Current and Future Drug and Device Therapies for Pediatric Heart Failure Patients: Potential Lessons from Adult Trials

Abstract

This review discusses the potential drug and device therapies for pediatric heart failure (HF) due to reduced systolic function. It is important to realize that most drugs that are used in pediatric HF are extrapolated from adult cardiology practices or consensus guidelines based on expert opinion rather than on evidence from controlled clinical trials. It is difficult to conclude whether the drugs that are well established in adult HF trials are also beneficial for children because of tremendous heterogeneity in the mechanism of HF in children and variations in the pharmacokinetics and pharmacodynamics of drugs from birth to adolescence. The lessons learned from adult trials can guide pediatric cardiologists to design clinical trials of the newer drugs that are in the pipeline to study their efficacy and safety in children with HF. This paper’s focus is that the reader should specifically think through the pathophysiological mechanism of HF and the mode of action of drugs for the selection of appropriate pharmacotherapy. We review the drug and device trials in adults with HF to highlight the knowledge gap that exists in the pediatric HF population.

Paediatric heart failure in Uyo: A retrospective analysis

“…Because the causes of heart failure in children differs significantly from that in adults, extrapolation of treatment modalities from adults to children is not ideal especially with the varying pharmacokinetics and pharmacodynamics of drugs observed from birth through adolescence. 2 In this study, use of antibiotics played a major role because of the predominance of acute lower respiratory tract infections and sepsis as causes of heart failure.…”

“…1 It is a subject that although widely studied, continues to present challenges in management especially in children with difficulties still existing in drug therapy because of the variation that exists not only in drug pharmacokinetics and pharmacodynamics as children grow from birth to adolescence but also in the causes of heart failure in children. 2 In Nigeria, the prevalence of paediatric heart failure is known to vary widely with rates ranging between 3%-15.5% with most of the studies being hospital based. [3][4][5][6][7][8] Globally, the incidence and prevalence of heart failure is difficult to ascertain owing to the lack of a consensus definition for heart failure however, a recent study by Shaddy et al gave incidence rates ranging between 0.87/100,000 (UK and Ireland), 7.4/100,000 (Taiwan), and 83.3/100,000 (Spain).…”

Congenital Heart Disease: The State-of-the-Art on Its Pharmacological Therapeutics

“…In 2013, the use of ACEIs was approved for the treatment of pediatric heart failure, regardless of etiology [46]. However, its effects have not been thoroughly studied [50]. To date, there is a class I recommendation for patients with left ventricular dysfunction for the use of ACEIs, as well as a class IIa recommendation for asymptomatic patients [14] Some studies have shown that adults with heart failure and children with dilated cardiomyopathy or systolic ventricular function treated with ACEIs had better survival at a one-and two-year follow-up compared with those treated with digoxin and potassium diuretics, such as spironolactone (Sections 2.5.3 and 2.3.2, respectively) [13,14].…”

“…In 2013, the use of ACEIs was approved for the treatment of pediatric heart failure, regardless of etiology [ 46 ]. However, its effects have not been thoroughly studied [ 50 ]. To date, there is a class I recommendation for patients with left ventricular dysfunction for the use of ACEIs, as well as a class IIa recommendation for asymptomatic patients [ 14 ].…”

“…Adjunctive medications with known benefits, such as arrhythmia prevention [ 121 ], symptom reduction [ 122 ], mitigation of neurohormonal activation [ 50 ], and closure of the patent ductus arteriosus in treating CHDs [ 123 ], are reported for angiotensin receptor-neprilysin inhibitors (ARNIs) [ 103 , 124 ], antiarrhythmics [ 125 ], digoxin [ 126 ], and non-steroidal anti-inflammatory drugs (NSAIDs) [ 127 ].…”