Outcome of carcinoid heart syndrome in patients enrolled in the SwissNet cohort.

BACKGROUND: Carcinoid heart disease is a rare disease which develops in patients with functional neuroendocrine tumors in an advanced tumor state. Patients diagnosed with carcinoid heart disease have a poor longtime prognosis with respect to morbidity and mortality and long-term data on patient outcomes are lacking. METHODS AND RESULTS: In this retrospective study, we analyzed outcomes of 23 patients with carcinoid heart disease enrolled into the SwissNet database. We observed that early diagnosis with echocardiographic surveillance of carcinoid heart disease during the course of the neuroendocrine tumor disease was beneficial to overall survival of patients. CONCLUSION: Through nationwide patient enrollment, the SwissNet registry is a powerful data tool to identify, follow-up and evaluate long-term patient outcomes in patients with rare neuroendocrine tumor driven pathologies including carcinoid heart syndrome with observational methods enabling better therapy optimization to improve patient`s long-term perspectives and survival. In line with the current ESMO recommendations, our data proposes that heart echocardiography should be included as part of the general physical assessment in patients with newly diagnosed NET.

Prevalence, one-year-incidence and predictors of carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) caused by neuroendocrine tumours (NET) is associated with an increased morbidity and mortality due to valvular dysfunction and right sided heart failure. The present study aimed to assess the prevalence and one-year-incidence of CHD in NET patients. Tumour characteristics, laboratory measurements, and echocardiographic findings were evaluated to identify predictors of CHD manifestation. METHODS: The study was an investigator-initiated, monocentric, prospective trial. Patients with NET without previously diagnosed CHD were included and underwent comprehensive gastroenterological and oncological diagnostics. Echocardiographic examinations were performed at baseline and after one year. RESULTS: Forty-seven NET patients were enrolled into the study, 64% of them showed clinical features of a carcinoid syndrome (CS). Three patients presented with CHD at baseline and three patients developed cardiac involvement during the follow-up period corresponding to a prevalence of 6% at baseline and an incidence of 6.8% within one year. Hydroxyindoleacetic acid (5-HIAA) was identified to predict the occurrence of CHD (OR, 1.004; 95% CI, 1.001-1.006 for increase of 5-HIAA), while chromogranin A (CgA), and Kiel antigen 67 (Ki 67%) had no predictive value. Six patients with CHD at twelve-month follow-up revealed a tendency for larger right heart diameters and increased values of myocardial performance index (MPEI) at baseline compared to NET patients. CONCLUSION: The prevalence at baseline and one-year-incidence of CHD was 6-7%. 5-HIAA was identified as the only marker which predict the development of CHD.

Carcinoid syndrome-Symptoms and therapeutic approaches.

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.

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.

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.

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.

Echocardiography in functional midgut neuroendocrine tumors: When and how often.

The management of patients with midgut neuroendocrine tumors (MNET) is rapidly evolving. Current preoperative detection rates of primary tumor sites are higher than ever and progression-free survival in patients with already advanced disease is expanding due to the implementation of novel efficacious treatment strategies. This survival benefit may potentially translate into a need for a multidisciplinary approach to an even more heterogenous variety of clinical conditions, among these, carcinoid syndrome (CS) and carcinoid heart disease (CHD). The latter often triggers substantial morbidity and mortality, hence a systematic screening, an accurate diagnosis, as well as effective interventions are critically important. The rarity of the disease has result in a relative lack of statistically powerful evidence, which in turn may have rendered significant variability between practices. In this regard, despite recent guidelines, the optimal follow-up of patients with CHD remain debatable to some authors, perhaps due to the preponderance of certain schools throughout the manuscript. Herein, we present a concise and practical guidance document on clinical screening and echocardiographic surveillance of patients with CHD based on a comprehensive review of the literature, and complemented by our experience at the Center for Carcinoid and Neuroendocrine Tumors at The Mount Sinai Hospital.

Carcinoid Valve Disease: A Case Report and Review.

In patients with carcinoid syndrome, the development of carcinoid valve disease typically carries an unfavorable prognosis. We present the case of a patient with significant valvular dysfunction secondary to carcinoid valve disease. Valve replacement surgery was complicated by the development of prosthetic valve degeneration, ultimately requiring percutaneous valve implantation in a valve-in-valve fashion. The technical details of the case, as well as a review of carcinoid valve disease, including its pathophysiology, clinical manifestations, diagnostic features and management considerations, are presented.

Noninvasive evaluation of right hemodynamics in carcinoid heart disease: A case report.

We report the case of a 67-year-old woman with a carcinoid tumor of midgut origin who developed carcinoid heart disease and died because of bowel perforation. Echocardiography allowed the diagnosis, recognizing the typical abnormalities of tricuspid and pulmonary valve leaflets. The sonographic examination also evidenced peculiar alterations of the right heart hemodynamics: end-diastolic reversal of flow at the level of the pulmonary valve, reduced respiratory excursion without enlargement of the inferior vena cava, and biphasic hepatic venous flow without respiratory variation. Echocardiography allowed both the diagnosis and the accurate assessment of the hemodynamic consequences of the disease. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:355-361, 2017.

Percutaneous balloon valvuloplasty in carcinoid pulmonary valve stenosis.

More than half of patients with carcinoid syndrome develop carcinoid valve disease. Both the tricuspid and pulmonary valve are often involved. Symptoms of carcinoid syndrome with flushing, diarrhea, and bronchospasm often precedes cardiac symptoms. We report a case of carcinoid initially presenting with rapid development of right heart failure due to severe pulmonary valve stenosis. In untreated carcinoid, there is a risk of carcinoid crisis with anesthesia and surgery. In local anesthesia, we performed a sub-acute balloon pulmonary valvuloplasty. The procedure was successful without any residual pulmonary valve stenosis and with immediately relief of dyspnea. The final diagnostic workup for the underlying malignancy continued the day after valvuloplasty. © 2015 Wiley Periodicals, Inc.

Results of Contemporary Valve Surgery in Patients with Carcinoid Heart Disease.

BACKGROUND: Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating from enterochromaffin cells and secreting mainly serotonin. The diagnosis is based on clinical symptoms, hormone blood levels, radiological and nuclear imaging, and histological confirmation. However, most patients have metastases at the time of diagnosis because the clinical signs often remain unnoticed or are attributed to other abdominal conditions. In up to 50% of patients the endocardium is affected due to a hormonally active tumor profile. The study aim was to report the outcome of surgical treatment in patients with carcinoid heart disease, including the data of radiological and nuclear imaging, histological diagnosis, and follow up information. METHODS: Between 2008 and 2014, a total of 39 consecutive patients (28 males, 11 females; mean age 66 years; range: 28-84 years) with carcinoid heart syndrome were operated on at the authors' institution. Valvular heart disease was diagnosed with two-dimensional echocardiography. The study population included 26 patients (67%) with severe metastatic disease, who underwent radiotherapy preoperatively, and 13 patients (33%) who were metastasis-free and did not receive preoperative systemic therapy. Follow up was available for all hospital survivors, all of whom underwent serial echocardiographic follow up postoperatively. Adverse cardiac events were defined as cardiac-related death, a need for valvular reintervention, the occurrence of valve prosthesis-related complications, or echocardiographic evidence of new, high-degree valvular dysfunction during follow up. RESULTS: The majority of patients (n = 34; 87%) underwent isolated tricuspid valve replacement, while simultaneous pulmonary valve replacement was performed in five patients (13%). Postoperative complications included reoperation for bleeding in five patients (13%) and new heart block requiring pacemaker implantation in 10 (25%). The in-hospital mortality was 5% (n = 2). The overall survival was 43% at six years postoperatively. At the latest follow up, 12 of the 17 survivors were in NYHA class I, and five in NYHA class II. The adverse cardiac event rate was 71%. Echocardiographically, 46% of patients (6/13) showed at least stationary or mild improvement in the right ventricular ejection fraction at follow up, with no evidence of paravalvular leak, infective endocarditis, or progressive other native valvular carcinoid affection. Postoperatively, the right atrial dimensions were preserved as normal in 23 patients (59%), mildly dilated in six (15%), moderately dilated in three (8%), and severely dilated in seven (18%). Valve-in-valve transcatheter aortic valve implantation was performed in two patients (12%) due to structural degeneration of the valve bioprosthesis and native valve disease progression. CONCLUSIONS: Despite advanced systemic disease, the surgical treatment of patients with carcinoid heart syndrome is associated with an acceptable perioperative risk and satisfactory mid-term survival. Those patients who survived valve surgery benefited from a significant improvement in their functional capacity. Percutaneous procedures may represent a useful tool to reduce the risk of late valvular reinterventions.

Valve Replacement in Patients with Carcinoid Heart Disease: Choosing the Right Valve at the Right Time.

BACKGROUND AND AIM OF THE STUDY: The prosthetic valve of choice in patients with carcinoid valve disease (CVD) remains controversial due to the limited life expectancy of patients with advanced-stage neuroendocrine tumors (NETs) on the one hand, and concerns regarding structural valve deterioration (SVD) on the other hand. METHODS: The records of 17 patients (11 females, seven males; mean age 65 ± 11 years; undergoing 18 operations) with primarily right heart failure due to CVD were reviewed. All patients received somatostatin analogs perioperatively. Hospital and follow up data (acquired via direct patient contact and echocardiography) collected included baseline characteristics, procedural details, and clinical outcomes. RESULTS: The primary NET site was the ileum (n = 11), lungs (n = 2) and stomach, colon and appendix (n = 1 each). In one patient the primary tumor location could not be identified. Preoperative urinary levels of 5-hydroxyindole acetic acid (5-HIAA; 61 ± 36 mg/24 h) and serum levels of chromogranin A (2926 ± 4057 ng/ml) were 10- and 50-fold greater than normal, respectively. A total of 23 valves was implanted: five tricuspid valve replacements (TVR; four tissue and one mechanical), TVR and pulmonary valve replacements (PVR; three tissue and one mechanical), and TVR and mitral valve replacements (MVR; one tissue and two mechanical). The 30-day mortality was 11% (n = 2). No patient experienced a carcinoid crisis. The mean follow up was 24 ± 21 months (range: 4-85 months). Four patients (receiving seven valves) developed SVD at 12, 14, 15, and 20 months after surgery, and all of these patients died. The actuarial four-year survival and freedom from SVD were 23 ± 14% and 43 ± 15%, respectively. CONCLUSIONS: The data acquired suggested that the main advantage of tissue valve prostheses, namely to avoid lifelong, intense anticoagulation, might be offset by accelerated SVD. The use of mechanical valves should be considered in CVD patients with a large primary tumor mass and persistent high urinary levels of 5-HIAA, and who are unresponsive to therapy.

Maximizing Information From Routine Staging Computed Tomography in Functional Neuroendocrine Neoplasms: Are There Findings Indicating the Presence of Carcinoid Heart Disease?

PURPOSE: The aim of this study was to evaluate signs of right-sided heart dysfunction on staging computed tomography (CT) as indirect indicators of carcinoid heart disease. PATIENTS AND METHODS: Patients with functionally active neuroendocrine neoplasm and different grades of tricuspid valve regurgitation (TR) were identified. Two readers independently reviewed contrast-enhanced staging CT performed within 90 days before or after echocardiography. Logistic regression and receiver operating analyses were used to asses the predictive value of right ventricle-left ventricle ratio (RV-LV ratio), ventricular septal bowing, retrograde contrast filling of the hepatic veins during contrast injection, and time to aortal enhancement greater than 100 Hounsfield units during bolus tracking for TR. RESULTS: Forty-four examinations were evaluated (11 with TR = 0, 16 with TR = 1, 9 with TR = 2, and 8 with TR = 3). Right ventricle-LV ratio was found to predict TR less than or equal to 1 versus TR greater than 1 (P = 0.0188) and TR less than or equal to 1 versus TR equals 2 (P = 0.0082). A prolonged time to aortal enhancement greater than 100 Hounsfield units during bolus tracking predicted TR less than or equal to 1 versus TR greater than 1 (P = 0.0077). Area under the curve for RV-LV ratio was 0.86 when differentiating TR less than or equal to 1 versus TR equals 2. With a cutoff of 1.07, sensitivity was 0.89, and specificity was 0.72. CONCLUSIONS: In patients with functionally active neuroendocrine neoplasm, an RV-LV ratio of more than 1.07 predicted TR with a relatively high sensitivity and moderate specificity and thus could serve as an indicator of subclinical carcinoid heart disease on routine staging CT.

Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids.

BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. RESULTS: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. CONCLUSIONS: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.

Determination of the optimal echocardiographic scoring system to quantify carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) is an important complication of metastatic neuroendocrine disease, requiring regular monitoring to enable intervention prior to right heart failure. We aimed to identify the most appropriate echocardiographic scoring systems for the quantitative assessment of CHD. METHODS: In this prospective study conducted between April and October 2012 in two European Neuroendocrine Tumor Society (ENETS) Centres of Excellence, patients with neuroendocrine tumours with liver metastases and/or carcinoid syndrome underwent transthoracic echocardiography and blood sampling for serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA). Each patient was assessed according to six echocardiographic scoring systems. The individual scoring systems' feasibility, observer variability, sensitivity, specificity and correlation with the concentration biomarkers were determined. RESULTS: 100 patients were included; 21% had echocardiographic evidence of CHD. All scores discriminated highly between those with/without CHD, with no single score performing significantly better than another. The severity, determined using all of the scoring systems, correlated with the concentration of both biomarkers, but the strongest correlations were seen between the Bhattacharyya score and serum NT-proBNP. CONCLUSION: All scoring systems are comparable in terms of sensitivity and specificity for the detection of CHD. There is a variation in the feasibility of the scoring systems due to varying complexity of the score components. All scores correlate with NT-proBNP and plasma 5-HIAA. The Westberg score appears to be the most optimal scoring system for use in screening of CHD whereas the more complex scoring systems are more suited to the patient with established disease who may require surgical intervention.