Lulu h1. IIaroutunian, hf.D. Catherine A. Neill, M.D., P.R.C.P.(Lond.) Baltimore, 3Td.
he literature on pulmonary complications of congenital heart disease has primarily emphasized pulmonary vascular disease in left-to-right shunts1-3 or the effects in infants of bronchial compression and obstruction due to cardiomegaly or dilated pulmonary artery branches.4 A number of scattered reports have considered the syndromes of congenital cardiopulmonary anomalies,“,‘j or the hemodynamic effects of hypoplasia or agenesis of a lung7 or a pulmonary artery.*sg The present review will attempt to delineate the major pulmonary complications encountered in a large population with congenital cardiac disease. An abbreviated classification of some of the more frequently encountered pulmonary complications is given in Table I. Although each of the complications listed above may be encountered at any age, certain problems such as atelectasis and recurrent pulmonary infections are particularly prevalent in infancy, Lvhile others are rare before the second decade of life. Hemoptysis, one of the most dramatic and potentially lethalz4jZ5 of all cardiopulmonary complications, may be the presenting symptom of many forms of pul-
monary involvement. This present review will emphasize hemoptysis due to acquired noninfective pulmonary complications of congenital heart disease, indicated by an asterisk in Table I. The most common causes of hemoptysis in the general population are chronic bronchitis and bronchiectasis, which together account for 20 per cent of cases. Unexplained hemoptysis is common, as illustrated in the series of Johnston and colleagues”6 in \vhich no cause \vas found in 44 per cent of 324 patients. Well-recognized cardiovascular causes of hemoptysisZ7 include pulmonary embolism, mitral stenosis, congenital telangiectasis, and hypertension with intrabronchial leakage from an aneurysm Hemoptysis in congenital heart disease has been most frequently described in pulmonary vascular obstructive disease (PVOD) including Eisenmenger’s complex,” .2? ,?S but it is also known to occur in patients with enlarged bronchial circulationlY or pulmonary venous congestion.“” The present review is based on 42 cases of hemoptysis in congenital heart disease, representing all those seen by us or brought
the Departments of Pediatrics and Medicine, The Johns Hopkins University Cardiac Center, The Johns Hopkins Hospital. Supported in part by Maternal and Child Health Service Training and Study Received for publication May 12, 1971. Reprint requests to: Dr. Catherine A. Neill. The Helen R. Taussig Children’s Hospital. Baltimore, Md.. 21205.
and The Helen Project,
B. Taussig ILHS.
Children’s 201. Hopkins
4, fib. 540-559
I. Pulmonary complications
due to these
Dextrocardia,ll other5 Scimitar syndrome6 Tetralogy,‘z other Kartagener’s triad1**13 Atrial septal defectI \‘arious anomalies including pid atresia
Extreme tetralogy,**6-1s otherl9J0 I’ostoperative tetralogy* Eisenmenger reaction*‘,3,18.21.*2 Mitral stenosis,12 Cor triatriatumz3 Large left-to-right shunts Endocardinl
basis for hemoplysis
in 42 cases
Extreme pulmonic stenosis (mostly tetralogy with outflow atresia) Enlarged bronchial arteries (usually associated with pulmonary vessels and with pulmonary arterial hypoplasia) Other collateral vessels Pulmonary vascular obstructive disease (PVOD) Primary pulmonary hypertension Eisenmenger reaction in left-to-right shunt or single ventricle NOD developing following systemic-pulmonary anastomosis so forth Associated puegnancy or 07~1 contruceptives Other
Xon itifect izje Bronchial artery enlargement Other collaterals enlarged Pulmonary vascular obstructive disease Pulmonary venous engorgement Pulmonary thromboembolism Postoperative complications, other Atelectasis, persistent or recurrent
Injerth~e15 Recurrent pneumonias I3acterial endocarditis, lung ‘Tuberculosis, histoplasmosis
Agenesis lung or lobe 1 Iypoplasia Absent pulmonary artery Rronchiectaeis I’cllmonary nrteriovenous Sequestration, other
to our attention during the past 3 or 4 years while we have been collecting data on pulmonary complications. We have not incidence of attempted to assess the hemoptysis in the different malformations, preferring to concentrate on the underlying pathophysiological mechanisms. The preponderance of patients with tetralogies and extreme pulmonic stenosis in the series is due to the large number of suc11 patients followed at The Johns Hopkins Hospital
of small 16 1 1 4
and 10 7 3
over the years in The Helen B. Taussig Children’s Cardiac Center; many have been followed from infancy to adult life. Patients with other types of malformations have either been transferred as they reached adolescence or have been followed I)y other physicians. Although there is some overlap, the basis for the hemoptysis in the 42 cases can be conveniently classified into 3 major groups (Table I I).
Ant. Heart I. October, 1972
Group I: Browhitrl
ucssels in extrctnc
(+)I + maiu 7 8
‘L‘OF ASD TOF
Levocardia Situs inversus Cor biloculare Absent left pulmonary
*TOF = Tetralogy of Fallot. ASD = atria1 septal defect. f+ = Complete atresia. f(+) = Extreme stenosis. If not indicated, stenosis was mild or moderate. §Shunt age(s) at time of subclavian-pulmonary artery anastomoses. IlRL = Pseudofibrosis pesent in both alkes. (I,) = mild changes in IeFt apex only. THemoptysis severity: +, less than 50 c.c.: ff, SO to 100 c.c.. +++. 100 to 500 c.c #Patient is still living at time of this rwort. **OHS = surgery (total correction). rt\ve are grateful to Dr. L. Bernstein of Australia for the follow-uu on this case.
28 13 18 22
10 7 21
pulmonary artery (i)
A,fe at onset
18 (hematemesis ;~t 6 years) 10
Ibars survival after 0 II set 5
Death and autopsy
I~ronchials enlarged at autopsy, apical cavitation, Aspergillus super infection, death following lobectomy Improved following central shunt at 40 years of age
Autopsy showed multiple thrombi, arteries, bronchials enlarged
OHS** 20 years, large hemoptysis further recurrence, good result Pulmonary osteoarthropathy, death OHS Pulmonary osteoarthropathy, death hemoptysis, right upper lobed9 attempted good result, prior
pulmonary no further
vnlvotomy hemoptysis developed
following attempted OHS, autopsy revealed bronchi& enlarged, history systemic thromboembolism OHS 23 years, good result, no further hemoptysis Massive hemoptysis from aneurysm right upper lobe 21 years, shock cerebral damage, death several months later Died following intrapulmonary hemorrhage at site of anastomosis subclavian-to-bronchial vessel, no right pulmonary artery or left pulmonary artery identified at autopsytt Intercostal pulnionnry artery aneurysm (postsurgiCal)
following 29 years,
The 17 patients in this group all had extreme right ventricular outflow obstruction. Rlany of those listed as tetralog> (tetrafogy of Faflot [TOF] in Table II I) had complete atresia of the right ventricular outflow tract. In some this atresia ~-3s of congenital origin and associated with aljsence or extreme hypoplasia of the main \Vhile in others the pulmonary artery, atresia was almost certainly of the acquired type previously described by our group.‘g Some authors list such patients “pulmonary atresia with venas ha\.ing tricular septal defect” or occasionally “pseudotruncus. ” They are, holvever, extreme examples of tetralogy of Fallot or, embryologically, of marked conaf hypeplasia. This group forms an unusual and probably unique series in that most of the patients lvere able to survive to 20 or more years of age, despite marked cyanosis, in part due to compensatory bronchial circulation, and in part due to surgical creation of one or more systemic-pulmonary anastomoses. The large majority of these anastomoses were Blalock-Taussig shunts or anastomoses bet\z-een the subclavian and pulmonary arteries (Table III). The anatomic diagnosis in all cases listed in Table III n-as confirmed l)y catheterization and angiocardiography and in most at subsequent open-heart surgery or autopsy. The age of onset of hemoptysis varied from 4 to 47 years and in most cases occurred from the lung with the less adequate pulmonary flow, namely the lung supplied 1,) bronchial x-essels. l’he pzllmonuvy vc~scz~lar bed. A variety of methods has tIeen used to study the pulmonary vascular bed in extreme pulmonary stenosis or atresia, including whole lung section, serial lung sections, postmortem angiography17 or bronchial arteriography,17,1g and lung I)iopsy.3o Detailed reviews of the techniques and findings are available in Cudkowicz’s” excellent monograph and in other texts.1s~31~3Z Three major changes have been defined, namely, thrombosis in the small pulmonary vessels (often associated with intimal fibrosis), increased size and tortuosity of the bronchial arteries, and relative hypoplasia of the pulmonary arterial walls. All 3 changes may contribute to hemoptysis and, not infrequently, may
interact. Iqor example, hypopl(lsit~ of the pztlnzontlyy clrterirll wall may predispose to aneurysmal dilatation and rupture; such ;L sequence of events has been recorded in pulmonary arterial stenosis with aneurysma1 poststenotic dilatation.“” One patient in our series (Case 12, Table III) \\:itll tetralogy of Fallot and right ventricular outflow atresia \vas noted to have marked hypopfasia of the right pulmonary artery when a sub~~la\-ian-pulrnotlary anastomosis \vas performed at 7 years of age. He developed progressive aneurysmal dilatation of the upper lobe artery over the years (Fig. 1, A and U), had his first hemoptysis at 20 years of age, and died of complications following a massive hemoptysis from the angioma of his right upper lol)e at age 21. The angioma appeared on angiography to be composed of a direct communicatiou between a large systemic (?bronchial) artery and the very hypoplastic right upper lobe brawl1 of the pulmonary artery (Fig. 1, Case 12). Plllmontrry thrombosis. Thrombosis affecting the small pulmonary arteries in patients lvitli severe pulmonary stenosis MYLS first described by Rich.“4 Ferencz3j noted these lesions to be more lvidespread and se\-ere in patients with cyanotic spells and observed regression in these thromtwtic lesions following establishment of a more adequate pulmonary blood flow after a shunt procedure.36 Although polycythemia and the possible attendant disorders of the clotting mechanism may contribute to in situ thromboses, the pathologic studies of Best and I-Ieath3i and FerenczJ5 showed no clear correlation bet\veen severity of thrombosis and hematocrit levels. Naeye, Kusserow, and JacobsoP produced thrombotic lesions in the small pulmonary arteries of 2 dogs by markedly reducing pulmonary flow to one lung without inducing polycythemia. The evidence is, thus, that decreased flow in the pulmonary arteries is the main factor producing in situ thrombosis. In the present series, pulmonary thrombosis in the small vessels was found at autopsy in 4 of the 7 autopsied cases. Fourteen of the 17 patients had a history of cyanotic spells in infancy, all had extreme reduction in pulmonary blood flow, and most a-ere at least 10 years of age before
complications of CHD: Hemoptysis
Fig. 1C. Arteriogram innominate artery. angiomatoid lesion chial artery to right the right subclavian subclavianpulmonary mosis.
Fig. 1, A and B. Case 12: angioma and fine reticular marking of bronchial circulation. A, Age 6 years. Lung fields clear. B, Age 20 years. Arrow indicates angiomatoid lesion in upper pole of the right hilum.
any palliative surgery was undertaken. Thus, all had multiple predisposing factors to in situ pulmonary thromboses. Thrombi may have been important in patients such as Case 4 (Table III) with severe cyanosis over many years, despite a shunt procedure, hemoptysis at 19 years of age, and an eventual good result from open-heart surgery. Enlarged bronchiul circulation. This is thought to be the major cause of hemoptysis in patients with decreased pulmonary arterial flow. Bronchial artery changes have been documented pathologically in many studies16Jg and some of the clinical and
of Case 12. Catheter tip in Upper arrow indicates round supplied by systemic (?) bronupper lobe communicating with artery. Lower arrow indicates artery end-to-end anasto-
radiologic manifestations have been described.28,40 Physiologic studies have shown increased bronchial flow in tetralogy of Fallot ranging from 0.14 to 2.8 L./min./h12.41-43 Although anatomic classifications of the bronchial arteries are available,17v44 data are Iacking on precisely which bronchial vessels enlarge in extreme pulmonic stenosis and on the rate of enlargement with age. Pathologic studies by Collisteri6 and others suggest that most collateral vessels arise in the hilum, but surgical findings frequently indicate massively enlarged pleural collaterals. Hales and Liebow3g have shown in postmortem studies that bronchial arteries near the hilum may dilate in infancy or even in intrauterine life and supply the pulmonary vessels by retrograde flow. In the present series, x-ray or fluoroscopic findings indicative of enlarged bronchial arteries were present in 8 of the 17 patients (Fig. 2) and dilated bronchials were described at operation or autopsy in 13. Finger clubbing, which was thought to
Am. Heart I. October, 1972
Fig. 2, A through E. Case 2: enlarged bronchials and pseudofibrosis. A, Age 21 years. Lungs show fine reticular pattern, bronchial circulation. B, Age 34 years. Tomogram reveals apical capping, pseudofibrosis, and cystic areas in upper lobes. c, Age 34 years. Angiogram shows multiple tortuous vessels (probably bronchial arteries) in upper lobes. Aorta fills from right ventricle. Main pulmonary artery not visualized. D, Age 38 years. Pleural capping and cystic areas. Compare with A and B. E, Age 43 years. Barium swallow shows irregular indentation of esophagus by collaterals. (Relevant area betwee 2 black lines.)
Fig. 3, A and B. Case 6: enlarged bronchial filling of pulmonary artery branches. A, Right ventricular amjocardiogram revealing pulmonary outflow atresia. B. Selective bronchial arteriogram showing right and left pulmonary arteries fill from bronchial artery. No filling of main pulmonary artery or right upper lobe branch. (Catheter tip in bronchial artery.)
be a sign of increased bronchial flo~v,~j was present in all and pulmonary osteoarthropathy was a major symptom in 2 of the group. Bronchial arteriograplly4Gr47 in vivo in Case 6 showed a dilated bronchial artery entering the left pulmonary artery near its origin and filling both right and left pulmonary arteries by retrograde flow (Fig. 3, B). There was no filling of the atretic main pulmonary artery or of the right upper lobe branch. Massive hemoptysis in the right upper lobe, supplied entirely by bronchial vessels, was the cause of this boy’s death and was attributed to probable rupture of an enlarged bronchial artery analogous to that seen on the left side, but without any communication to a true pulmonary vessel. ;\Iassive bleeding in this series, as previously noted, usually occurred from the lung or lobe \vith the least adequate pulmonary blood supply. For example, in Case 17, massive fatal hemoptysis occurred in the left lung with complete absence of a left pulmonary artery. Massive hemoptysis has been recorded as a major symptom at a relatively young age in the absence of one pulmonary artery w?thout other associated heart disease and has in such cases also been attributed to I)ronchial artery rupture.g Radiologic progrcsxiort. The fine retic.ular pulmonary markings and other stigmas of increased 1)roncllial flop, have Iwen described previously.40 Review of the 17 cases summarized in Table I I I showed that
prior to and accompanying the onset of hemoptysis an interesting series of clinical, pathologic, and radiologic changes may occur. The radiologic changes are l>est seen in the upper lobes (Figs. 2, 4, 5, 6, 7) and simulate chronic tuberculosis or histoplasmosis. The term “pseudofibrosis” seems most appropriate. We attribute the radiologic appearance to the late effects of 3 series of small pulmonary artery thromboses and infarctions associated with localized pleuritis resulting in apical pleural capping. The dilated bronchial arteries themselves probably play a role in forming the radiologic picture. The changes are more readily seen in lordotic views.4* Pseudofibrosis was seen in 9 patients of this group, all over I.5 years of age. In 2 patients the first hemoptysis preceded the abnormal radiologic appearance, while in others Lloth appeared virtually simultaneously resulting in much diagnostic difficulty. Case 2 is of particular interest in that, despite extensive pseudofibrosis (Fig. 2), pulmonary function studies showed only a moderate degree of restriction and a slight degree of obstructive ventilatory defect. The vital capacity was 71 per cent of predicted and a diffusion capacity was normal. This n-as interpreted to mean that, despite the radiologic changes, further surgery might I)e tolerated. At the age of 40, despite tile presence of severe pseudofibrosis and a history of recurrent small hemoptyses for 22 years, the patient underwent a central
rrrar1 I. 1972
Fig. 4. Sequence of events in ~udofil)rosia. IXagram d clinical, pathologic, and radiologic progrkon in hemoptysis and pxudofihosis. (We acknowledge the aid crI Dr. Willis Hurst in the preparation d this diaFam.)
A and II. Case 3. A, hgu 8 years.
Lung fields arc clear. n, Age 1Y years. MaterA apical pseudofibrosis
is preacnt. INet: right apicogran~ ‘ascending aorta to right pulmonary artcry shunt with striking improvement in cyanosis and poIycythtmia+ I lemoptyses have persisted, but to a lesser degree in the subsequent 4 years. Similar respiratory function findings, namely, a normal difiusing capacity and a slight reduction in vital capacity and forced expiratory volume per 1 second (FEVJ, not improved by Isuprel, have been observed in a few other subjects. In this patient and 7 others with pseudofibrosis, all studies were negative’for tuber-
culosis, histoplasmosis, and other granulomatous infections. Nevertheless, in advanced castes fibrosis may be associated with angiomatous cavitation and with secondary opportunistic infection,‘@ with Aspqillus, or other orgaGsm. Such a case is described in det;iil below. The presumed sequence of pathoIogic and radiologic changes in pseudofibrosis is outlinc4 in Fig. 4 and summ,arized in Table IV. Case 1. S. K. was first seen in 1948 at 12 years of agr with a history of frequent cyanotic epclls in infancy and cowtant cyana& from 6 months of age.
Severe cyanotic heart disease Survival for 15 or more years Reduced or absent pulmonary artery flow Enlarged bronchial artery circulation Apical pseudofibrosis Gwitary changes may be followed by secondary “[email protected]
Examination &owed a cyanotic boy with a hemoglobin of 24 Gm. and hematocrit of ,&2. No cardiac murmurs were present. an Auoroscopy the aorta was observed to be large and the pu1monary conys extremely concave. A pu1monary artery was visible on either side, but in addition there were many smaller vessels at both hilar areas extending almost to the periphery, which were thought to be collateral vessels. The electrocardiogram (ECG) showed right axis deviation and right ventric&r hypertrophy. Angiocardiography shewed early filling of the aorta from the right ventricle and no direct Aow into the pulmonary arteries, but bilar collateral vessels were visualized. This confirmed the clinical impression of pulmonary outflow atresia; the pulmonary arteries were thought to be patent distally as judged by their size on x-ray and by evidence of filling on angiocardiography. At operation in 1948, Dr. Blaiock noted many collateral vessels in the media&inum and found a small, quiet left pulmonary artery. A collateral which entered it far proximally was torn and a good deal of bleeding occurred. A left end-to-end subclavian-pulmonary anastomosis was performed. The patient tolerated the procedure well and developed a good continuous murmur. Postoperatively the hem&o&t dropped from 82 to 63, the hemoglobin, from 24 to 20 Gm., and the arterial saturation rose from 64 to 72 per cent. He returned 10 years later in 1958 at the age of 22. For about 6 years postoperatively cyanosis had been much less with an increase in exercise tolerance and rate of growth. However, for the past 4 years cyanosis had increased and the patient became more limited and began to have recurrent hemoptyses, He bad had a work-up in a sanatorium for tuberculosis; this diagnosis was excluded. Examination showed a continuous murmur of Grade I to 2 intensity over the left upper chest, an ejection &lick, and a loud singie second sound. Breath sounds were impaired over the right upper lung field with amphoric breathing and posttussive &es. The hemoglobin was 20 Gm. and the hematocrit, 70. Review of the chest x-rays showed that in 1948 there were no parenchymal lesions. By 1955 the film taken in the sanatorium showed a moderately extensive “fibrotic-appearing” infiltrate in the right upper lobe with probable cavitation, By 1958 x-ray and tomography50 showed many cavities containing inspissated material. Angiocardiography (Fig. 6) was repeated and again showed right ventricular outflow atresia. The right pulmonary artery was visualized very late while the left was visualized
Fig. 6. Case 1: pseudofibrosis and opportunistic infection, Aspergillus. Age 22 years. venous angiocardiogram reveals atresia of the right ventricular outflow tract. The left pulmonary artery fills from the aorta via an end-to-end subclavian pulmonaryy anastomosis. Right pulmonary artery not visualized. Bilateral upper lobe infiltrates are extensive and cystic on right.
shortly after the aorta, confirming that the subclavian-pulmonary anastomosis was still functioning. The opacification of the right apex was thought to be due to ‘“crowding of vessels in an area of consolidation.” Cardiac catheterization confirmed the Spresence of a ventricular septal defect and systemic levels of right ventricular pressure. Following discharge back to his home in Wisconsin, the patient continued to have hemoptysis; at one time he lost a pint of blood very rapidly. A right upper lobectomy was done. The lobe was found to. be contracted to about one third of normal size and completely fixed to the chest wal1. There was severe bleeding and “a large amount of collateral circulation.” Cystic lesions containing dense hemorrhagic and necrotic material were found from which Aspergillus was cultured. The patient developed postoperative pleural infection necessitating open drainage and died some days later. Autopsy confirmed the presence of ventricular septal defect with complete occlusion of the pulmonary artery at its origin and hypoplasia of the main pulmonary artery. Lung sections showed some thromboses in the small pulmonary artery branches. The pathology findings are summarized in a letter from Dr. Lawrence T. Giles of Madison, Wisconsin: “The lesion in the right upper lobe was an angiomatous one with numerous connections between the costal and bronchial arteries, some of which appeared aneurysmal. There were large cystic areas filled with Aapergillus. Dr. HeIen Dickie’s view was that there were preformed cavitary areas which then became occluded with Aspergillus. The main problem was failure of pulmonary artery blood supp1y to the
Am. Hrart J. October, 1972
Fig. 7, A through F. Case 14: intercostal pulmonary artery aneurysm following shunt for tetralogy. rl, Age 18 months. Lung fields are clear. B, Age 15 years during hemoptysis. Left midlung opacity and right apical pseudofibrosis. C, Right ventricular angiocardiogram showing atretic pulmonary outflow tract. Left lung filling from end-to-end subclavian pulmonary annstomosis. Note rib notching on left. Arrow indicates angiomatous lesion. II, Angiocardiogram closeup revealing intercostal :utcry supplies nngioma. E, Angiocardiogram, levophase, showing angioma supplied by intercostal artery and draining into pulmonary veins. F, Ten days after hemoptysis. Lung fields almost clear.
right lung, which was supplied by intercostal arteries. The episodes bleeding were from the angiomntous by these vessels.”
bronchi,d and of pulmonary lesions formed
DISCGSSION. Hemoptysis in enlarged bronchial arteries may occur from erosion of a tortuous dilated varicose bronchial artery directly into a broncllus,51 from localized pulmonary infarction at the bronchopulmonary anastomotic site, or from rupture of an atherosclerotic bronchial artery plaque. j2 Massive hemoptysis or intrapulmonary bleeding with bronchial artery rupture was the immediate cause of death in Cases 6, 13, and 17 in the present series and was a major contributing cause of death in Cases 1 and 12. Other collateral vessels. Hemoptysis is frequent in congenital pulmonary arteriovenous fistula.12 It may also occur in association with aberrant vessels from the descending aorta supplying a sequestered pulmonary lobe53 or in systemic-pulmonary arteriovenous fistula.54*55 An unusual type of systemic-pulmonary arteriovenous fistula causing hemoptysis is described below. Case 1-J. B. JY. was first seen at 10 months of age with a history of cyanosis dating from 3 months of age. A Grade 2 systolic murmur was audible down the left sternal border. X-ray showed a markedly concave pulmonary conus and a diagnosis of tetralogy of Fallot was made (Fig. 7). She developed severe cyanotic spells and by two years of age her hemoglobin was 17.8 Cm., hematocrit, 75. At operation, a left end-to-end subclavian-pulmonary artery anastomosis performed by Dr. Blalock, an incision was made in the third left intercostal space. Many collateral vessels were noted in the chest wall and mediastinum; the left pulmonary artery was small, about 6 mm. in diameter and of low pressure. Over the next few years the child did moderately well, although polycythemia increased slowly. The lung fields were noted to show an unusual reticular pattern suggesting increased bronchial flow and the vascularity of the left lung was greater than that of the right. At 12 years of age she had a sudden hemoptysis of bright red blood, lasting for 2 days, occurring in 2 episodes each amounting to approximately half a teacup. Two days later a patchy infiltrate was noted in the middle third of the left lung periphery and was attributed to a small infarct, although a lung scan did not show any area of decreased uptake. Three years later the patient was admitted with a history of three episodes of hemoptysis amounting to about 50 to 75 C.C. The sudden onset followed a class trip to Washington with more than usual activity and excitement. There had been no associated chills or fever. During the 10 days after admission, there were 5 gross hemoptyses of between 50 to 150
C.C. of bright red blood. X-ray (Fig. 7, B) showed a left midlung opacity. Emergency lobectomy was being considered when the episode subsided. Skin tests for tuberculosis and fungal infections were consistently negative, as were sputum cultures. Bronchoscopy showed blood to be issuing from the left upper lobe orifice. Selective right ventricular angiography showed a hypertrophied right ventricle, a narrow infundibulum with atresia of the pulmonary outflow tract, a large right aortic arch, and a functioning left end-toend Blalock-Taussig anastomosis (Fig. 7, C). An enlarged and hypertrophied highest intercostal artery arising at the level of T6 and supplying the upper 4 left intercostal spaces was noted. The fourth intercostal artery was markedly elongated, tortuous, and dilated with associated rib notching. The vessel appeared to be the principal contributor to a large mass of angiomatoid vessels in the lateral aspect of the left lung (Fig. 7, D), which then drained via the left pulmonary veins to the left atrium (Fix. 7, E). The angiomatoid malformation was noted to correspond to the surgical entry site. Over the ensuing 3 years the patient has remained clinically stable and no further hemoptyses have occurred. DISCUSSION. If the subclavian artery is used to perform a systemic-pulmonary anastomosis, various secondary vascular changes may occur, including dilatation of intercostal vessels great enough to produce unilateral rib notchingS6 or the rare late development of a subclavian steal syndrome.57 The degree of rib notching in the patient mentioned above \vas unusually striking and correlated with the extreme degree of intercostal artery enlargement, resulting in a unique type of systemicpulmonary arteriovenous fist&. This complication was not otherwise encountered, to our knowledge, in the almost 2,000 patients who have undergone ISMockTaussig anastomoses in this institution. This patient illustrates well the therapeutic dilemma sometimes encountered in the acute phase of hemoptysis in cyanotic patients, since lobectomy or pneumonectomy in this case would have resulted in the removal of the only efficient oxygenating lung.
Group II: Pulmonary obstructive disease
Hemoptysis has long been recognized as one of the cardinal symptoms of severe pulmonary hypertensive vascular disease.“,?? The incidence appears to rise sharply in the second decade of life, being rare under 10 years of age.58
Race and ser
! Shunt DiapJsis*
Primary pulmonary Hypertension PFO VSD (Eisenmenger’s) VSD (Eisenmenger’s)
Single ventricle Single ventricle
2.‘3 24 35
WF WM WM
TOF TOF TOF
PVOD 6 16 27
WM WM WF
Dextrocardia single ventricle, pulmonary st,enosis
basis for obstructive
Age at onset
with lransposition w&h transposition
27 28 29
i Years suruiml after onset
jollouhg 44 32 23
systemic-pulmonary +++ R
has been well defined.l An excellent diagram of the development of the dilatation lesion of the pulmonary arteriolar wall is available in Harris and Heath’s monograph.32 Small repeated hemoptyses can readily be visualized as occurring from the Grade V dilatation lesions typical of advanced pulmonary hypertension. Despite much study there is still some doubt as to whether these dilatation or angiomatoid lesions represent outgrowth of the small pulmonary arteries or dilated, degenerating bronchial arteries. Whichever theory is correct, the pathologic findings correlate well with the clinical vascular
Died following attempted OHS, pulmonary at,herosclerosis at autopsy
Death due to dissecting aneurysm of pulmonary artery, pulmonary atherosclerosis
Hemopt)ysis recurrent until death from cerebral embolism, thickened pulmonary vessels at, autopsy
Xale sibling died of primary pulmonary hypert.ension (autopsy)
13,18 16 26
Death and ! autopsy 1
nature of the hemoptyses, which are usually mild or moderate in degree and recur at unpredictable intervals. Clarkson”* found hemoptysis a bad prognostic sign in patients with ventricular septal defect and PVOD, since 7 of 11 patients, or 64 per cent, survived less than 7 years after the onset of this complication. In our series the anatomic diagnosis in all 15 patients in Group II was confirmed at one or more cardiac catheterizations (Table V). Hemoptysis first occurred between 12 and 34 years of age (mean, 22 years) and recurred in 10 of the 15. The series is unusual in that PVOD in 10 patients appeared as a late complication following a systemic-
Fig. 8, A through D. Case 23: PVOD following shunt for tetralogy. A, Age 24 years. Marked dilatation of right and left pulmonary arteries with decreased peripheral vascularity, i.e., “pruning effect.” B, Lateral view. Dilated pulmonary arteries frequently mistaken for enlarged hilar nodes. C, Aortogram, left anterior oblique view, reveals markedly dilated right subclavian artery anastomosing with pulmonary artery. D, Later view showing
pulmonary anastomotic procedure for tetralogy or for other cyanotic malformations originally associated with pulmonic stenosis.21Js The incidence of PVOD following such an anastomosis has been recently found by Dr. Taussig to be approximately 7 per cent over a 20 year period. The large number of such patients in the present paper should not be taken to mean that. this is a common complication of shunt procedures, but rather that when it does
occur, hemoptysis is a frequent manifestation. The radiologic and angiocardiographic findings in Case 23 of PVOD following a shunt procedure are illustrated in Fig. 8. Case 9 (Table III), in which the clinical and pathologic findings have been reported by Folger and Otken,5s is of interest in that the only recorded hemoptysis occurred when the patient was 21 years of age, before any cardiac surgery. It seems probable that the patient had many intrapulmonary
ANI. Heart J. October, 1972
Hemoptysis associatedwith pregnancy 01 owl contraceptives Hemoptysis
Ditzgnosis Age at onset
VSD, PVOD (Eisenmenger’s)
Aortic pulmonary PVOD
10 weeks pregnant 10 weeks pregnant
3 months pregnant 8 months pregnant
Truncus Tut. aortic arch, PVOD
TOF, PVOD following shunt TOF, PVOD following shunt. OHS
Varying hormones for metrorrhagia for 4 years 5 months after starting pill 21 months after startpill
TOF (Post OHS), no evidence PVOD TOF, shunt 13 years, no no evidence PVOD
10 weeks pregnant 6 months after starting pill 4% months after starting pill
thromboses predisposing to the ultimate development of pulmonary hypertension and pulmonary thromboembolism. Group II-A: Hemoptysis with pregnancy or oral contraceptives
Hemoptysis in 7 white women in the series (Table VI) appeared temporally and causally related to pregnancy or the use of oral contraceptives; 5 were cyanotic and had PVOD confirmed at one or more catheterizations. The sixth had had a successful total correction for tetralogy but had been cyanotic till about 18 years of age. She did not have PVOD. The seventh woman had a functioning Blalock-Taussig anastomosis and also did not have PVOD. The J,Iayo Clinic group in a recent papers8 reported that in 23 female patients over 16 years of age \vith Eisenmenger’s complex, one had an uncomplicated pregnancy and another had “infrequent hemoptyses during both of two pregnancies.” The over-all hazard of pregnancy in Eisenmenger’s complex is not yet clear from the
First pregnancy terminated by spontaneous abortion about 12 weeks, second pregnancy therapeutic abortion for hemoptysis (see text). First pregnancy spontaneous abortion, second pregnancy several small hemoptyses, prolonged bed rest’, live-born child Three mild recurrences in year since discontinuing hormones Died one month after onset, autopsy showed pulmonary thromboembolism and atherosclerosis Had 4 successful pregnancies, two spontaneous abortions prior to starting pill, no major hemopt’ysis after stepping pill until tenth week cf seventh pregnancy (spontaneous abortion) One mild recurrence 2 years after stopping pill during episode of “flu” Lung scan showed multiple pulmonary emboli, no recurrence 1 year after stopping pill
literature, but the major risk does seem to be pulmonary thromboembolism. The “tl~rombogenic” effects of both pregnancy and oral contraceptives continue to be much studied. A recent analysis of the available literature60 assesses the risk of major thromboembolism in a women taking oral contraceptives to be bet\iTeen 4 and 8 times that of a control. Oakley and Somerville1o reported a rapid downhill course in 3 patients with P\‘OD while on oral contraceptives; one developed inoperable pulmonary hypertension in a previously operable ventricular septal defect. One nith a complex cardiac malformation died of hemoptysis, xvhile tile third showed a striking increase in effort intolerance and developed splinter hemorrhages in the hand. These authors make the interesting suggestion that oral contraceptives may at least in some cases cause an acceleration of the otherwise more slowly progressive disease of pulmonary vascular obstruction. Pregnancy seems to have had a similar effect in our Case 33 described in detail below. Because of the tendency to spontaneous
1'0111mc s4 Nmaber 4
Fig. 9, A and B. Case 33: PVOD (Eisenmenger) hemoptysis during pregnancy. A, Age 24 years during hemoptysis. Pulmonary artery lordotic view. Collapse of the left upper lobe and shifting midline structures. Herniation of the right lung into the left upper hemithorax and accompanying infiltration. Tenting of left side of the diaphragm.
pulmonary tl~roml~oeml~olism in adult cyanotic patients I\-ith P\:wOD, the exact relationship of the medication to outcome is difficult to elucidate. For example, the age at death and the autopsy findings were I-cry similar in Case 21 (Table I’), a male, and in Case 36, a female, nrho de\.eloped massive pulmonary thromboembolism \vhile taking oral contraceptives. A detailed analysis of the problem in cardiac patients is necessary, hut at present, both pregnancy and oral contraceptives appear to carry a significantly greater risk of pulmonary tl~romboeniboIism in women \\.itll P\TOD than in the normal population. Case 33. K. M. was first seen at 7 weeks of age with a history of a cardiac murmur from one month of age. She was poorly nourished and had a harsh precordial systolic murmur. By 5 months of age the murmur persisted and some hepatomegaly was noted; the patient was digitalized. The heart on Iluoroscopy was markedly enlarged with a full pulmonary artery. K. M. improved in the second year of life. A harsh systolic murmur and thrill persisted down the left sternal border. The physical signs were always thought to be somewhat atypical for a ventricular septnl defect, since this diagnosis was not confidently made. By 9 years of age, K. WI. was acyanotic and very nc.tive. At that time there was no thrill and only a (;r:tde 1 to 2 blowing systolic mru-mur. Heart size on s-ray was normal although the pulmonary vascularity was still increased centrally, The ECG, previously not remarkable, showed marked right ven-
tricular hypertrophy. During the patient’s early teens, slight but definite cyanosis became apparent. Cardiac catheterization in 1959 at the age of 16 years showed a pulmonary artery pressure of 135/73 mm. Hg, a femoral artery pressure of 114/72 mm. Hg, and an arterial oxygen saturation of 88 per cent. A right-to-left shunt was detected by dye curves at the ventricular level, but no left-to-right shunt. K. M. married at age 21 and about one year later had the first hemoptysis. It amounted to only one teaspoon of bright red blood with no obvious precipitating cause. She was found to be 2 months pregnant. The following day a small infiltrate was seen in the left upper lobe, not visible on films taken 24 hours previously. She had a spontaneous abortion about 2 weeks later. No further hemoptysis or increase in symptoms occurred until 9 months later, about 11 weeks into her second pregnancy, when she had several small hemoptyses. She was hospitalized and while in the hospital she had several episodes of severe chest pain and repeated small hemoptyses (Fig. 9). A lung scan showed multiple areas of decreased uptake in both lung fields,“’ thought to be consistent with multiple areas of pulmonary embolism. Hysterotomy and bilateral salpingectomy were performed. There was no evidence of any pelvic vascular or inflammatory disease. She had a benign postoperative course and was kept on anticoagulants for 6 months. In the ensuing 3 years she has remained well. has had no further hemootvses and no decrease in exercise tolerance, and h:ls- adopted a child. COMMENT. ‘l’his patient’s llenloplysis seemed clearly related to hormonal changes induced by pregnancy, since llemoptysis occurred only during pregnancy and stopped
Hemoptysis from other causes Hemoptysis
alul autopsy i
Truncus Type II, atjelectasis left, lower lobe due to arterial compression
Pulmonary valvular stenosis (valvotomy at 7 years),
abruptly apeutic Group
VW, anomaly of right ventricle muscle bundle (OHS 16 years)
with either abortion. III: Other
Pulmonary venous congestion on the basis of a congenital defect may lead to hemoptysis in patients surviving into adult life.12.23 In 3 cases in our series, hemoptysis could not be attributed to collateral vessels, extreme pulmonary arterial hypoplasia, or PVOD. In one child of 5 years of age a single massive hemoptysis followed bronchoscopy; the presumed cause was erosion of the bronchial wall compressed by the overlying dilated left pulmonary artery (Table VII, Case 40). In Case 41 no cause was found for repeated small hemoptyses occurring for many years after successful pulmonary valvotomy. Wagenvoort and colleagues30 have commented on the marked vascular changes in the lungs in pulmonary stenosis with intact ventricular septum, and it is possible that the bleeding in this patient was from persisting dilated bronchial x-essels. The patient eventually died suddenly from pulmonary edema associated with heroin addiction.e2 In the third patient, hemoptysis was the presenting symptom of a postpericardiotomy syndrome and occurred about 3 or 4 weeks postoperativellr. J Je made a good recovery and the symptonl has not recurred.
Massive hemoptysis 24 hours following bronchoscopy, no recurrence, death due to congestive failure
Death attributed to pulmonary
6 months -I-
edema associated with heroin addict,ion, cause of hemoptysis uncertain Hemoptysis was presenting symptom; postpericardiotomy syndrome
Discussion Hemoptysis in the present series was seen almost exclusively in cyanotic patients and involved either bronchial or pulmonary arterial vessels. Hemoptysis due to pulmonary venous engorgement has been reported, but was not seen in our series. As more cyanotic malformations become amenable to corrective surgery in early life, it is probable that progressively fewer cyanotic adolescents and young adults will be seen, and bleeding from dilated bronchial vessels, an example of a disordered compensatory mechanism, may hopefully disappear. We hope that the present paper will stimulate further study of such patients by the techniques of toniography,50 selective bronchial arteriography,46s47 or radioisotope scanning.61 Such studies seem promising in the elucidation of the natural history of prolonged decrease in pulmonary blood flow. Investigation of patients with “pseudofibrosis” has shown only a rare instance of secondary “opportunistic” infection. In most cases, negative skin tests, sputum cultures, and viral studies suggest that the underlying etiology is vascular, as outlined in Fig. 4. The management of hemoptysis may present special problems if the affected lung is the major source of oxygenated blood. hlassive hemoptysis may well indicate rupture of a dilated I)ronchial artery and is a11 indication for detailed stltd?; and the
earliest possible corrective surgery. Frequent small hemoptyses in patients with pulmonic stenosis are probably associated with pulmonary tliron~l~oses in the small pulmonary arteries and are not necessarily a contraindication to corrective cardiac surgery, as indicated by successful postoperative course in several patients in this series. The management of hemoptysis in I’VOD may include venesections as a prophylactic measure and the usual techniques of reassurance, supression of cough, and so forth once hetnoptysis does occur. Summary I-Iemoptysis is reviewed as a rare but major complication of congenital heart disease. Forty-two patients \vith hemoptyses not associated with endocarditis, tuberculosis, or immediate postoperative complications are reviewed; all but 2 were cyanotic. Group I (17 patients) had extreme pulmanic stenosis or atresia, and hemoptysis was attributed to a combination of hemorrhage from enlarged tortuous bronchial arteries and thrombotic lesions in the small pulmonary arteries; one patient bled from a postoperative intercostal pulmonary artery aneurysm. In 9 patients all over 15 years of age, hemoptysis was associated with “pseudofibrosis” at the lung apices. The radiologic progression of this lesion, not previously described, is outlined. (;roup II (15 patients) had pulmonary \Tascular obstructive disease associated with varied intracardiac lesions. In 7 additional patients, all but two with PVOD, hetnoptysis was associated with pregnancy or oral contraceptives. The 3 patients in Group III had varying causes for hemoptysis, including erosion of a large aberrant vessel to the lung following bronclioscopy. The relevant literature is discussed and the use of newer techniques in investigating the pulmonary vascular bed in vivo is emphasized.
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We are grateful for the assistance of Dr. John P. Dorst, Mr. James F. Tedesco, R.B.P., and Mrs. Priscilla Schaff for their help in the preparation of this manuscript, and to Dr. Martin Donner for help in retrieving data in Case 14 (Fig. 7).
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