Sylvie Dinanian

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. Abbreviations: FAP = familial amyloid polyneuropathy, H = heart, H/M = heart-to-mediastinum activity ratio at 4 hours,HRV = heart rate variability, IVS = interventricular septal thickness, SDNN = standard deviation of all cycles, SPET = single-photon emission tomography.

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

Abstract. 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 disturbances and sudden 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 patients (42±12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4xa0h: 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, without 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 evaluate the extent of cardiac sympathetic denervation in FAP patients.

Circadian rhythm of blood pressure reflects the severity of cardiac impairment in familial amyloid polyneuropathy

BACKGROUNDnCardiac amyloidosis due to familial amyloid polyneuropathy (FAP) includes restrictive cardiomyopathy, thickened cardiac walls, conduction disorders and cardiac denervation. Impaired blood pressure variability has been documented in FAP related to the Val30Met mutation.nnnAIMSnTo document blood pressure variability in FAP patients with various mutation types and its relationship to the severity of cardiac involvement.nnnMETHODSnBlood pressure variability was analysed in 49 consecutive FAP patients and was compared with a matched control population. Cardiac evaluation included echocardiography, right heart catheterization, electrophysiological study, Holter electrocardiogram and metaiodobenzylguanidine (MIBG) scintigraphy.nnnRESULTSnA non-dipping pattern was found in 80% of FAP patients and in 35% of control patients (P<0.0001); this was due to a significantly lower diurnal blood pressure in FAP patients (FAP group, 113 ± 21 mmHg; control group, 124 ± 8 mmHg; P<0.0001), whereas nocturnal blood pressures were similar. Among FAP patients, a non-dipping pattern was significantly associated with haemodynamic involvement, cardiac thickening or conduction disorders. These associations did not depend on the average blood pressure levels. Impaired blood pressure variability was more frequent and more pronounced in patients with multiple criteria for severe cardiac amyloidosis.nnnCONCLUSIONnLow blood pressure variability is common in cardiac amyloidosis due to FAP. A non-dipping pattern was more frequently observed in FAP patients with haemodynamic impairment, cardiac thickening or conduction disorders. It is suggested that impairment of circadian rhythm of blood pressure reflects the severity of cardiac amyloidosis due to FAP.

Early detection of right ventricular functional abnormalities in patients with complex right premature ventricular contractions.

BackgroundRight ventricular (RV) premature contractions, although generally benign, may represent the first manifestation of arrhythmogenic RV cardiomyopathy. The diagnostic and prognostic value of RV functional abnormalities evidenced by equilibrium radionuclide angiocardiography (ERNA) with multiharmonic Fourier analysis has been validated in patients with severe RV arrhythmias suspected of being affected by arrhythmogenic RV cardiomyopathy. The aim of this study was to assess the prevalence of the same RV functional abnormalities in patients with frequent left bundle branch block pattern premature ventricular contractions (PVCs), without known heart disease, using ERNA as a screening tool. MethodsThe study included 377 consecutive patients (mean age: 40±15 years, males: 58%) presenting with complex PVCs. Cine mode and multiharmonic analysis were used to define global enlargement and areas of dyskinesia of both ventricles. Studies were classified as: normal, right and/or left ventricular abnormalities either localized or diffuse. ResultsERNA was normal in 302 patients (80%) and evidenced RV functional abnormalities in 75 patients (20%). Patients with RV outflow tract PVCs (n=276) were affected to the same extent as patients with right or left axis PVCs. ConclusionIn a specific population with complex left bundle branch block pattern PVCs, RV functional abnormalities were detected by ERNA in 20% of patients. Consequently, ERNA may serve as a screening tool by selecting patients who may require a specific management.