Significant Congenital Heart Disease Research Articles

PIN20 - Respiratory Illness (RI) and Respiratory Syncytial Virus (RSV)-Related Hospitalization (RSVH) in Infants with Congenital Diaphragmatic Hernia (CDH) in the Caress Registry (2005-2017)

To compare the hazard ratio for RI hospitalization (RIH) and RSVH in CDH infants versus: 1) non- risk infants (NR; those without morbidities, who received RSV prophylaxis as part of multiple births) and 2) infants prophylaxed for standard indications (SI; prematurity ≤35 weeks gestational age, chronic lung disease or significant congenital heart disease) in the Canadian RSV Evaluation Study of Palivizumab (CARESS). CARESS is a prospective study of children who received ≥1 injection of palivizumab across 32 Canadian sites. Neonatal and demographic data were collected at enrolment. Utilization, adherence, and respiratory illness event data were collected monthly. Demographic comparisons were performed using t-tests and chi-square tests. Cox proportional hazards analyses were conducted to compare RIH and RSVH risks across groups adjusted for potential confounders. 25,003 infants were enrolled; 163 CDH, 339 NR, and 20,551 SI. Palivizumab adherence, defined as receiving all expected injections during the RSV season within appropriate dose intervals, was 75% overall and similar across groups. 1724 infants were hospitalized on 2054 occasions (crude RIH rates: CDH 8.6%; NR: 2.4%; SI: 6.2%). CDH infants had a significantly increased RIH risk versus NR (HR=2.6, 95%CI 1.0-6.7, p=0.05) but not SI infants (HR= 1.0, 95%CI 0.6-1.8, p=0.92). Crude RSVH rates were: 0.6% (CDH), 0.3% (NR), and 1.3% (SI), with no significant difference in RSVH risk between CDH infants and the other two groups (NR: HR= 2.5, 95%CI 0.2-40.4, p=0.52; SI: HR= 0.6, 95%CI 0.1-4.3, p=0.61). Due to lung abnormalities and complex ventilation modalities in the neonatal period, CDH infants had an approximately 3-fold increased risk of RIH compared to NR but not SI infants. RSVH risk was similar across all groups. These findings imply that CDH infants may benefit from palivizumab, similar to other high risk groups.

Use of Palivizumab in Germany - Report from the German Synagis™ Registry 2009 - 2016.

Following national recommendations, palivizumab is administered in Germany to high-risk infants to prevent hospitalizations related to Respiratory Syncytial Virus infection. In this post marketing observational study (German SYNAGIS™ Registry) data on risk factors and the clinical course of children, who received at least one palivizumab injection between 2009-2016 (01 September to June 30) were entered into an internet-based data entry system by the attending physicians after informed consent. 63 572 immunizations were documented for 12 729 evaluable patients (EVP) from 2009 to 2016, with an average of 5.0 immunizations per patient per season. 45% of infants received more than 5 injections. The predominant primary reason for immunization was premature birth (74%). In the EVP the rate of hospitalizations with causal relationship to RSV was 0.7% (=92/12 729) or 1.2% in a worst case scenario including patients with missing RSV test. In patients with hemodynamically significant congenital heart disease as main indication, RSV-related hospitalization rate was 0.8%. Intensive care was necessary in 16.9% (median duration 3 days), mechanical ventilation in 8.0%. No death related to RSV infection was reported. Keeping in mind the limitations of an uncontrolled prospective observational study, our results confirm the effectiveness and safety of palivizumab prophylaxis. The total number of patients with hsCHD is lower than expected. A better adjustment to the regional epidemiology would probably reduce the need for more than 5 injections.

Past, Present and Future Approaches to the Prevention and Treatment of Respiratory Syncytial Virus Infection in Children.

IntroductionThe REGAL (RSV Evidence – A Geographical Archive of the Literature) series has provided a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This seventh and final publication covers the past, present and future approaches to the prevention and treatment of RSV infection among infants and children.MethodsA systematic review was undertaken of publications between January 1, 1995 and December 31, 2017 across PubMed, Embase and The Cochrane Library. Studies reporting data on the effectiveness and tolerability of prophylactic and therapeutic agents for RSV infection were included. Study quality and strength of evidence (SOE) were graded using recognized criteria. A further nonsystematic search of the published literature and Clinicaltrials.gov on antiviral therapies and RSV vaccines currently in development was also undertaken.ResultsThe systematic review identified 1441 studies of which 161 were included. Management of RSV remains centered around prophylaxis with the monoclonal antibody palivizumab, which has proven effective in reducing RSV hospitalization (RSVH) in preterm infants < 36 weeks’ gestational age (72% reduction), children with bronchopulmonary dysplasia (65% reduction), and infants with hemodynamically significant congenital heart disease (53% reduction) (high SOE). Palivizumab has also shown to be effective in reducing recurrent wheezing following RSVH (high SOE). Treatment of RSV with ribavirin has conflicting success (moderate SOE). Antibodies with increased potency and extended half-life are currently entering phase 3 trials. There are approximately 15 RSV vaccines in clinical development targeting the infant directly or indirectly via the mother.ConclusionPalivizumab remains the only product licensed for RSV prophylaxis, and only available for high-risk infants. For the general population, there are several promising vaccines and monoclonal antibodies in various stages of clinical development, with the aim to significantly reduce the global healthcare impact of this common viral infection.FundingAbbVie.Electronic supplementary materialThe online version of this article (10.1007/s40121-018-0188-z) contains supplementary material, which is available to authorized users.

Efficacy of a Novel Palivizumab Prophylaxis Protocol for Respiratory Syncytial Virus Infection in Congenital Heart Disease: A Multicenter Study

To analyze the efficacy of a novel palivizumab protocol for hemodynamically significant congenital heart disease (hsCHD) in subtropical areas without clear respiratory syncytial virus seasonality. Since July 2013, the National Health Insurance program has provided reimbursement for palivizumab prophylaxis with a novel monthly protocol in selected patients with hsCHD under 1 year of age. We performed a multicenter study to assess the trend of respiratory syncytial virus hospitalizations in patients with hsCHD from 2010 to 2016 during the prepalivizumab, transition, and postpalivizumab periods, and compared treatment and propensity-matched control groups. A total of 747 patients were enrolled in the study group and 809 in the control group. The male:female was 836:720. Cyanotic CHD was observed in 42.9% of patients. The mean age at diagnosis of CHD was 32.9 days. After 516 685 patient-days of follow-up and a mean of 3.9 doses of palivizumab in the treatment group, respiratory syncytial virus hospitalization rates decreased by 53% and 49% before and after match compared with the control group (P = .009 and .029, respectively). Hospitalization days and intensive care unit admission rate also decreased similarly in the treatment group. The efficacy of this protocol was more prominent in patients with cyanotic hsCHD. The annual respiratory syncytial virus-associated hospitalization rates also decreased significantly from the prepalivizumab to the palivizumab period (from 4.8% to 2.0%; P = .038). Palivizumab prophylaxis through the novel monthly protocol for patients with hsCHD is effective in reducing respiratory syncytial virus-related hospitalizations.

A Functional Aryl Hydrocarbon Receptor Genetic Variant, Alone and in Combination with Parental Exposure, is a Risk Factor for Congenital Heart Disease.

Recent experimental studies showed that ablation of the aryl hydrocarbon receptor (AhR) as well as its activation by exogenous ligands disrupt the molecular networks involved in heart formation and function, leading to congenital heart disease (CHD). However, no evidence is available about the role of AhR in humans. We assessed the prevalence of a functional AhR genetic variant (p.Arg554Lys) in CHD patients as well as its joint effects with parental exposure. A total of 128 CHD patients (76 males; age 6.2±6.7years) and 274 controls (160 males; age at birth) were genotyped for the AhR polymorphism by using the TaqMan® Drug Metabolism Genotyping assay. Both case and control parents completed a structured questionnaire on demographic, lifestyle and preconception exposures. Genotype (p=0.001) and allele (p<0.0001) distributions of AhR p.Arg554Lys differed significantly between patients and controls. A significant elevated CHD risk was found under dominant (OR=2.9, 95% CI 1.9-4.6, p<0.0001) and additive genetic models (OR=6.2, 95% CI 2-19, p=0.001). There was a significant interaction between 554-Lys allele and paternal smoking exposure (ORsmoking=1.6, 95% CI=0.9-2.9; ORallele=2.6, 95% CI=1.3-5; ORinteraction=4.9, 95% CI=2.4-9.9, p interaction<0.0001). Additionally, 554-Lys allele exacerbated the effect of maternal periconceptional exposure (ORexposure=1.6, 95% CI=0.8-3; ORallele=2.6, 95% CI=1.5-4.5; ORinteraction=5.7; 95% CI=2.6-12, p interaction<0.0001). Our findings showed that the AhR p.Arg554Lys polymorphism, alone and in combination with parental exposures, is associated with the CHD risk, highlighting the significant role of AhR in the cardiovascular development.

Management of Congenital Heart Disease Associated with Ellis-van Creveld Short-rib Thoracic Dysplasia

To evaluate clinical outcome of patients with Ellis-van Creveld syndrome (EVC) in whom congenital heart disease (CHD) repair was delayed intentionally to reduce the risk of postoperative respiratory morbidity and mortality. This retrospective review of 51 EVC c.1886+5G>T homozygotes born between 2005 and 2014 focused on 18 subjects who underwent surgery for CHD, subdivided into early (mean, 1.3 months) vs delayed (mean, 50.1 months) repair. Growth trajectories differed between control subjects and patients with EVC, and CHD was associated with slower weight gain. Relative to controls, infants with EVC had a 40%-75% higher respiratory rates (independent of CHD) accompanied by signs of compensated respiratory acidosis. Blood gases and respiratory rates approached normal values by age 4 years. Hemodynamically significant CHD was present in 23 children, 18 (78%) of whom underwent surgical repair. Surgery was performed at 1.3 ± 1.3 months for children born between 2005 and 2009 (n = 9) and 50.1 ± 40.2 months (P = .009) for children born between 2010 and 2014 (n = 9). The latter had shorter postoperative mechanical ventilation (1.1 ± 2.4 days vs 49.6 ± 57.1 days; P = .075), shorter intensive care duration of stay (16 ± 24 days vs 48.6 ± 44.2 days; P = .155), and no postoperative tracheostomies (vs 60%; P = .028) or deaths (vs 44%; P = .082). Among children with EVC and possibly other short-rib thoracic dysplasias, delayed surgical repair of CHD reduces postoperative morbidity and improves survival. Respiratory rate serves as a simple indicator for optimal timing of surgical repair.

LOW YIELD OF FETAL ECHOCARDIOGRAPHY WHEN NO SUSPICION OF HEART DISEASE BY REFERRING OBSTETRICIAN

The latest statement of the American Heart Association on the diagnosis of fetal congenital heart diseases (CHD) recommended that in the presence of factors that increase the risk of CHD above 3%, a referral for a fetal echocardiogram should be done. In the last two decades, we have seen an increase in the number of indications to perform a fetal echocardiogram. There is consensus that a fetal echocardiogram is needed in high-risk situations or when heart disease is suspected. The benefits of referring moderate risk pregnancies has been questioned when no fetal heart malformation is suspected at the obstetrical screening. Our main objective was to determine the number needed to test (NNT) to detect CHD in pregnancies with risk factors, but without a suspected heart malformation after obstetrical screening. This project is nested within cohort study assessing the results of prenatal CHD screening in all pregnancies in Québec. We are reviewing all fetal echocardiograms done between 2012 and 2016 in the 4 pediatric cardiology divisions in Québec. This abstract pertains to the results of the two institutions with complete data to date. Each suspected CHD was categorized according to the International Paediatric and Congenital Cardiac Code. CHDs were further categorized as moderate/severe CHD (likely to required early intervention) and mild/insignificant CHD (unlikely to require early intervention). For each indication, we calculated the yield (% of positive) and the NNT (number of exams to detect one case). A total of 5 889 pregnancies had analysable data. Moderate/severe CHD was observed or suspected in 3.0 % of fetuses. The NNT for fetuses with suspected CHD at obstetrical screening was 2.9 for all CHDs and 3.3 for moderate/severe CHDs (see also the Table). When no CHD was suspected at obstetrical screening, the NNT increased significantly to 33 for all CHD and 143 for moderate/severe CHD. Common indications such as increased nuchal translucency, familial history of CHD, pre-gestational diabetes and exposure to medication had very low yield and high NNT. These preliminary results show that when no CHD is suspected during obstetrical screening, common indications for fetal echocardiogram have a low yield of identifying a significant CHD. The final results of the complete cohort will include post- natal data allowing calculation of obstetrical false-negative and evaluation of the impacts of the current referral pattern on healthcare resources.

Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan.

ObjectiveThe aim of this study was to assess the safety and effectiveness of palivizumab for the prevention of lower respiratory tract infection (LRI) caused by respiratory syncytial virus (RSV) in children with immunocompromised conditions or Down syndrome.MethodsIn this multicenter, post-marketing surveillance study (December 2013 to December 2015), children aged ≤24 months with immunocompromised conditions or Down syndrome (without hemodynamically significant congenital heart disease) receiving palivizumab immunoprophylaxis during two RSV seasons were observed until 30 days after the final palivizumab injection. Safety [adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), serious ADRs (SADRs)] and effectiveness (frequency, incidence, and duration of hospitalization due to RSV infections) were assessed.ResultsOf 304 patients receiving palivizumab, 167 (54.9%) had immunocompromised conditions, and 138 (45.4%) had Down syndrome; 260 (85.5%) completed palivizumab immunoprophylaxis. The annual mean (±standard deviation) number of doses was 5.3 (±2.4) per season. Overall, 220 AEs occurred in 99 patients (32.6%), including 89 SAEs in 53 patients (17.4%). Of these, 33 AEs in 25 patients (8.22%) were considered ADRs, and 13 ADRs in 11 patients (3.62%) were considered SADRs. In four patients, five SADRs (nephroblastoma and asthma in the same patient, septic shock, device-related infection, and drug-induced liver injury) were previously unreported; however, none were considered drug-related. During the observation period, five RSV infections occurred and two patients required hospitalization.ConclusionPalivizumab was generally safe and effective for the prevention of LRI caused by RSV in newborns, infants, and children with immunocompromised conditions or Down syndrome up to the age of 24 months.Electronic supplementary materialThe online version of this article (doi:10.1007/s40272-017-0264-y) contains supplementary material, which is available to authorized users.

EFFECTIVENESS OF PALIVIZUMAB IN PREVENTING RSV HOSPITALIZATION IN HIGH-RISK CHILDREN: A PROSPECTIVE OBSERVATIONAL MULTICENTER STUDY

Background: Palivizumab is indicated for the prevention of serious respiratory syncytial virus (RSV) disease in high-risk infants.Aims: The purpose of the study was to assess the real-world effectiveness and safety of palivizumab in children at high risk for serious RSV disease during the 2014−2015 RSV season in the Russian Federation.Methods: A prospective, observational, multicentre, cohort study was conducted in a population of infants at high-risk for serious RSV illness: infants born ≤35 weeks of gestation and infants ≤24 months with bronchopulmonary dysplasia (BDP) or congenital heart disease (CHD), who were administered palivizumab immunoprophylaxis in routine clinical settings. The study was conducted at 16 investigational sites of European Russia and Western Siberia.Results: A total of 359 infants were enrolled (180 boys and 179 girls). Of them, 148 (41.2%) infants had BDP, 45 (12.5%) infants had hemodynamically significant CHD, and 166 (46.2%) children of prematurity were at the risk of RSV. The majority of infants (86.9%) received three or more injections during the course of study. Of the 359 participants enrolled, 11 (3.1%; 95% CI 1.5−5.4) patients were hospitalized for lower respiratory tract infection. A RSV diagnostic test was performed in 9 infants, and RSV was detected in one patient giving an overall incidence of RSV hospitalization as 0.3% (95% CI 0.0−1.5).Conclusions: This study showed that immunoprophylaxis with palivizumab was associated with a low rate of RSV hospitalization. Overall, therapy with palivizumab was well-tolerated and showed a favourable benefit-risk profile.

Fetal Cardiac US: Techniques and Normal Anatomy Correlated with Adult CT and MR Imaging.

Congenital heart disease (CHD) is an important cause of childhood mortality. Despite the widespread use of ultrasonography (US) as a screening tool, the prenatal detection rate is suboptimal. Improvement of the initial screening examination, which is performed in low-risk populations and often interpreted by community radiologists, targets a point in the screening process that is likely to have the largest population effect. If the goal of community-based screenings is to detect cases that may be abnormal and refer those to specialized centers for complete assessment, it is logical to use a checklist to confirm normal anatomy. This article presents a stepwise process to evaluate fetal cardiac anatomy using comparison with computed tomography (CT) and magnetic resonance (MR) images, which are more familiar to radiologists in busy general practices. In addition, this article presents a checklist for assessment of the four-chamber view and demonstrates the expected normal appearance of the outflow tract views as well as the additional views required for complex obstetric US. These additional views include the aortic arch and bicaval views, three-vessel view (3VV), and three-vessel trachea view (3TV). CHD may be isolated, but it may indicate aneuploidy or a syndrome that, if present, determines the prognosis. In isolated CHD, the prognosis is determined by the exact nature of the abnormalities. In particular, duct-dependent disease if undiagnosed results in circulatory collapse in the infant once the ductus closes. If the heart does not look normal, the patient should be referred for detailed evaluation. Timely diagnosis of significant CHD allows for development of a personalized pregnancy management plan. © RSNA, 2017.

INCIDENCE OF SERIOUS BACTERIAL INFECTION IN FEBRILE NEONATES LESS THAN 28 DAYS WITH BRONCHIOLITIS

BACKGROUND: Bronchiolitis is the most common reason for admission in infants under 12 months of age. There is uncertainty as to whether invasive tests to look for bacterial infections are necessary in febrile infants under 28 days of age who present with clinical findings consistent with bronchiolitis. OBJECTIVES: Several recent reviews suggest that babies 28 to 90 days of age with bronchiolitis are at relatively low risk of serious bacterial infection, with the exception of urinary tract infection (UTI). There has been no literature to date focusing exclusively on infants less than 28 days. DESIGN/METHODS: We conducted a multi-center retrospective chart review to determine the proportion of febrile infants less than 28 days of age admitted with bronchiolitis who were ultimately found to have a bacterial infection in their blood, urine, or cerebrospinal fluid. At each site all charts between March 2006 and May 2015 with an admission to hospital at age less than or equal to 28 days with a discharge diagnosis of bronchiolitis were reviewed. Exclusion criteria included lack of documented fever, gestational age at birth less than 36 weeks, known immunodeficiency, hemodynamically significant congenital heart disease, or congenital lung anomaly. RESULTS: Our sample included 226 neonates. There were 57 positive urine cultures, of which 34 were considered by the treating team to be contaminants, for a rate of UTI of 23 in 226, or 10.1%. Of the 23 UTIs, 16 had colony counts that were consistent with contamination based on the current CPS statement but which were treated as true infections. There were 6 positive blood cultures, of which 5 were considered to be contaminants, for a rate of bacteremia of 1 in 226. There were 2 positive cerebrospinal fluid (CSF) cultures. Both of the positive CSF cultures were considered to be contaminants, for a rate of meningitis of 0 in 226. CONCLUSION: Our results are consistent with those of studies in older infants in documenting an extremely low rate of serious bacterial infection other than UTI in infants less than 28 days admitted with clinical bronchiolitis, even though these febrile neonates have traditionally been thought to be at highest risk. This suggests that invasive CSF sampling and empiric antibiotic administration in this population may be safely avoided, though this would have to be confirmed in large-scale prospective studies. In our sample there was a significant risk of contamination and false positive bacterial cultures.

Respiratory syncytial virus hospitalization risk in the second year of life by specific congenital heart disease diagnoses.

Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12–23 months of age versus 0–11 months of age. However, RSV hospitalization risk at 12–23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12–23 months of age with CHD. Related CHD diagnoses were combined for analysis. Hospitalizations for RSV and unspecified bronchiolitis were described by length of stay, mechanical ventilation use, mortality, and total charges. Over the 17-year period, 1,168,886 live birth hospitalizations with CHD were identified. Multiple specific CHD conditions had an elevated odds ratio or relative risk of RSV hospitalization. Mean total RSV hospitalization charges were significantly higher among children with CHD relative to those without CHD ($19,650 vs $7,939 in 2015 dollars) for this period. Compared to children without CHD, children with Ebstein’s anomaly, transposition of the great arteries, aortic stenosis, heterotaxia, and aortic arch anomalies had 367-, 344-, 203-, 117- and 47-fold increased risk of inpatient RSV mortality, respectively. Unspecified bronchiolitis hospitalization odds and relative risk across CHD diagnoses were similar to those observed with RSV hospitalization; however, unspecified bronchiolitis hospitalizations were associated with shorter mean days of stay and less frequently associated with mechanical ventilation or mortality. Among children with more severe CHD diagnoses, RSV disease remains an important health risk through the second year of life. These data can help inform decisions regarding interventions to protect children with CHD from severe RSV disease during their second year of life.

Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Infants with Congenital Heart Disease.

IntroductionThe REGAL (RSV Evidence—a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This fourth publication covers the risk and burden of RSV infection in infants with congenital heart disease (CHD).MethodsA systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015 across PubMed, Embase, The Cochrane Library, and Clinicaltrials.gov. Studies reporting data for hospital visits/admissions for RSV infection among children with CHD as well as studies reporting RSV-associated morbidity, mortality, and healthcare costs were included. The focus was on children not receiving RSV prophylaxis. Study quality and strength of evidence (SOE) were graded using recognized criteria.ResultsA total of 1325 studies were identified of which 38 were included. CHD, in particular hemodynamically significant CHD, is an independent predictor for RSV hospitalization (RSVH) (high SOE). RSVH rates were generally high in young children (<4 years) with CHD (various classifications), varying between 14 and 357/1000 (high SOE). Children (<6 years) with RSV infection spent 4.4–14 days in hospital, with up to 53% requiring intensive care (high SOE). Infants (<2 years) with CHD had a more severe course of RSVH than those without CHD (high SOE). Case fatality rates of up to 3% were associated with RSV infection in children with CHD (high SOE). RSV infection in the perioperative period of corrective surgery and nosocomial RSV infection in intensive care units also represent important causes of morbidity (moderate SOE).ConclusionCHD poses a significant risk for RSVH and subsequent morbidity and mortality. RSV infection often complicates corrective heart surgery. To reduce the burden and improve outcomes, further research and specific studies are needed to determine the longer-term effects of severe RSV infection in young children with CHD.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-016-0142-x) contains supplementary material, which is available to authorized users.

CLINICAL AND EPIDEMIOLOGICAL FEATURES AND PREVENTION OF NOSOCOMIAL BRONCHIOLITIS WITH RSV ETIOLOGY IN CHILDREN OF SEVERE COURSE RISK GROUPS

Preterm infants and children with bronchopulmonary dysplasia, hemodynamically significant congenital heart diseases and number of other diseases are a group of severe risk of RSV bronchiolitis requiring hospitalization and intensive, including respiratory, therapy. RSV bronchiolitis can develop as at stationary phase due to nosocomial infection, and outpatient. The article presents current information about clinical and epidemiological features of nosocomial RSV bronchiolitis in children of severe course risk groups based on infection outbreaks analysis from literature and own data. It presents data on non-specific prevention of nosocomial RSV infection and experience of prevention with nosocomial spread of monoclonal antibody to virus F protein palivizumab.

Lecture 2: The Long-Term Prognosis of Significant Congenital Heart Disease in Kanagawa Children’s Medical Center (KCMC)

Lecture 2: The Long-Term Prognosis of Significant Congenital Heart Disease in Kanagawa Children’s Medical Center (KCMC)

Outcomes of Infants Receiving Palivizumab Prophylaxis for Respiratory Syncytial Virus in Canada and Italy: An International, Prospective Cohort Study.

Respiratory syncytial virus (RSV) infection frequently results in RSV-related hospitalization (RSVH) in young infants. We examined the outcomes of palivizumab recipients within the Canadian Registry (CARESS) and the Torino-Verona Italian Registry over the 2002-2014 RSV seasons. RSVHs were captured during the study seasons. Premature infants who received palivizumab (≤35 completed weeks' gestational age; group1) were compared with infants given palivizumab for underlying disorders regardless of gestational age (group 2). Variables and between-group incidences were analyzed. Risk factors associated with RSVH were assessed by logistic regression. A total of 14,468 palivizumab-exposed infants were enrolled (group 1, n = 9093; group 2, n = 4856; miscellaneous, n = 519). RSVH was significantly more frequent in group 2 (211/4856, 4.34%) versus group 1 infants (216/9093, 2.37% [relative risk 1.93; 95% confidence interval (CI): 1.60-2.33; P < 0.0001]). Infants with neuromuscular disorders (7.88%), airway anomalies (5.95%), bronchopulmonary dysplasia (4.75%) and hemodynamically significant congenital heart disease (4.10%) had the highest RSVH incidences. After multivariable logistic regression, only neuromuscular disease [odds ratio [OR] 4.29; 95% CI: 2.30-8.00; P < 0.01], airway anomalies (OR 3.23; 95% CI: 1.92-5.43; P < 0.01), Down syndrome (OR 2.25; 95% CI: 1.31-3.89; P < 0.01), hemodynamically significant congenital heart disease (OR 2.24; 95% CI: 1.52-3.31; P < 0.001), prematurity ≤28 completed weeks' gestational age (OR 1.82; 95% CI: 1.29-2.58; P < 0.001) and bronchopulmonary dysplasia (OR 1.81; 95% CI: 1.31-2.50; P < 0.001) significantly predicted RSVH. No significant association was detected with the number of doses administered or the time elapsed after the previous dose. RSVH rates are higher in infants given palivizumab for reasons other than prematurity. It is uncertain whether these findings relate to inadequate current palivizumab dosing protocols or to a specific increased RSVH risk inherent in infants with severe underlying comorbidities.

Perioperative management and outcomes of esophageal atresia and tracheoesophageal fistula

Background/PurposeEsophageal atresia/tracheoesophageal fistula (EA/TEF) is a rare congenital anomaly lacking contemporary data detailing patient demographics, medical/surgical management and outcomes. Substantial variation in the care of infants with EA/TEF may affect both short- and long-term outcomes. The purpose of this study was to characterize the demographics, management strategies and outcomes in a contemporary multi-institutional cohort of infants diagnosed with EA/TEF to identify potential areas for standardization of care. MethodsA multi-institutional retrospective cohort study of infants with EA/TEF treated at 11 children's hospitals between 2009 and 2014 was performed. Over the 5year period, 396 cases were identified in the 11 centers (7±5 per center per year). All infants with a diagnosis of EA/TEF made within 30days of life who had surgical repair of their defect defined as esophageal reconstruction with or without ligation of TEF within the first six months of life were included. Demographic, operative, and outcome data were collected and analyzed to detect associations between variables. ResultsPrenatal suspicion or diagnosis of EA/TEF was present in 53 (13%). The most common anatomy was proximal EA with distal TEF (n=335; 85%) followed by pure EA (n=27; 7%). Clinically significant congenital heart disease (CHD) was present in 137 (35%). Mortality was 7.5% and significantly associated with CHD (p<0.0001). Postoperative morbidity occurred in 62% of the population, including 165 (42%) cases with anastomotic stricture requiring intervention, anastomotic leak in 89 (23%), vocal cord paresis/paralysis in 26 (7%), recurrent fistula in 19 (5%), and anastomotic dehiscence in 9 (2%). Substantial variation in practice across our institutions existed: bronchoscopy prior to repair was performed in 64% of cases (range: 0%–100%); proximal pouch contrast study in 21% (0%–69%); use of interposing material between the esophageal and tracheal suture lines in 38% (0%–69%); perioperative antibiotics ≥24h in 69% (36%–97%); and transanastomotic tubes in 73% (21%–100%). ConclusionContemporary treatment of EA/TEF is characterized by substantial variation in perioperative management and considerable postoperative morbidity and mortality. Future studies are planned to establish best practices and clinical care guidelines for infants with EA/TEF. Level of EvidenceType of study: Treatment study. Level IV.

Abstract 13226: Shorter Left Ventricular Ejection Time is Associated With Adverse Outcomes in Heart Failure Patients With Reduced Ejection Fraction

Introduction: Worsening heart failure (HF) is thought to be associated with shorter left ventricular ejection time (LVET), but there are limited data describing the relationship between LVET and outcomes. We report the largest study to date describing the association between LVET and outcomes in an ambulatory HF population. Methods: We identified HF patients without significant structural or congenital heart disease who had an outpatient transthoracic echocardiogram (TTE) performed between 8/2008-7/2010 at Duke University Medical Center. We excluded patients with paced or irregular rhythms. All TTE were re-analyzed in triplicate. Multivariable logistic regression was used to evaluate the association between LVET and 1 year outcomes among HF patients with reduced ejection fraction (HFrEF) and patients with preserved ejection fraction (HFpEF). Results: We identified 545 HF patients (171 HFrEF, 374 HFpEF) meeting inclusion criteria. HFrEF patients were younger (median age was 60 (Quartile 1 to Quartile (Q1-Q3) 50-69) vs. 64 (Q1-Q3 53-74), with smaller proportion of females (30.4 vs. 56.4%) and similar ratio of African Americans (35.7 vs. 35.0%). Median EF among patients with HFrEF was 30% (Q1-Q3 25-35%) and with HFpEF was 54% (Q1-Q3 48-58%). There were no statistical differences in medical histories or neurohormonal therapies. Median LVET was shorter (280 vs. 315ms, p&lt;0.001), median pre-ejection period was longer (114 vs. 89ms, p&lt;0.001), and median relaxation time was shorter (351 vs 411ms, p&lt;0.001) among patients with HFrEF versus HFpEF. Death or HF hospitalization occurred in 46/171 HFrEF patients and 44/374 HFpEF patients. After adjustment, longer LVET was associated with lower odds of the composite of 1 year death/1 year HF hospitalization among HFrEF patients, but not among HFpEF (Table). Conclusion: Longer LVET is independently associated with improved outcomes among HFrEF patients supporting a potential role for increasing LVET as a therapeutic target.

Feasibility of low radiation dose retrospectively-gated cardiac CT for functional analysis in adult congenital heart disease

BackgroundThe use of cardiac computed tomography (CT) in the evaluation of adult congenital heart disease patients is limited due to concerns of high radiation doses. The purpose of this study was to prospectively assess whether low radiation dose cardiac CT is feasible to evaluate ventricular systolic function in adults with congenital heart disease. MethodsThe study group included 30 consecutive patients with significant congenital heart disease who underwent a total of 35 ECG-gated cardiac CT scans utilizing a 320-detector row CT scanner. Each study included a non-contrast scan and subsequent contrast-enhanced retrospectively-gated acquisition. Effective radiation dose was estimated by multiplying the dose length product by a k-factor of 0.014mSv/mGycm. ResultsThe mean age of the patients was 34.4±8.9years, 60% were men, and mean body mass index was 24.2±4.3kg/m2. A majority of patients (n=28, 93.3%) had contraindications to cardiac MRI. A tube potential of 80kV was used in 27 (77.1%) of the contrast-enhanced scans. The mean signal-to-noise and contrast-to-noise ratios were 11.5±3.9 and 10.3±3.7, respectively. The median radiation dose for non-contrast and contrast-enhanced images were 0.1mSv (0.07–0.2mSv) and 0.94mSv (0.5–2.1mSv), respectively. All 35 CT scans were successfully analyzed for ventricular systolic function. ConclusionsA low radiation contrast-enhanced, retrospectively-gated cardiac CT with a median radiation dose of less than 1mSv was successful in evaluating ventricular systolic function in 30 consecutive adult congenital heart disease patients who underwent a total of 35 scans.

Vascular Ring Diagnosis and Management: Notable Trends Over 25 Years.

Vascular rings (VRs) are recognized as uncommon but not rare cardiovascular malformations. We analyzed data from all patients born in Southern Nevada, who underwent diagnosis and management of VR from 1990 to 2015, RESULTS: From 1990 to 2015, a total of 92 patients were diagnosed prenatally and postnatally. Of the 92 patients, 73 (79%) had right aortic arch and aberrant left subclavian artery (RAA-ALS) with a left ductus arteriosus or ligamentum, 17 (19%) had a double aortic arch (DAA), and 2 (2%) had a pulmonary artery sling. Of the 92 patients, 75 had an isolated VR and 17 VR had significant additional congenital heart disease (CHD). Of the 75 patients with an isolated VR, 52 underwent surgical repair, and the most common surgical diagnosis was DAA in 6 (66%) of 9 for the period 1990 to 2005 versus less common in 9 (21%) of 43 during the period 2006 to 2015, P < .05. The isolated VR repair age significantly negatively correlated with increasing time from 1990 to 2015, R = -0.7 (P < .0001). Of the 75 isolated VR, 23 remain asymptomatic. The 17 VR with CHD were treated during infant palliation or intracardiac repair. Of the total 92 VR, 60 were born after a 2004 community introduction of the three-vessel fetal echocardiography view, from then the prenatal-detection rate has significantly increased-2004 to 2006, 0 (0%) of 9; 2007 to 2009, 1 (9%) of 11; 2010 to 2012, 11 (55%) of 20; and 2013 to 1015, 14 (70%) of 20 (P < .0001). Over 25 years in Southern Nevada, VR prenatal diagnosis has increased, isolated VR age at surgery has decreased, and the percentage of those with RAA-ALS has increased.