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.

Physiologic profile associated with severe multisystem inflammatory syndrome in children: a retrospective study.

OBJECTIVE: The purpose of this study was to describe the clinical presentation and physiologic profile of individuals with varying degrees of severity of multisystem inflammatory syndrome in children (MIS-C). METHODS: We performed a retrospective study of children diagnosed with MIS-C admitted to a single quaternary children's hospital from May 2020 to April 2021. We created an MIS-C severity score using the following parameters: hospital admission status (e.g., floor vs intensive care unit), need for inotropic or vasoactive medications, and need for mechanical ventilation. Univariate and multivariate analyses were performed to associate risk factors corresponding to the MIS-C severity score. RESULTS: The study included 152 children who were followed for 14 days post hospital admission. A stepwise forward selection process identified seven physiologic variables associated with "severe" MIS-C according to a logistic regression. Specifically, a combination of elevated creatinine (p = 0.013), international normalized ratio (p = 0.002), brain natriuretic peptide (p = 0.001), white blood cell count (p = 0.009), ferritin (p = 0.041), respiratory rate (p = 0.047), and decreased albumin (p = 0.047) led to an excellent discrimination between mild versus severe MIS-C (AUC = 0.915). CONCLUSION: This study derived a physiologic profile associated with the stratification of MIS-C severity. IMPACT: Based on a cohort of 152 individuals diagnosed with MIS-C, this study derived a nomenclature that stratifies the severity of MIS-C. Investigated demographic, presentational vital signs, and blood analytes associated with severity of illness. Identification of a multivariate physiologic profile that strongly associates with MIS-C severity. This model allows the care team to recognize patients likely to require a higher level of intensive care.

US Mortality Attributable to Congenital Heart Disease Across the Lifespan From 1999 Through 2017 Exposes Persistent Racial/Ethnic Disparities.

BACKGROUND: Congenital heart disease (CHD) accounts for ≈40% of deaths in US children with birth defects. Previous US data from 1999 to 2006 demonstrated an overall decrease in CHD mortality. Our study aimed to assess current trends in US mortality related to CHD from infancy to adulthood over the past 19 years and determine differences by sex and race/ethnicity. METHODS: We conducted an analysis of death certificates from 1999 to 2017 to calculate annual CHD mortality by age at death, race/ethnicity, and sex. Population estimates used as denominators in mortality rate calculations for infants were based on National Center for Health Statistics live birth data. Mortality rates in individuals ≥1 year of age used US Census Bureau bridged-race population estimates as denominators. We used joinpoint regression to characterize temporal trends in all-cause mortality, mortality resulting directly attributable to and related to CHD by age, race/ethnicity, and sex. RESULTS: There were 47.7 million deaths with 1 in 814 deaths attributable to CHD (n=58 599). Although all-cause mortality decreased 16.4% across all ages, mortality resulting from CHD declined 39.4% overall. The mean annual decrease in CHD mortality was 2.6%, with the largest decrease for those >65 years of age. The age-adjusted mortality rate decreased from 1.37 to 0.83 per 100 000. Males had higher mortality attributable to CHD than females throughout the study, although both sexes declined at a similar rate (≈40% overall), with a 3% to 4% annual decrease between 1999 and 2009, followed by a slower annual decrease of 1.4% through 2017. Mortality resulting from CHD significantly declined among all races/ethnicities studied, although disparities in mortality persisted for non-Hispanic Blacks versus non-Hispanic Whites (mean annual decrease 2.3% versus 2.6%, respectively; age-adjusted mortality rate 1.67 to 1.05 versus 1.35 to 0.80 per 100 000, respectively). CONCLUSIONS: Although overall US mortality attributable to CHD has decreased over the past 19 years, disparities in mortality persist for males in comparison with females and for non-Hispanic Blacks in comparison with non-Hispanic Whites. Determining factors that contribute to these disparities such as access to quality care, timely diagnosis, and maintenance of insurance will be important moving into the next decade.

Trisomy 18 Trends over the Last 20 Years.

OBJECTIVE: To evaluate the trends in hospitalizations for children with trisomy 18 over time and to determine the rate of invasive procedures on these children, using a large inpatient database. STUDY DESIGN: A retrospective analysis using the Kids' Inpatient Database from 1997 to 2016 was performed for trisomy 18. We evaluated survival to discharge as well as the presence of pulmonary, skeletal, neurologic, gastrointestinal, renal, and hematologic/bleeding problems. We also searched for the following interventions, if performed: gastrostomy tube placement, tracheostomy, or cardiac procedure. RESULTS: Over this period 10 151 admissions occurred in children with a diagnosis of trisomy 18. Between 1997 and 2016, the number of children admitted annually with trisomy 18 increased 74% from 1036 to 1798. The proportion of patients born prematurely remained stable at 14%-16% throughout the study. Gastrostomy tube placement increased 12-fold during the study period, tracheostomy increased 11-fold, and cardiac intervention increased 5-fold. The overall mortality rate decreased in those with trisomy 18 from 32% in 1997 to 21% in 2016. CONCLUSIONS: We highlight a decreased inpatient mortality rate during the study period. The number of children undergoing interventions such as gastrostomy tube and tracheostomy increased, as did the number of children undergoing cardiac intervention. Although the number of procedures has increased with the mortality rate decreasing, it is unclear at present whether the 2 are related.

Loss of Consciousness in the Young Child.

In the very young child (less than eight years of age), transient loss of consciousness represents a diagnostic and management dilemma for clinicians. While most commonly benign, syncope may be due to cardiac dysfunction which can be life-threatening. It can be secondary to an underlying ion channelopathy, cardiac inflammation, cardiac ischemia, congenital heart disease, cardiomyopathy, or pulmonary hypertension. Patients with genetic disorders require careful evaluation for a cardiac cause of syncope. Among the noncardiac causes, vasovagal syncope is the most common etiology. Breath-holding spells are commonly seen in this age group. Other causes of transient loss of consciousness include seizures, neurovascular pathology, head trauma, psychogenic pseudosyncope, and factitious disorder imposed on another and other forms of child abuse. A detailed social, present, past medical, and family medical history is important when evaluating loss of consciousness in the very young. Concerning characteristics of syncope include lack of prodromal symptoms, no preceding postural changes or occurring in a supine position, after exertion or a loud noise. A family history of sudden unexplained death, ion channelopathy, cardiomyopathy, or congenital deafness merits further evaluation. Due to inherent challenges in diagnosis at this age, often there is a lower threshold for referral to a specialist.

Immune thrombocytopenia following multisystem inflammatory syndrome in children (MIS-C) - a case series.

Patients with coronavirus disease 2019 (COVID-19) from novel coronavirus (SARS-CoV-2) infection may present with immune thrombocytopenia (ITP). Multisystem inflammatory syndrome in children (MIS-C) is a serious complication of SARS-CoV-2 causing systemic organ dysfunction. This case series presents the first reported cases of patients who developed ITP following MIS-C, while completing corticosteroid tapers. These patients responded to standard of care therapies for ITP and had appropriate platelet count recovery. We emphasize the importance of careful monitoring of those recovering from COVID-19 or MIS-C, to proactively identify clinical and laboratory abnormalities, in addition to long-term cardiovascular sequelae.

Chronic Maternal Hyperoxygenation and Effect on Cerebral and Placental Vasoregulation and Neurodevelopment in Fetuses with Left Heart Hypoplasia.

INTRODUCTION: In a pilot study of chronic maternal hyperoxygenation (CMH) in left heart hypoplasia (LHH), we sought to determine effect estimates of CMH on head size, vascular resistance indices, and neurodevelopment compared to controls. MATERIAL AND METHODS: Nine gravidae meeting the inclusion criteria (fetal LHH, ≥25.9 weeks' gestation, and ≥10% increase in percent aortic flow after acute hyperoxygenation) were prospectively enrolled. Controls were 9 contemporary gravidae with fetal LHH without CMH. Brain growth and Doppler-derived estimates of fetal cerebrovascular and placental resistance were blindly evaluated and compared using longitudinal regression. Postnatal anthropomorphic and neurodevelopmental assessments were compared. RESULTS: There was no difference in baseline fetal measures between groups. There was significantly slower biparietal diameter (BPD) growth in the CMH group (z-score change -0.03 ± 0.02 vs. +0.09 ± 0.05 units/week, p = 0.02). At 6 months postnatal age, the mean head circumference z-score in the CMH group was smaller than that of controls (-0.20 ± 0.58 vs. +0.85 ± 1.11, p = 0.048). There were no differences in neurodevelopmental testing at 6 and 12 months. DISCUSSION: In this pilot study, relatively diminished fetal BPD growth and smaller infant head circumference z-scores at 6 months were noted with in utero CMH exposure.

Familial clustering of cardiac conditions in patients with anomalous aortic origin of a coronary artery and myocardial bridges.

BACKGROUND: Anomalous aortic origin of a coronary artery is the second leading cause of sudden cardiac arrest/death in young athletes in the United States of America. Limited data are available regarding family history in this patient population. METHODS: Patients were evaluated prospectively from 12/2012 to 02/2017 in the Coronary Anomalies Program at Texas Children's Hospital. Relevant family history included the presence of CHD, sudden cardiac arrest/death, arrhythmia/pacemaker use, cardiomyopathy, and atherosclerotic coronary artery disease before the age of 50 years. The presence of one or more of these in 1st- or 2nd-degree relatives was considered significant. RESULTS: Of 168 unrelated probands (171 patients total) included, 36 (21%) had significant family history involving 19 (53%) 1st-degree and 17 (47%) 2nd-degree relatives. Positive family history led to cardiology referral in nine (5%) patients and the presence of abnormal tests/symptoms in the remaining patients. Coronary anomalies in probands with positive family history were anomalous right (27), anomalous left (five), single right coronary artery (two), myocardial bridge (one), and anomalous circumflex coronary artery (one). Conditions present in their family members included sudden cardiac arrest/death (15, 42%), atherosclerotic coronary artery disease (14, 39%), cardiomyopathy (12, 33%), CHD (11, 31%), coronary anomalies (3, 8%), myocardial bridge (1, 3%), long-QT syndrome (2, 6%), and Wolff-Parkinson-White (1, 3%). CONCLUSION: In patients with anomalous aortic origin of a coronary artery and/or myocardial bridges, there appears to be familial clustering of cardiac diseases in approximately 20% of patients, half of these with early occurrence of sudden cardiac arrest/death in the family.

Isolated coarctation of the aorta in the fetus: A diagnostic challenge.

Isolated coarctation of the aorta (CoA) is estimated by the Centers for Disease Control and Prevention to account for 4%-6% of all congenital heart disease (CHD) in the United States, with a reported prevalence of ~4 per 10 000 live births. Prenatal recognition of coarctation is important as it may improve neonatal survival and reduce morbidity. However, despite advances in imaging and the trend toward detailed aortic arch assessment as part of a comprehensive fetal echocardiogram, isolated CoA may still elude prenatal detection, with potentially lethal consequences if the diagnosis is not suspected and the patent ductus arteriosus (PDA) closes spontaneously in postnatal life. The purpose of this review is to outline the methods of antenatal aortic arch evaluation in the current era, discuss "red flags" that raise the suspicion for CoA, including associated anomalies and serve as a repository of the most up to date information regarding its diagnosis in utero and its perinatal management. Other aortic arch abnormalities, such as interrupted aortic arch, or CoA associated with complex single ventricles, are not included in this review.

Anomalous Coronary Arteries and Myocardial Bridges: Risk Stratification in Children Using Novel Cardiac Catheterization Techniques.

The evaluation of the vast majority of children with anomalous aortic origin of a coronary artery (AAOCA) and/or myocardial bridges is performed with non-invasive testing. However, a subset of these patients may benefit from invasive testing for risk stratification. All patients included in the Coronary Anomalies Program (CAP) at Texas Children's Hospital who underwent cardiac catheterization were included. Techniques included selective coronary angiograms (SCA), intravascular ultrasound (IVUS), and fractional flow reserve (FFR) measurements with provocative testing using adenosine and/or dobutamine infusions. Out of the 131 patients followed by the CAP between 12/12-4/16, 8 (6%) patients underwent 9 cath investigations at median age 13.1 (2.6-18.7) years and median weight 49.5 (11.4-142.7) kg. Six patients presented with cardiac signs/symptoms. Four patients had myocardial bridges of the left anterior descending (LAD) coronary artery, 2 patients had isolated AAOCA, and 2 patients had an anomalous left coronary artery (LCA) with an intramyocardial course of the LAD. SCA was performed in all patients. FFR was positive in 4/6 patients: IVUS showed >70% intraluminal narrowing in 3/5 patients. One patient had hemodynamic instability that reversed with catheter removal from the coronary ostium. Based on the catheterization data obtained, findings were reassuring in three patients, surgery was performed in three patients, and two patients are being medically managed/restricted from competitive sports. In our small cohort of patients, we demonstrated that IVUS and FFR can safely be performed in children and may help to risk stratify some patients with AAOCA and myocardial bridges.

Atrial septal defect closure is associated with improved clinical status in patients ≤ 10 kg with bronchopulmonary dysplasia.

Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post-ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD-ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD-ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre- to 8 weeks post-intervention, and pre- and post-intervention score slopes were created. These slopes were compared using mixed regression modeling with an interaction term. There was a significant difference in pre- versus post-intervention slope with the most score drop the first week post-intervention (-2.1 + /- 0.8, p = 0.014). The mean score also dropped through weeks 2 (slope -0.8 + /- 0.8, p = 0.013) and 4 (slope -1.0 + /- 0.5, p = 0.001) post-intervention. There was a significant difference in pre- and post-intervention slopes for diuretics (p = 0.018) and the combined score of respiratory support, FiO2 need, and respiratory symptoms (p = 0.018). This study demonstrated significant improvement in BPD-ASD score, diuretic need, and respiratory status after ASD closure in BPD-ASD patients ≤ 10 kg that was outside of the natural course of BPD. Our study was limited by its small, single-center, retrospective nature. Future studies should be performed in a larger multicenter population to both validate the scoring system and compare to non-intervention infants.

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.

Lesion-specific mortality due to congenital heart disease in U.S. adults from 1999 to 2017.

BACKGROUND: Adults with congenital heart disease (ACHD) comprise an increasing proportion of individuals living with CHD in the United States (US) although little is known regarding lesion or age-specific mortality in the modern era. Our study aimed to describe current era ACHD mortality rates by age and CHD lesion and provide temporal mortality rate trends for the last two decades. METHODS: We conducted a 19-year analysis (1999-2017) of publicly available, de-identified Multiple Cause of Death data compiled and produced by the National Center for Health Statistics. Age and lesion-specific mortality rates were calculated using joinpoint regression. RESULTS: ACHD mortality rates decreased by an average of 2%-4% per year for all adults. CHD lesions resulting in the highest ACHD-related mortality varied by age. Unlike the other lesions, mortality attributed to single ventricle physiology failed to improve in early adulthood (average of 1.6% increase per year). In decedents age 65 years or older, simpler forms of CHD like shunt lesions became more prominent contributors, accounting for 46% of deaths. CONCLUSION: Rates of mortality due to ACHD have declined significantly for adults with CHD, however, continued mortality due to single ventricle physiology remains an area requiring improved strategies to increase survival.

Myocarditis and pericarditis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

Myocarditis and/or pericarditis (also known as myopericarditis) are inflammatory diseases involving the myocardium (with non-ischemic myocyte necrosis) and/or the pericardial sac. Myocarditis/pericarditis (MPC) may present with variable clinical signs, symptoms, etiologies and outcomes, including acute heart failure, sudden death, and chronic dilated cardiomyopathy. Possible undiagnosed and/or subclinical acute myocarditis, with undefined potential for delayed manifestations, presents further challenges for diagnosing an acute disease and may go undetected in the setting of infection as well as adverse drug/vaccine reactions. The most common causes of MPC are viral, with non-infectious, drug/vaccine associated hypersensitivity and/or autoimmune causes being less well defined and with potentially different inflammatory mechanisms and treatment responses. Potential cardiac adverse events following immunization (AEFIs) encompass a larger scope of diagnoses such as triggering or exacerbating ischemic cardiac events, cardiomyopathy with potential heart failure, arrhythmias and sudden death. The current published experience does not support a potential causal association with vaccines based on epidemiologic evidence of relative risk increases compared with background unvaccinated incidence. The only evidence supporting a possible causal association of MPC with a vaccine comes from case reports. Hypersensitivity MPC as a drug/vaccine induced cardiac adverse event has long been a concern for post-licensure safety surveillance, as well as safety data submission for licensure. Other cardiac adverse events, such as dilated cardiomyopathy, were also defined in the CDC definitions for adverse events after smallpox vaccination in 2006. In addition, several groups have attempted to develop and improve the definition and adjudication of post-vaccination cardiovascular events. We developed the current case definitions for myocarditis and pericarditis as an AEFI building on experience and lessons learnt, as well as a comprehensive literature review. Considerations of other etiologies and causal relationships are outside the scope of this document.

Impaired Myocardial Perfusion on Stress CMR Correlates With Invasive FFR in Children With Coronary Anomalies.

BACKGROUND: Invasive fractional flow reserve (FFR) is considered the gold standard to evaluate coronary artery flow. Stress cardiovascular magnetic resonance (sCMR) is an emerging non-invasive tool to evaluate myocardial perfusion in children. We sought to compare sCMR with FFR to determine impaired intracoronary flow in children with anomalous aortic origin of a coronary artery (AAOCA) and/or myocardial bridge (MB) who presented concern for myocardial ischemia. METHODS: From December 2012 to May 2019, AAOCA and/or MB patients (<20 years old) were prospectively enrolled and underwent sCMR and FFR. Abnormal sCMR included perfusion/regional wall-motion abnormality in the involved coronary distribution. FFR was performed at baseline and with dobutamine/regadenoson and considered abnormal if <0.8 in the affected coronary segment. RESULTS: Of 376 patients evaluated, a total of 19 (age range, 0.2-17 years) underwent 24 sets of sCMR and FFR studies, with 5 repeat studies following intervention. Types of anomalies included 6 isolated MB/normal CA origins, 5 single CAs, 5 left AAOCAs, and 3 right AAOCAs. Seventeen patients (89.5%) had MB/intramyocardial course - 14 involving the left anterior descending coronary artery and 3 with multivessel involvement. sCMR correlated with FFR in 19/24 sets (7 sCMR and FFR positive, 12 sCMR and FFR negative) and it did not correlate in 5/24 sets. The positive percent agreement was 77.8%, negative percent agreement was 80.0%, and overall percent agreement was 79.2%. CONCLUSIONS: Assessment of myocardial perfusion using non-invasive sCMR concurred with FFR, particularly if performed with close proximity in time, and may contribute to risk stratification and decision making in children with AAOCA and/or MB.

Myocardial Ischemia in Children With Anomalous Aortic Origin of a Coronary Artery With Intraseptal Course.

BACKGROUND: Intraseptal anomalous aortic origin of a coronary artery is considered a benign condition. However, there have been case reports of patients with myocardial ischemia, arrhythmia, and sudden cardiac death. The purpose of this study was to determine the clinical presentation, myocardial perfusion on provocative stress testing, and management of children with anomalous aortic origin of a coronary artery with an intraseptal course in a prospective cohort. METHODS: Patients with anomalous aortic origin of a coronary artery and intraseptal course were prospectively enrolled from December 2012 to May 2019, evaluated, and managed following a standardized algorithm. Myocardial perfusion was assessed using stress imaging. Fractional flow reserve was performed in patients with myocardial hypoperfusion on noninvasive testing. Exercise restriction, ß-blockers, and surgical intervention were discussed with the families. RESULTS: Eighteen patients (female 6, 33.3%), who presented with no symptoms (10, 55.6%), nonexertional (4, 22.2%), and exertional symptoms (4, 22.2%), were enrolled at a median age of 12.4 years (0.3-15.9). Perfusion imaging was performed in 14/18 (77.8%) and was abnormal in 7/14 (50%); fractional flow reserve was positive in 5/8 (62.5%). All 4 patients with exertional symptoms and 3/10 (30%) with no or nonexertional symptoms had myocardial hypoperfusion. Coronary artery bypass grafting was performed in a 4-year-old patient; ß-blocker and exercise restriction were recommended in 4 patients not suitable for surgery. One patient had nonexertional chest pain and 17 were symptom-free at median follow-up of 2.5 years (0.2-7.1). CONCLUSIONS: Up to 50% of patients with intraseptal anomalous aortic origin of a coronary artery had inducible myocardial hypoperfusion during noninvasive provocative testing. Long-term follow-up is necessary to understand the natural history of this rare anomaly.

Right Ventricle-Dependent Coronary Circulation: Location of Obstruction Is Associated With Survival.

BACKGROUND: Pulmonary atresia with intact ventricular septum (PAIVS) with right ventricle-dependent coronary circulation (RVDCC) carries suboptimal outcomes primarily due to cardiac ischemia. We hypothesize clinical outcomes are affected by the level of coronary obstruction, a surrogate for vulnerable myocardium. METHODS: We conducted a single-institution retrospective analysis of all neonates with PAIVS with RVDCC from 1995 to 2017. RVDCC was defined as the presence of any coronary-cameral fistula with coronary obstruction proximal to the fistula and angiographic evidence of RV perfusion of the myocardium through the fistulous communication. Location of coronary obstruction was categorized as either proximal or distal segments, using the SYNTAX score criteria. Transplant-free survival was compared between patients with proximal and distal obstruction, then these groups were compared with patients without RVDCC. RESULTS: Of 103 neonates with PAIVS, 28 (27%) had RVDCC: 18 proximal (64%), 10 distal (36%). Median age at last follow-up for patients with RVDCC was 1.8 years (interquartile range, 0.3-8.1 years). All deaths (10 of 28, 36%) occurred at 6 months old or earlier. Proximal coronary artery obstruction was associated with decreased transplant-free survival relative to distal obstruction (hazard ratio = 3.63; 95% confidence interval, 1.01-13.00; P = .048). Transplant-free survival at 1 year was 33% and 70% in the proximal and distal obstruction groups, respectively. Compared with patients without RVDCC, patients with proximal obstruction had significantly lower transplant-free survival (P < .001), whereas patients with distal obstruction did not (P = .217). CONCLUSIONS: The location of coronary artery obstruction affects clinical outcome and may represent a potential branch point in the management for PAIVS with RVDCC.

Outcomes in Anomalous Aortic Origin of a Coronary Artery Following a Prospective Standardized Approach.

BACKGROUND: Anomalous aortic origin of a coronary artery (CA) is the second leading cause of sudden cardiac death in young athletes. Management is controversial and longitudinal follow-up data are sparse. We aim to evaluate outcomes in a prospective study of anomalous aortic origin of CA patients following a standardized algorithm. METHODS: Patients with anomalous aortic origin of a CA were followed prospectively from December 2012 to April 2017. All patients were evaluated following a standardized algorithm, and data were reviewed by a dedicated multidisciplinary team. Assessment of myocardial perfusion was performed using stress imaging. High-risk patients (high-risk anatomy-anomalous left CA from the opposite sinus, presence of intramurality, abnormal ostium-and symptoms or evidence of myocardial ischemia) were offered surgery or exercise restriction (if deemed high risk for surgical intervention). Univariate and multivariable analyses were used to determine predictors of high risk. RESULTS: Of 201 patients evaluated, 163 met inclusion criteria: 116 anomalous right CA (71%), 25 anomalous left CA (15%), 17 single CA (10%), and 5 anomalous circumflex CA (3%). Patients presented as an incidental finding (n=80, 49%), with exertional (n=31, 21%) and nonexertional (n=32, 20%) symptoms and following sudden cardiac arrest/shock (n=5, 3%). Eighty-two patients (50.3%) were considered high risk. Predictors of high risk were older age at diagnosis, black race, intramural course, and exertional syncope. Most patients (82%) are allowed unrestrictive sports activities. Forty-seven patients had surgery (11 anomalous left CA and 36 anomalous right CA), 3 (6.4%) remained restricted from sports activities. All patients are alive at a median follow-up of 1.6 (interquartile range, 0.7-2.8) years. CONCLUSIONS: In this prospective cohort of patients with anomalous aortic origin of a CA, most have remained free of exercise restrictions. Development of a multidisciplinary team has allowed a consistent approach and may have implications in risk stratification and long-term prognosis.

Coronary artery disease in a child with homozygous familial hypercholesterolemia: Regression after liver transplantation.

Children with homozygous familial hypercholesterolemia are at risk for early cardiovascular events secondary to coronary artery disease. Current medical therapy does not ameliorate this risk. Liver transplantation offers the most effective option to reduce circulating levels of low-density lipoprotein cholesterol and thereby reduce risk of cardiovascular events. Angiographic evidence of regression of coronary artery disease is presented.