Sustained paradoxical vasodilation and blood pressure lowering in response to sympathetic stimulation as markers of disease severity and poor survival in primary AL amyloidosis.

Abstract Background AL patients present sustained paradoxical vasodilation in response to sympathetic stimulation by cold pressor test (CPT). The clinical relevance of this finding is unknown. Purpose We investigated the association between CPT-induced vascular and hemodynamic responses with clinical characteristics of the disease in AL amyloidosis. Methods We consecutively recruited 113 newly diagnosed patients with AL amyloidosis before treatment initiation. High resolution ultrasonography was used to measure the maximum vasodilation of the brachial artery in response to a cold stimulus and 3 minutes after its withdrawal. Systolic (SBP) and diastolic blood pressure (DBP) were measured at the same timepoints. Clinical and laboratory makers of autonomic dysfunction were also measured in a subgroup of the population. All-cause and cardiovascular (CV) mortality were defined as end-points of the study. Results Sustained vasodilation post CPT (%pCPT) was associated with markers of autonomic dysfunction, namely dipping status (p<0.05) and sudomotor dysfunction (p=0.064) and with NYHA stage, baseline NTproBNP and heart failure (p<0.05 for all). DBP%pCPT was associated with the neuropathy symptom scale (NSS Autonomous, p=0.032), while SBP%pCPT was inversely associated with Mayo stage. Vasodilation%pCPT was independently associated with CV death (adjusted HR=1.154, p=0.017) while both DBP%pCPT (HR=0.955, p=0.027) and SBP%pCPT (HR=0.947, p=0.04) were independently associated with all cause death (adjusted for the core model including age, sex, SBP, Mayo stage and nerve involvement). Overall survival was worse in AL patients who demonstrated a decrease in SBP%pCPT than in those who exhibited an increase or kept it stable (log rank test, p=0.024). The same applies to DBP%pCPT(log rank test, p=0.002). Regarding CV death, Vasodilation%pCPT above 5.86% was associated with increased risk of CV death (log rank test, p=0.002). Conclusions In AL amyloidosis, sustained paradoxical vasodilation and decreased SBP and DBP in response to sympathetic stimulation were associated with autonomic dysfunction, more severe cardiac involvement and poor survival.