Treatment of Chronic Heart Failure The treatment of chronic heart failure has changed greatly over the years Not surprisingly, once it was recognized that the cause of congestive heart failure was a failing pump, treatment strategies were directed toward making the pump work better For centuries, the only treatment available for heart failure was digitalis First described by Withering in his classic monograph in 1785, this author praised the efficacy of the leaves of the common foxglove plant.52 With the advent of the understanding of the complex neurohormonal syndrome now recognized as heart failure, strategies for the treatment of heart failure have changed from that of increasing pump function to that of decreasing the maladaptive neurohormonal stimulation associated with heart failure In fact, no positive inotropic medication has been shown to increase survival in heart failure The following discussion focuses on the current strategies for the treatment of heart failure, particularly as related to children The development of an evidence base for the treatment of chronic heart failure is somewhat unique in that few drugs solely for the treatment of heart failure have been developed; angiotensin converting enzyme (ACE) inhibitors, β-adrenergic blockers, and adrenergic receptor blockers (ARBs) were developed initially for the treatment of hypertension The use of the term heart failure in children can have many different implications Patients with large left-to-right intracardiac shunts with pulmonary overcirculation and tachypnea can be described as being in heart failure despite that fact that ventricular performance is usually normal Surgical outcomes for the treatment of these types of lesions, even in the smallest and youngest of infants, are now good enough to recommend early surgical correction Thus, with few exceptions, long-term medical management of these structural lesions is unnecessary and is not discussed in this chapter Similarly, medical management of symptomatic valvar regurgitation is no longer routinely considered, since surgical correction is the treatment of choice in most cases Finally, an evidence base is lacking for the treatment of patients with cardiac failure with preserved ejection fraction, particularly children Because of this paucity of data, this type of heart failure is not discussed The remainder of this chapter focuses on the treatment of heart failure with reduced ejection fraction (HFrEF) in children and adults Digoxin As stated earlier, digitalis has been the mainstay of chronic heart failure treatment for centuries Even before physicians knew what actually caused edema, shortness of breath, and/or anasarca, it was understood that digitalis improved these maladies in addition to normalizing an irregular heart rate Once it was known that this syndrome of edema, shortness of breath, anasarca, and irregular heart rate was due to poor cardiac function, the use of digoxin as a treatment needed to be studied more carefully The mechanism of action is through inhibition of the sodium-potassium pump both within the heart and elsewhere Within the heart such inhibition results in increased contractility, while outside the heart it reduces the sympathetic outflow from the central nervous system53 and the release of renin by the kidney.53 Several studies have helped to define the role of digoxin in the treatment of heart failure,54–57 showing that, although digoxin does not improve survival, it may improve symptoms Current recommendations in adults are that physicians consider adding digoxin in patients with persistent symptoms of heart failure during therapy with diuretics along with an ACE inhibitor or ARB and a β-adrenergic blocker.58 Toxicity from digoxin was common when serum levels exceeded 2.0 ng/mL; therefore the early practice was to maintain levels to just below toxicity to achieve maximal benefit More recent retrospective analyses of this and other studies suggest that lower doses may be better than higher doses.59,60 There is now increasing evidence that lower levels of digoxin are safer and at least as efficacious as higher levels for the treatment of chronic heart failure Since digoxin appears to be helpful only in the treatment of symptomatic heart failure, there is little if any role for it in the treatment of asymptomatic heart failure In the most recent recommendations of the American Heart Association and the American College of Cardiology, digoxin is recommended only in the treatment of symptomatic HFrEF and is actually contraindicated in asymptomatic patients unless atrial fibrillation is present.58 The indications for the use of digoxin in pediatric heart failure are less clear The most recent recommendations of an expert group of pediatric cardiologists recognize that there are few data to support or refute its use in pediatric heart failure.61 In patients with left-to-right shunts such as ventricular septal defects, the data are conflicting as to whether digoxin has any beneficial hemodynamic effects.62–64 In one study, digoxin acutely worsened hemodynamics in children with heart failure due to left-to-right shunts.65 There are no data to either support or refute the use of digoxin in children with heart failure due to ventricular dysfunction Thus, in the absence of pediatric data, one can consider using the recommendations for digoxin in adult HFrEF with the caveats that these extrapolations become much less justifiable in the extremely young child or in the child with systemic ventricular dysfunction whose systemic ventricle is not of a left ventricular morphology Major side effects include arrhythmias and gastrointestinal and neurologic symptoms Digoxin interacts with many medications (e.g., amiodarone, carvedilol, verapamil, spironolactone, flecainide, propafenone), and interactions should be explored before digoxin therapy is instituted Diuretics Although diuretics have never been shown (and possibly never will be) to improve survival in heart failure, their use is considered important because of the need for anticongestive measures in the treatment of heart failure This is based largely on the significant symptomatic relief and hemodynamic improvement seen in patients with congestive heart failure treated with diuretics A large number of diuretics are available, including those that act on the renal loop of Henle (loop diuretics) and those that act in the distal tubules of the kidney (thiazides) Potassium-sparing diuretics are discussed in the later section on aldosterone antagonists Diuretics interfere with the retention of sodium in the kidney, and water follows this increased excretion of sodium passively This causes a decrease in filling pressure of the ventricle and a reduction in rightsided (e.g., hepatic) and left-sided (e.g pulmonary) congestion The most common side effects are depletion of electrolytes and fluid (e.g., hyponatremia, hypokalemia), elevated urea levels in the plasma, and even hypotension if excessive diuresis takes place There is some evidence from retrospective analyses of previous trials that diuretics that do not result in the sparing of potassium may actually be harmful in the treatment of heart failure, but further prospective studies are needed to confirm this.66,67 Inhibitors of the Renin-Angiotensin System As stated earlier, the primary thrust of the treatment of heart failure over the last quarter century has been directed toward inhibition of the initially adaptive and ultimately maladaptive neurohormonal response to low cardiac output The most ... The indications for the use of digoxin in pediatric heart failure are less clear The most recent recommendations of an expert group of pediatric cardiologists recognize that there are few data to support or refute its use in pediatric heart... In the most recent recommendations of the American Heart Association and the American College of Cardiology, digoxin is recommended only in the treatment of symptomatic HFrEF and is actually contraindicated in asymptomatic patients... or refute the use of digoxin in children with heart failure due to ventricular dysfunction Thus, in the absence of pediatric data, one can consider using the recommendations for digoxin in adult HFrEF with the caveats that these