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Background: Carcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome. Once the carcinoid syndrome has developed, a carcinoid cardiomyopathy can occur. Carcinoid heart disease (CaHD) remains a serious and rare complication associated with a significant increase in morbidity and mortality. Although carcinoid tumors have been known and studied for several years, there are still scarce data on the anesthetic management and the peri operative period., Case Presentation: We describe a case of a Caucasian 44-year-old woman with an unusual presentation of left CaHD with an ileal neuroendocrine tumor and liver metastases. Our preoperative somatostatin administration protocol, limit the cardiac damage. The maintenance of stable hemodynamics, the use of balanced anesthetic technique, all along with a good understanding of the pathology, played a major role in the successful management of anesthesia. This case report allows us to introduce our decision algorithm for the management of this type of pathology in our tertiary hospital, Cliniques Universitaires Saint-Luc., Conclusion: Despite the paucity of data, anesthetic management of patients with carcinoid tumor can be safely performed with effective hemodynamic monitoring and a good understanding of the pathophysiology. Knowledge and application of a clear institutional algorithm for octreotide administration and multidisciplinary consultation at a referral center are essential for the management of these patients., (© 2024. The Author(s).)

Carcinoid heart disease is a unique and serious cardiac complication of the neuroendocrine tumour that affects the right side of the heart, especially the tricuspid and pulmonic valves, eventually causing right heart failure. We present a middle-aged man with a history of well-differentiated neuroendocrine tumours of the small intestine with extensive metastases to the liver, mesentery and spine who is receiving monthly octreotide therapy. He presented with generalised fatigue, severe ascites and worsening dyspnoea. Both the transthoracic echocardiography and transoesophageal echocardiography revealed severe tricuspid and pulmonic regurgitations. He was considered a poor surgical candidate, underwent transcatheter pulmonic valve replacement with two bioprosthetic valve-in-valve implantations and was discharged in a stable condition., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND Carcinoid heart disease typically occurs in the presence of metastatic carcinoid tumor deposits in the liver, as vasoactive substances access the systemic circulation through the hepatic vein. Primary ovarian carcinoid tumors are rare neuroendocrine tumors, and can be associated with carcinoid syndrome and carcinoid heart disease. CASE REPORT We describe the case of a 40-year-old woman who presented with secondary amenorrhea, acne, hirsutism, and diarrhea. She was found to have a heart murmur on exam in the absence of severe symptoms of heart failure. Her investigations demonstrated elevated urinary 5-hydroxyindoleacetic acid (5-HIAA), chromogranin A, and free testosterone. Abdominal computed tomography enterography showed a large and hypervascular pelvic mass. Octreotide scintigraphy confirmed the diagnosis of primary ovarian carcinoid tumor in the setting of an intensely octreotide-avid mass with no evidence of distant metastases. Transesophageal echocardiography showed severe tricuspid regurgitation with severe dilation of the right heart chambers. She underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The pathology demonstrated a 14-cm carcinoid tumor of 'insular' type confined to the ovary, pT1apNX, grade 1, positive for chromogranin and synaptophysin (neuroendocrine markers) and positive mib-1 (Ki-67). Postoperatively, clinical and biochemical parameters improved significantly but her cardiac function regressed over time, resulting in a tricuspid valve replacement 6 years later. CONCLUSIONS Primary ovarian carcinoid tumors can result in carcinoid heart disease, even in the absence of liver metastases. Early diagnosis and treatment contribute to favorable outcomes.

Background: Carcinoid heart disease is the cardiac manifestation of carcinoid syndrome. There is limited research on rhythm management in patients with carcinoid heart disease. The association of typical atrial flutter and carcinoid heart disease in particular is poorly described., Case Presentation: Here we present a case of a 77-year-old German woman with carcinoid heart disease and recurrent typical atrial flutter complicating the postoperative course after tricuspid valve replacement and its successful long-term rhythm control by ablation therapy., Conclusion: There is limited evidence on rhythm management in patients with the rare diagnosis of carcinoid heart disease. Typical atrial flutter repeatedly complicated the postoperative course of our patient with carcinoid heart disease and could finally be treated curatively by ablation. Radiofrequency ablation should be considered as a valuable therapeutic component in the challenging therapy of this disease., (© 2022. The Author(s).)

Objective: Carcinoid heart disease is characterized by tricuspid valve regurgitation and varying degrees of pulmonary valve regurgitation or stenosis. Valve replacement procedures may be complicated by systemic effects of carcinoid syndrome, as well as hepatic dysfunction and right heart failure. This study was performed to identify factors that might be associated with improving early mortality rates and late outcomes., Methods: Between November 1985 and January 2018, 240 adult patients underwent surgery for carcinoid heart disease at the Mayo Clinic. We analyzed the association of multiple clinical and echocardiographic variables on early mortality and late survival., Results: The median (interquartile range) age of patients was 63 years (55-69), and 117 patients (49%) were male. Before operation, 157 patients (70%) had New York Heart Association class III or IV limitation. Somatostatin analogs were used in 221 patients (92%), and long-acting somatostatins were used in 130 patients (54%). Loop diuretic therapy was used preoperatively in 125 patients (52%). Early mortality rate was 29% (9/22) between 1985 and 1994, but decreased to 7% (6/81) during 1995 to 2004, and to 5% (7/128) from 2005 onward. Overall survival estimates at 1, 3, and 5 years were 69%, 48%, and 34%, respectively. Older age, advanced New York Heart Association class, and a nonlinear effect of creatinine were independently associated with overall mortality., Conclusions: Valve replacement for carcinoid heart disease has acceptable short-term mortality, and early risk has decreased in the current era. Earlier intervention may improve overall survival., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Neuroendocrine tumours are a rare malignancy, which can be complicated by a carcinoid syndrome and, in more rare cases, also valve destruction. The correct timing for surgical repair remains unknown. We report the first-in-men exercise cardiac magnetic resonance imaging with pulmonary artery catheter measurements in order to better understand the haemodynamic impact of isolated tricuspid valve insufficiency in a low symptomatic patient. Not pressure but volume overload is the key factor in the development of symptoms, as long as the right ventricular function is intact. Based on our findings, we referred the patient for tricuspid valve replacement. This case, together with the review of all carcinoid heart disease cases in our hospital (a large tertiary cardiology and oncology centre) since 2000, indicates a potential benefit for early intervention in carcinoid heart disease., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

We report the gratifying response of functioning metastatic neuroendocrine tumor with carcinoid heart disease (uncontrolled by long-acting octreotide) to treatment with 177 Lu-DOTATATE. This response favorably altered the clinical course of the patient, enabling corrective valvular surgery, enhancing health-related quality of life, improving symptoms (from New York Heart Association grade III at baseline to grade I after 6 cycles), stabilizing the disease, and substantially reducing the level of 5-hydroxyindole acetic acid. Avoiding concerns about volume overload by administering amino acids over a relatively prolonged period of 7.5-8 h during peptide receptor radionuclide therapy could be particularly helpful and could be conveniently adopted in this clinical setting. Considering the significantly shortened overall survival of patients with carcinoid heart disease, the relative paucity of available treatment options, and the risk of complications during corrective surgery on poorly controlled functioning disease, 177 Lu-DOTATATE can emerge as a potent option in this group of patients., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Competing Interests: Competing interests: None declared.

Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NET). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNET) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi), such as CC-223, could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice treated with either rapamycin alone or switched to CC-223 upon progression. Detailed signaling and RNA sequencing analyses were performed on tumors that were sensitive or progressed on mTOR treatment. Approximately 57% of mice bearing pNET tumors that progressed on rapalog therapy showed a significant decrease in tumor volume upon a switch to CC-223. Moreover, mice treated with an mTORKi exhibited decreased cardiac dilation and thickening of heart valves than those treated with placebo or rapamycin alone. In conclusion, in the majority of pNETs that progress on rapalogs, it is possible to reduce disease progression using an mTORKi, such as CC-223. Moreover, CC-223 had an additional transient cardiac benefit on valvular fibrosis compared with placebo- or rapalog-treated mice. These results provide the preclinical rationale to further develop mTORKi clinically upon progression on rapalog therapy and to further test their long-term cardioprotective benefit in those NET patients prone to carcinoid syndrome. Mol Cancer Ther; 16(11); 2432-41. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Severe carcinoid syndrome and carcinoid heart disease in neuroendocrine tumours can have a significant impact on a patient's quality of life and are a major cause of morbidity and mortality. We present a novel approach to managing a patient with medically uncontrollable carcinoid syndrome. Inferior and superior vena cava placement of transcatheter heart valves has been used to treat patients with right heart failure due to severe tricuspid and pulmonary regurgitation. However, this procedure has not been attempted to specifically reduce hormone secretion, primarily from the liver, in order to control carcinoid syndrome symptoms. We attempted this procedure in a patient with severe carcinoid disease and tricuspid regurgitation as a bridge to later definitive therapy. The procedure was technically successful, but did not improve carcinoid symptoms. The possible reasons for the failure are discussed here., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Transcatheter pulmonary valve implantation is established as a valuable option to reconstruct failing right ventricular outflow tract function. Percutaneous tricuspid valve-in-valve or valve-in-ring reconstruction is even applied with increasing acceptance. A 46-year-old woman with a diagnosis of carcinoid-dependent right heart failure underwent surgical bioprosthetic tricuspid and pulmonary valve replacement. Almost 1 year later, she presented again with markedly dilatated and reduced right heart function caused by degeneration of both biologic valves. We report a successful two-stage percutaneous transcatheter double-valve replacement with the use of a Melody valve in pulmonary and tricuspid positions., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Carcinoid heart disease is a frequent occurrence in patients with carcinoid syndrome and is responsible for substantial morbidity and mortality. The pathophysiology of carcinoid heart disease is poorly understood; however, chronic exposure to excessive circulating serotonin is considered one of the most important contributing factors. Despite recognition, international consensus guidelines specifically addressing the diagnosis and management of carcinoid heart disease are lacking. Furthermore, there is considerable variation in multiple aspects of screening and management of the disease. The aim of these guidelines was to provide succinct, practical advice on the diagnosis and management of carcinoid heart disease as well as its surveillance. Recommendations and proposed algorithms for the investigation, screening, and management have been developed based on an evidence-based review of the published data and on the expert opinion of a multidisciplinary consensus panel consisting of neuroendocrine tumor experts, including oncologists, gastroenterologists, and endocrinologists, in conjunction with cardiologists and cardiothoracic surgeons., (Copyright © 2017 American College of Cardiology Foundation. All rights reserved.)

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.

Carcinoid heart disease presents as right-sided heart failure attributable to the dysfunction of the tricuspid and pulmonary valves. Although surgical valve replacement is the mainstay of treatment when patients become symptomatic, it is associated with substantial perioperative mortality rates. We present a case of severe pulmonary valve stenosis secondary to carcinoid heart disease, treated successfully with percutaneous valve replacement. A 67-year-old man with severe pulmonary valve stenosis was referred to our center for pulmonary valve replacement. The patient had a history of metastatic neuroendocrine tumor of the small bowel with carcinoid syndrome, carcinoid heart disease, and tricuspid valve regurgitation previously treated with surgical valve replacement. Because of the patient's severe chronic obstructive pulmonary disease and hostile chest anatomy seen on a computed tomographic scan dating from previous cardiothoracic surgery, we considered off-label percutaneous valve replacement a viable alternative to open-heart surgery. A 29-mm Edwards Sapien XT valve was successfully deployed over the native pulmonary valve. There were no adverse sequelae after the procedure, and the patient was discharged from the hospital the next day. This case report shows that percutaneous valve replacement can be a valid option in carcinoid heart disease patients who are not amenable to surgical valve replacement.

Background: Carcinoid tumor with consecutive endocardial fibroelastosis of the right heart, known as carcinoid heart valve disease (CHVD) or Hedinger's syndrome, is accompanied by combined right-sided valvular dysfunction with regurgitation and stenosis of the affected valves. Cardiac surgery with replacement of the tricuspid and/or pulmonary valve is an established therapeutic option for patients with Hedinger's syndrome. Little is known about the long term outcome and the choice of prosthesis for the pulmonal position is still a matter of debate., Methods: The authors report three cases of pulmonary valve replacement with stentless bioprostheses (Medtronic Freestyle, Medtronic PLC, Minneapolis, MN, USA) due to severe pulmonary valve degeneration in consequence of Hedinger's syndrome., Results: All patients presented with re-stenosis of the pulmonal valve conduit at the height of the anastomoses in a premature fashion. Due to the increased risk for repeat surgical valve replacement, two patients were treated by transcatheter heart valves., Conclusion: We do not recommend the replacement of the pulmonary valve with stentless bioprostheses in patients with CHVD. These valves presented with an extreme premature degeneration and consecutive re-stenosis and heart failure.

Purpose: This study evaluates the prevalence of cardiac metastases in patients with serotonin producing neuroendocrine tumours (NET), examined with 18F-FDOPA PET/CT, and the relationship of these metastases to the presence of carcinoid heart disease (CHD) based on echocardiography., Background: CHD occurs in patients with serotonin producing NET. The diagnostic method of choice remains echocardiography. The precise prevalence of cardiac metastases is unknown given the limitations of standard technologies. Nuclear medicine modalities have the potential to visualize metastases of NET., Methods: All patients who underwent 18F-FDOPA PET/CT because of serotonin producing NET between November 2009 and May 2012 were retrospectively analyzed. The presence of cardiac metastasis was defined as myocardial tracer accumulation higher than the surrounding physiological myocardial uptake. Laboratory tests and transthoracic echocardiography (TTE) results were digitally collected., Results: 116 patients (62 male) underwent 18F-FDOPA PET/CT, mean age was 61±13 years. TTE was performed in 79 patients. Cardiac metastases were present in 15 patients, of which 10 patients also underwent TTE. One patient had both cardiac metastasis (only on 18F-FDOPA PET/CT) and echocardiographic signs of CHD. There were no differences in echocardiographic parameters for CHD between patients with and without cardiac metastases. TTE in none of the 79 patients showed cardiac metastases., Conclusion: The prevalence of cardiac metastases detected with 18F-FDOPA PET/CT in this study is 13%. 18F-FDOPA PET/CT can visualize cardiac metastases in serotonin producing NET patients. There appears to be no relationship between the presence of cardiac metastases and TTE parameters of CHD.

Background: Carcinoid heart disease is a rare form of valvular heart disease. We sought describe the spectrum of carcinoid heart disease identified by echocardiography and cardiac MRI., Method and Results: Two hundred fifty-two patients with carcinoid syndrome underwent a range of investigations including 2D transthoracic echocardiography, 3D transthoracic echocardiography and transesophageal echocardiography, and cardiac MRI. Fifty-two patients had evidence of carcinoid heart disease. Involvement of the tricuspid, pulmonary, mitral, and aortic valves were found in 47 (90%), 36 (69%), 15 (29%), and 14 (27%), respectively. Myocardial metastases were found in 2 (3.8%) patients. Several patterns of disease were identified depending on the extent and severity to which each leaflet and its associated subvalvular apparatus was affected. Thirteen of 15 (87%) patients with left-sided carcinoid involvement had a patent foramen ovale. Three patients with severe degree of shunting had severe valvular regurgitation. Patients with mild/moderate degree of shunting had mild or moderate valvular regurgitation. Three-dimensional transthoracic echocardiography/transesophageal echocardiography provided detailed anatomic information particularly for the tricuspid and pulmonary valves. Cardiac MRI allowed complementary assessment of valvular heart disease and delineation of myocardial metastases. Gallium-68 octreotide positron emission tomography identified neuroendocrine metastases., Conclusions: Carcinoid heart disease is a heterogeneous disease with a wide spectrum of echocardiographic findings. A multimodality approach is needed in patients with this complex pathology.

In a 56-year-old lady, a carcinoid tumor of the terminal ileum metastasized to regional lymph nodes, and the liver was removed by hemicolectomy in 2002. Following a history of cutaneous flushing, diarrhea, and bronchoconstriction 3 years later, a somatostatin therapy was instituted. As flushing and diarrhea resolved and levels of urinary excretion of 5-hydoxyindoleacetic acid decreased, shortness of breath was progressive and prompted a cardiac exam. Despite poor resolution, echocardiography revealed a thickening of the tricuspid valves (TK) with reduced mobility along with right atrial (RA) and right ventricular (RV) dilatation. The pulmonary valve was unobtrusive. Magnetic resonance (MR) imaging revealed extensive fibrous tissue extending from the valvular base to the tip of the tricuspid leaflets. Retraction and immobilization of the TK caused a mild stenosis and a large regurgitant flow. Because medical treatment of tricuspid regurgitation was ineffective, the TK was excised and a Hancock 25-mm bioprosthetic valve was implanted. The postoperative course was uncomplicated, and the patient recuperated and resumed normal daily activities., (2009 Wiley Periodicals, Inc.)

Background: The management of patients with carcinoid heart disease poses two major challenges for the anaesthetist: carcinoid crisis and low cardiac output secondary to right ventricular (RV) failure. Carcinoid crises may be precipitated by the administration of catecholamines and histamine-releasing drugs., Methods: We analysed a series of 11 patients [six males, median (range) age 60 (42-73) yr] with severe symptomatic carcinoid heart disease who underwent multivalve surgery (right-sided valves, n=8; right- and left-sided valves, n=3) between 2001 and 2007., Results: All patients received octreotide intraoperatively [650 (300-1050) microg] to prevent carcinoid symptoms and vasoplegia. Those patients on a greater preoperative octreotide regime required additional intraoperative octreotide [median (range) dose 320 (300-850) vs 750 (650-1050) mug]. Similarly, the use of greater doses of aprotinin (> 5 KIU) was associated with greater requirements for octreotide [475 (300-700) vs 750 (320-1050) microg] and higher glucose levels (> or =8.5 mmol litre(-1)). Catecholamines were generally required in those patients who presented with a worse New York Heart Association functional class. Overall mortality was 18% (n=2) and only one episode of mild intraoperative carcinoid crisis was observed., Conclusions: Carcinoid crisis and RV failure still remain the primary challenges for the anaesthesiologist while managing patients with carcinoid heart disease. Our study supports the administration of catecholamines to wean patients off cardiopulmonary bypass, particularly in the presence of myocardial dysfunction. Those patients on higher octreotide dosages may require close intraoperative glucose monitoring. Despite high operative mortality, surgical outcome has been improved potentially due to earlier patient referral and better perioperative management.

A 60-year-old man, known for stable coronary artery disease, was admitted for suspected unstable angina. In the previous month, the patient presented with progressive dyspnea on light exertion. In the preceding four months, he had experience occasional episodes of flushing and diarrhea, and had inexplicably lost 22.7 kg. Night sweats and fever were absent. ST segment elevation in the inferior leads and ST segment depression in the precordial leads were documented during an episode of chest pain. The coronary angiogram showed diffuse disease with 70% stenosis of the left anterior descending coronary artery and 50% stenosis on the second diagonal (D(2)). An echocardiogram showed a patent foramen ovale. Balloon angioplasty and stenting were performed on the two lesions. Two days later, prolonged chest pain recurred. Cardiac catheterization was repeated and showed occlusive thrombus within the stent on the D(2). Angioplasty was repeated. Symptoms recurred 36 h later, with the electrocardiogram showing ST segment elevation. The first angiogram was reviewed and vasospasm was suspected on a branch of the D(2), on the second marginal and in the distal circumflex artery. The diagnosis of vasospastic angina was retained. Beta-blockers were replaced by high doses of a calcium channel blocker with an excellent clinical response. The case described is of a patient with an acute coronary syndrome, vasospastic angina, in-stent thrombosis and carcinoid disease. Coronary vasospasm was attributed to serotonin, which was secreted by the carcinoid tumour that reached an atherosclerotic coronary vasculature through a patent foramen ovale, thereby avoiding pulmonary inactivation.

A patient with tricuspid and pulmonary regurgitation due to carcinoid syndrome successfully underwent double bioprosthetic valve replacement. This technique avoids anticoagulation treatment in a patient with hepatic dysfunction and facilitates future hepatic de-arterialization as a treatment option in carcinoid disease. Advances in treatment of carcinoid syndrome may have reduced the risk of early bioprosthetic degeneration.

We describe the recognition and management of two patients who developed intraoperative fracture of the right coronary artery (RCA). Both patients had a calcified RCA without a hemodynamically significant stenosis. Compression of the right atrioventricular groove during the surgical procedure resulted in fracture of the RCA, leading to ventricular arrhythmias and hemodynamic instability. Coronary bypass grafting without cardioplegic arrest was used for definitive diagnosis and treatment. Both patients made a rapid and uneventful recovery.

We report a unique case of carcinoid cardiopathy. The patient, a 59-year-old white woman with a known carcinoid tumor of the terminal ileum, presented with complete heart block and subsequently died. Because of her clinical presentation, we examined the conducting system at autopsy. The atrioventricular node was heavily infiltrated by metastatic carcinoid. The tumor was also seen in the surrounding atrial myocardium. No other metastatic lesions were seen in the heart. Carcinoid cardiopathy in the form of right-sided endocardial and valvular thickening has been well documented in the literature, and we found these features in our case as well. To our knowledge, carcinoid has never been documented in the cardiac conducting system until now. We found 2 cases of possible involvement of the conducting system reported in the literature. Unfortunately, the conducting system was not examined postmortem in either of these cases. If conducting system involvement is not unique to the present case, patients with metastatic carcinoid and cardiac problems may require different management. We hope that this case will stimulate further postmortem study of the conducting system in patients with metastatic carcinoid tumor.

Objective: To quantitate the pathologic features of carcinoid plaques in a relatively large number of surgical specimens from a single institution., Patients and Methods: Medical records, operative reports, and surgical specimens were reviewed from all patients with carcinoid heart disease who underwent cardiac valvular surgery at Mayo Clinic, Rochester, Minn, between 1980 and 2000., Results: The study group included 75 patients (45 men, 30 women) who ranged in age from 26 to 78 years (mean, 59 years). From these 75 patients, 139 valves had been excised surgically (73 tricuspid, 55 pulmonary, 6 mitral, 5 aortic). Pure regurgitation was the most common dysfunctional state of the tricuspid valve (80% [60/75]), mitral valve (97% [32/33]), and aortic valve (96% [23/24]). The pulmonary valve was more often both stenotic and insufficient (52% [37/71]) than purely regurgitant (30% [21/71]). In all cases, valve dysfunction was attributed to the presence of carcinoid plaques, which caused both thickening and retraction. Thickening was the result of both cellular proliferation and deposition of extracellular matrix. Proliferation of myofibroblasts was observed in all plaques and was mild in 49% (68/139) and moderate or severe in 51% (71/139). Extracellular matrix included collagen (in 99% of the 139 valves), myxoid ground substance (98% [136/139]), and elastin (20% [28/139]). Carcinoid plaques were also involved by neovascularization (94% [131/139]), chronic inflammation (94% [131/139]), and mast cell infiltration (64% [89/139]). Severe thickening was attributable primarily to collagen deposition in tricuspid valves and to myofibroblast proliferation and myxoid matrix in pulmonary valves., Conclusions: Among patients undergoing valvular surgery for carcinoid heart disease, tricuspid and pulmonary valves represented 92% of the excised valves (128/ 139). Although numerous cellular and extracellular features were common to the carcinoid plaques, variability in their relative expression produced appreciable differences in the histologic appearance among the plaques.

Patients with metastatic carcinoid tumours often undergo surgical procedures to reduce the tumour burden and associated debilitating symptoms. These procedures and anaesthesia can precipitate a life-threatening carcinoid crisis. To assess perioperative outcomes, we studied retrospectively the medical records of adult patients from 1983 to 1996 who underwent abdominal surgery for metastatic carcinoid tumours. Preoperative risk factors, intraoperative complications and complications occurring in the 30 days after surgery were recorded. Perioperative complications or death occurred in 15 of 119 patients (12.6%, exact confidence interval 7.2-19.9). None of the 45 patients who received octreotide intraoperatively experienced intraoperative complications compared with eight of the 73 patients (11.0%) who did not receive octreotide (P=0.023). The presence of carcinoid heart disease and high urinary output of 5-hydroxyindoleacetic acid preoperatively were statistically significant risk factors for perioperative complications.

A case is described of a 54 year old woman who had acute pericarditis with large exudative effusion accompanied by severe right and left ventricular failure. The patient was finally diagnosed with carcinoid heart disease from an ovarian carcinoid teratoma. She was treated with octreotide--a somatostatin analogue--followed by radical surgical resection of the neoplasm. At one year follow up only mild carcinoid tricuspid regurgitation remained. Only 16 cases of carcinoid heart disease from an ovarian primary have been described in literature. Moreover clinically manifest acute, nonmetastatic pericarditis and left heart failure are not considered as possible presentations of carcinoid heart disease, whatever the origin. In a recent series a small pericardial effusion was considered an infrequent and unexpected echocardiographic finding in carcinoid heart patients. One case of "carcinoid pericarditis" has previously been described as a consequence of pericardial metastasis. Left sided heart involvement is usually caused by bronchial carcinoids or patency of foramen ovale; both were excluded in the case presented.

Carcinoid heart disease occurs in approximately half of patients who have carcinoid syndrome and is the leading cause of death among these patients. It is typically manifest as right-sided valvular lesions, usually tricuspid insufficiency and pulmonary valve stenosis. This case report describes the unusual presentation of a patient with carcinoid heart disease and a large right-to-left shunt through a patent foramen ovale.

Background: Although serotonin has been postulated as an etiologic agent in the development of carcinoid heart disease, no direct evidence for different ambient serotonin levels in cardiac and noncardiac patients has been reported to date., Methods and Results: The present study reviews our experience with 604 patients in the Duke Carcinoid Database. Nineteen patients with proven carcinoid heart disease (by cardiac catheterization and/or echocardiogram) were compared with the remaining 585 noncardiac patients in the database with regard to circulating serotonin and its principal metabolite, 5-hydroxyindole acetic acid (5-HIAA). No significant demographic differences existed between the cardiac and noncardiac groups; however, typical carcinoid syndrome symptoms (ie, flushing and diarrhea) were almost threefold more common in the cardiac group (P < .001). Compared with the noncardiac group, heart disease patients demonstrated strikingly higher (P < .0001) mean serum serotonin (9750 versus 4350 pmol/mL), plasma serotonin (1130 versus 426 pmol/mL), platelet serotonin (6240 versus 2700 pmol/mg protein), and urine 5-HIAA (219 versus 55.3 mg/24 h) levels. The spectrum of heart disease among the 19 patients showed a strong right-sided valvular predominance, with tricuspid regurgitation being the most common valvular dysfunction (92% by cardiac catheterization; 100% by echocardiogram)., Conclusions: These data suggest that serotonin plays a major role in the pathogenesis of the cardiac plaque formation observed in carcinoid patients.

This three-part article examines the histologic and morphologic basis for stenotic and purely regurgitant tricuspid valves. In Part I, conditions producing tricuspid valve stenosis were reviewed. In Part II, conditions producing pure tricuspid regurgitation are discussed. In contrast to the relatively few causes of tricuspid stenosis, the causes of pure (no element of stenosis) tricuspid regurgitation are multiple. Some of the conditions producing pure regurgitation include floppy tricuspid valves, infective endocarditis, papillary muscle dysfunction, rheumatic disease, and Ebstein's anomaly.

This three-part article examines the histologic and morphologic basis for stenotic and purely regurgitant tricuspid valves. In Part I, conditions producing tricuspid valve stenosis are reviewed. In over 90% of stenotic tricuspid valves, the etiology is rheumatic disease. In isolated tricuspid stenosis, the etiology is either carcinoid or congenital. Rare causes of tricuspid stenosis include active infective endocarditis, metabolic or enzymatic abnormalities (Fabry's, Whipple's disease), and giant blood cysts.

Background: The carcinoid syndrome is a rare cause of acquired valvular heart disease. Although the typical echocardiographic features of carcinoid heart disease are well recognized, this large series provides new information about unusual manifestations of the disease as well as the role of Doppler echocardiography., Methods and Results: Between 1980 and 1989, 132 patients with carcinoid syndrome underwent echocardiographic study. The echocardiographic, Doppler, and clinical features of the 74 patients (56%) with echocardiographic evidence of carcinoid heart disease are described. Among these patients, 97% had shortened, thickened tricuspid leaflets. Tricuspid regurgitation was present in all 69 patients with carcinoid heart disease who underwent Doppler examination, and it was of moderate or severe degree in 62 patients (90%). Severe tricuspid regurgitation was characterized by a dagger-shaped Doppler spectral profile with an early peak pressure and rapid decline. The pressure half-time was prolonged (mean, 116 msec), which is consistent with associated tricuspid stenosis. The pulmonary valve appeared thickened, retracted, and immobile in 36 patients (49%) and was diminutive to the extent of not being visualized in an additional 29 patients (39%). Among the 47 patients who underwent Doppler evaluation of the pulmonary valve, regurgitation was present in 81%, and stenosis was present in 53%. Left-sided valvular involvement was present in five patients (7%), four of whom had patent foramen ovale or carcinoid tumor involving the lung. Previously undescribed myocardial metastases were present in three patients (4%) and were confirmed by biopsy in each case. Small pericardial effusions were present in 10 patients (14%). Patients with and without echocardiographic evidence of carcinoid heart disease did not differ with regard to sex, age, location of the primary tumor, duration of diagnosis, or duration of symptoms of carcinoid syndrome. However, the mean pretreatment level of urinary 5-hydroxyindoleacetic acid was higher in patients with carcinoid heart disease than in patients without carcinoid heart disease (270 versus 131 mg/24 hrs, p < 0.001). The symptom of dyspnea was more prevalent among patients with carcinoid heart disease than in patients without the disease (54% versus 27%, p = 0.003); as expected, heart murmurs were also noted more frequently in patients with disease (92% versus 43%, p < 0.0001). Treatment regimens and response to therapy were similar in the two groups. Survival of patients with echocardiographic evidence of carcinoid heart disease was reduced compared with those without cardiac involvement (p = 0.0003). ECG and chest roentgenographic findings in patients with carcinoid heart disease were nonspecific., Conclusions: The broad spectrum of carcinoid heart disease is detailed in this large series. This includes not only right-sided valvular lesions but also left-sided involvement, pericardial effusion, and myocardial metastases.

Carcinoid heart disease is a complication of a neuroendocrine carcinoid tumor. Morphologically, it is characterized by the formation of fibrotic plaques with deposition of extracellular matrix in the subendocardium, frequently causing heart valve dysfunction and cardiac failure. Because members of the transforming growth factor-beta (TGF-beta) family are known to stimulate fibroblasts in their production of extracellular matrix, we investigated the expression of the three isoforms of TGF-beta and the binding protein for latent TGF-beta 1 (LTBP) in carcinoid plaques of the right side of the heart, as well as from control tissue, using immunohistochemistry. Tissue specimens were obtained intraoperatively from nine consecutive patients undergoing valve replacement surgery. TGF-beta 1 and TGF-beta 3 were detected in the fibroblasts of all plaques analyzed, whereas TGF-beta 2 was only rarely expressed. The localization of LTBP was partly concordant with that of TGF-beta 1, but the positive staining for LTBP was extracellular. Sections from unaffected heart tissue contained few fibroblasts in the subendocardium, showing only weak or no immunostaining for TGF-beta 1, -beta 2, and -beta 3 and no staining for LTBP. These results suggest that TGF-beta may play a role in the proliferation of fibroblasts and their matrix production in carcinoid heart lesions.