British Heart Valve Society Carcinoid Heart Disease Dr C Hayward MB BChir MRCP , Dr S Bhattacharyya MD MRCP, Dr J Davar MD PhD Royal Free Hospital, London, UK

Case Presentation 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.

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.

Management 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.

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 Bhattacharyya S, Davar J, Dreyfus G, Caplin ME. Carcinoid Heart Disease. Circulation 2007; 116:2860-2865. 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. 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. 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. 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. 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.