Carcinoid heart disease (CHD) is a serious complication of metastatic neuroendocrine tumours (NETs) and a key driver of symptom burden, functional limitation, and overall prognosis. Up to 20% of patients with carcinoid syndrome have CHD at diagnosis, and approximately 50% develop cardiac involvement over the course of the disease.1,2 Beyond highlighting the prognostic burden of CHD, the case report from this issue, Hickson et al. https://doi.org/10.5837/bjc.2026.054, presents an opportunity to reflect on how developments in CHD management and adjunct tumour-directed therapies have contributed to improved outcomes in the last few decades.
Pathophysiology
The pathophysiology of CHD involves chronic exposure of the endocardium to vasoactive substances released by functioning NETs, leading to fibrotic plaque deposition.3 Valve leaflet thickening, retraction and fixation develop over time and result in predominantly right-sided valvular regurgitation, often accompanied by varying degrees of stenosis.
The vasoactive substances produced in carcinoid syndrome, primarily serotonin, undergo metabolism in the liver, lung and brain.4,5 In patients with hepatic metastases, liver clearance is bypassed, and persistent systemic exposure leaves the right heart vulnerable to damage. The left heart is typically spared due to clearance in the pulmonary circulation. However, in patients with a patent foramen ovale (PFO), as right atrial pressure rises with progressive tricuspid regurgitation, shunting of blood from the right atrium to the left atrium allows vasoactive substances to pass directly to the left side of the heart leading to left-sided valvular disease, and, in some cases, striking hypoxia. Bronchial carcinoid tumours can also cause left-sided valve disease, but this is rare. One additional anomaly can be seen with ovarian carcinoid, when right-sided valve lesions occur without hepatic metastases, as there is direct venous drainage from the ovary to the inferior cava (i.e. bypassing the hepatic bed).6 The pathophysiology of CHD highlights an important principle: this is not an isolated valvular disorder, but a consequence of uncontrolled hormonal activity.
Diagnosis and surveillance
Several biomarkers can predict the presence and severity of CHD, allowing more selective use of screening tools, particularly in patients with subtle symptoms. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is significantly higher in patients with CHD, and has a direct correlation to symptomatic status and overall survival.7 Plasma and urinary 5-HIAA (5-hydroxyindoleacetic acid, a metabolite of serotonin) levels are also higher in patients with CHD, and further increases correlate with CHD progression.4,8,9 In contrast, chromagranin A, a glycoprotein released by NET cells, is used to assess NET recurrence and tumour progression, but is not indicated as a screening test for CHD due to a low specificity for CHD.10
Transthoracic echocardiography is the primary screening tool for CHD and should be performed in all patients with positive biomarkers. The pattern of disease is pathognomonic and often involves thickened, immobile leaflets, most commonly affecting the tricuspid valve, with or without pulmonary valve disease.7,11 Right atrial and ventricular dilatation are typical; however, right ventricular (RV) function is often preserved until late in the disease course.11 Cardiac magnetic resonance imaging (MRI) offers incremental value in quantifying RV volumes and function, particularly when echocardiographic windows are suboptimal. Tissue characterisation, such as T1 mapping and late gadolinium enhancement (LGE), can also diagnose subendocardial cardiac metastases and myocardial fibrosis.12
Serial surveillance is recommended for patients with no disease or early CHD. High-risk patients with elevated biomarker levels or uncontrolled carcinoid disease often require more regular interval imaging within specialist NET pathways for early identification of progressive valvular disease.12
Patient selection for intervention
Over the last few decades, most specialist centres have refined their approach to selecting CHD patients for valve intervention, timing the surgery and completing presurgical work-up. Historically, surgical intervention was performed relatively late in the course of the disease when signs of advanced right-sided heart failure were established.13 Metastatic disease was often considered a relative contraindication for cardiac surgery. However, experience and case series from specialist centres now suggest a more nuanced approach.8,13–16
CHD patients who are most likely to benefit from valve intervention typically demonstrate symptomatic severe valvular disease, objective functional limitation, and a relatively good medium-term oncological prognosis.7,17,18 In these patients, intervention before the establishment of irreversible ventricular dysfunction is associated with significant symptomatic and functional improvement.
Aside from symptomatic relief, valve replacement in CHD can serve as a bridge to other oncologic therapies, including hepatic resection and debulking surgeries.19 Therefore, cardiac assessment should be undertaken in the context of the overall management of carcinoid disease. Ultimately, the decision for intervention must occur within a multi-disciplinary team (MDT) framework, incorporating cardiology, cardiac surgery, NET oncology, interventional radiography, gastroenterology, hepatobiliary surgery and anaesthesia, among other allied specialists.
Where possible we choose to operate on patients in whom the carcinoid syndrome is well controlled. Patients should be on somatostatin analogues, but if there is time to reduce tumour bulk, e.g. by trans-arterial chemoembolisation (TACE), we aim to do this prior to surgery. This helps reduce the risk of anaesthesia by controlling the carcinoid syndrome, but also slows the rate of damage to the newly replaced valve or valves. Hepatic resection cannot be safely undertaken in the setting of severe tricuspid regurgitation due to bleeding risk (these patients have a pulsatile liver on palpation). Clearly, if a patient presents in right heart failure, there is usually only time to diurese, and medically optimise with octreotide before pursuing valvular intervention. The key is then to plan early interventions to reduce tumour burden after surgery, as long delays will risk ongoing damage to the new valves and worsen outcome.
Assessment for surgery involves clinical assessment, transthoracic echocardiography and measurement of biomarkers. Cardiopulmonary exercise testing (CPET) provides quantifiable measures of exercise capacity and can identify clinically significant haemodynamic limitation in the context of preserved RV function.20 It can also give some assessment of surgical risk in borderline surgical candidates. Transoesphageal echo (TOE) is usually undertaken to ensure that transthoracic echo does not underestimate valvular disease. It is important to identify a PFO, either using TOE or bubble-contrast echocardiography, as these should be surgically closed at the time of valve surgery. In our institution, all patients undergo right heart catheterisation to directly measure cardiac and pulmonary pressures, in addition to left heart catheterisation, where appropriate. Cardiac MRI is undertaken where clinically indicated.
Surgical valve replacement
Surgical valve replacement remains the standard of care for advanced CHD.7,8,18 Given the fibrotic thickening and retraction seen in carcinoid valve disease, repair is not feasible. Tricuspid valve replacement is most commonly required, often accompanied by pulmonary valve intervention.3,10 Bioprosthetic valves are generally favoured to balance durability against the risks of long-term anticoagulation (NET patients often require repeat interventions) and prosthetic thrombosis.15,18
What has changed in recent years is not necessarily the surgical technique itself, but the peri-operative work-up. Structured protocols for prevention and management of carcinoid crisis, and improved anaesthetic planning have reduced operative mortality compared with earlier series.13 Continuous intravenous octreotide infusion remains a cornerstone of peri-operative management, mitigating the risk of carcinoid crisis during anaesthesia and surgical manipulation.13,14,16 Furthermore, elective intervention in a controlled setting has allowed optimisation of volume status, nutritional state and hormonal activity.13,15 This approach contrasts with earlier experiences in which patients presented acutely, with advanced right ventricular failure and uncontrolled biochemical activity.
Emerging transcatheter strategies
Transcatheter valve interventions play an increasing role in cardiological practice, yet their use in CHD is currently infrequent. Transcatheter techniques have been used for isolated pulmonary valve disease and for valve-in-valve procedures for patients with failing tissue valves.14 The nature of the restricted valve leaflets and the size of the defect mean tricuspid edge-to-edge repair is not an option. There is though, now, very early experience with percutaneous tricuspid valve replacement in native valves and, if the long-term outcomes are good, we may see rapid growth in this field.21 Careful patient selection remains paramount, and these interventions should be undertaken within specialist centres with both structural and NET expertise.
Tumour and hormonal control
The most transformative advances in CHD management have occurred within NET therapy. Several studies have demonstrated that higher levels of 5-HIAA are often seen in patients with cardiac involvement.16,17 Therefore, the use of long-acting somatostatin analogues, including octreotide and lanreotide, to suppress serotonin secretion, reduces carcinoid symptoms and exerts anti-proliferative effects, resulting in good outcomes post-valve replacement in CHD.4
For patients with progressive metastatic disease, peptide-receptor radionuclide therapy (PRRT) has expanded treatment options. Targeted delivery of radiolabelled somatostatin analogues aims to reduce tumour burden and hormonal output, indirectly improving suitability for valve intervention and, potentially, reducing valve deterioration after replacement.
Given the central role of hepatic metastases in systemic serotonin excess, liver-directed therapies, such as transarterial embolisation, chemoembolisation, selective internal radiation therapy and hepatic resection, remain highly relevant. Reduction in hepatic tumour load decreases circulating vasoactive mediators and contributes to the stabilisation of cardiac disease.7,19 The integration of these modalities, before and after valve intervention, reflects a refined approach to CHD management where cardiac surgery is no longer considered in isolation, but as part of an overarching oncological strategy.
Conservative management
Not all patients with CHD are candidates for intervention. Conservative management remains appropriate for individuals with advanced oncological and cardiac disease with limited prognosis or prohibitive operative risk. In such cases, optimisation of volume status with diuretic therapy, typically alongside mineralocorticoid antagonists and control of hormonal activity with somatostatin analogues, form the cornerstone of management.6,17
Multi-disciplinary care as the determinant of outcome
Improved outcomes in CHD practice are not attributable to a single innovation. They reflect significant developments to management approaches centred around proactive screening at diagnosis, structured surveillance pathways, early referral to specialist cardiology care, refined operative timing, standardised peri-operative care, integration of tumour-directed therapies, and close patient involvement. This coordinated model stands in contrast to historical practice, where cardiac and oncological management were often fragmented.12 Increasingly, specialist NET centres provide the infrastructure necessary for timely intervention and comprehensive follow-up, leading to improved outcomes. In our view, all patients presenting with CHD should be discussed with a specialist NET centre with experience of cardiac surgery.
Conclusion
CHD is a rare, complex and potentially life-limiting condition; however, valve replacement in the right patient can lead to important symptomatic and prognostic benefit. CHD must be managed as the cardiac expression of systemic disease, requiring coordinated multi-disciplinary expertise, which is only available in limited centres nationally. When the right patient is selected within a structured specialist framework, meaningful improvements in symptoms and quality of life are achievable. At the same time, it is important to recognise when valvular intervention is not appropriate, and palliation is appropriate.
Conflicts of interest
None declared.
Funding
None.
Editors’ note
See also the case report by Hickson et al. from this issue at https://doi.org/10.5837/bjc.2026.054.
References
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