Continuously elevated cardiac troponin I in two patients with multiple myeloma and fatal cardiac amyloidosis

A. Zabernigg*,1, R. Schranzhofer1, A. Kreczy2 and K. Gattringer1

1 General Hospital Kufstein, Department of Internal Medicine and Oncology, Endach 27, 6330 Kufstein; 2 Department of Pathology, University of Inssbruck, Müllerstraße 44, 6020 Innsbruck, Austria

*E-mail: a.zabernigg@kufnet.at

Myeloma-associated systemic amyloidosis (AL) with cardiac involvement has a poor prognosis, with a median survival of <1 year [1]. Standard therapy with oral melphalan and prednisolone is unsatisfactory, with an overall response rate for AL of 20%. The diagnosis of cardiac amyloidosis in patients with multiple myeloma is most commonly based on clinical findings, ECG and echocardiogram. Here we report two patients with a cardiac amyloidosis and continuously elevated cardiac troponin I (cTI) preceding the diagnosis of multiple myeloma.

Case 1
In February 2000, a 69-year-old man with a past history of arterial hypertension presented with congestive heart failure for the first time. Routine laboratory data and cardiac enzymes were in the normal range, as was the ECG. The echocardiogram showed a severe concentric left ventricular hypertrophy with a diastolic dysfunction. A cardiac catheterization showed normal coronary arteries. After another episode of congestive heart failure in October 2000, cTI was continuously elevated between 0.6 and 2.4 µg/l until January 2001. Because of the severe left ventricular hypertrophy, a restrictive cardiomyopathy was supposed. Gastric and rectal mucous membrane biopsies showed amyloid deposits. Laboratory investigations and bone marrow aspiration confirmed the diagnosis of a multiple myeloma immunoglobulin G lambda with multiple osteolytic bone lesions, stage IIIA. Despite treatment with melphalan and prednisone and adequate cardiac therapy, the patient died 6 months after the diagnosis of multiple myeloma due to intractable congestive heart failure.

Case 2
In September 2001, a 72-year-old man with a past history of arterial hypertension presented with congestive heart failure for the first time. The ECG showed intermittent artrial fibrillation and the course was complicated by ventricular fibrillation. The echocardiogram revealed a severe concentric left ventricular hypertrophy and a diastolic dysfunction. Laboratory investigations showed a haemoglobin level of 10.8 g/dl and cTI was continuously elevated between 0.9 and 11 µg/l for several weeks. Accidentally, an X-ray of the chest showed a solitary osteolytic lesion of the manubrium sterni. Laboratory investigations and a bone marrow biopsy confirmed a multiple myeloma, Bence–Jones {kappa} stage IIA. Amyloidosis was confirmed by rectal mucous membrane biopsies. Despite treatment with melphalan and dexamethasone, the patient died, also 6 months after the diagnosis, of multiple myeloma due to intractable congestive heart failure.

cTI is the most sensitive laboratory test for myocardial injury [2]. Cantwell et al. reported the first patient with multiple myeloma and an elevated cTI due to myocyte compression injury from amyloid infiltration, as demonstrated by electron microscopy [3]. In a retrospective analysis of 261 patients with primary systemic amyloidosis, Dispenzieri et al. showed that cardiac troponins were a negative predictive factor for survival [4]. We report two patients with a continuously mild elevation of cTI due to AL. In the light of a very new effective treatment strategy with dexamethasone and alpha interferon [5], the early detection of cardiac amyloidosis in patients with multiple myeloma could be of clinical importance. Cardiac TI is not specific, but could serve as a simple and sensitive laboratory test to detect cardiac amyloidosis in patients with multiple myeloma.

A. Zabernigg1*, R. Schranzhofer1, A. Kreczy2 & K. Gattringer1

1General Hospital Kufstein, Department of Internal Medicine and Oncology, Endach 27, 6330 Kufstein; 2Department of Pathology, University of Inssbruck, Müllerstraße 44, 6020 Innsbruck, Austria (*E-mail: a.zabernigg@kufnet.at)

References

1. Lee G, Foerster J, Lukens J et al. Wintrobe’s Clinical Hematology, 10th edition. Philadelphia, PA: Lippincott, Williams and Wilkins 1998; 2705–2724.

2. Antman E, Tanasijevic M, Thompson B et al. Cardiac-specific troponin I to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996; 335: 1342–1349.[Abstract/Free Full Text]

3. Cantwell R, Ronnier J A, Bjornsson J et al. Cardiac amyloidosis presenting with cardiac troponin I and angina pectoris. Clin Cardiol 2002; 25: 33–37.[ISI][Medline]

4. Dispenzieri A, Kyle R, Gertz M et al. Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet 2003; 361: 1787–1789.[CrossRef][ISI][Medline]

5. Dhodapkar M, Jacobson J, Husssein M et al. High dose dexamethasone with maintenance dexamethasone/alpha interferon leads to improved survival in patients with primary systemic amyloidosis: results of US Intergroup Trial Southwest Oncology Group (SWOG) S9628. Proc Am Soc Clin Oncol 2003 (Abstr 2278).