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.

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.

Carcinoid Heart Disease Management: A Multi-Disciplinary Collaboration.

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.

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.

Current Practice in Carcinoid Heart Disease and Burgeoning Opportunities.

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.

WITHDRAWN: Dealing With the Right Side: Carcinoid Heart Disease.

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.

Update in carcinoid heart disease - the heart of the matter.

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.

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review.

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.

Carcinoid Heart Disease: a Review.

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.

Interventional Strategies in Cancer-induced Cardiovascular Disease.

PURPOSE OF REVIEW: To highlight the range of illnesses and procedures that the interventional onco-cardiologists face in their daily practice, along with the recent additions to anti-cancer therapies and their related cardiotoxicity. RECENT FINDINGS: Immune checkpoint inhibitors (ICI) are not devoid of cardiotoxicity as thought earlier and lead to an increased incidence of myocarditis. Transcatheter valve replacement has been shown to be a safer alternative to surgical replacement in cancer patients. Interventional onco-cardiology is a novel field that addresses cardiovascular diseases in the setting of cancer. Traditionally excluding cancer patients from clinical trials has led to a dearth of information needed to tackle cardiac conditions like Takotsubo cardiomyopathy, malignant pericardial effusions, and radiation-induced vascular diseases encountered either exclusively or predominantly in this high-risk population. This review discusses the various treatment options available in the interventional armamentarium with a particular focus on ICI-myocarditis and transcatheter aortic valve replacement in cancer patients.

Carcinoid Heart Disease: Pathophysiology, Pathology, Clinical Manifestations, and Management.

Carcinoid heart disease (CHD) is a rare and potentially lethal manifestation of an advanced carcinoid (neuroendocrine) tumor. The pathophysiology of CHD is related to vasoactive substances secreted by the tumor, of which serotonin is most prominent in the pathophysiology of CHD. Serotonin stimulates fibroblast growth and fibrogenesis, which can lead to cardiac valvular fibrosis. CHD primarily affects right heart valves, causing tricuspid and pulmonic regurgitation and less frequently stenosis of these valves. Left heart valves are usually spared because vasoactive substances such as serotonin are enzymatically inactivated in the lung vasculature. The pathology of CHD is characterized by plaque-like deposition of fibrous tissue on valvular cusps, leaflets, papillary muscles, chordae, and ventricular walls. Symptomatic CHD usually presents between 50 and 70 years of age, initially as dyspnea and fatigue. Echocardiography is the mainstay of imaging and demonstrates thickened right heart valves with limited mobility and regurgitation. Treatment focuses on control of the underlying carcinoid syndrome, targeting subsequent valvular heart disease and managing consequent heart failure. Surgical valve replacement and catheter-directed valve procedures may be effective for selected patients with CHD.

Surgical aspects of valve replacement in carcinoid heart disease.

Tricuspid and pulmonary valve replacement in patients with advanced carcinoid heart disease (CaHD) reduces right heart failure and improves prognosis. The surgical literature is limited concerning description of technical aspects of valve replacement in CaHD. Although a dedicated multidisciplinary care is required for these frail patients, optimization of surgical technique is important and may lead to better postoperative outcomes.

Three-dimensional echocardiography assessment of carcinoid valvular heart disease: Images of each and all.

A 54-year-old male was found to have neuroendocrine carcinoma with hepatic metastasis. Two-dimensional (2D) transthoracic echocardiography (TTE) demonstrated dilated right ventricle and right atrium, and severe tricuspid and pulmonary regurgitation. Three-dimensional (3D) TTE en-face views showed thickened, retracted, and fixed tricuspid valve and pulmonic valve which remained widely open throughout the cardiac cycle. 3D TTE, particularly en-face views, demonstrates incremental value over 2D TTE by providing precise valvular anatomic details comparable to surgical findings. 3D TTE also offers a unique opportunity to assess all four valves simultaneously with en-face views to delineate their relationships with surrounding structures.

Early Outcomes of Surgery for Carcinoid Heart Disease.

BACKGROUND: The prognosis of patients with metastatic neuroendocrine neoplasms (NEN) continues to improve with modern oncological therapy. In the subgroup of patients with carcinoid syndrome, the development of carcinoid heart disease (CaHD) severely impacts long term survival. Valve surgery has been demonstrated to improve survival and symptoms in patients with CaHD. We sought to assess the outcomes of surgery for CaHD from a single Neuroendocrine Service. METHODS: We retrospectively reviewed outcomes of patients with CaHD and metastatic NEN who underwent valvular surgery over a 4-year period (2012-2016). RESULTS: Twenty (20) patients (mean age 64 years, range 29-77 years), all with metastatic small intestinal NEN treated with somatostatin analogues, underwent surgery. Tumour grade was: G1 (n=8), G2 (n=9), and unknown (n=3). Preoperative New York Heart Association (NYHA) class was III/IV in 15 patients (75%). The valves affected were: tricuspid (n=20; 19 replace, 1 repair), pulmonary (n=14; 14 replace), mitral (n=2; two replace) and aortic valve (n=2; two replace). Concomitant procedures included patent foramen ovale closure (n=9), right ventricular outflow tract (RVOT) (n=4) augmentation and coronary artery bypass grafting (n=3). There were two operative deaths (10%) due to right heart and liver failure. At 6 weeks, all surviving patients had symptom improvement (NYHA I/II). Median follow-up was 2±1.5 years (<1 month to 5 years). One asymptomatic patient developed RVOT obstruction after pulmonary replacement. Two patients had valvular recurrence. One and 2-year survival were 74% and 48% respectively. Of 13 late deaths, 12 were cancer-related (two with uncorrected progressive pulmonary regurgitation). CONCLUSIONS: Surgery for CaHD can be performed with satisfactory early results, leading to an improvement of cardiac symptoms, survival and enabling subsequent oncologic treatment. Further studies are required to improve longer term outcomes in these complex patients with CaHD.

[Carcinoid heart disease]. / Grande clinique intégrée. La maladie cardiaque carcinoïde.

Carcinoid syndrome is the term applied to a constellation of symptoms mediated by a variety of humoral factors produced by the well-differentiated neuroendocrine tumours (NET) localised usually in the gastrointestinal tract and the lungs. This syndrome includes a characteristic triad of diarrhea, flushing and cardiac disease. This cardiopathy occurs in 20 % of the cases and prevails on the right side of the heart. It evolves to a potentially severe heart failure. Therefore, early diagnosis and appropriate cardiac care are crucial to improve the prognosis of these patients. We report a case of a carcinoid syndrome with a trivalvular insufficiency and cardiac decompensation which required surgical replacement of the tricuspid and aortic valves.

Le syndrome carcinoïde est l'éponyme qui englobe une constellation de symptômes médiés par divers facteurs humoraux élaborés par des tumeurs neuroendocrines (NET) bien différenciées, situées le plus souvent au niveau du tube digestif et des poumons. Dans sa forme classique, il comprend une triade caractéristique associant diarrhée, flush cutané et cardiopathie. Cette cardiopathie est présente dans 20 % des cas et prédomine sur le versant droit du coeur. Cette affection peut évoluer vers une insuffisance cardiaque potentiellement sévère. C'est pourquoi un diagnostic et une prise en charge précoce semblent essentiels pour améliorer le pronostic de ces patients. Nous rapportons un cas de syndrome carcinoïde avec une insuffisance trivalvulaire et une décompensation cardiaque ayant nécessité une intervention chirurgicale de remplacement des valves tricuspide et aortique.

Carcinoid Heart Disease: a Comprehensive Review.

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.

Pulmonary and tricuspid valvuloplasty in carcinoid heart disease.

A 26-year-old female with carcinoid heart disease consisting of severe pulmonary and tricuspid valve stenosis was admitted with line associated sepsis. She recovered from sepsis with antibiotics and aggressive fluid resuscitation but became grossly volume overloaded with evidence of tense ascites and lower extremity edema. She developed worsening renal and hepatic function due to congestive nephropathy and hepatopathy, which did not respond to intravenous diuretics, and she was deemed too sick for surgical pulmonary and tricuspid valve replacement. Pulmonary and tricuspid valvuloplasty was performed as a rescue measure to alleviate her congestive symptoms and improve her candidacy for valve replacement. © 2016 Wiley Periodicals, Inc.

Mesenteric Fibrosis in Midgut Neuroendocrine Tumors: Functionality and Radiological Features.

BACKGROUND: Mesenteric fibrosis (MF) surrounding a lymph node metastasis is a known phenomenon in midgut neuroendocrine tumors (NETs) with characteristic radiological appearance. Its etiology is poorly understood as it affects some but not all midgut NET patients with lymphatic involvement. This study assessed a potential relationship of MF with carcinoid syndrome, urinary 5-hydroxyindoleacetic acid (5-HIAA), and carcinoid heart disease (CHD). METHODS: A cohort of 81 patients with pathologically proven NETs with the primary site in the midgut and mesenteric lymphatic metastases on imaging were retrospectively included. Imaging characteristics of lymphatic and hepatic metastases at diagnosis (size, number, burden, and morphologic features, including presence of MF), Ki67 grading, 5-HIAA, functionality, and development of CHD were analyzed. RESULTS: Overall, 54% of patients had MF. The presence of MF was more frequently associated with mesenteric vessel encasement (100 vs. 46% without MF; p < 0.001), presence of hepatic metastases (91 vs. 62%; p = 0.002), larger hepatic tumor burden (15 vs. 5%; p = 0.001), and functionality (86 vs. 43%; p < 0.001). Multivariate analysis revealed 5-HIAA ≥395 µmol/day (p = 0.020), age (p = 0.013), and largest lymphatic metastasis ≥24 mm (p = 0.009) as independent predictors of MF, while functionality (p = 0.098) and CHD (p = 0.070) showed a tendency towards significance. MF was associated with decreased time to development of CHD in functional midgut NETs (p = 0.043). CONCLUSIONS: We found a significant association of MF with metastatic patterns and with criteria of functionality. The association of MF with elevated 5-HIAA, and consecutively with carcinoid syndrome and potential development of CHD, suggests a linked pathophysiological mechanism, which might be similar to that of endocardial fibrosis.

Real-world treatment patterns, resource use and costs of treating uncontrolled carcinoid syndrome and carcinoid heart disease: a retrospective Swedish study.

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.

Carcinoid Heart Disease: Early Outcomes after Surgical Valve Replacement in Nine Patients.

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.