Atrial fibrillation mechanism

Warfarin has been the mainstay of oral anticoagulant therapy for many years, principally for atrial fibrillation, mechanical heart valves, or venous thromboembolism. Adverse-effects profile of patients on warfarin therapy parallel what would be seen in vitamin K deficiency. Dne to its inhibitory effect on VKOR in the liver, warfarin affects the fnnction of the MGP and has been associated with vascular calcification in various animal and human studies. 

Reentry mechanism Intranodal (AV node) reentry Extranodal reentry Reentrant tachyarrhythmia Atrial flutter Atrial fibrillation Ventricular tachycardia Ventricular fibrillation Conduction B/ocks ... 

Bileaflet mechanical valve and either atrial fibrillation, myocardial infarction, left atrial enlargement, endocardial damage, or low ejection fraction... 

Compare and contrast the risk factors for and the features, mechanisms, etiologies, symptoms, and goals of therapy of (1) sinus bradycardia (2) atrioventricular (AV) nodal blockade (3) atrial fibrillation (AF) (4) paroxysmal supraventricular tachycardia (PSVT) ... 

O Atrial fibrillation may be caused by both abnormal impulse formation and abnormal impulse conduction. Traditionally, AF was believed to be initiated by premature impulses initiated in the atria. However, it is now understood that in many patients AF is triggered by electrical impulses generated within the pulmonary veins.20 These impulses initiate the process of reentry within the atria, and AF is believed to be sustained by multiple reentrant wavelets operating simultaneously within the atria.21 Some believe that, at least in some patients, the increased automaticity in the pulmonary veins may be the sole mechanism of AF and that the multiple reentrant wavelet hypothesis may be incorrect.21 However, the concept of multiple simultaneous reentrant wavelets remains the predominant hypothesis regarding the mechanism of AF. 

Flosequinan has a positive inotropic effect and shows a tendency to increase the heart rate, atrioventricular conduction in patients with atrial fibrillation and neurohormonal activation. Although the precise mechanisms involved have remained unclear up to now [29], this drug has been used to treat congestive heart failure (CHF). The FDA approved flosequinan (Manoplax) in 1993. However, the drug was withdrawn a year later because the PROFILE (prospective randomized flosequinan longevity evaluation) study indicated that flosequinan had adverse effects on survival, and that beneficial effects on the symptoms of heart failure did not last beyond the first 3 months of therapy, after which patients on the dmg had a higher rate of hospitalization than patients taking a placebo [14]. 

Atrial fibrillation For the prevention of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms and paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms in patients without structural heart disease. 

The increased risk of thromboembolism associated with atrial fibrillation and with the placement of mechanical heart valves has long been recognized. Similarly, prolonged bed rest, high-risk surgical procedures, and the presence of cancer are clearly associated with an increased incidence of deep venous thrombosis and embolism. Antiphospholipid antibody syndrome is another important acquired risk factor. Drugs may function as synergistic risk factors in concert with inherited risk factors. 

Lai, L. P., Su, M. J., Lin, J. L., Lin, F. Y., Tsai, C. H., Chen, Y. S., Huang, S. K., Tseng, Y. Z., and Lien, W. P. (1999). Down-Regulation of L-Type Calcium Channel and Sarcoplasmic Reticular Ca(2+)-ATPase mRNA in Human Atrial Fibrillation Without Significant Change in the mRNA of Ryanodine Receptor, Calsequestrin and Phospholamban An Insight into the Mechanism of Atrial Electrical Remodeling. J Am Coll Cardiol 33(5) 1231-7. 

Mandapati, R., Skanes, A., Chen, J., Berenfeld, O., and Jalife, J. (2000). Stable Microreentrant Sources as a Mechanism of Atrial Fibrillation in the Isolated Sheep Heart. Circulation 101(2) 194-9. 

Nattel S, Kneller J, Zou R, Leon LJ. Mechanisms of termination of atrial fibrillation by Class I antiarrhythmic drugs evidence from clinical, experimental, and mathematical modeling studies. J Cardiovasc Electro-physiol 2 003 14(suppl) S133—S139. 

The risk of embolism associated with mechanical heart valves is 2 to 6% per patient per year despite anticoagulation and is highest with valves in the mitral position. Warfarin therapy (INR 2.5 to 3.5) is recommended in these patients. The addition of enteric-coated aspirin (100 mg/d) to warfarin (INR 3.0 to 4.5) in high-risk patients (preoperative atrial fibrillation, coronary artery disease, history of thromboembolism) with mechanical valves decreases the incidence of systemic embolism and death from vascular causes (1.9 vs. 8.5% per year), but increases the risk of bleeding. 

Mackstaller LL, Alpert JS. Atrial fibrillation a review of mechanism, etiology, and therapy. Clin Cardiol 1997 20(7) 640-650. 

It is well established that increased sympathetic nerve activity is associated with chronic heart failure (CHF) (Porter et al. 1990 Singh 2000 Olshansky 2005 Brodde et al. 2006 Watson et al. 2006). The increase in sympathetic activity is a compensatory mechanism that provides inotropic support to the heart and peripheral vasoconstriction. However, it promotes disease progression and worsens prognosis (Watson et al. 2006). The autonomic nervous system (ANS) is a very complex, balanced system that influences the initiation, termination, and perpetuation of atrial fibrillation (AF), and the AF affects the ANS (Olshansky, 2005). At rest, sympathetic and parasympathetic outflows are related reciprocally heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows (Porter et al. 1990). 

Brundel B, Henning R, et al. 2002b. Molecular mechanisms of remodeling in human atrial fibrillation. Cardiovasc Res 54 315-324. 

The authors discussed the possibility that A9-THC, the active ingredient of marijuana, can cause intra-atrial reentry by several mechanisms and thereby precipitate atrial fibrillation. 

Altered rate of automatic discharge or abnormality of the mechanism by which an impulse is generated from a centre in the nodes or conducting tissue, is one cause of cardiac arrhythmia, e.g. atrial fibrillation, flutter or tachycardia. 

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