Key result
ICD/CRT-D high-voltage intervention linked to ~61% higher soluble Klotho protein in HF patients.
Why the study?
Inflammatory cytokines and the NLRP3 inflammasome promote arrhythmias leading to ICD/CRT-D shocks, but the peri-shock inflammatory response and the role of cytokines, NLRP3, and soluble Klotho protein required evaluation.
Does ICD/CRT-D high-voltage intervention alter serum concentrations of inflammatory cytokines, NLRP3 inflammasome, and α-Klotho protein in patients with heart failure?
Observational (n=50)
No
Does ICD/CRT-D high-voltage intervention alter serum concentrations of inflammatory cytokines, NLRP3 inflammasome, and α-Klotho protein in patients with heart failure?
ICD/CRT-D high-voltage interventions in heart failure patients are associated with an acute inflammatory response and a significant increase in protective α-Klotho protein levels.
Does not yet alter heart failure device decisions; leaves open Klotho's role as protective marker.
Objectives: Inflammatory cytokines contribute to Implantable Cardioverter-Defibrillator/Cardiac Resynchronization Therapy with a Defibrillator (ICD/CRT-D) high-voltage intervention by promoting arrhythmias through direct cardiac effects and indirect systemic changes. The NLRP3 inflammasome can promotes arrhythmias by linking inflammation, oxidative stress, and structural changes. The aim of this study was to assess the inflammatory response in the peri-shock-period in patients with heart failure (HF) and implanted ICD/CRT-D and the initial analysis of the possible role of cytokines, NLRP3 and soluble Klotho protein in peri-shock period and the possibility of triggering arrhythmias. Methods: The study population consisted of 50 patients with diagnosed HF and implanted ICD/CRT-D devices. Blood samples were drawn up to max. 6 h after appropriate ICD/CRT-D intervention ("intervention group") or from patients qualified for ICD/CRT-D device replacement (ERI status) and with no intervention min in the previous 3 months ("control group"). Serum concentration of TNF-α, IL-1β, IL-6, IL-10, IL-17, NLRP3 inflammasome, soluble Klotho protein and FGF-23 complete blood count, were determined in all individuals. Results: /µL, 95% CI: 0.01-0.08, p = 0.0013). Serum concentration of soluble Klotho protein was significantly higher after device intervention (557.5 pg/mL, 95% CI: 495.5-619.5 vs. 895.2 pg/mL, 95% CI: 744.7-1,046.0, p < 0.0001), with no change in FGF-23 levels. Conclusion: In the peri-shock period, increased IL-6 and IL-10 serum concentrations and changes in 5-diff blood count (increased neutrophils and decreased eosinophils) are observed, which may be associated with a higher risk of ventricular arrhythmia in HF patients. A significant increase in α-Klotho protein concentration, should be taken into account in the development of future diagnostic methods and indicates an important protective role in the inflammatory process.
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Szyller et al. (2026) conducted an observational in Heart failure with implanted ICD/CRT-D (n=50). ICD/CRT-D high-voltage intervention vs. No intervention in the previous 3 months (ERI status) was evaluated on Serum concentration of soluble Klotho protein (p=<0.0001). ICD/CRT-D high-voltage intervention in heart failure patients was associated with significantly higher serum concentrations of soluble Klotho protein compared to controls (895.2 vs 557.5 pg/mL).
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