Pediatric Congestive Heart Failure

The most likely causes of pediatric congestive heart failure depend on the age of the child. Congestive heart failure in the fetus, or hydrops, can be detected by performing fetal echocardiography. In this case, congestive heart failure may represent underlying anemia (eg, Rh sensitization, fetal-maternal transfusion), arrhythmias (usually supraventricular tachycardia), or myocardial dysfunction (myocarditis or cardiomyopathy). Curiously, structural heart disease is rarely a cause of congestive heart failure in the fetus, although it does occur. Atrioventricular valve regurgitation in the fetus is a particularly troubling sign with respect to the prognosis. (See Etiology.)

Neonates and infants younger than age 2 months are the most likely group to present with congestive heart failure related to structural heart disease. The systemic or pulmonary circulation may depend on the patency of the ductus arteriosus, especially in patients presenting in the first few days of life. In these patients, prompt cardiac evaluation is mandatory. Myocardial disease due to primary myopathic abnormalities or inborn errors of metabolism must be investigated. Respiratory illnesses, anemia, and known or suspected infection must be considered and appropriately managed. (See Etiology, Presentation, Workup, and Treatment.)

In older children, congestive heart failure may be caused by left-sided obstructive disease (valvar or subvalvar aortic stenosis or coarctation), myocardial dysfunction (myocarditis or cardiomyopathy), hypertension, renal failure,[1] or, more rarely, arrhythmias or myocardial ischemia. Illicit drugs such as inhaled cocaine and other stimulants are increasingly precipitating causes of congestive heart failure in adolescents; therefore, an increased suspicion of drug use is warranted in unexplained congestive heart failure. (See Etiology and Presentation.)

Although congestive heart failure in adolescents can be related to structural heart disease (including complications after surgical palliation or repair), it is usually associated with chronic arrhythmia or acquired heart disease, such as cardiomyopathy.

Patient education

For patient education information, see the Heart Health Center, as well as Congestive Heart Failure.

Congestive heart failure occurs when the heart can no longer meet the metabolic demands of the body at normal physiologic venous pressures. Typically, the heart can respond to increased demands by means of 1 of the following:

• Increasing the heart rate, which is controlled by neural and humoral input

• Increasing the contractility of the ventricles, secondary to circulating catecholamines and autonomic input

• Augmenting the preload, medicated by constriction of the venous capacitance vessels and the renal preservation of intravascular volume

As the demands on the heart outstrip the normal range of physiologic compensatory mechanisms, signs of congestive heart failure occur. These signs include tachycardia; venous congestion; high catecholamine levels; and, ultimately, insufficient cardiac output with poor perfusion and end-organ compromise. (See the image below.)

Systolic dysfunction

Diminished cardiac output is caused by a complex interaction of various factors.[2] Systolic dysfunction is characterized by diminished ventricular contractility that results in an impaired ability to increase the stroke volume to meet systemic demands. Factors such as anatomic stresses (eg, coarctation of the aorta) that contribute to an increased afterload (end-systolic wall stress), as well as neurohormonal factors that increase systemic vascular resistance, also lead to systolic dysfunction.

Diastolic dysfunction

Diastolic dysfunction results from decreased ventricular compliance, necessitating an increase in venous pressure to maintain adequate ventricular filling. Causes of primary diastolic dysfunction include an anatomic obstruction that prevents ventricular filling (eg, pulmonary venous obstruction), a primary reduction in ventricular compliance (eg, cardiomyopathy, transplant rejection), external constraints (eg, pericardial effusion), and poor hemodynamics after the Fontan procedure (eg, elevated pulmonary vascular resistance).

Chronic heart failure

In chronic heart failure, myocardial cells die from energy starvation, from cytotoxic mechanisms leading to necrosis, or from the acceleration of apoptosis or programmed cell death. Necrosis stimulates fibroblast proliferation, which results in the replacement of myocardial cells with collagen. The loss of myocytes leads to cardiac dilation and an increased afterload and wall tension, which results in further systolic dysfunction. In addition, the loss of mitochondrial mass leads to increased energy starvation.

Acute heart failure

During acute congestive heart failure, the sympathetic nervous system and renin-angiotensin system act to maintain blood flow and pressure to the vital organs. Increased neurohormonal activity results in increased myocardial contractility, selective peripheral vasoconstriction, salt and fluid retention, and blood pressure maintenance. As a chronic state of failure ensues, these same mechanisms cause adverse effects.

The myocardial oxygen demand, which exceeds the supply, increases because of an increase in the heart rate, in contractility, and in wall stress. Alterations in calcium homeostasis and changes in contractile proteins occur, resulting in a hypertrophic response of the myocytes. Neurohormonal factors may lead to direct cardiotoxicity and necrosis.

Characteristic findings in children with heart failure

Many classes of disorders can result in increased cardiac demand or impaired cardiac function. Cardiac causes include arrhythmias (tachycardia or bradycardia), structural heart disease, and myocardial dysfunction (systolic or diastolic).

Noncardiac causes of congestive heart failure include processes that increase the preload (volume overload), increase the afterload (hypertension), reduce the oxygen-carrying capacity of the blood (anemia), or increase demand (sepsis). For example, renal failure can result in congestive heart failure due to fluid retention and anemia. Renal failure may also occur following heart transplantation as a result of long-term immunosuppression.[3]

Cardiac rhythm disorders may be caused by the following:

• Complete heart block

• Supraventricular tachycardia

• Ventricular tachycardia

• Sinus node dysfunction

Volume overload may be caused by the following:

• Structural heart disease (eg, ventricular septal defect,[4] patent ductus arteriosus, aortic or mitral valve regurgitation, complex cardiac lesions)

• Anemia

• Sepsis

Pressure overload may be caused by the following:

• Structural heart disease (eg, aortic or pulmonary stenosis, aortic coarctation)

• Hypertension

Systolic ventricular dysfunction or failure may be caused by the following:

• Myocarditis

• Dilated cardiomyopathy

• Malnutrition

• Ischemia

Diastolic ventricular dysfunction or failure may be caused by the following:

• Hypertrophic cardiomyopathy

• Restrictive cardiomyopathy

• Pericarditis

• Cardiac tamponade (pericardial effusion)

Thorough history taking and physical examination, including an assessment of the upper-extremity and lower-extremity blood pressures, are crucial in the evaluation of an infant or child with congestive heart failure.

Regardless of the etiology, the first manifestation of congestive heart failure is usually tachycardia. An obvious exception to this finding occurs in congestive heart failure due to a primary bradyarrhythmia or complete heart block.

As the severity of congestive heart failure increases, signs of venous congestion usually ensue. Left-sided heart failure is generally associated with signs of pulmonary venous congestion, whereas right-sided heart failure is associated with signs of systemic venous congestion. Marked failure of either ventricle, however, can affect the function of the other, leading to systemic and pulmonary venous congestion.

Later stages of congestive heart failure are characterized by signs and symptoms of low cardiac output. Generally, congestive heart failure with normal cardiac output is called compensated congestive heart failure, and congestive heart failure with inadequate cardiac output is considered decompensated.

Signs of congestive heart failure vary with the age of the child.[5] Signs of pulmonary venous congestion in an infant generally include tachypnea, respiratory distress (retractions), grunting, and difficulty with feeding. Often, children with congestive heart failure have diaphoresis during feedings, which is possibly related to a catecholamine surge that occurs when they are challenged with eating while in respiratory distress.

Right-sided venous congestion is characterized by hepatosplenomegaly and, less frequently, by edema or ascites. Jugular venous distention is not a reliable indicator of systemic venous congestion in infants, because the jugular veins are difficult to observe. In addition, the distance from the right atrium to the angle of the jaw may be no more than 8-10 cm, even when the individual is sitting upright.

Uncompensated congestive heart failure in an infant primarily manifests as a failure to thrive. In severe cases, failure to thrive may be followed by signs of renal and hepatic failure.

In older children, left-sided venous congestion causes tachypnea, respiratory distress, and wheezing (cardiac asthma). Right-sided congestion may result in hepatosplenomegaly, jugular venous distention, edema, ascites, and/or pleural effusions.

Older children with uncompensated congestive heart failure may have fatigue or lower-than-usual energy levels. Patients may complain of cool extremities, abdominal pain, nausea/vomiting, exercise intolerance, dizziness, or syncope.

Clinical findings may include hypotension, cool extremities with poor peripheral perfusion, a thready pulse, and decreased urine output. Chemical evidence of renal and liver dysfunction may be present, as well as a diminished level of consciousness. Children with uncompensated congestive heart failure, particularly older children, generally have a lower cardiac output than that which most experienced clinicians would estimate on the basis of the clinical signs.

Signs and symptoms of congestive heart failure include the following:

• Tachycardia

• Venous congestion - Right-sided (hepatomegaly, ascites, abdominal pain, pleural effusion, edema, jugular venous distention); left-sided (tachypnea, retractions, nasal flaring or grunting, rales, pulmonary edema)

• Low cardiac output - Fatigue or low energy, pallor, sweating, cool extremities, nausea/vomiting, poor growth, dizziness, altered consciousness, and syncope

Appropriate laboratory testing includes assessment of the following: oxygen saturation, complete blood count (CBC), hemoglobin concentration, electrolyte levels, calcium level, cardiac biomarkers, blood urea nitrogen (BUN) level, creatinine level, and renal[3] and hepatic function.

The CBC count can reveal signs of anemia or infection.

Brain natriuretic peptide (BNP) or N -terminal prohormone BNP (NT-proBNP) levels are elevated as a result of ventricular dilation. Elevation of serum BNP level is particularly useful in distinguishing patients with congestive heart failure from those with a primary respiratory process. BNP levels of more than 100 pg/mL are associated with congestive heart failure in adults and children. Normal levels may be slightly higher in neonates. Serial measurements of BNP levels in children with primary myocardial dysfunction and acute decompensated heart failure in which levels are persistently elevated and/or there is a lesser degree of decline in the first week of presentation are adverse prognostic factors.[6]

Cardiac troponin may be elevated in cases of myocarditis or after ischemic injury due to coronary anomaly or cardiomyopathy, as well as in noncardiac conditions in which cardiac perfusion may be compromised (sepsis).

The evaluation of serum electrolyte levels in the patient with congestive heart failure may demonstrate hyponatremia secondary to water retention. Elevated potassium levels may represent renal compromise or even tissue destruction due to low cardiac output. Significant tissue hypoxia increases serum lactate concentration and depletes the serum bicarbonate level. In more chronic congestive heart failure states, reduced renal blood flow may be expressed as increased BUN and creatinine levels.

A 12-lead electrocardiogram (ECG) may reveal evidence of structural or coronary artery disease or a complete atrioventricular block or arrhythmia.

Pulse oximetry, as well as a hyperoxia test in newborns, may be useful. The systemic saturation on room air is a more reliable measure of oxygenation than are observations for cyanosis alone, which are often misleading. The partial pressure of arterial oxygen (PaO2) when the patient is receiving 100% oxygen (hyperoxia test) may help in distinguishing intracardiac mixing malformations from pulmonary disease in the setting of hypoxia. Blood gas abnormalities may show respiratory alkalosis in mild forms of congestive heart failure or metabolic acidosis in patients with evidence of low cardiac output or ductal-dependent congenital heart disease.

In the presence of congestive heart failure, the cardiac silhouette is usually enlarged on the chest radiograph. As with BNP elevation, cardiac enlargement may help to distinguish patients with congestive heart failure from those with respiratory disease. However, exceptions may include restrictive cardiomyopathy, venous obstruction (total anomalous pulmonary venous obstruction), and diastolic dysfunction due to high ventilator mean airway pressures, displaying a normal cardiac size on chest radiographs. Increased pulmonary blood flow may be present, along with pulmonary edema or venous congestion. (See the image below.)

Echocardiography is indicated in any child with unexplained congestive heart failure to assess cardiac function and identify potential cardiovascular causes, particularly anatomic lesions and cardiomyopathy. On the other hand, congestive heart failure itself is not an echocardiographic diagnosis; therefore, the underlying etiology is best identified by means of detailed history taking and physical examination and often by means of chest radiography. When oral sedation is performed for echocardiography, note that children with a low cardiac output can depend on endogenous catecholamine levels to maintain tissue perfusion. Sedation can cause withdrawal of the endogenous catecholamine drive, resulting in cardiac decompensation.

The management of congestive heart failure (CHF) is difficult and sometimes dangerous without knowledge of the underlying cause. Consequently, the first priority is acquiring a good understanding of the etiology. The goals of medical therapy for congestive heart failure include the following:

• Reducing the preload

• Enhancing cardiac contractility

• Reducing the afterload

• Improving oxygen delivery

• Enhancing nutrition

As previously discussed, the causes of congestive heart failure vary, and they appear in different patients to variable degrees. Thus, the medical management of congestive heart failure in children should be tailored to the specific details of each case.

Preload reduction can be achieved with oral (PO) or intravenous (IV) diuretics (eg, furosemide, thiazides, metolazone). Venous dilators (eg, nitroglycerin) can be administered, but their use is less common in pediatric practice. Contractility can be supported with IV agents (eg, dopamine) or mixed agents (eg, dobutamine, inamrinone, milrinone). Digoxin appears to have some benefit in congestive heart failure, but the exact mechanism is unclear. Ivabradine may be considered to lower heart rate in stable symptomatic heart failure owing to dilated cardiomyopathy.

Afterload reduction is obtained orally through administration of angiotensin-converting enzyme (ACE) inhibitors or intravenously through administration of other agents, such as hydralazine, nitroprusside, and alprostadil. Pharmaceutical agents used in the treatment of congestive heart failure are summarized in the Table below.

Table. Pharmaceutical Agents Used in the Treatment of Congestive Heart Failure (Open Table in a new window)

Acute presentation of the ill newborn or infant with congestive heart failure warrants immediate concern regarding potential sepsis or ductal-dependent congenital heart disease. The evaluation and treatment of these patients are often best performed in the neonatal or pediatric intensive care unit (ICU).

The initial management involves the usual assessment of the patient's airway, breathing, and circulation (ABCs); achieving IV access; laboratory testing, including a blood culture; and empiric antibiotic therapy. Management of low cardiac output can be initiated by using a dopamine infusion of 5-10 mcg/kg/min; acidosis can be corrected with the administration of fluid and/or bicarbonate.

Calcium should be administered when hypocalcemia is documented. Because ductal-dependent structural heart disease is a common cause of congestive heart failure in early infancy, echocardiography should be considered early in the evaluation if a diagnosis is not immediately forthcoming.

Anatomic lesions that may appear early and that should be considered include the following:

• Coarctation or interruption of the aortic arch

• Total anomalous pulmonary venous return

• Hypoplastic left heart syndrome (or variants, including severe mitral valve stenosis and/or aortic valve stenosis or atresia)

• Truncus arteriosus

• Pulmonary atresia

• Transposition of the great arteries

Conditions to consider in young infants with a more protracted congestive heart failure course include those producing significant left-to-right shunts, including large ventricular septal defects, aortopulmonary shunts, and arteriovenous malformations.

Prostaglandin

An alprostadil (PGE1) infusion is indicated when ductal-dependent cardiac lesions are diagnosed or when they cannot be ruled out in a timely fashion. Absent femoral pulses or the inability to increase the systemic PaO2 to above 150mm Hg with a fraction of inspired oxygen (FiO2) of 1 suggests a ductal-dependent lesion, and treatment with PGE1 is warranted.

PGE1 may theoretically aggravate the condition in some children with total anomalous pulmonary venous connection and obstruction or in children with other etiologies of congestive heart failure, such as sepsis. Whenever possible, echocardiography should be performed before PGE1 treatment is begun. On the other hand, when critical heart disease is present and echocardiography is not immediately available, prostaglandin infusion can be lifesaving.

Nonstructural problems

Nonstructural cardiac problems that occur during this stage include tachyarrhythmias (usually supraventricular tachyarrhythmia [SVT]) and complete heart block. Prompt pharmacologic or electrical cardioversion is warranted in any patient with a tachyarrhythmia who presents with congestive heart failure. Primary cardiomyopathy or myopathic disease secondary to inborn errors of metabolism should be considered in the absence of structural cardiac disease or arrhythmia when cardiac dysfunction is present.

Long-standing but unrecognized congestive heart failure may present acutely; similarly, an acute presentation may represent an acute onset of acquired cardiac disease (myocarditis or arrhythmia). Management of acute decompensation involves treatment of presenting symptoms and adjustment or initiation of long-term therapy.

In older children with acute congestive heart failure, admit to the ICU for diuresis with IV furosemide. For patients with significant hypotension, IV dopamine (5-10 mcg/kg/min) or milrinone (0.3-1 mcg/kg/min) infusion is appropriate until stabilization is achieved. Older children may require the placement of a central venous or pulmonary artery catheter to monitor venous pressure and cardiac output during stabilization.

Nitrates (nitroprusside, nitroglycerin) or nesiritide may be useful in patients with elevated pulmonary capillary wedge pressure and pulmonary congestion due to their venous dilating effects. Nesiritide carries the additional theoretical benefits of reversing deleterious neurohumoral responses and increasing natriuresis. Small studies have been conducted to measure hemodynamic effects of nesiritide in children with dilated cardiomyopathy.[8, 9] However, nesiritide has demonstrated no mortality advantage compared with nitroglycerin for acute decompensated heart failure in a large adult trial.[10]

If the underlying cause of the congestive heart failure cannot be immediately corrected in a patient who is hemodynamically stable, outpatient management can be initiated by using several agents. Afterload reduction using an ACE inhibitor is indicated in the presence of left ventricular (LV) dysfunction, regardless of symptoms.

Afterload reduction is indicated in patients who have large left-to-right shunts at the ventricular or arterial level (ventricular septal defect or patent ductus arteriosus), left-sided regurgitant lesions (aortic insufficiency or mitral regurgitation), or poor systolic function (myocarditis or dilated cardiomyopathy). ACE inhibitors are the medications of choice. Alternatively, an angiotensin receptor blocker (ARB), such as losartan, may be used in patients in whom ACE adverse effects (particularly cough) may be unacceptable.[11]

In addition to afterload reduction (ACE inhibitor), low-dose furosemide (1 mg/kg/dose PO bid) may be initiated, with or without the addition of another agent for inotropic effect (digoxin), or beta-blockade (carvedilol) to treat mild symptoms of congestive heart failure.[12] The dose of digoxin (0.005-0.010 mg/kg/day PO divided twice daily, not to exceed 0.125-0.250 mg PO qd) is almost never increased, either for effect or according to digoxin levels, which are notoriously unreliable. However, the dose may be decreased in the presence of signs of toxicity. The suspicion of digoxin toxicity should increase if an infant is uninterested in feedings, gags, or vomits frequently. These symptoms are typically due to an overdose or renal failure.

For more severe congestive heart failure, diuretic therapy with oral furosemide may be increased to 2 mg/kg/dose orally 3 times daily or a second agent, such as hydrochlorothiazide or metolazone, can be added. To be most effective, hydrochlorothiazide and metolazone are best administered simultaneously with furosemide to achieve their synergistic effect.

Aldosterone antagonists

Aldosterone antagonists are potassium-sparing diuretics. Spironolactone or eplerinone have class I indication for use in heart failure in adults, including any patient with a left ventricular ejection fraction (LVEF) of less than 40% in the presence of even minimal symptoms.[13, 14, 15] Their mechanism of action in heart failure is unknown. Pediatric studies have not been performed, but these agents have been used in children for a variety of indications, including diuretic-induced hypokalemia. The usual dosage for children is spironolactone 1-3.3 mg/kg/day in single or divided doses.

Potassium

For patients taking more than 1 mg/kg of oral furosemide twice daily without ACE inhibitors, spironolactone should be added for its potassium-sparing effect and theoretical beneficial effects on cardiac remodeling. Adult studies have suggested that it prolongs survival in chronic heart failure.[16] Alternatively, serum potassium levels may be monitored, and appropriate supplementation should be provided. Supplemental potassium chloride may be required when high doses of diuretics are used, but most children are extremely averse to the taste of most preparations. Alternatively, aldosterone antagonists may be administered to treat chronic diuretic-induced hypokalemia.

Because ACE inhibitors and aldosterone antagonists cause potassium retention, supplemental potassium should be avoided except in the presence of documented hypokalemia in patients taking these medications.

Sodium

Hyponatremia often accompanies congestive heart failure and is caused by water retention in response to vasopressin (antidiuretic hormone), which is produced as a result of renin-angiotensin activation but may be exacerbated by the use of diuretics and by salt wasting by the kidney.

Sodium supplementation is almost never indicated in infants or children with congestive heart failure except in emergency situations. Severe hyponatremia is generally best managed by reducing the dose of diuretics or by restricting fluid intake, although the latter has little use in small children. In any child taking more than 2 mg/kg/d of furosemide, electrolyte levels should be checked every few months, as they should be in any child taking furosemide in conjunction with other diuretics or ACE inhibitors.

Beta blockers

Experience with beta-blocker therapy in pediatric patients has increased. The selective beta1-blocker metoprolol and the nonselective beta1-blocker and beta2-blocker carvedilol, used primarily in adults, have generally shown encouraging results in select patients with cardiomyopathy and mild or moderate chronic congestive heart failure. Adults using these beta blockers (carvedilol) have demonstrated an increased stroke volume and stroke work index during exercise, along with a decreased heart rate and LV chamber size.[17, 18]

In addition, carvedilol has been shown to decrease pulmonary artery mean and wedge pressures, decrease cardiac norepinephrine levels, and increase peripheral vasodilation by means of alpha1 blockade. For these reasons, in part, use of carvedilol has increased, particularly in cardiomyopathies.

However, a double-blind, randomized trial (carvedilol vs placebo) in pediatric patients with mild to moderate congestive heart failure failed to demonstrate a benefit in reduction of symptoms or mortality. The power of the study was affected by an unexpectedly high rate of improvement among all patients, including those who received placebo.[19] Thus, the exact indications and benefits of carvedilol therapy in children with heart failure remain somewhat unclear.[7]

I(f) current inhibitor

Ivabradine was approved by the FDA in April 2019 for children aged 6 months or older with stable symptomatic heart failure caused by dilated cardiomyopathy who are in sinus rhythm with an elevated heart rate. Ivabradine blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) ‘funny’ current, which regulates heart rate.

The primary endpoint or 20% or greater reduction of heart rate from baseline without producing bradycardia or symptoms was reached by 51 of 73 children taking ivabradine (70%) compared with 5 of 41 taking placebo (12%) at varying doses (odds ratio: 17.24; p < 0.0001). Between baseline and 12 months, there was a greater increase in left ventricular ejection fraction in patients taking ivabradine than placebo (13.5% vs. 6.9%; p = 0.024). New York Heart Association functional class or Ross class improved more with ivabradine at 12 months than placebo (38% vs. 25%; p = 0.24).[25]

Anemia

Often overlooked in the management of chronic congestive heart failure is the role of the oxygen-carrying capacity of the blood. Anemia aggravates congestive heart failure by increasing the demands for cardiac output, and careful attention to iron stores or the administration of red cell transfusions often results in a significant improvement.

Nutrition

Nutrition is crucial in the management of chronic congestive heart failure. Particularly during infancy, congestive heart failure increases the metabolic demands while making feeding itself more difficult. Enhanced caloric content feedings and, in some cases, nasogastric or gastrostomy feedings may be necessary to maintain the patient's growth.

Growth

The success of medical therapy of congestive heart failure in infants and small children is judged according to the child's growth. The failure to gain weight in the setting of marked congestive heart failure signifies that the current regimen is not sufficient. A failure to thrive is an indication for increased medical management or, when the option is available, surgical repair of structural heart disease.

Cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) has emerged as a useful therapy in the treatment of chronic congestive heart failure. CRT involves the use of biventricular pacemakers to improve ventricular function by electrically adjusting the timing of right and left ventricular contraction to optimize wall motion and increase filling time. In addition to increasing stroke volume, CRT may allow for reverse remodeling to delay disease progression. Clinical trials in adults with moderate to severe heart failure have demonstrated beneficial effects of CRT use, including reduction of symptoms, increased exercise capacity, and decreased morbidity and mortality.[20]

In pediatric practice, resynchronization therapy has been limited; the initial studies described the results for this modality instituted in children with chronic heart failure who required pacemakers for treatment of rhythm disorders. Use of this therapy is more difficult to institute in children, whose small size requires the use of surgically placed epicardial pacemakers rather than percutaneously placed pacemakers. As more registry and retrospective data have accumulated, use of this therapy has increased, and indications based on echocardiographic and electrocardiographic parameters continue to be refined.[21, 22]

Mechanical support

Mechanical support may be used in the treatment of acute heart failure (ie, myocarditis or postcardiotomy syndrome) or in chronic heart failure as a bridge to recovery or to a heart transplant. The choice of support therapy depends on the expected duration of use.

Extracorporeal membrane oxygenation (ECMO) therapy may be quickly initiated in unstable patients. Generally, its duration of use is limited to days or weeks because of complications related to infection or anticoagulation. ECMO is used to provide acute temporary support as a bridge to recovery or transplantation.

In a study of ECMO use in 108 patients (73 adults and 35 children), most of whom were suffering from postcardiotomy cardiac low output, Beiras-Fernandez et al found that pediatric patients who had undergone congenital heart surgery were among the patients who demonstrated the best results from ECMO.[23]

Ventricular assist devices (VADs; eg, Berlin Heart, EXCOR Pediatric System, Thoratec VAD) may be used to provide long-term ventricular support. The EXCOR Pediatric System is the first pulsatile mechanical circulatory support device specifically designed for children and was approved by the FDA in December 2011. The device consists of 1 or 2 external pneumatic blood pumps to support the left ventricle alone or both the left and right ventricles. EXCOR is available in graduated sizes to fit children from newborns to adolescents.[24] Also see FDA approves mechanical cardiac assist device for children with heart failure. Other devices, such as Thoratec HeartMate II, have not received approval for pediatric use but have been used in selected cases for appropriately sized patients. Currently, VADs are not approved forpermanent(destination) therapy in pediatric patients and should be considered only as a bridge to transplantation in appropriate candidates.[12]

In 2014, the International Society for Heart and Lung Transplantation (ISHLT) published updated guidelines for the evaluation and management of heart failure in children. Due to the lack of research trials in children, the majority of the recommendations were achieved by consensus.[12]

Acute Heart Failure

The ISHLT recommendations for management of acute HF are summarized below. All recommendations have a C level of evidence unless otherwise noted.[12]

Assessment and Monitoring

Class I

• Diagnosis of acute HF is based on signs and symptoms of HF combined with supportive evidence from chest X-ray imaging, ECG, echocardiography, and laboratory evaluations. (Level of evidence: B)
• Severity, including degree of congestion and adequacy of perfusion should be assessed.
• Evalute etiology of HF, with focus on identifying reversible causes (e.g., repairable CHD, myocarditis, tachycardia-induced cardiomyopathy, and hypothyroidism).
• Coronary angiography should be performed if coronary ischemia is suspected in the presence of other potential abnormalities that cannot be definitely excluded by non-invasive imaging.  
• Cardiac catheterization is indicated in patients with palliated or repaired CHD who present with acute HF if a non-invasive evaluation fails to establish a definitive diagnosis.  
• Perform serial testing to monitor for electrolyte abnormalities, hemoglobin levels, end-organ perfusion, and response to therapy.   
• In hospitalized patients: consider observation in an ICU; evaluate and monitor for arrhythmias with continuous ECG monitoring/telemetry. 
• Transfer patients with severe acute HF to a center with pediatric HF specialists and the expertise and ability to optimize medical therapy, evaluate for heart transplant, and if necessary, provide mechanical support.

Class IIa

• For patients with decompensated HF, place intra-arterial catheters for continuous blood pressure monitoring. 
• Consider central venous catheters should in decompensated HF to allow for measurement of central venous pressure and/or mixed venous saturations and to administer medications and fluids. 

Class III

• Pulmonary artery catheterization is not recommended for routine use, but may be appropriate in selected patients. 

Management

Class I

• IV inotropic support may be used temporarily in patients presenting as cardiogenic shock with poor systemic and end-organ perfusion.
• Vasodilators may be when hypotension is not present. Vasodilators may also be used in combination with diuretics for symptomatic relief in patients with pulmonary edema.
• Perform ongoing assessment of fluid status in all patients admitted to the hospital.
• Diuretics are the first-line therapy for patients with evidence of fluid overload.
• Monitor carefully for side effects of anti-congestive therapies, including renal function, electrolytes, and hypotension.

​Class IIa

• Intravenous inotropic support may be used temporarily in patients presenting as hypotension with evidence of low CO and compromised end-organ perfusion.
• The choice of inotropic agent in acute decompensated HF depends on clinical presentation. Milrinone and/or dobutamine can be used as first-line rescue therapy, with epinephrine playing a role in the face of refractory hypotension and poor end-organ perfusion.
• Fluid restriction for patients with acute HF, regardless of serum sodium level.

Class IIb

• Consider levosimendan for acute decompensated HF unresponsive to traditional inotropic therapy.

Class III

• Use of intravenous inotropic agents in the absence of clinical evidence of hypotension, impaired perfusion, low CO, and/or decreased end-organ perfusion is potentially harmful. (Level of evidence: B)

Medical Management of Chronic Heart Failure

The major recommendations for pharmacologic therapy are summarized in the table below.[12]

Table. Recommendations for Pharmacologic Therapy for Chronic Heart Failure (Open Table in a new window)

Device-Based Therapies

The recommendations for device-based therapies are summarized below.[12]

Class I

• Permanent pacemaker implantation for advanced second- or third-degree atrioventricular block associated with ventricular dysfunction. (Level of evidence: B)
• In the pediatric survivor of cardiac arrest after evaluation to define the cause of the event and to exclude any reversible/treatable causes, perform ICD implantation. (Level of evidence: B)
• In patients with tachycardia-induced cardiomyopathy when medical therapy fails, ablation therapy. (Level of evidence: B)

​Class IIa

• Cardiac resynchronization therapy (CRT) for patients with a systemic LV with an EF < 35%, complete left bundle branch block pattern, QRS duration (native or paced) > ULN for age, NYHA Class II-IV on GDMT. (Level of evidence: B)

• ICD implantation can be useful in the following groups:

  • Patient with unexplained syncope and at least moderate LV dysfunction and DCM. 

  • Adolescents with hypertrophic cardiomyopathy (HCM) and 1 or more major risk factors for sudden cardiac death (SCD).

  • Adolescent with AVC with 1 or more risk factors for SCD. 

  • Adolescent with a familial cardiomyopathy associated with SCD. 

• In adolescents with tachycardia-induced cardiomyopathy, consider ablation therapy for primary therapy. (Level of evidence: B)

Class IIb

• Consider CRT for patients with:

  • Systemic RV, with an EF < 35%, complete right bundle branch block pattern, QRS duration (native or paced) > ULN for age, NYHA Class II-IV on GDMT. 

  • Single ventricle, with an EF < 35%, complete bundle branch pattern, QRS duration (native or paced) > ULN for age, NYHA Class II-V on GDMT. 

• Consider ICD therapy for the following groups:

  • Patients with DCM who have an LVEF < 35% and who are in NYHA Class II or III. 

  • Patients with CHD with syncope in the presence of ventricular dysfunction. 

  • Adolescents with LVNC and moderately depressed ventricular function. 

  • Non-hospitalized patients with non-sustained or sustained ventricular tachycardia who required a VAD. 

• Consider ablation therapy in patients with frequent premature ventricular contraction and cardiomyopathy of unknown etiology when medical therapy fails. (Level of evidence: B)

Mechanical Circulatory Support

The recommendations for mechanical circulatory support (MCS) are summarized below.[12]

Class I

•  For children who are unable to be weaned from inotropic support and are showing early, reversible dysfunction of at least 1 other major organ system, consider implantation of a durable ventricular assist devices (VAD) as a bridge to transplantation 

Class IIa

• For a patient in cardiac arrest or cardiogenic shock with pulmonary compromise, ECMO should be considered for emergency cardiovascular support, as a bridge to recovery of function. 

• For a patient with isolated cardiac failure that is believed to be reversible, consider ECMO or a temporary VAD as a bridge to recovery of function. If recovery does not occur, then transition to a chronic VAD for bridge to transplantation or for destination therapy is reasonable. 

• For cardiogenic shock that is not believed to be due to a reversible underlying cause, consider use of a temporary VAD or ECMO for resuscitation of end-organ function rather than directly implanting a chronic VAD system. 

Class IIb

• Consider implantation of a chronic VAD system as long-term support for patients who are not eligible for transplantation, provided a system is available that permits discharge to home with regular outpatient follow-up.
• Use of BiVAD support should be reserved for patients who appear unlikely to achieve adequate hemodynamics from LVAD support alone.
• Children who are supported on a chronic VAD system may be considered for a recovery protocol and weaning from VAD if recovery of cardiac function is documented.

The goals of pharmacotherapy include symptom relief, improved cardiac output, shortened hospital stay, fewer emergency department visits, and decreased mortality.

Class Summary

Diuretics are reserved for congestive states.

Furosemide (Lasix)

Furosemide increases excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. The bioavailability of oral furosemide is 50%. If a switch is made from intravenous to oral administration, an equivalent oral dose should be used. Doses vary depending on the patient's clinical condition.

Class Summary

Diuretics are reserved for congestive states.

Hydrochlorothiazide (Microzide)

Hydrochlorothiazide inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as potassium and hydrogen ions.

Class Summary

Diuretics are reserved for congestive states.

Metolazone (Zaroxolyn)

Metolazone is a quinazoline diuretic with properties similar to those of thiazide diuretics. It inhibits sodium resorption at the cortical diluting site and the proximal convoluted tubule.

Class Summary

These agents are used for edema associated with congestive heart failure.

Spironolactone (Aldactone)

Spironolactone is used for the management of edema resulting from excessive aldosterone excretion. It competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.

Class Summary

Long-term use of the phosphodiesterase inhibitor milrinone has deleterious effects on survival in patients with heart failure. Improvement of CHF symptoms occurs as the trade-off for this increase in mortality. Inotropic agents are reserved for patients who need hemodynamic-directed treatment during acute decompensation, those refractory to maximal standard therapy, as palliation for end-stage heart failure, or as a bridge to transplantation for appropriate candidates. Milrinone may have an advantage over beta-agonists in that it can be used for acute inotropic support during introduction of beta-blocker therapy.

Digoxin therapy for heart failure has no benefit on mortality rates. However, it does improve NYHA functional class, hemodynamics, symptoms, exercise capacity, and quality of life and reduces hospitalizations for heart failure. Patients with worse NYHA functional class and lower left ventricular ejection fraction benefit most from digoxin therapy.

Milrinone

Milrinone is a bi-pyridine positive inotrope and vasodilator with little chronotropic activity. It differs in mode of action from both digitalis glycosides and catecholamines. This agent is used for the short-term management of acute decompensated heart failure.

Digoxin (Lanoxin)

Digoxin is a cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. It acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

Dopamine

Dopamine is a naturally occurring endogenous catecholamine that stimulates beta1- and alpha1-adrenergic and dopaminergic receptors in a dose-dependent fashion. It stimulates release of norepinephrine.

In low doses (2-5 ug/kg/min), dopamine acts on dopaminergic receptors in renal and splanchnic vascular beds, causing vasodilatation in these beds. In midrange doses (5-15 ug/kg/min), it acts on beta-adrenergic receptors to increase heart rate and contractility. In high doses (15-20 ug/kg/min), it acts on alpha-adrenergic receptors to increase systemic vascular resistance and raise blood pressure.

Dobutamine

Dobutamine is a sympathomimetic amine with stronger beta than alpha effects. It produces systemic vasodilation and increases the inotropic state. Vasopressors augment the coronary and cerebral blood flow during the low-flow state associated with shock.

Sympathomimetic amines with both alpha- and beta-adrenergic effects are indicated in cardiogenic shock. Dopamine and dobutamine are the drugs of choice to improve cardiac contractility, with dopamine the preferred agent in hypotensive patients. Higher dosages may cause an increase in heart rate, exacerbating myocardial ischemia.

Class Summary

These agents may be required for repletion of catecholamines and for the treatment of hypotension.

Epinephrine (Adrenalin)

Epinephrine is used for hypotension refractory to dopamine. Its alpha-agonist effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Its beta2-agonist effects include bronchodilation, chronotropic cardiac activity, and positive inotropic effects.

Class Summary

An alprostadil (PGE1) infusion is indicated when ductal-dependent cardiac lesions are diagnosed or when they cannot be ruled out in a timely fashion. Absent femoral pulses or the inability to increase the systemic PaO2 to above 150 mm Hg with a fraction of inspired oxygen (FiO2) of 1 suggests a ductal-dependent lesion, and treatment with PGE1 is warranted.

PGE1 may theoretically aggravate the condition in some children with total anomalous pulmonary venous connection and obstruction or in children with other etiologies of congestive heart failure, such as sepsis. Whenever possible, echocardiography should be performed before PGE1 treatment is begun. On the other hand, when critical heart disease is present and echocardiography is not immediately available, prostaglandin infusion can be lifesaving.

Alprostadil IV (Prostin VR)

Alprostadil is identical to the naturally occurring PGE1 and possesses various pharmacologic effects, including vasodilation and inhibition of platelet aggregation. It is a first-line medication used as palliative therapy to temporarily maintain patency of the ductus arteriosus before surgery.

This agent is beneficial in infants with congenital defects that restrict pulmonary or systemic blood flow and in patients who depend on a patent ductus arteriosus for adequate oxygenation and lower body perfusion. It produces vasodilation and increases cardiac output.

Class Summary

Use of ACE inhibitors (in the absence of contraindications to ACE inhibition) is the current criterion standard in the treatment of left ventricular dysfunction. ACE inhibitors have been shown to decrease mortality rates in both symptomatic and asymptomatic patients with left ventricular dysfunction and to reduce re-admissions caused by heart failure. The absolute benefits are greater in patients with severe heart failure.

The dosage necessary for maximal benefit is debatable. However, authorities have generally accepted that maximizing ACE inhibitor therapy is important and should be accomplished in conjunction with other necessary therapies.

Enalapril (Vasotec)

Enalapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. This agent helps control blood pressure and proteinuria. It decreases the pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance.

Enalapril has a favorable clinical effect when administered over a long period. It helps prevent potassium loss in distal tubules. Because the body conserves potassium, less oral potassium supplementation is needed.

Lisinopril (Prinivil, Zestril)

Lisinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Captopril

Captopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and reduces aldosterone secretion.

Class Summary

Angiotensin receptor blockers are as effective as ACE inhibitors in the treatment of heart failure. Their adverse-effect profile is similar to that of ACE inhibitors with regard to renal insufficiency or hyperkalemia, but they do not cause potentiation of bradykinin and therefore do not cause cough.

Losartan (Cozaar)

Losartan is an ARB that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, it does not affect the response to bradykinin, and it is less likely to be associated with cough and angioedema. It is used for patients unable to tolerate ACE inhibitors.

Class Summary

Preload reduction with vasodilators is thought to be helpful in acute decompensated heart failure by reducing congestions and minimizing cardiac oxygen demand. Afterload reduction is also thought to be helpful in some patients with acute decompensated heart failure by decreasing myocardial oxygen demand and improving forward flow.

Sublingual nitroglycerin spray, topical ointment, and IV nitroglycerin have been advocated in the treatment of pulmonary edema secondary to CHF. Morphine also has significant vasodilatory effects and can be useful.

Nitroglycerin (Nitro-Bid, Nitro-Dur, Minitran)

Nitroglycerin causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate (cGMP) production, resulting in a decrease in blood pressure.

Nitroprusside (Nitropress)

Nitroprusside produces vasodilation and increases inotropic activity of the heart. At higher dosages, it may exacerbate myocardial ischemia by increasing heart rate.

Class Summary

General guidelines for initiating beta-blocker therapy include treating all patients with left ventricular dysfunction except those who are acutely decompensated. Therapy should be initiated at low dosages, which should be increased gradually over several weeks. Patients' conditions may deteriorate over the short term, but they generally improve in the long term with continued therapy.

Carvedilol, bisoprolol, and metoprolol CR/XL are the only agents currently approved by the US Food and Drug Administration (FDA) for use in persons with heart failure. Carvedilol acts in 3 ways: as a beta-blocker, an alpha-blocker, and an antioxidant and may be more beneficial than metoprolol in heart failure.[19]

Carvedilol (Coreg, Coreg CR)

Carvedilol blocks beta1-, alpha-, and beta2-adrenergic receptor sites, decreasing adrenergic-mediated myocyte damage.

Metoprolol (Lopressor, Toprol XL)

Metoprolol is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During intravenous administration of metoprolol, carefully monitor the patient's blood pressure, heart rate, and electrocardiogram.

Class Summary

Indicated for children aged 6 months or older with stable symptomatic heart failure caused by dilated cardiomyopathy who are in sinus rhythm with an elevated heart rate.

Ivabradine (Corlanor)

Blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) ‘funny’ current, which regulates heart rate.

Class Summary

Human B-type natriuretic peptide (BNP) is a new class of drug in the treatment of heart failure. It is produced through recombinant DNA technology and has the same amino acid sequence as naturally occurring human BNP.

Nesiritide (Natrecor)

Nesiritide is a recombinant DNA form of human BNP that dilates veins and arteries. Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells. Binding to receptor causes increase in cGMP, which serves as second messenger to dilate veins and arteries. This, in turn, leads to smooth muscle relaxation and vasodilation. Venous and arterial dilation results in decreased preload and afterload and reductions in pulmonary capillary wedge pressure. Human BNP is indicated for temporary use in patients with acutely decompensated CHF.

Human BNP has additional beneficial effects for heart failure patients. Neurohormonal effects on the rennin-angiotensin-aldosterone system (RAAS) result in reductions in plasma norepinephrine and a trend toward a decrease in aldosterone levels. Renal effects include diuresis and natriuresis with at least preservation, if not an increase, in renal blood flow and glomerular filtration rate.