Pediatric heart failure therapy: why β1-receptor blocker, tissue ACE-I and mineralocorticoid-receptor-blocker?

Abstract

Pediatric heart failure (HF) treatment lagged behind the knowledge of pharmacological research and evidence-based clinical experience in adults. Considering the lack of prospective, double blind randomized studies in children, the review is focused on the preferred indication of specific β1-adrenoreceptor blockers (ARB), mineralocorticoid antagonists and tissue angiotensin-converting enzyme inhibitors (ACE-I). Our recommendations are based on the specificity in children, the effectiveness and the side-effect profile of HF-drugs, the receptor-physiological knowledge and the negative results of the few pediatric HF studies with an "evidence study label". In the interest of our pediatric patients, effective HF treatment has not longer to be postponed by balancing between evidence-based versus pathophysiology-based approach. At our institution, bisoprolol, lisinopril and spironolactone (BLS) are used treating HF in patients with left-right shunt lesions, reduced ejection fraction as well as during the inter-stage after HLHS-Hybrid approach. Chronic use of diuretics and fluid restriction is avoided, if always possible; intravascular volume deficiency stimulates further the neurohumoral axis. Pediatric HF needs to be treated with a strategy respecting the variable pathophysiology and the differences of receptor physiology between children and adult patients. The personalized treatment can be easily proofed by the surrogate parameters as heart rate, breath pattern, weight gain and image-derived parameters as well as biomarkers. Effective HF-therapy is also the basis for novel regenerative strategies in particular for young children with "end-stage" HF avoiding cardiac transplant or death.

Keywords: Pediatric heart failure; spironolactone; tissue ACE-inhibitor; β1-receptor blocker.

Figure 1

The figure shows our algorithm of pediatric heart failure (HF) therapy related to the clinical functional class (FC), LV-EF, LVEDD in relation to the RV-EF (right ventricular ejection fraction). The scheme classifies the severity of heart failure with mid-range (HFmrEF) and reduced ejection fraction (HFrEF); β-blocker therapy in terms of Bisoprolol, as a highly specific β1-selective AR-blocker, is recommended in all FC and even considered in infants and young children with FC IV, when catecholamines are continuously applicated in addition to PDE-3 inhibitors, as Milrinone and/or calcium sensitizer, Levosimendan (Giessen, personal experience, not proofed in randomized controlled studies). Diuretics as a first line HF-drug is not recommended; patients with FC I and II, diuretics are usually avoided; favoring adequate dosages of Bisoprolol (B), and the tissue angiotensin-converting inhibitor, Lisinopril (L); the combined treatment with low-dosed Spironolactone (S) is summarized as B-L-S therapy. FC III, when the indication for diuretics might be indicated on elevated filling pressures due to left atrial and pulmonary vein congestion, creation of a restrictive atrial septum defect (rASD) should be considered (32*). In young children (less than 5 years) and in particular infants, a surgically performed reversible pulmonary artery banding [rPAB; (33**)] is recommended in patients suffering left ventricular dilated cardiomyopathy (LV-DCM) with preserved right ventricular (pRV) function and the infant or young child is considered for cardiac transplantation (HTx, LVEDD, z-value >+4.5). In case of biventricular heart failure, resuscitation of a still patent, but constricted ductus arteriosus stenting or a surgical performed reverse Potts shunt should be considered together with generating a left-right-shunting rASD; further with or without additional bilateral PAB (back to “fetal”, parallel circulation); the strategy might be severe for bridging to cardiac transplant (HTx), avoiding assist device (AD) or cardiac recovery. BNP, brain natriuretic peptide; heart rate; SC, stem cell; &, and.