Prognostic Value of Heart Rate Variability Analysis in Patients with Carcinoid Syndrome

BACKGROUND/AIMS: Recently, a decrease in heart rate variability measures was found in patients with carcinoid syndrome suffering from carcinoid heart disease compared to those without cardiac involvement of carcinoid syndrome. The prognostic relevance of this finding, however, was not clear. PATIENTS AND METHODS: Therefore, 35 patients with carcinoid syndrome (21 men, age 56 +/- 11 years), all of them suffering from metastatic carcinoid tumors, were followed prospectively at our institution. Digital 24-hour Holter monitoring, echocardiography, and serum serotonin and urine 5-hydroxyindole acetic acid (5-HIAA) samplings were performed in all study patients at baseline. Indices of time domain heart rate variability obtained from Holter recordings included the standard deviation of all normal RR intervals (SDNN) representing overall variability, the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the percentage of the number of pairs of adjacent normal RR intervals differing by >50 ms (pNN50), both indices reflecting predominantly vagal influences on heart rate. RESULTS: During a mean follow-up of 18 +/- 7 months, 15 of 35 patients with carcinoid syndrome (43%) died. Patients with cardiac manifestation of the carcinoid syndrome showed a tendency towards an increased mortality in comparison to patients without cardiac involvement (p = 0.09). Patients with the combination of decreased heart rate variability (SDNN <100 ms) and presence of carcinoid heart disease had a significant worse prognosis (p = 0.04) compared to patients without carcinoid heart disease and preserved heart rate variability (SDNN > or =100 ms). CONCLUSIONS: The presence of carcinoid heart disease in combination with decreased heart rate variability is associated with the most adverse prognosis in the setting of carcinoid syndrome.