Impact of vericiguat on ventricular arrhythmic burden in patients with heart failure with reduced ejection fraction and implantable cardioverter defibrillator
G De Masi De Luca, Z Palama', P Palmisano, G Coluccia, A G Robles, A Scara, M Nesti, S Longo, F Barba, S Bonanno, L Zezza, G De Iaco, A Guido, L Sciarra, S RomanoAbstract
Background
Treatment with vericiguat has been shown to improve clinical outcomes in the VICTORIA trial [1], specifically lowering the risk of cardiovascular death and heart failure hospitalization in patients with heart failure and reduced ejection fraction (HFrEF) at high risk of worsening, with a more pronounced benefit in those with NT-proBNP <4000 pg/mL. Subsequently, the VICTOR trial [2] provided further evidence; although it did not reach its primary composite clinical endpoint, it suggested a reduction in sudden cardiac death (SCD) in stable HFrEF patients. Importantly, even with optimized guideline-directed medical therapy (GDMT), HFrEF patients exhibit a high residual ventricular arrhythmia (VA) burden. We investigated the impact of vericiguat on VA burden and its interaction with NT-proBNP levels and structural remodeling.
Methods
We performed an observational longitudinal analysis of 71 HFrEF patients (LVEF < 40%) with an ICD on optimized GDMT. The VA burden, defined as the total number of sustained and non-sustained ventricular tachycardia, ventricular fibrillation, and ICD therapies (anti-tachycardia pacing and ICD-shocks) was compared 6 months before and after vericiguat initiation, expressed as episodes per patient-month. A two-way ANOVA evaluated the interaction between vericiguat treatment, baseline NT-proBNP levels (<4000 vs > 4000 pg/mL), and structural remodeling (Δ LVEF <15% vs Δ LVEF >15%).
Results
In the overall cohort (n=71), no significant reduction in VA burden was observed (p=0.10). However, ANOVA revealed a significant interaction between vericiguat treatment and baseline NT-proBNP levels (F=5.12; p=0.027; η2 =0.10); post-hoc analysis confirmed a significant reduction in VA burden exclusively in the NT-proBNP < 4000 pg/mL group (p < 0.01). Crucially, the interaction between arrhythmic response and structural remodeling was non-significant (F=0.09; p=0.77; η2=0.02), Figure 1. This demonstrates a clear dissociation between electrical and mechanical response: vericiguat reduced arrhythmias independently of LVEF improvement.
Conclusions
In HFrEF patients on GDMT, vericiguat reduces VA burden specifically in clinically more stable patients. This anti-arrhythmic effect is independent of structural remodeling, providing a mechanistic explanation that aligns with recent evidence suggesting a reduction in SCD among stable heart failure populations.For image description, please refer to the figure legend and surrounding text.