Background: Cardiac complications are common in familial amyloidotic polyneuropathy (FAP), in which heart rate variability (HRV) is reduced. Although autonomic disturbances are well-established, mechanisms for reduced HRV, their relationship with left ventricular (LV) function in FAP are not well understood. Methods: Twenty-nine FAP patients and 29 healthy controls were studied using Doppler echocardiography. Patients' and controls' HRV were studied using power spectral analysis from 24-hour Holter-ECG recordings. Results: In FAP patients, all HRV parameters were lower (p<0.01 for all) than those in controls. Echocardiography showed a normal LV systolic function in patients. Relative filling time (FT/RR) was shorter (p<0.01) and total isovolumic time (t-IVT) was longer (p<0.01) in patients than in controls. E/Em was higher (p<0.01), as was Tei index (p=0.02) as compared to controls. T-IVT and Tei index correlated with stroke volume (SV) (r=-0.54, p<0.01 and r=-0.44, p<0.05, respectively) in patients. HRV was reduced in 9/29 (31%) patients, who had shorter FT/RR (p<0.01), longer t-IVT (p<0.01), higher Tei index (p=0.05), A wave (p<0.01) and E/Em (p<0.05) than in subjects without reduced HRV. FT/RR and t-IVT correlated with HRV spectral parameters (p<0.05 for all). The correlation between t-IVT and SV was stronger in patients with reduced HRV (r=-0.80, p<0.01) than in those without. QRS duration was not different in the two subgroups of patients. Conclusions: In a subset of patients with FAP, HRV was significantly reduced and appeared to be associated with shortened LV filling time and prolonged t-IVT, which reflect ventricular dyssynchrony, despite normal QRS. Thus, in addition to autonomic disturbances in FAP, ventricular dyssynchrony is another factor associated with reduced HRV. Correction of such disturbed ventricular function by cardiac resynchronization therapy may control patients' symptom. (C) 2010 Elsevier Ireland Ltd. All rights reserved.