Limited Relationship Between Echocardiographic Measures and Electrocardiographic Markers of Left Ventricular Size in Healthy Children.

Pediatric ECG standards have been defined without echocardiographic confirmation of normal anatomy. The Pediatric Heart Network Normal Echocardiogram Z-score Project provides a racially diverse group of healthy children with normal echocardiograms. We hypothesized that ECG and echocardiographic measures of left ventricular (LV) dimensions are sufficiently correlated in healthy children to imply a clinically meaningful relationship. This was a secondary analysis of a previously described cohort including 2170 digital ECGs. The relationship between 6 ECG measures associated with LV size were analyzed with LV Mass (LVMass-z) and left ventricular end-diastolic volume (LVEDV-z) along with 11 additional parameters. Pearson or Spearman correlations were calculated for the 78 ECG-echocardiographic pairs with regression analyses assessing the variance in ECG measures explained by variation in LV dimensions and demographic variables. ECG/echocardiographic measurement correlations were significant and concordant in 41/78 (53%), though many were significant and discordant (13/78). Of the 6 ECG parameters, 5 correlated in the clinically predicted direction for LV Mass-z and LVEDV-z. Even when statistically significant, correlations were weak (0.05-0.24). R2 was higher for demographic variables than for echocardiographic measures or body surface area in all pairs, but remained weak (R2 ≤ 0.17). In a large cohort of healthy children, there was a positive association between echocardiographic measures of LV size and ECG measures of LVH. These correlations were weak and dependent on factors other than echocardiographic or patient derived variables. Thus, our data support deemphasizing the use of solitary, traditional measurement-based ECG markers traditionally thought to be characteristic of LVH as standalone indications for further cardiac evaluation of LVH in children and adolescents.

Ensuring access to innovative therapies for children, adolescents, and young adults across Canada: The single patient study experience.

Innovative therapeutic approaches are needed to alleviate the burden of life-limiting, rare, and chronic conditions affecting children, adolescents, and young adults (CAYA). This includes a need for improved access to both clinical research and to non-approved or off-label therapies, together with, ultimately, more therapies achieving regulatory approval in Canada. The single patient study (SPS), also known as an open label individual patient (OLIP) study, was introduced by Health Canada to open access to non-marketed drugs where a clinical trial is not readily available, but the drug is considered too investigational to be managed on a standard Special Access Program. SPS is designed for patients who have a serious or life-threatening condition and have exhausted available treatment options. Our report summarizes this relatively new development in the Canadian regulatory environment and highlights the opportunities and challenges as identified by regulators, pharmaceutical representatives, academic researchers, and patient/parent advocates.

"Acquired" Brugada syndrome in a cardiac allograft.

INTRODUCTION: Brugada syndrome is an inherited channelopathy characterized by arrhythmia and an increased risk of sudden cardiac death (SCD). Implantation of a defibrillator for primary or secondary prevention is the only effective strategy to decrease the risk of SCD in Brugada syndrome. We present a case in which a cardiac donor had a pathogenic variant for Brugada syndrome, discovered on genetic testing after transplantation. CASE REPORT: A young child with dilated cardiomyopathy underwent orthotopic heart transplantation from a donor with in-hospital cardiac arrest in the context of fever and a normal ECG. Approximately 1 month after transplant, the donor's post mortem genetic testing revealed a pathogenic loss-of-function SCN5A variant associated with Brugada syndrome, which was confirmed on genetic testing on a post-transplant endomyocardial biopsy from the recipient. The recipient's post-transplant electrocardiographic monitoring revealed persistent right bundle branch block and progressive, asymptomatic sinus node dysfunction. The recipient was managed with precautionary measures including aggressive fever management, avoidance of drugs that increase arrhythmia risk in Brugada syndrome, and increased frequency of arrhythmia surveillance. The recipient remains asymptomatic at over 3 years post-transplant with preserved graft function and no documented ventricular arrhythmias. CONCLUSION: We describe the clinical course of "acquired" Brugada syndrome in a cardiac allograft recipient, which has not been previously reported. The time-sensitive nature of donor organ selection, especially in critically ill recipients, combined with the growing use of molecular autopsies in patients with unexplained etiologies for death may increasingly result in important donor genetic information being made available after transplantation.

A Research Ethics Framework for the Clinical Translation of Healthcare Machine Learning.

The application of artificial intelligence and machine learning (ML) technologies in healthcare have immense potential to improve the care of patients. While there are some emerging practices surrounding responsible ML as well as regulatory frameworks, the traditional role of research ethics oversight has been relatively unexplored regarding its relevance for clinical ML. In this paper, we provide a comprehensive research ethics framework that can apply to the systematic inquiry of ML research across its development cycle. The pathway consists of three stages: (1) exploratory, hypothesis-generating data access; (2) silent period evaluation; (3) prospective clinical evaluation. We connect each stage to its literature and ethical justification and suggest adaptations to traditional paradigms to suit ML while maintaining ethical rigor and the protection of individuals. This pathway can accommodate a multitude of research designs from observational to controlled trials, and the stages can apply individually to a variety of ML applications.

QTc and QRS Abnormalities are Associated with Outcome in Pediatric Heart Failure.

Adult studies have shown that depolarization and repolarization abnormalities are associated with worsening heart failure; however, this relationship is not well understood in pediatric congenital heart disease. We evaluated the association between QTc and QRS duration to systolic function and outcome in children with heart failure and reduced ejection fraction (HFrEF). We performed a retrospective, single-center, 14-year cohort study of HFrEF children. Clinical records, echocardiograms, and electrocardiograms were reviewed for every clinical encounter. Diagnosis, interventions, outcomes, QRS and QTc duration, and systolic function were collected. Repeated-measure ANOVA evaluated the association between depolarization and repolarization to cardiac function. Cox regression analysis examined the effects of age, time since diagnosis, and measured and change in QTc and QRS duration on time to transplant/death. We enrolled 136 cardiomyopathy (CM) and 47 structural heart disease (SHD) patients. Prolonged QRS (p = 0.0001) and QTc (p = 0.02) were associated with systolic dysfunction. This association was significant in SHD group (QRS p < 0.0001, QTc p = 0.048), but not CM group (QRS p = 0.5, QTc p = 0.3). Progressive lengthening of QTc was significantly associated with transplant or death in the overall cohort (HR 1.02, CI 1.011-1.028), SHD, (HR 1.020, CI 1.001-1.039), and CM (HR 1.017, CI 1.007-1.027). QTc and QRS prolongation are each associated with ventricular dysfunction in pediatric SHD with heart failure. QTc prolongation is an indication for poor outcomes in SHD and CM groups, leading to a higher risk of death or transplantation. Progressive lengthening of QTc over time in children with HFrEF may indicate increased risk in this population.

Developing a Mathematical Model of Intracellular Calcium Dynamics for Evaluating Combined Anticancer Effects of Afatinib and RP4010 in Esophageal Cancer.

Targeting dysregulated Ca2+ signaling in cancer cells is an emerging chemotherapy approach. We previously reported that store-operated Ca2+ entry (SOCE) blockers, such as RP4010, are promising antitumor drugs for esophageal cancer. As a tyrosine kinase inhibitor (TKI), afatinib received FDA approval to be used in targeted therapy for patients with EGFR mutation-positive cancers. While preclinical studies and clinical trials have shown that afatinib has benefits for esophageal cancer patients, it is not known whether a combination of afatinib and RP4010 could achieve better anticancer effects. Since TKI can alter intracellular Ca2+ dynamics through EGFR/phospholipase C-γ pathway, in this study, we evaluated the inhibitory effect of afatinib and RP4010 on intracellular Ca2+ oscillations in KYSE-150, a human esophageal squamous cell carcinoma cell line, using both experimental and mathematical simulations. Our mathematical simulation of Ca2+ oscillations could fit well with experimental data responding to afatinib or RP4010, both separately or in combination. Guided by simulation, we were able to identify a proper ratio of afatinib and RP4010 for combined treatment, and such a combination presented synergistic anticancer-effect evidence by experimental measurement of intracellular Ca2+ and cell proliferation. This intracellular Ca2+ dynamic-based mathematical simulation approach could be useful for a rapid and cost-effective evaluation of combined targeting therapy drugs.

A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. METHODS: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy <18 years of age at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest, and aborted SCD, that is, appropriate shock following primary prevention implantable cardioverter defibrillators. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with 10 repeated 4-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized by using the c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe [Sarcomeric Human Cardiomyopathy Registry], n=285). RESULTS: Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated sudden cardiac arrests, and 14 aborted SCD). Risk predictors included age at diagnosis, documented nonsustained ventricular tachycardia, unexplained syncope, septal diameter z-score, left ventricular posterior wall diameter z score, left atrial diameter z score, peak left ventricular outflow tract gradient, and presence of a pathogenic variant. Unlike in adults, left ventricular outflow tract gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated between patients with and without SCD events with a c-statistic of 0.75 and 0.76, respectively, and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72, respectively). CONCLUSION: Our study provides a validated SCD risk prediction model with >70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679.

2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients: Executive summary.

Guidelines for the implantation of cardiac implantable electronic devices (CIEDs) have evolved since publication of the initial ACC/AHA pacemaker guidelines in 1984 [1]. CIEDs have evolved to include novel forms of cardiac pacing, the development of implantable cardioverter defibrillators (ICDs) and the introduction of devices for long term monitoring of heart rhythm and other physiologic parameters. In view of the increasing complexity of both devices and patients, practice guidelines, by necessity, have become increasingly specific. In 2018, the ACC/AHA/HRS published Guidelines on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay [2], which were specific recommendations for patients >18 years of age. This age-specific threshold was established in view of the differing indications for CIEDs in young patients as well as size-specific technology factors. Therefore, the following document was developed to update and further delineate indications for the use and management of CIEDs in pediatric patients, defined as ≤21 years of age, with recognition that there is often overlap in the care of patents between 18 and 21 years of age. This document is an abbreviated expert consensus statement (ECS) intended to focus primarily on the indications for CIEDs in the setting of specific disease/diagnostic categories. This document will also provide guidance regarding the management of lead systems and follow-up evaluation for pediatric patients with CIEDs. The recommendations are presented in an abbreviated modular format, with each section including the complete table of recommendations along with a brief synopsis of supportive text and select references to provide some context for the recommendations. This document is not intended to provide an exhaustive discussion of the basis for each of the recommendations, which are further addressed in the comprehensive PACES-CIED document [3], with further data easily accessible in electronic searches or textbooks.

2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

Family screening for hypertrophic cardiomyopathy: Is it time to change practice guidelines?

AIMS: Current guidelines recommend initiating family screening for hypertrophic cardiomyopathy (HCM) after age 10 or 12 years unless early screening criteria are met. The aim was to evaluate if current screening guidelines miss early onset disease. METHODS AND RESULTS: Children who underwent family screening for HCM before age 18 years were analysed. Major cardiac events (MaCEs) were defined as death, sudden cardiac death (SCD), or need for major cardiac interventions (myectomy, implantable cardioverter-defibrillator insertion, transplantation). Of 524 children screened, 331 were under 10 years of age, 9.9% had echocardiographic evidence of HCM, and 1.1% were symptomatic at first screening. The median (interquartile range) age at HCM onset was 8.9 (4.7-13.4) years, and at MaCE was 10.9 (8.5-14.3) years with a median time to MaCE from HCM onset of 1.5 (0.5-4.1) years. About 52.5% phenotype-positive children and 41% with MaCEs were <10 years old. Only 69% children with early HCM met early screening criteria. Cox regression identified male gender, family history of SCD, and pathogenic variants in MYH7/MYBPC3 as a predictor of early onset HCM and MaCEs. CONCLUSION: A third of children not eligible for early screening by current guidelines had phenotype-positive HCM. MYH7 and MYBC3 mutation-positive patients were at highest risk for developing early HCM and experiencing an event or requiring a major intervention. Our findings suggest that younger family members should be considered for early clinical and genetic screening to identify the subset in need of closer monitoring and interventions.

Foley catheter for induction of labour: a UK observational study.

We conducted a prospective observational study of all inductions using Foley's catheter at our center between 2016 and 2018. Outcome data collected included induction to delivery time, mode of delivery, complication rates, patient and staff satisfaction. Ninety-nine women were included in our study. Median induction to delivery time was 28.3 h (IQR 19.7-34 h), 20 (20.2%) women required Caesarean section. No relevant complications were recorded. Patients and staff were satisfied with the technique overall.These results show transcervical Foley's catheter is a safe and effective method of induction of labour in the UK setting. It was shown to be feasible in the outpatient and previous Caesarean section groups.Impact statementWhat is already known on the subject? Foley catheter as an induction agent has already been shown to be as clinically effective as slow release prostaglandins with lower costs.What do the results of this study add? No study has been published on its use for routine inductions in the UK. Our results show that Foley's catheter is a safe, effective method for inducing labour in the UK.What are the implications of these findings for clinical practice and/or further research? This suggests this technique should be implemented more widely in the UK.

Riata lead failure in pediatric and congenital heart disease patients.

BACKGROUND: Implantable cardioverter defibrillator (ICD) lead failures occur at higher rates in pediatric and congenital heart disease (CHD) patients. OBJECTIVE: To determine the rate and timing of Riata lead failure in pediatric and CHD patients. METHODS: This was a retrospective, multicenter cohort study of pediatric patients and adults with CHD with implantation of a Riata or Riata ST lead between 2002 and 2009. The prevalence and timing of electrical failure and conductor coil externalization (CCE) were determined. RESULTS: Fifty-eight patients and 63 leads from seven centers were included. Median (interquartile range [IQR]) age at implant was 14.4 (11.5-18.7) years and median follow-up was 8.7 (7.3-11.1) years. The underlying diagnosis was a primary arrhythmia disorder in 45%, cardiomyopathy in 31%, and CHD in 28% of patients. Electrical failure occurred in 43% and CCE in 16% of leads at median lead ages of 4.7 (3.4-7.5) and 4.3 (3.9-7.0) years, respectively. Median lead survival free from electrical failure or CCE was 7.9 (95% confidence interval, 5.8-10.0) years. Forty-one percent of leads were functional at the end of the follow-up period, and 33% were extracted with a complication rate of 5%. CONCLUSIONS: The rate of Riata lead electrical failure was high in children and patients with CHD, while the rate of CCE was comparable with published data. Counseling on lead management should factor in the high rate of electrical failure with considerations for elective replacement.

SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Aims: To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. Methods and results: A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE. Conclusion: In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function.

Pediatric & Congenital Electrophysiology Society: building an international paediatric electrophysiology organisation.

The Pediatric and Congenital Electrophysiology Society (PACES) is a non-profit organisation comprised of individuals dedicated to improving the care of children and young adults with cardiac rhythm disturbances. Although PACES is a predominantly North American-centric organisation, international members have been a part of PACES for the last two decades. This year, PACES expanded its North American framework into a broadly expansive international role. On 12 May, 2015, paediatric electrophysiology leaders from within the United States of America and Canada met with over 30 international paediatric electrophysiologists from 17 countries and five continents discussing measures to (1) expand PACES' global vision, (2) address ongoing challenges such as limited resource allocation that may be present in developing countries, (3) expand PACES' governance to include international representation, (4) promote joint international sessions at future paediatric EP meetings, and (5) facilitate a global multi-centre research consortium. This meeting marked the inception of a formal international collaborative spirit in PACES. This editorial addresses some solutions to breakdown the continental silos paediatric electrophysiologists have practiced within; however, there remain ongoing limitations, and future discussions will be needed to continue to move the PACES global international vision forward.

Mutation location effect on severity of phenotype during exercise testing in type 1 long-QT syndrome: impact of transmembrane and C-loop location.

BACKGROUND: Targeted mutation site-specific differences have correlated C-loop missense mutations with worse outcomes and increased benefit of beta-blockers in LQT1. This observation has implicated the C-loop region as being mechanistically important in the altered response to sympathetic stimulation known to put patients with LQT1 at risk of syncope and sudden cardiac death. OBJECTIVE: The objective of this study was to determine if there is mutation site-specific response to sympathetic stimulation and beta-blockers using exercise testing. METHODS: This study is a retrospective review of LQT1 patients undergoing exercise testing at 3 academic referral centers. RESULTS: A total of 123 patients (age 28 ± 17 years, 59 male) were studied including 34 patients (28%) with C-loop mutations. There were no significant differences in supine, standing, peak exercise and 1-minute recovery QTc duration between patients with C-loop mutations and patients with alternate mutation sites. In 37 patients that underwent testing on and off beta-blockers, beta-blocker use was associated with a significant reduction in supine, standing and peak exercise QTc. This difference was not seen in the small group of patients (7/37) with C-loop mutations. There was no difference in QTc at 1 and 4 minutes into recovery. CONCLUSIONS: Genetically confirmed LQT1 patients in this study cohort with C-loop mutations did not demonstrate the expected increase in QTc in response to exercise, or resultant response to beta-blocker. The apparent increased risk of cardiac events associated with C-loop mutation sites and the marked benefit received from beta-blocker therapy are not reflected by exercise-mediated effects on QTc in this study population.

Epicardial Devices in Pediatrics and Congenital Heart Disease.

Epicardial cardiac implantable electronic device implant remains a common option in pediatric patients and certain patients with congenital heart disease due to patient size, complex anatomy, residual intracardiac shunts, and prior surgery precluding transvenous implant. Advantages include the lack of thromboembolic and vascular risks and ability to implant during concomitant surgery. Significant disadvantages include the occurrence of lead dysfunction that can result in bradycardia events in pacemaker patients, inappropriate shocks in implantable cardiac defibrillator patients, and overall a more invasive procedure.

COVID-19 Scientific Publications From the Centers for Disease Control and Prevention, January 2020-January 2022.

OBJECTIVE: High-quality scientific evidence underpins public health decision making. The Centers for Disease Control and Prevention (CDC) agency provides scientific data, including during public health emergencies. To understand CDC's contributions to COVID-19 science, we conducted a bibliometric evaluation of publications authored by CDC scientists from January 20, 2020, through January 20, 2022, by using a quality improvement approach (SQUIRE 2.0). METHODS: We catalogued COVID-19 articles with ≥1 CDC-affiliated author published in a scientific journal and indexed in the World Health Organization's COVID-19 database. We identified priority topic areas from the agency's COVID-19 Public Health Science Agenda by using keyword scripts in EndNote and then assessed the impact of the published articles by using Scopus and Altmetric. RESULTS: During the first 2 years of the agency's pandemic response, CDC authors contributed to 1044 unique COVID-19 scientific publications in 208 journals. Publication topics included testing (n = 853, 82%); prevention strategies (n = 658, 63%); natural history, transmission, breakthrough infections, and reinfections (n = 587, 56%); vaccines (n = 567, 54%); health equity (n = 308, 30%); variants (n = 232, 22%); and post-COVID-19 conditions (n = 44, 4%). Publications were cited 40 427 times and received 81 921 news reports and 1 058 893 social media impressions. As the pandemic evolved, CDC adapted to address new scientific questions, including vaccine effectiveness, safety, and access; viral variants, including Delta and Omicron; and health equity. CONCLUSION: The agency's COVID-19 Public Health Science Agenda helped guide impactful scientific activities. CDC continues to evaluate COVID-19 priority topic areas and contribute to development of new scientific work. CDC is committed to monitoring emerging issues and addressing gaps in evidence needed to improve health.