“Nihilism” of chronic heart failure therapy in children and why effective therapy is withheld

Abstract

Major advances in chronic heart failure (cHF) therapy have been achieved and documented in adult patients, while research regarding the mechanisms and therapy of cHF in children has lagged behind. Based on receptor physiological studies and pharmacological knowledge, treatment with specific ß1-adrenergic receptor blocker (ARB), tissue angiotensin-converting enzyme inhibitor (ACE-I), and mineralocorticoid antagonists have to be recommended in children despite lack of sufficient data derived from prospective randomized studies. At our institution, bisoprolol, lisinopril, and spironolactone have been firmly established to treat systolic cHF, hypoplastic left heart syndrome (HLHS) following hybrid approach and congenital left-right shunt diseases, latest in patients where surgery has to be delayed. Chronic therapy with long-acting diuretics and fluid restriction are not advocated because short-term effects are achieved at the expense of further neuro-humoral stimulation. It remains unclear why diuretics are recommended although evidence-based studies, documenting long-term benefit, are missing. However, that is true for all currently used drugs for pediatric cHF.Conclusion: This review focuses on the prevailing “nihilism” of cHF therapy in children with the goal to encourage physicians to treat pediatric cHF with a rationally designed therapy, which combines available agents that have been shown to improve survival in adult patients with cHF. Because of the lack of clinical trials, which generate the needed evidence, surrogate variables like heart and respiratory rate, weight gain, image-derived data, and biomarkers should be monitored and used instead. The recommended pharmacological therapy for systolic heart failure is also provided as the basis for utilizing reversible pulmonary arterial banding (PAB) as a novel strategy in young children with dilative cardiomyopathy (DCM) with preserved right ventricular function. What is Known: • Heart failure (HF) in children is a serious public health concern. • HF has numerous etiologies, but unspecific symptoms. • HF interplays among neuro-humoral, and molecular abnormalities. • Pediatric cHF-therapy is currently based on loop-diuretics, fluid restriction and digoxin. What is New: • Cardiac function analysis has to include cardiac synchrony and VVI. • Considering enormous potential of cardiac regeneration, therapy has to extend with selective ß1-ARB, tissue ACE-I and mineralocorticoid blockers, loop-diuretics avoided as ever possible. • Inhibition of the endogenous neuro-humoral stimulation is monitored by surrogate parameters as heart and breath rate and systolic and diastolic blood pressure. • Advocated HF therapy serves for regenerative strategies as reversible Pulmonary Artery Banding in DCM. Electronic supplementary materialThe online version of this article (doi:10.1007/s00431-016-2700-3) contains supplementary material, which is available to authorized users.

The impact of home hemodialysis in children with severe cardiac failure

“…Research in adult patients on the mechanism and therapies of dilated cardiomyopathy and cardiac failure is concordant on the value of ACE inhibitors, B-receptor antagonists, and mineralocorticoid antagonists 7,8 . However, the evidence in dialysis patients with heart failure, in particular children is scarce.…”

Current Therapy for Hypoplastic Left Heart Syndrome and Related Single Ventricle Lesions

“…In addition, time under anesthesia with slightly permissive hypercapnic ventilation can be held short, followed by immediate spontaneous breathing and early extubation. The heart rate and systemic vascular resistance (Rs) are perioperatively controlled by continuous infusion of the alpha-2 agonist clonidine, followed by early oral application of a ß1-receptor blocker (bisoprolol) together with tissue ACE-inhibitor (lisinopril) without jeopardizing the coronary perfusion pressure [41]. …”

“…In regard to the important role of the parents, the cardiovascular medications need to be safe, well understood and easily administered. The respiratory rate while sleeping, oral intake, body weight are monitored closely by the parents [30, 41]. In addition, interstage management requires close outpatient evaluation by an experienced pediatric cardiologist, in order to detect any hemodynamic imbalance prior to the development of any crisis [30].…”

Aetiology, diagnosis and management of heart failure in infants and children

“…(49)(50)(51)(52)(53)(54) Different types of diuretics, their mechanism of action, their short and long term effects and their common side effects are presented in Table IV.…”

“…Digoxin has been shown not to effect improvement of heart failure in paediatric patients with left to right shunts and preserved systolic function. (50) Common side effects of digoxin include arrhythmias, digitalis toxicity, particularly in patients with renal impairment or if used with amiodarone.…”