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Objective: The aim of this study was to evaluate the performance of different biomarkers for the detection of carcinoid heart disease (CHD) in neuroendocrine tumours (NETs), in particular serum 5-HIAA (s5HIAA)., Design: An explorative ancillary study of the French CrusoeNET cohort., Methods: Patients managed in the Lyon-EURACAN Center of Excellence (CoE) were included when they were aged of at least 18 years, treated and followed for an advanced/metastatic ileum or lung NET, a NET irrespective of the primary location or from unknown primary location but with clinical CS, and/or elevation of urinary 5-HIAA (u5HIAA) twice greater than the upper limit of normal. All patients included had 1 available serum stored within the local biobank between January 2021 and April 2022. Echocardiography was performed by 1 of the 3 expert cardiologists of the Lyon-EURACAN-CoE., Results: We included 138 patients with NETs, mainly of the small intestine and lung, and 19 of them had a CHD. Analysis showed that s5HIAA was well correlated with u5HIAA (ρ = 0.824 [0.76-0.88], P < .0001) and was a good biomarker for CHD detection (receiver operating characteristic curve = 0.85 [0.75-0.94], P < .0001). Using a threshold value of 757 nmol/L, the sensitivity and specificity for the detection of CHD were 84% and 80%, respectively., Conclusions: s5HIAA is highly sensitive and specific for CHD detection. It could be used as a pre-screening tool in centres where systematic and regular echocardiography by an expert cardiologist is not performed in this population., Competing Interests: Conflict of interest: C.L.-B. received financial support from IPSEN, Novartis, Keocyt, and AAA. T.W. received financial support from IPSEN, AAA, Novartis, Keocyt, and Roche to conduct clinical trials and/or ancillary studies. Other authors: none., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Tricuspid valve disease in carcinoid heart syndrome is usually diagnosed via screening echocardiography in patients with known carcinoid syndrome. Vasoactive intestinal peptide tumour (VIPoma) is a rare tumour with an incidence of 0.05%-2% that typically presents with symptoms related to the release of vasoactive intestinal peptide: flushing, diarrhoea and electrolyte abnormalities like hypokalaemia and hypochlorhydria. Historically, the cardiac valves are unaffected. We present a case where a finding of tricuspid regurgitation and stenosis on echocardiography prompted an expedited workup for malignancy ultimately leading to a diagnosis of VIPoma., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Carcinoid Heart Disease (CaHD) is defined as the constellation of all cardiac manifestations that occur in patients with carcinoid tumors. Cardiac manifestations are generally due to the paraneoplastic effects of vasoactive substances secreted by carcinoid tumors. These primarily cause cardiac valve dysfunction and resultant heart failure. Successful management of patients with CaHD requires a multidisciplinary team to address both the classical manifestations of carcinoid syndrome, as well as the additional manifestations of cardiac dysfunction. While the cornerstone of medical management for carcinoid syndrome are somatostatin analogs (SSAs), there is no evidence to suggest that the usage of SSAs influences the development or progression of CaHD. Additionally, while liver-directed therapies provide a survival benefit to symptomatic carcinoid syndrome patients with resectable disease, there are conflicting data on the survival benefit of hepatic resection among patients with CaHD. Cardiac surgery in patients with CaHD is a complex undertaking, and is the only definitive treatment for symptom management in CaHD with significant survival benefit for patients in advanced disease states. Two crucial surgical decisions to be made are determining which valve(s) should be replaced, and what prosthetic should be utilized. While challenging in this often medically frail population, cardiac surgery confers a survival benefit and should be pursued in cases of symptomatic CaHD or progressive right ventricular dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Conflicts of Interest None.

Background: The survival of patients with neuroendocrine tumors has substantially improved with modern treatment options. Although the associated carcinoid syndrome can be diagnosed early and controlled effectively, cardiologists still encounter patients with cardiac manifestations, particularly among individuals with persistently high levels of vasoactive mediators. Treatment options have been limited to surgical valve replacement in fully manifested disease. Since surgery is not always feasible, transcatheter valve implantation is becoming an interesting alternative., Case: A case of a 50-year-old woman with carcinoid syndrome and right-sided valvular heart disease is presented. Moderate pulmonary valve stenosis and severe tricuspid valve regurgitation were diagnosed during the evaluation and treatment of neuroendocrine tumor. The possibility of rare valve involvement and the need for interdisciplinary cooperation in the diagnosis, monitoring and treatment of patients with neuroendocrine tumors producing vasoactive substances must be emphasized., Conclusion: The patient had a typically presenting carcinoid syndrome with a rare cardiac manifestation. Although monitoring and treatment were carried out in accordance with recommendations and appropriate to the clinical condition, rapid progression of the metastatic disease ultimately precluded invasive cardiac intervention.

Carcinoid tumors (CT) are among the least studied tumors. It is a relatively rare and slow-growing tumor with good survival in its primary form. However, metastatic carcinoid tumor comes up with many different complications contributing to increased morbidity and mortality. Metastatic form of the disease has a wide spectrum of clinical manifestations and multisystem involvement including cardiovascular manifestations, neurological manifestations, and psychiatric manifestations and so on. In this review, we are centered towards the cardiovascular manifestations of the disease, which, by far, is one of the commonest causes of death in these patients. Being a neuroendocrine tumor, cardiovascular manifestations are mainly because of biologically active substances, produced by the tumor cells, remodeling the heart. Development of targeted therapies against carcinoid heart diseases is currently limited by lack of understanding of pathophysiology of the disease processes. In this review, we aim to figure out the spectrum of carcinoid heart diseases, along with the molecular biology of the changes going on, which, in turn, will not only pave a way to the development of targeted therapies but will also extend opportunities for molecular screening of the tumor and diagnosis at an early stage, thereby, reducing the morbidity and mortality., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Carcinoid heart disease (CaHD) is an important complication among patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS). CS patients (25%-65%) eventually develop CaHD; these patients face a significantly increased risk of morbidity and mortality. Guidance papers (eg, clinical practice guidelines, consensus guidelines, and expert statements) have been established by major organizations across the disciplines of cardiology and oncology; however, these recommendations are not routinely implemented. The aim of this article is to encourage the integration of current recommendations from national societies into clinical practice. Early screening upon recognition of CS and prior to the development of CaHD symptoms is paramount, as no existing therapies are approved to reverse the fibrotic damage to the heart once it occurs. Valvular replacement is the only definitive treatment for CaHD once it has developed. When patients are noted to have urinary 5-hydroxyindoleacetic acid (5-HIAA) levels ≥300 µmol/24 h and/or serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels >260 pg/mL, echocardiography is recommended. Systemic approaches to control tumor growth and hormonal secretion include somatostatin analogs (SSAs), followed by options including peptide receptor radiotherapy (PRRT), everolimus and liver embolization. Telotristat is the primary choice for control of diarrhea refractory to SSA. Diuretics are the mainstay of heart failure symptom management for patients who develop CaHD. Considerations for future research are discussed, including the ongoing TELEHEART (TELotristat Ethyl in a HEART biomarker study) trial involving telotristat and not yet activated CHARRT (Carcinoid Heart disease And peptide Receptor Radiotargetted Therapy) study involving PRRT with lutetium 177 (177Lu) dotatate., (© The Author(s) 2023. Published by Oxford University Press.)

Carcinoid heart disease is a frequent manifestation of carcinoid syndrome. It results from the release of a large amount of serotonin and subsequently fibrosis of right sided heart valves, that is, tricuspid and pulmonic valve. This article reviews the pathogenesis, clinical symptoms, diagnosis, treatment and prognosis of carcinoid heart disease. Recent developments in treating carcinoid heart disease have improved the poor prognosis associated with the disease., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The carcinoid syndrome (CS) is a constellation of symptoms attributed to hypersecretion of amines, prostaglandins and polypeptides. The cardinal symptoms of CS are flushing, diarrhea and bronchospasm; however, CS may present with various symptoms and signs, as: Skin: cutaneous flushes, cyanosis, pellagra, Gastrointestinal: diarrhea, nausea, abdominal cramps, vomiting, Heart: tricuspid and pulmonic valve thickening causing right heart failure, edema, Respiratory: wheezing, dyspnea.

Carcinoid heart disease (CHD) is the main complication of carcinoid syndrome (CS) associated with metastatic small intestine neuroendocrine tumours (NETs). The pathophysiology of CHD is partly understood but vasoactive hormones secreted by NETs, especially serotonin, play a major role, leading to the formation of fibrous plaques. These plaque-like deposits involve the right side of the heart in >90% of cases, particularly the tricuspid and pulmonary valves, which become thickened, retracted and immobile, resulting in regurgitation or stenosis. CHD represents a major diagnostic and therapeutic challenge for patients with NET and CS and is associated with increased risk of morbidity and mortality. CHD often occurs 2-5 years after the diagnosis of metastatic NET, but diagnosis of CHD can be delayed as patients are often asymptomatic for a long time despite severe heart valve involvement. Circulating biomarkers (5HIAA, NT-proBNP) are relevant tools but transthoracic echocardiography is the key examination for diagnosis and follow-up of CHD. However, there is no consensus on the optimal indications and frequency of TTE and biomarker dosing regarding screening and diagnosis. Treatment of CHD is complex and requires a multidisciplinary approach. It relies on antitumour treatment, control of CS and surgical valve replacement in cases of severe CHD. However, cardiac surgery is associated with a high risk of mortality, notably due to perioperative carcinoid crisis and right ventricular dysfunction. Timing of surgery is the most crucial point of CHD management and relies on the case-by-case determination of the optimal compromise between tumour progression, cardiac symptoms and CS control., (© 2023 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Opinion Statement: Cardiac surgery with tricuspid valve and potentially pulmonic valve replacement at an experienced center is currently the most effective strategy available for the treatment of carcinoid heart disease. Cardiac surgery for carcinoid heart disease requires a multidisciplinary team including cardiology, medical oncology, cardiothoracic anesthesia, and cardiac surgery. Without cardiac surgery, morbidity and mortality from carcinoid heart disease is high. Aggressive management of carcinoid before and after cardiac surgery is critical. Over time, though, circulating carcinoid hormones can lead to destruction of prosthetic valves as well, resulting in recurrent right heart failure. Percutaneous options for valve repair may be on the horizon for management of carcinoid heart disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Carcinoid heart disease (CHD) is a serious cardiac condition which is caused by elevated serotonin in the systemic circulation, secreted by neuroendocrine tumours (NET). It mostly affects the right-sided heart valves, where it causes fibrotic disturbances and is associated with worse survival. In this study, we describe a large cohort of patients with CHD and provide an insight into their survival over the past decades. All consecutive patients with a serotonin producing NET and CHD referred to the Netherlands Cancer Institute that presented with CHD or developed CHD during their follow up time were included from 1984 until 2021. Patients were divided into three time periods: 1984-2000, 2000-2010 and 2010-2018. Median N-terminal pro B-type natriuretic protein (NT-proBNP) and serum serotonin levels were stratified according to tricuspid regurgitation severity. Kaplan-Meier curves and log rank test were used for visualisation of survival. Cox regression was used for identification of the characteristics associated with disease specific mortality (DSM). A total of 84 patients with CHD were included of whom 49 (58.3%) were male. Median age at NET diagnosis was 62.3 (range 23.9-81.7) years, and median time to development of CHD was 1.1 (range 0-24.2) years. NT-proBNP was significantly higher when more severe tricuspid regurgitation (TR) was present (p = .027). Median survival from CHD diagnosis for 1984-2000, 2000-2010 and 2010-2018 were 1.3 (confidence interval [CI]: 0.9-1.6), 1.9 (CI: 1.2-2.6) and 3.9 (CI: 1.7-6.2) years (p = .025). Valve replacement surgery (VSR) occurred more frequent in later time periods. VSR (hazard ratio [HR] 0.33, p = .005) and NT-proBNP (HR 1.003, 1.00-1.005, p = .036) were significantly associated with DSM. The prognosis of patients with CHD has improved over the past decades, possibly caused by more VSR. NT-proBNP is a valuable biomarker in patients with CHD. Clinical practice should be aimed at timely diagnosis and intervention of CHD., (© 2022 British Society for Neuroendocrinology.)

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 (CHD) is a sequela of carcinoid liver metastases (LM). The true prevalence of CHD is unknown due to infrequent screening by transthoracic echocardiography (TTE). Octreotide is believed to protect against new and recurrent CHD, but supporting data are scant. This study determined CHD prevalence and outcomes in patients screened by TTE and treated with octreotide., Methods: Records of carcinoid patients from 2001 to 2021 were reviewed. Survival was estimated by Kaplan-Meyer curves and compared by log-rank., Results: Among 282 patients screened by TTE, overall survival was lower in CHD (n = 40) versus non-CHD (n = 242) patients (p < 0.001). Despite octreotide therapy, 21 patients developed CHD. Among patients with inoperable LM, survival was lower in CHD patients without valve replacement (VR) (p < 0.001), but similar between CHD patients with VR and non-CHD patients. CHD patients with VR and hepatic cytoreduction had survival similar to CHD patients without VR., Conclusion: VR improves survival in CHD patients with inoperable LM. Hepatic cytoreduction after VR should be reserved for carefully selected cases. Our data do not support a protective effect of octreotide., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Journal of Cardiothoracic and Vascular Anesthesia, 36 (2022) 2793-2802, http://dx.doi.org/10.1053/j.jvca.2021.10.030. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal., Competing Interests: Declaration of Competing Interest Dr. Neuburger is a consultant for Medtronic. The remaining authors do not have any financial or personal conflicts of interest to disclose.

Purpose: Carcinoid heart disease (CHD) is a life-threatening complication of carcinoid syndrome (CS) characterised by tricuspid regurgitation (TR). However, there is an unmet need for earlier diagnosis of CHD. We cross-sectionally assessed the prevalence and potential predictive or diagnostic markers for CS and CHD in a contemporary cohort of patients with small intestinal neuroendocrine tumours (SI-NETs)., Methods: Biochemical characteristics, hepatic tumour load, measures of arterial and endothelial function, atherosclerosis, and transthoracic echocardiography were analysed in a prospective cross-sectional setting., Results: Among the 65 patients studied, 29 (45%) had CS (CS+ ), and 3 (5%) CHD. CS+ was characterised by significantly higher hepatic tumour load, S-5-HIAA and fP-CgA, higher frequency of diarrhoea and flushing, and more frequent PRRT compared to CS- (for all, P < 0.05). Central systolic, central mean, and central end-systolic blood pressures were significantly higher in CS+ than in CS- (for all, P < 0.05). Subjects with grades 2-4 TR had higher hepatic tumour burden, fP-CgA, and S-5-HIAA compared to those with grades 0-1 TR, but measures of vascular function did not differ. fP-CgA (P = 0.017) and S-5-HIAA (P = 0.019) but not proBNP increased significantly according to the severity of TR., Conclusion: Although CS is common, the prevalence of CHD was found to be lower in a contemporary cohort of SI-NET patients than previously anticipated. Measures of arterial or endothelial function or carotid atherosclerosis do not identify subjects with mild TR. Echocardiography remains the most sensitive means to diagnose CHD in CS patients with high tumour burden and elevated CgA and 5-HIAA., (© 2022. The Author(s).)

Carcinoid heart disease (CHD) is a severe complication of carcinoid syndrome (CS) found primarily in patients with small intestine neuroendocrine neoplasms (SI-NENs). Patients who develop CHD have significantly worse morbidity and mortality outcomes, highlighting the importance of clinical practice recommendations for CHD screening, diagnosis, and treatment that are both consistent and practical. CHD is characterized by white plaque-like deposits on the endocardial surface of heart structures, generally affecting the right heart valves, causing tricuspid and pulmonary regurgitation and, less commonly, valve stenosis. Cardiac imaging is essential for both the diagnosis and management of CHD. Previously, imaging for CHD was mostly achieved by echocardiography, but more recently, imaging has become multimodal. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 5-hydroxyindoleacetic acid in the urine (u5-HIAA) are currently the most effective markers used in screening CS patients and evaluating CHD severity. Managing patients with CHD is challenging since both systemic malignant disease and cardiac involvement must be treated concurrently. Early diagnosis and surgical intervention when required are critical to patient prognosis, especially in those without primary tumor resection. Valve replacement surgery is the most effective treatment for patients with advanced carcinoid heart disease for alleviating cardiac symptoms and contributing to survival outcomes. To deliver effective patient treatment, multidisciplinary team collaboration is needed. This review summarizes current research findings on CHD pathogenesis, clinical and epidemiological features, useful biomarkers and imaging modalities, and treatment strategies.

Background: Carcinoid heart disease (CHD) is a rare complication of hormonally active neuroendocrine tumors that often requires surgical intervention. Data on cardiac implantable electronic device (CIED) implantation in patients with CHD are limited., Objective: The purpose of this study was to evaluate the experience of CIED implantation in patients with CHD., Methods: Patients with a diagnosis of CHD and a CIED procedure from January 1, 1995, through June 1, 2020, were identified using a Mayo Clinic proprietary data retrieval tool. Retrospective review was performed to extract relevant data, which included indications for implant, procedural details, complications, and mortality., Results: A total of 27 patients (55.6% male; mean age at device implant 65.6 ± 8.8 years) with cumulative follow-up of 75 patient-years (median 1.1 years; interquartile range 0.4-4.6 years) were included for analysis. The majority of implanted devices were dual-chamber permanent pacemakers (63%). Among all CHD patients who underwent any cardiac surgery, the incidence of CIED implantation was 12%. The most common indication for implantation was high-grade heart block (66.7%). Device implant complication rates were modest (14.8%). No patient suffered carcinoid crisis during implantation, and there was no periimplant mortality. Median time from implant to death was 2.5 years, with 1-year mortality of 15%., Conclusion: CHD is a morbid condition, and surgical valve intervention carries associated risks, particularly a high requirement for postoperative pacing needs. Our data suggest that CIED implantation can be performed relatively safely. Clinicians must be aware of the relevant carcinoid physiology and take appropriate precautions to mitigate risks., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Neuroendocrine tumors (NETs, originally termed &#8220;carcinoids&#8221;) create a relatively rare group of neoplasms with an approximate incidence rate of 5 to 8 cases per 10 000 persons. NETs predominantly demonstrate indolent disease biology for many years. They become symptomatic when they are large enough or when they metastasize to the liver or the lungs, bones, or other sites. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome. Signs and symptoms of carcinoid syndrome are bronchospasm, flushing, diarrhea and cramping, cyanosis and pellagra. White plaque-like deposits on the endocardial surface of heart structures are characteristic for carcinoid heart disease. The treatment of patients with carcinoid syndrome is multi-faceted due to the necessity to manage simultaneously the systemic cancer disease as well as the signs of carcinoid syndrome and includes resection or debulking of tumor mass, biological treatment with somatostatin analogues and peptide receptor radionuclide treatment.

Carcinoid heart disease (CHD) is a paraneoplastic cardiac manifestation occurring in patients with carcinoid syndrome (CS) and advanced neuroendocrine malignancy. In about 20-40% of patients with CS, chronic exposure to tumor-released circulating vasoactive peptides typically results in right-sided valvular fibrosis leading to valve dysfunction and right heart failure. CHD remains a significant cause of morbidity and mortality. The management of patients with CHD is complex, as both the systemic malignant disease and the heart involvement have to be addressed. Early diagnosis and timely surgical intervention in selected patients are of utmost importance and offer a survival benefit. In patients with advanced carcinoid heart disease, valve replacement surgery is the most effective option to alleviate cardiac symptoms and contribute to survival outcomes. A collaboration of a multidisciplinary team in centers with experience is required to provide optimal patient management. Here, we review the current literature regarding CHD presentation, pathophysiology, diagnostic tools, and available treatment strategies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Carcinoid heart disease (CaHD) develops from vasoactive substances released by neuroendocrine tumors, which can cause significant patient morbidity and mortality without surgical intervention. We performed a systematic review and meta-analysis to elucidate granular perioperative details and long-term outcomes in these patients., Methods: Electronic search of Ovid, Scopus, Cumulative Index of Nursing and Allied Health Literature, and Cochrane Controlled Trials Register was performed to examine surgical treatment of carcinoid disease. Nine articles comprising 416 patients were selected. Study-level data were extracted and pooled for meta-analysis., Results: Mean patient age was 63 years (95% confidence interval, 57-70) with 53% (95% confidence interval, 46-61) of patients being male. In addition, 75% (95% confidence interval, 54-96) of neuroendocrine tumors originated from the small bowel or colon and 98% (95% confidence interval, 93-100) had liver metastases. Right heart failure was present in 48% (95% confidence interval, 14-81). Moderate or severe regurgitation was present in 97% (95% confidence interval, 95-99) of tricuspid and 72% (95% confidence interval, 58-83) of pulmonary valves. In addition, 99% (95% confidence interval, 98-100) of tricuspid and 59% (95% confidence interval, 38-79) of pulmonary valves were replaced. Bioprosthetic valves were used in 80% (95% confidence interval, 68-93) of tricuspid positions. Mean hospital duration of stay was 16 days (95% confidence interval, 7-25). Thirty-day mortality was 9% (95% confidence interval, 6-12). Mean follow-up was 25 months (95% confidence interval, 11-39). Median survival was 3 years (95% confidence interval, 2.5-3.5)., Conclusion: For patients >18 years of age, surgical treatment of carcinoid heart disease can be performed with a reasonable safety profile. However, overall survival appears to have ongoing effects of the primary disease., (Copyright © 2021. Published by Elsevier Inc.)

Carcinoid heart disease is a complex clinical entity frequently complicating the course of neuroendocrine tumors and carcinoid syndrome and is associated with significant morbidity and mortality. Although the pathogenesis of carcinoid heart disease remains poorly understood, it appears that the exposure to excessive circulating levels of serotonin contribute a key role, triggering a cascade of events that ultimately results in the development of plaque-like material on the endocardial surfaces of the valve leaflets. The occurrence of carcinoid heart disease may initially run an asymptomatic period, followed by the development of symptoms of congestive cardiac failure. The diagnosis of carcinoid heart disease is suspected by raised biomarkers, such as serum NT-pro-BNP and confirmed by imaging modalities, with echocardiogram being the gold standard to date. Carcinoid heart disease treatment remains challenging as in addition to cardiac dysfunction, tumor burden needs to be tackled with, hence requiring a multidisciplinary approach. Therapy comprises watchful waiting during the first initial stages of the disease; medications for heart failure; optimal control of serotonin secretion from the NET with pharmacotherapy, interventional means or even surgical techniques; and, in selected patients, cardiac valve replacement. The current review summarizes the literature on the diagnosis and management of carcinoid heart disease., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose of Review: The development of carcinoid heart disease (CHD) is a fibrotic complication of neuroendocrine neoplasms (NEN) which is associated with a poor prognosis. This review aims to summarise the clinical features, investigations and management of this condition., Recent Findings: CHD can affect up to 50% of NET patients with carcinoid syndrome. However, it is often not screened for appropriately and recognised late when patients become symptomatic. A screening strategy with biomarkers and multimodality imaging is necessary for early recognition. Management by an experienced multidisciplinary team with appropriate medical therapeutic strategies and where indicated surgical intervention is needed to optimise clinical outcomes. CHD is a poor prognostic factor, but recently, outcomes have improved due to the multidisciplinary approach and centralised care of CHD-NET patients.

Background: Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality., Methods: MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes., Results: Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3-65% and 3-42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266-1,381 versus 67.5-575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791-2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase)., Conclusions: Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Competing Interests: Competing interests: None declared.

Purpose of Review: Carcinoid heart disease is a rare disorder that is associated with significant morbidity and mortality. In this review of the literature, we will present current concepts in diagnosis and management of carcinoid heart disease., Recent Findings: Recent expert consensus guidelines highlight the role of echocardiography and screening with NT-proBNP for the evaluation of carcinoid heart disease. Advances in medical therapy along with better surgical outcomes highlight the experience and expertise that has been gained in the treatment of carcinoid heart disease. Carcinoid heart disease occurs in patients with neuroendocrine tumors who have carcinoid syndrome. Serotonin appears to play a central role in the development of carcinoid heart disease. Cardiac biomarkers and multimodality imaging can be used to aid in screening and diagnosis. The mainstay of treatment of carcinoid heart disease is surgery.

Carcinoid heart disease is the collective term for all cardiac manifestations that develop in patients with carcinoid. The cardiac manifestations of carcinoid tumors are attributed to the paraneoplastic effects of vasoactive substances released by the malignant cells. The clinical manifestations of carcinoid heart disease include valvular destruction leading to valvular regurgitation and stenosis, right-sided heart failure, and metastatic carcinoid disease. A combination of biomarkers and cardiac imaging is used in screening and diagnosis of carcinoid heart disease in patients with carcinoid syndrome. The management of carcinoid heart disease involves medical and surgical treatment and requires a multidisciplinary approach for optimized care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Development of carcinoid heart disease (CHD) is the major negative prognostic factor in patients with the carcinoid syndrome. The only effective treatment is valve replacement. However, the selection of candidates and determination of optimal timing remain unclear. Considerable variability in local screening and treatment strategies exist. Methods: In this single-centre study, we retrospectively analysed the diagnostic process and outcome of all CHD patients who underwent valve surgery between 2000 and 2016. We propose a new CHD screening and management algorithm. Results: All patients ( n  = 15), mean age 64 ± 7, underwent tricuspid valve surgery. In 14 of them (93%) an additional valve was replaced. In only a minority of patients (27%) CHD diagnosis was established by screening. Survival after 1, 3, 12 and 24 months was 93%, 80%, 53% and 33%, respectively. Causes of death included infections and critical illness immediately postoperatively, and tumour progression and right heart failure in the longer term. There was a trend ( p  = .099) towards better preoperative right ventricular function in the patients who survived more than 12 months postoperatively (TAPSE 20 mm ± 4) compared to those who died between 3 to 12 months after surgery (TAPSE 16 mm ± 1). The former group had a shorter mean interval from diagnosis of the carcinoid syndrome to cardiac diagnosis than the latter (13 vs. 105 months, p  = .014). Conclusion: Mortality after valve replacement for CHD remains high. A probably underestimated cause is late referral for cardiac surgery. We propose a systematic, multidisciplinary approach to all carcinoid syndrome patients.

Carcinoid heart disease is the collective term for all cardiac manifestations in patients who have carcinoid syndrome. Carcinoid heart disease has a multifactorial pathophysiology, and the right side of the heart is usually involved. Symptoms and signs vary depending upon the affected cardiac components; most typical is right-sided heart failure secondary to diseased tricuspid and pulmonary valves. Despite no single ideal diagnostic test, strong suspicion, coupled with serologic and imaging results, usually enables diagnosis. Advances in imaging, such as speckle-tracking echocardiography and cardiac magnetic resonance, have improved the diagnostic yield. Treatment is challenging, warrants a multidisciplinary approach, and can be medical or surgical depending on the cardiac manifestations. Investigators are exploring the therapeutic use of monoclonal antibodies and new somatostatin analogues. In this review, we cover current knowledge about the pathophysiology, diagnosis, and treatment of carcinoid heart disease.

Objectives: To quantify healthcare resource use (HRU) and costs in relation to carcinoid syndrome (CS) and carcinoid heart disease (CHD) in a real-world setting, and to provide perspective on treatment patterns., Materials and Methods: Patient data and HRU were collected retrospectively from three Swedish healthcare registers. Adult patients diagnosed with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) grade 1 or 2 and CS who purchased somatostatin analogs (SSAs), and experienced controlled (defined by SSAs use) and uncontrolled (defined by SSAs dose escalation) CS for ≥8 months during the study period were included. Patients diagnosed with CHD from the date of the GEP-NET diagnosis were included in the CHD study group., Results: Overall, total HRU cost increased with uncontrolled CS and CHD. Total resource cost was 15,500€/patient during controlled CS (8 months), rising to 21,700€/patient during uncontrolled CS (8 months), representing an increase of ∼40% (6200€/patient). Costs/patient were driven mainly by SSA use, tumor-related medical interventions and examinations. The total mean cost/year of disease was 1100€/patient without CHD, compared to 4600€/patient with CHD, a difference of 3500€/patient. Excluding SSA cost burden, the main drivers of increased cost in CHD patients were surgical interventions and echocardiography., Conclusions: This study provides a comprehensive overview of the treatment patterns and burden of uncontrolled CS symptoms and CHD using Swedish national register data. Increases in medical interventions and examinations HRU and increased SSA use suggest that SSA dose escalation alone may not effectively control the symptoms associated with uncontrolled CS, highlighting an unmet treatment need in this patient group.

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.)

Carcinoid heart disease remains a major cause of morbidity and mortality among patients with carcinoid syndrome and metastatic neuroendocrine tumors. Screening of all patients with N-terminal pro-B-type natriuretic peptide and transthoracic echocardiography is critical for early detection, as early symptoms and signs have low sensitivity for the disease. Cardiac surgery, in appropriate cases, is the only definitive therapy for advanced carcinoid heart disease, and it improves patient symptoms and survival. Management of carcinoid heart disease is complex, and multidisciplinary assessment of cardiac status, hormonal syndrome, and tumor burden is critical in guiding optimal timing of surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

BACKGROUND Carcinoid tumor, benign, low-grade malignant, and high-grade malignant, can be associated with the release of vasoactive substances that cause symptoms including cutaneous flushing, diarrhea, and bronchospasm. In 50-60% of patients with carcinoid syndrome, the vasoactive substances cause fibrosis of the pulmonary and tricuspid heart valves which lead to regurgitation and right-sided heart failure. The right side of the heart is usually affected because monoamine oxidases in the lungs usually inactivate the vasoactive substances. CASE REPORT A 62-year-old woman presented with a four-month history of diarrhea and abdominal discomfort. The patient had bilateral pelvic masses and elevated serum CA125 and an elevated urinary 5-hydroxyindoleacetic acid (5-HIAA). Total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) identified a primary appendiceal carcinoid tumor with bilateral ovarian metastases. Post-operatively, a computed tomography (CT) scan showed cardiomegaly. Transthoracic echocardiography showed morphologic changes that affected all four heart valves, consistent with carcinoid heart disease but without a patent foramen ovale (PFO). The patient was evaluated for valve replacement surgery, but surgery was not performed due to the degree of heart failure. CONCLUSIONS This report describes a rare case of carcinoid heart disease with involvement of all four cardiac valves, but without the presence of a PFO, possibly due to a large amount of vasoactive substances in the patient's circulation, as supported by the patient's elevated urinary 5-HIAA. This rare presentation highlights the importance of early diagnosis and treatment with tumor resection and, if possible, Cardiac valve replacement to prevent irreversible heart failure.

Aim: To describe the early outcomes of carcinoid patients undergoing surgical heart valve replacement., Methods: In a retrospective study, records of patients with symptomatic carcinoid heart disease referred for valve surgery between 2012 and 2016 were reviewed. The perioperative and early postoperative outcomes were analyzed., Results: Nine patients, with a mean age of 61 years (range 55-70 years) underwent cardiac surgery for carcinoid syndrome. 3 patients had quadruple valve replacement, 5 had tricuspid and pulmonary valves changed, while one had tricuspid, pulmonary, and aortic valves replaced. Right-sided valves were replaced with biological valves in 8 patients and a mechanical valve in 1 patient. Left-sided valves were replaced with a mechanical valve in 2 patients and with a biological valve in 1 patient. Mean postoperative follow-up was 24 months (range 6-50 months, median 16 months). All patients had a good left ventricle except one, in whom it was mildly impaired. The right ventricle was severely dilated in 4 patients, moderately in 2, and mildly in 3. One patient died of heart failure 10 days postoperatively. Functional improvement was noted in all survivors, and they were in New York Heart Association class I at last follow up., Conclusion: Although carcinoid syndrome is a rare and progressive disease, valve replacement in symptomatic patients is a reasonable option with survival benefit, low early postoperative mortality, without valve-related complications, and with functional improvement. Cardiac assessment is required in all patients with carcinoid disease from the earliest time of medical treatment to improve patients' result.

Background: Carcinoid heart disease is a frequent complication of carcinoid syndrome. It is related to the release by the carcinoid tumor and/or its metastases of bioactive substances such as serotonin. It is characterized by right-sided valvular involvement and can lead to right-sided heart failure. It is a prognostic factor of carcinoid syndrome., Case Presentation: We report the case of a 53-year-old African woman with an endocrine tumor of her small intestine complicated by carcinoid heart disease, revealed by right-sided heart failure. The diagnosis was confirmed by transthoracic echocardiography, which showed a severe tricuspid regurgitation with a patent foramen ovale, and by increased serum chromogranin A and urinary 5-hydroxyindoleacetic acid. Initially she was treated with medical therapy (furosemide and injection of somatostatin). Afterwards she was proposed for surgery. The evolution of her treatment was good., Conclusions: Carcinoid syndrome is complicated in 60% of the cases of a heart disease, and is responsible for an important morbidity and mortality. The prognosis of patients with carcinoid heart disease has improved in recent years through somatostatin analogues and the cardiac surgery.

Neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasms. These tumors can produce a wide variety of hormones that can lead to syndromes of hormone excess, such as carcinoid syndrome. We present the case of a 47-year-old man who presented with right upper quadrant abdominal pain and emesis. He was found to have metastatic pancreatic NET and was treated with systemic chemotherapy. He subsequently developed dyspnea on exertion and was found to have severe right-sided heart disease secondary to elevated levels of serum serotonin. He was successfully treated with surgical tricuspid and pulmonic valve replacement. True carcinoid syndrome with pancreatic NETs is rare, but, as a treatable complication of the disease, is an important entity for which oncologists should be familiar.

Rare neuroendocrine tumours (NETs) that most commonly arise in the gastrointestinal tract can lead to carcinoid syndrome and carcinoid heart disease. Patients with carcinoid syndrome present with vasomotor changes, hypermotility of the gastrointestinal system, hypotension and bronchospasm. Medical therapy for carcinoid syndrome, typically with somatostatin analogues, can help control symptoms, inhibit tumour progression and prolong survival. Carcinoid heart disease occurs in more than 50% of these patients and is the initial presentation of carcinoid syndrome in up to 20% of patients. Carcinoid heart disease has characteristic findings of plaque-like deposits composed of smooth muscle cells, myofibroblasts, extracellular matrix and an overlying endothelial layer which can lead to valve dysfunction. Valvular dysfunction can lead to oedema, ascites and right-sided heart failure. Medical therapy of carcinoid heart disease is limited to symptom control and palliation. Valve surgery for carcinoid heart disease should be considered for symptomatic patients with controlled metastatic carcinoid syndrome. A multidisciplinary approach is needed to guide optimal management., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) 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.)