AFib Differential Diagnosis: Determining Other Causes

Summary: AFib is associated with a variety of underlying pathologies that shouldn't be missed.
AFib Differential Diagnosis: Determining Other Causes

Atrial fibrillation (AFib) is the most common serious abnormal cardiac arrhythmia. Characterized by a rapid and irregular heartbeat, AFib increases the risk of thromboembolic stroke and heart failure. With a prevalence of around 1% in the general population and a heightened prevalence of 6% in people over 60 years old, the number of cases of AFib is predicted to increase dramatically over the coming decades.

When AFib is suspected, palpating the pulse is a good initial test, but EKG showing irregular P waves is needed in order to confirm the diagnosis. While the cause of a significant proportion of AFib cases is unknown, AFib is associated with a variety of underlying pathologies that shouldn't be missed. Thus, when AFib is suspected, here are a few things that should be on your AFib differential.

It can be easy to focus on rate and rhythm control when a patient is diagnosed with AFib. However, the etiology of AFib can be multifactorial and an indicator of deeper underlying disease in which rate control is not the first line. Categorizing your differential can be helpful in making sure the correct diagnosis can be made. One easy way to do so is to think about AFib in terms of three buckets: cardiac, metabolic, or hyperadrenergic state.

Cardiac abnormalities

While AFib can appear in a normal heart, it can also be a sign of underlying cardiac dysfunction. Cardiac causes of AFib can be further broken down into 3 primary categories:

  • Structural defects that cause abnormal stretching and remodeling of the heart can lead to AFib and should be further examined if clinically indicated. These include valvular defects such as mitral stenosis or regurgitation, congenital defects such as an atrial septal defect, or previous cardiac injuries such as previous MI or cardiac infection. 
  • Performing high-quality auscultation followed by an echocardiogram could be an important part of the diagnostic process.
  • Conduction abnormalities cannot be forgotten as these can sometimes lead to sudden cardiac death. Several to keep in mind are sick sinus syndrome, Wolf Parkinson White syndrome, or short qt syndrome. When examining the EKG, it's important to keep these possible abnormalities in mind.
  • Conditions that increase cardiac workload can also predispose a patient to AFib. These include any previous injury such as MI or PE or modifiable risk factors such as hypertension. Additional causes could include pericarditis or rheumatic heart disease.
  • A good clinical history and physical exam is needed to help exclude these causes.



Metabolic causes should also be on your differential as a potential cause of AFib. A detailed clinical and medications history can be an easy way to help patients who are experiencing episodes of AFib or point to an underlying cause. Several metabolic disturbances to keep in mind on your AFib differential are: 

Electrolyte disturbances
  • Low K, low Mg, and low Ca are possible electrolyte disturbances that can lead to AFib. Besides a blood draw, these ion changes can also lead to ECG changes that can be easily screened for.
Carbon monoxide poisoning
  • Carbon monoxide (CO) intoxication is one of the major public health hazards which may go unnoticed as this is a colorless, odorless, and tasteless gas. The manifestations of the CO poisoning are far-reaching. Although CO affects almost every organ in the body, cerebral and myocardial involvement are predominant due to the hypoxia-induced cellular damage. 
Many medications can cause or exacerbate existing atrial fibrillation. Some keep in mind are:
  • Antiarrhythmics: Certain medications used to treat cardiac rhythm abnormalities can also cause AFib.
  • Asthma medications: Theophyline and albuterol are 2 commonly used medications that can lead to episodes of AFib.
  • Certain antidepressants: Antidepressants such as TCAs can cause or exacerbate episodes of AFib. 
  • Alcohol can also cause AFib, especially after episodes of heavy ingestion in what is colloquially known as holiday heart syndrome. 


Hyperadrenergic state

A hyperadrenergic state is a broad bucket that refers to an elevated sympathetic response. While signs of a hyperadrenergic state can be subtle, it is important to keep these causes on your AFib differential as rhythm and rate control might not always be the first-line treatment. 

  • Hyperthyroidism is a well-known cause of atrial fibrillation with a 16–60% prevalence of AFib in patients with known hyperthyroidism. Rhythm control is usually not recommended in patients with hyperthyroidism and atrial fibrillation as nearly two-thirds of patients revert to normal sinus rhythm 8 to 10 weeks after achieving a euthyroid state.
  • Postoperative atrial fibrillation (POAF) is common after both cardiothoracic and noncardiothoracic surgery. AFib has been reported in 5 to 40% of patients in the early postoperative period following coronary artery bypass graft (CABG), in 37 to 50% after valve surgery, 64% undergoing mitral valve replacement plus CABG, 49% undergoing aortic valve replacement (AVR) plus CABG, and in 12% after cardiac transplantation.
  • POAF after cardiac surgery tends to occur within 2 to 4 days after the procedure with a peak incidence on a postoperative day.
Obstructive sleep apnea
  • AFib is strongly associated with occurrences of obstructive sleep apnea, possibly due to associated risk factors of obesity and age. In addition, hypoxemia caused by OSA leads to sympathetic nervous system disturbances that can lead to AFib. Risk of recurrent AFib after is diminished by OSA treatment with CPAP. The presence of untreated OSA in patients after cardioversion is associated with an 82% risk of recurrence of AFib within 1 year, which is double the rate seen in patients in whom OSA is treated effectively.
  • The Association of Sleep Medicine considers AFib patients to be at high risk for sleep-disordered breathing and recommends sleep apnea symptom evaluation.
  • COPD is associated with a 28% increased risk of developing AFib, and that having frequent COPD exacerbations increases the AFib risk approximately 2-fold.

Atrial fibrillation is associated with a variety of causes, ranging across organ systems. While lifestyle changes, rate, and rhythm control are considered first-line therapies, it is important to keep your differential diagnosis broad and screen for other conditions that might cause or exacerbate AFib. Adequately diagnosing and treating these conditions is vital to reducing the burden of AFib.



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