P.O. Box 2925 Riyadh – 11461KSATel: +966 1 2520088 ext 40151Fax: +966 1 2520718Email: sha@sha.org.saURL: www.sha.org.sa

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Received 26 July 2013; revised 7 August 2013; accepted 19 August 2013.Available online 28 August 2013

⇑ Corresponding author at: Department of Cardiology, Ghaem Hospi-tal, School of Medicine, Mashhad University of Medical Sciences,Mashhad, Iran. Tel.: +98 5118012739.E-mail addresses: Bigdelul@mums.ac.ir, bigdelul@gmail.com (L. Bigde-

lu).

Carcinoid heart disease and the utilityof 3D trans-thoracic and trans-esophagealechocardiography: Two clinical cases

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http://dx.doi.org/10.1016/j.jsha.2013.08.004

Afsoon Fazlinezhad a,c, Zahra Moravvej c,e, Ali Azari b,c,d, Leila Bigdelu a,c,d,⇑

a Department of Cardiology, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhadb Department of Cardiac Surgery, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhadc Member of Cardiovascular Research Center, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences,Mashhadd Member of Preventive Cardiovascular Care Research Center, Imam Reza Hospital, School of Medicine, Mashhad Universityof Medical Sciences, Mashhade Students Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad

Carcinoid tumors are rare neuroendocrine malignancies. We present two cases of metastatic carcinoid tumors,complicated by carcinoid syndrome and by cardiac valve involvement. Carcinoid syndrome is characterized bysecretory diarrhea, episodic flushing, and bronchospasm. Cardiac involvement occurs in up to 50% of patients withmetastatic carcinoid tumors which commonly causes abnormalities of the right sided valves. Echocardiography is thebest available and non invasive technique for diagnosis. Characteristic features of carcinoid heart disease arethickened, shortened, retracted, and fixed or partially fixed valve leaflets. Three-dimensional (3D) echocardiographyprovided an en face view of pulmonary and tricuspid valve, not obtainable by two-dimensional echocardiography, andimproved delineation of the relationship between these structures and cardiac chambers.

� 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

Keywords: Carcinoid heart disease, Echocardiography, Pulmonary, Three-dimensional, Tricuspid, Valve

Introduction

Carcinoid tumors first described by Lubarsh in1888 have been reported in a number of

organs, most commonly including the gastrointes-tinal (GI) tract, respiratory tract and ovaries [1,2].

This tumor is often associated with a syndromecharacterized by secretory diarrhea, episodic flush-ing, and bronchospasm [3,4]. Carcinoid syndromeis thought to occur after liver metastases which al-lows high levels of 5-hydroxytriptamine (5-HT) insystemic circulation [3,5]. Cardiac involvement

Figure 1. Two-dimensional trans-thoracic echocardiogram: Four-chamber view showing RV and RA enlargement. The color Dopplerdemonstrating severe free tricuspid regurgitation.

Figure 2. Real-Time three-dimensional capture: Anterior enface view of mitral and tricuspid valves showing the thickened and retractedtricuspid leaflet without coaptation.

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occurs in up to 50% of patients and predominantlyaffects the endocardium and right cardiac valves[3,5,6]. Left side cardiac involvement is lesscommon (7%) as the lung parenchyma inactivatestumor substrates [2,4]. Left side valvular involve-ment is due to the presence of patent foramen ovale(PFO), or less commonly as a consequence of highcirculatory levels of serotonin, or pulmonarymetastasis [5]. We present two cases of metastaticcarcinoid tumors, complicated by carcinoid syn-drome and demonstrate the utility of 3D TTE andTEE in assessment of cardiac valve involvement.

Case 1A 43-year-old man presented with four-year his-

tory of unprovoked cutaneous flashing. He alsocomplained of an intermittent watery diarrhea,

unrelated to meals, and an exacerbatingexcertional dyspnea over the last two years.Peripheral edema accompanied these symptomsduring this month before presentation. He was re-ferred to Ghaem hospital with right-sided heartfailure symptoms. On clinical examination, hewas wasted, had an elevated jugular venous pres-sure with CV wave, pan-systolic murmur (3/6)over the left lower sternal border, as well asmid-systolic murmur (2/6) and early to mid-dia-stolic murmur over the left upper sternal border.On abdominal examination, the liver span wasenlarged.

Twenty-four hour urinary 5-hydroxyindolaceticacid (5-HIAA) was elevated at 780 lmol/24 h.Upper gastrointestinal endoscopy was normal.Colonoscopy showed a mass in the cecum with

Figure 3. Two-dimensional trans-thoracic echocardiogram: Short axis view at the level of aortic valve showing thickened and narrowed mainpulmonary artery.

Figure 4. Two-dimensional trans-thoracic echocardiogram: (A) Four-chamber view revealing RA and RV enlargement and thickened TV leaflets.(B) Off-axis view showing free tricuspid regurgitation.

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histological compatibility for well differentiatedneuroendocrine carcinoid tumor. Hepatomegalywith multiple metastases was confirmed usingabdominal computed tomography (CT) scan. Spir-al lung CT-scan was normal.

Two- and three-dimensional (2D, 3D) transtho-racic echocardiography (TTE) and trans-esopha-geal echocardiography (TEE) was performedusing Philips iE33 equipped with a matrix arrayTTE and TEE transducer (Philips medical system,Andover, MA). 2D and 3D TTE revealed severeright ventricular enlargement and dysfunction,and septal flattening in diastole consistent withvolume overload. Tricuspid valve (TV) leafletswere retracted, thickened, and fixed in mid

position without systolic coaptation causing se-vere free tricuspid regurgitation (TR) and mildlyincreased trans-valvular gradient up to 5mmhg(Figs. 1 and 2). Sub-valvular apparatus was alsovisualized. Chordae tendinae were thickenedand partially fused. Pulmonary valve leaflets werealso severely retracted, thickened and shortenedcausing severe pulmonary regurgitation (PR).The main pulmonary trunk was narrowed(Fig. 3). However, mitral and aortic valve func-tions, left ventricle (LV) and atrium (LA) dimen-sions were within normal limits. After a suitablecontrol of the systemic disease, the patientunderwent replacement of the pulmonary and tri-cuspid valves with biologic valves. Histological

Figure 5. Real-time three-dimensional capture: Ventricular view of tricuspid valve revealed severely retracted, fixed and non-coaptated leaflets.

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examination of the excised valves confirmed thediagnosis of carcinoid heart disease. Patient sur-vived surgery and was discharged in goodcondition.

Case 2

A 48-year-old man with carcinoid syndromepresented with worsening dyspnea on minimalexertion (class III to IV, New York Heart Associa-tion). He had presented peripheral edema a fewweeks ago. His symptoms of carcinoid syndromewere episodic facial flushing and diarrhea beingwell controlled with somatostatin analogue. Clini-cal examination showed an elevated jugular ve-nous pressure. Heart auscultation demonstratedpan-systolic murmur over the left lower sternalborder which increased with inspiration and dia-stolic murmur over the left second intercostalspace. In abdominal examination, his liver wasmassively enlarged. He had mild pedal edema.The primary source of carcinoid tumor was inthe small intestine which had previously under-gone surgery due to obstructive symptoms. Multi-ple hyponodular masses were reported inabdominal CT-scan being consistent with livermetastases. Urinary 5-HIAA level was 975 lmol/24 h. Liver function tests were normal.

The patient underwent 2D and 3D TTE and TEEusing Philips iE33 equipped with a matrix arrayTTE and TEE transducer (Philips medical system,Andover, MA). 2D TTE and Doppler echocardiog-raphy revealed RV and RA enlargement with mildRV dysfunction and severe TR (Fig. 4). TV wasmarkedly thickened, fixed and shortenedassociated with thickening of chordae tendinea(Fig. 5). The pulmonary valve was thickened andpoorly mobile, resulting in severe pulmonary

regurgitation. The pulmonary valve annulus wasalso restricted. Real time 3D TEE provided moreanatomical information on all three cusps of thepulmonary valve, as well as allowing assessmentof the main pulmonary artery and annulus of pul-monary valve and visualization of the right ventri-cle tract outflow. Valve replacement surgery wasrecommended, but due to patient’s refusal for sur-gery, medical therapy for right heart failure symp-toms was continued.

Discussion

Carcinoid heart disease is a rare cause of valvu-lar heart disease [6,7]. It often affects right sidevalves resulting in unique morphology and echo-cardiographic characteristics [3,6]. Patients withcarcinoid heart disease typically present withsymptoms of right-sided heart failure (hepato-megaly, edema, ascites, fatigue, and low cardiacoutput), and when symptoms are advanced(NYHA class 3 or 4), outlook is poor [3]. Theinvolvement of left side heart valves and foramenovale is also seen in carcinoid heart disease. 2Dechocardiography is usually the first available toolfor diagnosis; however, 3D TEE and TTE have at-tained incremental value for better visualizationof PV and TV.

Abnormality of TV includes straightened,immobile and thickened valve leaflets and sub-valvular apparatus. In most severe cases, leafletsbecome fixed and non-coaptated causing regurgi-tation or stenosis of the tricuspid with a character-istic ‘‘dagger-shaped’’ profile. Chordae tendinaeand papillary muscles may be thickened, fusedand shortened [2,5,8]. Moreover, the right ventri-cle becomes dilated and the right atrium is also

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enlarged. The present report showed that the 3DTEE and TTE visualized all the leaflets of TV fromeither atrial or ventricular side. The technique im-proved the evaluation of coaptation zone anddelineation of sub-valvular structures, and en-abled us to compare the leaflets simultaneously.

Abnormality of pulmonary valve is less commonthan TV involvement. The changes are similar toTV deformity including thickened and straight-ened valve with retraction and reduction in excur-sion of valve leaflets in severe cases [9]. In thesecases, the 3D TEE and TTE produced an en-faceview of the all three pulmonary leaflets simulta-neously [10].

Conclusion

The present medical cases, where the tricuspidand pulmonary valves are involved, are consid-ered as a minority of carcinoid valve disease cases.The combination of echocardiographic imagingand 5-HIAA level provided useful insights, lead-ing to the accurate and undoubted diagnosis,which was subsequently verified by the histologi-cal study. Echocardiography is vitally important inthe evaluation of patients with carcinoid syn-drome and suspected carcinoid heart involve-ment. Advanced techniques such as 3D TEE andTTE proved to be helpful in assessing the cardiacinvolvement particularly the pulmonary valve

which cannot be entirely evaluated by 2Dechocardiogram.

References

[1] Galanti G, Stefani L, Luca A, Pellicano G, Bechi P. A case ofcarcinoid heart metastases. J Echocardiogr 2013. http://dx.doi.org/10.1007/s12574-013-0186-9.

[2] Weinreich C, Ross IR, Kotze T, Levitt N, Steyn R.Carcinoid heart disease: two clinical cases and a review.JEMDSA 2011;16(1):58–63.

[3] Bhattacharyya S, Davar J, Dreyfus G, Caplin ME.Carcinoid heart disease. Circulation 2007;116(24):2860–5.

[4] Bhattacharyya S, Toumpanakis C, Burke M, Taylor AM,Caplin ME, Davar J. Features of carcinoid heart diseaseidentified by 2-and 3-dimensional echocardiography andcardiac mri. Circ Cardiovasc Imaging 2010;3(1):103–11.

[5] Fox DJ, Khattar RS. Carcinoid heart disease: presentation,diagnosis, and management. Heart 2004;90(10):1224–8.

[6] Pellikka PA, Tajik AJ, Khandheria BK, Seward JB, CallahanJA, Pitot HC, et al.. Carcinoid heart disease. Clinical andechocardiographic spectrum in 74 patients. Circulation1993;87(4):1188–96.

[7] Aggeli C, Felekos I, Kazazaki C, Giannopoulos D, KartalisA, Pitsavos C, et al.. Echocardiographic imaging oftricuspid and pulmonary valve abnormalities in primaryovarian carcinoid tumor. Cardiovasc Ultrasound2010;8(1):37.

[8] Santos AR, Stuart B, Cotrim C, Almeida AR, Fazendas P,Lopes L, et al.. Carcinoid heart – case report. Rev PortCardiol 2012;31(10):661–5.

[9] Connolly H, Pellikka P. Carcinoid heart disease. CurrCardiol Rep 2006;8(2):96–101.

[10] Bhattacharyya S, Burke M, Caplin ME, Davar J. Utility of3d transoesophageal echocardiography for the assessmentof tricuspid and pulmonary valves in carcinoid heartdisease. Eur J Echocardiogr 2011;12(1):E4.