Serotonin, Chemotherapy Tied To Carcinoid Heart Disease Progression

Progression of heart-valve disease is linked both with higher peak urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, and treatment with cytotoxic chemotherapy.

Researchers in the United States made this finding as a result of a retrospective study identifying factors associated with progression of carcinoid heart disease. To date, these factors have been poorly understood. However, carcinoid tumours can cause right-sided valvular heart disease by releasing vasoactive substances into the circulation. Moreover, although such a mechanism was not documented in this study, cytotoxic chemotherapy may cause bursts of serotonin release.

Dr Jacob E Moller and colleagues from the Mayo Clinic, Rochester, Minnesota, studied 71 patients with carcinoid syndrome who had serial echocardiographic studies done more than one year apart and another 32 patients referred directly for surgery after initial echocardiographic evaluation.

Investigators determined a score for carcinoid heart disease on the basis of valvular anatomy and function and right-ventricle function. They considered an increase of more than 25% in the score between studies suggestive of disease progression.

Tumour progression was assessed on the basis of abdominal computed tomography scans and changes in level of urinary 5-HIAA.

Twenty-five (35%) of the 71 patients with serial echocardiographic studies had an increase of more than 25% in the cardiac score. In contrast to patients whose score changed less than that, these patients also had higher urinary peak 5-HIAA levels and were more likely to have biochemical progression and to have received chemotherapy.

Further analysis indicated a higher peak urinary 5-HIAA level and previous chemotherapy were predictors of an increase in the cardiac score that exceeded 25%.

Serotonin is thus related to the progression of carcinoid heart disease, and the risk of progressive disease is higher in patients who receive chemotherapy than in those who do not, these authors conclude.

N Engl J Med 2003;348:1005-1015.