Electrophysiological and genetic insights into atrial fibrillation

S.M. Chaldoupi

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

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Abstract

In this PhD thesis we evaluated the role of the autonomic nervous system (ANS) and the genetic background on atrial substrates required for the initiation and perpetuation of atrial fibrillation (AF), one of the most common arrhythmia. It was shown that dispersion of refractoriness, an electrophysiological substrate for the initiation and perpetuation of AF, is not influenced by the electrical remodeling during AF and it is mainly enhanced in the left atrium (LA) of patients with idiopathic AF. The influence of the ANS on dispersion of refractoriness is rather limited and dependent on the degree of electrical remodeling and the atrial site. In patients with early remodeling dispersion of refractoriness is not influenced by autonomic blockade (AB); while in patients with advanced remodeling due to long-lasting AF, dispersion of refractoriness after AB is only decreased in the right atrium (RA). However, the influence of ANS on complex fractionated electrograms (CFAEs) is greater. Areas of CFAEs can represent critical regions for maintaining AF sites, since they can be related to anatomic and electrical changes of the atrial myocardium. CFAEs are influenced by systemic blockade of the ANS. Such blockade reduced the prevalence of CFAEs in the atria of patients with long-lasting AF, and prevented the time-dependant rise of CFAEs in patients with a new episode of AF and thus in the early- phase of AF. The presence of CFAEs is thus, at least partly, influenced by the status of the ANS. The detection of CFAEs, however, has been controversial among studies. The most accurate technique to identify these areas is unipolar recordings with subtraction of remote ventricular activity (gold standard). With the bipolar technique, some areas with CFAEs may be missed while other areas may be erroneously identified as presenting CFAEs. CFAEs derived from activation times in unipolar recordings without QRS subtraction and a catheter placed perpendicular to the endocardial atrial wall come closest to the gold standard. In this thesis we also studied the role of Cx40 protein in AF. Based on literature it was concluded that heterogeneous distribution of Cx40 protein in the atria during AF can contribute to the stabilization of AF and altered expression of Cx40 protein in the myocardial sleeves of the thoracic veins may be the substrate for the firing foci that can trigger AF. However, Cx40 polymorphism was not present in a big cohort of patients with unexplained ischemic cerebrovascular events and it could not be used as a genetic marker in order to predict idiopathic AF in this population. Additionally it was shown that patients bearing this polymorphism had a reduced expression of Cx40 protein in their atria. However, the presence of this polymorphism was not associated with the prevalence of post-operative AF after cardiothoracic surgery.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Utrecht University
Supervisors/Advisors
  • Hauer, R.N.W., Primary supervisor, External person
  • de Bakker, JMT, Supervisor
  • Doevendans, Pieter, Supervisor
  • Loh, KP, Co-supervisor
Award date10 Nov 2011
Publisher
Print ISBNs978-90-393-5666-1
Publication statusPublished - 10 Nov 2011

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