CARCINOID HEART DISEASE MAY OCCUR IN patients with carcinoid syndrome. The main symptoms of flushing, diarrhea, and occasional wheezing are caused mainly by 5-hydroxytryptamine or serotonin, that is liberated from carcinoid tumors that originate from chromaffin cells (neuroendocrine cells) of the terminal ileum. These tumors of the small intestine contain neurosecretory granules that release a variety of biogenic amines that include serotonin, histamine, bradykinins, tachykinins, and prostaglandins. Involvement of the heart occurs in about half of carcinoid syndrome cases. It is seen mainly in patients with malignant tumors that have metastasized to the liver.

HEART DAMAGE

Bioactivity amines, principally, serotonin, liberated from a malignant tumor causes deformation of the tricuspid valve that leads to tricuspid regurgitation. The pulmonary valve becomes deformed by the plaque-like material resulting in a leaky, incompetent valve (pulmonary regurgitation) or a tight, stenotic valve (pulmonary stenosis). In a clinical study of carcinoid heart disease, 97% of patients had right-sided valvular involvement; severe tricuspid valve regurgitation occurred in all patients and severe pulmonary valve regurgitation in 72%.

A whitish colored plaque forms mainly on the right side of the heart and only in less than 3% of cases are the mitral and aortic valves of the left heart affected. The lesions of the valves and endocardium are caused by serotonin that reaches a high concentration in the right heart. Minimal quantities reach the left side of the heart because 5-hydroxytryptamine is destroyed in the lungs by monoamine oxidase. Some serotonin is destroyed in the liver and in the brain.

The anorectic drugs fenfluramine and dexfenfluramine exert their effects through interference in serotonin metabolism. It is interesting that they were associated with lesions identical to that seen in carcinoid syndrome.

DIAGNOSIS

Carcinoid tumors are rare. They arise from enterochromaffin cells typically located in the gastrointestinal tract. At the time of diagnosis, more than 30% of patients have disseminated disease characterized by cutaneous vasomotor flushing, secretory diarrhea, and mild bronchospasm. In carcinoid heart disease, 5-hydroxytryptamine is metabolized to 5-hydroxyindoleacetic acid (5-HIAA). Elevated levels of 5-HIAA in the urine confirm the diagnosis. Echocardiography confirms thickening of the tricuspid and pulmonary valves with tricuspid and pulmonary valve regurgitation and in some cases, pulmonary valve stenosis. The lesions in the heart may cause right-sided heart failure. Because the blood cannot be ejected adequately through the pulmonary valve, the right ventricle work is increased. Because the tricuspid valve leaks, blood regurgitates into the veins of the neck and back toward the liver, which becomes pulsatile with each heartbeat. The malignant tumor may spread to involve the muscle of the heart. These metastatic carcinoid tumors of the heart are about 2 cm and can be detected by echocardiography.

TREATMENT

There are no specific treatments for carcinoid heart disease. The noncardiac symptoms may be controlled with somatostatin, but the action of this drug is only minutes. Octreotide has been shown to be much more effective in reducing flushing diarrhea and urinary levels of 5-HIAA.

CLINICAL STUDY

Moller et al. studied the poorly understood factors associated with the progression of carcinoid heart disease. They studied 71 patients who underwent serial echocardiographic studies performed more than one year apart and 32 patients referred directly for surgical intervention. These workers concluded that high serotonin levels are related to the progression of carcinoid heart disease, and the risk of progressive heart disease is higher in patients who receive chemotherapy.

Somatostatin is a potent inhibitor of many processes including serotonin. In this nonrandomized study it appears that somatostatin was ineffective in preventing development of carcinoid heart disease. Findings suggested that although serotonin is related to development of carcinoid disease, neither somatostatin therapy nor hepatic dearterialization prevents the progression of chronic lesions. Patients in the study who received cytotoxic chemotherapy had the highest risk of progressive carcinoid heart disease. The exact mechanism involved in the progression of carcinoid disease requires further clarification.