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(1) Introduction: Adolescents with complex congenital heart disease (CCHD) show brain tissue injuries in regions associated with cognitive deficits. Alteration in cerebral arterial perfusion (CAP), as measured by arterial transit time (ATT), may lead to perfusion deficits and potential injury. Our study aims to compare ATT values between CCHD patients and controls and assess the associations between ATT values, MD values, and cognitive scores in adolescents with CCHD. (2) Methods: 37 CCHD subjects, 14-18 years of age, who had undergone surgical palliation and 30 healthy controls completed cognitive testing and brain MRI assessments using a 3.0-Tesla scanner. ATT values and regional brain mean diffusivity [MD] were assessed for the whole brain using diffusion tensor imaging. (3) Results: The mean MoCA values [23.1 ± 4.1 vs. 28.1 ± 2.3; p < 0.001] and General Memory Index, with a subscore of WRAML2 [86.8 ± 15.4 vs. 110.3 ± 14.5; p < 0.001], showed significant cognitive deficits in CCHD patients compared to controls. The mean global ATT was significantly higher in CCHD patients versus controls (mean ± SD, s, 1.26 ± 0.11 vs. 1.19 ± 0.11, p = 0.03), respectively. The partial correlations between ATT values, MD values, and cognitive scores (p < 0.005) showed significant associations in areas including the hippocampus, prefrontal cortices, cerebellum, caudate, anterior and mid cingulate, insula, thalamus, and lingual gyrus. (4) Conclusions: Adolescents with CCHD had prolonged ATTs and showed correlation with clinical measurements of cognitive impairment and MRI measurements of brain tissue integrity. This suggests that altered CAP may play a role in brain tissue injury and cognitive impairment after surgical palliation.
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INTRODUCTION: Adolescents with single ventricle congenital heart disease (SVHD) show functional deficits, particularly in memory and mood regulation. Hippocampi are key brain structures that regulate mood and memory; however, their tissue integrity in SVHD is unclear. Our study aim is to evaluate hippocampal volumes and their associations with memory, anxiety, and mood scores in adolescents with SVHD compared to healthy controls. METHODS: We collected brain magnetic resonance imaging data from 25 SVHD (age 15.9 ± 1.2 years; 15 male) and 38 controls (16.0 ± 1.1 years; 19 male) and assessed memory (Wide Range Assessment of Memory and Learning 2, WRAML2), anxiety (Beck Anxiety Inventory, BAI), and mood (Patient Health Questionnaire 9, PHQ-9) functions. Both left and right hippocampi were outlined and global volumes, as well as three-dimensional surfaces were compared between groups using ANCOVA and associations with cognitive and behavioral scores with partial correlations (covariates: age and total brain volume). RESULTS: The SVHD group showed significantly higher BAI (p = .001) and PHQ-9 (p < .001) scores, indicating anxiety and depression symptoms and significantly reduced WRAML2 scores (p < .001), suggesting memory deficits compared with controls. SVHD group had significantly reduced right global hippocampal volumes (p = .036) compared with controls, but not the left (p = .114). Right hippocampal volume reductions were localized in the CA1, CA4, subiculum, and dentate gyrus. Positive correlations emerged between WRAML2 scores and left (r = 0.32, p = .01) and right (r = 0.28, p = .03) hippocampal volumes, but BAI and PHQ-9 did not show significant correlations. CONCLUSION: Adolescents with SVHD show reduced hippocampal volumes, localized in several sites (CA1, CA4, subiculum, and dentate gyrus), which are associated with memory deficits. The findings indicate the need to explore ways to improve memory to optimize academic achievement and ability for self-care in the condition.
Subject(s)
Heart Diseases , Hippocampus , Adolescent , Hippocampus/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Memory , Memory Disorders/diagnostic imagingABSTRACT
Adolescents with single ventricle heart disease (SVHD) exhibit mood and cognitive deficits, which may result from injury to the basal ganglia structures, including the caudate nuclei. However, the integrity of the caudate in SVHD adolescents is unclear. Our aim was to examine the global and regional caudate volumes, and evaluate the relationships between caudate volumes and cognitive and mood scores in SVHD and healthy adolescents. We acquired two high-resolution T1-weighted images from 23 SVHD and 37 controls using a 3.0-Tesla MRI scanner, as well as assessed mood (Patient Health Questionnaire-9 [PHQ-9]; Beck Anxiety Inventory [BAI]) and cognition (Montreal Cognitive Assessment [MoCA]; Wide Range Assessment of Memory and Learning-2; General Memory Index [GMI]) functions. Both left and right caudate nuclei were outlined, which were then used to calculate and compare volumes between groups using ANCOVA (covariates: age, gender, and head-size), as well as perform 3D surface morphometry. Partial correlations (covariates: age, gender, and head-size) were used to examine associations between caudate volumes, cognition, and mood scores in SVHD and controls. SVHD subjects showed significantly higher PHQ-9 and BAI scores, indicating more depressive and anxiety symptoms, as well as reduced GMI scores, suggesting impaired cognition, compared to controls. SVHD patients showed significantly reduced caudate volumes (left, 3,198.8 ± 490.1 vs. 3,605.0 ± 480.4 mm3 , p < 0.004; right, 3,162.1 ± 475.4 vs. 3,504.8 ± 465.9 mm3 , p < 0.011) over controls, and changes were localized in the rostral, mid-dorsolateral, and caudal areas. Significant negative correlations emerged between caudate volumes with PHQ-9 and BAI scores and positive correlations with GMI and MoCA scores in SVHD and controls. SVHD adolescents show significantly reduced caudate volumes, especially in sites that have projections to regulate mood and cognition, which may result from developmental and/or hypoxia-/ischemia-induced processes.
Subject(s)
Adolescent Behavior , Caudate Nucleus/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Mood Disorders/diagnostic imaging , Ventricular Dysfunction/diagnostic imaging , Adolescent , Adolescent Behavior/psychology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Female , Humans , Male , Mental Status and Dementia Tests , Mood Disorders/epidemiology , Mood Disorders/psychology , Organ Size , Ventricular Dysfunction/epidemiology , Ventricular Dysfunction/psychologySubject(s)
Coronavirus Infections , Heart Transplantation , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Child , China , Humans , SARS-CoV-2 , Tissue DonorsABSTRACT
BACKGROUND: Adolescents with single ventricle heart disease (SVHD) who have undergone the Fontan procedure show cognitive/memory deficits. Mammillary bodies are key brain sites that regulate memory; however, their integrity in SVHD is unclear. We evaluated mammillary body (MB) volumes and their associations with cognitive/memory scores in SVHD and controls. METHODS: Brain MRI data were collected from 63 adolescents (25 SVHD; 38 controls) using a 3.0-Tesla MRI scanner. Cognition and memory were assessed using Montreal Cognitive Assessment (MoCA) and Wide Range Assessment of Memory and Learning 2. MB volumes were calculated and compared between groups (ANCOVA, covariates: age, sex, and total brain volume [TBV]). Partial correlations and linear regression were performed to examine associations between volumes and cognitive scores (covariates: age, sex, and TBV). RESULTS: SVHD group showed significantly lower MoCA and WRAML2 scores over controls. MB volumes were significantly reduced in SVHD over controls. After controlling for age, sex, and TBV, MB volumes correlated with MoCA and delayed memory recall scores in SVHD and controls. CONCLUSION: Adolescents with SVHD show reduced MB volumes associated with cognitive/memory deficits. Potential mechanisms of volume losses may include developmental and/or hypoxic/ischemic-induced processes. Providers should screen for cognitive deficits and explore possible interventions to improve memory.
Subject(s)
Cognition , Cognitive Dysfunction/diagnostic imaging , Fontan Procedure/adverse effects , Magnetic Resonance Imaging , Mammillary Bodies/diagnostic imaging , Memory Disorders/diagnostic imaging , Memory , Univentricular Heart/surgery , Adolescent , Case-Control Studies , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/psychology , Female , Humans , Male , Mammillary Bodies/physiopathology , Memory Disorders/physiopathology , Memory Disorders/psychology , Neuropsychological Tests , Predictive Value of Tests , Treatment OutcomeABSTRACT
BACKGROUND: An easy-to-operate ECG recorder should be useful for newborn screening for heart conditions, by health care workers - or parents. We developed a one-piece electrode strip and a compact, 12lead ECG recorder for newborns. METHOD: We enrolled 2582 newborns in a trial to assess abilities of parents to record a 12lead ECG on their infants (2-4â¯weeks-old). Newborns were randomized to recordings by parents (1290) or our staff (1292 controls). Educational backgrounds of parents varied, including 64% with no more than a high school diploma. RESULTS: For newborns randomized to parent recorded ECGs, 94% of parents completed a 10-minute recording. However, 42.6% asked for verbal help, and 12.7% needed physical help. ECG quality was the same for recordings by parents versus staff. CONCLUSIONS: By use of a one-piece electrode strip and a compact recorder, 87% of parents recorded diagnostic quality ECGs on their newborn infants, with minimal assistance.
Subject(s)
Arrhythmias, Cardiac/diagnosis , Electrocardiography/instrumentation , Mass Screening/instrumentation , Parents , Electrodes , Equipment Design , Female , Humans , Infant, Newborn , Male , MiniaturizationABSTRACT
BACKGROUND: The left atrium (LA) modulates left ventricular filling pressure and is a strong prognosticator in heart failure. Although anthracycline exposure may lead to impaired left ventricular (LV) function, the effects on LA function are not well-described in the younger population. We aim to evaluate LA function in children exposed to anthracyclines. METHODS: Children exposed to anthracyclines with pre- and post-treatment echocardiographic imaging were enrolled. Measures of LA function (LA ejection fraction [LA EF], global longitudinal strain [GLS], and peak GLS rate) were quantified using 2D speckle tracking echocardiography pre- and post-anthracycline therapy and were compared. Segments with poor tracking were excluded. RESULTS: Fifty-five children (age 13 [SD 5] years) treated with anthracyclines were evaluated. LA EF, GLS, and peak GLS rate were lower after anthracycline exposure. Mean changes were as follows: LA EF (pre-73.5 [SD 7.7]% vs post-70.6 [SD 8.2]%, P = 0.06), GLS (-34.2 [SD 8.4]% vs -31.9 [SD 7.1]%, P = 0.09), peak GLS rate (2.2 [SD 0.8] s-1 vs 2.0 [SD 0.6] s-1 , P = 0.18). When stratified by pre- (≤12 years old) vs post-puberty (>12 years old), prepubescent patients (n = 21) had statistically significant changes in pre/post LA GLS (P = 0.01) and LA EF (P = 0.01). In models adjusted for radiation dose, age, gender, body surface area, or cumulative anthracycline dose, there were no significant relationships in the absolute difference between pre/post LA EF (P = 0.34) or LA GLS (P = 0.18). CONCLUSIONS: In children exposed to anthracyclines, short-term effects on LA function were minimal in those with preserved LV EF. Age-dependent LA susceptibility to anthracycline requires further study.
Subject(s)
Anthracyclines/adverse effects , Atrial Function, Left/drug effects , Cancer Survivors/statistics & numerical data , Echocardiography/methods , Adolescent , Adult , Atrial Function, Left/physiology , Child , Child, Preschool , Female , Heart Atria/drug effects , Heart Atria/physiopathology , Humans , Infant , Male , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Donor-specific HLA antibodies (DSA) are associated with increased rates of rejection and of graft failure in cardiac transplantation. The goal of this study was to determine the association of preformed and posttransplant development of newly detected DSA (ndDSA) with antibody-mediated rejection (AMR) and characterize the clinical relevance of complement-activating DSA in heart allograft recipients. METHODS: The study included 128 adult and 48 pediatric heart transplant patients transplanted between 2010 and 2013. Routine posttransplant HLA antibody testing was performed by IgG single-antigen bead test. The C3d single-antigen bead assay was used to identify complement-activating antibodies. Rejection was diagnosed using International Society for Heart and Lung Transplantation criteria. RESULTS: In this study, 22 patients were transplanted with preexisting DSA, and 43 patients developed ndDSA posttransplant. Pretransplant (P < 0.05) and posttransplant (P < 0.001) ndDSA were associated with higher incidence of AMR. Patients with C3d + DSA had significantly higher incidence of AMR compared with patients with no DSA (P < 0.001) or patients with C3d-DSA (P = 0.02). Nine (36%) of 25 patients with AMR developed transplant coronary artery disease compared with 17 (15.9%) of 107 patients without AMR (P < 0.05). Among the 47 patients who received ventricular assistant device (VAD), 7 of 9 VAD+ patients with preformed DSA experienced AMR compared with 7 of 38 VAD+ patients without preformed DSA, indicating presensitization to donor HLA significantly increased the risk of AMR (P < 0.01). CONCLUSIONS: Preformed and posttransplant ndDSA were associated with AMR. C3d + DSA correlates with complement deposition on the graft and higher risk of AMR which may permit the application of personalized immunotherapy targeting the complement pathway.
Subject(s)
Complement Activation/immunology , Graft Rejection/immunology , HLA Antigens/immunology , Heart Diseases/surgery , Heart Transplantation/adverse effects , Isoantibodies/blood , Adolescent , Adult , Child , Child, Preschool , Complement C3d/analysis , Complement C3d/immunology , Female , Graft Rejection/blood , Graft Rejection/epidemiology , Graft Rejection/prevention & control , Graft Survival/immunology , Heart Diseases/mortality , Heart-Assist Devices , Histocompatibility Testing/methods , Humans , Incidence , Infant , Isoantibodies/immunology , Kaplan-Meier Estimate , Male , Middle Aged , Tissue Donors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Single ventricle heart disease (SVHD) adolescents show cognitive impairments and anxiety and depressive symptoms, indicating the possibility of brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites in SVHD remains unclear. We examined brain tissue changes in SVHD compared to controls using T2-relaxometry procedures, which measure free water content and show tissue injury. METHODS: Proton-density and T2-weighted images, using a 3.0-Tesla MRI, as well as anxiety (Beck anxiety inventory [BAI]), depressive symptoms (patient health questionnaire-9 [PHQ-9]), and cognition (wide range assessment of memory and learning 2 [WRAML2] and Montreal cognitive assessment [MoCA]) data were collected from 20 SVHD (age: 15.8 ± 1.1 years, male/female: 11/9) and 36 controls (age: 16.0 ± 1.1 years, male/female: 19/17). Whole-brain T2-relaxation maps were calculated, normalized to a common space, smoothed, and compared between groups and sexes (analysis of covariance; covariates: age, sex; p < 0.001). RESULTS: SVHD subjects showed significantly increased BAI and PHQ-9 and reduced MoCA and WRAML2 scores over controls. Several brain regions in SVHD showed increased T2-relaxation values (chronic injury), including the cingulate, and insula, hippocampus/para-hippocampal gyrus, thalamus, hypothalamus, amygdala, frontal white matter, corpus callosum, brainstem, and cerebellar areas. Decreased T2-relaxation values (acute injury) emerged in a few regions, including the prefrontal and cerebellar cortices in SVHD over controls. In addition, male SVHD showed more brain changes over female SVHD. CONCLUSIONS: Adolescents with SVHD showed significant brain injury with variable male-female differences in areas that control cognition, anxiety, and depression, which may contribute to functional deficits found in the condition.
Subject(s)
Anxiety/etiology , Brain Injuries/diagnostic imaging , Brain Injuries/etiology , Cognitive Dysfunction/etiology , Depression/etiology , Heart Diseases/pathology , Heart Diseases/psychology , Adolescent , Anxiety/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cross-Sectional Studies , Depression/diagnostic imaging , Female , Humans , Male , Sex FactorsABSTRACT
INTRODUCTION: In 2012, the American College of Cardiology's (ACC) Adult Congenital and Pediatric Cardiology Council established a program to develop quality metrics to guide ambulatory practices for pediatric cardiology. The council chose five areas on which to focus their efforts; chest pain, Kawasaki Disease, tetralogy of Fallot, transposition of the great arteries after arterial switch, and infection prevention. Here, we sought to describe the process, evaluation, and results of the Infection Prevention Committee's metric design process. METHODS: The infection prevention metrics team consisted of 12 members from 11 institutions in North America. The group agreed to work on specific infection prevention topics including antibiotic prophylaxis for endocarditis, rheumatic fever, and asplenia/hyposplenism; influenza vaccination and respiratory syncytial virus prophylaxis (palivizumab); preoperative methods to reduce intraoperative infections; vaccinations after cardiopulmonary bypass; hand hygiene; and testing to identify splenic function in patients with heterotaxy. An extensive literature review was performed. When available, previously published guidelines were used fully in determining metrics. RESULTS: The committee chose eight metrics to submit to the ACC Quality Metric Expert Panel for review. Ultimately, metrics regarding hand hygiene and influenza vaccination recommendation for patients did not pass the RAND analysis. Both endocarditis prophylaxis metrics and the RSV/palivizumab metric passed the RAND analysis but fell out during the open comment period. Three metrics passed all analyses, including those for antibiotic prophylaxis in patients with heterotaxy/asplenia, for influenza vaccination compliance in healthcare personnel, and for adherence to recommended regimens of secondary prevention of rheumatic fever. CONCLUSIONS: The lack of convincing data to guide quality improvement initiatives in pediatric cardiology is widespread, particularly in infection prevention. Despite this, three metrics were able to be developed for use in the ACC's quality efforts for ambulatory practice.
Subject(s)
Ambulatory Care/organization & administration , Cardiac Surgical Procedures , Cardiology/organization & administration , Infection Control/standards , Surgical Wound Infection/prevention & control , Child , Heart Defects, Congenital , Humans , United StatesABSTRACT
PURPOSE: Cardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL). METHODS: LV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method. RESULTS: Peak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 ± 3.6 ° versus 12.9 ± 2.3 °, P = 0.003) and patients with DMD (8.6 ± 3.6 ° versus 10.5 ± 3.6 °, P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH. CONCLUSION: Breath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Subject(s)
Heart Ventricles/diagnostic imaging , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging, Cine/methods , Muscular Dystrophy, Duchenne/diagnostic imaging , Respiratory Mechanics/physiology , Adult , Female , Humans , Male , Young AdultABSTRACT
INTRODUCTION: Adolescents and young adults with congenital heart disease (CHD) show a range of memory deficits, which can dramatically impact their clinical outcomes and quality of life. However, few studies have identified predictors of these memory changes. The purpose of this investigation was to identify predictors of memory deficits in adolescents and young adults with CHD after surgical palliation compared to healthy controls. METHOD: One hundred fifty-six adolescents and young adults (80 CHD and 76 controls; age 14-21 years) were recruited and administered an instrument to assess memory [Wide Range Assessment of Memory and Learning Second Edition - general memory index (GMI) score] and completed questionnaires that measure anxiety, depression, sleepiness, health status, and self-efficacy. Descriptive and non-parametric statistics were used to assess group differences, and logistic regression to identify predictors of memory deficits. RESULTS: CHD subjects consisted of 58% males, median age 17 years, 43% Hispanic, and medians of 2 previous heart surgeries and 14 years since last surgery. Memory deficits (GMI ≤ 85) were identified in 50% CHD compared to 4% healthy controls (median GMI 85 vs. 104, p < 0.001). Of GMI subscale medians, CHD subjects had significantly worse memory performance vs. healthy controls (verbal 88 vs. 105, p < 0.001; attention 88 vs. 109, p < 0.001; working memory 86 vs. 108, p < 0.001). No significant differences appeared between groups for visual memory. Multiple clinical and psychosocial factors were identified which were statistically different on bivariate analyses between the subjects with and without memory deficits. By multivariate analysis, male gender, number of surgeries, anxiety, and self-efficacy emerged as independent predictors of memory deficits. CONCLUSION: Adolescents and young adults with CHD, more than a decade since their last surgery, show significant verbal, attention, and working memory deficits over controls. To enhance patient memory/self-care, clinicians should explore ways to reduce anxiety, improve self-efficacy, and increase use of visual patient education material, especially in CHD males.
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BACKGROUND: Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. METHODS: In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. FINDINGS: Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3-2·2] vs 2·2 [1·3-3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in the placebo group died of fat embolism, and another patient in the placebo group withdrew from the trial to address long-standing digestive issues. All other adverse events were mild: short-lived headaches coincident with seasonal allergies occurred in one patient given eplerenone, flushing occurred in one patient given placebo, and anxiety occurred in another patient given placebo. INTERPRETATION: In boys with Duchenne muscular dystrophy and preserved ejection fraction, addition of eplerenone to background ACEI or ARB therapy attenuates the progressive decline in left ventricular systolic function. Early use of available drugs warrants consideration in this population at high risk of cardiac death, but further studies are needed to determine the effect of combination cardioprotective therapy on event-free survival in Duchenne muscular dystrophy. FUNDING: BallouSkies, Parent Project for Muscular Dystrophy, US National Center for Advancing Translational Sciences, and US National Institutes of Health.
Subject(s)
Cardiomyopathies/diagnosis , Cardiomyopathies/drug therapy , Mineralocorticoid Receptor Antagonists/therapeutic use , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/drug therapy , Spironolactone/analogs & derivatives , Adolescent , Cardiomyopathies/epidemiology , Child , Cohort Studies , Double-Blind Method , Early Diagnosis , Eplerenone , Follow-Up Studies , Humans , Male , Muscular Dystrophy, Duchenne/epidemiology , Spironolactone/therapeutic use , Young AdultABSTRACT
Coxsackievirus B (CVB) infection is a common cause of acute viral myocarditis. The clinical presentation of myocarditis caused by this enterovirus is highly variable, ranging from mildly symptoms to complete hemodynamic collapse. These variations in initial symptoms and in the immediate and long term outcomes of this disease have impeded development of effective treatment strategies. Nine cynomolgus monkeys were inoculated with myocarditic strains of CVB. Virological studies performed up to 28 days post-inoculation demonstrated the development of neutralizing antibody in all animals, and the presence of CVB in plasma. High dose intravenous inoculation (n = 2) resulted in severe disseminated disease, while low dose intravenous (n = 6) or oral infection (1 animal) resulted in clinically unapparent infection. Transient, minor, echocardiographic abnormalities were noted in several animals, but no animals displayed signs of significant acute cardiac failure. Although viremia rapidly resolved, signs of myocardial inflammation and injury were observed in all animals at the time of necropsy, and CVB was detected in postmortem myocardial specimens up to 28 days PI. This non-human primate system replicates many features of illness in acute coxsackievirus myocarditis and demonstrates that myocardial involvement may be common in enteroviral infection; it may provide a model system for testing of treatment strategies for enteroviral infections and acute coxsackievirus myocarditis.
Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Coxsackievirus Infections/pathology , Myocarditis/pathology , Myocardium/pathology , Administration, Oral , Animals , Coxsackievirus Infections/complications , Coxsackievirus Infections/immunology , Coxsackievirus Infections/virology , Disease Models, Animal , Echocardiography , Enterovirus B, Human/physiology , Female , Immunity, Humoral , Injections, Intravenous , Macaca fascicularis , Myocarditis/complications , Myocarditis/immunology , Myocarditis/virology , Myocardium/immunology , Myocardium/metabolism , Viral LoadABSTRACT
Thymectomy is performed in infants during cardiothoracic surgery leaving many patients with reduced thympopoiesis. An association between immune disorders and regulatory T cells (Treg) after incidental thymectomy has not been investigated. Questionnaires soliciting symptoms of atopic or autoimmune disease and biomarkers were measured in children and adults with congenital heart disease and either reduced or preserved thymopoiesis. Tregs were examined. Atopic or autoimmune-like symptoms and elevated anti-dsDNA antibodies were common after surgery in individuals with low thymopoiesis. Total Treg number and function were maintained but with fewer naïve Treg. TCR spectratypes were similar to other memory T cells. These data suggest that thymectomy does not reduce total Treg number but homeostasis is affected with reduced naïve Treg. Prevalence of autoimmune or atopic symptoms after surgery is not associated with total number or proportion of Tregs but appears to be due to otherwise unknown factors that may include altered Treg homeostasis.
Subject(s)
Autoimmunity , Heart Defects, Congenital/surgery , T-Lymphocytes, Regulatory/immunology , Thymectomy/adverse effects , Thymus Gland/immunology , Adolescent , Adult , Age Factors , Antibodies, Antinuclear/immunology , Autoimmunity/immunology , Cardiac Surgical Procedures/adverse effects , Child , Child, Preschool , Heart Defects, Congenital/pathology , Humans , Infant , Infant, Newborn , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism , Thymus Gland/metabolism , Thymus Gland/pathology , Young AdultABSTRACT
The thymus begins involution in childhood and historically it was thought to be nonfunctional by adulthood, thus presenting no contraindication to the routine practice of thymectomy during cardiothoracic surgery. More recent data suggest, however, that the thymus remains active into adulthood and is responsible for the low-level production of normal T cells. We hypothesize, therefore, that incidental thymectomy during cardiothoracic surgery in infancy causes long-term changes in the cellular immune system. To investigate this hypothesis, we quantified peripheral T-cell subsets and T-cell recombination excision circles in children with congenital heart disease to measure the impact of cardiothoracic surgical procedures and thymectomy performed during a period of immunologic development. We found that cardiothoracic surgical procedures, especially if they include thymectomy, impair T-cell production and produce long-term decreases in total lymphocyte count and CD4(+) and CD8(+) T-cell subsets, suggesting that long-term maintenance of lymphocyte populations is disturbed.