(123I-mIBG And Defibrillation for Atrial Fibrillation): Enhanced sympathetic activity as a mechanism of Atrial Fibrillation recurrence

AF is the most common arrhythmia; its incidence and prevalence will increase
more than twofold over the coming years. The role of the autonomic nervous
system (ANS) in onset and perpetuation of AF remains incompletely understood.
Indeed, the ANS plays a role in the at least in some, but probably in many
patients. There are patients that specifically experience AF during high vagal
tone, or, conversely during exercise. This notion, however, has had modest
impact on the clinical care of patients.
We recently showed that stimulation of the ganglionated plexi resulted in a
disparate response on activation time and conduction velocity, indicating that
there is a direct electrophysiological effect of the ANS that may facilitate
AF8. Similarly, stimulation of the ganglionated plexi during AF changes the
complexity of the arrhythmia, conduction velocity, number of epicardial
breakthroughs and fractionation index in particular.

We do harm by subjecting a considerable number of patients to rhythm control
strategies who will eventually fail, which puts a burden on the individual
patient and the health care budget. On the other hand, there are patients with
an unfavourable baseline profile who do unexpectedly well upon cardioversion,
and these patients may be currently undertreated.

123I-mIBG scintigraphy allows non-invasive quantification of the sympathetic
activity in the heart and has been shown a valuable tool for assessing
prognosis for example in patients after myocardial infarction and patients with
heart failure. The data on atrial fibrillation are limited, but there are
reports that support 123I-mIBG scintigraphy for risk stratification for the
development of atrial fibrillation. The time course of the sympathetic activity
in the heart, and, more importantly the cause of increased sympathetic activity
in the heart is unknown. It may very well be that the increased sympathetic
activity observed in patients with atrial fibrillation is the result of the
ongoing arrhythmia, rather than an independent phenomenon that causes the
arrhythmia. This is a relevant distinction, because it will heavily impact on
the targeted clinical strategy to prevent recurrence of atrial fibrillation in
these patients.

Patients with novel onset or recurrent atrial fibrillation have an altered
myocardial sympathetic activity. The quantification of sympathetic activity
with 123I-mIBG scintigraphy, as well as its change over time after restoration
of sinus rhythm, can be used to target therapy and predict AF recurrence.
The extent of sympathetic activity and its change over time are correlated with
markers of electrical, structural and autonomic remodeling, as assessed by
circulating biomarkers.

Patients with novel onset or recurrent atrial fibrillation, scheduled for
elective electrical cardioversion are eligible for this study. Patients should
be adequately anticoagulated according to the current guidelines2. Patients
with rhythm disturbances other than atrial fibrillation or a history of
catheter or surgical ablation will be excluded. Patients with an emergency
indication for cardioversion will be excluded.
Patients will undergo 123I-mIBG scintigraphy within 7 days before the elective
cardioversion is performed, and a questionnaire on the occurrence of AF and AF
related complaints in the past months will be filled out. Blood samples will be
collected during the cardioversion procedure. Rate/rhythm control management
will be performed according to clinical protocols and at the discretion of the
treating cardiologist, but will preferably remain unchanged during follow-up.
Six weeks after the cardioversion, the patients will be seen at the Cardiology
outpatient clinic (as is standard clinical care), a second 123I-mIBG scan will
be performed and blood samples will be collected again. The rhythm at that time
will be confirmed. Additional visits to the outpatient clinic will be planned 6
and 12 months after cardioversion. At those visits, cardiac rhythm will be
confirmed, blood samples will be collected, and a questionnaire on the
occurrence of AF and AF related complaints over the past months will be filled
out.

123I-mIBG scan

1 maal inclusiegesprek met onderzoeker
2 maal 123I-mIBG scans (voor cardioversie, 6wk na cardioversie)
4 maal bloedafname
4 maal SF-36 questionnaire
2 maal extra polikliniek bezoek (6 en 12 maanden)