Introduction
Atrial fibrillation (AFib) poses a significant risk for stroke and is linked with increased mortality. AFib affects more than 2 million people in the United States. Sometimes AFib goes away on its own, while for some people, AFib is an ongoing heart problem lasting for years. Moreover, AFib is associated with structural heart conditions and other extra-cardiac factors, such as hypertension, obesity, diabetes, and sleep apnea. A person with AFib has a fivefold higher risk of stroke and a twofold higher risk of cardiac-related death.
What Is AFib?
AFib is an arrhythmia of the heart due to abnormal electrical activity in the atria (upper chamber of the heart) that leads them to fibrillate. It is represented as a tachyarrhythmia, which means the heart rate is often fast. This cardiac arrhythmia can be paroxysmal, which is less than seven days, or it can be persistent, which is more than seven days. Irregular rhythm causes turbulence in blood flow through the heart and has a high possibility of forming a blood clot, which can eventually dislodge and cause a stroke.
What Is the Mechanism of AFib?
There is a wide variety of pathophysiological mechanisms in the development of AFib. However, most of them account for cardiac remodeling, particularly atria, which results in structural and complex electrical defects, which eventually become the reason for deranged rhythm in AFib.Remodeling-associated changes in AFib can be grouped into the following three categories:
1) Electrical remodeling.
2) Structural remodeling.
3) Autonomic remodeling.
What Is Electrical Remodeling in AFib?
One of the most marked mechanisms driving AFib is the electrical remodeling happening in the cells of atrial muscles. Various types of ionic currents are found to change in AFib, and research has shown its contribution to the development of AFib.
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Changes in Ca2+ Handling:
In the atria, it contributes to the development and worsening of AFib. In addition, numerous studies suggest a connection between modified calcium handling and delay after depolarization, leading to ectopic foci formation and AFib initiation.
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Increased K+ Currents:
It is also intimately associated with electrical remodeling in AFib. For example, K+ currents are increased in AFib, which alters resting potential and certain activation phases, leading to decreased atrial refractoriness and wavelength.
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Gap Junction Function Alteration:
The gap junction function is directly associated with conduction velocity, which is a determinant of AFib. Slow conduction velocity allows reentry, permitting the initiation and maintenance of AFib. Electrical changes in the heart lead to secondary changes in the atria’s contractile function, which reduces maximum tension and speeds of tension activation and relaxation.
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Re-entry:
The mechanism of AFib requires an awareness of re-entry as a mechanism. Re-entry is not a disorder of impulse formation but a disorder of impulse propagation (increased numbers) that occurs when an impulse repetitively travels around an abnormal circuit. Re-entry occurs when an impulse activates an area; for example, A premature beat emerging in area B fails to go to area A because the intervening tissue stays refractory from the prior sinus beat. Instead, the premature stimulus transits slowly via an alternative path back to area A, thus allowing area A enough time to recover and be excited. Area A, in turn, re-excites area B, and this cycle sustains itself. This cycle describes the mechanism of a typical atrial flutter.
What Is Structural Remodeling in AFib?
Structural remodeling is the most apparent atrial change that occurs in AFib. These remodelings are characterized by changes in tissue properties, that is, atrial size, fibrosis, and cellular ultrastructure. These changes predispose the atria to flaws in electrical conduction. Various elements contribute to fibrosis underlying AFib, including cell structure, neurohormonal activity, oxidative stress, and even AFib itself contributes to worsening tissue properties. Evidence from genetic studies of cardiac fibrosis suggests that the atria are especially sensitive to profibrotic signaling due to the increased response of atrial fibroblasts (cells of fibrous tissue) than ventricular (lower chambers of the heart) fibroblasts.
The mechanism of fibrotic tissue’s causes of AFib is examined in detail by various research that concludes that cells of muscles of the heart (cardiomyocytes) in fibrotic atria are separated more distantly than those in non-diseased atria. These fibroblasts and extracellular matrix essentially form a physical conduction barrier that lowers electrical coupling between cardiomyocytes, and susceptibility to reentry increases. There is also an upsurge in fibroblast proliferation in AFib, which is linked to increases in the observable trait of activated fibroblasts (myofibroblast). Interactions between cardiomyocytes and myofibroblasts negatively affect conduction organization, leading to an increased tendency to ectopic activity and arrhythmias due to reentry. An increase in fibroblast-myocyte interactions also alters conduction through fibroblast functioning as an electric sink and paracrine activity (a type of cellular communication where cell signals induce changes in adjacent cells), leading to a slowing of conduction, depolarization of resting potential in cardiomyocyte, varying effects on action potential span, and the induction of spontaneous depolarization all of which bring about to re-entry and ectopy.
Increased atrial size favors AFib as reentrant circuits develop more readily with bigger atrial size due to the additional area for rotor formation. Atrial size also affects tissue properties, causing raised atrial stretch, commonly associated with increased atrial tissue remodeling. AFib also occurs at the ultrastructural level. Multiple defects in cardiomyocyte ultrastructure are observed.
What Is Autonomic Remodeling in AFib?
The autonomic nervous system exerts substantial control of cardiac electrophysiology. Thus defects in autonomic function are also associated with AFib.The autonomic nervous system extensively controls the heart through extrinsic (outside the heart) and intrinsic (inside the heart) nervous tissues. These extrinsic nerves comprise the vagal nerve and nerves emerging from the paravertebral ganglion. Autonomic dysfunction is reflected as raised sympathetic activity in AFib. Autonomic changes are also observed in endurance exercise, which increases AFib susceptibility related to autonomic changes, atrial fibrosis, and dilation. This effect is also observed in the increased prevalence of AFib in endurance athletes.
Conclusion
AFib is a complex disease that is caused by the structural alterations in the atria that therefore result in complex electrophysiological patterns and defects that generate dysfunction in the atria and autonomic system, which then induce a vicious cycle of aggravated atrial and ventricular electrical, structural, and autonomic remodeling events that promote and maintain AFib.
