Valvular Disorders in Carcinoid Heart Disease

Shi-Min Yuan About the author

Abstract

Carcinoid heart disease is a rare but important cause of intrinsic right heart valve disorders leading to right heart failure. Occasionally, left-sided heart valves may also be involved. The characteristic cardiac pathological findings of carcinoid heart disease are endocardial thickening as a result of fibrous deposits on the endocardium. Echocardiographic examination and right heart catheterization are very useful for the diagnosis of the lesion. If more cardiac valves are affected, multiple valve replacement should be considered. The management of the pulmonary valve lesion depends on the extent of the diseased valve, either by valvulotomy, valvectomy, or valve replacement. Percutaneous valve implantations in the pulmonary and in the inferior vena cava positions have been advocated for high-risk patients.

Keywords:
Carcinoid Heart Disease; Heart Failure; Pulmonary Valve Stenosis; Tricuspid Valve Insufficiency

INTRODUCTION

Carcinoid heart disease, also known as Hedinger syndrome, is rare affecting at least 20% of patients with carcinoid syndrome. It is considered as a result of high circulating hormone levels, mainly serotonin, impacting on the heart, leading to most commonly valvular fibrosis[11 Pellikka PA, Tajik AJ, Khandheria BK, Seward JB, Callahan JA, Pitot HC, et al. Carcinoid heart disease. Clinical and echocardiographic spectrum in 74 patients. Circulation. 1993;87(4):1188-96.]. It is an important cause of intrinsic right heart valve disorders with significant morbidity and mortality secondary to right heart failure[22 Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.]. Cardiac involvement in carcinoid disease generally results in right-sided valvular lesions, accompanied by tricuspid insufficiency and pulmonary stenosis. The typical valvular lesions of carcinoid heart disease include both tricuspid regurgitation and pulmonary valve stenosis, and the evolving right heart failure may lead to more prominent symptoms[33 Nielsen MS, Manners JM. Valve replacement in carcinoid syndrome. Anaesthetic management for tricuspid and pulmonary valve surgery. Anaesthesia. 1979;34(5):494-9.]. In addition, Materazzo et al.[44 Materazzo C, Meazza R, Stefanelli M, Biasi S. Left valvular involvement in carcinoid: description of a case. G Ital Cardiol. 1994;24(4):429-33.] and Le Métayer et al.[55 Le Métayer P, Constans J, Bernard N, Roudaut R, Pellegrin JL, Lacoste D, et al. Carcinoid heart disease: two cases of left heart involvement diagnosed by transthoracic and transoesophageal echocardiography. Eur Heart J. 1993;14(12):1721-3.] reported left-sided cardiac involvement in carcinoid disease.

PATHOLOGY

Carcinoid heart disease are caused by endocardial deposition of pearly fibrotic plaques (notable for absence of elastic fibers) that generally extend to the right-sided valves, leading to multiple patterns of severe valve dysfunction. Plaque formation causes annular constriction, leaflet thickening, and fusion of the subvalvular apparatus. Marked degeneration of the leaflet architecture leads to severe retraction and noncoaptation of the valve[66 Warner RR, Castillo JG. Carcinoid heart disease: the challenge of the unknown known. J Am Coll Cardiol. 2015;66(20):2197-200.]. Typically, carcinoid heart disease involves the right-sided endocardium, valves and subvalvular apparatus[11 Pellikka PA, Tajik AJ, Khandheria BK, Seward JB, Callahan JA, Pitot HC, et al. Carcinoid heart disease. Clinical and echocardiographic spectrum in 74 patients. Circulation. 1993;87(4):1188-96.]. The deposition of carcinoid plaques, fibrous tissue, myofibroblasts and collagen results in annular constriction, leaflet thickening and retraction, and subvalvular fusion and shortening[77 Castillo JG, Adams DH, Fischer GW. Absence of the tricuspid valve due to severe carcinoid heart disease. Rev Esp Cardiol. 2010;63(1):96.]. Tricuspid regurgitation was almost universal at 92-100%, followed by tricuspid stenosis (38-44%), pulmonary regurgitation (31-38%), and pulmonary stenosis (25-31%). The prevalence of left-sided disease was 0-39%, and most of the advanced right-sided cardiac abnormalities had a lower frequency of left-sided disease than did those with mild right-sided abnormalities[88 Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790-5.]. Luis et al.[99 Luis SA, Pellikka PA. Carcinoid heart disease: diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(1):149-58.] defined the proportions of the valve pathologies of carcinoid heart disease (Table 1).

Table 1
Relative proportions of valvular pathologies in carcinoid heart disease.

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[22 Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.]. Cardiac carcinoid plaques have been related to the exposure of the right heart to serotonin and other tumor byproducts released from hepatic metastases[1010 Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-15.]. Ninety-seven percent of the patients with cardiac involvement had tricuspid valve disease, of whom 90% displayed moderate or severe tricuspid regurgitation; smaller numbers had coexistent tricuspid stenosis. Pulmonary valve pathology was noted in 88% of patients, of whom 81% had pulmonary regurgitation, 53% had pulmonary stenosis, and only 7% had left-sided involvement, in whom the most typical feature was mild-to-moderate mitral regurgitation[22 Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.].

In carcinoid heart disease, the characteristic cardiac pathological findings are endocardial plaques of fibrous tissues[1111 Basson MD, Ahlman H, Wangberg B, Modlin IM. Biology and management of the midgut carcinoid. Am J Surg. 1993;165(2):288-97.]. 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 tumor 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[22 Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.]. Serotonin is a common product of carcinoid tumors and it contributes to cardiac failure as a result of fibrous deposits on the endocardium. Most such tumors contain tryptophan hydroxylase, which is able to produce serotonin after hydroxylation and subsequent decarboxylation of the tryptophan. 5-Hydroxyindoleacetic acid (5-HIAA) is the main metabolite, an oxidation product, of serotonin. In urine samples, 5-HIAA can be detected for the determination of serotonin levels in the body. There is a significant correlation between carcinoid heart disease and elevated urinary 5-HIAA excretion, which is indicative of serotonin production. However, non-carcinoid heart disease patients reported in literature have significantly lower serotonin release[1212 Zuetenhorst JM, Bonfrer JM, Korse CM, Bakker R, van Tinteren H, Taal BG. 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(7):1609-15.]. Zuetenhorst et al.[1313 Zuetenhorst JM, Korse CM, Bonfrer JM, Bakker RH, Taal BG. Role of natriuretic peptides in the diagnosis and treatment of patients with carcinoid heart disease. Br J Cancer. 2004;90(11):2073-9.] also found that median levels of N-terminal pro B-type natriuretic peptide and 5-HIAA were significantly higher in patients with carcinoid heart disease compared to those without (894 ng/L vs. 89 ng/L, P<0.001; 815 mmol/24 hours vs. 206 mmol/24 hours, P=0.007), but no significant differences were detected in atrial natriuretic peptide levels. Dilation of the right atrium and ventricle as well as thickening of the tricuspid valve and degree of regurgitation were statistically significant correlated with N-terminal pro B-type natriuretic peptide levels. Patients in the progression of carcinoid heart disease with a cardiac score increase >25% had a significant higher urinary peak 5-HIAA levels than those <25% (265 mg/24 hours vs. 189 mg/24 hours; P=0.004)[1010 Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-15.]. Patients with carcinoid syndrome therefore have raised concentrations of 24 hour urinary 5-HIAA. In a large series of patients with carcinoid syndrome and cardiac involvement the mean 24 hour urinary excretion of 5-HIAA was 10-fold higher than the reference value (reference value, 50 mmol/L/24 hours). Some studies suggest that a positive correlation exists between urinary concentrations of 5-HIAA, disease progression and worsening prognosis. This has been attributed to the fact that higher circulating concentrations of vasoactive substances produced by the tumor (especially 5-HT causing fibroblast proliferation) are likely to induce more cardiac damage. In patients with both right- and left-sided carcinoid heart disease, urinary values of 5-HIAA appear to be higher in patients without interatrial shunts compared to those with interatrial shunts[22 Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.].

DIAGNOSIS

The characterized triad symptoms of carcinoid syndrome are cutaneous vasomotor flushing, gastrointestinal hypermotility and cardiac involvement[1414 Castillo JG, Silvay G, Solís J. Current concepts in diagnosis and perioperative management of carcinoid heart disease. Semin Cardiothorac Vasc Anesth. 2013;17(3):212-23.]. Symptoms of flushing and diarrhea were almost threefold more common in the cardiac group. Circulating serotonin levels were more than twofold higher in the cardiac group. Urine levels of the serotonin metabolite 5-HIAA were almost fourfold higher in the heart disease patients compared with the noncardiac group (219±124 mg/24 hours vs. 55.3±141 mg/24 hours, P<0.001). Elevated serum serotonin (above the upper limit of normal range, i.e., >1500 µmol/mL) was 100% sensitive but only 46% specific for carcinoid heart disease[88 Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790-5.]. Carcinoid tumors secrete a variety of agents, including kallikrein, histamine, prostaglandins, adrenocorticotropic hormone, gastrin, calcitonin, and growth hormone; however, serotonin has received the most attention in hypotheses concerning the genesis of heart disease. Elevated urinary 5-HIAA is a less-than-ideal serotonin surrogate because it misses 10% of patients with true elevated circulating serotonin levels[88 Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790-5.]. These symptoms are caused by the release of vasoactive substances, mainly 5-HT as well as 5-hydroxytryptophan, histamine, bradykinin, tachykinins, and prostaglandins[1515 Connolly HM, Schaff HV, Abel MD, Rubin J, Askew JW, Li Z, et al. Early and late outcomes of surgical treatment in carcinoid heart disease. J Am Coll Cardiol. 2015;66(20):2189-96.]. Tricuspid valve disease (especially regurgitation) was most prevalent. The left-sided valve lesions tended to be less common and of milder severity than their right-sided counterparts. Cardiac catheterization and echocardiography had an overall concordance of 91% on the basis of valvular lesions[88 Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790-5.]. Some 92% had New York Heart Association class III or IV symptoms of congestive heart failure, and 8% had class II symptoms. Right-sided filling pressures were mildly to moderately elevated, whereas left-sided filling pressures were generally normal[88 Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790-5.]. In such patients, physical examination usually reveals a systolic murmur along the left sternal edge, produced by tricuspid regurgitation; concomitant murmurs of pulmonary stenosis or regurgitation may also be present[22 Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.]. In many patients, the structural valvular lesions will lead to symptomatic right-sided heart failure (edema, hepatomegaly, fatigue with exertion, and low cardiac output)[1010 Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-15.]. 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-HIAA[1616 Connolly HM. Carcinoid heart disease. Accessed Apr 5 2014. Available at: http://www.uptodate.com/contents/carcinoid-heart-disease
http://www.uptodate.com/contents/carcino...
]. Laboratory tests may reveal an elevated γ-glutamyl transpeptidase due to liver metastases[1717 Voigt PG, Braun J, Teng OY, Koolbergen DR, Holman E, Bax JJ, et al. Double bioprosthetic valve replacement in right-sided carcinoid heart disease. Ann Thorac Surg. 2005;79(6):2147-9.]. Patients with carcinoid heart disease typically present with symptoms of right heart failure (hepatomegaly, edema, ascites, fatigue and low cardiac output)[66 Warner RR, Castillo JG. Carcinoid heart disease: the challenge of the unknown known. J Am Coll Cardiol. 2015;66(20):2197-200.]. The diagnosis of carcinoid heart disease can be delayed as hepatic dysfunction and may conceal the signs and symptoms of right heart failure[1717 Voigt PG, Braun J, Teng OY, Koolbergen DR, Holman E, Bax JJ, et al. Double bioprosthetic valve replacement in right-sided carcinoid heart disease. Ann Thorac Surg. 2005;79(6):2147-9.]. Right ventricular enlargement and decreased right ventricular function can also be noted on echocardiography[1818 Heidecker B, Moore P, Bergsland EK, Merrick SH, Rao RK. Transcatheter pulmonic valve replacement in carcinoid heart disease. Eur Heart J Cardiovasc Imaging. 2015;16(9):1046.]. Echocardiographic examination and right heart catheterization are very useful in defining the disease. Catheterization confirms severe tricuspid incompetence with a v-wave in the right atrium and marked regurgitation evident on right ventricular angiography[33 Nielsen MS, Manners JM. Valve replacement in carcinoid syndrome. Anaesthetic management for tricuspid and pulmonary valve surgery. Anaesthesia. 1979;34(5):494-9.]. Characteristic echocardiographic findings include endocardial thickening and lack of compliance of the right ventricle, in addition to the typical thickening of both pulmonary and tricuspid valves, with significant pulmonary stenosis and tricuspid insufficiency[1717 Voigt PG, Braun J, Teng OY, Koolbergen DR, Holman E, Bax JJ, et al. Double bioprosthetic valve replacement in right-sided carcinoid heart disease. Ann Thorac Surg. 2005;79(6):2147-9.]. The echocardiographic visualization of carcinoid heart disease is listed in Table 2.

Table 2
Echocardiographic findings of carcinoid heart disease[11 Pellikka PA, Tajik AJ, Khandheria BK, Seward JB, Callahan JA, Pitot HC, et al. Carcinoid heart disease. Clinical and echocardiographic spectrum in 74 patients. Circulation. 1993;87(4):1188-96.,88 Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790-5.,99 Luis SA, Pellikka PA. Carcinoid heart disease: diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(1):149-58.].

TREATMENT

Commonly diuretic therapy and supportive therapy are essential for peripheral edema, hepatic congestion and ascites[99 Luis SA, Pellikka PA. Carcinoid heart disease: diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(1):149-58.]. Medical treatment include somatostatin analogs (such as, octreotide and lanreotide) for reducing urinary 5-HIAA, cytotoxic chemotherapy for extensive disease and dual endothelin receptor antagonist (such as, bosentan) for preventing valvular and mural fibrosis and improving heart function[99 Luis SA, Pellikka PA. Carcinoid heart disease: diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(1):149-58.]. The somatostatin analogues act by binding to somatostatin receptors, inhibiting secretion of tumor byproducts, and alleviating symptoms in the majority of patients[1010 Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-15.]. Relief of symptoms can be achieved surgically by debulking the tumor, and sometimes, in those with hepatic metastases, by hepatic artery ligation or embolization[22 Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.].

The surgical indications of carcinoid heart disease are, 1) symptomatic right ventricular failure; 2) severe valvular dysfunction; 3) systemic venous pressure elevation[66 Warner RR, Castillo JG. Carcinoid heart disease: the challenge of the unknown known. J Am Coll Cardiol. 2015;66(20):2197-200.]; and 4) as a prelude to planned surgical hepatic tumor resection[99 Luis SA, Pellikka PA. Carcinoid heart disease: diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(1):149-58.]. Whereas, the contraindications are, 1) end-stage metastatic disease, and 2) patients with poorly controlled carcinoid symptoms despite octreotide therapy, or hepatic dearterialization[1515 Connolly HM, Schaff HV, Abel MD, Rubin J, Askew JW, Li Z, et al. Early and late outcomes of surgical treatment in carcinoid heart disease. J Am Coll Cardiol. 2015;66(20):2189-96.]. When the pulmonary insufficiency is mild and very well tolerated and when the left heart filling pressures are normal, pulmonary valve replacement is unnecessary. The optimal surgical approach to right-sided valvular lesions remains a subject of debate. Tricuspid valve replacement has been accepted by most centers, however, the management of pulmonary valvular disorder remains debatable. If pulmonary valve regurgitation is left untreated, there would be right ventricular overload in the long run; whereas in patients with pulmonary valve replacement, the postoperative recovery appear to be more favorable[66 Warner RR, Castillo JG. Carcinoid heart disease: the challenge of the unknown known. J Am Coll Cardiol. 2015;66(20):2197-200.]. By comparison, the limitations for homograft use for pulmonary valve replacement are homograft constriction, homograft calcification, homograft plaque deposition; while the advantages of bioprosthesis are remarkable in better short-term outcomes, longer valve durability, free of anticoagulate uptake and uncommon carcinoid involvement[1515 Connolly HM, Schaff HV, Abel MD, Rubin J, Askew JW, Li Z, et al. Early and late outcomes of surgical treatment in carcinoid heart disease. J Am Coll Cardiol. 2015;66(20):2189-96.]. When the pulmonary and tricuspid valves are both involved, open pulmonary valvulotomy is a reasonable option. If more cardiac valves are affected, multiple valve replacement should be considered. In most cases, involvement of the valve leaflets is too extensive to allow surgery for commissurotomy or valvotomy, and pulmonary valvectomy surgery is required. Narine et al.[1919 Narine KK, Dohmen PM, Daenen W. Tricuspid and pulmonary valve involvement in carcinoid disease. Tex Heart Inst J. 2000;27(4):405-7.] recommend the use of mechanical prostheses in carcinoid heart disease with a concern of the fibrous degeneration of the bioprosthetic valves. Some reports of surgical treatment of tricuspid insufficiency due to carcinoid disease describe use of mechanical prostheses[2020 Aroesty JM, DeWeese JA, Hoffman MJ, Yu PN. Carcinoid heart disease. Successful repair of the valvular lesions under cardiopulmonary bypass. Circulation. 1966;34(1):105-10.,2121 Carpena C, Kay JH, Mendez AM, Redington JV, Zubiate P, Zucker R. Carcinoid heart disease. Surgery for tricuspid and pulmonary valve lesions. Am J Cardiol. 1973;32(2):229-33.], and pulmonary valve replacement has been advocated[2222 McGuire MR, Pugh DM, Dunn MI. Carcinoid heart disease. Restrictive cardiomyopathy as a late complication. J Kans Med Soc. 1978;79(12):661-2, 665.]. Due to the increased risk for repeat surgical valve replacement, percutaneous stent implantation into the pulmonary artery, followed by the implantation of a balloon expandable transcatheter heart valve is warranted. A simplified approach including pulmonary valvectomy and bioprosthetic tricuspid valve replacement surgery are the procedures of choice. While surgical valve replacement is currently the gold standard treatment for symptomatic carcinoid valve disease, transcatheter pulmonary valve replacement should be considered as an alternative approach in high-risk candidates[1818 Heidecker B, Moore P, Bergsland EK, Merrick SH, Rao RK. Transcatheter pulmonic valve replacement in carcinoid heart disease. Eur Heart J Cardiovasc Imaging. 2015;16(9):1046.]. Percutaneous valve implantation in the pulmonary and in the inferior vena cava positions may offer a novel, minimally invasive option avoiding open-heart surgery in the high-risk patients[2323 Laule M, Pschowski R, Pape UF, Pavel M, Stangl V, Baumann G, et al. Staged catheter-based valve treatment of severe carcinoid heart disease. Neuroendocrinology. 2015;103(3-4):259-62.]. The Medtronic Melody® valve and the Edwards SAPIEN® valve are in use today for percutaneous pulmonary valve implantation (PPVI) in children and in adults with congenital heart disease[2424 Lurz P, Bonhoeffer P, Taylor AM. Percutaneous pulmonary valve implantation: an update. Expert Rev Cardiovasc Ther. 2009;7(7):823-33.,2525 Jalal Z, Thambo JB, Boudjemline Y. The future of transcatheter pulmonary valvulation. Arch Cardiovasc Dis. 2014;107(11):635-42.]. Surgical complications can include bleeding, carcinoid crises, right ventricular dysfunction, cardiac conduction disorders, renal failure and sepsis[99 Luis SA, Pellikka PA. Carcinoid heart disease: diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(1):149-58.].

DEBATES

Contrary to conventional guidelines of heart valve operation and choices of heart valve prosthesis[2626 Feguri GR, Macruz H, Bulhões D, Neves A, Castro RM, Fonseca L, et al. Aortic valve replacement with different types of prosthesis: are there differences in the outcomes during hospital phase? Rev Bras Cir Cardiovasc. 2008;23(4):534-41.,2727 Tenório EM, Moraes Neto F, Chauvaud S, Moraes CR. Experience with the posterior leaflet extension technique for correction of rheumatic mitral insufficiency in children. Rev Bras Cir Cardiovasc. 2009;24(4):567-9.], most surgeons prefer bioprostheses in the tricuspid position because of the lower propensity to thrombosis in carcinoid heart disease. However, questions have been raised about the long-term durability of porcine valves exposed to the metabolic products of carcinoid tumors. Progression onto a pulmonary valve homograft and onto a tricuspid bioprosthetic valve has been reported[2828 Ohri SK, Schofield JB, Hodgson H, Oakley CM, Keogh BE. Carcinoid heart disease: early failure of an allograft valve replacement. Ann Thorac Surg. 1994;58(4):1161-3.,2929 Ridker PM, Chertow GM, Karlson EW, Neish AS, Schoen FJ. Bioprosthetic tricuspid valve stenosis associated with extensive plaque deposition in carcinoid heart disease. Am Heart J. 1991;121(6 Pt 1):1835-8.]. While most surgeons would prefer to use a bioprosthetic valve for replacement of the tricuspid valve, many reports of the surgical treatment of carcinoid heart disease describe the use of mechanical valves, because of the concern about secondary development of carcinoid lesions in bioprostheses. An antibiotic sterilized aortic homograft can be a candidate prosthesis for pulmonary valve replacement[33 Nielsen MS, Manners JM. Valve replacement in carcinoid syndrome. Anaesthetic management for tricuspid and pulmonary valve surgery. Anaesthesia. 1979;34(5):494-9.]. In addition, pulmonary valvotomy or valvectomy, as opposed to pulmonary valve replacement, remains controversial[33 Nielsen MS, Manners JM. Valve replacement in carcinoid syndrome. Anaesthetic management for tricuspid and pulmonary valve surgery. Anaesthesia. 1979;34(5):494-9.]. Patients who have no contraindication for valve surgery and whose cardiac symptoms develop at an early stage of the disease should undergo operation. The comparisons of the valve prosthesis of choice are shown in Table 3.

Table 3
Advantages and disadvantages of valvular prostheses of choices for carcinoid heart disease patients[66 Warner RR, Castillo JG. Carcinoid heart disease: the challenge of the unknown known. J Am Coll Cardiol. 2015;66(20):2197-200.,1515 Connolly HM, Schaff HV, Abel MD, Rubin J, Askew JW, Li Z, et al. Early and late outcomes of surgical treatment in carcinoid heart disease. J Am Coll Cardiol. 2015;66(20):2189-96.,2828 Ohri SK, Schofield JB, Hodgson H, Oakley CM, Keogh BE. Carcinoid heart disease: early failure of an allograft valve replacement. Ann Thorac Surg. 1994;58(4):1161-3.].

OUTCOMES

Severity of tricuspid valve regurgitation was an important predictor of outcome[1010 Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-15.].

In these patients with advanced metastatic carcinoid disease, prognosis was poor, with a median survival of only 2.6 years after diagnosis of cardiac involvement. The severity and hemodynamic consequence of carcinoid heart disease contributes to the high mortality[1010 Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-15.]. Analysis of 17 series with carcinoid heart disease patients who had undergone surgical biological tricuspid valve replacement revealed a 30-day mortality of 20%. It was suggested that biological valves have an acceptable lifespan in carcinoid heart disease[3030 Schaefer A, Sill B, Schoenebeck J, Schneeberger Y, Reichenspurner H, Gulbins H. Failing stentless bioprostheses in patients with carcinoid heart valve disease. J Cardiothorac Surg. 2015;10:41. doi: 10.1186/s13019-015-0238-5.
https://doi.org/10.1186/s13019-015-0238-...
,3131 Mabvuure N, Cumberworth A, Hindocha S. In patients with carcinoid syndrome undergoing valve replacement: will a biological valve have acceptable durability? Interact Cardiovasc Thorac Surg. 2012;15(3):467-71.]. Long-standing severe pulmonary valve regurgitation, as seen after pulmonary valvectomy, may have a detrimental effect on right ventricular remodeling[1515 Connolly HM, Schaff HV, Abel MD, Rubin J, Askew JW, Li Z, et al. Early and late outcomes of surgical treatment in carcinoid heart disease. J Am Coll Cardiol. 2015;66(20):2189-96.]. Schoen et al.[3232 Schoen FJ, Hausner RJ, Howell JF, Beazley HL, Titus JL. Porcine heterograft valve replacement in carcinoid heart disease. J Thorac Cardiovasc Surg. 1981;81(1):100-5.] reported a case of carcinoid heart disease, in which they observed carcinoid plaque that involved the tricuspid bioprosthesis at postmortem examination. The 3-year mortality for patients with carcinoid heart disease showed a 31% survival rate, significantly lower than that of patients without cardiac involvement[22 Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.]. Conradi et al.[3333 Conradi L, Schaefer A, Mueller GC, Seiffert M, Gulbins H, Blankenberg S, et al. Carcinoid heart valve disease: transcatheter pulmonary valvein-valve implantation in failing biological xenografts. J Heart Valve Dis. 2015;24(1):110-4.] reported transcatheter pulmonary valve replacement resulted in a favorable acute outcome in both of their patients, with adequate valve function and good heart function. The patients tolerated the procedure well without any complications. The perioperative mortality rate was reduced from >20% to currently <10%[1010 Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-15.]. The overall operative mortality was 10%[1515 Connolly HM, Schaff HV, Abel MD, Rubin J, Askew JW, Li Z, et al. Early and late outcomes of surgical treatment in carcinoid heart disease. J Am Coll Cardiol. 2015;66(20):2189-96.]. The survival between the cardiac and noncardiac groups was not statistically different (survival from onset of symptoms: 13.6 years vs. 9.7 years; survival from time of diagnosis: 4.8 years vs. 7 years)[88 Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790-5.].

CONCLUSION

Carcinoid heart disease is a rare cause of right-side heart valve disease. Echocardiography remains a reliable method for the definite diagnosis. Valve replacement is currently the gold standard treatment for symptomatic carcinoid valve disease. However, debates remain in terms of the choice of heart valve prosthesis. The surgical management of the pulmonary valve relies on the pathological extent and patient's condition. Transcatheter pulmonary valve replacement should be considered as an alternative approach in high-risk candidates.

  • This study was carried out at The First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, Fujian Province, People's Republic of China.
  • No financial support.

REFERENCES

  • 1
    Pellikka PA, Tajik AJ, Khandheria BK, Seward JB, Callahan JA, Pitot HC, et al. Carcinoid heart disease. Clinical and echocardiographic spectrum in 74 patients. Circulation. 1993;87(4):1188-96.
  • 2
    Fox DJ, Khattar RS. Carcinoid heart disease: presentation, diagnosis, and management. Heart. 2004;90(10):1224-8.
  • 3
    Nielsen MS, Manners JM. Valve replacement in carcinoid syndrome. Anaesthetic management for tricuspid and pulmonary valve surgery. Anaesthesia. 1979;34(5):494-9.
  • 4
    Materazzo C, Meazza R, Stefanelli M, Biasi S. Left valvular involvement in carcinoid: description of a case. G Ital Cardiol. 1994;24(4):429-33.
  • 5
    Le Métayer P, Constans J, Bernard N, Roudaut R, Pellegrin JL, Lacoste D, et al. Carcinoid heart disease: two cases of left heart involvement diagnosed by transthoracic and transoesophageal echocardiography. Eur Heart J. 1993;14(12):1721-3.
  • 6
    Warner RR, Castillo JG. Carcinoid heart disease: the challenge of the unknown known. J Am Coll Cardiol. 2015;66(20):2197-200.
  • 7
    Castillo JG, Adams DH, Fischer GW. Absence of the tricuspid valve due to severe carcinoid heart disease. Rev Esp Cardiol. 2010;63(1):96.
  • 8
    Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790-5.
  • 9
    Luis SA, Pellikka PA. Carcinoid heart disease: diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2016;30(1):149-58.
  • 10
    Møller JE, Connolly HM, Rubin J, Seward JB, Modesto K, Pellikka PA. Factors associated with progression of carcinoid heart disease. N Engl J Med. 2003;348(11):1005-15.
  • 11
    Basson MD, Ahlman H, Wangberg B, Modlin IM. Biology and management of the midgut carcinoid. Am J Surg. 1993;165(2):288-97.
  • 12
    Zuetenhorst JM, Bonfrer JM, Korse CM, Bakker R, van Tinteren H, Taal BG. 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(7):1609-15.
  • 13
    Zuetenhorst JM, Korse CM, Bonfrer JM, Bakker RH, Taal BG. Role of natriuretic peptides in the diagnosis and treatment of patients with carcinoid heart disease. Br J Cancer. 2004;90(11):2073-9.
  • 14
    Castillo JG, Silvay G, Solís J. Current concepts in diagnosis and perioperative management of carcinoid heart disease. Semin Cardiothorac Vasc Anesth. 2013;17(3):212-23.
  • 15
    Connolly HM, Schaff HV, Abel MD, Rubin J, Askew JW, Li Z, et al. Early and late outcomes of surgical treatment in carcinoid heart disease. J Am Coll Cardiol. 2015;66(20):2189-96.
  • 16
    Connolly HM. Carcinoid heart disease. Accessed Apr 5 2014. Available at: http://www.uptodate.com/contents/carcinoid-heart-disease
    » http://www.uptodate.com/contents/carcinoid-heart-disease
  • 17
    Voigt PG, Braun J, Teng OY, Koolbergen DR, Holman E, Bax JJ, et al. Double bioprosthetic valve replacement in right-sided carcinoid heart disease. Ann Thorac Surg. 2005;79(6):2147-9.
  • 18
    Heidecker B, Moore P, Bergsland EK, Merrick SH, Rao RK. Transcatheter pulmonic valve replacement in carcinoid heart disease. Eur Heart J Cardiovasc Imaging. 2015;16(9):1046.
  • 19
    Narine KK, Dohmen PM, Daenen W. Tricuspid and pulmonary valve involvement in carcinoid disease. Tex Heart Inst J. 2000;27(4):405-7.
  • 20
    Aroesty JM, DeWeese JA, Hoffman MJ, Yu PN. Carcinoid heart disease. Successful repair of the valvular lesions under cardiopulmonary bypass. Circulation. 1966;34(1):105-10.
  • 21
    Carpena C, Kay JH, Mendez AM, Redington JV, Zubiate P, Zucker R. Carcinoid heart disease. Surgery for tricuspid and pulmonary valve lesions. Am J Cardiol. 1973;32(2):229-33.
  • 22
    McGuire MR, Pugh DM, Dunn MI. Carcinoid heart disease. Restrictive cardiomyopathy as a late complication. J Kans Med Soc. 1978;79(12):661-2, 665.
  • 23
    Laule M, Pschowski R, Pape UF, Pavel M, Stangl V, Baumann G, et al. Staged catheter-based valve treatment of severe carcinoid heart disease. Neuroendocrinology. 2015;103(3-4):259-62.
  • 24
    Lurz P, Bonhoeffer P, Taylor AM. Percutaneous pulmonary valve implantation: an update. Expert Rev Cardiovasc Ther. 2009;7(7):823-33.
  • 25
    Jalal Z, Thambo JB, Boudjemline Y. The future of transcatheter pulmonary valvulation. Arch Cardiovasc Dis. 2014;107(11):635-42.
  • 26
    Feguri GR, Macruz H, Bulhões D, Neves A, Castro RM, Fonseca L, et al. Aortic valve replacement with different types of prosthesis: are there differences in the outcomes during hospital phase? Rev Bras Cir Cardiovasc. 2008;23(4):534-41.
  • 27
    Tenório EM, Moraes Neto F, Chauvaud S, Moraes CR. Experience with the posterior leaflet extension technique for correction of rheumatic mitral insufficiency in children. Rev Bras Cir Cardiovasc. 2009;24(4):567-9.
  • 28
    Ohri SK, Schofield JB, Hodgson H, Oakley CM, Keogh BE. Carcinoid heart disease: early failure of an allograft valve replacement. Ann Thorac Surg. 1994;58(4):1161-3.
  • 29
    Ridker PM, Chertow GM, Karlson EW, Neish AS, Schoen FJ. Bioprosthetic tricuspid valve stenosis associated with extensive plaque deposition in carcinoid heart disease. Am Heart J. 1991;121(6 Pt 1):1835-8.
  • 30
    Schaefer A, Sill B, Schoenebeck J, Schneeberger Y, Reichenspurner H, Gulbins H. Failing stentless bioprostheses in patients with carcinoid heart valve disease. J Cardiothorac Surg. 2015;10:41. doi: 10.1186/s13019-015-0238-5.
    » https://doi.org/10.1186/s13019-015-0238-5.
  • 31
    Mabvuure N, Cumberworth A, Hindocha S. In patients with carcinoid syndrome undergoing valve replacement: will a biological valve have acceptable durability? Interact Cardiovasc Thorac Surg. 2012;15(3):467-71.
  • 32
    Schoen FJ, Hausner RJ, Howell JF, Beazley HL, Titus JL. Porcine heterograft valve replacement in carcinoid heart disease. J Thorac Cardiovasc Surg. 1981;81(1):100-5.
  • 33
    Conradi L, Schaefer A, Mueller GC, Seiffert M, Gulbins H, Blankenberg S, et al. Carcinoid heart valve disease: transcatheter pulmonary valvein-valve implantation in failing biological xenografts. J Heart Valve Dis. 2015;24(1):110-4.

Publication Dates

  • Publication in this collection
    Sep-Oct 2016

History

  • Received
    06 Apr 2016
  • Accepted
    16 May 2016
Sociedade Brasileira de Cirurgia Cardiovascular Rua Afonso Celso, 1178 Vila Mariana, CEP: 04119-061 - São Paulo/SP Brazil, Tel +55 (11) 3849-0341, Tel +55 (11) 5096-0079 - São Paulo - SP - Brazil
E-mail: bjcvs@sbccv.org.br