Anomalous Aortic Origin of a Coronary Artery.

BACKGROUND: Although anomalous aortic origin of a coronary artery (AAOCA) is associated with risk of sudden cardiac arrest (SCA), there is a spectrum of disease, with the appropriate management for many remaining unclear. Increasing data warrant review for an updated perspective on management. METHODS: A panel of congenital cardiac surgeons, cardiologists, and imaging practitioners reviewed the current literature related to AAOCA and its management. Survey of relevant publications from 2010 to the present in PubMed was performed. RESULTS: The prevalence of AAOCA is 0.4% to 0.8%. Anomalous left coronary artery is 3 to 8 times less common than anomalous right coronary, but carries a much higher risk of SCA. Nevertheless, anomalous right coronary is not completely benign; 10% demonstrate ischemia, and it remains an important cause of SCA. Decision-making regarding which patients should be recommended for surgical intervention includes determining anatomic features associated with ischemia, evidence of ischemia on provocative testing, and concerning cardiovascular symptoms. Ischemia testing continues to prove challenging with low sensitivity and specificity, but the utility of new modalities is an active area of research. Surgical interventions focus on creating an unobstructed path for blood flow and choosing the appropriate surgical technique given the anatomy to accomplish this. Nontrivial morbidity has been reported with surgery, including new-onset ischemia. CONCLUSIONS: A proportion of patients with AAOCA demonstrate features and ischemia that warrant surgical intervention. Continued work remains to improve the ability to detect inducible ischemia, to risk stratify these patients, and to provide guidance in terms of which patients warrant surgical intervention.

Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDL receptor (LDLR) function. Given that severely elevated LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating a largely unmet need for aggressive LDLR-independent lipid-lowering therapies in young patients with HoFH. Here we present the first evaluation of the efficacy and safety of evinacumab, a novel LDLR-independent lipid-lowering therapy, in pediatric patients with HoFH from parts A and B of a 3-part study. METHODS: The phase 3, part B, open-label study treated 14 patients 5 to 11 years of age with genetically proven HoFH (true homozygotes and compound heterozygotes) with LDL-C >130 mg/dL, despite optimized lipid-lowering therapy (including LDLR-independent apheresis and lomitapide), with intravenous evinacumab 15 mg/kg every 4 weeks. RESULTS: Evinacumab treatment rapidly and durably (through week 24) decreased LDL-C with profound reduction in the first week, with a mean (SE) LDL-C reduction of -48.3% (10.4%) from baseline to week 24. ApoB (mean [SE], -41.3% [9.0%]), non-high-density lipoprotein cholesterol (-48.9% [9.8%]), and total cholesterol (-49.1% [8.1%]) were similarly decreased. Treatment-emergent adverse events were reported in 10 (71.4%) patients; however, only 2 (14.3%) reported events that were considered to be treatment-related (nausea and abdominal pain). One serious treatment-emergent adverse event of tonsillitis occurred (n=1), but this was not considered treatment-related. CONCLUSIONS: Evinacumab constitutes a new treatment for pediatric patients with HoFH and inadequately controlled LDL-C despite optimized lipid-lowering therapy, lowering LDL-C levels by nearly half in these extremely high-risk and difficult-to-treat individuals. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04233918.

Adherence With Lipid Screening Guidelines in Children With Acquired and Congenital Heart Disease: An Observational Study Using Data From The MarketScan Commercial and Medicaid Databases.

Background Universal lipid screening in children provides an opportunity to mitigate the lifetime risk of atherosclerosis, particularly in children with chronic conditions that are predisposed to early atherosclerosis. In response, national guidelines recommend additional early screening in a subset of cardiac conditions. The penetration of such guidelines has not been evaluated. Methods and Results We performed a retrospective study of a geographically representative sample of US children using the MarketScan Commercial and Medicaid claims databases. The study population was children with cardiac disease between ages 2 and 18 years and ≥3 years of continuous coverage from January 1, 2013, to June 30, 2018, divided into 4 major strata of heart disease. We assessed the likelihood of screening between these classifications and compared with healthy children and calculated multivariate models to identify patient factors associated with screening likelihood. Of the eligible 8.4 million children, 155 000 children had heart disease, of which 1.8% (31 216) had high-risk conditions. Only 17.5% of healthy children underwent lipid screening. High-risk children were more likely to be screened (odds ratio [OR], 2.1; 95% CI, 2.09-2.19; P<0.001) than standard-risk children, but that likelihood varied depending on strata of cardiac disease (22%-77%). Timing of screening also varied, with most occurring between ages 9 and 11 years. Among cardiac conditions, heart transplantation (OR, 16.8; 95% CI, 14.4-19.7) and cardiomyopathy (OR, 2.9; 95% CI, 2.8-3.1) were associated with the highest likelihood of screening. Conclusions Children with cardiac disease are more likely to undergo recommended lipid screening than healthy children, but at lower rates and later ages than recommended, highlighting the importance of quality improvement and advocacy for this vulnerable population.

Anomalous aortic origin of a coronary artery: learning from the past to make advances in the future.

PURPOSE OF REVIEW: To review anomalous aortic origin of a coronary artery (AAOCA) anatomy, prevalence, mechanism and risk of ischemia, presentation, evaluation, management, and future directions. RECENT FINDINGS: Although most anatomic variants of AAOCA are benign, a small number are associated with increased risk of sudden death. A complete evaluation, including the use of advanced noninvasive imaging and provocative testing should be performed on nearly every patient with AAOCA. On the basis of recent studies, the ischemic risk appears to be greatest with a left anomalous coronary artery but an anomalous right coronary artery is not benign. Other risk factors include: a left anomalous coronary with an intramural course, high take-off, or slit-like orifice, and a right anomalous coronary with a longer intramural course. Exercise restriction is rarely recommended. Management primarily consists of nonoperative care, or surgical repair in those who are symptomatic or who have high-risk variants. Surgery itself continues to evolve; however, it is not benign, with a higher than expected chance of morbidity. SUMMARY: Advances have been made over the past decade regarding management of patients with AAOCA; however, the mechanism of ischemia and ability to predict risk is still incompletely understood. Management decisions should be based on anatomy, results of investigations, and shared decision-making with patients and their families. Surgery may be recommended for those at higher risk and should be done at centers experienced in AAOCA surgery. Future research should be collaborative in order to share experiences and insights to help advance our understanding of risk and ultimately to improve patient management.

Total anomalous origin of the coronary arteries from the pulmonary artery: a systematic review.

BACKGROUND: Although rare, coronary artery anomalies can have significant clinical implications. Total anomalous origin of the coronary arteries from the pulmonary artery (TCAPA) represents a rare subtype of coronary artery anomaly for which little is known. The aim of this review was to characterise the presentation, utilised diagnostic modalities, associated cardiac lesions, and treatment strategies in patients with TCAPA. METHODS: A systematic review was performed for cases of TCAPA using PubMed, Embase, and Web of Science. Keywords searched included "total anomalous origin of the coronary arteries from the pulmonary artery," "single ostium anomalous coronary artery from the pulmonary artery," and "anomalous origin of both coronary arteries from the pulmonary artery." RESULTS: Fifty-seven cases of TCAPA were identified in 50 manuscripts. Fifty-eight per cent of patients were male and the median age at presentation was 10 days (mean 1.71 ± 6.6 years, range 0 days-39 years). Most patients were symptomatic at the time of presentation; cyanosis (n = 22) and respiratory distress (n = 14) were the most common symptoms. Cases were most commonly diagnosed at autopsy (n = 26, 45.6%), but operative intervention was pursued in 22 cases (45.6%); aortic re-implantation (n = 14) and a Takeuchi-type repair (n = 7) were the most common routes of repair. CONCLUSIONS: The clinical presentation of patients with TCAPA was found to be variable, likely related to the presence of associated cardiac lesions. TCAPA should be considered in patients with suspected anomalous origin of the left coronary artery from the pulmonary artery for the serious consequences that can occur if not promptly corrected.

Normative Values for Cardiopulmonary Exercise Stress Testing Using Ramp Cycle Ergometry in Children and Adolescents.

OBJECTIVES: To provide sex, age, and race specific reference values for ramp cycle ergometer cardiopulmonary exercise test (CPET) in children in the US. STUDY DESIGN: Retrospective review was conducted of all cardiopulmonary CPET data from our Exercise Physiology Laboratory on healthy children and adolescents (6-18 years) with body mass index between the 5th and 95th percentiles and structurally normal hearts who performed a ramp cycle ergometry stress test between 1999 and 2015. Twenty-eight exercise variables were included: peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, peak work rate, resting and peak heart rate and blood pressure, resting pulmonary function testing, and ventilatory responses to progressive exercise using breath-by-breath gas exchange. Owing to the nonlinear association between CPET results and age, fractional polynomials were used in the mixed-effects regression models to describe the sex- and age-specific normative values with 95% CIs, after adjusting for race and body mass index. RESULTS: We analyzed data on 1829 children (average age, 13.6 ± 2.6 years; 52% male). After 12 years of age, males generally had higher peak values for aerobic capacity and work rate. There were progressive increases with age for both sexes in resting pulmonary function and ventilatory response to exercise, peak aerobic and work rate, and oxygen pulse. Notably, there was an age-related decrease in ventilatory equivalents of oxygen and carbon dioxide at the ventilatory anaerobic threshold. CONCLUSIONS: Future research using prospective, inclusive, and statistically planned cohorts with standardized laboratory approaches and confirmed interoperability should be considered as a focus for validating normative pediatric CPET values in the future.

Adherence with lipid screening guidelines in standard- and high-risk children and adolescents.

Because atherosclerosis begins in childhood, universal lipid screening is recommended with special attention to conditions predisposing to early atherosclerosis. Data about real-world penetration of these guidelines is not available. METHODS: Retrospective cohort study using MarketScan® commercial and Medicaid insurance claims databases, a geographically representative sample of U.S. children. Subjects who passed through the 9- to 11-year window and had continuous insurance coverage between 1/1/2013 and 12/31/2016 were studied. Multivariable models were calculated, evaluating the association between other patient factors and the likelihood of screening. The primary hypothesis was that screening rates would be low, but that high-risk conditions would be associated with a higher likelihood of screening. RESULTS: In total, 572,522 children (51% male, 33% black, 11% Hispanic, 51% Medicaid) were studied. The prevalence of high-risk conditions was 2.2%. In unadjusted and adjusted analyses, these subjects were more likely to be screened than standard-risk subjects (47% vs. 20%, OR: 3.7, 95% CI 3.5-3.8, P < .001). Within this group, the diagnosis-specific likelihood of screening varied (26-69%). Endocrinopathies (OR 5.4, 95% CI 5.2-5.7), solid organ transplants (OR 5.0, 95% CI 3.8-6.6), and metabolic disease (OR 3.9, 95% CI 3.1-5.0, all P < .001) were associated with the highest likelihood of undergoing screening. CONCLUSIONS: Despite national recommendations, lipid screening was performed in a minority of children. Though subjects with high-risk conditions had a higher likelihood of screening, rates remained low. This study highlights the need for research and advocacy regarding obstacles to lipid screening of children in the United States.

Outcomes after anomalous aortic origin of a coronary artery repair: A Congenital Heart Surgeons' Society Study.

OBJECTIVES: It remains unclear when sudden cardiac event risk outweighs surgical risk for patients with anomalous aortic origin of a coronary artery. The Congenital Heart Surgeons' Society sought to characterize the surgical risks by determining the techniques, complications, and outcomes of repair. METHODS: Between January 2000 and September 2018, 682 patients with anomalous aortic origin of a coronary artery aged 30 years or less were enrolled. Demographic, morphologic, operative, imaging, and ischemia-related data were analyzed. RESULTS: There were 395 of 682 (57%) surgical patients (45 centers, median follow-up 2.8 years). In addition to primary repair (87% unroofing, 26% commissural manipulation), 13 patients had 15 coronary-related reoperations. Of 358 patients with pre/postoperative aortic insufficiency assessment, 27 (8%) developed new mild or greater aortic insufficiency postoperatively, and 7 (2%) developed new moderate or greater aortic insufficiency. Freedom from mild aortic insufficiency differed in those with versus without commissural manipulation (85%/91% at 6 months, 83%/90% at 1 year, and 77%/88% at 3 years, respectively) (P = .05). Of 347 patients with preoperative/postoperative ejection fraction, 6 (2%) developed new abnormal ejection fraction (<50%) within 30 days of surgery which persisted. Although 64 of 395 patients (16%) had preoperative ischemia, after surgery 51 of 64 patients (80%) no longer had ischemia (13 = new postoperative ischemia, P < .0001). Four patients died postoperatively (preoperatively 2 asymptomatic, 1 symptomatic, 1 in extremis). Composite surgical adverse event rates were 7% to 13% in the entire cohort (increasing/decreasing by presentation/anatomy/repair strategy). CONCLUSIONS: Anomalous aortic origin of a coronary artery surgery may relieve ischemia with low mortality; however, it can result in a variety of important morbidities, varying by the group evaluated. Strategies avoiding commissural manipulation may decrease the risk of developing aortic insufficiency. Understanding these risks should inform surgical decision-making and support the need for standardized assessment and management.

Isolated Single Right Coronary Artery in a Pediatric Patient.

Anatomic single coronary arteries are quite rare but can be a potential cause of sudden cardiac death. We present the first case of a pediatric patient with an anatomic single right coronary artery (Lipton type R1 or Shirani-Roberts type IIA), of a type which has been associated with adult-onset ischemic cardiac disease. We review the evaluation and management of this young patient.

Features associated with myocardial ischemia in anomalous aortic origin of a coronary artery: A Congenital Heart Surgeons' Society study.

OBJECTIVES: We sought to determine anatomic features associated with evidence of myocardial ischemia and sudden cardiac events (arrest or death) for patients with anomalous aortic origin of a coronary artery. METHODS: We enrolled 560 patients, less than or equal to 30 years, at diagnosis from 40 institutions. Ischemia was defined as the presence of exertional syncope, a sudden cardiac event (arrest/death), or abnormal investigation results. Data on detailed anatomic features were abstracted from echocardiography, computed tomography, magnetic resonance imaging, operative, and/or surgeon-completed reports. RESULTS: There were 236 patients with negative ischemia test results, and 49 with evidence of ischemia (including 18 who presented with a sudden cardiac event); 275 asymptomatic patients who had not undergone provocative ischemia testing were excluded from primary analyses. Patients with ischemia (vs without), were more likely to have left anomalous coronary arteries (28/49 vs 46/236; P < .0001). Of patients with ischemia (vs without), those with anomalous left coronary arteries were more likely to have an intramural coronary artery course, or a high or slit-like coronary artery orifice. Of patients with ischemia (vs without), those with anomalous right coronary arteries were more likely to have a longer intramural course. Among patients with ischemia, the occurrence of sudden cardiac events was not shown to have any associated anatomic features. CONCLUSIONS: Anatomic features including coronary artery involved, intramural course and length, and orifice anomalies were associated with evidence of myocardial ischemia for patients with anomalous aortic origin of a coronary artery. These features might importantly inform risk stratification and decisions regarding surgical management.

Severe hypertriglyceridemia associated with everolimus drug-eluting stent placement in an infant.

We report a case of severe hypertriglyceridemia associated with an everolimus drug-eluting stent in an infant with pulmonary vein stenosis. We review from current literature the mechanisms by which everolimus may cause dyslipidaemia, pharmacokinetics of everolimus in drug-eluting stents, and treatments of hypertriglyceridemia. This case demonstrates the need to closely monitor serum triglyceride levels after everolimus drug-eluting stent placement in infants.

Introduction to anomalous aortic origin of a coronary artery.

Anomalous aortic origin of a coronary artery (AAOCA) occurs when both coronary arteries arise from the same aortic sinus from a single ostium or two separate ostia. While most coronary anomalies are benign, the two most common subtypes that predispose to sudden cardiac death in the young are interarterial anomalous right coronary artery and interarterial anomalous left coronary artery. Practitioners face many challenges with AAOCA. Diagnosing patients may be difficult because children and adolescents are often asymptomatic and first presentation may be sudden death or sudden cardiac arrest. Risk stratification is also challenging as determining which unique characteristics place the child at highest risk of sudden death has not been adequately delineated and ischemic testing may give false negative results. Last, there is significant variability in decision making regarding management of youth with AAOCA. Future research is needed to help determine the best way to identify at-risk children and which treatment is the safest and most efficacious.

Effects of Exercise Restriction on Patients With Anomalous Aortic Origin of a Coronary Artery.

BACKGROUND: Management of young patients with anomalous aortic origin of a coronary artery (AAOCA) may involve exercise restriction. We sought to identify the association of exercise restriction with changes over time in body mass index (BMI) and exercise capacity in this cohort. METHODS: We performed a retrospective review of patients with AAOCA seen at The Children's Hospital of Philadelphia between January 1, 1998, and August 31, 2014. Linear mixed model repeated-measures analysis assessed changes in BMI and exercise capacity. RESULTS: We included 72 patients with a median age at presentation of 12.6 years (interquartile range: 10.1-15.8) and mean follow-up of 3.6 ± 3.0 years. The majority had an anomalous right coronary artery (71%) and interarterial ± intramural coronary course (90%). Surgery was performed in 54%, more often in those with interarterial/intramural course ( P < .001) and symptoms ( P = .003). Most patients (82%) were exercise-restricted on presentation, and restricted patients were older than those who were not restricted ( P = .01). There was no significant difference between restricted and nonrestricted patients in initial BMI z scores, percentage of patients with BMI over 85th percentile (26%) or exercise capacity variables. In univariable analysis, exercise restriction over time was not associated with change in BMI z score ( P = .25) or change in exercise variables. Restriction was not associated with significant change in these variables in multivariable analysis. CONCLUSIONS: Although further investigation is warranted to determine the degree of adherence to exercise restriction, the recommendation of restriction alone is not associated with increasing BMI or decreasing exercise performance in the short-term.

Quality of life and exercise performance in unoperated children with anomalous aortic origin of a coronary artery from the opposite sinus of valsalva.

BACKGROUND: Anomalous aortic origin of a coronary artery is a congenital cardiac condition that can be associated with increased risk of sudden death. To date, quality of life and exercise performance have not been evaluated in patients with this condition who do not undergo surgical repair. METHODS: We carried out a cross-sectional analysis of patients with unoperated anomalous aortic origin of a coronary artery at our institution from 1 January, 2000 to 31 January, 2016. We prospectively assessed quality of life using standardised questionnaires. Medical records were reviewed for clinical and exercise stress test data. Statistical analyses were performed using Student's t-tests and Spearman's correlation coefficients. RESULTS: In total, 56 families completed the questionnaires. The average age at enrolment was 14.7±6 years. The majority were male (n=44, 78.6%) and had interarterial anomalous right coronary artery (n=38, 67.9%). Patients had normal quality of life on the PedsQL 4.0 Report, Child Health Questionnaire Child Form 87, and SF-36v2. Their parents had normal quality of life on the PedsQL 4.0 Parent Report, but parents of exercise-restricted patients had decreased Physical Functioning, General Health Perception, Emotional Impact on Parent, and Physical Summary scores (p<0.001-0.048) on the Child Health Questionnaire Parent Form 50. CONCLUSIONS: Patients with unoperated anomalous aortic origin of a coronary artery appear to have normal quality of life, but parents of exercise-restricted patients have decreased general health and emotional and physical quality of life scores. Improved counselling of families may be beneficial in this group. Future studies with more patients should evaluate quality of life and exercise performance over time.

A Comparison of Perioperative Management of Anomalous Aortic Origin of a Coronary Artery Between an Adult and Pediatric Cardiac Center.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) presents in varying age-groups. Assuming management algorithms differ between pediatric and adult institutions, we compared the perioperative management of patients with AAOCA at two such centers. METHODS: A retrospective review was conducted at a pediatric and an adult institution of patients 14 years or older who underwent surgical repair of AAOCA between January 2000 and May 2014. RESULTS: Twenty patients from the pediatric center (median age: 16.5 years, range: 14-18 years) and nine patients from the adult center (median age: 40 years, range: 37-52 years) were included. An anomalous aortic origin of a right coronary artery was the most frequent pathology at each institution. Chest pain was the most common presenting symptom at both institutions. Preoperative echocardiography was performed in 95% patients at the pediatric center and in 100% of patients at the adult center. Cardiac catheterization was utilized more frequently at the adult center, and cardiac magnetic resonance imaging more commonly employed at the pediatric center. Isolated coronary unroofing was performed in 19 of 20 cases at the pediatric center and in only 2 (22%) cases at the adult institution, both by congenitally trained cardiac surgeons. More concomitant cardiac procedures were performed at the adult center with associated longer operative times and hospital stays. CONCLUSION: Management strategies for AAOCA vary depending on both patient-specific factors and expertise of the managing team. Further studies are needed to optimally standardize diagnostic and treatment pathways regardless of location venue.

Coronary artery anomalies in children: what is the risk?

PURPOSE OF REVIEW: To better understand the risk of sudden death from coronary anomalies. RECENT FINDINGS: Most coronary anomalies are benign, but there are certain coronary anomalies that increase the risk of sudden cardiac death (SCD) in the young, notably anomalous aortic origin of a coronary artery from the wrong sinus. Previously, the risk of SCD attributed to certain coronary anomalies was felt to be quite high, as the risk assessment was based on autopsy series. Recent studies have shown that the risk attributed to anomalous coronary arteries is much lower than once believed. Risk appears to be highest with anomalous left coronary artery from the right sinus of Valsalva with interarterial course, notably when the young patient is participating in vigorous physical exertion, such as with competitive sports. SUMMARY: Treatment strategies may include exercise restriction or surgical repair. Management decisions should be based on a complete understanding of the risk for SCD because of anomalous coronary arteries. Future directions should focus on better methods to risk stratify these pediatric patients.