Atrial fibrillation pathophysiology

https://https://www.youtube.com/watch?v=6FLE6HWiImM%7C350}}

Resident Survival Guide

Sinus rhythm

Atrial fibrillation

Atrial Fibrillation Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Atrial Fibrillation from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Special Groups Postoperative AF Acute Myocardial Infarction Wolff-Parkinson-White Preexcitation Syndrome Hypertrophic Cardiomyopathy Hyperthyroidism Pulmonary Diseases Pregnancy ACS and/or PCI or valve intervention Heart failure
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram EKG Examples A-Fib with LBBB
Chest X Ray
Echocardiography
Holter Monitoring and Exercise Stress Testing
Cardiac MRI
Treatment
Rate and Rhythm Control
Cardioversion Overview Electrical Cardioversion Pharmacological Cardioversion
Anticoagulation Overview Warfarin Converting from or to Warfarin Converting from or to Parenteral Anticoagulants Dabigatran
Maintenance of Sinus Rhythm
Surgery Catheter Ablation AV Nodal Ablation Surgical Ablation Cardiac Surgery
Specific Patient Groups
Primary Prevention
Secondary Prevention
Supportive Trial Data
Cost-Effectiveness of Therapy
Case Studies
Case #1
Atrial fibrillation pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Atrial fibrillation pathophysiology
CDC on Atrial fibrillation pathophysiology
Atrial fibrillation pathophysiology in the news
Blogs on Atrial fibrillation pathophysiology
Directions to Hospitals Treating Atrial fibrillation pathophysiology
Risk calculators and risk factors for Atrial fibrillation pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The primary pathologic or structural change observed in patients with atrial fibrillation is progressive fibrosis of the atria. This fibrosis is primarily due to atrial dilatation, however genetic causes and inflammation may also play a role in some individuals. There are other functional processes that contribute to the development and persistence of atrial fibrillation including hemodynamic stress (stretching of the atrium), atrial ischemia, activation of the neurohormonal system, ectopic activity in the pulmonary vein, multiple wavelets of electrical activity in the atrium, and catecholamine excess. The mechanism in most patients is likely to be multifactorial.

Pathophysiology

Triggers

Onset of atrial fibrillation is dependent upon specific triggers and tissue substrate capable of maintaining atrial fibrillation. The following triggers are know to initiate atrial fibrillation:

• Sympathetic or parasympathetic stimulation
• Ectopic activity in muscular sleeves that extend from the left atrium into the proximal parts of pulmonary veins
• Atrial stretch
• Bradycardia
• Premature atrial beats
• Accessory AV (atrio-ventricular) pathways

Ectopic Foci in the Pulmonary Vein

• Younger patients with paroxysmal atrial fibrillation will sometimes have ectopic foci of electrical activity in the pulmonary vein that can be ablated. There are cells in the pulmonary vein whose electrical properties resemble those of the myocytes of the atrium. These patients generally have high grade ectopic activity on Holter monitoring. While the pulmonary vein is a common source of these ectopic foci, there may also be foci present in the atrium itself. While the pulmonary vein may function as a trigger, it is the heterogeneity of conduction that may sustain the atrial fibrillation

Re-enterant Wavelets or Multiple Wavelets Phenomenon

• Presence of these triggers produce re-enterant wavelets of electrical activity due to shortened effective refractory period (ERP)
• It has been hypothesized that if there is a greater atrial mass, delayed atrial conduction times, and a shortened atrial refractory period, then this promotes the propagation of wavelets. This hypothesis is supported by the observation that prolongation of intra atrial conduction times is associated with a recurrence of atrial fibrillation.

Molecular Pathogenesis and Role of Mechano-electric Feedback

• Mechanosensitivity of cardiac myocytes is thought to play a pivotal role in initiation of atrial fibrillation:

Altered myocyte stress/strain

• Alteration of extacellular matrix strain of the myocytes leads to opening of specific stretch-activated channels (SAC) via cytoskeletal linkages to integrins.

Catecholamine Release Secondary to Atrial Stretch

• Stress/strain may lead to release of catecholamines leading to alpha and beta receptor activation in regions of greatest hemodynamic stress, as occurs in states of hypertension, mitral valvulitis and congestive heart failure.

Actiavtion of G-protein Coupled Pathways

• Stimulation of alpha and beta receptors leads to downstream activation of G-protein coupled pathways within the cardiac myocytes.
• Beta adrenergic stimulation leads to activation of adenlyl cyclase and in turn increased cAMP production.
• Alpha receptor stimulation causes activation of phosphatidylinositol (PI) second messenger system that, via phospholipase C (PLC) action, synthesizes IP3 and diacylglycerol (DAG).
• Protein kinases A (PKA) and C (PKC), activated by cAMP and PI pathways, respectively, produce a change in intra-cellular calcium level, via opening of L-type calcium channels and sarcoplasmic reticulum (SR) calcium release.
• Moreover, protein kinase C causes mitogen-activated protein kinase (MAPK) to be activated downstream, which turns on immediate early gene (IEG) program to initiate hypertrophy and cardiac remodelling. This produces a viscous cycle that maintains an arrhythmogenic environment.
• The calcium influx due to opening to L-type calcium channels is a regulator of atrial excitation-contraction coupling.

Dilation of the Atria

Dilatation of the atria can be due to almost any structural abnormality of the heart that can cause a rise in the intra-cardiac pressures. This includes:

• Hypertension, most likely the most common cause of atrial dilation in the current era.
• Valvular heart disease (such as mitral stenosis, mitral regurgitation, and tricuspid regurgitation).
• Congestive heart failure.
• Coronary Artery Bypass Graft Surgery.

Once dilatation of the atria has occurred, this begins a chain of events that leads to the activation of the renin aldosterone angiotensin system (RAAS) and subsequent increase in matrix metaloproteinases and disintegrin, which leads to atrial remodeling and fibrosis, with loss of atrial muscle mass.

Inflammation of the Atria

• Any inflammatory state that affects the heart can cause fibrosis of the atria. This is typically due to sarcoidosis but may also be due to autoimmune disorders that create autoantibodies against myosin heavy chains. Mutation of the lamin AC gene is also associated with fibrosis of the atria that can lead to atrial fibrillation.

Stretch-induced Depolarization of Fibroblasts

• Patchy atrial fibrosis may precede the occurrence of atrial fibrillation and the magnitude of fibrosis may progress with a prolonged duration of atrial fibrillation.

Fibrosis of the SA Node

• Fibrosis is not limited to the muscle mass of the atria, and may occur in the sinus node (SA node) and atrioventricular node (AV node), correlating with sick sinus syndrome. Prolonged episodes of atrial fibrillation have been shown to correlate with prolongation of the sinus node recovery time, suggesting that dysfunction of the SA node is progressive with prolonged episodes of atrial fibrillation.

.

References

Template:WikiDoc Sources CME Category::Cardiology