Current Concepts in the Recognition and Management of Pediatric Cardiogenic Shock and Congestive Heart Failure

Authors: Paul A. Checchia, MD, FAAP, Assistant Professor of Pediatrics, Loma Linda University School of Medicine; Medical Director, Pediatric Cardiac ICU and Intermediate Care Unit, Loma Linda University Children’s Hospital, CA; Ann Dietrich, MD, FAAP, FACEP, Associate Professor, Ohio State University; Education Medical Director, ACEP Ohio Chapter; Attending Physician, Children’s Hospital; Ohio BTLS State Medical Director, Columbus, OH; and Ronald M. Perkin, MD, MA, FAAP, FCCM, Professor and Associate Chairman, Department of Pediatrics, Loma Linda University School of Medicine; Director, Pediatric Critical Care, Loma Linda University Children’s Hospital, CA.

Peer Reviewer: Martha S. Wright, MD, Associate Professor of Pediatrics, Case Western Reserve University; Associate Director, Pediatric Emergency Medicine, Rainbow Babies and Children’s Hospital, Cleveland, OH.

Cardiogenic failure in the child may present with subtle findings, but requires aggressive and appropriate management. The age of the child, history, and physical examination direct the emergency department (ED) physician to the appropriate diagnostic evaluation and subsequent consultation.

—The Editor


Cardiac shock is the pathophysiological state in which an abnormality of cardiac function is responsible for failure to maintain adequate tissue oxygenation.1,2 The final common pathway is depressed cardiac output, which in most instances is the result of decreased myocardial contractility. Cardiogenic shock or congestive heart failure (CHF) during infancy and childhood represents a diagnostic and therapeutic challenge because of its myriad etiologies (See Table 1.)

Table 1. Cardiogenic Shock Etiologies
Conduction Abnormalities
• Supraventricular tachycardia
• Ventricular dysrhythmias
• Bradycardia
• Hypoxic/Ischemic Events
      Cardiac arrest
      Prolonged shock
      Head injury
      Anomalous origin of the coronary arteries
      Excessive catecholamine state
      Cardiopulmonary bypass
      Acute myocardial infarction
• Infectious
• Metabolic
      Glycogen storage disease
      Nutritional deficiencies (thiamine, selenium, carnitine)
      Disorders of fatty acid metabolism
      Hypocalcemia, hypophosphatemia
• Connective Tissue Diseases, Inflammatory
      Systemic lupus erythematous
      Juvenile rheumatoid arthritis
      Polyarteritis nodosa
      Kawasaki disease
      Acute rheumatic fever
• Neuromuscular Disorders
      Duchenne's muscular dystrophy
      Myotonic dystrophy
      Limb-Girdle (Erb)
      Spinal muscular atrophy
      Friedreich's ataxia
• Toxin Hypersensitivity
      Carbon monoxide
• Other
      Familial dilated cardiomyopathy
Congenital Heart Disease

In contrast to hypovolemic shock, compensatory responses can have deleterious effects in patients with cardiogenic shock.1-6Compensatory responses are nonspecific and imprecise, and in patients with cardiogenic shock they may contribute to the progression of shock by further depressing cardiac function.

Compensatory Responses

The Sympathetic Nervous System. The baroreceptor-mediated increase in sympathetic tone that occurs with ventricular dysfunction has several consequences, including increased myocardial contractility, tachycardia, arterial vasoconstriction and thus increased cardiac afterload, and venoconstriction with increased cardiac preload.3

Increased local and circulating concentrations of norepinephrine may contribute to myocyte hypertrophy, either directly through stimulation of a1- and b-adrenergic receptors or secondarily by activating the renin-angiotensin-aldosterone system. Norepinephrine is directly toxic to myocardial cells, an effect mediated through calcium overload, the induction of apoptosis, or both.3,5,7 Norepinephrine-induced death of myocytes can be prevented by concomitant, nonselective b-adrenergic blockade or combined b- and a-adrenergic blockade. In the past, b-adrenergic blockade was thought to be contraindicated in patients with heart failure. However, if patients can tolerate short-term b-adrenergic blockade, ventricular function subsequently improves.8-12 There is little data on the use of beta-blockers in children with heart failure.

The Renin-Angiotensin-Aldosterone System. The activity of the renin-angiotensin-aldosterone system is also increased in most patients with heart failure.3-5 As with plasma norepinephrine, the degree of increase in plasma renin activity provides a prognostic index in these patients.3 Patients with mild heart failure may have little or no increase in either plasma renin activity or the plasma aldosterone concentrations. However, normal plasma renin and aldosterone values would be inappropriate in these patients because of their increased extracellular-fluid and total blood volumes.13,14 Among patients with severe heart failure, the values for plasma renin and aldosterone are high.

Through renal vasoconstriction, stimulation of the renin-angiotensin-aldosterone system, and direct effects on the proximal convoluted tubule, increased renal adrenergic activity contributes to the avid renal sodium and water retention that occurs in patients with heart failure. The kidneys become adversaries of the heart, lungs, and liver.

Aldosterone has an important role in the pathophysiology of heart failure. Aldosterone promotes the retention of sodium, the loss of magnesium and potassium, sympathetic activation, parasympathetic inhibition, myocardial and vascular fibrosis, baroreceptor dysfunction, vascular damage, and impaired arterial compliance.13,14 Many physicians have assumed that inhibition of the renin-angiotensin-aldosterone system by an angiotensin converting enzyme (ACE) inhibitor will adequately suppress the formation of aldosterone. In addition, treatment with an aldosterone-receptor blocker in conjunction with an ACE inhibitor has been considered relatively contraindicated because of the potential for serious hyperkalemia. However, there is increasing evidence to suggest that ACE inhibitors only transiently suppress the production of aldosterone.13,14 Furthermore, treatment with the aldosterone-receptor blocker spironolactone, in conjunction with an ACE inhibitor, is pharmacologically effective, well tolerated, and does not lead to serious hyperkalemia.13,15

Other adverse consequences of long-term activation of the renin-angiotensin-aldosterone system in patients with CHF include a progressive remodeling of the heart and vasculature, which is mediated, in part, by the induction of various cytokines and growth factors.14 Most of these actions support or increase arterial blood pressure and maintain glomerular filtration. Vasoconstriction and the release of aldosterone in response to angiotensin occur in seconds or minutes, in keeping with their roles of supporting the circulation after hemorrhage, dehydration, or postural change. Other actions, such as vascular growth and ventricular hypertrophy, take days or weeks.16

An ACE inhibitor is now considered first-line therapy in patients with heart failure.9 These drugs have improved survival in patients with chronic heart failure of all degrees of severity. Moreover, ACE inhibition reverses left ventricular hypertrophy, a common harbinger of heart failure.17,18

The amino acid sequence of angiotensin II has long been known and compounds that competitively inhibit its action have been studied almost as long. The recently released angiotensin-receptor antagonist losartan appears to be beneficial in some patients with heart disease.16

Nonosmotic Release of Arginine Vasopressin. Water retention in excess of sodium retention may occur in patients with heart failure and lead to hyponatremia. In fact, hyponatremia is a very ominous prognostic indicator in patients with heart failure.3 Hyponatremia may be partly due to the increased water intake caused by the increased thirst associated with heart failure. However, increased water intake alone rarely causes hyponatremia. In patients with heart failure and hyponatremia, hypo-osmolality, which inhibits the release of arginine vasopressin in normal subjects, is associated with persistently high plasma concentrations of arginine vasopressin.4 This observation suggests a pivotal role for arginine vasopressin in hyponatremia. In preliminary studies of patients with heart failure, a nonpeptide, orally active antagonist of arginine vasopressin, proved effective in reversing impaired urinary diluting capacity, increasing solute-free water excretion, and correcting hyponatremia.3

Natriuretic Peptides. The natriuretic peptide family consists of three peptides: atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide.19

Atrial natriuretic peptide (ANP) is a 28-amino-acid peptide that is normally synthesized in the atria and to a lesser extent in the cardiac ventricles and is released into the circulation during atrial distention. In patients with heart failure, ANP concentrations rise as atrial pressures increase. Increased atrial-wall tension, reflecting increased intravascular volume, is the dominant stimulus for its release.19 Brain or B-type natriuretic peptide is a 32-amino-acid peptide that is primarily synthesized in the ventricles, and its release into the circulation is also increased in patients with heart failure. Because plasma concentrations of brain natriuretic peptide are increased in patients with early heart failure or left ventricular dysfunction, plasma brain natriuretic peptide may be a sensitive diagnostic marker of heart failure.3,19

In patients with early heart failure, increased secretion of ANP and brain natriuretic peptide may attenuate or delay systemic and renal arterial vasoconstriction, venoconstriction with increased cardiac preload, and renal sodium retention.10 The volume-contracting and vasodilative properties of ANP reduce systemic vascular resistance, decrease intracardiac filling pressure, and improve myocardial performance. However, responsiveness to natriuretic peptides decreases as heart failure worsens, even as the plasma concentrations of the peptides rise.19

Endothelial Hormones. A crucial vascular structure is the endothelium, not only because it is strategically located between the circulating blood and the vascular smooth muscle, but also because it is a source of a variety of mediators regulating vascular tone and growth as well as platelet function and coagulation.20 However, the endothelium is both a target for and a mediator of cardiovascular disease.

Prostacyclin and prostaglandin E are vasodilating hormones produced from arachidonic acid in many cells. Angiotensin II, norepinephrine, and renal nerve stimulation increase the synthesis of these vasodilating prostaglandins, which then attenuate the vasoconstrictor effects of these three stimuli.3 These vasodilatory prostaglandins may thus counterbalance the neurohormone-induced renal vasoconstriction that occurs in heart failure.

Nitric oxide is an even more potent vasodilator than prostacyclin and prostaglandin E. Endothelial cells contain a constitutive nitric oxide synthase, the activity of which may be blunted in heart failure.3,20,21 Thus, the constrictor action of the endogenous vasoconstrictors whose concentrations are elevated in heart failure, including angiotensin II, norepinephrine, and arginine vasopressin, may be increased by a concomitant decrease in nitric oxide synthesis in endothelial cells.3

The endothelins are peptides of 21 amino acids that are produced in a wide variety of cells. Endothelin-1 is the only family member produced in endothelial cells, and it is also produced in vascular smooth-muscle cells.22 Hypoxia, shear stress, and hormones that are associated with the development of CHF stimulate the production of endothelin-1.22 Endothelin-1 can stimulate aldosterone secretion and decrease kidney perfusion and function, both of which contribute to the retention of sodium and water and increased intravascular volume. Endothelin-1 also stimulates hypertrophy of the heart and increases sympathetic activity and arterial vasoconstriction. Endothelin-1 is one of the most potent vasoconstrictors, and plasma endothelin concentrations are increased in some patients with heart failure.22,23 High plasma endothelin-1 concentrations are associated with a poor prognosis in patients with heart failure.23

Locally produced endothelin-1 has been implicated in closure of the ductus arteriosus at birth.22 Inhibition of the production and action of endothelin-1 by prostacyclin or prostaglandin E may prevent closure of the ductus.

Cytokines. It is becoming increasingly apparent that proinflammatory cytokines play an important role in modulating the structure and function of the diseased heart.5,24,25 The plasma concentrations of some cytokines, such as tumor necrosis factor alpha (TNF-a), are increased in patients with heart failure.3,24,25 TNF-a, which is produced under a variety of stresses, exerts negative inotropic effects, and can produce left ventricular remodeling, pulmonary edema, cardiomyopathy, and is a major mediator of apoptosis.25,26 Various cytokines and TNF-a, in particular, represent new targets for therapeutic intervention in patients with heart failure.

Ventricular Dilation and Hypertrophy. The ventricle responds to abnormal loading conditions by chamber dilation and hypertrophy. Ventricular dilation causes an increase in end-diastolic ventricular volume, which results in an increased stroke volume and an improvement of cardiac output. Another compensatory mechanism is hypertrophy of the myocardium.5,27 However, both these mechanisms increase oxygen requirements and make the heart more susceptible to ischemia.

Myocardial hypertrophy is an early milestone during the clinical course of heart failure and an important risk factor for subsequent cardiac morbidity and mortality.28 In response to a variety of mechanical, hemodynamic, hormonal, and pathologic stimuli (discussed throughout this manuscript), the heart adapts to increased demands of cardiac work by increasing muscle mass through the initiation of a hypertrophic response. However, initiation of this hypertrophic response may result in heart muscle failure and even the loss of myocytes as a result of programmed cell death (apoptosis).5,7,26

Downward Spiral in Cardiogenic Shock. In summary, diminished cardiac output initiates baroreceptor-mediated neurohumoral events, particularly the activation of the sympathetic nervous system, the activation of the renin-angiotensin-aldosterone system, and the nonosmotic release of vasopressin, all of which attempt to maintain arterial perfusion to vital organs.

However, over time, these neurohumoral events may have deleterious effects that include pulmonary edema, hyponatremia, increased cardiac afterload and preload, and cardiac remodeling.

As myocardial contractility deteriorates and cardiac output decreases, systemic vascular resistance increases, in response to neurohumoral mediators, in order to maintain circulatory stability. However, this increase in afterload adds to the heart’s workload and further decreases pump function. Therefore, in cardiogenic shock, a vicious cycle is established: Ventricular dysfunction is exacerbated by neurohumoral vasoconstriction, and vice versa. Because of the self-perpetuating cycle, compensated phases of cardiogenic shock may not be observed; patients are tachycardic, hypotensive, diaphoretic, oliguric, and acidotic. Extremities are cool and mental status is altered. Hepatomegaly, jugular venous distention, rales, and peripheral edema may be observed. Cardiac output is depressed, and elevations in central venous pressure, pulmonary wedge pressure, and systemic vascular resistance are observed.

Diastolic Heart Failure. Another form of CHF and cardiogenic shock is caused by diastolic dysfunction.27,29,30 Impaired myocardial relaxation changes the pressure-to-volume relationship during diastole and increases ventricular pressure at any volume. This lack of myocardial relaxation is hemodynamically unfavorable because increased left ventricular diastolic pressure will be transmitted to the lung and result in pulmonary edema and dyspnea. Such patients present with "heart failure" but may have normal left ventricular systolic function.27 Heart failure in the presence of a normal cardiac silhouette on the chest roentgen-ogram should suggest the possibility of diastolic dysfunction.

Diastolic heart failure is an insidious disease. Insults to the myocardium are followed by a series of compensatory changes that are beneficial in the short run but have long-term deleterious effects. Structured remodeling and other factors, including myocardial ischemia, left ventricular hypertrophy, increased heart rate, and abnormal calcium flux, can impair diastolic function and cause an increase in left ventricular filling pressure.27,29,30

Both ischemia and hypertrophy impair relaxation in early diastole; ischemia is caused by restricting the supply of high-energy phosphates required for rapid removal of calcium from the cytoplasm and hypertrophy by slowing the rate of actin-myosin dissociation.29 Hypertrophy also decreases left ventricular compliance in all phases of diastole.29

Therefore, when approaching a patient with cardiogenic shock, it is important to characterize both systolic and diastolic function; therapy designed to improve systolic function may impair myocardial diastolic function.29

Molecular Basis for Myocyte Dysfunction. Advances in molecular biology techniques have lead to a greater understanding of the exact mechanisms involved in both normal and abnormal myocardial contractions. A large portion of this work has centered on calcium handling by the myocyte.

Briefly, contraction is generated by an action potential. Depolarization leads to the opening of ionic channels causing a small influx of calcium that is amplified by calcium-induced calcium release from the sarcoplasmic reticulum. It is this sarcoplasmic calcium that binds to the contractile apparatus, leading to contraction.

The contractile apparatus is composed of actin, myosin, tropomyosin, and troponin. Troponin is a complex of three subunits named troponin I, C, and T.31,32 The troponin complex acts as the regulatory mechanism in the contraction process. The calcium that is released from the sarcoplasmic reticulum binds to the troponin C subunit, causing a conformational change in the entire troponin complex. This change results in the movement of tropomyosin, allowing crossbridging to occur between actin and myosin, and thus contraction.31,32

There appears to be a change in the phosphorylation state of troponin I in CHF. One group found that there is less phosphorylation of troponin I in failing human hearts vs. normal controls.33 When troponin I is dephosphorylated in the failing heart, it appears to be more sensitive to calcium, producing greater myofilament activation in response to a comparable increase in calcium concentration. This could be considered an adaptive response as the failing myocardium attempts to increase contractility. However, it is unclear if, similar to the neurohumoral adaptations, this beneficial response eventually becomes deleterious since the increased calcium sensitivity may lead to impaired myocardial relaxation and produce diastolic dysfunction.

Recognition and Clinical Findings

The appropriate management of CHF in infancy is critically dependent upon the specific etiology. Accurate and rapid diagnosis is of prime importance.

Physicians must be aware of the subtle findings associated with cardiogenic failure in the child, such as feeding intolerance, irritability, and respiratory distress. Since each of these findings can easily mimic other, more common diseases, recognition of the child in CHF begins with a careful history and physical examination and is supplemented by chest radiography, electrocardiography, and echocardiography.

Two-dimensional and Doppler echocardiographic studies provide important information about the size, thickness, and performance of the heart, as well as delineation of any cardiac malformations. Doppler investigation of the diastolic mitral inflow pattern is useful in assessing the presence of diastolic dysfunction.

The importance of age at presentation must be stressed. The age at presentation depends on the anatomic abnormality, the degree of pulmonary vascular resistance, the patency of the ductus arteriosus, and the limited cardiac reserve of the young infant.34

Birth. Most cardiac anomalies do not demonstrate failure for days to weeks because they depend on the ductus arteriosis or elevated perinatal pulmonary vascular resistance for palliation. Depressed myocardial function, rather than structural defects, is the more common etiology for CHF in the immediate perinatal period. Because the fetal and neonatal myocardium functions at near maximal capacity, the cardiac output is high at rest, and total body and myocardial oxygen consumption are elevated and supply-demand inequity can readily develop. Additionally, neonatal myocardium cannot effectively oxidize fatty acids as an energy source, and depends on carbohydrates from intake and glycogen stores for energy production.

Heart failure in the first day of life is usually caused by neonatal heart muscle dysfunction resulting from asphyxia, sepsis, hypoglycemia, hypocalcemia, or myocarditis. Structural abnormalities that may play a role at this early age include tricuspid or pulmonary regurgitation or systemic arteriovenous fistula. Contributing neonatal heart rate abnormalities that may cause failure include paroxysmal supraventricular tachycardia or congenital complete heart block.

First Week of Life. A common cause of heart failure in the first week of life is the hypoplastic left heart syndrome. These infants present with a sudden onset of a "shock-like" state when the patent ductus arteriosus closes.35 Other entities that present this early include aortic stenosis, total anomalous pulmonary venous return, and pulmonary stenosis. Heart rate abnormalities and heart muscle dysfunction discussed above remain possibilities.

One to Six Weeks. The coarctation syndrome may present during this time period with sudden onset of severe CHF.35 This usually occurs when the patent ductus arteriosus constricts. The progressive fall of pulmonary vascular resistance during the first month of life results in worsening of left-to-right shunts. Examples include large ventricular septal defects and atrioventricular canal anomalies.36 Additionally, anomolous origin of the coronary artery should be considered in an infant exhibiting signs of angina: poor feeding, irritability, and sweating with feeds.37

Later in Infancy. Most of the conditions noted above may present in this age group, but generally the symptoms will appear before the infant is 6 weeks old. Exceptions include patients with myocarditis, endocardial fibroelastosis, and those for whom heart failure is secondary to systemic hypertension or endocrine abnormalities (hypothyroidism or adrenal insufficiency). Although endocardial fibroelastosis has been decreasing in frequency, a form of familial cardiomyopathy secondary to carnitine deficiency has recently been described.38 One acquired condition that must be kept in mind is Kawasaki disease, which may cause coronary arteritis and aneurysm.39 If sufficient myocardial dysfunction results from these insults, infants may develop heart failure.

Childhood and Adolescence. CHF in childhood or adolescence is not common. Older children who have congenital heart disease may develop CHF because of the onset of valvular regurgitation or tachydysrythmias.

Acquired heart disease causing heart failure is relatively more common at this age. Myocarditis may cause heart muscle dysfunction in this group. In addition, diseases that cause valvular regurgitation, such as rheumatic fever or bacterial endocarditis, may also cause heart failure. Unfortunately, substance abuse, such as cocaine or glue sniffing, must be added to the differential diagnosis of myocardial infarction and CHF in the adolescent.

Diagnostic Findings

Clinical Findings. In infancy, poor feeding is one of the important symptoms of CHF. Infants with heart failure may take very long to feed, with a noticeable increase in respiratory effort; hence they frequently consume less than their required caloric intake. Because of this inadequate caloric intake and an increased metabolic rate, weight gain is slow. Caregivers may also notice an increase in sweating, which is a consequence of increased adrenergic activity. These infants are prone to have recurrent lower respiratory infections.

Older children may have a reduced level of exercise tolerance; careful questioning about the degree of physical activity is important. Paroxysmal nocturnal dyspnea may also be a symptom in older children. If there has been a significant degree of fluid retention from CHF, a recent increase in weight may be elicited.

The classic presentation of CHF in infants is a pale and sweaty child with an increased respiratory rate. Other common clinical findings are tachycardia, a gallop rhythm, cardiomegaly, tachypnea, and hepatomegaly.

Cardiomegaly may be difficult to diagnose clinically in infants because of their small thorax. However, the diagnosis would be supported by lateral displacement of the point of maximum impulse and a sternal heave. The definitive way of confirming cardiomegaly is the presence of an enlarged cardiac shadow on a chest x-ray film or echocardiography.

With systemic vasoconstriction, caused by the alpha-adrenergic adaptive response to heart failure, peripheral pulses will be diminished in intensity as compared to central arterial pulsations. In addition, the extremities will be cool and mottled with a prolonged capillary refill (> 3 seconds). However, in the case of high-output cardiac failure secondary to a large aortic runoff from a patent ductus arteriosus, one may palpate bounding pulses.

Most of the signs of left-sided failure result from pulmonary congestion. Tachypnea is an important early sign reflecting pulmonary venous congestion. As this congestion worsens, breathing becomes more labored, as noted with intercostal retractions, nasal flaring, grunting, and use of accessory muscles.

Adventitial lung sounds are usually not diagnostic of heart failure. Wheezing has been associated with pulmonary congestion. This wheezing may be caused by airway edema ensuing from an accumulation of lung water, or by airway compression from the enlarged left atrium, and may cause the diagnosis to be confused with viral bronchiolitis in infants. Crackles frequently are not heard during CHF in infants; hence their absence does not preclude the diagnosis of pulmonary congestion.

Enlargement of the liver reflects systemic venous congestion, and usually results from defects producing left-sided heart failure. However, hepatomegaly may also be seen with purely right-sided heart failure, such as defects producing pulmonary hypertension or isolated pulmonary stenosis. In older children, distension of the external jugular vein is evidence of systemic venous congestion. Peripheral edema is rarely seen in children as a consequence of CHF.

Elevated serum level of cardiac troponin, either I or T, is a highly sensitive and specific indicator of myocardial damage. They can be elevated within 1-2 hours following acute myocardial injury and remain detectable up to 14 days following myocardial infarction.40 One group demonstrated that cardiac troponin I has a similar sensitivity and specificity profile in pediatrics.41 Measurement of serum levels give an indication of ongoing myocardial cell injury and death in the child presenting with cardiogenic shock.


It is obvious from the above description that the clinical findings of CHF in the child may be very similar to other disease states such as respiratory distress, dehydration, and sepsis.42 The therapy for each, however, can be markedly divergent. Yet, each needs to be tended to quickly in order to avoid further morbidity or even mortality.

Fluid therapy must be used with caution in the patient with CHF, but it can be life saving in the child with severe dehydration or sepsis. A high index of suspicion of CHF in addition to other entities will allow the physician treating the child to tailor fluid management to meet the child’s need. Clues obtained from the history and physical examination, such as an absence of increased fluid losses or the presence of hepatomegaly, will raise the question of CHF rather than dehydration. Small volume boluses with frequent monitoring of vital signs can lead to a logical treatment plan. Boluses of even 2-5 mL per kilogram will allow the physician to gauge the hemodynamic response. If these maneuvers do not decrease the heart rate or raise the blood pressure, a cardiac source must be considered higher on the list of possibilities.

Although volume expansion and correction of metabolic derangements (e.g., pH, glucose, calcium, magnesium) may enhance cardiac function temporarily, pharmacological interventions are often necessary to improve cardiac function. This approach to treatment relies on the use of drugs having the ability to restore or augment myocardial contractility, improve cardiac output, and bring about a restoration and maintenance of blood flow. There is not a usual drug or dose in shock; instead, therapy must be continually tailored to the patient’s response. The proper choice of drug or drugs requires knowledge of the exact hemodynamic disturbance and of the pharmacology of the drugs.

Tables 2 and 3 list the general supportive and pharmacological measures employed in the treatment of severe CHF or cardiogenic shock. These measures are designed to increase tissue oxygen supply, decrease tissue oxygen requirements, and correct metabolic abnormalities.

Table 2. General Principles in Management of Severe CHF or Cardiogenic Shock
Minimize myocardial oxygen demands
• Intubation, mechanical ventilation
• Maintain normal core temperature
• Provide sedation
• Correct anemia
Maximize myocardial performance
• Correct arrhythmias
• Optimize preload
      Salt and water restriction
      Augment preload by fluid challenges
      Diuretics, venodilators for congestion
• Improve contractility
      Provide oxygen
      Guarantee ventilation
      Correct acidosis and other metabolic abnormalities
      Inotropic drugs
• Reduce afterload
      Provide sedation and pain relief
      Correct hypothermia
      Appropriate vasodilator use
Exclude congenital or traumatic heart disease
Explore surgical and other interventional therapies

Table 3. Inotropic and Vasoactive Drugs Utilized in the Management of Cardiogenic Shock
Drug Dosage Mechanism Usual Effect/Cautions
Dopamine 0.5-3 mcg/kg/min Dopaminergic Dilation in renal, mesenteric, cerebral vasculature
5-10 mcg/kg/min ß-adrenergic Mostly inotropic (increased cardiac output)
10-25 mcg/kg/min æ-adrenergic Increased heart rate, vascular resistance, and blood pressure
Dobutamine 1-20 mcg/kg/min ß-adrenergic Inotropic, vasodilation
Epinephrine 0.02-0.1 mcg/kg/min ß-adrenergic Inotropic
0.1-5.0 mcg/kg/min æ- and ß-adrenergic Increased vascular resistance and blood pressure
Norepinephrine 0.05-0.5 mcg/kg/min Mostly æ-adrenergic Increased vascular resistance
(Isuprel) IV infusion: Beta-1 and beta-2 May cause extreme tachycardia and increased myocardial
0.05-1.0 mcg/kg/min adrenergic effects oxygen consumption (possible myocardial ischemia). Beta-2
effects produce systemic vasodilation.
Phosphodiesterase Inhibitors
Drug Dosage Mechanism Usual Effect/Cautions
(Primacor) Loading dose: Phosphodiesterase Inotropic, vasodilation
50 mcg/kg over inhibition
10-15 min.
0.25-0.75 mcg/kg/min
(Inocor) Loading dose: Phosphodiesterase Inotropic, vasodilation
0.75 mg/kg (slowly) inhibition thrombocytopenia
3-10 mcg/kg/min
Drug Dosage Mechanism Usual Effect/Cautions
Nitroglycerin 1-5 mcg/kg/min Vasodilator Systemic and pulmonary vasodilation
Nitroprusside 0.5-10 mcg/kg/min Vasodilator Systemic and pulmonary vasodilation
(Inderal) IV: 0.01-0.25 mg/kg Beta-blocker Monitor for hypotension, decreased heart rate, cardiac
PO: 0.5 mg/kg/day output.
(Tenormin) 1-2 mg/kg/day Beta-1 adrenergic Will decrease heart rate and may decrease cardiac
(maximum: 2 mg/kg), blocker output and renin release.
given every day
(Brevibloc) IV infusion: 50-300 mcg/kg/min Beta-1 adrenergic May produce hypotension, bradycardia. Effects will not
(begin at 50 or 100 mcg/kg/min blocker with selective be apparent for 30 minutes after infusion begins, so
and titrate) cardiac effects titrate carefully (half-life:9 min). May compromise
myocardial function.
(Capoten) Neonates and children: Begin Inhibits angiotensin- Results in increased sodium excretion and mixed
at 0.15-0.3 mg/kg/dose PO converting enzyme arterial and venous dilation (reduces both afterload and
q8h, then titrate to effect preload). May cause hypotension, proteinuria,
neutropenia, hyperkalemia.
Older children and adolescents:
12.5-25 mg/dose q8h
(Vasotec) IV: 0.005-0.01mg/kg/dose Inhibits angiotensin- Results in increased sodium excretion and vasodilation. May
converting enzyme produce hypotension.
Prostaglandin E1
(Prostin) IV infusion: 0.05-0.1 mcg/kg/min Direct smooth muscle Pulmonary, systemic and ductus arteriosus vasodilatation
relaxant Hypotension, tachycardia, fever, apnea
To mix infusions, the "rule of 6" may be utilized: Mix 6 mg/kg in 100 mL D5W; then 1 mL/hr = 1 mcg/kg/min.
For a dosage where < 1 mcg/kg/min is indicated: Mix 0.6 mg/kg in 100 mL D5W; then 1 mL/hr = 0.1 mcg/kg/min.
Dosage ranges are approximate, and effects are simplified. Actual doses must be titrated to the individual patient response.
All drugs shown may have harmful side effects. Amrinone and milrinone are not rapidly metabolized and can have increased toxicity with prolonged use.

Myocardial Contractility

Inotropic Agents. The catecholamines are the most potent positive inotropic agents available; however, effects are not limited to inotropy. They also possess chronotropic properties and complex effects on vascular beds of the various organs of the body. Consequently, the choice of an agent may depend as much on the state of the circulation as it does on the myocardium. The available catecholamines are norepinephrine, epinephrine, isoproterenol, dopamine, and dobutamine.1,43-45 These catecholamines have been used extensively in infants and children. Other novel dopamine receptor agonists, like dopexamine and fenoldopam, are being developed for the management of CHF and the preservation of renal function.46,47

The digitalis glycosides may augment myocardial contractility, but because of a narrow therapeutic to toxic ratio, long half-life, and dependence of clearance on renal (digoxin) or hepatic function, their use in patients with cardiogenic shock should be avoided in the early stages of treatment.

Amrinone and milrinone are newer drugs that belong to a class of nonglycoside, nonsympathomimetic inotropic agents.48-50 They appear to act via a potent and selective inhibition of phosphodiesterase. Intravenous administration of amrinone or milrinone increases cardiac output and reduces cardiac filling pressures and systemic vascular resistance with minimal effect on the heart rate and systemic blood pressure. These drugs are particularly useful in the treatment of cardiogenic shock because they increase contractility and reduce afterload by peripheral vasodilation without a consistent increase in myocardial oxygen consumption. Both of these agents require careful bolus dosing prior to initiating an infusion—a rapid infusion of the bolus dose may cause hypotension. Since both of these drugs have relatively long half-lives, they should be used cautiously in the presence of significant hypotension. Milrinone may be preferred over amrinone because of amrinone’s greater tendency to cause thrombocytopenia.

Afterload Reduction

Vasoactive Drugs. Neurohumoral compensatory mechanisms that initially compensate for a fall in output of the failing heart in time become a major part of the problem. The kidney’s response to a decrease in cardiac output leads to expansion of extracellular fluid volume and, ultimately, to circulatory congestion and edema. Systemic vasoconstriction will raise aortic impedance, which while tending to maintain perfusion pressure in the face of declining cardiac output, eventually impairs ventricular function. Therefore, one of the rationales of treatment is to counteract these physiological responses; for example, the use of vasodilators to oppose systemic vasoconstriction, angiotensin-converting enzyme inhibitors to block the renin-angiotensin system, and diuretics to prevent or reverse abnormal fluid retention.10,17,51

Numerous vasodilators, representing several different pharmacological classes, have been shown to improve cardiac performance and lessen clinical symptoms by means of arterial and venous smooth muscle relaxation. (See Table 3.) Arterial relaxation should result in an increase in ejection fraction, an increase in stroke volume, and a decrease in end systolic left ventricular volume. Some evidence suggests that some vasodilator drugs may increase left ventricular compliance, which should shift blood into the periphery and reduce right and left ventricular diastolic volume, with attendant beneficial effects on pulmonary and systemic capillary pressure. This, in turn, ought to be reflected in decreased edema, reduced myocardial wall stress, and improved diastolic perfusion of the myocardium.

For treatment of cardiogenic shock, intravenous vasodilators with rapid onset of action and short half-life are preferred. Selection of a vasodilator agent should depend on its principal hemodynamic effects and on the specific hemodynamic abnormalities in individual patients. Factors that increase systemic resistance, such as hypothermia, acidosis, hypoxia, pain, and anxiety, should be treated before considering vasodilator drugs.

The use of vasodilators in shock is generally limited to situations in which cardiac dysfunction is associated with elevated ventricular filling pressures, elevated systemic vascular resistance, and normal or near-normal systemic arterial blood pressure. Occasionally, the combination of vasodilator and inotropic therapy results in hemodynamic improvement not attainable with either drug alone.

There is a growing awareness that right ventricular dysfunction plays a pivotal role in some of the most frequently encountered and important cardiopulmonary disorders in children, including congenital heart disease, the acute respiratory distress syndrome, bronchopulmonary dysplasia, and other chronic pulmonary disorders.34 The ability of the right ventricle to respond to increased pulmonary vascular resistance seen in these situations often determines outcome. Measures to decrease pulmonary vascular resistance have, therefore, become more common in the treatment of many seriously ill pediatric patients. Such measures include supplemental oxygen, hyperventilation, alkalosis, inhaled nitric oxide, prostaglandin E1, prostacyclin, analgesia, and sedation.34,52


Patients presenting with pulmonary edema require immediate measures to guarantee oxgenation and ventilation. Oxygen should be administered at 3-6 L/min by mask or nasal cannula. The need for intubation and mechanical ventilation should be assessed. Diuretics such as furosemide are frequently used to reduce preload and to improve the congestive symptoms present.53 This may be given orally or intravenously, depending on the severity of CHF, with 1-2 mg/kg used as a starting dose to be given every eight hours. With large and repeated doses, fluid depletion or electrolyte abnormalities are possible. Thiazide diuretics and spironolactone are usually reserved for ongoing management and rarely have a role to play in the emergency department.

Interventional Cardiology

Over the past decade, transcatheter interventions have become increasingly important in the treatment of patients with congenital heart lesions.54 These procedures may be broadly grouped as dilations (e.g., septostomy, valvuloplasty, angioplasty, and endovascular stenting) or as closures (e.g., vascular embolization and device closure of defects). Balloon valvulopasty has become the treatment of choice for patients in all age groups with simple valvular pulmonic stenosis and, although not curative, seems at least comparable to surgery for congenital aortic stenosis in newborns to young adults. Balloon angioplasty is successfully applied to a wide range of aortic, pulmonary artery, and venous stenoses. Stents are useful in dilating lesions of which the intrinsic elasticity results in vessel recoil after balloon dilation alone. Catheter-delivered coils are used to embolize a wide range of arterial, venous, and prosthetic vascular connections. Although some devices remain investigational, they have been successfully used for closure of many arterial ducts and atrial and ventricular septal defects.

Surgical Intervention

It must be emphasized that a number of congenital cardiac defects may present in severe CHF and cardiogenic shock. Diagnosis of these defects is critical because surgery may be required before hemodynamic stability can be achieved.

Cardiac function can be supported temporarily by mechanical means including intra-aortic balloon counterpulsation, left-ventricular assist device, and extracorporeal membrane oxygenation.9 Cardiac transplantation has become an important tool for treating patients with severe myocardial dysfunction who would otherwise succumb to their heart disease.

Specific Etiologies

Cardiac Arrythmias. Although a common cause of adult morbidity and mortality, primary cardiac arrhythmias are uncommon in pediatric ED patients. A recent study found an incidence of 55.1 arrhythmias for every 100,000 pediatric ED visits.55 Tachyarrhythmias were the most common in all age groups except infants, in which bradycardia tended to dominate. Unfortunately, interpretation of pediatric electrocardiograms can be difficult due to developmental variations in criteria. Horton et al found that 32% of pediatric ECGs performed in the ED were interpreted differently by a pediatric cardiologist and that in 7% of these cases these interpretations might have resulted in a different patient outcome or disposition.56

Bradycardia in an infant, while a cardiac symptom, most often has hypoxemia as the underlying cause. When presented with an infant suffering from symptomatic bradycardia, basic emergency principles of airway and breathing management may lead to cardiac improvement in a significant number of cases.

Symptomatic bradycardia in children requiring cardiac pacing usually involves diseases of the atrioventricular node.57 Children with congenital complete atrioventricular block (CCAVB) may present at any age because of symptoms of bradycardia (e.g., fatigue or syncope). Also, many of these children are asymptomatic and are diagnosed because of a low resting heart rate on physical examination. The only recognized therapy for CCAVB is permanent cardiac pacing. Most patients with CCAVB, even if asymptomatic, are believed to need permanent pacing during their lifetime to avoid the possibility of sudden cardiac death.

Supraventricular tachycardia (SVT) can be defined as a sustained, accelerated, nonsinus cardiac rhythm originating above the level of the atrioventricular (AV) junction. SVT encompasses a broad classification of arrhythmias; the most common forms of SVT seen in children are AV reentrant tachycardia and AV nodal reentrant tachycardia. (See Table 4.)57-60 SVT may occur in 1 of every 250 to 1000 children and accounts for up to 90% of arrhythmias in this age group.

Table 4. Classification of Supraventricular Tachycardia
AV node is necessary limb of tachycardia circuit (adenosine expected to terminate arrhythmia)
Atrioventricular re-entry tachycardia (AVRT)
     Orthodromic AVRT:Tachycardia involving a circuit utilizing the atrioventricular node as the antegrade limb and an accessory connection between ventricle and atrium as the retrograde limb.
     Antidromic AVRT: Tachycardia involving a circuit utilizing an accessory connection as the antegrade limb and the atrioventricular node as the retrograde limb.
Atrioventricular nodal re-entry tachycardia (AVNRT)
     Tachycardia involving a circuit, the two limbs of which are intimately associated with the atrioventricular node. The atria and ventricles are activated as offshoots of the circuit. The common type of AVNRT is typified by slow conduciton antegradely and fast conduction retrogradely, the uncommon type by fast conduction antegradely and slow conduction retrogradely.
AV node is not necessary limb of tachycardia circuit (adenosine not expected to terminate arrhythmia)
Atrial tachycardias
     Atrial tachycardia: Tachycardia characterized by discrete atrial activity on the surface electrocardiogram with varying ventricular response resulting either from a micro re-entry circuit or ectopic focus confined within the atria.
     Atrial flutter: Tachycardia characterized by a sawtooth undulation of the baseline on the surface electrocardiogram probably resulting from conduction around a reentry circuit within the atria.
     Atrial fibrillation: Tachycardia characterized by chaotic low voltage 'fibrillatory' waves on the surface electrocardiogram with an irregularly irregular ventricular response, resulting from disordered atrial activity.

The classic ECG characteristic of accessory connection-mediated orthodromic tachycardia is a narrow QRS tachycardia with a retrograde P wave inscribed after the QRS in the ST segment. Antidromic SVT has a wide QRS morphology and resembles ventricular tachycardia. Both antidromic and orthodromic SVT are reentrant in nature, so they can have an abrupt onset and termination.

The diagnosis of SVT is suspected by the presence of signs and symptoms. Infants and small children develop signs and symptoms of cardiopulmonary distress, which increase with the duration of the tachycardia. The infant who has a long episode (several hours) of SVT will present with tachypnea, loss of interest in feeding, and irritability, progressing over 24-48 hours to lethargy, sternal and intercostal retractions, and signs of cardiovascular impairment (i.e., weak pulse and ashen color).

In contrast, the young child may complain of chest discomfort or "pain," or a funny feeling in his or her heart. The older individual will complain of flutter, palpitations, or heart racing. Depending on the specific form of the tachycardia and its rate and duration, as well as the physiologic state of the patient prior to the onset, the patient may become faint, dizzy, and even frankly syncopal.

The diagnosis of SVT can only be made by electrocardiographic recording of the arrhythmia during an episode. Before assessing an abnormally fast heart rate, it is important to recall normal heart rates, which vary with age and level of activity. (See Table 5.) It is also important to differentiate between SVT and sinus tachycardia because sinus tachycardia rarely if ever causes hemodynamic compromise. Table 5 summarizes the distinguishing features of the two conditions.

Table 5. Heart Rates in Infants and Children
Normal heart rate
Heart Rate (beats/min)
Age Resting (awake) Resting (sleeping) Exercise*
Newborn 100-180 80-160 Up to 220
1 wk – 3 mo 100-220 80-200 Up to 220
3 mo – 2 yr 80-150 70-120 Up to 200
2 yr – 10 yr 70-110 60-90 Up to 200
10 yr – adult 55-90 50-90 Up to 200
*In young infants: crying, agitation, illness, stress.
A comparison of sinus tachycardia and SVT
Sinus tachycardia SVT
Rate < 230 bpm if < 2 mos Usually 240-300 bpm in infants
< 210 bpm in older children 150-240 bpm in older children
QRS duration Narrow complex Usually narrow complex; rarely wide complex
P waves Always present May not be visible
Always precede QRS complex May follow QRS complex
Normal axis (0 - +90 ) May be inverted leads II, III, aVF
Regularity Regular, slows gradually Abrupt onset, very regular, ends suddenly
Influence of Agitation Fluctuates No change
Adapted from Robinson B, Anisman P, Eshaghpour E. Is that fast heartbeat dangerous? Contemporary Pediatrics 1996;13:52-85.

SVT that causes circulatory instability (i.e., CHF, diminished peripheral perfusion, or hypotension) is most expeditiously treated with synchronized electrical cardioversion at a starting dose of 0.5 J/kg. If intravenous access is already available, adenosine may be administered before cardioversion, but cardioversion should not be delayed while intravenous access is achieved. Adenosine is also the drug of choice for conversion of SVT in stable children.60-62Verapamil should not be used in infants because cardiac arrest has been reported following its administration,63,64and its use is discouraged in children since it may cause hypotension and myocardial depression.

Adenosine is an endogenous nucleoside that causes a temporary block through the AV node and therefore interrupts the reentry circuits that involve the AV node and that are responsible for the underlying mechanism for the vast majority of SVT episodes in infants and children. Adenosine is very effective, and side effects are minimal because its half-life is only seconds. With continuous ECG monitoring, 0.1 mg/kg should be given as a rapid intravenous bolus. Because adenosine is metabolized by red blood cell adenosine deaminase, a higher dose may be required for peripheral venous administration than will be necessary if the drug is administered into a central vein.62 If there is no effect, the dose may be doubled. The maximum single dose of adenosine should not exceed 12 mg.61

Chronic therapy is based on the age of the child, severity of the episode and existence of cardiac disease. For a brief episode of SVT which is well tolerated, chronic therapy may not be initiated. Most infants with SVT will be treated with propranolol or digoxin. If Wolff-Parkinson-White (WPW) is present, digoxin is usually not used. Since many children will outgrow their tachcardia by 1 year of age (the properties of the bypass tract and the AV node change such that sustained tachycardia is no longer possible) drug therapy may be stopped at that time and the child carefully monitored for further episodes of SVT. Approximately 20-30% of children will have further episodes of SVT. Radiofrequency catheter ablation can be curative and carries a low complication risk.65-66 Other alternative therapies include flecainide, amiodarone, and sotalol. Selection of therapy is based on frequency and complexity of the episodes of SVT.

Acquired Disorders

Myocarditis. Myocarditis, a relatively common inflammatory disease of the heart, may present with few symptoms or may progress rapidly to cardiogenic shock.67-71 There is compelling evidence that myocarditis can evolve into a chronic dilated cardiomyopathy with persistent ventricular dysfunction.67,72 The reported mortality rates for children with myocarditis vary and have been as high as 57%. However, a recent review found that 86% of children with myocarditis were free from death or cardiac transplant at 1 month after onset and 79% after 2 years.67 This trend to improved outcomes may reflect a greater understanding of the disease process and supportive care.

The numerous infectious and noninfectious causes of myocarditis are well documented. The most commonly implicated viral infections are the enteroviruses, specifically coxsackie B and echovirus. Additionally, respiratory syncytial virus infection has been implicated as a cause of myocardial damage in children.73 Autoimmune pathways are implicated as the primary mechanisms by which viral myocarditis occurs.72,74 Animal models of myocarditis demonstrate that the essential component of virus-associated myocardial injury is the development of cellular immune reactivity to myocardial antigens.74 Autoantibodies against cardiac myosin isoforms following coxsackie B infection have been documented. Various cytokines, including IL-1, TNF-a, and IL-2, have been demonstrated in experimental animal models of myocarditis. Recent evidence suggests that a viral mechanism contributes not only to the acute phase of myocarditis but also to the evolution of ongoing heart disease.72

The diagnosis of myocarditis may be suspected in a child with a chest radiograph that shows acute cardiomegaly and pulmonary venous congestion. The ECG may be abnormal, with ST segment changes, T-wave inversion, and low QRS voltages being commonly found. Arrhythmias requiring treatment complicate the early course in up to 30% of patients. Unexplained ventricular tachycardia may be the only manifestation of myocarditis. The echocardiogram will usually reveal global ventricular systolic dysfunction and left ventricular dilatation with or without regional wall motion abnormalities. The echocardiogram is critical to rule out structural anomalies of the heart. Cardiac troponin levels may also be elevated.75 The "gold standard" for diagnosing acute myocarditis remains the endomyocardial biopsy.

The treatment of viral myocarditis remains supportive. Therapies such as diuretics, afterload reducing agents, and antiarrhythmic agents are used for more severe cases to support cardiac function. Inotropic agents should be utilized with caution. Inotropic agents often do not improve contractility and hemodynamics in children with acute myocardial infections and may precipitate life-threatening arrhythmias. The use of a circulatory-assist device may be beneficial in patients with fulminant myocarditis.70 The use of high-dose steroids and antiviral agents remain controversial.72,74,76,77 The use of immunoglobin is being investigated. Although the majority of children with myocarditis will have a good outcome, approximately 20-30% will develop irreversible dilated cardiomyopathy or sudden death.

Septic Shock. Cardiac function can also be depressed in patients with shock of noncardiac origin. While myocardial dysfunction in such patients is not completely understood, the following mechanisms have been proposed: 1) specific toxic substances released during the course of shock that have a direct cardiac depressant effect; 2) myocardial edema; 3) adrenergic receptor dysfunction; 4) impaired sarcolemmic calcium flux; and 5) coronary blood flow/metabolic demand mismatch resulting in impaired myocardial systolic and diastolic function.1

The presence of myocardial dysfunction in patients with septic shock has been recognized for many years.78 A reversible depression of left and right ventricular ejection fraction, with associated ventricular dilation, can be demonstrated using radionuclide cineangiography with simultaneous thermodilution cardiac output measurements. The presence of a circulating myocardial depressant substance was demonstrated by one group with an in vitro assay using spontaneously beating rate myocardial cells.79 The mechanism of action of the myocardial depressant substance(s) was recently shown to be attributable to a synergistic effect of TNF and IL-1.80 At the subcellular level, these cytokines probably produce depressant activity in a nitric oxide-mediated mechanism.81

Recently, a group reported that cardiac troponin I (cTn I) was elevated in 12 of 15 patients with septic shock, compared with one of six critically ill control patients, with a significantly higher median value in the septic patients.82 There was a positive correlation between norepinephrine/epinephrine infusion rate and cTn I and a negative correlation between left ventricular stroke work index and cTn I.

This study does not support the concept that functional loss is the sole cause for decreased myocardial performance, and it documents a significant degree of myocardial cell injury occurring in the context of septic shock. This group has opened a new door in the investigation of myocardial dysfunction in septic shock. The presence of cardiac cell injury and the mechanism by which it occurs requires further study. Cardiac cell injury may be a consequence of the hypotension/shock that patients with septic shock have developed, may be caused or worsened by the use of catecholamines, or may be linked with the action of a circulating myocardial depressant substance.

Kawasaki Syndrome. Kawasaki syndrome (KS) is an acute, febrile, multisystem vasculitis that almost exclusively affects young children.39,83-87 First described in 1967 by Dr. Tomisaku Kawasaki of Tokyo, Japan, it now has been recognized as occurring in all regions of the world among children of diverse ethnic groups.83 Its occurrence is common enough in all parts of North America that all physicians treating children should be familiar with its diagnosis and treatment. Originally thought to be a benign febrile exanthem, it soon was recognized that fever could be prolonged and that significant adverse cardiac effects were common, especially the development of coronary aneurysms that could lead to myocardial infarction, serious arrhythmias, and sudden death.

The peak incidence of KS is between 1 and 2 years of age, and 80% of cases occur in children 4 years old and younger.83 The disease rarely occurs in children older than 8 years and although children as young as 6 weeks may have classic clinical features, diagnosis within the first 3 months of life is uncommon.

Despite a few areas of encouraging study, the search for the cause of Kawasaki disease has so far been inconclusive.39 The high fevers and the vigorous acute-phase response on laboratory evaluation have made an infectious agent seem likely. Furthermore, the seasonality of the illness, its epidemic nature, and the fact that few children have a second episode of Kawasaki disease suggest infection and acquired immunity. Searches using culture, microscopic examination, and polymerase chain reaction techniques optimized for a plethora of viruses and bacteria have not, however, recovered any single agent consistently.39

The criteria for diagnosis, established in 1971 by a Japanese research committee, are based solely on the clinical findings of the disease. (See Table 6.)84 Prodromal symptoms are rare. Illness usually begins with high fever of 39ºC to 40ºC, which may be continuous or spiking in nature. Although the diagnostic criteria used for case reviews include fever for five days, it is not essential to wait five days before making the diagnosis and initiating therapy.

Table 6. Kawasaki Syndrome
Diagnostic Criteria
Diagnosis is established when fever has been present for > 5 days, 4 of the following 5 symptoms are present, and other diagnoses have been excluded; if coronary aneurysms are documented, only 3 of the 5 are required.
      • Erythema, edema, or desquamation of the hands and feet
      • Polymorphous rash
      • Conjunctival injection (bilateral, non-exudative)
      • Lesions of the mouth: Red or cracked lips, strawberry tongue, or injected mucosa
      • Cervical lymphadenopathy
Associated Findings
System Signs or Symptoms
CNS Meningistus, irritability, sensorineural hearing loss, CSF* pleocytosis
Ophthalmologic Anterior uveitis
Cardiovascular Tachycardia, gallop rhythm myocarditis, pericardial effusion, mitral insufficiency, conduction abnormalities, coronary artery ectasia, myocardial infarction
Gastrointestinal Vomiting, diarrhea, pancreatitis, gallbladder hydrops, hyperbilirubinemia
Renal/Urologic Sterile pyuria, microscopic hematuria, albuminuria
Hematologic Hypercoaguable state (thrombocytosis with platelet activation), peripheral gangrene
Musculoskeletal Arthritis, neck pain
*CSF=cerebrospinal fluid
Differential Diagnosis
Infectious Diseases Allergic or Rheumatic Diseases Toxic Disease
Scarlet fever Drug reaction Acrodynia
Measles Stevens-Johnson Syndrome
Epstein Barr virus Systemic JRA
Toxic shock syndrome Systemic lupus erythematosis
Scalded skin syndrome Serum Sickness
Leptospirosis Infantile Periarteritis Nodosa
Rocky Mountain spotted fever

A blotchy exanthem, appearing urticarial, scarlatiniform, morbilliform, erythematous, or any combination of these, appears between days 1 and 5 of the fever. It is seen on extremities and the trunk, with pronounced involvement of the groin in many cases. The rash is not vesicular. Palms and soles do not show discrete lesions, but are deeply erythematous and often become tensely edematous also.

Two to four days after the onset of fever, the bulbar conjunctivae become injected. This may be subtle or pronounced and may be accompanied by the finding of anterior uveitis on slit-lamp examination. There is no conjunctival exudate. Bright red lips with cracking and bleeding, along with a strawberry tongue, reminiscent of group A streptococcal disease, appear at about day 3-5. Erythema of the oral mucosa may also be seen.

Adenitis, occasionally appreciable before the onset of fever, develops in two-thirds of patients. It can be profound, bilateral, or solitary and painful to the child, but it is never suppurative. Usually cervical in location, it is the least frequently observed of the diagnostic criteria for Kawasaki disease.

Not all KS patients have illnesses that fulfill classic diagnostic criteria.83,88-90 Children with KS manifested by fever and fewer than four of the other features, so-called "atypical" or "incomplete" KS, are at risk for coronary aneurysms. Atypical KS is most common in young infants, who are unfortunately at greatest risk for coronary disease, and recognition of such cases is difficult.86 KS should be in the differential diagnosis of prolonged fever in infants; occasionally, prolonged fever is virtually the sole manifestation of KS. In such cases, diagnosis is often based on the finding of coronary aneurysms by echocardiography.

Kawasaki disease is a systemic arteritis, with particular involvement of the coronary arteries.85,91 Intense infiltration of vessel walls with inflammatory cells is seen in biopsy specimens of various tissues from acutely ill children. Involvement of the initmal layer is seen during the acute phase of illness, with panvasculitis and aneurysm formation usually in the subacute phase. The coronary arteries are most commonly affected, but aneurysms have been located in other medium-sized arteries such as the brachial, internal iliac, and intercostal arteries.86 Aneurysms may be saccular or fusiform and may either persist or heal, occasionally with scarring and stenosis.85 The involvement of vessels occasionally leads to acute thrombosis, with ischemic injury.86,92 Its predilection for the coronary circulation has made this disease the leading cause of acquired heart disease in children of developed countries.93 Echocardiography is the primary modality for identifying patients with coronary involvement. Echocardiograms should be obtained initially and repeated at 3-6 weeks after the onset of fever.83,93

Myocardial infarction in children presents with different symptoms than in adults. A review of 195 cases of myocardial infarction caused by KS in Japan indicated that the main symptoms were shock, unrest, vomiting, and abdominal pain; chest pain was most common in older children.94 KS patients with myocardial infarction have typical ECG and cardiac enzyme changes.

Children who have coronary artery involvement may require coronary artery bypass grafting or, if severe, cardiac transplantation.95,96

In addition to coronary vessel involvement, Kawasaki disease may effect other areas of the heart. Carditis with variable impairment of cardiac function, pericarditis with effusion, mitral and aortic valvulitis, and conduction system inflammation have been observed. However, unlike infectious myocarditis or ischemia, there is not an elevation of cardiac troponin I in the carditis of Kawasaki disease.97 Therefore, there does not appear to be direct involvement of the myocyte during Kawasaki disease.

Standard treatment of KS in the acute phase is with IVIG and aspirin. The benefit of IVIG in reducing the manifestations and complications of Kawasaki disease has been shown by several investigators. It was shown in a prospective multicenter trial to reduce the incidence of coronary aneurysms from 17% to 4%. Various dosing regimens have been used in different centers, but recent data support the use of a single dose of 2 grams per kilogram, infused over 10-12 hours.83,98

In many patients, the clinical response to the infusion of IVIG is striking, with the abatement of fever and improved laboratory indices within 24 hours. Gallop rhythm, CHF, and even cardiogenic shock usually resolve rapidly after administration of IVIG.83

Aspirin is used in the treatment of Kawasaki disease because of its anti-inflammatory and antiplatelet functions. A high dose (100 mg per kg of body weight a day orally, divided, every 6 hours) has been shown to be safe and effective in reducing fever and clinical illness.86 The duration of high-dose aspirin treatment varies, but most continue it through day 10-14 of the illness and until the patient has been afebrile for 48-72 hours. The dose is then reduced (to 3 to 5 mg per kg a day as a single dose).86 Aspirin can be discontinued when acute-phase reactants such as the erythrocyte sedimentation rate return to normal 4-6 weeks later.

Although corticosteroids are the treatment of choice in other forms of vasculitis, their use has been limited in children with KS.99 Renewed interest in steroid therapy has developed because of recent data suggesting that steroid therapy may be beneficial and that its adverse effects with short-term use are low.100,101

Blunt Cardiac Injury. Obstructive shock due to tension pneumothorax or pericardial tamponade, myocardial contusion, and spinal shock may complicate the management of pediatric trauma. Blunt cardiac injury can cause myocardial contusion, myocardial concussion, aneurysm, septal defects, chamber rupture, valvular rupture, and damage to the pericardium.102-104 Each of these entities has separate presentations, although the lesions are often concurrent. The majority of blunt injuries to the heart are myocardial contusions; devastating events such as ventricular rupture are rare.

In one study reporting 184 cases, an important finding was that all children who developed heart failure or serious cardiac arrhythmia during their hospital course initially presented to the emergency department either in shock or with a serious arrhythmia.102 Trauma patients with a suspected cardiac injury should be promptly evaluated with echocardiography. Elevated serum troponin I levels may predict the presence of echocardiographic abnormalities.105


Cardiomyopathies are diseases of the heart muscle.106 Since the term cardiomyopathy was introduced, the definition has been modified and now refers to structural or functional abnormalities of the myocardium that are not secondary to hypertension, valvular or congenital heart disease, or pulmonary vascular disease. Many cardiomyopathies observed in infants, children, and adolescents result from genetic defects and, therefore, are another type of congenital heart disease. Like their gross anatomic counterparts, these diseases present clinically at any age and can cause sudden death, CHF, arrhythmia, asymptomatic murmers, and virtually every type of cardiologic complaint.38

From a functional standpoint, cardiomyopathies are classified into three categories. They are: 1) dilated cardiomyopathy, also called congestive cardiomyopathy, in which the left or both ventricles are enlarged and hypocontractile to variable degrees; in general, systolic dysfunction is the main clinical feature, with resultant signs and symptoms of CHF; 2) hypertrophic cardiomyopathies, formerly known as idiopathic hypertrophic subaortic stenosis, characterized by left ventricular hypertrophy that may be asymmetric; systolic function is usually preserved, and symptoms may result from left ventricular outflow tract (LVOT) obstruction, diastolic dysfunction, or arrhythmias, resulting in sudden death; and 3) restrictive cardiomyopathies, recognized by markedly dilated atria, with generally normal ventricular dimensions and systolic function; diastolic filling is impaired, and symptoms result from pulmonary and right-sided systemic venous congestion; syncope may also be a presenting feature.38,106-109

Dilated Cardiomyopathy. Dilated cardiomyopathy (DCM) is reported to be the most common form of cardiomyopathy. In studies of children presenting with DCM, 2-15% had biopsy proven myocarditis, whereas 85-90% had no cause indentified.106 Familial forms of DCM have been described, with as many as 30% of patients having a familial DCM.

Inborn errors in several mitochondrial metabolic pathways are associated with cardiomyopathy. The pathways primarily involved are those of fatty-acid oxidation and oxidative phosphorylation.38, 110-112 Mitochondrial b oxidation of fatty acids (mainly long-chain fatty acids) is the main source of cardiac energy; inborn errors among the enzymes and transport proteins in this pathway occur in an estimated one per 10,000 live births.38 In the early 1980s, reports surfaced of an association between carnitine deficiency (carnitine is required to transport long-chain fatty acids into the mitochondria) and cardiomyopathy, which sometimes was reversible with oral carnitine supplementation. Subsequent studies documented that all disorders of carnitine transport, mitochondrial carnitine shuttling, and long-chain fatty acid oxidation enzymes may be associated with abnormalities in plasma and tissue levels of carnitine.38,110,111

A common finding is episodic clinical crises precipitated by fasting (often during an infectious illness), which increase the dependence of tissues such as heart, liver, and skeletal muscle on fatty-acid oxidation for energy. These crises may result in sudden death, hepatic encephalopathy, or coma with hypoketotic hypoglycemia and, in conjunction with some defects, hyperammonemia and/or dicarboxylic aciduria.38

On gross inspection of the heart, the child morphologic feature of DCM is biventricular dilation; the atria are generally enlarged as well. Mural thrombi may be present, and the myocardium is pale and sometimes mottled. The endocardium is usually thin and translucent, however, focal sclerosis may be seen.

Histologic features classically include myocyte hypertrophy and degeneration, and varying degrees of interstitial fibrosis are seen.106 Occasional small clusters of lymphocytes may be present. If lymphocytes are also seen, this disorder must be differentiated from myocarditis in which the lymphocytes are associated with areas of myocyte damage and necrosis.

If no identifiable and treatable cause of the DCM is found, therapy typically is supportive and consists of an anticongestive regimen, control of significant arrythmias, and minimizing the risk for thromboembolic complications.106 Children who present with critical illness frequently require intubation and mechanical ventilation.

Intravenous inotropic support is used to improve cardiac function and output during episodes of decompensation. The mainstays of therapy have been dobutamine and dopamine. Dopamine is begun in low doses to improve renal perfusion and diuresis. Myocardial phosphodiesterase inhibitors, such as amrinone or milrinone, possess positive inotropic effects and afterload-reducing properties and improve left ventricular relaxation. They are useful when a combination of these effects is desired. Nitroprusside can also be used for afterload reduction but may have greater blood pressure effects.

When these patients are well enough to begin oral medications, digoxin is usually instituted as IV inotropic agents are weaned. Oral captopril or enalapril should also be started as IV afterload-reducing agents are being decreased. b-adrenergic blocking agents have been used in adults and may become useful in children.106 Diuretic therapy is used to enhance diuresis and is given intravenously initially.

Arrhythmias are common in children with DCM. In some cases, improvement in cardiac function with medical management of CHF and normalizing electrolyte imbalances is all the treatment that is required; however, if significant arrhythmias persist, antiarrhythmic therapy is warranted. If symptomatic bradyarrhythmias occur, temporary pacing may be necessary during the acute phase of illness.

Intracavitary thrombus formation and systemic embolizaiton have been reported in young patients with DCM, and anticoagulation should be considered. If a thrombus is identified, patients are usually anticoagulated with heparin and then switched to warfarin. If a thrombus is not seen, antiplatelet drugs (e.g., aspirin or dipyridamole) may be useful in preventing thrombus formation.

In children with metabolic causes of DCM, careful attention to biochemical derangement is important. Correction of metabolic acidosis and diagnosis of the underlying cause is paramount. Oral feeding should be discontinued until stabilization has occurred. IV fluid and dextrose replacement should be considered to provide energy and reduce the ongoing catabolic process.38,113

Hypertrophic Cardiomyopathy. Hypertrophic cardiomyopathy (HCM) is a heterogeneous clinical disorder with a myriad of morphologic, clinical, and pathophysiologic features.114 The diagnosis of hypertrophic heart disease may be considered only after the exclusion of systemic hypertension, coronary artery disease, aortic valve disease, coarctation of the aorta, and congenital heart diseases predisposing to hypertrophy.106

The most characteristic morphologic abnormality in patients with HCM is a hypertrophied and nondilated left ventricle. Because the left ventricular cavity is usually normal in size, the increased left ventricular mass must be caused by an increase in ventricular wall thickness. The distribution of hypertrophy is typically asymmetric, although concentric hypertrophy certainly can occur. In addition, atrial enlargement, thickening of the mitral valve leaflets, and ventricular wall fibrosis are commonly seen.

Infants who present with HCM usually have marked septal hypertrophy and commonly are found to have biventricular outflow tract obstruction and signs of CHF. Many of these infants have concentric hypertrophy, however. In the most typical form of HCM, hypertrophy does not develop until later in life, usually after the onset of puberty. The morphologic expression of HCM may not be complete until adulthood.

In some young children with early-onset HCM caused by metabolic or mitochondrial disease, infiltration with glycogen within the myocardium is notable.106,109 In addition, large numbers of abnormal mitochondria may be seen.

Several pathophysiologic components of the HCM process thus far identified include diastolic dysfunction, systolic dysfunction and LVOT obstruction, coronary artery abnormalities leading to myocardial ischemia, and arrhythmias.106,114,115 The symptoms displayed by affected patients are usually the result of combinations of these mechanisms and the relative contribution of each component.114

The classically described pathophysiologic abnormality in patients with HCM is diastolic dysfunction and abnormalities of ventricular relaxation. Left ventricular diastolic dysfunction is evident in all patients with HCM, whether or not LVOT obstruction is present. Despite normal or decreased left ventricular end-diastolic volume, compliance is decreased.

Because left ventricular function in patients with HCM is typically hyper-contractile, positive inotropic agents are contraindicated; if necessary, these agents must be used with caution.106 Systolic dysfunction is uncommon, except in a few preterminal patients; pulmonary venous congestion usually occurs secondary to diastolic dysfunction in the face of normal or supranormal systolic function. Inotropic support in such setting can cause an increase in the systolic gradient and a concomitant deterioration in clinical status or initiation of ventricular arrhythmias leading to poor cardiac output. Likewise, by decreasing preload, diuretic agents may worsen the outflow obstruction; however, their cautious use, in combination with a b-blocking agent, has been shown to decrease pulmonary congestion.106

Currently, the preferred drug in the treatment of symptomatic children is a b-blocking agent, such as propranolol or atenolol. Presumably, these drugs are effective for patients with HCM because of their sympatholytic effects, thereby reducing heart rate, left ventricular contractility, and wall stress.106 Approximately one-third of symptomatic patients obtain complete relief of their symptoms with standard doses of oral propranolol; higher doses are sometimes indicated, however, as long as the side effects are not limiting. Clearly, these agents have no effect on the extent of hypertrophy, the progression toward increased hypertrophy, or the actual reduction of ventricular arrhythmias. Furthermore, it does not eliminate the risk of sudden death.

Congenital Heart Defects

Left Ventricular Outflow Obstruction. During the newborn period, coarctation of the aorta, critical aortic stenosis, and hypoplastic left heart syndrome may all present with CHF or cardiogenic shock secondary to left ventricular outflow obstruction. 35,116-118 With left ventricular outflow obstruction, left ventricular output is severely decreased, which leads to left atrial dilatation and pulmonary venous congestion. The increase in left atrial pressure and size leads to a left to right shunt that increases pulmonary blood flow. Systemic perfusion is maintained in all these entities via the ductus arteriosus. The ductus provides not only systemic blood flow but also decreases the blood flow to the lungs. With the closure of the ductus, the child develops cardiogenic shock. Infants with hypoplastic left heart syndrome also have atrial left to right shunting because of the hypoplasia of the left ventricle.

The presentation of patients with coarctation of the aorta depends on the age of the patient, the severity of the obstruction, and any associated cardiac anomalies. 35,117 In neonates, as the patent ductus arteriosus closes, the full effect of the obstruction caused by the coarctation is revealed. When the coarctation is severe, these neonates typically present within the first 3 weeks of life with tachypnea, poor feeding, and CHF, progressing to cardiogenic shock. Discrepant pulses, blood pressure measurements, and differential cyanosis may be present between the right arm and either leg. In infants with associated ventricular septal defect, the CHF caused by an increased left-to-right shunt may be more severe and occur at an earlier time.

The term hypoplastic left heart syndrome (HLHS) describes a collection of cardiac anomalies involving hypoplasia or absence of the left ventricle. In its classic form, the aortic and mitral valves are atretic or nearly atretic.35 All cases involve a left ventricle that does not form or extend to the apex of the heart. Untreated, HLHS is a fatal disorder, and almost all patients die within the first month of life.

Immediately after birth, these neonates may appear normal because the anomalies that comprise HLHS are often compatible with normal intrauterine systemic oxygenation and perfusion. In these patients, the flow of blood after delivery is as follows: Pulmonary venous blood passes across an atrial septal venous blood from the superior and inferior vena cavae. The blood passes into the right ventricle through the tricuspid valve and then through the pulmonary valve into the main pulmonary artery. The blood then either travels to the branch pulmonary arteries or through the patent ductus arteriosus (PDA) to supply the descending aorta in an antegrade manner or the transverse arch and ascending aorta (including the coronary arteries) in a retrograde manner. The timing and severity of the presentation is dependent on three variables: 1) the patency of the ductus arteriosus; 2) the restriction to blood flow at the level of the atrial defect; and 3) the ratio of the pulmonary vascular resistance to the systemic vascular resistance.35

In neonates with HLHS, systemic blood flow is dependent on a PDA. As the ductus begins to constrict, blood is less able to cross from the pulmonary circuit to the systemic circuit. This results in hypoperfusion of the renal, hepatic, and gastrointestinal organ systems while overcirculation of the pulmonary system occurs. These neonates develop tachypnea, respiratory distress, and metabolic acidosis that progress to shock. The type of presentation typically occurs between 24 and 48 hours of life.

The age of presentation of patients with valvar aortic stenosis varies based on the severity of the obstruction to flow past the aortic valve. Ten to 15% of patients present before the age of 1 year.35 These infants typically present with symptoms of CHF, including tachycardia, tachypnea, difficulty with feeding, and poor growth; or, in critical cases, cardiogenic shock requiring resuscitation, as in patients with hypoplastic left heart syndrome or critical coarctation of the aorta. The classic systolic ejection murmur may be absent in these infants.35

The diagnosis of patients with left ventricular outflow obstruction is suspected by the clinical presentation and confirmed by echocardiography. Chest radiography typically shows the nonspecific findings of mild cardiomyopathy and a mild to moderate increase in pulmonary vascular markings.

Management of these infants with left ventricular outflow obstruction is similar and focuses on stabilization of the airway, breathing, and circulation. These children should be intubated and intravenous access should be established as rapidly as possible. The closure of the ductus arteriosus should be reversed, when possible, by initiation of a continuous infusion of prostaglandin E1(PGE1).35,116-118 Adverse effects that may be anticipated include apnea, fever, hypotension, and seizures. Once the ductus arteriosus is reopened, a delicate balance between systemic and pulmonary circulation must be maintained. It is optimal to allow low oxygen saturations, which increases pulmonary vascular resistance, limiting the pulmonary blood flow and enhancing systemic perfusion. Any child with metabolic acidosis should be cautiously corrected with sodium bicarbonate to a pH of 7.25 to 7.3. Dopamine may also be required to improve ionotropic function.

Children with coarctation of the aorta and critical aortic stenosis require surgical correction following medical stabilization. The child with HLHS may undergo one of three treatment options: no treatment, surgical palliation with a stage I Norwood procedure, or cardiac transplantation.35 Survival following the Norwood procedure is as high as 70% in some centers, with these children requiring subsequent staged repairs (hemi-Fontan and then modified Fontan). Organ availability is the greatest obstacle to cardiac transplantation. Of patients who received a transplanted heart at one center, the actuarial survival rate at one month was 91%, at one year 84%, and at five years 76%.119

Pulmonary Overcirculation (Left-to-Right Shunt Lesions). Children with left-to-right shunt lesions more commonly present with signs of pulmonary overcirculation rather than cyanosis or shock.36,118 As the gradual decrease in pulmonary vascular resistance occurs, these children develop a progressive increase in their left-to-right shunt. The most common lesions that may be associated with this type of pulmonary overcirculation include a large ventricular septal defect (VSD), an atrioventricular septal defect, or a large patent ductus arteriosus. Children with a large VSD are initially managed medically (muscular defects tend to undergo spontaneous closure more often than perimembranous defects), but if the defect fails to close or the child has significant failure to thrive, surgical repair is indicated. Children with atrioventricular septal defects require medical stabilization followed by surgical correction. Approximately 50% of children with Trisomy 21 (Down syndrome) will have congenital heart disease and of these up to 40% will have a form of an atrioventricular canal defect. All children with Trisomy 21 should be evaluated by a cardiologist shortly after birth.120 Children with a large patent ductus arteriosus require medical stabilization followed by surgical ligation of the ductus arteriosus.

Coronary Anomalies. The anomalous left coronary artery (ALCA) that arises arises from the pulmonary artery relies on the initial high pulmonary vascular pressure and resistance for perfusion of the coronary bed.37,121 In the neonate, the pulmonary artery pressure and resistance decreases, which leads the myocardium to become dependent on collateral circulation. This leads to subendocardial and papillary muscle ischemia and subsequent myocardial infarction and mitral valve regurgitation. As the heart loses muscle function and volume overload ensues from the regurgitant mitral valve, profound CHF occurs. It is important to differentiate this disease process from idiopathic and viral cardiomyopathy. There is a distinct ECG pattern associated with the presence of an anomalous left coronary artery. One group identified three ECG variables that best discriminated ALCA from myocarditis/dilated cardiomyopathy, including Q wave width in lead I, and Q wave depth and ST segment amplitude in lead aVL.122 The anomalous left coronary artery is successfully treated surgically, with the vast majority of children regaining excellent ventricular function within months of reimplantation.


There are multiple causes of CHF and cardiogenic shock in the pediatric patient. When cardiac output becomes inadequate to maintain systemic perfusion commensurate with the requirements of metabolizing tissues, the body responds with a variety of adaptive or compensatory mechanisms. At times these mechanisms may become maladaptive. Advanced heart failure is therefore a dynamic state in which numerous mechanical, molecular, immunologic, ischemic, proarrhythmic, and vascular forces contribute to symptoms and continuing deterioration. Recognition of these processes in the individual patient directs therapy or may even enable regression of myocardial dysfunction.


1. McConnell MS, Perkin RM. Shock States. In: Fuhrman BP, Zimmerman JJ (eds). Pediatric Critical Care. St. Louis CV Vosby Co.; 1998:293-306.

2. O’Laughlin MP. CHF in children. Pediatr Clin North Am 1999;46:263-273.

3. Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med 1999;341:577-585.

4. Benedict CR. Neurohumoral aspects of heart failure. Cardiol Clin 1994;12:9-19.

5. Baig MK, Mahon N, McKenna WJ, et al. The pathophysiology of advanced heart failure. Heart Lung 1999;28:87-101.

6. Hollenberg SM, Kavinsky CJ, Parillo JE. Cardiogenic Shock. Ann Intern Med 1999;131:47-59.

7. Narula J, Kharbandu S, Khan B. Apoptosis and the heart. Chest 1997;112:1358-1362.

8. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996;334:1349-1355.

9. Westaby S, Franklin O, Burch M. New developments in the treatment of cardiac failure. Arch Dis Child 1999;81:276-277.

10. O’Connor CM, Gattis WA, Swedberg K. Current and novel pharmacologic approaches in advanced heart failure. Heart and Lung 1999;28:227-239.

11. Konstam MA, Remme WJ. Treatment guidelines in heart failure. Progress in Cardiovascular Diseases 1998;41(Supp 1):65-72.

12. Frishman WH. Carvedilol. N Engl J Med 1998;339:1759-1765.

13. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-717.

14. Weber KT. Aldosterone and spironolactone in heart failure. N Engl J Med 1999;341:753-755.

15. Richards AM, Nicholls MG. Aldosterone antagonism in heart failure. Lancet 1999;354:789-790.

16. Goodfriend TL, Elliott ME, Catt KJ. Angiotensin receptors and their antagonists. N Engl J Med 1996;334:1649-1654.

17. Pitt B. Blockade of the renin-angiotensin system. Cardiol Clin 1994;12:101-113.

18. Brown NJ, Vaughan DE. Angiotensin-converting enzyme inhibitors. Circulation 1998;97:1411-1420.

19. Levin ER, Garnder DG, Samson WK. Natriuretic peptides. N Engl J Med 1998;339:321-328.

20. Luscher TF. The endothelium and cardiovascular disease – A complex relation. N Engl J Med 1994;330:1081-1083.

21. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002-2012.

22. Levin ER. Endothelins. N Engl J Med 1995;333:356-363.

23. Pacher R, Stanek B, Hulsmann M, et al. Prognostic impact of big endothelin-1 plasma concentrations compared with invasive hemodynamic evaluation in severe heart failure. J Am Coll Cardiol 1996;27:633-641.

24. Mann DL, Young JB. Basic mechanisms in CHF: Recognizing the role of proinflammatory cytokines. Chest 1994;105:897-904.

25. Herrera-Garza EH, Stetson SJ, Cubillos-Garzon A, et al. Tumor necrosis factor-a: A mediator of disease progression in the failing human heart. Chest 1999;115:1170-1174.

26. Williams RS. Apoptosis and heart failure. N Engl J Med 1999;341:759-760.

27. Gausch WH. Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction. JAMA 1994;271:1276-1280.

28. Hunter JJ, Chien KR. Signaling pathways for cardiac hypertrophy and failure. N Engl J Med 1999;341:1276-1283.

29. Weinberger HD. Diagnosis and treatment of diastolic heart failure. Hospital Practice 1999;34:115-126.

30. Grossman W. Diastolic dysfunction in CHF. N Engl J Med 1991;325:1557-1564.

31. Solaro RJ, Rarick HM. Troponin and tropomyosin: Proteins that switch on and tune in the activity of cardiac myofilaments. Circ Res 1998;83:471-480.

32. Katus HA, et al. Proteins of the troponin complex. Laboratory Medicine 1992;23:311-317.

33. Boder GS, Oakeley AE, Allen PD, et al. Troponin I phosphorylation in the normal and failing adult human heart. Circulation 1997; 96:1445-1500.

34. Barst RJ. Recent advances in the treatment of pediatric pulmonary artery hypertension. Pediatr Clin North Am 1999;46:331-345.

35. Fedderly RT. Left ventricular outflow obstruction. Pediatr Clin North Am 1999;46:369-383.

36. Driscoll DJ. Left-to-right shunt lesions. Pediatr Clin North Am 1999;46:355-368.

37. Mahle WT. A dangerous case of colic: Anomalous left coronary artery presenting with paroxysms of irritability. Pediatr Emerg Care 1998;14:24-27.

38. Canter CE, Strauss AW. Cardiomyopathies – When to think of congenital causes. Contemporary Pediatrics 1995;12:25-40.

39. Rowley AH, Shulman ST. Kawasaki syndrome. Pediatr Clin North Am 1999;46:313-329.

40. Adams JE III, et al. Cardiac troponin I: A marker with high specificity for cardiac injury. Circulation 1993;88:101-106.

41. Hirsch R, Landt Y, Porter S, et al. Cardiac troponin I in pediatrics: Normal values and potential use in the assessment of cardiac injury. J Pediatr 1997;130:872-877.

42. Woodward GA, Mahle WT, Forkey HC, et al. Sepsis, septic shock, acute abdomen? The ability of cardiac disease to mimic other medical illnesses. Pediatr Emerg Care 1996;12:317-324.

43. Seri I. Cardiovascular, renal, and endocrine actions of dopamine in neonates and children. J Pediatr 1995;126:333-344.

44. Fisher DG, Schwartz PH, Davis AL. Pharmacokinetics of exogenous epinephrine in critically ill children Crit Care Med 1993; 21:111-117.

45. Abdulla R, Young S, Barnes SD. The pediatric cardiology pharmacopoeia. Pediatr Card 1997;18:162-183.

46. Murphy MB, Elliot WJ. Dopamine and dopamine receptor agonists in cardiovascular therapy. Crit Care Med 1990;18:S14-S18.

47. Gollub SB, Elkayam U, Young JB, et al. Efficacy and safety of a short term intravenous infusion of dopexamine in patients with severe CHF: A randomized, double-blind, parallel, placebo-controlled multicenter study. J Am Coll Cardiol 1991;18:383-390.

48. Prielipp RC, MacGregor DA, Butterworth JF, et al. Pharmacodynamics and pharmocokinetics of milrinone administration to increase oxygen delivery in critically ill patients. Chest 1996;109:1291-1301.

49. Lawless ST, Zaritsky A, Miles M. The acute pharmacokinetics and pharmacodynamics of amrinone in pediatric patients. J Clin Pharmacol 1991;31:800.

50. Chang AC, Atz AM, Wernovsky G, et al. Milrinone: Systemic and pulmonary hemodynamic effects in neonates after cardiac surgery. Crit Care Med 1995;23:1907-1914.

51. Visser FC, Visser CA. Current controversies with ACE inhibitor treatment in heart failure. Cardiology 1996;87(suppl 1):23-28.

52. Pacher R, Globits S, Watte M, et al. Beneficial hemodynamic effects of prostaglandin E1 infusion in catecholamine-dependent heart failure: Results of a prospective, randomized, controlled study. Crit Care Med 1994;22:1084-1090.

53. Brater DC. Diuretic Therapy. N Engl J Med 1998;339:387-395.

54. Pihkala J, Nykanen D, Freedom RM, et al. Interventional cardiac catheterizaiton. Pediatr Clin North Am 1999;46:441-464.

55. Sacchetti A, Moyer V, Baricella R, et al. Primary cardiac arrhythmia in children. Pediatr Emerg Care 1999;15:95-98.

56. Horton LA, Mosee S, Brenner J. Use of the electrocardiogram in a pediatric emergency department. Arch Pediatr Adolesc Med 1994;148:184-188.

57. Case CL. Diagnosis and treatment of pediatric arrhythmias. Pediatr Clin North Am 1999; 46:347-354.

58. O’Connor BK, Dick M. What every pediatrician should know about supraventricular tachycardia. Pediatr Ann 1991;20:368-376.

59. Robinson B, Anisman P, Eshaghpour E. Is that fast heartbeat dangerous? Contemporary Pediatrics 1996;13:52-85.

60. Kugler JD, Danford DA. Management of infants, children, and adolescents with paroxysmal supraventricular tachycardia. J Pediatr 1996;129:324-338.

61. Losek JD, Endom E, Dietrich A, et al. Adenosine and pediatric supraventricular tachycardia in the emergency department: Multicenter study and review. Ann Emerg Med 1999;33:185-191.

62. Ng GA, Martin W, Rankin AC. Imaging of adenosine bolus transit following intravenous administration: Insights into antiarrhythmic efficiency. Heart 1999;82:163-169.

63. Epstein ML, Kiel EA, Victorica BE. Cardiac decompensation following verapamil therapy in infants with supraventricular tachycardia. Pediatrics 1985;75:737-740.

64. Garland JS, Berens RJ, Losek JD, et al. An infant fatality following verapamil therapy for supraventricular tachycardia: Cardiovascular collapse following intravenous verapamil. Pediatr Emerg Care 1985; 1:198-200.

65. Morady F. Radio-frequency ablation as treatment for cardiac arrhythmias. N Engl J Med 1999;340:534-543.

66. Lashus AG, Case CL, Gillette PC. Catheter ablation treatment of supraventricular tachycardia-induced cardiomyopathy. Arch Pediatr Adolesc Med 1997;151:264-266.

67. Lee KJ, McCrindle WB, Bohn DJ, et al. Clinical outcomes of acute myocarditis in childhood. Heart 1999;82:226-233.

68. Zales VR, Wright KL. Endocarditis, pericarditis, and myocarditis. Pediatr Ann 1997;26:116-121.

69. Nakagawa M, Sato A, O Kagawa H, et al. Detection and evaluation of asymptomatic myocarditis in school children. Chest 1999;116:340-345.

70. McCarthy RE, Boehmer JP, Hruban RH, et al. Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Engl J Med 2000;342:690-695.

71. Hoyer MH, Fischer DR. Acute myocarditis simulating myocardial infarction in a child. Pediatrics 1991;87:250-253.

72. Kawai C. From myocarditis to cardiomyopathy: Mechanisms of inflammation and cell death. Circulation 1999;99:1091-1100.

73. Checchia P, et al. Myocardial injury in children with respiratory syncytial virus infection. Pediatrics 1998;102:706.

74. Lange LG, Schreiner GF. Immune mechanisms of cardiac disease. N Engl J Med 1994;330:1129-1135.

75. Lauer B, Niederan C, Kuhl U, et al. Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol 1997;30:1354-1359.

76. Mason JW, O’Connell JB, Herskowitz A, et al. A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med 1995;333:269-275.

77. Ino T, Okabo M, A Kimoto K, et al. Corticosteroid therapy for ventricular tachycardia in children with silent lymphocytic myocarditis. J Pediatr 1995;126:304-308.

78. Parker MM. Myocardial dysfunction in sepsis: Injury or depression. Crit Care Med 1999;27:2035-2036.

79. Parrillo JE, Burch C, Shelhamer JH, et al. A circulating myocardial depressant substance in humans with septic shock. J Clin Invest 1985;76:1539-1553.

80. Kumar A, Thota V, Dee L, et al. Tumor necrosis factor-alpha and interleukin-1 beta are responsible for depression of in vitro myocardial cell contractility induced by serum from humans with septic shock. J Exp Med 1996;183:949-958.

81. Kumar A, Brar R, Wany R, et al. Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility. Am J Physiol 1999;276:R265-R276.

82. Turner A, Tsamitros M, Bellomo R. Myocardial cell injury in septic shock. Crit Care Med 1999;27:1775-1780.

83. Melish ME. Kawasaki Syndrome. Pediatrics in Review 1996; 17:153-162.

84. Bradley DJ, Glode MP. Kawasaki disease: The mystery continues. West J Med 1998;168:23-24.

85. Burns JC, Mason WH, Glode MP, et al. Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease. J Pediatr 1991;118:680-686.

86. Taubert KA, Shulman ST. Kawasaki disease. Am Fam Physician. 1999;59:3093-3102.

87. Laupland KB, Davies HD. Epidemiology, etiology, and management of Kawasaki disease: State of the art. Pediatr Cardiol 1999;20:177-183.

88. Pfafferott C, Wirtzfeld A, Permanetter B. Atypical Kawasaki syndrome: How many symptoms have to be present? Heart 1997;78:619-621.

89. Rosenfeld EA, Corydon KE, Shulman ST. Kawasaki disease in infants less than one year of age. J Pediatr 1995;126:524-529.

90. Burns JC, Wiggins JW, Toews WH, et al. Clinical spectrum of Kawasaki disease in infants younger than 6 months of age. J Pediatr 1986;109:759-763.

91. Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997;337:1512-1523.

92. McConnell ME, Hannon DW, Steed RD, et al. Fatal obliterative coronary vasculitis in Kawasaki disease. J Pediatr 1998;133:259-261.

93. Pahl E. Kawasaki disease: Cardiac sequelae and management. Pediatr Ann 1997;26:112-115.

94. Kato H, Ichinose E, Kawasaki T. Myocardial infarction in Kawasaki disease: Clinical analyses in 195 cases. J Pediatr 1986;108:923-927.

95. Mavrondis C, et al. Pediatric coronary artery bypass for Kawasaki, congenital, post arterial switch, and iatrogenic lesions. Ann Thorac Surg 1999;68:506-512.

96. Checchia P, et al. Cardiac transplantation for Kawasaki disease. Pediatrics 1997;100:695-699.

97. Checchia P, et al. Cardiac troponin I measurements in the acute phase of Kawasaki disease. Proceedings: The Sixth International Kawasaki Disease Symposium. 1999.

98. Terai M, Shulman ST. Prevelance of coronary artery abnormalities in Kawasaki disease is highly dependent on gamma globulin dose but independent of salicylate dose. J Pediatr 1997;131:888-893.

99. Newburger JW. Treatment of Kawasaki disease: Corticosteorids revisited. J Pediatr 1999;135:411-413.

100. Shinobara M, Sone K, Tomomasa T, et al. Corticosteroids in the treatment of the acute phase of Kawasaki disease. J Pediatr 1999;135:465-469.

101. Wright DA, Newburger JW, Baker A, et al. Treatment of immune globulin-resistant Kawasaki disease with pulsed doses of corticosteroids. J Pediatr 1996;128:146-149.

102. Dowd MD, Krug S. Pediatric blunt cardiac injury: Epidmiology, clinical features, and diagnosis. J Trauma 1996;40:61-67.

103. Bromberg BI, Mazzaiotti MV, Canterce, et al. Recognition and management of nonpenetrating cardiac trauma in children. J Pediatr 1996;128:536-541.

104. Prete R, Chilcott M. Blunt trauma to the heart and great vessels. N Engl J Med 1997;336:626-632.

105. Greenberg MD, Rosen. Evaluation of the patient with blunt chest trauma. Emerg Med Clinc North Am 1999;17:51-62.

106. Towbin JA. Pediatric myocardial disease. Pediatr Clin North Am 1999; 46:289-308.

107. Cetta F, O’Leary PW, Seward JB, et al. Idiopathic restrictive cardiomyopathy in childhood: Diagnostic features and clinical course. Mayo Clin Proc 1995;70:634-640.

108. Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. N Engl J Med 1994;331:1564-1575.

109. Gottesman GS, Hoffman JW, Vogler C, et al. Hypertrophic cardiomyopathy in a newborn infant. J Pediatr 1999;134:114-118.

110. Kelly DP, Strauss AW. Inherited cardiomyopathies. N Engl J Med 1994;330:913-919.

111. Tyni T, Pihko H. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Acta Pediatr 1999;88:237-245.

112. Depre C, Vanoverschelde J, Taeqtmeyer H. Glucose for the heart. Circulation 1999;99:578-588.

113. Mathur A, Sims HF, Gopalakrishman D, et al. Molecular heterogeneity in very long-chain Acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death. Circulation 1999;99:1337-1343.

114. Spirito P, Seidman CE, McKenna WJ, et al. The management of hypertrophic cardiomypathy. N Engl J Med 1997;336:775-785.

115. Nagueh SF, Lakkis NM, Middleton KJ, et al. Doppler estimation of left ventricular filling pressure in patients with hypertrophic cardiomyopathy. Circulation 1999;99:254-261.

116. Perkin RM, McConnell MS. Unusual causes of pediatric shock: Diagnostic and management pearls to improve patient outcomes. Pediatr Emerg Med Reports 1996;1:53-64.

117. Swift JD, Perkin RM, Pickren JS et al. Evaluation and management of children with hypertensive emergencies. Pediatr Emerg Med Reports 1998;3:39-50.

118. Mulla N, Chinnock R. Pediatric cardiac emergencies: Managing children with CHF, hypercyanotic spells and heart transplants in the ED. Pediatr Emerg Med Reports 1996;1:13-20.

119. Razzouk AJ, Chinnock RE, Gundry SR, et al. Transplantation as a primary treatment for hypoplastic left heart syndrome. Ann Thorac Surg 1998;62:1-8.

120. Amark K, Sunnegard H. The effect of changing attitudes to Downs syndrome in the management of complete atrioventricular septal defects. Arch Dis Child 1999;81:151-154.

121. Berger S, Dhala A, Friedberg DZ. Sudden cardiac death in infants, children, and adolescents. Pediatr Clin North Am 1999;46:221-234.

Physician CME Questions

33. All of the following are common causes of CHF in childhood or adolescence except:

A. myocarditis.

B. Kawasaki syndrome.

C. hypolastic left heart syndrome.

D. rheumatic fever.

34. Which of the following are symptoms of CHF in infancy?

A. Poor feeding

B. Increased sweating

C. Recurrent lower respiratory infections

D. Increased respiratory effort with feeding

E. All of the above

35. Which of the following, when elevated, is a highly sensitive and specific indicator of myocardial injury?

A. Creatine phosphokinase

B. Troponin I

C. pH

D. Troponin IV

36. Which of the following makes digitalis glycosides an undesirable agent during the acute management of cardiogenic shock?

A. It augments myocardial contractibility.

B. Short half-life

C. Pulmonary elimination

D. Narrow therapeutic to toxic ratio

37. The most common cause of bradycardia in an infant is:

A. congenital heart block.

B. hypoxemia.

C. congenital heart disease.

D. Kawasaki syndrome.

38. A 3-week-old child presents with a heart rate of 300 beats/min, normal oxygenation, and a blood pressure of 100/60. Initial therapy would be:

A. adenosine.

B. verapamil.

C. synchronized electrical cardioversion.

D. flecainide.

39. The most common viral cause of myocarditis is:

A. coxsackie B.

B. respiratory syncytial virus.

C. parainfluenzae.

D. adenovirus.

40. Which of the following ECG patterns is not associated with the presence of an anomalous left coronary artery?

A. Q wave width in lead I

B. Q wave depth in lead aVL

C. ST segment amplitude in lead II

D. ST segment amplitude in lead aVL