Publications by authors named "Paolo G Rusconi"

13 Publications

  • Page 1 of 1

A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys.

Pediatr Res 2019 02 17;85(3):398-404. Epub 2018 Dec 17.

Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Oishei Children's Hospital, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA.

Background: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time.

Methods: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing.

Results: With the exception of serum myoglobin, there were no statistical differences or apparent dose-response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P = .0006).

Conclusions: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-018-0256-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779032PMC
February 2019

Infantile Onset Hypertrophic Cardiomyopathy Secondary to PRKAG2 Gene Mutation is Associated with Poor Prognosis.

J Pediatr Genet 2018 Dec 2;7(4):180-184. Epub 2018 Jun 2.

Division of Pediatric Cardiology, Department of Pediatrics, Jackson Memorial Hospital, University of Miami/Miller School of Medicine, Miami, Florida, United States.

Hypertrophic cardiomyopathy (HCM) is the second most prevalent form of cardiomyopathy in children. The etiology of the HCM is heterogeneous, so is the age of onset of symptoms. The HCM associated with metabolic disorders and genetic syndromes presents early in childhood. There are very few case reports of early-onset infantile HCM secondary to the PRKAG2 gene. Here, we report a case of HCM in a neonate diagnosed prenatally and eventually diagnosed with a missense mutation in the PRKAG2 gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1657763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234042PMC
December 2018

Association of left atrial pressure with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy.

Cardiol Young 2018 Nov 31;28(11):1333-1337. Epub 2018 Jul 31.

1Department of Pediatrics,Division of Pediatric Cardiology,Jackson Memorial Hospital/University of Miami Miller School of Medicine,Miami,FL,USA.

Background: Enlargement of the left atrium is a non-invasive marker of diastolic dysfunction of the left ventricle, a determinant of prognosis in children with cardiomyopathy. Similarly, N-terminal prohormone brain natriuretic peptide is a useful marker in the management of children with cardiomyopathy and heart failure. The aim of this study is to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy.

Methods: This was a retrospective study reviewing the medical records of patients <18 years of age, who were diagnosed with cardiomyopathy or acute myocarditis with eventual development of cardiomyopathy. Left atrial volume by transthoracic echocardiogram and pulmonary capillary wedge pressure, a surrogate of left atrial pressure, obtained by means of cardiac catheterisation were analysed. In addition, N-terminal prohormone brain natriuretic peptide levels obtained at the time of the cardiac catheterisation were also reviewed. Statistical analysis was performed to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide levels.

Results: There was a linear correlation of left atrial pressure estimated in the cardiac catheterisation with indexed left atrial volume (r=0.63; p<0.001) and left atrial volume z-scores (r=0.59; p<0.001). We found no statistically significant association between the left atrial pressure and N-terminal prohormone brain natriuretic peptide levels.

Conclusions: Left atrial volume measured non-invasively by echocardiography can be used as a surrogate for left atrial pressure in assessing diastolic dysfunction of the left ventricle in children with cardiomyopathy. The larger the size of the left atrium, worse is the diastolic function of the left ventricle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951118001312DOI Listing
November 2018

Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: A report from the Pediatric Heart Transplant Study (PHTS) group.

Pediatr Transplant 2017 Aug 4;21(5). Epub 2017 Apr 4.

Pediatric Heart Transplant Study (PHTS) Group, Birmingham, AL, USA.

We aimed to determine whether malignancy after pediatric HTx for ACM affects overall post-HTx survival. Patients <18y listed for HTx for ACM in the PHTS database between 1993 and 2014 were compared to those with DCM. A 2:1 matched DCM cohort was also compared. Wait-list and post-HTx survival, along with freedom from common HTx complications, were compared. Eighty subjects were listed due to ACM, whereas 1985 were listed for DCM. Although wait-list survival was higher in the ACM group, post-HTx survival was lower for the ACM cohort. Neither difference persisted in the matched cohort analysis. Primary cause of death in the ACM group was infection, which was higher than the DCM group. Malignancy rates were not different. All ACM malignancies were due to PTLD without primary cancer recurrence or SMN. Long-term graft survival after pediatric HTx for ACM is no different than for matched DCM peers, nor is there an increased risk of any malignancy. However, risk of infection and death from infection after HTx are higher in the ACM group. Further studies are needed to assess the effects of prior chemotherapy on susceptibility to infection in this group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.12923DOI Listing
August 2017

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

Clinics (Sao Paulo) 2014 ;69 Suppl 1:55-72

Division of Pediatric Clinical Research, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884162PMC
http://dx.doi.org/10.6061/clinics/2014(sup01)11DOI Listing
December 2014

Pediatric cardiomyopathies: causes, epidemiology, clinical course, preventive strategies and therapies.

Future Cardiol 2013 Nov;9(6):817-48

Department of Pediatrics, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, 9th Floor, Miami, FL 33136, USA.

Pediatric cardiomyopathies, which are rare but serious disorders of the muscles of the heart, affect at least one in every 100,000 children in the USA. Approximately 40% of children with symptomatic cardiomyopathy undergo heart transplantation or die from cardiac complications within 2 years. However, a significant number of children suffering from cardiomyopathy are surviving into adulthood, making it an important chronic illness for both pediatric and adult clinicians to understand. The natural history, risk factors, prevalence and incidence of this pediatric condition were not fully understood before the 1990s. Questions regarding optimal diagnostic, prognostic and treatment methods remain. Children require long-term follow-up into adulthood in order to identify the factors associated with best clinical practice including diagnostic approaches, as well as optimal treatment approaches. In this article, we comprehensively review current research on various presentations of this disease, along with current knowledge about their causes, treatments and clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/fca.13.66DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903430PMC
November 2013

Associations between fibroblast growth factor 23 and cardiac characteristics in pediatric heart failure.

Pediatr Nephrol 2013 Oct 6;28(10):2035-42. Epub 2013 Jun 6.

Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, 1120 NW 14th St., Miami, FL 33136, USA.

Background: In adults with heart failure, elevated levels of fibroblast growth factor 23 (FGF23) are associated with mortality. Data on FGF23 levels in pediatric heart failure are lacking.

Patients And Methods: We conducted a cross-sectional study of 17 healthy children (mean age 13 years) and 20 pediatric patients with heart failure (mean age 12 years) who underwent echocardiography and for whom the following measurements were taken: plasma FGF23 and parathyroid hormone (PTH) and serum phosphate, creatinine and N-terminal prohormone brain natriuretic peptide (NT-proBNP). Symptom severity was assessed with the New York Heart Association and the Ross classification systems.

Results: Of the 20 patients, 11 had dilated cardiomyopathy, four had congenital heart disease, three had hypertrophic cardiomyopathy, one had a failing heart transplant and one had pulmonary hypertension. Mean phosphate levels in these patients were within the reported reference range for healthy children. Median PTH levels were in the normal range in patients and controls. The median FGF23 level was higher in patients versus controls (110.9 vs. 66.4 RU/ml; P = 0.03) and higher in patients on diuretics versus other patients (222.4 vs. 82.1 RU/ml; P = 0.01). Levels of FGF23 and NT-proBNP were directly correlated (r = 0.47, P = 0.04), and patients with greater physical functional impairment had higher FGF23 levels (142.5 in those with moderate-severe limitation vs. 92.8 RU/ml in those with no limitation; P = 0.05). Among patients with dilated cardiomyopathy, higher FGF23 levels were associated with a greater left ventricular end-diastolic diameter (r = 0.63, P = 0.04).

Conclusion: FGF23 levels are elevated in children with heart failure and are associated with diuretic use, severity of heart failure and left ventricular dilation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-013-2515-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755096PMC
October 2013

Outcomes of restrictive cardiomyopathy in childhood and the influence of phenotype: a report from the Pediatric Cardiomyopathy Registry.

Circulation 2012 Sep 27;126(10):1237-44. Epub 2012 Jul 27.

Division of Cardiology, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.

Background: Restrictive cardiomyopathy (RCM) has been associated with poor prognosis in childhood. The goal of the present analysis was to use the Pediatric Cardiomyopathy Registry to analyze outcomes of childhood RCM, with a focus on the impact of phenotype comparing pure RCM with cases that have additional features of hypertrophic cardiomyopathy (HCM).

Methods And Results: We analyzed the Pediatric Cardiomyopathy Registry database (1990-2008; N=3375) for cases of RCM. Cases were defined as pure when RCM was the only assigned diagnosis. Additional documentation of HCM at any time was used as the criterion for RCM/HCM phenotype. RCM accounted for 4.5% of cases of cardiomyopathy. In 101 (66%), pure RCM was diagnosed; in 51 (34%), there was a mixed phenotype. Age at diagnosis was not different between groups, but 10% of the pure RCM group was diagnosed in infancy versus 24% of the RCM/HCM group. Freedom from death was comparable between groups with 1-, 2-, and 5-year survival of RCM 82%, 80%, and 68% versus RCM/HCM 77%, 74%, and 68%. Transplant-free survival was 48%, 34%, and 22% and 65%, 53%, and 43%, respectively (P=0.011). Independent risk factors at diagnosis for lower transplant-free survival were heart failure (hazard ratio 2.20, P=0.005), lower fractional shortening z score (hazard ratio 1.12 per 1 SD decrease in z score, P=0.014), and higher posterior wall thickness in the RCM/HCM group only (hazard ratio 1.32, P<0.001). Overall, outcomes were worse than for all other forms of cardiomyopathy.

Conclusions: Transplant-free survival is poor for RCM in childhood. Survival is independent of phenotype; however, the RCM/HCM phenotype has significantly better transplant-free survival.

Clinical Trials Registration: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00005391.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.112.104638DOI Listing
September 2012

Competing risks for death and cardiac transplantation in children with dilated cardiomyopathy: results from the pediatric cardiomyopathy registry.

Circulation 2011 Aug 25;124(7):814-23. Epub 2011 Jul 25.

Department of Pediatrics (D820), Miller School of Medicine, University of Miami, P.O. Box 016820, Miami, FL 33101, USA.

Background: Pediatric dilated cardiomyopathy (DCM) is the leading indication for heart transplantation after 1 year of age. Risk factors by etiology at clinical presentation have not been determined separately for death and transplantation in population-based studies. Competing risks analysis may inform patient prioritization for transplantation listing.

Methods And Results: The Pediatric Cardiomyopathy Registry enrolled 1731 children diagnosed with DCM from 1990 to 2007. Etiologic, demographic, and echocardiographic data collected at diagnosis were analyzed with competing risks methods stratified by DCM etiology to identify predictors of death and transplantation. For idiopathic DCM (n=1192), diagnosis after 6 years of age, congestive heart failure, and lower left ventricular (LV) fractional shortening z score were independently associated with both death and transplantation equally. In contrast, increased LV end-diastolic dimension z score was associated only with transplantation, whereas lower height-for-age z score was associated only with death. For neuromuscular disease (n=139), lower LV fractional shortening was associated equally with both end points, but increased LV end-diastolic dimension was associated only with transplantation. The risks of death and transplantation were increased equally for older age at diagnosis, congestive heart failure, and increased LV end-diastolic dimension among those with myocarditis (n=272) and for congestive heart failure and decreased LV fractional shortening among those with familial DCM (n=79).

Conclusions: Risk factors for death and transplantation in children varied by DCM etiology. For idiopathic DCM, increased LV end-diastolic dimension was associated with increased transplantation risk but not mortality. Conversely, short stature was significantly related to death but not transplantation. These findings may present an opportunity to improve the transplantation selection algorithm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.110.973826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199969PMC
August 2011

Danon disease: characteristic late gadolinium enhancement pattern on cardiac magnetic resonance imaging.

Cardiol Young 2011 Dec 19;21(6):707-9. Epub 2011 May 19.

Department of Pediatrics, Miller School of Medicine, University of Miami, Florida 33136, USA.

Danon disease is a rare entity associated with the clinical triad of mental retardation, skeletal myopathy, and severe hypertrophic cardiomyopathy. We report two cases of Danon disease and describe the results of the cardiac magnetic resonance imaging studies that were conducted to assess the pattern of cardiac hypertrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951111000564DOI Listing
December 2011

Serial measurements of serum NT-proBNP as markers of left ventricular systolic function and remodeling in children with heart failure.

Am Heart J 2010 Oct;160(4):776-83

Divisions of Pediatric Cardiology, Miami, FL, USA.

Background: Increasing serum levels of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) are associated with worsening heart failure (HF) in adults. We determined whether changes in NT-proBNP level are associated with changes in symptoms and left ventricular (LV) systolic function and remodeling in children with HF secondary to dilated cardiomyopathy.

Methods: We retrospectively examined associations between serum NT-proBNP levels and NYHA/Ross functional class, LV systolic and diastolic diameter (LVSD-z and LVDD-z), LV ejection fraction (LVEF), and LV shortening fraction (LVSF-z) using generalized linear mixed models. Fluctuation in functional class of subjects was also modeled using logistic regression and receiver operating characteristic (ROC) curves.

Results: In 36 children (14 males), a 10-fold increase in NT-proBNP serum levels was associated (P < .001) with a 9.8% decrease in LVEF, a 3.25-unit drop in LVSF-z, a 1.53-unit increase in LVDD-z, a 2.64-unit increase in LVSD-z, and an increased odds of being in functional class III/IV (OR 85.5; 95% CI, 10.9 to 671.0). An NT-proBNP level greater than 1000 pg/mL identified children constantly or intermittently in functional class III-IV with 95% sensitivity and 80% specificity. The reliability of a single NT-proBNP value was 0.61, but the means for two and three NT-proBNP values were 0.76 and 0.82, respectively.

Conclusions: In children with HF, NT-proBNP is associated with cardiac symptoms and indices of LV systolic dysfunction and remodeling. NT-proBNP >1000 pg/mL identifies highly symptomatic children. Within subject serial measurements of NT-proBNP are needed for a reliable and accurate determination of disease status and/or course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2010.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964279PMC
October 2010

Ventricular remodeling and survival are more favorable for myocarditis than for idiopathic dilated cardiomyopathy in childhood: an outcomes study from the Pediatric Cardiomyopathy Registry.

Circ Heart Fail 2010 Nov 10;3(6):689-97. Epub 2010 Sep 10.

Washington University at St Louis, 1 Children’s Place, St Louis, MO 63110, USA.

Background: Myocarditis is a cause of a new-onset dilated cardiomyopathy phenotype in children, with small studies reporting high rates of recovery of left ventricular (LV) function.

Methods And Results: The presenting characteristics and outcomes of children with myocarditis diagnosed clinically and with biopsy confirmation (n=119) or with probable myocarditis diagnosed clinically or by biopsy alone (n=253) were compared with children with idiopathic dilated cardiomyopathy (n=1123). Characteristics at presentation were assessed as possible predictors of outcomes. The distributions of time to death, transplantation, and echocardiographic normalization in the biopsy-confirmed myocarditis and probable myocarditis groups did not differ (P≥0.5), but both groups differed significantly from the idiopathic dilated cardiomyopathy group (all P≤0.003). In children with myocarditis, lower LV fractional shortening z-score at presentation predicted greater mortality (hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98; P=0.03) and greater LV posterior wall thickness predicted transplantation (hazard ratio, 1.17; 95% confidence interval, 1.02 to 1.35; P=0.03). In those with decreased LV fractional shortening at presentation, independent predictors of echocardiographic normalization were presentation with an LV end-diastolic dimension z-score >2 (hazard ratio, 0.36; 95% confidence interval, 0.22 to 0.58; P<0.001) and greater septal wall thickness (hazard ratio, 1.16; 95% confidence interval, 1.01 to 1.34; P=0.04).

Conclusions: Children with biopsy-confirmed or probable myocarditis had similar proportions of death, transplantation, and echocardiographic normalization 3 years after presentation and better outcomes than those of children with idiopathic dilated cardiomyopathy. In children with myocarditis who had impaired LV ejection at presentation, rates of echocardiographic normalization were greater in those without LV dilation and in those with greater septal wall thickness at presentation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005391.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCHEARTFAILURE.109.902833DOI Listing
November 2010

Usefulness of tissue Doppler echocardiography for evaluating ventricular function in children without heart disease.

Am J Cardiol 2003 Mar;91(5):570-4

Department of Pediatrics, University of Miami/Jackson Memorial Medical Center, Florida 33101, USA.

Tissue Doppler echocardiographic imaging (TDI) is a novel method for accurately evaluating ventricular function. Currently, scant data are available on the distribution of tissue Doppler indexes in healthy children in the age range of 1 to 18 years. The aims of this study were to assess the distribution of tissue Doppler indexes of systolic and diastolic ventricular function in healthy children, to assess the influence of age on these indexes, and to compare them with conventional Doppler indexes. A total of 151 consecutive children aged 1 to 18 years were enrolled in the study. Nine different (7 diastolic and 2 systolic) TDI parameters were assessed. Peak velocities of systolic and diastolic excursions of the mitral and tricuspid annuli were obtained from the apical 4-chamber view. Mean velocities of early diastolic recoil of mitral and tricuspid annuli were measured from the apical 4-chamber view. The mean velocity of early diastolic relaxation of the left ventricular posterior wall was measured in the parasternal long-axis view. Results showed a statistically significant difference in some of the TDI indexes among the different pediatric age groups. Most of the TDI indexes showed a very weak correlation with age. There was no significant correlation (p >0.05) between peak velocities of the early diastolic mitral inflow Doppler pattern (E wave) and the corresponding TDI index. In contrast, there was a significant (p <0.001) correlation between the corresponding Doppler indexes in the tricuspid annulus. We conclude that TDI is a valuable tool for assessing ventricular function, particularly diastolic function. Establishment of normative data for TDI in the pediatric age group should broaden the clinical applicability of this useful modality for assessing ventricular function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0002-9149(02)03308-8DOI Listing
March 2003