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Pediatric Chronic Heart Failure: Age-Specific Considerations of Medical Therapy
1Children's Heart Centre, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. karel.koubsky@fnmotol.cz.
Insights
Pediatric chronic heart failure (CHF) treatment differs from adults due to unique pathophysiology. This review discusses optimizing medical therapy for pediatric CHF, focusing on unique molecular and cellular mechanisms.
Area of Science:
- Cardiology
- Pediatric Medicine
- Pharmacology
Background:
- Chronic heart failure (CHF) is rare in children but has high mortality.
- Pediatric CHF treatment often relies on adult guidelines, with limited evidence for pediatric efficacy.
- Pediatric CHF pathophysiology may differ from adults at molecular and cellular levels, impacting therapeutic approaches.
Purpose of the Study:
- To review the main pathophysiological goals of medical treatment for pediatric CHF with systemic left ventricular dysfunction.
- To discuss current and emerging pharmacotherapies for pediatric CHF.
- To highlight the need for pediatric-specific evidence and therapeutic strategies.
Main Methods:
- Review of existing literature on pediatric CHF pathophysiology and treatment.
- Discussion of pharmacological agents based on their mechanisms of action and evidence in pediatric populations.
- Analysis of differences between adult and pediatric CHF.
Main Results:
- Pediatric CHF pathophysiology involves different molecular pathways, potentially leading to less fibrosis and hypertrophy than in adults.
- Key therapeutic goals include optimizing preload/afterload, reducing cardiomyocyte apoptosis/necrosis and fibrosis, and managing myocardial oxygen consumption.
- Cornerstone therapies include ACE inhibitors (ACEI), beta blockers, and mineralocorticoid receptor antagonists, with potential benefits from tissue ACEI and β1-selective beta blockers.
Conclusions:
- Pediatric CHF requires tailored therapeutic strategies that consider its unique pathophysiology.
- Optimizing myocardial conditions is crucial for harnessing the regenerative potential of the pediatric myocardium.
- Further research is needed to establish evidence-based guidelines for pediatric CHF pharmacotherapy, including novel agents like angiotensin receptor-neprilysin inhibitors and SGLT2 inhibitors.
Abstract:
Chronic heart failure (CHF) is a rare entity in children but carries a burden of high mortality and morbidity. Medical treatment of pediatric CHF is largely based on guidelines for the adult population. In contrast to adults, evidence for the efficacy of medications in treating CHF in children is sparse. This may be due to the difficulty of conducting high-powered studies in children or to true differences in the mechanisms of CHF pathophysiology. Recent observations suggest that CHF in children differs from adults at the molecular and cellular levels. Different pathways are involved, leading to less fibrosis and hypertrophy than in adults, with potential implications for therapy. The main pathophysiological goals of medical treatment of pediatric CHF due to systemic left ventricular dysfunction are discussed in this review. These include preload and afterload optimization, diminishing cardiomyocyte apoptosis and necrosis as well as interstitial fibrosis, and optimizing myocardial oxygen consumption. The pediatric myocardium should be provided with optimal conditions to achieve its regenerative potential. The cornerstones of medical CHF therapy are angiotensin converting enzyme inhibitors (ACEI), beta blockers and mineralocorticoid receptor antagonists. There are potential benefits of tissue ACEI and ?1-selective beta blockers in children. Angiotensin receptor blockers are an alternative to ACEI and their slightly different mechanism of action may confer certain advantages and disadvantages. Diuretics are employed to achieve a euvolemic state. Digoxin is used more frequently in children than in adults. Promising new drugs already routinely used in adults include angiotensin receptor-neprilysin inhibitors and sodium-glucose contransporter 2 inhibitors. Key words: Pediatric heart failure, Heart failure with reduced ejection fraction (HFrEF), ACE inhibitor, Beta blocker, Digoxin.
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