Patient-Funded Research By Professor Bianca Brundel Into How to Prevent Afib
November 22, 2022
- Summary: GGA Atrial Fibrillation Trial is Patient-Funded Research Into How to Prevent Afib
- Reading time: 4–5 minutes
A favorite presenter at the Get in Rhythm. Stay in Rhythm.® Atrial Fibrillation Patient Conferences in 2021 and 2022 was Professor Bianca Brundel, PhD, from the physiology department at the Amsterdam University Medical Center in The Netherlands.
Dr. Brundel is at the leading edge of practical basic science research for afib. At the conferences, she gave afib patients actionable ways to help manage their afib and provided updates on her patient-driven research. In addition, she shared information on testing how toxic triggers drive afib progression and how those findings will be used to discover effective treatments and diagnostics. She also discussed patient involvement in research, including how to get involved. She founded the nonprofit Atrial Fibrillation Innovation Platform, which promotes studies in collaboration with patients. She is also the project leader of CIRCULAR, a project funded by the Dutch government based on co-creating research with afib patients and StopAfib.org.
Based on what we have learned from her, we in the patient community are stepping up to help fund some of Dr. Brundel’s research. For example, she and her colleagues recently showed that structural damage to the heart results from “derailment in cardiomyocyte proteostasis” and that this damage could be counteracted by heat shock proteins (HSPs).
A potent drug called GGA (geranylgeranylacetone) can induce heat shock proteins in the heart. In a dog model of afib, they showed that oral treatment with the drug GGA prevents damage and protects against afib onset and progression.
GGA is a non-toxic HSP-inducer, and since 1984, it has been registered in several Asian countries to treat gastric ulcers. GGA also protects against afib progression and accelerates recovery from damage in experimental afib models. In addition, three days of oral treatment with GGA induces HSP levels in the atrial tissue of patients undergoing cardiac surgery. The researchers believe oral treatment with GGA can reverse afib-induced damage and prevent post-operative afib (POAF) from cardiac surgery.
With our help as a patient community, they aim to study the effect of GGA on the development of afib. The primary objective will be to determine if the HSP-inducing and protective effects of GGA can prevent the development of new afib in 42 patients who have elective cardiac bypass surgery. Afib damages the heart through structural and electrical remodeling. Thus, the secondary objectives are to assess the protective effects of GGA on damage by quantifying the amount of structural and electrical remodeling. This will be done by determining the amount of arrhythmogenic substrate using high-resolution mapping during open-heart surgery. They will also determine the duration and number of POAF episodes (afib burden).
If this non-toxic, well-tolerated oral medication can prevent afib, it could also open doors for treating existing afib.
We, as patients, can be involved in research to help answer important questions. We can make a difference. This research is such a worthy cause for our support as a patient community. Won’t you join us in supporting this research?
All funds donated will go directly to support this research project. We will send 100% (after credit card fees) directly to the non-profit Atrial Fibrillation Innovation Platform (AFIP) that supports Professor Brundel’s patient-focused research.
This Giving Season, will you help support vital patient-driven afib research through a charitable contribution? You can Donate here:
Or, if you have questions to help you make a Qualified Charitable Distribution (QCD) from your retirement fund, please let us know.
Thank you for your support of this vital patient-initiated research.
Here are some additional resources to help you learn more:
- GGA Atrial Fibrillation Trial abstract (below) from lead investigators Prof. Dr. Bianca JJM Brundel and Prof. Natasja MS de Groot. Both are world-renowned researchers with extensive research labs. Prof. de Groot is an electrophysiologist and basic science researcher at Erasmus Medical Center in The Netherlands. Please help support their patient-focused research.
- Patient-Driven Afib Research Update (recordings), by Bianca J.J.M. Brundel, PhD, at the 2022 Get in Rhythm. Stay in Rhythm.® Atrial Fibrillation Patient Conference—If you don’t yet have a StopAfib Library account, sign up here by following these three simple steps: (1) enter your first and last names and email address and click the “Create Your Account Now” button; (2) click the Create Your Library Account Here link; (3) enter your desired password (twice) and then click the “Submit” button followed by the “Accept” button. Now you can click on the link above to access the recordings.
- Atrial Fibrillation, Nature Reviews Disease Primers, authored by Bianca JJM Brundel (first author), Natasja MS de Groot (senior author), Mellanie True Hills, Gregory YH Lip, Xun Ai, and Myrthe F. Kuipers.
ABSTRACT: GGA Atrial Fibrillation Trial: GeranylGeranylAcetone prevents post-operative Atrial Fibrillation onset
By: Prof. Dr. Bianca JJM Brundel and Prof. Natasja MS de Groot
Universities: Amsterdam UMC, VUmc and Erasmus Medical Center and VU Medical Center, the Netherlands
Patient Platforms: Non-profit Atrial Fibrillation Innovation Platform and StopAfib.org
Atrial fibrillation (AF) is the most common age-related, progressive cardiac rhythm disorder and is associated with serious complications such as stroke, heart failure, impaired cognitive function and increased mortality.
In The Netherlands, there are approximately 45,000 new AF patients every year and this number is most likely underestimated as many people may have undiagnosed (asymptomatic) paroxysmal AF.
At present, there is no curative therapy. Though ablative therapy initially seemed promising, many patients have recurrences or require multiple, expensive ablation procedures. Pharmacological therapy for AF is only moderately effective; its usage is limited by pro-arrhythmogenicity or non-cardiovascular toxicities. In addition, the response of an individual patient to anti-arrhythmic drug therapy can often not be predicted and usage is therefore based on ‘trial-and-error.’
Electrical cardioversion is only temporarily effective and AF recurs in up to 87% of patients. Also, there are no drugs preventing progression from paroxysmal to persistent AF. De novo AF is frequently observed after cardiac surgery with incidences of 30%–45% and is associated with increased morbidity and mortality.
Importantly, the persistence of AF is rooted in the presence of electropathology which is defined as complex electrical conduction disorders caused by structural damage of atrial tissue. Hence, pharmacological therapy of AF should be directed at resolving structural damage. Brundel et al. recently showed that structural damage results from derailment in cardiomyocyte proteostasis (protein expression, function and clearance) and that this could be normalized by overexpression of heat shock proteins (HSPs).
A potent HSP-inducing drug is geranylgeranylacetone (GGA). We showed previously in the dog model of AF, that oral treatment with GGA prevents the induction of electropathology and protects against AF onset and progression. GGA (Selbex®, teprenone capsules, Eisai, Japan) has already been applied clinically in Japan since 1984 as an antiulcer drug with no reported serious adverse reactions. GGA enhances the binding of heat shock transcription factor 1 to the promoter sequences of hsp genes, resulting in induced expression of HSP70 and HSP27. We recently observed that oral treatment with 400 mg GGA during 3 days results in significant induction of HSP27 and HSP70 expression in atrial tissue of patients undergoing cardiac surgery. Since GGA is a non-toxic HSP-inducer, with protective effects against AF progression in experimental models, we hypothesize that oral treatment with GGA reverses AF-induced electropathology and thereby prevents development of AF in patients undergoing cardiac surgery (POAF).
The primary aim of this project is to determine the HSP-inducing and hence protective effects of GGA on development of de novo AF episodes after elective cardiac bypass surgery in N=42 patients. Secondary objectives include assessment of the protective effects of GGA on electropathology by quantifying the degree of a) structural remodelling (determination correlation atrial tissue and blood-based biomarkers levels) and b) electrical remodelling by determining the extensiveness of the arrhythmogenic substrate using epicardial high resolution mapping and c) the duration and number of POAF episodes (burden).
The acquired data is compared to an existing database from the Halt&Reverse project which is used for matching of the GGA-treated patients based on age, gender and cardiovascular diseases (Brundel&deGroot, LSH-Impulse grant (40-43100-98-008) and CVON-AFFIP project (DeGroot&Brundel, Dutch Heart Foundation (2013T144)).
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