Atrial fibrillation

Atrial fibrillation is an abnormal heart rhythm characterized by rapid and irregular beating of the atrial chambers of the heart. It often begins as short periods of abnormal beating, which become longer or continuous over time. It may also start as other forms of arrhythmia, such as atrial flutter, that transform into AF.
Episodes can be asymptomatic. Symptomatic episodes may involve heart palpitations, fainting, lightheadedness, loss of consciousness, or shortness of breath. Atrial fibrillation is associated with an increased risk of heart failure, dementia, and stroke. It is a type of supraventricular tachycardia.
Atrial fibrillation frequently results from bursts of tachycardia that originate in muscle bundles extending from the atrium to the pulmonary veins. Pulmonary vein isolation by transcatheter ablation can restore sinus rhythm. The ganglionated plexi can also be a source of atrial fibrillation, and are sometimes also ablated for that reason. Not only the pulmonary vein, but the left atrial appendage and ligament of Marshall can be a source of atrial fibrillation and are also ablated for that reason. As atrial fibrillation becomes more persistent, the junction between the pulmonary veins and the left atrium becomes less of an initiator and the left atrium becomes an independent source of arrhythmias.
High blood pressure and valvular heart disease are the most common modifiable risk factors for AF. Other heart-related risk factors include heart failure, coronary artery disease, cardiomyopathy, and congenital heart disease. In low- and middle-income countries, valvular heart disease is often attributable to rheumatic fever. Lung-related risk factors include COPD, obesity, and sleep apnea. Cortisol and other stress biomarkers, as well as emotional stress, may play a role in the pathogenesis of atrial fibrillation.
Other risk factors include excess alcohol intake, tobacco smoking, diabetes mellitus, subclinical hypothyroidism, and thyrotoxicosis. However, about half of cases are not associated with any of these aforementioned risks. Healthcare professionals might suspect AF after feeling the pulse and confirm the diagnosis by interpreting an electrocardiogram. A typical ECG in AF shows irregularly spaced QRS complexes without P waves.
Healthy lifestyle changes, such as weight loss in people with obesity, increased physical activity, and drinking less alcohol, can lower the risk for AF and reduce its burden if it occurs. AF is often treated with medications to slow the heart rate to a near-normal range or to convert the rhythm to normal sinus rhythm. Electrical cardioversion can convert AF to normal heart rhythm and is often necessary for emergency use if the person is unstable. Ablation may prevent recurrence in some people. For those at low risk of stroke, AF does not necessarily require blood-thinning though some healthcare providers may prescribe an anti-clotting medication. Most people with AF are at increased risk of stroke. For those at more than low risk, experts generally recommend an anti-clotting medication. Anti-clotting medications include warfarin and direct oral anticoagulants. While these medications reduce stroke risk, they increase rates of major bleeding.
Atrial fibrillation is the most common serious abnormal heart rhythm and, as of 2020, affects more than 33 million people worldwide. As of 2014, it affected about 2 to 3% of the population of Europe and North America. The incidence and prevalence of AF is increasing. In the developing world, about 0.6% of males and 0.4% of females are affected. The percentage of people with AF increases with age with 0.1% under 50 years old, 4% between 60 and 70 years old, and 14% over 80 years old being affected. The first known report of an irregular pulse was by Jean-Baptiste de Sénac in 1749. Thomas Lewis was the first doctor to document this by ECG in 1909.

Signs and symptoms

Atrial fibrillation is usually accompanied by symptoms related to a rapid heart rate. Rapid and irregular heart rates may be perceived as the sensation of the heart beating too fast, irregularly, or skipping beats or exercise intolerance.
Other possible symptoms include congestive heart failure symptoms such as fatigue, shortness of breath, or swelling. Loss of consciousness can also occur on atrial fibrillations due to lack of oxygen and blood to the brain. The abnormal heart rhythm is sometimes only identified with the onset of a stroke or a transient ischemic attack. It is not uncommon for a person to first become aware of AF from a routine physical examination or electrocardiogram, as it often does not cause symptoms.
Since most cases of AF are secondary to other medical problems, the presence of chest pain or angina, signs and symptoms of hyperthyroidism such as weight loss and diarrhea, and symptoms suggestive of lung disease can indicate an underlying cause. A history of stroke or TIA, as well as high blood pressure, diabetes, heart failure, or rheumatic fever, may indicate whether someone with AF is at a higher risk of complications.

Rapid heart rate

Presentation is similar to other forms of tachycardia and may be asymptomatic. Palpitations and chest discomfort are common complaints. The rapid uncoordinated heart rate may result in reduced output of blood pumped by the heart, resulting in inadequate blood flow and therefore inadequate oxygen delivery to the rest of the body. Common symptoms of uncontrolled atrial fibrillation may include shortness of breath both when upright and when lying flat, dizziness, and sudden onset of paroxysmal nocturnal dyspnoea, shortness of breath during the night. This may progress to swelling of the lower extremities, a manifestation of congestive heart failure. Due to inadequate cardiac output, individuals with AF may also complain of lightheadedness.
AF can cause respiratory distress due to congestion in the lungs. By definition, the heart rate will be tachycardic. Blood pressure may be variable, and often difficult to measure as the beat-by-beat variability causes problems for most digital non-invasive blood pressure monitors. For this reason, when determining the heart rate in AF, direct cardiac auscultation is recommended. Low blood pressure is most concerning, and a sign that immediate treatment is required. Many of the symptoms associated with uncontrolled atrial fibrillation are a manifestation of congestive heart failure due to the reduced cardiac output. The affected person's respiratory rate often increases in the presence of respiratory distress. Pulse oximetry may confirm the presence of too little oxygen reaching the body's tissues, related to any precipitating factors such as pneumonia. Examination of the jugular veins may reveal elevated pressure. Examination of the lungs may reveal crackles, which are suggestive of pulmonary edema. Examination of the heart will reveal a rapid irregular rhythm.

Causes

AF is linked to several forms of cardiovascular disease but may occur in otherwise normal hearts. Cardiovascular factors known to be associated with the development of AF include high blood pressure, coronary artery disease, mitral valve stenosis, mitral regurgitation, left atrial enlargement, hypertrophic cardiomyopathy, pericarditis, congenital heart disease, and previous heart surgery. People with congenital heart disease tend to develop atrial fibrillation at a younger age, that is more likely to be of right atrial origin than of left origin, and have a greater risk of progressing to permanent atrial fibrillation.
Additionally, lung diseases may play a role in certain people. Sepsis also increases the risk of developing new-onset atrial fibrillation. Disorders of breathing during sleep, such as obstructive sleep apnea, are also associated with AF. OSA, specifically, was found to be a very strong predictor of atrial fibrillation. Patients with OSA were shown to have an increased incidence of atrial fibrillation and a study done by Gami et al. demonstrated that increased nocturnal oxygen desaturation from OSA severity was correlated with higher incidences of atrial fibrillation. Obesity is a risk factor for AF. Hyperthyroidism and subclinical hyperthyroidism are associated with AF development.
Caffeine consumption does not appear to be associated with AF; excessive alcohol consumption is linked to AF. Low-to-moderate alcohol consumption also appears to be associated with an increased risk of developing atrial fibrillation, although the increase in risk associated with drinking less than two drinks daily appears to be small. Tobacco smoking and secondhand tobacco smoke exposure are associated with an increased risk of developing atrial fibrillation. Long-term endurance exercise that far exceeds the recommended amount of exercise appears to be associated with a modest increase in the risk of atrial fibrillation in middle-aged and elderly people.
Major stress biomarkers indicate that stress plays a significant role in causing atrial fibrillation. There is some evidence that night shift working may be linked to a diagnosis of AF.
Atrial fibrillation is associated with elevated levels of inflammatory markers and clotting factors. Mendelian randomization indicates a causal relationship of inflammation leading to atrial fibrillation.

Genetics

Family history in a first-degree relative is associated with a 40% increase in risk of AF. This finding led to the mapping of different loci such as 10q22-24, 6q14-16 and 11p15-5.3 and discover mutations associated with the loci. Mutations have been found in the genes of K⁺ channels and Na⁺ channels which affect the processes of polarization-depolarization of the myocardium, cellular hyper-excitability, shortening of effective refractory period favoring re-entries.
Using genome-wide association study, which screen the entire genome for single-nucleotide polymorphism, three susceptibility loci have been found for AF. In these loci there are SNPs associated with a 30% increase in risk of recurrent atrial tachycardia after ablation. There are also SNPs associated with loss of function of the Pitx2c gene, responsible for re-entries. There are also SNPs close to ZFHX3 genes involved in the regulation of Ca²⁺. A 2018 meta-analysis of GWAS studies identified 97 locis associated with AF, of which 70 were newly identified associations: they are associated with genes that encode transcription factors, such as TBX3 and TBX5, NKX2-5 or PITX2, involved in the regulation of cardiac conduction, modulation of ion channels and in cardiac development.