Restrictive cardiomyopathy

Restrictive cardiomyopathy from amyloid deposition within the myocardium is a well-described complication of multiple myeloma; however, myelomatous involvement of pericardium with subsequent cardiac tamponade has rarely been described. Optimal treatment for malignant involvement of the pericardium by myeloma cells has yet to be established. The following description is of a patient with myocardial and pericardial manifestations of multiple myeloma. Treatment of the malignant pericardial effusion was implemented with intrapericardial administration of bleomycin. This therapy resulted in no recurrence of pericardial effusion at nine days follow-up. Despite the absence of detectable recurrent effusion, the patient died suddenly from causes felt unrelated to pericardial disease.

Restrictive cardiomyopathy from amyloid deposition in the myocardium is a well-described complication of multiple myeloma; however, myelomatous involvement of the pericardium with subsequent cardiac tamponade has been described in only a few reports.[1-3] Optimal treatment for malignant involvement of the pericardium by myeloma cells has yet to be established. The following patient had myocardial and pericardial manifestations of multiple myeloma, and the treatment protocol used in his management is described.

CASE REPORT

A 67-year-old white man was well until 10 months prior to admission when he developed signs and symptoms of congestive heart failure. A radionuclide ventriculogram demonstrated a left ventricular ejection fraction of 62 percent. At that time, the patient was also found to have a total serum protein value of 10.6 g/dl and a serum albumin level of 2.7 g/dl. Serum protein electrophoresis and immunoglobulin characterization revealed an IgA lambda monoclonal gammopathy (serum IgA concentration 8.68 g/dl). Urine protein electrophoresis revealed monoclonal lambda chain Bence-Jones proteins. Bone marrow biopsy specimen demonstrated hypercellularity with diffuse plasma cell infiltrates, while initial skeletal roentgenographic survey revealed multiple lytic lesions involving the calvarium, vertebra, ribs, pelvis, and extremities consistent with the diagnosis of multiple myeloma. In addition, the patient was given a presumptive diagnosis of cardiac amyloidosis on the basis of clinical congestive heart failure with normal left ventricular ejection fraction. No further evaluation for amyloidosis was initiated, and treatment with prednisone and melphalan was initiated. After six months of theraphy, the patient's chemotherapy protocol was changed to vincristine, cytoxan, melphalan, prednisone, BCNU, and hydroxydaunorubicin due to poor clinical response.

The patient presented to our hospital with a three-week history of progressive lower extremity edema and decreased urine output. Physical examination on admission revealed a blood pressure of 90/64 mm Hg without orthostatic changes, distant heart sounds, a pulsus paradoxus of 8 mm Hg, and marked lower extremity edema. At the time of admission, the patient's BUN value was 141 mg/dl, and serum creatinine level was 4.2 mg/dl. Admission chest x-ray film revealed a large cardiac silhouette without pulmonary congestion. Echocardiogram revealed a large pericardial effusion and substantial hypertrophy of the right and left ventricular walls with an echogenic pattern of infiltrative cardiomyopathy highly suggestive of cardiac amyloid deposition. A diagnostic right heart catheterization revealed a central venous pressure of 23 mm Hg, a right ventricular pressure of 40/24 mm Hg, and a pulmonary artery pressure of 23 mm Hg. Right atrial tracings revealed a prominent x but dampened y descent. A diagnosis of cardiac tamponade was established, and a percutaneous pericardial drain was placed which initially removed 1.3 L of hemorrhagic fluid. After drainage, the patient's blood pressure rose to the 110/70 mm Hg range, and urine output increased from 400 ml/24 h (predrainage) to 1,500 ml/24 h (postdrainage). The pericardial drain was left in place and continued to drain 400 to 800 ml per day. Pericardial fluid cytology (Fig 1) was positive for malignant plasma cells (concentration 4,968 cells/cu mm). Bleomycin, 20 mg in 30 ml of normal saline solution was introduced into the pericardial space via the drainage catheter and the catheter clamped. The patient's position was changed every 15 min for 4 h at which time the pericardial catheter was unclamped and allowed to drain to gravity. Acetaminophen, 650 mg every 4 h, was given prophylactically for the initial 24 h after bleomycin administration. The patient tolerated the procedure well without developing fever, chest pain, or other complications. After 48 h, the patient's pericardial drainage ceased, repeat echocardiography showed insignificant residual pericardial fluid, and the catheter was then removed. The patient underwent echocardiographic evaluation on four occasions during the next nine days, which revealed no recurrent pericardial effusion. Thirty six hours after his last echocardiogram, the patient became acutely hypoxemic and died suddenly. The cause of death was felt to be most consistent with massive pulmonary embolism clinically, but this could not be confirmed as the patient's family denied permission for autopsy, and no diagnostic studies could be obtained due to the suddenness of his death.

DISCUSSION

Infiltration of the pericardium by malignant cells is a common autopsy finding in patients with metastatic cancer.[4] While malignant pericardial effusions are frequently associated with tumors of the lung and breast, pericardial involvement in patients with multiple myeloma is distinctly unusual. Less than ten cases of multiple myeloma involving the pericardium have been described since 1966, with many of these cases being diagnosed only at autopsy.[1-3] Three patients with multiple myeloma presenting with symptomatic pericardial effusion have been described in detail. These three patients presented with dyspnea, enlargement of cardiac silhouette, and failed to improve with aggressive treatment of presumed congestive heart failure. Neoplastic plasmacytoid cells were identified by pericardiocentesis in two patients,[1,2] while the third case was diagnosed at autopsy.[3] Myelomatous involvement of the heart at autopsy varied from extensive myocardial and pericardial infiltration of plasma cells to isolated involvement of the epicardial fat, and was the sole extraskeletal site of involvement in one instance.[3] Myelomatous involvement of the pericardial space in the setting of cardiac amyloidosis has not previously been described. It is of interest that myeloma of the IgA class, as in the present case, is more frequently associated with systemic amyloidosis as compared to IgG myeloma, and can present with atypical features, including soft tissue or meningeal involvement.[5-7]

The majority of patients with pericardial metastases are clinically asymptomatic.[4] In patients presenting with cardiac tamponade, however, malignancy is a common etiologic finding. The acute treatment of malignant pericardial effusion with cardiac tamponade involves the prompt removal of pericardial fluid by pericardiocentesis usually under echocardiographic guidance.[4] The long-term management of malignant pericardial effusions, however, remains controversial. The creation of a pericardial window has been shown to be quite effective and has until recently been considered to be the treatment of choice for malignant pericardial effusion.[8] The procedure requires thoracotomy under general anesthesia and can be associated with significant morbidity and mortality in an already debilitated patient population. More recently, the intrapericardial administration of sclerosing agents such as tetracycline, quinacrine, talc, and OK-432 have been used for the palliative treatment of malignant pericardial effusion.[2,9] Intrapericardial tetracycline has been utilized most extensively to date, with successful long-term control of effusions in 20 of 22 cases reported by Shephard and colleagues.[9] Unfortunately, the use of tetracycline in this clinical setting has been associated with several complications, including arrhythmias, fever, and pain. Intrapericardial bleomycin has also been used in the treatment of malignant pericardial effusions with favorable results.[10-13] This therapy has been associated with minimal side effects, with the only reported complication being fever. Hence, bleomycin is being increasingly utilized as a treatment for both malignant pleural and pericardial effusions.

Appropriate therapy for myelomatous involvement of the pericardium has yet to be defined. A subject described by Goldberg and Mori[3] presenting with cardiac tamponade was treated by surgical creation of a pericardial window. The patient died four days after his operation. Imamura and associates[2] treated a patient with intrapericardial administration of the experimental sclerosing agent, OK-432, after which 1,400 rads of radiation therapy were delivered to the pericardium. The patient died six months later from systemic plasmacytoma without evidence of recurrent pericardial effusion. We elected to treat the patient described with bleomycin, as the patient represented a poor surgical candidate for pericardial window placement and because intrapericardial bleomycin has been reported to be effective with few side effects. We did not observe any immediate complications of therapy. Given our patient's average of 450 ml per day of pericardial drainage before pericardial sclerosis, we were encouraged by the lack of development of recurrent effusion nine days after pericardial sclerosis. We cannot comment on the long-term effectiveness of therapy in this particular case, as the patient died from unknown causes which did not appear to be secondary to recurrent tamponade.

In summary, this case and others indicate that a pericardial effusion of malignant plasma cells should be considered in the unusual patient with myeloma who develops cardiac tamponade. Cytologic examination of aspirated pericardial fluid can confirm the diagnosis without the need for open pericardial biopsy. The optimal treatment of myeloma involving the pericardial space remains to be determined. The intrapericardial instillation of sclerosing agents should be considered, especially in patients in whom control of recurrent effusion would significantly add to quality of life or life expectancy.

REFERENCES

[1] Garrett TJ, McCans JL, Parker JO. Fatal involvement of the heart with multiple myeloma. Can Med Assoc J 1972; 107:979-80

[2] Imamura T, Tamura K, Taguchi T, Makino S, Seita M. Intrapericardial instillation of OK-432 for the management of malignant pericardial effusion: report of three cases. Jpn J Med 1989; 28:62-66

[3] Goldberg E, Mori K. Multiple myeloma with isolated visceral (epicardial) involvement and cardiac tamponade. Chest 1970; 57:584-87

[4] Press OW, Livingston R. Management of malignant pericardial effusion and tamponade. JAMA 1987; 257:1088-92

[5] Truong LD, Kim HS, Estrada R. Meningeal myeloma. Am J Clin Pathol 1982; 78:532-35

[6] Mancilla-Jumenez R, Tavassoli FA. Solitary meningeal plasmacytoma: report of a case with electron microscopic and immunohistologic observations. Cancer 1976; 38:798-806

[7] Hobbs JR. Immunochemical classes of myelomatosis. Br J Haematol 1969; 16:599-606

[8] Hankins JR, Satterfield JR, Aisner J. Pericardial window for malignant pericardial effusion. Ann Thorac Surg 1980; 30:465-71

[9] Shephard FA, Ginsberg JS, Evans WK, Scott JG, Oleksiuk F. Tetracycline sclerosis in the management of malignant pericardial effusion. J Clin Oncol 1985; 3:1678-82

[10] van der Gaast A, Kok TC, van der Linden NH, Slinter TA. Intrapericardial instillation of bleomycin in management of malignant pericardial effusion. Eur J Cancer Clin Oncol 1989; 25:1505-06

[11] Maher ER, Buckman R. Intrapericardial instillation of bleomycin in malignant pericardial effusion. Am Heart J 1986; 11:613-14

[12] Cormican MC. Intrapericardial bleomycin for the management of cardiac tamponade secondary to malignant pericardial effusion. Br Heart J 1990; 63:61-62

[13] Ostrowski MJ. Intracavitary therapy with bleomycin for the treatment of malignant pleural effusions. J Surg Oncol 1989; 1:(suppl)7-13

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