Atrial Fibrillation

Question 1

What type of arrhythmia is AF and why?

Answer 1

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is classed as a supraventricular arrhythmia since the problem arises from cardiac tissue above the Bundle of His. It is usually referred to as a supraventricular tachyarrhythmia since patients often present with heart rates above 100 beats per minute (bpm) and frequently above 160bpm. Heart rate may however be normal or low.

Question 2

AF information

Answer 2

As a result of poor blood flow through the left atrium, patients are at risk of thromboembolic strokes. Strokes associated with AF tend to be more severe than other ischaemic strokes.
In addition, the reduction in cardiac output associated with AF and a fast heart rate can result in symptoms of heart failure.

Patients with AF may be asymptomatic and first presentation may be a stroke rather than cardiac symptoms.

AF prevalence also increases with age, as does the risk of stroke. Stroke risk reduction should be considered in all patients with AF although anticoagulation may not be required in the absence of other factors.

Question 3

Describe the normal rhythm of the heart

Answer 3

The normal conduction pathway through the heart starts in the sino-atrial (SA) node in the right atrium. This tissue acts as a pacemaker since it has the fastest rate of spontaneous depolarisation in the myocardium.

From there the wave of depolarisation spreads through the atria eventually reaching the atrio-ventricular (AV) node.

As the wave of depolarisation moves through the AV node and Bundle of His, there is a delay that allows the atria to fully contract.

Once through the AV node the impulse moves down the septum via the right and left bundle branches to the apex then up through the walls of the right and left ventricles via the Purkinje network resulting in co-ordinated contraction of the ventricles.

This cycle is then repeated at a rate dependant on SA node depolarisation.

Question 4

Describe cardiac conduction in AF

Answer 4

Unlike normal sinus rhythm, atrial depolarisation is not controlled by the SA node. Rather, there are multiple areas of the atria that spontaneously depolarise in an uncontrolled and uncoordinated manner.

Mechanically, this results in uncoordinated contraction of the atria at different times producing no single contraction and inefficient emptying.
The AV node will also be subject to frequent impulses originating from different parts of the atria.

The inherent delay in conduction through the AV node and Bundle of His limits the number of impulses passing through and protects the ventricles to some extent.

The number of impulses passing through will be dependant on the inherent refractoriness of the AV node and the magnitude of the impulse reaching it.
**

Question 5

What is the diagnosis of AF

Answer 5

Only an ECG can be used to diagnosis

Patients with suspected AF may present in different ways.

Acutely, they may have symptoms of palpitation, heart racing, fluttering in their chest or chest discomfort / pain. They may present with symptoms of heart failure, usually shortness of breath, as a result of the reduced cardiac output associated with AF.
Chest pain may be a problem, especially in patients with underlying coronary heart disease.

Unfortunately, the first presentation may be a stroke and this occurs in about 1 in 5 cases of first strokes.

Alternatively, AF may be identified in otherwise asymptomatic patients and is detected on routine health checks or, for example, surgical pre-assessment. AF can only be diagnosed after an ECG, although the peripheral pulse may identify possible AF. In patients with infrequent symptoms a 24, 48 or 72 hour ECG may be required. In some patients an implantable loop recorder may be required.

All patients should also have an echocardiogram to identify structural heart problems or left ventricular dysfunction.

Question 6

How is peripheral pulse assessed for AF?

Answer 6

When a patient presents with symptoms suggestive of AF the peripheral pulse should be palpated. Usually the radial pulse is palpated although larger arteries, such as the carotid, can be used if the radial pulse is hard to use.

Although AF is generally associated with a fast heart rate, the pulse rate may be normal, or even slow, especially if the patient is being treated with a rate controlling medication for other conditions.

Usually, the heart rate and the rhythm are assessed. The rhythm will be irregular in AF although this can be difficult to determine if the heart rate is high.

More specifically, the rhythm in AF is described as irregularly irregular since some rhythm disorders produce an irregular rhythm with an underlying pattern. In AF there is no pattern.

Question 7

Discuss what an AF ECG looks like compared to a normal ECG

Answer 7

An ECG measures the magnitude and direction of electrical activity in the myocardium. The standard 12-lead ECG does so from 12 different aspects. Arrhythmias will show up on all leads although some will be clearer than others. A single lead ECG may be the only type available outside the hospital setting but, depending on quality, will be sufficient to show the cardiac rhythm.

In normal sinus rhythm, the ECG consist of a:

• • P-wave due to atrial depolarisation and contraction
• • PR interval as the wave of depolarisation moves through the AV node
• • QRS complex due to ventricular depolarisation and contraction
• • T-wave due to ventricular repolarisation

These should be in a 1:1:1 ratio as per the following image

Electrocardiogram in Atrial Fibrillation
Since there is no co-ordinated contraction of the atria in AF, there are no P-waves on the ECG. There may however be random fibrillatory waves as a result of the random electrical activity in the atria.

Since impulses will pass through the AV node at irregular intervals the gap between QRS complexes (R-R interval) is variable.

Not only will it be variable, but there is no pattern to the variability (irregularly irregular).
The heart rate is not part of the diagnostic criteria. AF can exist with fast, normal or slow heart rates.

A related condition is atrial flutter. In this situation, there may be so-called flutter waves rather than P-waves. These are typically in a ‘saw-tooth’ pattern and the R-R interval may be regular.

Question 8

What are causes of AF?

Answer 8

The exact cause of AF is unknown. However a number of factors are associated with the development of AF. Other factors can be considered triggers e.g. caffeine, alcohol.
AF can also exist in the absence of cardiac and non-cardiac disease and in individuals who are fit and healthy.

Cardiac cause:
* Coronary heart disease
* hypertension
* mitral valve disease
* HF

Non-cardiac causes:
* Thryotoxicosis
* infection
* electrolyte imbalance
* asthma and COPD
* lung cancer
* pulmonary embolism
* diabetes
* drug (including caffeine)

Question 9

What are causes of AF?

Answer 9

The exact cause of AF is unknown. However a number of factors are associated with the development of AF. Other factors can be considered triggers e.g. caffeine, alcohol.
AF can also exist in the absence of cardiac and non-cardiac disease and in individuals who are fit and healthy.

Cardiac cause:
* Coronary heart disease
* hypertension
* mitral valve disease
* HF

Non-cardiac causes:
* Thryotoxicosis
* infection
* electrolyte imbalance
* asthma and COPD
* lung cancer
* pulmonary embolism
* diabetes
* drug (including caffeine)

Question 10

What is non-valvular AF?

Answer 10

The term ‘Non-valvular AF’ (NVAF) refers to patients whose AF is not due to mitral or rheumatic heart disease or who have a mechanical heart valve.

The direct-acting anticoagulants (DOACs – see later) are not indicated in ‘Valvular AF’ (VAF). If these patients require anticoagulation, warfarin should be used.

Question 11

What are the differen classes of AF? What are these?

Answer 11

• First diagnosed
• Paroxysmal
• Persistent
• Long-standing persistent
• Permanent

Question 12

What are treatment option types for AF?

Answer 12

**
1.Stroke and Systemic Embolism Risk Reduction**

Potentially the most devastating impact of AF. Stroke risk assessment should be completed in all patients with AF. A decision to anticoagulate should be based on the balance between stroke risk and bleeding risk.

2.Symptom Control

Symptoms can range from none, to breathlessness due to potentially life threatening heart failure or chest pain due to myocardial infarction

**Rate control: **
* One strategy for managing symptoms.
* Basis of management of permanent AF if heart rate high.

Rhythm control:
* Alternative strategy for managing symptoms.
* Should be considered in paroxysmal or persistent AF.

3.Management of Concomitant Cardiovascular Disease

A number of other cardiovascular diseases may contribute to the development of AF or be a consequence of AF. These will also need to be managed.

Question 13

Where can embolisms form?

Answer 13

Patients with any type of AF are at risk of developing a left atrial thrombus. Specifically, the thrombus forms in the left atrial appendage (LAA). However AF on its own carries a low risk of thrombosis. Other factors that affect blood flow through the atrium, or affect coagulation, are required for anticoagulation to be considered.

Although stroke is generally considered the most serious consequence of embolism of LAA thrombus, this assumes that the thrombus travels up a carotid artery to the brain, when it could also travel down the aorta and lodge in an artery in the systemic circulation.

Question 14

What does warfarin reduce stroke risk by? What does aspirin reduce stroke risk by?

Answer 14

• Warfarin reduces the risk of stroke by 65%
• Aspirin only reduces the risk by 20% (and some of this is offset by bleeding risk)

Question 15

What is HASBLED stand for and what score is considered high risk?

Answer 15

Question 16

What does CHADS2VAS2 stand for?

Answer 16

Question 17

When should AC be offered in strokes?

Answer 17

Question 18

1. What are the doses of DOACs for AF
2. There reduced dose
3. Criteria for dose reduction?

Answer 18

Question 19

What is used in permanent AF for symptom control?

Answer 19

In patients with symptomatic permanent AF there is a strategy of controlling the ventricular response to AF to a rate that minimises symptoms (i.e rate controlling agent used)

Question 20

What drugs may be used for rate control in permanent AF?

Answer 20

. There are three main options for controlling heart rate:
* Beta-blockers (mainly atenolol or bisoprolol)
* Rate limiting calcium channel blockers (verapamil and diltiazem)
* Digoxin

The combination of a beta-blocker or a rate limiting channel blocker with digoxin may be required. The use of Beta-blockers and rate limiting calcium channel blockers in combination should be avoided.

Patients who fail to respond to one or more of these options could be considered for amiodarone. This would only be commenced after specialist advice.

Beta-blockers or rate limiting calcium channel blockers are preferred as they are effective at controlling heart rate, both at rest and on exercise. Digoxin is poor at controlling the increase in heart rate and symptoms associated with exercise.

Question 21

Why are B-blockers and RL CCB preferred over digoxin for rate control?

Answer 21

Beta-blockers or rate limiting calcium channel blockers are preferred as they are effective at controlling heart rate, both at rest and on exercise. Digoxin is poor at controlling the increase in heart rate and symptoms associated with exercise.

Question 22

What b-blockers are typically used for rate-control?

What doses may be used?

What can be a problem with these agents?

Answer 22

• Bisoprolol is frequently used because of once dailt dosing, although this is an off-license indication
• High doses may be needed (bisoprolol up to 20mg OD, atenolol up to 100mg BD - both off-licence)
• Fatigue can be a problem, especially at high doses

Question 23

What are rate-limiting CCB contrainidcated in?

What other condition may inclince use of CCB?

What drug is off-licenced?

Answer 23

• Plain tablrt formulations sometimes used initally then swithced to controlled release once effective dose known
• CI if LVSD / HF
• Useful if patient also HT
• Dilitazem is off-licence

Question 24

What is digoxin concentration guided by

Answer 24

Doses guided by plasms concentration measurement (1-2mcg/L)

Sample must not be taken within 6 hours of last dose

Question 25

If using rate-limiting agents, what is the target HR?

Answer 25

<110 bpm or <80 bpm if patient remains symptomatic

Question 26

What is used for symptom control in paroxysmal and persistant AF?

Answer 26

Unlike permanent AF where restoration of normal sinus rhythm is not an option, with these types of AF it may be possible using either non-pharmacological therapies (e.g. direct current cardioversion or radio-frequency ablation) or medicines.

A rhythm control strategy (to help the heart maintain a sinus rhythm) or rate control strategy (i.e. allow the heart to go into AF, but control the rate) may be used. Often both are employed (if the rhythm control fails, rate control limits symptoms).

Both are equally effective in terms of clinical outcomes.

In some patients an ‘as required’ rhythm control strategy is used (Pill in Pocket).

Question 27

What are examples of rhythm controlling agents?

Answer 27

• Flecainide / Propfenone (class 1c)
• Amiodarone (mainly class III)
• Sotalol (class II/III)
• Dronedarone (Class III)

Question 28

Can Flecainide and Propafenone be used long-term?

What are CI?

What are they often used with?

Answer 28

• Can be used long-term or flecaidine can be used as a pill in pocket
• CI if LVSD/ HF/ history of MI/structural heart disease
• OFten used with a B-blocker

Question 29

Can amiodarone be used long-term?

Answer 29

No should not be used long-term. It is very effective but use limited by short term and long term toxicity

Question 30

Dose of amiodarone?

Answer 30

200 mg 3 times a day for 1 week, then reduced to 200 mg twice daily for a further week, followed by maintenance dose, usually 200 mg daily or the minimum dose required to control arrhythmia.

The usual maintenance dose is 200 mg a day, or less if appropriate

Question 31

True or False
Amiodarone causes QT prolongation

Answer 31

True

Question 32

Important side-effects of amiodarone?

Answer 32

Healthcare professionals are reminded that amiodarone can cause serious adverse reactions affecting the eyes, heart, lung, liver, thyroid gland, skin, and peripheral nervous system that may persist for a month or longer after treatment discontinuation. Some of these reactions may be life-threatening but onset can be delayed;

BNF information:

Corneal microdeposits
Patients taking amiodarone may develop corneal microdeposits (reversible on withdrawal of treatment). However, if vision is impaired or if optic neuritis or optic neuropathy occur, amiodarone must be stopped to prevent blindness and expert advice sought.

**Thyroid function **
Amiodarone contains iodine and can cause disorders of thyroid function; both hypothyroidism and hyperthyroidism can occur. Hypothyroidism can be treated with replacement therapy without withdrawing amiodarone if it is essential; careful supervision is required.

**Hepatotoxicity **
Amiodarone is also associated with hepatotoxicity and treatment should be discontinued if severe liver function abnormalities or clinical signs of liver disease develop.

Pulmonary toxicity
If new or progressive shortness of breath or cough develops in patients taking amiodarone (or recently stopped), pulmonary toxicity should always be suspected. Pulmonary toxicity is usually reversible following early withdrawal of amiodarone.

NICE informtion:

Nausea, vomiting, and taste disturbance commonly occur with loading doses of amiodarone but resolve with dose reduction.

Pulmonary toxicity (including pneumonitis and fibrosis) may present as dyspnoea (which may be severe and unexplained by the current cardiac status), non-productive cough, and deterioration in general health (fatigue, weight loss, and fever).
If pulmonary toxicity is suspected, seek immediate specialist advice; the person may require admission.

Thyroid dysfunction (hypothyroidism or hyperthyroidism) may develop in approximately 4% of people taking maintenance doses of amiodarone.
Check thyroid function tests (TFTs) every 6 months, and seek specialist advice if TFTs are abnormal.

Hepato-biliary disorders including cirrhosis, hepatitis, and jaundice are associated with amiodarone treatment. Asymptomatic increase in liver function test values is common, and persistent elevation of liver function test values to greater than 2 to 3 times the upper limit of normal (or twice previously elevated levels) occurs in 1.2% of people taking maintenance doses of amiodarone. Hepatotoxicity is rare, and death caused by severe hepatotoxicity is rarer.
Monitor liver function every 6 months. If severe liver function abnormalities or clinical signs of liver disease (for example jaundice) develop, stop amiodarone treatment and seek specialist advice.

Cardiac toxicity, such as severe bradycardia and conduction disturbances, are associated with high doses of amiodarone, especially in elderly people. If this occurs, stop treatment with amiodarone.
If bradycardia is severe and symptomatic, refer to secondary care for consideration of a pacemaker.

Visual disorders are common, and most people develop corneal microdeposits during treatment with amiodarone. These rarely interfere with vision, but drivers may be dazzled by headlights at night.
If vision is impaired or if neuropathy or optic neuritis (very rare) occurs, stop amiodarone treatment (to prevent blindness), and seek specialist advice. The manufacturer recommends annual eye examinations in all people taking amiodarone; however, expert opinion suggests that these are only necessary for people with visual symptoms.

Neurological symptoms, such as tremor, ataxia, and (rarely) peripheral neuropathy, have been associated with amiodarone treatment. These are usually seen with loading doses and improve when maintenance treatment is started. Peripheral neuropathy may occur in people who have been taking amiodarone for a long time.

**Photosensitivity reactions **are common and may persist for several months after stopping amiodarone treatment. A blue-grey skin discolouration has been reported in approximately 2% of people taking amiodarone. This discolouration occurs in unprotected light-exposed skin and slowly disappears following treatment discontinuation.
Advise the person to:
Shield their skin from light during treatment with amiodarone and for several months after stopping treatment.
Use a wide spectrum sunscreen with a sun protection factor of at least 30 (for example Uvistat® or Sunsense® Ultra).

Question 33

Monitoring requirements for amiodarone

Answer 33

Amiodarone is always initiated in secondary care, where the following baseline assessments are performed:

• Thyroid function tests.
• Liver function tests.
• Serum electrolyte and urea measurement.
• Chest radiography.
• Electrocardiography.

Regular monitoring is required for the following:
* Thyroid function tests (TFTs) — every 6 months and for 12 months after discontinuation.
(Seek specialist advice if thyroid function tests are abnormal.)
* Liver function tests — every 6 months.
* Serum electrolyte and urea measurement — every 6 months.
* Electrocardiography — every 12 months.

• The manufacturer recommends annual eye examinations for all people taking amiodarone [ABPI, 2017d]; however, expert opinion in a Drug & Therapeutics Bulletin on the use of amiodarone suggests that these are only necessary for people with visual symptoms [DTB, 2003].
• Regular monitoring may be performed in primary or secondary care (depending on locally agreed shared care guidelines).
• • Liver function tests required before treatment and then every 6 months.
• Serum potassium concentration should be measured before treatment.
• Chest x-ray required before treatment.

Thyroid function tests should be performed before treatment, then at 6-monthly intervals, and for several months after stopping treatment (particularly in the elderly). Clinical assessment of thyroid function alone is unreliable. Thyroxine (T4) may be raised in the absence of hyperthyroidism; therefore tri-iodothyronine (T3), T4, and thyroid-stimulating hormone (thyrotrophin, TSH) should all be measured. A raised T3 and T4 with a very low or undetectable TSH concentration suggests the development of thyrotoxicosis.

If concomitant use of amiodarone with sofosbuvir and daclatasvir, simeprevir and sofosbuvir, or sofosbuvir and ledipasvir cannot be avoided because other anti-arrhythmics are not tolerated or contraindicated, patients should be closely monitored, particularly during the first weeks of treatment. Patients at high risk of bradycardia should be monitored continuously for 48 hours in an appropriate clinical setting after starting concomitant treatment. Patients who have stopped amiodarone within the last few months and need to start sofosbuvir and daclatasvir, simeprevir and sofosbuvir, or sofosbuvir and ledipasvir should be monitored.

Question 34

Interactions with amiodarone

Answer 34

https://cks.nice.org.uk/topics/atrial-fibrillation/prescribing-information/amiodarone-not-initiated-in-primary-care/

Beta-blockers
Only specialists should co-prescribe a beta-blocker and amiodarone. Hypotension, bradycardia, ventricular fibrillation, and asystole have been seen in a few people given amiodarone with propranolol, metoprolol, or sotalol.
Calcium-channel blockers
Avoid concurrent treatment with amiodarone, or use with caution. Cardiac depression can occur with concurrent treatment.
Colestyramine
Colestyramine appears to reduce amiodarone levels by about 50%. If colestyramine is started, monitor the person for decreased amiodarone effects. If necessary, seek specialist advice about adjusting the amiodarone dose, or consider prescribing an alternative to colestyramine.
Centrally acting anticholinesterases
The risk of adverse effects, including bradycardia, may be increased if amiodarone is given with a centrally acting anticholinesterase (such as galantamine, donepezil, or rivastigmine).
Drugs that prolong the QT interval
Only specialists should co-prescribe amiodarone and drugs that prolong the QT interval. This is because of the risk of additive effects, which may lead to serious and potentially life-threatening torsades de pointes arrhythmias. Examples of drugs that are known to have a high risk of causing QT prolongation include:
Antiarrhythmics, such as sotalol, disopyramide, and quinidine.
Antihistamines, such as astemizole and terfenadine.
Antipsychotics, such as amisulpride, haloperidol, and droperidol.
Antibiotics, such as erythromycin and clarithromycin.
Antidepressants, such as citalopram, escitalopram, clomipramine, and amitriptyline; and lithium.
Drugs that affect the liver enzyme cytochrome P450 isoenzyme 3A4
Drugs that inhibit CYP 3A4 may increase serum concentration of amiodarone with the potential for toxicity. Examples include erythromycin, azole antifungals, and protease inhibitors. Grapefruit juice should also be avoided.
Concomitant use of fluconazole with amiodarone is contraindicated [ABPI, 2015].
Drugs that induce CYP 3A4 may decrease serum concentrations of amiodarone with the potential for loss of efficacy. Examples include carbamazepine, rifampicin, midazolam, lidocaine, fentanyl, sildenafil, St John’s wort, and phenytoin. Amiodarone may also inhibit the hepatic metabolism of phenytoin resulting in an increase in phenytoin plasma levels.
Digoxin
Amiodarone may increase plasma levels of digoxin because of reduced renal digoxin clearance. If concurrent use is indicated, prescribe half the recommended dose of digoxin, and monitor the person closely in view of potential toxicity.
Hepatitis C drugs
Concomitant use of amiodarone and some drugs used to treat hepatitis C (Harvoni® [sofosbuvir with ledipasvir] or a combination of Sovaldi® [sofosbuvir] and Daklinza® [daclatasvir], or Sovaldi® and Olysio® [simeprivir]) may increase the risk of severe bradycardia or heart block [EMA, 2015; MHRA, 2015]. The summary of product characteristics for Sovaldi® states that life-threatening cases of severe bradycardia and heart block have been observed when sofosbuvir is used in combination with another direct-acting antiviral and concomitant amiodarone (with or without other drugs that lower heart rate). Amiodarone should therefore only be used in patients taking Sovaldi and another DAA when other alternative anti-arrhythmic treatments are not tolerated or are contraindicated. Patients should be monitored closely [ABPI, 2016].
Simvastatin
Rarely, myopathy and rhabdomyolysis have been reported in people taking amiodarone with high doses of simvastatin. The dose of simvastatin should not exceed 20 mg a day in people taking amiodarone unless the clinical benefit is likely to outweigh the increased risk of myopathy and rhabdomyolysis.
Stimulant laxatives
Concurrent use of amiodarone and a stimulant laxative (such as senna) may cause hypokalaemia, thus increasing the risk of torsades de pointes. Consider prescribing other types of laxatives (for example bulk forming [such as ispaghula husk] or osmotic laxatives [such as lactulose]).
Warfarin
The anticoagulant effects of warfarin are increased by amiodarone. The onset of this interaction may be slow (up to 2 weeks), with the peak effect occurring about 7 weeks after warfarin treatment is started. Reduce the dose of warfarin by one-third to two-thirds if amiodarone is added, and monitor the international normalized ratio (INR) once a week for the first 7 weeks of concurrent treatment.
Be aware that amiodarone has a long half-life (25–100 days); thus, interactions may occur for some time after drug withdrawal.

Question 35

Can Sotalol prolong QT interval?
When should sotalol be reduced/discontinued?

Answer 35

Yes

Manufacturer advises reduce dose or discontinue if corrected QT interval exceeds 550 msec.

Question 36

What class of drugs other than rhythm controlling agent does Sotalol belong too?

Answer 36

B-blocker

Question 37

Dronedarone has less long term toxicity than amiodarione.

What adverse effects can this agent have?

Question 38

Dronedarone has less long term toxicity than amiodarione.

What adverse effects can this agent have?

Answer 38

Liver injury
Liver injury including life-threatening acute liver failure reported rarely; discontinue treatment if 2 consecutive alanine aminotransferase concentrations exceed 3 times upper limit of normal.

Heart failure
New onset or worsening heart failure reported. If heart failure or left ventricular systolic dysfunction develops, discontinue treatment.

**Pulmonary toxicity **
Interstitial lung disease, pneumonitis and pulmonary fibrosis reported. Investigate if symptoms such as dyspnoea or dry cough develop and discontinue if confirmed.

Question 39

What monitoring is required with dronedarone?

Answer 39

Monitor for heart failure.

Perform ECG at least every 6 months—consider discontinuation if atrial fibrillation reoccurs.

Measure serum creatinine before treatment and 7 days after initiation—if raised, measure again after a further 7 days and consider discontinuation if creatinine continues to rise.

Monitor liver function before treatment, 1 week and 1 month after initiation of treatment, then monthly for 6 months, then every 3 months for 6 months and periodically thereafter.

Question 40

Can dronedarone prolong QT

Answer 40

yes - CI if prolonged QT

Question 41

What is the choice of rhythm control in AF patients?

Answer 41

Question 42

What is the only rhythm controlling agent suitable for AF

Answer 42

amiodarone

Question 43

Antithrombotic therapy after an acute coronary syndrome in atrial fibrillation patients requiring anticoagulation

Answer 43

Antithrombotic therapy after elective percutaneous intervention in atrial fibrillation patients requiring anticoagulation