Carcinoid heart disease: presentation, diagnosis, and management

ricuspid and pulmonary valve regurgitation usually occurs as a secondary phenomenon caused by dilatation of the valve ring secondary to right ventricular failure or pulmonary hypertension, respectively.Primary diseases of the tricuspid or pulmonary valves are uncommon, but the more likely causes might include congenital abnormalities, rheumatic heart disease, or infective endocarditis.Carcinoid heart disease is a rare, but interesting and important cause of intrinsic tricuspid and pulmonary valve disease leading to significant morbidity and mortality caused by right heart failure.When treated medically, and in appropriate cases surgically, significant benefits in overall quality of life and long term survival can be achieved.We review the current literature regarding the pathophysiological basis of the disease, the cardiovascular complications, and the currently available treatment strategies. AETIOLOGY AND PATHOPHYSIOLOGY cCarcinoid tumours are rare neuroendocrine malignancies arising from neural crest amine precursor uptake decarboxylation cells.Approximately 90% of all carcinoid tumours are located in the gastrointestinal system of which the most common sites are the appendix and terminal ileum.Other less common sites include the bronchus and gonads.The most malignant of the carcinoid tumours tend to arise from the ileum and must be invasive or metastasise to produce the carcinoid syndrome which is characterised by facial flushing, intractable secretory diarrhoea, and bronchoconstriction.The incidence of carcinoid tumours is approximately 1 in 75 000 of the population 1 of whom about 50% develop carcinoid syndrome.Once the carcinoid syndrome has developed, approximately 50% of these patients develop carcinoid heart disease which typically causes abnormalities of the right side of the heart.Usually, only carcinoid tumours that invade the liver result in pathological changes to the heart.The cardiac manifestations are caused by the paraneoplastic effects of vasoactive substances such as 5-hydroxytryptamine (5-HT or serotonin), histamine, tachykinins, and prostaglandins released by the malignant cells rather than any direct metastatic involvement of the heart.Ordinarily, the vasoactive tumour products are inactivated by the liver, lungs, and brain, but the presence of hepatic metastases may allow large quantities of these substances to reach the right side of the heart without being inactivated by the liver.The characteristic pathological findings are endocardial plaques of fibrous tissue that may involve the tricuspid valve, pulmonary valve, cardiac chambers, venae cavae, pulmonary artery, and coronary sinus.The fibrous reaction may involve not only the valve leaflets, but also the subvalvar apparatus including the tendinous chords and papillary muscles of the tricuspid valve, and more rarely the mitral valve in cases with left sided involvement.The fibrous tissue in the plaques results in distortion of the valves leading to either stenosis, regurgitation, or both.The preferential right heart involvement is most likely related to inactivation of the vasoactive substances by the lungs.In the 5-10% of cases with left sided valvar pathology, one should suspect either extensive liver metastases, bronchial carcinoid, or a patent foramen ovale. 2 3 Although the precise cause for the plaque formation is not entirely clear, the direct actions of serotonin and bradykinin have been implicated by animal studies.4 This finding is corroborated by the observation that the appetite suppressant drug fenfluramine, which releases serotonin, has been noted to cause valvar distortion similar to that seen in carcinoid heart disease.5 NATURAL HISTORYMany carcinoid tumours are slow growing and follow a prolonged course of up to 20 or more years from the development of the carcinoid symptoms.However, the development of cardiac pathology in the carcinoid patient heralds a decline in clinical outcome.Three year mortality data for patients with carcinoid heart disease shows a 31% survival rate, whereas carcinoid patients without cardiac involvement have approximately twice the survival rate.One study showed mean survival in those with carcinoid heart disease to be reduced to 1.6 years compared to 4.6 years in those without cardiac involvement.6 Nevertheless, there is good evidence to suggest that