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Elevation of the tumor marker CA125 in right heart failure.

Abstract: Carbohydrate antigen 125, known as a marker for ovarian cancer, has been reported to be elevated in heart failure caused by left ventricular dysfunction. A case of elevated carbohydrate antigen 125 in isolated right heart failure due to atrial septal defect with preserved left ventricular function is reported.

Key Words: CA125, heart failure, left ventricular dysfunction

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Carbohydrate antigen 125 (CA125) is traditionally referred to as a "tumor marker." But elevation of CA125 is not specific for malignancy, and it is raised markedly in some patients with heart failure. All these reports were in patients with systolic left ventricular dysfunction, and there is some correlation between the level of CA125 and clinical and hemodynamic status. However, we are reporting a case with marked elevation of CA125 in a patient with atrial septal defect and right-sided heart failure with preserved left ventricular function.

Case Report

A 70-year-old female was admitted with abdominal distention and pedal edema progressing over a month. She was breathless on minimal exertion but had no orthopnea. Physical examination revealed massive ascites, hepatomegaly, elevated jugular venous pressure and a basal ejection systolic murmur. An initial diagnosis of heart failure was made, but additional intraabdominal pathology was also considered to explain her disproportionate ascites. There was cardiomegaly on chest radiograph and electrocardiogram showed atrial fibrillation and incomplete right bundle branch block. CA125 level was markedly elevated at 1176 U/mL (normal < 30 U/mL). Investigation by transthoracic and later transesophageal echo showed a 17 to 18 mm secundum atrial septal defect (ASD) with left-to-right shunt and enlarged right-sided chambers, but normal left ventricular function. Abdominal ultrasound confirmed ascites and also showed echogenic calcified areas in the pelvis suggestive of fibroid or ovarian mass. However, computed tomographic (CT) scan of the abdomen, transvaginal ultrasound, and laparoscopy failed to show any significant intraabdominal, and specifically ovarian, pathology. Treatment with digoxin and diuretics improved her fluid overload and exercise tolerance. Cardiac catheterization confirmed ASD with left-to-right shunt, and also showed that the left ventricular function, pulmonary artery pressures, and coronary arteries were normal. CA125 level had fallen to 28 U/mL in about one month. She later successfully underwent ASD closure with a 26 mm Amplatzer device and continues to do well a year later with normal CA125 level.

Discussion

In the above patient, CA125 level returned to normal within four weeks of treatment with digoxin and diuretics. A year after device closure of the ASD she continues to do well, with normal CA125 level. This suggests that it was the heart failure which produced the elevation of CA125, and makes it unlikely that other factors such as occult malignancy could have been responsible. The association between heart failure and elevated tumor markers is not widely appreciated. (1) This knowledge could have avoided invasive and expensive investigations to identify an intraabdominal tumor in this patient. However, previous reports of elevated CA125 are in patients with left ventricular systolic dysfunction and heart failure, as in patients awaiting cardiac transplantation. (2-4) Indeed, the level of CA125 has been suggested as a marker of the clinical and hemodynamic status in patients with heart failure. (3) In a study of 118 patients being evaluated for heart transplantation, CA125 level significantly correlated with the severity of heart failure and prognosis. (2) The site of production of CA125 is unknown. Previous reports of elevated CA125 in heart failure have been in patients with left ventricular systolic dysfunction and raised pulmonary venous pressure. The patient reported here had normal left ventricular function, and heart failure was purely right sided, due to the large left-to-right shunt. This combination has not been reported in the literature previously. The mechanism of production of CA125 is hypothesized to be increased secretion of the marker by the activated peritoneal mesothelium, either directly or indirectly through mediators such as interleukin-6 acting on the liver. (5-7)
I shall not waste my days in trying to prolong them.
--Ian L. Fleming


Accepted June 15, 2004.

References

1. Nagele H, Bahlo M, Klapdor R, et al. CA 125 and its relation to cardiac function. Am Heart J 1999;137:1044-1049.

2. Soma L, Allen M, Tobin L, et al. CA-125 concentrations in patients awaiting cardiac transplantation. Clin Chem 2002;48:2289-2290.

3. D'Aloia A, Faggiano P, Aurigemma G, et al. Serum levels of carbohydrate antigen 125 in patients with chronic heart failure: relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities, and short-term prognosis. J Am Coll Cardiol 2003;41:1805-1811.

4. Faggiano P, D'Aloia A, Bignotti T, et al. One biologic marker (carbohydrate antigen-CA 125), two different diseases (ovarian cancer and congestive heart failure): practical implications of monitoring CA 125 serum levels. A case report. Ital Heart J 2003;4:497-499.

5. Turk HM, Pekdemir H, Buyukberber S, et al. Serum CA 125 levels in patients with chronic heart failure and accompanying pleural fluid. Tumour Biol 2003;24:172-175.

6. Miralles C, Orea M, Espana P, et al. Cancer antigen 125 associated with multiple benign and malignant pathologies. Ann Surg Oncol 2003;10:150-154.

7. Eltabbakh GH, Belinson JL, Kennedy AW, et al. Serum CA-125 measurements > 65 U/mL. Clinical value. J Reprod Med 1997;42:617-624.

RELATED ARTICLE: Key Points

* Congestive heart failure is associated with elevated CA125, and is described in patients with left ventricular dysfunction and congestive heart failure.

* This patient is unique in that she had isolated right ventricular failure due to atrial septal defect, with normal left ventricular function.

Boban Mathew, MD, DM, MRCP, Vishal Bhatia, MD, IR Mahy, MD, FRCP, Imad Ahmed, MD, and Lisa Francis, MBBS, MRCP

From the Division of Cardiology, the Department of Internal Medicine, and the State University of New York, Buffalo, NY; and Torbay Hospital, Torquay, UK.

Reprint requests to Boban Mathew, MD, DM, MRCP, 565 Abott Road, Buffalo, NY, 14220. Email: bmathew6@yahoo.com
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Title Annotation:Case Report
Author:Francis, Lisa
Publication:Southern Medical Journal
Date:Oct 1, 2004
Words:969
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