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Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis

Lookup NU author(s): Professor Kimon Stamatelopoulos, Dr Aikaterini GatsiouORCiD, Professor Konstantinos StellosORCiD

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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.

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Author(s): Stamatelopoulos K, Georgiopoulos G, Athanasouli F, Nikolaou P-E, Lykka M, Roussou M, Gavriatopoulou M, Laina A, Trakada G, Charakida M, Delialis D, Petropoulos I, Pamboukas C, Manios E, Karakitsou M, Papamichael C, Gatsiou A, Lambrinoudaki I, Terpos E, Stellos K, Andreadou I, Dimopoulos MA, Kastritis E

Publication type: Article

Publication status: Published

Journal: Circulation Research

Year: 2019

Volume: 125

Issue: 8

Pages: 744-758

Online publication date: 27/09/2019

Acceptance date: 09/08/2019

Date deposited: 07/10/2019

ISSN (print): 0009-7330

ISSN (electronic): 1524-4571

Publisher: Lippincott Williams & Wilkins

URL: https://doi.org/10.1161/CIRCRESAHA.119.314862

DOI: 10.1161/CIRCRESAHA.119.314862

PubMed id: 31401949

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