The carcinoid syndrome results from bioactive compounds such as serotonin released by carcinoid tumors (Chapter 15); systemic manifestations include flushing, diarrhea, dermatitis, and bronchoconstriction. Carcinoid heart disease refers to the cardiac manifestation caused by the bioactive compounds and occurs in one half of patients in whom the systemic syndrome develops. Cardiac lesions typically do not occur until there is a massive hepatic metastatic burden, since the liver normally inactivates circulating mediators before they can affect the heart. Classically, endocardium and valves of the right heart are primarily affected since they are the first cardiac tissues bathed by the mediators released by gastrointestinal carcinoid tumors. The left side of the heart is afforded some measure of protection because the pulmonary vascular bed degrades the mediators. However, left-sided heart carcinoid lesions can occur in the setting of atrial or ventricular septal defects and right-to-left flow, or they can arise in association with primary pulmonary carcinoid tumors.
Table 11.6 Cardiovascular Effects of Noncardiac Neoplasms
ModifiedfromSchoenFJ,etal:Cardiaceffectsofnon-cardiacneoplasms,Cardiol Clin 2:657,1984.
http://ebooksmedicine.net
Fig. 11.31 Carcinoidheartdisease.(A)Characteristicendocardialfibrotic(light gray) lesion“coating”therightventricleandtricuspidvalve,andextendingontothechordaetendineae.(B)Microscopicappearanceofthethickenedendocardium,whichcontainssmoothmusclecellsandabundantacidmucopolysaccharides(blue-greeninthisMovatstain,whichcolorstheunderlyingendocardialelastictissueblack).
The mediators elaborated by carcinoid tumors include serotonin (5-hydroxytryptamine), kallikrein, bradykinin, histamine, prostaglandins, and tachykinins. Although it is not clear which of these is causative, plasma levels of serotonin and urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid correlate with the severity of right-sided heart lesions. The valvular plaques in carcinoid syndrome also are similar to lesions that occur with the administration of fenfluramine (an appetite suppressant) or ergot alkaloids (for migraine headaches); of interest, these agents either affect systemic serotonin metabolism or directly bind to hydroxytryptamine receptors on heart valves.
MORPHOLOGYThecardiovascularlesionsassociatedwiththecarcinoidsyndromearedistinctive,glisteningwhite,intimal,plaquelikethickeningsontheendocardialsurfacesofthecardiacchambersandvalveleaflets(
Fig.11.31 ).Thelesionsarecomposedofsmoothmusclecellsandsparsecollagenfibersembeddedinanacidmucopolysaccharide–richmatrix.Underlyingstructuresareintact.Withright-sidedinvolvement,typicalfindingsaretricuspidinsufficiencyandpulmonicstenosis.
Although permanent ventricular assist device implantation is increasingly an option for management of end-stage heart disease, cardiac transplantation remains the treatment of choice for patients with intractable heart failure. Without transplantation, medically managed end-stage heart failure carries a 50% 1-year mortality rate, and less than 10% of patients survive 5 years. Over 5000 heart transplantation procedures are performed annually worldwide, mostly for DCM and IHD.
The major complications of cardiac transplantation are acute cardiac rejection and allograft arteriopathy.
The immunosuppression required for allograft survival also increases the risk for opportunistic infections and certain malignancies (e.g., Epstein-Barr virus–associated lymphoma).