PATHOPHYSIOLOGY AND NATURAL HISTORY CARCINOID HEART DISEASE Carcinoid heart disease: relationship of circulating vasoactive substances

Cardiac ultrasound investigation of 68 prospectively studied patients with histologically proven midgut carcinoid tumors showed right heart disease in 66%. The abnormal findings included morphologic and functional aberrations of the tricuspid valve in 52% and 83%, respectively, right atrial and ventricular enlargement in 53% and 30%, and paradoxical systolic septal contractions in 19%. The patients with the most pronounced right heart disease had significantly higher (p<.01) plasma levels of the tachykinins neuropeptide K and substance P as well as higher (p<.001) urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid. These patients also had the most extensive tumor disease. The occurrence of echocardiographic abnormalities of the left heart was similar to that in healthy individuals of the same age, but abnormalities were less frequent among the patients with severe right heart disease. Electrocardiographic changes were nonspecific. Right heart disease thus seems to be present more often than previously reported in patients with malignant midgut carcinoid tumors. The severity of cardiac involvement does not seem to be related to the duration of carcinoid disease but more to the extent of the disease, i.e., higher plasma levels of serotonin and tachykinins. Circulation 77, No. 2, 264-269 1988. PATIENTS with carcinoid syndrome often develop a characteristic heart disease previously reported to occur in 19% to 53% of cases. l-6 In a majority of the patients the endocardial fibrous lesions considered to be pathognomonic of carcinoid heart disease2' 7-10 involve the cavities and valves of the right heart. Only a small number of cases with typical changes of the left heart have been reported. l -13 In many patients with carcinoid heart disease, the predominant terminal symptoms and death may be attributed directly to the cardiac disease.1' 14-17 The pathogenesis of carcinoid heart lesions has not yet been elucidated. Investigators have postulated etiologic' agents released from the tumor, such as serotonin, kallikrein, bradykinin, histamine, gastrin, ACTH, and prostaglandins.13 HowFrom the Departments of Cardiology, Endocrinology, Clinical Physiology, and the Ludwig Institute for Cancer Research, University Hospital, Uppsala, and the Department of Clinical Chemistry, Karolinska Hospital, Stockholm Sweden. Supported by the Faculty of Medicine, University of Uppsala, the Ludwig Institute for Cancer Research and the Swedish National Association against Heart and Chest Diseases, Swedish Medical Research Council (07464), Swedish Cancer Society (2313). Address for correspondence: Lennart Lundin, Department of Cardiology, Medical Clinic, University Hospital, S-751, 85 Uppsala, Sweden. Received June 23, 1987; revision accepted Oct. 15. 1987. 264 ever, none of these substances has been found responsible for the characteristic cardiac lesions. The present study was designed to investigate prospectively the extent of cardiac disease in patients with carcinoid tumors by means of ultrasound investigation. In an effort to study possible etiologic agents the urinary excretion of 5-hydroxyindoleacetic acid (5HIAA) and the plasma levels of the tachykinins neuropeptide K (NPK) and substance P (SP) were compared in patients with midgut carcinoid tumors and different degrees of carcinoid heart disease.