Open Access 14-04-2025 | Atrial Fibrillation | Trial Designs

Geranylgeranylacetone as Prevention for Postoperative Atrial Fibrillation (GENIALITY)

Authors: Kennedy S. Ramos, Soufiane Nassiri, Leonoor F. J. Wijdeveld, Reinier L. van der Palen, Myrthe F. Kuipers, Mellanie True Hills, Pieter Slijkerman, Daniel H. van Raalte, M. Louis Handoko, Natasja M. S. de Groot, Nimrat Grewal, Robert J. M. Klautz, Etto C. Eringa, Bianca J. J. M. Brundel

Published in: Cardiovascular Drugs and Therapy

Abstract

Purpose

Interestingly, 30–50% of patients undergoing elective cardiothoracic surgery develop postoperative AF (PoAF). Unfortunately, preventive PoAF therapy is still suboptimal. In our previous studies, we showed that oral Geranylgeranylacetone (GGA) administration increased cardioprotective heat shock protein (HSP) protecting against AF onset and progression in clinically relevant animal model studies.

Methods

The GENIALITY study is a phase II single-center, double-blind, placebo-controlled randomized trial comparing the efficacy of GGA in preventing PoAF. Participants (N = 146) are adult patients, without any registered history of AF, undergoing elective open-heart surgery for valvular disease, coronary artery bypass grafting, or concomitant, and are allocated with ratio 1:1 in treatment or placebo groups. Daily administration of 300 mg of GGA or placebo starts 5 days before until 3 days after surgery. Cardiac rhythm will be monitored using a Holter monitoring post-surgery until hospital discharge. Additionally, blood samples, right atrial appendage tissue, and epicardial adipose tissue will be collected to assess proteostasis levels.

Results

The primary endpoint is the assessment of PoAF incidence in the GGA group compared to the placebo group. Secondary endpoints include the evaluation of HSP levels through biochemical analysis in both blood and atrial tissue.

Conclusion

The GENIALITY study aims to reduce PoAF incidence in the GGA group compared to the placebo group. Herewith, we expect to obtain proof of concept for a beneficial effect of GGA in preventing PoAF in patients undergoing cardiothoracic surgery.

Trial Registration

Clinical Trial Information System (CTIS) registry: 2024–514743-28–00. Authorized on September 30th 2024.

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Title: Geranylgeranylacetone as Prevention for Postoperative Atrial Fibrillation (GENIALITY)
Authors: Kennedy S. Ramos
Soufiane Nassiri
Leonoor F. J. Wijdeveld
Reinier L. van der Palen
Myrthe F. Kuipers
Mellanie True Hills
Pieter Slijkerman
Daniel H. van Raalte
M. Louis Handoko
Natasja M. S. de Groot
Nimrat Grewal
Robert J. M. Klautz
Etto C. Eringa
Bianca J. J. M. Brundel
Publication date: 14-04-2025
Publisher: Springer US
Keywords: Atrial Fibrillation
Shock
Shock
Heart Surgery
Heart Surgery
CABG
CABG
Published in: Cardiovascular Drugs and Therapy
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-025-07693-2

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