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4. Contributors

Author

Abrams, Dominic J., primary, Alexander, Mark E., additional, Alexander, Peta M.A., additional, Allan, Catherine, additional, Baird, Christopher W., additional, Bergersen, Lisa, additional, Beroukhim, Rebecca, additional, Bevilacqua, Laura M., additional, Bezzerides, Vassilios, additional, Blume, Elizabeth D., additional, Breitbart, Roger E., additional, Brown, David W., additional, Callahan, Ryan, additional, Carreon, Chrystalle Katte, additional, Castellanos, Daniel A., additional, Chen, Ming Hui, additional, Cheng, Henry, additional, Colan, Steven D., additional, Daly, Kevin P., additional, de Ferranti, Sarah D., additional, del Nido, Pedro J., additional, DeWitt, Elizabeth, additional, DiNardo, James, additional, Dionne, Audrey, additional, Emani, Sitaram M., additional, Esch, Jesse J., additional, Esteso, Paul, additional, Feins, Eric N., additional, Freed, Michael D., additional, Friedman, Kevin, additional, Fulton, David R., additional, Fynn-Thompson, Francis, additional, Garbern, Jessica C., additional, Garcia-Mancebo, Julia, additional, Gauthier, Naomi, additional, Geggel, Robert L., additional, Geisser, Diana L., additional, Gellis, Laura, additional, Geva, Tal, additional, Ghbeis, Muhammad Bakr, additional, Ghelani, Sunil J., additional, Goldberg, Sarah W., additional, Gurvitz, Michelle, additional, Hames, Daniel L., additional, Harrild, David M., additional, Hartz, Jacob, additional, Hickey, Patricia, additional, Hoganson, David, additional, Jenkins, Kathy, additional, Kane, David, additional, Kaza, Aditya K., additional, Kheir, John N., additional, Kumar, R. Krishna, additional, Kwon, Michael H., additional, Lacro, Ronald V., additional, Landzberg, Michael J., additional, Lang, Peter, additional, LaRovere, Joan M., additional, Levine, Jami, additional, Lock, James Ernest, additional, Lyon, Shannon, additional, Mah, Douglas Y., additional, Marx, Gerald R., additional, Maschietto, Nicola, additional, Matte, Gregory S., additional, Mayer, John E., additional, Mills, Kimberly I., additional, Mistry, Kshitij, additional, Mullen, Mary P., additional, Nasr, Viviane G., additional, Nathan, Meena, additional, Newburger, Jane W., additional, O’Brien, Patricia, additional, O’Brien, Sharon E., additional, O’Leary, Edward T., additional, Porras, Diego, additional, Powell, Andrew J., additional, Prakash, Ashwin, additional, Pu, William T., additional, Quiat, Daniel, additional, Quinn, Brian, additional, Quinonez, Luis, additional, Rathod, Rahul H., additional, Rhodes, Jonathan, additional, Roberts, Amy E., additional, Rodriguez-Monserrate, Carla P., additional, Ronai, Christina, additional, Saia, Theresa, additional, Saleeb, Susan F., additional, Salvin, Joshua W., additional, Sanders, Stephen P., additional, Schidlow, David, additional, Shafer, Keri M., additional, Siegel, Bryan D., additional, Singh, Michael N., additional, Singh, Tajinder, additional, Teele, Sarah A., additional, Thiagarajan, Ravi R., additional, Triedman, John K., additional, Tworetzky, Wayne, additional, Valente, Anne Marie, additional, VanderPluym, Christina, additional, Walsh, Edward P., additional, Wu, Fred Ming-Chieh, additional, and Yin, Suellen, additional

Published
2025
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15. De novo Damaging Variants, Clinical Phenotypes and Post-Operative Outcomes in Congenital Heart Disease

Author

Boskovski, Marko T, Homsy, Jason, Nathan, Meena, Sleeper, Lynn A, Morton, Sarah, Manheimer, Kathryn B, Tai, Angela, Gorham, Joshua, Lewis, Matthew, Swartz, Michael, Alfieris, George M, Bacha, Emile A, Karimi, Mohsen, Meyer, David, Nguyen, Khanh, Bernstein, Daniel, Romano-Adesman, Angela, Porter, George A, Goldmuntz, Elizabeth, Chung, Wendy K, Srivastava, Deepak, Kaltman, Jonathan R, Tristani-Firouzi, Martin, Lifton, Richard, Roberts, Amy E, Gaynor, J William, Gelb, Bruce D, Kim, Richard, Seidman, Jonathan G, Brueckner, Martina, Mayer, John E, Newburger, Jane W, and Seidman, Christine E

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Genetics, Patient Safety, Congenital Structural Anomalies, Clinical Research, Human Genome, Transplantation, Heart Disease, Cardiovascular, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adolescent, Child, Child, Preschool, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 3, DNA Copy Number Variations, Female, Heart Defects, Congenital, Heart Transplantation, Humans, Infant, Kaplan-Meier Estimate, Machine Learning, Male, Odds Ratio, Phenotype, Proportional Hazards Models, Exome Sequencing, genomics, congenital heart disease, heart transplantation, mortality, survival, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundDe novo genic and copy number variants are enriched in patients with congenital heart disease, particularly those with extra-cardiac anomalies. The impact of de novo damaging variants on outcomes following cardiac repair is unknown.MethodsWe studied 2517 patients with congenital heart disease who had undergone whole-exome sequencing as part of the CHD GENES study (Congenital Heart Disease Genetic Network).ResultsTwo hundred ninety-four patients (11.7%) had clinically significant de novo variants. Patients with de novo damaging variants were 2.4 times more likely to have extra-cardiac anomalies (P=5.63×10-12). In 1268 patients (50.4%) who had surgical data available and underwent open-heart surgery exclusive of heart transplantation as their first operation, we analyzed transplant-free survival following the first operation. Median follow-up was 2.65 years. De novo variants were associated with worse transplant-free survival (hazard ratio, 3.51; P=5.33×10-04) and longer times to final extubation (hazard ratio, 0.74; P=0.005). As de novo variants had a significant interaction with extra-cardiac anomalies for transplant-free survival (P=0.003), de novo variants conveyed no additional risk for transplant-free survival for patients with these anomalies (adjusted hazard ratio, 1.96; P=0.06). By contrast, de novo variants in patients without extra-cardiac anomalies were associated with worse transplant-free survival during follow-up (hazard ratio, 11.21; P=1.61×10-05) than that of patients with no de novo variants. Using agnostic machine-learning algorithms, we identified de novo copy number variants at 15q25.2 and 15q11.2 as being associated with worse transplant-free survival and 15q25.2, 22q11.21, and 3p25.2 as being associated with prolonged time to final extubation.ConclusionsIn patients with congenital heart disease undergoing open-heart surgery, de novo variants were associated with worse transplant-free survival and longer times on the ventilator. De novo variants were most strongly associated with adverse outcomes among patients without extra-cardiac anomalies, suggesting a benefit for preoperative genetic testing even when genetic abnormalities are not suspected during routine clinical practice. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01196182.

Published
2020

19. Improvement in Pediatric Cardiac Surgical Outcomes Through Interhospital Collaboration

Author

Gaies, Michael, Pasquali, Sara K, Banerjee, Mousumi, Dimick, Justin B, Birkmeyer, John D, Zhang, Wenying, Alten, Jeffrey A, Chanani, Nikhil, Cooper, David S, Costello, John M, Gaynor, J William, Ghanayem, Nancy, Jacobs, Jeffrey P, Mayer, John E, Ohye, Richard G, Scheurer, Mark A, Schwartz, Steven M, Tabbutt, Sarah, and Charpie, John R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Heart Disease, Patient Safety, Cardiovascular, Clinical Trials and Supportive Activities, Pediatric, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Good Health and Well Being, Cardiac Surgical Procedures, Child, Preschool, Cooperative Behavior, Critical Care, Female, Heart Defects, Congenital, Hospital Mortality, Humans, Infant, Infant, Newborn, Intensive Care Units, Male, Morbidity, Postoperative Complications, Quality Improvement, Registries, United States, cardiac surgery, collaborative learning, congenital, outcomes, pediatric, quality, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundPatients undergoing complex pediatric cardiac surgery remain at considerable risk of mortality and morbidity, and variation in outcomes exists across hospitals. The Pediatric Cardiac Critical Care Consortium (PC4) was formed to improve the quality of care for these patients through transparent data sharing and collaborative learning between participants.ObjectivesThe purpose of this study was to determine whether outcomes improved over time within PC4.MethodsThe study analyzed 19,600 hospitalizations (18 hospitals) in the PC4 clinical registry that included cardiovascular surgery from August 2014 to June 2018. The primary exposure was 2 years of PC4 participation; this provided adequate time for hospitals to accrue data and engage in collaborative learning. Aggregate case mix-adjusted outcomes were compared between the first 2 years of participation (baseline) and all months post-exposure. We also evaluated outcomes from the same era in a cohort of similar, non-PC4 hospitals.ResultsDuring the baseline period, there was no evidence of improvement. We observed significant improvement in the post-exposure period versus baseline for post-operative intensive care unit mortality (2.1% vs. 2.7%; 22% relative reduction [RR]; p = 0.001), in-hospital mortality (2.5% vs. 3.3%; 24% RR; p = 0.001), major complications (10.1% vs. 11.5%; 12% RR; p

Published
2019

28. Evolving Cost-Quality Relationship in Pediatric Heart Surgery

Author

Pasquali, Sara K., Thibault, Dylan, Hall, Matt, Chiswell, Karen, Romano, Jennifer C., Gaynor, J. William, Shahian, David M., Jacobs, Marshall L., Gaies, Michael G., O’Brien, Sean M., Norton, Edward C., Hill, Kevin D., Cowper, Patricia A., Shah, Samir S., Mayer, John E., and Jacobs, Jeffrey P.

Published
2022
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30. Estimating Resource Utilization in Congenital Heart Surgery

Author

Pasquali, Sara K., Chiswell, Karen, Hall, Matt, Thibault, Dylan, Romano, Jennifer C., Gaynor, J. William, Shahian, David M., Jacobs, Marshall L., Gaies, Michael G., O’Brien, Sean M., Norton, Edward C., Hill, Kevin D., Cowper, Patricia A., Pinto, Nelangi M., Shah, Samir S., Mayer, John E., and Jacobs, Jeffrey P.

Published
2020
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45. Refining The Society of Thoracic Surgeons Congenital Heart Surgery Database Mortality Risk Model With Enhanced Risk Adjustment for Chromosomal Abnormalities, Syndromes, and Noncardiac Congenital Anatomic Abnormalities

Author

Jacobs, Jeffrey P., O’Brien, Sean M., Hill, Kevin D., Kumar, S. Ram, Austin, Erle H., III, Gaynor, J. William, Gruber, Peter J., Jonas, Richard A., Pasquali, Sara K., Pizarro, Christian, St. Louis, James D., Meza, James, Thibault, Dylan, Shahian, David M., Mayer, John E., Jr., and Jacobs, Marshall L.

Published
2019
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46. Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine

Author

Cole, Alexis R., Perry, Dorothy A., Raza, Ali, Nedder, Arthur P., Pollack, Elizabeth, Regan, William L., van den Bosch, Sarah J., Polizzotti, Brian D., Yang, Edward, Davila, Daniel, Afacan, Onur, Warfield, Simon K., Ou, Yangming, Sefton, Brenda, Everett, Allen D., Neil, Jeffrey J., Lidov, Hart G.W., Mayer, John E., and Kheir, John N.

Published
2019
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47. Tri-layered elastomeric scaffolds for engineering heart valve leaflets

Author

Masoumi, Nafiseh, Annabi, Nasim, Assmann, Alexander, Larson, Benjamin L, Hjortnaes, Jesper, Alemdar, Neslihan, Kharaziha, Mahshid, Manning, Keefe B, Mayer, John E, and Khademhosseini, Ali

Subjects
Biotechnology, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, Bioengineering, Cardiovascular, Stem Cell Research, Transplantation, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, Musculoskeletal, Animals, Anisotropy, Aortic Valve, Elastomers, Heart Valve Prosthesis, Humans, In Vitro Techniques, Materials Testing, Microscopy, Electron, Scanning, Polymers, Pulmonary Valve, Sheep, Tissue Engineering, Tissue Scaffolds, Microfabricated elastomer, Electrospinning, Biodegradable scaffold, Anisotropic mechanical properties, Heart valve tissue engineering
Abstract

Tissue engineered heart valves (TEHVs) that can grow and remodel have the potential to serve as permanent replacements of the current non-viable prosthetic valves particularly for pediatric patients. A major challenge in designing functional TEHVs is to mimic both structural and anisotropic mechanical characteristics of the native valve leaflets. To establish a more biomimetic model of TEHV, we fabricated tri-layered scaffolds by combining electrospinning and microfabrication techniques. These constructs were fabricated by assembling microfabricated poly(glycerol sebacate) (PGS) and fibrous PGS/poly(caprolactone) (PCL) electrospun sheets to develop elastic scaffolds with tunable anisotropic mechanical properties similar to the mechanical characteristics of the native heart valves. The engineered scaffolds supported the growth of valvular interstitial cells (VICs) and mesenchymal stem cells (MSCs) within the 3D structure and promoted the deposition of heart valve extracellular matrix (ECM). MSCs were also organized and aligned along the anisotropic axes of the engineered tri-layered scaffolds. In addition, the fabricated constructs opened and closed properly in an ex vivo model of porcine heart valve leaflet tissue replacement. The engineered tri-layered scaffolds have the potential for successful translation towards TEHV replacements.

Published
2014

48. Electrospun PGS:PCL Microfibers Align Human Valvular Interstitial Cells and Provide Tunable Scaffold Anisotropy

Author

Masoumi, Nafiseh, Larson, Benjamin L, Annabi, Nasim, Kharaziha, Mahshid, Zamanian, Behnam, Shapero, Kayle S, Cubberley, Alexander T, Camci‐Unal, Gulden, Manning, Keefe B, Mayer, John E, and Khademhosseini, Ali

Subjects
Regenerative Medicine, Bioengineering, Cardiovascular, Heart Disease, Actins, Animals, Biomimetic Materials, Cell Survival, Cells, Cultured, Collagen, Decanoates, Elastic Modulus, Extracellular Matrix, Glycerol, Heart Valves, Humans, Polyesters, Polymers, Swine, Tensile Strength, Tissue Engineering, Tissue Scaffolds, Vimentin, aortic valve, electrospinning, human valvular interstitial cells, mechanical properties, tissue engineered heart valve, Medicinal and Biomolecular Chemistry, Biomedical Engineering, Medical Biotechnology
Abstract

Tissue engineered heart valves (TEHV) can be useful in the repair of congenital or acquired valvular diseases due to their potential for growth and remodeling. The development of biomimetic scaffolds is a major challenge in heart valve tissue engineering. One of the most important structural characteristics of mature heart valve leaflets is their intrinsic anisotropy, which is derived from the microstructure of aligned collagen fibers in the extracellular matrix (ECM). In the present study, a directional electrospinning technique is used to fabricate fibrous poly(glycerol sebacate):poly(caprolactone) (PGS:PCL) scaffolds containing aligned fibers, which resemble native heart valve leaflet ECM networks. In addition, the anisotropic mechanical characteristics of fabricated scaffolds are tuned by changing the ratio of PGS:PCL to mimic the native heart valve's mechanical properties. Primary human valvular interstitial cells (VICs) attach and align along the anisotropic axes of all PGS:PCL scaffolds with various mechanical properties. The cells are also biochemically active in producing heart-valve-associated collagen, vimentin, and smooth muscle actin as determined by gene expression. The fibrous PGS:PCL scaffolds seeded with human VICs mimick the structure and mechanical properties of native valve leaflet tissues and would potentially be suitable for the replacement of heart valves in diverse patient populations.

Published
2014

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