Opinion statement
Carcinoid is a rare neuroendocrine tumor that typically originates in the gastrointestinal tract and can result in a constellation of symptoms, mediated by vasoactive substances, referred to as carcinoid syndrome. Carcinoid valve and heart disease is characterized by the plaque-like, endocardial fibrous tissue deposits, primarily affecting the right heart endocardium and valves, which result as a consequence of the disease process. Potential mechanisms for the carcinoid valve disease include the complex role of excess serotonin and its interaction with serotonin receptors and transporters. Carcinoid valve and heart disease is a frequent occurrence in patients with carcinoid syndrome and is accountable for substantial morbidity and mortality. Cardiac surgery remains the most effective treatment option for carcinoid valve disease and a multidisciplinary approach at an experienced center is recommended for patients with metastatic carcinoid and carcinoid heart disease.
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Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. 1997;79:813–29.
Pellikka PA, Tajik AJ, Khandheria BK, et al. Carcinoid heart disease. Clinical and echocardiographic spectrum in 74 patients. Circulation. 1993;87:1188–96.
Lundin L, Norheim I, Landelius J, et al. Carcinoid heart disease: relationship of circulating vasoactive substances to ultrasound-detectable cardiac abnormalities. Circulation. 1988;77:264–9.
Anderson AS, Krauss D, Lang R. Cardiovascular complications of malignant carcinoid disease. Am Heart J. 1997;134:693–702.
Bhattacharyya S, Toumpanakis C, Caplin ME, et al. Analysis of 150 patients with carcinoid syndrome seen in a single year at one institution in the first decade of the twenty-first century. Am J Cardiol. 2008;101:378–81.
Palaniswamy C, Frishman WH, Aronow WS. Carcinoid heart disease. Cardiol Rev. 2012;20:167–76. doi:10.1097/CRD.1090b1013e31824c31866e.
Chaowalit N, Connolly HM, Schaff HV, et al. Carcinoid heart disease associated with primary ovarian carcinoid tumor. Am J Cardiol. 2004;93:1314–5.
Wilkowske MA, Hartmann LC, Mullany CJ, et al. Progressive carcinoid heart disease after resection of primary ovarian carcinoid. Cancer. 1994;73:1889–91.
Bernheim AM, Connolly HM, Pellikka PA. Carcinoid heart disease in patients without hepatic metastases. Am J Cardiol. 2007;99:292–4.
Roberts WC. A unique heart disease associated with a unique cancer: carcinoid heart disease. Am J Cardiol. 1997;80:251–6.
Pandya UH, Pellikka PA, Enriquez-Sarano M, et al. Metastatic carcinoid tumor to the heart: echocardiographic-pathologic study of 11 patients. J Am Coll Cardiol. 2002;40:1328–32.
Ferrans VJ, Roberts WC. The carcinoid endocardial plaque: an ultrastructural study. Hum Pathol. 1976;7:387–409.
Bernheim AM, Connolly HM, Hobday TJ, et al. Carcinoid heart disease. Prog Cardiovasc Dis. 2007;49:439–51.
Simula DV, Edwards WD, Tazelaar HD, et al. Surgical pathology of carcinoid heart disease: a study of 139 valves from 75 patients spanning 20 years. Mayo Clinic Proc. 2002;77:139–47.
Bhattacharyya S, Schapira AH, Mikhailidis DP, et al. Drug-induced fibrotic valvular heart disease. Lancet. 2009;374:577–85. Review of potential mechanisms in the development of drug-induced valvular heart disease including interaction of serotonin, serotonin transporter, and 5HT2B receptors. Carcinoid valve disease is believed to be caused by a similar mechanism.
Rothman RB, Baumann MH, Savage JE, et al. Evidence for possible involvement of 5-HT2B receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000;102:2836–41.
Sareyyupoglu B, Connolly HM, Schaff HV. Surgical excision of right ventricular carcinoid tumor in a symptomatic patient without carcinoid valve disease. J Thorac Cardiovasc Surg. 2010;140:e23–5.
Melmon KL, Sjoerdsma A, Mason DT. Distinctive clinical and therapeutic aspects of the syndrome associated with bronchial carcinoid tumors. Am J Med. 1965;39:568–81.
Feldman JM, Lee EM. Serotonin content of foods: effect on urinary excretion of 5-hydroxyindoleacetic acid. Am J Clin Nutr. 1985;42:639–43.
Richter G, Stockmann F, Conlon JM, et al. Serotonin release into blood after food and pentagastrin. Studies in healthy subjects and in patients with metastatic carcinoid tumors. Gastroenterology. 1986;91:612–8.
Sjöblom S-M. Clinical presentation and prognosis of gastrointestinal carcinoid tumours. Scand J Gastroenterol. 1988;23:779–87.
Tomassetti P, Migliori M, Simoni P, et al. Diagnostic value of plasma chromogranin A in neuroendocrine tumours. Eur J Gastroenterol Hepatol. 2001;13:55–8.
Modlin I, Gustafsson B, Moss S, et al. Chromogranin A—biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol. 2010;17:2427–43.
Korse CM, Taal BG, de Groot CA, et al. Chromogranin-A and N-Terminal pro-brain natriuretic peptide: an excellent pair of biomarkers for diagnostics in patients with neuroendocrine tumor. J Clin Oncol. 2009;27:4293–9.
Lundin L, Öberg K, Landelius J, et al. Plasma atrial natriuretic peptide in carcinoid heart disease. Am J Cardiol. 1989;63:969–72.
Bhattacharyya S, Toumpanakis C, Caplin ME, et al. Usefulness of N-terminal pro–brain natriuretic peptide as a biomarker of the presence of carcinoid heart disease. Am J Cardiol. 2008;102:938–42.
Ross EM, Roberts WC. The carcinoid syndrome: comparison of 21 necropsy subjects with carcinoid heart disease to 15 necropsy subjects without carcinoid heart disease. Am J Med. 1985;79:339–54.
Haugaa KH, Bergestuen DS, Sahakyan LG, et al. Evaluation of right ventricular dysfunction by myocardial strain echocardiography in patients with intestinal carcinoid disease. J Am Soc Echocardiogr. 2011;24:644–50.
Bhattacharyya S, Toumpanakis C, Burke M, et al. Features of carcinoid heart disease identified by 2- and 3-dimensional echocardiography and cardiac MRI. Circ Cardiovasc Imaging. 2010;3:103–11.
Bhattacharyya S, Burke M, Caplin ME, et al. Utility of 3D transoesophageal echocardiography for the assessment of tricuspid and pulmonary valves in carcinoid heart disease. Eur J Echocardiogr. 2011;12:E4.
Lee KJ, Connolly HM, Pellikka PA. Carcinoid pulmonary valvulopathy evaluated by real-time 3-dimensional transthoracic echocardiography. J Am Soc Echocardiogr. 2008;21:407.e401–2.
Dumaswala B, Bicer EI, Dumaswala K, et al. Live-real time three-dimensional transthoracic echocardiographic assessment of the involvement of cardiac valves and chambers in carcinoid disease. Echocardiography. 2012;29:751–6.
Kubota A, Yamada Y, Kagimoto S, et al. Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201–995 in treatment of human endocrine tumors. J Clin Invest. 1994;93:1321–5.
Rinke A, Müller H-H, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group. J Clin Oncol. 2009;27:4656–63.
Öberg K. Biotherapies for GEP-NETs. Best practice & research clinical. Gastroenterology. 2012;26:833–41.
Öberg K, Norheim I, Lundqvist G, et al. Cytotoxic treatment in patients with malignant carcinoid tumors: response to streptozocin—alone or in combination with 5-FU. Acta Oncol. 1987;26:429–32.
Ansell SM, Pitot HC, Burch PA, et al. A Phase II study of high-dose paclitaxel in patients with advanced neuroendocrine tumors. Cancer. 2001;91:1543–8.
Ritzel U, Leonhardt U, Stockmann F, et al. Treatment of metastasized midgut carcinoids with decarbazine. Am J Gastroenterol. 1995;90:627–31.
Bushnell DL, O'Dorisio TM, O'Dorisio MS, et al. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010;28:1652–9.
Lillegard JB, Fisher JE, McKenzie TJ, et al. Hepatic resection for the carcinoid syndrome in patients with severe carcinoid heart disease: does valve replacement permit safe hepatic resection? J Am Coll Surg. 2011;213:130–6.
Bernheim AM, Connolly HM, Rubin J, et al. Role of hepatic resection for patients with carcinoid heart disease. Mayo Clin Proc. 2008;83:143–50.
Connolly H, Pellikka P. Carcinoid heart disease. Curr Cardiol Rep. 2006;8:96–101.
Connolly HM, Nishimura RA, Smith HC, et al. Outcome of cardiac surgery for carcinoid heart disease. J Am Coll Cardiol. 1995;25:410–6.
Bernheim A, Connolly H, Pellikka P. Carcinoid heart disease. Curr Treat Options Cardio Med. 2007;9:482–9.
Connolly HM, Schaff HV, Mullany CJ, et al. Carcinoid heart disease: impact of pulmonary valve replacement in right ventricular function and remodeling. Circulation. 2002;106:I–51–6.
Connolly HM, Schaff HV, Mullany CJ, et al. Surgical management of left-sided carcinoid heart disease. Circulation. 2001;104:I–36–40.
Arghami A, Connolly HM, Abel MD, et al. Quadruple valve replacement in patients with carcinoid heart disease. J Thorac Cardiovasc Surg. 2010;140:1432–4.
Ridker PM, Chertow GM, Karlson EW, et al. Bioprosthetic tricuspid valve stenosis associated with extensive plaque deposition in carcinoid heart disease. Am Heart J. 1991;121:1835–8.
Schoen FJ, Hausner RJ, Howell JF, et al. Porcine heterograft valve replacement in carcinoid heart disease. J Thor Cardiovasc Surg. 1981;81:100–5.
Stulak JM, Dearani JA, Burkhart HM, et al. The increasing use of mechanical pulmonary valve replacement over a 40-year period. Ann Thorac Surg. 2010;90:2009–15.
Powell B, Al Mukhtar A, Mills GH. Carcinoid: the disease and its implications for anaesthesia. Contin Educ Anaesthes Crit Care Pain. 2011;11:9–13.
Weingarten TN, Abel MD, Connolly HM, et al. Intraoperative management of patients with carcinoid heart disease having valvular surgery: a review of one hundred consecutive cases. Anesth Analg. 2007;105:1192–9. This publication details the anesthetic management of consecutive carcinoid heart disease patients undergoing cardiac surgery at a single center and highlights the importance of a multidiscplinary approach in perioperative management and improvement in perioperative survival over time.
Møller JE, Pellikka PA, Bernheim AM, et al. Prognosis of carcinoid heart disease: analysis of 200 cases over two decades. Circulation. 2005;112:3320–7. This study demonstrates the improvement in prognosis for metastatic carcinoid disease and carcinoid heart disease over two decades and suggests the important contribution of valvular surgery.
Robiolio PA, Rigolin VH, Wilson JS, et al. Carcinoid heart disease: correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92:790–5.
Westberg G, Wängberg B, Ahlman H, et al. Prediction of prognosis by echocardiography in patients with midgut carcinoid syndrome. Br J Surg. 2001;88:865–72.
Eriksson BK, Larsson EG, Skogseid BM, et al. Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors. Cancer. 1998;83:2293–301.
Oberg K. Chemotherapy and biotherapy in the treatment of neuroendocrine tumors. Ann Oncol. 2001;12:S111–4.
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Dr. J. Wells Askew declares that he has no conflict of interest. Dr. Heidi M. Connolly declares that she has no conflict of interest.
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Askew, J.W., Connolly, H.M. Carcinoid Valve Disease. Curr Treat Options Cardio Med 15, 544–555 (2013). https://doi.org/10.1007/s11936-013-0265-2
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DOI: https://doi.org/10.1007/s11936-013-0265-2