Impact of Liver Transplantation on Cardiac Autonomic Denervation in Familial Amyloid Polyneuropathy

Abstract

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to the deposition of a genetic variant transthyretin essentially produced by the liver, and characterized by both sensorimotor and autonomic neuropathy. Liver transplantation (LT) is the most effective treatment to stop the progression of the disease. Cardiac amyloid infiltration is usually associated with cardiac denervation, restrictive cardiomyopathy, conduction disturbances, and sometimes sudden death. Whether the cardiac involvement related to amyloid deposition may be altered after LT remains unclear. We conducted the present study to define the outcome of cardiac involvement after LT in 31 patients with FAP (age, 39 +/- 12 yr). Patients were evaluated before and after LT (24 +/- 15 mo). Cardiac sympathetic denervation was assessed by both iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy and heart rate variability (HRV) analysis. The scintigraphic importance of sympathetic denervation was evaluated globally on planar imaging using heart-to-mediastinum activity ratio (H/M) measured 4 hours after injection, and regionally using single-photon emission tomography (SPET) imaging. Amyloid myocardial infiltration was assessed by echocardiography. Diffuse sympathetic denervation was found when using cardiac MIBG planar imaging in patients evaluated before LT and compared with 12 control subjects (H/M: 1.45 +/- 0.29 vs. 1.98 +/- 0.35, p < 0.001). On SPET images, defects were diffuse in 12 patients and focal in 19 patients, with predominance at the inferior and apical segments. No change in sympathetic innervation was found in patients after LT as assessed either with planar imaging (H/M after LT: 1.46 +/- 0.28, p = not significant vs. H/M before LT) or with SPET imaging. HRV nonspectral indexes showed that the standard deviation of all cycles was significantly lower in patients compared with control subjects, and remained unchanged after LT. Conduction disturbances and ventricular arrhythmias were associated with low cardiac MIBG uptake, and progressed after LT. The left ventricular wall was slightly thickened in patients, and a further increase was observed after LT (posterior wall from 9.2 +/- 1.8 to 10.1 +/- 2.3 mm, p = 0.02; septal wall from 10.6 +/- 2.7 to 12.1 +/- 4, p = 0.046). Neurologic status stabilized in 26 patients, but worsened in the 5 patients who had the most severe cardiac sympathetic denervation before LT as measured by MIBG imaging. The magnitude of the cardiac sympathetic denervation remained stable 2 years after LT in patients with FAP, whereas the cardiac amyloid infiltration progressed. The importance of cardiac sympathetic denervation found in FAP patients before LT was associated with a neurologic worsening after LT.

Evaluation of Myocardial Changes in Familial Amyloid Polyneuropathy after Liver Transplantation

“…However, IVS and PWT were increased in several Swedish FAP ATTR Val30Met patients with later onset compared with Portuguese and Japanese patients (7). A similar finding was reported from a French group (13 …”

The heart in liver transplantation

“…Furthermore, increased intrahepatic resistance also leads to an independent increase in kidney sodium retention and further increases portal venous flow. -Progressive improvement of all abnormalities, although possible initial worsening of diastolic function [40,50,132] -15-25% of deaths caused by cardiac events in post LT -No improvement of sympathetic cardiac denervation, progression of cardiac amyloid infiltration [26,128,129] no differences in mortality rates [83] t n a l p s n a r t e r P Prevalence 6-26% [68][69][70] 27.5% valvular dysfunction [83] Prevalence 4% [82] Greater prevalence with 40-90% prevalence prolonged cQT [41,46,149] Prevalence 2-14% [52][53][54][55][56] EKG abnormalities 46% [14] more severe disease Frontiers in Liver Transplantation prolong ventricular repolarization, i.e. anti-arrythmics such as amiodarone, or antibiotics such as erythromycin [47].…”

“…One should keep in mind that this condition may induce heart disease associated with amyloid deposition, which may lead to cardiac denervation, restrictive cardiomyopathy, conduction disturbances and death. Echocardiography and autonomic function testing are important for the evaluation of these patients when considering LT [26].…”

Nuclear imaging in cardiac amyloidosis

“…The severity of cardiac sympathetic denervation found in FAP patients before LT was associated with a neurological worsening after LT. Therefore, an objective measurement of cardiac adrenergic innervation, such as that obtained by MIBG imaging, could help guide the indications for LT in FAP patients in the early stages of the disease [16].…”