TY - JOUR
T1 - Geranylgeranylacetone as Prevention for Postoperative Atrial Fibrillation (GENIALITY)
AU - Ramos, Kennedy S.
AU - Nassiri, Soufiane
AU - Wijdeveld, Leonoor F. J.
AU - van der Palen, Reinier L.
AU - Kuipers, Myrthe F.
AU - Hills, Mellanie True
AU - Slijkerman, Pieter
AU - van Raalte, Daniel H.
AU - Handoko, M. Louis
AU - de Groot, Natasja M. S.
AU - Grewal, Nimrat
AU - Klautz, Robert J. M.
AU - Eringa, Etto C.
AU - Brundel, Bianca J. J. M.
PY - 2025/4/1
Y1 - 2025/4/1
N2 - PurposeInterestingly, 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.MethodsThe 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.ResultsThe 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.ConclusionThe 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 RegistrationClinical Trial Information System (CTIS) registry: 2024-514743-28-00. Authorized on September 30th 2024.
AB - PurposeInterestingly, 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.MethodsThe 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.ResultsThe 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.ConclusionThe 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 RegistrationClinical Trial Information System (CTIS) registry: 2024-514743-28-00. Authorized on September 30th 2024.
KW - Heat shock proteins
KW - Prevention
KW - Cardiothoracic surgery
KW - Postoperative atrial fibrillation
KW - SHOCK-PROTEIN INDUCER
KW - SUBSTRATE
U2 - 10.1007/s10557-025-07693-2
DO - 10.1007/s10557-025-07693-2
M3 - Article
SN - 0920-3206
JO - Cardiovascular Drugs and Therapy
JF - Cardiovascular Drugs and Therapy
ER -