Management of carcinoid heart disease.

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.

Rare Case of Neuroendocrine Metastasis to the Left Ventricle.

Carcinoid syndrome is a constellation of signs and symptoms caused by different hormones produced by carcinoid tumors. Very rarely, those tumors can metastasize to the heart and cause cardiac involvement of the tumor. This study presents a very rare case of secondary cardiac tumor affecting the left ventricle from a metastatic carcinoid tumor originating from the small intestine without carcinoid valvular heart disease.

Carcinoid Heart Disease and a Complicated Course of Progressive Gastroenteropancreatic Neuroendocrine Neoplasia: A Case Report.

Introduction: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a relatively rare, heterogenous group of malignancies originating from secretory cells of the neuroendocrine system. Carcinoid syndrome is a complication of neuroendocrine tumours, characterized by a triad of flushing, bronchospasm, and diarrhoea. This is due to the release of serotonin and other vasoactive substances by the tumour. Elevated levels of serotonin can also cause fibrotic changes in the structures of the heart, which can lead to cardiac complications termed carcinoid heart disease. We report the case of a 64-year-old man diagnosed with carcinoid heart disease 19 years after his initial diagnosis of grade 2 GEP-NET with liver metastases. Case Presentation: The patient presented with symptoms of shortness of breath, lower limb swelling, abdominal swelling, and chest pain. He was on treatment with subcutaneous lanreotide 120 mg twice weekly prior to admission. An echocardiogram showed moderate tricuspid regurgitation and mitral regurgitation but preserved left ventricular systolic function, consistent with right heart failure. A CT pulmonary angiogram showed a small volume left lingula pulmonary embolism with bilateral pleural effusions and stable pericardial effusion with evidence of right ventricular strain. The patient was started on IV furosemide 40 mg twice daily, SC octreotide 100 µg three times daily, and therapeutic tinzaparin. The patient was discharged following successful diuresis. Conclusion: This case report highlights the importance of regular echocardiogram and cardiovascular checkups in patients with carcinoid tumours and liver metastases. A multidisciplinary approach involving medical oncologists, cardiothoracic surgeons, and cardiologists is vital in ensuring early treatment and preventing late-stage complications of carcinoid heart disease.

Anesthetic key points in a patient with a terminal ileum neuroendocrine tumor and a rare carcinoid left heart disease presented for non-cardiac surgery: case report.

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.

Left ventricular myxoma with carcinoid heart disease: A case report of a 14-year-old child from Jimma Medical Center of Ethiopia.

Understand the importance of considering alternative diagnosis in patients presenting with atypical features, specially when they are not responding to the standard treatment. Understand the importance of considering common presentations of rare cases. Underscoring the critical importance of timely recognition and appropriate management of potentially life-threatening conditions.

Screening for carcinoid heart disease: Trends and future Perspectives.

Background: Screening for carcinoid heart disease (CHD), has historically lacked consensus expert guidelines. In 2017, the North American Neuroendocrine Tumor Society (NANETS) released expert recommendations for CHD screening among NET patients to improve CHD detection. The objective of this study is to evaluate CHD screening trends and utility of screening guidelines over more than two decades at a single tertiary care center. Materials and methods: Patients with NETs referred for abdominal surgical evaluation at a single tertiary care center were included, 300 patients from 1999 to 2018 and 34 patients from 2021 to 2022. Lab values for the following NANETS-proposed criteria at any point during their treatments were recorded: NETs with liver metastasis, blood serotonin >5 times upper limit of normal (>1000 ng/mL), NT-ProBNP >260 pg/mL and clinical features suggestive of CHD. Results: 85 % (285/334) of patients included in this study met one or more expert-recommended CHD screening criteria. However, 40 % (132/285) of patients meeting one or more criteria received CHD screening via echocardiogram at some point following NET diagnosis. While rates of screening for patients increased from the first decade to the second decade (32 % vs 40.6 %), the rates were much higher after guideline publication (70 %, 24/34). Furthermore, patients meeting multiple screening criteria were more likely to have evidence of structural valve disease. Conclusions: Results of this study suggest that utilization of these four expert-recommended screening criteria have greatly increased rates of CHD screening via echocardiogram and could assist in improving early CHD detection, especially for patients meeting multiple criteria.

Carcinoid Heart Syndrome With Metastatic Low-Grade Neuroendocrine Tumor of the Liver: A Rare Case.

We present a rare and complex case of a 76-year-old male patient with a history of low-grade neuroendocrine tumor (NET) of the small intestine, status post resection, who presented with recurrence of the tumor in the liver and subsequent carcinoid heart syndrome (CHS). The recurrent liver tumor caused severe tricuspid regurgitation and CHS, highlighting the rare association between NETs and CHS, particularly in the elderly population. This case underscores the importance of multidisciplinary care and close monitoring for patients with recurrent NETs and potential cardiac complications.

Carcinoid syndrome with right-sided valve involvement - a case report and review of the literature.

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 Heart Disease With Hypoxemia.

Patent foramen ovale (PFO) complicated with carcinoid heart disease (CHD) can cause severe hypoxia and worsening clinical conditions. We report the case of a patient with CHD in poor general condition with multiple severe valve regurgitations and PFO, who underwent successful percutaneous closure of the PFO.

A systematic review and meta-analysis of the diagnosis and surgical management of carcinoid heart disease.

Introduction: Carcinoid heart disease (CHD), a complication of carcinoid syndrome (CS), is a rare condition that can lead to right sided valvular heart disease and has been traditionally associated with a poor prognosis. We conducted a systematic review and meta-analysis to explore the accuracy of biomarkers and echocardiography in diagnosing CHD amongst patients who are already known to have neuroendocrine tumours and to assess whether surgical management of CHD leads to a reduction in mortality. Methods: A systematic literature search of MEDLINE, EMBASE, EBM Reviews, Google Scholar, ClinicalTrials.gov was conducted. All studies on patients with carcinoid heart disease (CHD) reporting on biomarkers, echocardiographic and surgical outcomes were included. The National Heart, Lung, and Blood Institute quality assessment tool was used to assess the methodological study quality. Data analysis was performed using Stata Statistical Software and R Studio, and individual meta-analyses were performed for biomarkers, echocardiographic findings, and surgical outcomes. Results: A total of 36 articles were included in the systematic review analysis. N terminal pro-brain natriuretic peptide (NTproBNP) and 5-hydroxyindole acetate (5-HIAA) levels were higher in patients with CHD compared with those without CHD. 32% of CS patients had echocardiographic evidence of cardiac involvement, of which 79% involved tricuspid valve abnormalities. Moderate-severe tricuspid regurgitation was the most common echocardiographic abnormality (70% of patients). However, these analyses had substantial heterogeneity due to the high variability of cardiac involvement across studies. Pooled surgical mortality for CHD was 11% at 1 month, 31% at 12 months and 56% at 24 months. When assessing surgical outcomes longitudinally, the one-month surgical results showed a trend towards more recent surgeries having lower mortality rates than those reported in earlier years, however this was not statistically significant. Discussion: There is not enough data in current literature to determine a clear cut-off value of NTproBNP and 5-HIAA to help diagnose or determine CHD severity. Surgical management of CHD is yet to show significant mortality benefit, and there are no consistent comparisons to medical treatment in current literature.

Managing end-stage carcinoid heart disease: A case report and literature review.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors, often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients' quality of life. Cardiovascular complications of GEP-NENs, primarily tricuspid and pulmonary valve disease, and right-sided heart failure, are the leading cause of death, even compared to metastatic disease. CASE SUMMARY: We present a case of a 35-year-old patient with progressive dyspnea, back pain, polyneuropathic leg pain, and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases. During the initial presentation, serum biomarkers were not evaluated, and the patient received five cycles of doxorubicin, which he did not tolerate well, so he refused further therapy and was lost to follow-up. After 10 years, he presented to the emergency room with signs and symptoms of right-sided heart failure. Panneuroendocrine markers, serum chromogranin A, and urinary 5-hydroxyindoleacetic acid were extremely elevated (900 ng/mL and 2178 µmol/L), and transabdominal ultrasound confirmed hepatic metastases. Computed tomography (CT) showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis. Furthermore, an Octreoscan showed lesions in the heart, thoracic spine, duodenum, and ascendent colon. A standard transthoracic echocardiogram confirmed findings of carcinoid heart disease. The patient was not a candidate for valve replacement. He started octreotide acetate treatment, and the dose escalated to 80 mg IM monthly. Although biochemical response and symptomatic improvement were noted, the patient died. CONCLUSION: Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors, usually with liver metastases, which manifests as right-sided heart valve dysfunction leading to right-sided heart failure. Carcinoid heart disease and tumor burden are major prognostic factors of poor survival. Therefore, they must be actively sought by available biochemical markers and imaging techniques. Moreover, imaging techniques aiding tumor detection and staging, somatostatin receptor positron emission tomography/CT, and CT or magnetic resonance imaging, should be performed at the time of diagnosis and in 3- to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery. Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered, while any delay can worsen right-sided ventricular failure.

Does Telotristat Have a Role in Preventing Carcinoid Heart Disease?

Carcinoid heart disease (CHD) is a frequent and life-threatening complication in patients with carcinoid tumors. Its clinical management is challenging is some cases since serotonin-induced valve fibrosis leads to heart failure. Telotristat is an inhibitor of tryptophan-hydroxylase (TPH), a key enzyme in serotonin production. Telotristat use in patients with carcinoid syndrome and uncontrollable diarrhea under somatostatin analogs is approved, but its specific role in patients with CHD is still not clear. IN this context, we aimed to explore the effect of telotristat in heart fibrosis using a mouse model of serotonin-secreting metastasized neuroendocrine neoplasm (NEN). To this aim, four treatment groups (n = 10/group) were evaluated: control, monthly octreotide, telotristat alone, and telotristat combined with octreotide. Plasma serotonin and NT-proBNP levels were determined. Heart fibrosis was histologically evaluated after 6 weeks of treatment or when an individual mouse's condition was close to being terminal. Heart fibrosis was observed in all groups. Non-significant reductions in primary tumor growth were observed in all of the treated groups. Feces volume was increased in all groups. A non-significant decrease in feces volume was observed in the octreotide or telotristat-treated groups, while it was significantly reduced with the combined treatment at the end of the study compared with octreotide (52 g reduction; p < 0.01) and the control (44.5 g reduction; p = 0.05). Additionally, plasma NT-proBNP decreased in a non-significant, but clinically relevant, manner in the octreotide (28.2% reduction), telotristat (45.9% reduction), and the octreotide + telotristat (54.1% reduction) treatment groups. No significant changes were observed in plasma serotonin levels. A similar non-significant decrease in heart valve fibrosis was observed in the three treated groups. In conclusion, Telotristat alone and especially in combination with octreotide decreases NT-proBNP levels in a mouse model of serotonin-secreting metastasized NEN, when compared with the control and octreotide, but its effect on heart valve fibrosis (alone and in combination) was not superior to octreotide in monotherapy.

Plasma or serum 5-hydroxyindoleacetic acid can be used interchangeably in patients with neuroendocrine tumours.

5-hydroxyindole acetic acid, a metabolite of serotonin, is used in the diagnosis and monitoring of patients with neuroendocrine tumours, in particular patients with small intestinal neuroendocrine tumours associated with the carcinoid syndrome. Analysis of 5-hydroxyindole acetic acid was commonly performed in urine, but blood-based assays are now becoming available. The objective of this study was to assess how 5-hydroxyindole acetic acid compares in plasma and serum as a biochemical marker of neuroendocrine tumours. Twenty-four-hour urine, plasma and serum samples were obtained from 80 patients with neuroendocrine tumours and 30 healthy volunteers. We developed a liquid chromatography tandem mass spectrometry assay for plasma and serum 5-hydroxyindole acetic acid. Comparison was made between them, and their cut-off was determined using a receiver-operating characteristic curve. A close correlation was shown between plasma and serum 5-hydroxyindole acetic acid. At a cut-off of 135 nmol/l, a sensitivity of 91.2% with a specificity of 61.9% was obtained for both compared to the urinary assay. A statistically significant agreement was shown when plasma and serum 5-hydroxyindole acetic acid were compared with the currently used urine assay in patients with neuroendocrine tumours; κ = 0.675 (95% CI 0.49 to 0.86), p < 0.001 and healthy volunteers; 0.967 (95% CI 0.828 to 0.999), p = <0.001. In conclusion, 5-hydroxyindole acetic acid in plasma and serum were comparable, hence either sample type can be used interchangeably.

Hedinger Syndrome-Lessons Learnt: A Single-Center Experience.

BACKGROUND: Hedinger syndrome (HS) or carcinoid heart disease (CD) is a rare and challenging manifestation of malignant neuroendocrine tumours (NETs) involving the heart. We aimed to report our experience with surgical strategies and midterm results in HS patients. METHODS: Eleven patients (58 ± 11 (range 41 to 79 years); 5 females) with HS who underwent cardiac surgery in our department between 07/2005 and 05/2023 were analysed. RESULTS: All patients showed a New York Heart Association (NYHA) class III-IV and in all the tricuspid valve (TV) was involved. Four patients received a TV replacement, and three TV reconstruction. Recently, to preserve the geometry and function of the compromised right ventricle (RV), we have applied the TV "bio-prosthesis in native-valve" implantation technique with the preservation of the valve apparatus (tricuspid valve implantation: TVI) in four cases. Concomitant procedures included pulmonary valve replacement in four, pulmonary implantation in one, and aortic valve replacement in three cases. To treat RV failure, we adapted a combined TandemHeart®-CytoSorb® haemoperfusion strategy in Patient #10 and venoarterial extracorporeal membrane oxygenation (V-A ECMO) support avoidance, after experiencing an ECMO-induced carcinoid-storm-related death in Patient #8. Mortality at 30 days was 18% (2/11). The median follow up was 2 ± 2.1 years (range 1 month to 6 years) with an overall mortality during the follow-up period of 72.7% (8/11). CONCLUSIONS: HS surgery, despite being a high-risk procedure, can efficiently prolong survival, and represents a safe and feasible procedure. However, patient selection seems to be crucial. Further follow up and larger cohorts are needed.

Quadruple Valve Replacement in Carcinoid Heart Disease: A Case Report.

This report details a rare case of left-sided carcinoid heart disease (CHD). In CHD, vasoactive substances released from carcinoid tumors cause fibrous tissue formation on the right side of the heart. These substances are usually inactivated by monoamine oxidase A in the lungs, safeguarding the left side of the heart. Exceptions include the presence of a patent foramen ovale (PFO), pulmonary metastasis, or elevated serotonin levels. Intriguingly, our patient exhibited significant left-sided involvement without these factors, ultimately requiring a quadruple valve replacement surgery. After eight months post-operation, the patient is stable with no cardiovascular complications. This rare case of CHD, along with its outcome, hints at potential unidentified etiologies for left-sided CHD and underscores valve replacement as a viable treatment.

Metastatic well differentiated serotonin-producing pancreatic neuroendocrine tumor with carcinoid heart disease: a case report.

Background: Less than two percent of pancreatic neuroendocrine tumors (NETs) produce serotonin. Serotonin can cause carcinoid syndrome and less commonly carcinoid heart disease (CHD). CHD is associated with increased mortality and requires a more aggressive approach. Here we present a rare case of a serotonin-producing pancreatic NET complicated by CHD at presentation and discuss timing of systemic therapy, liver-directed therapy, and heart failure management. Case Description: A 36-year-old white man presented with diarrhea, lower extremity edema, and exertional dyspnea. He was found to have a well-differentiated serotonin-producing pancreatic NETs grade three with bilobar liver metastasis complicated by carcinoid syndrome and CHD. His symptoms and disease burden improved with somatostatin analog and liver-directed therapy with bland embolization to control carcinoid symptoms and obtain rapid hormonal control to prevent progression of CHD. He concurrently received diuretics to manage his heart failure and was considered for valvular replacement surgery, which was deferred for optimal hormonal control. Conclusions: Our case highlights the importance of multidisciplinary care for patients with pancreatic NETs and early identification and management of CHD. Although uncommon, serotonin-producing pancreatic NETs can present with CHD and require combination of somatostatin analogs, liver-directed therapy, and heart failure management.

Patent foramen ovale in carcinoid heart disease: The potential role for and risks of percutaneous closure prior to cardiothoracic surgery.

Neuroendocrine tumours (NETs) are rare but once metastasised, can lead to the release of vasoactive substances into the systemic circulation, and the classical features of carcinoid syndrome (CS) such as flushing and diarrhoea. A consequence of CS is carcinoid heart disease (CHD) which primarily affects the right-sided heart valves and can eventually lead to right heart failure. In this cohort, tricuspid and/or pulmonary valve replacement provides symptomatic relief. A patent foramen ovale (PFO) in patients with CHD can lead to the shunting of oxygen deficient blood to the systemic circulation causing hypoxaemia and reduced exercise tolerance. Additionally, the haemodynamic changes caused by regurgitant right-sided heart valves can increase the patency of a PFO allowing the passage of vasoactive substances to the systemic circulation thereby affecting the left-sided heart valves. We present data on the incidence of PFO in patients referred for surgery at our centre, in which the standard approach is to close the defect at time of cardiothoracic surgery. In addition, we present a series of four cases that highlight how the option of percutaneous PFO closure prior to open valve surgery may reduce haemodynamic instability and open a window of opportunity to enhance preoperative status. Percutaneous PFO closure then acts as a bridge to definitive cardiothoracic surgery, although there are risks in such an approach.