Browsing by Author "McCrindle, Brian W."
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Item Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination(AHA, 2022-02) Truong, Dongngan T.; Dionne, Audrey; Muniz, Juan Carlos; McHugh, Kimberly E.; Portman, Michael A.; Lambert, Linda M.; Thacker, Deepika; Elias, Matthew D.; Li, Jennifer S.; Toro-Salazar, Olga H.; Anderson, Brett R.; Atz, Andrew M.; Bohun, C. Monique; Campbell, M. Jay; Chrisant, Maryanne; D’Addese, Laura; Dummer, Kirsten B.; Forsha, Daniel; Frank, Lowell H.; Frosch, Olivia H.; Gelehrter, Sarah K.; Giglia, Therese M.; Hebson, Camden; Jain, Supriya S.; Johnston, Pace; Krishnan, Anita; Lombardi, Kristin C.; McCrindle, Brian W.; Mitchell, Elizabeth C.; Miyata, Koichi; Mizzi, Trent; Parker, Robert M.; Patel, Jyoti K.; Ronai, Christina; Sabati, Arash A.; Schauer, Jenna; Sexson Tejtel, S. Kristen; Shea, J. Ryan; Shekerdemian, Lara S.; Srivastava, Shubhika; Votava-Smith, Jodie K.; White, Sarah; Newburger, Jane W.; Pediatrics, School of MedicineBackground: 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.Item Design and Rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial(Elsevier, 2018) Goldberg, David J.; Zak, Victor; Goldstein, Bryan H.; McCrindle, Brian W.; Menon, Shaji C.; Schumacher, Kurt R.; Payne, R. Mark; Rhodes, Jonathan; McHugh, Kimberly E.; Penny, Daniel J.; Trachtenberg, Felicia; Hamstra, Michelle S.; Richmond, Marc E.; Frommelt, Peter C.; Files, Matthew D.; Yeager, James L.; Pemberton, Victoria L.; Stylianou, Mario P.; Pearson, Gail D.; Paridon, Stephen M.; Pediatrics, School of MedicineThe Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short-term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double blind, placebo controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co., Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation.Item Examination of Adverse Reactions After COVID-19 Vaccination Among Patients With a History of Multisystem Inflammatory Syndrome in Children(American Medical Association, 2023-01-03) Elias, Matthew D.; Truong, Dongngan T.; Oster, Matthew E.; Trachtenberg, Felicia L.; Mu, Xiangyu; Jone, Pei-Ni; Mitchell, Elizabeth C.; Dummer, Kirsten B.; Sexson Tejtel, S. Kristen; Osakwe, Onyekachukwu; Thacker, Deepika; Su, Jennifer A.; Bradford, Tamara T.; Burns, Kristin M.; Campbell, M. Jay; Connors, Thomas J.; D'Addese, Laura; Forsha, Daniel; Frosch, Olivia H.; Giglia, Therese M.; Goodell, Lauren R.; Handler, Stephanie S.; Hasbani, Keren; Hebson, Camden; Krishnan, Anita; Lang, Sean M.; McCrindle, Brian W.; McHugh, Kimberly E.; Morgan, Lerraughn M.; Payne, R. Mark; Sabati, Arash; Sagiv, Eyal; Sanil, Yamuna; Serrano, Faridis; Newburger, Jane W.; Dionne, Audrey; Pediatric Heart Network MUSIC Study Investigators; Pediatrics, School of MedicineImportance: 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.Item Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design(Public Library of Science, 2023-06-23) Gross, Rachel; Thaweethai, Tanayott; Rosenzweig, Erika B.; Chan, James; Chibnik, Lori B.; Cicek, Mine S.; Elliott, Amy J.; Flaherman, Valerie J.; Foulkes, Andrea S.; Witvliet, Margot Gage; Gallagher, Richard; Gennaro, Maria Laura; Jernigan, Terry L.; Karlson, Elizabeth W.; Katz, Stuart D.; Kinser, Patricia A.; Kleinman, Lawrence C.; Lamendola-Essel, Michelle F.; Milner, Joshua D.; Mohandas, Sindhu; Mudumbi, Praveen C.; Newburger, Jane W.; Rhee, Kyung E.; Salisbury, Amy L.; Snowden, Jessica N.; Stein, Cheryl R.; Stockwell, Melissa S.; Tantisira, Kelan G.; Thomason, Moriah E.; Truong, Dongngan T.; Warburton, David; Wood, John C.; Ahmed, Shifa; Akerlundh, Almary; Alshawabkeh, Akram N.; Anderson, Brett R.; Aschner, Judy L.; Atz, Andrew M.; Aupperle, Robin L.; Baker, Fiona C.; Balaraman, Venkataraman; Banerjee, Dithi; Barch, Deanna M.; Baskin-Sommers, Arielle; Bhuiyan, Sultana; Bind, Marie-Abele C.; Bogie, Amanda L.; Buchbinder, Natalie C.; Bueler, Elliott; Bükülmez, Hülya; Casey, B. J.; Chang, Linda; Clark, Duncan B.; Clifton, Rebecca G.; Clouser, Katharine N.; Cottrell, Lesley; Cowan, Kelly; D'Sa, Viren; Dapretto, Mirella; Dasgupta, Soham; Dehority, Walter; Dummer, Kirsten B.; Elias, Matthew D.; Esquenazi-Karonika, Shari; Evans, Danielle N.; Faustino, E. Vincent S.; Fiks, Alexander G.; Forsha, Daniel; Foxe, John J.; Friedman, Naomi P.; Fry, Greta; Gaur, Sunanda; Gee, Dylan G.; Gray, Kevin M.; Harahsheh, Ashraf S.; Heath, Andrew C.; Heitzeg, Mary M.; Hester, Christina M.; Hill, Sophia; Hobart-Porter, Laura; Hong, Travis K. F.; Horowitz, Carol R.; Hsia, Daniel S.; Huentelman, Matthew; Hummel, Kathy D.; Iacono, William G.; Irby, Katherine; Jacobus, Joanna; Jacoby, Vanessa L.; Jone, Pei-Ni; Kaelber, David C.; Kasmarcak, Tyler J.; Kluko, Matthew J.; Kosut, Jessica S.; Laird, Angela R.; Landeo-Gutierrez, Jeremy; Lang, Sean M.; Larson, Christine L.; Lim, Peter Paul C.; Lisdahl, Krista M.; McCrindle, Brian W.; McCulloh, Russell J.; Mendelsohn, Alan L.; Metz, Torri D.; Morgan, Lerraughn M.; Müller-Oehring, Eva M.; Nahin, Erica R.; Neale, Michael C.; Ness-Cochinwala, Manette; Nolan, Sheila M.; Oliveira, Carlos R.; Oster, Matthew E.; Payne, R. Mark; Raissy, Hengameh; Randall, Isabelle G.; Rao, Suchitra; Reeder, Harrison T.; Rosas, Johana M.; Russell, Mark W.; Sabati, Arash A.; Sanil, Yamuna; Sato, Alice I.; Schechter, Michael S.; Selvarangan, Rangaraj; Shakti, Divya; Sharma, Kavita; Squeglia, Lindsay M.; Stevenson, Michelle D.; Szmuszkovicz, Jacqueline; Talavera-Barber, Maria M.; Teufel, Ronald J., II; Thacker, Deepika; Udosen, Mmekom M.; Warner, Megan R.; Watson, Sara E.; Werzberger, Alan; Weyer, Jordan C.; Wood, Marion J.; Yin, H. Shonna; Zempsky, William T.; Zimmerman, Emily; Dreyer, Benard P.; Pediatrics, School of MedicineImportance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.Item Results of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial(American Heart Association, 2020-02-25) Goldberg, David J.; Zak, Victor; Goldstein, Bryan H.; Schumacher, Kurt R.; Rhodes, Jonathan; Penny, Daniel J.; Petit, Christopher J.; Ginde, Salil; Menon, Shaji C.; Kim, Seong-Ho; Kim, Gi Beom; Nowlen, Todd T.; DiMaria, Michael V.; Frischhertz, Benjamin P.; Wagner, Jonathan B.; McHugh, Kimberly E.; McCrindle, Brian W.; Shillingford, Amanda J.; Sabati, Arash A.; Yetman, Anji T.; John, Anitha S.; Richmond, Marc E.; Files, Matthew D.; Payne, R. Mark; Mackie, Andrew S.; Davis, Christopher K.; Shahanavaz, Shabana; Hill, Kevin D.; Garg, Ruchira; Jacobs, Jeffrey P.; Hamstra, Michelle S.; Woyciechowski, Stacy; Rathge, Kathleen A.; McBride, Michael G.; Frommelt, Peter C.; Russell, Mark W.; Urbina, Elaine M.; Yeager, James L.; Pemberton, Victoria L.; Stylianou, Mario P.; Pearson, Gail D.; Paridon, Stephen M.; Pediatrics, School of MedicineBackground: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. Methods: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. Results: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (-0.2%) in the placebo group (P=0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus -9±193 [-0.9%] mL/min, P=0.012), ventilatory equivalents of carbon dioxide (-0.8 versus -0.06, P=0.014), and work rate (+3.8 versus +0.34 W, P=0.021). There was no difference in change of myocardial performance index, the natural log of the reactive hyperemia index, or serum brain-type natriuretic peptide level. Conclusions: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold.Item The NHLBI Study on Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC): Design and Objectives(Elsevier, 2022) Truong, Dongngan T.; Trachtenberg, Felicia L.; Pearson, Gail D.; Dionne, Audrey; Elias, Matthew D.; Friedman, Kevin; Hayes, Kerri H.; Mahony, Lynn; McCrindle, Brian W.; Oster, Matthew E.; Pemberton, Victoria; Powell, Andrew J.; Russell, Mark W.; Shekerdemian, Lara S.; Son, Mary Beth; Taylor, Michael; Newburger, Jane W.; Pediatrics, School of MedicineBackground: The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. Methods: This multicenter observational cohort study will enroll at least 600 patients <21 years old who meet the Centers for Disease Control and Prevention case definition of MIS-C across multiple North American centers over 2 years. The study will collect detailed hospital and follow-up data for up to 5 years, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF) <45% during the acute illness. The primary outcomes are the worst LVEF and the highest coronary artery z-score of the left anterior descending or right coronary artery. Other outcomes include occurrence and course of non-cardiac organ dysfunction, inflammation, and major medical events. Independent adjudication of cases will classify participants as definite, possible, or not MIS-C. Analysis of the outcomes will include descriptive statistics and regression analysis with stratification by definite or possible MIS-C. The MUSIC study will provide phenotypic data to support basic and translational research studies. Conclusion: The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.Item Time-Related Risk of Pulmonary Conduit Re-replacement: A Congenital Heart Surgeons’ Society Study(Elsevier, 2021-06) Callahan, Connor P.; Jegatheeswaran, Anusha; Blackstone, Eugene H.; Karamlou, Tara; Baird, Christopher W.; Ramakrishnan, Karthik; Herrmann, Jeremy L.; Brown, John W.; Nelson, Jennifer S.; Polimenakos, Anastasios C.; Lambert, Linda M.; Eckhauser, Aaron W.; Kirklin, James K.; DeCampli, William M.; Aghaei, Nabi; St. Louis, James D.; McCrindle, Brian W.; Medicine, School of MedicineBackground Patients receiving a right ventricle to pulmonary artery conduit (PC) in infancy will require successive procedures or replacements, each with variable longevity. We sought to identify factors associated with time-related risk of a subsequent surgical replacement (PC3) or transcatheter pulmonary valve insertion (TPVI) after a second surgically placed PC (PC2). Methods From 2002 to 2016, 630 patients from 29 Congenital Heart Surgeons’ Society member institutions survived to discharge after initial valved PC insertion (PC1) at age ≤ 2 years. Of those, 355 underwent surgical replacement (PC2) of that initial conduit. Competing risk methodology and multiphase parametric hazard analyses were used to identify factors associated with time-related risk of PC3 or TPVI. Results Of 355 PC2 patients (median follow-up, 5.3 years), 65 underwent PC3 and 41 TPVI. Factors at PC2 associated with increased time-related risk of PC3 were smaller PC2 Z score (hazard ratio [HR] 1.6, P < .001), concomitant aortic valve intervention (HR 7.6, P = .009), aortic allograft (HR 2.2, P = .008), younger age (HR 1.4, P < .001), and larger Z score of PC1 (HR 1.2, P = .04). Factors at PC2 associated with increased time-related risk of TPVI were aortic allograft (HR: 3.3, P = .006), porcine unstented conduit (HR 4.7, P < .001), and older age (HR 2.3, P = .01). Conclusions Aortic allograft as PC2 was associated with increased time-related risk of both PC3 and TPVI. Surgeons may reduce risk of these subsequent procedures by not selecting an aortic homograft at PC2, and by oversizing the conduit when anatomically feasible.