Presence Of Carcinoid Heart Disease Research Articles

Survival and disease recurrence in patients operated for small intestinal neuroendocrine tumors at a referral hospital

Background and objectivesSmall intestinal neuroendocrine tumors (SI-NETs) are slow growing but have frequently metastasized at the time of diagnosis. Most patients are operated with either curative intent or with intent to prolong overall survival. In the current study we have examined overall and disease-free survival in patients operated for SI-NETs. MethodsAll patients with a histological diagnosis of SI-NET at St Olav's hospital in the period 1998–2018 were reviewed retrospectively. Patient, disease and treatment characteristics including European Neuroendocrine Tumor Society (ENETS) TNM staging classification, surgery type, time to recurrence and survival were recorded. ResultsA total of 186 patients were identified, whereof 54.3% male, median age at operation 68 years. The majority (n = 141 (75.8%)) underwent elective surgery and surgery was considered curative (radical) in 120 (64.5%) patients. Median estimated overall survival was 9.7 years (95% CI 7.6–11.8) for the entire population. Stage of disease, carcinoid heart disease, age, elective surgery, preoperatively known SI-NET, curative surgery and synchronous cancer were associated with survival in a multivariate analysis. Thirty-six of 120 (30%) patients had disease recurrence after a median follow-up time of 5.5 years, with a median estimated recurrence-free survival of 9.1 (5.4–12.9) years. Recurrence free survival was associated with age and synchronous cancer. ConclusionsPatients with SI-NETs had long overall survival which seemed influenced by stage of disease, presence of carcinoid heart disease, an elective surgery, preoperatively known SI-NET, age and synchronous cancer. Appropriate preoperative diagnostic procedures and elective surgeries seem beneficial and should be aimed for.

Myocardial metastases on 6-[18F] fluoro-L-DOPA PET/CT: a retrospective analysis of 116 serotonin producing neuroendocrine tumour patients.

PurposeThis study evaluates the prevalence of cardiac metastases in patients with serotonin producing neuroendocrine tumours (NET), examined with 18F-FDOPA PET/CT, and the relationship of these metastases to the presence of carcinoid heart disease (CHD) based on echocardiography.BackgroundCHD occurs in patients with serotonin producing NET. The diagnostic method of choice remains echocardiography. The precise prevalence of cardiac metastases is unknown given the limitations of standard technologies. Nuclear medicine modalities have the potential to visualize metastases of NET.MethodsAll patients who underwent 18F-FDOPA PET/CT because of serotonin producing NET between November 2009 and May 2012 were retrospectively analyzed. The presence of cardiac metastasis was defined as myocardial tracer accumulation higher than the surrounding physiological myocardial uptake. Laboratory tests and transthoracic echocardiography (TTE) results were digitally collected.Results116 patients (62 male) underwent 18F-FDOPA PET/CT, mean age was 61±13 years. TTE was performed in 79 patients. Cardiac metastases were present in 15 patients, of which 10 patients also underwent TTE. One patient had both cardiac metastasis (only on 18F-FDOPA PET/CT) and echocardiographic signs of CHD. There were no differences in echocardiographic parameters for CHD between patients with and without cardiac metastases. TTE in none of the 79 patients showed cardiac metastases.ConclusionThe prevalence of cardiac metastases detected with 18F-FDOPA PET/CT in this study is 13%. 18F-FDOPA PET/CT can visualize cardiac metastases in serotonin producing NET patients. There appears to be no relationship between the presence of cardiac metastases and TTE parameters of CHD.

The Association of a Panel of Biomarkers with the Presence and Severity of Carcinoid Heart Disease: A Cross-Sectional Study

PurposeMetastatic neuroendocrine tumors secrete serotonin and other vasoactive substances that are responsible for carcinoid syndrome and carcinoid heart disease. We sought to evaluate the discriminatory utility of diagnostic biomarkers in determining the presence and severity of carcinoid heart disease in patients with metastatic neuroendocrine tumors.Patients and methodsA cross-sectional study of patients with neuroendocrine tumors with documented liver metastases and/or carcinoid syndrome between April 2009–October 2012 in 5 tertiary referral centers. Serum was analyzed for Chromogranin A, Chromogranin B and N-terminal pro Brain Natriuretic Peptide (NT-proBNP). Plasma was analyzed for Neurokinin A and 5-Hydroxyindoleacetic acid (5HIAA). Echocardiography was used to determine the presence and severity of carcinoid heart disease. Non-parametric receiver operating characteristic curves were constructed for biomarkers, and the area under the curve determined. The severity of cardiac involvement was correlated with the concentration of each biomarker.ResultsA total of 187 patients were identified of whom 37 (20%) had carcinoid heart disease. Significantly higher median values of all biomarkers were found in the patients with cardiac involvement. NT-proBNP and plasma 5HIAA had the highest areas under the curve for the prediction of carcinoid heart disease [NT-proBNP 0.82 (95% confidence interval 0.74–0.90, p<0.0001) and 5HIAA 0.85 (95% confidence interval 0.78–0.92, p<0.0001]. NT-proBNP was moderately correlated (r = 0.48, p<0.001) whereas plasma 5HIAA was only weakly correlated (r = 0.34, p<0.001) with the echocardiographic severity score.ConclusionNT-proBNP and plasma 5HIAA are both sensitive and specific biomarkers for the presence of carcinoid heart disease whereas only NT-proBNP is moderately correlated with disease severity.

Analysis of association between carcinoid heart disease and mesenteric fibrosis in patients with midgut carcinoid tumour

e15650 Background: Valvular heart disease in patients with carcinoid syndrome is due to development of fibrosis and endocardial thickening in the heart. The most accepted theory relating to development of heart disease is secretion of serotonin (5- hydroxy tryptamine) by the tumour or metastases. Mesenteric fibrosis develops as a result of peptides e.g.TGF beta released by local metastases. Both complications cause significant morbidity and mortality in patients with carcinoid syndrome. Aim: to evaluate the relationship of carcinoid heart disease and mesenteric fibrosis. Methods: We analysed retrospectively all patients (n=200) who had metastatic (liver metatstasis) neuroendocrine tumour and carcinoid syndrome with the primary clearly identified within the small bowel or caecum. We aimed to evaluate clinically symptoms of mesenteric ischemia and small bowel obstruction and also radiological presence of desmoplasia and small bowel dilatation. All patients underwent clinical and echocardiographic cardiovascular assessment to determine the presence of carcinoid heart disease. Results: Of 200 patients 42 had echocardiographic evidence of carcinoid heart disease. 4 patients had evidence of both mesenteric desmoplasia and carcinoid heart disease. 38 patients had carcinoid heart disease alone. Of the remaining 158 patients who had no evidence of carcinoid heart disease, 24 of them had evidence of desmoplasia and/or clinical evidence of sub-acute bowel obstruction where no other cause could be found. The remaining 134 patients had none of these complications. Comparing the relationship of Carcinoid heart disease and mesenteric fibrosis using two tailed exact Fisher's test, p value is 0.45, demonstrating they are statistically independent. We are currently assessing the effect on mortality. Conclusions: Carcinoid heart disease and mesenteric fibrosis (and its effects) are important determinants in morbidity and mortality of patients with midgut neuroendocrine tumour. Although carcinoid heart disease and mesenteric fibrosis are part of the same patho-physiologic process affecting patients with midgut neuroendocrine tumour, the results suggest that progression of these complications is independent of each other. No significant financial relationships to disclose.

Usefulness of N-terminal Pro–Brain Natriuretic Peptide as a Biomarker of the Presence of Carcinoid Heart Disease

We sought to investigate whether N-terminal pro-brain natriuretic peptide (NT-pro-BNP) can be used as a biomarker for the detection of carcinoid heart disease (CHD); 200 patients with carcinoid syndrome were screened for CHD using transthoracic echocardiography. A carcinoid score was formulated to quantify severity of CHD. NT-pro-BNP was measured in all patients before echocardiography. Patients were categorised into New York Heart Association class. CHD was present in 39 patients (19.5%). NT-pro-BNP was significantly higher in those with CHD (median 1,149 pg/ml) than in those without CHD (median 101 pg/ml, p <0.001). The sensitivity and specificity of NT-pro-BNP at a cut-off level of 260 pg/ml for detection of CHD were 0.92 and 0.91, respectively. NT-pro-BNP positively correlated both with carcinoid score (r = 0.81, p <0.001) and New York Heart Association class (p <0.001). The number of patients screened to diagnose 1 case of CHD decreased from 5.1 to 1.4. In conclusion, NT-pro-BNP seems to be an excellent biomarker of CHD. A high negative predictive value may allow it to provide a screening test for CHD.

Perianaesthetic risks and outcomes of abdominal surgery for metastatic carcinoid tumours

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

Prognostic Value of Heart Rate Variability Analysis in Patients with Carcinoid Syndrome

Background/Aims: Recently, a decrease in heart rate variability measures was found in patients with carcinoid syndrome suffering from carcinoid heart disease compared to those without cardiac involvement of carcinoid syndrome. The prognostic relevance of this finding, however, was not clear. Patients and Methods: Therefore, 35 patients with carcinoid syndrome (21 men, age 56 ± 11 years), all of them suffering from metastatic carcinoid tumors, were followed prospectively at our institution. Digital 24-hour Holter monitoring, echocardiography, and serum serotonin and urine 5-hydroxyindole acetic acid (5-HIAA) samplings were performed in all study patients at baseline. Indices of time domain heart rate variability obtained from Holter recordings included the standard deviation of all normal RR intervals (SDNN) representing overall variability, the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the percentage of the number of pairs of adjacent normal RR intervals differing by >50 ms (pNN50), both indices reflecting predominantly vagal influences on heart rate. Results: During a mean follow-up of 18 ± 7 months, 15 of 35 patients with carcinoid syndrome (43%) died. Patients with cardiac manifestation of the carcinoid syndrome showed a tendency towards an increased mortality in comparison to patients without cardiac involvement (p = 0.09). Patients with the combination of decreased heart rate variability (SDNN <100 ms) and presence of carcinoid heart disease had a significant worse prognosis (p = 0.04) compared to patients without carcinoid heart disease and preserved heart rate variability (SDNN ≧100 ms). Conclusions: The presence of carcinoid heart disease in combination with decreased heart rate variability is associated with the most adverse prognosis in the setting of carcinoid syndrome.