Address for correspondence : Bibhuti B Das, MD, Division of Pediatric Cardiology, Suite # 334, University of Louisville, Louisville, KY 40202, USA.E-mail: bdas99@hotmail.com

Management:

It is reasonable to admit that most treatment strategies used in children with chronic heart failure have been extrapolated from trials in adults. Although there is good rationale for doing this, there are significant differences between the substrate for left ventricle dysfunction between children and adults. (24) In general, pharmacotherapy for chronic compensated heart failure has three goals: the rapid relief of symptoms, slowing of the pathophysiological process involved in left ventricle remodeling and increasing patient survival. Despite the standard pharmacotherapy ( Table-1 ), some children and young adults with heart failure remain in a chronic decompensated state. These patients require intravenous inotropes and vasodilator medications. Some of these patients with end-stage heart failure become inotrope-dependent, and are candidates for newer therapies including but not limited to ventricular assist device as a bridge to transplantation or recovery. Evidence-based medicine for management of pediatric heart failure does not exist at this time. Until large, multicenter trials of children with heart failure are performed, the best course for pediatric cardiologists is to follow the adult literature, cautiously introduce accepted therapies, and follow patients closely.

Diuretics :

Diuretics are needed to relieve the volume overload and congestive symptoms, but can activate the renin-angiotensin-aldosterone axis and sympathetic nervous system. Therefore, diuretics except spironolactone have no long-term benefits and do not prevent the disease progression in chronic heart failure. Loop diuretics are preferable to most other diuretics secondary to their effectiveness and potency. Combination therapy has been shown to be more effective than monotherapy with one class at escalating dose because sequential sites in the nephron can be blocked. New diuretics called aquaretic which are vasopressin receptor antagonists are available. (25) Two vasopressin antagonists currently being used in clinical trials are tolvaptan (vasopressin receptor-2 antagonist) and conivaptan (combined vasopressin receptor-1a and -2 antagonists). (26) The potential value of these agents is the fact that they cause elimination of water, without the loss of electrolytes, thus potentially negating the need for frequent follow-up of serum electrolytes levels.

Aldosterone antagonist:

Aldosterone antagonists (spironolactone and eplerenone) have been shown to reduce mortality in adults with heart failure. (27) Plasma aldosterone levels are elevated in heart failure, both because of increased production and reduced hepatic clearance. The mechanisms of aldosterone mediated potentiation of heart failure include increased myocardial fibrosis, increased angiotensin converting enzyme and endothelin activity, increased free radical production, and decreased adrenal nitric oxide. Low dose spironolactone is considered to be an inhibitor of renin-angiotensin-aldosterone axis, rather than diuretic.

Digoxin :

Digoxin inhibits the sarcolemmal sodium-potassium-adenosine triphophatase pump which results in increased intracellular sodium and subsequent increase in intracellular calcium through inhibition of sodium-calcium exchanger. This increase in intracellular calcium results in increased contractility. Other beneficial effects of digoxin include reduction of sympathetic tone and norepinephrine levels. Recent observations suggest that digitalis may have additional effects on cardiac cell function in both the short and long term that include intracellular effects, interactions with specific sodium-potassium-adenosine triphophatase isoforms in different cellular locations, effects on intracellular (including nuclear) signaling, and long-term regulation of intracellular ionic balances through circulating ouabain-like compounds. (28) Digoxin improves symptoms and decreases hospitalization, but there is no evidence that it improves survival in adults. (29-30) The effect of digoxin on symptoms and /or survival in children with heart failure is unknown.


Angiotensin converting enzyme inhibitors are the mainstay of treatment in all patients with systolic left ventricle dysfunction. (31) The mechanism by which angiotensin converting enzyme inhibitors benefit patients with heart failure include vasodilation, ventricular remodeling, improved renal function, and blunting the hypertrophic and apoptotic effects of angiotensin II within the myocardium. (32) Angiotensin converting enzyme inhibitors appear to exhibit a class effect and all members of this class may be equally effective. Potential side effects are hyperkalemia if used concomitantly with spironolactone, cough and angioedema due to decrease degradation of bradykinin, renal dysfunction and azotemia. The low dose angiotensin converting enzyme inhibitors are recommended in patients receiving spironolactone in order to avoid potential hyperkalemia. It is recommended to start beta blocker therapy along with angiotensin converting enzyme inhibitors if there is no contraindication. Angiotensin receptor blockers directly block the effects of angiotensin II no matter which pathway of production (angiotensin converting enzyme or chymase). In adults, angiotensin receptor blockers appear to be as effective as angiotensin converting enzyme inhibitors in improving symptoms, reducing mortality, reducing wedge pressure, and increasing cardiac output. (33) If patient is intolerant to angiotensin converting enzyme inhibitors then use angiotensin receptor blockers instead. Currently angiotensin receptor blockers available are losartan, valsartan and irbesartan. There is little data available on the use of angiotensin receptor blockers in children.