Paroxysmal Atrial Fibrillation

Etiology

Atrial fibrillation is commonly associated with conditions that alter the structure of the heart. Important causes and risk factors for AF are as follows:

Cardiac Causes

• Hypertensive heart disease 
• Coronary artery disease 
• Valvular heart disease 
• Heart failure 
• Congenital heart disease
• Cardiomyopathy
• Infiltrative cardiac disease 
• Sick sinus syndrome
• Pre-excitation syndrome

Non-Cardiac Causes

• Chronic lung disease 
• Pulmonary embolism
• Electrolyte abnormalities
• Acute infections 
• Thyroid disorders
• Pheochromocytoma
• Hypothermia
• Post-surgical (seen in 35% to 50% of patients post coronary artery bypass graft)[3] 

Risk Factors

• Age-related fibrosis
• Diabetes
• Obesity 
• Metabolic syndrome 
• Obstructive sleep apnea
• Chronic kidney disease
• High-intensity exercise
• Genetic factors

Epidemiology

Researchers of a 2010 study systematically reviewed 184 population-based studies for AF and estimated that approximately 33.5 million individuals in the world have AF.[4] AF prevalence has gradually increased over the last few decades. Based on the Centers for Disease Control and Prevention (CDC) estimate in 2017, 2.6 to 6.1 million people in the United States have AF. Further, the prevalence increases with age, and approximately 9% of all adults aged greater than 80 have AF.[5][6] Europe has a higher prevalence of AF compared to the United States. Similar to the prevalence, the incidence of AF increases with age. In all age groups, males are more commonly affected than females. Despite a high prevalence of risk factors, African Americans tend to have lower AF incidence compared to Caucasians.[6]

Pathophysiology

The underlying mechanism for AF is related to a complex interaction between triggers and substrate. Triggers are responsible for initiating the event (arrhythmia), and substrate will maintain that arrhythmia. Triggers arise when the action potential induces after-depolarization that is strong enough to overcome recovering repolarization.[7] This after-depolarization can cause extra systole but cannot maintain persistent arrhythmia. Impulses from such extrasystoles, however, are discharged at high frequency. When these impulses encounter the myocardium with variable excitability or refractoriness, it gives rise to functional electrical blocks. Re-entry circuits arise, which in turn gives rise to new impulse waves generating additional re-entry circuits that help maintain persistent arrhythmia to overcome such blocks.[8]

The most common site for ectopic foci and trigger origin is the left atrial muscular sleeve extending into the pulmonary vein. Myocardial cells in this region display a shorter refractory period compared to surrounding myocardium and patients without AF. Pulmonary vein isolation (PVI) performed during catheter ablation for AF aims to isolate this region from the surrounding myocardium dissipating further development of AF. Occasionally, AF can be triggered by other arrhythmias such as AVRT/ Atrial flutter and even premature atrial contractions (PACs). Atrial remodeling arising from electrical, structural, and autonomic changes of the myocardium promotes both trigger and substrate. These changes lead to altered sympathovagal activity, a shorter refractory period, and increased atrial inducibility propagating AF.[9][10] Inflammatory and oxidative changes are also noted at the molecular level, which can be correlated with the high C-reactive protein (CRP) level. AF can cause hemodynamic and electrophysiological changes causing increased susceptibility to new episodes of AF.[11]

History and Physical

Clinical presentation for AF can range from asymptomatic incidental findings on an electrocardiogram (ECG) to a catastrophic stroke with an undiagnosed underlying irregular rhythm. More commonly, symptoms are similar to other arrhythmias like palpitations, dyspnea at rest or exertion, angina-like symptoms, fatigue or decreased exercise tolerance, lightheadedness, diaphoresis, dizziness, and pre-sync and syncope. AF can also masquerade as symptoms of heart failure exacerbation like weight gain, pedal edema, and pulmonary congestion.

All patients presenting with the above symptoms should have a detailed history, including past medical/cardiac history. On physical examination, patients should be examined for an irregularly irregular pulse, signs of heart failure like jugular vein distension (JVD), pedal edema, and lung crackles. In valvular AF, mitral stenosis/regurgitation murmur can be heard. A history of prior investigation of underlying causes, anticoagulation choices, and previously attempted methods for rate/rhythm control is important.

Evaluation

As mentioned above, all patients being evaluated for AF should have a detailed history and physical exam. Diagnosis of AF is based on characteristic ECG findings. ECG findings as seen in patients with AF:

• The absence of distinct “P” waves
• Irregularly irregular R-R interval.
• Narrow QRS complex tachycardia, typically with the heart rate between 110 and 160; QRS duration fewer than 0.12 seconds unless accompanied by pre-existing bundle block, aberrant conduction, or accessory pathway
• Fibrillatory waves may be present, which can mimic “P” waves.

Ashman phenomenon: QRS morphology is usually unaffected in AF. However, in cases with aberrant ventricular conduction, bundle branch block can occur due to an abrupt change in length of the cardiac cycle. These aberrantly conducted beats are usually of right bundle branch block morphology.[12]

Further evaluation should include a workup to identify the cause of AF. Patients should be tested for electrolyte abnormalities, endocrine disorders (specifically hyperthyroid), drug-induced causes, infections, drug or chemical withdrawal, and echocardiography to check for structural heart disease. In patients presenting with ischemic stroke and with no prior history of AF, 72-hour Holter monitoring improves the detection rate of silent paroxysmal AF.[13]

Treatment / Management

Treatment strategy involves antithrombotic therapy and selection between rate or rhythm control. Previous randomized studies such as Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) and Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) have shown no superiority with one compared to other.[14][15][16](A1)

Antithrombotic Therapy

AF is associated with a 5-fold increased risk of stroke. Whether all patients with AF need anticoagulation regardless of risk factor status is debatable. The embolic risk in patients with AF is estimated using the CHA2DS2-VASc risk model (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke, vascular disease, sex).[17] A higher CHA2DS2-VASc score correlates with a higher risk of ischemic stroke per year. The risk of AF-related ischemic strokes increases from 1.3% to 2.2% as the CHA2DS2-VASc score increases from 1 to 2. Benefits with antithrombotic therapy are well documented in moderate to high-risk AF patients (CHA2DS2-VASc score equal to 2). However, its use in low-risk patients (CHA2DS2-VASc score less than 2) is often controversial as benefits are not well-defined.[18][19](A1)

The benefits of anticoagulation should be balanced against the risk of bleeding. HAS-BLED scoring system (hypertension, abnormal renal/liver function, stroke, bleeding history, labile international normalized ratio, elderly, drugs/alcohol) is widely used to estimate the risk of bleeding from anticoagulation. The HAS-BLED score equal to 3 is associated with an increased risk of bleeding. Once the patient’s individualized stroke risk is determined, the selection of antithrombotic therapy varies from one patient to another. Compared to warfarin-aspirin, monotherapy is not recommended for primary stroke prevention in patients with AF.[20] Warfarin therapy needs constant monitoring with International Normalized Ratio (INR) to maintain the therapeutic range between 2.0 to 3.0, which usually requires bridging with heparin while initiating therapy. Several newer non-vitamin K antagonist oral anticoagulants (NOAC) have a shorter duration of action, not requiring heparin bridging. Trials such as RE-LY, ROCKET-AF, ARISTOTLE have shown similar effectiveness and decreased intracranial bleeding risk with NOACs (apixaban, rivaroxaban, dabigatran, edoxaban) when compared head-to-head with warfarin.[21][22][23] NOACs, do not require routine INR testing, but they have challenges with access to rapid reversal agents. This is an area of rapid development. In patients with prosthetic heart valves and valvular AF, warfarin remains the preferred drug of choice. The selection of antithrombotic agents should be based on account of risk factors, cost tolerability, patient preference, and potential drug interaction.(A1)

Rate Control

Rate control is the preferred strategy for all asymptomatic AF patients. Guidelines on target heart rate in patients selected for rate control are lacking. A previously conducted randomized trial (RACE II) to assess heart rate goal in patients with AF showed no outcome difference between lenient and strict heart rate control; however, sufficient evidence to assess the impact on all-cause mortality was lacking. Physicians usually attempt to control heart rate control with agents such as beta-blockers (metoprolol, esmolol, propranolol), nondihydropyridine calcium-channel blockers (verapamil, diltiazem), or digoxin. All 3 classes of drugs are given intravenously (IV) for acute rate control and can be switched to oral therapy for chronic management. In patients with chronic heart failure with reduced ejection fraction, carvedilol therapy has shown significant improvement in left ventricular ejection fraction. Due to the negative inotropic properties of calcium channel blockers, physicians do not use these not preferred in such patients. Digoxin is usually reserved for patients who do not achieve rate control with beta-blockers or calcium channel blockers alone. Amiodarone can be used as second-line therapy when treatment with other agents has failed.[23] In patients refractory to medical therapy, AV node ablation with a permanent pacemaker placement can effectively control and regularize ventricular heart rate. Low doses of magnesium have shown synergistic effects on rate control.[24](A1)

Rhythm Control

The decision to achieve rhythm control either with pharmacological or non-pharmacological (electric) methods is based on the presence or absence of symptoms, age, and other comorbidities. Rhythm control with pharmacological therapy alone is associated with increased side effects and a lower success rate.[25] The risk and side effects of specific antiarrhythmics should be considered before drug selection. Class I sodium channel blocking agents (flecainide, propafenone, disopyramide) have negative, inotropic action, and healthcare professionals should avoid these agents in patients with a history of coronary artery disease or heart failure. Class III agents (sotalol, dofetilide) have a 3% risk of causing QT prolongation and should be initiated while in hospital. Other class III antiarrhythmic like amiodarone has greater long-term efficacy; however, over 20% of patients develop toxicities during long-term therapy. Drug therapy is most commonly used in adjunction to direct current cardioversion (DCCV). DCCV is associated with a high immediate success rate.[26] It is commonly performed in patients with hemodynamic compromise and patients with new-onset AF (fewer than 48 hours) who are candidates for rhythm control. Patients undergoing DCCV should have preexisting atrial thrombus ruled out with either transthoracic or transesophageal echocardiography. Anticoagulation with warfarin 3 weeks prior and 4 weeks after DCCV is recommended for patients when the duration of AF is greater than 48 hours. The risk of AF recurrence post-DCCV is high and can be reduced with the use of antiarrhythmic medications. In patients with contraindication to antiarrhythmic therapy, catheter or surgical ablation can be attempted. Ablation is performed with the aim to electrically isolate the pulmonary vein (trigger foci) from the rest of the atrial myocardium. Catheter ablation is associated with high success rates (70%). No significant difference in AF burden was noted between catheter ablation and oral antiarrhythmic therapy; however, overall symptoms and quality of life were significantly better in patients receiving ablation.[27] A surgical ablation is a reasonable option for AF patients undergoing cardiac surgery for other indications. The decision to perform catheter ablation or antiarrhythmic medications used to maintain sinus rhythm is guided by patient symptoms and the risk/benefits of each therapy.(A1)

Differential Diagnosis

1. Sinus tachycardia
2. Atrial flutter
3. Atrial flutter with variable block
4. Atrial tachycardia (AT)
5. Multifocal atrial tachycardia (MAT)
6. Wolff-Parkinson-White syndrome (WPW)
7. Atrioventricular nodal reentry tachycardia (AVNRT)
8. Atrioventricular reentry tachycardia (AVRT)
9. Junctional ectopic tachycardia

Prognosis

AF is associated with increased cardiovascular mortality.[14] Anticoagulation in all patients with a CHA2DS2-VASc score equal to 2 has shown an improved prognosis. Patients not on anticoagulation are at high risk for thromboembolic events. Fifty-five percent of AF patients are not on antithrombotic therapy, which accounts for over 50,000 strokes annually.[28] The prognosis for AF-related stroke is worse compared to non-AF-related cerebrovascular events. Patients with heart failure are at increased risk of developing AF-related complications. Elevated high sensitivity C-reactive protein (hs-CRP) and troponins have been implicated with adverse outcomes in AF patients.[29]

Complications

Complications associated with AF include the following:[30]

1. Thromboembolism including stroke
2. New-onset heart failure or worsening of existing heart failure
3. Acute myocardial infarction
4. Hemodynamic instability leading to cardiogenic shock
5. Sudden death from Wolff-Parkinson-White syndrome
6. Tachycardia-induced cardiomyopathy