Cold pressor test and paradoxical blood pressure reduction in AL amyloidosis

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Abstract

Background

Patients with AL amyloidosis present sustained paradoxical vasodilation in response to sympathetic stimulation by cold pressor test (CPT). The clinical relevance of this finding is unknown. We investigated the clinical role of CPT induced vascular and hemodynamic responses.

Methods

We prospectively recruited 113 treatment-naïve AL amyloidosis patients. High resolution ultrasonography was used to measure the peak percent change of the brachial artery during CPT and 3 minutes after its’ withdrawal (postCPT), defined as sustained response. Peripheral and aortic (central) systolic (SBP) and diastolic blood pressure (DBP) were measured at the same timepoints before and 12 months after treatment initiation. All-cause and cardiovascular mortality were recorded (median follow-up 26 months). The same tests were performed in ten healthy volunteers.

Results

Sustained vasodilation and reductions in central systolic (%CSBP_post) and peripheral diastolic BP were observed in AL as compared to controls (p<0.01 for all) and were associated with all-cause and cardiovascular death after adjustment for disease-related risk factors (p<0.05 for all). %CSBP_post provided incremental value over Mayo stage. Mechanistic analyses revealed associations of %CSBP_post with markers of neurological and cardiac dysfunction and of myocardial infiltration. Longitudinally, at 12 months, %CSBP_post further decreased in patients with earlier poor hematologic response to disease-specific treatment.

Conclusions

Using a noninvasive readily available method in treatment-naïve AL amyloidosis patients, sustained reduction of central SBP after sympathetic stimulation was associated with cardiac dysfunction, poor survival and response to treatment.

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