Cardiac pheochromocytomas

CURRENT REVIEW

Cardiac Pheochromocytomas Victor A. Jebara, MD, Miguel Sousa Uva, MD, Arnaud Farge, MD, Christophe Acar, MD, Michel Azizi, MD, Pierre Fransois Plouin, MD, Pierre Corvol, MD, Juan-Carlos Chachques, MD, Patrice Dervanian, MD, Jean-Noel Fabiani, MD, Alain DeLoche, MD, and Alain Carpentier, MD, PhD Departments of Cardiovascular Surgery and Hypertension, Hbpital Broussais, Paris, France

Cardiac pheochromocytomas are rare. Thirty cases have been reported in the literature. We report the cases of 2 more patients in whom the diagnosis was established using coronary angiography and who underwent surgical resection using cardiopulmonary bypass. We also review the literature on the subject. (Ann Thoruc Surg 2992;53:356-62)

E

xtraadrenal pheochromocytomas are rare. They are usually located in the abdomen. Thoracic pheochromocytomas constitute 1%to 2% of all cases of pheochromocytoma and are most often found in the posterior mediastinum. Cardiac pheochromocytomas are extremely rare, with only 30 cases reported in the literature [l-231. Diagnosis and management of these tumors constitute a challenging problem to both the medical team and the surgical team. The purpose of this study is to report two additional cases of cardiac pheochromocytoma and to present a review of the literature on the subject.

Case Reports Pa tien t 1 A 26-year-old man was referred for resection of a cardiac pheochromocytoma. He was first seen at the age of 20 years because of bouts of arterial hypertension and headache. Two years later he was receiving &blockers and was still hypertensive. Diagnostic workup revealed extremely elevated levels of blood and urinary catecholamines. Pheochromocytoma was suspected. Attempts to localize the tumor using iodine 131-labeled metaiodobenzylguanidine (I-MIBG) scintigraphy, computed tomography, and abdominal aortography failed. Antihypertensive drugs were again prescribed, and the patient was discharged. Two years later he was readmitted for a hypertensive crisis and arrthymias. Blood and urinary catecholamine levels were still elevated, and total-body magnetic resonance images, computed tomographic (CT) scan, I-MIBG scintiscan, and abdominal aortogram were still negative. An exploratory laparotomy was performed, and no tumor was found. Six months later the patient was examined again. Total-body magnetic resonance images, CT scan, and I-MIBG scintiscan were again normal. Staged venous sampling showed a consistently higher level of catecholAddress reprint requests to Dr Jebara, Department of Cardiovascular Surgery, HBpital Broussais, 96 rue Didot, 75014 Paris, France.

0 1992 by The Society of Thoracic Surgeons

amines in the superior vena cava than in simultaneous venous samples from other sites. Coronary angiography showed a highly vascularized tumor on the posterior aspect of the heart. The blood supply of the tumor was derived from the left circumflex artery. The patient was referred for surgical intervention. After adequate anesthetic preparation, a median sternotomy was performed and revealed a 4 x 3-cm reddish brown mass on the left atrial roof. Manipulation of this tumor resulted in arrhythmias and hypertension. Cardiopulmonary bypass was instituted, and the aorta was cross-clamped after cardioplegic arrest of the heart. The mass was then easily resected together with the underlying left atrial wall. An autologous pericardial patch was inserted to close the left atrium. The postoperative course was uneventful, and histological study showed the tumor to be an extraadrenal paraganglioma. Two years later, the patient is normotensive and doing well without medication.

Patient 2 A 42-year-old woman was referred to our hospital for surgical treatment of a cardiac pheochromocytoma. She had a 10-year history of hypertension, was receiving antihypertensive therapy, and was considered to be in stable condition. In July 1989, she started complaining of

Fig 1. Aortogram showing the vascular blush on the anterior surface of the heart and behind the aorta.

0003-4975/92/$5.00

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magnetic resonance images, and I-MIBG scintiscan were all negative. Aortography and coronary angiography established the diagnosis by showing a highly vascular mass extending from the roof of the left atrium to the anterior surface of the heart (Fig 1).The blood supply of the tumor was derived from both the left main and right coronary arteries (Fig 2). The distal coronary vessels were normal. The patient was referred for surgical intervention. After appropriate preoperative preparation with a-and pblockers, a median sternotomy was performed. Incision of the pericardium revealed a large reddish brown tumor appended to the anterior wall of the right ventricle, originating from the aortic root and the pulmonary trunk and encompassing both vessels. The tumor extended posteriorly between the aorta and the pulmonary artery and adhered to the roof of the left atrium and to the right pulmonary artery (Fig 3). Cardiopulmonary bypass was instituted between the femoral artery and both venae cavae. Manipulation of the tumor had no effect on blood pressure or cardiac rhythm. After cardioplegic arrest of the heart, the tumor was dissected sharply from the right ventricular wall. At the level of the aorta, subadventitial dissection of the tumor was undertaken. The first 2 cm of the right coronary artery was totally enveloped in the mass and had to be resected. Similarly, a 2 x 2-cm patch of the pulmonary artery was resected to completely liberate the mass anteriorly. Posteriorly, the tumor was sharply dissected from the left atrium and from the right pulmonary artery. The left main coronary artery was mobilized, and collateral vessels to the tumor were clipped. After total extirpation of the mass, a primary anastomosis between the right

B Fig 2 . Coronary angiography showed the blood supply of the tumor from (A) the right coronary artery (rca) and ( B ) the left main coronary artery.

bouts of paroxysmal hypertension with episodes of palpitations and profuse perspiration. A complete workup was done and revealed markedly elevated levels of blood and urinary catecholamines. Pheochromocytoma was suspected. Abdominal CT scan showed a solid 2-cm mass in the left adrenal gland. Magnetic resonance imaging and I-MIBG scintigraphy did not confirm the typical aspect of pheochromocytoma. As no other localizations could be found, an exploratory laparotomy was performed and the mass resected. Pathological study indicated a nonsecreting adenoma of the adrenal gland. Postoperatively the patient continued to be hypertensive. Two months after operation, the patient was readmitted for further studies. Abdominal and thoracic CT scans,

Fig 3 . Exact localization of the tumor. (Ao = aorta; LA = left atrium; LMCA = left main coronary artery; PA = pulmonary artery; RCA = right coronary artery; RV = right ventricle.)

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REVIEW JEBARA ET AL CARDIAC PHEOCHROMOCYTOMAS

Table 1 . Summay of Patient Data Clinical Presentation

Age Sex

Reference

Positive Diagnosis

Joffre et a1 (1972) [l] Besterman et a1 (1974) [2] Wilson et a1 (1974) [3]

32 36 32

F F M

HT HTflabor HT

Palubinskas et a1 (1980) [4]

49

M

NA

76 43 29 42 NA

F M F M NA

HT, CHF HT HT HT NA

NA NA

NA NA NA NA

I-MIBG I-MIBG

59

F

24

F

HT, angina pectoris HT

Coronary angiography I-MIBG

18 30 36

F M F

HTflabor HT HT

I-MIBG I-MIBG I-MIBG

Awoke and Perlstein (1985) [ l l ]

41

F

I-MIBG

Cooley et a1 (1985) [12] Fisher et a1 (1985) [13] Geisler et a1 (1985) [14] David et a1 (1986) [15]

42 85 26 35

M M M F

Headache, arrhythmias HT, arrhythmias HT HT Dyspnea, sweating

Dunn et a1 (1986) [16]

48

M

HT

38

M

HT

Conti et a1 (1986) [17] Shimoyama et a1 (1987) [18] Stowers et a1 (1987) [19]

47 49 28

M F F

Kawasuji et a1 (1989) [20]

46

M

HT HT, headache Dyspnea, headache HT, headache

Lee et a1 (1990) [21] Peiffert et a1 (1990) [22]

31 30

F M

HT HT

Feltynowski et a1 (1990) [23] Jebara et a1 (1991) present study

40 26

M M

HT HT

42

F

HT, sweating

Voci e t a1 (1982) (51 Saad et a1 (1983) [6] Hodgson et a1 (1984) [7l Shirkoda and Wallace (1984) [8] Shapiro et a1 (1984) [9]

...

...

Orringer et a1 (1985) [lo]

...

...

Bil. = bilateral; CHF = congestive heart failure; available; 2D = two-dimensional.

HT

=

hypertension;

Angiogram Angiogram Staged venous sampling Staged venous sampling Autopsy I-MIBG Autopsy I-MIBG I-MIBG

...

1 negative

...

Negative laparotomy , negative thoracotomy

... ...

Negative laparotomy, positive thoracotomy

..

I-MIBG I-MIBG Coronary angiography 2-D echo, I-MIBG 2-D echo Coronary angiography I-MIBG Staged venous sampling Coronary angiography =

Other Locations

Negative laparotomy ... ... Negative laparotomy 2 Laparotomies, Right adrenal pheochromocytoma 1 negative 3 negative ... laparotomies ... Bone metastasis Negative laparotomy ... Negative laparotomy .. Negative laparotomy ... 2 Laparotomies, Bladder pheochromocytoma 1 negative 2 Laparotomies,

2-D echo, biopsy I-MIBG Autopsy 2-D echo, coronary angiography Staged venous sampling I-MIBG

I-MIBG

Previous Operation

... Abdominal paraaortic pheochromocytoma Bone metastasis

... ... ... ... ...

Positive thoracotomy Carotid body tumor

...

Negative laparotomy

...

Negative thoracotomy 2 Negative laparotomies

... ... ...

Bil. carotid body tumors Carotid body tumor

...

...

...

...

...

...

...

Negative laparotomy

...

...

... Bil. carotid body tumors

Negative laparotomy

.. ..

Negative laparotomy

...

...

iodine 131-labeled metaiodobenzylguanidine;

NA = not

Ann Thorac Surg 19!32;53:35641

Fig 4 . Sites of cardiac pheochromocytomas: left atrium (n = 19), interatrial septum (n = 7), and anterior surface of heart (n = 6 ) .

coronary artery and the aorta was performed, and a 2 x 2-cm patch of autologous pericardium was inserted to close the pulmonary artery. At the completion of the operation, there was minimal bleeding from the tumor bed behind the aortic root, which was controlled with interrupted sutures and Surgicel (Johnson & Johnson, New Brunswick, NJ). The postoperative course was marked by respiratory failure, which necessitated ventilatory support for 72 hours. The patient was discharged on the 18th postoperative day. She was normotensive with normal catecholamine levels. Histologically, the tumor was an extraadrenal pheochromocytoma.

Comment Pheochromocytomas are functionally active chromaffin paragangliomas of the sympathetic nervous system. In adults, the majority of chromaffin cells are concentrated in the adrenal medulla, but small quantities can be found along the aorta, in the walls of blood vessels, and in the heart, prostate, and ovaries. These aberrant collections of chromaffin cells may constitute the site of ectopic pheochromocytomas. Pheochromocytomas secrete catecholamines and are usually responsible for arterial hypertension. They are encountered in less than 0.1% of all hypertensive patients [ l l , 211. Ninety-eight percent of all pheochromocytomas are found in the abdomen. Less than 2% occur in the chest, usually in the posterior mediastinum [9, 10, 15, 231. Cardiac pheochromocytomas are exceedingly rare. We were able to find 30 cases reported in the literature [l-231. Table 1shows a clinical summary of these 30 cases plus our 2 cases. There were 15 men and 14 women (sex not available for 3). Age ranged between 18 and 85 years (mean age, 40 years). The most common clinical presen-

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tation was arterial hypertension, usually associated with headache, palpitations, and sweating. At the time of diagnosis of the cardiac pheochromocytoma, clinical manifestations had been present for 2 months to 22 years. Two patients were seen because of a hypertensive crisis during labor [2, 101. Three patients had undergone a previous resection of abdominal pheochromocytomas 22 years, 9 years, and 1 year previously [3, 91. In all patients there were marked biochemical abnormalities that triggered the search for a pheochromocytoma. For no patient was there a family history of pheochromocytoma as is typically reported with chemodectomas, which are paragangliomas of the parasympathetic nervous system. Associated chemodectomas of the carotid body were found and resected in 5 patients [12, 16, 221; two were bilateral. The diagnosis of cardiac pheochromocytoma was consistently difficult to establish. In most instances, multiple locating procedures were performed in different combinations over several years before the site of the lesion was localized. Furthermore, during the diagnostic workup, negative exploratory laparotomy was performed in 17 of the 32 patients [ 1 4 , 6-10, 14, 16, 21, present study], 2 of whom died postoperatively [7, 141. The most useful study to establish the diagnosis of cardiac pheochromocytoma was I-MIBG scintigraphy. This technique resulted in localization of the tumor in 18 of the 22 patients in whom it was used. However, two I-MIBG scintiscanswere obtained in each of our 2 patients and did not allow us to localize the pheochromocytoma. Two-dimensionalechocardiographic studies showed an abnormal cardiac or pericardial mass in 5 patients, thereby directing attention to the heart [12, 15, 20-221. In these patients the diagnosis of cardiac pheochromocytoma was confirmed using I-MIBG scintigraphy in 3, coronary angiography in 1, and biopsy at thoracotomy in 1. Echocardiography was particularly helpful when the tumor was intracardiac. In 7 other patients, the diagnosis of cardiac pheochromocytoma was established using coronary angiography [l, 2, 15, 19, 221. This is a valuable procedure because it shows the exact location of the tumor as well as its relation to the coronary vessels. It also indicates the origin of the blood supply of the pheochromocytoma and thus helps in the planning of the surgical intervention. Although a CT scan was performed in the majority of patients, this technique established the diagnosis in only 1 of them [MI. However, in every instance, after cardiac involvement was revealed using another technique, retrospective analysis of the CT scan showed the exact location of the tumor. The failure of conventional CT scanning to disclose the lesions may have resulted from failure to administer intravenous contrast medium, from slow infusion of contrast medium (during which time the tumor may enhance to the same degree as the cardiac chambers), or from failure to consider the middle mediastinum as a potential site for a pheochromocytoma [9]. Magnetic resonance imaging, with its superior softtissue contrast, appears to be a modality with great potential for diagnosing mediastinal masses [17, 241.

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Table 2 . Details of Surgical Intervention Location

Incision

Cardiopulmonary Bypass

LA roof Interatrial septum Interatrial septum LA roof, A 0 root LA roof Anterior surface of heart Interatrial septum LA roof

MS RT RT MS RT MS

Yes No No Yes No No

MS MS

Yes Yes

LA roof Anterior surface of heart LA roof LA roof Interatrial septum LA roof

RT MS

No Yes

RT RT MS MS

Yes Yes Yes Yes

MS MS

Yes NA

MS

MS

No Yes

Stowers et a1 (1987) [19]

LA roof Anterior surface of heart LA roof Anterior surface of heart LA roof

MS

Yes

Kawasuji et a1 (1989) (201 Lee et a1 (1990) [21]

Interatrial septum Interatrial septum

MS MS

Yes Yes

Peiffert et a1 (1990) [22] Feltynowski et a1 (1990) [23]

LA roof Anterior surface of heart LA roof LA roof, anterior surface of heart

MS MS

Yes No

MS

Yes Yes

Reference Besterman et a1 (1974) [2] Wilson et a1 (1974) [3] Palubinskas et a1 (1980) [4] Saad et a1 (1983) [6] Shirkoda and Wallace (1984) [8] Shapiro et a1 (1984) [9]

... Omnger et a1 (1985) [lo]

... Awoke and Perlstein (1985) [ l l ] Cooley et a1 (1985) [12] David et a1 (1986) [15] Dunn et a1 (1986) [16] Conti et a1 (1986) [17] Shimoyama et a1 (1987) [18]

Jebara et a1 (1991) present study

...

A 0 = aorta, aortic; pulmonary artery;

MS

CABG = coronary artery bypass grafting; LA = left atrial; SVC = superior vena cava. RT = right thoracotomy;

However, at present, experience with the diagnosis of cardiac pheochromocytoma using this procedure is very limited. The several MRIs obtained in our 2 patients did not help us establish the diagnosis. However, as with the CT scans, retrospective analysis of the images allowed visualization of the cardiac tumor. Staged venous sampling directed the diagnosis to the heart in 4 patients [3, 4, 16, present study] by showing a consistently higher level of catecholaminesin the superior vena cava or its tributary veins compared with simultaneous venous samples obtained elsewhere. In 3 patients the diagnosis of cardiac pheochromocytoma was established at postmortem examination [5, 7, 141. Two of these patients died after a negative exploratory laparotomy, as mentioned previously.

Technique Transection PA

... ... ... ... ...

+ A0

Cured Cured Cured Cured Cured Cured Died (bleeding) Not cured (metastasis) Cured Cured

... CABG LA patch LA patch

Outcome

...

Cardiac autotransplantation Coronary sinus patch

...

Cured Died (bleeding) Died (bleeding) Died (bleeding) Cured Cured

...

Cured Cured

Transection A 0 + PA, LA patch LA patch Transection SVC, LA patch, CABG Transection AO, PA, SVC

Cured

...

...

LA patch PA patch, CABG MS = median stemotomy;

Cured Cured Cured Cured Cured Cured

NA = not available;

PA =

With the advent of modem imaging techniques, cardiac pheochromocytomas will become an increasingly more frequently recognized cause of surgically correctable hypertension [lo]. The fact that the majority of the 30 cases reviewed have been reported in the past 5 to 6 years supports this thesis. Pheochromocytomas of the heart are most often found on the roof of the left atrium (n = 19). Other locations include the interatrial septum (n = 7) and the anterior surface of the heart (n = 6) (Fig 4). Surgical excision of these tumors usually results in permanent cure and relief of symptoms. Operation was performed on 25 patients (Table 2). All underwent careful anesthetic preparation using a- or Pblockers or both before operation. Median stemotomy was performed in

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19 patients and posterolateral thoracotomy in 6. In 6 patients, intraoperative manipulation of the tumor resulted in hemodynamic instability and arrhythmias. Cardiopulmonary bypass was used in 17 patients. This technique permits total exclusion of the heart after aortic cross-clamping and cardioplegic arrest. The tumor can be excised without risk of hypertension or arrhythmias and with minimal blood loss. Furthermore, aortic crossclamping allows safe dissection of the mass from the underlying myocardium and from the coronary vessels. It also allows the performance of coronary artery procedures to completely excise the mass, as was necessary in 4 patients [lo, 19,21, present study]. In our patient 2,2 cm of the right coronary artery was resected, and direct reimplantation into the aorta was performed. In 8 patients, a segment of left atrial wall had to be resected with the tumor and was replaced by a pericardial or Dacron patch [lo, 19-21, present study]. This was done in our patient 1, whereas in our patient 2, a segment of the pulmonary trunk was resected and replaced with a pericardial patch. Some authors [2, 19, 21, 221 advocate transection of the great vessels to obtain direct access to pheochromocytomas of the roof of the left atrium. Even though the technique appears interesting and may offer technical advantages in certain instances, it did not seem necessary to our 2 patients. In 1985, Cooley and colleagues [12] described a new surgical approach to treat extensive tumors involving the posterior surface of the heart: cardiac autotransplantation after complete excision of the mass. We believe this technique deserves consideration in select patients with large invasive tumors. Of the 25 patients who underwent surgical excision of the cardiac pheochromocytoma, 21 survived and 20 were reported to be completely cured. All four deaths were due to massive bleeding and occurred either intraoperatively or shortly after operation [9-121. Nonlethal hemorragic complications were encountered in 4 other patients (2, 6, 191. In fact, bleeding from the tumor bed (usually retroaortic) is the most common complication of this operation. In 1patient, hypertension persisted postoperatively and was found to be associated with multiple skeletal metastases [9]. Malignant pheochromocytoma of the heart was encountered at the postmortem examination of another patient, a 76-year-old woman who died of chronic hypertension and heart failure and in whom generalized metastases were found [5]. We thank Patricia Retaggi for the preparation of the manuscript.

References 1. Joffre F, Carcy B, Putois J, Giron J. Difficult& du diagnostic artkriographique des phkochromocytomes. J Radio1 Electrol 1972;45307-10. 2. Besterman E, Bromley LL, Peart WS. An intrapericardial phaeochromocytoma. Br Heart J 1974;36:31%20. 3. Wilson AC, Bennett RC, Niall JF, Clarebrough JK, Doyle AE,

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Louis WJ. An unusual case of intrathoracic pheochromocytoma. Aust N Z J Surg 1974;44:2732. 4. Palubinskas AJ, Roizen MF, Conte FA. Localization of a functioning pheochromocytoma by venous sampling and radioenzymatic analysis. Radiology 1980;136:495-6. 5. Voa V, Olson H, Beilin L. A malignant primary cardiac pheochromocytoma. Surg Rounds 1982;9:88-90. 6. Saad MF, Frazier OH, Hickey RC, Samaan NA. Intrapericardial pheochromocytoma. Am J Med 1983;75:371-6. 7. Hodgson SF, Sheps SG, Subramanian R, Lie JT, Carney JA. Catecholamine-secreting paraganglioma of the interatrial septum. Am J Med 1984;77:157-61. 8. Shirkoda A, Wallace S. Computed tomography of juxtacardiac pheochromocytoma. J Comput Tomogr 1984;8:207-9. 9. Shapiro 8, Sisson J, Kalff V, et al. The location of middle mediastinal pheochromocytomas. J Thorac Cardiovasc Surg 1984;87814-20. 10. Orringer MB, Sisson JC, Glazer G, et al. Surgical treatment of cardiac pheochromocytomas. J Thorac Cardiovasc Surg 1985; 89753-7. 11. Awoke S, Perlstein R. Dopamine- and norepinephrinesecreting intrapericardial pheochromocytoma in a normotensive patient. South Med J 1985;78:994-8. 12. Cooley DA, Reardon MJ, Frazier OH, Angelini P. Human cardiacexplantation and autotransplantation: application in a patient with a large cardiac pheochromocytoma. Tex Heart Inst J 1985;12171-6. 13. Fischer MR, Higgins CB, Andereck W. MR imaging of an intrapericardial pheochromocytoma. J Comput Assist Tomogr 1985;9:1103-5. 14. Geisler F, Barth G, Jaeck D, et al. Un cas de phkochromocytome B localisation cardiaque. Presse Med 1985;141024-6. 15. David TE, Lenkei SC, Marquez-Julio A, Goldberg JA, Meldrum DAN. Pheochromocytoma of the heart. Ann Thorac Surg 1986;41:98-100. 16. Dunn GD, Sapsford RN, Hemingway AP, et al. Functioning middle mediastinal paraganglioma (phaeochromocytoma) associated with intercarotid paragangliomas. Lancet 1986: 10613. 17. Conti VR, Saydhari R, Amparo EG. Paraganglioma of the heart. The value of magnetic resonance imaging in the preoperative evaluation. Chest 1986;90:604-6. 18. Shimoyama Y, Kawada K, Imamura H. A functioning intrapericardial paraganglioma (pheochromocytoma). Br Heart J 1987;57:3803. 19. Stowers SA, Gilmore P, Stirling M, et al. Cardiac pheochromocytoma involving the left main coronary artery presenting with exertional angina. Am Heart J 1987;114423-7. 20. Kawasuji M, Matsunaga Y, Iwa T. Cardiac phaeochromocytoma of the interatrial septum. Eur J Cardiothorac Surg 1989;3:175-7. 21. Lee HH, Brenner WI, Vardhan I, Hyatt J, Terlecki M. Cardiac pheochromocytoma originating in the interatrial septum. Chest 1990;9776&2. 22. Peiffert B, Amrein D, Hubert T, et al. Phkochromocytome rktrocardiaque associk B une double localisation carotidienne. Ann Chir 1990;44:611-4. 23. Feltynowski T, Januszewiczz W, Jakubowski W, et al. Intrapericardial pheochromocytoma:a case report. Cor Vasa 1990; 32:145-8. 24. Jebara VA, Corbi P, Acar C, et al. Surgical management of benign non myxomatous, cardiac tumors: analysis of 9 cases. Eur Heart J 1989;10:226.