Browsing by Subject "congenital heart disease"

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    Branch Pulmonary Artery Valve Implantation Reduces Pulmonary Regurgitation and Improves Right Ventricular Size/Function in Patients With Large Right Ventricular Outflow Tracts.
    (JACC. Cardiovascular interventions, 2018-03) Qureshi, Athar M; Bansal, Neha; McElhinney, Doff B; Boudjemline, Younes; Forbes, Tom J; Maschietto, Nicola; Shahanavaz, Shabana; Cheatham, John P; Krasuski, Richard; Lamers, Luke; Chessa, Massimo; Morray, Brian H; Goldstein, Bryan H; Noel, Cory V; Wang, Yunfei; Gillespie, Matthew J
    The authors sought to assess the intermediate-term effects of percutaneous placed valves in the branch pulmonary artery (PA) position.Most patients with large right ventricular outflow tracts (RVOTs) are excluded from available percutaneous pulmonary valve options. In some of these patients, percutaneous branch PA valve implantation may be feasible. The longer-term effects of valves in the branch PA position is unknown.Retrospective data were collected on patients with significant pulmonary regurgitation who had a percutaneous branch PA valve attempted.Percutaneous branch PA valve implantation was attempted in 34 patients (18 bilateral and 16 unilateral). One-half of the patients were in New York Heart Association (NHYA) functional class III or IV pre-implantation. There were 2 failed attempts and 6 procedural complications. At follow-up, only 1 patient had more than mild valvar regurgitation. The right ventricular end-diastolic volume index decreased from 147 (range: 103 to 478) ml/m2 to 101 (range: 76 to 429) ml/m2, p < 0.01 (n = 16), and the right ventricular end-systolic volume index decreased from 88.5 (range: 41 to 387) ml/m2 to 55.5 (range: 40.2 to 347) ml/m2, p < 0.01 (n = 13). There were 5 late deaths. At a median follow-up of 2 years, all other patients were in NYHA functional class I or II.Percutaneous branch PA valve implantation results in a reduction in right ventricular volume with clinical benefit in the intermediate term. Until percutaneous valve technology for large RVOTs is refined and more widely available, branch PA valve implantation remains an option for select patients.
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    Characteristics of pediatric pulmonary hypertension trials registered on ClinicalTrials.gov.
    (Pulm Circ, 2017-04) Awerbach, Jordan D; Krasuski, Richard A; Hill, Kevin D
    The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs. Interventional pediatric (ages 0-17 years) PH trials registered on ClinicalTrials.gov from June 2005 through December 2014 were analyzed. There were 45 pediatric PH trials registered during the study period. Median (IQR) projected trial enrollment was 40 (24-63), with seven trials (16%) targeting > 100 participants. Industry was the most common trial sponsor (n = 23, 50%), with only two (4.4%) NIH-sponsored trials. Phosphodiesterase inhibitors were the most frequently studied drug (n = 18, 39%). Single group study designs were used in 44% (n = 20) with an active comparator (parallel, factorial, or cross-over designs) in 25 trials, including 22 with randomization and ten that were double-blinded. Study outcomes varied markedly with inconsistent use of known surrogate and composite endpoints. One-third of trials (n = 15, 33%) were terminated, predominantly due to poor participant enrollment. Of the 17 completed trials, 11 had published results and only three efficacy trials met their primary endpoint. There are unique challenges to drug development in pediatric PH, including enrolling patients, identifying appropriate study endpoints, and conducting randomized, controlled, double-blind trials where the likelihood of meeting the study endpoint is optimized.
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    Genetic Etiology of Left-Sided Obstructive Heart Lesions: A Story in Development.
    (Journal of the American Heart Association, 2021-01-12) Parker, Lauren E; Landstrom, Andrew P
    Congenital heart disease is the most common congenital defect observed in newborns. Within the spectrum of congenital heart disease are left-sided obstructive lesions (LSOLs), which include hypoplastic left heart syndrome, aortic stenosis, bicuspid aortic valve, coarctation of the aorta, and interrupted aortic arch. These defects can arise in isolation or as a component of a defined syndrome; however, nonsyndromic defects are often observed in multiple family members and associated with high sibling recurrence risk. This clear evidence for a heritable basis has driven a lengthy search for disease-causing variants that has uncovered both rare and common variants in genes that, when perturbed in cardiac development, can result in LSOLs. Despite advancements in genetic sequencing platforms and broadening use of exome sequencing, the currently accepted LSOL-associated genes explain only 10% to 20% of patients. Further, the combinatorial effects of common and rare variants as a cause of LSOLs are emerging. In this review, we highlight the genes and variants associated with the different LSOLs and discuss the strengths and weaknesses of the present genetic associations. Furthermore, we discuss the research avenues needed to bridge the gaps in our current understanding of the genetic basis of nonsyndromic congenital heart disease.
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    Immediate Post-operative Enterocyte Injury, as Determined by Increased Circulating Intestinal Fatty Acid Binding Protein, Is Associated With Subsequent Development of Necrotizing Enterocolitis After Infant Cardiothoracic Surgery.
    (Frontiers in pediatrics, 2020-01) Watson, John D; Urban, Tracy T; Tong, Suhong S; Zenge, Jeanne; Khailova, Ludmilla; Wischmeyer, Paul E; Davidson, Jesse A
    Objectives: 1 Measure serial serum intestinal fatty acid binding protein levels in infants undergoing cardiac surgery with cardiopulmonary bypass to evaluate for evidence of early post-operative enterocyte injury. 2 Determine the association between immediate post-operative circulating intestinal fatty acid binding protein levels and subsequent development of necrotizing enterocolitis. Design: Observational cohort study. Intestinal fatty acid binding protein was measured pre-operatively, at rewarming, and at 6 and 24 h post-operatively. Percent of goal enteral kilocalories on post-operative day 5 and episodes of necrotizing enterocolitis were determined. Multivariable analysis assessed for factors independently associated with clinical feeding outcomes and suspected/definite necrotizing enterocolitis. Setting: Quaternary free-standing children's hospital pediatric cardiac intensive care unit. Patients: 103 infants <120 days of age undergoing cardiothoracic surgery with cardiopulmonary bypass. Interventions: None. Results: Median pre-operative intestinal fatty acid binding protein level was 3.93 ng/ml (range 0.24-51.32). Intestinal fatty acid binding protein levels rose significantly at rewarming (6.35 ng/ml; range 0.54-56.97; p = 0.008), continued to rise slightly by 6 h (6.57 ng/ml; range 0.75-112.04; p = 0.016), then decreased by 24 h (2.79 ng/ml; range 0.03-81.74; p < 0.0001). Sixteen subjects (15.7%) developed modified Bell criteria Stage 1 necrotizing enterocolitis and 9 subjects (8.8%) developed Stage 2 necrotizing enterocolitis. Infants who developed necrotizing enterocolitis demonstrated a significantly higher distribution of intestinal fatty acid binding protein levels at both 6 h (p = 0.005) and 24 h (p = 0.005) post-operatively. On multivariable analysis, intestinal fatty acid binding protein was not associated with percentage of goal enteral kilocalories delivered on post-operative day 5. Higher intestinal fatty acid binding protein was independently associated with subsequent development of suspected/definite necrotizing enterocolitis (4% increase in odds of developing necrotizing enterocolitis for each unit increase in intestinal fatty acid binding protein; p = 0.0015). Conclusions: Intestinal fatty acid binding protein levels rise following infant cardiopulmonary bypass, indicating early post-operative enterocyte injury. Intestinal fatty acid binding protein was not associated with percent of goal enteral nutrition achieved on post-operative day 5, likely due to protocolized feeding advancement based on clinically observable factors. Higher intestinal fatty acid binding protein at 6 h post-operatively was independently associated with subsequent development of necrotizing enterocolitis and may help identify patients at risk for this important complication.
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    Relationship of ventricular assist device support duration with pediatric heart transplant outcomes.
    (The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2022-01) Butto, Arene; Mao, Chad Y; Wright, Lydia; Wetzel, Martha; Kelleman, Michael S; Carboni, Michael P; Dipchand, Anne I; Knecht, Kenneth R; Reinhardt, Zdenka; Sparks, Joshua D; Villa, Chet; Mahle, William T

    Background

    There is wide variability in the timing of heart transplant (HTx) after pediatric VAD implant. While some centers wait months before listing for HTx, others accept donor heart offers within days of VAD surgery. We sought to determine if HTx within 30 days versus ≥ 30 after VAD impacts post-HTx outcomes.

    Methods

    Children on VAD pre-HTx were extracted from the Pediatric Heart Transplant Study database. The primary endpoints were post-HTx length of hospital stay (LOS) and one-year survival. Confounding was addressed by propensity score weighting using inverse probability of treatment. Propensity scores were calculated based on age, blood type, primary cardiac diagnosis, decade, VAD type, and allosensitization status.

    Results

    A total of 1064 children underwent VAD prior to HTx between 2000 to 2018. Most underwent HTx ≥ 30 days post-VAD (70%). Infants made up 22% of both groups. Patients ≥ 12 years old were 42% of the < 30 days group and children 1 to 11 years comprised 47% of the ≥ 30 days group (p < 0.001). There was no difference in the prevalence of congenital heart disease vs. cardiomyopathy (p = 0.8) or high allosensitization status (p = 0.9) between groups. Post-HTx LOS was similar between groups (p = 0.11). One-year survival was lower in the < 30 days group (adjusted mortality HR 1.76, 95% CI 1.11-2.78, p = 0.016).

    Conclusions

    A longer duration of VAD support prior to HTx is associated with a one-year survival benefit in children, although questions of patient complexity, post-VAD complications and the impact on causality remain. Additional studies using linked databases to understand these factors will be needed to fully assess the optimal timing for post-VAD HTx.