Carcinoid Hjärtsjukdom

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1 Carcinoid Hjärtsjukdom

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3 CARCINOID TUMORS 20/milj/år FORE-GUT 10% bronchial pancreatic gastric duodenal MID-GUT 70% 40% appendiceal jejunal 30% (6/m/år) ileal prox colonic HIND-GUT 20% distal colonic rectal

4 CARCINOID SYMTOM FLUSH DIARRE URIN 5-HIAA FÖRHÖJDA KLASSISKT CARCINOID SYNDROM BRONCH-KONSTRIKTION CYANOS ÖDEM TARM- OBSTRUKTION HÖGERSIDIG HJÄRTSJUKDOM CARCINOID HJÄRTSJUKDOM

5 Causes of deaths in 39 deceased patients (of 103 patients) with carcinoid tumors Causes of death No % Tumor progression 18 45,2 Cardiac insufficiency 14 36,0 Myocardial infarction 1 2,5 Intestinal necrosis 1 2,5 Cushing s syndrome 1 2,5 Pulmonary emboli 1 2,5 Sepsis 1 2,5 Unknown 2 5,3 Total number deceased patients 39 (Norheim et al 1987)

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8 Mainly stroma. acid mucopolysaccarides, collagen, reticulum fibers. no elastin Low number of cells. myofibroblasts. low proliferating activity

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12 CARDIAC INVESTIGATION Physical examination ECG Chest X-ray Cardiac ultrasound - general appearance - cardiac findings - 2D imaging (M-mode) - Doppler Hemodynamic investigation Coronary angiography

13 CARDIAC ULTRASOUND Size of the heart chambers Movement and characteristics of the chamber walls Morfology and movement of the cardiac valves Blood flow through the valves by Doppler

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30 Carcinoid Heart Disease Normal

31 Frequency of abnormalities of the right heart on transthoracic ultrasound investigation of 68 patients with malignant midgut carcinoid tumors no % Tricuspid valve abnormalities 38/63 60 thickness increased 30/62 48 motion decreased 18/61 30 regurgitation by Doppler 19/23 83 Right atrial enlargement 32/60 53 Right ventricular enlargement 20/67 30 massive enlargement 9/67 13 Right ventricular wall thickness enlarged 12/63 19 Paradoxical septal motion 18/67 26 Any right sided pathologic finding 45/68 66 Normal 23/68 34 (Lundin et al 1988)

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35 Subgroups of patients with respect to cardiac ultrasound findings Group I Group II Group III Normal findings Signs of right heart disease Severe right heart disease tricuspid valve abnormalities right atrial and ventricular enlargement paradoxical interventricular septal contractions

36 Atrial superficial wall layer thickness in 31 carcinoid patients Transesophageal echocardiography Carcinoid patients Controls Group I (n=31) II (n=16) III (=8) (n=12) Right atrium 2,00 ±0,29*** 2,00 ±0,26*** 3,0 ±0,53 1,36 ±0,22*** Left atrium 1,36 ±0,24 1,16 ±0,24 1,19 ± 0,26 1,38 ±0,23 *** indicate significant (p<0,001) differences when group III was compared to groups I, II and controls. Mean dimensions ±SD are given in mm.

37 CLINICAL DIAGNOSIS Physical examination ECG Chest X-ray Cardiac ultrasound - 2D imaging - Doppler Hemodynamic investigation Coronary angiography

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39 Aortic pressure Right atrial pressure V A

40 Preoperative hemodynamic data in 12 patients subjected to reconstructive valvular surgery due to carcinoid heart disease mean range Pressures (mm Hg) Right atrium mean 13, v-vawe 22, Right ventricle systolic 32, end-diastolic 12, Pulmonary artery systolic 21, mean 13, Left ventricle end-diastolic 7, Peak systolic pulmonary valve gradient 12, Cardiac output (l/min) 3,55 2,8-4,9 Cardiac index (l/min/sqm) 2,08 1,6-3,0

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43 Preoperative hemodynamic data in 12 patients subjected to reconstructive valvular surgery due to carcinoid heart disease mean range Pressures (mm Hg) Right atrium mean 13, v-vawe 22, Right ventricle systolic 32, end-diastolic 12, Pulmonary artery systolic 21, mean 13, Left ventricle end-diastolic 7, Peak systolic pulmonary valve gradient 12, Cardiac output (l/min) 3,55 2,8-4,9 Cardiac index (l/min/sqm) 2,08 1,6-3,0

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45 Valvular surgery

46 INDIKATION FÖR KLAFFKIRURGI Symtom på RV-svikt Trötthet Dyspné Ödem Markerad Carcinoid hjärtsjukdom på EKO Tumörsjukdomen under kontroll Kemiska tumörmarkörer Radiologoiskt chromogranin 5-HIAA Bör svara på Sandostatin

47 Antal operationer / år Antal

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49 VALVULAR SURGERY (40 PATIENTS) TRICUSPID VALVE Bioprosthetic valve replacement 40 PULMONARY VALVE Bioprosthetic valve replacement 26 Homograft 2 Commisurotomy 3 Valvulotomy 2 No intervention 7

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56 < 1 v 1-4 v 1-3 m 3-6 m 6-12 m 1-2 år 2-3 år 3-6 år 6-10 år >10 år Överlevnad postoperativt Lever Avlidna

57 Carcinoid tumor HYPOTHESIS Vasoactive substances Growth factors Endothelial damage Connective tissue proliferation Matrix production Carcinoid Heart Disease

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59 In conclusion Ultrasound detectable cardiac abnormalities are common among patients with malignant mid-gut carcinoid tumors. The microscopical, macroscopical and echocardiographical abnormalities are characteristic and pathognomonic. Reconstructive valvular surgery is of obvious benificial value in patients with cardiac decompensation due to severe carcinoid heart disease. The extent of the cardiac disease seems to be related to circulating tumour-released substances. TGF-b seems to be involved in the local fibrous tissue production.

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