From the Guidelines
Infections trigger atrial fibrillation through a complex interplay of inflammation, autonomic dysregulation, and metabolic derangements that alter atrial electrophysiology and create an arrhythmogenic substrate. The most recent and highest quality study 1 highlights the role of inflammation in inducing atrial fibrillation, with lymphomononuclear inflammatory infiltrates found in atrial biopsies from patients with atrial fibrillation. This inflammatory response can alter atrial electrophysiology by affecting ion channels and gap junctions, creating an arrhythmogenic substrate.
The study 1 also notes that inflammatory markers such as C-reactive protein, interleukin (IL)-1β, 2,6, and 8, and TNF-α increase in patients with or at increased risk of postoperative atrial fibrillation. Furthermore, the activity of the NLRP3 inflammasome in atrial cardiomyocytes increases in patients with paroxysmal atrial fibrillation.
In addition to inflammation, infections also activate the sympathetic nervous system, increasing catecholamine levels that enhance automaticity and trigger atrial ectopic beats 1. The resulting tachycardia and increased cardiac demand can lead to atrial stretch and remodeling.
Other factors that contribute to the development of atrial fibrillation during infections include metabolic disturbances such as hypoxemia, electrolyte abnormalities (particularly hypokalemia and hypomagnesemia), and acid-base imbalances that further destabilize cardiac electrical activity 1.
In patients with pre-existing cardiac disease or structural abnormalities, these infection-induced changes can more readily precipitate atrial fibrillation. The combination of inflammation, autonomic dysregulation, hemodynamic stress, and metabolic derangements creates the perfect storm for triggering and sustaining atrial fibrillation during infectious states.
Key mechanisms involved in the pathophysiology of infection-induced atrial fibrillation include:
- Inflammation and oxidative stress
- Autonomic dysregulation
- Metabolic derangements
- Atrial stretch and remodeling
- Alterations in ion channels and gap junctions
These mechanisms are supported by the most recent and highest quality studies 1, which highlight the complex interplay of factors that contribute to the development of atrial fibrillation during infections.
From the Research
Pathophysiology of Atrial Fibrillation
The pathophysiology of atrial fibrillation (AF) is complex and multifactorial. Infections can trigger AF through various mechanisms, including:
- Inflammation: Infections can lead to inflammation, which plays a significant role in the onset and recurrence of AF 2, 3, 4, 5, 6.
- Electrical and structural remodeling: Inflammation causes and accelerates the electrical and structural remodeling of the atria, leading to the formation of an AF substrate 3, 6.
- Pro-inflammatory cytokines: Inflammatory molecules, such as pro-inflammatory cytokines, enhance the AF substrate and maintain AF, forming a vicious cycle 3, 6.
Role of Inflammation
Inflammation is a key driver of AF, and multiple markers of inflammation have been shown to be elevated in AF patients 4, 5, 6. The inflammatory cascade induces fibrotic changes in the myocardium, an arrhythmogenic process that stimulates further inflammation 6. The nidus of inflammation is not clear but seems to be related to the pulmonary veins 6.
Bacterial Infections
Certain bacterial infections, such as Helicobacter pylori and Chlamydia pneumoniae, have been hypothesized to be involved in the pathogenesis of AF 4. Chronic bacterial infection is the most likely event to initiate and maintain an inflammatory process, leading to AF.
Therapeutic Implications
Current therapeutic approaches to AF have high recurrence rates and no life prolongation value 5. Addressing the fundamental mechanisms of AF initiation and maintenance, including inflammation, may lead to the development of new therapeutic strategies for AF 3, 5, 6. Biological agents and immunomodulators that inhibit the inflammatory cascade are being explored as potential treatments for AF 6.