Organization of Excitation in People With Atrial Fibrillation
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Observational

Summary: 
      Atrial fibrillation (AF) is a condition in which the upper chambers of the heart, the atria,
      undergo an irregular beating rhythm. Despite the fact that AF is the most common type of
      sustained cardiac rhythm disturbance the investigators still do not understand it entirely
      and its current therapies are only marginally effective. The overall goal of our project is
      to determine the organization and mechanisms of electrical activation patterns during AF in
      humans.
    

Detailed description: 
      Experiments in animal hearts demonstrated that some cases of atrial fibrillation (AF) may be
      maintained by a small number of drivers in the form of self-sustained, reentrant, electrical
      impulses located in the posterior left atrium (LA) wall, near the pulmonary veins (PV/LA
      junction). In those experiments, the fastest rotors acted as the highest frequency drivers
      that maintained the overall activity. This resulted in a hierarchy of local excitation
      frequencies throughout both atria. More recently, clinical studies have confirmed the
      existence of a hierarchical organization in the rate of activation of different regions in
      the atria of patients with paroxysmal and chronic atrial fibrillation. However, the
      mechanisms underlying such a hierarchical distribution of frequencies in human AF has not
      been explored. Our project will try to demonstrate the general hypothesis that both local
      activation frequency and degree of regularity, while different in different parts of the
      atrium, are distributed non-randomly, with different patterns of distribution in paroxysmal
      versus chronic AF patients. We further surmise that such patterns are the result of
      interrupted propagation of impulses emanating from the drivers localized at the site of
      highest frequency and organization activity, with a gradual reduction of activation frequency
      as the distance from the driver increases. To test our hypotheses we will use a combination
      of clinical and numerical studies. For the clinical part we will gather patients data in a
      collaborative site at Rochester, NY. The data obtained in that site will be analyzed and
      interpreted at the Institute for Cardiovascular Research in SUNY Upstate Medical University.
      For the numerical part, simulations on computer models of AF will be performed solely in the
      Institute for Cardiovascular Research. Our Specific Aims are: 1. Characterize the frequency
      of activation during AF in patients after heart surgery and relate it to the presence of
      fibrosis. 2. In computer simulations, to study the mechanisms of initiation and maintenance
      of AF at the PV/LA junction using three different computer models with increasing anatomical
      complexity (the description of the computer simulations is available only in the grant
      application). Successful achievement of our specific aims should help us advance
      understanding of the mechanisms and manifestations of this complex arrhythmia and may help to
      directly improve the efficacy of pharmacological and ablative therapies of AF in patients.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with paroxysmal and chronic atrial fibrilation (AF).
      
Biospecimen description: 
      Biopsys
    
Keywords: Paroxysmal Atrial Fibrillation; Permanent/Persistent Atrial Fibrillation