Heart Failure in Children: Etiology and Treatment

Rossano, Joseph W.; Shaddy, Robert E.

doi:10.1016/j.jpeds.2014.04.055

Cited by 71 publications

(56 citation statements)

References 56 publications

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“…In addition, the improved recognition and management of acute heart failure at initial diagnosis or at exacerbation with enhanced intensive care unit level care may have led to better transplant-free survival in the more recent decade. Finally, more pediatric centers are now providing multidisciplinary heart failure care for these children which may lead to improved outcomes in these patients (44). …”

Section: Discussionmentioning

confidence: 99%

Survival Without Cardiac Transplantation Among Children With Dilated Cardiomyopathy

Singh

Canter

Shi

et al. 2017

Journal of the American College of Cardiology

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Background Studies of children with dilated cardiomyopathy (DCM) have suggested that improved survival has been primarily due to utilization of heart transplantation. Objectives We determined transplant-free survival for these children over 20 years and sought to identify the clinical characteristics at diagnosis that predicted death. Methods Children less than 18 years old with some type of DCM enrolled in the Pediatric Cardiomyopathy Registry were divided by year of diagnosis into an early cohort (1990–1999) and a late cohort (2000–2009). Competing risks and multivariable modeling were used to estimate the cumulative incidence of death, transplant, and echocardiographic normalization by cohort and to identify the factors associated with death. Results Of 1953 children, 1199 were in the early cohort and 754 were in the late cohort. Most children in both cohorts had idiopathic DCM (64% vs. 63%, respectively). Median age (1.6 vs. 1.7 years), left ventricular (LV) end diastolic z-scores (+4.2 vs. +4.2) and LV fractional shortening (16% vs. 17%) at diagnosis were similar between cohorts. Although the rates of echocardiographic normalization (30% and 27%) and heart transplantation (24% and 24%) were similar, the death rate was higher in the early cohort than in the late cohort (18% vs. 9%; p = 0.04). Being in the early cohort (hazard ratio [HR], 1.4; 95% CI, 1.04–1.9; p = 0.03) independently predicted death. Conclusions Children with DCM have improved survival in the more recent era. This appears to be associated with factors other than heart transplantation, which was equally prevalent in both eras.

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Section: Discussionmentioning

confidence: 99%

Survival Without Cardiac Transplantation Among Children With Dilated Cardiomyopathy

Singh

Canter

Shi

et al. 2017

Journal of the American College of Cardiology

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“…While surgical interventions have dramatically improved outcomes and longevity in patients with CHD, many patients still progress to heart failure, a population that has grown significantly over the last decade (30). In contrast to adult patients, in whom ischemic heart disease is the predominant etiology of heart failure, children with CHD are frequently exposed to acute or chronic ventricular pressure and volume overload, which if untreated can progress to ventricular dysfunction and ultimately to heart failure.…”

Section: We Demonstrate For the First Time That Intramyocardial Injecmentioning

confidence: 99%

Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload

Wehman

Sharma

Pietris

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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(MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n ϭ 5) or placebo (n ϭ 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P Ͻ 0.01), increased RV fractional area of change, and improved myocardial strain mechanics relative to placebo (P Ͻ 0.01). The MSC-treated myocardium demonstrated enhanced neovessel formation (P Ͻ 0.0001), superior recruitment of endogenous c-kitϩ cardiac stem cells to the RV (P Ͻ 0.0001) and increased proliferation of cardiomyocytes (P ϭ 0.0009) and endothelial cells (P Ͻ 0.0001). Hypertrophic changes in the RV were more pronounced in the placebo group, as evidenced by greater wall thickness by echocardiography (P ϭ 0.008), increased cardiomyocyte cross-sectional area (P ϭ 0.001), and increased expression of hypertrophy-related genes, including brain natriuretic peptide, ␤-myosin heavy chain and myosin light chain. Additionally, MSC-treated myocardium demonstrated increased expression of the antihypertrophy secreted factor, growth differentiation factor 15 (GDF15), and its downstream effector, SMAD 2/3, in cultured neonatal rat cardiomyocytes and in the porcine RV myocardium. This is the first report of the use of MSCs as a therapeutic strategy to preserve RV function and attenuate remodeling in the setting of pressure overload. Mechanistically, transplanted MSCs possibly stimulated GDF15 and its downstream SMAD proteins to antagonize the hypertrophy response of pressure overload. These encouraging results have implications in congenital cardiac pressure overload lesions. stem cell therapy; congenital heart disease; right ventricle; pressure overload CONGENITAL HEART DISEASE (CHD) is the leading cause of morbidity and mortality in children with birth defects. While surgical interventions have dramatically improved outcomes and longevity in patients with CHD, many patients still progress to heart failure, a population that has grown significantly over the last decade (30). In contrast to adult patients, in whom ischemic heart disease is the predominant etiology of heart failure, children with CHD are frequently exposed to acute or chronic ventricular pressure and volume overload, which if untreated can progress to ventricular dysfunction and ultimately to heart failure. Further, patients with CHD who develop right ventricular (RV) dysfunction have the poorest outcomes (23, 26), particularly in those patients with univentricular heart disease i...

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“…The prevalence of pediatric heart failure has increased dramatically in the last three decades, resulting in frequent hospitalizations, development of significant comorbidities, and protracted heart transplantation waiting-list times [1]. Given the current limitations in medical therapy and the limited number of donors available for pediatric heart transplantation, the potential for an effective cell-based therapy for pediatric heart failure patients is an attractive option.…”

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confidence: 99%

Pediatric End-Stage Failing Hearts Demonstrate Increased Cardiac Stem Cells

Wehman

Sharma

Mishra

et al. 2015

The Annals of Thoracic Surgery

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Background We sought to determine the location, expression, and characterization of cardiac stem cells (CSCs) in children with end-stage heart failure (ESHF). We hypothesized ESHF myocardium would contain an increased number of CSCs relative to age-matched healthy myocardium, and ESHF-derived CSCs would have diminished functional capacity as evidenced by reduced telomere length. Methods Tissue samples were obtained from the explanted hearts of children undergoing heart transplantation with ESHF, defined as New York Heart Association class III or IV and ejection fraction less than 0.20, and from age-matched congenital heart disease patients with normal myocardium. The expression profile of cardiac-specific stem cell markers was determined using quantitative real time polymerase chain reaction and immunofluorescence. Cardiac stem cell growth reserve was assessed with telomere length. Results There were 15 ESHF and 15 age-matched congenital heart disease patients. End-stage heart failure myocardium demonstrated increased expression of c-kit+ and islet-1+ CSCs by 2.0- and 2.5-fold, respectively, compared with myocardium from congenital heart disease patients. There was no difference in expression of c-kit+ CSCs with advancing age from infants to children in ESHF myocardium. The c-kit+ CSCs isolated from ESHF patients demonstrated significantly reduced telomere length, suggesting a diminished functional capability in these cells (8.1 ± 0.6 kbp versus 6.3 ± 0.3 kbp; p = 0.015). Conclusions End-stage heart failure myocardium demonstrated an age-independent increase in CSCs relative to healthy myocardium; however, these CSCs from ESHF patients may have diminished proliferative ability and reduced functionality as an autologous cell therapy candidate. Further investigation is necessary to determine the role of ESHF-derived CSCs within the myocardium.

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Heart Failure in Children: Etiology and Treatment

Cited by 71 publications

References 56 publications

Survival Without Cardiac Transplantation Among Children With Dilated Cardiomyopathy

Survival Without Cardiac Transplantation Among Children With Dilated Cardiomyopathy

Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload

Pediatric End-Stage Failing Hearts Demonstrate Increased Cardiac Stem Cells

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