ArticleCirculation. Heart failure2015
Age-related differences in phosphodiesterase activity and effects of chronic phosphodiesterase inhibition in idiopathic dilated cardiomyopathy.
Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Postnatal Development Shapes the Cardiac Response to Milrinone.bioRxiv : the preprint server for biology · 2026Article
- Pediatric heart failure: Current approach and treatment.JHLT open · 2025Article
- Phosphodiesterase 5 and its inhibitors with ischaemic heart disease: a Mendelian randomization analysis and a real-world study.European heart journal. Cardiovascular pharmacotherapy · 2025Article
- Circulating and Cardiac Tissue miRNAs in Children with Dilated Cardiomyopathy.Journal of cardiovascular development and disease · 2023Article
- Integrated analysis of miRNA-mRNA interaction in pediatric dilated cardiomyopathy.Pediatric research · 2022Article
- Multiple-model machine learning identifies potential functional genes in dilated cardiomyopathy.Frontiers in cardiovascular medicine · 2022Article
- Serum response factor deletion 5 regulates phospholamban phosphorylation and calcium uptake.Journal of molecular and cellular cardiology · 2021Article
- Important Considerations in Pediatric Heart Failure.Current cardiology reports · 2020Review
- Pediatric Heart Failure: An Evolving Public Health Concern.The Journal of pediatrics · 2020Article
- Increased myocyte calcium sensitivity in end-stage pediatric dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2019Article
- Elamipretide Improves Mitochondrial Function in the Failing Human Heart.JACC. Basic to translational science · 2019Article
- A PDE3A Promoter Polymorphism Regulates cAMP-Induced Transcriptional Activity in Failing Human Myocardium.Journal of the American College of Cardiology · 2019Article
- From pediatrics to geriatrics: Mechanisms of heart failure across the life-course.Journal of molecular and cellular cardiology · 2019Review
- Evaluation of Drug-Related Receptors in Children With Dilated Cardiomyopathy.Frontiers in pediatrics · 2019Article
- Acute isoproterenol leads to age-dependent arrhythmogenesis in guinea pigs.American journal of physiology. Heart and circulatory physiology · 2018Article
- Differential Response to Heart Failure Medications in Children.Progress in pediatric cardiology · 2018Article
- Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.Pediatric research · 2017Article
- Genetics of paediatric cardiomyopathies.Current opinion in pediatrics · 2017Review
- Article
- Exosomes from pediatric dilated cardiomyopathy patients modulate a pathological response in cardiomyocytes.American journal of physiology. Heart and circulatory physiology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDespite the application of proven adult heart failure therapies to children with idiopathic dilated cardiomyopathy (IDC), prognosis remains poor. Clinical experience with phosphodiesterase 3 inhibitors (PDE3i) in pediatric patients with IDC, however, demonstrates improved heart failure symptoms without the increased incidence of sudden death seen in adults treated with PDE3i. We sought to determine age-related differences in PDE activity and associated intracellular signaling responsible for the efficacy and relative safety of chronic PDE3i in pediatric heart failure. METHODS AND
resultscAMP levels, PDE activity, and phospholamban phosphorylation (pPLB) were determined in explanted human left ventricular myocardium (pediatric n=41; adult n=88). Adults and children with IDC (not treated with PDE3i) had lower cAMP and pPLB compared with nonfailing controls. In contrast to their adult counterparts, pediatric IDC patients chronically treated with PDE3i had elevated cAMP (P=0.0403) and pPLB (P=0.0119). In addition, total PDE- and PDE3-specific activities were not altered in pediatric IDC patients on PDE3i, whereas adult IDC patients on PDE3i demonstrated higher total PDE-specific (74.6±13.8 pmol/mg per minute) and PDE3-specific (48.2±15.9 pmol/mg per minute) activities in comparison with those of nonfailing controls (59.5±14.4 and 35.5±12.8 pmol/mg per minute, respectively).
conclusionsElevated cAMP and higher pPLB may contribute to sustained hemodynamic benefits in pediatric IDC patients treated with PDE3i. In contrast, higher total PDE and PDE3 activities in adult IDC patients treated with PDE3i may perpetuate lower myocardial cAMP and pPLB levels, limiting the potential benefits of PDE3i therapy.
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