Carcinoid heart disease: relationship of circulating vasoactive substances to ultrasound-detectable cardiac abnormalities.

Abstract

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][15][16][17] 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 (5-HIAA) 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. MethodsStudy population. Cardiac ultrasound studies were performed in 68 consecutive patients (36 women and 32 men) with a midgut type of malignant carcinoid tumor admitted to the Department of Internal Medicine, University Hospital, Uppsala, Sweden, over a 6 year period (1979)(1980)(1981)(1982)(1983)(1984)(1985). The diagnosis of a carcinoid tumor was histologically proven by the Grimelius and Mason silver-staining techniques18' 19 on tumor tissue obtained at biopsy or operation. The patients median age was 64 years (range 38 to 83) and at the time of the cardiac investigation, carcinoid...

Long-Term Serotonin Administration Induces Heart Valve Disease in Rats

“…28 Carcinoid heart disease is thought to be a consequence of hyperserotoninemia, but other substances such as tachykinins and bradykinin have not been ruled out as pathogens. 2,5 We found that serotonin injections induced clinical signs such as flushing, loose stools, and anorexia. After 3 months, cardiac disease with pathological echocardiographs and histopathological changes similar to those seen in the carcinoid heart disease appeared.…”

“…The primary tumor is often small and asymptomatic because its hormonally active secretagogues (serotonin, neuropeptide K, bradykinin, and substance P) are broken down by first-pass metabolism in the liver. 2 When metastasizing to the liver, hormonally active tumor products are secreted into the liver vein, giving rise to the carcinoid syndrome with vasomotor symptoms, bronchospasm, diarrhea, and in 50% of the patients, valvular heart disease. In a study at the Mayo Clinic, preoperative examination of 75 patients with carcinoid heart disease revealed tricuspid regurgitation in all 75, tricuspid stenosis in 15, pulmonary valve regurgitation in 58, pulmonary stenosis in 50, mitral regurgitation in 33, and aortic regurgitation in 24 patients.…”

Metastatic Carcinoid Tumors: A Clinical Review

“…Carcinoid heart disease (CHD) is a late complication and occurs in 20%-70% of patients with metastatic carcinoid tumors [23,24]. In many patients, the cause of death is attributed directly to cardiac disease [25].…”

“…In several studies, urinary 5-HIAA excretion, which is indicative for the amount of serotonin production, was significantly higher in patients with CHD than in those without CHD [23,24,27]. Not only a high serotonin level, but also the duration of exposure to serotonin, is important in the development of CHD [27].…”

Role of natriuretic peptides in the diagnosis and treatment of patients with carcinoid heart disease

“…Carcinoid heart disease (CHD) is a well-known complication of long-lasting exposure to high levels of serotonin (Tornebrandt et al, 1986;Lundin et al, 1988;Robiolio et al, 1995;Westberg et al, 2001;Zuetenhorst et al, 2003). Many carcinoid patients die from cardiac causes (Ross and Roberts, 1985) and the detection of CHD in an early stage is important to adjust therapy and hence improve prognosis.…”