Fontan operation for single ventricle palliation. The clinical significance of these findings is not clear. We hypothesized that features of portal hypertension would be significantly related to major adverse events. METHODS: A retrospective review of 73 adult and pediatric post-Fontan patients referred for a liver evaluation from 2001 to 2011 was performed. The relationship between features of portal hypertension (VAST score ≥2, 1 point each for Varices, Ascites, Splenomegaly or Thrombocytopenia) and a major adverse event (death, need for transplant, or hepatocellular carcinoma) was examined using logistic regression. RESULTS: 73 post-Fontan patients (30% female, 73% Caucasian, 66% systemic left ventricle (SLV), mean age 24±11 years, mean interval from Fontan 17±6 years) were included in analysis. Features of portal hypertension (VAST score ≥2) were present in 26 (36%), and there were 19 major adverse events: death (n=12), transplant (n=6), and HCC (n=1). A significant relationship was found between VAST score ≥2 and major adverse events (OR=9.8, 95% CI [2.9-32.7]). After adjusting for time since Fontan, SLV, age, hemoglobin and type of failure, VAST score ≥2 remained significant (OR=9.1, 95% CI [1.4-57.6]). CONCLUSION: Fontan patients with features of portal hypertension have a 9-fold increased risk for a major adverse event. Therapies targeted to manage clinical manifestations of portal hypertension, and early referral to heart transplant may help delay major adverse events. Future prospective studies are needed to confirm these findings.

Safe and effective use of a glycemic control protocol for neonates in a cardiac ICU.

OBJECTIVE: To investigate the safety and efficacy of a hyperglycemia protocol in neonates with critical cardiac illness. Neonates are often regarded as high risk for hypoglycemia while receiving continuous insulin infusions and thus have been excluded from some clinical trials. DESIGN: A retrospective review. SETTING: A pediatric cardiac ICU in a tertiary academic center. INTERVENTIONS: Neonates with critical cardiac illness who developed hyperglycemia were placed on an insulin-hyperglycemia protocol at the attending physician's discretion. Insulin infusions were titrated based on frequent blood glucose monitoring. MEASUREMENTS: Critical illness hyperglycemia was defined as a blood glucose less than 140 mg/dL. Hypoglycemia was defined as moderate (≤ 60 mg/dL) or severe (≤ 40 mg/dL). Initiating blood glucose, lowest blood glucose during insulin infusion, doses of insulin, duration of insulin, and time to blood glucose greater than 140 mg/dL were evaluated. MAIN RESULTS: A total of 44 patients were placed on the protocol between January 2009 and October 2011. The majority of insulin infusions were initiated in the early postoperative period (33 of 44, 75%). Moderate hypoglycemia occurred in two patients (4.5%), with blood glucose levels of 49 and 53 mg/dL. No episodes of severe hypoglycemia occurred. A total of 345 discrete blood glucose levels were analyzed; two of these being greater than 60 mg/dL (0.58%). Mean blood glucose prior to starting insulin was 252 ± 45 mg/dL and time until euglycemia was 6.1 ± 3.9 hours. The mean duration of insulin infusion was 24.6 ± 38.7 hours, mean peak dose was 0.10 ± 0.05 units/kg/hour, and mean insulin dose was 0.06 ± 0.02 units/kg/hour. For postoperative patients, mean time after bypass until onset of hyperglycemia was 2.2 ± 2.6 hours. CONCLUSIONS: A glycemic control protocol can safely and effectively be applied to neonates with critical cardiac disease. Neonates with critical cardiac illness should be included in clinical trials evaluating the benefits of glycemic control.