Original article Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability Nicolas Delahaye 1 , Sylvie Dinanian 2 , Michel S. Slama 2 , Hichem Mzabi 3 , Didier Samuel 3 , David Adams 4 , Pascal Merlet 5 , Dominique Le Guludec 1 1 Department of Nuclear Medicine, Bichat Hospital, Paris, France 2 Department of Cardiology, A. Béclère Hospital, Paris, France 3 Department of Hepatic Surgery, P. Brousse Hospital, Paris, France 4 Department of Neurology, Bicètre Hospital, Paris, France 5 SHFJ, DSV-CEA, Orsay, France &misc:Received 19 October 1998 and in revised form 6 January 1999 &p.1:Abstract. Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin pro- duced by the liver and characterized by both sensorimo- tor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sud- den deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 pa- tients (42±12 years) before liver transplantation by io- dine-123 metaiodobenzylguanidine (MIBG) scintigra- phy, heart rate variability analysis, coronary angiogra- phy, radionuclide ventriculography, rest thallium single- photon emission tomography (SPET) and echocardiogra- phy. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echo- cardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age- matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36±0.26 versus 1.98±0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, with- out correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evalu- ate the extent of cardiac sympathetic denervation in FAP patients. &kwd:Key words: Familial amyloid polyneuropathy – Meta- iodobenzylguanidine – Heart rate variability – Autonom- ic nervous system Eur J Nucl Med (1999) 26:416–424 Introduction Familial amyloid polyneuropathy (FAP) is a rare heredi- tary form of amyloidosis predominantly found in several countries including Portugal [1], Japan and Scandinavia. FAP type I is characterized by a progressive sensorimo- tor polyneuropathy and often severe autonomic neuropa- thy with symptoms such as alternating diarrhoea and constipation, orthostatic hypotension, urinary retention and dry mouth and eyes. Amyloid deposition of a genet- ic variant transthyretin (TTR: pre-albumin) essentially produced by the liver is responsible for this disease. The MET-30 variant is by far the commonest [2] (substitu- tion of valine for methionine in position 30 in the pre-al- bumin molecule). The only effective treatment of FAP is liver transplantation, which can stop the progress of neu- rological impairment or even improve the neurological status [3–6]. Although the left ventricular systolic function is nor- mal in most FAP type I patients [7, 8], sinus node dys- functions, disturbances of atrioventricular and intraven- European Journal of Nuclear Medicine Vol. 26, No. 4, April 1999 – © Springer-Verlag 1999 Correspondence to: N. Delahaye, Service de Médecine Nucléaire, Hôpital Bichat, 46 rue Henri Huchard, F-75018 Paris, France&/fn-block: