Early detection of sympathetic myocardial denervation in patients with familial amyloid polyneuropathy type I.

Introduction Type I familial amyloid polyneuropathy (FAP I) is an autosomal dominant inherited disorder due to a genetic defect in transthyretin and is characterized by deposition of amyloid in various organs and tissues.The principal manifestations are related to neuropathy and dysautonomia. The aim of this study was to assess cardiac involvement and to correlate the findings with neurological status. Methods: 34 patients with FAP (15 male and 19 female; mean age 43 ′ 15 years) underwent I 1 2 3 -labeled metaiodobenzylguanidine (MIBG) myocardial scintigraphy in order to evaluate cardiac sympathetic innervation. In addition they underwent ambulatory blood pressure monitoring (ABPM) and two-dimensional and Doppler echocardiography. Neurological involvement was quantified according to a neurophysiologic score (EMG; 0 = no abnormality and 100% = maximal disability), Results: The mean value of cardiac MIBG uptake was 1.75 ′ 0.5 (normal = 2.6 ′ 0.3) and correlated inversely with the EMG score (r = -0,67; p = 0.001). In 27 (79%) of the 34 patients there was a decrease in MIBG accumulation, in 18 (53 %) an alteration in the circadian BP pattern and/or an increase in systolic and/or diastolic BP loads at night, and in 17 (50 %) left ventricular hypertrophy and/or diastolic dysfunction. Twenty-two patients were symptomatic and had a mean EMG score of 37.7 ′ 25% (group I). The remaining 12 were asymptomatic and without neurological involvement (group II). Group I was characterized by older age (48 ′ 15 vs. 33 ′ 10.2 years, p = 0.01), lower MIBG uptake (1.5 ′ 0.4 vs. 2.2 ′ 0.5, p = 0.001), higher systolic (129 ′ 16 vs. 119 ′ 6 mmHg, p = 0.01) and diastolic daytime BP (82 ′ 10 vs. 76 ′ 6 mmHg, p = 0.05), and higher systolic (119 ′ 17 vs. 105 ′ 7 mmHg, p = 0.01) and diastolic nocturnal BP (71 ′ 11 vs. 62 ′ 9 mmHg, p = 0.01) than patients in group II. In 2½2 patients in group I and in 6/12 in group II there was a decrease in cardiac MIBG activity. Sixteen patients in group I and 2 in group II had abnormal circadian BP pattern. Left ventricular hypertrophy was only seen in group I. Conclusions: Patients with FAP have a high incidence of cardiac denervation and an abnormal circadian BP pattern. These alterations in cardiac autonomic function precede the development of clinical manifestations and may be an important factor in determining the optimal timing for liver transplantation, which is currently the only way to control the progression of the disease.