Abstract
Heart failure in children occurs with a heterogenous group of congenital and acquired diseases. Systolic ventricular dysfunction is the most common cause of pediatric heart failure; however, primary diastolic dysfunction can occur, particularly in patients with restrictive cardiomyopathy or complex congenital heart disease. Residual lesions, cyanosis, pulmonary hypertension, arrhythmias, and Fontan physiology are important contributors to heart failure severity. Heart failure in children ranges from acute decompensation with venous congestion and/or low cardiac output to more indolent manifestations such as growth failure or fatigue. Children with heart failure due to congenital heart disease may have a gradual decline in functional status that can be difficult to ascertain without close follow-up. Hepatic, renal, and infectious complications are important comorbidities that exacerbate heart failure. The approach to the child with heart failure includes instituting treatments to relieve acute symptoms and improve cardiac output, identifying underlying causes and comorbidities amenable to intervention, and risk stratifying patients to guide long-term management. Children with dilated cardiomyopathy are particularly challenging because they have dichotomous outcomes ranging from death or heart transplantation to normalization of function. Medical therapies in children with heart failure are largely based on data from adults with heart failure, despite significant differences in underlying cause and comorbidities. Advanced heart failure therapies such as ventricular assist devices and transplantation have transformed long-term outcomes in this population. Achieving optimal outcomes in children with heart failure requires a multidisciplinary patient-centered team with expertise in medical and surgical therapies, pharmacology, arrhythmias, and critical and palliative care.
Key Words
heart failure, cardiomyopathy, congenital heart disease, pediatrics
Historical Perspective: Pediatric Heart Failure
The definition of heart failure has expanded over the millennia from a clinical syndrome of fluid retention and fatigue to include structural and physiologic disruptions of normal genetic, metabolic, and neurohormonal processes. The Ebers Papyrus, dating from 1500 BC, contains one of the earliest descriptions of the symptoms of heart failure, including fluid retention in association with weakness of the heart, even distinguishing between pulmonary and hepatic congestion. Histologic analysis performed on the lungs of a 3500-year-old Egyptian mummy showed evidence of massive intraalveolar displacement and siderosis consistent with acute decompensated heart failure with pulmonary edema and pulmonary hemorrhage. A portrayal of a child with ascites and a dark discolored face can be found in a 1620 baroque painting by Giovanni Lanfranco of St. Luke, suggesting the presence of heart failure in association with a cyanotic heart lesion. In 1882 John Keating published an extensive description of the symptoms of dyspnea, dropsy, and palpitations in a child with ventricular dilation. Interestingly, Keating classified several distinct morphologic cardiac features associated with these symptoms as ventricular dilation, dilation with hypertrophy, or hypertrophy alone.
Causes of Pediatric Heart Failure
Currently heart failure is conceptualized as a clinical and pathophysiologic syndrome that begins with an event that causes disruption of normal myocardial function. Although the clinical signs and symptoms of heart failure in children are similar to those seen in adults, the underlying cardiac diseases that lead to heart failure differ significantly. In an analysis of a large US database comparing pediatric and adult heart failure hospitalizations, the most common cause of heart failure in children was congenital heart disease (60% of patients), and a higher proportion of children underwent an interventional procedure to treat heart failure than in the adult cohort (60% versus 0.3%). This highlights the fact that a large proportion of pediatric patients admitted with clinical heart failure have venous congestion secondary to ventricular volume overload from a left-to-right shunt or valvular regurgitation. Treatment strategies in the pediatric heart failure population with high cardiac output and normal ventricular function are directed toward surgical or catheter intervention. The specific therapies depend on the underlying congenital heart defect and are addressed in other sections of this book. The remainder of this chapter will focus on the pediatric patient with heart failure due to primary or secondary myocardial dysfunction or a congenital heart lesion not amenable to surgical or interventional repair. Among children undergoing heart transplantation the causes of end-stage heart failure are split relatively evenly between cardiomyopathy and congenital heart disease; in the adult heart transplant population the causes of end-stage heart failure are ischemic cardiomyopathy in 35% and congenital heart disease in only 3%. The most common underlying causes of heart failure in children are listed in Box 72.1 .
Systolic Heart Failure (HFrEF)
- •
Cardiomyopathy
- •
Dilated
Idiopathic/genetic
Metabolic
Ischemic
Arrhythmogenic
Infiltrative
Infectious/inflammatory
Endocrine
Toxic (chemotherapy, cocaine)
- •
Mixed cardiomyopathy
Hypertrophic
Restrictive
- •
- •
Congenital heart disease
- •
Postcardiopulmonary bypass
- •
Valvular insufficiency or residual shunt
- •
Outflow tract obstruction
- •
Cyanosis
- •
Diastolic Heart Failure (HFpEF)
- •
Cardiomyopathy
- •
Hypertrophic
- •
Restrictive
- •
- •
Hypertension
- •
Congenital heart disease
- •
Single-ventricle physiology
- •
Shone’s complex
- •
HFrEF, Heart failure with reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction.
Clinical Manifestations of Pediatric Heart Failure
Similar to adults, clinical heart failure in children with systolic ventricular dysfunction and a reduced ejection fraction, known as HFrEF, includes the signs and symptoms of venous congestion and/or poor perfusion and low cardiac output ( Fig. 72.1 ). In 2003 Nohria and colleagues proposed a simple algorithm to assess the clinical status of adult patients in decompensated heart failure that proved useful in directing therapy and predicting outcome. Patients were assigned to a category based on fluid status, “wet” or “dry,” and peripheral perfusion, “warm” or “cold” ( Fig. 72.2 ).
Recently there has been increasing recognition that the clinical syndrome of heart failure can also occur in the setting of a preserved ejection fraction, known as HFpEF. In heart failure with a preserved ejection fraction (HFpEF), symptoms of dyspnea and venous congestion are the result of elevated diastolic filling pressures and decreased ventricular compliance. Decreased ventricular filling and a low stroke volume can lead to poor perfusion and a low cardiac output state, which manifests as poor growth and fatigue in children. In adults, HFpEF is more commonly found in older adults, patients with systemic hypertension, and in women. HFpEF can occur in pediatric patients with hypertrophic, restrictive, or noncompaction cardiomyopathy or complex congenital heart disease such as left ventricular outflow tract obstruction.
The management of children who successfully transition from acute decompensated heart failure to chronic compensated heart failure includes the use of tools to grade heart failure severity and quantify the impact of symptoms on the patient’s health-related quality of life and functional status. In the adult heart failure population, New York Heart Association functional class or heart failure–specific quality of life questionnaires such as the Kansas City Cardiomyopathy or the Minnesota Living With Heart Failure questionnaires have been shown to be correlate with clinical outcomes. Despite a lack of validation against mortality or worsening heart failure, the Ross Heart Failure Classification system ( Box 72.2 ) has been adopted as a tool to serially monitor children less than 5 years of age and has been used as an outcome measure in several clinical trials.
Ross Heart Failure Class
- I
No limitations
- II
Mild tachypnea or diaphoresis with feedings in infants, dyspnea at exertion in older children, no growth failure
- III
Marked tachypnea or diaphoresis with feedings or exertion and prolonged feeding times with growth failure from CHF
- IV
Symptomatic at rest with tachypnea, retractions, grunting, or diaphoresis
CHF, Congestive heart failure.
Neurohormonal Activation in Pediatric Heart Failure
In adults the recognition that chronic activation of the sympathetic nervous system and upregulation of the renin-angiotensin-aldosterone system (RAAS) in response to myocardial injury play a key role in ongoing myocardial damage revolutionized the treatment of heart failure in the early 1990s. Neurohormonal and RAAS activation results in vasoconstriction, cardiac hypertrophy, and through alteration in collagen turnover by myofibroblasts, leads to the development of myocardial fibrosis. The neurohormonal response to heart failure in children has not been as well characterized and may differ from adults, due to the difference in causes of heart failure in children. Small studies have demonstrated upregulation of the sympathetic nervous system and the RAAS in children with cardiomyopathy. In children with dilated cardiomyopathy, serum brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NTproBNP) levels have been shown to correlate well with the degree of heart failure, and a decrease in these levels may be a predictor of a positive response to medical therapy. In the congenital heart disease population there has been more equivocal associations of heart failure with activation of the autonomic system and the RAAS. Markers of neurohormonal activation and elevations in serum BNP level have been demonstrated to correlate with heart failure in patients with congenital heart disease, but the levels are often lower compared to patients with cardiomyopathy. In children with single ventricle and heart failure, absolute BNP and NTproBNP levels were lower than those seen in adults and children with dilated cardiomyopathy; however, higher BNP and NTproBNP levels were associated with worse outcome.
Pediatric Cardiomyopathies and Heart Failure
In 1980 the World Health Organization (WHO) classified cardiomyopathy subtypes largely based on morphology. Since its inception in 1995 the National Institutes of Health (NIH)-funded Pediatric Cardiomyopathy Registry has used echocardiography for case definition for hypertrophic, dilated, noncompaction, and restrictive cardiomyopathy ( Fig. 72.3 ). More recently, revisions to the WHO classification system have been proposed by the European Society of Cardiology and the American Heart Association in an effort to formulate a more comprehensive approach designed to include genetic and pathophysiologic characteristics that span across the morphologic classes. Although these efforts are broader in scope, a primarily morphologic classification continues to be the most commonly applied approach in the clinical setting.
Primary pediatric cardiomyopathy is a rare disease, occurring in 1.1 to 1.2 per 100,000 children. The incidence of pediatric cardiomyopathy has been estimated by studies across the world to be 0.75 to 1.3 per 100,000 children. Dilated and hypertrophic cardiomyopathy are the most common subtypes with annual incidences of 0.3 to 0.7 per 100,000 and 0.2 to 0.5 per 100,000, respectively. Genetic testing has become more accepted in this population, and the importance of mutations in genes controlling the sarcomere, cytoskeleton, desmosome, and metabolic pathways is being increasingly recognized.
Viral myocarditis is an important cause of pediatric cardiomyopathy and heart failure in children. Establishing the diagnosis of myocarditis is of great importance because the rate of recovery of normal function is high, even in patients who present with severe decompensated heart failure. Acquired cardiomyopathies are also an important cause of heart failure in children (see Box 72.1 ). These include cardiomyopathy secondary to tachyarrhythmias, (e.g., ectopic atrial tachycardia), volume or pressure overload lesions such as left-to-right shunts or valvar stenosis or regurgitation, and coronary ischemic events due to Kawasaki disease or anomalous origin of the coronary arteries. Acquired cardiomyopathies can also occur due to an infectious, endocrinologic, or toxic insult. The most common example of a toxin-induced cardiomyopathy is the cardiomyopathy that can occur after the use of chemotherapeutic agents such as anthracycline.
The incidence of heart failure differs significantly among the subtypes of cardiomyopathy. In children with dilated cardiomyopathy, heart failure is the presenting finding in 70% to 90%, whereas only 9% to 28% of hypertrophic cardiomyopathy patients present with heart failure. Patients with hypertrophic or restrictive cardiomyopathy can present with HFpEF or HFrEF. In HFpEF cases, heart failure symptoms result from increased venous congestion due to decreased ventricular compliance and left atrial hypertension. Patients with a mixed type of cardiomyopathy (hypertrophic/dilated, noncompaction/dilated, restrictive/dilated) may have symptoms of both HFrEF and HFpEF due to a higher ventricular filling pressure than expected in the presence of systolic dysfunction.
Dilated Cardiomyopathy
Dilated cardiomyopathy typically affects the left ventricle but may be bilateral and is characterized by ventricular dilation and impaired systolic function ( Fig. 72.3 ). Mitral insufficiency may be present secondary to dilation of the valve annulus.
Clinical Presentation.
Infants and children with dilated cardiomyopathy most often present with signs of biventricular congestive heart failure. Manifestations of heart failure in infants include respiratory distress with tachypnea, retractions, and grunting. Poor feeding and failure to thrive by weight criteria with relative preservation of length often occurs. In the older child, clinical signs of pulmonary edema are often present, and gastrointestinal complaints are common. Cardiomyopathies associated with an inborn error of metabolism can appear as congestive heart failure as metabolic demand outstrips supply or as toxic metabolites accumulate. Infants with these disorders can have associated hypoglycemia, metabolic acidosis, and/or encephalopathy.
Physical Examination.
On physical examination, signs of congestive heart failure include pulmonary edema, hepatomegaly, and poor peripheral perfusion. Cardiac findings include tachycardia, pulsus alternans, distant heart tones, an S 3 gallop, and often a murmur of mitral regurgitation. Jugular venous distention is uncommonly observed in the infant but is a useful indicator of central venous hypertension in the older child. Failure to thrive is common in patients with long-standing cardiomyopathy. Neurologic abnormalities, including hypotonia and generalized muscle weakness, are important findings leading to the diagnosis of cardiomyopathy associated with inborn errors of metabolism.
Cardiac Evaluation.
Electrocardiography typically demonstrates increased left ventricular forces, flattening or inversion of the ST-T waves, and atrial enlargement. Low-voltage R waves and elevated ST-T segments are more characteristic of myocarditis .If there an anomalous left coronary artery originating from the pulmonary artery or another rare coronary obstructive lesion, the electrocardiogram may have evidence of myocardial ischemia. The electrocardiogram is an important diagnostic tool that can diagnose the presence of a tachyarrhythmia, such as permanent junctional reciprocating tachycardia, ectopic atrial tachycardia, or junctional tachycardia, that may result in ventricular dysfunction.
Chest radiography often shows pulmonary venous congestion and cardiomegaly. Congestive heart failure can be exacerbated by infectious respiratory disease, and the chest radiograph is essential in diagnosing these processes, including pneumonia. Atelectasis, particularly of the left lower lobe, is commonly seen in severe cardiomyopathy because of compression of the left bronchus.
Echocardiography allows the quantitative determination of ventricular volume and function, both systolic and diastolic. It is essential to rule out anatomic causes of ventricular dysfunction, such as left ventricular outflow tract obstruction, coarctation, primary valvular disease, or coronary artery anomalies. The severity of atrioventricular valve regurgitation can be determined by using color flow Doppler. If tricuspid regurgitation is present, continuous wave Doppler of the jet allows estimation of pulmonary artery pressure. Thrombi secondary to low cardiac flow may be seen most commonly in the left ventricular apex and in the left atrial appendage.
Cardiac magnetic resonance imaging (MRI) has been used in adult dilated cardiomyopathy to evaluate the degree of myocardial fibrosis.
Exercise stress testing with determination of maximal oxygen consumption has been shown to be useful in the prediction of 1-year survival in adult patients with dilated cardiomyopathy. An oxygen consumption of less than 15 mL/kg/min is associated with a poorer 1-year survival. Although these data have not been validated in children, exercise testing is recommended in the evaluation of the older child with dilated cardiomyopathy being considered for heart transplantation.
Cardiac catheterization is not routinely performed to establish the diagnosis of dilated cardiomyopathy. If anatomic abnormalities such as anomalous left coronary artery or aortic coarctation cannot be reliably excluded with noninvasive imaging, coronary angiography and aortography should be performed. Hemodynamic measurements such as cardiac output, ventricular filling pressures, and pulmonary vascular resistance may be helpful in determining both the effectiveness of therapy and the long-term prognosis. When significant ventricular outflow tract obstruction or valvular insufficiency is found, hemodynamic measurements may help to determine the relative contribution of the associated lesions to the heart failure syndrome. Endomyocardial biopsy may show distinctive histologic or ultrastructural findings that may be helpful in diagnosing myocarditis or certain metabolic diseases. However, myocardial biopsy may have only 60% sensitivity in detecting myocarditis, even when multiple biopsy specimens are obtained, because of the focal nature of myocardial involvement. Demonstration of myocardial fibrosis may indicate a worse prognosis.
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy is characterized by myocardial hypertrophy of the left and/or right ventricle ( Fig. 72.3 ). Tremendous heterogeneity exists in morphology, natural history, and the functional course of hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy may involve either ventricle alone or together. The most common form of hypertrophy is asymmetric, involving the interventricular septum; however, concentric hypertrophy also occurs. Disease severity and symptoms, in particular, obstruction to ventricular outflow and myocardial ischemia, are related, although not consistently, to the extent and location of the hypertrophy. Systolic ventricular function is normal or hyperdynamic until later phases of the disease. Obstruction to left or right ventricular outflow is common because of septal hypertrophy and the presence of systolic anterior motion of the mitral valve. The anterior mitral leaflet is pulled anteriorly by the Venturi effect during early systole, making contact with the septum and exacerbating subaortic obstruction. Repeated contact between the anterior leaflet and the septum may result in extensive leaflet fibrosis and further dysfunction.
Clinical Presentation.
Significant heterogeneity exists in morphology, natural history, and the functional course of hypertrophic cardiomyopathy, and heart failure is rarely the presenting symptom in children with hypertrophic cardiomyopathy. The presenting finding of hypertrophic cardiomyopathy in children may be a murmur of outflow tract obstruction or an electrocardiogram with abnormal findings. Diastolic dysfunction in hypertrophic cardiomyopathy results from decreased ventricular compliance because of increased wall tone, decreased chamber volume, and myocardial fibrosis. Diastolic ventricular pressure is increased, and the volume of filling is reduced, leading to symptoms of dyspnea, angina, presyncope or syncope on exertion due to systemic and pulmonary venous congestion, and low cardiac output.
Physical Examination.
Clinical findings in children with hypertrophic cardiomyopathy can be subtle. Patients with no obstruction to outflow will have no murmur or faint systolic murmurs appreciated at the apex. Patients with latent obstruction have a grade I or II/VI systolic apical murmur that increases to grade III/VI with provocation (e.g., Valsalva maneuver, assuming the upright posture, systemic hypotension) Patients with obstruction at rest will have a grade III to IV/VI murmur that radiates to the left sternal border and the axilla, reflecting the obstruction to flow and mitral regurgitation. Right ventricular involvement in hypertrophic cardiomyopathy may be difficult to detect, especially in the infant or young child. In the older child a prominent A wave in the jugular venous pulse may be found.
Cardiac Evaluation.
Electrocardiography often shows abnormal findings in patients with hypertrophic cardiomyopathy, with the most common finding being that of left ventricular hypertrophy with or without a strain pattern. Signs of right ventricular hypertrophy may be appreciated in patients with prominent right ventricular or septal involvement. The QRS axis may be abnormal. Abnormal Q waves mimicking myocardial infarction are sometimes present. These reflect the increased forces of the hypertrophied septum.
Holter monitoring is used routinely to determine the presence of associated dysrhythmias and to assess the risk for malignant arrhythmias.
Chest radiography results are often normal. Radiographic findings can include left ventricular, left atrial, or right atrial enlargement. Additional findings may include pulmonary vascular congestion and a bulge along the left heart border, reflecting anterior extension of septal hypertrophy.
Transthoracic echocardiography is the most common modality used to establish the diagnosis of hypertrophic cardiomyopathy (see Fig. 72.3 ). The echocardiogram can determine the extent and location of the hypertrophy, the pressure gradient across the outflow tracts, and the degree of systolic and diastolic dysfunction. In addition, the severity and direction of mitral regurgitation can be estimated, and associated mitral valve abnormalities can be detected. Other noninvasive modalities such as cardiac MRI may be useful to identify patients at risk for sudden death.
Cardiac catheterization and invasive studies are rarely necessary but may be indicated in selected cases to evaluate the degree of ventricular outflow obstruction. Catheterization also is performed in a therapeutic intervention such as alcohol septal ablation or for the investigation of end-stage disease as part of the evaluation for cardiac transplantation. Invasive electrophysiologic studies have been used to provoke malignant arrhythmias and to guide antiarrhythmic therapy.
Restrictive Cardiomyopathy
Restrictive cardiomyopathy is a rare form of pediatric cardiomyopathy characterized by diastolic ventricular dysfunction in the face of relatively preserved systolic function and normal wall thickness. Markedly elevated diastolic filling pressures and low cardiac output are the hemodynamic hallmarks of the disease. Atrial enlargement is often present along with elevated atrial and ventricular end-diastolic pressures. The differential diagnosis of restrictive physiology includes secondary causes of diastolic dysfunction, such as constrictive pericarditis, myocarditis with associated myocardial fibrosis, coronary artery disease, and conditions increasing left ventricular mass such as left ventricular outflow tract obstruction or systemic hypertension. Systemic diseases or treatments can cause a restrictive cardiac physiology because of infiltration or injury. These include amyloid heart disease, scleroderma, doxorubicin (Adriamycin) or radiation, infiltrating neoplasms, and hemochromatosis.
Clinical Presentation.
The clinical presentation of the patient with restrictive cardiomyopathy is often subtle because of the indolent nature of diastolic dysfunction. In small children, low cardiac output is manifested by growth failure or exercise intolerance. Acute pulmonary edema is rare; however, evidence of chronic systemic or pulmonary venous congestion is common. Systemic venous hypertension leads to ascites, peripheral edema, and hepatomegaly. Resting tachypnea and dyspnea on exertion also are common; in addition, a dry cough may be described in older children. Syncope also may be a presenting sign and carries a higher risk of death than do other presenting signs and symptoms.
Arrhythmias are a common presenting sign of restrictive cardiomyopathy. Marked atrial dilation occurs in association with the elevated ventricular filling pressures and can lead to atrial flutter or fibrillation or supraventricular tachycardia. Complete heart block has been described in patients with desmin cardiomyopathy. Ventricular arrhythmias are less common but may occur, especially in the setting of depressed ventricular function. Atrial thrombi can form secondary to atrial dilation or atrial arrhythmias or both, and a thromboembolic event can be the presenting sign of restrictive cardiomyopathy.
Physical Examination.
Findings on physical examination include generalized growth failure, often with short stature, in conjunction with poor weight gain. Evidence of “right heart failure” is common, including hepatomegaly, jugular venous distention, and ascites. Borderline systemic hypotension can be present in advanced disease. The cardiac examination results can be unremarkable. An S 3 or S 4 may be audible; the P 2 may be accentuated in the setting of significant pulmonary hypertension. A murmur of tricuspid insufficiency may be present. A prominent apical impulse can be felt.
Cardiac Evaluation.
Electrocardiography is characterized by biatrial enlargement. Nonspecific ST-T wave changes may be noted. In the setting of pulmonary hypertension, right ventricular enlargement may be present. The electrocardiogram is essential to making the diagnosis of atrial arrhythmias or heart block associated with restrictive cardiomyopathy.
Echocardiography reveals prominent atrial enlargement with normal or even mildly reduced ventricular dimensions (see Fig. 72.3 ). The atrial four-chamber view is distinctive, and the appearance analogous to a “mushroom,” with the ventricle reassembling the stalk and the atrium, the cap. The hepatic veins and inferior vena cava are frequently quite dilated, reflecting elevated venous pressures. Pericardial effusion may be seen. Systolic ventricular function is normal or mildly reduced, but atrioventricular inflow patterns are frequently abnormal, reflecting diastolic dysfunction and elevated filling pressures.
Chest radiography findings can be normal, although careful inspection often reveals the presence of atrial enlargement. Pulmonary venous congestion may be present.
Holter monitoring is important in the clinical management to evaluate for the presence of tachyarrhythmias or bradycardia.
Cardiac MRI may help to distinguish constrictive pericarditis from restrictive cardiomyopathy. MRI can reliably evaluate the pericardial thickness and can lead to the diagnosis of constrictive pericarditis, allowing prompt surgical intervention.
Cardiac catheterization also may help in differentiating constrictive from restrictive processes. In restrictive cardiomyopathy, markedly elevated ventricular diastolic pressures are present, and in contrast to constrictive pericarditis, the end-diastolic pressure on the left is often higher than that on the right. In constrictive pericarditis, equalization of ventricular end-diastolic, atrial, and pulmonary artery end-diastolic pressures may be found. Maneuvers such as volume infusion may be necessary to bring out differences in ventricular filling pressures. Cardiac catheterization also may yield important information on the prognosis of patients with restrictive cardiomyopathy. Pulmonary vascular resistance may be elevated at the time of diagnosis, secondary to left atrial hypertension. Low cardiac output or high pulmonary vascular resistance or both are important predictors of poor outcome and herald the need for cardiac transplantation.
Other Cardiomyopathies
Left ventricular noncompaction cardiomyopathy is a recently recognized, rare form of cardiomyopathy. Diagnosis is based purely on structural features seen on imaging. Two-dimensional transthoracic echocardiogram is most commonly used for diagnosis. Characteristic echocardiographic findings of noncompaction are multiple, prominent myocardial trabeculations (minimum of four) and deep intertrabecular recesses communicating with the left ventricular cavity in the absence of any other cardiac lesions. Color Doppler imaging demonstrates blood flow through these deep recesses in continuity with the ventricular cavity. Its clinical manifestations are highly variable but in severe cases can be associated with left ventricular systolic impairment, cardiac arrhythmias, and systemic thromboembolism. Diastolic dysfunction has been linked to abnormal relaxation and restrictive filling due to excessive trabeculation. An association with some form of neuromuscular disorder is common. Treatment and prognosis differs depending on clinical signs and symptoms.
Arrhythmogenic right ventricular cardiomyopathy is a heritable heart-muscle disorder that causes progressive replacement of right ventricular myocardium by fibrofatty tissue. Arrhythmogenic right ventricular cardiomyopathy is infrequently identified in children. It is characterized clinically by ventricular arrhythmias of right ventricular origin that may lead to sudden death, mostly in young adults and athletes.
Genetic Basis for Pediatric Cardiomyopathy
Genetic syndromes, neuromuscular diseases, inborn errors of metabolism, mitochondrial disorders, and mutations in genes encoding structural components of the cardiomyocyte, including the sarcomere and cytoskeleton, have all been described in children with cardiomyopathies. There is significant overlap in the genetic mutations identified in phenotypically distinct cardiomyopathies. Mutations in genes controlling the sarcomere, beta-myosin heavy chain, and myosin-binding proteins have been described in pediatric dilated, hypertrophic, noncompaction and restrictive cardiomyopathies. Hypertrophic cardiomyopathy has largely been considered a disease of the sarcomere, with mutations in beta-myosin heavy chain ( MYH7 gene) and myosin binding protein C3 ( MYBPC3 gene) combining to explain approximately 80% of mutation-positive cases. Dilated cardiomyopathy is inherited in over 30% of cases, and patterns of inheritance can be autosomal dominant, X-linked, or recessive. Inborn errors of metabolism and genetic syndromic causes are responsible for a significant number of dilated cardiomyopathy cases in infancy. In adolescence, neuromuscular disorders, including Duchenne muscular dystrophy, account for a large number of cases. Noncompaction cardiomyopathy is also commonly identified in patients with genetic syndromic conditions or inborn errors of metabolism, such as Barth syndrome, an X-linked disorder with mitochondrial dysfunction and abnormal cardiolipin metabolism. Recent data indicate that mutations in sarcomeric genes were the most prevalent in patients with noncompaction. Restrictive cardiomyopathy is the least common cardiomyopathy and has been associated with mutations in desmin and sarcomere genes. A genetic abnormality for arrhythmogenic right ventricular cardiomyopathy has been demonstrated in nearly 50% of cases, with an autosomal dominant pattern of inheritance. Desmosomal protein abnormalities are often implicated in the pathogenesis of the disease. Electrocardiographic abnormalities are detected in up to 90% of arrhythmogenic right ventricular cardiomyopathy patients.
Outcomes of Heart Failure in Children With Cardiomyopathy
Children with dilated cardiomyopathy who present with heart failure have a high risk of death or heart transplantation within the first year after presentation, in which in-hospital mortality is approximately 11% and survival at 1 year after presentation ranges between 25% and 30%. The majority of events occur within 6 months of presentation. Long-term data demonstrate that improvement of ventricular function and stabilization of heart failure symptoms can occur in children with dilated cardiomyopathy and are more common in the infant and young child ( Fig. 72.4 ). Conditional 5-year survival in children with dilated cardiomyopathy who survive more than 1 year after presentation is excellent and ranges between 90% and 95%. Although heart failure is uncommon as the presenting symptom in hypertrophic cardiomyopathy, when it occurs, it is associated with ventricular systolic dysfunction and is associated with worse outcome. The prognosis of restrictive cardiomyopathy in children is grave, with reports of 34% to 53% 2-year transplant-free survival after presentation. Heart failure is also significant risk factor for death or transplant in patients with restrictive or noncompaction cardiomyopathy. In a study consisting of noncompaction cardiomyopathy in the pediatric population the mortality rate associated was 12.8%. Cardiac arrhythmias and ventricular dysfunction were associated with highest risk of death.
Congenital Heart Disease and Heart Failure
Survival in infants and children with congenital heart disease has vastly improved over the past 30 years, due to earlier detection of disease, better medical management, and improved results following cardiac surgical intervention. As they age, patients with complex congenital heart disease are at risk for heart failure. The etiology of heart failure in patients with congenital heart disease is multifactorial. Myocardial dysfunction secondary to ischemia, cyanosis, and fibrosis following cardiopulmonary bypass is an important component of heart failure in this population. Hemodynamic stresses from volume overload as a result of residual left-to-right shunt lesions or valvar insufficiency pressure overload resulting from valvular disease and other obstructive lesions such as coarctation of the aorta, pulmonary hypertension caused by chronic exposure to a left-to-right shunt, ventricular dysfunction or comorbidities such as obstructive sleep apnea, systemic arterial hypertension resulting from acquired renal disease or essential hypertension, and coronary artery disease related to congenital heart disease or the aging process can all play an important role in the development of heart failure.
The congenital heart disease lesions at highest risk for heart failure are shown in Fig. 72.5 . The single-ventricle population constitutes the largest proportion of congenital heart disease patients who develop heart failure. Heart failure can also be the consequence of failure of the subpulmonary ventricle, as is found in patients with tetralogy of Fallot, or as a result of failure of a systemic right ventricle, as is present following the Mustard or Senning procedure or in corrected transposition of the great arteries. HFpEF can occur because of diastolic dysfunction in complex left ventricular outflow tract obstruction (Shone’s complex).
In Fontan patients, atrial arrhythmias and manifestations of low cardiac output such as progressive exercise intolerance, cyanosis, or poor somatic growth are common. Heart failure in the Fontan patient can occur as a result of poor flow through the Fontan circuit in the setting of normal ventricular function and is known colloquially as the failing Fontan. The heart failure syndrome associated with the failing Fontan is characterized by the effects of high venous pressures and includes ascites, protein-losing enteropathy, plastic bronchitis, and chronic effusions. In this population heart failure symptoms are more insidious, with a gradual deterioration of exercise performance and a high incidence of growth failure.
Outcomes of Heart Failure in Congenital Heart Disease Patients
Heart failure is a significant risk factor for late mortality and morbidity in the congenital heart disease population. It is the most common cause of hospitalization in adult patients with congenital heart disease, and mortality after the onset of heart failure is high. In a large study of adults admitted to the hospital with heart failure and congenital heart disease, 2-year mortality was 35%. Factors associated with worse outcome in children with congenital heart disease and heart failure include the presence of complex heart disease, arrhythmia, older age, shorter duration of heart failure and cyanosis. In the Fontan population, increased morbidity at the time of the Fontan procedure and the presence of AV valve regurgitation predict increased risk of death and/or transplantation late after the Fontan.
Comorbidities in Pediatric Heart Failure
Arrhythmias
Heart failure can be exacerbated by the presence of tachyarrhythmias (atrial or ventricular) or bradyarrhythmias (junctional rhythm or heart block) ( Table 72.1 ). Arrhythmias can arise in response to hemodynamic stress such as elevated intracardiac pressure or volume overload, as the result of an underlying cardiac injury such as ischemia or fibrosis, or can be due to a genetic mutation that disrupts the ion channels controlling electrical activation of the myocardium.
| Predisposing Factors in Heart Failure | ECG Findings | Acute Treatment | Special Considerations in Heart Failure | |
|---|---|---|---|---|
| Supraventricular Tachyarrhythmias | ||||
| Atrial flutter/ intraatrial reentry tachycardia | Atrial scar, prior surgical incisions (repaired CHD) Atrial enlargement Sinus node dysfunction (sick sinus syndrome) |
|
| Class I antiarrhythmic agents are generally avoided in patients with ventricular dysfunction Consider pace-termination if pacemaker in situ |
| Atrial fibrillation (AF) | Left atrial pressure/volume overload; mitral valve disease |
|
| Class I antiarrhythmic agents are generally avoided in patients with ventricular dysfunction |
| Ventricular Tachyarrhythmias | ||||
| Premature ventricular contractions (PVCs) | Sympathetic activation Electrolyte abnormalities |
|
| Rarely, high PVC burden can cause or worsen LV dysfunction—consider Rx or ablation |
| Nonsustained ventricular tachycardia (NSVT) | Ventricular scar; prior surgical incisions (repaired CHD) | ≥3 consecutive PVCs, duration <30 s |
| Possible predictor of malignant ventricular arrhythmias, depending on underlying disease—consider EPS ± ICD |
| Ventricular tachycardia (VT) | Ventricular scar; prior surgical incisions (repaired CHD) |
|
| ICD placement Polymorphic VT in the setting of prolonged QTc (torsades de pointes): Rx with magnesium, lidocaine, isoproterenol; consider overdrive pacing |
| Ventricular fibrillation (VF) | Ischemia; electrolyte abnormalities; scar |
|
| ICD placement |
| Bradyarrhythmias | ||||
| Junctional bradycardia | Sinus node dysfunction (Fontan, atrial switch) |
|
| Bradycardia and lack of AV synchrony can contribute to heart failure |
| Complete heart block | Post cardiac surgery; ischemia; genetic disease |
|
| Bradycardia and lack of AV synchrony can contribute to heart failure Pacemaker-induced ventricular dysfunction due to dyssynchronous ventricular pacing |
Tachyarrhythmias impair ventricular filling, leading to fluid retention and poor perfusion and in some cases sudden death. In cardiomyopathy patients, genetic mutations in arrhythmogenic genes such as SCN5A and LMNA have been described in patients with dilated cardiomyopathy and arrhythmias. In congenital heart patients, atrial flutter and intraatrial reentrant tachycardias are common, particularly in patients with residual atrioventricular valve disease or the Fontan procedure. Ventricular arrhythmias are relatively uncommon in patients with dilated cardiomyopathy, except in those with a history of cardiac ischemia, but have been described in up to 25% of patients with heart failure due to noncompaction or restrictive cardiomyopathy.
Bradyarrhythmias can worsen heart failure by decreasing cardiac output due to a nonphysiologic slow rate or loss of atrioventricular synchrony. Junctional rhythm is a particular concern in the Fontan patient because of the increased dependence of cardiac output on atrioventricular synchrony. Complete heart block has been described in cardiomyopathy patients with mutations in the desmin or LMNA gene and is not uncommon in patients following repair of congenital heart disease. Mechanical dyssynchrony has been described with right ventricular pacing in complete heart block and is a risk factor for the development of ventricular dysfunction and heart failure in both cardiomyopathy and congenital heart disease patients.
Pulmonary Hypertension
Elevated pulmonary vascular resistance is an important comorbidity in patients with end-stage heart failure due to the risk of right heart failure and increased morbidity after heart transplant. Patients with restrictive cardiomyopathy and congenital heart disease are at risk for the development of pulmonary vascular disease. In patients with the Fontan circulation, pulmonary vascular disease can be contributing factor to heart failure because pulmonary blood flow is highly dependent on the presence of low pulmonary artery pressures.
Renal
The cardiorenal syndrome has been described for centuries as an important component of heart failure. The complex interaction between the heart and kidney has been identified as a risk factor for worse outcome and as a potential therapeutic target. Renal dysfunction is common in children with decompensated heart failure and has been associated with a higher hazard ratio of death and the need for mechanical circulatory support. Approximately 15% of children listed for heart transplant have evidence of worsening renal function and the incidence of renal dysfunction in children with end-stage heart failure undergoing ventricular assist device placement has been reported to be as high as 55%. Renal dysfunction is a risk factor for death on the heart transplant waiting list and death early after transplantation. Hyponatremia, which may be due to an increase in free water retention or disruption of the sodium-potassium exchange in the kidney, has been associated with worse outcome in pediatric heart failure patients.
Hepatic
Chronically elevated central venous pressures can lead to hepatic fibrosis and cirrhosis in patients with right heart failure due to congenital heart disease, restrictive cardiomyopathy, or in patients with the Fontan circulation. Fibrosis has been documented by liver histology early after the Fontan procedure, with evidence of cirrhosis increasing over time. Cirrhosis is a risk factor for hepatocellular carcinoma and is an important consideration when assessing candidacy for heart transplantation.
Cyanosis
Significant cyanosis can occur in patients with unrepaired or palliated congenital heart disease and a right-to-left shunt. Cyanosis impairs oxygen delivery and exacerbates the symptoms of fatigue and exercise intolerance. In patients with the Fontan procedure, oxygen saturation usually falls between 5% and 8% with maximal exercise.
Respiratory
Respiratory failure in children with cardiomyopathy and heart failure is largely secondary to the effects of pulmonary edema. Children with congenital heart disease often have underlying restrictive lung disease that contributes to poor exercise intolerance in patients with heart failure. Scoliosis is also more common in congenital heart disease patients compared with normal children and may impair exercise performance and lung function.
Infection
Congenital heart disease patients with prosthetic valve or conduit material or residual left-to-right shunts are at risk for endocarditis. Endocarditis can cause or exacerbate heart failure symptoms. Consideration should always be given to the possibility of endocarditis in a patient with congenital heart disease presenting with new heart failure symptoms.
Anemia
In adults with heart failure, anemia and iron deficiency has been identified as a common comorbidity that impacts outcome. Anemia is common in children with heart failure and in adults with complex congenital heart disease. There are no data in children correlating anemia with outcomes in heart failure.
Growth
Growth failure is common in children with heart failure due to increased metabolic demand and decreased intake. Obesity occurs less commonly in children with heart failure, with 8% of children listed for heart transplantation classified as overweight. In patients with the Fontan physiology, obesity has been associated with heart failure and worse outcome. At the time of listing for heart transplant between 23% and 43% of children are underweight. Underweight and overweight have been identified as risk factors for waiting list mortality in children with cardiomyopathy. In children less than 2 years of age, moderate to severe wasting was an independent risk factor for death on the transplant waiting list.
Psychosocial Stress and Functional Status
Heart failure has a negative effect on quality of life and functional status in children. Decreased health-related quality of life in both the psychosocial and physical domains on the Child Health Questionnaire have been described in children with dilated cardiomyopathy, with young age and less ventricular dilation associated with better functional status. Worse health-related quality of life has been associated with worse clinical outcomes in children with dilated cardiomyopathy. Measures of parental well-being, including emotional state, have also been associated with worse outcome in children with dilated cardiomyopathy.
In adolescents with a Fontan circulation, the Pediatric Quality of Life Inventory demonstrated significant physical impairment in 45% of patients and significant psychosocial impairment in 30% of patients, which worsened over time. Impairment in the physical and psychosocial domain was associated with worse exercise performance and the outcomes of death or transplantation.
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