Carcinoid heart disease
- Heidi M Connolly, MD, FASE
Heidi M Connolly, MD, FASE
- Section Editor — Congenital Heart Disease
- Professor of Medicine
- Mayo Medical School
Carcinoid tumors are rare, arising in 1.2 to 2.1 per 100,000 people in the general population per year . They can arise anywhere in the body, but are most commonly found in the gastrointestinal tract (midgut carcinoids) and bronchus (foregut carcinoids) (table 1). Primary midgut carcinoid tumors metastasize to the liver or regional lymph nodes and may present with bowel obstruction. In 20 to 30 percent of patients, the initial presentation occurs as a result of hormone production, called the carcinoid syndrome. (See "Clinical characteristics of carcinoid tumors".)
The most common manifestations of the carcinoid syndrome are vasomotor changes (flushing) (picture 1), gastrointestinal hypermotility (secretory diarrhea), bronchospasm, and hypotension (table 2). These symptoms are caused by the release of vasoactive substances, including serotonin (5-hydroxytryptamine), 5-hydroxytryptophan, histamine, bradykinin, tachykinins, and prostaglandins (table 3). The diagnosis of carcinoid syndrome is usually suspected by the clinical features and confirmed by identification of the primary tumor, localization of metastatic lesions, and detection of increased urinary excretion of the by-product of serotonin metabolism, 5-hydroxyindoleacetic acid (5-HIAA) (figure 1). (See "Clinical features of the carcinoid syndrome" and "Diagnosis of the carcinoid syndrome and tumor localization".)
Progress in the medical and surgical management of patients with carcinoid disease has resulted in improved symptoms and survival. (See "Staging, treatment, and posttreatment surveillance of nonmetastatic, well-differentiated gastrointestinal tract neuroendocrine (carcinoid) tumors".)
However, carcinoid heart disease, which eventually occurs in over 50 percent of patients with carcinoid syndrome and may be the initial presentation of carcinoid disease in as many as 20 percent of patients [2,3], remains a major cause of morbidity and mortality among patients with carcinoid syndrome [4,5].
Pathologic findings — Carcinoid heart disease is characterized by pathognomonic plaque-like deposits of fibrous tissue. These deposits occur most commonly on the endocardium of valvular cusps, leaflets, papillary muscles and cords, cardiac chambers, and occasionally on the intima of the pulmonary arteries or aorta (figure 2) [6,7].
- Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer 1997; 79:813.
- Pellikka PA, Tajik AJ, Khandheria BK, et al. Carcinoid heart disease. Clinical and echocardiographic spectrum in 74 patients. Circulation 1993; 87:1188.
- 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.
- 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.
- Bhattacharyya S, Davar J, Dreyfus G, Caplin ME. Carcinoid heart disease. Circulation 2007; 116:2860.
- 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.
- 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 Clin Proc 2002; 77:139.
- 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.
- Connolly HM, Schaff HV, Mullany CJ, et al. Surgical management of left-sided carcinoid heart disease. Circulation 2001; 104:I36.
- Roberts WC. A unique heart disease associated with a unique cancer: carcinoid heart disease. Am J Cardiol 1997; 80:251.
- Mansencal N, Mitry E, Forissier JF, et al. Assessment of patent foramen ovale in carcinoid heart disease. Am Heart J 2006; 151:1129.e1.
- Roth BL. Drugs and valvular heart disease. N Engl J Med 2007; 356:6.
- Bhattacharyya S, Schapira AH, Mikhailidis DP, Davar J. Drug-induced fibrotic valvular heart disease. Lancet 2009; 374:577.
- 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.
- Denney WD, Kemp WE Jr, Anthony LB, et al. Echocardiographic and biochemical evaluation of the development and progression of carcinoid heart disease. J Am Coll Cardiol 1998; 32:1017.
- Zuetenhorst JM, Bonfrer JM, Korse CM, et al. Carcinoid heart disease: the role of urinary 5-hydroxyindoleacetic acid excretion and plasma levels of atrial natriuretic peptide, transforming growth factor-beta and fibroblast growth factor. Cancer 2003; 97:1609.
- Møller JE, Connolly HM, Rubin J, et al. Factors associated with progression of carcinoid heart disease. N Engl J Med 2003; 348:1005.
- Moertel CG. Treatment of the carcinoid tumor and the malignant carcinoid syndrome. J Clin Oncol 1983; 1:727.
- Wilkowske MA, Hartmann LC, Mullany CJ, et al. Progressive carcinoid heart disease after resection of primary ovarian carcinoid. Cancer 1994; 73:1889.
- Chaowalit N, Connolly HM, Schaff HV, et al. Carcinoid heart disease associated with primary ovarian carcinoid tumor. Am J Cardiol 2004; 93:1314.
- 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.
- 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.
- Dobson R, Valle JW, Burgess MI, et al. Variation in Cardiac Screening and Management of Carcinoid Heart Disease in the UK and Republic of Ireland. Clin Oncol (R Coll Radiol) 2015; 27:741.
- Davar J, Connolly HM, Caplin ME, et al. Diagnosing and Managing Carcinoid Heart Disease in Patients With Neuroendocrine Tumors: An Expert Statement. J Am Coll Cardiol 2017; 69:1288.
- Dobson R, Burgess MI, Banks M, et al. The association of a panel of biomarkers with the presence and severity of carcinoid heart disease: a cross-sectional study. PLoS One 2013; 8:e73679.
- Bhattacharyya S, Toumpanakis C, Caplin ME, Davar J. Usefulness of N-terminal pro-brain natriuretic peptide as a biomarker of the presence of carcinoid heart disease. Am J Cardiol 2008; 102:938.
- Bhattacharyya S, Toumpanakis C, Chilkunda D, et al. Risk factors for the development and progression of carcinoid heart disease. Am J Cardiol 2011; 107:1221.
- 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.
- Lee KJ, Connolly HM, Pellikka PA. Carcinoid pulmonary valvulopathy evaluated by real-time 3-dimensional transthoracic echocardiography. J Am Soc Echocardiogr 2008; 21:407.e1.
- Bastarrika G, Cao MG, Cano D, et al. Magnetic resonance imaging diagnosis of carcinoid heart disease. J Comput Assist Tomogr 2005; 29:756.
- Mollet NR, Dymarkowski S, Bogaert J. MRI and CT revealing carcinoid heart disease. Eur Radiol 2003; 13 Suppl 6:L14.
- Connolly HM, Schaff HV, Abel MD, et al. Early and Late Outcomes of Surgical Treatment in Carcinoid Heart Disease. J Am Coll Cardiol 2015; 66:2189.
- 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:I51.
- Voigt PG, Braun J, Teng OY, et al. Double bioprosthetic valve replacement in right-sided carcinoid heart disease. Ann Thorac Surg 2005; 79:2147.
- Arghami A, Connolly HM, Abel MD, Schaff HV. Quadruple valve replacement in patients with carcinoid heart disease. J Thorac Cardiovasc Surg 2010; 140:1432.
- McDonald ML, Nagorney DM, Connolly HM, et al. Carcinoid heart disease and carcinoid syndrome: successful surgical treatment. Ann Thorac Surg 1999; 67:537.
- DiSesa VJ, Mills RM Jr, Collins JJ Jr. Surgical management of carcinoid heart disease. Chest 1985; 88:789.
- 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.
- Schoen FJ, Hausner RJ, Howell JF, et al. Porcine heterograft valve replacement in carcinoid heart disease. J Thorac Cardiovasc Surg 1981; 81:100.
- Connolly HM, Nishimura RA, Smith HC, et al. Outcome of cardiac surgery for carcinoid heart disease. J Am Coll Cardiol 1995; 25:410.
- Pislaru SV, Hussain I, Pellikka PA, et al. Misconceptions, diagnostic challenges and treatment opportunities in bioprosthetic valve thrombosis: lessons from a case series. Eur J Cardiothorac Surg 2015; 47:725.
- Thorburn CW, Morgan JJ, Shanahan MX, Chang VP. Long-term results of tricuspid valve replacement and the problem of prosthetic valve thrombosis. Am J Cardiol 1983; 51:1128.
- Mason RA, Steane PA. Carcinoid syndrome: its relevance to the anaesthetist. Anaesthesia 1976; 31:228.
- Caplin ME, Buscombe JR, Hilson AJ, et al. Carcinoid tumour. Lancet 1998; 352:799.
- Vaughan DJ, Brunner MD. Anesthesia for patients with carcinoid syndrome. Int Anesthesiol Clin 1997; 35:129.
- 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.
- Robboy SJ, Norris HJ, Scully RE. Insular carcinoid primary in the ovary. A clinicopathologic analysis of 48 cases. Cancer 1975; 36:404.
- Hajdu SI, Winawer SJ, Myers WP. Carcinoid tumors. A study of 204 cases. Am J Clin Pathol 1974; 61:521.
- Godwin JD 2nd. Carcinoid tumors. An analysis of 2,837 cases. Cancer 1975; 36:560.
- Robiolio PA, Rigolin VH, Harrison JK, et al. Predictors of outcome of tricuspid valve replacement in carcinoid heart disease. Am J Cardiol 1995; 75:485.
- Møller JE, Pellikka PA, Bernheim AM, et al. Prognosis of carcinoid heart disease: analysis of 200 cases over two decades. Circulation 2005; 112:3320.
- Pathologic findings
- Role of serotonin
- CLINICAL MANIFESTATIONS
- Physical examination
- Initial test findings
- - Electrocardiogram
- - Chest radiograph
- DIAGNOSIS AND EVALUATION
- When and how to initially test for carcinoid heart disease
- - Patients with carcinoid syndrome
- Role of biomarkers
- - Patients with tricuspid and/or pulmonic valve disease
- Approach to diagnosis and evaluation
- - Echocardiography
- - CMR and CT
- Approach to management
- Diuretic therapy
- Telotristat ethyl
- Cardiac surgery
- - Choice of valve prosthesis
- - Anesthesia management
- Treatment of carcinoid syndrome
- SUMMARY AND RECOMMENDATIONS