S Ramos Kennedy, Nassiri Soufiane, Wijdeveld Leonoor F J, van der Palen Reinier L, Kuipers Myrthe F, Hills Mellanie True, Slijkerman Pieter, van Raalte Daniel H, Handoko M Louis, de Groot Natasja M S, Grewal Nimrat, Klautz Robert J M, Eringa Etto C, Brundel Bianca J J M
Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, Amsterdam University Medical Center, Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Physiology, 1081 HV Amsterdam, The Netherlands.
Department of Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Cardiovasc Drugs Ther. 2025 Apr 14. doi: 10.1007/s10557-025-07693-2.
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.
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.
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.
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.
有趣的是，30%至50%接受择期心胸外科手术的患者会发生术后房颤（PoAF）。遗憾的是，预防性PoAF治疗仍不尽人意。在我们之前的研究中，我们表明，在临床相关动物模型研究中，口服香叶基香叶基丙酮（GGA）可增加心脏保护热休克蛋白（HSP），预防房颤的发生和进展。
GENIALITY研究是一项II期单中心、双盲、安慰剂对照随机试验，比较GGA预防PoAF的疗效。参与者（N = 146）为成年患者，无任何房颤登记病史，因瓣膜疾病、冠状动脉旁路移植术或两者同时进行择期心脏直视手术，并按1:1的比例分配至治疗组或安慰剂组。在手术前5天开始每日服用300 mg GGA或安慰剂，持续至术后3天。术后使用动态心电图监测心律直至出院。此外，将采集血样、右心耳组织和心外膜脂肪组织，以评估蛋白质稳态水平。
主要终点是比较GGA组与安慰剂组的PoAF发生率。次要终点包括通过血液和心房组织的生化分析评估HSP水平。
GENIALITY研究旨在降低GGA组与安慰剂组相比的PoAF发生率。据此，我们期望获得GGA对接受心胸外科手术患者预防PoAF有益作用的概念验证。试验注册：临床试验信息系统（CTIS）注册：2024 - 514743 - 28 - 00。于2024年9月30日获得授权。
