- ACC - American College of Cardiology
- ACCP - American College of Chest Physicians
- A fib - Atrial fibrillation
- AHA - American Heart Association
- bpm - beats per minute
- CAD - Coronary Artery Disease
- DVT - Deep vein thrombosis
- ECHO - short for Echocardiography. ECHO is an ultrasound of the heart that enables visualization of the anatomy and function of the heart.
- EF - Ejection fraction
- INR - International normalized ratio
- PCI - Percutaneous coronary intervention (heart cath and associated procedures - stents, angioplasty, etc.)
- PE - Pulmonary embolism
- TEE - TransEsophageal ECHO. Heart ECHO performed through the esophagus.
- TIA - Transient ischemic attack
- AV node (AtrioVentricular node) - bundle of specialized cells that conducts depolarization from the atria into the ventricles (see Illustration of cardiac conduction)
- Depolarization - wave of positive charge initiated by the SA node that spreads through the atria and ventricles causing muscle contraction and a heartbeat
- Nonvalvular A fib - A fib that occurs in the absence of mitral valve disease or a prosthetic heart valve
- Paroxysmal A fib - A fib that comes on suddenly, continues for less than a week, and then reverts back to sinus rhythm spontaneously (AHA definition)
- Permanent A fib - A fib that lasts longer than 7 days and has failed to convert with cardioversion or cardioversion has not been attempted (AHA definition)
- Persistent A fib - A fib episodes that last longer than 7 days (AHA definition)
- Rapid ventricular rate - when the AV node transfers depolarizations from the atria to the ventricles at a rapid rate (> 100 bpm)
- SA node (SinoAtrial Node) - bundle of specialized cells that initiates depolarization of the atria. The SA node is the built-in pacemaker of the heart (see Illustration of cardiac conduction).
- Sinus rhythm - the normal heart rhythm
- Atrial Fibrillation (A fib) is the most common heart arrhythmia
- It has an estimated prevalence in the general population of of 0.4 - 1.0%
- The prevalence increases with age. An estimated 8% of people older than 80 years have A fib.
- The median age of patients with A fib is 75 years 
- RISK FACTORS
- Age - most important
- Male sex
- Heart Diseases
- Coronary artery disease
- Acute heart attack
- Congestive heart failure
- Left ventricular hypertrophy
- Valvular heart disease (most often mitral valve)
- Wolff-Parkinson-White syndrome
- Heavy alcohol intake
- Obstructive Sleep Apnea
- Surgery (postoperative A fib)
- Pulmonary embolism 
- Atrial Fibrillation is a heart arrhythmia
- It occurs when multiple foci of electrical activity in the atria initiate depolarization at the same time. The multiple depolarizations disrupt the regular signal from the SA node, the heart's regular pacemaker.
- This causes uncoordinated contractions of the atria
- The AV node transmits depolarizations from the atria to the ventricles at an irregular rate. The rate can range from very slow ( < 50 bpm) to very fast (> 100 bpm, also called "rapid ventricular rate")
- A rapid ventricular rate can sometimes cause heart failure because the rapid contractions do not produce good cardiac output
- Atrial fibrillation increases the risk of stroke
- Abnormal blood flow in the atria can cause blood to "pool" (lose flow) in certain areas of the atria. Pooled blood has a tendency to form a clot.
- A common area for blood to pool is in the left atrial appendage (see atrial appendage). The left atrial appendage is believed to be the source of > 90% of clots in nonvalvular A fib. 
- Clots can break free, travel to the brain, and cause a stroke
- A fib has a wide range of symptoms. Some people have no symptoms and are unaware that they have it, while others have overt heart failure. Some people are not aware they have A fib until they have a stroke.
- A fib can start suddenly and then revert back to sinus rhythm on its own. This is called paroxysmal or "sudden" A fib. A fib can also be persistent.
- Symptoms of A fib include:
- Irregular heartbeat
- Heart failure in susceptible patients
- Chest pain in susceptible patients
- PHYSICAL EXAM
- Auscultation of the heart will typically reveal a an irregular heartbeat consistent with A fib
- The pulse will also be irregular
- Signs of heart failure (pulmonary and lower extremity edema) may be present in susceptible individuals
- A fib can also occur after a pulmonary embolism
- DIAGNOSTIC STUDIES
- The AHA recommends the following workup for A fib:
- Transthoracic ECHO
- Labs for thyroid, kidney, and liver function
- In select cases, the following may be indicated:
- Holter monitor
- Transesophageal ECHO - if cardioversion is being considered
- Exercise testing - to evaluate adequacy of rate control
- Electrophysiological study - in patients who are considering ablation 
- Electrocardiogram (ECG or EKG)
- If A fib is suspected, it should be confirmed with an EKG
- A fib has a distinct pattern on EKG. There are no distinct P-waves, only a wavy line, and ventricular depolarizations (QRS complexes) occur at irregular intervals
- Holter monitor or Event monitor
- If A fib comes and goes (paroxysmal), then it may not be captured on a single EKG
- A holter monitor is a device worn for 24 hours that records a continuous EKG reading
- A holter monitor may be needed to diagnose A fib that comes and goes (paroxysmal)
- An event monitor is like a Holter monitor, but it only starts recording when the patient senses symptoms and pushes a button
- Heart echocardiogram (ECHO)
- A heart ECHO should be performed on all patients with newly-diagnosed A fib
- An ECHO can detect structural and functional abnormalities including heart valve diseases which are risk factors for A fib
- An ECHO can be performed in two ways - transthoracic and transesophageal
- A transthoracic ECHO is performed with a probe placed on the chest wall. A transesophageal echocardiogram (TEE) is performed with a probe that is run down the esophagus.
- The transesophageal ECHO (TEE) produces better images and allows better visualization of the left atrium and left atrial appendage where blood clots may be seen
- TEE may be preferred in patients who have suffered a stroke or in those who are to undergo cardioversion of their A fib. If TEE detects a clot then cardioversion should be delayed until anticoagulation has been achieved (see cardioversion recs below). 
- All patients with A fib should be anticoagulated according to their individual risk factors (See stroke prevention below).
- The issue then becomes whether to pursue a rate control or rhythm control strategy. In studies, neither approach has been shown to be superior to the other (see AFFIRM study below)
- Catheter ablation is a relatively new way to pursue a rhythm control strategy, but it has not been compared to other therapies for significant outcomes like stroke and mortality (see RAAFT-2 study, and Ablation study).
- Rate control in A fib involves slowing or preventing the rapid ventricular rate that the arrhythmia may produce
- Several classes of medications can be used to do this
- The medications work by blocking the AV node and slowing conduction of depolarization from the atria to the ventricles (see cardiac conduction illustration)
- Medications used for rate control in A fib include:
- AHA rate control recommendations
- The AHA recommends that beta blockers or nondihydropyridine calcium channel blockers be used first-line to control heart rate in A fib
- A heart rate control (resting heart rate < 80 bpm) strategy is reasonable for symptomatic management of A fib
- A lenient rate control strategy (resting heart rate < 110 bpm) may be reasonable with asymptomatic patients where left ventricular systolic function is preserved (see RACE II study below)
- Nondihydropyridine calcium channel antagonists should not be used in decompensated heart failure
- Oral amiodarone may be useful for ventricular rate control when other measures are unsuccessful or contraindicated
- AV nodal ablation with permanent ventricular pacing is reasonable when pharmacological management is inadequate and rhythm control is not achievable
- When pre-excitation syndromes are present with A fib (see Wolff-Parkinson-White), digoxin, nondihydropyridine calcium channel antagonists, and amiodarone should not be administered 
- Rhythm control in A fib involves converting the A fib arrhythmia back to a sinus rhythm and preventing its recurrence
- There are three methods for achieving rhythm control: medications (pharmacological cardioversion), electrical cardioversion (heart shock), and catheter ablation
- The AHA guidelines for 2014 give a list of reasons that a rhythm control strategy may be preferred over a rate control strategy
- Factors that may favor a rhythm control strategy:
- Symptomatic A fib
- Difficulty in achieving adequate rate control
- Younger patient age
- Tachycardia-mediated cardiomyopathy
- First episode of A fib
- A fib that is precipitated by an acute illness
- Patient preference 
- Medications for rhythm control
- A number of antiarrhythmic medications can be used to convert A fib back into a sinus rhythm
- These medications are most effective when initiated in the first 7 days after the onset of A fib
- The medications can have serious side effects and are typically administered by cardiologists in a hospital setting. Some of them can also be used in an outpatient setting to maintain sinus rhythm in appropriate patients.
- Antiarrhythmic medications are able to maintain sinus rhythm in about 50% of patients who use them 
- Medications used to convert A fib and maintain sinus rhythm include:
- Amiodarone - convert A fib and maintain sinus rhythm
- Dofetilide- convert A fib and maintain sinus rhythm
- Dronedarone- maintain sinus rhythm
- Flecainide- convert A fib and maintain sinus rhythm
- Ibutilide- convert A fib
- Propafenone- convert A fib and maintain sinus rhythm
- Sotalol- maintain sinus rhythm 
- Electrical Cardioversion
- Electrical cardioversion can be performed to convert A fib back into a sinus rhythm
- During the procedure, patients are sedated and an electrical shock is applied to the heart
- The procedure may be necessary in patients who are unstable and need immediate conversion. It may also be performed as an elective outpatient procedure.
- Catheter ablation
- Catheter ablation is a relatively new procedure where a probe is used to ablate tissue in the left atrium
- The areas surrounding the entrance of the pulmonary veins are typically ablated. These areas are a common source for ectopic atrial foci that have been found to initiate A fib.
- There are two ways the tissue is ablated. One method ablates tissue with radiofrequency energy and the other by freezing the tissue. A study published in 2016 compared the two methods and found them to be equally effective (see PMID 27042964).
- Catheter ablation has a success rate around 70% at one year post-ablation. At 2 years, success (defined as no atrial arrhythmia) has dropped to less than 50% in some trials.
- Repeat ablation is necessary in about 12 - 20% of patients [4,9,11]
- Catheter ablation is currently only recommended for symptomatic A fib. There are no guidelines that recommend its use solely for the purpose of discontinuing anticoagulation.
- Two studies that compared catheter ablation to antiarrhythmic medications are discussed below - see RAAFT-2 study and ThermoCool AF trial. These studies primarily looked at the effects of ablation on A fib recurrence.
- In 2018, a study was published that compared ablation to medical therapy in patients with NYHA class II-IV heart failure. The study outcomes were death from any cause or hospitalization for worsening heart failure. That study is detailed below.
- Design: Randomized, controlled trial (N=363, length - 37.8 months) in patients with NYHA II - IV heart failure and A fib
- Baseline characteristics: Median age - 64 years | NYHA class I - 11%, II - 59%, III - 28%, IV - 2% | A fib type: Paroxysmal - 33%, Persistent - 67% | Median EF - 32%
- Group 1 (179 patients): Ablation followed by warfarin for 6 months. After 6 months, treatment was at provider's discretion.
- Group 2 (184 patients): Medical therapy at provider's discretion
- All patients were required to have an implantable cardioverter–defibrillator (ICD) device or a cardiac resynchronization therapy defibrillator (CRT-D)
- Primary outcome: Composite of death from any cause or hospitalization for worsening heart failure
- Primary outcome: Group 1 - 28.5%, Group 2 - 44.6% (HR 0.62, 95%CI [0.43 - 0.87], p=0.007)
- Overall mortality: Group 1 - 13.4%, Group 2 - 25% (HR 0.53, 95%CI [0.32 - 0.86], p=0.01)
- CHF hospitalization: Group 1 - 20.7%, Group 2 - 35.9% (HR 0.56, 95%CI [0.37 - 0.83], p=0.004)
- In Group 1, 15.6% of patients did not receive ablation. In Group 2, 9.8% of patients received ablation.
- In Group 1, 25% of patients had a repeat ablation
- Findings: Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy.
- AHA catheter ablation recommendations
- The 2014 AHA recommendations state that catheter ablation may be useful for symptomatic A fib that is refractory or intolerant to to at least one class I or III antiarrhythmic medication. Catheter ablation should not be performed for the sole intent of obviating the need for anticoagulation. 
- StraightHealthcare analysis
- The results of the CASTLE-AF trial are impressive, particularly for the mortality benefit
- A larger trial in a more diverse population of A fib patients is needed
Atrial fibrillation after cardiac surgery
- Atrial fibrillation is one of the most common complications after cardiac surgery occurring in 20 - 50% of patients. Affected patients may be treated with either a rhythm or rate control strategy.
- In 2016, the CTSN study was published that compared the two strategies in patients with postoperative A fib after CABG and/or heart valve surgery.
- The CTSN study randomized 523 patients with no prior history of A fib who experienced A fib after cardiac surgery
- Main inclusion criteria: postoperative A fib that persisted for more than 60 minutes or recurrent episodes of A fib during the index hospitalization (≤7 days after surgery); hemodynamically stable; underwent elective cardiac surgery to treat coronary artery disease or heart valve disease
- Main exclusion criteria: prior history of A fib
- Baseline characteristics: average age 69 years; heart valve disease - 55%; index procedure, CABG - 40%, valve repair - 16%, valve replacement - 24%, CABG + valve repair - 3.3% CABG + valve replacement - 16%; taking beta blocker - 59%; taking calcium channel blocker - 21%
- Patients were randomized to 1 of 2 groups:
- Group 1 (262 patients) - Rate control with a target resting heart rate < 100 bpm
- Group 2 (261 patients) - Rhythm control with amiodarone. If A fib persisted for 24 - 48 hours after randomization, direct current cardioversion was recommended.
- The average time to the onset of postoperative A fib was 2.4 days
- If patients remained in A fib or had recurrent A fib 48 hours after randomization, anticoagulation with warfarin (INR 2 - 3) was recommended, and bridging with LMWH was allowed. Anticoagulation was recommended to be continued for 60 days unless complications occurred.
- PRIMARY OUTCOME: Total number of days in the hospital (including emergency department visits) within 60 days after randomization
- After 60 days, the following was seen:
- Primary outcome (median # of days): Group 1 - 5.1 days, Group 2 - 5.0 days (p=0.76)
- Hospital readmission (any cause) Group 1 - 18.5 events/100 patient-months, Group 2 - 18.5 events/100 patient-months (p=0.99)
- Stable heart rhythm (no A fib) at discharge: Group 1 - 89.9%, Group 2 - 93.5% (p=0.14)
- Met criteria for anticoagulation: Group 1 - 46.2%, Group 2 - 31.8%
- Received direct-current cardioversion: Group 1 - 9.2%, Group 2 - 13.8%
- In Group 1, 26.7% of patients received amiodarone or direct-current cardioversion
- In Group 2, 23.8% of patients did not complete the full course of amiodarone, typically due to side effects. These patients received beta blockers, calcium channel blockers, or both.
- There was no significant difference in serious or nonserious adverse events between the groups
- Professional guidelines:
- The AHA recommends rate control with a beta blocker as first-line treatment in patients who develop A fib after postoperative cardiac or thoracic surgery
- A nondihydropyridine calcium channel blocker is recommended as an alternative if a beta blocker is inadequate 
- StraightHealthcare analysis:
- Postoperative A fib is a common complication of cardiac surgery. It is also a very transient condition with 90% of patients returning to a normal rhythm within days.
- In the CTSN study, there was no significant difference between a rate or rhythm control strategy in patients with postoperative A fib. Rate control with appropriate anticoagulation if necessary is likely the safest and most practical approach to postoperative A fib in hemodynamically stable patients.
- STROKE PREVENTION
- CHADS₂ SCORE
- One of the challenges in A fib is deciding who to anticoagulate
- The risk of stroke must be weighed against the risk of bleeding with anticoagulation
- A widely accepted stroke risk stratification tool is the CHADS₂ scoring system
- The CHADS₂ scoring system assigns a score to patients with A fib based on stroke risk factors
- For each risk factor present, the patient receives 1 point, except in the case of prior stroke, TIA, or thromboembolism where the patient receives 2 points
- The score can then be used to quantify a person's stroke risk to determine if, and how, they should be anticoagulated
- The tables below detail the CHADS₂ score criteria and the associated risk of stroke
|CHADS₂ risk criteria||Score|
|Prior stroke, TIA, or thromboembolism||2|
|Age ≥ 75||1|
|Annual risk of stroke based on CHADS₂ score|
|CHADS₂ score||Stroke Rate (%/year)|
- CHA₂DS₂-VASc SCORE
- Another tool used to assess stroke risk in atrial fibrillation is the CHA₂DS₂-VASc score
- In 2014, the AHA/ACC recommended using the CHA₂DS₂-VASc score in evaluating stroke risk
- The tables below detail the CHA₂DS₂-VASc score criteria and the associated risk of stroke
|CHA₂DS₂-VASc risk criteria||Score|
|Prior stroke, TIA,
|Age ≥ 75||2|
(CAD or PVD)
|Age 65 - 74||1|
|Annual risk of stroke based on CHA₂DS₂-VASc score|
|CHA₂DS₂-VASc SCORE||Stroke Rate
- AHA/ACC ANTITHROMBOTIC RECOMMENDATIONS
- The 2014 AHA/ACC recommendations for anticoagulation in nonvalvular A fib are based on the CHA₂DS₂-VASc score
|≥ 2||One of the following:
|1||One of the following:
- ACCP ANTITHROMBOTIC RECOMMENDATIONS
- The ACCP recommendations for anticoagulation in nonvalvular A fib are based on the CHADS₂ criteria
|0||None or Aspirin|
(Warfarin INR 2 - 3)
- ANTICOAGULATION BEFORE CARDIOVERSION
- Patients with A fib who are to undergo cardioversion (electrical or pharmacological) typically receive anticoagulation
- The guidelines differ slightly depending on several variables: patient stability, length of A fib, whether transesophageal echo (TEE) is planned
- In 2016, a study was published that compared edoxaban to enoxaparin-warfarin in patients undergoing electrical cardioversion for A fib. The study found that edoxaban was equivalent in both efficacy and safety to enoxaparin-warfarin. [PMID 27590218]
- AHA recommendations for anticoagulation before cardioversion in A fib
- A fib with known duration < 48 hours
- Patients with high stroke risk - IV heparin, LMWH, factor Xa inhibitor, or direct thrombin inhibitor is recommended before or immediately after cardioversion followed by long-term anticoagulation. Long-term anticoagulation should be based on thromboembolic risk.
- Patients with low thromboembolic risk - IV heparin, LMWH, a new oral anticoagulant, or no antithrombotic may be considered for cardioversion
- A fib with duration of ≥ 48 hours or unknown duration
- Stable patients - anticoagulate with warfarin for at least 3 weeks prior to and 4 weeks after cardioversion [Level I recommendation]
- Stable patients - anticoagulation with dabigatran, rivaroxaban, or apixaban is reasonable for ≥ 3 weeks prior to and 4 weeks after cardioversion [Level IIa recommendation]
- Unstable patients - anticoagulate as soon as possible and continue for at least 4 weeks
- TEE planned - for patients with no anticoagulation during the preceding 3 weeks, it is reasonable to perform a TEE prior to cardioversion, and then cardiovert if no LA thrombus is identified, provided anticoagulation is achieved before TEE and maintained after cardioversion for at least 4 weeks 
- Medications used to anticoagulate patients with A fib include the following:
- Direct thrombin inhibitors (dabigatran, Pradaxa®)
- Factor Xa inhibitors (rivaroxaban, Xarelto®, apixaban, Eliquis®)
- Warfarin (Coumadin®)
- Antiplatelet medications used to prevent stroke in patients with A fib include the following:
- ATRIAL APPENDAGE CLOSURE
- The left atrial appendage is an outpocketing in the left atrium (see atrial appendage). In patients with A fib, blood tends to pool in the appendage and clots can form. The left atrial appendage is believed to be the source of > 90% of clots in A fib.
- A device called the Watchman® device has been developed which closes off the appendage so that blood cannot pool in it
- The device is inserted during a procedure that is similar to a heart cath
- The PROTECT AF study compared atrial appendage closure to warfarin therapy in patients with atrial fibrillation
- The PROTECT AF study enrolled 707 adults with nonvalvular A fib
- Main inclusion criteria: paroxysmal, persistent, or permanent nonvalvular AF; CHADS₂ score ≥ 1
- Main exclusion criteria: patent foramen ovale with atrial septal aneurysm and right-to-left shunt
- Baseline characteristics: average age 72 years; CHADS₂ score, 1 ∼ 30%, 2 ∼ 35%, 3 ∼ 20%, 4 ∼ 9%, 5 ∼ 4%; A fib category, paroxysmal - 41%, persistent - 21%, permanent - 36%, unknown - 1%; A fib onset, < 1 year - 18%, ≥ 1 year - 76%, unknown - 5.5%
- Patients were randomized in a 2:1 ratio to 1 of 2 groups:
- Group 1 (463 patients) - Watchman® device insertion + warfarin for 45 days. If device was positioned correctly, then warfarin was stopped and clopidogrel + aspirin was taken up until 6 months post insertion, then aspirin alone indefinitely
- Group 2 (244 patients) - Warfarin with target INR of 2 - 3
- PRIMARY OUTCOME: Composite of stroke, cardiovascular death, or systemic embolism
- PRIMARY SAFETY OUTCOME: Composite of major bleeding, pericardial effusion, or device embolization
- After an average follow-up of 18 months, the following was seen:
- Primary outcome: Group 1 - 3 events/100 patient-years, Group 2 - 4.9 events/100 patient-years (Rate ratio 0.62, 95%CI [0.35 - 1.25])
- Primary safety outcome: Group 1 - 7.4 events/100 patient-years, Group 2 - 4.4 events/100 patient-years (Rate ratio 1.69, 95%CI [1.01 - 3.19])
- All-cause mortality: Group 1 - 3 events/100 patient-years, Group 2 - 4.8 events/100 patient-years (Rate ratio 0.62, 95%CI [0.34 - 1.24])
- In Group 2, the INR was therapeutic (between 2 - 3) 66% of the time
- In Group 1, 86% of implanted patients were able to stop warfarin at 45 days. At 6 months, 92% of implanted patients were able to stop.
- The Watchman® device was successfully implanted in 88% of patients (91% of those where implantation was attempted)
- Risks of the procedure included pericardial effusion (4.8%), procedure-related stroke (1.1%), and device embolization (0.6% of patients) 
- After an average follow-up of 3.8 years, the following was seen:
- Primary outcome: Group 1 - 2.3 events/100 patient-years, Group 2 - 3.8 events/100 patient-years (HR 0.61, 95%CI [0.38 - 0.97], p=0.04)
- Primary safety outcome: Group 1 - 3.6 events/100 patient-years, Group 2 - 3.1 events/100 patient-years (HR 1.21, 95%CI [0.78 - 1.94], p=0.41)
- All-cause mortality: Group 1 - 14.5%, Group 2 - 21.5% (HR 0.66, 95%CI [0.45 - 0.98], p=0.04) 
- After an average follow-up of 5 years, the following was seen:
- Primary outcome: Group 1 - 2.24 events/100 patient-years, Group 2 - 3.66 events/100 patient-years (p=0.04)
- StraightHealthcare analysis:
- In the PROTECT AF studies, the Watchman® device was superior to warfarin in improving outcomes in A fib. It would be interesting to see how the device performs against newer anticoagulants (e.g. Factor Xa inhibitors, direct thrombin inhibitors).
- The Watchman® device may be a good option for some patients. Patients who receive the device must take aspirin indefinitely.
- STOPPING ANTICOAGULATION
- Stopping anticoagulation after cardioversion or ablation
- After A fib cardioversion or catheter ablation, the question arises as to whether a patient can stop their anticoagulation
- Unfortunately, there are no good studies or guidelines to help make this decision
- Further complicating the matter is that A fib is often asymptomatic, so patients may be unaware that they are still having episodes
- The decision to stop anticoagulation after successful cardioversion or catheter ablation is based on individual risk factors and the patient's willingness to accept unknown risks
- In cases where A fib is the result of a known correctable cause (ex. hyperthyroidism), anticoagulation may be stopped after the underlying disease has been corrected
- Stopping anticoagulation before procedures
- Professional guidelines for stopping anticoagulants before procedures in patients with A fib are available at the link below
- ANTICOAGULATION + ANTIPLATELET THERAPY
- In some cases, anticoagulation and antiplatelet therapy are both indicated in the same patient. An example of this would be a patient with atrial fibrillation who has heart stents placed. In this scenario, anticoagulation, aspirin, and a P2Y12 inhibitor are all indicated.
- Recommendations for combining anticoagulation and antiplatelet therapy are reviewed at the link below
- A FIB STUDIES
- The AFFIRM study enrolled 4060 patients with atrial fibrillation
- Main inclusion criteria: age ≥ 65 years; A fib deemed to be recurrent and likely symptomatic; additional risk factors for stroke or death
- Baseline characteristics: average age 70 years; hypertension - 51%; CAD - 26%; history of CHF - 23%; previously failed antiarrhythmic drug - 17.6%
- Patients were randomized to 1 of 2 groups:
- Group 1 (2027 patients) - Rate control only with beta blockers, calcium channel blockers, and/or digoxin. Target rate was ≤ 80 bpm resting and ≤ 110 bpm with six-minute walk test. Continuous anticoagulation with warfarin was mandated.
- Group 2 (2033 patients) - Rhythm control with common antiarrhythmic drugs. Cardioversion as needed. Anticoagulation with warfarin could be stopped if sinus rhythm was maintained for 4 - 12 weeks.
- PRIMARY OUTCOME: Overall mortality
- After an average follow-up of 3.5 years, the following was seen:
- Primary outcome: Group 1 - 25.9%, Group 2 - 26.7% (p=0.08)
- Stroke or brain bleed: Group 1 - 7.4%, Group 2 - 8.9% (p=0.93)
- Any hospitalization: Group 1 - 73%, Group 2 - 80% (p<0.001)
- The following adverse events were more common in Group 2 than Group 1: pulmonary event 7.3% vs 1.7%; GI event 8% vs 2.1%; bradycardia 6% vs 4.2%; prolonged QT interval 1.9% vs 0.3%
- During the course of the study, 248 patients crossed over from the rate control group to the rhythm control group. 86 of these patients crossed back over to rate control by the end of the study.
- During the course of the study, 594 patients crossed over from the rhythm control group to the rate control group. 61 of these patients crossed back over to rhythm control by the end of the study.
- More than 85% of the patients in Group 1 took warfarin throughout the study. In Group 2, about 70% of patients took warfarin throughout the study 
- StraightHealthcare analysis:
- In the AFFIRM study, neither rhythm or rate control was shown to be superior to the other. The rhythm control group had significantly more hospitalizations and adverse events.
- The rhythm control group also had more than double the number of crossovers as the rate control group which speaks to the limited efficacy of antiarrhythmic medications
- The RACE II study enrolled 614 patients with permanent atrial fibrillation
- Main inclusion criteria: permanent A fib for 12 months; age ≤ 80 years; average resting heart rate > 80 bpm; current use of anticoagulation or aspirin
- Baseline characteristics: average age 68 years; median duration of A fib - 18 months; previous cardioversion - 72%; CAD - 18%; valvular heart disease - 20%; CHADS2 score, 0 or 1 - 61%, 2 - 26%, 3 to 6 - 13%; average resting heart rate - 96
- Patients were randomized to 1 of 2 groups:
- Group 1 (311 patients) - Lenient rate control - target resting heart rate of < 110 bpm
- Group 2 (303 patients) - Strict rate control - target resting heart rate of < 80 bpm, target heart rate of < 110 bpm during moderate exercise
- Medications used to control heart rate were beta blockers, calcium channel blockers, and digoxin
- PRIMARY OUTCOME: Composite of death from cardiovascular causes, hospitalization for heart failure, stroke, systemic embolism, major
bleeding, and arrhythmic events including syncope, sustained ventricular tachycardia, cardiac arrest, life-threatening adverse effects of rate-control drugs, and implantation of
a pacemaker or cardioverter–defibrillator
- After a follow-up of 3 years, the following was seen:
- Primary outcome: Group 1 - 12.9%, Group 2 - 14.9% (HR 0.84, 95%CI [0.58 - 1.21])
- Heart failure: Group 1 - 3.8%, Group 2 - 4.1% (HR 0.97, 95%CI [0.48 - 1.96])
- Stroke: Group 1 - 1.6%, Group 2 - 3.9% (HR 0.35, 95%CI [0.13 - 0.92])
- The average resting heart rate in Group 1 at the end of the dose adjustment phase was 93 bpm
- The average resting heart rate in Group 2 at the end of the dose adjustment phase was 76 bpm 
- StraightHealthcare analysis:
- The RACE II study showed that a lenient rate control strategy (resting heart rate < 110 bpm) is just as safe, and possibly better than a strict rate control strategy (resting heart rate of < 80 bpm, heart rate of < 110 bpm during moderate exercise)
- The RAAFT-2 study enrolled 127 patients with treatment-naïve, paroxysmal A fib
- Main inclusion criteria: symptomatic, recurrent, paroxysmal A fib lasting more than 30 seconds (≥ 4 episodes in past 6 months); experienced at least 1 episode that was documented by surface EKG 6 months before randomization; no previous antiarrhythmic drug treatment
- Main exclusion criteria: ejection fraction < 40%; left atrial diameter larger than 5.5 cm; moderate-to-severe left ventricular hypertrophy; valvular heart disease; coronary artery disease; cardiac surgery within the last 6 months
- Baseline characteristics: average age 55 years; average number of A fib episodes in past 6 months ∼ 40; average CHADS2 score - 0.6;
- Patients were randomized to 1 of 2 groups:
- Group 1 (66 patients) - Radiofrequency ablation
- Group 2 (61 patients) - Antiarrhythmic drugs (physician's discretion, 69% flecainide, 25% propafenone)
- After randomization, patients underwent a 90-day blanking period where antiarrhythmic drugs were titrated or ablation was performed. Events in the blanking period did not count towards the outcome measures.
- All patients were given a transtelephonic monitoring system to record symptomatic events in addition to standard biweekly recordings
- PRIMARY OUTCOME: First documented atrial tachyarrhythmia of more than 30 seconds (symptomatic or asymptomatic A fib,
atrial flutter, or atrial tachycardia), detected by either scheduled or unscheduled electrocardiogram, Holter, transtelephonic monitor, or rhythm strip
- After 21 months of follow-up, the following was seen:
- Primary outcome: Group 1 - 54.5%, Group 2 - 72.1% (HR 0.56, 95%CI [0.35 - 0.90], p=0.02)
- First recurrence of symptomatic A fib: Group 1 - 41%, Group 2 - 57% (HR 0.52, 95%CI [0.3 - 0.89], p=0.02)
- In Group 1, 13.6% of patients underwent re-ablation
- In Group 1, 4 patients experienced cardiac tamponade and 1 patient had severe pulmonary vein stenosis 
- StraightHealthcare analysis:
- The RAAFT-2 study showed that radiofrequency ablation for the initial treatment of paroxysmal A fib is more effective in preventing episodes of recurrent atrial arrhythmia than antiarrhythmic medications. It's important to note that more than half of the patients in the radiofrequency group had a recurrence of an atrial arrhythmia at almost 2 years post-ablation.
- Radiofrequency ablation was associated with some serious adverse events (cardiac tamponade and severe pulmonary vein stenosis)
- A study in the JAMA enrolled 167 patients with paroxysmal A fib that had not responded to 1 antiarrhythmic drug
- Main inclusion criteria: at least 3 symptomatic episodes of paroxysmal A fib within the 6 months prior to randomization; A fib that did not respond to at least 1 antiarrhythmic drug
- Main exclusion criteria: A fib of more than 30 days in duration; EF < 40%; amiodarone within previous 6 months; previous heart valve surgery
- Baseline characteristics: average age 56 years; median A fib duration ∼ 5.8 years; average EF - 62%; previous drug failure, propafenone - 50%, sotalol - 35%, flecainide ∼ 28%, amiodarone ∼ 8%
- Patients were randomized in a 2:1 ratio to 1 of 2 groups:
- Group 1 (106 patients) - Radiofrequency catheter ablation
- Group 2 (61 patients) - Antiarrhythmic drug that had not been previously used (amiodarone was not allowed)
- Follow-up was over a 9 month period that started at different times in each group. In the ablation group, follow-up started 3 months after the initial ablation procedure. In the antiarrhythmic drug group, follow-up started 14 days after titration on their new antiarrhythmic drug.
- Patients were given transtelephonic heart monitoring devices and were required to transmit weekly for 8 weeks and monthly thereafter. In addition, they were required to transmit all symptomatic episodes.
- PRIMARY OUTCOME: Freedom from treatment failure. Treatment failure was defined as symptomatic A fib, repeat ablation > 80 days after the first ablation, absence of entrance block confirmed in all pulmonary veins at the end of the ablation procedure, changes in antiarrhythmic drugs after initial titration, or side effect of antiarrhythmic drug requiring discontinuation.
- During the 9 month follow-up period, the following was seen:
- Primary outcome: Group 1 - 66%, Group 2 - 16% (HR 0.30, 95%CI [0.19 - 0.47], p<0.001)
- Freedom from atrial arrhythmia: Group 1 - 63%, Group 2 - 17% (HR 0.29, 95%CI [0.18 - 0.45], p<0.001)
- Additional ablations were performed in 12.6% of the patients in Group 1 within 80 days of the initial procedure
- Major treatment related adverse events occurred in 4.9% of patients in Group 1 and 8.8% of patients in Group 2 
- StraightHealthcare analysis:
- In this small study, ablation was superior to antiarrhythmic medications in preventing A fib recurrence in patients with paroxysmal A fib who had failed a prior antiarrhythmic drug
- The study is limited by the fact that one of the most effective antiarrhythmics used to treat A fib, amiodarone, was not allowed
- MEDICATION STUDIES
- Warfarin vs direct thrombin inhibitors (dabigatran, Pradaxa®)
- Warfarin vs Factor Xa inhibitors (apixaban, Eliquis®, rivaroxaban, Xarelto®, edoxaban, Savaysa®)
- Antiplatelet medications
What is PMID? PI = Manufacturer's Package Insert
- # PMID
1 - 16908781 AHA 2006 A fib GL
2 - 22315257 ACCP GL on thrombosis
3 - 22858728 AHA 2012 update on oral antithrombotics
4 - 22168644 NEJM review of ablation
5 - 22869839 Bleeding study with combined therapy
6 - 21177058 2011 AHA focused update
7 - 12466506 AFFIRM study
8 - 20231232 RACE II study
9 - 20103757 Ablation vs meds
10 - 19683639 PROTECT AF
11 - 24549549 RAAFT-2
12 - 24682348 AHA 2014 A Fib GL
13 - 24682347
14 - 24682348 AHA 2014 A fib GL
15 - 25399274 PROTECT-AF follow-up