This a 6 week old female who presents to the emergency room with the chief complaints of lethargy, poor feeding, and respiratory distress. She was well until 2 weeks prior to presentation when she developed a febrile illness with cough, rhinorrhea, and emesis. She subsequently developed progressive respiratory distress. Her parents report that she sweats a lot on her forehead when feeding. Her parents have also noted her to be increasingly lethargic, with tachypnea, and retractions.
She is the product of a G3P2, full term, uncomplicated pregnancy. Delivery was unremarkable except for meconium stained fluid. She did well at delivery and in the nursery. Her pediatric follow-up has been poor.
Exam: VS T 36.8, RR 72, HR 160, BP 92/68. Oxygen saturation in room air is 99%. She is a mildly cachetic, acyanotic infant who was pale, lethargic, and tachypneic, with mild to moderate subcostal and intercostal retractions. HEENT exam is unremarkable. Neck is supple without lymphadenopathy. Her skin is clear with no rashes or other significant skin lesions. Her lungs have scattered crackles with slightly decreased aeration in the left lower lobe. The precordium is mildly active. Her heart is of regular rate and rhythm, with a Grade II/VI holosystolic murmur at the mid lower left sternal border with radiation to the cardiac apex. The S1 is normal and the S2 is prominent. An S4 gallop is noted at the cardiac apex. There are no rubs or valve clicks. Her abdomen is soft, non-distended, and non-tender. The liver edge is palpable 3 to 4 cm below the right costal margin. There are no palpable masses or splenomegaly. Bowel sounds are hypoactive. Her extremities are symmetric and cool, with peripheral pulses 1+/4+ in all extremities with no radial-femoral delay. The capillary refill is 4 to 5 seconds (delayed).
A chest x-ray shows moderate cardiomegaly with a moderate degree of pulmonary edema. There are no pleural effusions. A 12 lead electrocardiogram shows a sinus tachycardia, normal PR and QTc intervals, and a left axis deviation. Voltage evidence of biventricular hypertrophy is present. No significant Q-waves or ST segment changes are noted. An echocardiogram reveals a large perimembranous ventricular septal defect with non-restrictive left to right shunting. All cardiac chambers are dilated. Left ventricular contractility is at the lower range of normal. There is no pericardial effusion.
She is admitted to the hospital and loaded with digoxin, and also started on diuretics and afterload reduction. Her symptoms improve and she is discharged on 24 calorie/ounce formula due to poor weight gain on standard 20 calorie/ounce formula. She continues to have poor weight gain on higher caloric density formula and continues to have symptoms of heart failure on medical management. She is referred for surgical correction of the ventricular septal defect at 6 months of age.
Heart failure (or congestive heart failure) is defined as the inability of the myocardium to meet the metabolic requirements of the body. This may arise as a consequence of excessive work or volume load imposed on the myocardium, primary alterations in myocardial performance, metabolic derangements, or a combination of these elements. Heart failure leads to a neurohormonal response, which contributes to the symptoms associated with heart failure and increased morbidity and mortality.
In the pediatric age group, the underlying abnormality is often a large left to right intracardiac shunt, most commonly a ventricular septal defect, or an obstructive lesion, such as an aortic coarctation. In contrast to heart failure in adults, pediatric patients often have normal left ventricular function. Exceptions to this may include patients with myocarditis, dilated cardiomyopathy, ischemia-reperfusion injury following cardiopulmonary bypass, or a congenital coronary artery anomaly.
Heart failure can be classified into 4 functional classes:
1) Volume overload: Large left to right shunts, valvular insufficiency, or systemic arteriovenous fistulae.
2) Pressure overload: Outflow or inflow obstruction.
3) Disorders affecting the inotropic state: Myocarditis, electrolyte disturbances, hypoxia, acidosis, various cardiomyopathies, coronary artery lesions, endocrine or metabolic derangements, septic shock, toxic shock.
4) Alterations in the chronotropic state: Supraventricular or ventricular tachycardia, complete heart block.
To better understand congestive heart failure in pediatric patients, especially infants, one must have an understanding of the developing heart. Fetal and newborn hearts function at a high diastolic volume (high on the Frank-Starling contractility curve) and therefore have limited diastolic reserve. As afterload or volume load on the young heart increases, there is relatively limited ability to develop additional contractility. This is thought to be, at least in part, due to a relative paucity of the contractile mass in the developing heart, incomplete neural innervation, and low norepinephrine stores. An increase in heart rate is the dominant mechanism to increase cardiac output in all patients with heart failure, but this is especially important in infants and younger children.
There are several neurohormonal and biochemical derangements in congestive heart failure, which perpetuates its symptomatology and leads to chronic heart failure. Alterations in calcium handling occur within the myocardium secondary to impairment of sarcoplasmic reticulum function, anaerobic metabolism, and developing acidosis. The fall in cardiac output and changes in regional circulation accompanying heart failure leads to an activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system. Activation of these systems can lead to direct myocardial toxicity, peripheral vasoconstriction, and increased renal sodium and water reabsorption. Cardiac beta-receptors are down-regulated causing a reduced inotropic response to beta-adrenergic stimulation. Myocardial remodeling including hypertrophy, cell injury, and fibrosis, interferes with normal myocyte function and increases susceptibility to arrhythmias.
Clinical findings in congestive heart failure can be broken down into signs and symptoms of impaired myocardial performance, pulmonary congestion, and systemic venous congestion.
The signs and symptoms of impaired myocardial performance include:
1) Cardiomegaly: Represents ventricular hypertrophy and/or dilatation.
2) Tachycardia: Mediated by an increased adrenergic drive. This is the body's attempt to improve cardiac output and oxygen delivery.
3) Gallop rhythm: Represents either increased flow across the AV valves in the presence of a large left to right shunt, or rapid filling of a non-compliant ventricle.
4) Atrioventricular valve regurgitation: Due to ventricular dilatation, decreased ventricular contractility, and at times infarction of papillary muscles.
5) Decreased or increased arterial pulsations depending on the lesion leading to heart failure. Extremities are usually cool, with weak peripheral pulses secondary to systemic vasoconstriction. Arterial pulses may be bounding with lesions causing a large diastolic runoff as seen with large arteriovenous fistulas, patent ductus arteriosus, or an aortopulmonary window (other aorto-pulmonary communication).
6) Growth failure: A consequence of decreased systemic perfusion and raised energy requirements.
7) Diaphoresis (especially with feeding): Represents increased adrenergic activity.
The signs and symptoms of pulmonary congestion include:
1) Tachypnea: Secondary to interstitial and bronchiolar edema.
2) Wheezing: Due to external compression on airways, e.g., from an enlarged left atrium.
3) Rales: Implies the process is severe, with involvement of the alveolar spaces.
4) Mild cyanosis: Secondary to impaired gas exchange (pulmonary edema).
7) Persistent cough.
The signs and symptoms of systemic venous congestion include:
1) Hepatomegaly: This may be associated with a mild elevation in the bilirubin level and liver function tests.
2) Jugular venous distention: Seen only in older children and adolescents.
3) Peripheral edema: Facial edema is most common in infants and children. Extremity edema may be seen in older children and adolescents. Ascites is usually only seen in older age groups with very advanced heart failure.
It must be remembered that the signs and symptoms of congestive heart failure in pediatric patients with congenital heart disease will begin at varying ages depending on whether the patient has a ductal dependent lesion or a left to right shunt. Patients with large left to right shunts, such as those with a large ventricular septal defect or atrioventricular canal, may not present with symptoms until 4 to 6 weeks of age when the pulmonary vascular resistance has decreased sufficiently to allow development of interstitial and alveolar pulmonary edema. Ductal dependent lesions (e.g., hypoplastic left heart syndrome, aortic coarctation, pulmonary atresia) most often will present in the newborn period as cyanosis. Occasionally these patients will not present until 1 week or more of life after the ductus arteriosus has closed and the patient presents in a shock-like state.
There are several laboratory studies utilized in the diagnosis and assessment of congestive heart failure in the pediatric patient. A chest x-ray is one of the more useful studies in the initial assessment of a patient with suspected heart failure. This allows evaluation of heart size and contour, pulmonary vascularity, presence of pleural effusions, abdominal and cardiac situs (i.e., whether situs inversus or dextrocardia is present), aortic arch sidedness (occasionally, since the X-ray sign of a right or double aortic arch is very subtle), and lung expansion. An electrocardiogram is most useful in instances where heart failure is secondary to an arrhythmia, anomalous coronary artery, or myocarditis. Echocardiography is useful in all patients with heart failure to assess for structural anomalies, cardiac function, and cardiac chamber sizes. Since filling chamber enlargement is one of the initial abnormalities in heart failure, the earliest sign of heart failure will be cardiomegaly (before pulmonary edema) on chest x-ray (CXR), and the earliest sign of heart failure on an echocardiogram will be enlargement of the filling chambers (left atrium for left sided heart failure, right atrium for right sided heart failure) and/or decreased ventricular contractility.
Other useful laboratory studies may include an arterial blood gas (in very ill patients), serum electrolytes (including calcium and magnesium levels), and a complete blood count (to help rule out the presence of anemia). Pediatric patients with heart failure will often have a mild hyponatremia, resulting from increased renal water retention rather than a true negative sodium balance. Mild hyponatremia, therefore, does not need to be treated. Administering supplemental sodium may actually worsen the patient's fluid retention and heart failure.
The major goals in the treatment of congestive heart failure include relief of pulmonary and systemic venous congestion, improvement of myocardial performance, and reversal of the underlying disease process (if possible). Historically, digoxin has been one of the most widely used pharmacologic agents in the treatment of heart failure in infants and children. In addition to its positive inotropic effect, digoxin exerts beneficial effects via sympathetic-inhibiting actions via baroreceptor, central, and adrenergically mediated mechanisms. Other inotropic agents used in the treatment of acute heart failure include dopamine, dobutamine, and phosphodiesterase inhibitors (milrinone and amrinone).
Diuretic therapy plays an integral part in the treatment of pediatric patients with congestive heart failure. The three most commonly utilized classes of diuretics include the loop diuretics (furosemide-Lasix, bumetanide-Bumex), potassium sparing diuretics (spironolactone), and thiazide diuretics (hydrochlorothiazide). The benefits of diuretic therapy include improvement in systemic, pulmonary, and venous congestion. Spironolactone may exert additional beneficial effects by attenuating the development of aldosterone-induced myocardial fibrosis, and catecholamine release. This currently remains under investigation. Potential complications of diuretic therapy include volume contraction, electrolyte abnormalities (hyponatremia, hypo- or hyperkalemia, hypochloremia), and metabolic alkalosis or acidosis. Electrolyte balance should be carefully monitored, especially during aggressive diuresis, as the failing myocardium is more sensitive to arrhythmias induced by electrolyte dyscrasias.
The use of afterload reduction is one of the newer concepts in the management of heart failure. Relaxation of arteriolar smooth muscle helps to decrease the systemic vascular resistance and augment cardiac output. Venodilatation exerts its effect on preload by increasing venous capacitance, thus lowering filling pressures. The angiotensin-converting enzyme (ACE) inhibitors decrease systemic vascular resistance and have a favorable effect on the body's neurohormonal response to heart failure and cardiac remodeling. Several adult studies have demonstrated improved symptoms and survival with the use of ACE inhibitors in patients with heart failure. Their role in the treatment of heart failure in children is less well defined. They are thought to have beneficial hemodynamic effects in patients with decreased systemic ventricular contractility, and those patients with large left to right shunts. ACE inhibitors should be started at a low dose then gradually increased, especially in infants. The phosphodiesterase inhibitor milrinone is often used in the intensive care setting of acute, new onset systemic ventricle dysfunction (e.g., myocarditis), and in the immediate post-operative setting following cardiopulmonary bypass (ischemia-reperfusion injury).
Treatment of chronic heart failure with the use of beta-blockers, such as carvedilol, is now an accepted practice in the adult population. Several studies have shown a reduction in both hospitalization and mortality. The beneficial effects are thought to be derived from the reversal of myocardial dysfunction occurring secondary to sympathetic activation and down-regulation of beta-adrenergic receptors, coronary artery vasodilatation, and possible anti-oxidant effects. The present state of knowledge for use in the pediatric population is based on anecdotal experience from unblinded, non-randomized studies of small sample size. Therefore, beta-blockers should be used with caution in infants and children with chronic heart failure until more experience is gained with these agents.
Other non-pharmacologic therapeutic measures that may be considered in patients with congestive heart failure include elevation of the head and shoulders to 30 to 45 degrees, bedrest, dietary changes (higher caloric intake, and a low sodium diet in older children and adolescents), packed red blood cell transfusion, iron supplementation, and the administration of supplemental oxygen. It must be remembered that oxygen is a pulmonary vasodilator, therefore in patients with known large left to right shunt lesions, administration of oxygen will decrease pulmonary vascular resistance, increase the degree of left to right shunting, and worsen the degree of pulmonary edema.
For acute pulmonary edema, several treatment methods are used which help to understand the underlying pathophysiology. Within the alveolus, the major force which holds water in the interstitial and vascular space is the plasma oncotic pressure. The force attempting to push water out into the alveolar space is the hydrostatic fluid pressure. Pulmonary edema basically occurs when the hydrostatic force pushing the fluid out, exceeds the oncotic force holding the fluid in. The air pressure within the alveolus has some effect as well. It is slightly positive (pushing the fluid out of the alveolus into the interstitium) when we exhale, since we exhale against partial resistance. The air pressure is negative when we inhale (which favors drawing fluid into the alveolus). To treat acute pulmonary edema, the hydrostatic force pushing the fluid out into the alveolar space can be reduced by reducing back pressure (preload and afterload reduction) by the following therapeutic measures: 1) diuresis, 2) vasodilation (increases vascular capacitance), and 3) augmenting contractility (reduces back pressure). An alternative means to treat acute pulmonary edema is to increase the pressure within the alveolus to counterbalance the excessive hydrostatic pressure with positive pressure ventilation via mask CPAP (continuous positive airway pressure) or through an endotracheal tube with a ventilator. This literally pushes the fluid out of the alveolus back into the interstitium and vascular space. The most important parameter to increase to reverse pulmonary edema is the PEEP, which is the positive end-expiratory pressure. With a ventilator, inspiration is under positive pressure driving the fluid out of the alveolar space. However, during exhalation, the positive pressure declines permitting the fluid to return. A high PEEP (10 to 20 mmHg) will prevent this and keep the lungs clear until other measures can be taken to control the pulmonary edema.
Other measures of historical interest only, include phlebotomy (to balance the humors) and rotating tourniquets. These measures are not as effective as the other therapies mentioned.
In patients with heart failure, the treatment plan should ultimately deal with the underlying condition. This may include surgical repair of a shunt lesion or valvular anomaly, interventional cardiac procedures, radiofrequency ablation, control of hypertension, anti-inflammatory treatment for rheumatic carditis, pacemaker implantation, carnitine supplementation, adenoidectomy and weight loss for patients with airway obstruction, pulmonary hypertension and right heart failure, or cardiac transplantation.
The prognosis of the pediatric patient with heart failure depends largely on the primary condition. In those patients with large left to right shunts, such as a ventricular septal defect, medical therapy will often maintain the patient in a well compensated state until the VSD spontaneously begins to close or it is decided the defect needs to be surgically repaired. Repair of congenital heart defects with large left to right shunts (VSD, ASD, AV canal), or those with valvular abnormalities carry a low surgical mortality in the hands of an experienced pediatric cardiovascular surgeon. The majority of patients with myocarditis, who present in heart failure, will improve with medical management. Patients with cardiomyopathies or hypoplastic left heart syndrome will occasionally require a heart transplant as a last resort. In these cases, the prognosis is much more guarded. Those patients with arrhythmia induced heart failure will often respond well to anti-arrhythmic therapy and/or electrophysiology study and radiofrequency ablation.
1. What is the most common congenital heart defect with a left to right shunt causing congestive heart failure in the pediatric age group?
. . . . . a. Atrial septal defect
. . . . . b. Atrioventricular canal
. . . . . c. Ventricular septal defect
. . . . . d. Patent ductus arteriosus
. . . . . e. Aortopulmonary window
2. True/False: Jugular venous distention is a common finding in infants with heart failure.
3. What is the most likely age an infant with a large ventricular septal defect will begin manifesting symptoms of congestive heart failure?
. . . . . a. 1 day
. . . . . b. 1 week
. . . . . c. 1 month
. . . . . d. 6 months
. . . . . e. 1 year
4. True/False. Administration of supplemental oxygen to a child with a large left to right shunt lesion will help improve the degree of congestive heart failure.
5. What is the dominant mechanism with which infants and young children increase their cardiac output?
. . . . . a. By increasing ventricular contractility
. . . . . b. By increasing heart rate
. . . . . c. By increasing ventricular end-diastolic volume
. . . . . d. By decreasing heart rate
. . . . . e. By increasing respiratory rate
6. True/False: All neurohormonal and sympathetic responses of the body to heart failure are beneficial.
7. The earliest sign of congestive heart failure on a chest X-ray is:
. . . . . a. Increased heart size.
. . . . . b. Kerley B lines.
. . . . . c. Central pulmonary vascular congestion.
. . . . . d. Pulmonary edema.
. . . . . e. Pleural effusion.
1. Fisher DJ, Feltes TF, Moore JW, et al. Management of acute congestive cardiac failure. In: The Science and Practice of Pediatric Cardiology, 2nd edition. 1998, Baltimore: Williams & Wilkins, pp. 2329-2343.
2. Park MK. Pediatric Cardiology for Practitioners, 3rd edition. 1996, St. Louis: Mosby- YearBook Inc, pp. 401-411.
3. Schwartz SM, Duffy JY, Pearl JM, Nelson DP. Cellular and molecular aspects of myocardial dysfunction. Crit Care Med 2001;29(10 Suppl.):S214-S219.
4. Shaddy RE. Optimizing treatment for chronic congestive heart failure in children. Crit Care Med 2001;29(10 Suppl.):S237-S240.
5. Wessel DL. Managing low cardiac output syndrome after congenital heart surgery. Crit Care Med 2001;29(10 Suppl.):S220-S230.
Answers to questions
1.c, 2.False, 3.c, 4.False, 5.b, 6.False, 7.a