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Emily WasilcoCurrent Research and Treatment Strategies for Atrial Fibrillation: A Literature ReviewFerris State UniversityAbstractOf all cardiac arrhythmias, atrial fibrillation (AF) remains the most common in adults. It greatly decreases quality of life and increases mortality risk due to high threat for stroke. Early detection and prompt treatment of atrial fibrillation is essential to control heart rate and irregular rhythm, inhibit further remodeling of the heart and most importantly prevent stroke and onset of heart failure. Up to this point, the most common treatment of atrial fibrillation has been use of beta blockers, anti-arrhythmics and warfarin. As more evidence is being gathered about the pathology of AF, newer treatment strategies are being introduced that may prove to replace these well established therapies. This paper will focus on effective treatment for atrial fibrillation, by reviewing both past and current research trends on the use of drug therapy, anticoagulants and surgical interventions. Current Research and Treatment Strategies for Atrial Fibrillation: A Literature ReviewOf all cardiac arrhythmias, atrial fibrillation (AF) remains the most common, affecting 2.3 million people in the United States (Altman, R. & Vidal, H.O, 2011). It greatly decreases a patients’ quality of life, increases mortality risk by 30%, with 15% of strokes the result of this arrhythmia (Aldhoon, B., Melenovsky, V., Peichl, P., Kautzner J., 2010). While 8% of patients affected are over the age of eighty, there is 1% of the population younger than age sixty who also suffer from this cardiac condition (Gutierrez, C. & Blanchard, D.G., 2011). Early detection and prompt treatment of atrial fibrillation is essential to control heart rate and irregular rhythm, inhibit further remodeling of the heart and most importantly prevent stroke and onset of heart failure. Up to this point, the most common treatment of atrial fibrillation has been use of beta blockers, anti-arrhythmics and warfarin. As more evidence is being gathered about the pathology of AF, newer treatment strategies are being introduced that may prove to replace these well established therapies. This paper will focus on effective treatment for atrial fibrillation, by reviewing both past and current research trends on the use of drug therapy, anticoagulants and surgical interventions. Before discussing treatment, the next two paragraphs will provide a review on AF etiology and pathology to enhance understanding. The majority of patients with atrial fibrillation have experienced cardiovascular injuries in the past, as a result of underlying disease processes, such as heart failure, coronary artery disease, hypertension, diabetes or cardiomyopathy. However, in rare instances, it may occur in those without a history of cardiac damage and these patients are often asymptomatic until the problem is severe or a stroke has occurred. (Aldhoon, et.al, 2010)Whatever the mechanism or trigger for a patient with AF, the clinical pathophysiology is still not fully understood, but the results are erratic, uncoordinated contraction or quivering of the atria of the heart. Due to this inefficient contraction, the ventricles are unable to fill fully during diastole, which decreases cardiac output and increases the ventricular response rate to 90-170 bpm (Gutierrez & Blanchard, 2011). The heart works so much harder with this rate increase, becoming fatigued with less blood being pumped into circulation, decreasing oxygenation of the body. Additionally, blood begins to back up around the left atrial appendage, which begins to clot as a result of stasis (Gutierrez, & Blanchard, 2011). Eventually, these clots can break off and travel to the brain, resulting in a massive stroke. Further, if AF remains untreated or persists, the structural elements of the heart can be irreparably remodeled and enlarged, making it far more difficult to convert the rhythm back to normal (Aldhoon et al., 2010). In the treatment of atrial fibrillation (AF), the patient is usually managed by either rate control or rhythm control, with the addition of anticoagulants to both of these regimens. However, rate control is used more often because studies have shown rhythm control is associated with more hospitalizations related to cardiac or thromboembolic events (Gutierrez & Blanchard, 2011). The overall goal of these treatments is to convert the heart rhythm to a normal sinus rhythm, and decrease the ventricular response rate to 80 beats per minute (bpm) or less at rest or 110 bpm or less during exertion (Gutierrez & Blanchard, 2011). These control methods can be achieved by means of electrical conversion, various pharmaceuticals or surgical interventions.Pharmacological therapy for atrial fibrillation will be considered next, with one study focusing on AF patients who also have heart failure, which is common finding. The first study (Chen, & Wongcharoen, 2009), discusses patients who have AF and also those who have AF with heart failure. It examined the most effective strategies for management, by means of rate or rhythm control for both sets of patients. The study by Chen (2009), showed that the most successful anti-arrhythmics for conversion of rhythm in AF with heart failure, are potassium channel blockers, namely amiodarone and dofetilide. These two medications showed a decreased risk for hospitalization and recurrence of AF, compared to other anti-arrhythmic drugs, and had a conversion rate of 31.3% for amiodarone and 59% for dofetilide (Chen & Wongcharoen, 2009). The use of the anti-arrhythmic dronedarone was stopped early during this study by Chen (2009), due to a severe worsening of symptoms in heart failure patients. In AF patients without heart failure, the anti-arrhythmic drugs flecainide and propafenone, still remain the gold standard of treatment. The study by Chen (2009), concluded with only 60% of all the patients fully converted to a normal sinus rhythm using the rhythm control strategy. While success of conversion via rhythm control was higher in this study than those in the past, it still held a higher risk of mortality, stroke and heart failure complications (Chen & Wongcharoen, 2009). In regards to pharmacological rate control, Chen (2009) indicated that beta blockers are highly effective at keeping the patient’s heart rate within parameters at rest and during exercise 70% of the time, whether they have only AF or AF with heart failure. Additionally, the use of the beta blocker carvedilol, not just improved heart rate, but also demonstrated that over time there is an improvement in morbidity and mortality in heart failure patients (Chen & Wongcharoen, 2009). Chen (2009) also examined the use of calcium channel blockers, and while they controlled rate 59% of the time in both sets of patients, they increased mortality in AF patients with heart failure. The drug digoxin proved to be somewhat effective for rate control in this study by Chen (2009), for both sets of patients, but had several drawbacks. Of particular concern, was that the drugs efficacy decreases during activities requiring exertion, so it should only be used with AF patients at rest. Additionally, it showed no reduction in mortality in patients who have been successfully converted to sinus rhythm, so it would be most effective as an adjunct therapy (Chen & Wongcharoen, 2009). Compared to the rhythm control strategy, Chen (2009) indicated that these methods of rate control greatly reduced hospitalizations, heart failure complications and improved the patient’s ejection fraction, in some instances by up to 10%.In some instances, when the patient arrives to the emergency department, there is little time to wait for oral drugs to begin working, especially if the patient is unstable. The next study (Hassan, Ahmad, Kamalakannan, Khoury, Kakish, Maria, Ahmed, Pires, Kronick, Oral & Morady, 2007), focuses on this and considers converting AF to normal sinus rhythm in the acute care setting, by comparing the use of either the intravenous (IV) short acting beta blocker esmolol, or the calcium channel blocker diltiazem. This was questioned when Hassan et. al (2007) stated that “prior studies suggested that IV diltiazem reduces the probability of spontaneous conversion of AF to sinus rhythm compared to esmolol” (p. 227). In this study by Hassan et al. (2007), 42% of the patients receiving diltiazem and 39% of the patients receiving esmolol converted spontaneously to normal sinus rhythm within 24 hours. This study concluded by indicating that these medications are nearly equal in effectiveness for conversion of AF and in control of ventricular response rate, when used in the acute care setting (Hassan et al., 2007).Another article from The Journal of Clinical Pharmacology, considers a group of four studies that show promise by using inhibitors of the renin-angiotensin system as a prevention strategy for atrial fibrillation, especially for patients with heart failure. These studies contained patients who were at high risk for atrial fibrillation, most with left ventricular dysfunction and underlying cardiac damage. Angiotensin II has been proven to play a key role in the remodeling of ventricles and is hypothesized to result in atrial remodeling as well (Kalus, Coleman & White, 2006). After reviewing all of the data from these studies, the journal concluded that angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARB), significantly decrease the risk of acquiring AF (Kalus et al, 2006). The study by Chen (2009), also noted that the use of the ARB irbesartan and the ACE inhibitor enalapril, have a protective effect on the heart, and greatly decrease the rate of AF recurrence especially after cardioversion. However, further research needs to be done to establish the scientific evidence and pharmacologic mechanisms behind these preventative therapies.As mentioned earlier, stroke prevention is a very important aspect of treatment for atrial fibrillation also and involves anticoagulation therapy. For nearly fifty years, the oral anticoagulant warfarin has been the standard therapy for patients with atrial fibrillation with a high risk for stroke (Altman & Vidal, 2011). Also advantageous, is the fact that warfarin has an available antidote (vitamin K) if bleeding becomes an issue and is very inexpensive. While warfarin is highly effective, decreasing patient risk of stroke by 64%, according to a study by Ansell (2010), it has multiple disadvantages as well. Warfarin therapy requires frequent monitoring of prothrombin (PT) and international normalized ratio (INR), which is done by means of blood draws. According to the study by Altman and Vidal (2011), in order to be effective in preventing stroke, the INR must be 2.0-3.0, which is a very narrow window only achieved in 55-60% of patients. Additionally, warfarin has many food and drug interactions and a slow onset of action, usually requiring the patient to be started on intravenous heparin until warfarin can take effect in 3-6 days. This drug also has a long half life, which makes it a challenge when scheduling procedures that require blood loss (Altman & Vidal, 2011).There are several new oral anticoagulants on the market that may prove to be just as effective as warfarin, but with far fewer restrictions and regulations. The most successful so far has been the newly released drug dabigatran, commonly known by the brand name Pradaxa. According to the study by Ansell (2010), while dabigatran was clearly superior in preventing stroke when compared to warfarin, it also resulted in a higher occurrence of myocardial infarctions and intracranial bleeding. This study (Ansell, 2010) also pointed out that more patients discontinued therapy on dabigatran than warfarin, due to gastrointestinal side effects. An advantage is that this drug does not require blood monitoring or dietary restrictions as are necessary with warfarin. Another more recent study by Altman and Vidal (2011) indicated that risk of hemorrhagic stroke was decreased by 74% and risk of systemic embolism by 35% when using dabigatran. However, this drug did result in a higher incidence of bleeding risk, which is concerning because there is no antidote available to reverse it or a lab test to measure therapeutic levels (Altman & Vidal, 2011). So, while this drug appears highly effective, any time a patient with AF stops taking it, due to side effects or bleeding, they are subtherapeutic and at high risk for stroke.Two other drugs nearing their end of clinical trials and studies that show promise for AF patients are rivaroxaban and apixaban. The study by Altman and Vidal (2011), showed that rivaroxaban has greatly decreased intracranial bleeding when compared to warfarin, but there is not yet enough clinical evidence to show its efficacy in preventing stroke for atrial fibrillation patients. Definitive evidence has also not yet been established for the drug apixaban and AF patients, but the drug has been used successfully for orthopedic patients and in prevention of venous thromboembolism (Ansell, 2010). According to Altman and Vidal (2011) the drug tecarfarin, which is very similar in structure to warfarin is also being extensively studied at this time. Studies have shown that tecarfarin keeps more stable INR levels when compared to warfarin, has a specific antidote, a faster onset of action and has very few drug or food interactions because it is metabolized differently that warfarin (Altman & Vidal, 2011). Also, there are three oral anticoagulants in the very early stages of clinical trials; betrixaban, YM 150 and edoxaban, which will provide additional possibilities for stroke prevention in AF patients (Ansell, 2010). However, until more research and evidence has been established, warfarin will still be the standard well established method of stroke prevention for AF.Often times even with pharmacological treatment for atrial fibrillation, the patient may not achieve optimum results and may benefit from surgery, but generally this is reserved for those with AF as a secondary diagnosis. In particular, patients with mitral valve disease and AF, whether persistent or paroxysmal, are known to benefit greatly from surgical intervention (De Cecco, Buffa, David & Fedeli, 2010). Originally, the Cox Maze procedure, developed in 1993, was the only option for surgical treatment of AF, which was technically challenging and hard to replicate from patient to patient (Hamman & Theologes, 2009). However, researchers through clinical studies have now developed new, more successful and consistent ways to perform this procedure on patients with AF, which will be the focus of the next few paragraphs. The first study by Hamman and Theologes (2009), employed the use of a diode-pumped laser system to simplify the original Cox-Maze ablation procedure, and treated 28 patients with AF. Nearly all of these patients had severe heart failure and had been treated pharmacologically with the rhythm control method for their AF. During the follow-up period, the study determined that 95% of the patients were free of AF, 19% were in atrial flutter, but none of the patients required repeat ablation (Hamman & Theologes, 2009). However, five of these patients did require a cardioversion, one a pacemaker defibrillator, and five patients died during the follow-up period of three years. Hamman and Theologes (2009) also indicated that, “over half of the patients were on beta blockers, one third were on anti-arrhythmics and less than half were still anticoagulated” (p. 233). Despite some imperfections and the fact that this procedure will no doubt benefit from further research, at this time it is used safely for patients with standalone AF.A study by De Cecco et al. (2010), reviews the results of minimally invasive surgical procedures for AF compared to the more conventional full length sternotomy surgeries for AF. The minimally invasive route, such as the modified Cox-Maze procedure, cryoablation or radiofrequency ablation, shows a success rate of freedom from AF at 85-94%, which is comparable to full length sternotomy (De Cecco et al., 2010). However, because these surgeries are higher in technicality, they require longer cardiopulmonary bypass time, prolonged aortic clamping and longer operative time. These procedures aren’t associated with as many postoperative complications as a full length sternotomy, with the most common being revision for minor bleeding and need for pacemaker placement (De Cecco, et al., 2010). In regards to full length sternotomy used for the traditional Cox Maze procedure for AF, the study by De Cecco et al. (2010) emphasized the greater number of complications experienced by patients, including respiratory complications, phrenic nerve injury, hemorrhage, sternal instability and mediastinitis. Additionally, a sternotomy is also far more painful during recovery time than the minimally invasive route, because the entire sternal bone is split open. The study (De Cecco et al., 2010) concluded by indicating that both types of procedures have their advantages and disadvantages, and depending on the patient’s history and stability, may be more or less favorable. Another study (Hiari, 2011), discussed new approaches that show promise for surgical treatment of AF, all of which are modifications of the Cox Maze procedure, and could be used for standalone AF. These include microwave energy, dry unipolar radiofrequency devices and bipolar radiofrequency ablation devices. The Hiari (2011) study indicated that microwave energy has been somewhat inconsistent in success, but in a study conducted this year, 80% of patients returned to normal sinus rhythm when this procedure was combined with atrial reduction. Sixteen studies have been performed on the unipolar radiofrequency method, and while freedom from AF was an average of 78%, the range of success was between 42-92% (Hiari, 2011). Currently, the bipolar radiofrequency ablation device has been used more commonly to assist with the traditional Cox Maze rather than used independently, because it has been associated with less freedom from AF at follow-up (Hiari, 2011). This study (Hiari, 2011), showed that a lot more research is required in this area, but that with time many of these procedures could be far more effective and less technical than the traditional Cox Maze.To conclude this review, it can be seen that there is a tremendous amount of research surrounding atrial fibrillation and that so much is still unknown about this arrhythmia. After a better understanding of the pathophysiology of AF is obtained through clinical studies, even more effective treatment or prevention strategies may be developed. At this time, no matter what the treatment method, there is no cure, or way to assure with confidence that patients will maintain in a normal sinus rhythm after conversion out of AF. Newer pharmacological interventions are needed, especially for patients with AF in heart failure, because so many anti-arrhythmic medications are contraindicated for them due to increased mortality risk. Further progress on studies regarding the renin-angiotensin system and its effect on development of AF and heart failure could also advance prevention strategies. In regards to anticoagulation medications to promote stroke prevention, these studies highlighted a number of new drugs that are proving to be effective. However, there are still quite a few dangers associated with them, so more research is needed and until then warfarin still remains an optimum choice for many patients. As surgical innovation continues to become more technologically advanced in the treatment of AF, there may be more options for standalone AF patients. Currently, most patients only have the surgical option when AF is their secondary diagnosis, because of the risks associated with surgery requiring a full length sternotomy. As clinical research continues to support the innovative tactics to perform minimally invasive surgical procedures, there may be more options for patients with standalone AF patients. As this review of literature clearly indicates, the future of treatment for atrial fibrillation shows great promise. Potentially gaining a better understanding of this dangerous arrhythmia and providing patients with higher quality of life and superior treatment.ReferencesAldhoon, B., Melenovsky, V., Peichl, P., Kautzner J. (2010). New insights into mechanisms of atrial fibrillation. Physiological Research/Academia Scientiarum Bohemoslovaca, 59(1), 1-12. Retrieved from . PMID: 19249911Altman, R. & Vidal, H.O. (2011). Battle of oral anticoagulants in the field of atrial fibrillation scrutinized from a clinical practice (the real world) perspective. Thrombosis Journal, 9, 12-20. Retrieved from Health Reference Center Academic. doi: J. (2010). Warfarin versus new agents: interpreting the data. Hematology, 2010, 221-228.Retrieved from . PMID: 21239798Chen, S.-A., & Wongcharoen, W. (2009). Management of atrial fibrillation in patients with heart failure: from drug therapy to ablation. Expert Review of Cardiovascular Therapy, 7(3), 311+. Retrieved from Health Reference Center Academic. doi: Cecco, C.N., Buffa V., David, V. & Fedeli S. (2010). Novel approaches for the surgical treatment of atrial fibrillation: time for a guideline revision? Vascular Health and Risk Management, 6, 439-47. Retrieved from . PMID: 20730059Gutierrez, C. & Blanchard, D.G. (2011). Atrial fibrillation: diagnosis and treatment. American Family Physician, 83 (1), 61-68. Retrieved from , B.L., & Theologes, T.T. (2009). Surgical treatment of atrial fibrillation with diode-pumped laser. Baylor University Medical Center Proceedings, 22(3), 230-233. Retrieved from Health Reference Center Academic, . Gale Document ID: A203232184Hassan, S., Ahmad, S., Kamalakannan, D., Khoury, R., Kakish, E., Maria, V., Ahmed, S., Pires, L.A., Kronick, S.L., Oral, H., & Morady, F. (2007). Conversion of atrial fibrillation to sinus rhythm during treatment with intravenous esmolol or diltiazem: a prospective, randomized comparison. Journal of Cardiovascular Pharmacology and Therapeutics, 12(3), 227-231. Retrieved from Sage Journals Online. doi: 10.1177/1074248407303792Hiari, N. (2011). Surgical treatment of atrial fibrillation: a review. Cardiology Research and Practice, 2011, 1-6. Retrieved from Health Reference Center Academic. doi: , J., Coleman, C, & White, C. (2006). The impact of suppressing the renin-angiotensin system on atrial fibrillation. Journal of Clinical Pharmacology, 46(1), 21-28. Retrieved from http:cgi-bin/refsvc?jid=2109&accno=2009327360 ................
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