Christopher Knoll’s research while affiliated with Phoenix Children's Hospital and other places

Objective To describe the utilization patterns and outcomes of pediatric patients supported with oxygenators during their ventricular assist device (VAD) course. Design Multi-center, retrospective cohort study using data from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. Setting Data query from the ACTION registry, which collects clinical data on pediatric patients with end-stage heart disease, reported cases of combined oxygenator-VAD use. Patients Sixty-one pediatric patients (27 female) from 21 contributing ACTION centers were supported on oxygenators during their VAD course between 2013-2024. The median age was 272 days (IQR 68-1334), and the median weight was 7.9kg (IQR 4.4-12). The majority had congenital heart disease (CHD), with 66% having single-ventricle pathology. Interventions None. Measurement and Main Results The study population demonstrated high illness severity at the time of VAD implant, with 97% requiring inotropic support, 79% requiring mechanical ventilation, and 46% on ECMO. The total median duration of VAD support was 45 days (IQR 16-163). Of the 61 patients, 44% achieved transplant or recovery. The mortality rate was high at 52%, and was associated with younger age, smaller size, CHD and pre-implant use of neuromuscular blocking agents. Adverse events included infection (36%), major bleeding (36%), central nervous system injuries (21%), and dialysis (20%). None demonstrated clinically significant association with oxygenator support timing, but mortality was associated with higher adverse events rates, particularly pulmonary hemorrhage, dialysis, and infections (especially mediastinitis). Conclusion Pediatric patients requiring oxygenators during VAD therapy exhibit high illness severity and frequent adverse events. Mortality is high and associated with younger age, smaller size, CHD, pre-implant use of neuromuscular blocking agents as well frequency of on-device adverse events, particularly pulmonary hemorrhage, dialysis, and infections. Oxygenator support likely reflects disease severity rather than directly contributing to mortality. Further investigation is needed to optimize patient selection and management strategies. Research In Context Over the past two decades, pediatric VAD utilization has increased. Support from collaborative networks like ACTION has enabled investigation of nuanced strategies, such as temporary oxygenator use, providing a platform to evaluate feasibility, safety, and patient-specific considerations across diverse populations. In adult populations, oxygenator use alongside VADs has been employed for respiratory failure, ARDS, RV support, and as a bridge to lung transplant or transition from ECMO. However, these strategies have not been systematically studied in pediatric cohorts until now. This study presents the most comprehensive review of pediatric (or adult) oxygenator-VAD support to date, characterizing patient populations, utilization patterns, and associated outcomes. It provides foundational data for guiding future research into management strategies in this high-risk group. At the Bedside Pediatric patients requiring oxygenator support during VAD therapy were typically younger, smaller, and had complex congenital heart disease, particularly single-ventricle physiology. These characteristics were associated with higher mortality and reflect a population with profound critical illness at baseline. This cohort experienced high rates of adverse events, including major bleeding, infections, dialysis, and neurologic injury. While oxygenator timing was not independently associated with outcomes, mortality exceeded 50% and was linked to complications such as dialysis, pulmonary hemorrhage, and infections. Clinicians should view oxygenator-VAD support as a surrogate marker for extreme illness severity rather than a direct contributor to poor outcome. This study highlights the need for tailored management strategies and informs clinician and family decision-making in this high-risk population.

Prinzmetal angina is a rare cause of intermittent chest pain in paediatrics. Here, we report the case of a 2-year-old female who presented with episodic chest pain, malaise, diaphoresis, fatigue, and poor perfusion on exam. During her hospitalisation, these episodes were associated with significant low cardiac output as evidenced by lactic acidosis and low mixed venous oxygen saturations. Her workup revealed an actin alpha cardiac muscle 1 (ACTC1) gene mutation and associated left ventricular non-compaction with decreased systolic function. She was started on oral heart failure medications as well as a calcium channel blocker but continued to have episodes which were found to promptly resolve with nitroglycerine. She was ultimately listed for cardiac transplant given her perceived risk of sudden death.

Purpose: We sought to establish whether nucleated red blood cells (NRBCs) are predictive of disposition, morbidity, and mortality for pediatric patients presenting to the emergency department (ED). Methods: A single-center retrospective cohort study examining all ED encounters from patients aged younger than 19 years between January 2016 and March 2020, during which a complete blood count was obtained. Univariate analysis and multivariable logistic regression were used to test the presence of NRBCs as an independent predictor of patient-related outcomes. Results: The prevalence of NRBCs was 8.9% (4195/46,991 patient encounters). Patient with NRBCs were younger (median age 4.58 vs 8.23 years; P < 0.001). Those with NRBCs had higher rates of in-hospital mortality (30/2465 [1.22%] vs 65/21,741 [0.30%]; P < 0.001), sepsis (19% vs 12%; P < 0.001), shock (7% vs 4%; P < 0.001), and cardiopulmonary resuscitation (CPR) (0.62% vs 0.09%; P < 0.001). They were more likely to be admitted (59% vs 51%; P < 0.001), have longer median hospital length of stay {1.3 (interquartile range [IQR], 0.22-4.14) vs 0.8 days (IQR, 0.23-2.64); P < 0.001}, and median intensive care unit (ICU) length of stay (3.9 [IQR, 1.87-8.72] vs 2.6 days [IQR, 1.27-5.83]; P < 0.001). Multivariable regression revealed presence of NRBCs as an independent predictor for in-hospital mortality (adjusted odds ratio [aOR], 2.21; 95% confidence interval [CI], 1.38-3.53; P < 0.001), ICU admission (aOR, 1.30; 95% CI, 1.11-1.51; P < 0.001), CPR (aOR, 3.83; 95% CI, 2.33-6.30; P < 0.001), and 30-day return to the ED (aOR, 1.15; 95% CI, 1.15-1.26; P < 0.001). Conclusions: The presence of NRBCs is an independent predictor for mortality, including in-hospital mortality, ICU admission, CPR, and readmission within 30 days for children presenting to the ED.

Purpose: We sought to establish whether nucleated red blood cells (NRBCs) are predictive of disposition, morbidity, and mortality for pediatric patients presenting to the emergency department (ED). Methods: A single center retrospective cohort study examining all ED encounters from patients<19 years old between January 2016 and March 2020, during which a CBC was obtained. Univariate analysis and multivariable logistic regression were used to test presence of NRBCs as independent predictor of patient-related outcomes. Results: The prevalence of NRBCs was 8.9% (4,195/46,991 patient encounters). Patient with NRBCs were younger (median age 4.58 vs 8.23 years; P<0.001). Those with NRBCs had higher rates of in-hospital mortality (30/2,465 [1.22%] vs 65/21,741 [0.30%]; P<0.001), sepsis (19% vs 12%; P<0.001), shock (7% vs 4%; P<0.001), and CPR (0.62% vs 0.09%; P<0.001). They were more likely to be admitted (59% vs 51%; P<0.001), have longer median hospital length of stay (LOS) (1.3 [IQR: 0.22, 4.14] vs. 0.8 days [0.23, 2.64]; P<0.001), and median intensive care unit (ICU) LOS (3.9 [IQR: 1.87, 8.72] vs 2.6 days [IQR: 1.27, 5.83]; P<0.001). Multivariable regression revealed presence of NRBCs as an independent predictor for in-hospital mortality (adjusted odds ratio (aOR) 2.21 95% CI 1.38-3.53; p<0.001), ICU admission (aOR 1.30 95% CI 1.11, 1.51), CPR (aOR 3.83 95% CI 2.33-6.30; p<0.001), and 30-day return to the ED (aOR 1.15 95% CI 1.15-1.26; P<0.001). Conclusions: Presence of NRBCs is an independent predictor for mortality, including in-hospital mortality, ICU admission, CPR, and readmission within 30 days for children presenting to the ED.

Background Learning networks have emerged in medicine as a novel organizational structure that contains elements of quality improvement, education, and research with the goal of effecting rapid improvements in clinical care. In this article, the concept of a learning network is defined and highlighted in the field of pediatric heart failure and transplantation. Methods Learning networks are defined, with particular attention paid to the recent creation of the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) for children with heart failure and those being supported with ventricular assist devices (VAD). Results The mission, goals, and organizational structure of ACTION are described, and recent initiatives promoted by ACTION are highlighted, such as stroke reduction initiatives, practice harmonization protocols, and use of ACTION data to support the recent US Food and Drug Administration approval of newer VAD for pediatric patients. Conclusions The learning network, exemplified by ACTION, is distinguished from traditional clinical research collaboratives by contributions in research, quality improvement, patient-reported outcomes, and education, and serves as an effective vehicle to drive clinical improvement in the care of children with advanced heart failure.