Medicina

The Pathophysiology of Atrial Fibrillation (AF) and the Importance of Sinus Rhythm
Remodeling of the atria caused by atrial fibrillation makes it more difficult to return to sinus rhythm, more difficult to respond to treatment, and increases vulnerability to relapse.1
Classification
* The American College of Cardiology (ACC), the American Heart Association Task Force (AHA), and theEuropean Society of Cardiology Committee (ESC), in collaboration with the Heart Rhythm Society have established guidelines for the classification of AF2
* First-detected episode of AF – may or may not be symptomatic; the actual duration of the episode and previous undetected episodes may be uncertain2
* Recurrent AF - 2 or more episodes2
* Paroxysmal AF - self-terminating, spontaneouslyconverts to sinus rhythm2
* Persistent AF - lasts longer than 7 days, is not self-terminating and usually requires medical intervention2
* Permanent AF – refractory to cardioversion or has persisted for a long period of time2
* Lone AF – occurring in a patient younger than 60 years who has no clinical or echocardiographic evidence of cardiopulmonary disease, including hypertension2* Valvular and nonvalvular AF – occurs in a patient who has evidence or history of rheumatic mitral valve disease, who has a prosthetic heart valve, or who has valve repair; all other forms of AF are classified as nonvalvular AF2
Atrial Fibrillation Begets Atrial Fibrillation
* One of the main challenges of atrial fibrillation is the tendency of the disease to become chronic over time,during which a combination of molecular and structural changes make it difficult to achieve and maintain sinus rhythm3
Electrical Remodeling
* The concept that AF is self-perpetuating has been studied extensively in a goat model using an automatic atrial fibrillator that detected spontaneous termination of AF and reinduced AF by electrical stimulation. At first, the electrically induced AFterminated spontaneously. However, with repeated inductions, AF episodes became progressively more sustained until AF persisted and at a more rapid rate. The increasing propensity to AF was associated with progressive shortening of the effective refractory period as well as with increasing episode duration2 (See Figure)
* Electrophysiological remodeling has led to the phrase “atrial fibrillationbegets atrial fibrillation,” originally coined by Wijffels and colleagues2,3
* In addition to remodeling and changes in electrical refractoriness, prolonged AF disturbs atrial contractile function. After a period of persistent AF, recovery of atrial contraction can be delayed for days or weeks following the restoration of sinus rhythm2

Figure. Posterior view of principalelectrophysiological mechanisms of atrial fibrillation. A. Focal activation. The initiating focus (indicated by the star) often lies within the region of the pulmonary veins. The resulting wavelets represent fibrillatory conduction, as in multiple-wavelet reentry. B. Multiple wavelet reentry. Wavelets (indicated by arrows) randomly reenter tissue previously activated by the same or another wavelet. The routes thewavelets travel vary. LA indicates left atrium; PV, pulmonary vein; ICV, inferior vena cava; SCV, superior vena cava; and RA, right atrium. Adapted from Konings.2,4

* Electrophysiological remodeling occurs on 2 time scales: rapid (seconds or minutes) and slower (days or weeks).
* Rapid electrophysiological remodeling involves translational modulation of Ica and ITO ionic currents byaltered pH, intracellular Ca2+, phosphorylation and oxidation state, and metabolic regulation of pore forming alpha and beta subunits3
* Slower changes are due to changes in the rate of translation, synthesis, and degradation of ion channel subunits in the myocyte membranee.
Structural Remodeling
* The most frequent structural changes in AF are atrial fibrosis and loss of atrial...