Publications by authors named "Anthony C Chang"

71 Publications

Publishing Artificial Intelligence Research Papers: A Tale of Three Journals.

J Biomed Inform 2021 Feb 5:103708. Epub 2021 Feb 5.

Elsevier Biomedical Informatics Journals. Electronic address:

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http://dx.doi.org/10.1016/j.jbi.2021.103708DOI Listing
February 2021

Artificial intelligence and COVID-19: Present state and future vision.

Authors:
Anthony C Chang

Intell Based Med 2020 Dec 7;3:100012. Epub 2020 Nov 7.

The Sharon Disney Lund, Medical Intelligence and Innovation Institute (MI3), Children's Hospital of Orange County, USA.

The COVID-19 pandemic has lead to catastrophic number of deaths and revealed that much work still remains with data and artificial intelligence. To fully comprehend the dynamics of a pandemic with relevance to artificial intelligence, a primer on global health concepts is first presented. Following this, various aspects of diagnosis and therapy and the relationship to artificial intelligence are presented along with a future projection of an ideal deployment of artificial intelligence in a pandemic. Final thoughts are made about lessons learned and what lies ahead.
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http://dx.doi.org/10.1016/j.ibmed.2020.100012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648181PMC
December 2020

The Next Frontier in Pediatric Cardiology: Artificial Intelligence.

Pediatr Clin North Am 2020 10;67(5):995-1009

The Sharon Disney Lund Medical Intelligence and Innovation Institute (MI3), Children's Hospital of Orange County, 1120 W La Veta Ave, STE 860, Orange, CA 92868, USA. Electronic address:

Artificial intelligence (AI) in the last decade centered primarily around digitizing and incorporating the large volumes of patient data from electronic health records. AI is now poised to make the next step in health care integration, with precision medicine, imaging support, and development of individual health trends with the popularization of wearable devices. Future clinical pediatric cardiologists will use AI as an adjunct in delivering optimum patient care, with the help of accurate predictive risk calculators, continual health monitoring from wearables, and precision medicine. Physicians must also protect their patients' health information from monetization or exploitation.
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http://dx.doi.org/10.1016/j.pcl.2020.06.010DOI Listing
October 2020

A primer on artificial intelligence for the paediatric cardiologist.

Cardiol Young 2020 Jul 22;30(7):934-945. Epub 2020 Jun 22.

Children's Hospital of Orange County, Orange, CA92868, USA.

The combination of pediatric cardiology being both a perceptual and a cognitive subspecialty demands a complex decision-making model which makes artificial intelligence a particularly attractive technology with great potential. The prototypical artificial intelligence system would autonomously impute patient data into a collaborative database that stores, syncs, interprets and ultimately classifies the patient's profile to specific disease phenotypes to compare against a large aggregate of shared peer health data and outcomes, the current medical body of literature and ongoing trials to offer morbidity and mortality prediction, drug therapy options targeted to each patient's genetic profile, tailored surgical plans and recommendations for timing of sequential imaging. The focus of this review paper is to offer a primer on artificial intelligence and paediatric cardiology by briefly discussing the history of artificial intelligence in medicine, modern and future applications in adult and paediatric cardiology across selected concentrations, and current barriers to implementation of these technologies.
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http://dx.doi.org/10.1017/S1047951120001493DOI Listing
July 2020

Artificial intelligence in pediatric cardiology and cardiac surgery: Irrational hype or paradigm shift?

Authors:
Anthony C Chang

Ann Pediatr Cardiol 2019 Sep-Dec;12(3):191-194

Medical Director, The Sharon Disney Lund Medical Intelligence and Innovation Institute (MI3), Children's Hospital of Orange County, Founder AIMed, Orange, CA, USA.

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http://dx.doi.org/10.4103/apc.APC_55_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716326PMC
September 2019

Application of artificial intelligence in pediatrics: past, present and future.

World J Pediatr 2019 Apr 17;15(2):105-108. Epub 2019 Apr 17.

The Sharon Disney Lund Medical Intelligence and Innovation Institute (MI3), Children's Hospital of Orange County, Orange, CA 92868, USA.

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http://dx.doi.org/10.1007/s12519-019-00255-1DOI Listing
April 2019

Echocardiographic MRI: an innovative fusion of functional and anatomic assessment strategy for CHD.

Cardiol Young 2019 Jan 31;29(1):88-89. Epub 2018 Oct 31.

Children's Hospital of Orange County,Pediatric Heart Institute,Orange,CA 92868,USA.

We present a pilot case using an innovative fusion of echocardiogram and MRI achieved with a MATLAB-based imaging programme to explore the feasibility of this imaging strategy in the functional and anatomic assessment of a patient with repaired tetralogy of Fallot requiring pulmonary valve intervention. Echocardiogram and MRI neutralises the disadvantages and limitations of each individual imaging modality and yields important anatomic and haemodynamic information crucial to the treatment decision-making process. Future image fusion strategies can apply to three-dimensional images and image-directed therapy for CHD.
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http://dx.doi.org/10.1017/S1047951118001749DOI Listing
January 2019

Rapidly progressive heart failure requiring transplantation in muscular dystrophy: a need for frequent screening.

Cardiol Young 2017 Nov 10;27(9):1836-1840. Epub 2017 Jul 10.

1Children's Hospital of Orange County,Orange,California,United States of America.

Fukuyama congenital muscular dystrophy weakens both skeletal and cardiac muscles, but the rate of cardiomyopathic progression can accelerate faster than that of skeletal muscles. A 14-year-old boy with Fukuyama congenital muscular dystrophy presented with mild skeletal myopathy but severe cardiomyopathy requiring heart transplantation within 1 year of declining heart function. These patients need frequent screening regardless of musculoskeletal symptoms.
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http://dx.doi.org/10.1017/S1047951117001251DOI Listing
November 2017

Association of Freestanding Children's Hospitals With Outcomes in Children With Critical Illness.

Crit Care Med 2016 Dec;44(12):2131-2138

1Division of Pediatric Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR.2Section of Biostatistics, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR.3Department of Statistics, LSU Health Sciences Center, New Orleans, LA.4Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Orange County, Orange, CA.5Medical Intelligence and Innovation Institute (MI3), Children's Hospital of Orange County, Orange, CA.6Virtual PICU Systems, LLC, Los Angeles, CA.7Division of Pediatric Critical Care, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.8Division of Critical Care Medicine, Department of Pediatrics and Anesthesiology, Children's Hospital Los Angeles, USC Keck School of Medicine, Los Angeles, CA.

Objectives: Little is known about the relationship between freestanding children's hospitals and outcomes in children with critical illness. The purpose of this study was to evaluate the association of freestanding children's hospitals with outcomes in children with critical illness.

Design: Propensity score matching was performed to adjust for potential confounding variables between patients cared for in freestanding or nonfreestanding children's hospitals. We tested the sensitivity of our findings by repeating the primary analyses using inverse probability of treatment weighting method and regression adjustment using the propensity score.

Setting: Retrospective study from an existing national database, Virtual PICU Systems (LLC) database.

Patients: Patients less than 18 years old admitted to one of the participating PICUs in the Virtual PICU Systems, LLC database were included (2009-2014).

Interventions: None.

Measurements And Main Results: A total of 538,967 patients from 140 centers were included. Of these, 323,319 patients were treated in 60 freestanding hospitals. In contrast, 215,648 patients were cared for in 80 nonfreestanding hospitals. By propensity matching, 134,656 patients were matched 1:1 in the two groups (67,328 in each group). Prior to matching, patients in the freestanding hospitals were younger, had greater comorbidities, had higher severity of illness scores, had higher incidence of cardiac arrest, had higher resource utilization, and had higher proportion of patients undergoing complex procedures such as cardiac surgery. Before matching, the outcomes including mortality were worse among the patients cared for in the freestanding hospitals (freestanding vs nonfreestanding, 2.5% vs 2.3%; p < 0.001). After matching, the majority of the study outcomes were better in freestanding hospitals (freestanding vs nonfreestanding, mortality: 2.1% vs 2.8%, p < 0.001; standardized mortality ratio: 0.77 [0.73-0.82] vs 0.99 [0.87-0.96], p < 0.001; reintubation: 3.4% vs 3.8%, p < 0.001; good neurologic outcome: 97.7% vs 97.1%, p = 0.001).

Conclusions: In this large observational study, we demonstrated that ICU care provided in freestanding children's hospitals is associated with improved risk-adjusted survival chances compared to nonfreestanding children's hospitals. However, the clinical significance of this change in mortality should be interpreted with caution. It is also possible that the hospital structure may be a surrogate of other factors that may bias the results.
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http://dx.doi.org/10.1097/CCM.0000000000001961DOI Listing
December 2016

Pediatric Cardiac Intensive Care: A Transition to Maturity.

Pediatr Crit Care Med 2016 08;17(8 Suppl 1):S110-1

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http://dx.doi.org/10.1097/PCC.0000000000000824DOI Listing
August 2016

Birth Tourism and Neonatal Intensive Care: A Children's Hospital Experience.

Am J Perinatol 2016 12 16;33(14):1415-1419. Epub 2016 May 16.

Cardiology Division, Children's Hospital of Orange County, Orange, California.

 The aim of this article is to examine characteristics of birth tourism (BT) neonates admitted to a neonatal intensive care unit (NICU).  This was a retrospective review over 3 years; BT cases were identified, and relevant perinatal, medical, social, and financial data were collected and compared with 100 randomly selected non-birth tourism neonates.  A total of 46 BT neonates were identified. They were more likely to be born to older women (34 vs. 29 years;  < 0.001), via cesarean delivery (72 vs. 48%;  = 0.007), and at a referral facility (80 vs. 32%;  < 0.001). BT group had longer hospital stay (15 vs. 7 days;  = 0.02), more surgical intervention (50 vs. 21%;  < 0.001), and higher hospital charges (median $287,501 vs. $103,105;  = 0.003). One-third of BT neonates were enrolled in public health insurance program and four BT neonates (10%) were placed for adoption.  Families of BT neonates admitted to the NICU face significant challenges. Larger studies are needed to better define impacts on families, health care system, and society.
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http://dx.doi.org/10.1055/s-0036-1584139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819895PMC
December 2016

Report of the National Heart, Lung, and Blood Institute Working Group: An Integrated Network for Congenital Heart Disease Research.

Circulation 2016 Apr;133(14):1410-8

From Department of Pediatrics and Communicable Diseases, University of Michigan C.S. Mott Children's Hospital, Ann Arbor (S.K.P., M.G.G.); Department of Surgery, Johns Hopkins All Children's Heart Institute, St. Petersburg, FL (J.P.J.); National Institute of Mental Health, National Institutes of Health, Bethesda, MD (G.K.F.); Children's Hospital Association, Overland Park, KS (D.B.); Department of Cardiology, Boston Children's Hospital, MA (E.D.B.); Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (K.M.B., G.P., V.L.P., J.R.K.); Department of Pediatrics, Emory University, Atlanta GA (R.C., R.V.); Department of Pediatrics, Children's Hospital of Orange County, Orange, CA (A.C.C.); Department of Pediatrics and Medicine, Columbia University, New York, NY (W.K.C.); Division of Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA (T.R.-C.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (L.H.C.); Departments of Pediatrics (C.B.F.) and Surgery (W.J.G.), Children's Hospital of Philadelphia, PA; Division of Research, Kaiser Permanente Northern California, Oakland, CA (A.S.G.); ArborMetrix Inc, Ann Arbor, MI (P.H.); Department of Pediatrics, George Washington University School of Medicine, Children's National Medical Center, Washington, DC (G.R.M.); and Departments of Critical Care Medicine and Paediatrics, The Hospital for Sick Children and The University of Toronto School of Medicine, ON, Canada (S.M.S.).

The National Heart, Lung, and Blood Institute convened a working group in January 2015 to explore issues related to an integrated data network for congenital heart disease research. The overall goal was to develop a common vision for how the rapidly increasing volumes of data captured across numerous sources can be managed, integrated, and analyzed to improve care and outcomes. This report summarizes the current landscape of congenital heart disease data, data integration methodologies used across other fields, key considerations for data integration models in congenital heart disease, and the short- and long-term vision and recommendations made by the working group.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.115.019506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932890PMC
April 2016

Innovation in Pediatric Cardiac Intensive Care: An Exponential Convergence Toward Transformation of Care.

World J Pediatr Congenit Heart Surg 2015 Oct;6(4):588-96

Pediatric Intensive Care Unit, Cincinnati Children's Hospital, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA.

The word innovation is derived from the Latin noun innovatus, meaning renewal or change. Although companies such as Google and Apple are nearly synonymous with innovation, virtually all sectors in our current lives are imbued with yearn for innovation. This has led to organizational focus on innovative strategies as well as recruitment of chief innovation officers and teams in a myriad of organizations. At times, however, the word innovation seems like an overused cliché, as there are now more than 5,000 books in print with the word "innovation" in the title. More recently, innovation has garnered significant attention in health care. The future of health care is expected to innovate on a large scale in order to deliver sustained value for an overall transformative care. To date, there are no published reports on the state of the art in innovation in pediatric health care and in particular, pediatric cardiac intensive care. This report will address the issue of innovation in pediatric medicine with relevance to cardiac intensive care and delineate possible future directions and strategies in pediatric cardiac intensive care.
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http://dx.doi.org/10.1177/2150135115606087DOI Listing
October 2015

Toward unreasonable effectiveness of cardiac ICU data: artificial intelligence in pediatric cardiac intensive care.

Pediatr Crit Care Med 2014 Jul;15(6):565-7

Division of Pediatric Cardiology; Heart Institute; and, Medical Intelligence and Innovation Institute (MI3), Children's Hospital of Orange County, Orange, CA Pediatric Cardiac Intensive Care Unit, Children's Hospital of Orange County, Orange, CA.

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http://dx.doi.org/10.1097/PCC.0000000000000176DOI Listing
July 2014

Prevention of metabolic decompensation in an infant with mutase deficient methylmalonic aciduria undergoing cardiopulmonary bypass.

World J Pediatr 2014 Feb 25;10(1):83-5. Epub 2014 Jan 25.

Division of Metabolic Disorders, CHOC Children's Foundation, Department of Pediatrics, University of California Irvine School of Medicine, Orange, CA, USA,

Background: Effects of circulatory arrest upon an inborn error of metabolism patient are unknown.

Methods: A retrospective chart review was performed of outcome and biochemical parameters obtained during palliative cardiac surgery for a mutase-deficient methylmalonic aciduria patient with Ebstein's cardiac anomaly was performed.

Results: The levels of ammonia, methylmalonic acid, free carnitine, and propionylcarnitine of the patient were improved. The patient survived surgery following institution of four metabolic treatment principles: 1) restriction of toxic substrate; 2) promotion of anabolism via administration of carbohydrate and lipid calories; 3) administration of detoxifying levocarnitine and sodium benzoate; and 4) cobalamin enzymatic co-factor administration. The patient died from post-operative dysrhythmia and was posthumously determined to have compound heterozygosity for mutations predicting severe, cobalamin non-responsive disease: c.322C>T/c.1233del3 (p.R108C/p.ΔI412).

Conclusion: Metabolic decompensation is preventable during cardiopulmonary bypass and cardioplegia using four principles of metabolic treatment.
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http://dx.doi.org/10.1007/s12519-014-0458-0DOI Listing
February 2014

Primary prevention of sudden cardiac death of the young athlete: the controversy about the screening electrocardiogram and its innovative artificial intelligence solution.

Authors:
Anthony C Chang

Pediatr Cardiol 2012 Mar 12;33(3):428-33. Epub 2012 Feb 12.

Heart Institute, Children's Hospital of Orange County, Orange, CA, USA.

The preparticipation screening for athlete participation in sports typically entails a comprehensive medical and family history and a complete physical examination. A 12-lead electrocardiogram (ECG) can increase the likelihood of detecting cardiac diagnoses such as hypertrophic cardiomyopathy, but this diagnostic test as part of the screening process has engendered considerable controversy. The pro position is supported by argument that international screening protocols support its use, positive diagnosis has multiple benefits, history and physical examination are inadequate, primary prevention is essential, and the cost effectiveness is justified. Although the aforementioned myriad of justifications for routine ECG screening of young athletes can be persuasive, several valid contentions oppose supporting such a policy, namely, that the sudden death incidence is very (too) low, the ECG screening will be too costly, the false-positive rate is too high, resources will be allocated away from other diseases, and manpower is insufficient for its execution. Clinicians, including pediatric cardiologists, have an understandable proclivity for avoiding this prodigious national endeavor. The controversy, however, should not be focused on whether an inexpensive, noninvasive test such as an ECG should be mandated but should instead be directed at just how these tests for young athletes can be performed in the clinical imbroglio of these disease states (with variable genetic penetrance and phenotypic expression) with concomitant fiscal accountability and logistical expediency in this era of economic restraint. This monumental endeavor in any city or region requires two crucial elements well known to business scholars: implementation and execution. The eventual solution for the screening ECG dilemma requires a truly innovative and systematic approach that will liberate us from inadequate conventional solutions. Artificial intelligence, specifically the process termed "machine learning" and "neural networking," involves complex algorithms that allow computers to improve the decision-making process based on repeated input of empirical data (e.g., databases and ECGs). These elements all can be improved with a national database, evidence-based medicine, and in the near future, innovation that entails a Kurzweilian artificial intelligence infrastructure with machine learning and neural networking that will construct the ultimate clinical decision-making algorithm.
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http://dx.doi.org/10.1007/s00246-012-0244-5DOI Listing
March 2012

Determination of cardiac output in critically ill children: are we any closer to the ideal methodology?.

Authors:
Anthony C Chang

Pediatr Crit Care Med 2012 Jan;13(1):99

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http://dx.doi.org/10.1097/PCC.0b013e31822882d8DOI Listing
January 2012

Carotid intima-media thickness is increased in patients with mucopolysaccharidoses.

Mol Genet Metab 2011 Dec 10;104(4):592-6. Epub 2011 Sep 10.

Division of Metabolic Disorders, Pediatric Subspecialty Faculty, CHOC Children's, Orange, CA, USA.

Background: The feasibility of carotid artery intima-media thickness (C-IMT), an established cardiovascular disease marker, as a cardiac risk marker in mucopolysaccharidosis (MPS) patients was explored.

Objectives: To determine if C-IMT is abnormal in MPS versus unaffected controls, and if C-IMT correlates with coronary artery diameter in MPS.

Material And Methods: Measurements of C-IMT via neck ultrasound and echocardiographic parameters, including coronary artery diameters, were obtained from MPS and control patients, and compared.

Results: Sixteen MPS subjects (6 MPS I, 6 MPS II, 2 MPS III, 1 MPS VI, 1 MPS VII) and sixteen age, ethnicity, and gender-matched controls were enrolled. Median MPS and control subject ages were 8.3±4.5 and 8.6±4.3 years, respectively (p=0.73). Mean MPS and control C-IMTs were 0.54±0.070 and 0.48±0.034 mm (p=0.0029). No differences in left main, left anterior descending, or right coronary artery diameters were seen between MPS and controls. A significant proportion of MPS subjects had mitral insufficiency (14/16; p=0.0002), aortic insufficiency (10/16; p=0.0021), and left ventricular dilatation (7/16, p=0.037) versus controls. C-IMT did not correlate significantly with age, height, weight, coronary measurements, or duration of treatment.

Conclusion: C-IMT in MPS patients is increased compared to matched controls, likely reflective of arterial intima-medial glycosaminoglycan accumulation. MPS subjects demonstrated a high percentage of left-sided valvular insufficiency and ventricular dilatation. Additional studies should be performed in MPS patients to determine if C-IMT correlates with arterial elasticity, biomarkers of vascular dysfunction, and higher risk of cardiovascular events.
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http://dx.doi.org/10.1016/j.ymgme.2011.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924772PMC
December 2011

Management of the postoperative pediatric cardiac surgical patient.

Crit Care Med 2011 Aug;39(8):1974-84

Children's Hospital of Orange County, Orange, CA, USA.

Objective: To review the salient aspects and latest advances in the management of the postoperative pediatric cardiac patient.

Data Source: A Medline-based literature source.

Conclusion: The practice of pediatric cardiac intensive care has evolved considerably over the last several years. These efforts are the result of a collaborative effort from all subspecialties involved in the care of pediatric patients with congenital heart disease. Discoveries and innovations that are representative of this effort include the extension of cerebral oximetry from the operating room into the critical care setting; mechanical circulatory devices designed for pediatric patients; and surgery in very low birth weight neonates. Advances such as these impact postoperative management and make the field of pediatric cardiac intensive care an exciting, demanding, and evolving discipline, necessitating the ongoing commitment of various disciplines to pursue a greater understanding of disease processes and how to best go about treating them.
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http://dx.doi.org/10.1097/CCM.0b013e31821b82a6DOI Listing
August 2011

Cardiac intensive care of the adult with congenital heart disease: basic principles in the management of common problems.

World J Pediatr Congenit Heart Surg 2011 Jul;2(3):430-44

Rady Children's Hospital and UCSD School of Medicine, San Diego, CA, USA.

Although there has been an intense interest in the care of the adult with congenital heart disease (ACHD), these guidelines are usually not focused on the concepts of immediate postoperative care. The 2 most common perioperative complications are heart failure and atrial dysrhythmias. The broad etiological categories for ACHD and heart failure include primary pump failure (systolic dysfunction) and hypertrophy (diastolic dysfunction) of the right, left, or single ventricle. Some conditions with a pressure-loaded systemic right ventricle as well as patients with a functionally single ventricle may be particularly prone to develop heart failure; in others, right heart failure may occur in patients with Ebstein anomaly or with tetralogy of Fallot after corrective repair but with varying degrees of pulmonary insufficiency, and left heart failure can be a result of mitral or aortic insufficiency. The management of postoperative atrial tachycardia in the ACHD patient actually begins prior to surgery. Assessment of arrhythmia history, complete determination of risk, inducibility and arrhythmia substrate, preoperative planning of pacing sites, and optimal pacing strategies all assist to bring about optimal postoperative outcomes. Ideal perioperative care of the ACHD involves a multidisciplinary team of pediatric and adult cardiologists, pediatric and adult intensivists, cardiac surgeons, and nursing staff along with a myriad of adult subspecialists such as pulmonology, nephrology, endocrinology, and others including psychiatry.
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http://dx.doi.org/10.1177/2150135111407936DOI Listing
July 2011

Introduction to the proceedings of the eighth international conference of the pediatric cardiac intensive care society.

World J Pediatr Congenit Heart Surg 2011 Jul;2(3):380-1

Divisions of Critical Care and Cardiology, The Congenital Heart Institute of Florida (CHIF), All Children's Hospital - Johns Hopkins Medicine, University of South Florida College of Medicine, Saint Petersburg, FL, USA.

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http://dx.doi.org/10.1177/2150135111406294DOI Listing
July 2011

Quality and safety in the pediatric cardiac intensive care unit: it is time to leave the pit stop and the cockpit and perfect the handover.

Authors:
Anthony C Chang

Pediatr Crit Care Med 2011 May;12(3):361-2

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http://dx.doi.org/10.1097/PCC.0b013e318216d617DOI Listing
May 2011

Mechanisms for progenitor cell-mediated repair for ischemic heart injury.

Curr Stem Cell Res Ther 2012 Jan;7(1):2-14

CHOC Children's Hospital Research Institute, University of California, Irrine, Orange, 92868, USA.

Recent studies have shown that treatments involving injection of stem cells into animals with damaged cardiac tissue result in improved cardiac functionality. Clinical trials have reported conflicting results concerning the recellularization of post-infarct collagen scars. No clear mechanism has so far emerged to fully explain how injected stem cells, specifically the commonly used mesenchymal stem cells (MSC) and endothelial precursor cells (EPC), help heal a damaged heart. Clearly, these injected stem cells must survive and thrive in the hypoxic environment that results after injury for any significant repair to occur. Here we discuss how ischemic preconditioning may lead to increased tolerance of stem cells to these harsh conditions and increase their survival and clinical potential after injection. As injected cells must reach the site in numbers large enough for repair to be functionally significant, homing mechanisms involved in stem cell migration are also discussed. We review the mechanisms of action stem cells may employ once they arrive at their target destination. These possible mechanisms include that the injected stem cells (1) secrete growth factors, (2) differentiate into cardiomyocytes to recellularize damaged tissue and strengthen the post-infarct scar, (3) transdifferentiate the host cells into cardiomyocytes, and (4) induce neovascularization. Finally, we discuss that tissue engineering may provide a standardized platform technology to produce clinically applicable stem cell products with these desired mechanistic capacities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544365PMC
http://dx.doi.org/10.2174/157488812798483449DOI Listing
January 2012

Captopril induced reversible acute renal failure in a premature neonate with double outlet right ventricle and congestive heart failure.

World J Pediatr 2011 Feb 30;7(1):89-91. Epub 2010 Dec 30.

Department of Surgical Intensive Care Unit, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.

Background: captopril is well tolerated in most patients. There is no report of acute deterioration in renal function after administration of captopril in neonates with congestive heart failure secondary to congenital heart defects with large left-to-right shunts.

Methods: we report a premature neonate with double outlet right ventricle and congestive heart failure who developed acute renal failure after administration of captopril at a low dose of 0.1 mg/kg per 8 hours.

Results: on the third day after captopril therapy, the levels of serum creatinine and blood urea nitrogen increased to 2.6 mg/dl and 73 mg/dl respectively, and hyperkalemia appeared. Captopril was discontinued immediately. On the fourth day, the infant developed oliguria which persisted for 24 hours and resolved on the fifth day when the serum potassium normalized to 4.5 mmol/L. The level of serum creatinine peaked at 3.9 mg/dL on the sixth day and gradually decreased to normal on the ninth day after administration of captopril. The captopril-induced acute renal failure resolved completely after cessation of the drug.

Conclusions: attention should be given to captopril therapy in premature neonates with congestive heart failure secondary to congenital heart disease with large left-to-right shunts. Routine hemodynamic examination and biochemical monitoring are suggested before and during captopril therapy.
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http://dx.doi.org/10.1007/s12519-011-0252-1DOI Listing
February 2011

Hemodynamics and cerebral oxygenation following repair of tetralogy of Fallot: the effects of converting from positive pressure ventilation to spontaneous breathing.

Congenit Heart Dis 2010 Sep-Oct;5(5):416-21

Division of Pediatric Critical Care Medicine, Children's Hospital of Orange County, Orange, California 92868, USA.

Purpose: Following corrective surgery for tetralogy of Fallot (TOF), approximately one-third of these patients develop low cardiac output (CO) due to right ventricular (RV) diastolic heart failure. Extubation is beneficial in these patients because the fall in intrathoracic pressure that occurs with conversion from positive pressure breathing to spontaneous breathing improves venous return, RV filling and CO. We hypothesized that if CO were to increase but remain limited following extubation, the obligatory increase in perfusion to the respiratory pump that occurs with loading of the respiratory musculature may occur at the expense of other vital organs, including the brain.

Materials And Methods: We conducted a retrospective analysis of all patients undergoing repair of TOF and monitoring of cerebral oxygenation using near infrared spectroscopy. We evaluated the following parameters two hours prior to and following extubation: mean and systolic arterial blood pressure (MBP, SBP), right atrial pressure (RAP), heart rate (HR) and cerebral oxygenation.

Results: The study included 22 patients. With extubation, MBP and SBP increased significantly from 67.3 ± 6.5 to 71.1 ± 8.4 mm Hg (P= 0.004) and from 87.2 ± 8.6 to 95.9 ± 10.9 mm Hg (P= 0.001), respectively, while the HR remained unchanged (145 vs. 146 bpm). The RAP remained unchanged following extubation (11.9 vs. 12.0 mm Hg). Following extubation, cerebral oxygen saturations increased significantly from 68.5 ± 8.4 to 74.2 ± 7.9% (P < 0.0001). Cerebral oxygen saturations increased by ≥5% in 11 of 22 patients and by ≥10% in 5 of 22 patients.

Conclusion: We conclude that converting from positive pressure ventilation to spontaneous negative pressure breathing following repair of TOF significantly improves arterial blood pressure and cerebral oxygenation.
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http://dx.doi.org/10.1111/j.1747-0803.2010.00445.xDOI Listing
March 2011

Angiotensin Converting Enzyme Inhibitor (ACEI)-Induced Acute Renal Failure in Premature Newborns with Congenital Heart Disease.

J Pediatr Pharmacol Ther 2010 Oct;15(4):290-6

Children's Hospital of Orange County, Orange, California, Department of Pharmacy.

We report three cases of angiotensin converting enzyme inhibitor (ACEI) induced nephrotoxicity in preterm infants with congenital heart disease. Patients developed acute renal failure after starting captopril or enalapril at doses commonly prescribed for term neonates. There was no underlying renal disease found in these infants and the acute renal failure was reversible upon discontinuation of the ACEI. Conservative starting doses of ACEI should be used in patients with multiple risk factors for nephrotoxicity. A summary of previously reported ACEI induced renal failure in premature infants and congenital heart disease is included.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042267PMC
October 2010

Advances in diagnosis and treatment of pulmonary arterial hypertension in neonates and children with congenital heart disease.

World J Pediatr 2010 Feb 9;6(1):13-31. Epub 2010 Feb 9.

Pediatric Cardiac Surgery Foundation, Bangkok, Thailand.

Background: This article aims to review recent advances in the diagnosis and treatment of pulmonary arterial hypertension in neonates and children with congenital heart disease.

Data Sources: Articles on pulmonary arterial hypertension in congenital heart disease were retrieved from PubMed and MEDLINE published after 1958.

Results: A diagnosis of primary (or idiopathic) pulmonary arterial hypertension is made when no known risk factor is identified. Pulmonary arterial hypertension associated with congenital heart disease constitutes a heterogenous group of conditions and has been characterized by congenital systemic-to-pulmonary shunts. Despite the similarities in histologic appearance of pulmonary vascular disease, there are differences between pulmonary arterial hypertension secondary to congenital systemic-to-pulmonary shunts and those with other conditions with respect to pathophysiology, therapeutic strategies, and prognosis. Revision and subclassification within the category of secondary pulmonary arterial hypertension based on pathophysiology were conducted to improve specific treatments. The timing of surgical repair is crucial to prevent and minimize risk of postoperative pulmonary arterial hypertension. Drug therapies including prostacyclin, endothelin-receptor antagonist, phosphodiesterase inhibitor, and nitric oxide have been evolved with promising results in neonates and children.

Conclusions: Among the different forms of congenital heart diseases, an early correction generally prevents subsequent development of pulmonary arterial hypertension. Emerging therapies for treatment of patients with idiopathic pulmonary arterial hypertension also improve quality of life and survival in neonates and children with congenital heart disease associated with pulmonary arterial hypertension. Heart and lung transplantation or lung transplantation in combination with repair of the underlying cardiac defect is a therapeutic option in a minority of patients. Partial repair options are also beneficial in some selected cases. Randomized controlled trials are needed to evaluate the safety and efficacy of these therapies including survival and long-term outcome.
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http://dx.doi.org/10.1007/s12519-010-0002-9DOI Listing
February 2010

[Levosimendan, a new inotropic drug: experience in children with acute heart failure].

Arch Argent Pediatr 2009 Apr;107(2):139-45

Unidad de Cuidados Intensivos UCI 35, Recuperación Cardiovascular, Hospital Nacional de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.

Introduction: Low cardiac output syndrome occurs frequently in pediatric patients after cardiac surgery. Catecholamines are used as inotropic drugs to treat this threatening condition, but may cause undesirable and potentially harmful side effects. This study was performed to evaluate the efficacy and safety of levosimendan (LEVO) in pediatric patients with low cardiac output syndrome.

Patients And Methods: Open prospective, quasi-experimental cohort. LEVO was given as compassionate treatment in patients with refractory post-surgical low cardiac output syndrome. Every patient received an IV infusion of LEVO at 6 microg/kg during a fifteen minutes period, followed by a 24 h IV infusion at 0.1 microg/kg/min. Clinical improvement of cardiac output was the primary end point of the study. Two independent observers performed clinical evaluation, bidimensional echocardiogram, hemodynamic and laboratory tests were performed pre and after LEVO infusion.

Results: LEVO was infused in 18 opportunities (fourteen children). The response was considered successful in 9/18 interventions (50%; p= 0.004). Both inotropic score (12.1 vs. 6,1, p= 0.01) and A-VDO(2)2 (26.78 +/- 11.5% vs. 20.81 +/- 7.72%, p= 0.029) showed reduction, while SvO2 improved (69.5 +/- 11.4% vs. 76 +/- 9.29%, p= 0.03). No adverse effects were noticed. Four patients died, none of them related to LEVO administration.

Conclusions: LEVO improved cardiac output in 50% of the interventions with post-surgical LCOS and no adverse effect was observed.
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http://dx.doi.org/10.1590/S0325-00752009000200008DOI Listing
April 2009

Neonates with congenital cardiac defects and pulmonary hypertension.

Cardiol Young 2009 May;19 Suppl 1:4-7

CHOC Heart Institute, Children's Hospital of Orange County, Orange, California 92868, United States of America.

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http://dx.doi.org/10.1017/S1047951109003874DOI Listing
May 2009

Databases for assessing the outcomes of the treatment of patients with congenital and paediatric cardiac disease--the perspective of critical care.

Cardiol Young 2008 Dec;18 Suppl 2:130-6

Department of Paediatric Intensive Care, The Royal Brompton Hospital, London, United Kingdom.

The development of databases to track the outcomes of children with cardiovascular disease has been ongoing for much of the last two decades, paralleled by the rise of databases in the intensive care unit. While the breadth of data available in national, regional and local databases has grown exponentially, the ability to identify meaningful measurements of outcomes for patients with cardiovascular disease is still in its early stages. In the United States of America, the Virtual Pediatric Intensive Care Unit Performance System (VPS) is a clinically based database system for the paediatric intensive care unit that provides standardized high quality, comparative data to its participants [https://portal.myvps.org/]. All participants collect information on multiple parameters: (1) patients and their stay in the hospital, (2) diagnoses, (3) interventions, (4) discharge, (5) various measures of outcome, (6) organ donation, and (7) paediatric severity of illness scores. Because of the standards of quality within the database, through customizable interfaces, the database can also be used for several applications: (1) administrative purposes, such as assessing the utilization of resources and strategic planning, (2) multi-institutional research studies, and (3) additional internal projects of quality improvement or research.In the United Kingdom, The Paediatric Intensive Care Audit Network is a database established in 2002 to record details of the treatment of all critically ill children in paediatric intensive care units of the National Health Service in England, Wales and Scotland. The Paediatric Intensive Care Audit Network was designed to develop and maintain a secure and confidential high quality clinical database of pediatric intensive care activity in order to meet the following objectives: (1) identify best clinical practice, (2) monitor supply and demand, (3) monitor and review outcomes of treatment episodes, (4) facilitate strategic healthcare planning, (5) quantify resource requirements, and (6) study the epidemiology of critical illness in children.Two distinct physiologic risk adjustment methodologies are the Pediatric Risk of Mortality Scoring System (PRISM), and the Paediatric Index of Mortality Scoring System 2 (PIM 2). Both Pediatric Risk of Mortality (PRISM 2) and Pediatric Risk of Mortality (PRISM 3) are comprised of clinical variables that include physiological and laboratory measurements that are weighted on a logistic scale. The raw Pediatric Risk of Mortality (PRISM) score provides quantitative measures of severity of illness. The Pediatric Risk of Mortality (PRISM) score when used in a logistic regression model provides a probability of the predicted risk of mortality. This predicted risk of mortality can then be used along with the rates of observed mortality to provide a quantitative measurement of the Standardized Mortality Ratio (SMR). Similar to the Pediatric Risk of Mortality (PRISM) scoring system, the Paediatric Index of Mortality (PIM) score is comprised of physiological and laboratory values and provides a quantitative measurement to estimate the probability of death using a logistic regression model.The primary use of national and international databases of patients with congenital cardiac disease should be to improve the quality of care for these patients. The utilization of common nomenclature and datasets by the various regional subspecialty databases will facilitate the eventual linking of these databases and the creation of a comprehensive database that spans conventional geographic and subspecialty boundaries.
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http://dx.doi.org/10.1017/S1047951108002886DOI Listing
December 2008