AIMS: Reverse ventricular remodelling, defined as a decrease in left ventricular end-systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear. METHODS AND RESULTS: We evaluated paired core-lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF. Reverse ventricular remodelling was defined as a >5% LVEF increase or >15% LVESVI relative decrease between baseline and 8 months. We evaluated the association between baseline biomarkers and their changes with reverse ventricular remodelling in the prospectively randomized controlled VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial. Of 419 patients (median age 66 [interquartile range 57-74] years, 27.4% women), 206 (49.2%) had reverse ventricular remodelling (either a 5% LVEF increase or a 15% LVESVI decrease). There were no differences in baseline biomarker concentrations between patients with versus those without reverse ventricular remodelling on follow-up. However, in patients with reverse ventricular remodelling there were significant decreases in biomarkers relating to inflammation and cardiac metabolism; particularly the tumour necrosis factor superfamily member 13B (ratio 0.82, 95% confidence interval [CI] 0.77-0.88), growth differentiation factor-15 (ratio 0.74, 95% CI 0.66-0.84), and insulin-like growth factor binding protein 7 (ratio 0.80, 95% CI 0.73-0.88). CONCLUSIONS: Reverse ventricular remodelling in patients with HFrEF is associated with a decrease of biomarkers related to inflammation and cardiac metabolism.

Bayer AG Wuppertal Germany

Charité University Medicine German Heart Center Berlin Germany

Department of Cardiology Institute for Clinical and Experimental Medicine IKEM Prague Czech Republic

Department of Cardiology University Medical Centre Groningen Groningen The Netherlands

Hatter Institute for Cardiovascular Research in Africa Faculty of Health Sciences Department of Medicine and Cardiology University of Cape Town Cape Town South Africa

INECO Neurociencias Oroño Fundación INECO Rosario Argentina

National Heart Centre Singapore Duke National University of Singapore Singapore Singapore

Saw Swee Hock School of Public Health National University of Singapore and National University of Singapore and National University Health System Singapore Singapore

The Inova Center of Outcomes Research Inova Heart and Vascular Institute Falls Church VA USA

Unidad de Cirugía Cardiovascular de Guatemala Guatemala City Guatemala

University of Alberta Canadian VIGOUR Centre Edmonton AB Canada

University of Groningen Groningen The Netherlands

Volgograd State Medical University Regional Cardiology Centre Volgograd Volgograd Russian Federation

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