Carcinoid heart disease, also known as Hedinger syndrome, is a known complication of neuroendocrine tumours (NETs) and is particularly prevalent in patients who develop carcinoid syndrome.

Epidemiology

Cardiac lesions are present in approximately 50% of patients with carcinoid syndrome ¹.

Clinical presentation

Presentation may be subtle but will eventually progress to right-predominant features of heart failure ². Clinical examination findings may vary, but the jugular venous pressure is often raised, and both systolic and diastolic murmurs can be heard on praecordial auscultation ².

Additionally, patients will often have clinical features of carcinoid syndrome, such as facial flushing, chronic severe diarrhoea, bronchospasm, and hypotension ^2,3.

Pathology

Ordinarily, vasoactive neuroendocrine substances (serotonin, bradykinin, histamine, prostaglandin, etc.) produced from NETs that enter the bloodstream are inactivated by the liver ^2,3. However, in the presence of liver metastases from these tumours, the vasoactive neuroendocrine substances can bypass the liver and affect the right side of the heart ^2,3. 

Important exceptions to needing liver metastases to develop carcinoid heart disease are in the cases of:

• a primary bronchial carcinoid tumour ²

• a primary ovarian carcinoid tumour, as vasoactive neuroendocrine substances from this tumour inherently bypass the liver because the ovarian vein drains directly into the inferior vena cava ⁴

Location

Although the exact mechanism is unclear, the main consequences of these vasoactive neuroendocrine substances reaching the heart are characteristic plaque-like deposits of fibrous tissue, most commonly affecting the tricuspid valve apparatus and the pulmonary valve ^2,3. This causes thickening of the valve leaflets with short, thickened, and fused chordae and papillary muscles, which results in mixed tricuspid regurgitation (predominant) and stenosis, and mixed pulmonary regurgitation (predominant) and stenosis ^2,3.

Less commonly, the endocardial surface of cardiac chambers and the intimal layer of great vessels may be additionally affected ^2,3. Furthermore, in the presence of an intracardiac right-to-left shunt (e.g. patent foramen ovale) or a primary bronchial carcinoid tumour, left-sided disease can also occur, although this occurs in fewer than 10% of all affected patients ^2,3. 

Radiographic features

Plain radiograph

Plain chest radiograph is most commonly unremarkable unless there is significant right-heart dysfunction ^1,3. Carcinoid heart disease plaques do not calcify and thus, are not visible on plain radiographs ³.

Ultrasound

Echocardiography

Echocardiography is a pragmatic imaging modality, and provides direct visualisation of right-sided valvular lesions and chambers ^1-3. Rarely, carcinoid heart disease may affect left sided valvular structures in the presence of an intracardiac right-to-left shunt. Features include ¹¹:

• thickening and restriction of the tricuspid valve leaflets

  • morphology classically appears "club-like"

  • restricted excursion with failure of coaptation

• tricuspid valve regurgitation

  • often severe, associated with systolic reversal of the hepatic venous Doppler waveform

  • concomitant tricuspid valve stenosis

• right atrial enlargement

• right ventricular enlargement and dysfunction

• pulmonary valve regurgitation

• pulmonary valve stenosis

• pericardial effusion ^1-3

CT/MRI

Cross-sectional imaging demonstrate the same radiographic features appreciated on echocardiography, but in greater detail. In particular, these imaging modalities allow for greater visualisation of ^3,5-8:

• tricuspid and pulmonary valves, which are thickened, shortened, and retracted

  • there may be late gadolinium hyperenhancement of both tricuspid and pulmonary valves in delayed enhanced cardiac MRI sequences, but this is considered non-specific

• valulvar lesions, which are often fixed with minimal movement during the cardiac cycle

• right-sided cardiac chambers, which demonstrate features of volume overload (e.g. chamber enlargement, paradoxical motion of the interventricular septum, etc.)

• pericardial effusion

If carcinoid heart disease is suspected, cross-sectional imaging should also be performed in order to detect the primary carcinoid tumour.

Treatment and prognosis

Management includes ²:

• pharmacotherapy: using a similar armamentarium to that used in heart failure, using somatostatin analogues such as octreotide

• surgery: resection of the primary carcinoid tumour, valvular surgery