کارسینوئید بیماری قلبی: یک راهنما برای غربالگری و زمان سنجی مداخله جراحی Carcinoid heart disease: a guide for screening and timing of surgical intervention

Introduction Neuroendocrine tumours Well-differentiated neuroendocrine tumours (NETs) are rare malignancies, occurring in 5.25 per 100,000 people per year [1]. The majority of NETs develop in the small intestine, particularly in the ileum, and in the bronchopulmonary system. Less frequently NETs arise from other sites within the gastrointestinal tract, including colon, rectum and stomach [2]. Some of these tumours, in particular small intestinal NETs, secrete various vasoactive substances, including serotonin (5-hydroxytryptamine; 5-HT), tachykinins, prostaglandins, histamine, and kallikrein. Typically, the liver inactivates these substances when released into the portal circulation. However, when a serotoninproducing NET metastasises to the liver, direct access to the systemic circulation may result in carcinoid syndrome. Carcinoid syndrome is characterised by episodic cutaneous flushing, hypotension, gut hypermotility with diarrhoea, and bronchospasms [3–5]. Carcinoid heart disease Patients with carcinoid syndrome are at risk to develop carcinoid heart disease (CaHD), also known as Hedinger syndrome. Since the introduction of somatostatin analogues, the incidence of CaHD has dropped from over 50% [6] to approximately 20% in patients with carcinoid syndrome [7]. CaHD is most likely caused by the paraneoplastic effects of vasoactive substances excreted by the tumour, particularly serotonin [5, 7, 8]. Although patients with CaHD are often asymptomatic in the early stages of the disease [9], signs of right heart failure are associated with disease progression. The disease is characterised by plaque-like deposits of fi- brous tissue involving the endocardium of the valve leaflets, cardiac chambers, and less frequently the intima of the pulmonary arteries and aorta [10]. Primarily the right side of the heart is affected, due to thickening and retraction of the tricuspid and pulmonary valve leaflets, with subsequent regurgitation and/or stenosis. Left-sided valve involvement occurs in less than 10% of patients with CaHD and is commonly observed in patients with a right-to-left shunt (e. g. patent foramen ovale) and elevated right heart-sided pressures, bronchial NETs or severe carcinoid syndrome with high amounts of vasoactive substances [6]. Sporadically, left-sided valvular disease is present in the absence of rightsided valve involvement [11, 12]. There is no clear explanation for the predominant right-sided valve involvement. Vasoactive substances excreted by the tumour are thought to be largely inactivated within the pulmonary circulation [13]. The presence of CaHD has a detrimental effect on the prognosis of NET patients and therefore early diagnosis and treatment, if possible, are of major importance [6, 14]. More specifically, the cause of death in CaHD patients is attributable to cardiac involvement in almost half of the cases [15].