Cardiac physiology in a normal child is an elegant balance requiring many components to work on an interactive basis. In children with congenital or acquired heart disease, some of those parts do not function properly from the start; others develop problems with time or under duress. This chapter begins with a discussion of the syndrome of heart failure. The pathophysiology of heart failure is reviewed, followed by the diagnosis and management of left heart failure (including heart transplantation). This is followed by a more detailed discussion of the primary conditions that can lead to heart failure. We explore the diagnosis and management of various forms of cardiomyopathy, a set of intrinsic cardiac muscle disorders with often overlapping phenotypes. Finally, we present the diagnosis and management of right heart failure as a manifestation of pulmonary hypertension.

Definition and Pathophysiology

Heart failure is a clinical syndrome that develops as a final common pathway of diverse cardiac injuries. Symptoms result from an impairment in the heart’s ability to adequately relax and/or contract. Historically, heart failure was defined as a pure mechanical or hemodynamic condition that resulted from an inability of the heart to provide enough cardiac output to meet the metabolic demands of the body. Therapy was directed at altering these hemodynamic derangements by increasing cardiac output, typically with medications that increased heart rate and contractility, and by decreasing metabolic demands. However, there has been a paradigm shift in the approach to heart failure in recent years. We now better understand the compensatory neurohormonal mechanisms and complex molecular signaling cascades that are activated in the setting of decreased cardiac output. These mechanisms cause adverse remodeling that perpetuates the cycle of heart failure.

Patients with heart failure have traditionally been categorized by their functional capabilities, using either the New York Heart Association (NYHA) or Ross classification schemes (Table 13-1). In recent years, the American College of Cardiology and American Heart Association have advocated the additional use of a staging system for heart failure that emphasizes the structural condition of the heart as well as the prevention, evolution, and progression of heart failure (Figure 13-1).1 It is meant to complement the NYHA classification system, which has been used to describe functional limitations rather than structural abnormalities. Stage A and B patients might best be thought of as “pre–heart failure” patients, in that they are at risk for heart failure but have not yet developed symptoms. Whereas in the following section, we will primarily address the assessment and management of stage C and D heart failure in children, the subsequent section will discuss specific cardiomyopathies, which may present at any stage of the heart failure spectrum. Referral to a cardiologist for evaluation and surveillance of a child with any stage of heart failure is recommended.

The term “heart failure” has been used broadly to include volume overloaded conditions due to left-to-right shunt lesions with otherwise normal myocardial function. This section, however, will focus specifically on heart failure as the syndrome that occurs as a result of myocardial dysfunction and injury. Here, we discuss the presentation and management of the failing systemic (ie, left) ventricle; later in this chapter, we discuss the approach to the failing pulmonary (ie, right) ventricle in the context of pulmonary hypertension.

Left Heart Failure

Clinical Presentation

In the setting of a biventricular circulation, left heart failure can generally be described in 1 of 3 ways: acute decompensation, chronic compensation, and acute-on-chronic decompensation. It is essential for the general pediatrician or emergency room physician to recognize early that a child may be at risk for decompensated heart failure and, subsequently, to assess, categorize, and initiate treatment for this condition when present.

Symptoms of left heart failure in children may be subtle and nonspecific and often vary with the age at presentation. Constitutional symptoms include decreased activity level, decreased appetite, and increased fussiness. Failure to thrive by weight criteria may be masked by fluid retention. Infants are classically diaphoretic and short of breath with feeding, whereas older children may display dyspnea on exertion or easy fatigability. Gastrointestinal symptoms due to decreased intestinal perfusion are common in left heart failure at any age, manifesting as decreased appetite, poor tolerance of feeds, abdominal pain, or nausea and vomiting. Classic “cardiac” symptoms such as chest pain and palpitations occur but are less common in children than in adults with heart failure.

Although one should always look for signs of congestion of both the right- and left-sided circulations, these are also less commonly seen in children with heart failure as compared with adults. Such signs include facial swelling, elevated jugular venous distension, hepatomegaly, ascites, dependent edema, and pulmonary rales. Assessment of vital signs may reveal tachypnea, tachycardia, and hypotension. On cardiac examination, the point of maximal impulse may be laterally displaced and prolonged, and S3 and S4 gallops may be present. One should also assess for diminished peripheral pulses and delayed capillary refill.

Diagnostic Testing

With respect to ancillary testing, a chest x-ray often shows cardiomegaly and pulmonary congestion. An electrocardiogram (ECG) may reveal an underlying or secondary arrhythmia or show abnormal ventricular voltages and evidence of ischemia including ST-T wave changes. Laboratory studies that can indicate secondary end-organ hypoperfusion include creatinine and liver function tests. B-type natriuretic peptide (BNP), a hormone released primarily by cardiac ventricular cells in response to elevated filling pressures, can be measured in the blood as well. Although BNP and cardiac enzymes, including troponin I, troponin T, and CK-MB, may be helpful in certain circumstances, their full utility in pediatric heart failure is still under evaluation.

Suspicion for decompensated left heart failure should prompt early cardiology consultation for further evaluation. Such testing may include echocardiography, to assess ventricular function and anatomy, and cardiac catheterization, for information including hemodynamics, coronary anatomy, and endomyocardial biopsy.

Differential Diagnosis

Early differentiation of acute decompensated heart failure from common conditions such as sepsis and an acute abdomen is of paramount importance. Whereas the initial resuscitation of a child with sepsis often includes large intravenous fluid boluses and peripheral vasoconstrictors, this approach could potentially harm a child in cardiogenic shock. If a hypotensive or tachycardic child has a known history of heart disease, or if he or she does not mount the expected response to fluid boluses, decompensated heart failure should be suspected. There are many potential underlying conditions that can lead to left heart failure; see Tables 13-2, 13-3, and 13-4 for etiologies of the most common cardiomyopathies.

Treatment

Most treatments for an acute decompensation are aimed at the singular goal of supporting cardiac output. Depending on the child’s volume status, diuresis may be more helpful than fluid resuscitation by shifting the patient’s status on the Frank-Starling curve. When vasoactive medications are needed, our center often uses a combination of milrinone with or without dopamine. Choice of these temporizing agents may vary widely between centers.

Chronic heart failure management, in contrast, is primarily aimed at interrupting the underlying pathophysiologic mechanisms of myocyte dysfunction. The pillars of heart failure management are angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and aldosterone antagonists. Each of these agents attacks a different arm of the sympathetic nervous system or renin-angiotensin-aldosterone axis, whose maladaptive compensatory drive would otherwise promote myocyte hypertrophy and fibrosis in the heart failure patient. Stabilization and improvement of ventricular function by this process of reverse remodeling, coupled with improved loading conditions, can often be achieved with the help of these medications.

In addition to these agents of neurohormonal blockade, chronic heart failure management may also include agents such as thiazides and loop diuretics to achieve a euvolemic state. Digoxin, which was once used widely in the field, has now been largely relegated to use at low doses in symptomatic (rather than asymptomatic) left ventricular dysfunction. The evidence for use of all of these agents has been largely extrapolated from adult heart failure studies; specific comments on the pediatric data behind their use are available in the International Society of Heart and Lung Transplant Practice Guidelines for Management of Heart Failure in Children.2 A summary of commonly used heart failure medications can be found in Table 13-5.

Cardiac resynchronization therapy is used frequently in adult patients with heart failure whose QRS duration by ECG and ejection fraction by echocardiogram meet certain criteria. Its utility in pediatric patients is being increasingly explored. To use cardiac resynchronization therapy, an electrophysiologist implants a pacemaker with a separate lead for each ventricle. The signal to pace each ventricle is timed to maximize cardiac output using ECG and/or echocardiographic guidance.

Mechanical Circulatory Support

When medical interventions, including inotropic support, are unsuccessful at bringing a child back to a compensated state, mechanical circulatory support may be indicated. For example, extracorporeal membrane oxygenation may be used to temporarily support the circulation as well as the lungs. Due to many issues including the size of the circuit, extracorporeal membrane oxygenation is not a viable long-term solution for cardiac support.

An increasing number of pediatric centers are using ventricular assist devices (VADs) for children with stage D heart failure that is refractory to maximal medical therapy. These devices are placed by a cardiothoracic surgeon in the operating room with the goal of unloading a ventricle and providing reliable cardiac output. A surgically implanted cannula typically pulls blood from the apex of the ventricle into a mechanical pump, which then delivers blood back to the body via a second cannula in the aorta. A similar device can be placed on the right side of the heart if needed, although support of the left heart alone is often adequate. The pump is a portable pneumatic device that is connected to a larger driver. All VADs currently used in the pediatric population are paracorporeal; that is, they sit outside of the body, in close proximity to the patient. The recent development of VADs of various sizes has expanded their use to patients as small as a full-term neonate. Several pediatric centers have also started implanting continuous flow VADs in select patients; largely due to their durability and portability, these are now commonly used in adult patients with heart failure.

The major advantage of VADs is the functionality that they give a patient with end-stage heart. A child can be awake, enterally fed, and participate in an active cardiac rehabilitation program with a properly functioning VAD (Figure 13-2). The most common complications are related to bleeding, thrombosis, and infection. Although many adult patients with heart failure have a VAD placed indefinitely (“destination therapy”) or with the explicit goal of myocardial recovery that allows explantation (“bridge to recovery”), the majority of pediatric patients who have a VAD will only have their VAD explanted at the time of heart transplantation (“bridge to transplant”).

Transplantation

Heart transplantation may be an option for the child who has progressive heart failure that is unresponsive to maximal medical therapy.3 The evaluation of a child for transplantation involves a multidisciplinary team that considers relative morbidity and mortality with and without transplantation, comorbid conditions, and psychosocial support for the child and family. Donor heart allocation in the United States is managed by the United Network for Organ Sharing. A computer-based algorithm takes blood type, waiting time, category of need, size, and distance between the donor and recipient into account when prioritizing who gets an offer for a potential donor heart. Waiting times vary widely for individual patients, centers, and regions. For those who wait for many months, meticulous heart failure management is of paramount importance.

Prognosis

Children with heart failure can survive into adulthood with a good quality of life. Most of these patients, however, should be seen regularly, and for life, by both their primary care physician and a cardiologist. Those who undergo transplantation can expect good outcomes. In 2010, median survival for pediatric heart transplantation recipients was more than 14 years.4 The majority of transplantation recipients report excellent functional status with respect to physical, cognitive, and psychological well-being.5,6

The general pediatrician who sees a patient after heart transplantation should understand that the child has traded the morbidities of heart failure for another set of morbidities. The immunosuppressive medications that work to prevent a recipient from rejecting his or her donor organ add the general risks of infection and malignancy, in addition to adverse side effects specific to each medication (Table 13-6). The following tips may help the primary care physician when caring for posttransplantation patients: (1) call early with concerns about infection or possible rejection; (2) do not administer live virus vaccines without prior discussion with a transplantation specialist; and (3) use care when prescribing other medications, including all antibiotics, because drug–drug interactions may affect the metabolism and effectiveness of immunosuppressive medications. These caveats aside, the care team should always keep in mind that the overall goal of heart transplantation is to give the child as good a quality of life as possible.

Definition and Epidemiology

Cardiomyopathies are primary heart muscle diseases characterized by abnormally enlarged, thickened, or stiffened myocardium that adversely affect systolic function, diastolic function, or both.7 Some children with cardiomyopathies maintain lifelong stability. However, the abnormal chambers, walls, or contractility of the affected heart can lead to a progressive or acute loss of effective pump function, serve as substrate for potential arrhythmias, degenerate to congestive heart failure with the potential need for heart transplantation, or result in sudden cardiac death. This section will discuss primary cardiac muscle disorders as well as those that may occur secondary to certain systemic or toxic exposures. It is worth noting that cardiac dysfunction in children can also result from coronary artery disease, hypertension, valve disease, pulmonary vascular disease, or other structural congenital heart disease.

Cardiomyopathy is the leading reason for heart transplantations and sudden deaths in children, with 100,000 children affected worldwide. The majority of diagnoses are made in infants under the age of 12 months, followed by children 12 to 18 years of age.8 The 4 main categories of cardiomyopathy representing primary disease of the heart muscle include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). A more recently recognized cardiomyopathy is left ventricular noncompaction (LVNC), which may or may not be associated with other forms of congenital heart disease and other cardiomyopathy phenotypes. There is accumulating evidence that most primary cardiomyopathies have a genetic basis that may occur sporadically or be inherited in families.9