Clinical Focus


  • Advanced Heart Failure and Transplant Cardiology

Academic Appointments


Professional Education


  • Fellowship: Stanford University Pediatric Cardiology Fellowship (2020) CA
  • Board Certification: American Board of Pediatrics, Pediatric Cardiology (2018)
  • Fellowship: Stanford University Pediatric Cardiology Fellowship (2018) CA
  • Board Certification: American Board of Pediatrics, Pediatrics (2014)
  • Residency: University of Washington Pediatric Residency (2014) WA
  • Medical Education: Perelman School of Medicine University of Pennsylvania (2011) PA
  • Fellowship, Stanford University, Pediatric Cardiology (2018)
  • Residency, University of Washington, Pediatrics (2014)
  • PhD, University of Pennsylvania, Bioengineering (2011)
  • MD, University of Pennsylvania Perelman School of Medicine (2011)

All Publications


  • Contemporary Pediatric Heart Transplant Waitlist Mortality. Journal of the American College of Cardiology Power, A., Sweat, K. R., Roth, A., Dykes, J. C., Kaufman, B., Ma, M., Chen, S., Hollander, S. A., Profita, E., Rosenthal, D. N., Barkoff, L., Chen, C. Y., Davies, R. R., Almond, C. S. 2024; 84 (7): 620-632

    Abstract

    In 2016, the United Network for Organ Sharing revised its pediatric heart transplant (HT) allocation policy.This study sought to determine whether the 2016 revisions are associated with reduced waitlist mortality and capture patient-specific risks.Children listed for HT from 1999 to 2023 were identified using Organ Procurement and Transplantation Network data and grouped into 3 eras (era 1: 1999-2006; era 2: 2006-2016; era 3: 2016-2023) based on when the United Network for Organ Sharing implemented allocation changes. Fine-Gray competing risks modeling was used to identify factors associated with death or delisting for deterioration. Fixed-effects analysis was used to determine whether allocation changes were associated with mortality.Waitlist mortality declined 8 percentage points (PP) across eras (21%, 17%, and 13%, respectively; P < 0.01). At listing, era 3 children were less sick than era 1 children, with 6 PP less ECMO use (P < 0.01), 11 PP less ventilator use (P < 0.01), and 1 PP less dialysis use (P < 0.01). Ventricular assist device (VAD) use was 13 PP higher, and VAD mortality decreased 9 PP (P < 0.01). Non-White mortality declined 10 PP (P < 0.01). ABO-incompatible listings increased 27 PP, and blood group O infant mortality decreased 13 PP (P < 0.01). In multivariable analyses, the 2016 revisions were not associated with lower waitlist mortality, whereas VAD use (in era 3), ABO-incompatible transplant, improved patient selection, and narrowing racial disparities were. Match-run analyses demonstrated poor correlation between individual waitlist mortality risk and the match-run order.The 2016 allocation revisions were not independently associated with the decline in pediatric HT waitlist mortality. The 3-tier classification system fails to adequately capture patient-specific risks. A more flexible allocation system that accurately reflects patient-specific risks and considers transplant benefit is urgently needed.

    View details for DOI 10.1016/j.jacc.2024.05.049

    View details for PubMedID 39111968

  • Uncertain benefit of statins in pediatric heart transplant recipients: A PHTS analysis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Townsend, M., Khoury, M., Koehl, D., Kirklin, J. K., Cantor, R., Beasley, G., Chen, C., Boyle, G., Parent, J. J., Baez Hernandez, N., Halnon, N. 2023

    Abstract

    BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure in pediatric heart transplant recipients (HTRs). Early statin use has been shown to reduce CAV incidence and all-cause mortality in adult HTRs. We sought to evaluate the contemporary prevalence and trends of statin use in pediatric HTRs and the association between statin use with CAV development and graft failure.METHODS: Patients aged <17years at the time of primary heart transplant who survived to ≥3years without CAV were identified from the Pediatric Heart Transplant Society database (2001-2018). Statin use in the first 3years posttransplant was defined as consecutive, intermediate, or absent. Kaplan-Meier survival, multivariable modeling, and propensity score-matched analyses evaluated associations between statin use and CAV incidence and graft survival, with subanalyses performed on subjects aged ≥10years at transplant.RESULTS: Among 3,485 (of which 1,086 aged ≥10 years) HTRs, 584 (17%) received consecutive statin therapy, 647 (19%) received intermediate use, and 2,254 (65%) received no statin therapy. Statin use varied widely between sites, with increasing use in the ≥10-year-old cohort over time. By multivariate analysis, statin use was not associated with graft loss. Consecutive statin use was also not associated with graft survival or freedom from CAV development when compared to absent statin use in unmatched or propensity-matched analyses.CONCLUSIONS: While statins remain commonly utilized in pediatric HTRs, early consecutive statin therapy did not decrease CAV incidence or graft loss. The differing effects of statins on CAV development and progression in pediatric vs adult HTRs suggest differing risk and mediating factors and require further study.

    View details for DOI 10.1016/j.healun.2023.11.021

    View details for PubMedID 38065240

  • Hemodynamic Predictors of Renal Function After Pediatric Left Ventricular Assist Device Implantation. ASAIO journal (American Society for Artificial Internal Organs : 1992) Chen, C. Y., Montez-Rath, M. E., May, L. J., Maeda, K., Hollander, S. A., Rosenthal, D. N., Krawczeski, C. D., Sutherland, S. M. 2021; 67 (12): 1335-1341

    Abstract

    Although renal function often improves after pediatric left ventricular assist device (LVAD) implantation, recovery is inconsistent. We aimed to identify hemodynamic parameters associated with improved renal function after pediatric LVAD placement. A single-center retrospective cohort study was conducted in patients less than 21 years who underwent LVAD placement between June 2004 and December 2015. The relationship between hemodynamic parameters and estimated glomerular filtration rate (eGFR) was assessed using univariate and multivariate modeling. Among 54 patients, higher preoperative central venous pressure (CVP) was associated with eGFR improvement after implantation (p = 0.012). However, 48 hours postimplantation, an increase in CVP from baseline was associated with eGFR decline over time (p = 0.01). In subgroup analysis, these associations were significant only for those with normal pre-ventricular assist device renal function (p = 0.026). In patients with preexisting renal dysfunction, higher absolute CVP values 48 and 72 hours after implantation predicted better renal outcome (p = 0.005). Our results illustrate a complex relationship between ventricular function, volume status, and renal function. Additionally, they highlight the challenge of using CVP to guide management of renal dysfunction in pediatric heart failure. Better methods for evaluating right heart function and volume status are needed to improve our understanding of how hemodynamics impact renal function in this population.

    View details for DOI 10.1097/MAT.0000000000001460

    View details for PubMedID 34860188

  • The Stanford acute heart failure symptom score for patients hospitalized with heart failure. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Almond, C. S., Chen, S., Dykes, J. C., Kwong, J., Burstein, D. S., Rosenthal, D. N., Kipps, A. K., Teuteberg, J., Murray, J. M., Kaufman, B. D., Hollander, S. A., Profita, E., Yarlagadda, V. Y., Sacks, L. D., Chen, C. 2020

    Abstract

    BACKGROUND: Currently, there are no simple tools to evaluate the acute heart failure (HF) symptom severity in children hospitalized with acute decompensated HF (ADHF). We sought to develop an inpatient HF score (HFS) that could be used as a clinical tool and for clinical trials.METHODS: Pediatric HF clinicians at Stanford reviewed the limitations of existing HFSs, which include lack of calibration to the inpatient setting, omission of gastrointestinal symptoms, need for multiple age-based tools, and scores that prioritize treatment intensity over patient symptoms. To address these, we developed an acute HFS corresponding to the 3 cardinal symptoms of HF: difficulty with breathing, feeding, and activity. The score was iteratively improved over a 3-year pilot phase until no further changes were made. The inter-rater reliability (IRR) across a range of providers was assessed using the final version. Peak HFSs were analyzed against mortality and length of stay (LOS) for all pediatric HF discharges between July and October 2019.RESULTS: The final HFS was a 4-point ordinal severity score for each of the 3 symptom domains (total score 0-12). Among clinicians who scored 12 inpatients with ADHF simultaneously, the intraclass correlation (ICC) was 0.94 (respiratory ICC = 0.89, feeding ICC = 0.85, and activity ICC = 0.80). Score trajectory reflected our clinical impression of patient response to HF therapies across a range of HF syndromes including 1- and 2-ventricle heart disease and reduced or preserved ejection fraction. Among the 28 patients hospitalized during a 3-months period (N = 28), quartiles of peak score were associated with LOS (p < 0.01) and in-hospital mortality (p < 0.01): HFS 0 to 3 (median LOS of 5 days and mortality of 0%), HFS 4 to 6 (median LOS of 18 days and mortality of 0%), HFS 5 to 9 (median LOS of 29 days and mortality of 23%), and HFS 10 to 12 (median LOS of 121 days and mortality of 50%).CONCLUSION: This simple acute HFS may be a useful tool to quantify and monitor day-to-day HF symptoms in children hospitalized with ADHF regardless of etiology or age group. The score has excellent IRR across provider levels and is associated with major hospital outcomes supporting its clinical validity. Validation in a multicenter cohort is warranted.

    View details for DOI 10.1016/j.healun.2020.08.002

    View details for PubMedID 33032871

  • Donor heart selection during the COVID-19 pandemic: A case study JOURNAL OF HEART AND LUNG TRANSPLANTATION Chen, C., Chen, S. F., Hollander, S. A., Rosenthal, D., Maeda, K., Burgart, A., Almond, C. S., Chen, S. 2020; 39 (5): 497–98
  • RECENT TRENDS IN RIGHT HEART MECHANICAL SUPPORT STRATEGIES IN CHILDREN REQUIRING LVAD SUPPORT Dykes, J., Ahmed, H., Power, A., Murray, J., Chen, C., Chen, S., Rosenthal, D. N., Maeda, K., Almond, C. ELSEVIER SCIENCE INC. 2020: 1052
  • Donor heart selection during the COVID-19 pandemic: A case study. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Chen, C. Y., Chen, S. F., Hollander, S. A., Rosenthal, D. n., Maeda, K. n., Burgart, A. n., Almond, C. S., Chen, S. n. 2020; 39 (5): 497–98

    View details for DOI 10.1016/j.healun.2020.03.018

    View details for PubMedID 32362395

  • Donor-specific anti-HLA antibody production following pediatric ABO-incompatible heart transplantation PEDIATRIC TRANSPLANTATION Chen, C., Warner, P., Albers, E. L., Kemna, M. S., Delaney, M., Hong, B. J., Law, Y. M. 2019; 23 (2)

    View details for DOI 10.1111/petr.13332

    View details for Web of Science ID 000459211900010

  • Blood flow reprograms lymphatic vessels to blood vessels JOURNAL OF CLINICAL INVESTIGATION Chen, C., Bertozzi, C., Zou, Z., Yuan, L., Lee, J. S., Lu, M., Stachelek, S. J., Srinivasan, S., Guo, L., Vincente, A., Mericko, P., Levy, R. J., Makinen, T., Oliver, G., Kahn, M. L. 2012; 122 (6): 2006–17

    Abstract

    Human vascular malformations cause disease as a result of changes in blood flow and vascular hemodynamic forces. Although the genetic mutations that underlie the formation of many human vascular malformations are known, the extent to which abnormal blood flow can subsequently influence the vascular genetic program and natural history is not. Loss of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76) resulted in a vascular malformation that directed blood flow through mesenteric lymphatic vessels after birth in mice. Mesenteric vessels in the position of the congenital lymphatic in mature Slp76-null mice lacked lymphatic identity and expressed a marker of blood vessel identity. Genetic lineage tracing demonstrated that this change in vessel identity was the result of lymphatic endothelial cell reprogramming rather than replacement by blood endothelial cells. Exposure of lymphatic vessels to blood in the absence of significant flow did not alter vessel identity in vivo, but lymphatic endothelial cells exposed to similar levels of shear stress ex vivo rapidly lost expression of PROX1, a lymphatic fate-specifying transcription factor. These findings reveal that blood flow can convert lymphatic vessels to blood vessels, demonstrating that hemodynamic forces may reprogram endothelial and vessel identity in cardiovascular diseases associated with abnormal flow.

    View details for DOI 10.1172/JCI57513

    View details for Web of Science ID 000304736300011

    View details for PubMedID 22622036

    View details for PubMedCentralID PMC3366395

  • Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling BLOOD Bertozzi, C. C., Schmaier, A. A., Mericko, P., Hess, P. R., Zou, Z., Chen, M., Chen, C., Xu, B., Lu, M., Zhou, D., Sebzda, E., Santore, M. T., Merianos, D. J., Stadtfeld, M., Flake, A. W., Graf, T., Skoda, R., Maltzman, J. S., Koretzky, G. A., Kahn, M. L. 2010; 116 (4): 661–70

    Abstract

    Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.

    View details for DOI 10.1182/blood-2010-02-270876

    View details for Web of Science ID 000280502800025

    View details for PubMedID 20363774

    View details for PubMedCentralID PMC3324297

  • Engineering of fiber-reinforced tissues with anisotropic biodegradable nanofibrous scaffolds. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference Nerurkar, N. L., Baker, B. M., Chen, C., Elliott, D. M., Mauck, R. L. 2006; 1: 787–90

    Abstract

    The repair of dense fiber-reinforced tissues poses a significant challenge for the tissue engineering community. The function of these structures is largely dependent on their architectural form, and as such, scaffold organization is an important design parameter in generating tissue analogues. To address this issue, we have recently utilized electrospinning to instill controllable fiber anisotropy in nanofibrous scaffolds. This abstract details the mechanical characterization of the bulk and local properties of these scaffolds, and points to their potential application in the repair and/or generation of fiber-reinforced tissues that recapitulate the native form.

    View details for PubMedID 17946860