Glutamine Suppletion Minimizes the Atrial Fibrillation Burden

Atrial fibrillation (AF) is the most common age-related, progressive cardiac
rhythm disorder that 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.
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 commercially
available dietary supplement able to induce cardio-protective HSPs and
registered in our country is L-glutamine. L-glutamine is a semi-essential amino
acid, which enhances the binding of heat shock transcription factor 1 to the
promoter sequences of hsp genes, resulting in induced expression of HSP70 and
HSP27 in organs, including the heart. In addition, administration of
L-glutamine before cardiopulmonary bypass surgery protected against CPB-induced
inflammation responses in humans and in experimental models. Furthermore,
L-glutamine was found to induce HSP70 levels in serum of critically ill
patients, and correlated with improved outcome. Although the role of
L-glutamine as an inducer of HSP expression and protector against various
diseases including ischemic heart diseases and heart failure has been
recognized, their potential protective role in AF progression has not been
investigated.

The primary objective is to examine whether L-glutamine suppletion in patients
diagnosed with AF induces HSP levels in blood samples. Furthermore, the AF
incidence and burden will be derived and HSP levels will be correlated with the
AF incidence and burden. Positive outcomes of this first pilot study aimed at
prevention of cardiomyocyte damage and subsequently reduction of AF episodes
will be a breakthrough in therapy of AF.

The Glutaminimize AF trial is a prospective interventional trial with invasive
measures (blood drawing) with a scheduled duration of 6 months. Patients with
diagnosed AF and frequent symptomatic AF episodes will start with oral intake
(10gr twice daily) of the L-glutamine supplement after signing written informed
consent.

Baseline measurements
Clinical history of the patient, including start date/year of AF symptoms,
diagnosis date, symptoms, AF incidence, AF burden and prior AF therapy is
evaluated. Additional to the standard clinical care for AF patients, laboratory
tests will be performed for testing of the kidney, liver, thyroid function,
glucose level and HSP level. A start date of oral intake of the L-glutamine
supplement will be chosen with the patient. Patients will be asked to keep up a
diary where they keep track of their L-glutamine intake, AF occurrence,
symptoms and potential side-effects.

Investigational product
L-glutamine dietary supplement (oral intake of 20gr KABI Glutamine powder, of
which 10gr L-glutamine, twice daily).

Follow up
Patients will be evaluated at a dedicated outpatient clinic at 3 and 6 months
after start of L-glutamine intake. The evaluation will consist mainly of
standard AF follow-up care: patient interview (including evaluation of AF
occurrence and symptoms) and a 12-leads ECG. Additionally, at the 3 month and 6
month follow-up a laboratory test for HSP levels is done and L-glutamine intake
and potential side-effects (using the patient diary) are checked together with
the patient. The patient diary and interview will be used to derive the AF
incidence and burden at the moment of follow-up. At 6 months follow-up the
blood sample will also be tested for kidney, liver, thyroid function and
glucose levels.

Oral intake of L-glutamine supplement (KABI Glutamine, 20 gr sachets of which
10 gr L-glutamine, twice daily)

For participants of this study potential benefits are reduction of AF burden,
including AF symptoms. The patient will be compensated for travel expenses
during this study. The investigators will not be compensated for their
participation with regards to this study. Patients will be evaluated at a
dedicated outpatient clinic at 3 and 6 months after inclusion for follow-up.
Adverse events are classified as either only *adverse* or *serious adverse*
based on the guidelines of our institutional medical ethical committee.