INTRODUCTION — Heart failure (HF) results from structural or functional cardiac disorders that impair the ability of the ventricle(s) to fill with and/or eject blood. The presentation of pediatric HF is diverse because of the numerous underlying cardiac etiologies (table 1) and varying clinical settings.
The management of HF in children will be presented here. The etiology, clinical manifestations, and diagnostic evaluation of HF in children are discussed separately. (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis".)
GENERAL MEASURES — General measures that can be applied to all pediatric patients with HF include correcting reversible conditions that may be causing or contributing the HF symptoms, ensuring adequate nutrition, and promoting healthy and safe exercise.
Reversible contributors — Patients with HF may have comorbidities that can exacerbate or contribute to cardiac dysfunction. A thorough evaluation should be performed in all patients to identify such contributors and appropriate therapy should be provided if warranted. Examples include:
●Iron deficiency and anemia – Iron deficiency, with or without anemia, is common in patients with HF and is associated with worse symptoms and clinical outcomes [1-5]. Iron studies and appropriate therapy should be considered in all children with HF even in absence of anemia. Patients with HF and comorbid iron deficiency may not respond adequately to oral iron supplementation . Thus, some patients may require intravenous iron therapy. (See "Iron deficiency in infants and children <12 years: Treatment" and "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Iron supplementation'.)
●Hypertension. (See "Nonemergent treatment of hypertension in children and adolescents".)
●Renal failure. (See "Chronic kidney disease in children: Overview of management".)
●Acidosis. (See "Approach to the child with metabolic acidosis".).
●Malnutrition. (See 'Nutritional support' below and "Poor weight gain in children younger than two years in resource-abundant settings: Management" and "Poor weight gain in children older than two years in resource-abundant settings".)
●Respiratory disorders (eg, asthma, obstructive sleep apnea, interstitial lung disease). (See "An overview of asthma management" and "Management of obstructive sleep apnea in children" and "Approach to the infant and child with diffuse lung disease (interstitial lung disease)".)
●Thyroid disorders (hypo- or hyperthyroid state) or adrenal insufficiency. (See "Acquired hypothyroidism in childhood and adolescence" and "Clinical manifestations and diagnosis of Graves disease in children and adolescents" and "Clinical manifestations and diagnosis of adrenal insufficiency in children".)
Nutritional support — Caloric intake and growth should be carefully assessed in infants and children with HF. Children with HF often have increased caloric needs due to an increased metabolic demand. In addition, patients with HF often tire with feeding and their intake may be limited. Some children may need a daily intake >120 kcal/kg for optimal growth. In order to provide adequate caloric intake, intermittent or continuous nasogastric or gastrostomy tube feeds may be required. In addition, salt and fluid restriction is recommended in children with severe HF to reduce volume overload. (See "Overview of enteral nutrition in infants and children".)
Growth failure and poor weight gain are common in infants and children with HF and are associated with poor outcome [7,8]. Approximately one-quarter of children with cardiomyopathy manifest growth failure during the course of their illness [8,9]. In a registry study that analyzed data from >900 children with dilated cardiomyopathy, children with poor weight gain (defined as body mass index or weight-for-height <5th percentile for age) had an increased risk of death compared with children of normal weight (hazard ratio 2.1; 95% CI 1.7-3.6) .
Exercise and physical activity — Promoting healthy and safe physical activity in patients with HF is an important part of management. The challenge is to balance routine daily physical activity while minimizing any potential risks from exercise. Recommendations should be tailored for each individual based on his or her specific diagnosis and a comprehensive assessment of the child's exercise capacity. This should generally include formal cardiopulmonary exercise testing if feasible (ie, if the child is old enough to cooperate, typically beginning around age 6 or 7 years). (See "Exercise testing in children and adolescents: Principles and clinical application", section on 'Limitations in young children'.)
Physical activity and exercise in patients with congenital heart disease (CHD) are discussed in greater detail separately. (See "Physical activity and exercise in patients with congenital heart disease".)
In adults with chronic HF, cardiovascular rehabilitation programs have been shown to improve exercise performance, physical activity, and quality of life ; however, data in children are limited. In a single-center study, 15 of 16 children with complex CHD demonstrated improved exercise performance after participation in a cardiac rehabilitation program . Furthermore, a study of 20 hospitalized children awaiting heart transplantation demonstrated that even those on inotropic support can safely participate in exercise training programs with relatively moderate to high compliance . Further studies are needed to evaluate the long-term benefits of exercise rehabilitation in children with HF.
APPROACH TO HF MANAGEMENT — The management of pediatric HF is dependent on its etiology and severity [13-15]. Management begins with a thorough assessment of the underlying cause of HF. The causes of pediatric HF can be divided into pathophysiologic categories (table 1). This categorization helps guide the approach to management. (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis", section on 'Etiology and pathophysiology'.)
Our management approach is generally consistent with the 2014 International Society of Heart and Lung Transplantation (ISHLT) guidelines for the treatment of HF in children, which are primarily based on the adult literature . Modifications for specific pediatric diagnoses were recommended based on expert consensus that was largely informed by clinical experience, small case series, and physiologic studies.
Goals of therapy — Therapeutic goals for children with HF are to relieve symptoms, decrease morbidity (including the risk of hospitalization), slow the progression of HF, and improve patient survival and quality of life.
Unstable patients — In patients who present with severe cardiorespiratory compromise (ie, shock or impending cardiac arrest), prompt initiation of treatment to restore adequate perfusion should be provided even if the underlying etiology is uncertain. Guidance for management of shock is summarized in the figures and discussed in detail separately:
Structural heart disease with preserved ventricular function — For patients with preserved ventricular function who have HF symptoms due to structural heart defects causing volume overload (eg, septal defects, patent ductus arteriosus) or pressure overload (eg, pulmonic stenosis, aortic stenosis, other right or left ventricular outflow tract obstruction) (table 1), the mainstay of management involves surgical or catheter-based interventions to correct the underlying defects. Medical therapy may be needed for stabilization or symptom relief while awaiting a more definitive intervention. (See 'Pharmacologic therapy' below.)
The appropriate intervention depends upon the specific defect. Common examples include:
●Atrial septal defects – Management involves surgical or percutaneous closure of the defect. (See "Isolated atrial septal defects (ASDs) in children: Management and outcome", section on 'Closure procedures'.)
●Ventricular septal defects – Surgical closure is generally preferred. (See "Management of isolated ventricular septal defects (VSDs) in infants and children", section on 'Closure interventions'.)
●Patent ductus arteriosus – Surgical ligation is used in young infants; percutaneous occlusion is more commonly used in older infants and children. (See "Management of patent ductus arteriosus (PDA) in term infants, children, and adults", section on 'Management approach'.)
●Valvular aortic stenosis – Percutaneous balloon aortic valvotomy is the therapy of choice. (See "Subvalvar aortic stenosis (subaortic stenosis)".)
●Pulmonic stenosis – Percutaneous balloon valvotomy is usually performed. (See "Pulmonic stenosis in infants and children: Management and outcome".)
Interventions for other congenital heart defects are discussed in separate topic reviews.
Impaired ventricular function — For patients with ventricular systolic dysfunction or those who require stabilization before surgical or catheter-based correction, therapy is provided based on the stage of HF (table 2):
●Stage A – For patients at risk for HF who have normal cardiac function and size, we recommend not treating with HF-specific therapies. Predisposing conditions should be treated if possible, as previously discussed. (See 'Reversible contributors' above.)
●Stage B – For asymptomatic patients with abnormal systemic ventricular function, pharmacologic therapy consists of angiotensin-converting enzyme (ACE) inhibitors. Angiotensin II receptor blockers (ARBs) can be used in patients who are intolerant of ACE inhibitors. (See 'Renin-angiotensin-aldosterone system inhibition' below.)
Based on adult guidelines, beta blockers can be considered in children with asymptomatic systolic LV dysfunction. It is important to note, however, that adult studies to support this recommendation are limited to patients with ischemic heart disease. (See 'Beta blockers' below.)
●Stage C – For patients with current or past symptoms and structural or functional heart disease, we suggest initial treatment with an ACE inhibitor plus a mineralocorticoid receptor antagonist. Oral diuretic therapy should be provided as needed for fluid overload. After a few weeks of stability, a beta blocker is usually added in patients with persistent left ventricle dilation and dysfunction. Low-dose digoxin can be added if needed for additional symptom relief. (See 'Pharmacologic therapy' below.)
For patients with stage C HF that is associated with severe limitation of activity, significant growth failure, intractable arrhythmias, or restrictive cardiomyopathy, early referral to a pediatric transplant center should be considered to optimize medical therapy and the timing of listing for heart transplant. (See 'Heart transplantation' below.)
●Stage D – Interventions for patients with end-stage HF who are refractory to oral medical therapy may include intravenous administration of inotropes and diuretics and nonpharmacologic interventions such as positive pressure ventilation, cardiac resynchronization therapy (CRT), mechanical circulatory support, and heart transplantation. Some patients present in stage D (decompensated state) and after initial acute therapy with inotropes may be able to transition to oral HF therapy as described above for patients in stage C. (See 'Drug therapy for advanced HF' below and 'Nonpharmacologic interventions for advanced HF' below.)
PHARMACOLOGIC THERAPY — Pharmacologic therapy is primarily used in patients with ventricular pump dysfunction. Drug therapy is also used initially to stabilize and relieve symptoms in patients with either volume or pressure overload with preserved ventricular function who are awaiting correction of the underlying defect.
Evidence for efficacy — For most of the agents used in the management of children with HF, the evidence supporting efficacy comes largely from adult studies. Because HF is common in adults, there is a substantial amount of clinical trial data to guide management decisions. Treatment strategies are based on observations that left ventricular (LV) systolic dysfunction activates sympathetic nervous and renin-angiotensin systems. This response is initially physiologic (and compensatory), but persistent activation is maladaptive and contributes to progressive LV dilation and dysfunction (remodeling), and worsening HF. Data from clinical trials have shown that drugs targeted to block the effects of neuro-hormonal activation (eg, beta blockers, angiotensin-converting enzyme [ACE] inhibitors) not only reverse LV remodeling but also improve survival in patients with HF. (See "Overview of the management of heart failure with reduced ejection fraction in adults" and "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Management of specific agents'.)
However, the prevalence of HF in the pediatric population is substantially lower than in adults which limits the ability to conduct similar trials in children. As a result, treatment of HF in children is based in large part on indirect evidence from adult studies. This approach is supported by observations that children with HF have neuro-hormonal changes and systemic ventricular remodeling similar to that described in adults with HF [16-19].
Diuretics — Diuretics decrease preload by promoting natriuresis, and provide relief of volume overload symptoms such as pulmonary and peripheral edema. Diuretics are used to treat children with stage C or D HF (table 2):
●Loop diuretics – Loop diuretics inhibit sodium and chloride reabsorption in the thick ascending limb of the loop of Henle. Furosemide is the most commonly used loop diuretic. A study of 62 hospitalized children with HF and fluid overload demonstrated the efficacy and safety of furosemide . Bumetanide and torsemide are more potent drugs, which are used less frequently and reserved for more severe or furosemide-resistant fluid overload. Side effects of loop diuretics include electrolyte abnormalities (hyponatremia, hypochloremia, and hypokalemia), metabolic alkalosis, and renal insufficiency. Long-term therapy can lead to nephrocalcinosis and ototoxicity. These complications occur most commonly with prolonged high-dose intravenous (IV) therapy . Increased risk of bone fractures has also been reported .
●Thiazide diuretics – Thiazide diuretics inhibit reabsorption of sodium and chloride ions from the distal convoluted tubules of kidneys. They generally are used as second-line agents and often in combination with a loop diuretic. Commonly used thiazide diuretics are chlorothiazide, hydrochlorothiazide, and metolazone.
Renin-angiotensin-aldosterone system inhibition — HF leads to activation of the renin-angiotensin-aldosterone system (RAAS) and increased sympathetic tone. Agents that block RAAS activation include ACE inhibitors, angiotensin II receptor blockers (ARBs), and angiotensin receptor-neprilysin inhibitors (ARNIs). These agents decrease afterload and promote reversal of ventricular remodeling.
ACE inhibitors — ACE inhibitors are an accepted first-line component of therapy for children with stage B and C HF (table 2).
ACE inhibitors are generally well tolerated in children and adverse effects are uncommon . Blood pressure and renal function should be monitored when initiating therapy, especially in neonates .
Clinical trials in adults have shown that ACE inhibitors improve survival in patients with symptomatic HF and reduce the rate at which asymptomatic patients with severe LV dysfunction develop symptomatic HF. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Sacubitril-valsartan, ACE inhibitor, or ARB'.)
Clinical trial data on the use of ACE inhibitors in children are limited and have been difficult to interpret due to healthier baseline cohorts, smaller sample size, and shorter duration of follow-up compared with adult studies.
In a randomized, placebo-controlled, crossover trial of enalapril in 18 subjects (mean age 14 years old) who were 4 to 19 years post-Fontan operation, the use of enalapril for 10 weeks was not associated with change in cardiac function or exercise performance . In a subsequent randomized, placebo-controlled study of enalapril in 230 infants with single ventricle anatomy and predominantly normal systemic ventricular function, somatic growth, ventricular function, HF severity, and one-year mortality were similar in the enalapril and placebo groups . In another randomized placebo-controlled trial of perindopril in 57 children with Duchenne muscular dystrophy (DMD) with normal LV ejection fraction (LVEF), LV function was similar in both groups at the trial's end (three years) . However, fewer patients in the perindopril group had LVEF <45 percent at five years (4 versus 28 percent) and fewer deaths were observed in the perindopril group at 10 years (7 versus 34 percent) [27,28]. The small size of the study limits drawing a firm conclusion regarding a possible mortality benefit.
Small nonrandomized trials and observational studies in other types of pediatric HF patients have demonstrated physiologic benefits and improvements in short-term outcomes [29-31]. Other studies have found no benefit or only limited efficacy [32,33].
Despite the inconsistencies and limitations of the pediatric data, it is reasonable to believe that the well-established benefits of ACE inhibitors in adult HF patients likely apply to pediatric patients as well.
ACE inhibitors inhibit the formation of angiotensin II, a potent vasoconstrictor that also promotes myocyte hypertrophy, fibrosis, and aldosterone secretion . Thus, ACE inhibitors benefit patients in HF first by reducing afterload, improving cardiac output, and, on chronic use, by mediating reversal of LV remodeling. (See "Pharmacologic therapy of heart failure with reduced ejection fraction: Mechanisms of action", section on 'ACE inhibitors'.)
Angiotensin II receptor blockers (ARBs) — In children with HF, there is a paucity of data on the use of ARBs, which block the angiotensin receptor (eg, candesartan, losartan, valsartan). Thus, ACE inhibitors are the preferred class of drugs for inhibition of the RAAS. ARBs are usually reserved for patients unable to tolerate ACE inhibitors due to cough or angioedema. (See "Pharmacologic therapy of heart failure with reduced ejection fraction: Mechanisms of action", section on 'Angiotensin II receptor blockers' and "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Sacubitril-valsartan, ACE inhibitor, or ARB'.)
Angiotensin receptor-neprilysin inhibitor (ARNI) — The combination drug sacubitril-valsartan (a neprilysin inhibitor plus an ARB) is the only agent in this class. Sacubitril-valsartan has been shown to reduce mortality when compared with enalapril in adults with HF. The PANORAMA-HF trial was designed to evaluate the efficacy and safety of sacubitril-valsartan in pediatric patients with HF due to systolic dysfunction (LVEF ≤40 percent) [34,35]. The trial enrolled 360 patients who were randomly assigned to sacubitril-valsartan or enalapril. Patients are being followed for 52 weeks and the full results of the trial are not yet available. Based on preliminary results from the PANORAMA-HF trial, the US Food and Drug Administration (FDA) approved sacubitril-valsartan for use in children ≥1 year old in 2019 . The FDA's approval of this drug for pediatric use was based upon an unpublished analysis of 110 pediatric patients enrolled in the PANORAMA-HF trial, the results of which are available only on the FDA label . At 12 weeks, patients treated with sacubitril-valsartan had greater reduction in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with those receiving enalapril (44 versus 33 percent, respectively); however, the difference was not statistically significant. According to the FDA label, adverse reactions observed in pediatric patients treated with sacubitril-valsartan were similar to those observed in adult patients (hypotension and hyperkalemia, being the most common). Additional data from the complete trial will be important to fully assess the safety and efficacy of this agent in pediatric patients. (See "Pharmacologic therapy of heart failure with reduced ejection fraction: Mechanisms of action", section on 'Angiotensin receptor-neprilysin inhibitor (ARNI)' and "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Sacubitril-valsartan, ACE inhibitor, or ARB'.)
Mineralocorticoid receptor antagonists — MRAs (eg, spironolactone, eplerenone) decrease sodium reabsorption and potassium excretion in the collecting ducts of kidneys. Their potassium-sparing diuretic effect makes them particularly suitable for use in conjunction with loop diuretics and thiazides. Both spironolactone and eplerenone have been shown to reduce mortality in adults with HF when added to standard therapy [37,38]. This effect is independent of their diuretic effect and is mediated by inhibition of myocardial fibrosis, an important component of LV remodeling . A randomized trial in 42 boys with cardiomyopathy secondary to Duchenne muscular dystrophy demonstrated that the addition of MRA therapy (eplerenone in this trial) to ACE inhibitor or ARB therapy attenuated the decline in left ventricular systolic function . Side effects include hyperkalemia (with both drugs) and gynecomastia (with spironolactone).
Beta blockers — Beta blocker therapy (eg, carvedilol or metoprolol) is usually added to an established regimen of diuretics and an ACE inhibitor. Beta blockers are used in children who are stable on other HF medications, have systolic dysfunction with stage C HF (table 2), and have a systemic LV (as opposed to certain congenital heart defects with a systemic right ventricle [RV]). Beta blockers are discontinued in patients with decompensated HF.
●Carvedilol is initiated at a low dose (approximately one-eighth of the eventual target dose, usually a dose of 0.05 mg/kg per dose given orally twice a day) and increased every two weeks to minimize side effects. In general, the dose is doubled after observing the response to the new higher test dose in clinic to a maximum dose of 0.4 mg/kg given orally twice a day. Side effects that may preclude dose increase include dizziness, fatigue, hypotension, bradycardia, bronchospasm, and hypoglycemia.
●Metoprolol is initiated at 0.1 mg/kg per dose orally twice daily and increased slowly (usually every two weeks) as needed up to 1 mg/kg/day (maximum daily dose in adults: 2 mg/kg/day or 200 mg/day, whichever is less). Side effects are similar to those of carvedilol.
Beta blockers counteract the maladaptive effects of chronic sympathetic activation of the myocardium. In adults with HF, they improve patient survival, reverse LV remodeling, and decrease myocardial fibrosis. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker'.)
As is the case with ACE inhibitors, studies of beta blockers in children with HF have been limited by small sample size, relatively short follow-up, and the use of surrogate endpoints. A 2009 systematic review of beta blocker therapy in children with HF concluded there were not enough data to recommend or discourage their use .
In a multicenter randomized trial of 161 children with HF and ventricular pump dysfunction, there were no differences in the number of patients who improved (56 percent in both groups), worsened (24 percent with carvedilol versus 30 percent with placebo), or were unchanged (19 versus 15 percent) . However, the study was thought to be underpowered as the clinical course of all children enrolled was better than expected. There was a trend towards clinical improvement in children with a systemic LV, but not in those with a systemic RV, suggesting that the response to carvedilol may be affected by the morphology of the child's systemic ventricle .
A subsequent clinical trial in 89 pediatric HF patients also found no difference in clinical improvement with carvedilol compared with conventional treatment; however, improvements in echocardiographic parameters and serum BNP levels were noted with carvedilol .
In several small observational studies, beta blocker therapy has been associated with improved symptoms, improvement in ventricular function, and delay in time to transplant or death in children with HF [45-49]. Carvedilol therapy has also been shown to preserve LV function after exposure to anthracyclines at six months follow-up , and to improve LV function when added to ACE inhibitor therapy in patients with DMD and dilated cardiomyopathy . In a large, retrospective multicenter review of the Pediatric Health Information System (PHIS) database, a beta blocker was prescribed upon discharge in 37 percent of pediatric patients admitted with acute decompensated HF .
Digoxin — Digoxin is most commonly used in the treatment of infants and children with stage C HF who have persistent symptoms despite treatment with other agents (eg, diuretics and ACE inhibitors). In this setting, digoxin may provide physiologic benefit and symptom relief. These benefits are generally seen with a low dose (trough level 0.5 to 0.9 ng/mL). Potential adverse effects (arrhythmias) are rare with this low level.
Digoxin was previously the mainstay of HF management until the 1990s, but its role diminished after it was found not to reduce mortality in adults with HF although it consistently reduced hospitalizations in these studies [53,54]. (See "Secondary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Digoxin'.)
Digoxin has a positive inotropic effect (mediated by Na+/K+ ATPase inhibition and increase in intracellular Ca+), a negative chronotropic effect that slows atrial conduction, and vagotonic properties that counter symptoms and signs mediated by the activation of the sympathetic nervous system in HF .
●Sodium-glucose cotransporter 2 (SGLT2) inhibitors – SGLT2 inhibitors (eg, dapagliflozin, empagliflozin) are emerging as an important component of HF therapy in adult patients based upon clinical trial data demonstrating that these agents improve survival, reduce HF hospitalizations, and improve HF symptoms. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Sodium-glucose co-transporter 2 inhibitors'.)
Data on use of SGLT2 inhibitors in pediatric patients with HF are extremely limited. None of the available SGLT2 inhibitors are approved by the FDA for this indication in children.
In a retrospective single-center study of 38 pediatric patients with HF receiving standard medical therapy, the addition of dapagliflozin was associated with modest improvements in BNP levels and ventricular EF measurements . The drug was generally well tolerated; however, six patients (16 percent) experienced a symptomatic urinary tract infection requiring antibiotic treatment.
●Ivabradine – Ivabradine is not a routine component of pediatric HF management. However, it is an option for patients with symptomatic stable chronic HF with reduced ejection fraction who either continue to have a high resting heart rate despite beta blocker and/or digoxin therapy or who have a contraindication or intolerance to beta blocker or digoxin use.
The efficacy of ivabradine in reducing resting heart rate and its safety were demonstrated in a clinical trial involving 116 children with dilated cardiomyopathy (DCM) and symptomatic chronic HF receiving stable HF therapy who were randomly assigned to treatment with ivabradine or placebo . The ivabradine dose was adjusted to achieve a 20 percent reduction in resting heart rate, which was achieved in 70 percent of children on ivabradine versus 12 percent of those on placebo. Among secondary endpoints analyzed at one year, the degree of improvement in left ventricular ejection fraction from baseline was greater in ivabradine-treated patients compared with placebo (13.5 versus 6.9 percent). However, the degree of reduction in N-terminal pro–B-type natriuretic peptide levels from baseline was similar in both groups. The proportion of patients with stable or improved New York Heart Association or Ross functional class was also similar in both groups. Bradycardia occurred more frequently in the ivabradine group (11 versus 2.4 percent); approximately 5 percent of patients in the ivabradine group experienced symptomatic bradycardia. Other adverse events were similar in both groups.
Clinical trials in adult patients have demonstrated that ivabradine reduces HF hospitalizations, but an effect on mortality has not been demonstrated. For this reason, its use is limited to patients with chronic HF who do not achieve adequate heart rate reduction despite standard HF therapy, including maximum tolerated dose of beta blocker.
Ivabradine is approved by the FDA for treatment of stable symptomatic HF due to DCM in pediatric patients ≥6 months old . Ivabradine should not be used in patients with acute decompensated HF, hypotension, sinus node dysfunction, heart block, pacemaker dependence (heart rate maintained exclusively by pacemaker), or severe hepatic impairment. In addition, it should be avoided in patients taking medications that are strong cytochrome CYP34A inhibitors (table 3) since these would increase ivabradine plasma concentrations.
●Pulmonary vasodilators — Pulmonary vasodilators are used in children with right HF due to pulmonary hypertension. This is discussed in detail separately. (See "Pulmonary hypertension in children: Management and prognosis", section on 'Targeted pulmonary hypertension therapy'.)
●Nesiritide – We suggest not routinely using nesiritide for management of pediatric acute HF. Use of this agent (where available) is generally limited to carefully selected patients with acute decompensated HF who have not achieved adequate reduction in filling pressures with other interventions and who have acceptable hemodynamics (ie, no hypotension or shock). Nesiritide is no longer available in the United States.
Nesiritide is a recombinant B-type natriuretic peptide that reduces preload and afterload by promoting diuresis, natriuresis, and arterial and venous dilation, thereby improving cardiac output without a direct inotropic effect on the myocardium. In a prospective, open-label study in 63 children with refractory HF, nesiritide was associated with improved urine output, serum creatinine, and cardiac function [60,61]. However, trials in adults with acute decompensated HF have failed to demonstrate improvement in mortality, HF hospitalization rate, or symptoms with nesiritide use. In addition, there is an associated increased risk of hypotension. (See "Treatment of acute decompensated heart failure: Specific therapies", section on 'Approach to vasodilator therapy'.)
Drug therapy for advanced HF — IV diuretics and inotropic agents are generally used in hospitalized patients with stage D HF (table 2).
Inotropes — Inotropic agents are used in the setting of low cardiac output (eg, during acute exacerbations of HF to improve cardiac output and to stabilize patients awaiting heart transplantation). Their effect is mediated through higher intracellular cyclic adenylate monophosphate (cAMP) levels, either by increased production (catecholamines) or by decreased degradation (phosphodiesterase III inhibition).
Catecholamines — Sympathomimetic stimulation by catecholamine agents improves myocardial contractility and may have an additional beneficial effect on peripheral vascular beds . Dopamine is the preferred drug during decompensated HF (usually in combination with intravenous milrinone). Dobutamine has the additive effect of reducing afterload. Low-dose epinephrine is used in the setting of refractory hypotension and/or poor end-organ perfusion. (See "Use of vasopressors and inotropes", section on 'Dopamine' and "Use of vasopressors and inotropes", section on 'Dobutamine' and "Use of vasopressors and inotropes", section on 'Epinephrine'.)
An arterial catheter and central venous catheter facilitate safe administration, close monitoring, and careful titration of these medications targeting optimal end-organ perfusion, as measured by urine output, serum lactate, and mixed venous saturations.
Milrinone — IV milrinone, a phosphodiesterase III inhibitor, is the preferred drug for decompensated HF at most institutions. Milrinone increases contractility and reduces afterload without a significant increase in myocardial oxygen consumption . A randomized, double-blind, placebo-controlled trial in pediatric postoperative cardiac surgery patients demonstrated that children treated with high-dose milrinone infusion (0.75 mcg/kg/min) were at a lower risk for the development of low cardiac output syndrome (LCOS) compared with children treated with placebo (12 versus 26 percent) .
To avoid hypotension, milrinone is initially administered as an IV infusion starting at a dose of 0.25 mcg/kg/min (without a pre-infusion bolus) and titrated upwards slowly as needed to a maximum dose of 1 mcg/kg/min.
Milrinone therapy is generally provided in the hospital setting. However, several centers (including ours) use home milrinone in selected patients awaiting heart transplantation. In our practice, home milrinone infusion therapy is used in children who are clinically stable without end-organ dysfunction, with no history of arrhythmias, who generally are on a milrinone dose ≤0.5 mcg/kg/min and a stable regimen of oral diuretic therapy, and who are under continuous adult supervision. Small case series support the safe use of milrinone in this setting [65,66].
NONPHARMACOLOGIC INTERVENTIONS FOR ADVANCED HF — Therapeutic interventions for selected patients with advanced HF refractory to pharmacologic therapy (stage D) may include:
●Positive pressure ventilation
●Mechanical circulatory support in patients with end-stage HF
Noninvasive ventilation — Noninvasive ventilation (NIV), such as high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), or bilevel positive airway pressure (BiPAP) ventilation, can be effective in alleviating respiratory distress from cardiogenic pulmonary edema. NIV promotes alveolar recruitment, improves lung compliance, and leads to decreased LV preload and afterload . Although there is high-quality evidence of the benefit of NIV in adult patients with cardiogenic pulmonary edema, pediatric data are limited [68,69]. (See "Noninvasive ventilation for acute and impending respiratory failure in children".)
Cardiac resynchronization therapy — Cardiac resynchronization therapy (CRT) may be an option for some children with stage C and D HF (table 2) who do not respond adequately to optimal medical therapy, particularly patients with reduced EF (ie, <35 percent) and a left bundle branch block (LBBB) pattern on electrocardiogram (ECG).
Intraventricular conduction delay or LBBB may worsen HF by causing ventricular dyssynchrony. CRT uses biventricular pacing to minimize ventricular dyssynchrony. In adult patients with LV dysfunction, HF, and LBBB, CRT has been shown to improve hemodynamics and symptoms. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system" and "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Rationale for CRT'.)
The effectiveness of CRT in the pediatric population is difficult to evaluate because of the complex anatomic substrates of congenital heart disease (CHD), scar formation from multiple cardiac surgeries, and a higher proportion of right bundle-branch block (RBBB) and RV failure than in the adult population . Guidelines used in adult patients provide a useful reference ; however, the typical adult HF scenario of an LVEF ≤35 percent with LBBB is relatively uncommon in children .
There are no randomized controlled trials evaluating CRT in pediatric HF; data on the outcomes of pediatric CRT are limited to case reports and several retrospective single-center and multicenter studies with heterogeneous CHD populations [70,73]. In a multicenter, retrospective analysis of 103 children and young adults with CHD and prolonged QRS on ECG, CRT was associated with improvement of ventricular EF from 26 to 40 percent . In another single-center retrospective case-control study of 63 patients with symptomatic HF with reduced EF and prolonged QRS on ECG, CRT was associated with improved heart transplant-free survival .
The placement of transvenous, endocardial pacing systems is limited in pediatric patients due to patient size, and, in CHD patients, due to surgically altered venous anatomy. Although transvenous leads have been successfully placed in patients who are <50 kg, doing so may not be in the best long-term interest of the patient because of the lifelong risk of venous thrombosis, infection, and lead failure necessitating lead extraction. In patients <50 kg, epicardial lead placement is often necessary which involves a sternotomy and/or a thoracotomy.
Mechanical circulatory support — In children with decompensated HF with low cardiac output syndrome unresponsive to medical therapy, mechanical circulatory support (MCS) can be life-saving. MCS maintains end-organ function and reduces myocardial oxygen requirements. It is used as a bridge to recovery (extracorporeal membrane oxygenation [ECMO]) in patients with secondary cardiomyopathy or to heart transplantation (ECMO or ventricular assist device [VAD]). In a report from the International Society for Heart and Lung Transplantation (ISHLT), one-third of pediatric heart transplant recipients received MCS as a bridge to transplantation .
The options include the following:
●Extracorporeal membrane oxygenation – ECMO is a total heart-lung bypass device and is used in the setting of imminent or actual cardiac arrest, such as postcardiotomy shock following cardiac surgery and acute myocarditis. Cannulation can be performed percutaneously, and ECMO can provide full cardiopulmonary support for days to weeks. A multicenter registry review of 3416 neonatal and 4181 pediatric cardiac ECMO cases showed a survival to discharge rate of 38 and 45 percent, respectively . If myocardial recovery does not occur or is not expected to occur within two to three weeks, ECMO may be used as a bridge to a more durable VAD placement and subsequent heart transplantation.
●Ventricular assist device – VAD, a cardiac-only support device, can offer either univentricular or biventricular support. Multiple devices exist and differ by flow design (pulsatile, centrifugal, or axial), pump location relative to patient (implantable, paracorporeal, or extracorporeal), and delivery system (percutaneous or central) . They are primarily used in patients awaiting heart transplantation and have yielded favorable results [78,79]. In a national registry study of 364 pediatric patients who underwent durable VAD implants between 2012 and 2016, 72 percent were alive at six months and nearly 50 percent had undergone transplant . Adolescent patients (age 11 to 19 years) had the highest survival (81 percent survival), whereas survival among infants (age <1 year) was only 47 percent. Serious adverse events were common and included infection, bleeding, and stroke . VAD options are limited in small children awaiting heart transplantation due to body size and anatomic considerations, though new devices are under development [81,82].
The choice of device depends on the etiology of HF, the patient's cardiac anatomy, the expected length of support, the availability of devices, and the expertise of the center's clinicians. Serious complications associated with ECMO and VAD include bleeding (eg, gastrointestinal and intracranial hemorrhage), thromboembolism (eg, stroke), and infection. (See "Short-term mechanical circulatory assist devices".)
Heart transplantation — Heart transplantation is recommended for end-stage HF refractory to medical therapy (stage D). It may also be considered for less severe HF (stage C) associated with severe limitation of activity, significant growth failure, intractable arrhythmias, or restrictive cardiomyopathy [75,83]. Early referral to a pediatric transplant center should be considered to optimize medical therapy and the timing of listing for heart transplant. The decision to pursue heart transplantation is based upon the expected survival with medical therapy, quality of life, alternative options for treatment, and estimation of survival post-transplantation. (See 'Outcome' below and "Heart transplantation in adults: Indications and contraindications".)
MANAGEMENT AND PREVENTION OF HF COMPLICATIONS — Patients with HF are at risk for complications, including thromboembolism, arrhythmias, and sudden cardiac death.
Thromboembolism — Children with HF due to systemic ventricular dysfunction are at risk for the formation of intracardiac thrombi, which may result in pulmonary embolus, cerebral embolic strokes, and, in some cases, death.
The optimal strategy for prevention of thromboembolism in children with HF is uncertain. There are no controlled trials in children. Many experts (including the authors of this topic review) use aspirin for prevention of thromboembolism in children with moderate left ventricular (LV) dysfunction, and warfarin or low molecular weight heparin (LMWH) for children with severe LV dysfunction, particularly in the presence of an indwelling catheter and/or a history of prior thrombus. Aspirin can also be considered in children with restrictive cardiomyopathy if there is marked atrial dilation. (See "Antithrombotic therapy in patients with heart failure", section on 'Role of antithrombotic therapy'.)
Children who develop intracardiac thrombi, or other clinically significant thromboembolic events, are managed with anticoagulation therapy (initially with unfractionated heparin or LMWH, and subsequently with either LMWH or warfarin). Management of thrombosis in children is discussed in greater detail separately. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome".)
Arrhythmias — In patients with decreased ventricular function, sustained atrial and ventricular tachyarrhythmias can rapidly impair hemodynamics. In these patients, management of the arrhythmia is essential. This may include:
●Cardioversion or defibrillation if necessary (eg, if the patient is acutely unstable). (See "Management of supraventricular tachycardia (SVT) in children", section on 'Cardioversion' and "Atrial tachyarrhythmias in children", section on 'Acute management' and "Management and evaluation of wide QRS complex tachycardia in children", section on 'Unstable patient'.)
●Antiarrhythmic therapy – Antiarrhythmic therapy is warranted if the arrhythmia is persistent (ie, does not resolve with correction of electrolyte abnormalities or other possible triggers) and poorly tolerated. Antiarrhythmic medications should not be used routinely for prevention of arrhythmia in children with HF who have not previously had arrhythmia.
●Ablation therapy, particularly in the setting of chronic atrial tachyarrhythmias. (See "Management of supraventricular tachycardia (SVT) in children", section on 'Catheter ablation' and "Atrial tachyarrhythmias in children", section on 'Atrial ectopic tachycardia and focal atrial tachycardia'.)
The management (both acute and chronic) of specific arrhythmias is discussed in separate topic reviews:
●Supraventricular tachycardia (including atrioventricular reentrant tachycardia [AVRT] and atrioventricular nodal reentrant tachycardia [AVNRT]). (See "Management of supraventricular tachycardia (SVT) in children", section on 'Acute management'.)
●Focal atrial tachycardia and atrial ectopic tachycardia. (See "Atrial tachyarrhythmias in children", section on 'Atrial ectopic tachycardia and focal atrial tachycardia'.)
●Ventricular tachycardia. (See "Management and evaluation of wide QRS complex tachycardia in children", section on 'Initial management' and "Management and evaluation of wide QRS complex tachycardia in children", section on 'Chronic management'.)
Sudden cardiac death — Implantable cardioverter defibrillator (ICD) placement is recommended for patients with HF who have survived sudden cardiac arrest (ie, aborted sudden cardiac death [SCD]). (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in children", section on 'Survivors of SCA'.)
In addition, ICD placement is generally indicated for patients who are at high risk for SCD due to ventricular arrhythmia, including patients with HF or cardiomyopathy who have a history of unexplained syncope or recurrent, sustained ventricular dysrhythmias .
The general principles of ICD use and efficacy in children are similar in many respects to those in adults and application of adult guidelines for ICD implantation is generally the approach in the older adolescent (ie, ≥16 years). (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions", section on 'Indications'.)
There are some unique considerations for ICD placement in pediatric patients, including the longevity of the device and lead, the size of the patient relative to the device, and the increased physical activity, particularly in young children. In addition, many children with ICDs outlive their devices and leads, necessitating complex extraction and multiple replacement procedures. These issues need to be carefully considered when evaluating therapeutic options in children with HF. The risks and benefits of each approach differ by age, size, and overall assessment of risk for SCD.
The risk of sudden death in children with end-stage HF awaiting transplantation is approximately 1 percent . In contrast to adults, there is little pediatric evidence to guide decision-making regarding ICD placement for primary prevention of SCD in children with cardiomyopathy. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".)
ICD placement in children with hypertrophic cardiomyopathy is discussed in greater detail separately. (See "Hypertrophic cardiomyopathy in children: Management and prognosis", section on 'Prevention of sudden cardiac death (ICD placement)'.)
LONG-TERM HEALTH MAINTENANCE — Longitudinal care for children with HF should be closely coordinated with the child's cardiologist. Important aspects of long-term health care maintenance in children with HF include:
●Immunizations – Children with HF should receive all routine childhood vaccinations, including pneumococcal conjugate vaccine and yearly influenza vaccine. In addition, respiratory syncytial virus (RSV) immunoprophylaxis should be provided to eligible infants (table 4) and pneumococcal polysaccharide vaccine should be provided to children ≥2 years. (See "Seasonal influenza in children: Prevention with vaccines" and "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Congenital heart disease' and "Pneumococcal vaccination in children".)
●Monitoring of growth parameters – It is important to monitor growth and development in children with HF, as it is in all children. Poor weight gain may be the main clinical sign of HF in young infants and children. (See "Normal growth patterns in infants and prepubertal children".)
●Monitoring for cardiac symptoms – Between visits with the cardiac specialist, the primary care provider should monitor for symptoms related to HF (eg, poor weight gain, tachypnea, dyspnea, syncope). If the patient develops new or worsening HF symptoms, the patient should be promptly referred to the specialist for cardiac evaluation. (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
●Treatment of respiratory illnesses – Respiratory illnesses can be associated with considerable morbidity and mortality in children with HF. It is important to promptly recognize acute respiratory illnesses and to provide appropriate treatment if warranted. (See "Community-acquired pneumonia in children: Outpatient treatment".)
●Exercise and sports participation – Promoting healthy and safe physical activity in patients with HF is an important part of management. The challenge is to balance routine daily physical activity and limiting inactivity while minimizing any potential risks from exercise. Recommendations should be tailored for each individual based on his or her specific diagnosis and a comprehensive assessment of the child's exercise capacity. (See 'Exercise and physical activity' above and "Physical activity and exercise in patients with congenital heart disease".)
●Antibiotic prophylaxis – Antibiotic prophylaxis for the prevention of bacterial endocarditis should be provided to cyanotic patients and those with indwelling central lines. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
●Planning of non-cardiac surgery – Children with HF are at increased risk for adverse events when undergoing surgery and other procedures under anesthesia. Careful perioperative planning (including consultation with cardiac anesthesia, coordination with the cardiologist, and appropriate postprocedural monitoring) are important for pediatric patients with HF undergoing surgery or other procedures requiring anesthesia/sedation.
●Airplane travel – Airplane travel should be avoided in children with HF who are in an unstable or decompensated condition. Supplemental oxygen may be warranted in select patients during airplane travel. (See "Approach to patients with heart disease who wish to travel by air or to high altitude".)
OUTCOME — Outcomes for pediatric patients with HF vary considerably depending on the underlying etiology and severity of HF.
●Outcomes for children with HF – Among patients hospitalized for management of HF, mortality ranges from 6 to 15 percent [52,85-90]. In a study using data from the Nationwide Emergency Department Sample database of 5971 pediatric heart failure-related emergency department visits in 2010, 60 percent required hospital admission . The median duration of hospitalization was 6 days. Among admitted patients, the mortality rate was 5.9 percent. Independent risk factors for mortality included comorbid renal failure and respiratory failure.
For patients with New York Heart Association (NYHA)/Ross class II and III HF symptoms (table 5), medical management appears to improve outcomes. In the Pediatric Carvedilol Study, a prospective clinical trial involving 161 children with predominantly class II and III HF, medical management included angiotensin-converting enzyme (ACE) inhibitors in nearly all children, diuretics and digoxin in approximately 85 percent, beta blocker therapy (carvedilol) in two-thirds, and spironolactone in approximately one-third . Over the eight-month study period, 56 percent of patients demonstrated clinical improvement (defined as improvement in HF class and/or moderate to marked improvement in global assessment score), 18 percent remained stable, and 26 percent worsened, including 11 deaths (7 percent) and 18 cardiac transplantations (11 percent).
For children with dilated cardiomyopathy (DCM), outcomes depend on the etiology, the degree of left ventricular (LV) dysfunction, and the severity of symptoms . In a registry study of 549 children with DCM who were diagnosed between 2000 and 2009 and followed for a median of one year, 27 percent recovered normal LV function and size, 24 percent underwent heart transplantation, and 9 percent died (median time from diagnosis to death was 3.2 months) . The most frequent diagnoses in this cohort included idiopathic DCM (63 percent), myocarditis (17 percent), familial DCM (12 percent), and neuromuscular disease (eg, Duchenne muscular dystrophy; 5 percent); most patients (>70 percent) had heart failure symptoms at diagnosis. Independent risk factors for mortality included presence of heart failure symptoms at diagnosis, neuromuscular disease, and lower LV shortening fraction; myocarditis was associated with better survival. Mortality in this cohort was considerably lower than in an earlier cohort diagnosed with DCM from 1990 to 1999 and followed for a median of 1.6 years (9 versus 18 percent, respectively), though rates of heart transplantation were similar (24 percent in both cohorts).
●Outcomes after heart transplantation – Outcomes following pediatric cardiac transplantation are described in reports from the Registry of the International Society for Heart and Lung Transplantation (ISHLT), which includes data on >15,000 pediatric heart transplantations performed at >100 centers around the world from 1982 to 2018 [92-95]. Overall median survival following heart transplantation ranges from 13 years for adolescents recipients to 22 years for infant transplant recipients . Mortality is highest in the first year following transplant. Survival has improved considerably over time, with estimated five-year post-transplant survival of 82 percent for patients transplanted in the era from 2009 to 2014 compared with 60 percent for those transplanted in 1982 to 1989 .
Risk factors for mortality following heart transplantation include :
•Age of the recipient – The risk of mortality in the first year after transplant is higher in infants compared with older children. However, among one-year conditional survivors, infants generally have a better long-term prognosis compared with adolescents.
•Age of the donor – Older age is associated with higher mortality.
•Longer allograft ischemic time.
•Poor pretransplant renal function.
•Requiring ECMO or ventilator support prior to transplant.
•Type of cardiac disease – Mortality is higher among children with congenital heart disease compared with dilated cardiomyopathy.
Among survivors of pediatric heart transplantation, functional status at up to three years post-transplant is generally good, with >80 percent of patients reporting normal activity or only minor limitations in strenuous activity. Hospitalizations for the treatment of rejection and/or infection are common, occurring in 30 to 40 percent of patients in the first three years after transplantation .
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in children".)
SUMMARY AND RECOMMENDATIONS
●Goals of therapy – Therapeutic goals for children with heart failure (HF) are to relieve symptoms, decrease morbidity (including the risk of hospitalization), slow the progression of HF, and improve patient survival and quality of life. (See 'Goals of therapy' above.)
●General measures – General measures that can be applied to all pediatric HF patients include correcting reversible conditions that may be causing or contributing to the HF symptoms (eg, anemia, hypertension, renal failure, obesity, malnutrition, respiratory disorders), ensuring adequate nutrition, and promoting healthy and safe exercise. (See 'General measures' above.)
●Patients with structural heart disease – For patients with preserved ventricular function who have HF symptoms due to structural heart defects causing volume overload (eg, septal defects, patent ductus arteriosus) or pressure overload (eg, pulmonic stenosis, aortic stenosis, other right or left ventricular outflow tract obstruction) (table 1), the mainstay of management involves surgical or catheter-based interventions to correct the underlying defects. Medical therapy may be needed for stabilization or symptom relief while awaiting a more definitive intervention. (See 'Structural heart disease with preserved ventricular function' above.)
●Heart failure management – Pharmacologic therapy is generally warranted for patients with ventricular pump dysfunction and those who require stabilization before surgical or catheter-based intervention. Because pediatric data are limited, pharmacologic treatment for children with HF is largely based on evidence from clinical trials involving adults with HF. (See 'Impaired ventricular function' above and 'Evidence for efficacy' above.)
•Stage B – For asymptomatic patients with abnormal ventricular function, we suggest pharmacologic therapy with an angiotensin-converting enzyme (ACE) inhibitor (Grade 2B). Angiotensin II receptor blockers (ARBs) can be used in patients who are intolerant of ACE inhibitors. (See 'Renin-angiotensin-aldosterone system inhibition' above.)
•Stage C – For patients with current or past HF symptoms due to structural or functional heart disease, we suggest initial treatment with an ACE inhibitor plus a mineralocorticoid receptor antagonist (Grade 2B). In addition, oral diuretic therapy is provided as needed to treat fluid overload. After a few weeks of stability, if there is no improvement in LV dilation and dysfunction, we suggest adding a beta blocker (Grade 2B). Low-dose digoxin may be added if needed for symptom relief. (See 'Pharmacologic therapy' above.)
•Stage D – Interventions for patients with end-stage HF who are refractory to oral medical therapy may include intravenous administration of inotropes and diuretics and nonpharmacologic interventions such as positive pressure ventilation, cardiac resynchronization therapy, mechanical circulatory support, and heart transplantation. (See 'Drug therapy for advanced HF' above and 'Nonpharmacologic interventions for advanced HF' above.)
●Complications of HF – Management of pediatric patients with HF includes assessment of risk for complications, including thromboembolism, arrhythmias, and sudden cardiac death. (See 'Management and prevention of HF complications' above.)
●Long-term health maintenance – Longitudinal care for children with HF should be closely coordinated with the child's cardiologist. Important aspects of long-term health care maintenance in children with HF include routine immunizations, monitoring of growth parameters, prompt recognition and treatment of respiratory illnesses, antibiotic prophylaxis if warranted, counseling regarding exercise, planning of non-cardiac surgery, and advice regarding air travel. (See 'Long-term health maintenance' above.)
●Outcome – Outcomes for pediatric patients with HF vary considerably depending on the underlying etiology and severity of HF. Among patients hospitalized for management of HF, mortality is approximately 5 to 15 percent. (See 'Outcome' above.)
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