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Background: Amyloidosis is characterized by extracellular deposits of insoluble proteins that cause tissue damage. The three main types are monoclonal light chain (AL), wild-type transthyretin (wt-TTR) and mutated transthyretin (m-TTR) amyloidosis. Cardiac amyloidosis (CA) raises diagnostic challenges. Objective: To assess the diagnostic accuracy of99mTc-HMDP-scintigraphy for typing CA, differentiating CA from non-amyloid left ventricle hypertrophy (LVH), and predicting outcomes. Methods: 121 patients with suspected CA underwent99mTc-HMDP-scintigraphy in addition to standard investigations. Results: CA was diagnosed in all AL (n = 14) and wt-TTR (n = 21). Among m-TTR (n = 34), 26 had CA, 4 neuropathy without CA and 4 were asymptomatic carriers. Of the 52 patients with non-amyloid heart disease, 37 had LVH and served as controls.99mTc-HMDP cardiac uptake occurred in all wt-TTR, in m-TTR with CA except two and in one AL. A visual score ≥ 2 was 100% specific for diagnosing TTR-CA. Among TTR-CA, heart-to-skull retention (HR/SR) correlated with CA severity (LVEF and NT-proBNP). Median follow-up was 111 days (50;343). In a multivariate Cox model including clinical, echocardiographic and scintigraphic variables, NYHA III-IV and HR/SR > 1.94 predicted acute heart failure and/or death. Conclusions: This preliminary study suggests that99mTc-HMDP-scintigraphy may aid differentiation between transthyretin and AL-CA as well as CA from other LVHs.99mTc-HMDP-scintigraphy appears to provide prognostic information in CA. [ABSTRACT FROM AUTHOR]

BACKGROUND There are conflicting results in the literature concerning the relationship between obesity and arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV). The discrepancies could be due to differences in carotid-femoral distance measurement and/or to the presence of pathologies frequently associated with obesity and which increase arterial stiffness. In this study, we examine the relationship between PWV and weight, without and with associated cardiovascular risk factors (diabetes and/or dyslipidemia). METHODS PWV was assessed with a Complior SP device (Alam Medical, France) in 2,034 patients referred for ambulatory blood pressure monitoring. The carotid-femoral distance used to calculate PWV was measured with a flexible tape and from the estimated straight carotid-femoral distance obtained with a published equation. RESULTS In the whole cohort, PWV did not differ significantly according to weight (9.6±2.1, 9.8±2.2 and 9.7±1.9 m/s in normal weight, overweight and obese subjects, respectively, with the distance measured with a tape). PWV was significantly higher in the four groups of patients with cardiovascular risk factors (e.g., 11.1 ±2.4, 11.0 ±2.7 and 10.4 ±2.0 m/s in normal weight, overweight, and obese subjects, respectively, in the group treated for diabetes and dyslipidemia) than in the group of patients without cardiovascular risk factors (8.5 ± 1.6, 8.8 ± 1.7 and 8.5 ± 1.2 in normal weight, overweight, and obese subjects, respectively). There was no relationship between PWV value and weight status, whether or not there were cardiovascular risk factors, and whatever the distance used to calculate PWV. CONCLUSIONS In our cohort, obesity perse was not associated with increased arterial stiffness. [ABSTRACT FROM AUTHOR]

Background: Amyloidosis is characterized by extracellular deposits of insoluble proteins that cause tissue damage. The three main types are monoclonal light chain (AL), wild-type transthyretin (wt-TTR) and mutated transthyretin (m-TTR) amyloidosis. Cardiac amyloidosis (CA) raises diagnostic challenges., Objective: To assess the diagnostic accuracy of (99m)Tc-HMDP-scintigraphy for typing CA, differentiating CA from non-amyloid left ventricle hypertrophy (LVH), and predicting outcomes., Methods: 121 patients with suspected CA underwent (99m)Tc-HMDP-scintigraphy in addition to standard investigations., Results: CA was diagnosed in all AL (n = 14) and wt-TTR (n = 21). Among m-TTR (n = 34), 26 had CA, 4 neuropathy without CA and 4 were asymptomatic carriers. Of the 52 patients with non-amyloid heart disease, 37 had LVH and served as controls. (99m)Tc-HMDP cardiac uptake occurred in all wt-TTR, in m-TTR with CA except two and in one AL. A visual score ≥ 2 was 100% specific for diagnosing TTR-CA. Among TTR-CA, heart-to-skull retention (HR/SR) correlated with CA severity (LVEF and NT-proBNP). Median follow-up was 111 days (50;343). In a multivariate Cox model including clinical, echocardiographic and scintigraphic variables, NYHA III-IV and HR/SR > 1.94 predicted acute heart failure and/or death., Conclusions: This preliminary study suggests that (99m)Tc-HMDP-scintigraphy may aid differentiation between transthyretin and AL-CA as well as CA from other LVHs. (99m)Tc-HMDP-scintigraphy appears to provide prognostic information in CA.

Senile systemic amyloidosis (SSA) is characterized by infiltration of amyloid transthyretin fibrils in the myocardium. SSA occurs mainly (but not always) in elderly men. SSA leads to hypertrophic and/or restrictive cardiomyopathy complicated by conduction disturbances, atrial arrhythmia and systemic embolization (stroke…). That is why SSA needs a special care and to be diagnosed. Cardiac SSA diagnosis needs to exclude two other forms of cardiac amyloidosis: AL amyloidosis (light chain) and hereditary transthyretin amyloidosis (genetic testing). Scintigraphic 99mTc-DPD heart retention is observed in cardiac amyloidosis. DPD heart retention is more frequent in cardiac transthyretin amyloidosis than in cardiac AL amyloidosis. Specific treatments of cardiac TTR amyloidosis are in development., (Copyright © 2013. Published by Elsevier Masson SAS.)

Decreasing the bioavailability of serotonin (5-HT) by inhibiting its biosynthesis may represent a useful adjunctive treatment of pulmonary hypertension (PH). We assessed this hypothesis using LP533401, which inhibits the rate-limiting enzyme tryptophan hydroxylase 1 (Tph1) expressed in the gut and lung, without inhibiting Tph2 expressed in neurons. Mice treated repeatedly with LP533401 (30-250 mg/kg per day) exhibited marked 5-HT content reductions in the gut, lungs, and blood, but not in the brain. After a single LP533401 dose (250 mg/kg), lung and gut 5-HT contents decreased by 50%, whereas blood 5-HT levels remained unchanged, suggesting gut and lung 5-HT synthesis. Treatment with the 5-HT transporter (5-HTT) inhibitor citalopram decreased 5-HT contents in the blood and lungs but not in the gut. In transgenic SM22-5-HTT+ mice, which overexpress 5-HTT in smooth muscle cells and spontaneously develop PH, 250 mg/kg per day LP533401 or 10 mg/kg per day citalopram for 21 days markedly reduced lung and blood 5-HT levels, right ventricular (RV) systolic pressure, RV hypertrophy, distal pulmonary artery muscularization, and vascular Ki67-positive cells (P < 0.001). Combined treatment with both drugs was more effective in improving PH-related hemodynamic parameters than either drug alone. LP533401 or citalopram treatment partially prevented PH development in wild-type mice exposed to chronic hypoxia. Lung and blood 5-HT levels were lower in hypoxic than in normoxic mice and decreased further after LP533401 or citalopram treatment. These results provide proof of concept that inhibiting Tph1 may represent a new therapeutic strategy for human PH.