Effusive-constrictive radiation pericarditis

Effusive-Constrictive

Radiation

Two Cases Illustrating

Pericarditis

Value of Angiocardiography

in Diagnosis * ISRAEL STEINBERG, xo.t n’ew York,

New York

R

ADIATION pericarditis, which apparently may be of the effusive-constrictive type, is important to recognize. It may simulate isolated myocardial disease and result in considerable disability; whereas, if correctly diagnosed, pericardiocentesis when there is cardiac tamponade, and pericardiectomy for constrictive pericarditis, may be life-saving. In 2 women treated by mastectomy and irradiation therapy for cancer of the breast effusive-constrictive pericarditis developed which was diagnosed 20 and 3 years, respectively, following radiation therapy. Death, probably owing to cardiac tamponade and constrictive pericarditis, occurred in the first case; creation of a pericardial window with drainage of pericardial fluid into the left pleural space alleviated the symptoms of cardiac tamponade in the second patient. In both cases, angiocardiography played a significant role in diagnosis and indication of the treatment. REPORT

sure was 110/60 mm. Hg, and venous pressure, 200 mm. saline. The circulation time was prolonged (23 sec.). The liver and spleen were enlarged and there was ankle edema. Roentgenoscopy of the thorax revealed a left pleural effusion and diminished pulsations of an enlarged cardiac silhouette. Left thoracentesis yielded 750 ml. of clear, yellow fluid. Microscopic study of the fluid showed lymphocytes; the culture was sterile. Forty-five minutes following the chest tap acute pulmonary edema developed, but responded to emergency treatment, which also included reinstitution of digitalis therapy. Angiocardiography: The conventional chest roentgenograms, following thoracentesis, showed absence of the left breast, a large globular appearing heart, a moderate left pleural effusion, and parenchymal fibrosis in the left perihilar region (Fig. 1). Angiocardiography was performed on October 18 in the erect frontal and left anterior oblique views. There was prolongation of the circulation time (and opacification) of normal-sized cardiac chambers. In frontal view, the heart was surrounded and elevated by fluid (Fig. 2, A and B). The left pulmonary artery was obliterated except for some tiny basilar branches. Films in the left oblique view showed marked diminution of caliber and obliteration of the left pulmonary artery, beginning 4 cm. beyond its origin (Fig. 2C). Anterior and retrosternal accumulation of the pericardial effusion was evident. The patient died suddenly five hours after angiocardiography and before pericardiocentesis was performed. Autopsy Findings: The left lung was markedly adherent to the chest wall, and 500 ml. of strawcolored fluid was found in the left pleural cavity. Microscopic study revealed fibrosis of the alveolar septa of the left lung with intimal fibrosis and narrowing of the lumina of the medium-sized arteries. In marked contrast was a normal right lung. The pericardial sac contained 500 ml. of straw-colored fluid. The anterior surface of the pericardium was

OF CASES

woman (preCASE 1. A 56 year old Caucasian viously reported’) was admitted to the Cornell Division of Bellevue Hospital on Sept. 14, 1953, with complaints of hemoptysis of one week’s duration. A left radical mastectomy for cancer had been performed in 1933, 20 years earlier. This had been followed by irradiation therapy (dosage unknown) over a period of five years. In 1948, an excised ulcer of the left anterior chest wall showed radiation necrosis on gross In 1951, the patient and microscopic examination. had also been hospitalized for “heart failure” and had improved after digitalis therapy. On physical examination in 1953 the heart was enlarged with a large left pleural effusion; blood pres* From the Departments of Medicine and Radiology, N. Y. This work was supported by the Health Research t Recipient of Career Scientist Award of the Health I-258 and U-1648.

The New York Hospital-Cornell Council Research

434

Medical

School, New York,

of the City of New York under Contract U-1648. Council of the City of New York under Contract

THE AMERICANJOURNAL OF CARDIOLOGY

Radiation

Pericarditis

adherent to the posterior surface of the sternum and chest \vall. ‘The heart was small, and the chambers were of normal size; the ventricular walls were of normal thickness. Microscopically, there was fibrosis of the parietal pericardium. CASE 3. .4 34 year old Caucasian woman was admitted to the hospital on July 11, 1962. with a history of enlargement of the heart of 15 months’ duration. l‘he patient had been well until June 1959, when, following detection of a lump in the right breast of 6 months’ duration, a right radical mastectomy was performed. ,4 mass of the left breast also was found. and 11 days later a left simple mastectomy, bilateral oiiphorectomy. hysterectomy and appendectomy were performed. This was followed by radiation therapy over the thorax. total dose 6.000 r in a period of 31 days. (This was the only information obtained regarding the dosage.) In December 1960, 20 months prior to admission, she began having mild dyspnea and fatigue on exertion. In April 1961, 15 months prior to admission, cardiac enlargement was found in a roentgenogram of the chest. Severe dyspnea on slight exertion began and was somewhat relieved by digitalis therapy. Subsequently, she was suspected of having myocarditis and kept on strict bed rest. Despite this, edema of the legs, pains in the chest. and palpitation of the heart continued. Physical ewminution on admission to The New York Hospital revealed a tall (5 ft., 11 in.), thin woman lveighing 67.8 kg. and without radiation scars or pigmentation of the skin over the anterior thorax. Both breasts were absent and the operative scars of the anterior thorax and axillae were well healed. The lungs were clear. The heart sounds were not diminished, and a rough systolic murmur (grade 2/6) was heard over the base of the heart. The blood

FIG.

1.

Chse 1.

enlargemrnt

~.lonr~o,lloI7nl/,_ont~~ triProcnt~fllo:rrr~n sllo\z~s silhouette, absence of the left fibrosrs and fluid at the lctt base.

of the cardiac

breast. left perihilar

pressure was 84, ‘52 mm. Hg. and thr l)ru~‘ \ras regular. The electrocardiogram \\-as normal except for depression of the %‘I’ segments, consistent \\-ith digitalis effect or myocardial disease. or both. roentqenogr ams Angiocardiography: Conventional of the chest disclosed translucency of the thorax. owing to absence of the breasts. Right apical pleuritis and thickening and left midthorax haziness \vere pronounced, and the cardiac silhouette \vas enlarged (Fig. 3, A and B). Angiocardiography on .July 13 was performed in the supine frontal and obliclrte positions. The superior and inferior venac cavae were dilated. ‘I‘he cardiac chambers were of normal size but vvere slightly rotated to the left anterior oblique position. A soft-tissue density of pericardial

-;

A

I3 C Angmardrograms. A, frontalrrectviewdemonstrates pericardial fluid (arrow) beyond the outr-r border of the opacified right atrium (RA) with elevation of the heart above the diaphragm, Only small lower lobe branches of the left pulmonary artery are evident. B, frontalviewshows the large soft-tissue density (arrow) beyond the left border of the opacified left ventricle (LV). C, left anterioroblique view also shows pericardial fluid retrosternally. ‘The

FE.

2.

Case 1.

left pulmonary

artery

VOLUME 19, MARCH

is constricted

1967

soon after

its origin

(arrow).

(Reproduced

with

permission

of the

publisher.‘)

Steinberg

436

A

B

FIG. 3. Case 2. Conventional teleroentgenograms. A, frontalviewshows absence of breasts, prominence of the cardiac silhouette, especially in the region of the diaphragm, and fibrosis of the apex of the right lung. B, lateralview demonstrates the retrosternal prominence of the cardiac silhouette.

B

A

FIG. 4. Case 2. Angiocardiogroms. A, frontal(sup’me) angiocardiogram reveals marked elevation of the right cardiac chambers by pericardial fluid and pericardial fluid (arrows) adjacent to the opacified outer border of the right atrium (RA). B, later film also shows marked elevation of the left cardiac chambers and pericardial fluid (arrows) beyond the opacified left ventricular cavity (LV). THE

AMERICAN

JOURNAL

OF CARDIOLOGY

Radiation

FIG.

5.

Case

2.

‘12leroenigenopmn

taken

2 years

later

than

Figure

3.

right apical librosis of the lung and absence of both breasts. effusion adjacent to the outer border of the right atrium measured 6 mm. ; adjacent to the outer border ofthe opacified left ventricle it measured 15 mm. The heart was markedly elevated by the fluid (50 mm.) above the diaphragm. The preliminary circulation time (Decholin”‘) was 16 seconds (average normal is S-10 seconds), and this was confirmed by prolonged opacification of the cardiovascular structures (Fig 4, A and B). Operation and Follow-up Examinations: The patient was discharged on July 14 and returned to a hospital in her home town where three attempts to perform pericardiocentesis failed, so pericardiectomy was done in September 1962. The pericardial fluid \vas aspirated, and sufficient pericardium was resected to permit drainage of pericardial fluid into the left hemithorax. She then improved. In .January 1965, the patient experienced fatigue, tachycardia. chest pains and postural hypotension with attacks of syccope. She had had angiocardiography and cardiac catheterization at another hospital. ‘The angiocardiograms, when evaluated on her admission to The New York Hospital on April 5, were found free of pericardial effusion and thickening. Physical examination showed well healed scars of previous bilateral mastectomies, and probably because of the mastectomies, the apex of the heart was unusually forceful. There was a loud systolic ejection (grade 31’6) murmur best heard along the left border of the sternum and at the base of the heart. A faint, soft, blowing diastolic murmur was also detected at the aortic area. The blood pressure was VOLUME

19,

MARCH

1967

437

Pericarditis

A,

frontal

B, lateral

view

shows

the

cnrdi;lc silhouette,

norncd

view.

llOj70 mm. Hg. and. the heart was regular at a rate of 110. The lungs were clear, the liver \vas not palpable, and there was no edema of the legs. The electrocardiogram showed a regular heart rate of 103 and pronounced S-T segment and ‘I‘ \vave changes attributed to digitalis and myocardial disease. Roentgeqyams of the chest showed right apical and perihilar fibrosis (Fig. 5, A and B). The heart \vas normal in size. Selective supraaortic and left ventricular angiography showed mild (grade 1) aortic and mitral insufficiency; the coronary arteries were normal (Fig. 6, A and B). A high blood bromide content (145 mg. ‘g) was found, and although the exact nature of the heart disease could not be determined and may perhaps be due to myocardial radiation,2 some of the excessive weakness, postural hypotension and exhaustion was attributed to the bromism. She \vas discharged on Apri: 8. Recent communication (June 10. 1966) disclosed that she is well and doing part-time teaching.

There therapy of

producing

monary that

is general

the

damaged, 1940,

Thomas9

thoracic

radiation

fibrosis-6 and

irradiation

and

may

pericardirun

develop.

1945.

in

is capable

pneurnonitis

effusive,

Leach7 in

that disease

and

It is not as well

hearts,‘,”

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agreement

for malignant

fibrotic

also and

Fried 1943,

Wachtler”’

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be

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and

Goldberg3

Blumenfeld in

pul-

appreciated

1953,

and Hurst2

438

Steinberg

FIG.6. Case2. A, selctzwsupraualuular anrtopzmin the left anterior oblique position shows mild aortic regurgitation. R, srkctiae left oentriculogram in the left anterior oblique position also shows mild mitral insufficiency, probably owing to radiation myocarditis. and Gimlettel’ in 1959 and Connolly and BurchellL2 in 1961 described cases of irradiation pericarditis exhibiting effusive and constrictive manifestations. Because of the rarity of pulmonary and pericardial fibrosis following irradiation treatment of thoracic structures, other factors such as individual susceptibility or tolerance to irradiation and not the radiation dosage alone have been held responsible for the development of irradiation fibrosis by some authors.Q7 The pericardial effusion in Case 1 was apparently chronic, a period of 20 years having elapsed following radiation therapy before cardiac symptoms appeared. In contrast, the second patient had a more subacute course, in that only two years elapsed before enlargement of the cardiac silhouette (pericardial effusion) developed. In the 2 cases reported here, involvement of the lungs as well as the pericardium are in accord with Wachtler’s’o supposition that since the pericardium and heart are less sensitive to radiation therapy than the lungs, the latter would also be damaged. Perhaps the excision of both breasts in the second patient also enhanced roentgen penetration of the thorax and was an important factor for development of pulmonary fibrosis and pericarditis. Both patients were at first suspected of having heart disease, and pericardial effusive-constrictive disease was overlooked because the cardiorespiratory complaints were attributed to myo-

cardial failure rather than to the pericarditis. Enlargement of the cardiac silhouette with diminution in pulsations of the heart eventually incriminated the pericardium in Case 1. In Case 2, because the heart sounds and pulsations were vigorous and because localization of the pericardial effusion was chiefly along the diaphragmatic border of the heart, the diagnosis of pericardial effusion was more difficult and required angiocardiography for the definitive diagnosis (Fig. 4, A and B). In both instances, once pericardial effusion was diagnosed, there arose the possibility of its being due to metastatic breast cancer.F’Z13 Cellular studies of the pericardial fluid during life in 1 patient and postmortem examination in the other ruled out this possibility. In the living patient (Case 2), persistence of tachycardia, cardiac murmurs, chest pain and mild aortic and mitral incompetence (Fig. 6, A and B) may also be related to irradiation damage to the heart.2 Angiocardiography has long proved valuable for the diagnosis of pericardial effusion.‘J4 In Case 1 the characteristic appearance of pericardial effusion in the angiocardiogram in frontal view, i.e., the heart surrounded by fluid, was demonstrated (Fig. 2, A and B). A similar situation was also revealed after angiocardiography in Case 2 (Fig. 4, A and B), although more of the fluid was at the diaphragm rather than in the usual location adjacent to the right atria1 and left ventricular borders. By demonstrating normal-sized cardiac chambers, their prolonged opacification and venous hypertension, the diagnosis of effusive-constrictive pericarditis or cardiac tamponade was warranted. Finally, the autopsy findings in Case 1 corroborated the clinical and angiocardiographic diagnosis of effusive-constrictive pericarditis. In Case 1 angiocardiography also accurately foretold the considerable amount of pulmonary fibrosis by demonstrating the avascularity of the left lung (Fig. 2, A and C).

SUMMARY Two patients who probably had received excessive dosages of irradiation therapy following mastectomy for cancer developed symptoms and clinical signs of effusive-constrictive pericarditis. Both patients were at first suspected of having isolated myocardial disease and were treated for heart failure with digitalis. Angiocardiography, however, demonstrated pericardial effusions, delayed circulation times, venous hypertension and normal-sized cardiovascular strucTHE

AMERICAN

JOURNAL

OF

CARDIOLOGY

Radiation tures. These data established the diagnosis of effLlsi\-e-constrictive pericarditis. The first patient died before pericardiocentesis could be performed. In the second patient, cardiac tamponade was alleviated by making a pericardial-plellral window. Persistence of the weakness and exhaustion, assotach>zardia, ciated with lnild aortic and mitral regurgitation, suggests In)-ocardial disease due perhaps to irraIn 1 patient angiocardiography also diation. showed severe attenuation of the left pulmonary artery due to left pulmonary fibrosis. At autops)-, radiation pulmonary fibrosis of the left lung (the side of mastectomy) was found. Pericarditis and pericardial effusions are ominous developments following neoplastic disRarely, ease and are usually due to metastases. irradiation

pericarditis,

which

is usually

asso-

ciatcd with pulmonarv fibrosis, mav be the cause of pericardiA1 effusion: Because of the danger of cardiac tamponade and heart failure owing to constrictive pericarditis, early diagnosis is imFor this angiocardiography is valuportant. able. ADDENDUM Since this paper was accepted for publication, Cohn and associates15 have reported, in abstract, a series of 20 patients treated for thoracic malignant disease, the majority of whom developed pericardial disease following irradiation to the area of the heart. REFERENCES 1. STEINBERG,

Roentgen

GAL, H. V. and FINBY, N. diagnosis of pericardial effusion: New

I., VON

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Pericarditis angioc;~rclio~r;lphic

,$??iOl.,78: 321. 1958.

observations.

b/l. ./. Romt-

2. Iiu~sr, D. \I;. Radiation fibrosis of pericxtliu~n Casr report with postwith cardiac t;lrnponade: n~ortcnl studies and revir\v of 1iter;rturc. (hnarl. nl. ‘,I. J., 81 : 377, 1959. 3. FRIED, .I. LZ. and GOLDBERG, li. Post-irratliiltion changes in thr: lungs and thorax: .2 clinical, rocntgcnological, and pathological study, with enlphasis on the late and tcrlninal stagrs. .Inl. J. Koentqwol.,43: 877, 1940. 4. JLNNINGS, F. L. and ARDEN, A. Dexlopnux~t of radiation pneuinonitis. Arch. Path., 74: 351. 1962. 5. SMITH, J. C. Radiation pnrulnonitis: Case report of bilateral rcxtion after unilateral irradiation. Am. Rw. Rrsj. Ibis., 89: 264, 1964. 6. SI.A.rER. S. R., KROOP, I. G. and %UCKERMAN, s. Constrictive pericurditis caused by solitary Inetatatic carcinoma of the pericardium and complicated by radiation fibrosis of the nxdiastinum. i1m. Hart