TY - JOUR
TI - Reactive vasodilation predicts mortality in primary systemic light-chain amyloidosis
AU - Stamatelopoulos, K.
AU - Georgiopoulos, G.
AU - Athanasouli, F.
AU - Nikolaou, P.-E.
AU - Lykka, M.
AU - Roussou, M.
AU - Gavriatopoulou, M.
AU - Laina, A.
AU - Trakada, G.
AU - Charakida, M.
AU - Delialis, D.
AU - Petropoulos, I.
AU - Pamboukas, C.
AU - Manios, E.
AU - Karakitsou, M.
AU - Papamichael, C.
AU - Gatsiou, A.
AU - Lambrinoudaki, I.
AU - Terpos, E.
AU - Stellos, K.
AU - Andreadou, I.
AU - Dimopoulos, M.A.
AU - Kastritis, E.
JO - Circulation Research
PY - 2019
VL - 125
TODO - 8
SP - 744-758
PB - Lippincott Williams and Wilkins
SN - 0009-7330, 1524-4571
TODO - 10.1161/CIRCRESAHA.119.314862
TODO - corticosteroid;  lenalidomide;  nitric oxide;  proteasome inhibitor, adrenergic stimulation;  adult;  age;  all cause mortality;  amyloidosis;  Article;  autonomic dysfunction;  blood flow;  blood vessel reactivity;  cardiovascular risk;  cohort analysis;  controlled study;  correlation analysis;  echography;  female;  gender;  hazard ratio;  human;  hypotension;  major clinical study;  male;  middle aged;  mortality;  priority journal;  prognosis;  risk factor;  survival rate;  systemic light chain amyloidosis;  systemic light chain amyloidosis;  systolic blood pressure;  vascular disease;  vasodilatation;  aged;  AL amyloidosis;  blood pressure;  diagnostic imaging;  laser Doppler flowmetry;  mortality;  pathophysiology, Aged;  Blood Pressure;  Female;  Humans;  Immunoglobulin Light-chain Amyloidosis;  Laser-Doppler Flowmetry;  Male;  Middle Aged;  Regional Blood Flow;  Survival Rate;  Vasodilation
TODO - RATIONALE: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. OBJECTIVE: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. METHODS AND RESULTS: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex-and risk factors-matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (=4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41-13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17-3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45-12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. CONCLUSIONS: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL. VISUAL OVERVIEW: An online visual overview is available for this article. © 2019 American Heart Association, Inc.
ER -