Carcinoid Heart Disease

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.

I. 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.

II. 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.

III. 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.

IV. 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.

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