Beta-blockers in pediatric heart failure Myocardial injury Decreased myocardial performance Decreased stroke volume and cardiac output Neuro-hormonal response Activation of renin-angiotensin system Activation of sympathic nervous system Other mechanisms Sodium and fluid retention Franck-Starling mechanisms Systemic vasoconstriction Increased heart rate Increased myocardial contractility Systemic vasoconstriction Calcium release Hypertrophy Fibrosis, apoptosis Increased preload Increased afterload Increased myocardial demand Further ventricular wall stress Remodeling ventricle (dilatation, hypertrophy) Worsening heart failure Figure 1 The pathophysiological mechanisms of chronic heart failure. and morbidity (De Luca et al 2006). Elevated left ventricular ﬁlling pressures increase pulmonary and right ventricle pres- sures resulting in pulmonary and systemic congestion. This “hemodynamic congestion” may have deleterious effects on subendocardial coronary perfusion and drainage from coronary veins with subsequent diastolic dysfunction (Georghiade et al 2006). Pulmonary wedge pressure may be used as a surrogate marker of disease progression (Chen and Schrier 2006). Treatment of HF in children The rational management of chronic HF in pediatric patients requires comprehensive knowledge of the pathophysiological mechanisms and must be individualized according to age and Therapeutics and Clinical Risk Management 2007:3(5) underlying cardiac disease (Auslander and Artman 2000; Clark 2000; Ross 2001). The beneﬁcial effect of diuretics to reduce congestion and ﬂuid retention is widely accepted. Aldosterone antagonists in association with furosemide not only compensate for potas- sium loss, but also may prevent ﬁbrosis as a consequence of chronic HF and activation of the renin-angiotensin system. Several trials have demonstrated the signiﬁcant beneﬁt of angiotensin converting enzyme inhibitors on survival in adults with chronic HF. These agents can prevent car- diac remodeling through reduction of angiotensin II and aldosterone effects, and decrease myocardial wall stress by decreasing cardiac afterload (Stern et al 1990). 849