Neonatal cardiovascular disease significantly contributes to perinatal morbidity and mortality.1 Of the 20,000 infants born annually with congenital heart disease in the United States, about one half will be seriously ill during the first year of life. Many will become symptomatic early in the neonatal period. Thus, a cardiac defect must be suspected when one is evaluating a sick neonate. Many forms of congenital cardiac defects, such as an atrial septal defect, do not become hemodynamically significant until later in life. Some defects go unnoticed throughout life. This article will concentrate on some of the cardiovascular abnormalities that may present problems in the neonatal period.
The fetal circulation is characterized by low resistance of the systemic and placental circulations and high resistance of the pulmonary circulation, with several communications existing between circuits.1-3
Well-oxygenated placental blood enters the right atrium, with one half shunted across the foramen ovale into the left heart, providing fully oxygenated blood to the brain. Superior-vena-caval blood flows across the right atrium into the right ventricle, where it mixes with the remainder of the placental return. Entering the pulmonary artery, this blood meets high vascular resistance, and most of it is diverted across the patent ductus arteriosus to the descending aorta.
At birth, many events occurring almost simultaneously alter resistance of the two circuits and rearrange flow patterns. As the lungs expand with air, pulmonary vascular resistance drops and pulmonary blood flow increases significantly. With clamping of the umbilical cord, both the systemic resistance and left-heart pressures increase. As the leftatrial pressure rises, the foramen ovale functionally closes. Sometime in the first few hours of life, there is also functional closure of the ductus arteriosus. Thus, intercommunication between the pulmonary and the systemic circuits is eliminated, establishing normal postnatal flow patterns.
Vital signs reflect cardiovascular status. Aberrations in heart rate, respiratory rate, or blood pressure may be due to primary cardiovascular disease or secondary to dysfunction of other organ systems.1,2
The average heart rate for full-term infants at rest is 120 beats per minute. In premature infants at rest the rate is slightly higher, averaging 140 beats per minute. During the first week of life there may be substantial variability in the resting heart rate, as well as interbeat variation. Rates from 70 to 180 beats per minute have been recorded in normal infants. Sinus bradycardias and tachycardias are common, and if they exist in the absence of structural cardiac defects or hypoxia, they are benign. The same holds true for atrial or ventricular premature contractions.
The upper limit of normal for the sleeping respiratory rate is 45 per minute in the fullterm infant and 60 per minute in the premature infant. Rates higher than these are considered abnormal, and underlying cardiac, pulmonary, or metabolic problems should be sought.
The normal intra-aortic blood pressure in a full-term infant averages 72/47 mm. Hg and in the premature infant averages 64/39 mm. Hg. Accurate blood-pressure determination in neonates has been facilitated by availability of the Doppler technique. Blood pressures should be ascertained in both upper extremities and one lower extremity. Equality of all three readings rules out the presence of coarctation of the aorta and interrupted aortic arch syndromes. Both systolic and diastolic pressures increase with advancing postnatal age. Systolic readings higher than 90 mm. Hg should be considered significantly elevated and warrant investigation if persistent.
The electrocardiogram, chest x-ray, determination of arterial blood gases, echocardiograph, and cardiac catheterization are among the diagnostic procedures that may be called upon to identify abnormal cardiac anatomy or function.
The neonatal electrocardiogram is a very useful diagnostic tool in any cardiac evaluation.1*3"6 In the neonate, there is a wide range of normal as well as a day-to-day change in the normal pattern, reflecting changing hemodynamics of the perinatal period.
During fetal life the right ventricle is responsible for systemic output at systemic pressures. This burden leads to a disparity in ventricular myocardial development, which is reflected in the ECG of the normal full-term infant as right-ventricular dominance - i.e., right-axis deviation (+90 to +150 degrees), tall R waves, and upright T waves in the right precordial leads. The T waves in the right precordium gradually become negative over the first three days of life as the pulmonary vascular resistance falls and the right-ventricular work load diminishes. As the burden of maintaining systolic output is taken over by the left ventricle, the QRS axis moves leftward (+30 to +90 degrees) over the first month of life. At that time, left-ventricular forces show dominance in the precordial leads, and an adult R/S progression is common and normal.
The premature infant's ECG is more variable than that of a full-term infant. In general, the premature newborn demonstrates less right-ventricular dominance. The postmature infant demonstrates more right-ventricular preponderance than the normal full-term infant. In both the premature and the postmature infant, the progressive changes in QRS axis, T-wave direction, and precordial R/S progression occur as they do in the normal full-term infant.
Despite the wide range of normal findings in neonatal ECGs, there are criteria that can serve as a guide in determining whether an ECG tracing reflects normal cardiac function and anatomy. A P wave greater than 3 mm. in any standard or unipolar lead indicates right-atrial hypertrophy. Left-atrial hypertrophy is represented by a prolonged duration of a P wave to greater than 0.10 second. Any neonatal ECG that maintains extreme rightaxis deviation with tall R waves and upright T waves in the right precordial leads on serial tracing after the fifth day of age may be interpreted as consistent with right-ventricular hypertrophy. Left- ventricular hypertrophy is suggested by the finding of a normal adult QRS axis and precordial R/S progression. A right or left superior axis (0 to -180 degrees), in conjunction with a prolonged PR interval and a RR pattern in the right precordial leads, suggests an endocardial cushion defect.
The chest x-ray in the newborn period is critical in any cardiac evaluation. An anteroposterior (AP) and a lateral film are required for a complete assessment of cardiac size and shape, great-vessel size, shape, and location, lung expansion, clarity, and the degree of pulmonary perfusion.
Examination of these aspects of an x-ray can be difficult in the neonate. Lack of patient cooperation and other technical problems often interfere with film quality, often making it difficult to judge whether or not a study is normal. For example, a poor inspiratory film may give the impression of cardiomegaly when heart size is actually normal. A large thymus superimposed over the cardiac silhouette may give the false impression of massive cardiomegaly. If inspiration is adequate, the heart size should be no greater than 75 per cent of the thoracic width on an AP projection. Lung fields should be clear, with pulmonary vascularity visible around the hilum. Very dark lungs indicate pulmonary hypoperfusion, and excessive vascular markings, especially at the outer third of the lung fields, may represent pulmonary overcirculation and/or congestion. When the cardiac status is assessed, the presence or absence of primary lung disease should be determined.
Arterial blood gas determination is a useful evaluation of cardiopulmonary function.1 Blood gas data can be helpful in differentiating between pulmonary and cardiac disease in the infant with respiratory distress and cyanosis. There are three very common neonatal mechanisms for arterial desaturation. Alveolar hypoventilation is characterized by a low Po2 (< 60 mm. Hg) and increased Pco2 (> 50 mm. Hg). Depending on the degree and duration of hypoxia, the arterial pH may also be low.
A second mechanism for arterial desaturation is right-to-left shunting of blood. This can occur through intracardiac and intrapulmonar^ communications and between major vessels. When right-to-left shunting is present and ventilation is normal, the Po2 is decreased (< 60 mm. Hg) and the Pco2 is normal (35-45 mm. Hg).
The third situation is an imbalance in the ventilation/perfusion ratio. The findings in ventilation/perfusion unevenness are the same as in right-to-left shunting.
The hypoxia test is a useful method for identifying which mechanism is responsible for arterial desaturation, especially when one wants to distinguish between the two mechanisms. After arterial blood gases are obtained in room air, 100 per cent oxygen is delivered to the patient, preferably by nasal prongs. Fifteen minutes later, another arterial blood gas determination is performed. If alveolar hypoventilation is the problem, the Po2 will rise to a level above 300 mm. Hg. If the problem is a right-to-left shunt, the Po2 will not significantly increase. Ventilation/ perfusion disparity will respond with an increase in the Po2 to greater than 300 mm. Hg, but much more slowly than in the case of alveolar hypoventilation. Thus, this test can be helpful in distinguishing between heart and lung disease. However, one must remember that intrapulmonary right-to-left shunting can occur with the respiratory-distress syndrome, when no cardiac lesion is present.
Echocardiography is becoming increasingly useful as a noninvasive technique for evaluating cardiac anatomy. Investigators have now compiled the normal echo pattern for virtually every intracardiac and great-vessel structure.7,8 Abnormal patterns or measurements have been correlated with findings at cardiac catheterization, so that variations from normal can be properly interpreted to represent specific anatomic defects. At present, echocardiography can be used in the assessment of nearly all structural lesions seen in the neonate. Since it is noninvasive and the results are immediately available, this test should be performed on every sick neonate in whom a cardiac defect is suspected.
Cardiac catheterization is the definitive procedure for identifying abnormal cardiac anatomy or function. Since it is stressful - especially in the critically ill neonate - catheterization should be performed only after all other diagnostic procedures have been tried and have failed to provide information necessary for optimal management of the infant.
A catheterization should be performed when the infant is in optimum condition. If congestive heart failure is present, efforts should be made to improve the clinical status by administering a cardiotonic regimen before catheterization. Acidosis and hypoxia should be treated and the infant kept in a thermoneutral environment. A cardiothoracic surgical team should be readily available at the institution where the catheterization is performed, in the event that lifesaving palliative or corrective surgery is immediately required.
Two circumstances that require immediate cardiac catheterization are marked decrease in pulmonary blood flow and significant leftventricular outflow obstruction (aortic stenosis or coarctation of the aorta). These situations are not amenable to medical management, and immediate catheterization followed by appropriate surgical intervention is indicated.
The mortality associated with cardiac catheterization is 6 to 7 per cent in the neonate. This reflects the usually poor clinical status of neonates who require this procedure. The major complications are arrhythmias, myocardial perforation, torn blood vessels, hypotension, hypothermia and acidosis, blood loss, and the hemodynamic effects of infusion of contrast media for associated radiologic procedures. Careful planning and technique can eliminate or minimize these risks. In the sick neonate, sedation should not be used, a thermoneutral environment should be maintained throughout the procedure, and acidosis must be promptly corrected if it develops. The number of angiograms and the amount oí contrast material used should be limited.
Continuous monitoring of the fetal heart rate has made it possible for pediatricians to diagnose a limited number of cardiac problems before birth.2 Fetal tachycardia (180/ minute) or fetal bradycardia (100/minute) in the absence of any obvious cause for fetal distress should arouse suspicion that a congenital arrhythmia or conduction defect may be present.
Various forms of supraventricular tachycardia and complete heart block have been detected through the use of fetal monitoring. If there is a persistent tachycardia or bradycardia before birth, an ECG should be obtained at birth to determine conduction in a more detailed fashion. Complete heart block can occur as an isolated congenital-conduction defect or may be associated with congenitally corrected transposition of the great vessels. This finding may be benign, or it may be associated with anomalies that are hemodynamically significant.
CONGESTIVE HEART FAILURE
Congestive heart failure in infants can have many causes, and an understanding of the underlying physiology may be helpful in recognizing its signs in the neonatal period.
Physiology. Congestive heart failure is caused by either left-ventricular failure or rightventricular failure.
Left-ventricular failure is the result of volume or pressure overload, or primary myocardial disease. As a volume or pressure burden is placed on the left ventricle, the chamber dilates and the muscle hypertrophies in order to increase contractility and maintain cardiac output in the face of increased work; the left ventricle compensates for the hemodynamic aberration. If the process is progressive, contractile force will eventually diminish as the sarcomere stretches past a critical length in accordance with Starling's Law. When this occurs, cardiac failure results.1"3,9
Cardiac output decreases and left-ventricular end-diastolic volume increases, with backlogging and congestion in the pulmonary venous bed. As congestion increases, the hydrostatic pressure within the pulmonary capillary bed exceeds the oncotic pressure, and a transudation of fluid into the interstitium and alveoli occurs. The excessive fluid in the pulmonary bed and interstitium decreases pulmonary compliance and leads to hypoventilation and hypoxia. Occasionally, the process is severe enough to produce frank cyanosis.
Right-ventricular failure results from excessive sustained volume or pressure overload or primary myocardial disease, as it may follow left-ventricular failure or occur independently. Congestion occurs in systemic veins rather than the lungs. In right-heart failure, the problem is compounded by excessive fluid retention. As the right ventricle fails and forward output diminishes, the arterial blood volume decreases. Appropriate physiologic mechanisms are then activated, and there is an increased production of antidiuretic hormone, renin, and aldosterone. The net result is an increase in salt and water retention, which augments the signs of congestive heart failure.
Clinical and laboratory findings. Left-ventricular failure causes tachycardia, tachypnea, dyspnea with feeding, and occasionally mild cynasosis. With severe decompensation, a shocklike picture develops, with thready pulses, hypotension, and poor responsiveness. Right-ventricular failure is usually manifested by hepatomegaly. It is rare to see pitting edema and neck-vein distention in the neonate. Occasionally the dorsum of the hands and feet becomes edematous, having a "doughy" feeling.
The chest x-ray usually demonstrates cardiomegaly with pulmonary vascular congestion. The ECG varies, depending on the cause of congestive heart failure (CHF). Arterial blood gases usually indicate mild desaturation and a mixed respiratory and metabolic acidosis.
Etiology. Congestive heart failure develops in a sequential manner and therefore requires time to become clinically apparent. The time of appearance of congestive heart failure is dependent on the underlying mechanisms (Table 1). If congestive heart failure is present at birth, it is secondary to uterine causes. When it occurs, the underlying problems may include intrauterine tachyarrhythmias and severe anemias - i.e., erythroblastosis fetalis, fetal-placental bleeding, feto-fetal transfusion, and large arteriovenous fistulas.
Congestive heart failure may develop shortly after birth in infants with congenital malformations. Infants born with hypoplastic left-heart syndrome or isolated tricuspid insufficiency often develop signs of heart failure within the first days of life. Congenital structural cardiac lesions become clinically recognizable or apparent with the passage of time. In the first week of life, the lesions most often responsible for CHF are coarctation of the aorta, aortic stenosis, total anomalous pulmonary venous congestion with pulmonary venous obstruction, severe pulmonary stenosis, transposition of the great vessels, with a ventricular septal defect, and hypoplastic left-heart syndrome.
Solitary lesions producing left-to-right shunts, such as ventricular septal defect, are usually not hemodynamically significant in the neonatal period. The increased pulmonary vascular resistance of a full-term infant prevents significant left-to-right shunting. Pulmonary resistance falls to adult levels at about six weeks of age. At that time, the shunt becomes significant and signs of CHF begin to develop. In the premature infant, left-to-right shunting may occur earlier, even in the neonatal period. The pulmonary vascular resistance never reaches the level it does in the full-term infant. Thus, significant shunting and CHF may dominate the clinical picture in a premature infant with a patent ductus arteiosus in the first week of life.
ONSET OF CONGESTIVE HEART FAILURE RELATED TO MECHANISM
Primary myocardial diseases may also be responsible for CHF in the first two weeks of life. These include infectious myocarditis, endocardial fibroelastosis, and Pompe's disease.
Management. Once congestive heart failure is recognized, its cause must be established and appropriate therapy instituted. Heart failure secondary to severe hemolytic anemia should be treated with either a packed red-blood-cell transfusion or partial exchange transfusion. Anemia and CHF secondary to acute bleeding require replacement of whole blood to reexpand intravascular volume. High-output failure secondary to arteriovenous fistula will respond best to ligation of the fistula if it is surgically accessible.
CHF associated with structural malformations should be managed with a cardiotonic regimen and restricted salt and water intake. The basic component oí any cardiotonic regimen is digoxin, which is the most commonly used cardiac glycoside. Digoxin increases myocardial contractility and improves cardiac output. It should be administered by the parenteral route (intramuscularly or intravenously) to assure appropriate absorption. The digitalizing dose for a full-term infant is 40 to 60 micrograms per kilogram. The total dose is divided into three doses and administered over a 16-to-24-hour period. The premature infant should receive 40 /t¿g./kg. as a digitalizing dose, divided into three doses given over 16 to 24 hours. The maintenance dose is onefourth to one-third of the digitalizing dose, given daily in two divided doses. During digitalization and early maintenance therapy, the infant should be closely observed, with frequent (hourly) recording of vital signs and continuous ECG monitoring. The ECG is used to measure digitalis toxicity. The commonest sign of toxicity is bradycardia (rate less than 110/min.). If this occurs, the dose should be reduced.
It is often necessary to add diuretics to the cardiotonic regimen. Rapid diuresis is achieved with such potent agents as furosemide or ethacrynic acid, with the former used more commonly. A dose of 0.5 to 1.0 mg./kg. of furosemide is given intramuscularly or intravenously. The primary action of this drug is inhibition of sodium reabsorption in the loop of Henle.
Serum electrolytes must be monitored daily, especially if digoxin is also being used. Additional potassium may be added to the diet, or spironolactone may be used in order to preserve total body potassium. After stabilization, if chronic administration of diuretics is required to control the signs of CHF, chlorothiazide is usually the drug of choice. It can be given orally in a dosage of 2 to 5 mg./ kg./day in two divided doses. Usually, this is required on an every-other-day schedule in conjunction with digoxin.
Fluids should not exceed 80 ml./kg./day, and sodium should be restricted to 1 to 2 mEq/kg./day.
The patient should be positioned with head elevated at a 30-degree angle in a thermoneutral environment. Oxygen should be administered if there is arterial desaturation secondary to hypoventilation. Daily fluid intake and output should be monitored carefully. The infant should be weighed daily to judge effectiveness of therapeutic measures. If adequate calories are being administered, the infant should gain about 15 gm ./kg./day, with excessive weight gain indicating fluid retention.
ACYANOTIC CONGENITAL HEART DISEASE
This category of heart disease includes defects with large left-to-right shunts, lesions producing left-ventricular outflow obstruction, cardiomyopathies, and arrhythmias. The primary clinical problem that these defects produce is congestive heart failure, varying in severity from mild signs of cardiac failure to a shocklike picture. In addition to signs of congestive failure, there may be mild cyanosis if pulmonary congestion significantly reduces pulmonary compliance, leading to hypoventilation. This category includes atrial septal defect, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, aortic stenosis, endocardial fibroelastosis, myocarditis, Pompe's disease and common neonatal arrhythmias.
Atrial-septal defects are common congenital lesions, accounting for 10 to 15 per cent of all congenital cardiac defects.1 There are two varieties of atrial septal defects. The secundum type usually consists of an isolated interatrial communication. About 25 per cent of secundum septal defects have associated partial anomalous pulmonary venous return. Although this is a commonly observed lesion in older children, it is not a clinical problem in the neonatal period and will not be further discussed.
Ostium-primum atrial-septal defects belong in the category of endocardial cushion defects. They are usually associated with other defects affecting the mitral and tricuspid valves and the ventricular septum. If the lesion is limited to the atrial septum, clinical problems are unlikely in the neonatal period. The presence of several defects increases the possibility of neonatal heart failure. The spectrum of cushion defects is wide, and the clinical, laboratory, and anatomic findings are equally variable.3-9
Ventricular septal defects (VSDs) are the commonest congenital cardiac lesion, accounting for 25 per cent of all forms of CHD.2*3 They can be placed into the following categories: right-ventricular outflow defects, inflow defects, and combined inflow and outflow defects. The commonest variety is the inflow defect located in the membranous portion of the ventricular septum, accounting for about 80 per cent of all VSDs. The inflow defects are located in the muscular septum behind the septal leaflet of the tricuspid valve. Combined defects are large communications encompassing both muscular and membranous septums, and are usually part of an endocardial cushion complex.
Isolated outflow or inflow defects are considered small if right-ventricular systolic pressure is less than one-third of systemic, moderate if right-ventricular pressure is between one-third and two-thirds of systemic, and large if the right-ventricular peak systolic pressure is more than two-thirds of systemic pressure. The small defects rarely present a clinical problem in spite of the harsh, often loud, holosystolic murmur heard maximally at the mid-left sternal border. These patients do not develop CHF, cardiomegaly, or ECG changes.
The larger lesions do not create clinical problems during the early neonatal period. Regardless of the size of the septal defect at birth, significant left-to-right flow through the communication cannot occur until pulmonary vascular resistance falls. In the full-term infant this happens at about six weeks of age. Pulmonary resistance is lower in premature infants, so large defects may cause clinical problems at an earlier time.
When significant shunting occurs, the left ventricle bears the burden of maintaining cardiac output in the face of a large "runoff." Thus, left-ventricular hypertrophy develops in order to meet this work load. If systemic demands cannot be met, signs of CHF develop. The infant feeds poorly, sweats when fed, is tachypneic or in respiratory distress, and fails to thrive. Heart and respiratory rates are increased, and there are inspiratory retractions and râles on auscultation. A harsh holosystolic murmur radiating to the axilla is heard at the mid-left sternal border. Chest x-ray reveals pulmonary overcirculation, vascular congestion, and significant cardiomegaly. The ECG shows a Ie ft- axis deviation (0 to -f 60 degrees), and there is evidence of left- or biventricular hypertrophy. Arterial blood gases reveal mild oxyhemoglobin desaturation and mild to moderate combined metabolic and respiratory acidosis.
After stabilization of the clinical condition with cardiotonic drugs, cardiac catheterization is performed. The procedure includes a complete right-heart study, a left-ventricular angiogram to clearly define the location and size of the defect, and an aortic-root injection in order to rule out the presence of a coexisting patent ductus arteriosus. If medical management is successful, vital signs become normal, the infant is able to feed well and grow appropriately, and no further invasive studies are necessary before the age of two years. At that time, catheterization will reveal either no change in flow across the defect, with persistent pulmonary hypertension, a smaller defect with less shunting and a decrease in pulmonary pressure, or early signs of development of pulmonary vascular obstructive disease indicated by decreased flow and no change in pulmonary pressure. If the first or last situation exists, surgical correction should be scheduled. If there is indication that the lesion is decreasing in size, continued medical management is suggested, since 60 to 80 per cent of these defects close spontaneously.
When a large defect does not respond to a cardiotonic regimen in the neonatal period, palliative or corrective surgery should be carried out at that time. Small defects rarely, if ever, require treatment.
Patent ductus arteriosus accounts for 10 per cent of all congenital cardiac defects.1 Its incidence increases at high altitudes, where ambient oxygen tension is lower, and it occurs more often in girls. Patency during fetal life is maintained by a normally low intrauterine Po2. The rise in Po2 after birth stimulates constriction and functional closure. Anatomic closure ensues over the next few weeks.2,8"10
When the ductus remains patent after birth, a shunt between the pulmonary and systemic circuit exists. The magnitude and the direction of flow through the shunt are determined by the degree of pulmonary vascular resistance. Usually, the flow through the ductus is left-to-right, from the descending aorta to the pulmonary artery, leading to pulmonary overcirculation with left atrial and ventricular diastolic overload. Significant volume overload associated with a large PDA may lead to an early onset of CHF, especially in the premature infant. The pulmonary vascular resistance in the premature infant is lower than that of the full-term infant, and thus CHF associated with a large PDA is often encountered in this group. If the pulmonary vascular resistance increases because of such clinical conditions as the respiratory distress syndrome, the magnitude and direction of the shunt may change. The flow may simply decrease, or the shunt may reverse and become right-to-left, producing central cyanosis.
The exact role of a PDA in the pathophysiology of RDS has not been fully defined. The spectrum of severity of RDS is wide. If a PDA exists simultaneously, it is the responsibility of the clinician to determine whether the direction of flow through the ductus is left-toright, nonexistent, or right-to-left. If evidence suggests a significant left-to-right shunt (which would complicate the clinical picture of RDS), then measures should be taken to eliminate the shunt. If RDS is so severe that the flow through the shunt is right-to-left, it is suggested that the shunt be left alone, since ligation of a PDA in the face of pulmonary hypertension may lead to right-heart failure. If the flow through the patent ductus is leftto-right, the chest x-ray shows cardiomegaly with pulmonary overcirculation. Also, echocardiography will indicate an abnormal leftatrial/aortic size ratio, which is a reliable indicator of left-atrial diastolic volume overload. When the direction of flow is right-to-left one should be able to demonstrate a discrepancy in Po2 between the right brachial artery and the descending aorta. Also, the ECG indicates right-ventricular dominance and right-axis deviation. The chest x-ray reveals a normal heart size, and pulmonary circulation is normal or decreased.
Management of an isolated PDA depends on clinical manifestations. In the absence of CHF, close follow-up and surgery by age two are indicated. Signs of CHF dictate use of a cardiotonic regimen. If medical management is unsuccessful, surgical ligation is necessary. Pharmacologic closure of a patent ductus by indomethacin has been described, but the role of this drug requires further evaluation. The agent acts by overcoming the effect of prostaglandin E1.
Coarctation of the aorta accounts for 6 per cent of congenital cardiac lesions.1 The defect is a constriction of the descending aorta distal to the site of insertion of the ductus arteriosus. This lesion is one of the commonest causes of CHF during the first month of life, and most cases are associated with other defects such as PDA, VSD, aortic-arch anomalies, and abnormalities of the aortic and/or mitral valves.2,9
Significant aortic constriction causes a pressure overload on the left ventricle. Whether or not CHF occurs depends on the degree of constriction. The presence of a PDA or VSD usually guarantees the development of CHF early in the neonatal period, since the left ventricle is faced with both a pressure and a volume overload.
Clinically, aside from the signs of CHF, there is a pulse and blood-pressure differential between the brachial and femoral arteries. An ejection murmur is audible at the left base and in the interscapular region. Other murmurs may be audible if associated lesions coexist. Chest x-ray reveals cardiomegaly and pulmonary congestion, and the ECG indicates leftventricular hypertrophy and a left-axis deviation. Cardiac catheterization is indicated after CHF has been controlled. A search for associated lesions is mandatory with Ie ft- ventricular and aortic-root angiograms. If CHF is intractable, resection of the coarctation is recommended. When a left-to- right shunt and a coarctation coexist and there is significant cardiac failure, the usual policy is to eliminate the pressure overload by resection of the coarctation. CHF secondary to volume overload can usually be successfully managed with a cardiotonic regimen.
Aortic stenosis. Severe congenital valvular aortic stenosis may lead to myocardial hypertrophy and CHF in the neonatal period because of pressure overload on the left ventricle.1"3 A systolic ejection murmur is audible at the right base and mid-left sternal border and is transmitted to the neck. A thrill is usually palpable at the right base and mid-left sternal border. The chest x-ray demonstrates left ventricular hypertrophy and pulmonary venous distention. Poststenotic dilatation of the aorta may also be present. The ECG reveals a leftaxis deviation and left-ventricular hypertrophy. An ST-T -wave-strain pattern may be present in the left precordial leads.
Cardiac failure secondary to aortic stenosis is usually not responsive to medical management. Prompt surgical intervention is necessary in severe cases.
Cardiomyopathies. The three major myocardial disorders observed in the neonatal period are Pompe's disease, endocardial fibroelastosis and infectious myocarditis.
Pompe's disease (glycogen-storage disease type II) is a familial, autosomal-recessive metabolic disorder that results in abnormal deposition of glycogen in the myocardial tissue as well as skeletal muscle and liver. This is caused by a deficiency of the enzyme 1,4glucosidase. As glycogen stores in the myocardium increase, myocardial function becomes impaired and cardiac failure develops.
Affected infants present with cardiac failure, hypotonia, large tongue, and failure to thrive. Murmurs are usually absent. The chest x-ray reveals a cardiomegaly and pulmonary congestion. The ECG displays a significant increase in voltage in the left precordial leads, and there are usually ST-T- wave abnormalities. A classic diagnostic ECG finding is a short PR interval. The diagnosis is confirmed by skeletal-muscle biopsy, with a finding of more than 1.5 per cent glycogen by wet weight diagnostic of the disorder.
The defect is lethal, and death occurs within the first year of life. Medical management is usually ineffective in controlling the signs of cardiac failure. Death is usually preceded by ventricular arrhythmias.
Endocardial fibroelastosis has been observed with decreasing frequency in recent years, for no apparent reason. Pathologically, there is a proliferation of subendocardial fibroelastic tissue, leading to the formation of a stiff, thickened endocardium that interferes with ventricular contraction. The result is left-ventricular failure.
The initiai clinical manifestation is CHF, and a murmur is usually absent. The chest x-ray reveals cardiomegaly and pulmonary vascular congestion. The ECG in this disorder demonstrates increased left-ventricular forces, with T-wave abnormalities in the left precordial leads. Cardiac catheterization reveals a poorly contracting Ie ft- ventricular wall with a decreased ejection fraction and elevated leftventricular end-diastolic pressure.
There are no specific diagnostic tests for this disorder, and the diagnosis can be confirmed only at postmortem examination. While most infants in whom this diagnosis is made clinically die in eany infancy, the exact prognosis is unknown because of the inability to identify this condition prior to death.
Infectious myocarditis is a viral syndrome transmitted in utero. The viruses implicated have included group-B Coxsackie viruses, mumps, influenza, rubella, cytomegalovirus, and herpes simplex. CHF develops early in the neonatal period. Significant specific murmurs are absent. Cardiomegaly and pulmonary congestion are the usual findings on chest x-ray, and the ECG reveals low QRS voltage in the precordial leads, with flattened T waves. Arrhythmias are common and often responsible for death. The prognosis depends on both the severity of illness and the type of organism present. Treatment is symptomatic and includes administration of digoxin in low dosage and oxygen.
Figure 1. ECG of a patient with PAT, demonstrating hairline regularity of ORS complexes and absent P waves.
Arrhythmias may cause early congestive heart failure in the neonate. The most common of these are paroxysmal atrial tachycardia atrial flutter, and complete heart block.1,3,9
Paroxysmal atrial tachycardia is a form of supraventricular tachycardia that is characterized by a ventricular rate in excess of 200 beats per minute. P waves are usually not discernible, and the QRS complexes occur with hairline regularity (Figure 1). The associated hemodynamic problem is a decrease in ventricular filling time, which leads to decreased cardiac output and pulmonary congestion if sustained for more than 24 hours.
Figure 2. Lead V1 of an ECG of a patient with WPW. Note the slurring of the upswing of the R wave, which represents the delta wave.
Neonatal supraventricular tachycardias are usually not associated with structural cardiac defects. Occasionally, there is an associated conduction defect, such as the Wolf-Parkinson-White (WPW) variety of pre-excitation syndrome. Once the arrhythmia is controlled, the ECG reveals the classic findings of WPW, which include a very short PR interval, with a prolonged QRS interval secondary to delta waves. The delta wave is a slurring of the initial part of the R wave observed in the precordial leads (Figure 2).
Paroxysmal atrial tachycardia usually responds to high doses of digitalis administered over a short period. A total dose of 75 mg./kg. is administered intravenously over an 18-hour period. Fifty per cent of the total is given by rapid infusion, and the remaining one half is given in two doses every six hours. A response generally occurs after the first dose. Carotid stimulation is usually not effective in breaking the arrhythmia. After sinus rhythm is restored, the infant should be placed on maintenance digoxin therapy for at least the first six months of life. PAT not associated with WPW usually does not recur. However, arrhythmias secondary to a pre-excitation conduction defect are prone to recur frequently. Quinidine, procainamide, or propranolol may also be required to achieve better control if the arrhythmia recurs. If medical management is not successful and the patient is in congestive heart failure, direct-current cardioversion at 10 watt-seconds is indicated and should be performed in a catheterization laboratory.
Atrial flutter is another form of supraventricular tachycardia. Here, the atrial rate is greater than 250 beats per minute, and often as high as 300 to 400. When atrial rates are this rapid, atrioventricular block develops, because the refractory period of the node will not permit 1:1 conduction to the ventricles. Thus, there are varying degrees of block, which serve as a safeguard against excessively rapid ventricular rates. "Sawtooth" flutter waves, representing P waves, are seen on ECG (Figure 3). The QRS frequency is not regular and varies with the degree of block. Clinical manifestations, associated conduction defects, and treatment are the same as for paroxysmal atrial tachycardia.
Figure 3. ECG of a patient with atrial flutter demonstrating the "saw tooth" pattern of the P waves, varying degree of block, and irregular R-R intervals.
Complete congenital heart block is the result of interrupted conduction between the atria and the ventricles. The result is a slow ventricular rate, with impulses originating from the His-Purkinje system. The diagnosis can be made antenatally with fetal electrocardiography. The rates vary from 30 to 90 beats per minute, and the infant is usually asymptomatic. The defect generally exists as an isolated entity. However, associated congenital cardiac defects (such as corrected transposition of the great vessels) exist in about 30 per cent of these infants.
The ECG reveals a lack of association between the atrial and ventricular electrical activity. The narrow, normal-appearing QRS complexes are generated from the bundle of His, are stable, and are responsive to autonomic stimulation, allowing for variation in rate on demand. If wide QRS complexes are present, the impulse is generated from a site lower than the bundle of His, and the patient is at risk of developing ventricular arrhythmias. This type of impulse is not responsive to exercise demands and is not stable. Here, treatment is indicated, and a pacemaker should be implanted.
Central cyanosis occurs when 5 gm./dl. or more of reduced hemoglobin is present in capillary blood.1,2,12,13 Clinically, cyanosis appears as a bluish discoloration in the periphery of extremities and circumoral area. Occasionally, cyanosis is so severe that an infant will have generalized bluish discoloration. Significant anemia may interfere with the clinical manifestation of cyanosis in spite of severe arterial desaturation. Situations that may mimic cyanosis without arterial desaturation are polycythemia and acrocyanosis (secondary to vasomotor instability).
There are two mechanisms responsible for true central cyanosis. The first is replacement of normal hemoglobin with defective hemoglobin, which cannot combine with oxygen. The second mechanism entails the entrance of unsaturated hemoglobin into the arterial circulation through either intrapulmonary or intracardiac shunts. Central cyanosis in the neonate is usually due to a pulmonary, cardiac, central-nervous-system, or hematologic disorder, or a combination of these.
The hematologic problem associated with central cyanosis is congenital or acquired methemoglobinemia. The acquired form is secondary to exposure to aniline dyes and nitrites. The congenital form of this disorder is due to a specific enzyme deficiency.
In spite of a cyanotic appearance, the infant does not appear ill. There is no change in color when 100 per cent oxygen is administered. A sample of the infant's blood has a chocolate appearance in room air.
The diagnosis is made by absorption spectroscopy. A clinical trial of 1 to 2 mg./kg. of methylene blue intravenously will resolve the cyanosis if methemoglobinemia is the problem.
Central-nervous-system depression leads to alveolar hypoventilation. In this situation, the Pco2 is elevated and the Po2 is reduced. In the absence of complicating pulmonary and cardiac disease, chest x-ray and ECG are normal and respirations are not labored. The infant is usually hypotonic and responds poorly to stimulation. Administration of supplementary oxygen leads to an increase in Po2.
Pulmonary disorders are by far the commonest cause of neonatal cyanosis, and at times the most difficult to differentiate from cardiac causes. Infants with primary pulmonary disease have labored respirations, tachypnea, retractions, stridor, and grunting; arterial desaturation is usually present, and the Pco2 may be low, normal, or elevated. Most patients with pulmonary disease respond to administration of 100 per cent oxygen with an elevation of the arterial Po2 to >300 mm. Hg.
Figure 4. A. Chest x-ray of a patient with tetralogy of Fallot. Note the small heart and the decreased pulmonary circulation. B. Chest x-ray of a patient with transposition of the great vessels, demonstrating cardiomegaly and increased pulmonary circulation.
Cardiac disease responsible for central cyanosis (Table 2) falls into two general categories. The first group of lesions share the common problem of right-ventricular outflow-tract obstruction, with resulting decreased pulmonary blood flow and intracardiac right-to-left shunting of blood. The second group of lesions are complex anatomic defects that result in intracardiac mixing of pulmonary and systemic venous return. These defects are usually associated with increased pulmonary blood flow and often signs of congestive heart failure. Figure 4 illustrates the x-ray difference between the two categories of lesions.
Cyanotic defects with decreased pulmonary blood flow include tetralogy of Fallot, pulmonary stenosis with intact ventricular septum, pulmonary atresia, and tricuspid atresia.
Tetralogy of Fallot accounts for 10 per cent of congenital heart lesions and 75 per cent of cyanotic lesions.1 The defects in this lesion consist of infundibular and pulmonary valvular stenosis and a large ventricular septal defect. As a result of right-ventricular outflow obstruction, systemic venous blood flows from the right ventricle through the ventricular septal defect into the aorta, producing central cyanosis. An infant with tetralogy of Fallot who becomes cyanotic in the neonatal period has severe obstruction to pulmonary flow.
CARDIAC DISEASE RESPONSIBLE FOR CENTRAL CYANOSIS
The chest x-ray reveals marked pulmonary hypoperfusion, with a small, boot-shaped heart, and the electrocardiographic findings are those of persistent right-axis deviation and right-ventricular hypertrophy. These laboratory findings in a patient with marked central cyanosis require urgent cardiac catheterization in order to define the lesion. Catheterization should be followed by a surgical procedure that will increase pulmonary blood flow. Complete repair is usually not possible in the neonatal period. Palliative procedures include the Blalock-Taussig (anastomosis of either subclavian artery to the ipsilateral pulmonary artery) or the Waterston (side-to-side anastomosis between the ascending aorta and pulmonary artery).
Pulmonary stenosis with intact ventricular septum accounts for about 7 per cent of all congenital cardiac defects. Severe valvular stenosis associated with an intact ventricular septum may obstruct right-ventricular and right-atrial pressures. Right-atrial pressure exceeds that of the left atrium, and a right-toleft shunt occurs across the foramen ovale, leading to central cyanosis.
In these patients, the ECG findings are those of right-axis deviation often greater than +120 degrees, with marked rightventricular hypertrophy and ST-T wave changes observed in the right precordial leads. A "J" type of depression of the ST segment in the right precordial leads indicates rightventricular strain. Chest x-ray reveals pulmonary undercirculation and cardiomegaly. These critically ill infants require immediate cardiac catheterization, followed by pulmonary valvulotomy.
Pulmonary atresia with an intact ventricular septum is often referred to as hypoplastic right-heart syndrome. The lesion is uncommon, accounting for 1 per cent of all congenital defects. The pulmonary outflow tract is atretic, and the right ventricle is usually severely underdeveloped. As systemic venous blood enters the tiny right-ventricular chamber, most is regurgitated back into the right atrium and across the foramen ovale into the left atrium and left ventricle to produce central cyanosis. A patent ductus arteriosus is the only possible source of pulmonary blood flow. If this closes, the infant abruptly becomes severely hypoxic.
The ECG shows a normal axis of +30 to + 120 degrees and left- ventricular preponderance. Roentgenographic findings are those of pulmonary undercirculation, with moderate to marked increase in heart size. Catheterization must be carried out promptly and should be followed by a surgical procedure designed to increase pulmonary blood flow (such as a Waterston shunt). A pulmonary valvulotomy should be performed to decompress the right ventricle and promote flow through the chamber, with the hope that this will stimulate chamber growth and development.
Tricuspid atresia accounts for 3 per cent of cases of congenital cardiac disease. The tricuspid valve is completely obstructed, and systemic venous return is shunted across the foramen ovale or atrial septal defect into the left atrium, producing central cyanosis. Blood enters the pulmonary artery either by means of a ventricular septal defect or through a patent ductus arteriosus. Pulmonary blood flow may be initially increased, with signs of CHF. However, pulmonary obstruction becomes progressively worse and pulmonary undercirculation soon develops.
Clinically, a heart murmur reflecting flow across a VSD may be present. Cyanosis is apparent, and hepatomegaly may exist if the interatrial communication is inadequate. Eighty per cent of the patients have a left superior axis on ECG. There is evidence of leftventricular hypertrophy, and the waves are tall and notched. The chest x-ray reveals normal to decreased pulmonary circulation and a normal to slightly enlarged cardiac silhouette.
If pulmonary blood flow is inadequate and the patient is severely hypoxic, Waterston shunt is indicated in the neonatal period to increase pulmonary blood flow. After six months of age the procedure of choice is a Glenn shunt, which anastomoses the superior vena cava to the right pulmonary artery. If pulmonary circulation is adequate, close observation and/or medical management of CHF is indicated. Eventually, pulmonary flow will become inadequate and surgical intervention will be necessary.
Cyanotic defects with increased pulmonary blood flow include transposition of the great arteries, hypoplastic left-heart syndrome, single ventricle, and truncus arteriosus.
Transposition of the great arteries (TGA) is a common form of cyanotic congenital heart disease. The lesion consists of a reversed anterior-posterior anatomic relationship of the aorta and pulmonary artery, with the aorta originating from the morphologic right ventricle and the pulmonary artery originating from the morphologic left ventricle. The net result is that pulmonary and aortic circuits operate in parallel rather than in series. However, pure parallel circuitry is incompatible with life. Thus, viability depends on the number and the size of the communications between the two circuits.
The possible sites of intercommunication are the foramen ovale, patent ductus arteriosus, and VSD. The foramen ovale and the ductus close shortly after birth, producing severe cyanosis and hypoxemia. A patient with a ventricular septal defect usually does not develop cyanosis as severe as one without a VSD. In fact, most patients with both TGA and VSD are not recognized until about one month of age, when they develop CHF. Many patients with TGA and VSD also have pulmonary stenosis. The decreased pulmonary blood flow associated with this latter lesion may protect against the development of CHF.
Symptoms occur in the early neonatal period, when the ventricular septum is intact. Clinically, the patient appears cyanotic and dyspneic. There are usually no murmurs or signs of CHF on physical examination. The ECG reveals right-ventricular hypertrophy and an axis that is appropriate for age. The heart is normal in size on x-ray but has the appearance of an egg on its side, because of the narrow superior mediastinal shadow. Pulmonary vascular markings are normal. If a VSD exists, there is a holosystolic murmur audible at the mid-left sternal border and the chest x-ray reveals marked pulmonary overcirculation and an increase in heart size. Overt signs of CHF are usually not present in the early neonatal period.
Cardiac catheterization is necessary to confirm the diagnosis and define the exact anatomic defects. At the time of catheterization, a balloon septostomy should be done to improve mixing at the atrial level. Successful septostomy is demonstrable by an increase in arterial Po2. If the septostomy is successful, the patient can be observed for about one year, at which time a Mustard operation is performed. This procedure reroutes atrial blood so that systemic venous return is directed to the left ventricle and the pulmonary venous return is directed into the right ventricle and out the aorta.
If a VSD is present, a cardiotonic regimen may be required during the first year of life, until the Mustard procedure can be done. Pulmonary artery banding is done electively in these patients at three to six months of age to lower pulmonary artery pressure and decrease pulmonary blood flow, since these patients tend to develop pulmonary vascular obstructive disease at a relatively early age.
Hypoplastic left-heart syndrome consists of mitral atresia, hypoplastic left ventricle and aortic valve, and an underdeveloped ascending aorta. This syndrome, which accounts for about 1 per cent of all congenital cardiac defects, is one of the commonest causes of early severe heart failure and cyanosis.
The left heart is virtually functionless. Systemic and pulmonary venous return mix in the right heart and exit through the pulmonary artery, producing central cyanosis. Most of the systemic flow is from the pulmonary artery across a patent ductus to the descending aorta. Retrograde flow into the aortic arch provides blood to the brachiocephalic vessels. The limited size of the foramen ovale obstructs pulmonary venous return, leading to pulmonary congestion and edema.
Clinically, patients with this syndrome are cyanotic and in severe CHF. If murmurs exist, they are nonspecific. The chest x-ray reveals pulmonary vascular congestion and marked cardiomegaly. Marked right-ventricular hypertrophy with practically no left-ventricular forces is the significant ECG finding. Here, an echocardiogram will confirm the diagnosis and eliminate the need to perform cardiac catheterization on a patient with a surgically uncorrectable problem. A cardiotonic regimen is of little help in the management of these critically ill infants. Death occurs early in the neonatal period.
Single ventricle accounts for 1 per cent of congenital cardiac lesions and is due to embryologie development of only one of the two ventricles or, rarely, to failure of septal development. Most cases of single ventricle exist in conjunction with other cardiac defects.
Patients are generally cyanotic and in congestive heart failure. Because of associated anomalies, ECG, x-ray, and clinical findings may be confusing. Cardiac catheterization is needed to confirm the diagnosis and identify its associated defects. Management is as variable as the associated defects. For example, a cardiotonic regimen is employed to control heart failure; pulmonary artery banding is used if failure is intractable, and if there is significant pulmonary obstruction, a systemic-to-pulmonary shunt is indicated in order to improve oxygenation.
Truncus arteriosus describes a defect in which one major vessel arises from both ventricles. The pulmonary artery arises from the truncal vessel in a variety of ways, and a ventricular septal defect is also present. Blood from both the right and left ventricle meet and mix in the truncal vessel, producing clinical cyanosis. Defects in the origin of the pulmonary artery from the truncal vessel may lead to obstruction of pulmonary blood flow and aggravate the degree of cyanosis. Another common problem in patients with truncus arteriosus is a defective truncal valve, leading to truncal valve insufficiency and CHF.
Mild cyanosis and early CHF are common findings. Examination reveals a harsh holosystolic murmur at the left sternal border and a decrescendo diastolic murmur, representing truncal insufficiency (if this defect is present). The second heart sound is single. Cardiomegaly and pulmonary plethora are the usual findings on chest x-ray, and the ECG demonstrates left- or biventricular hypertrophy.
A cardiac catheterization is necessary to define the complex of anomalies that may exist. Medical management is usually successful; however, the presence of truncal insufficiency makes this lesion more difficult to treat with a cardiotonic regimen. Occasionally, the pulmonary artery requires banding in order to control intractable heart failure. Medical management or surgical palliation is the recommended early management. Total correction is attempted when the infant is older.
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ONSET OF CONGESTIVE HEART FAILURE RELATED TO MECHANISM
CARDIAC DISEASE RESPONSIBLE FOR CENTRAL CYANOSIS