Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis. Issue 8 (27th September 2019)

• Record Type: Journal Article
• Authors: Stamatelopoulos, Kimon; Georgiopoulos, Georgios; Athanasouli, Fani; Nikolaou, Panagiota-Efstathia; Lyka, Marita; Roussou, Maria; Gavriatopoulou, Maria; Laina, Aggeliki; Trakada, Georgia; Charakida, Marietta; Delialis, Dimitris; Petropoulos, Ioannis; Pamboukas, Constantinos; Manios, Efstathios; Karakitsou, Marina; Papamichael, Christos; Gatsiou, Aikaterini; Lambrinoudaki, Irene; Terpos, Evangelos; Stellos, Konstantinos; Andreadou, Ioanna; Dimopoulos, Meletios A.; Kastritis, Efstathios
• Is Part Of: Circulation research. Volume 125:Issue 8(2019)
• Publication Date: 2019-09-27
• Subjects: autonomic nervous system -- brachial artery -- case-control studies -- immunoglobulin light-chain amyloidosis -- mortality -- ultrasonography -- vasodilation; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.119.314862
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.