Carcinoid Heart Disease Management: A Multi-Disciplinary Collaboration

Abstract

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.

Does Telotristat Have a Role in Preventing Carcinoid Heart Disease?

“…This is a very significant clinical marker, since NT-proBNP is released by heart atria and ventricles in response to the increased wall stress, which is a consequence of volume and/or pressure overload [44,45]. Specifically, NT-proBNP levels positively correlate with the severity of CS, the New York Heart Association (NYHA) functional class, and overall mortality [46,47]. In consequence, currently NT-proBNP is regularly determined in patients for monitoring CHD in combination with echocardiography [3,47].…”

Carcinoid Heart Disease: A Comprehensive Review and Update on Pathophysiology, Diagnosis, and Management

“…Not only this but the 5-HT2B receptor signalling also involves the activation of nitric oxide synthase (NOS), leading to the production of nitric oxide (NO). 11 NO acts as a signalling molecule that can induce vasodilation and influence various cellular functions, including cell proliferation and apoptosis.…”

“…The activation of the 5-HT2B receptor further amplifies this process by triggering a signalling cascade that increases the secretion of inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-α). 1,11 These cytokines exacerbate tissue inflammation and fibrosis, worsening the condition. Additionally, the receptor activates the MAPK pathway, involving a series of phosphorylation events that culminate in the activation of extracellular signal-regulated kinases (ERK1/2).…”

“…The initial stages of CaHD may be marked by nonspecific symptoms such as fatigue and dyspnea, particularly on exertion, which can be attributed to the involvement of the tricuspid and pulmonary valves. 11,14 These early signs are often challenging to detect due to the low-pressure system of the pulmonary circulation, where even significant valvular disease might be tolerated for extended periods without clear clinical manifestations. The interval between symptom onset to the diagnosis of CaHD can range widely, averaging 24-48 months but potentially extending up to five years.…”

“…A level exceeding 300 mmol/24 h is indicative of a heightened risk for CaHD, highlighting the need for holistic patient evaluation. 11,26 However, dietary factors and certain medications may influence 5-HIAA levels, necessitating dietary restrictions prior to testing to avoid false-positive results. Moreover, the prognostic value of posttreatment 5-HIAA levels, particularly a threshold of 100 mg/24 h, significantly aids in predicting CaHD progression, as confirmed through serial echocardiographic assessments.…”