Cardiac Disease in the Wheezing Child

CRITICAL REVIEW C a r d i a c D i s e a s e in t h e W h e e z i n g C h i l d Arthur ]. Moss, M.D., and Larry V. McDonald,

M.D.

C i n c e the heart and lungs are intimately related ^ functionally as well as anatomically, it is not surprising that disease in one may lead to dysfunction or disease in the other. Thus, with severe pulmonary disease and particularly with certain types of heart disease, it is often difficult on clinical grounds alone to determine whether the basic pathologic process is in the heart or in the lungs. The purpose of this review is to illustrate how failure to establish the primary source can lead to unnecessary and potentially hazardous delays in diagnosis.

In the presence of overt heart failure, cor pulmonale is generally easily recognized; however, in its subclinical form, it often escapes detection, but available evidence indicates that an arterial oxygen pressure below 50 mm Hg, an arterial carbon dioxide tension over 45 mm Hg, or a vital capacity of less than 60 percent of the predicted value is evidence of cor pulmonale.

HEART DISEASE SECONDARY TO PULMONARY DISEASE

PULMONARY DISEASE SECONDARY TO HEART DISEASE

Cor pulmonale is the term used to denote heart disease as a consequence of pulmonary disease. It is a broad subject which will be discussed here only briefly. Cor pulmonale may occur with any severe pulmonary process, but in children it is most commonly recognized in cystic fibrosis. Cor pulmonale may be acute or chronic, overt with evidence of heart failure, or covert with no clinical signs of heart failure. The cardiac disease process was originally believed to be limited to the right ventricle, but there has been growing evidence that the left ventricle may also be involved. The major determining factors are believed to be ( 1 ) increased pulmonary vascular resistance secondary mainly to hypoxia and ( 2 ) the metabolic disturbance caused by pulmonary insufficiency. The former imposes a heavy afterload on the right ventricle, and the latter exerts an unfavorable effect on the myocardium of both ventricles.

Heart disease results in pulmonary dysfunction or disease by one or more mechanisms. These include tracheal obstruction, bronchial obstruction, and pulmonary vascular congestion.

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F r o m the Department of Pediatries, University of California School of Medicine, Los Angeles. Supported in part by a grant from the National Cystic Fibrosis Research Program. Presented at the 41st Annual Scientific Assembly, American College of Chest Physicians, Anaheim, Calif, Oct 2 7 , 1 9 7 5 . Reprint requests: Dr. Moss, Department of Pediatrics, University of California School of Medicine, Los Angeles 90024

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Treatment is aimed primarily at the lungs, although decongestive measures are indicated when heart failure is present.

Tracheal

Obstruction

Tracheal obstruction is due to abnormalities of the aortic arch, most commonly a double aortic arch, in which a vascular ring is formed which surrounds and compresses the trachea and esophagus (Fig 1 ) . In early infancy, children with tracheal obstruction have symptoms of wheezing, retractions, and a crowing stridor on both inspiration and expiration. There is commonly a history of recurrent pulmonary infections. Murmurs are generally neither present nor audible, and the condition is frequently misdiagnosed as croup, bronchitis, or asthma. The tendency for these patients to lie with the head and neck in a hyperextended position is one of the clinical hallmarks of this disease. Forcible flexion of the neck is resisted, since it aggravates the obstruction and accentuates the symptoms. A simple barium swallow establishes the diagnosis (Fig 2 ) . One may wish to precisely delineate the abnormality and exclude associated cardiac lesions by cardiac cathe48

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terization and angiocardiographic studies. Treatment is surgical. In patients with mild or intermittent symptoms, surgery can often be safely delayed, but with severe symptoms the condition may be life-threatening, and surgical intervention must be undertaken on an urgent basis. Case Report. This five-week-old girl was admitted to the hospital for evaluation of stridor and wheezing. Inspiratory and expiratory wheezing had been noted at birth, but because a thoracic roentgenogram was normal, no specific therapeutic measures were instituted. The symptoms persisted, and a second roentgenogram taken when the patient was three weeks of age was again normal. The mother was assured that the problem was not serious and that the symptoms would probably disappear with time. When the patient was five weeks of age, because of persistence of the symptoms, a barium swallow was performed. An area of esophageal narrowing was noted, and the diagnosis of tracheal vascular ring was established. On examination at the time of admission, inspiratory and expiratory wheezes were heard, and the infant intermittently assumed the hyperextended position described previously. A cineaortogram demonstrated a double aortic arch. Because of the severity and persistence of symptoms, surgery was performed on the fifth day of hospitalization. The vascular ring was released, with ligation of a patent ductus arteriosus and left aortic arch, and recovery was uneventful. F I G U R E 1. Vascular ring due to double aortic arch. Aorta; and MPA, main pulmonary artery.

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Comment. In this case, diagnosis was established relatively early in life and appropriate therapy was instituted; however, had the mother failed to persist in her efforts, the outcome could have been quite different.

Bronchial

Obstruction

Bronchial obstruction may occur as a result of any cardiac condition in which there is a large left-toright shunt but is most commonly due to a ventricular septal defect or a large patent ductus arteriosus. Also, any condition associated with massive cardiomegaly may compress the bronchi. With large left-toright shunts, the dilated tense pulmonary artery and the distended left atrium compress various portions of the bronchial tree, causing atelectasis or emphysema depending on the degree of obstruction (Fig 3 ) . The sites of predilection are ( 1 ) the left main bronchus, ( 2 ) the left upper bronchus, and ( 3 ) the right middle bronchus. With massive cardiomegaly the left main bronchus may be completely obstructed, with atelectasis of the entire left lung (Fig 7,8

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F I G U R E 2 . Vascular ring formed by anomalous left subclavian artery crossing behind esophagus from right aortic arch and by ligamentum arteriosum crossing in front of trachea. Shadow of right descending aorta and oblique esophageal impression of anomalous subclavian artery is well demonstrated (from D e s i l e t s ) . 6

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Because the magnitude of the left-to-right shunt is limited by the high pulmonary vascular resistance in the neonatal period, bronchial obstruction secondary to heart disease is rare in infants under two months of age. The peak incidence occurs between two and nine months of age, when the bronchial cartilages are soft and the pulmonary arterial pressure tends to be high. In these cases, cyanosis is absent, and murmurs may be absent or inaudible. Thus, the rapid noisy respirations often lead to a false impression of primary pulmonary disease. CHEST, 7 1 : 2 , FEBRUARY,

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F I G U R E 5 . Thoracic roentgenogram in three-month-old infant with ventricular septal defect, showing cardiomegaly, hypervascular lung fields, and atelectasis of left lower and right middle lobes (case 1).

F I G U R E 3. Bronchial compression by enlarged pulmonary artery and distended left atrium (redrawn from Stanger ). et a l 7 < p 7 6 2 >

The presence of cardiomegaly on the thoracic roentgenogram or of a heart murmur should lead one to suspect the true nature of the disease and direct one's attention to the heart. Case Reports. C A S E 1. This baby girl was first seen at three months of age, with a history of recurrent respiratory infections, poor feeding, and diaphoresis for a period of two months. Physical examination revealed a loud holosystolic murmur, and cardiomegaly was demonstrated on the chest roentgenogram. A large ventricular septal defect was suspected and was confirmed by cardiac catheterization. Decongestive measures were instituted, and the patient was subse-

quently discharged. One month later, she was readmitted with a history of episodes of wheezing. The right middle and left lower lobes were opacified on a chest roentgenogram ( F i g 5 ) . Absence of extreme cardiomegaly, absence of significant hepatomegaly, and repeat hemodynamic data suggestive of only a moderate left-to-right shunt led to the suspicion of independent pulmonary disease. The results of evaluation from an immunologic and infectious standpoint were normal. Open pulmonary biopsy did not reveal any evidence of basic pulmonary disease. T h e dosage of digoxin was increased, with some improvement in the patient's condition; however, she continued to have intermittent wheezing, with recurrent infections involving the left lower and right middle lobes. Because of an associated chronic diarrhea, it was suspected that the patient might have a milk allergy with gastrointestinal and pulmonary symptoms. Dramatic improvement was noted when her diet was changed to a soybase formula, but this lasted for only a few months.

F I G U R E 4. Pulmonary atelectasis in six-month-old infant with endocardial fibroelastasis. a, Thoracic roentgenogram. Lower lobe of left lung (lateral border along arrows) is collapsed, b, Postmortem bronchogram showing obstruction of left bronchus. Obstruction is not complete, as evidenced by emphysematous upper lobe of left lung. Contrast material was probably too viscid to pass through narrowed left bronchus ( F r o m Stanger et a l ) . 7

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Respiratory infections and wheezing reappeared; and finally, at the age of 17 months, the patient was readmitted to the hospital for closure of the ventricular septal defect. This was successfully accomplished, and there has been no recurrence of the respiratory symptoms. Now, at the age of three years, the patient tolerates milk products without evidence of diarrhea and has no respiratory problems. C A S E 2. This 15-month-old girl was admitted to the hospital for evaluation of persistent pulmonary infiltrates of one year's duration and an associated patent ductus arteriosus. Physical findings included bilateral rales and wheezes, a grade-3 systolic ejection murmur maximal at the pulmonic area, a loud single second heart sound in the pulmonic area, and moderate hepatomegaly. Roentgenographic examination showed atelectasis of the left lower lobe ( F i g 6 ) . Cardiac catheterization demonstrated a left-to-right shunt at the ductal level, which increased with administration of oxygen. T h e pulmonary arterial pressure was two-thirds that of systemic. Wheezing continued and did not respond to administration of bronchodilator drugs and a hypoallergenic diet. The result of evaluation from an immunologic and infectious standpoint were normal. The patient was discharged from the hospital. One month later, because of the persistence of cough and wheezing, the atelectatic areas on the chest roentgenogram, and a failure to thrive, the patient was readmitted for ligation of the patent ductus arteriosus; however, at operation, occlusion of the ductus was not followed by a fall in pulmonary arterial pressure, so it was believed that the patient had severe irreversible pulmonary vascular obstructive disease, and the duct was left open. A pulmonary biopsy at the time of surgery showed nonspecific chronic inflammatory changes without pulmonary vascular disease. After long and careful deliberation, it was concluded that the persistent pulmonary hypertension was on the basis of pulmonary parenchymal disease, possibly aggravated by a left-to-right shunt. In view of the microscopic evidence against pulmonary vascular disease, it was decided to reoperate and close the ductus. This was accomplished successfully, and tiie patient was subsequently discharged after an uneventful postoperative period; however, one month later, she was readmitted with overt evidence of heart failure. There was no wheezing, but the atelectatic areas remained.

The patient's condition responded to adjustment of the dosage of digoxin and furosemide, and she again was discharged. The patient's course therafter was one of steady deterioration. Finally, she was readmitted at the age of 2 2 months in terminal condition. Despite heroic measures, the patient died two days later. Autopsy examination revealed no other cardiac abnormalities. Careful quantitiative analysis of several sections of pulmonary tissue demonstrated advanced pulmonary vascular disease with both medial and intimal involvement. Comment. The first patient was considered to have bronchial asthma with an incidental ventricular septal defect. It was only after repeated visits and prolonged observation that the true cause of her pulmonary symptoms was recognized. The second case was difficult and perplexing. It was believed by some observers that her basic problem was pulmonary, whereas others believed the patent ductus arteriosus to be the seat of her trouble. To the very end, there was disagreement concerning the appropriate course of action. The cause of death in this case appears to have been heart failure secondary to severe pulmonary vascular disease which was, in turn, secondary to cardiac disease.

Pulmonary Vascular

Congestion

Pulmonary vascular congestion is most commonly a consequence of left ventricular failure due to ventricular septal defect or patent ductus arteriosus. It is now generally recognized that left ventricular failure during the early part of infancy is isolated initially and is not necessarily associated with hepatomegaly. Cough and wheezing are prominent symptoms and are due to mucosal edema and secretions in the small-bore bronchi. The symptoms tend to be episodic in nature, and the condition is frequently misdiagnosed as bronchial asthma or bronchiolitis, particularly when a cardiac murmur is absent or is inaudible because of noisy respirations. Cardiomegaly on the thoracic roentgenogram should lead to the suspicion that the primary disease is in the heart. 9

The clinical picture is often complicated by associated areas of atelectasis or emphysema arising from bronchial compression by a large tense pulmonary artery and a distended left atrium, as previously described. This tends to further complicate the diagnosis and may contribute to an erroneous impression of primary pulmonary disease. Certain cardiac abnormalities without left ventricular failure also may cause pulmonary vascular congestion with tachypnea, cough, and wheezing. These include pulmonary venous obstruction or stasis due to anomalous pulmonary venous connection, cor triatriatum, and left atrial obstruction due to a supravalvular mitral ring ' or to mitral stenosis. 1015

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F I G U R E 6. Thoracic roentgenogram in 15-month-old infant with patent ductus arteriosus and chronic pulmonary disease ( c a s e 2 ) . Note cardiomegaly, atelectasis of left lower lobe, and diffuse pulmonary infiltrates.

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In anomalous pulmonary venous connection, one or more of the pulmonary veins connect directly or indirectly to the right atrium. The anomalous CHEST, 7 1 : 2 , FEBRUARY,

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ventricular hypertrophy should lead one to suspect total anomalous pulmonary venous return with obstruction. In cor triatriatum the pulmonary veins enter a common chamber which connects by way of a small orifice to the left atrium. The restrictive nature of the connecting orifice leads to the same type of pulmonary vascular congestion as total anomalous pulmonary venous return. The same is true of obstruction within the left atrium or at the level of the mitral valve. Case Report. This seven-week-old boy was admitted to the hospital with a one-week history of fatigue on feeding and of tachypnea. Physical examination revealed an undernourished infant with supraclavicular and substernal retractions, audible inspiratory wheezes, and a respiratory rate of 8 0 / min. A grade 2 systolic ejection murmur was heard along the entire left sternal border. A gallop rhythm was present, and the liver was enlarged. Roentgenographic examination showed increased pulmonary vascular markings with cardiomegaly. An electrocardiogram showed evidence of right ventricular hypertrophy. The presumptive diagnosis was heart failure due to total anomalous pulmonary venous return. The infant promptly received therapy with digitalis and was prepared for cardiac catheterization; but before this could be accomplished, he experienced cardiac arrest and died. Autopsy examination confirmed the clinical impression of total anomalous pulmonary venous return.

F I G U R E 7. Total anomalous pulmonary venous connection to portal vein in six-week-old infant. Left pulmonary veins are obscured behind heart, but right pulmonary veins ( R U and R L ) are visualized. Pulmonary veins empty into anomalous channel ( C P V ) , which descends below diaphragm to join portal vein ( P ) ( F r o m Lucas and S c h m i d t ) . 2 2

channel is often stenotic and causes localized or generalized pulmonary venous congestion. This situation is particularly apt to occur when all four pulmonary veins connect anomalously (total anomalous venous return), and especially when they connect by way of a common channel to vessels below the diaphragm (Fig 7 ) . In the great majority of the latter cases, there is obstruction of the anomalous vessel, and diffuse pulmonary vascular congestion occurs. Since the symptoms appear in the early days or weeks of life, and because cardiac output in this condition is low, cardiomegaly is generally not present. The condition is easily confused with primary pulmonary disease, particularly with idiopathic respiratory distress syndrome, because of the hazy appearance of the lungs. 2 2

Unless recognized and corrected surgically, the patient dies during the first three to six months of life. The persistence of the pulmonary process, the ground-glass appearance of the lungs, and sometimes the presence of a systolic or continuous murmur with electrocardiographic evidence of right CHEST, 7 1 : 2 , F E B R U A R Y ,

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Comment. This case illustrates the dominance of pulmonary symptoms in total anomalous pulmonary venous return and the fulminant course which may ensue if appropriate therapy is not instituted. The presence of a murmur, as in this patient, should arouse suspicion of primary cardiac disease; however, in the majority of instances, a murmur is not present or is inaudible because of noisy respirations. Cardiopulmonary symptoms in this condition are an indication for urgent surgical intervention. SUMMARY

Cardiac and pulmonary disease are so closely interrelated that it is often difficult to determine in young infants which is the primary offender. As illustrated in these case reports, failure to recognize the true nature of the disease process may lead to unnecessary procedures and delays which can be lifethreatening. Statistically, the wheezing infant very likely is suffering from primary pulmonary disease; however, congenital cardiac abnormalities can cause pulmonary symptoms which completely dominate the clinical picture and lead to erroneous diagnoses. Although rare, the basis of cough and wheezing may be a vascular ring which encircles and compresses the trachea. Lesions associated with large left-to-right shunts, such as ventricular septal defect and patent ductus arteriosus, also can cause cough and wheezing because of bronchial compression by a large tense pulmonary artery and a distended left atrium. These same lesions also produce isolated left CARDIAC DISEASE I N THE WHEEZING CHILD

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ventricular failure with pulmonary venous congestion and episodes of cough and wheezing. Anomalous pulmonary venous return, cor triatriatum, supra valvular mitral ring, or mitral stenosis are other lesions which can cause cough and wheezing secondary to pulmonary venous obstruction, REFERENCES 1 World Health Organization Expert Committee: Chronic cor pulmonale. Circulation 2 7 : 5 9 4 - 6 1 5 , 1 9 6 3 2 Baum G L , Schwartz A, Llamas R, et al: Left ventricular function in chronic obstructive lung disease. N Engl J Med 2 & 5 : 3 6 1 - 3 6 5 , 1971 3 Siassi B, Moss A J, Dooley R R : Clinical recognition of cor pulmonale in cystic fibrosis. J Pediatr 7 8 : 7 9 4 - 8 0 5 , 1971 4 Niwayama G; Unusual vascular ring formed by the anomalous left pulmonary artery, with tracheal obstruction. Am Heart J 5 9 : 4 5 4 - 4 6 1 , 1960 5 Blumenthal S, Ravitch M M : Seminar on aortic vascular rings and other anomalies of the aortic arch. Pediatrics 2 0 : 8 9 6 - 9 0 6 , 1957 6 Desilets D T : Roentgenologic examination of the heart. In Moss AJ, Adams F H ( e d s ) : Heart Disease in Infants, Children, and Adolescents. Baltimore, Williams and W i l kins, 1968, chap 7 7 Stanger P, Lucas RV Jr, Edwards J E : Anatomic factors causing respiratory distress in acyanotic congenital cardiac disease: Special reference to bronchial obstruction. Pediatrics 4 3 : 7 6 0 - 7 6 9 , 1969 8 Bryk D: Atelectasis, emphysema, and heart disease. Am J Dis Child 1 1 0 : 1 0 0 - 1 0 4 , 1965 9 Rudolph A M : Diagnosis and treatment: Respiratory distress and cardiac disease in infancy. Pediatrics 3 5 : 9 9 9 1002, 1965 10 Blake HA, Hall RJ, Manion W C : Anomalous pulmonary

venous return. Circulation 3 2 : 4 0 6 - 4 1 4 , 1965 11 Robinson A E , Chen J T T , Bradford W D , et al: Kerley B lines in total anomalous pulmonary venous connection below the diaphragm (type I I I ) . Am J Cardiol 2 4 : 4 3 6 4 4 0 , 1969 12 Mody MR, Gallen W J , Lepley D: Total anomalous pulmonary venous drainage below the diaphragm. Am J Cardiol 2 4 : 5 7 5 - 5 7 9 , 1969 13 Gathman G E , Nadas AS: Total anomalous pulmonary venous connection: Clinical and physiologic observations of 7 5 pediatric patients. Circulation 4 2 : 1 4 3 - 1 5 4 , 1970 14 Behrendt DM, Aberdeen E, Waterston DJ, et al: Total anomalous pulmonary venous drainage in infants: 1. Clinical and hemodynamic findings, methods, and results of operation in 37 cases. Circulation 4 6 : 3 4 7 - 3 5 6 , 1972 15 Breckenridge IM, deLeval M, Stark J, et al: Correction of total anomalous pulmonary venous drainage in infancy. J Thorac Cardiovasc Surg 6 6 : 4 4 7 - 4 5 3 , 1973 16 Niwayama G: Cor triatriatum. Am Heart J 5 9 : 2 9 1 - 3 1 7 , 1960 17 Park MK, Ricketts HJ, Guntheroth W G : Cor triatriatum, an operable form of pulmonary hypertension. Am J Dis Child 1 2 3 : 5 0 0 - 5 0 3 , 1972 18 Shone J D , Sellers RD, Anderson RC, et al: The developmental complex of parachute mitral valve, supravalvular ring of left atrium, suboartic stenosis, and coarctation of aorta. Am J Cardiol 1 1 : 7 1 4 - 7 2 5 , 1963 19 Mehrizi A, Hutchins GM, Wilson E F , et al: Supravalvular mitral stenosis. J Pediatr 6 7 : 1 1 4 1 - 1 1 4 9 , 1965 2 0 Van der Horst R L , Hastreiter AR: Congenital mitral stenosis. Am J Cardiol 2 0 : 7 7 3 - 7 8 3 , 1967 2 1 Selzer A, Cohn K E : Natural history of mitral stenosis: A review. Circulation 4 5 : 8 7 8 - 8 9 0 , 1972 22 Lucas RV, Schmidt R E : Anomalous venous connections; Pulmonary and systemic. In Moss AJ, Adams F H ( e d s ) : Heart Disease in Infants, Children, and Adolescents. Baltimore, Williams and Wilkins, 1968, chap 32

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