Atrial Fibrillation: Causes

Pathogenesis (disease development)

Atrial fibrillation (AF) is a cardiac arrhythmia in which there is intraatrial (“within an atrium (located)”) excitation circuitry due to micro-reentry (= reentry of excitations), resulting in atrial fibrillation rates of 350 to 600 beats/min. Due to the frequency filtering function of the AV node, this results in irregular atrioventricular (“concerning the section between the atrium and the ventricle”) conduction or absolute arrhythmia (cardiac arrhythmia in which the heart beats irregularly). This leads to the fact that the pumping function through the atria can no longer be perceived. This significantly limits cardiac output (HRV), as the lack of atrial contraction contributes to a 20% reduction in cardiac output. The balance between sympathetic and parasympathetic inputs is an important predictor of atrial fibrillation:

  • Vagally induced AF generally occurs at night or postprandially
  • Adrenergically determined atrial fibrillation usually manifests during the daytime

The cause of fibrillation is cardiac in about 2/3 of cases and extracardiac in about 1/4. Gender differences (gender medicine): women with VHF suffer more often from arterial hypertension (high blood pressure), valvular vitiation (valvular heart disease) and diastolic dysfunction (“heart failure with preserved EF”, HFpEF). Few patients (approximately 10%) with AF have idiopathic AF, termed “lone atrial fibrillation,” meaning that these are patients without structural heart disease or vascular risk factors, and the age of patients is usually less than 65 years.

Etiology (Causes)

Biographic Causes

  • Genetic burden from parents, grandparents:
      • There is twice the risk of atrial fibrillation if at least one parent already had atrial fibrillation. 14.8% of patients had a first-degree relative who also had AF.
      • With a family history of AF: relative risk (RR): 1.92-fold risk; multiple close family members affected: 4-fold risk (RR 3.63).Phenotypic variability of AF: 19.9% genetic factors, 3.5% common environmental factors, and 76.6% specific environmental influences.
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: LOC729065
        • SNP: rs2200733 in gene LOC729065
          • Allele constellation: TT (1.5-fold).
          • Allele constellation: CT (1.4-fold)
          • Allele constellation: CC (0.86-fold)
        • SNP: rs10033464 in an intergenic region.
          • Allele constellation: TT (1.4-fold).
          • Allele constellation: CT (1.28-fold)
          • Allele constellation: GG (0.92-fold)
      • 150 SNPs that explain about 11.2% of all diseases; genes: e.g., KCNH2 (information for a potassium channel, the target of amiodarone or sotalol); SCN5A (information for the sodium channel, on which antiarrhythmic drugs such as flecainide and propafenone act).
  • Age – older age
  • Height – with the relative risk increasing significantly with a 10 cm increase in height (tall people also have a large atrium)
  • Hormonal factors – climacteric (menopause) in women.

Behavioral causes

  • Nutrition
    • Opulent meal (sumptuous food)
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol* (woman: > 15 g/day; man: > 20 g/day) (trigger for symptomatic paroxysmal atrial fibrillation: 35% of cases)
      • Holiday heart syndrome: alcohol-triggered arrhythmia]; significant dose-dependent deterioration in left ventricular function after alcohol (ejection fraction (EF): reduction from an average of 58% to an average of 52%; in healthy individuals: 50-60%.
      • Increase in VCF as a function of alcohol dose.
    • Tobacco (smoking)
      • Also passive smoking during childhood: 14.3% developed atrial fibrillation (VHF) a mean of 40.5 years after reaching adulthood; passing on the smoking habit to children resulted in a 34% increased risk of developing VHF among them
      • of the smoking habit to the children resulted in a 34% increased risk of developing atrial fibrillation in them
    • Caffeine consumption (coffee, energy drinks) (trigger for symptomatic paroxysmal atrial fibrillation: 28% of cases).
  • Drug use
    • Amphetamines (indirect sympathomimetic).
    • Cannabis (hashish and marijuana)
    • Cocaine
  • Physical activity
    • Physical inactivity
    • Physical overload
    • Competitive sports
      • VHF is more common in competitive “middle-aged and older endurance athletes with long training history” (51 ± 9 years), probably because of left atrial overstretching; the higher the training intensity, the higher the VHF risk
      • Strength-based competitive sports such as American football – former National Football League (NFL) players were 6 times more likely to suffer from VCF than men in a population-based control group
  • Psycho-social situation
    • Trouble
    • Emotional stress / (Eu) stress
    • Frequent sleep deprivation/poor sleep quality (insomnia/sleep disturbance) (trigger for symptomatic paroxysmal atrial fibrillation: 23% of cases)
    • Bereavement (30 days after bereavement, 41% increased risk of AF; 1.34-fold increased risk for those younger than 60 years)
    • Weekly work hours > 55 hours (1.4-fold increased risk).
  • Overweight (BMI ≥ 25; obesity).
    • Excessive body mass index (BMI; body mass index) was responsible for approximately 20% of cases with VCF:
      • BMI in men: 31% increased risk.
      • BMI in women: 18% increased risk

Causes due to disease

  • Binge Eating Disorder (BED) – eating disorder with occurrence of excessive binge eating, independent of hunger pangs (BMI; body mass index) > 30; 75% increase in risk).
  • Chronic renal insufficiency (kidney weakness; restriction of kidney function).
  • Chronic obstructive pulmonary disease (COPD) (11%).
  • Cor pulmonale – dilatation (widening) and/or hypertrophy (enlargement) of the right ventricle (main chamber) of the heart due to pulmonary hypertension (increase in pressure in the pulmonary circulation, which may be due to various diseases of the lung
  • Diabetes mellitus (21%)
  • Gastroesophageal reflux disease (synonyms: GERD, gastroesophageal reflux disease; gastroesophageal reflux disease (GERD); gastroesophageal reflux disease (reflux disease); gastroesophageal reflux; reflux esophagitis; reflux disease; reflux esophagitis; peptic esophagitis) – inflammatory disease of the esophagus (esophagitis) caused by the pathological reflux of acidic gastric juice and other gastric contents (? )
  • Heart failure (cardiac insufficiency; NYHA classes II-IV), including tachycardiomyopathy (structural myocardial damage (cardiomyopathy) resulting from a permanently excessive heart rate (a tachycardia: pulse > 100 beats per minute)) (29%)
  • Valvular heart disease (esp. mitral valve/valve located between the left atrium and left ventricle; aortic valve) (36%)
  • Cardiac arrhythmias – atrial tachyarrhythmias (atrial cardiac arrhythmia, which is a combination of too fast cardiac action (tachycardia) and cardiac arrhythmia) occur more frequently in association with pathological bradycardia (heartbeat below 60 beats per minute) (more than 50% of bradycardia-symptomatic pacemaker patients also develop VHF within 6 years after implantation)
  • Hypercapnia – too much carbon dioxide in the blood.
  • Hypertension (high blood pressure), especially when the left atrium is dilated (69%)
    • 24-hour blood pressure measurement: if 40% of daily systolic values were above 135 mmHg, there is a nearly 50% higher risk of subsequent atrial fibrillation compared with the average population.
  • Hyperthyroidism* (hyperthyroidism; most common cause: Graves’ disease) incl. latent hyperthyroidism (mild form of hyperthyroidism) (7%).
  • Hypoxia (oxygen deficiency)
  • Cardiomyopathies (heart muscle diseases), including primary electrical heart muscle diseases (11%).
  • Congenital heart diseases (congenital heart defects (cardiac vitias), KHF) – atrial septal defects (hole in the septum between the two atria of the heart) and other congenital (congenital) heart diseases).
  • Left ventricular hypertrophy – tissue enlargement (hypertrophy) that affects the myocardium (heart muscle) of the left ventricle (heart chamber).
  • Pulmonary embolism (obstruction of the pulmonary arteries with thrombi).
  • Pulmonary emphysema (pulmonary hyperinflation)
  • Coronary artery disease (CAD) (28%) [more common in acute coronary syndrome, less common in chronic CAD!]
  • Metabolic syndrome
  • Myocardial infarction (heart attack)
  • Orthostatic hypotension (drop in blood pressure that occurs when changing to an upright posture); risk increase 40%, whether indicator or causative is not yet clear
  • Renal insufficiency (process leading to a slowly progressive reduction in renal function).
    • EGRF value: 60-89 ml/min per 1.73 m2, incidence 9% higher (hazard ratio: 1.09)
    • EGRF value < 30 ml/min per 1.73 m2), incidence 103% higher (HR: 2.03).
  • Pericarditis (inflammation of the pericardium)/carditis (inflammation of the heart).
  • Rheumatic fever
  • Rheumatoid arthritis – chronic inflammatory multisystem disease, usually manifested in the form of synovitis (inflammation of the synovial membrane).
  • Arrhythmias such as:
    • Sick sinus syndrome (SSS) [synonyms: sinus node syndrome, sinus node disease; this syndrome groups together several nomotopic (= orthotopic) cardiac arrhythmias originating in the sinus node: e.g., sinus bradycardia, intermittent sinus arrest, or a complete block between the sinus node and atrial myocardium (= sinuatrial block); an alternation between supraventricular tachycardia (SVES), systolic pauses and sinus bradycardia – this is also called tachycardia-bradycardia syndrome]
    • WPW syndrome (Wolff-Parkinson-White syndrome; cardiac arrhythmia triggered by an electrical circular excitation (circus movement) between the atria and the ventricles).
  • Sleep-related breathing disorders (SBAS):
    • Obstructive sleep apnea syndrome (OSAS; breathing disorder in which there are repeated obstructions of the upper airway during sleep due to the slackened base of the tongue (obstruction = narrowing, shifting)) – is thus a predictive parameter for atrial fibrillation
    • Central sleep apnea syndrome (ZSAS; repeated respiratory arrests due to lack of activation of respiratory muscles).
  • Sepsis (blood poisoning)
  • Disturbances of the electrolyte balance (magnesium, potassium, subnormal or in the lower normal range; see below “Drug therapy“).
  • Atrial fibrosis → atrial fibrillation (AF) and cryptogenic apoplexy (“Embolic Stroke of Undetermined Source” (ESUS)).
  • Thyrotoxicosis* – derailed hyperthyroidism.

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

  • Glomerular filtration rate (GFR) ↓
    • EGRF value: 60-89 ml/min per 1.73 m2, incidence (frequency of new cases) 9% higher (hazard ratio: 1.09)
    • EGRF value: < 30 ml/min per 1.73 m2, incidence 103% higher (HR: 2.03)
  • Free thyroxine fT4) – slightly elevated levels of fT4 in the blood, still within the normal range (highest quartiles).

Medication

  • Antiepileptic drugs
  • Β2-sympathomimetic (e.g., salbutamol).
  • COX-2 inhibitor (synonym: COX-2 inhibitor).
  • Glucocorticoids
  • Non-steroidal anti-inflammatory drugs (NSAID; non steroidal anti- inflammatory drugs) [excl. acetylsalicylic acid].
  • Thyroid hormone therapy (L-thyroxine (levothyroxine)) (more common in VHF patients compared with the overall population)

Surgeries

  • After surgical procedures* (= perioperative atrial fibrillation), especially after cardiac surgery, atrial fibrillation is a common complication; it is more common in mitral valve procedures (up to 73%) than in bypass surgery (10-33%) Perioperative atrial fibrillation is associated with an increased long-term risk of ischemic stroke, especially after noncardiac surgery.
  • Postoperative AF (within 30 days of a surgical procedure):
    • Thoracic surgery: 17.7 percent (95 percent confidence interval: 12.2-21.5 percent)
      • Coronary artery bypass grafting (transient atrial fibrillation in 20% to 40% of cases) (see also under sequelae)
    • Nonthoracic surgery: 7.63 percent (95% confidence interval: 4.39-11.98 percent)
    • Replacement of the aortic valve using a catheter (TAVI) or open technique: up to 50% of patients develop VHF

Environmental exposure – intoxications (poisonings).

  • Noise
  • Low temperatures

Other causes

* Atrial fibrillation temporal and therefore reversible.