Atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a prevalence of 1% in the general population. The prevalence increases with age and It reaches more than 8% in the ninth decade of life AF is a disease characterized by uncoordinated and disorganized atrial beats, producing a rapid and irregular heart rhythm (i.e., irregular heartbeats).

Epidemiology of atrial fibrillation

AF is a growing public health problem due to the aging of the population. The estimated prevalence of AF is 0.4-1% in the general population, but increases with age to 8% in people aged 80 years or older. Similarly, while the incidence of AF is less than 0.1% per year in people under 40 years of age, increases to more than 1.5% per year among women and 2% among men over 80 years of age. AF is considered one of the growing cardiovascular epidemics in the XXI century, along with congestive heart failure, type 2 diabetes. 2 and metabolic syndrome.

AF is one of the main causes of morbidity and mortality, and increases the risk of death, congestive heart failure and embolic events, including stroke. It aggravates heart failure and, in turn, heart failure promotes the FA. One in 6 strokes occur in a patient with AF and the increased risk of stroke depends on the number of additional risk factors. Furthermore, quality of life is considerably impaired in patients with AF, mainly due to their inability to perform normal daily activities due to the risk of symptom exacerbation.

AF is the most common arrhythmia in clinical practice and represents a large socioeconomic burden that is responsible for approximately one third of hospitalizations due to cardiac rhythm disorders. Additionally, over the past 20 years, hospitalizations for AF have increased by 66% due to an aging population, increasing prevalence of chronic heart disease, more frequent diagnosis through the use of ambulatory monitoring devices, and other factors.

Healthcare costs

AF is a public health problem with a cost of approximately €3,000 [about $3,600] per year per patient. The total economic burden is close to €13.5 billion (approximately €15. 7 billion dollars) in the European Union. In a European study, the average costs of hospitalization for a patient with AF were estimated to be €1,363, €5,252, €2,322, €6,360, and €6,445 in Greece, Italy, Poland, Spain, and the Netherlands, respectively. Inpatient care and interventional procedures were identified as the major sources of costs, accounting for more than 70% of total annual costs across the five countries. The US FRACTAL Registry study found that patients with recent AF Initially treated with traditional treatments added approximately $4,000-$5,000 to annual direct healthcare costs, a number that increases significantly in patients with multiple AF recurrences.

FA Classification

The American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC) guidelines on atrial fibrillation recommend the following classification system, which is based on simplicity and clinical relevance. These categories are not mutually exclusive, and an individual patient may have several episodes of paroxysmal AF and occasional persistent AF, or the reverse.

All AF patients are initially classified into the first detected AF category. These patients may (or may not) have had other previous episodes that have not been detected. If a first detected episode ends on its own in less than 7 days and another episode begins later, the case has been changed to the paroxysmal AF category. Although episodes in this category last up to 7 days, in most patients with paroxysmal AF the episodes end on their own in less than 24 hours. If, however, the episode lasts more than 7 days, it is unlikely to end on its own and is called persistent AF. In this case, the episode could be terminated with cardioversion. If cardioversion is not effective or is not attempted, and the episode continues for a long time (for example, a year or more), it is permanent AF.

Episodes that are less than 30 seconds long are not included in this system. Cases in which AF is secondary to a primary disease that could be the cause of AF are also not considered. With this system it is not always clear what a case of AF should be called. For example, a case may fit the category of paroxysmal AF some of the time, while other times it could have the characteristics of persistent AF. The most appropriate category can be decided by determining which is most common in the case being evaluated.

In addition to the previous classification, it is important to classify the event according to the ventricular response presented, which is of capital importance from the point of view of treatment and important hemodynamic implications.

The ACC/AHA/ESC guidelines describe additional categories of AF based on other patient characteristics:

• Benign idiopathic or recurrent atrial fibrillation of the adult - absence of clinical or echocardiographic findings of other cardiovascular diseases (including hypertension) or related lung disease, and age below 60.

• FA does not valve - absence of rheumatic mitral valve disease, heart valve prosthesis or mitral valve disease.

• Secondary - occurs in the context of a primary disease that may be the cause of the FA, such as acute myocardial infarction, cardiac surgery, pericarditis, myocarditis, hyperthyroidism, pulmonary embolism, pneumonia or other acute lung disease.

Etiology

AF can be due to various cardiac causes, but can occur in normal hearts. Known associations include:

• hypertension;
• primary heart disease, such as coronary disease, mitral stenosis (due to rheumatic heart disease or mitral prolapse), mitral insufficiency, hypertrophic cardiomyopathy, pericarditis, congenital heart disease, previous cardiac surgery;
• lung diseases (neumonia, lung cancer, pulmonary embolism, sarcoidosis);
• Excessive alcohol consumption (e.g., in the canopy, may cause holiday heart syndrome or holiday heart syndrome; women who drink more than two cups a day are 60% more likely to develop a FA);
• hyperthyroidism;
• carbon monoxide poisoning;
• dual pacemakers in the presence of normal atrioventricular conduction;
• family history of FA could increase the risk of FA. In a study in more than 2200 patients with FA, 30% had family members with FA. It has been suggested that several genetic mutations might be involved.

Pathophysiology

AF is characterized by a high frequency of excitation of the atrium, which results in desynchronized atrial contractions and irregular ventricular excitations. It is associated with structural changes of the myocardium, caused by different conditions or risk factors, generating a histological structure suitable for the development of AF. Normally, the period of time that elapses between one ventricular contraction and the next is 0.35 seconds. However, in atrial fibrillation, an additional period of up to 0.6 seconds occurs until one of the irregular impulses reaches the atrioventricular node. In this way, the interval between ventricular contractions varies between 0.35 and 0.95 seconds, generating irregular heartbeats and a higher frequency of ventricular excitation due to the high frequency of atrial impulses generated by fibrillation.

Genesis of FA

The prevalent hypothesis for the onset of AF consists of a rapid depolarization of the atria, which favors the re-entry of propagation waves. Myocytes located in the valves of the pulmonary veins in the left atrium generate ectopic foci of depolarization and promote the formation of reentrants. These ectopic foci are generated due to a spontaneous depolarization of the cardiomyocytes of the pulmonary veins. This spontaneous depolarization involves a diastolic release of Ca²⁺ from the endoplasmic reticulum, which activates Na⁺ entry through a Na⁺ Ca< exchanger. sup>2+, along with hyperphosphorylation of protein kinases: protein kinase A (PKA), calcium calmodulin kinase II and the ryanodine receptor type 2.

AF appears to begin with paroxysmal episodes that increase in frequency until progressing to persistent AF. According to the Euro Heart Survey, 80% of patients analyzed with paroxysmal AF still had paroxysmal AF after one year, while 30% of patients with persistent AF progressed to permanent AF.

Perpetuation of AF

The structural and electrophysiological changes of the myocardium promote the stabilization of reentries and the perpetuation of AF. Under normal conditions, the wave propagation is fast, while the recovery period of myocardial excitability (known as the effective refractory period) is slow. On the contrary, abnormalities of atrial cardiomyocytes, fibrotic changes, formation of interstitial matrix deposits or alterations in potassium channels, decrease cardiac conduction velocity and reduce the effective refractory period, generating re-entry circuits. There are other hypotheses.:

• Reentry Rotors: generation of mobile or fixed spirals of reentry into the tissue. They are usually movements of propagation of circular waves around scars and non-conducting fibrous regions, which generate re-entry circuits.
• Multiple independent depolarization waves: generated by functional and structural reentry. They perpetuate the spread.
• Electrical dissociation of the epicardial and endocardial: propagation waves are different in the different histological layers.

Clinical manifestations of AF

AF is a disease that considerably disrupts the lives of patients, mainly due to their inability to perform normal daily activities due to complaints of palpitations, chest pain, dyspnea, fatigue or feelings of dizziness. However, the discovery of the presence of AF may arise through the presentation of an associated entity, such as embolic complications or exacerbation of heart failure.

It must be taken into account that when blood is not completely expelled out of the cardiac chambers, it can accumulate and form a clot. If a clot in the atria leaves the heart and blocks a brain artery, a cerebrovascular accident (also called a stroke) occurs. Approximately 15% of strokes result from AF.

Most cases of AF are secondary to other medical problems, so the presence of chest pain or angina, symptoms of hyperthyroidism such as weight loss and diarrhea, and symptoms indicative of lung disease would point to an underlying cause. A history of stroke or transient ischemic attack (TIA), as well as hypertension, diabetes, heart failure, and rheumatic fever, may indicate that a patient with AF is at higher risk of complications.

Individuals can experience periods of symptomatic and asymptomatic AF. Over time, palpitations may disappear, so patients in whom the arrhythmia has become permanent may remain asymptomatic. This is particularly common among the elderly. Some patients experience symptoms only during paroxysmal AF, or only intermittently, during episodes of sustained AF.

Risk factors for the development of acute myocardial infarction

Approximately 30 to 45% of AMI cases and 20 to 25% of persistent AMI cases occur in young patients without demonstrable underlying disease. However, there are several underlying factors that put patients at higher risk of developing AMI, including age, obesity, hypertension, atrioventricular fibrillation (AF), congestive heart failure (CHF), and valvular heart disease.

Although AMI can occur in the elderly without any underlying heart disease, changes in cardiac structure and function that accompany aging, such as increased myocardial stiffness, may be associated with AF.

According to the Framingham Heart Study, the lifetime risks of developing AF are 1 to 4 for men and women age 40 and older. Lifetime risks remain higher even in the absence of prior CHF or myocardial infarction (1 of 6).

The treatment of patients with AF and its associated entities is a major challenge. The AF AWARE (Atrial Fibrillation Awareness And Risk Education) survey, presented in June 2009, was carried out in 11 countries (including Spain) with 810 cardiologists and 825 patients with AF. The conclusions were the following: AF is a complex disease that doctors consider difficult to treat; Early identification and treatment of AF could help reduce the serious risks related to AF; Patients need to better understand AF, its consequences and its treatment; AF negatively affects patients' quality of life; and AF represents a socioeconomic burden.

Non-modifiable risk factors

Genetics

Population studies have shown that there is heritability of AF, associated with a 40% increase in the risk of suffering from it if first-degree relatives with AF are present. This finding led to the mapping of different loci such as 10q22-24, 6q14-16 and 11p15-5.3 and the discovery of mutations associated with these loci. 15 gain and loss of function mutations have been found in potassium channel genes, including mutations in KCNE1-5, KCNH2, KCNJ5 or ABCC9 among others. Also six variations in sodium channel genes including SNC1-4B, SNC5A and SNC10A. All these mutations affect the polarization-depolarization processes of the myocardium, cellular hyperexcitability and the shortening of the Effective Refractory Period, favoring reentries.

Other mutations in genes such as GJA5 affect some types of cellular junctions, such as the gap junction, generating cellular uncoupling that promotes reentries and a slow conduction velocity.

Through GWAS (Genome Wide Association Study) studies, which scan the entire genome for SNP (Single Nucleotide Polymorphism) type variants, 3 susceptibility loci for FA have been found (4q25, 1q21 and 16q22). In these loci there are SNPs associated with a 30% increase in risk of recurrent atrial tachycardia after ablation, SNPs associated with loss of function of the Pitx2c gene (associated with the cellular development of pulmonary valves)., responsible for reentries, and SNPs close to ZFHX3 genes involved in calcium regulation.

A GWAS meta-analysis study conducted in 2018 revealed the discovery of 70 new loci associated with AF. Different polymorphisms were identified associated with genes that encode transcription factors, such as TBX3 and TBX5, NKX2-5 or PITX2, involved in the regulation of cardiac conduction, the modulation of ion channels and in cardiac development. New genes involved in tachycardia (CASQ2) or associated with an alteration in cardiomyocyte communication (PKP2) have also been identified.

Age

It is the most prominent risk factor for AF. Studies carried out from 1998 to 2007 show that individuals between 60 and 89 years of age have a risk of AF that is 4-9 times greater than people between 50 and 59 years of age. Therefore, there is a higher risk of AF in older people.

Sex

The incidence of AF is different in men and women. FHS studies show a higher incidence (per 1000 person-years) in men than in women, in European and North American populations. In Asian populations, and in general, both in developed and developing countries, a higher incidence in men than in women. The risk factors associated with AF are also distributed differently according to sex. In men, coronary heart disease is more common, while in women, high systolic pressure or valvular alterations.

Ethnicity

The prevalence of AF is lower in populations of African ancestry than in populations of European ancestry. African ancestry is associated with a protective effect of FA, due to the low presence of SNPs with guanine alleles, compared to European ancestry, where more frequent mutations have been seen. The rs4611994 variant for the PITX2< gene /i> is associated with the risk of AF in both African and European populations. Other studies reveal that Hispanics and Asians have a lower risk of AF compared to Europeans. Furthermore, the risk of AF in non-European populations is associated with risk factors characteristic of these populations, such as hypertension.

Modifiable factors

Sedentary lifestyle and physical activity

A sedentary lifestyle increases the risk factors associated with AF such as obesity, hypertension or diabetes mellitus, which favor remodeling processes of the atrium due to inflammation or alterations in depolarization processes of cardiomyocytes due to elevation of sympathetic tone. A Sedentary lifestyle is associated with a higher risk of AF compared with physical activity. In both men and women, moderate exercise reduces the risk of AF progressively, but sports or intense physical exercise can increase the risk of suffering from AF, as has been seen in athletes. It is due to a remodeling of the cardiac tissue, and an increase in vagal tone, which shortens the Effective Refractory Period, favoring reentries from the pulmonary veins.

High blood pressure

According to the CHARGE Consortium, both systolic blood pressure and diastolic pressure are predictive factors for the risk of AF. Systolic blood pressure values close to normal limits increase the risk associated with AF. Also associated with AF are diastolic dysfunction, increased left atrial pressure, volume and size, and left ventricular hypertrophy typical of chronic hypertension. All of these atrial remodelings are related to heterogeneous conduction and the formation of reentrants from the pulmonary veins.

Tobacco

According to the CHARGE Consortium the incidence of AF in smokers is 1.44 times higher than in non-smokers. Tobacco increases susceptibility to AF through different processes: It increases the release of catecholamines and promotes coronary vasoconstriction, which leads to ischemia. In addition, it accelerates atherosclerosis, due to its oxidative stress effect due to lipid oxidation and inflammation, which leads to thrombosis. Finally, nicotine induces the formation of type III collagen patterns in the atrium and has profibrotic effects. All of this modifies the atrial tissue, favoring AF re-entry.

Other diseases

There is a relationship between risk factors such as obesity and hypertension, with the appearance of diseases such as diabetes mellitus and apnea-hypopnea syndrome during sleep, specifically, obstructive sleep apnea. These diseases are associated with an increased risk of AF due to their remodeling effects on the atrial substrate.

Treatment of AF

Therapeutic objectives

The main objectives of the treatment of atrial fibrillation are to prevent temporary transient hemodynamic instability and prevent cerebrovascular attack. In emergencies, when hemodynamic collapse is imminent due to uncontrolled tachycardia, immediate cardioversion may be indicated.

The main factors that determine the treatment of atrial fibrillation are its duration and evidence of hemodynamic instability. Maintaining normal sinus rhythm is the ultimate therapeutic goal for patients with AF. Current treatments for AF focus on restoring and maintaining normal sinus rhythm and controlling heart rate with the primary goal of treating the arrhythmia itself and preventing strokes. Double Since the AF patient population is not homogeneous and no single therapeutic approach can be recommended, there are two general approaches. The first is to attempt to restore and maintain sinus rhythm (“rhythm control approach”), while the second is to control the rate of ventricular response to prevent deterioration of ventricular function and minimize symptoms (" rate control approach"). The initial treatment decision for AF primarily involves a rate or rhythm control strategy, but the initially chosen strategy may be unsuccessful and the alternative strategy must be adopted.

Cardioversion is indicated in new-onset AF lasting less than 48 hours and in hemodynamic instability. If rate and rhythm control cannot be maintained with medication or cardioversion, it may be necessary to perform electrophysiological studies with ablation of the involved pathway.

Randomized studies have been conducted to compare the results of rhythm control versus rate control strategies in patients with AF. The AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) study found no difference in the rate of mortality or stroke among patients assigned to one strategy or the other. However, there was a lower risk of adverse events with rate control strategy.

Regardless of whether rate control or rhythm control strategies are attempted, attention should be directed to antithrombotic therapy for the prevention of thromboembolism.

Therapeutic options

The goals of AF treatment can be achieved with pharmacological and non-pharmacological therapeutic options:

Pharmacological options

Pharmacological treatment is the main first-line therapeutic choice in the treatment of AF. The ACC, AHA, and ESC (American College of Cardiology/American Heart Association Task Force/European Society of Cardiology) consensus guidelines have collaborated to generate recommendations for the treatment of AF.

Antiarrhythmic drugs

The basis for maintaining sinus rhythm is the use of antiarrhythmics. These drugs are often used in pharmacological cardioversion or in the prevention of AF relapse and alter the flow of ions in cardiac tissue, reducing its excitability and setting the stage for spontaneous and long-lasting cardioversion. The drugs act by prolonging the effective refractory period (ERP) by blocking sodium ions (class I drugs) or potassium ions (class II drugs) or a mixture of both. These medications are often used along with electrical cardioversion.

But despite the widespread use of antiarrhythmic drugs for conversion and long-term suppression of AF, their use is limited due to issues related to intermediate efficacy, tolerability, and the potential for severe ventricular and/or proarrhythmic effects. or toxicity in various organs. Serious side effects leading to increased mortality have been observed in clinical studies with antiarrhythmic drugs and, therefore, safety has become a key issue when considering treatment with new antiarrhythmic drugs.

Antiarrhythmic drugs have their own characteristics that depend on the ionic currents they block. They are usually grouped into four broad categories in the modified Vaughan Williams classification, based on the dominant electrophysiological effect.

• Type 1 A: disopiramide, procainamide, quinidina
• Type 1 B: lidocaine, mexiletin
• Type 1 C: phlecainide, propafenone
• Type II: betabloquentes (e.g., propanolol)
• Type III: amiodarone, dronedarona (approved in July 2009), bretilio, dofetilida, ibutilida, sotalol
• Type IV: antagonists of non-dihydropyridinic calcium channels (verapamilo and diltiazem)

Maintenance of sinus rhythm

Class I drugs act by blocking sodium channels in cardiac cells. Class IA drugs, such as disopyramide and quinidine, are effective in restoring and maintaining normal rhythm, although their use is limited by their propensity to cause other rhythm problems. These side effects do not appear to be dose dependent.

Class IB medications, such as lidocaine and phenytoin, are not used very often in AF. They are reserved for patients with underlying heart disease and rhythm disorders other than AF.

Class IC medications commonly used to stop AF include propafenone and flecainide. In patients without a history of coronary heart disease and with normal heart function, these medications are very effective in returning them to normal rhythm. Flecainide is usually taken twice a day, while propafenone can be taken up to three times a day. However, its side effects include unstable heart rhythms, an excessive slowing of the heart rate, and heart failure. Consequently, these medications, although effective, are generally reserved for younger patients with AF and without structural heart disease. Patients taking these medications should be monitored by their doctor.

Class III drugs work by blocking potassium channels in cardiac cells. Some of them are amiodarone and sotalol. Amiodarone is considered one of the most effective antiarrhythmics in comparative studies. However, safer alternatives have been investigated because, although amiodarone is generally well tolerated, it has side effects that can affect different parts of the body: skin (blue-gray discoloration, photosensitivity), thyroid (hyper or hypothyroidism), eyes (deposits). corneal), lungs (fibrosis), liver (altered liver function). Sotalol is also a beta blocker and slows the heart rate, although in higher doses it acts to stabilize the heart rate. Its main side effects involve a slow heart rate and low blood pressure that cause symptoms of lethargy, dizziness, and fainting.

Frequency control

Rate control is achieved with drugs that act by increasing the degree of blockage in the AV node, with a real decrease in the number of impulses that are conducted to the ventricles. This can be done with:

• Beta blockers (preferably cardioselective beta-blockers such as metoprolol, atenolol, bisoprolol)
• Antagonists of calcium channels (i.e. diltiazem and verapamilo)
• cardiotonic glycosides (i.e. digoxin) – limited use other than the elderly and sedentary patient

In addition to these drugs, amiodarone has some AV node blocking effects, especially when administered intravenously, and can be used in case of contraindication or lack of effectiveness (especially due to hypotension) of other drugs.

Anticoagulation

Most patients with AF have an increased risk of stroke. The exception is patients with benign recurrent AF in adults, whose risk is very low and independent of the type of AF. A systematic review of risk factors for stroke in patients with non-valvular AF concluded that a history of Stroke or TIA was the strongest risk factor for future stroke, followed by older age, hypertension, and diabetes. Embolization is much more likely in patients younger than 65 years than in patients older than 75.

Anticoagulants may be necessary to compensate for the increased risk of stroke. However, with warfarin, if the annual risk is less than 2%, the risks associated with warfarin treatment outweigh the risk of stroke due to AF.

AF in the setting of mitral stenosis is associated with a 17-fold increase in the risk of stroke.

Acute anticoagulation

If urgent anticoagulation is required (for example, for cardioversion), heparin or similar drugs achieve their objective much faster than warfarin, which takes several days to reach adequate concentrations. After a recent embolic stroke, anticoagulation may be risky, because the damaged brain area has a certain tendency to bleed (hemorrhagic transformation).

Chronic anticoagulation

In patients with non-valvular AF, anticoagulation with warfarin can reduce stroke by 60%, while antiplatelet agents can reduce it by 20%.

Cardioversion

Cardioversion is performed to restart and restore sinus rhythm in patients with persistent AF and can be achieved through drugs or electrical shocks:

• Electric cardioversion involves restoring normal heart rate by applying a continuous electrical discharge.
• Chemistry is performed with drugs such as amiodarone, dronedarone (available soon), procainamide, ibutylide, propafenone or phlecainide.

The need for cardioversion may be immediate when arrhythmia is the primary factor responsible for acute heart failure, hypotension, or worsening angina in a patient with coronary artery disease. Cardioversion carries a risk of thromboembolism unless prevention with anticoagulants is initiated before treatment. However, there is no evidence that the risk of thromboembolism or stroke is different between pharmacological and electrical methods.

Non-pharmacological treatments

Cardioversion

In patients with AF where the heart rate cannot be controlled with drugs and it is not possible to restore sinus rhythm with cardioversion, non-pharmacological alternatives are available. On numerous occasions, pharmacological therapy fails, usually due to intolerance to the medications, especially in older people, or those who present additional complications such as chronic obstructive pulmonary disease (COPD) or heart failure, which limits the use of calcium channel blocking medications or beta blockers. One of the most used techniques is ablation.

Ablation is a method that is increasingly used to treat cases of recurrent AF that do not respond to conventional treatments. It can be performed by cryoablation or by radiofrequency (where low and high temperatures are used respectively).

Catheter ablation destroys the areas of tissue that cause abnormal electrical signals. Isolation of the pulmonary veins leading to the left atrium is one of the ablation techniques of choice, with satisfactory results of less than 80% and a complication rate of 4-7%, with cauterization of the esophagus being the most feared.

Ablation of the atrioventricular node together with implantation of a permanent pacemaker provides highly effective control of heart rate and improves symptoms in some patients with AF. In general, the patients most likely to benefit from this strategy are those who have rapid ventricular rates during AF that cannot be adequately controlled with rate or rhythm control.

Ablation of atrial fibrillation is performed in young patients with paroxysmal fibrillation and who do not have other associated diseases, although it is also reasonable for people with persistent atrial fibrillation and failure of antiarrhythmic drugs. It is not a curative therapy, but rather helps control the heart rate and reduce symptoms, but patients must continue taking anticoagulant treatments. 70% of patients achieve an improvement in their quality of life, but typically require a second procedure to achieve this. Less than 1% have complications, such as pulmonary stenosis or stroke.

Another technique that is used is electroshock (defibrillation or electrical cardioversion). It consists of a single intense electrical shock through the heart, which generates an effective refractory period for a few seconds. Afterwards, the heart itself is capable of generating a normal rhythm. It is not possible in patients who have other cardiac complications. It is a technique also used for the treatment of ventricular fibrillation.

Aerobic exercise

Apart from pharmacological options, aerobic exercise could be postulated as a preventive measure by acting on the risk factors for atrial fibrillation. In addition, moderate aerobic exercise improves the symptoms of atrial fibrillation.

Despite this, the relationship between aerobic exercise and atrial fibrillation is controversial: atrial fibrillation is highly prevalent in athletes and is associated with high-intensity aerobic exercise. On the other hand, aerobic exercise could provide the following benefits: improvement in the quality of life of patients, reduction in risk factors and usefulness as a preventive/therapeutic measure.

The future in the treatment of atrial fibrillation

While pacemakers, defibrillators, radiofrequency ablation, and surgery have increasingly played a role in the treatment of atrial fibrillation, pharmacological treatment remains an important first-line treatment. However, these drugs are limited by their serious side effects and, as a result, there is still a pressing need for improved antiarrhythmic drugs. However, the therapeutic landscape has changed favorably with the recent approval of dronedarone, an antiarrhythmic that reduces hospitalizations due to cardiovascular causes in patients with atrial fibrillation (paroxysmal or intermittent) or atrial flutter. Its manufacturer has announced the launch of a prevention and risk mitigation strategy called mPACT™ (Multaq® Partnership for Appropriate Care and Treatment) to achieve safe use of the drug. although the phase III clinical trial had to be suspended due to lack of of the drug. The PALLAS study in patients with permanent atrial fibrillation had to be suspended for drug safety reasons. The PALLAS trial (2011) was stopped for safety reasons due to the finding that "the Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events.' The FDA later added a black box warning indicating that the risk of death, stroke, and hospitalization for congestive heart failure doubled in patients with permanent atrial fibrillation.