An Overview Of Atrial Fibrillation Biology Essay

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Atrial fibrillation (AF) is a common sustained cardiac arrhythmia. (1,nice). AF is described as uncoordinated atrial activation which leads to worsening of the function of atrial. The atria will quiver rather than contract due to the irregular electrical impulses and thus, the efficiency of the atria to pump blood into ventricles are disrupted. AF occurs when difference in refractory period within atrial tissue happens and this is normally caused by coexistence of fibrosis and healthy atrial muscle fibres in the atria(1). The risk factors of evolving AF include aging, diabeties, hypertention, valve disease. (nice) Dietary and lifestyle can also precipitate risk of AF, such as alcohol or caffeine consumption and stress. White Caucasians are the most presenters among the data. In UK, the prevalence of AF is around 1% of the population. It is more common in males than females. The prevalence also rises with aging. (4) AF can be asymptomatic or comes with symptoms such as breathlessness, palpitations, dizziness and chest pain. AF can be diagnosed based on electrocardiogram (ECG) if irregular pulse is detected(1). Absence of P waves, irregular ventricular rhythm, or irregular baseline fluctuations can be an indication of AF.(5) Atrial rate can reach 350-600 beats per minute while ventricles rate ranging from 100 to 180 beats per minute. Other test such as echocardiogram is carried out to assist in identifying any other heart disease like stroke risk factors, chest x-ray to check if there is any lung problem due to AF, and finally blood test, which can be useful as anaemia or hyperthyroidism may complicate AF.(3) AF is classified into few categories based on the clinical features. These are paroxysmal AF (AF stop spontaneously in less than 7 days and frequently within 2 days), persistant AF (AF not self terminating, persist for more than 7 days or prior to cardioversion therapy) and permanent AF, which is not terminating or relapse upon termination. Recurrent may occur in paroxymal and persistant AF while permanent AF shows established pattern.(nice) AF increases the risk of getting heart failure, thromboembolism and stroke. Trend of morbidity and mortality due to AF in Scotland between 1986 and 1996 was studied and it showed that hospitalizations with AF have increased 2 to 3 folds. Number of deaths and strokes associated with AF has increased as well.(6)

Atrial fibrillation is complicated with congestive cardiac failure (CCF) (or congestive heart failure) and stroke. (NICE) In this case, the patient was presented with decompensated CCF. CCF is a condition where the heart is unable to produce sufficient cardiac output to meet the metabolic demands of the body. In addition, increase in venous pressure causes accumulation of fluid in lungs and body, leading to congestion. These two cardiac diseases are extremely linked together. Patient with either disorder may have increased risk of developing the other. Coexist of both disease carries a worse prognosis. A study was performed to investigate the relationship between AF and CCF and the coexistence of both diseases influence on mortality. 921 patients that were diagnosed with AF, 238 of them had CCF while another 144 developed it afterward. Another 931 patients with CCF, AF was diagnosed in 24% of the patients while 17% developed it later. Animal studies showed that rapid ventricular response in AF can lead to dilated cardiac muscle disease. Lost of atrial transport leading to decrease in cardiac output may cause CCF. On the other hand, CCF may cause rapid atrial filling pressure and atrial dilatation. It also causes atrial fibrosis and abnormal impulse conduction, which then predispose to AF. Medications available for AF and CCF are beta blockers, digoxin, angiotensin converting enzyme inhibitor and angiotensin receptor blocker. Beta blocker is beta adrenoreceptor antagonist which selectively blocks β1- and β2- receptor. Metoprolol selectively acts on β1- receptors in the heart which leads to decrease in heart rate. (RND) Digoxin is a cardiac glycoside. It increases parasympathetic activity and inhibit Na+/K+ pump. It slows down AV conduction leading to heart rate decrease. Inhibition of Na+/K+ pump leads to slow extrusion of Ca+. This causes increase in release of calcium during action potential, leading to increased contractility of the heart. 2 main treatments for AF and CCF are rate and rhythm control. (NICE) Rate control aims at reducing the rapid heart rate by using chronotropic drugs or surgery while rhythm control involves the application of cardioversion to change the arrhythmia caused by AF back to normal sinus rhythm. Cardioversion is available in 2 forms, electrical and pharmacological intervention, which uses antiarryhthmic drugs. However, the most appropriate starting treatment for patient is still remain controversy. Patient treated with either of the treatment needs antithrombotic therapy to prevent thromboembolic events. Warfarin is an anticoagulant. It inhibits Vitamin K reductase, thus interfering clotting factors II, VII, IX and X. Furosemide was given to this patient due to oedema. Furosemide acts on the ascending loop of Henle, inhibits the Na+/K+/2Cl- carrier, thus prevents the reabsorption of NaCl and increases excretion of water.(RND) Potassium supplement can be given to prevent hypokalemia.

Initial therapy for AF is debatable. Maintenance of sinus rhythm (normal rhythm) by antiarrhythmic drugs is often used as the starting therapy as if results in less symptoms, better exertion tolerance, lower risk of stroke following discontinuation of long term anticoagulant therapy and better quality of life. However, the respond of AF towards antiarrhythmic drugs is poor normally, and associated with serious side effects too. Another approach towards AF is rate control therapy. It is more simple and less toxic compared to antiarrhythmic drugs, however, anticoagulation becomes more important.(8) Results showed that the number of treatment crossover was significantly higher in the group of patient that received rhythm control therapy as initial therapy(due to therapy failure). An increased in mortality rate was also identified in the rhythm control group. Patients in the rhythm control group were associated with higher event of hospitalizations and side effects as well. The analysis concluded that rate control therapy should be considered as main therapy if rhythm control does not produce satisfactory result.(8) Another study was conducted to compare the effectiveness of rhythm control and rate control in patients with AF and CCF. Among the 1009 patients, 2-year mortality rate is checked and results showed that there was no significant difference between both of the groups (31% from rate control versus 29% from rhythm control).(9) There was no significant difference in the quality of life between the group treated with electrical cardioversion and patient assigned with rate control as well.(9) Class I agents of antiarrythmic drugs increased mortality and it should be avoided in patient with structural heart disease.(specific)(10)

According to NICE guidelines, permanent AF is treated with rate control therapy. In many patient with CCF and AF, rhythm control is unlikely to succeed(10) Thus, rate control plays important part as rapid heart rates can worsen function of left ventricle, which then precipitate CCF. Digoxin, beta blocker and calcium channel blocker (CCB) are normally used. Digoxin has been used for long time in the treatment of AF, it is also useful in the management of CCF as it has negative inotropic effect however, it shows less efficacy in controlling the heart rate during exertion.(nice) Combination therapy of digoxin and beta blocker is normally used for AF that is not well-managed with a single therapy. A retrospective analysis was carried out to investigate the use of beta blocker (carvedilol) on 136 patients with concomitant AF and CHF. 84 patients were given carvedilol while the rest were assigned with placebo. Therapy with carvedilol showed a significant improvement in left ventricular ejection fraction (reduced in ejection fraction can manifest heart failure) compared to placebo. It also showed reduction in mortality or hospitalizations due to CCF. (11) Effect of metoprolol CR/XL in congestive heart failure was investigated as well. Patients in New York Heart Association (NYHA) functional class II to IV and with ejection fraction 0 to 40 or less, stabilized were included into the study. All cause of mortality was lower among patients treated with metoprolol. The same trend goes to sudden deaths and deaths due to deterioration of heart failure.(12) Study on 5 drugs (digoxin, diltazem, atenolol, digoxin and atenolon, digoxin and diltazem) was performed to compare 24 hours ventricular rate in patient with chronic AF. The mean of VR was lowest in patients with combination therapy of digoxin and atenolol. This combination therapy showed significant lower VR than on digoxin, diltazem and atenolol alone. It also resulted in lowest mean VR during exercise. This concluded that combination therapy of digoxin and beta bloker produced most promising result in controlling heart rate, and also reflected that synergistic effect of this 2 drugs might be useful for future development. (13) The effectiveness of combination therapy of beta blocker and digoxin was also examined in another study. 47 patients with persistent AF and heart failure were enrolled into this study. The study was separated into two phases: in 1st phase, efficacy of digoxin is compared with combination therapy of digoxin and carvedilol for 4 months while in 2nd phase, digoxin of the combination therapy was taken out in a double-blinded manner, thus comparison between digoxin and carvedilol can be made. This phase lasted for 6 months. Combination therapy showed better outcome as mean 24 hours-ventricular rate was significantly reduced. The symptom scores, left ventricular ejection fraction (LVEF) and NYHA also showed improvement. In phase 2, withdrawal of digoxin from the combination therapy resulted in a significant increase in the 24-hours mean heart rate and decrease in LVEF. There was no significant difference between carvedilol and digoxin noted in the parameters.(carve and digo) NICE guidelines recommend that in patient with AF and need rate control therapy, beta blockers or rate-limiting CCB should be the main therapy, and if mootherapy is not adequate, digoxin can act as adjuvant therapy.

Antithrombotic therapy is normally provided to patient with permanent AF to prevent ischaemic stroke and other thromboembolic events. 9% to 20% of AF Patients with vulvular heart disease such as mitral stenosis will develop stroke. Elderly and patients with poor heart function are also at higher risk of developing systemic emboli. (nice) Anticoagulant such as warfarin and antiplatelet like aspirin are normally used in this therapy. A meta-analysis was carried out to determine the efficacy and safety of warfarin and aspirin for stroke prevention in patients with AF. 16 trials which covered 9874 patients were included into the meta-analysis. Adjusted-dose warfarin and aspirin were proved to be effective in reducing percentage of stroke among the patients. In addition, warfarin shows better outcome then aspirin, however, it increased major extracranial bleeding as well.(14) A systemic review was done on 5 randomised controlled trials (RCT) to evaluate the long term management of anticoagulation and antiplatelet in patients with non-rheumatic AF (no heart valve damage). There was no significant difference in mortality due to stroke. Non-fatal stroke occurred more significantly in patients with antiplatelet therapy. More events of bleeding in patients treated with anticoagulation therapy were observed. However, the result showed lack of uniformity among the 5 trials thus resulting in uncertainty about the effectiveness of long term anticoagulation and antiplatelet therapy. (systemic) International normalized ration (INR) values plays important role in determining the risk of stroke or other thromboembolic events and bleeding. The risk of stroke in patient with AF is said to be greatly reduced by anticoagulation and INR values of 2.0 and greater. A group of patient with nonvulvular AF was studied to examine the use of warfarin and aspirin and also INR value. Results showed patients that were taking warfarin with INR less than 2.0 (1.5 to 1.9 showed similar trend with INR less than 1.5) have higher number of stroke and risk of death compared to patient taking warfarin with INR greater than 2. The mortality rate of patients taking aspirin also showed the same trend. This study concluded that warfarin or aspirin produces full effect of anticoagulation at INR values of 2 or greater.(INR) Combination of warfarin and aspirin does not produce synergistic effect in anticoagulation therapy but increases the risk of bleeding. Thus, concomitant use of aspirin and warfarin is not encouraged. NICE guidelines recommend that in patients with permanent AF, assessment of risk and benefit should be performed and discussed with the patient before antithrombotic therapy is given. For those that need the therapy, adjusted-dose warfarin should be given, with a target INR range 2.0 to 3.0. Aspirin with a dose of 75mg to 300 mg should be given if warfarin is not appropriate for the patient.