Adrenergic receptor genotype influences heart failure severity and ß-blocker response in children with dilated cardiomyopathy.
2015; 77 (2): 363-369
Procollagen type III amino-terminal propeptide: a serum biomarker of left ventricular remodelling in paediatric dilated cardiomyopathy
CARDIOLOGY IN THE YOUNG
2015; 25 (2): 228-236
Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and β-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM).Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: α2cdel322-325, β1Arg389, and β2Arg16. Data were analyzed by genotype and β-blocker use. Mean age at enrollment was 8.5 y.One-year event-free survival was 51% in advanced and 80% in stable DCM. High-risk genotypes were associated with higher left ventricular (LV) filling pressures, higher systemic and pulmonary vascular resistance, greater decline in LV ejection fraction (P < 0.05), and a higher frequency of mechanical circulatory support while awaiting transplant (P = 0.05). While β-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving β-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving β-blockers (interaction P < 0.05).Our study identifies genetic risk markers that may help in the identification of patients at risk for developing decompensated HF and who may benefit from early institution of β-blocker therapy before progression to decompensated HF.
View details for DOI 10.1038/pr.2014.183
View details for PubMedID 25406899
Reliability of echocardiographic measurements of left ventricular systolic function in potential pediatric heart transplant donors.
journal of heart and lung transplantation
2015; 34 (1): 100-106
Procollagen type III amino-terminal propeptide is a collagen III cleavage product released in blood. The serum levels of this propeptide in adults with dilated cardiomyopathy are associated with cardiac remodelling and prognosis. The utility of procollagen type III amino-terminal propeptide as a biomarker in paediatric dilated cardiomyopathy is unknown.This was a prospective, longitudinal study of children with dilated cardiomyopathy and changes in procollagen type III amino-terminal propeptide. The serum level of propeptide was measured serially, compared with paediatric normal values, and correlated with clinical status and left ventricular size and function on echocardiograms and cardiac magnetic resonance imaging.Procollagen type III amino-terminal propeptide was measured serially in 149 samples from 39 patients, age 9.0±6.4 years, followed up for 16.8±16.3 months. Procollagen type III amino-terminal propeptide in dilated cardiomyopathy was higher than in normal children. On multivariate analyses, procollagen type III amino-terminal propeptide had a positive correlation with left ventricular dilation, left ventricular end-diastolic diameter index (p<0.0001), and left ventricular end-diastolic diameter Z-score (p=0.0003), and a negative correlation with shortening fraction changes over time (p=0.001). Patients with myocarditis (n=12) had higher procollagen type III amino-terminal propeptide values than those with idiopathic dilated cardiomyopathy (n=20).Procollagen type III amino-terminal propeptide increases with left ventricular dilation and decreases with improvement in systolic function in paediatric dilated cardiomyopathy, indicating a role as a biomarker of cardiac remodelling in children. The diagnostic utility of procollagen type III amino-terminal propeptide to differentiate myocarditis from idiopathic dilated cardiomyopathy warrants further investigation.
View details for DOI 10.1017/S1047951113001820
View details for Web of Science ID 000349387000005
View details for PubMedID 24192074
HLA desensitization with bortezomib in a highly sensitized pediatric patient
2014; 18 (8): E280-E282
Thrombotic events in critically ill children with myocarditis
CARDIOLOGY IN THE YOUNG
2014; 24 (5): 840-847
Echocardiogram reports, but not images, are usually available for the evaluation of potential donor hearts. To assess the reliability of local reports of potential pediatric heart donors, we compared echocardiographic measurements of left ventricular (LV) systolic function between local hospitals and a central echocardiography laboratory.We identified all potential donors aged <18 years managed by the California Transplant Donor Network from 2009 to 2013. Echocardiograms and reports were obtained from local hospitals. All studies were reviewed in a central laboratory by an experienced pediatric cardiologist blinded to local reports. Local and central measurements of fractional shortening (FS) were compared using the Bland-Altman method (mean difference ± 2 standard deviations). LV function was categorized based on FS as normal or mild, moderately, or severely depressed.There were 70 studies from 59 donors with local and central measurements of FS. The mean difference between local and central FS was 3.9 ± 9.0. The limits of agreement ranged from -14.2 to 22. Twenty-five studies had discordant measurements of LV function, with 17 discordant by 1 category and 8 by 2 or more categories. Of 55 studies categorized as normal by local measurement, 6 were moderately to severely depressed by central review. Of 15 studies categorized as depressed by local measurement, 3 were normal by central review.Local and central measurements of LV systolic function were discordant in 36% of studies. Given such discordance, efforts to obtain and view actual echocardiographic images should be part of the standard evaluation of potential pediatric heart donors.
View details for DOI 10.1016/j.healun.2014.08.019
View details for PubMedID 25307622
Hypoalbuminemia and poor growth predict worse outcomes in pediatric heart transplant recipients
2014; 18 (3): 280-287
Children with myocarditis have multiple risk factors for thrombotic events, yet the role of antithrombotic therapy is unclear in this population. We hypothesised that thrombotic events in critically ill children with myocarditis are common and that children with myocarditis are at higher risk for thrombotic events than children with non-inflammatory dilated cardiomyopathy.This is a retrospective chart review of all children presenting to a single centre cardiac intensive care unit with myocarditis from 1995 to 2008. A comparison group of children with dilated cardiomyopathy was also examined. Antithrombotic regimens were recorded. The primary outcome of thrombotic events included intracardiac clots and any thromboembolic events.Out of 45 cases with myocarditis, 40% were biopsy-proven, 24% viral polymerase chain reaction-supported, and 36% diagnosed based on high clinical suspicion. There were two (4.4%) thrombotic events in the myocarditis group and three (6.7%) in the dilated cardiomyopathy group (p = 1.0). Neither the use of any antiplatelet or anticoagulation therapy, use of intravenous immune globulin, presence of any arrhythmia, nor need for mechanical circulatory support were predictive of thrombotic events in the myocarditis, dilated cardiomyopathy, or combined groups.Thrombotic events in critically ill children with myocarditis and dilated cardiomyopathy occurred in 6% of the combined cohort. There was no difference in thrombotic events between inflammatory and non-inflammatory cardiomyopathy groups, suggesting that the decision to use antithrombotic prophylaxis should be based on factors other than the underlying aetiology of a child's acute decompensated heart failure.
View details for DOI 10.1017/S1047951113001145
View details for Web of Science ID 000346331200009
View details for PubMedID 24016733
Hot Topics in Tetralogy of Fallot
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2013; 62 (23): 2155-2166
Children with end-stage cardiac failure are at risk of HA and PG. The effects of these factors on post-transplant outcome are not well defined. Using the PHTS database, albumin and growth data from pediatric heart transplant patients from 12/1999 to 12/2009 were analyzed for effect on mortality. Covariables were examined to determine whether HA and PG were risk factors for mortality at listing and transplant. HA patients had higher waitlist mortality (15.81% vs. 10.59%, p = 0.015) with an OR of 1.59 (95% CI 1.09-2.30). Survival was worse for patients with HA at listing and transplant (p ≤ 0.01 and p = 0.026). Infants and patients with congenital heart disease did worse if they were HA at time of transplant (p = 0.020 and p = 0.028). Growth was poor while waiting with PG as risk factor for mortality in multivariate analysis (p = 0.008). HA and PG are risk factors for mortality. Survival was worse in infants and patients with congenital heart disease. PG was a risk factor for mortality in multivariate analysis. These results suggest that an opportunity may exist to improve outcomes for these patients by employing strategies to mitigate these risk factors.
View details for DOI 10.1111/petr.12239
View details for Web of Science ID 000333807400015
View details for PubMedID 24646199
Adult and pediatric perspectives on heart retransplant.
World journal for pediatric & congenital heart surgery
2013; 4 (1): 75-79
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. We explore "hot topics" to highlight areas of emerging science for clinicians and scientists in moving toward a better understanding of the long-term management of patients with repaired TOF. From a genetic perspective, the etiology of TOF is multifactorial, with a familial recurrence risk of 3%. Cardiac magnetic resonance is the gold standard assessment tool based on its superior imaging of the right ventricular (RV) outflow tract, pulmonary arteries, aorta, and aortopulmonary collaterals, and on its ability to quantify biventricular size and function, pulmonary regurgitation (PR), and myocardial viability. Atrial re-entrant tachycardia will develop in more than 30% of patients, and high-grade ventricular arrhythmias will be seen in about 10% of patients. The overall incidence of sudden cardiac death is estimated at 0.2%/yr. Risk stratification, even with electrophysiologic testing and cardiac magnetic resonance, remains imperfect. Drug therapy has largely been abandoned, and defibrillator placement, despite its high risks for complications and inappropriate discharges, is often recommended for patients at higher risk. Definitive information about optimal surgical strategies for primary repair to preserve RV function, reduce arrhythmia, and optimize functional status is lacking. Post-operative lesions are often amenable to transcatheter intervention. In selected cases, PR may be treated with transcatheter valve insertion. Ongoing surveillance of RV function is a crucial component of clinical assessment. Except for resynchronization with biventricular pacing, no medical therapies have been shown to be effective after RV dysfunction occurs. In patients with significant PR with RV dilation, optimal timing of pulmonary valve replacement remains uncertain, although accepted criteria are emerging.
View details for DOI 10.1016/j.jacc.2013.07.100
View details for Web of Science ID 000328073000002
At the Ethics of the Heart II: Ethical and Policy Challenges in Congenital Heart Disease Conference, March 16-17, 2012 in Philadelphia, Pennsylvania, one of the sessions focused on the issues related to end-stage heart failure in patients with congenital heart disease including utilizing the therapy of heart transplantation. This article will summarize the session related to repeat heart transplant that was based on discussion of actual patient cases, two adults and one pediatric, presented, respectively, by an adult and a pediatric heart transplant specialist. Outcome data related to retransplant for both adult and pediatric heart transplant populations are reviewed. The complicated ethical issues related to considerations of beneficence versus nonmalfeasance by a medical care team for an individual patient, patient autonomy related to adherence, and obligations to society to fairly allocate the scarce precious resource of donor organs are discussed.
View details for DOI 10.1177/2150135112469972
View details for PubMedID 23799759