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


Cell replacement strategy is a new era in therapy for patients with myocardial dysfunction. It has been postulated that therapies directly targeted at replacing or regenerating damaged myocardial tissue could prevent progression to heart failure and therefore would be an important contribution to the treatment of ischemic damage to the myocardium. Many cell types have been successfully transplanted into damaged myocardium, including fetal cardiomyocytes, skeletal myoblasts, embryonic stem cells, and bone marrow-derived stem cells. (84-88) The best characterized of these is skeletal myoblast, an immature muscle cell that retains the ability to proliferate. Several studies have used human autologous skeletal myoblasts transplantation to determine if engraftment of these cells leads to long-term improvements in left ventricle function. (89-90) However, these exciting progresses have many unanswered questions including potential arrhythmic and oncogenic potential of these cells, which can only be resolved by larger clinical trials with long-term follow-up.

	Standard dose	Mechanism of action	Comments
Diuretics		Relieve congestive symptoms; Do not change the long-term outcome	Excess use of diuretics can reduce the preload and cardiac output, resulting in neurohormonal activation and fluid retention- a vicious cycle
1. Furosemide	1 mg/kg dose BID up to max 6 mg/kg/day
2. Chlorothiazide	10 mg/kg dose BID up to max 2 gm/day
3. Metolazone	0.1 mg/kg dose BID up to max 20 mg/day
Digoxin	3 to 4 mcg/kg dose BID	Increases inotropy; Attenuates neurohormonal activation; No effect on mortality	No relationship between serum digoxin level and worsening heart failure, change in left ventricle ejection fraction and exercise tolerance in adults
Angiotensin converting enzyme inhibitors		Decrease mortality and morbidity; Blocks the conversion of angiotensin I to II and activates bradykinin and kallidin; Cause vasodilation and natriuresis; Reduce afterload >	Mitigate the process of angiotensin-mediated maladaptation to heart failure; Decrease Qp:Qs and improve weight gain in children with left to right shunts
1. Captopril	0.1 mg/kg dose TID up to max 2 mg/kg/dose
2. Enalapril	0.1 mg/kg dose BID up to max 0.5 mg/kg/day
Beta-blockers		Decrease morbidity and mortality; Carvedilol has vasodilatory, antioxidant, antiproliferative and anti apoptotic properties, Reversing cardiac remodeling	Dosing is extrapolated from adult data, extreme caution should be used because there could be exacerbation of heart failure
1. Metoprolol	0.1 mg/kg dose BID up to max 1 mg/kg dose
2. Carvedilol	0.05 mg/kg/dose BID up to max 0.4 mg/kg/dose
Aldosterone antagonist Spironolactone	1 mg/kg dose BID up to max 200 mg/day	Decreases mortality and morbidity; Improves endothelial vasodilator dysfunction; Suppress vascular angiotensin conversion.	Should be used with caution in patients with hyponatremia, renal insufficiency, hyperkalemia and hepatic disease

(BID=twice daily, TID= three times daily, max=maximum, Qp: Qs=pulmonary to systemic blood flow ratio, LVEDP=left ventricular end - diastolic pressure, mg/kg = milligram per kilogram)

Summary :

The pace at which the knowledge base has expanded and the number of new studies published, there is a need to rethink about future management of heart failure in children and young adults caused by systemic ventricular dysfunction. We have discussed some of the current and newer drugs and therapies that are on the horizon including angiotensin converting enzyme inhibitor, beta-blocker, nesiritide, angiotensin receptor blocking agent, calcium sensitizing agent, modulation of the cytokine response, endothelin receptor antagonist, vasopressin antagonist, cardiac resynchronization therapy and/or implantable defibrillator and ventricular assist device support in pediatric patients. Most of the newer drugs are undergoing clinical trials in adults and future clinical trial designs should include pediatric population to make further progress in the management of chronic heart failure in children and young adults.

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