Atrial Fibrillation: Pathophysiology, Standard Treatment, and Modifiable Risk Factors

Atrial Fibrillation: Pathophysiology, Standard Treatment, and Modifiable Risk Factors

Joy Stepinski, MSN, RN-BC

March 4, 2023

Defining atrial fibrillation

Atrial fibrillation (A fib or AF) is considered to be the most common type of heart arrhythmia [1]. The sinus node, located in the right atrium, is a group of specialized cells that serve as an internal pacemaker for the human body. This is important because the node spontaneously generates the heartbeat. It releases an electrical impulse that causes the cardiac cells within the two upper chambers, or atria, to become excitable and conduct the impulse to the surrounding cells. Instead of the impulse spreading across the atria in an organized manner, the electrical activity causes the atria to quiver (or fibrillate) instead of contract [2].

In atrial fibrillation, different problems arise. Impulses can fire at a rapid rate, causing an increased heart rate. Normally the contraction of the atria sends the blood down into the lower heart chambers (ventricles). However, with the irregular rhythm, less blood enters the ventricles [2]. This can lead to a reduced cardiac output, which may be decreased by 30%. Cardiac output refers to the amount of blood that the heart pumps in one minute. Some people may not have any AF symptoms, although others can feel heart palpitations. Patients may experience issues due to the decreased cardiac output, such as feeling tired, having shortness of breath, experiencing low blood pressure, and possibly fainting.

AF has a few different classifications. Paroxysmal AF is temporary and usually resolves within seven days. On the other hand, persistent AF is referenced if symptoms are longer than that time period [3]. When a patient presents with AF, the goal of treatment is typically to convert the rhythm back to sinus (normal) rhythm [2].

Risk factors discussed in the literature are age, heart disease, high blood pressure, lung disease, weight, obstructive sleep apnea, diabetes mellitus, alcohol and tobacco use, and drug use. Additionally, one meta-analysis of non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use [4] found that risk of AF incidence was increased by 12% when patients took NSAIDs. If people were new to these medications, their risk increased by 53%. The authors reported that AF was a cardiovascular adverse effect of NSAIDs.

Informed decision-making

In general, when facing a decision with how to proceed, considering the effectiveness and side effects of the recommended treatment are important. Decisions about medical care can have life consequences, and those decisions are always ultimately up to the patient. Asking the healthcare provider for research on the risks and percentage of people who benefit from the treatment can help you decide which path you would like to take, if any. Reviewing the pros and cons is essential, as some options may have more serious side effects than others. Finding out about other nonpharmaceutical alternatives is important, too, in decision-making.

Standard treatment

Standard treatment for atrial fibrillation includes medication and/or a procedure in an effort to accomplish a more normalized rhythm. Drugs may be prescribed, such as amiodarone, which is an antiarrhythmic medication. If drugs do not work to control the rhythm, then procedures are recommended, including cardioversion, ablation, high-intensity ultrasound, radiofrequency ablation, or cryoablation [5]. According to the American Heart Association, different medication is prescribed to control the heart rate and rhythm, as well as prevent stroke [6]. These medications can include blood thinners like antiplatelets and anticoagulants, and antiarrhythmic drugs like beta blockers, calcium channel blockers, digoxin, sodium channel blockers, and potassium channel blockers. The purpose of blood thinners is to prevent stroke, due to the blood that pools in the atria and subsequently can cause clots that travel to the brain. Stroke risk is about five times more likely in patients with AF [3, 4]. Other complications include heart failure and more frequent hospitalization.

In looking at the ramifications of blood thinners, all of the side effects include risk of bleeding. This includes antiplatelets like aspirin [6]. Anticoagulants are medications such as warfarin, which has been prescribed for a long time, and other newer medications like dabigatran, rivaroxaban, edoxaban, and apixaban. Warfarin, or Coumadin, may cause death of skin tissue or gangrene, kidney injury, and purple toe syndrome, among other side effects [7]. Patients must have regular lab draws to monitor the International Normalized Ratio (INR) because of the narrow therapeutic range, as well as eat a consistent serving of foods with vitamin K.

Newer blood thinners are not without risk. For example, apixaban (Eliquis) causes serious side effects, such as easy bruising, unusual bleeding, dizziness, weakness, lightheadedness, black stools, pink urine, back pain, muscle weakness, and loss of bladder or bowel control [8]. In a study involving 5,599 patients, participants were randomly assigned either apixaban or aspirin to treat atrial fibrillation [9]. The results generally favored apixaban to aspirin, although most results seemed comparable. For example, 1.6% of subjects on apixaban experienced primary outcome events, versus 3.7% for aspirin users. On death rates, 3.5% of patients on apixaban died as opposed to 4.4% on the aspirin. Regarding major bleeding, 1.4% experienced this complication on apixaban and 1.2% on aspirin.

Beta blockers (atenolol, carvedilol, metoprolol) and calcium channel blockers (diltiazem and verapamil) are used to control the heart rate. Side effects are numerous. For instance, potential side effects of verapamil are chest pain, fast or slow heart rate, anxiety, and wheezing. The medication can cause cardiac failure, worsening heart arrhythmia, low blood pressure, liver toxicity, Duchenne’s muscular dystrophy, and fatal cardiovascular events [10].

Heart rhythm controlling medications, including sodium channel blockers (flecainide, propafenone, and quinidine) and potassium channel blockers (amiodarone, sotalol, dofetilide, and dronedarone) have potential serious complications. These medications attempt to restore the heart rhythm to normal, but come with some hefty alerts, including risk of death. For example, amiodarone has the warning of pulmonary, hepatic, and cardiac toxicity that can lead to fatality [11]. The indications for flecainide include paroxysmal AF with disabling symptoms, but not recommended in chronic atrial fibrillation due to insufficient research. According to RxList [12], “there is no evidence from controlled trials that the use of TAMBOCOR (flecainide) favorably affects survival or the incidence of sudden death.”

The Cochrane Database of Systematic Reviews published a review to determine the long-term treatment effect of antiarrhythmic drugs on death, stroke, and adverse events [13]. The results found that there was moderate to high certainty evidence that metoprolol, quinidine, propafenone, flecainide, amiodarone, dofetilide, dronedarone, and sotalol reduced recurrence of AF. Low certainty evidence was available for disopyramide. However, in 43 to 67% of people, recurrence of the arrythmia was observed. The authors further concluded that risk of mortality increased with patients taking sotalol. Limited data was available regarding mortality for disopyramide, flecainide, and propafenone. Yet flecainide showed an increase of adverse effects. Despite evidence that antiarrhythmic drugs increase adverse events, cause new or more frequent occurrence of pre-existing arrhythmias, and may increase mortality, there was no evidence that these medications are of much benefit. The authors do not recommend these medications as first-line treatment and advise consideration of other strategies, such as a rate-controlled approach, no treatment, pulmonary vein catheter ablation, or short-term use (such as in hospitalized patients) with specific people exhibiting paroxysmal AF.

The Cochrane Database also published a review of 22 randomized trials, totaling 1,899 adults [5]. The conclusions were that all-cause mortality rates were similar between people who underwent a procedure to treat the AF and those who did not. According to the review, patients who chose a procedure were twice more likely to experience freedom from the arrythmia and no longer needed to take medications three months after the surgery. However, of those participants, the possibility of requiring a permanent pacemaker after the procedure was higher. The type of surgery completed did not have a benefit of one over another.

Despite this review, careful scrutiny of risks associated with these procedures is warranted. Electrical cardioversion, a treatment that delivers an electric shock to the heart to attempt to restore rhythm, has the potential to dislodge a blood clot in the heart’s left atrium [14]. This can lead to a stroke. Furthermore, complications include a worsening arrythmia, pacemaker, or implantable cardiac defibrillator (ICD). Cardiac ablation is a procedure that involves using radiofrequency energy to destroy the heart tissue causing the irregular heartbeat [15]. Potential complications are cardiac tamponade, heart failure, coagulopathy, anemia, and early mortality. In one study, early mortality occurred in 1 in 200 patients (n = 60,203 admissions), defined by death during initial admission or within 30-day readmission [16]. Another study evaluated outcomes of inpatient hospital procedural volumes (n = 54,597) and determined that low AF ablation volume was associated with worse outcomes. These included complications like cardiac perforation, vascular complications, and early mortality [17]. In other words, the cardiac ablation is pursued, seek a healthcare center that frequently performs this procedure. Even more, seek a cardiologist who has performed many ablations. Inquiring about ablation volume of the provider is quite appropriate.

Modifiable risk factors

Lifestyle factors are worth considering in treatment for atrial fibrillation and could show positive benefits. A published review [18] discussed established modifiable risk factors and potential lifestyle changes that may relieve AF burden. Risk factors noted were obesity, obstructive sleep apnea, hypertension, diabetes mellitus, and alcohol consumption.

Obesity is a large factor related to AF. According to a meta-analysis that reviewed 16 studies totaling 123,249 participants, obesity increased the risk of AF by 49%. This risk rose as body mass index (BMI) increased [19]. Another study investigated the effect of weight loss on AF [20]. The research enrolled patients diagnosed with AF (n = 1,415) and a BMI ≥27 kg/m2. The goal was to decrease body weight by 10%. Upon the results, the participants were grouped into three categories with group 1 losing ≥ 10%, group 2 losing 3 to 9%, and group 3 losing <3% of weight. Arrhythmia-free survival was highest among group 1 and also resulted in a 6-fold arrhythmia-free survival more than other groups. Weight fluctuation of > 5% noted a 2-fold AF recurrence. One reason obesity is of concern is due to the effect of electrostructural remodeling, meaning that there are changes to the heart’s size and shape, as well as left atrial enlargement, which can lead to persistent AF [17]. An additional risk factor is that of pericardial fat, or fat around the heart. When patients lose weight, this fat tissue can decrease.

Directly related to BMI is obstructive sleep apnea (OSA), diagnosed in 40% of obese people. If left untreated, OSA can double the risk of AF recurrence even after treatment with electrical cardioversion. Treatment with continuous positive airway pressure may reduce this risk. One study assessed the risk of OSA in 524 patients [21], of which 151 were diagnosed with AF or atrial flutter and 373 with general cardiovascular disease. The results showed that OSA was higher in the AF group (49%) versus the general cardiology group (37%). The authors discussed that OSA may initiate or predispose a patient to AF due to the pathophysiology it causes, including low blood oxygen levels, carbon dioxide retention, the initiation of hyperventilation by chemoreceptors, increased sympathetic drive, and severe increases in blood pressure.

Alcohol consumption has been a known cardiovascular risk factor. Significant intake has been correlated with higher risk of AF, hypertension, left ventricular hypertrophy (thickening of the wall of the left ventricle), OSA, and cardiomyopathy. One review [22] discussed that cardiovascular disease progression that may lead to AF. Alcohol may cause inflammation of the atrial cardiac cells and lead to oxidative stress (which causes an imbalance between free radicals and antioxidants). Additionally, drinking may lead to hypertension, OSA, and left ventricular changes. This can all lead to changes in the left atrium, including remodeling, dilation, elevated pressure, and fibrosis, and activate electrophysiological effects. The review reported that one meta-analysis enrolled 859,420 subjects with a 12-year follow-up. Of those, 12,554 were diagnosed with AF. The study found that AF incidence increased by 8% for each extra alcoholic drink per day. The review expressed that a safe level of alcohol was not determined for patients with a history of AF.

Furthermore, the authors expressed that alcohol use plays a role in 16% of hypertensive disease. If a person consumes more than 14 drinks per week, hypertension incidence has shown to increase by 40%. Approximately two-thirds of patients with AF also have diagnosed high blood pressure. According to the writers, alcohol reduction can lower blood pressure, as well as decrease AF incidence by 40% if a systolic blood pressure under 130 mmHG can be achieved. Alcohol also can contribute to obesity, especially when consuming more than 21 drinks per week. According to the authors, one study showed that modest alcohol consumption before sleep contributed to sleep-disordered breathing, which encompasses OSA. The rationales discussed were that alcohol leads to depressed arousal symptoms, low level of muscle tone in the oropharyngeal cavity, sleep fragmentation, and reduced uptake of oxygen by hemoglobin.

One suggestion is to swap out alcohol for green tea. There are many studies available that discuss the benefits of green tea on the cardiovascular system. In one such Chinese study [23], a total of 801 participants were enrolled. Patients with AF totaled 401 and the control group was 400. Green tea habits and AF incidence were reviewed. The results showed that subjects in a low frequency group had a decreased incidence of AF, compared with the high frequency group. Low frequency was defined as tea leaves less than 25% of the cup. The green tea protection showed was decreased as intake rose.

Another recommendation by two coauthors is to consider diet [24]. Nutrition may have a tremendous impact upon AF. A plant-based diet has shown to reduce risk and prevalence of hypertension, improve insulin resistance, decrease risk and prevalence of obesity, lessen mediators of the inflammatory response, and prevent or reverse atherosclerosis and coronary artery disease events. Because inflammation has a role in AF, a plant-based diet would be beneficial due to anti-inflammatory and antioxidant components. Whole-food plant-based diets are also rich in carbohydrates found in starchy plant food. In fact, diets of low-carbohydrates were shown to increase incidence of AF, according to one study of 13,385 participants [25]. An additional study demonstrated that adherence to a Mediterranean diet, which included foods heavily comprised of plants, was not frequently reported by patients diagnosed with AF [26]. A diet comprised mostly of plant food can be a valuable tool in reducing AF risk factors like hypertension, coronary artery disease, obesity, and diabetes, and play a role in reducing inflammation [24].

Exercise is another lifestyle factor that is important to consider. Leading a sedentary lifestyle is a major risk factor for cardiovascular disease. One research reviewed the activity of 2,442 patients [27] diagnosed with AF and managed by cardiologists in a European study that involved nine countries. The participants self-reported their physical activity. The authors investigated the influence of activity on AF progression at a one-year follow-up visit. The research showed that patients diagnosed with AF who exercised at any level of intensity showed a lower risk of death, compared with patients without any activity. Additionally, exercise was inversely related to cardiovascular death, thrombolytic event, and bleeding. The article discussed that exercise as a benefit to cardiovascular health has been demonstrated in other studies, such as the Framingham Heart Study.

Conclusion

In this review of AF many points were discussed, such as pathophysiology, risk factors, standard treatment, and modifiable risk factors. To conclude, one summary of 10 steps to control AF was published in the American Journal of Lifestyle Medicine [28]. Most of these have been reviewed above:

1.       Treat obesity and aim for 10% weight loss

2.       Consume a mostly plant-based diet

3.       Engage in moderate exercise and yoga

4.     Strive for blood pressure  130/80 mmHg

5.       Obtain restful and adequate sleep, and treat sleep apnea

6.       Improve stress

7.       Quit smoking

8.       Address anxiety

9.       Address depression

10.   Treat chronic diseases (which may improve or resolve by addressing the previous 9 points)

In closing, experiencing heart palpitations, shortness of breath, lightheadedness, fatigue, and any other symptoms related to atrial fibrillation can be very scary. Validating and recognizing these feelings are important. Addressing lifestyle factors can make a big impact on relieving atrial fibrillation symptoms. There is hope in an improved quality of life.

References

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2.       Frazer, Cynthia. (2016). Atrial Fibrillation. MEDSURG Nursing, 25(2), 125-126.

3.       Reynaldo, Rhea, Inocian, Ergie & Patterson, Kathryn. (2021). Stroke Prevention in Patients with Atrial Fibrillation. MEDSURG Nursing, 30(6), 403-406,422.

4.       Liu, G., Yan, Y. P., Zheng, X. X., Xu, Y. L., Lu, J., Hui, R. T., & Huang, X. H. (2014). Meta-analysis of nonsteroidal anti-inflammatory drug use and risk of atrial fibrillation. The American Journal of Cardiology, 114(10), 1523-1529.

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