Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction d isturbances and sudden deaths can occur. The neurological status of the hea rt has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42+/-12 years) before liver transplan tation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rat e variability analysis, coronary angiography, radionuclide ventriculography , rest thallium single-photon emission tomography (SPET) and echocardiograp hy. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltrati on was found at echocardiographic examination. Cardiac MIBG uptake was dram atically 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 v ariability analysis showed a considerable scatter of values, with high valu es in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with M IBG uptake at 3, h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ accordin g 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 ou t correlation with conduction disturbances. Results of the heart rate varia bility analysis were more variable and this technique does not seem to be t he best way to evaluate the extent of cardiac sympathetic denervation in FA P patients.