Atrial Fibrillation

Intro

• AF is a form of supraventricular tachyarrhythmia, characterised by uncoordinated atrial activity, resulting in an irregularly irregular ventricular response.
• Epidemiology: M:F = 1.5. 0.5% incidence at 40-50yo; 5-15% incidence at 80yo.

Risk factors, disease associations and potentially reversible precipitants for atrial fibrillation
Risk factors and disease associations	Potentially reversible precipitants
Obesity Hypertension Type 2 diabetes/impaired glucose tolerance Smoking Obstructive sleep apnoea Coronary artery disease Valvular heart disease Heart failure Chronic kidney disease	Hyperthyroidism Alcohol excess Electrolyte abnormalities Sepsis Anaemia Medications

Classification

• Acute / new onset: first detectable episode of AF, whether symptomatic or not
• Paroxysmal: recurrent self-limiting episodes that terminates within 7 days (usually in the first 48 hours)
• Persistent: episodes that persist for longer than 7 days, or require cardioversion
• Long-standing persistent: where episodes persist for > 1 year and aim is still rhythm control
• Permanent: refractory to cardioversion or where SR cannot be maintained; permanent AF is labelled where the rhythm is the final accepted rhythm (by both patient and doctor)

Presentation

• Many patients present symptomatically: palpitations, dizziness, SOB. Some present as TIA/stroke.
• Some patients are asymptomatic

Investigations

• Bloods: FBC/UEC/CMP/LFT/TSH. Also fasting lipids and HbA1c for complete cardiovascular screen.
• ECG; consider Holter if paroxysmal AF is suspected and not captured on the ECG
• CXR
• TTE: assess for underlying structural or valvular heart disease
• Stress testing: if coronary artery disease is suspected
• Sleep study if OSA is suspected

ECG

• Irregularly irregular rhythm
• No P waves
• Absence of an isoelectric baseline
• Variable ventricular rate
• QRS complexes usually < 120ms, unless pre-existing bundle branch block, accessory pathway, or rate-related aberrant conduction
• Fibrillatory waves may be present and can be either fine (amplitude < 0.5mm) or coarse (amplitude > 0.5mm)
• Fibrillatory waves may mimic P waves leading to misdiagnosis

Management

Treat any underlying cause – anaemia, thyrotoxicosis etc.

The key features of management are:

1. Rate vs rhythm control
2. Anticoagulation

All patients with a new diagnosis of AF (whatever the type) should be referred to a cardiologist.

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Acute Management

Aims of treatment:

1. Slow ventricular response rate
2. Treat any associated conditions e.g. cardiac failure, myocardial ischaemia, severe hypertension, PE etc.
3. Determine whether cardioversion is necessary/appropriate

	Compromised	Not Compromised
Method	Urgent synchoronised DC cardioversion	Generally chemical cardioversion with IV amiodarone, sotalol or flecainide
Only consider if:	AF of recent onset (<48 hours) Pts condition is rapidly deteriorating AF is likely to be the precipitating cause of the pt’s instability (often, CCF etc. are the CAUSE of AF, rather than AF being the cause)	AF of recent onset (<48 hours) NO significant underlying cause which is going to hinder success e.g. pulmonary emboli, cardiac failure

Control of ventricular response rate

• In urgent situations, can use any of the drugs listed below
• IV route is rarely necessary – oral therapy (digoxin) usually suffices

Drug	Dosage	Route	Frequency
Digoxin
Loading	0.5-1mg	Orally	Immediately
First 24 hours	0.25-0.5mg (max 1.5-2mg in 24 hrs)	Orally	Every 4-6 hours
Maintenance	62.5-500μg	Orally	Daily
Verapamil	1mg/min (up to 15mg)	IV	Continuous infusion, with BP monitoring
Metoprolol	2.5mg – 5mg	IV	Over 1 minute up to three doses
Diltiazem	0.25mg/kg	IV	Over 2 mins
Amiodarone (with accessory pathway – WPW)
Loading Dose	5mg/kg	IV via central line	Infusion over 20 min to 2 hours
Then	10-15mg/kg	IV via central line	Infusion over 24 hours

Electrical Cardioversion

1. AF Duration < 48 Hours:
   • Patients can be cardioverted without prior anticoagulation due to a very low risk of thromboembolic stroke in the following month.
   • Procedure: Perform synchronized direct current (DC) cardioversion with the QRS complex, starting with a 100J DC shock following induction with propofol.
2. AF Duration > 48 Hours:
   • Cardioversion should be preceded by:
     • Transesophageal echocardiography (TOE) with 95% sensitivity for detecting atrial thrombus.
     • Alternatively, 3-4 weeks of adequate anticoagulation before elective cardioversion.
   • Patients should be anticoagulated during the cardioversion procedure and continue anticoagulation for at least the following month.

Alternative Approach:

• Asymptomatic Patients with Low Stroke Risk:
  • Consider a “watch and wait” approach to see if the acute AF episode resolves spontaneously, as most acute episodes self-resolve within 24 hours.
• High Stroke Risk Patients:
  • Initiate oral anticoagulation immediately, as these patients are likely to require lifelong anticoagulation regardless of AF episode resolution.

Chemical Cardioversion

Drug	Administration
Sotalol	80mg orally, immediately followed by 80-160mg orally q12h OR 0.5-1.5mg/kg IV, over 10-20 minutes
Flecainide	50-100mg orally, 2-3 times daily (in pts with N LV function) OR 2mg/kg IV over 30 min
Amiodarone	400mg orally, 3 times daily, aiming eventually to ↓ to about 200mg per day OR 5mg/kg IV, via a central line over 20 min to 2 hours, then 10-15mg/kg over 24 hours

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Longer Term Management

Aims

1. Maintain Sinus Rhythm (SR):
   • Strive to keep the patient in sinus rhythm as much as possible, provided this can be achieved without significant inconvenience or risk of side effects from antiarrhythmic medications or procedures.
2. Management during Atrial Fibrillation (AF):
   • Control ventricular response rate effectively.
   • Ensure appropriate anticoagulation to prevent thromboembolic events.
3. Consideration of Invasive Procedures:
   • If ventricular rate remains poorly controlled despite antiarrhythmic therapy, more invasive options such as His bundle ablation with pacemaker implantation or surgical interventions can be considered.
4. Rhythm Control vs. Rate Control:
   • Evaluate and decide between rhythm control and rate control strategies based on individual patient factors and clinical presentation.

Rhythm vs Rate Control

• No mortality differences between rate or rhythm control.
• Because AF-related symptoms can be quite significant, cardiologists and patients often pursue rhythm control together in the first instance.

• Rhythm control
  • is the preferred option in patients who are more symptomatic and do not have significant underlying structural heart disease. 
  • It becomes harder to maintain SR if there is significant underlying structural disease, or if the AF is longstanding. 
  • Because AF is often poorly tolerated by heart failure patients in terms of symptom burden and risk of decompensation, one must consider rhythm control early in the treatment of a patient with signs of clinical heart failure and AF.
  • Rhythm control involves the use of cardioversion (DCCV or chemical) and then medications to maintain the rhythm in SR.
• Rate control
  • is preferred in asymptomatic individuals, those with significant underlying structural heart disease, or those with longstanding AF. 
  • Rate control uses AV node blocking agents to slow the ventricular rate

Cardioversion

If onset of AF was > 48 hours, or if duration unknown, and patient haemodynamically stable:

• Rate control with medication.
• Oral anticoagulant for at least 3 weeks. Alternatively, do TOE, and if TOE shows left atrial thrombus, then for anticoagulation 3 weeks. If no thrombus, then heparin cover is all that’s required.
• DCCV or chemical cardioversion (after 3 weeks of anticoagulation, or heparin cover if TOE shows no thrombus).
• If successful cardioversion, determine stroke risk. If low, require anticoagulants for 4 weeks post-cardioversion. If high, for life-long anticoagulation (even if SR is maintained).

	Electrical	Pharmacological
Indications	Pts with episodes of relatively recent onset (days to months) esp. with a self-limiting/treatable underlying condition (e.g. recent surgery, AMI) and/or no previous episodes of AF Pts who have previously had successful cardioversions followed by acceptably long periods of SR (≥6 months)	If maintenance antiarrhythmic therapy is being initiated e.g. pt has experienced frequent recurrences of AF in absence of such therapy
Method	Synchronised DC cardioversion Precede by anticoagulation (warfarin for 3-4 weeks), or TOE	Sotalol Amiodarone Flecainide

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Maintenance of Sinus Rhythm

• Without antiarrhythmic treatment, high recurrence rate of AF following cardioversion (approximately 65% at one year)
• Any of drugs used for chemical cardioversion can be used for maintenance – most have similar efficacy
• Flecainide has the highest success rate, but must not be used if there’s underlying structural heart disease. 
• In selected patients, flecainide + rate control agent makes a good ‘pill in the pocket’ approach for oral cardioversion for paroxysmal AF.
• Failure of one antiarrhythmic to maintain SR is weak predictor of failure of other agents – ∴ can try other drugs in refractory cases
• All antiarrhythmics can→QT prolongation ∴ check ECG a few days after starting or ↑ing dose

Drug	Administration	Side Effects
Amidoarone Multiple pharmacological actions, including class III activity	Needs loading dose – start in hospital Maintenance – 100-200mg daily Eliminated very slowly Can be used safely in heart failure(First line of choice for patients with heart failure) Avoid in younger patients Monitor TFTs every 6 months	Sleep disturbance Photosensitivity Corneal deposits Pulmonary fibrosis Thyrotoxicosis hepatic dysfunction ∴ need baseline and regular follow-up TFT’s, LFT’s
Sotalol Class III and β-blocker activity	Good first choice for younger patients (<65yrs, with preserved Renal Fn Maintenance – 40-160mg twice daily Renally excreted	SE’s associated with β-blockers Highest rate of Prolongs QT→torsades ↓dose in pts with renal impairment
Flecainide Class Ic activity	Good first choice, In compbinaiton of rate control drug, in patients without structural heart disease Use in conjunction with AV node inhibiting drug (β-blocker or Ca ch blocker)	Ventricular proarrhythmia Precipitation of heart failure Dizziness Visual disturbances Avoid in pts with IHD or LV impairment

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Control of Ventricular Rate

Choices:

• Calcium channel blockers – verapamil or diltiazem
• β-blockers – other than sotalol. Combination with Calcium channel blockers can precipitate cardiac failure/excessive bradycardia.
• Digoxin – provides inadequate control with exertion (∴need additional/alternative therapy for longer-term rate control), and does NOT revert to SR. NO negative inotropic effects, ∴ useful in cardiac failure due to LV dysfunction.
• All drugs used for this purpose can→excessive bracycardia in SR, through inhibition of SA and/or AV nodes

• Australian Recommendations
  • Digoxin 62.5μg orally, daily (according to age, plasma creatinine, and plasma digoxin level – steady state achhieved in ~5days). AND/OR
  • Diltiazem controlled-release 180-360mg OR verapamil SR 160-480mg orally, daily OR
  • Atenolol 25-200mg orally, daily OR metoprolol 25-100mg orally, twice daily

Catheter Ablation (Pulmonary Vein Isolation)

• In symptomatic AF that’s failed medical therapy and where rhythm control is still pursued, catheter ablation can be trialled. Many patients with AF has a focus on the pulmonary vein which can act as a trigger for AF.
• Risks include stroke, oesophageal fistulas, and cardiac tamponade. 
• There’s a chance that ablation will fail: ie ablated tissue can recover conduction, requiring repeat ablation. Also, other risk factors (eg atrial dilatation) can still cause AF.

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Anticoagulation

Considerations for Choosing Anticoagulation

• Patient-specific factors: Age, renal function, bleeding risk, comorbid conditions, patient preferences, and potential drug interactions.
• Risk Assessment: Use tools like CHA2DS2-VASc score for stroke risk and HAS-BLED score for bleeding risk.
• Renal Function: Regular monitoring and dose adjustments based on renal function are critical for NOACs.
• Reversal Agents: Availability of reversal agents for NOACs and warfarin, and the management plan for bleeding complications.

Special Populations

• Elderly: Careful dose adjustment and monitoring due to increased bleeding risk.
• Renal Impairment: Adjust dosing according to renal function.
• Patients with Valvular AF: Warfarin is preferred over NOACs.

Stroke and Bleeding

AF increases the risk of thromboembolic stroke.

• If patient has ‘valvular AF’ (prosthetic valves or rheumatic valve disease, especially mitral stenosis), then anticoagulation with warfarin is required (aim INR 2-3).
• If patient has non-valvular AF, determine stroke risk (CHADS2 or CHA2DS2VASc score): 
• CHADS2/CHADVASC2:
  • If CHADS2 is 2 or more, need anticoagulation.
  • If CHADS2 is 1, consider anticoagulation.
  • If CHADS2 is 0, no anticoagulation is required.

Use of aspirin for CHADS2 of 0 or 1 is controversial – the original study showed aspirin provided a non significant reduction in stroke risk. 

• The risk of bleeding is determined by the HAS-BLED score. 
• A HAS-BLED of 3 or more is determined high risk of bleeding, but this does not exclude a patient from taking anticoagulants (balance risk vs benefit)

CHA2DS2-VASc	Score	HAS-BLED	Score
Congestive heart failure	1	Hypertension (systolic blood pressure >160 mm Hg)	1
Hypertension	1	Abnormal renal and liver function (1 point each)	1 or 2
Age ≥75 y	2	Stroke	1
Diabetes mellitus	1	Bleeding tendency/predisposition*	1
Stroke/TIA/TE	2	Labile INRs (if on warfarin)*	1
Vascular disease (prior MI, PAD, or aortic plaque)	1	Elderly (eg, age >65 y)	1
Aged 65 to 74 y	1	Drugs or alcohol (1 point each)*	1 or 2
Sex category (ie, female sex)	1
Maximum score	9	Maximum score	0

Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500-1510.

Vitamin K Antagonists

1. Warfarin (Coumadin, Marevan)
   • • see warfarin link
   • Indications: Stroke prevention in AF, especially in patients with valvular AF or those with contraindications to NOACs.
   • Dosage: Varies; titrated to maintain an INR (International Normalized Ratio) of 2.0-3.0.
   • Monitoring: Requires regular INR monitoring and dose adjustments based on INR results.
   • Dietary Considerations: Patients should maintain consistent vitamin K intake and be aware of potential drug interactions.

Antiplatelet Therapy

1. Aspirin
   • Indications: Generally not recommended for stroke prevention in AF due to lower efficacy compared to anticoagulants.
   • Dosage: 75-100 mg daily.
   • Use: May be considered in patients who refuse or have contraindications to anticoagulation.

Switching Between Anticoagulants

• Warfarin to NOAC: Stop warfarin and start NOAC once INR is below 2.0.
• NOAC to Warfarin: Start warfarin and continue NOAC until INR is therapeutic.
• NOAC to NOAC: Stop the first NOAC and start the second at the time the next dose of the first would have been due.

• Novel Oral Anticoagulants (NOACs) – see NOACs link 

NOACs are recommended for:

• Stroke prevention in patients with non-valvular atrial fibrillation (NVAF) and one or more risk factors, such as:
  • Previous stroke, transient ischemic attack (TIA), or systemic embolism.
  • Age ≥ 75 years.
  • Hypertension.
  • Diabetes mellitus.
  • Heart failure (moderate to severe).

Available NOACs in Australia

1. Dabigatran (Pradaxa)
   • Dosage: Typically 150 mg twice daily. Dose adjustment to 110 mg twice daily for patients aged ≥ 80 years or with increased bleeding risk.
   • Renal function: Contraindicated if creatinine clearance (CrCl) < 30 mL/min.
2. Rivaroxaban (Xarelto)
   • Dosage: 20 mg once daily with food. Reduce to 15 mg once daily for patients with CrCl 30-49 mL/min.
   • Renal function: Contraindicated if CrCl < 15 mL/min.
3. Apixaban (Eliquis)
   • Dosage: 5 mg twice daily. Reduce to 2.5 mg twice daily for patients with at least two of the following: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 133 μmol/L.
   • Renal function: Contraindicated if CrCl < 25 mL/min.
4. Edoxaban (Lixiana)
   • Dosage: 60 mg once daily. Reduce to 30 mg once daily for patients with CrCl 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of certain P-glycoprotein inhibitors.
   • Renal function: Contraindicated if CrCl < 15 mL/min.

Key Considerations

• Renal Function Monitoring:
  • Regular monitoring of renal function is crucial, especially in elderly patients and those with pre-existing renal impairment.
  • Adjust doses based on renal function as per individual NOAC recommendations.
• Bleeding Risk:
  • Assess bleeding risk using tools like HAS-BLED score.
  • Counsel patients on recognizing signs of bleeding and the importance of adherence to dosing schedules.
• Drug Interactions:
  • Be aware of potential drug interactions, particularly with medications that influence NOAC metabolism (e.g., certain antifungals, antiretrovirals, anticonvulsants).
• Reversal Agents:
  • Have a plan for managing major bleeding or urgent surgery, including the availability of reversal agents:
    • Dabigatran: Idarucizumab (Praxbind).
    • Rivaroxaban and Apixaban: Andexanet alfa (not widely available in Australia) or consider prothrombin complex concentrates.

Transitioning from Warfarin to NOACs

• When switching from warfarin to a NOAC, stop warfarin and start the NOAC once the INR is below 2.0 (specific cut-off may vary slightly depending on the NOAC).

Patient Education and Follow-Up

• Education:
  • Inform patients about the importance of adherence, potential side effects, and when to seek medical attention.
  • Provide clear instructions on dosing and what to do if a dose is missed.
• Follow-Up:
  • Regular follow-up visits to monitor adherence, renal function, and any potential side effects or complications.

Special Populations

• Elderly Patients:
  • Adjust dosing for age-related renal decline and increased bleeding risk.
• Patients with Extreme Body Weight:
  • Dose adjustments or careful monitoring may be necessary.

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PILL IN THE POCKET APPROACH 

• Paroxysmal AF with no structural disease then when they get the palpitations – single dose of flecanide 50-100mg and a beta blocker.
• If they are still symptomatic after rate controll organise a holter monitor – if mostly at over 100/min then risk of tachycardia mediated cardiomyopathy.

non-pharmacological

1. Monitoring and Follow-Up

Regular Check-Ups:

• Schedule regular follow-up appointments to monitor heart rate, rhythm, and the effectiveness of treatment.
• Periodic reassessment of stroke risk and bleeding risk if on anticoagulation therapy.

Patient Education:

• Educate the patient about recognizing symptoms of AF and potential complications like stroke or heart failure.
• Provide information on when to seek immediate medical attention (e.g., if they experience severe chest pain, shortness of breath, or signs of stroke).

2. Physical Activity

• Encourage regular, moderate-intensity aerobic exercise, such as walking, swimming, or cycling.
• Aim for at least 150 minutes of moderate-intensity exercise per week, as per general physical activity guidelines.
• Advise against excessive or high-intensity exercise without medical clearance, as it may exacerbate AF in some individuals.

3. Diet and Nutrition

• Promote a heart-healthy diet, such as the Mediterranean diet, which includes:
  • Plenty of fruits, vegetables, whole grains, and legumes.
  • Healthy fats, primarily from olive oil, nuts, and fish.
  • Reduced intake of saturated fats, trans fats, and processed foods.
• Encourage maintaining a healthy weight to reduce cardiovascular risk.

4. Weight Management

• Advise weight loss for overweight or obese patients, as obesity is a risk factor for AF.
• Provide or refer to weight management programs that include dietary advice and physical activity.

5. Alcohol Consumption

• Recommend limiting alcohol intake, as excessive consumption can trigger or worsen AF.
• Advise patients to follow Australian guidelines, which suggest no more than 10 standard drinks per week and no more than 4 standard drinks on any one day.

6. Caffeine and Stimulants

• Discuss the effects of caffeine on AF. Moderate caffeine consumption (e.g., up to 400 mg per day) is generally considered safe, but individual tolerance varies.
• Advise avoiding excessive caffeine intake and energy drinks.

7. Smoking Cessation

• Strongly encourage patients to quit smoking, as smoking increases the risk of cardiovascular disease and AF.
• Provide resources or referrals for smoking cessation programs, including counseling and pharmacotherapy options.

8. Managing Comorbid Conditions

• Emphasize the importance of controlling hypertension, diabetes, and hyperlipidemia through lifestyle changes and medication adherence.
• Regularly monitor and manage these conditions to reduce AF-related complications.

9. Stress Reduction

• Encourage techniques for stress management, such as mindfulness, yoga, meditation, or other relaxation methods.
• Discuss the impact of stress and anxiety on heart health and AF symptoms.

10. Sleep and Rest

• Highlight the importance of adequate and quality sleep, as poor sleep and sleep apnea can exacerbate AF.
• Screen for sleep apnea and refer for sleep studies if indicated. Advise on good sleep hygiene practices.

11. Avoiding Triggers