# Effect of spironolactone on monocyte subsets in atrial fibrillation: IMPRESS-AF randomised controlled trial

## TL;DR

This study found that spironolactone temporarily reduced certain inflammatory monocyte markers in patients with atrial fibrillation.

## Contribution

The study is the first to show spironolactone's short-term effects on specific monocyte subsets in atrial fibrillation.

## Key findings

- Spironolactone reduced Mon3 count and CD14 expression on Mon1 at 12 months.
- High Mon1 count at 12 months predicted better diastolic function at 24 months.
- Effects of spironolactone on monocyte markers were not sustained at 24 months.

## Abstract

Monocyte subsets differentially influence pathophysiology of heart failure and atrial fibrillation (AF) through inflammation, fibrosis, and angiogenesis. Spironolactone has antifibrotic properties. This study investigated the effect spironolactone on monocyte subsets and monocyte effects for peak oxygen consumption (peakVO2), diastolic function and brain natriuretic peptide (BNP) in the IMPRESS-AF randomised controlled trial population (2-year treatment with spironolactone 25 mg vs placebo).

CD14++CD16-CCR2+(Mon1), CD14++CD16+CCR2+(Mon2) and CD14+CD16++CCR2-(Mon3) monocyte subsets were analysed by flow cytometry and compared between spironolactone and placebo groups at 12 months and 24 months after randomisation. PeakVO2, diastolic function (echocardiographic E/'e) and BNP were measured at baseline and 24 months. Linear regression was used to assess the effects of monocytes on the outcomes (Python 3.10 modules).

Monocyte data were available in 225 (90%) IMPRESS-AF patients (age 72[67-77], 78% male). At 12-month the spironolactone group had fewer Mon3 (50[36-74] vs 60[44-90] cells/microL, p=0.02), and lower CD14 expression on Mon1 (1.37[1.17-1.59] vs 1.48[1.24-1.70], p=0.04); no difference remained by 24 months (p>0.05). A high 12-month Mon1 count independently predicted lower E/e’ at 24 months (p=0.02).

Spironolactone temporarily reduced proinflammatory monocyte markers (Mon3 count and CD14 expression on Mon1). Mon1 may have a positive effect on diastolic dysfunction in AF.