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

Buchanan-Hughes, Amy; Pashley, Alex; Feuilly, Marion; Marteau, Florence; Pritchard, David M.; Singh, Simron

doi:10.1159/000506744

Cited by 23 publications

(25 citation statements)

References 43 publications

(178 reference statements)

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“…Previous studies have clearly demonstrated the role of serotonin using an assay of urinary 5‐HIAA in CaHD, 9 , 11 and in our study, we also found a significant increase of serotonin in patients presenting with CaHD. However, in a previous study, we reported that CaHD may progress in the first 3 years after the initial management of digestive endocrine tumor despite accurate therapeutic management.…”

Section: Discussionsupporting

confidence: 85%

“…Previous studies have reported that the development of CaHD was related to an increased level of serotonin, previous use of chemotherapy, and the presence of a patent foramen ovale (PFO). 9 , 10 , 11 However, it is difficult to define an optimal follow‐up for patients initially free from cardiac involvement. The aim of this study was to assess the prevalence and the progression of CaHD nowadays by annual echocardiographic follow‐up.…”

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confidence: 99%

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Progression of Carcinoid Heart Disease in the Modern Management Era

Baron

Szymanski

Hergault

et al. 2021

JAHA

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Background The development of carcinoid heart disease (CaHD) is still relatively unclear. It is difficult to define an optimal follow‐up for patients without any cardiac involvement at baseline. The aim of this study was to assess the prevalence and natural history of CaHD by annual echocardiographic examinations. Methods and Results We studied 137 consecutive patients (61±12 years, 53% men) with proven digestive endocrine tumor and carcinoid syndrome between 1997 and 2017. All patients underwent serial conventional transthoracic echocardiographic studies. Right‐sided and left‐sided CaHD were systematically assessed. We used a previous validated echocardiographic scoring system of severity for the assessment of CaHD. An increase of 25% of the score was considered to be significant. Mean follow‐up was 54±45 months. Prevalence of CaHD was 27% at baseline and 32% at 5‐year follow‐up. Disease progression was reported in 28% of patients with initial CaHD followed up for >2 years (n=25). In patients without any cardiac involvement at baseline, occurrence of disease was 21%. CaHD occurred >5 years from the initial echocardiographic examination in 42% of our cases, especially in patients presenting with new recurrence of a digestive endocrine tumor. An increase of urinary 5‐hydroxyindoleacetic acid by 25% during follow‐up was identified as an independent predictor of CaHD occurrence during follow‐up (hazard ratio [HR], 5.81; 95% CI, 1.19–28.38; P =0.03), as well as a maximum value of urinary 5‐hydroxyindoleacetic acid >205 mg/24 h during follow‐up (HR, 8.41; 95% CI, 1.64–43.07; P =0.01). Conclusions Our study demonstrates that in patients without initial CaHD, cardiac involvement may occur late and is related to serotonin. Our data emphasize the need for cardiologic follow‐up in patients with recurrence of the tumor process.

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Section: Discussionsupporting

confidence: 85%

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confidence: 99%

Progression of Carcinoid Heart Disease in the Modern Management Era

Baron

Szymanski

Hergault

et al. 2021

JAHA

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“…More pronounced valvular dysfunction may lead to increased right ventricular strain and eventual right-sided heart failure. CHD is associated with diminished survival [ 20 ], with a recent study demonstrating an approximately two-year reduction in median survival when compared to patients characterized by CS only [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Arterial function, biomarkers, carcinoid syndrome and carcinoid heart disease in patients with small intestinal neuroendocrine tumours

Schalin‐Jäntti

Matikainen

2022

Endocrine

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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.

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“…This reuptake deficit could also explain the increased serotonin catabolism evidenced by the increase in urinary 5-HIAA in our work. This molecule is a product of the metabolism of serotonin whose stability in urines allows to have an appreciation of the level of activity of the serotonergic system as it is now clearly established in carcinoid heart disease [ 31 ]. We were able to show a link between the severity of the valve lesions, the platelet count and the urinary 5-HIAA thus showing the probable activation of the serotonergic system.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the spontaneous degenerative mitral valve disease in FVB mice

et al. 2021

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Background The development of new non-surgical treatments dedicated to mitral valve degeneration is limited by the absence of relevant spontaneous and rapidly progressing animal experimental models. Animals We characterized the spontaneous mitral valve degeneration in two inbred FVB mouse strains compared to C57BL/6J and investigated a contribution of the serotonergic system. Methods Males and females FVB/NJ and FVB/NRj were compared to the putative C57BL/6J control at 12, 16, 20 and 24 weeks of age. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-β1 and plasma natriuretic peptide concentrations were measured. Myocardium and mitral valves were characterized by histology. mRNA mitral expression of 5-HT2A and 5-HT2B receptors was measured in the anterior leaflet. Cardiac anatomy and function were assessed by echocardiography. Results Compared to C57BL/6J, FVB mice strains did not significantly differ regarding body weight increase, arterial blood pressure and heart rate. A progressive augmentation of plasma pro-ANP was observed in FVB mice. Nevertheless, no cardiac hypertrophy or left-ventricular fibrosis were observed. Accordingly, plasma TGF-β1 was not different among the three strains. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length. The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium. Conclusion The FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.

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

Cited by 23 publications

References 43 publications

Progression of Carcinoid Heart Disease in the Modern Management Era

Progression of Carcinoid Heart Disease in the Modern Management Era

Arterial function, biomarkers, carcinoid syndrome and carcinoid heart disease in patients with small intestinal neuroendocrine tumours

Characterization of the spontaneous degenerative mitral valve disease in FVB mice

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