Cardiomyopathies, inflammatory diseases of the heart (pericarditis, myocarditis), and Kawasaki disease commonly require intensive care and monitoring. This article focuses on the diagnosis and management of these diseases individually.
Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and most of the cases are idiopathic. Genetic mutations have been found in 20% to 50% of the idiopathic cases;1 however, multiple etiologies have been implicated including viral infections, medications, toxins, thyroid disease, arrhythmias, and muscular dystrophies2(Table 1). A recent cohort of pediatric patients revealed the most common identifiable causes of dilated cardiomyopathy were myocarditis and neuromuscular disease.3
Identifiable Causes of Dilated Cardiomyopathy
Clinical presentation. Presentation of dilated cardiomyopathy is usually gradual with signs and symptoms consistent with those of congestive heart failure and low cardiac output including dyspnea, poor capillary refill, and infants who feed poorly. Physical examination reveals tachypnea, tachycardia, hepatomegaly, peripheral edema, and crackles or wheezing on lung auscultation. Findings on cardiac examination can include an S3 gallop rhythm and a holosystolic murmur consistent with functional mitral or tricuspid regurgitation. In severe cases, children may present in decompensated cardiogenic shock with tachycardia, hypotension, poor distal perfusion, and cold extremities.
Evaluation. Cardiomegaly and pulmonary venous congestion seen on chest radiography can sometimes be the first indication of cardiac disease. Electrocardiogram (ECG) generally shows sinus tachycardia and can show increased left ventricular forces and ST-T wave abnormalities. Patients should be evaluated for arrhythmias as these can be an insidious cause of the myopathy. Echocardiogram is the test of choice for diagnosis and shows enlarged cardiac chambers with decreased systolic function (Figure 1). Given the potential for targeted therapies, an investigation for the underlying cause of DCM should be aimed at those etiologies that have treatment available. Evaluation for structural heart disease, infection, systemic inflammatory conditions, autoimmunity, and endocrinopathies should be undertaken. In rare cases, muscle or endomyocardial biopsies may be warranted. Cardiac enzymes including troponin may be helpful in assessing the current degree of dysfunction, and B-type natriuretic peptide (BNP) can be used to aid in diagnosis and monitor response to therapy.
A four-chamber echocardiogram view of the heart showing a dilated left ventricle.
Diagnosis. The diagnosis of DCM is made when there is echocardiographic evidence of left ventricular dilation, left atrial enlargement, and decreased systolic function. Cardiac magnetic resonance imaging (MRI) is becoming increasingly popular to assess for acute changes in the myocardium and for quantifying the degree of cardiac dysfunction.
Management. Management of DCM targets restoring normal cardiac output and end-organ perfusion. Pediatric intensive care unit (PICU) management often includes diuretics, cardiac inotropes, afterload reducing agents, and in severe cases may include mechanical ventilation and mechanical cardiac support. Once patients have stabilized, diagnostic studies can be performed and if an underlying treatable cause is identified, therapy can be initiated.4 Goals of managing chronic heart failure are aimed at modulating neurohormonal responses and slowing the progression of myocardial injury. Angiotension-converting enzyme inhibitors (ACE-I), aldosterone antagonists, and beta-blockers are indicated for long-term management.5 Select patients may require anticoagulation or antiplatelet therapy to avoid potential thromboembolic complications of low cardiac output. Close longitudinal observation is required to monitor for progression of the cardiac dysfunction, which can lead to a need for mechanical ventricular assist devices and heart transplantation.
Outcomes. The prognosis is relatively poor for pediatric DCM; a study reports a cardiac event-free survival of 65% to 72% at 1 year and 50% to 63% at 5 years.3
Hypertrophic cardiomyopathy (HCM) is caused by several mutations and is characterized by asymmetric hypertrophy of the left ventricle, without dilation, in the absence of secondary causes.6 The myocardium shows poorly organized myocytes and a family history is found in nearly one-half of the cases. HCM is present in approximately 1 in 500 of the general population and is the most common cause of sudden death in adolescents, including competitive athletes.7
Clinical presentation. Patients have a variety of clinical signs and symptoms along a spectrum ranging from a new systolic ejection murmur on one end, to sudden cardiac death on the other. Symptoms generally do not occur until early adulthood with the most common symptoms being exertional limitation, chest pain, and dyspnea. Physical examination reveals a systolic ejection murmur related to subaortic stenosis. Malignant arrhythmias may result in syncope or pre-syncope and raise the risk for sudden cardiac death.
Evaluation. Evaluation should include an ECG, which is abnormal in approximately 95% of patients with HCM.8 Significant findings include prominent Q-waves, atrial enlargement, left axis deviation, and T-wave abnormalities. Echocardiography demonstrates increased left ventricular wall thickness and asymmetric septal hypertrophy. Cardiac MRI is useful in those patients in whom echocardiogram is not diagnostic.
Diagnosis. The diagnosis of HCM is made when there is an increased left ventricular wall thickness greater than or equal to 15 mm in the absence of secondary to causes such as aortic stenosis, athlete's heart, or systemic arterial hypertension. Left ventricular diastolic dysfunction is related to the extent of hypertrophic myocardium.
Management. Patients with HCM may develop hemodynamic instability due to left-ventricular outflow tract obstruction from volume depletion or when cardiac inotropy and chronotropy increase the outflow gradient. Medical management may include exercise restriction and cardiac medications. Beta-blockers are used for patients with severe outflow tract obstruction to reduce the left ventricular outflow gradient and minimize myocardial oxygen demand, allowing for slower heart rate and enhanced cardiac filling during diastole. Calcium-channel blockers improve diastolic relaxation and reduce the outflow gradient. Diuretics can reduce ventricular filling pressures and must be used cautiously due to risk of underfilling and increasing the outflow gradient. For refractory symptoms, surgical myectomy may be indicated. Ventricular arrhythmias are the underlying etiology for sudden cardiac death, and antiarrhythmics or implantable cardiac defibrillators are indicated as the primary prevention for people who are high risk.9 First-degree family members should be screened for the presence of HCM.
The least common subtype of cardiomyopathy, restrictive cardiomyopathy, is characterized by normal ventricular chamber size and function, but with diastolic dysfunction due to decreased ventricular compliance and filling.10 Symptoms result from severe diastolic dysfunction and elevated filling pressures.
Clinical presentation. Patients will present with symptoms of left and right sided cardiac failure including tachypnea, shortness of breath, peripheral edema, growth failure, and exercise intolerance. Examination may show significant jugular venous distention that becomes more prominent in inspiration (Kussmaul's sign), an S3 or S4 gallop, hepatosplenomegaly, ascites, and a prominent P2 (secondary to pulmonary hypertension).
Evaluation. ECG usually shows biatrial enlargement and ST-segment abnormalities, whereas chest X-ray generally shows cardiomegaly and pulmonary venous congestion. Echocardiography generally shows normal-sized ventricular cavities and wall thickness with enlarged right and left atria. Doppler evaluation of the atrioventricular valve inflow pattern can assist in the diagnosis. Cardiac MRI may also show fibrosis, necrosis, or inflammation, which can be consistent with an underlying cause.11 Serum BNP levels are often significantly elevated.
Diagnosis. Cardiac catheterization will confirm restrictive cardiomyopathy and elevated left ventricle end-diastolic pressure, as well as possible pulmonary hypertension. For patients with an inconclusive noninvasive diagnostic evaluation, an endomyocardial biopsy can be performed at the time of catheterization. Biopsy generally shows fibrosis, hypertrophy, and collagen deposition.12
Management. As this specific pathology is a syndrome of diastolic heart failure, the treatment options are limited. Congestive heart failure symptoms can be managed with diuretics, beta-blockers, and ACE-I. However, patients who are preload dependent and who have excessive diuresis can lead to low cardiac output. Beta-blockers and calcium channel blockers may improve ventricular relaxation and filling. Anticoagulation may be warranted if atrial dilation is severe to decrease potential for thrombus formation. Despite optimal medical management, long-term prognosis remains poor, and those with significant heart failure symptoms are referred for heart transplantation.
Inflammatory Diseases of the Heart and Pericardium
Acute pericarditis is the most common disorder involving the pericardium and although the exact etiology is usually unknown, viral etiologies are often assumed to be the cause in developed countries. Additional etiologies include bacterial, fungal, systemic diseases, tuberculous, drugs, or toxins.
Clinical presentation. Typical symptoms include fever and chest pain. The chest pain is pleuritic in nature and is improved by learning forward. On physical examination, there can be a friction rub auscultated throughout the cardiac cycle; however, this may not be present in patients with large pericardial effusions. Patients with large pericardial effusions can present with symptoms of cardiac tamponade including poor peripheral perfusion, jugular venous distension, and hepatomegaly.
Evaluation. ECG is the most helpful test in the diagnosis of acute pericarditis and is the most common cause of ST elevation in children (Figure 2). ECG changes are usually classified into four stages: Stage 1: ST-segment elevation appears in almost all leads, especially lateral and inferior leads with PR-interval depression; Stage 2: ST- and PR-segment returns to normal baseline; Stage 3: Diffuse T-wave inversion; and Stage 4: ECG returns to normal usually 2 to 4 weeks after onset of disease below.13
Electrocardiogram characteristic of acute pericarditis with diffuse ST segment elevation.
Large pericardial effusions often result in low-voltage QRS and QRS alternans.13 QRS alternans is defined as periodic change in QRS amplitude. Chest radiography is useful and can be used to quickly assess for an enlarged cardiac silhouette and other noncardiac etiologies. Echocardiography should be performed in all cases to assess for pericardial effusions. Other diagnostic testing for etiology is usually not indicated. In severe and rapid development of pericardial effusions, cardiac tamponade physiology may occur, which is a life-threatening emergency requiring immediate evacuation of the pericardial fluid.
Diagnosis. Acute pericarditis is diagnosed based upon the presence of two of the following: chest pain that is consistent with pericarditis, pericardial friction rub, suggestive changes on ECG, and new or worsening pericardial effusion.14
Management. If there is a known etiology of the acute pericarditis, therapy should be directed to the underlying cause. Nonsteroidal anti-inflammatory drug (NSAID) therapy is generally considered first line and serves to reduce inflammation and relieve pain.14 Colchicine can be used alone or conjunction with NSAIDs and can reduce symptoms and decrease the rate of recurrent pericarditis.15 Steroid therapy is generally only considered for treatment of an underlying systemic inflammatory disease, or for cases that are refractory to NSAIDs and colchicine, or where NSAID use would be contraindicated.15
Myocarditis results from the inflammation of the heart muscle, which can lead to heart failure. The cause of myocarditis includes infection, hypersensitivity reaction, toxin mediated, and systemic inflammatory disease.16 In North America, infectious viral illness is the most common etiology in children, with the causative agents being enterovirus, adenovirus, parvovirus B19, human herpesvirus-6, hepatitis C, Epstein-Barr virus, and cytomegalovirus below.17 There has been an evolution over the past 20 years from enteroviruses and adenoviruses to parvovirus and human herpesvirus-6.18
Clinical presentation. Patients have variable clinical presentations including cardiogenic shock, arrhythmias, chest pain, respiratory distress, and even sudden death.18 Physical examination may show signs of cardiac dysfunction including tachypnea, intercostal retractions, rales, gallop, functional mitral, or tricuspid regurgitation. Fulminant myocarditis results in signs of low cardiac output syndrome including poor perfusion, hypotension, weak pulses, peripheral edema, hepatomegaly, and altered mental status.18
Evaluation. Initial evaluation should be targeted to determine the extent of cardiac involvement. ECG is usually abnormal, although findings are neither sensitive nor specific.19 Laboratory studies of cardiac biomarkers including troponin and BNP levels are usually elevated in the setting of acute myocarditis.20,21 Chest radiograph is abnormal in about half of cases revealing cardiomegaly, pleural effusions, and pulmonary vascular congestion.22 An echocardiogram typically shows left ventricular systolic dysfunction. Other possible findings include wall motion abnormalities and mitral regurgitation.18 It is important to rule out intrinsic cardiac disease including anomalous left coronary artery from the pulmonary artery or other acquired heart disease. Cardiac MRI is most helpful for diagnosis of myocarditis due to its ability to accurately assess cardiac function, chamber size, wall thickness, and to localize tissue injury, edema, and fibrosis.18
Diagnosis. Histological diagnosis of myocardial inflammation is the gold standard for the definitive diagnosis of myocarditis and can be obtained during cardiac catheterization with endomyocardial biopsy.18 However, less invasive diagnostic classification can be made based on biomarkers, ECG findings, and abnormal cardiac function on echocardiogram or cardiac MRI.23
Management. Initial management is mainly supportive and should focus on stabilization of the patient including cautious fluid resuscitation or diuresis depending on the volume status of the patient. In mild cases, afterload reduction with ACE-I is initiated. In some cases, inotropic support with milrinone, dopamine, or dobutamine may be required. In severe cases, mechanical ventilation and mechanical circulatory support including extracorporeal membrane oxygenation or ventricular assist devices may be needed as a bridge to either cardiac recovery or cardiac transplantation. Directed therapy with intravenous immunoglobulin (IVIG), steroids, and other immunomodulators is controversial and there have been no conclusive data that any of the immune therapies are efficacious in the treatment of acute myocarditis.16,24,25 Despite the lack of conclusive data, IVIG is frequently administered as first-line therapy below.26
Outcomes. In the United States, the overall survival rate for children with acute fulminant myocarditis is greater than that seen in adults and is reported to be as high as 90%.27 Patients with acute fulminant myocarditis often require substantial hemodynamic support acutely in the intensive care unit, including inotropic agents, mechanical ventilation, and possibly temporary mechanical circulatory support. However, most patients appear to have full recovery with a small percentage requiring cardiac transplantation.27
Kawasaki disease is a common vasculitis of childhood that can cause coronary artery aneurysms, carditis, heart failure, and endocarditis.28 The pathogenesis remains unclear; however, some suggest the clinical and epidemiological features of Kawasaki are best explained by infection with an as-yet-unidentified ubiquitous agent, likely a virus entering via the respiratory route. A genetic basis for susceptibility has also been suggested.29 In the US, Kawasaki disease is estimated to have an annual incidence of 20 per 100,000 children with the number of cases peaking in winter and spring.30
Clinical presentation. Patient's generally present between ages 6 months and 5 years with unexplained prolonged fever along with a constellation of symptoms.31 Classic Kawasaki disease is diagnosed based on the presence of a fever lasting 5 or more days, accompanied by a constellation of findings shown in Table 2.32 Hemodynamic instability during the acute phase of Kawasaki disease is uncommon; however, an entity designated as Kawasaki disease shock syndrome was described in 2009.33 The exact cause of severe hypotension is unknown; however, it is most likely multifactorial, including vasculitis with ongoing capillary leak, myocardial dysfunction, and cytokine dysregulation. Patients with Kawasaki disease with hypotension might require hemodynamic support in the PICU and are at high risk for their disease to be refractory to first-line therapy.
Diagnostic Criteria for Classic Kawasaki Disease
Evaluation. Although laboratory studies are not required for the diagnosis of Kawasaki disease, they can be used to support the diagnosis of Kawasaki disease and some laboratory values are used in the diagnosis of atypical Kawasaki disease.32 Ancillary findings include leukocytosis, thrombocytosis, anemia, transaminitis, hypoalbuminemia, sterile pyuria, elevated C-reactive protein, and erythrocyte sedimentation rate. Echocardiography should be performed to evaluate for cardiac involvement including aneurysmal dilation of the coronary arteries, ventricular dysfunction, and pericardial effusion.
Diagnosis. The diagnosis of Kawasaki disease requires fever to be present for 5 days or longer along with four signs of mucocutaneous involvement without another explanation (Table 2).32 Atypical forms of the disease exist and diagnostic criteria have been described.
Management. A single dose of IVIG (2 g/kg) plus high-dose aspirin (80–100 mg/kg) daily has been shown to prevent coronary abnormalities, increase rate of defervescence, and normalize inflammatory markers.32 The single large dose of IVIG plus aspirin has become the standard regimen in North America. For those patients with Kawasaki disease shock syndrome, hemodynamic support with vasopressors may be required. Approximately 10% to 20% of patients do not respond to standard primary therapy with IVIG and high-dose aspirin, and this subpopulation is at an increased risk of coronary complications.32 Additionally, patients with Kawasaki disease shock syndrome are at higher risk for their disease to be refractory to IVIG therapy.32 Corticosteroids are not recommended for routine first-line use and are reserved for recurrent or refractory disease. Refractory cases of Kawasaki disease may require alternative therapies.29,32