British Heart Valve SocietyCarcinoid Heart Disease

Dr C Hayward MB BChir MRCP , Dr S Bhattacharyya MD MRCP, Dr J Davar MD PhD

Royal Free Hospital, London, UK

Clinical History• 60 year old female.• 6 month history of flushing, diarrhoea, fatigue and

dyspnoea on exertion. NYHA Class III at presentation.

Investigations• CT abdomen: multiple liver metastases and a small bowel

mesenteric mass. Liver Biopsy: consistent with low grade carcinoid tumour.

• 24 hour Urinary 5-HIAA: 800µmol/24 hours.

Case Presentation

Cardiac Investigations

• ECG – sinus tachycardia. Normal axis.• CXR – Cardiothoracic ratio > 50%. • Echocardiogram:

– Right Ventricle: dilated and mildly impaired (TAPSE 13cm).

– Tricuspid Valve: severe “free flowing” tricuspid regurgitation.

– Pulmonary Valve: severe pulmonary regurgitation, moderate pulmonary stenosis.

– NT-proBNP: 700 pg/ml.

Medical•Reduction of peripheral oedema with diuretics.

Valve Surgery•Replacement of tricuspid and pulmonary valve:

Pulmonary homograft.Pericardial tissue valve – tricuspid valve.

Length of hospital stay 5 days. Required permanent pacemaker for complete heart block.

Outcome 6 months post surgery•Diuretics weaned off.•Functional NYHA Class I. Climb > 5 flights of stairs.

Management

Clinical Manifestations

• Carcinoid syndrome consists of a triad: flushing, diarrhoea and bronchospasm.

• Between 20-50% of all patients with carcinoid syndrome will develop carcinoid heart disease.

• Vasoactive substances such as 5-hydroxytryptamine produced by neoplastic cells are able to travel to the right heart via the hepatic vein/IVC and are thought to be responsible for deposition of endocardial plaques of fibrous tissue.

• Classically patients develop signs and symptoms of right heart failure: fatigue, oedema and ascites.

Pathology – “Carcinoid Plaque”• Right-sided lesions more

common than left. • Preferential right-sided

involvement due to inactivation of vasoactive substances by lungs.

• 5–10% have left-sided valvular pathology due to either high tumour load, bronchial carcinoid or patent foramen ovale.

• Plaque - composed of smooth muscle cells + myofibroblasts forming white fibrous layer (arrow) lining endocardial surface of cardiac valves superficial to normal valve

Echocardiographic Features – Tricuspid Valve

• Typically thickened, retracted, valve leaflets. Leaflets do not co-apt (arrow).

• Anatomical features leads to predominantly tricuspid regurgitation (TR).

• Classical “Dagger” shaped Doppler profile of severe TR (arrow).

Echocardiographic Features – Pulmonary Valve

• Fixed, thickened cusps (arrow).

• Non-coaptation of cusps (*).

• Predominantly pulmonary stenosis with varying degrees of regurgitation (arrow).

Biochemical Markers

• Elevated urinary 5-hydroxyindolacetic acid is a highly sensitive but poorly specific maker of carcinoid heart disease.

• NT-proBNP > 260pg/ml has greater than 90% sensitivity and negative predictive value for significant carcinoid heart disease. This may allow its use as a screening test.

• NT-proBNP also correlated with disease severity and NYHA Class.

Management

Medical Management•Poor outcome when managed medically.•3 year survival 68% without cardiac involvement compared to 31% with cardiac involvement.•Diuretics mainstay of therapy.

Valve Surgery•High peri-operative risk (10% -20% depending on institution).•Valve replacement improves symptom status (functional NYHA Class).•Emerging data suggest may improve prognosis.

Conclusions

• Carcinoid heart disease = common complication of carcinoid syndrome but is a rare cause of all acquired valvular heart disease

• 5-HT is produced by metastatic tumour cells in the liver → deposition of endocardial plaques.

• Right sided valvular dysfunction is common and presents with characteristic echocardiographic appearances. Left sided valve lesions in 5-10% of cases of carcinoid heart disease.

• Medical management alone is associated with poor survival.

• Valve surgery improves symptoms and may improve prognosis.

Further Reading

1.Bhattacharyya S, Davar J, Dreyfus G, Caplin ME. Carcinoid Heart Disease. Circulation 2007; 116:2860-2865. 2.Lundin L, Norheim I, Landelius J, Oberg K, Theodorsson-Norheim E. Relationship of circulating vasoactive substances to ultrasound detectable cardiac abnormalities. Circulation 1988;77:264-269. 3.Bhattacharyya S, Toumpanakis D, Burke M, Taylor AM, Caplin ME, Davar J. Features of carcinoid heart disease identified by 2- and 3-dimensional echocardiography and cardiac MRI. Circ Cardiovasc Imaging 2010:3:103-111.4.Korse CM, Taal BG, de Groot CA, Bakker RH, Bonfrer JM. Chromogranin-A and N-terminal pro-brain natriuretic peptide: an excellent pair of biomarkers for diagnostics in patients with neuroendocrine tumor. J Clin Oncol. 2009;27:4293-4299. 5.Bhattacharyya S, Toumpanakis C, Caplin M, Davar J. Usefulness of N-Terminal Brain Natriuretic Peptide As A Biomarker Of The Presence Of Carcinoid Heart Disease. American Journal of Cardiology 2008;102:938-942.6.Moller JE, Pellikka PA, Bernheim AM, Schaff HV, Rubin J, Connolly HM. Prognosis of carcinoid heart disease: An analysis of 200 cases over two decades. Circulation 2005;112:3320-3327.