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Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis

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Kimon Stamatelopoulos, Georgios Georgiopoulos, Fani Athanasouli, Panagiota Efstathia Nikolaou, Marita Lykka, Maria Roussou, Maria Gavriatopoulou, Aggeliki Laina, Georgia Trakada, Marietta Charakida, Dimitris Delialis, Ioannis Petropoulos, Constantinos Pamboukas, Efstathios Manios, Marina Karakitsou, Christos Papamichael, Aikaterini Gatsiou, Irene Lambrinoudaki, Evangelos Terpos, Konstantinos Stellos & 3 more Ioanna Andreadou, Meletios A. Dimopoulos, Efstathios Kastritis

Original languageEnglish
Pages (from-to)744-758
Number of pages15
JournalCirculation Research
Volume125
Issue number8
DOIs
Publication statusPublished - 27 Sep 2019

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    • King's College London

    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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