Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

OBJECTIVES: Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. METHODS: A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. RESULTS: The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. CONCLUSION: Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

Prevalence of cardiovascular manifestations in patients with hypermobile Ehlers-Danlos syndrome at the University of Miami.

Cardiovascular system involvements have been frequently reported in hypermobile Ehlers-Danlos Syndrome (hEDS). Mitral valve prolapse (MVP) and aortic root dilatation are included in the 2017 international classification criteria for hEDS. Different studies have found conflicting results regarding the significance of cardiac involvement in hEDS patients. We conducted a retrospective review of cardiac involvement in patients diagnosed with hEDS based on the 2017 International diagnostic criteria to provide further evidence toward more defined and reliable diagnostic criteria and recommended cardiac surveillance. A total of 75 hEDS patients with at least one diagnostic cardiac evaluation were included in the study. The most common reported cardiovascular complaints were lightheadedness (80.6%), followed by palpitations (77.6%), fainting (44.8%), and chest pain (32.8%). Of the 62 echocardiogram reports, 57 (91.9%) showed trace/trivial to mild valvular insufficiency, and 13 (21%) had additional abnormalities such as grade I diastolic dysfunction, mild aortic sclerosis, and trivial or small pericardial effusion. Of the 60 electrocardiograms (ECG) reports, 39 (65%) were normal, and 21 (35%) reported minor abnormalities or normal variants. Even though many hEDS patients in our cohort experienced cardiac symptoms, the presence of a significant cardiac abnormality was very low.

Establishment of Myocardial Strain Measurement Data in Pediatric Patients Without Structural Heart Disease: A Single Center Study.

Accurate assessment of LV systolic function remains a challenge, especially in the pediatric population. Myocardial strain measurement by 2D speckle tracking echocardiography (2DSTE) is a relatively new modality for assessment of regional and global myocardial wall motion. This study aims to establish the normative value among various pediatric age groups at a large pediatric tertiary care institution and to describe the challenges encountered in establishing such strain data. Transthoracic echocardiograms were acquired in 121 healthy children (age 0-21 years) and were retrospectively analyzed. The global longitudinal strain (GLS) was obtained by 2D speckle tracking using Philips Epiq7® and QLAB post processing software. The normative value for left ventricular GLS (%) obtained in our study was - 20.8 ± 2.3 (< 1 year); - 21.4 ± 2.2 (1-4 years); - 19.6 ± 2.4 (5-9 years); - 19.4 ± 2.6 (10-14 years); - 18.9 ± 3.0 (15-21 years). There was a statistically significant difference in GLS between the different age groups. The BMI (kg/m2) of assessed subjects were 14.6 ± 2.3 (< 1 year); 16.3 ± 1.5 (1-4 years); 16.7 ± 2.3 (5-9 years); 21.3 ± 4.6 (10-14 years); 23.9 ± 5.9 (15-21 years). There was no significant difference in GLS by gender or by BMI found in our study. We present our experience with establishment of normative values of 2DSTE in our pediatric echocardiography lab. This study shows that age is the major determinant of variation in peak GLS in healthy subjects, emphasizing the importance of establishment of normative data among various age groups in pediatrics.

Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: an analysis of data from the Pediatric Cardiomyopathy Registry.

BACKGROUND: Treatment of children with hypertrophic cardiomyopathy might be improved if the risk of death or heart transplantation could be predicted by risk factors present at the time of diagnosis. METHODS: We analysed data from the Pediatric Cardiomyopathy Registry, which collected longitudinal data for 1085 children with hypertrophic cardiomyopathy from 1990 to 2009. Our goal was to understand how patient factors measured at diagnosis predicted the subsequent risk of the primary outcome of death or heart transplantation. The Kaplan-Meier method was used to calculate time-to-event rates from time of diagnosis to the earlier of heart transplantation or death for children in each subgroup. Cox proportional-hazards regression was used to identify univariable and multivariable predictors of death or heart transplantation within each causal subgroup. FINDINGS: The poorest outcomes were recorded for the 69 children with pure hypertrophic cardiomyopathy with inborn errors of metabolism, for whom the estimated rate of death or heart transplantation was 57% (95% CI 44-69) at 2 years. Children with mixed functional phenotypes also did poorly, with rates of death or heart transplantation of 45% (95% CI 32-58) at 2 years for the 69 children with mixed hypertrophic and dilated cardiomyopathy and 38% (95% CI 25-51) at 2 years for the 58 children with mixed hypertrophic and restrictive cardiomyopathy. For children diagnosed with hypertrophic cardiomyopathy at younger than 1 year, the rate of death or transplantation was 21% (95% CI 16-27) at 2 years. For children diagnosed with hypertrophic cardiomyopathy and a malformation syndrome, the rate of death or transplantation was 23% (95% CI 12-34) at 2 years. Excellent outcomes were reported for the 407 children who were diagnosed with idiopathic hypertrophic cardiomyopathy at age 1 year or older, with a rate of death or heart transplantation of 3% (95% CI 1-5) at 2 years. The risk factors for poor outcomes varied according to hypertrophic cardiomyopathy subgroup, but they generally included young age, low weight, presence of congestive heart failure, lower left ventricular fractional shortening, or higher left ventricular end-diastolic posterior wall thickness or end-diastolic ventricular septal thickness at the time of cardiomyopathy diagnosis. For all hypertrophic cardiomyopathy subgroups, the risk of death or heart transplantation was significantly increased when two or more risk factors were present and also as the number of risk factors increased. INTERPRETATION: In children with hypertrophic cardiomyopathy, the risk of death or heart transplantation was greatest for those who presented as infants or with inborn errors of metabolism or with mixed hypertrophic and dilated or restrictive cardiomyopathy. Risk stratification by subgroup of cardiomyopathy, by characteristics such as low weight, congestive heart failure, or abnormal echocardiographic findings, and by the presence of multiple risk factors allows for more informed clinical decision making and prognosis at the time of diagnosis. FUNDING: US National Institutes of Health and Children's Cardiomyopathy Foundation.

A Descriptive Analysis of Febrile Seizure Hospitalizations in Children with Congenital Heart Disease in the United States.

BACKGROUND: Febrile seizure (FS) is the most common convulsive disorder in children. This study analyzed the national proportion of congenital heart disease (CHD) and hospital resource utilization among children admitted for FSs in the U.S. METHODS: This is a retrospective cross-sectional analysis of pediatric patients up to six years with a primary diagnosis of FS in 2016 and 2019 using the Kids Inpatient Database (KID). The demographic, hospital, and clinical characteristics of children with and without CHD were compared using the chi-square test for categorical variables and linear regressions for continuous variables. Multivariate logistic analysis was conducted to evaluate the impact of CHD on the mean length of hospital stay. RESULTS: An estimated 10,039 children were admitted with the primary diagnosis of FS. Out of these, 117 (1.2%) had a discharge diagnosis of CHD. The mean age for children with and without CHD was 1.4 years (SD 1.60) and 1.5 years (SD 1.501), respectively. Children with CHD who required hospitalization for FS had longer mean lengths of hospital stay (2.1 days vs. 1.6 days), with an adjusted odd ratio of 0.43 (95% CI: 0.07-0.99; p-value: 0.017). Similarly, the hospital charges for children with CHD were higher than those without CHD ($30,960.28 vs. $21,005.11). CONCLUSION: Children with CHD who required inpatient admission for FSs in the U.S. were associated with increased length of hospital stay and higher resource utilization when compared with those without CHD. This highlights the need for preventive measures among this vulnerable population.

Pediatric Heart Failure Inpatient Mortality: A Cross-Sectional Analysis.

Background Heart failure constitutes significant morbidity and mortality among the pediatric population. Few data exist on the prevalence and mortality rate of pediatric heart failure (pHF) in the United States. Objectives This study aimed to determine the in-hospital mortality and the principal diagnoses in pediatric patients with heart failure who died while being hospitalized in the United States. Methods This is a retrospective cross-sectional study using data from the 2019 Kid Inpatient Database (KID). The KID contained data on hospitalized children below 21 years of age. Using Stata 17 software (StataCorp LLC, College Station, Texas), the data were searched for heart failure diagnoses using International Classification of Diseases 10th revision Clinical Modification (ICD-10-CM) codes. By using the "rank" command in Stata, the most common principal diagnoses were placed in descending order of frequency, and these were further divided into different ICD-10 code categories. Results There were 16,206 pHF admissions in 2019. Of these admissions, 1,023 (6.31%) patients died. The top five principal ICD 10 code categories among all pHF deaths in descending order were circulatory system (17.95%), congenital/chromosomal abnormalities (17.43%), respiratory system (10.28%), infectious diseases (9.24%, and perinatal diseases (7.90%). Among all pHF deaths, sepsis of unspecified organisms (5.14%), hypoplastic left heart syndrome (HLHS) (3.19%), and acute respiratory failure with hypoxia (3.14%) were the most common primary diagnoses. Conclusion and significance Pediatric heart failure in-hospital overall mortality is 6.31%, and sepsis of unspecified organisms, HLHS, and acute respiratory failure are the most common principal diagnoses among these children. Preventive measures and prompt treatment of infections are paramount to reducing pHF mortality.

A Case of Lown-Ganong-Levine Syndrome: Due to an Accessory Pathway of James Fibers or Enhanced Atrioventricular Nodal Conduction (EAVNC)?

BACKGROUND Lown-Ganong-Levine syndrome, includes a short PR interval, normal QRS complex, and paroxysmal tachycardia. The pathophysiology of this syndrome includes an accessory pathway connecting the atria and the atrioventricular (AV) node (James fiber), or between the atria and the His bundle (Brechenmacher fiber). Similar features are seen in enhanced atrioventricular nodal conduction (EAVNC), with the underlying pathophysiology due to a fast pathway to the AV node, and with the diagnosis requiring specific electrophysiologic criteria. CASE REPORT A 17-year-old man presented with a history of recurrent narrow-complex and wide-complex tachycardia on electrocardiogram (ECG). An electrophysiologic study showed an unusually short atrial to His (AH) conduction interval and a normal His to ventricle (HV) interval, without a delta wave. Two stable AH intervals coexisted in the same atrial pacing cycle length. In the recovery curve study, this pathway had a flat conduction curve without an AH increase until the last 60 ms, before reaching the effective refractory period. These ECG changes did not respond to an adenosine challenge. When this pathway became intermittent, there was a paradoxical response to adenosine challenge with conduction via a short AH interval, but without conduction block. Catheter ablation of the AV nodal region resulted in a normalized AH interval, decremental conduction properties, and resulted in a positive response to an adenosine challenge. CONCLUSIONS In this case of Lown-Ganong-Levine syndrome, electrophysiologic studies supported the role of the accessory pathway of James fibers.

Issues in solid-organ transplantation in children: translational research from bench to bedside.

In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.

Issues in solid-organ transplantation in children: translational research from bench to bedside

In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.