Clinical Focus


  • Pediatric Cardiology
  • Pediatric Cardiac Intensive Care

Academic Appointments


Administrative Appointments


  • Medical Director - Cardiovascular ICU, Lucile Packard Children's Hospital (2023 - Present)
  • Medical Director - CVICU Consultation Service, Lucile Packard Children's Hospital (2017 - Present)
  • Associate Program Director - Pediatric Cardiology Fellowship, Lucile Packard Children's Hospital (2018 - 2020)
  • Associate Medical Director - Cardiovascular ICU, Lucile Packard Children's Hospital (2020 - 2023)

Professional Education


  • Residency: Cincinnati Children's Hospital Medical Center Pediatric Residency (2011) OH
  • Fellowship: Cincinnati Children's Hospital Medical Center (2014) OH
  • Fellowship: LPCH/Stanford (2015) CA
  • Medical Education: Georgetown University (2008) DC
  • MS, University of Cincinnati, Master of Science in Clinical and Translational Research (2014)
  • Board Certification: American Board of Pediatrics, Pediatrics (2011)
  • Board Certification: American Board of Pediatrics, Pediatric Cardiology (2014)

All Publications


  • Peritoneal Dialysis vs Furosemide for Prevention of Fluid Overload in Infants After Cardiac Surgery: A Randomized Clinical Trial. JAMA pediatrics Kwiatkowski, D. M., Goldstein, S. L., Cooper, D. S., Nelson, D. P., Morales, D. L., Krawczeski, C. D. 2017

    Abstract

    Fluid overload after congenital heart surgery is frequent and a major cause of morbidity and mortality among infants. Many programs have adopted the use of peritoneal dialysis (PD) for fluid management; however, its benefits compared with those of traditional diuretic administration are unknown.To determine whether infants randomized to PD vs furosemide for the treatment of oliguria have a higher incidence of negative fluid balance on postoperative day 1, as well as avoidance of 10% fluid overload; shorter duration of mechanical ventilation, intensive care unit stay, and inotrope use; and fewer electrolyte abnormalities.This single-center, unblinded, randomized clinical trial compared methods of fluid removal after cardiac surgery from October 1, 2011, through March 13, 2015, in a large tertiary pediatric hospital in Ohio. The parents or guardians of all eligible infants (aged <6 months) undergoing cardiac surgery with catheter placement for PD were approached for inclusion. No patients were withdrawn for adverse effects. Recruitment was powered for the primary outcome, and analysis was based on intention to treat. Patients randomized to PD were hypothesized to have superior outcomes.Infants received intravenous furosemide (1 mg/kg every 6 hours) or a standardized PD regimen.The primary end point was incidence of negative fluid balance on postoperative day 1. Secondary end points included incidence of fluid overload, duration of mechanical ventilation and intensive care unit stay, electrolyte abnormalities and repletion doses, duration of inotropic administration, and mortality.Seventy-three patients (47 boys [64%] and 26 girls [35%]; median age, 8 [interquartile range {IQR}, 6-14] days) received treatment and completed the trial. No difference was found between the PD and furosemide groups in the incidence of negative fluid balance on the first postoperative day. The furosemide group was 3 times more likely to have 10% fluid overload (odds ratio [OR], 3.0; 95% CI, 1.3-6.9), was more likely to have prolonged ventilator use (OR, 3.1; 95% CI, 1.2-8.2), and had a longer duration of inotrope use (median, 5.5 [IQR, 4-8] vs 4.0 [IQR, 3-6] days) and higher electrolyte abnormality scores (median, 6 [IQR, 4-7] vs 3 [IQR, 2-5]) compared with the PD group. No statistically significant differences in mortality (3 patients [9.4%] in the furosemide group vs 1 patient [3.1%] in the PD group) or length of cardiac intensive care unit (median, 7 [IQR, 6-12] vs 9 [IQR, 5-15] days) or hospital (15 [IQR, 10-28] vs 14 [IQR, 9-22] days) stay were observed. No serious complications were observed. Dialysis was discontinued early in 9 of 41 patients in the PD group for pleural-peritoneal communication.Use of PD is safe and allows for superior fluid management with improved clinical outcomes compared with diuretic administration. Use of PD should be strongly considered among infants at high risk for postoperative acute kidney injury and fluid overload.clinicaltrials.gov Identifer: NCT01709227.

    View details for DOI 10.1001/jamapediatrics.2016.4538

    View details for PubMedID 28241247

  • Impact of Congenital Heart Disease on the Outcomes of Very Low Birth Weight Infants. American journal of perinatology Chen, X., Bhombal, S., Kwiatkowski, D. M., Ma, M., Chock, V. Y. 2024

    Abstract

    OBJECTIVE: To investigate the association of congenital heart disease (CHD) with morbidity and mortality of very low birth weight (VLBW) infants.STUDY DESIGN: This matched case-control study included VLBW infants born at a single institution between 2001 and 2015. The primary outcome was mortality. Secondary outcomes included necrotizing enterocolitis, bronchopulmonary dysplasia (BPD), sepsis, retinopathy of prematurity, and intraventricular hemorrhage. These outcomes were assessed by comparing VLBW-CHDs with control VLBW infants matched by gestational age within a week, birth weight within 500g, sex, and birth date within a year using conditional logistic regression. Multivariable logistic regression analyzed differences in outcomes in the VLBW-CHD group between two birth periods (2001-2008 and 2009-2015) to account for changes in practice.RESULTS: In a cohort of 44 CHD infants matched with 88 controls, the mortality rate was 27% in infants with CHD and 1% in controls (p<0.0001). The VLBW-CHDs had increased BPD; (odds ratio [OR]: 7.70, 95% confidence interval [CI]: 1.96-30.29) and sepsis (OR: 10.59, 95% CI: 2.99-37.57) compared with the control VLBWs. When adjusted for preoperative ventilator use, the VLBW-CHDs still had significantly higher odds of BPD (OR: 6.97, 95% CI: 1.73-28.04). VLBW-CHDs also had significantly higher odds of both presumed and culture-positive sepsis as well as late-onset sepsis than their matched controls. There were no significant differences in outcomes between the two birth periods.CONCLUSION: VLBW-CHDs showed higher odds of BPD, sepsis, and mortality than VLBW infants without CHD. Future research should focus on the increased mortality and specific complications encountered by VLBW infants with CHD and implement targeted strategies to address these risks.KEY POINTS: · Incidence of CHD is higher in preterm infants than in term infants but the incidence of their morbidities is not well described.. · VLBW infants with CHD have higher odds of mortality, bronchopulmonary dysplasia, and sepsis.. · Future research is needed to implement targeted preventive responses..

    View details for DOI 10.1055/s-0044-1781460

    View details for PubMedID 38408479

  • Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults. JAMA network open Gist, K. M., Menon, S., Anton-Martin, P., Bigelow, A. M., Cortina, G., Deep, A., De la Mata-Navazo, S., Gelbart, B., Gorga, S., Guzzo, I., Mah, K. E., Ollberding, N. J., Shin, H. S., Thadani, S., Uber, A., Zang, H., Zappitelli, M., Selewski, D. T. 2024; 7 (1): e2349871

    Abstract

    In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown.To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90).This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023.The primary exposure was time to CRRT initiation from intensive care unit admission.The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]).Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]).In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

    View details for DOI 10.1001/jamanetworkopen.2023.49871

    View details for PubMedID 38165673

    View details for PubMedCentralID PMC10762580

  • Intensive Care Unit Analgosedation After Cardiac Surgery in Children with Williams Syndrome : a Matched Case-Control Study. Pediatric cardiology Mills, M., Algaze, C., Journel, C., Suarez, G., Lechich, K., Kwiatkowski, M. D., Schmidt, A. R., Collins, R. T. 2023

    Abstract

    OBJECTIVE: Cardiovascular abnormalities are common in patients with Williams syndrome and frequently require surgical intervention necessitating analgesia and sedation in a population with a unique neuropsychiatric profile, potentially increasing the risk of adverse cardiac events during the perioperative period. Despite this risk, the overall postoperative analgosedative requirements in patients with WS in the cardiac intensive care unit have not yet been investigated. Our primary aim was to examine the analgosedative requirement in patients with WS after cardiac surgery compared to a control group. Our secondary aim was to compare the frequency of major ACE and mortality between the two groups.DESIGN: Matched case-control study.SETTING: Pediatric CICU at a Tertiary Children's Hospital.PATIENTS: Patients with WS and age-matched controls who underwent cardiac surgery and were admitted to the CICU after cardiac surgery between July 2014 and January 2021.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Postoperative outcomes and total doses of analgosedative medications were collected in the first six days after surgery for the study groups. Median age was 29.8 (12.4-70.8) months for WS and 23.5 (11.2-42.3) months for controls. Across all study intervals (48h and first 6 postoperative days), there were no differences between groups in total doses of morphine equivalents (5.0mg/kg vs 5.6mg/kg, p=0.7 and 8.2mg/kg vs 10.0mg/kg, p=0.7), midazolam equivalents (1.8mg/kg vs 1.5mg/kg, p=0.4 and 3.4mg/kg vs 3.8mg/kg, p=0.4), or dexmedetomidine (20.5 mcg/kg vs 24.4 mcg/kg, p=0.5 and 42.3 mcg/kg vs 39.1 mcg/kg, p=0.3). There was no difference in frequency of major ACE or mortality.CONCLUSIONS: Patients with WS received similar analgosedative medication doses compared with controls. There was no significant difference in the frequency of major ACE (including cardiac arrest, extracorporeal membrane oxygenation, and surgical re-intervention) or mortality between the two groups, though these findings must be interpreted with caution. Further investigation is necessary to elucidate the adequacy of pain/sedation control, factors that might affect analgosedative needs in this unique population, and the impact on clinical outcomes.

    View details for DOI 10.1007/s00246-023-03321-8

    View details for PubMedID 37882809

  • Peritoneal catheters in neonates undergoing complex cardiac surgery: a multi-centre descriptive study. Cardiology in the young Kwiatkowski, D. M., Alten, J. A., Raymond, T. T., Selewski, D. T., Blinder, J. J., Afonso, N. S., Coghill, M. T., Cooper, D. S., Koch, J. D., Krawczeski, C. D., Mah, K. E., Neumayr, T. M., Rahman, A. K., Reichle, G., Tabbutt, S., Webb, T. N., Borasino, S. 2023: 1-10

    Abstract

    The use of peritoneal catheters for prophylactic dialysis or drainage to prevent fluid overload after neonatal cardiac surgery is common in some centres; however, the multi-centre variability and details of peritoneal catheter use are not well described.Twenty-two-centre NEonatal and Pediatric Heart Renal Outcomes Network (NEPHRON) study to describe multi-centre peritoneal catheter use after STAT category 3-5 neonatal cardiac surgery using cardiopulmonary bypass. Patient characteristics and acute kidney injury/fluid outcomes for six post-operative days are described among three cohorts: peritoneal catheter with dialysis, peritoneal catheter with passive drainage, and no peritoneal catheter.Of 1490 neonates, 471 (32%) had an intraoperative peritoneal catheter placed; 177 (12%) received prophylactic dialysis and 294 (20%) received passive drainage. Sixteen (73%) centres used peritoneal catheter at some frequency, including six centres in >50% of neonates. Four centres utilised prophylactic peritoneal dialysis. Time to post-operative dialysis initiation was 3 hours [1, 5] with the duration of 56 hours [37, 90]; passive drainage cohort drained for 92 hours [64, 163]. Peritoneal catheter were more common among patients receiving pre-operative mechanical ventilation, single ventricle physiology, and higher complexity surgery. There was no association with adverse events. Serum creatinine and daily fluid balance were not clinically different on any post-operative day. Mortality was similar.In neonates undergoing complex cardiac surgery, peritoneal catheter use is not rare, with substantial variability among centres. Peritoneal catheters are used more commonly with higher surgical complexity. Adverse event rates, including mortality, are not different with peritoneal catheter use. Fluid overload and creatinine-based acute kidney injury rates are not different in peritoneal catheter cohorts.

    View details for DOI 10.1017/S104795112300135X

    View details for PubMedID 37337694

  • Contemporary care and outcomes of critically ill children with clinically diagnosed myocarditis. Journal of cardiac failure Peng, D. M., Kwiatkowski, D. M., Lasa, J. J., Zhang, W., Banerjee, M., Mikesell, K., Joong, A., Dykes, J. C., Tume, S. C., Niebler, R. A., Teele, S. A., Klugman, D., Gaies, M. G., Schumacher, K. R. 2023

    Abstract

    PURPOSE: To describe contemporary management and outcomes in children with myocarditis admitted to the cardiac intensive care unit (CICU) and to identify characteristics associated with mortality.METHODS: All patients in the Pediatric Cardiac Critical Care Consortium (PC4) registry from 8/2014-6/2021 diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated factors associated with in-hospital mortality.RESULTS: There were 847 CICU admissions for myocarditis in 51 centers. Median age was 12 years (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%) and 60 (7.1%) had cardiac arrest during the admission. Mechanical ventilation was required in 339 patients (40%) and mechanical circulatory support (MCS) in 177 (21%): extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation (eCPR) in 43 (5%), VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (p<0.001). Mortality was similar between ECMO-only, ECMO-to-VAD, and VAD-only groups. Median time from CICU admission to ECMO was 2.0 hours (IQR 0-9.4) and to VAD was 9.9 days (IQR 6.3-16.8). Time to MCS was not associated with mortality. In multivariable modeling of patient characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation or ECMO were independent predictors of mortality.CONCLUSION: This contemporary cohort of children admitted to the CICU with myocarditis frequently received high-resource therapies however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury, and receipt of mechanical ventilation or ECMO were independently associated with mortality.

    View details for DOI 10.1016/j.cardfail.2023.04.010

    View details for PubMedID 37150502

  • Impact of Weight on Ventricular Assist Device Outcomes in Dilated Cardiomyopathy Patients in Pediatric Centers: An ACTION Registry Study. ASAIO journal (American Society for Artificial Internal Organs : 1992) Kwiatkowski, D. M., Shezad, M., Barnes, A. P., Ploutz, M. S., Law, S. P., Zafar, F., Morales, D. L., O'Connor, M. J. 2023

    Abstract

    Ventricular assist device (VAD) options vary for children in different weight groups. This study evaluates contemporary device usage and outcomes for children based on weight. Data from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry were examined for patients with dilated cardiomyopathy (DCM) in 4 weight cohorts: <8 kg, 8-20 kg, 21-40 kg, and >40 kg, for devices implanted 3/2013-10/2020. Adverse event rates and ultimate outcome (deceased, alive on device, transplanted, or ventricular recovery) were analyzed. 222 DCM patients were identified with 24% in cohort 1, 23% in cohort 2, 15% in cohort 3, and 38% in cohort 4. Of 272 total implants, paracorporeal pulsatile devices were most common (95%) in cohorts 1 and 2 and intracorporeal continuous devices (81%) in cohorts 3 and 4. Stroke was noted in 17%, 12%, 6%, and 4% of cohorts, respectively (Cohort 1 vs. 4 and 2 vs. 4 - p = 0.01; other comparisons - not significant). Incidences of major bleeding, device malfunction, and infection was not different. All cohorts had >90% positive outcomes. Stroke incidence was higher in smaller cohorts, but other outcomes were similar. Positive outcomes were attained in over 90% across all weight groups, demonstrating excellent outcomes using current VADs in this DCM population.

    View details for DOI 10.1097/MAT.0000000000001861

    View details for PubMedID 37071761

  • Early postoperative weight-based fluid overload is associated with worse outcomes after neonatal cardiac surgery. Pediatric nephrology (Berlin, Germany) Brandewie, K. L., Selewski, D. T., Bailly, D. K., Bhat, P. N., Diddle, J. W., Ghbeis, M., Krawczeski, C. D., Mah, K. E., Neumayr, T. M., Raymond, T. T., Reichle, G., Zang, H., Alten, J. A. 2023

    Abstract

    Evaluate the association of postoperative day (POD) 2 weight-based fluid balance (FB-W) > 10% with outcomes after neonatal cardiac surgery.Retrospective cohort study of 22 hospitals in the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) registry from September 2015 to January 2018. Of 2240 eligible patients, 997 neonates (cardiopulmonary bypass (CPB) n = 658, non-CPB n = 339) were weighed on POD2 and included.Forty-five percent (n = 444) of patients had FB-W > 10%. Patients with POD2 FB-W > 10% had higher acuity of illness and worse outcomes. Hospital mortality was 2.8% (n = 28) and not independently associated with POD2 FB-W > 10% (OR 1.04; 95% CI 0.29-3.68). POD2 FB-W > 10% was associated with all utilization outcomes, including duration of mechanical ventilation (multiplicative rate of 1.19; 95% CI 1.04-1.36), respiratory support (1.28; 95% CI 1.07-1.54), inotropic support (1.38; 95% CI 1.10-1.73), and postoperative hospital length of stay (LOS 1.15; 95% CI 1.03-1.27). In secondary analyses, POD2 FB-W as a continuous variable demonstrated association with prolonged durations of mechanical ventilation (OR 1.04; 95% CI 1.02-1.06], respiratory support (1.03; 95% CI 1.01-1.05), inotropic support (1.03; 95% CI 1.00-1.05), and postoperative hospital LOS (1.02; 95% CI 1.00-1.04). POD2 intake-output based fluid balance (FB-IO) was not associated with any outcome.POD2 weight-based fluid balance > 10% occurs frequently after neonatal cardiac surgery and is associated with longer cardiorespiratory support and postoperative hospital LOS. However, POD2 FB-IO was not associated with clinical outcomes. Mitigating early postoperative fluid accumulation may improve outcomes but requires safely weighing neonates in the early postoperative period. A higher resolution version of the Graphical abstract is available as Supplementary information.

    View details for DOI 10.1007/s00467-023-05929-7

    View details for PubMedID 36973562

    View details for PubMedCentralID 5716912

  • Clinical Predictive Tool for Pediatric Cardiac Patients on Extracorporeal Membrane Oxygenation Therapy and Ultrafiltration. ASAIO journal (American Society for Artificial Internal Organs : 1992) Sedler, J., Sutherland, S. M., Uber, A. M., Jahadi, O., Ryan, K. R., Yarlagadda, V. V., Kwiatkowski, D. M. 2023

    Abstract

    Fluid overload is common among pediatric cardiac patients receiving extracorporeal membrane oxygenation (ECMO) and is often treated with in-line ultrafiltration (UF) or continuous renal replacement therapy (CRRT). We assessed whether CRRT was associated with poor outcomes versus UF alone. Additionally, we identified characteristics associated with progression from UF to CRRT. Retrospective chart review of 131 patients age ≤18 years treated with ECMO at a single quaternary center. Data were collected to compare patient demographics, characteristics, and outcomes. A receiver operator curve (ROC) was used to create a tool predictive of the need for CRRT at the time of UF initiation. Patients who required CRRT had a higher creatinine and blood urea nitrogen at time of UF initiation (p = 0.03 and p < 0.01), longer total ECMO duration (p < 0.01), lower renal recovery incidence (p = 0.02), and higher mortality (p ≤ 0.01). Using ROC analysis, presence of ≤3 of 7 risk variables had a positive predictive value of 87.5% and negative predictive value of 50.0% for use of UF alone (area under the curve 0.801; 95% CI: 0.638-0.965, p = 0.002). Pediatric cardiac patients treated with ECMO and UF who require CRRT demonstrate worse outcomes versus UF alone. A novel clinical tool may assist in stratifying patients at UF initiation.

    View details for DOI 10.1097/MAT.0000000000001924

    View details for PubMedID 36947828

  • Staged versus Complete Repair in Tetralogy of Fallot with Pulmonary Atresia. The Annals of thoracic surgery Boucek, K., Mastropietro, C. W., Beall, J., Keller, E., Beshish, A., Flores, S., Chlebowski, M., Yates, A. R., Choudhury, T. A., Mueller, D., Kwiatkowski, D. M., Migally, K., Karki, K., Willett, R., Radman, M. R., Reddy, C., Piggott, K., Capone, C. A., Kapileshwarkar, Y., Vijayakumar, N., Prentice, E., Suguna Narasimhulu, S., Martin, R. H., Costello, J. M. 2023

    Abstract

    We sought to compare outcomes for infants with tetralogy of Fallot with pulmonary atresia (TOF/PA) and confluent pulmonary arteries who underwent staged or primary complete surgical repair.This retrospective study included infants undergoing initial surgical intervention between 0-60 days of age with TOF/PA without aortopulmonary collaterals from 2009 to 2018 at 20 centers. The primary outcome was days alive and out of hospital in first year of life (DAOH365). Secondary outcomes were mortality at 1 year of age and a composite major complication outcome. Multivariable modeling with generalized estimating equations were utilized to compare outcomes between groups.Of 221 subjects, 142 underwent staged repair and 79 underwent primary complete repair. There was no significant difference in median DAOH365 between the staged and primary repair groups [(317 days (interquartile range, 278-336 days) versus 338 days (interquartile range, 314-348 days), respectively; adjusted P = 0.13]. Nine staged repair patients (7%) died in the first year of life vs. 5 primary repair patients (6%; adjusted OR: 1.00; 95% CI, 0.25-3.95). At least one major complication occurred in 37% of patients who underwent staged repair versus 41% of patients who underwent primary complete repair (p = 0.75), largely driven by the need for unplanned cardiac reinterventions.For infants with TOF/PA with confluent pulmonary arteries, a surgical strategy of staged or primary complete repair resulted in statistically similar DAOH365, early mortality, and morbidity. Word count232.

    View details for DOI 10.1016/j.athoracsur.2023.01.029

    View details for PubMedID 36739070

  • Peritoneal Catheters in Neonates after Complex Heart Surgery: A Multicenter Study Kwiatkowski, D. M., Alten, J., Afonso, N. S., Coghill, M. T., Cooper, D. S., Koch, J. D., Krawczeski, C. D., Mah, K., Neumayr, T., Rahman, F., Raymond, T. T., Reichle, G., Selewski, D., Tabbutt, S., Webb, T., Borasino, S. SPRINGER. 2023: S10-S11
  • The development and efficacy of a paediatric cardiology fellowship online preparatory course. Cardiology in the young Motonaga, K. S., Sacks, L., Olson, I., Balasubramanian, S., Chen, S., Peng, L., Feinstein, J. A., Silverman, N. H., Hanley, F. L., Axelrod, D. M., Krawczeski, C. D., Arunamata, A., Kwiatkowski, D. M., Ceresnak, S. R. 2022: 1-6

    Abstract

    BACKGROUND: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship.METHODS: The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests.RESULTS: 151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants' comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship.CONCLUSION: An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.

    View details for DOI 10.1017/S1047951122003626

    View details for PubMedID 36440543

  • Neonatal Congenital Heart Disease Surgical Readiness and Timing PEDIATRICS Kwiatkowski, D. M., Ball, M. K., Savorgnan, F. J., Allan, C. K., Dearani, J. A., Roth, M. D., Roth, R. Z., Sexson, K. S., Tweddell, J. S., Williams, P. K., Zender, J. E., Levy, V. Y. 2022; 150

    View details for DOI 10.1542/peds.2022-056415D

    View details for Web of Science ID 000917985900003

    View details for PubMedID 36317977

  • Criteria for Early Pacemaker Implantation in Patients With Postoperative Heart Block After Congenital Heart Surgery. Circulation. Arrhythmia and electrophysiology Duong, S. Q., Shi, Y., Giacone, H., Navarre, B., Gal, D., Han, B., Sganga, D., Ma, M., Reddy, C. D., Shin, A., Kwiatkowski, D. M., Dubin, A. M., Scheinker, D., Algaze, C. A. 2022: e011145

    Abstract

    Guidelines recommend observation for atrioventricular node recovery until postoperative days (POD) 7 to 10 before permanent pacemaker placement (PPM) in patients with heart block after congenital cardiac surgery. To aid in surgical decision-making for early PPM, we established criteria to identify patients at high risk of requiring PPM.We reviewed all cases of second degree and complete heart block (CHB) on POD 0 from August 2009 through December 2018. A decision tree model was trained to predict the need for PPM amongst patients with persistent CHB and prospectively validated from January 2019 through March 2021. Separate models were developed for all patients on POD 0 and those without recovery by POD 4.Of the 139 patients with postoperative heart block, 68 required PPM. PPM was associated with older age (3.2 versus 1.0 years; P=0.018) and persistent CHB on POD 0 (versus intermittent CHB or second degree heart block; 87% versus 58%; P=0.001). Median days [IQR] to atrioventricular node recovery was 2 [0-5] and PPM was 9 [6-11]. Of the 100 cases of persistent CHB (21 in the validation cohort), 59 (59%) required PPM. A decision tree model identified 4 risk factors for PPM in patients with persistent CHB: (1) aortic valve replacement, subaortic stenosis repair, or Konno procedure; (2) ventricular L-looping; (3) atrioventricular valve replacement; (4) and absence of preoperative antiarrhythmic agent (in POD 0 model only). The POD 4 model specificity was 0.89 [0.67-0.99] and positive predictive value was 0.94 [95% CI 0.81-0.98], which was stable in prospective validation (positive predictive value 1.0).A data-driven analysis led to actionable criteria to identify patients requiring PPM. Patients with left ventricular outflow tract surgery, atrioventricular valve replacement, or ventricular L-Looping could be considered for PPM on POD 4 to reduce risks of temporary pacing and improve care efficiency.

    View details for DOI 10.1161/CIRCEP.122.011145

    View details for PubMedID 36306332

  • Procedural Outcomes of Pulmonary Atresia Intact Ventricular Septum in Neonates: A Multicenter Study. The Annals of thoracic surgery Cheung, E. W., Mastropietro, C. W., Flores, S., Amula, V., Radman, M., Kwiatkowski, D., Puente, B. N., Buckley, J. R., Allen, K., Loomba, R., Kakri, K., Chiwane, S., Cashen, K., Piggott, K., Kapileshwarkar, Y., Gowda, K. M., Badheka, A., Raman, R., Costello, J. M., Zang, H., Iliopoulos, I., Collaborative Research from the Pediatric Cardiac Intensive Care Society (CoRe-PCICS) Investigators 2022

    Abstract

    BACKGROUND: Multicenter contemporary data describing short-term outcomes following initial interventions of neonates with pulmonary atresia intact ventricular septum (PA-IVS) are limited. This multicenter study aims to describe characteristics and outcomes of PA-IVS neonates following their initial catheter or surgical intervention and identify factors associated with major adverse cardiac events (MACE).METHODS: Neonates with PA-IVS who underwent surgical or catheter intervention between 2009-2019 in 19 centers were reviewed. Risk factors for MACE, defined as cardiopulmonary resuscitation, mechanical circulatory support, stroke, or in-hospital mortality, were analyzed using multivariable logistic regression model.RESULTS: We reviewed 279 neonates: 79 (28%) underwent right ventricular decompression, 151 (54%) underwent systemic-to-pulmonary shunt or ductal stent placement only, 36 (13%) underwent right ventricular decompression with shunt or ductal stent placement, and 11 (4%) underwent transplantation. MACE occurred in 57 patients (20%): 26 (9%) received mechanical circulatory support, 37 (13%) received cardiopulmonary resuscitation, 16 (6%) suffered stroke, 23 (8%) died. The presence of two major coronary artery stenoses (adjusted OR: 4.99; 95% CI: 1.16-21.39) and lower weight at first intervention (adjusted OR: 1.52, 95% CI: 1.01-2.27) were significantly associated with MACE. Coronary ischemia was the most frequent presumed mechanism of death (n=10).CONCLUSIONS: In a multicenter cohort, one in five neonates with PA-IVS experienced MACE following their initial intervention. Patients with two major coronary artery stenoses or lower weight at time of initial procedure were most likely to experience MACE and warrant vigilance during pre-intervention planning and post-intervention management.

    View details for DOI 10.1016/j.athoracsur.2022.07.055

    View details for PubMedID 36070807

  • Pulmonary Atresia with Intact Ventricular Septum: Midterm Outcomes from a Multicenter Cohort. Pediatric cardiology Iliopoulos, I., Mastropietro, C. W., Flores, S., Cheung, E., Amula, V., Radman, M., Kwiatkowski, D., Puente, B. N., Buckley, J. R., Allen, K. Y., Loomba, R., Karki, K. B., Chiwane, S., Cashen, K., Piggott, K., Kapileshwarkar, Y., Gowda, K. M., Badheka, A., Raman, R., Zang, H., Costello, J. M., Collaborative Research from the Pediatric Cardiac Intensive Care Society Investigators 2022

    Abstract

    Contemporary multicenter data regarding midterm outcomes for neonates with pulmonary atresia with intact ventricular septum are lacking. We sought to describe outcomes in a contemporary multicenter cohort, determine factors associated with end-states, and evaluate the effect of right ventricular coronary dependency and coronary atresia on transplant-free survival. Neonates treated during 2009-2019 in 19 United States centers were reviewed. Competing risks analysis was performed to determine cumulative risk of each end-state, and multivariable regression analyses were performed to identify factors associated with each end-state and transplant-free survival. We reviewed 295 patients. Median tricuspid valve Z-score was-3.06 (25%, 75%:-4.00,-1.52). Final end-state was biventricular repair for 45 patients (15.2%), one-and-a half ventricle for 16 (5.4%), Fontan for 75 (25.4%), cardiac transplantation for 29 (9.8%), and death for 54 (18.3%). Seventy-six patients (25.7%) remained in mixed circulation. Cumulative risk estimate of death was 10.9%, 16.1%, 16.9%, and 18.8% at 1, 6months, 1year, and 5years, respectively. Tricuspid valve Z-score was inversely, and coronary atresia positively associated with death or transplantation [odds ratio (OR)=0.46, (95% confidence interval (CI)=0.29-0.75, p<0.001) and OR=3.75 (95% CI 1.46-9.61, p=0.011), respectively]. Right ventricular coronary dependency and left coronary atresia had a significant effect on transplant-free survival (log-rank p<0.001). In a contemporary multicenter cohort of patients with PAIVS, consisting predominantly of patients with moderate-to-severe right ventricular hypoplasia, we observed favorable survival outcomes. Right ventricular coronary dependency and left, but not right, coronary atresia significantly worsens transplant-free survival.

    View details for DOI 10.1007/s00246-022-02954-5

    View details for PubMedID 35751685

  • Modifying the Renal Angina Index for Predicting AKI and Related Adverse Outcomes in Pediatric Heart Surgery. World journal for pediatric & congenital heart surgery Gist, K. M., SooHoo, M., Mack, E., Ricci, Z., Kwiatkowski, D. M., Cooper, D. S., Krawczeski, C. D., Alten, J. A., Goldstein, S. L., Basu, R. K. 2022; 13 (2): 196-202

    Abstract

    Background:Reliable prediction of severe acute kidney injury (AKI) and related poor outcomes has the potential to optimize treatment. The purpose of this study was to modify the renal angina index in pediatric cardiac surgery to predict severe AKI and related poor outcomes. Methods: We performed a multicenter retrospective study with the population divided into a derivation and validation cohort to assess the performance of a modified renal angina index assessed at 8 h after cardiac intensive care unit (CICU) admission to predict a complex outcome of severe day 3 AKI or related poor outcomes (ventilation duration >7 days, CICU length of stay >14 days, and mortality). The derivation sample was used to determine the optimal cut-off value. Results: There were 298 and 299 patients in the derivation and validation cohorts, respectively. The incidence of severe day 3 AKI and the complex outcome was 1.7% and 28% in the derivation and validation cohort. The sensitivity analysis for fulfillment of renal angina was a score >8 with a sensitivity of 63%, specificity of 73%, and negative predictive value of 83%. The cardiac renal angina index predicted the composite outcome with an area under the curve of 0.7 (95% confidence interval: 0.62-0.78). Renal angina patients had a significantly higher probability of the complex outcome when compared to individual risk and injury categories. Conclusions: We operationalized the renal angina index for use after cardiac surgery. Further revision and modification of the construct with integration of biomarkers in a prospective cohort are necessary to refine the prediction model.

    View details for DOI 10.1177/21501351211073615

    View details for PubMedID 35238710

  • Direct Discharge to Home From the Pediatric Cardiovascular ICU. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Gal, D. B., Kwiatkowski, D. M., Cribb Fabersunne, C., Kipps, A. K. 1800

    Abstract

    OBJECTIVES: To describe direct discharge to home from the cardiovascular ICU.DESIGN: Mixed-methods including retrospective Pediatric Cardiac Critical Care Consortium and Pediatric Acute Care Cardiology Collaborative data and survey.SETTING: Tertiary pediatric heart center.PATIENTS: Patients less than 25 years old, with a cardiovascular ICU stay of greater than 24 hours and direct discharge to home from January 1, 2016, to December 8, 2020, were included. Select data describing patients discharged from acute care internally and nationally from Pediatric Acute Care Cardiology Collaborative sites were compared with the direct discharge to home cohort.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Encounter- and patient-specific characteristics. Seven-day and 30-day readmission and 30-day mortality served as surrogate safety markers. A survey of cardiovascular ICU frontline providers assessed comfort and skills related to direct discharge to home. There were 364 direct discharge to home encounters that met inclusion criteria. The majority of direct discharge to home encounters were associated with a surgery or procedure (305; 84%). There were 27 encounters (7.4%) for medical technology-dependent patients requiring direct discharge to home. Unplanned 7-day readmissions among direct discharge to home patients was 1.9% compared with 4.6% (p = 0.04) of patients discharged from acute care internally. Readmission among those discharged from acute care internally did not differ from those at Pediatric Acute Care Cardiology Collaborative sites nationally. Frontline cardiovascular ICU providers had mixed levels of confidence in technical aspects and low levels of confidence in logistics of direct discharge to home.CONCLUSIONS: Cardiovascular ICU direct discharge to home was not associated with increased unplanned readmissions compared with patients discharged from acute care and may be safe in select patients. Frontline cardiovascular ICU providers feel time constraints challenge direct discharge to home. Further research is needed to identify patient characteristics associated with safe direct discharge to home and systems needed to support this practice.Summary statistics are described using proportions or medians with interquartile ranges (IQRs) and were performed using Microsoft Excel (Microsoft, Redmond, WA). Two-sample tests of proportions were used to compare readmission frequency of the DDH cohort compared with internal and national PAC3 data using STATA Version 15 (StataCorp, College Station, TX).

    View details for DOI 10.1097/PCC.0000000000002883

    View details for PubMedID 35044343

  • Postoperative Acute Kidney Injury in Williams Syndrome Compared With Matched Controls. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Yokota, R., Kwiatkowski, D. M., Journel, C., Adamson, G. T., Zucker, E., Suarez, G., Lechich, K. M., Chaudhuri, A., Collins, R. T. 2022

    Abstract

    Cardiovascular manifestations occur in over 80% of Williams syndrome (WS) patients and are the leading cause of morbidity and mortality. One-third of patients require cardiovascular surgery. Renal artery stenosis (RAS) is common in WS. No studies have assessed postoperative cardiac surgery-related acute kidney injury (CS-AKI) in WS. Our objectives were to assess if WS patients have higher risk of CS-AKI postoperatively than matched controls and if RAS could contribute to CS-AKI.This was a retrospective study of all patients with WS who underwent cardiac surgery at our center from 2010 to 2020. The WS study cohort was compared with a group of controls matched for age, sex, weight, and surgical procedure.Patients underwent cardiac surgery and postoperative care at Lucile Packard Children's Hospital Stanford.There were 27 WS patients and 43 controls (31% vs 42% female; p = 0.36). Median age was 1.8 years (interquartile range [IQR], 0.7-3.8 yr) for WS and 1.7 years (IQR, 0.8-3.1 yr) for controls.None.Postoperative hemodynamics, vasopressor, total volume input, diuretic administration, and urine output were collected in the first 72 hours. Laboratory studies were collected at 8-hour intervals. Multivariable analysis identified predictors of CS-AKI.Controlled for renal perfusion pressure (RPP) and vasoactive inotrope score (VIS), compared with controls, the odds ratio (OR) of CS-AKI in WS was 4.2 (95% CI, 1.1-16; p = 0.034). Higher RPP at postoperative hours 9-16 was associated with decreased OR of CS-AKI (0.88 [0.8-0.96]; p = 0.004). Increased VIS at hour 6 was associated with an increased OR of CS-AKI (1.47 [1.14-1.9]; p = 0.003). Younger age was associated with an increased OR of CS-AKI (1.9 [1.13-3.17]; p = 0.015).The OR of CS-AKI is increased in pediatric patients with WS compared with controls. CS-AKI was associated with VIS at the sixth postoperative hour. Increases in RPP and mean arterial pressure were associated with decreased odds of CS-AKI.

    View details for DOI 10.1097/PCC.0000000000002872

    View details for PubMedID 34982759

  • Fluid Accumulation After Neonatal Congenital Cardiac Surgery; Clinical Implications and Outcomes. The Annals of thoracic surgery Bailly, D. K., Alten, J. A., Gist, K. M., Mah, K. E., Kwiatkowski, D. M., Valentine, K. M., Diddle, J. W., Tadphale, S., Clarke, S., Selewski, D. T., Banerjee, M., Reichle, G., Lin, P., Gaies, M., Blinder, J. J. 2022

    Abstract

    To determine the association between fluid balance metrics and mortality and other postoperative outcomes after neonatal cardiac surgery in a contemporary multi-center cohort.Observational cohort study across 22 hospitals in neonates (≤30 days) undergoing cardiac surgery. We explored overall % fluid overload, postoperative day 1 % fluid overload, peak % fluid overload, and time to first negative daily fluid balance. The primary outcome was in-hospital mortality. Secondary outcomes included postoperative duration of mechanical ventilation, and intensive care unit (ICU) and hospital length of stay. Multivariable logistic or negative binomial regression was used to determine independent associations between fluid overload variables and each outcome.The cohort included 2223 patients. In-hospital mortality was 3.9% (n=87). Overall median peak % fluid overload was 4.9%, (interquartile range 0.4-10.5%). Peak % fluid overload and postoperative day 1 % fluid overload were not associated with primary or secondary outcomes. Hospital resource utilization increased on each successive day of not achieving a first negative daily fluid balance and was characterized by longer duration of mechanical ventilation (incidence rate ratio 1.11, 95% confidence interval 1.08-1.14, ICU length of stay (incidence rate ratio 1.08, 95% confidence interval 1.03-1.12), and hospital length of stay (incidence rate ratio 1.09, 95% confidence interval 1.05-1.13).Time to first negative daily fluid balance, but not % fluid overload is associated with improved postoperative outcomes in neonates after cardiac surgery. Specific treatments to achieve an early negative fluid balance may decrease postoperative care durations.

    View details for DOI 10.1016/j.athoracsur.2021.12.078

    View details for PubMedID 35245511

  • Impact of a clinical pathway on acute kidney injury in patients undergoing heart transplant. Pediatric transplantation Algaze, C. A., Margetson, T. D., Sutherland, S. M., Kwiatkowski, D. M., Maeda, K., Navaratnam, M., Samreth, S. P., Price, E. P., Zook, N. B., Yang, J. K., Hollander, S. A. 2021: e14166

    Abstract

    BACKGROUND: To evaluate the impact of a clinical pathway on the incidence and severity of acute kidney injury in patients undergoing heart transplant.METHODS: This was a 2.5-year retrospective evaluation using 3years of historical controls within a cardiac intensive care unit in an academic children's hospital. Patients undergoing heart transplant between May 27, 2014, and April 5, 2017 (pre-pathway) and May 1, 2017, and November 30, 2019 (pathway) were included. The clinical pathway focused on supporting renal perfusion through hemodynamic management, avoiding or delaying nephrotoxic medications, and providing pharmacoprophylaxis against AKI.RESULTS: There were 57 consecutive patients included. There was an unadjusted 20% reduction in incidence of any acute kidney injury (p=.05) and a 17% reduction in Stage 2/3 acute kidney injury (p=.09). In multivariable adjusted analysis, avoidance of Stage 2/3 acute kidney injury was independently associated with the clinical pathway era (AOR -1.3 [95% CI -2.5 to -0.2]; p=.03), achieving a central venous pressure of or less than 12mmHg (AOR -1.3 [95% CI -2.4 to -0.2]; p=.03) and mean arterial pressure above 60mmHg (AOR -1.6 [95% CI -3.1 to -0.01]; p=.05) in the first 48h post-transplant, and older age at transplant (AOR - 0.2 [95% CI -0.2 to -0.06]; p=.002).CONCLUSIONS: This report describes a renal protection clinical pathway associated with a reduction in perioperative acute kidney injury in patients undergoing heart transplant and highlights the importance of normalizing perioperative central venous pressure and mean arterial blood pressure to support optimal renal perfusion.

    View details for DOI 10.1111/petr.14166

    View details for PubMedID 34727417

  • Maternal Hyperoxygenation Testing in Fetuses with Hypoplastic Left-Heart Syndrome: Association with Postnatal Atrial Septal Restriction. Fetal diagnosis and therapy Mardy, C., Kaplinski, M., Peng, L., Blumenfeld, Y. J., Kwiatkowski, D. M., Tacy, T. A., Maskatia, S. A. 2021: 1-12

    Abstract

    INTRODUCTION: In fetuses with hypoplastic left-heart syndrome (HLHS), maternal hyperoxygenation (MHO) may aid risk stratification. We hypothesized that pulmonary vein (Pvein) velocity time integral (VTI) change with MHO would more reliably identify neonates who undergo emergent atrial septoplasty (EAS) than changes in pulmonary arterial pulsatility index (PA PI).METHODS: Fetuses with HLHS who underwent MHO testing at our institution between 2014 and 2019 were identified. Data were reviewed in a blinded, retrospective manner. Pvein VTI ratio (prograde:retrograde) was calculated. The primary outcome was neonatal EAS.RESULTS: Twenty-seven HLHS fetuses underwent MHO, and 5 (19%) underwent EAS. Without MHO, a Pvein VTI ratio <3 conferred 60% sensitivity and 100% specificity for EAS. With MHO, a Pvein VTI ratio <6.5 conferred 100% sensitivity and specificity. For an intermediate group of fetuses with a baseline Pvein VTI ratio 3-7, the ratio decrease with MHO conferred 100% sensitivity and specificity. Compared to the Pvein VTI ratio, PA PI was less accurate in identifying EAS neonates.DISCUSSION/CONCLUSION: Addition of MHO appears to improve the diagnostic ability of the Pvein VTI ratio to identify HLHS fetuses who undergo EAS. The Pvein VTI ratio change may more accurately identify fetuses who undergo EAS than change in PA PI and has less interobserver variability.

    View details for DOI 10.1159/000519322

    View details for PubMedID 34673647

  • Standardized Training for Physicians Practicing Pediatric Cardiac Critical Care. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Tabbutt, S., Krawczeski, C., McBride, M., Amirnovin, R., Owens, G., Smith, A., Wolf, M., Rhodes, L., Hehir, D., Asija, R., Teele, S. A., Ghanayem, N., Zyblewski, S., Thiagarajan, R., Yeh, J., Shin, A. Y., Schwartz, S. M., Schuette, J., Scahill, C., Roth, S. J., Hoffman, T. M., Cooper, D. S., Byrnes, J., Bergstrom, C., Vesel, T., Scott, J. P., Rossi, A., Kwiatkowski, D., DiPietro, L. M., Connor, C., Chen, J., Charpie, J., Bochkoris, M., Affolter, J., Bronicki, R. A. 2021

    Abstract

    OBJECTIVES: In the vast majority of Children's Hospitals, the critically ill patient can be found in one of three locations: the PICU, the neonatal ICU, and the cardiac ICU. Training, certification, and maintenance of certification for neonatology and critical care medicine are over seen by the Accreditation Council for Graduate Medical Education and American Board of Pediatrics. There is no standardization of training or oversight of certification and maintenance of certification for pediatric cardiac critical care.DATA SOURCES: The curricula from the twenty 4th year pediatric cardiac critical care training programs were collated, along with the learning objectives from the Pediatric Cardiac Intensive Care Society published "Curriculum for Pediatric Cardiac Critical Care Medicine."STUDY SELECTION: This initiative is endorsed by the Pediatric Cardiac Intensive Care Society as a first step toward Accreditation Council for Graduate Medical Education oversight of training and American Board of Pediatrics oversight of maintenance of certification.DATA EXTRACTION: A taskforce was established of cardiac intensivists, including the directors of all 4th year pediatric cardiac critical care training programs.DATA SYNTHESIS: Using modified Delphi methodology, learning objectives, rotational requirements, and institutional requirements for providing training were developed.CONCLUSIONS: In the current era of increasing specialized care in pediatric cardiac critical care, standardized training for pediatric cardiac critical care is paramount to optimizing outcomes.

    View details for DOI 10.1097/PCC.0000000000002815

    View details for PubMedID 34554132

  • Learning networks in pediatric heart failure and transplantation. Pediatric transplantation O'Connor, M. J., Lorts, A., Kwiatkowski, D., Butts, R., Barnes, A., Jeewa, A., Knoll, C., Fenton, M., McQueen, M., Cousino, M. K., Shugh, S., Rosenthal, D. N. 2021: e14073

    Abstract

    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.

    View details for DOI 10.1111/petr.14073

    View details for PubMedID 34138489

  • A Contemporary Study of Pathologic Kidney Findings in Congenital Heart Disease DeRussy, B., Miller, P., Kambham, N., Kwiatkowski, D., Salmi, D., Troxell, M. SPRINGERNATURE. 2021: 1000–1001
  • Hyperoxia During Cardiopulmonary Bypass Is Associated With Mortality in Infants Undergoing Cardiac Surgery. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Beshish, A. G., Jahadi, O., Mello, A., Yarlagadda, V. V., Shin, A. Y., Kwiatkowski, D. M. 2021

    Abstract

    OBJECTIVES: Patients undergoing cardiac surgery using cardiopulmonary bypass have variable degrees of blood oxygen tension during surgery. Hyperoxia has been associated with adverse outcomes in critical illness. Data are not available regarding the association of hyperoxia and outcomes in infants undergoing cardiopulmonary bypass. We hypothesize that among infants undergoing cardiac surgery, hyperoxia during cardiopulmonary bypass is associated with greater odds of morbidity and mortality.DESIGN: Retrospective study.SETTING: Single center at an academic tertiary children's hospital.PATIENTS: All infants (< 1 yr) undergoing cardiopulmonary bypass between January 1, 2015, and December 31, 2017, excluding two patients who were initiated on extracorporeal membrane oxygenation in the operating room.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: The study included 469 infants with a median age of 97 days (interquartile range, 14-179 d), weight 4.9 kg (interquartile range, 3.4-6.4 kg), and cardiopulmonary bypass time 128 minutes (interquartile range, 91-185 min). A PaO2 of 313 mm Hg (hyperoxia) on cardiopulmonary bypass had highest sensitivity with specificity greater than 50% for association with operative mortality. Approximately, half of the population (237/469) had hyperoxia on cardiopulmonary bypass. Infants with hyperoxia were more likely to have acute kidney injury, prolonged postoperative length of stay, and mortality. They were younger, weighed less, had longer cardiopulmonary bypass times, and had higher Society of Thoracic Surgeons and the European Association for Cardio-Thoracic Surgery mortality scores. There was no difference in sex, race, preoperative creatinine, single ventricle physiology, or presence of genetic syndrome. On multivariable analysis, hyperoxia was associated with greater odds of mortality (odds ratio, 4.3; 95% CI, 1.4-13.2) but failed to identify an association with acute kidney injury or prolonged postoperative length of stay. Hyperoxia was associated with greater odds of mortality in subgroup analysis of neonatal patients.CONCLUSIONS: Hyperoxia occurred in a substantial portion of infants undergoing cardiopulmonary bypass for cardiac surgery. Hyperoxia during cardiopulmonary bypass was an independent risk factor for mortality and may be a modifiable risk factor. Furthermore, hyperoxia during cardiopulmonary bypass was associated with four-fold greater odds of mortality within 30 days of surgery. Hyperoxia failed to identify an association with development of acute kidney injury or prolonged postoperative length of stay when controlling for covariables. Validation of our data among other populations is necessary to better understand and elucidate potential mechanisms underlying the association between excess oxygen delivery during cardiopulmonary bypass and outcome.

    View details for DOI 10.1097/PCC.0000000000002661

    View details for PubMedID 33443979

  • A Fetal Risk Stratification Pathway for Neonatal Aortic Coarctation Reduces Medical Exposure. The Journal of pediatrics Maskatia, S. A., Kwiatkowski, D., Bhombal, S., Davis, A. S., McElhinney, D. B., Tacy, T. A., Algaze, C., Blumenfeld, Y., Quirin, A., Punn, R. 2021

    Abstract

    To test the hypothesis that a fetal stratification pathway will effectively discriminate between infants at different levels of risk for surgical coarctation and reduce unnecessary medicalization.We performed a pre-post non-randomized study in which we prospectively assigned fetuses with prenatal concern for coarctation to one of three risk categories and implemented a clinical pathway for postnatal management. Postnatal clinical outcomes were compared with a historical control group that were not triaged based on the pathway.The study cohort included 109 fetuses, 57 treated along the fetal coarctation pathway, and 52 historical controls. Among mild-risk fetuses, 3% underwent surgical coarctation repair (0% of those without additional heart defects), compared with 27% of moderate-risk and 63% of high-risk. Combined fetal aortic, mitral and isthmus z-score best discriminated which patients underwent surgery, AUC=0.78(0.66,0.91). Patients triaged according to the fetal coarctation pathway had reduced delivery location changes (76% vs 55%, p=0.025), and umbilical venous catheter placement (74% vs 51%, p=0.046) compared with historical controls. Trends towards shorter intensive care unit stay, hospital stay and time to enteral feeding did not reach statistical significance.A stratified risk-assignment pathway effectively identifies a group of fetuses with low rate of surgical coarctation, and reduces unnecessary medicalization in infants who do not undergo aortic surgery. Incorporation of novel measurements or imaging techniques may improve specificity of high-risk criteria.

    View details for DOI 10.1016/j.jpeds.2021.06.047

    View details for PubMedID 34181988

  • Systemic Absorption of Lidocaine from Continuous Erector Spinae Plane Catheters After Congenital Cardiac Surgery: A Retrospective Study. Journal of cardiothoracic and vascular anesthesia Caruso, T. J., Lin, C. n., O'Connell, C. n., Weiss, D. n., Md, G. B., Wu, M. n., Kwiatkowski, D. n., Maeda, K. n., Tsui, B. C. 2020

    Abstract

    To examine postoperative serum lidocaine levels in patients with intermittent lidocaine bolus erector spinae plane block (ESPB) catheters after cardiac surgery with or without cardiopulmonary bypass (CPB).A retrospective study.Single-center pediatric quaternary teaching hospital.Patients who received ESPB catheters after congenital cardiac surgery from April 2018 to March 2019.Postoperative serum lidocaine levels were extracted from the record.Twenty-seven of 40 patients were included in the final analyses (19 with CPB and 8 with no CPB, age 1-47 years, undergoing congenital heart repair). Patients who received ropivacaine or were missing data were excluded. The initial intraoperative bolus of lidocaine ranged from 0- to- 3.72 mg/kg, and the range of postoperative intermittent lidocaine boluses ranged from 0.35- to- 0.83 mg/kg, which were administered every hour. Serum lidocaine levels were measured by the hospital laboratory and ranged from <0.05- to- 3.0 μg/mL in the CPB group and from <0.05- to- 3.2 μg/mL in the no- CPB group. CPB was not associated with differences in lidocaine levels when controlling for time (P = 0.529). Lidocaine concentrations ranged from 0.50- to- 1.68 μg/mL in the CPB group and 0.86- to- 2.07 μg/mL in the no- CPB group. There was a normally distributed overall mean peak level of 1.818 ± standard deviation of 0.624 μg/mL, with 95% confidence interval of 0.57- to- 3.06 μg/mL. No patients had clinical signs of toxicity.Postoperative serum lidocaine concentrations did not appreciably differ due to CPB. Serum lidocaine concentrations did not reach near- toxic doses despite the presence of additional lidocaine in the cardioplegia. The results suggested that lidocaine for ESPBs after cardiac surgery is below systemic toxic range at the doses described.

    View details for DOI 10.1053/j.jvca.2020.05.040

    View details for PubMedID 32622712

  • Characteristics and Surgical Outcomes of Patients with Late Presentation of Anomalous Left Coronary Artery from the Pulmonary Artery: A Multicenter Study. Seminars in thoracic and cardiovascular surgery Kwiatkowski, D. M., Mastropietro, C. W., Cashen, K. n., Chiwane, S. n., Flores, S. n., Iliopoulos, I. n., Karki, K. B., Migally, K. n., Radman, M. R., Riley, C. M., Sassalos, P. n., Smerling, J. n., Costello, J. M. 2020

    Abstract

    We sought to describe the clinical course and outcomes of patients who are diagnosed with anomalous left coronary artery from the pulmonary artery (ALCAPA) after infancy. We conducted a retrospective evaluation of patients who underwent ALCAPA surgery between 1/2009 - 3/2018 at 21 US centers. Clinical presentation, inpatient management, and postoperative outcomes of patients repaired ≥ 1 year of age were described. To characterize this cohort, we compared these data to patients repaired before 1 year of age. Of 248 ALCAPA patients, 71 (29%) underwent repair ≥ 1 year of age. Among this subset, the median age at diagnosis was 8.3 years. Chronic arrhythmia occurred in 7%. Patients had good postoperative recovery of LV dysfunction (90%) and LV dilation (75%), although a low incidence of recovery of mitral regurgitation (40%). Compared to infants, older patients were more likely to present with cardiac arrest (11% vs 1%) and less likely to have moderate or worse left ventricle (LV) dysfunction or mitral regurgitation. Older patients had significantly less postoperative ECMO use, and shorter ICU and hospital stay. In the older cohort, operative mortality occurred in only one patient and no patient died after discharge (median follow-up 2.7 years). Survival of patients who presented with ALCAPA beyond infancy was excellent, although chronic mitral regurgitation and chronic arrhythmia were not uncommon. Patients who underwent ALCAPA repair ≥ 1 year of age were less likely to present with LV dysfunction but more likely to present with cardiac arrest than younger patients.

    View details for DOI 10.1053/j.semtcvs.2020.08.014

    View details for PubMedID 32858217

  • Prevalence and Risk Factors Associated with Renal Dysfunction in Patients with Single Ventricle Congenital Heart Disease after Fontan Palliation CONGENITAL HEART DISEASE Patel, S. R., Kwiatkowski, D. M., Andrei, A., Devareddy, A., Shi, H., Krawczeski, C. D., Ebert, N., Deal, B. J., Langman, C. B., Marino, B. S. 2020; 15 (4): 181–95
  • The Use of Clevidipine for Hypertension in Pediatric Patients Receiving Mechanical Circulatory Support. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Wu, M. n., Ryan, K. R., Rosenthal, D. N., Jahadi, O. n., Moss, J. n., Kwiatkowski, D. M. 2020

    Abstract

    Limited data exist regarding the management of hypertension in pediatric patients on mechanical circulatory support. Hypertension is a known risk factor for stroke and low cardiac output in patients requiring mechanical circulatory support and a narrow therapeutic window of blood pressure is often targeted. Traditional short-acting infusions to treat hypertension, such as sodium nitroprusside, may lead to accumulation of toxic metabolites in patients with renal dysfunction. Our primary objective was to describe use of clevidipine, a continuous short-acting calcium channel blocking medication, for blood pressure control in pediatric patients on mechanical circulatory support.Single-center retrospective cohort study.A 26-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California.Mechanical circulatory support patients admitted to cardiovascular ICU who received clevidipine infusions between October 1, 2016, and March 31, 2019.Clevidipine infusion.Data from a cohort of 38 patients who received a total of 45 clevidipine infusions were reviewed. The cohort had a median age of 2.7 years and included neonates. No patient had record of hypotensive events, code events, or received low-dose epinephrine or code-dosed epinephrine related to a clevidipine infusion. Median duration of clevidipine infusion was 4.1 days (1.5-9.2 d). Eleven patients transitioned from clevidipine to enteral antihypertensive agents, and 26 clevidipine infusions were administered as a single agent without sodium nitroprusside. Seven patients were switched from sodium nitroprusside to clevidipine to avoid cyanide toxicity, a majority of whom had elevated serum creatinine.In this pediatric cardiac cohort, clevidipine infusions were effective at hypertension management and were not associated with hypotensive or code events. This report details the largest cohort and longest duration of clevidipine administration within a pediatric population and did not demonstrate hypotensive events, even among neonatal populations. Clevidipine may be a reasonable cost-effective alternative antihypertensive medication compared to traditional short-acting agents.

    View details for DOI 10.1097/PCC.0000000000002562

    View details for PubMedID 32796396

  • Parents Request Withdrawing Feeding From Neurologically Impaired Newborn. The Annals of thoracic surgery Kwiatkowski, D. M., Fifer, C. G., Cohen, M. S. 2019; 108 (5): 1280–82

    View details for DOI 10.1016/j.athoracsur.2019.06.005

    View details for PubMedID 31653288

  • Rasburicase versus intravenous allopurinol for non-malignancy-associated acute hyperuricemia in paediatric cardiology patients. Cardiology in the young Moss, J. D., Wu, M., Axelrod, D. M., Kwiatkowski, D. M. 2019: 1–5

    Abstract

    OBJECTIVES: Limited data exist for management of hyperuricemia in non-oncologic patients, particularly in paediatric cardiac patients. Hyperuricemia is a risk factor for acute kidney injury and may prompt treatment in critically ill patients. The primary objective was to determine if rasburicase use was associated with greater probability normalisation of serum uric acid compared to allopurinol. Secondary outcomes included percent reduction in uric acid, changes in serum creatinine, and cost of therapy.DESIGN: A single-centre retrospective chart review.SETTING: A 20-bed quaternary cardiovascular ICU in a university-based paediatric hospital in California.PATIENTS: Patients admitted to cardiovascular ICU who received rasburicase or intravenous allopurinol between 2015 and 2016.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Data from a cohort of 14 patients receiving rasburicase were compared to 7 patients receiving IV allopurinol. Patients who were administered rasburicase for hyperuricemia were more likely to have a post-treatment uric acid level less than 8 mg/dl as compared to IV allopurinol (100 versus 43%; p = 0.0058). Patients who received rasburicase had a greater absolute reduction in post-treatment day 1 uric acid (-9 mg/dl versus -1.9 mg/dl; p = 0.002). There were no differences in post-treatment day 3 or day 7 serum creatinine or time to normalisation of serum creatinine. The cost of therapy normalised to a 20 kg patient was greater in the allopurinol group ($18,720 versus $1928; p = 0.001).CONCLUSION: In a limited paediatric cardiac cohort, the use of rasburicase was associated with a greater reduction in uric acid levels and associated with a lower cost compared to IV allopurinol.

    View details for DOI 10.1017/S1047951119001653

    View details for PubMedID 31451121

  • Vasoplegia after pediatric cardiac transplantation in patients supported with a continuous flow ventricular assist device. The Journal of thoracic and cardiovascular surgery Sacks, L. D., Hollander, S. A., Zhang, Y., Ryan, K. R., Ford, M. A., Maeda, K., Murray, J. M., Almond, C. S., Kwiatkowski, D. M. 2019

    Abstract

    OBJECTIVE: To determine the association between continuous flow ventricular assist devices and the incidence of vasoplegia following orthotopic heart transplant in children. Moreover, to propose a novel clinical definition of vasoplegia for use in pediatric populations.METHODS: This is a single-center, retrospective cohort study set in the cardiovascular intensive care unit of a tertiary children's hospital. All patients aged 3years and older who underwent orthotopic heart transplant at Stanford Universitybetween April 1, 2014, and July 31, 2017, were included. Vasoplegia was defined by the use of vasoconstrictive medication, diastolic hypotension, preserved systolic heart function, and absence of infection or right atrial pressure or central venous pressure <5mm Hg.RESULTS: Of 44 eligible patients, 21 were supported using a continuous flow ventricular assist device. Following heart transplant, 14 patients (32%) developed vasoplegia by the study definition. Development of vasoplegia was associated with pretransplant use of a continuous flow ventricular assist device (52% vs 13%) with a relative risk of 4.02 (95% confidence interval, 1.30-12.45; P=.009). No other variables were predictive of vasoplegia in univariable analysis. Presence of vasoplegia was not associated with adverse outcomes, although there were trends towards higher incidence of acute kidney injury and increased length of hospital stays.CONCLUSIONS: Children receiving continuous flow ventricular assist device support are at increased risk for vasoplegia following orthotopic heart transplant, using a novel definition of vasoplegia. Anticipation of this complication will allow for prompt intervention, thereby minimizing hemodynamic instability and impact on patient outcomes.

    View details for PubMedID 30929985

  • Intraoperative Methadone Is Associated with Decreased Perioperative Opioid Use Without Adverse Events: A Case-Matched Cohort Study. Journal of cardiothoracic and vascular anesthesia Robinson, J. D., Caruso, T. J., Wu, M. n., Kleiman, Z. I., Kwiatkowski, D. M. 2019

    Abstract

    To determine if there is an association of intraoperative methadone use and total perioperative opioid exposure in patients undergoing congenital heart surgeries.Retrospective, case-match cohort study.Single center quaternary care teaching hospital.Seventy-four patients with congenital heart disease (CHD) undergoing surgical repair or palliative surgery.Thirty-seven patients undergoing CHD surgeries receiving intraoperative methadone were matched to 37 patients based upon age and procedure who did not receive intraoperative methadone. The primary study outcome was to evaluate total opioid use in intravenous milligrams of morphine equivalents per kilogram (mg ME/kg) within the first 36-hours postoperatively. Mann-Whitney U test was used to compare total opioid exposure.The total opioid use was compared between groups. The methadone cohort required less opioids intraoperatively, in the first 12 hours postoperatively, and during the first 36 hours postoperatively (2.51 v 4.39 mg ME/kg, p < 0.001; 0.43 v 1.28 mg ME/kg, p = 0.001; and 0.83 v 1.91 mg ME/kg, p < 0.001) compared with the matched control cohort. There were no differences in clinical outcomes or adverse events. A dose-dependent reduction in opioid consumption in high- versus low-dose groups also was not observed.Intraoperative methadone use was associated with a decrease in perioperative opioid exposure in patients undergoing congenital heart surgery and was not associated with adverse events or prolonged durations of mechanical ventilation or ICU stay.

    View details for DOI 10.1053/j.jvca.2019.09.033

    View details for PubMedID 31699597

  • Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery PEDIATRIC NEPHROLOGY Uber, A. M., Montez-Rath, M. E., Kwiatkowski, D. M., Krawczeski, C. D., Sutherland, S. M. 2018; 33 (11): 2193–99
  • Association of dead space ventilation and prolonged ventilation after repair of tetralogy of Fallot with pulmonary atresia. The Journal of thoracic and cardiovascular surgery Koth, A. M., Kwiatkowski, D. M., Lim, T. R., Bauser-Heaton, H., Asija, R., McElhinney, D. B., Hanley, F. L., Krawczeski, C. D. 2018

    Abstract

    BACKGROUND: We set out to determine whether patients with tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (TOF/PA/MAPCA) are at risk for elevated dead space ventilation fraction (VD/VT), and whether this is associated with prolonged mechanical ventilation. We hypothesized that elevated VD/VT (>20%) in the first 24hours after unifocalization surgery is associated with increased risk for prolonged mechanical ventilation (>7days).METHODS: All patients with TOF/PA/MAPCA undergoing unifocalization surgery between January 2003 and December 2015 were included in this study. Average VD/VT was calculated over the first 24hours after surgery. Demographic and surgical data were collected. Outcome data included duration of mechanical ventilation. Patients were separated into 2 groups: elevated VD/VT and normal DVSF. Groups were compared using the Student t test, Wilcoxon rank-sum test, and chi2 test. Univariable and multivariable regression analyses were performed with VD/VT as a continuous variable to test for association.RESULTS: Of the 265 included patients, 127 (48%) had an elevated VD/VT. The 2 groups did not differ significantly in any demographic characteristic. Patients with an elevated VD/VT had longer cardiopulmonary bypass times (P=.03), were more likely to have delayed sternal closure, and more likely to have prolonged respiratory failure (odds ratio, 2.2; 95% confidence interval, 1.2-4.0; P=.007). The percent VD/VT was associated with duration of mechanical ventilation in univariable (P<.001) and multivariable (P<.001) regression analyses when controlled for age, weight and bypass time.CONCLUSIONS: Elevated postoperative VD/VT is associated with prolonged mechanical ventilation in patients with TOF/PA/MAPCA following unifocalization. Elevated postoperative VD/VT may be an early indicator of patients who will require prolonged duration of mechanical ventilation, allowing optimization of medical management to promote better outcomes.

    View details for PubMedID 29884495

  • First-stage palliation strategy for univentricular heart disease may impact risk for acute kidney injury CARDIOLOGY IN THE YOUNG Goldstein, B. H., Goldstein, S. L., Devarajan, P., Zafar, F., Kwiatkowski, D. M., Marino, B. S., Morales, D. S., Krawczeski, C. D., Cooper, D. S. 2018; 28 (1): 93–100

    Abstract

    Norwood palliation for patients with single ventricle heart disease is associated with a significant risk for acute kidney injury, which portends a worse prognosis. We sought to investigate the impact of hybrid stage I palliation (Hybrid) on acute kidney injury risk.This study is a single-centre prospective case-control study of seven consecutive neonates with single ventricle undergoing Hybrid palliation. Levels of serum creatinine and four novel urinary biomarkers, namely neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, and kidney injury molecule-1, were obtained before and after palliation. Acute kidney injury was defined as a ⩾50% increase in serum creatinine within 48 hours after the procedure. Data were compared with a contemporary cohort of 12 neonates with single ventricle who underwent Norwood palliation.Patients who underwent Hybrid were more likely to be high-risk candidates (86 versus 25%, p=0.01) compared with those who underwent Norwood. Despite similar preoperative serum creatinine levels, there was a trend towards higher levels of postoperative peak serum creatinine (0.7 [0.63, 0.94] versus 0.56 [0.47, 0.74], p=0.06) and rate of acute kidney injury (67 versus 29%, p=0.17) in the Norwood cohort. Preoperative neutrophil gelatinase-associated lipocalin (58.4 [11, 86.3] versus 6.3 [5, 16.2], p=0.07) and interleukin-18 (30.6 [9.6, 167.2] versus 6.3 [6.3, 16.4], p=0.03) levels were higher in the Hybrid cohort. Nevertheless, longitudinal mixed-effect models demonstrated Hybrid palliation to be a protective factor against increased postoperative levels of neutrophil gelatinase-associated lipocalin (estimate -1.8 [-3.0, -9.0], p<0.001) and liver fatty acid-binding protein (-49.3 [-89.7, -8.8], p=0.018).In this single-centre case-control study, postoperative acute kidney injury risk did not differ significantly by single ventricle stage I treatment strategy; however, postoperative elevation in novel urinary biomarkers, consistent with subclinical kidney injury, was encountered in the Norwood cohort but not in the Hybrid cohort.

    View details for PubMedID 28889816

  • Comprehensive Management Considerations of Select Noncardiac Organ Systems in the Cardiac Intensive Care Unit. World journal for pediatric & congenital heart surgery Huff, C., Mastropietro, C. W., Riley, C., Byrnes, J., Kwiatkowski, D. M., Ellis, M., Schuette, J., Justice, L. 2018; 9 (6): 685–95

    Abstract

    As the acuity and complexity of pediatric patients with congenital cardiac disease have increased, there are many noncardiac issues that may be present in these patients. These noncardiac problems may affect clinical outcomes in the cardiac intensive care unit and must be recognized and managed. The Pediatric Cardiac Intensive Care Society sought to provide an expert review of some of the most common challenges of the respiratory, gastrointestinal, hematological, renal, and endocrine systems in pediatric cardiac patients. This review provides a brief overview of literature available and common practices.

    View details for DOI 10.1177/2150135118779072

    View details for PubMedID 30322370

  • Acute Kidney Injury in Children. Advances in chronic kidney disease Sutherland, S. M., Kwiatkowski, D. M. 2017; 24 (6): 380-387

    Abstract

    Acute kidney injury (AKI) has become one of the more common complications seen among hospitalized children. The development of a consensus definition has helped refine the epidemiology of pediatric AKI, and we now have a far better understanding of its incidence, risk factors, and outcomes. Strategies for diagnosing AKI have extended beyond serum creatinine, and the most current data underscore the diagnostic importance of oliguria as well as introduce the concept of urinary biomarkers of kidney injury. As AKI has become more widespread, we have seen that it is associated with a number of adverse consequences including longer lengths of stay and greater mortality. Though effective treatments do not currently exist for AKI once it develops, we hope that the diagnostic and definitional strides seen recently translate to the testing and development of more effective interventions.

    View details for DOI 10.1053/j.ackd.2017.09.007

    View details for PubMedID 29229169

  • Acute kidney injury in congenital heart disease. Current opinion in cardiology Gist, K. M., Kwiatkowski, D. M., Cooper, D. S. 2017

    Abstract

    PURPOSE OF REVIEW: Acute kidney injury (AKI) is associated with significant morbidity and mortality in patients with congenital heart disease undergoing cardiac surgery or in pediatric patients with congestive heart failure.RECENT FINDINGS: This review describes the definition and various manifestations of AKI, the impact of biomarkers on the diagnosis of AKI, the importance of fluid overload as a consequence of AKI and its long-term impact.SUMMARY: There are novel biomarkers for AKI detection that should facilitate early recognition and intervention to prevent or attenuate the effects of AKI and fluid overload. Previous conventional wisdom that survivors of AKI fully recover renal function without subsequent consequences is flawed.

    View details for PubMedID 29028633

  • Acute kidney injury in pediatric patients. Best practice & research. Clinical anaesthesiology Kwiatkowski, D. M., Sutherland, S. M. 2017; 31 (3): 427-439

    Abstract

    Acute kidney injury (AKI) is highly prevalent among hospitalized children, especially those who are critically ill. The incorporation of pediatric elements into consensus definitions has led to a greater understanding of pediatric AKI epidemiology, risk factors, and outcomes. The best available data suggest that AKI occurs in 5% and 27% of non-critically ill and critically ill children, respectively. Additionally, AKI and fluid overload are independently associated with worse outcomes including mortality. Currently, the diagnosis of AKI relies upon urine output and creatinine measurements, both of which pose unique problems in children. However, novel biomarker discovery and new risk stratification techniques have led to enhanced detection and diagnostic strategies. Although no specific treatments exist, strategies designed to prevent AKI are being developed and there is growing evidence that early detection may improve outcomes. We hope that advances in AKI management will follow the diagnostic innovations seen in the past decade.

    View details for DOI 10.1016/j.bpa.2017.08.007

    View details for PubMedID 29248148

  • Does a Spoonful of Insulin Make the Acute Kidney Injury Go Down? PEDIATRIC CRITICAL CARE MEDICINE Kwiatkowski, D. M., Krawczeski, C. D. 2017; 18 (7): 721–22

    View details for PubMedID 28691962

  • Acute kidney injury and fluid overload in infants and children after cardiac surgery. Pediatric nephrology Kwiatkowski, D. M., Krawczeski, C. D. 2017

    Abstract

    Acute kidney injury is a common and serious complication after congenital heart surgery, particularly among infants. This comorbidity has been independently associated with adverse outcomes including an increase in mortality. Postoperative acute kidney injury has a complex pathophysiology with many risk factors, and therefore no single medication or therapy has been demonstrated to be effective for treatment or prevention. However, it has been established that the associated fluid overload is one of the major determinants of morbidity, particularly in infants after cardiac surgery. Therefore, in the absence of an intervention to prevent acute kidney injury, much of the effort to improve outcomes has focused on treating and preventing fluid overload. Early renal replacement therapy, often in the form of peritoneal dialysis, has been shown to be safe and beneficial in infants with oliguria after heart surgery. As understanding of the pathophysiology of acute kidney injury and the ability to confidently diagnose it earlier continues to evolve, it is likely that novel preventative and therapeutic interventions will be available in the future.

    View details for DOI 10.1007/s00467-017-3643-2

    View details for PubMedID 28361230

  • Fluid overload independent of acute kidney injury predicts poor outcomes in neonates following congenital heart surgery. Pediatric nephrology (Berlin, Germany) Mah, K. E., Hao, S. n., Sutherland, S. M., Kwiatkowski, D. M., Axelrod, D. M., Almond, C. S., Krawczeski, C. D., Shin, A. Y. 2017

    Abstract

    Fluid overload (FO) is common after neonatal congenital heart surgery and may contribute to mortality and morbidity. It is unclear if the effects of FO are independent of acute kidney injury (AKI).This was a retrospective cohort study which examined neonates (age < 30 days) who underwent cardiopulmonary bypass in a university-affiliated children's hospital between 20 October 2010 and 31 December 2012. Demographic information, risk adjustment for congenital heart surgery score, surgery type, cardiopulmonary bypass time, cross-clamp time, and vasoactive inotrope score were recorded. FO [(fluid in-out)/pre-operative weight] and AKI defined by Kidney Disease Improving Global Outcomes serum creatinine criteria were calculated. Outcomes were all-cause, in-hospital mortality and median postoperative hospital and intensive care unit lengths of stay.Overall, 167 neonates underwent cardiac surgery using cardiopulmonary bypass in the study period, of whom 117 met the inclusion criteria. Of the 117 neonates included in the study, 76 (65%) patients developed significant FO (>10%), and 25 (21%) developed AKI ≥ Stage 2. When analyzed as FO cohorts (< 10%,10-20%, > 20% FO), patients with greater FO were more likely to have AKI (9.8 vs. 18.2 vs. 52.4%, respectively, with AKI ≥ stage 2; p = 0.013) and a higher vasoactive-inotrope score, and be premature. In the multivariable regression analyses of patients without AKI, FO was independently associated with hospital and intensive care unit lengths of stay [0.322 extra days (p = 0.029) and 0.468 extra days (p < 0.001), respectively, per 1% FO increase). In all patients, FO was also associated with mortality [odds ratio 1.058 (5.8% greater odds of mortality per 1% FO increase); 95% confidence interval 1.008,1.125;p = 0.032].Fluid overload is an important independent contributor to outcomes in neonates following congenital heart surgery. Careful fluid management after cardiac surgery in neonates with and without AKI is warranted.

    View details for PubMedID 29128923

  • Incidence, risk factors, and outcomes of acute kidney injury in adults undergoing surgery for congenital heart disease. Cardiology in the young Kwiatkowski, D. M., Price, E., Axelrod, D. M., Romfh, A. W., Han, B. S., Sutherland, S. M., Krawczeski, C. D. 2016: 1-8

    Abstract

    Acute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes.This single-centre, retrospective cohort study was performed in a quaternary cardiovascular ICU in a paediatric hospital including all consecutive patients ⩾18 years between 2010 and 2013.Data from 118 patients with a median age of 29 years undergoing cardiac surgery were analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36% of patients developed kidney injury, with 5% being moderate to severe (stage 2/3). Among higher-complexity surgeries, incidence was 59%. Age ⩾35 years, preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and perioperative vancomycin use were significant risk factors for kidney injury development. In multivariable analysis, age ⩾35 years and vancomycin use were significant predictors. Those with kidney injury were more likely to have prolonged duration of mechanical ventilation and cardiovascular ICU stay in the univariable regression analysis.We demonstrated that acute kidney injury is a frequent complication in adults after surgery for CHD and is associated with poor outcomes. Risk factors for development were identified but largely not modifiable. Further investigation within this cohort is necessary to better understand the problem of kidney injury.

    View details for PubMedID 27869053

  • Right Ventricular Outflow Tract Obstruction: Pulmonary Atresia With Intact Ventricular Septum, Pulmonary Stenosis, and Ebstein's Malformation. Pediatric critical care medicine Kwiatkowski, D. M., Hanley, F. L., Krawczeski, C. D. 2016; 17 (8): S323-9

    Abstract

    The objectives of this review are to discuss the anatomy, pathophysiology, clinical course, and current treatment strategies for pulmonary atresia with intact ventricular septum, pulmonary stenosis, and Ebstein's anomaly.MEDLINE and PubMed.Considerable advances have been made in management strategies for these complex congenital heart lesions, which have led to improved outcomes.

    View details for DOI 10.1097/PCC.0000000000000818

    View details for PubMedID 27490618

  • Acute Kidney Injury and Cardiorenal Syndromes in Pediatric Cardiac Intensive Care. Pediatric critical care medicine Cooper, D. S., Kwiatkowski, D. M., Goldstein, S. L., Krawczeski, C. D. 2016; 17 (8): S250-6

    Abstract

    The objectives of this review are to discuss the definition, diagnosis, and pathophysiology of acute kidney injury and its impact on immediate, short-, and long-term outcomes. In addition, the spectrum of cardiorenal syndromes will be reviewed including the pathophysiology on this interaction and its impact on outcomes.MEDLINE and PubMed.The field of cardiac intensive care continues to advance in tandem with congenital heart surgery. As mortality has become a rare occurrence, the focus of cardiac intensive care has shifted to that of morbidity reduction. Acute kidney injury adversely impact outcomes of patients following surgery for congenital heart disease as well as in those with heart failure (cardiorenal syndrome). Patients who become fluid overloaded and/or require dialysis are at a higher risk of mortality, but even minor degrees of acute kidney injury portend a significant increase in mortality and morbidity. Clinicians continue to seek methods of early diagnosis and risk stratification of acute kidney injury to prevent its adverse sequelae.

    View details for DOI 10.1097/PCC.0000000000000820

    View details for PubMedID 27490607

  • Acute Kidney Injury Has a Long-Term Impact on Survival After Stage 1 Palliation of Univentricular Hearts-It's Not Just Just One and Done PEDIATRIC CRITICAL CARE MEDICINE Cooper, D. S., Goldstein, S. L., Kwiatkowski, D. M. 2016; 17 (7): 697–98

    View details for PubMedID 27387777

  • Dexmedetomidine Is Associated With Lower Incidence of Acute Kidney Injury After Congenital Heart Surgery. Pediatric critical care medicine Kwiatkowski, D. M., Axelrod, D. M., Sutherland, S. M., Tesoro, T. M., Krawczeski, C. D. 2016; 17 (2): 128-134

    Abstract

    Recent data have suggested an association between the use of dexmedetomidine and a decreased incidence of acute kidney injury in adult patients after cardiopulmonary bypass. However, no study has focused on this association among pediatric populations where the incidence of acute kidney injury is particularly high and of critical significance. The primary objective of this study was to assess the relationship between the use of postoperative dexmedetomidine and the incidence of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass. The secondary objective was to determine whether there was an association between dexmedetomidine use and duration of mechanical ventilation or cardiovascular ICU stay.Single-center retrospective matched cohort study.A 20-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California.Children less than 18 years old admitted after cardiac surgery with cardiopulmonary bypass between January 1, 2012, and May 31, 2014.None.Data from a cohort of 102 patients receiving dexmedetomidine during the first postoperative day after cardiac surgery were compared to an age- and procedure-matched cohort not receiving dexmedetomidine. Cohorts had similar baseline and demographic characteristics. Patients receiving dexmedetomidine were less likely to develop acute kidney injury (24% vs 36%; odds ratio, 0.54; 95% CI, 0.29-0.99; p = 0.046). After adjusting for age, bypass time, nephrotoxin use, and vasoactive inotropic score, the use of dexmedetomidine was associated with a lower incidence of acute kidney injury with adjusted odds ratio of 0.43 (95% CI, 0.27-0.98; p = 0.048). There was no difference between the cohorts with respect to the duration of mechanical duration (1 d each; p = 0.98) or cardiovascular ICU stays (5 vs 6 d; p = 0.91).The use of a dexmedetomidine infusion in pediatric patients after congenital heart surgery was associated with a decreased incidence of acute kidney injury; however, it was not associated with changes in clinical outcomes. Further prospective study is necessary to validate these findings.

    View details for DOI 10.1097/PCC.0000000000000611

    View details for PubMedID 26673841

  • Training Pathways in Pediatric Cardiac Intensive Care: Proceedings From the 10th International Conference of the Pediatric Cardiac Intensive Care Society. World journal for pediatric & congenital heart surgery Anand, V., Kwiatkowski, D. M., Ghanayem, N. S., Axelrod, D. M., DiNardo, J., Klugman, D., Krishnamurthy, G., Siehr, S., Stromberg, D., Yates, A. R., Roth, S. J., Cooper, D. S. 2016; 7 (1): 81-88

    Abstract

    The increase in pediatric cardiac surgical procedures and establishment of the practice of pediatric cardiac intensive care has created the need for physicians with advanced and specialized knowledge and training. Current training pathways to become a pediatric cardiac intensivist have a great deal of variability and have unique strengths and weaknesses with influences from critical care, cardiology, neonatology, anesthesiology, and cardiac surgery. Such variability has created much confusion among trainees looking to pursue a career in our specialized field. This is a report with perspectives from the most common advanced fellowship training pathways taken to become a pediatric cardiac intensivist as well as various related topics including scholarship, qualifications, and credentialing.

    View details for DOI 10.1177/2150135115614576

    View details for PubMedID 26714998

  • Short QT Interval Prevalence and Clinical Outcomes in a Pediatric Population CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Guerrier, K., Kwiatkowski, D., Czosek, R. J., Spar, D. S., Anderson, J. B., Knilans, T. K. 2015; 8 (6): 1460-1464

    Abstract

    Risk associated with short QT interval has recently received recognition. European studies suggest a prevalence of 0.02% to 0.1% in the adult population, but similar studies in pediatric patients are limited. We sought to determine the prevalence of short QT interval in a pediatric population and associated clinical characteristics and outcomes.Retrospective review of an ECG database at a single pediatric institution. The database was queried for ECGs on patients ≤21 years with electronically measured QTc of 140 to 340 ms. Patients with QTc of 140 to 340 ms confirmed by a pediatric electrophysiologist were identified for chart review for associated clinical characteristics, symptoms, and outcome. Patients with and without symptoms were compared in an attempt to identify variables associated with outcome. The query included 272 504 ECGs on 99 380 unique patients. Forty-five patients (35 men, 76%) had QTc ≤340 ms, for a prevalence of 0.05%. Median age was 15 years (interquartile range, 2-17), median QT 330 ms (interquartile range, 280-360), and median QTc 323 ms (IQR, 313-332). Women had significantly shorter QTc compared with men (312 versus 323 ms; P=0.03). Two deaths were noted in chart review--one from respiratory failure and the second of unknown pathogenesis in a patient with dilated cardiomyopathy.Short QT interval was a rare finding in this pediatric population, with a prevalence of 0.05%. Male predominance was identified, although the median QT interval was significantly shorter in women. There seem to be no unifying clinical characteristics for this pediatric patient cohort with short QT interval.

    View details for DOI 10.1161/CIRCEP.115.003256

    View details for Web of Science ID 000366604600022

    View details for PubMedID 26386018

  • Acute Kidney Injury After Cardiovascular Surgery in Children Perioperative Kidney Injury Kwiatkowski, D. M., Krawczeski, C. D. Springer New York. 2015; 1: 99–109
  • Improved outcomes with peritoneal dialysis catheter placement after cardiopulmonary bypass in infants JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Kwiatkowski, D. M., Menon, S., Krawczeski, C. D., Goldstein, S. L., Morales, D. L., Phillips, A., Manning, P. B., Eghtesady, P., Wang, Y., Nelson, D. P., Cooper, D. S. 2015; 149 (1): 230-236

    Abstract

    Acute kidney injury (AKI) is common in infants after cardiopulmonary bypass and is associated with poor outcomes. Peritoneal dialysis improves outcomes in adults with AKI after bypass, but pediatric data are limited. This retrospective case-matched study was conducted to determine if the practice of peritoneal dialysis catheter (PDC) placement during congenital heart surgery is associated with improved clinical outcomes in infants at high risk for AKI.Forty-two infants undergoing congenital heart surgery with planned PDC placement (PDC+) were age-matched to infants undergoing similar surgery without PDC placement (PDC-). Demographic, baseline and outcome data were compared. Our primary outcome was negative fluid balance on postoperative days 1 to 3. Secondary outcomes included time to negative fluid balance, time to extubation, frequency of electrolyte corrective medications, inotrope scores, and other clinical outcomes.Baseline data did not differ between groups. The PDC+ group had a higher percentage of negative fluid balance on postoperative days 1 and 2 (57% vs 33%, P = .04; 85% vs 61%, P = .01). The PDC+ group had shorter time to negative fluid balance (16 vs 32 hours, P < .0001), earlier extubation (80 vs 104 hours, P = .02), improved inotrope scores (P = .04), and fewer electrolyte imbalances requiring correction (P = .03). PDC-related complications were rare.PDC use is safe and associated with earlier negative fluid balance and improved clinical outcomes in infants at high risk for AKI. Routine PDC use should be considered for infants undergoing cardiopulmonary bypass. Further prospective studies are essential to prove causative effects of PDC placement in this population.

    View details for DOI 10.1016/j.jtcvs.2013.11.040

    View details for Web of Science ID 000350550100066

    View details for PubMedID 24503323

  • Diuretics Handbook of Pediatric Cardiovascular Drugs Kwiatkowski, D. M., Donnellan, A., Cooper, D. S. Springer London. 2014; 2: 6
  • Biomarkers of acute kidney injury in pediatric cardiac patients BIOMARKERS IN MEDICINE Kwiatkowski, D. M., Goldstein, S. L., Krawczeski, C. D. 2012; 6 (3): 273-282

    Abstract

    Acute kidney injury is a common and significant complication among pediatric patients with congenital heart disease, occurring most commonly after cardiopulmonary bypass. Current laboratory methods of diagnosis are not timely enough to guide management decisions, thus spurring interest in discovering new biomarkers of acute injury. Several promising candidates, including NGAL, IL-18 and KIM-1, have been the subject of recent investigation and may facilitate earlier and more accurate diagnosis of renal injury within this cohort. There is little evidence demonstrating that it will be possible to rely upon one particular biomarker as a single agent, and evidence supports that the use of biomarker panels will be most effective. Further clinical validation and broader commercial availability of these novel biomarkers will probably revolutionize the care of pediatric cardiac patients with renal injury.

    View details for DOI 10.2217/BMM.12.27

    View details for Web of Science ID 000306455100004

    View details for PubMedID 22731900

  • The Utility of Outpatient Echocardiography for Evaluation of Asymptomatic Murmurs in Children CONGENITAL HEART DISEASE Kwiatkowski, D., Wang, Y., Cnota, J. 2012; 7 (3): 283-288

    Abstract

      The purpose of this study is to review sedated outpatient echocardiograms performed to evaluate asymptomatic murmurs in children between the ages of 1 month and 4 years and describe outcomes of tests done to determine if utility varies among age of study and referral type (primary care physician vs. pediatric cardiologist.) We aim to describe the yield in a contemporary cohort which has increased availability and quality of diagnostic aids such as fetal ultrasound, newborn pulse oximetry, and neonatal echocardiography.  Retrospective cohort study.  Cincinnati Children's Hospital Medical Center: Outpatient Echocardiography Laboratory.  Children between 1 month and 4 years of age with asymptomatic murmurs who are referred for outpatient echocardiogram for evaluation of murmur.  Primary diagnosis of echocardiography studies, classified into severity score. Results.  Four hundred sixty-two sedated echocardiograms were studied. Six (1%) echocardiograms showed severe pathology, and no severe pathology was shown in the echocardiograms ordered at the age of over 6 months old. The yield of studies decreased as age increased. The incidence of abnormal pathology was higher among tests ordered by cardiologists, across all severity levels (P < .0001).  Among echocardiograms ordered for children over 1 year of age with an asymptomatic murmur, there was no severe and little moderate disease. Cardiac disease is significantly less likely when echocardiograms are ordered without referral to a pediatric cardiologist. The workup for asymptomatic murmurs does not require an echocardiogram, and these results may aid clinicians when deciding whether evaluation of a child should include this study.

    View details for DOI 10.1111/j.1747-0803.2012.00637.x

    View details for Web of Science ID 000304437100019

    View details for PubMedID 22348237

  • A Teenager with Marfan Syndrome and Left Ventricular Noncompaction PEDIATRIC CARDIOLOGY Kwiatkowski, D., Hagenbuch, S., Meyer, R. 2010; 31 (1): 132-135

    Abstract

    We report a teenager with Marfan syndrome who presented to Cincinnati Children's Hospital Medical Center as part of a preoperative evaluation for an orthopedic procedure after asymptomatic arrhythmia was recognized. Continuous cardiac monitoring showed frequent premature ventricular contractions and nonsustained runs of ventricular tachycardia. Cardiac magnetic resonance imaging showed left ventricular noncompaction (LVNC), prompting insertion of an implantable cardiac defibrillator. Although Marfan syndrome is associated with cardiac lesions, it has not previously been described with LVNC. Likewise LVNC has been seen in association with other cardiac lesions; however, this report represents the first reference of LVNC in the context of Marfan syndrome.

    View details for DOI 10.1007/s00246-009-9552-9

    View details for Web of Science ID 000273675400027

    View details for PubMedID 19795159

  • Catalytic asymmetric allylation of ketones and a tandem asymmetric allylation/diastereoselective epoxidation of cyclic enones JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Kim, J. G., Waltz, K. M., Garcia, I. F., Kwiatkowski, D., Walsh, P. J. 2004; 126 (39): 12580-12585

    Abstract

    A simple procedure is reported for the catalytic asymmetric allylation of ketones, utilizing titanium tetraisopropoxide, BINOL, 2-propanol additive, and tetraallylstannane as allylating agent. A variety of ketone substrates, including acetophenone derivatives and alpha,beta-unsaturated cyclic enones, reacted to form tertiary homoallylic alcohols in good yields (67-99%) and with high levels of enantioselectivity (generally >80%). A novel one-pot enantioselective allylation/diastereoselective epoxidation has also been introduced. Thus, upon completion of the allyl addition to conjugated cyclic enones, 1 equiv of tert-butyl hydroperoxide is added and the directed epoxidation of the allylic double bond ensues to afford the epoxy alcohol with high diastereoselectivity.

    View details for DOI 10.1021/ja047758t

    View details for Web of Science ID 000224219900077

    View details for PubMedID 15453790

  • Antimitogenic effects of HDL and APOE mediated by cox-2-dependent IP activation JOURNAL OF CLINICAL INVESTIGATION Kothapalli, D., Fuki, I., Ali, K., Stewart, S. A., Zhao, L., Yahil, R., Kwiatkowski, D., Hawthorne, E. A., FitzGerald, G. A., Phillips, M. C., Lund-Katz, S., Pure, E., Rader, D., Assoian, R. K. 2004; 113 (4): 609-618

    Abstract

    HDL and its associated apo, APOE, inhibit S-phase entry of murine aortic smooth muscle cells. We report here that the antimitogenic effect of APOE maps to the N-terminal receptor-binding domain, that APOE and its N-terminal domain inhibit activation of the cyclin A promoter, and that these effects involve both pocket protein-dependent and independent pathways. These antimitogenic effects closely resemble those seen in response to activation of the prostacyclin receptor IP. Indeed, we found that HDL and APOE suppress aortic smooth muscle cell cycle progression by stimulating Cox-2 expression, leading to prostacyclin synthesis and an IP-dependent inhibition of the cyclin A gene. Similar results were detected in human aortic smooth muscle cells and in vivo using mice overexpressing APOE. Our results identify the Cox-2 gene as a target of APOE signaling, link HDL and APOE to IP action, and describe a potential new basis for the cardioprotective effect of HDL and APOE.

    View details for DOI 10.1172/JCI200419097

    View details for Web of Science ID 000189008000016

    View details for PubMedID 14966570