Publications by authors named "Lazaros Kochilas"

59 Publications

Are Mechanical Prostheses Valid Alternatives To Ross Procedure In Young Children Under 6 Years Old?

Ann Thorac Surg 2020 Dec 23. Epub 2020 Dec 23.

Department of Pediatrics, Emory University.

Background: Aortic valve replacement (AVR) in young children is associated with technical difficulties and potential morbidity. In contrast to the versatile Ross operation, mechanical prostheses (MP) are uncommonly utilized.

Methods: We examined transplant-free survival and cardiac reoperation among 124 small children (1-6 years) who underwent Ross (n=84) or MP (n=40) for congenital disease (1982-2003) using the Pediatric Cardiac Care Consortium database. We explored variables influencing outcomes.

Results: Children who received MP were operated in earlier era, were more likely to have aortic regurgitation, conotruncal abnormalities, prior aortic valve surgery, and to need Konno annular enlargement. While there was no significant difference in hospital mortality (1.2% vs. 5.0%, p=0.24) or 15-year transplant-free survival (94.1% vs. 87.5%, p=0.16) between Ross and MP recipients, survival diverged with later follow-up (91.3% vs. 68.9% respectively at 25-years, p=0.01). On multivariable regression analysis, the association of MP use and transplant-free survival changed over time: (HR=0.8, 95%CI=0.1-4.4, p=0.78) vs. (HR=6.0, 95%CI=0.6-63.1, p=0.13) before and after 17-years. Cumulative incidence of cardiac reoperation at 10-years was 37.7% and 53.6% following Ross and MP, respectively (p=0.05). The most common reoperation following Ross was conduit replacement, and pacemaker+/-AICD, and following MP was pacemaker+/-AICD and redo AVR.

Conclusions: Over the study period, there was a trend for increased Ross utilization. Interestingly, MP use was associated with comparable operative mortality and survival up to 17 years, albeit with higher redo AVR need. On longer follow-up, survival diverged with increased attrition in MP group, likely due to late valve and reoperation-related complications.
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http://dx.doi.org/10.1016/j.athoracsur.2020.12.014DOI Listing
December 2020

Long-Term Survival and Causes of Death in Children with Trisomy 21 After Congenital Heart Surgery.

J Pediatr 2020 Dec 24. Epub 2020 Dec 24.

Long Beach Memorial Heart and Vascular Institute, Long Beach, CA; Children's Heart Institute, MemorialCare Miller Children's and Women's Hospital, Long Beach, CA. Electronic address:

Objective: To evaluate long-term transplant-free survival and causes of death in the trisomy 21 (T21) population after surgery for congenital heart disease (CHD) in comparison with patients who are euploidic.

Study Design: This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, enriched with prospectively collected data from the National Death Index and the Organ Procurement and Transplantation Network for patients with sufficient direct identifiers. Kaplan-Meier survival plots were generated and multivariable Cox proportional hazards models were used to examine risk factors for mortality between patients with T21 and 1:1 matched patients with comparable CHD who are euploidic.

Results: A long-term survival analysis was completed for 3376 patients with T21 (75 155 person-years) who met inclusion criteria. The 30-year survival rate for patients with T21 ranged from 92.1% for ventricular septal defect to 65.3% for complex common atrioventricular canal. Of these, 2185 patients with T21 were successfully matched with a patient who was euploidic. After a median follow-up of 22.86 years (IQR, 19.45-27.14 years), 213 deaths occurred in the T21 group (9.7%) compared with 123 (5.6%) in the euploidic comparators. After adjustment for age, sex, era, CHD complexity, and initial palliation, the hazard ratio of CHD-related mortality was 1.34 times higher in patients with T21 (95% CI, 0.92-1.97; P = .127).

Conclusions: CHD-related mortality for patients with T21 after cardiac surgical intervention is comparable with euploidic comparators. Children with T21 require lifelong surveillance for co-occurring conditions associated with their chromosomal abnormality.
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http://dx.doi.org/10.1016/j.jpeds.2020.12.058DOI Listing
December 2020

Incidence and Timing of Thrombosis After the Norwood Procedure in the Single-Ventricle Reconstruction Trial.

J Am Heart Assoc 2020 12 7;9(24):e015882. Epub 2020 Dec 7.

Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta Department of Pediatrics Emory University Atlanta GA.

Background Thrombosis is common in infants undergoing staged surgeries for single-ventricle congenital heart disease. The reported incidence and timing of thrombosis varies widely, making it difficult to understand the burden of thrombosis and develop approaches for prevention. We aimed to determine the timing and cumulative incidence of thrombosis following the stage I Norwood procedure and identify clinical characteristics associated with thrombosis. Methods and Results We analyzed data from the Pediatric Heart Network Single Ventricle Reconstruction trial from 2005 to 2009 and identified infants with first-time thrombotic events. In 549 infants, the cumulative incidence of thrombosis was 21.2% (n=57) from stage I through stage II. Most events occurred during stage I (n=35/57, 65%), with a median time to thrombosis of 15 days. We used a Cox proportional hazards model to estimate the association of clinical variables with thrombosis. After adjusting for baseline variables, boys had a higher hazard of thrombosis (adjusted hazard ratio [HR], 2.69; 95% CI, 1.44-5.05; =0.002), non-hypoplastic left heart syndrome cardiac anatomy was associated with a higher early hazard of thrombosis (adjusted HR, 3.93; 95% CI, 1.89-8.17; <0.001), and longer cardiopulmonary bypass time was also associated with thrombosis (per 10-minute increase, adjusted HR, 1.07; 95% CI, 1.01-1.12; =0.02). Lower oxygen saturation after the Norwood procedure increased the hazard for thrombosis in the unadjusted model (HR, 1.08; 95% CI, 1.02-1.14; =0.011). Conclusions Thrombosis affects 1 in 5 infants through Stage II discharge, with most events occurring during stage I. Male sex, non-hypoplastic left heart syndrome anatomy, longer cardiopulmonary bypass time, and lower stage I oxygen saturation were associated with thrombosis.
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http://dx.doi.org/10.1161/JAHA.120.015882DOI Listing
December 2020

Major birth defects and cancer.

BMJ 2020 12 2;371:m4464. Epub 2020 Dec 2.

Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

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http://dx.doi.org/10.1136/bmj.m4464DOI Listing
December 2020

Atrioventricular Valve Regurgitation in the Single Ventricle: Back to Hippocrates.

Authors:
Lazaros Kochilas

J Am Coll Cardiol 2020 07;76(4):432-434

Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2020.06.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561464PMC
July 2020

Early characteristics of bone deficits in children with Fontan palliation.

Cardiol Young 2020 Apr 20;30(4):468-475. Epub 2020 Feb 20.

Department of Pediatrics, Emory University, Atlanta, GA, USA.

Background: This is a cross-sectional study aiming to understand the early characteristics and background of bone health impairment in clinically well children with Fontan circulation.

Methods: We enrolled 10 clinically well children with Fontan palliation (operated >5 years before study entrance, Tanner stage ≤3, age 12.1 ± 1.77 years, 7 males) and 11 healthy controls (age 12.0 ± 1.45 years, 9 males) at two children's hospitals. All patients underwent peripheral quantitative CT. For the Fontan group, we obtained clinical characteristics, NYHA class, cardiac index by MRI, dual x-ray absorptiometry, and biochemical studies. Linear regression was used to compare radius and tibia peripheral quantitative CT measures between Fontan patients and controls.

Results: All Fontan patients were clinically well (NYHA class 1 or 2, cardiac index 4.85 ± 1.51 L/min/m2) and without significant comorbidities. Adjusted trabecular bone mineral density, cortical thickness, and bone strength index at the radius were significantly decreased in Fontan patients compared to controls with mean differences -30.13 mg/cm3 (p = 0.041), -0.31 mm (p = 0.043), and -6.65 mg2/mm4 (p = 0.036), respectively. No differences were found for tibial measures. In Fontan patients, the mean height-adjusted lumbar bone mineral density and total body less head z scores were -0.46 ± 1.1 and -0.63 ± 1.1, respectively, which are below the average, but within normal range for age and sex.

Conclusions: In a clinically well Fontan cohort, we found significant bone deficits by peripheral quantitative CT in the radius but not the tibia, suggesting non-weight-bearing bones may be more vulnerable to the unique haemodynamics of the Fontan circulation.
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http://dx.doi.org/10.1017/S1047951120000293DOI Listing
April 2020

Valve Replacement in Children with Single Ventricle Physiology.

Pediatr Cardiol 2020 Jan 16;41(1):129-133. Epub 2019 Nov 16.

Department of Pediatrics, Ward Family Heart Center, Children's Mercy Hospital, 2401 Gillham Rd, Kansas City, MO, 64108, USA.

Severe atrioventricular valve (AVV) or semilunar valve (SLV) regurgitation in the setting of a single ventricle physiology may proceed to valve replacement if repair strategies fail. Outcome data for these children are limited. We present transplant-free survival of a case series of children with single ventricle physiology undergoing either atrioventricular replacement (AVVR) or semilunar valve replacement (SLVR) from a multi-institutional, US-based registry (Pediatric Cardiac Care Consortium-PCCC). Outcomes were derived from PCCC and by linkage with the National Death Index (NDI) and Organ Procurement Transplant Network (OPTN). Fifty children with single ventricle physiology were identified to have received either AVVR (n = 38) or SLVR (n = 12). There were 17 in-hospital deaths including 8 intraoperative deaths (all intraoperative deaths were among children requiring AVVR). The in-hospital mortality was 42% and 8% for AVVR and SLVR, respectively. Among the 33 children surviving to hospital discharge, follow-up was available in 15 (46%). Death or cardiac transplant after hospital discharge occurred in 10-death in 4 (all among those requiring AVVR), cardiac transplant in 6 (2 following AVVR, 4 following SLVR). Valve replacement in children with single ventricle physiology, especially AVVR, is associated with poor outcomes. Alternative palliation strategies should be considered in children with single ventricle physiology with significant AVV or SLV regurgitations.
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http://dx.doi.org/10.1007/s00246-019-02234-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329296PMC
January 2020

Postoperative and long-term outcomes in children with Trisomy 21 and single ventricle palliation.

Congenit Heart Dis 2019 Sep 22;14(5):854-863. Epub 2019 Jul 22.

Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.

Objective: Patients with Trisomy 21 (T21) and single ventricle (SV) physiology present unique challenges compared to euploidic counterparts. This study reports postoperative and long-term outcomes in patients with T21 and SV palliation.

Design: This retrospective cohort study from the Pediatric Cardiac Care Consortium (PCCC) included patients with T21 (<21 years old) that underwent surgical palliation for SV between 1982 and 2008 and control patients without known genetic anomaly following Fontan palliation for similar diagnoses. Kaplan-Meier survival plots were created based on death events obtained from the PCCC and by linkage with the National Death Index (NDI) and the Organ Procurement and Transplantation Network (OPTN) through 2014 for patients with adequate identifiers.

Results: We identified 118 children with T21 who underwent initial surgical SV palliation. Among 90 (75.6%) patients surviving their first surgery, 66 (73.3%) underwent Glenn anastomosis and 25 (27.8%) completed Fontan palliation with in-hospital survival of 80.3% and 76.0%, respectively. Fifty-three patients had sufficient identifiers for PCCC-NDI-OPTN linkage. Ten-year survival, conditioned on discharge alive after the Fontan procedure, was 66.7% compared to 92.2% for 51 controls without genetic anomaly (P = .001). Median age at death for T21 patients following initial surgical SV palliation was 2.69 years (IQR 1.34-7.12) with most deaths (89.2%) attributed to the underlying congenital heart disease (CHD).

Conclusions: Children with T21 and SV are at high risk for procedural and long-term mortality related to their genetic condition and underlying CHD. Nevertheless, a select group of patients can successfully complete Glenn or Fontan palliation, reaching satisfactory long-term survival.
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http://dx.doi.org/10.1111/chd.12823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329297PMC
September 2019

Long-Term Survival of Patients With Coarctation Repaired During Infancy (from the Pediatric Cardiac Care Consortium).

Am J Cardiol 2019 09 6;124(5):795-802. Epub 2019 Jun 6.

Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; Children's Healthcare of Atlanta, Atlanta, Georgia.

Patients who undergo coarctation repair during infancy have excellent early survival but long-term survival is unknown. We aimed to describe the long-term survival of patients with coarctation repaired during infancy and determine predictors of mortality. We performed a retrospective cohort study using data from the Pediatric Cardiac Care Consortium for patients with coarctation who underwent surgical repair before 12 months of age between 1982 and 2003. Long-term transplant-free survival was obtained by linkage with the National Death Index and the Organ Sharing Procurement Network. Kaplan Meier survival plots were constructed, and univariate and multivariable analyses were performed to determine predictors of mortality. We identified 2,424 coarctation patients who met inclusion criteria. At 20 years postoperatively, 94.5% of all patients and 95.8% of those discharged after initial operation remained alive, respectively. Significant multivariable predictors of mortality included surgical weight <2.5 kg (hazard ratio [HR] 3.70, 95% confidence interval [CI] 2.19 to 6.24), presence of a genetic syndrome (HR 2.40, 95% CI 1.13 to 5.10), and repair before 1990 (HR 1.91, 95% CI 1.09 to 3.34). None of the other factors examined including age at repair, gender, coarctation type, or surgical approach were found to be statistically significant. Over half of the deaths were due to the underlying congenital heart disease or other cardiovascular etiology. Overall long-term survival of patients who undergo coarctation repair during infancy is excellent. However, patients do experience small continued survival attrition throughout early adulthood. Ongoing monitoring of this cohort is necessary to assess late mortality risk.
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http://dx.doi.org/10.1016/j.amjcard.2019.05.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702038PMC
September 2019

We Can Learn From the Past, but We Must Pave the Future of Congenital Heart Disease Research-Reply.

JAMA Cardiol 2019 06;4(6):600

Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.

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http://dx.doi.org/10.1001/jamacardio.2019.1076DOI Listing
June 2019

Long-term outcomes after intervention for pulmonary atresia with intact ventricular septum.

Heart 2019 07 2;105(13):1007-1013. Epub 2019 Feb 2.

Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.

Objective: Pulmonary atresia with intact ventricular septum (PA/IVS) can be treated by various operative and catheter-based interventions. We aim to understand the long-term transplant-free survival of patients with PA/IVS by treatment strategy.

Methods: Cohort study from the Pediatric Cardiac Care Consortium, a multi-institutional registry with prospectively acquired outcome data after linkage with the National Death Index and the Organ Procurement and Transplantation Network.

Results: Eligible patients underwent neonatal surgery or catheter-based intervention for PA/IVS between 1982 and 2003 (median follow-up of 16.7 years, IQR: 12.6-22.7). Over the study period, 616 patients with PA/IVS underwent one of three initial interventions: aortopulmonary shunt, right ventricular decompression or both. Risk factors for death at initial intervention included earlier birth era (1982-1992), chromosomal abnormality and atresia of one or both coronary ostia. Among survivors of neonatal hospitalisation (n=491), there were 99 deaths (4 post-transplant) and 10 transplants (median age of death or transplant 0.7 years, IQR: 0.3-1.8 years). Definite repair or last-stage palliation was achieved in the form of completed two-ventricle repair (n=201), one-and-a-half ventricle (n=39) or Fontan (n=96). Overall 20-year survival was 66%, but for patients discharged alive after definitive repair, it reached 97.6% for single-ventricle patients, 90.9% for those with one-and-a-half ventricle and 98.0% for those with complete two-ventricle repair (log-rank p=0.052).

Conclusions: Transplant-free survival in PA/IVS is poor due to significant infantile and interstage mortality. Survival into early adulthood is excellent for patients reaching completion of their intended path independent of type of repair.
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http://dx.doi.org/10.1136/heartjnl-2018-314124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571047PMC
July 2019

Mortality Following Pediatric Congenital Heart Surgery: An Analysis of the Causes of Death Derived From the National Death Index.

J Am Heart Assoc 2018 11;7(22):e010624

2 Children's Healthcare of Atlanta Atlanta GA.

Background Prior research has focused on early outcomes after congenital heart surgery, but less is known about later risks. We aimed to determine the late causes of death among children (<21 years of age) surviving their initial congenital heart surgery. Methods and Results This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a US-based registry of interventions for congenital heart defects (CHD). Excluding patients with chromosomal anomalies or inadequate identifiers, we matched those surviving their first congenital heart surgery (1982-2003) against the National Death Index through 2014. Causes of death were obtained from the National Death Index to calculate cause-specific standardized mortality ratios (SMRs). Among 31 132 patients, 2527 deaths (8.1%) occurred over a median follow-up period of 18 years. Causes of death varied by time after surgery and severity of CHD but, overall, 69.9% of deaths were attributed to the CHD or another cardiovascular disorder, with a SMR for CHD/cardiovascular disorder of 67.7 (95% confidence interval: 64.5-70.8). Adjusted odds ratios revealed increased risk of death from CHD/cardiovascular disorder in females [odds ratio=1.28; 95% confidence interval (1.04-1.58); P=0.018] with leading cardiovascular disorder contributing to death being cardiac arrest (16.8%), heart failure (14.8%), and arrhythmias (9.1%). Other major causes of death included coexisting congenital malformations (4.7%, SMR: 7.0), respiratory diseases (3.6%, SMR: 8.2), infections (3.4%, SMR: 8.2), and neoplasms (2.1%, SMR: 1.9). Conclusions Survivors of congenital heart surgery face long-term risks of premature mortality mostly related to residual CHD pathology, heart failure, and arrhythmias, but also to other noncardiac conditions. Ongoing monitoring is warranted to identify target factors to address residual morbidities and improve long-term outcomes.
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http://dx.doi.org/10.1161/JAHA.118.010624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404427PMC
November 2018

Long-Term Outcomes in Single-Ventricle Congenital Heart Disease.

Circulation 2018 12;138(23):2718-2720

Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (M.E.O., J.H.K., D.S., L.K.K.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309811PMC
December 2018

Long-term Outcomes of Tetralogy of Fallot: A Study From the Pediatric Cardiac Care Consortium.

JAMA Cardiol 2019 01;4(1):34-41

Department of Pediatrics, Emory University School of Medicine.

Importance: Tetralogy of Fallot (TOF) is a surgically repairable form of cyanotic congenital heart disease. Multicenter data for long-term survival following repair are sparse.

Objective: To evaluate the long-term transplant-free survival of TOF by surgical strategy adjusted for era and patient characteristics.

Design, Setting, And Participants: Retrospective cohort study enriched with data from the National Death Index and the Organ Procurement and Transplantation Network through 2014. Multicenter cohort from the Pediatric Cardiac Care Consortium (PCCC), a large, US-based clinical registry for interventions for congenital heart disease. The cohort included patients with adequate identifiers for linkage with the National Death Index and the Organ Procurement and Transplantation Network who were enrolled in the PCCC registry between 1982 and 2003 and survived surgical repair of simple TOF. Data were analyzed between September 2015 and April 2018.

Exposures: We examined patient-associated and surgery-associated risk factors affecting survival.

Main Outcomes And Measures: We analyzed the transplant-free survival during early (<6 years) and late (≥6 years) phase after TOF surgical repair.

Results: Of the 3283 patients who survived repair for simple TOF and met the study's inclusion criteria, 56.4% were male and 43.6% were female. Twenty-five-year survival following TOF repair was 94.5%. Multivariable analysis demonstrated increased risk of early mortality with staged repair (HR, 2.68; 95% CI, 1.59-4.49) and non-valve-sparing operation (HR, 3.76; 95% CI, 1.53-9.19). Presence of a genetic abnormality was associated with increased risk of death both in the early (HR, 3.64; 95% CI, 2.05-6.47) and late postoperative phase (HR, 4.41; 95% CI, 2.62-7.44).

Conclusions And Relevance: Long-term survival after simple TOF repair is excellent. Staged repair and non-valve-sparing operations were negatively associated with survival in the early postrepair phase but not the late postrepair phase. These data are important for patients with repaired TOF and their caretakers and may guide surgical strategies for optimizing the long-term outcomes of this population.
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http://dx.doi.org/10.1001/jamacardio.2018.4255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439686PMC
January 2019

Factors Associated With Interstage Mortality Following Neonatal Single Ventricle Palliation.

World J Pediatr Congenit Heart Surg 2018 11;9(6):616-623

1 Division of Cardiothoracic Surgery, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.

Background: Several advances have led to improved hospital survival following neonatal palliation (NP) of single ventricle (SV) anomalies. Nonetheless, a number of patients continue to suffer from interstage mortality (ISM) prior to subsequent Glenn. We aim to study patients' characteristics and anatomic, surgical, and clinical details associated with ISM.

Methods: A total of 453 SV neonates survived to hospital discharge following NP. Competing risk analysis modeled events after NP (Glenn, transplantation, or death) and examined variables associated with ISM.

Results: Competing risk analysis showed that one year following NP, 10% of patients had died, 87% had progressed to Glenn, 1% had received heart transplantation, and 2% were alive without subsequent surgery. On multivariable analysis, factors associated with ISM were as follows: weight ≤2.5 kg (hazard ratio, HR = 2.4 [1.2-4.6], P = .013), premature birth ≤36 weeks (HR = 2.0 [1.0-4.0], P = .05), genetic syndromes (HR = 3.2 [1.7-6.1], P < .001), unplanned cardiac reoperation (HR = 2.1 [1.0-4.4], P = .05), and prolonged intensive care unit (ICU) stay >30 days following NP (HR = 2.5 [1.4-4.5], P < .001). Palliative surgery type (shunt, Norwood, band) was not associated with ISM, although aortopulmonary shunt circulation after Norwood was (HR = 5.4 [1.5-19.2] P = .01). Of interest, underlying SV anatomy was not associated with ISM (HR = 1.1 [0.6-2.2], P = .749).

Conclusions: In our series, ISM following NP occurred in 10% of hospital survivors. As opposed to hospital death, underlying SV anomaly was not associated with ISM. Conversely, several patient factors (prematurity, low weight, and genetic syndromes) and clinical factors (unplanned reoperation and prolonged ICU stay following NP) were associated with ISM. Vigilant outpatient management that is individualized to specific clinical and social needs, taking into account all associated factors, is warranted to improve survival in high-risk patients.
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http://dx.doi.org/10.1177/2150135118787723DOI Listing
November 2018

Outcomes of Mechanical Mitral Valve Replacement in Children.

Ann Thorac Surg 2019 01 26;107(1):143-150. Epub 2018 Sep 26.

Department of Pediatrics, Ward Family Heart Center, Children's Mercy Hospital, Kansas City, Missouri. Electronic address:

Background: Mitral valve anomalies in children are rare but frequently severe, recalcitrant, and not often amenable to primary repair, necessitating mechanical mitral valve replacement (M-MVR). This study examined outcomes of a cohort undergoing a first M-MVR at age younger than 21 years.

Methods: We queried the Pediatric Cardiac Care Consortium, a multi-institutional United States-based cardiac intervention registry, for patients undergoing first M-MVR for 2-ventricle congenital heart disease. Survival and transplant status through 2014 were obtained from Pediatric Cardiac Care Consortium and linkage with the National Death Index and the Organ Procurement and Transplantation Network.

Results: We identified 441 patients (median age, 4.3 years; interquartile range, 1.3 to 10.1 years) meeting study criteria. The commonest disease necessitating M-MVR was atrioventricular canal (44.3%). Early mortality (death <90 days after M-MVR) was 11.1%; there was increased risk of early death if age at M-MVR was younger than 2 years (odds ratio, 7.8; 95% confidence interval [CI], 1.1 to 56.6) and with concurrent other mechanical valve placement (odds ratio, 8.5; 95% CI, 2.0 to 35.6). In those surviving more than 90 days after M-MVR, transplant-free survival was 76% at 20 years of follow-up (median follow-up, 16.6 years; interquartile range, 11.9 to 21.3 years). Adjusted analysis in those who survived more than 90 days showed elevated risk of death/transplant for boys (hazard ratio, 1.5; 95% CI, 1.0 to 2.3), age at M-MVR younger than 2 years (10-year survival: hazard ratio, 4.3; 95% CI, 1.2 to 15.1), and nonbileaflet prosthesis placement (hazard ratio, 2.4; 95% CI, 1.3 to 4.3).

Conclusions: M-MVR is a viable strategy in children with unrepairable mitral valve disease. Age younger than 2 years at the first M-MVR is associated with significant early risk of death and poorer long-term survival.
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http://dx.doi.org/10.1016/j.athoracsur.2018.07.069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288372PMC
January 2019

Long-Term Survival After Arterial Versus Atrial Switch in d-Transposition of the Great Arteries.

Ann Thorac Surg 2018 12 31;106(6):1827-1833. Epub 2018 Aug 31.

Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; Emory University Rollins School of Public Health, Atlanta, Georgia; Children's Healthcare of Atlanta, Atlanta, Georgia. Electronic address:

Background: The arterial switch operation (ASO) became the procedure of choice for dextro-transposition of the great arteries (d-TGA) nearly 30 years ago, but the long-term results of this operation are unknown. We aimed to compare the long-term transplant-free survival of patients with d-TGA who underwent ASO versus atrial switch in the Pediatric Cardiac Care Consortium.

Methods: We performed a retrospective cohort study of d-TGA patients undergoing ASO or atrial switch in the United States between 1982 and 1991. Long-term transplant-free survival was obtained by linking Pediatric Cardiac Care Consortium data with the National Death Index and the Organ Procurement and Transplant Network. Kaplan-Meier survival plots were constructed, and multivariable regression was used to compare long-term transplant-free survival.

Results: Of 554 d-TGA patients who underwent ASO (n = 259) or atrial switch (n = 295), the 20-year overall transplant-free survival was 82.1% for those undergoing ASO and 76.3% for those who had atrial switch procedure. Adjusted overall transplant-free survival beyond 10 years after operation was superior for ASO compared with atrial switch (hazard ratio 0.07, 95% confidence interval: 0.01 to 0.52, p = 0.009). During this period, the ASO had higher in-hospital mortality than the atrial switch (21.6% versus 12.9%, p = 0.007). After excluding patients with in-hospital mortality, the transplant-free survival 20 years after repair was 97.7% for the ASO patients versus 86.3% for the atrial switch patients.

Conclusions: Despite initial higher in-hospital mortality for ASO during the study period, there is a significant long-term transplant-free survival advantage for ASO as compared with atrial switch for d-TGA surgery. Ongoing monitoring is required to assess late risk of cardiovascular disease.
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http://dx.doi.org/10.1016/j.athoracsur.2018.06.084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240478PMC
December 2018

Trends in Long-Term Mortality After Congenital Heart Surgery.

J Am Coll Cardiol 2018 05;71(21):2434-2446

Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia. Electronic address:

Background: Congenital heart surgery has improved the survival of patients with even the most complex defects, but the long-term survival after these procedures has not been fully described.

Objectives: The purpose of this study was to evaluate the long-term survival of patients (age <21 years) who were operated on for congenital heart defects (CHDs).

Methods: This study used the Pediatric Cardiac Care Consortium data, a U.S.-based, multicenter registry of pediatric cardiac surgery. Survival analysis included 35,998 patients who survived their first congenital heart surgery at <21 years of age and had adequate identifiers for linkage with the National Death Index through 2014. Survival was compared to that in the general population using standardized mortality ratios (SMRs).

Results: After a median follow-up of 18 years (645,806 person-years), 3,191 deaths occurred with an overall SMR of 8.3 (95% confidence interval [CI]: 8.0 to 8.7). The 15-year SMR decreased from 12.7 (95% CI: 11.9 to 13.6) in the early era (1982 to 1992) to 10.0 (95% CI: 9.3 to 10.8) in the late era (1998 to 2003). The SMR remained elevated even for mild forms of CHD such as patent ductus arteriosus (SMR 4.5) and atrial septal defects (SMR 4.9). The largest decreases in SMR occurred for patients with transposition of great arteries (early: 11.0 vs. late: 3.8; p < 0.05), complete atrioventricular canal (31.3 vs. 15.3; p < 0.05), and single ventricle (53.7 vs. 31.3; p < 0.05).

Conclusions: In this large U.S. cohort, long-term mortality after congenital heart surgery was elevated across all forms of CHD. Survival has improved over time, particularly for severe defects with significant changes in their management strategy, but still lags behind the general population.
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http://dx.doi.org/10.1016/j.jacc.2018.03.491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978758PMC
May 2018

A Modified Algorithm for Critical Congenital Heart Disease Screening Using Pulse Oximetry.

Pediatrics 2018 05;141(5)

Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia;

: media-1vid110.1542/5727212367001PEDS-VA_2017-4065 OBJECTIVES: Determine the performance of the American Academy of Pediatrics (AAP) critical congenital heart disease (CCHD) newborn screening algorithm and the impact of an alternative algorithm.

Methods: Screening was performed on term infants without a known CCHD diagnosis at or near 24 hours of age at a tertiary birth hospital by using the AAP algorithm from 2013 to 2016. Retrospective review from the birth hospital and the area's sole pediatric cardiac center identified true- and false-positives and true- and false-negatives. A simulation study modeled the results of a modified screening algorithm with a single repeat pulse oximetry test instead of 2.

Results: Screening results were collected on 77 148 newborns . By using the current AAP algorithm, 77 114 (99.96%) infants passed screening, 18 infants failed for an initial saturation of <90%, and 16 failed after not attaining a passing pulse oximetry level after 3 tests. There was 1 true-positive (total anomalous pulmonary venous return), 33 false-positives, and 6 false-negatives, yielding an overall specificity of 99.96%, a sensitivity of 14.3%, and a false-positive rate of 0.043%. Among false-positives, 10 (31.3%) had significant non-CCHD disease. Simulating the modified algorithm, sensitivity remained at 14.3%, and the false-positive rate increased to 0.054%.

Conclusions: Although CCHD screening in a tertiary care birth hospital may not detect many new cases of CCHD, it can detect other important diseases in newborns. Modifying the screening algorithm to 1 repeat pulse oximetry test instead of 2 may detect additional infants with significant disease without a substantial increase in the false-positive rate.
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http://dx.doi.org/10.1542/peds.2017-4065DOI Listing
May 2018

Outcomes after surgical coronary artery revascularisation in children with congenital heart disease.

Heart 2018 09 22;104(17):1417-1423. Epub 2018 Feb 22.

Department of Pediatrics, Emory University, Atlanta, Georgia, USA.

Objective: Surgical coronary revascularisation in children with congenital heart disease (CHD) is a rare event for which limited information is available. In this study, we review the indications and outcomes of surgical coronary revascularisation from the Pediatric Cardiac Care Consortium, a large US-based multicentre registry of interventions for CHD.

Methods: This is a retrospective cohort study of children (<18 years old) with CHD who underwent surgical coronary revascularisation between 1982 and 2011. In-hospital mortality and graft patency data were obtained from the registry. Long-term transplant-free survival through 2014 was achieved for patients with adequate identifiers via linkage with the US National Death Index and the Organ Procurement and Transplantation Network.

Results: Coronary revascularisation was accomplished by bypass grafting (n=72, median age 6.8 years, range 3 days-17.4 years) or other operations (n=65, median age 2.6 years, range 5 days-16.7 years) in 137 patients. Most revascularisations were related to the aortic root (61.3%) or coronary anomalies (27.7%), but 10.9% of them were unrelated to either of them. Twenty in-hospital deaths occurred, 70% of them after urgent 'rescue' revascularisation in association with another operation. Long-term outcomes were available by external linkage for 54 patients surviving to hospital discharge (median follow-up time 15.0 years, max follow-up 29.8 years) with a 15-year transplant-free survival of 91% (95% CI 83% to 99%).

Conclusions: Surgical coronary revascularisation can be performed in children with CHD with acceptable immediate and long-term survival. Outcomes are dependent on indication, with the highest mortality in rescue procedures.
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http://dx.doi.org/10.1136/heartjnl-2017-312652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092219PMC
September 2018

Design for the sacubitril/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study).

Am Heart J 2017 Nov 17;193:23-34. Epub 2017 Jul 17.

Novartis Pharmaceuticals Corporation, Shanghai, China. Electronic address:

Background: Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown.

Study Design: This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52-week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy.

Conclusion: The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function.
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http://dx.doi.org/10.1016/j.ahj.2017.07.006DOI Listing
November 2017

Long-Term Transplant-Free Survival After Repair of Total Anomalous Pulmonary Venous Connection.

Ann Thorac Surg 2018 Jan 25;105(1):186-192. Epub 2017 Aug 25.

Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta, Georgia.

Background: Long-term survival, risk of transplantation, and causes of death after repair of total anomalous pulmonary venous connection (TAPVC) remain unknown. By linking the Pediatric Cardiac Care Consortium with the National Death Index and the United Network for Organ Sharing, we evaluated long-term transplant-free survival in children undergoing repair of TAPVC.

Methods: We identified 777 infants within the Pediatric Cardiac Care Consortium who underwent TAPVC repair (median 21 days; interquartile range, 5 to 80) and had sufficient personal identifiers for linkage with the National Death Index and United Network for Organ Sharing. Sixty-six deaths, ten cardiac transplantations, and one bilateral lung transplantation had occurred by the end of 2014. Data collected included age and weight at time of procedure, TAPVC type, associated cardiac lesions, and postoperative length of stay. The study cohort was divided into simple and complex TAPVC based on the presence of an associated cardiac lesion. Parametric survival plots were constructed, and risk factor analyses were performed to identify demographic and clinical characteristics associated with long-term outcomes.

Results: Mortality or need for transplantation was 9.7% with a median follow-up of 18.4 years and a median age of death or transplant of 0.74 years. The risk of mortality and transplant after TAPVC repair was highest during the first 18 months after hospital discharge. Cardiac causes accounted for the majority of deaths. Multivariate regression models for transplant-free survival demonstrated that complex TAPVC, mixed TAPVC, and postoperative length of stay were associated with increased risk of death/transplant.

Conclusions: Transplant-free survival after TAPVC repair is excellent, with most deaths or transplant events occurring early. Factors associated with the worst long-term outcomes included complex TAPVC, mixed TAPVC, and prolonged postoperative length of stay.
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http://dx.doi.org/10.1016/j.athoracsur.2017.05.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729081PMC
January 2018

The thoracic duct and the Fontan patient.

Echocardiography 2017 Sep 22;34(9):1347-1352. Epub 2017 Aug 22.

Emory University, Atlanta, GA, USA.

Background: Ultrasound imaging of adults with heart failure and increased central venous pressure (CVP) has shown significant thoracic duct (TD) dilation from impedance in lymphatic drainage. Elevated CVP and abnormal lymphatic drainage are implicated in severe Fontan complications, including protein losing enteropathy (PLE) and plastic bronchitis (PB). Systematic studies of TD and lymphatic circulation in children are limited, and their cervical TD normative values have not been established.

Methods: Thoracic duct imaging was attempted prospectively during routine echocardiograms performed 7/2014-9/2016 in children 5-21 years old with normal cardiovascular physiology and Fontan palliation. TD insertion to the central venous system (lympho-venous junction) was assessed with an S12-4 MHz transducer. For the first 34 patients, only TD ostia were measured, but ostium shape variability at the lympho-venous junction led to including the TD arch 5-10 mm proximal to the ostium for the remaining cohort.

Results: Seventy-nine total subjects were studied: 58 controls, 13 Fontan patients with normal systemic ventricular ejection fraction (EF) (>50%), and 8 Fontan patients with decreased EF (≤50%). Combined Fontan subjects had larger TD ostial diameters compared to controls when normalized by body surface area (median 2.6 mm/m vs. 2 mm/m ) (P=.04).

Conclusion: To our knowledge, this is the first systematic study of ultrasonographic TD imaging in children. Fontan patients have larger TD diameters, reflecting the impaired lymphatic circulation in patients with this physiology. Further research may provide important associations between sonographic TD features with the functional status of patients with Fontan circulation.
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http://dx.doi.org/10.1111/echo.13639DOI Listing
September 2017

Long-Term Outcomes of Children With Trisomy 13 and 18 After Congenital Heart Disease Interventions.

Ann Thorac Surg 2017 Jun 26;103(6):1941-1949. Epub 2017 Apr 26.

Miller Children's and Women's Hospital, Long Beach, California. Electronic address:

Background: The purpose of this study is to report short- and long-term outcomes after congenital heart defect (CHD) interventions in patients with trisomy 13 or 18.

Methods: A retrospective review of the Pediatric Cardiac Care Consortium (PCCC) identified children with trisomy 13 or 18 with interventions for CHD between 1982 and 2008. Long-term survival and cause of death were obtained through linkage with the National Death Index.

Results: A total of 50 patients with trisomy 13 and 121 patients with trisomy 18 were enrolled in PCCC between 1982 and 2008; among them 29 patients with trisomy 13 and 69 patients with trisomy 18 underwent intervention for CHD. In-hospital mortality rates for patients with trisomy 13 or trisomy 18 were 27.6% and 13%, respectively. Causes of in-hospital death were primarily cardiac (64.7%) or multiple organ system failure (17.6%). National Death Index linkage confirmed 23 deaths after discharge. Median survival (conditioned to hospital discharge) was 14.8 years (95% confidence interval [CI]: 12.3 to 25.6 years) for patients with trisomy 13 and 16.2 years (95% CI: 12 to 20.4 years) for patients with trisomy 18. Causes of late death included cardiac (43.5%), respiratory (26.1%), and pulmonary hypertension (13%).

Conclusions: In-hospital mortality rate for all surgical risk categories was higher in patients with trisomy 13 or 18 than that reported for the general population. However, patients with trisomy 13 or 18, who were selected as acceptable candidates for cardiac intervention and who survived CHD intervention, demonstrated longer survival than previously reported. These findings can be used to counsel families and make program-level decisions on offering intervention to carefully selected patients.
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http://dx.doi.org/10.1016/j.athoracsur.2017.02.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526352PMC
June 2017

Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population.

Cardiol Young 2017 Jan;27(1):59-68

7Department of Pediatrics,Division of Cardiology,The Children's Hospital of Philadelphia,Philadelphia,PennsylvaniaUnited States of America.

Background: Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients. Methods and results This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman's Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6-33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (-0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (-0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63-0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].

Conclusions: Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
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http://dx.doi.org/10.1017/S1047951116000093DOI Listing
January 2017

Reply.

J Pediatr 2017 04 15;183:201. Epub 2016 Dec 15.

Department of Pediatrics Emory University School of Medicine; Children's Healthcare of Atlanta Atlanta, Georgia.

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http://dx.doi.org/10.1016/j.jpeds.2016.11.061DOI Listing
April 2017

Databases for Congenital Heart Defect Public Health Studies Across the Lifespan.

J Am Heart Assoc 2016 10 26;5(11). Epub 2016 Oct 26.

Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.

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http://dx.doi.org/10.1161/JAHA.116.004148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210337PMC
October 2016

Letter by Kochilas et al Regarding Article, "Report of the National Heart, Lung, and Blood Institute Working Group: An Integrated Network for Congenital Heart Disease Research".

Circulation 2016 09;134(12):e256-7

From Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta, GA (L.K.K., M.E.O.); and Department of Pediatrics, University of Minnesota, Minneapolis (L.G.S.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.023194DOI Listing
September 2016

In-Hospital Vital Status and Heart Transplants After Intervention for Congenital Heart Disease in the Pediatric Cardiac Care Consortium: Completeness of Ascertainment Using the National Death Index and United Network for Organ Sharing Datasets.

J Am Heart Assoc 2016 08 9;5(8). Epub 2016 Aug 9.

Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, GA.

Background: The long-term outcomes of patients undergoing interventions for congenital heart disease (CHD) remain largely unknown. We linked the Pediatric Cardiac Care Consortium (PCCC) with the National Death Index (NDI) and the United Network for Organ Sharing Dataset (UNOS) registries to study mortality and transplant occurring up to 32 years postintervention. The objective of the current analysis was to determine the sensitivity of this linkage in identifying patients who are known to have died or undergone heart transplant.

Methods And Results: We used direct identifiers from 59 324 subjects registered in the PCCC between 1982 and 2003 to test for completeness of case ascertainment of subjects with known vital and heart transplant status by linkage with the NDI and UNOS registries. Of the 4612 in-hospital deaths, 3873 were identified by the NDI as "true" matches for a sensitivity of 84.0% (95% CI, 82.9-85.0). There was no difference in sensitivity across 25 congenital cardiovascular conditions after adjustment for age, sex, race, presence of first name, death year, and residence at death. Of 455 known heart transplants in the PCCC, there were 408 matches in the UNOS registry, for a sensitivity of 89.7% (95% CI, 86.9-92.3). An additional 4851 deaths and 363 transplants that occurred outside the PCCC were identified through 2014.

Conclusions: The linkage of the PCCC with the NDI and UNOS national registries is feasible with a satisfactory sensitivity. This linkage provides a conservative estimate of the long-term death and heart transplant events in this cohort.
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http://dx.doi.org/10.1161/JAHA.116.003783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015299PMC
August 2016

Pulse oximetry screening: a review of diagnosing critical congenital heart disease in newborns.

Med Devices (Auckl) 2016 11;9:199-203. Epub 2016 Jul 11.

Children's Healthcare of Atlanta, Emory University, Atlanta, GA, USA.

Congenital heart disease (CHD) is one of the most common birth defects, with an incidence of nine out of every 1,000 live births. The mortality of infants with CHD has decreased over the past 3 decades, but significant morbidity and mortality continue to occur if not diagnosed shortly after birth. Pulse oximetry was recommended as a screening tool to detect critical CHD in 2011 by the American Academy of Pediatrics and the American Heart Association. Pulse oximetry is a tool to measure oxygen saturation, and based on the presence of hypoxemia, many cardiac lesions are detected. Due to its ease of application to the patient, providing results in a timely manner and without the need for calibrating the sensor probe, pulse oximetry offers many advantages as a screening tool. However, pulse oximetry has also important limitations of which physicians should be aware to be able to assess the significance of the pulse oximetry measurement for a given patient. This review aims to highlight the benefits and shortcomings of pulse oximetry within the context of screening for critical CHD and suggests future avenues to cover existing gaps in current practices.
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http://dx.doi.org/10.2147/MDER.S102146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946827PMC
July 2016