Atrial fibrillation: diagnosis.

• Background              

  

  A supraventricular tachyarrhythmia, with chaotic and irregular conduction of depolarisation through the atrium and then ventricles.
  Caused by PIRATES.
  Cardiorespiratory:
  • Pulmonary: PE, pleural effusion, COPD, lung cancer, pneumonia.
  • Ischaemic heart disease (inc. acute MI) and other cardiac diseases: HTN, HF, cardiomyopathy, pericardial disease, myxoma.
  • Rheumatic valve disease and mitral stenosis.
  Toxic and metabolic:
  • Alcohol ('holiday heart'), smoking, caffeine.
  • Thyrotoxicosis
  • Electrolyte abnormalities (↓K+,↓Mg2+).
  • Sugar (diabetes), Sepsis.
  'Lone AF' if it is idiopathic.

  Epidemiology

  • Commonest arrhythmia, affecting 10% over 80 years old.
  • Commoner in men.

  Classification by timeframe

  Acute AF

  Onset within previous 48 hrs, either 'new-onset' or a recurrent episode.

  Chronic AF

  Sub-classified as:
  • Paroxysmal AF: self-terminates <7 days, usually 48 hrs.
  • Persistent AF: lasts >7 days, or <7 days but requires cardioversion. 'Long standing' if >1 year.
  • Permanent AF: refractory to cardioversion.

• Pathophysiology

• Signs and symptoms

  Symptoms:
  • Palpitations
  • Syncope
  • SOB
  • Angina, reflecting rate-related ischaemia.
  • 20% are asymptomatic.
  Signs:
  • Pulse: ↑HR, irregularly irregular, and apical pulse may be faster than radial.
  • ↓BP
  • Absent a waves in JVP.
  Symptoms of complications:
  • Stroke/TIA.
  • Pulmonary oedema (acute HF).

• Investigations

  ECG

  Findings:
  • Absent P waves, replaced with small, irregular f waves, reflecting depolarisation beginning randomly at various foci in the atrium.
  • Irregularly irregular RR interval.
  • If HR >100, known as AF with rapid ventricular response or 'fast AF'. Prolonged episodes may lead to transient ischaemic changes such as ST depression, though persistent changes (and a compatible history) may suggest MI as the underlying cause of the AF.
  If the ECG is normal but paroxysmal AF is suspected, use 24h ambulatory ECG, or consider an event recorder if episodes >24h apart.

  Other investigations

  Bloods:
  • FBC: anaemia may exacerbate heart failure.
  • U+E and TSH to look for cause.
  • Investigate other CV risk factors: lipids, glucose.
  • LFT and coag pre-warfarin.
  Imaging:
  • Trans-thoracic echo: look for cardiac causes and complications. Especially important if there is a suspicion of structural disease or pre-cardioversion. Consider trans-oesophageal echo if abnormality found.
  • CXR: may show heart failure.

• Management

  Management of AF involves:
  1. Rate or rhythm control. Rate control – slowing the heart – is 1st line for most patients. Rhythm control – regularizing the arrhythmia – is an alternative in certain patients.
  2. Reducing the risk of thromboembolism, especially stroke.

  Thromboprophylaxis

  Indications:
  • Consider in all patients with chronic AF with a CHA2DS2-VASc score of ≥1 in men or ≥2 in women, balancing against ↑bleeding risk as assessed with HAS-BLED.
  • Important in any patient undergoing cardioversion as that is a high risk time for embolism.
  Drugs:
  • Direct oral anticoagulants (DOACs) for most.
  • Warfarin if there is a mechanical valve or moderate to severe mitral stenosis.
  If there is low risk – CHA2DS2-VASc of 0 in men or 1 in women – offer no treatment (preferred) or aspirin.

• Rate and rhythm control in AF

  Rate control

  1st-line options:
  • β-blocker: metoprolol, bisoprolol.
  • Rate-limiting calcium channel blocker: verapamil, diltiazem.
  • Consider digoxin if they are sedentary. In active patients it is ineffective at slowing sympathetic-driven ↑HR.
  2nd-line. Combine any 2 of:
  • β-blocker, diltiazem, and/or digoxin.

  Rhythm control

  Offered if rate control has been unsuccessful, or as an alternative 1st line treatment for:
  • New-onset AF (<48 hours).
  • AF with a reversible cause.
  • AF leading to HF or haemodynamic instability: ↓BP, chest pain, loss of consciousness.
  • Patients in whom it is considered more suitable based on clinical judgement e.g. younger patients, especially if active and want to avoid rate control.
  Electrical cardioversion:
  • Preferred choice if there is haemodynamic instability: SBP <90, syncope, acute HF, MI.
  • Shock carried out under short-acting general anaesthetic, followed by second shock with higher joules if no success with first.
  • If not anticoagulated, give heparin or LMWH first, but not if this delays treatment in a life-threatening situation.
  Pharmacological cardioversion:
  • Indications: if symptoms are milder and situation is less urgent. Bolus followed by infusion if AF continues. Again, anticoagulate first.
  • Flecainide or propafenone IV (class 1c) if there is no structural heart disease. Both are -ve inotropes and carry risk of ↓BP.
  • Amiodarone (class 3) if there is structural or ischaemic heart disease. Give through central line as there is a risk of thrombophlebitis if peripheral.
  If cardioversion is elective:
  • Thromboprophylaxis 3 weeks before. This should always be done – where possible – when duration of AF is >48 hours, as there has been time for clot formation. Alternatively can do a transoesophageal echo to rule out a thrombus, and then cardiovert safely.
  • Consider amiodarone 4 weeks pre and up to 12 months post, especially if high risk of failure.
  Maintaining long-term rhythm control post-cardioversion:
  • β-blocker is 1st line as per NICE, though classically considered a rate-control agent rather than an antiarrhythmic.
  • Other options: amiodarone, sotalol, flecainide, propafenone, dronedarone (multichannel blocker, mainly K+).
  As an alternative to continuous therapy in patients with paroxysmal AF, offer PRN sotalol or flecainide ('pill in the pocket') if they meet the following criteria:
  • Infrequent episodes.
  • Understand how and when to take it.
  • No structural (LVF, valvular) or ischaemic heart disease.
  • SBP >100 and HR >70.
  Consider no treatment at all if episodes are very infrequent.

  Catheter ablation

  • Indications: if medically refractory or has contraindications to medical therapy. Also consider in younger patients, to avoid lifetime of medication.
  • Methods: radiofrequency, cryotherapy, or microwave. Often targets an area around the insertion of the pulmonary veins, where fibrillation may originate.
  • 'Ablate and pace' – ablation of the AV node followed by pacemaker insertion – can be considered in permanent AF with LV dysfunction.

• Complications

  • Stroke (5x risk).
  • Acute HF and pulmonary oedema.
  • Cardiomyopathy and heart failure.

• Warfarin

  Mechanism

  • Vitamin K antagonist (VKA) which works by inhibiting vitamin K1 reductase → ↓hepatic synthesis of clotting factors 2 (aka thrombin), 7, 9, and 10.
  • Onset takes a few days as clotting factors have half-life up to 80 hrs.

  Management

  • Check FBC, LFT, and coag at baseline.
  • Check INR initially after 48 hrs, then daily until stable in target range, then weekly/monthly.
  • Aim for INR 2.5 (±0.5) in AF and post-VTE. Aim for 3.0 for cardioversion or aortic mechanical valve, and 3.5 for mitral mechanical valve or in recurrent VTE while on warfarin. In healthy individuals, INR is 1 (0.8-1.2).
  • INR is a standardised prothrombin time (PT), a measure of extrinsic pathway function. Sample must be a full tube, to ensure correct dilution with the liquid citrate anticoagulant also in the tube.
  • Perioperatively, stop warfarin 5 days before. Give standard surgical thromboprophylaxis once admitted (e.g. prophylactic dose LMWH), except for high risk patients (e.g. recent VTE, mitral mechanical valve, AF with previous stroke) who may be given bridging therapy (e.g. treatment dose LMWH). If bridging post-op, don't start until 48 hrs later.
  • No need to stop warfarin before dental extraction (provided INR <4.0) or endoscopy without biopsy (provided INR <3.0).

  Contraindications

  • Bleeding disease
  • Haemorrhagic stroke
  • Active PUD
  • Pregnancy
  • Severe HTN.

  Drug interactions

  Agents which raise levels (some via enzyme inhibition):
  • Antibiotics: macrolides, metronidazole, ciprofloxacin, co-trimoxazole, isoniazid.
  • CV: statins, amiodarone.
  • Psych: SSRIs, valproate.
  • Omeprazole
  • Liver disease.
  • Diet and lifestyle: acute alcohol, grapefruit and cranberry juice. Patients must avoid binge drinking.
  Enzyme inducers lower levels, PC-BRAS2:
  • Phenytoin
  • Carbamazepine
  • Barbiturates
  • Rifampicin
  • Chronic Alcohol
  • St John's wort and Smoking. The latter is debatable, but cessation may trigger ↑INR.
  Aspirin and NSAIDs:
  • Increase bleeding risk due to their antiplatelet effects.
  • Should not be used alongside warfarin, but can be considered in some high risk situations e.g. unstable IHD (post MI), valve replacement patients.

  Side effects

  • Bleeding
  • GI: nausea, vomiting, diarrhoea.
  • Hepatic: jaundice, hepatic dysfunction.
  • Skin necrosis, especially with protein C or S deficiency.

  Warfarin reversal

  ↑INR but no bleed:
  • INR >5: withhold 1 or 2 doses and reduce subsequent maintenance dose.
  • INR >8: stop warfarin, give vitamin K (phytomenadione) PO, repeat if needed after 24 hrs, and restart warfarin when INR <5.
  ↑INR (>5) plus bleed:
  • Minor: stop warfarin, give vitamin K IV, restart warfarin when INR <5. May need repeat vitamin K after 24 hrs if INR >8 initially.
  • Major bleed: stop warfarin, give vitamin K IV plus prothrombin complex concentrate (factors 2, 7, 9, 10) or FFP (2nd line).
  Think about potential causes e.g. interactions, overdose.

• Direct oral anticoagulants (DOACs)

  Aka novel oral anticoagulants (NOACs).

  Mechanisms and drugs

  • Thrombin inhibitor: dabigatran.
  • Factor Xa inhibitors: rivaroxaban, apixaban, edoxaban.

  Indications and management

  • Indications: non-valvular AF, DVT/PE.
  • Not used in valvular AF (requires warfarin).
  • Do not require regular coagulation monitoring.
  • Should be withheld 2 days before and after surgery.

  Efficacy and safety vs. warfarin

  • Similar reduction in stroke, from around 5% per year (no treatment) to 1.5% (warfarin or DOAC).
  • Similar or lower risk of major bleed: 3% per year (warfarin, rivaroxaban, dabigatran), 2% (apixaban). A 'major' bleed is one that is fatal, occurs in a sensitive site (e.g. brain, joint, eye), or large (Hb drop >2 g/dL or requiring transfusion).
  • Lower fatality rate when major bleeding occurs: 11% (warfarin), 7.5% (DOACs). Likely because a higher proportion of major bleeds on warfarin are intracranial. This is despite the limited availability of reversal agents for DOACs, and calls into question the belief that warfarin is preferable because it has reversal agents.
  • Reversal agents are now becoming available for DOACs, but are expensive: idarucizumab (dabigatran), andexanet alfa (all DOACs).
  • Taking all this into account, all-cause mortality is slightly lower for DOACs (10% relative reduction vs. warfarin).

• Antiarrythmic agent classes

  The Vaughan Williams classification.

  Class 1

  • Fast Na+ channel blockers. Reduces rate and magnitude of depolarization, and increase (class 1a) or decrease (class 1b) the refractory period.
  • 1a procainamide and quinidine, 1b lidocaine and phenytoin, 1c flecainide and propafenone.

  Class 2

  • β-blockers, reducing HR and conduction.

  Class 3

  • K+ channel blockers, prolonging repolarization thus increasing action potential duration and effective refractory period.
  • Amiodarone, sotalol (also a β-blocker, class 2).

  Class 4

  • Rate-limiting CCBs. Block L-type calcium channels, reducing HR and conduction, especially at AV node.
  • Verapamil and diltiazem.

  Class 5

  • Other mechanisms.
  • Adenosine, digoxin, magnesium sulfate.

• Amiodarone

  Mechanism

  • K+, Na+, and Ca2+ channel blocker, and α and β-adrenergic receptor blocker.
  • Prolongs cardiac action potential, prolongs refractory period, and slows sinus and AV nodes.

  Side effects

  Extensive tissue binding leads to lots of SEs, including:
  • Skin: photosensitivity, slate grey appearance, thrombophlebitis.
  • Thyroid dysfunction, due to its iodine content.
  • Pulmonary fibrosis.
  • Hepatotoxicity
  • GI symptoms.
  • Neuro: parkinsonism/tremor, peripheral neuropathy.

  Management

  Monitor LFT and TFT.

• Digoxin

  Mechanism

  • Inhibit Na+-K+ ATPase → ↑intracellular Ca2+ (+ve inotrope).
  • Also ↓HR via antiadrenergic effects.

  Side effects

  • Dizziness, palpitations, bradycardia.
  • Blurred vision, xanthopsia (yellow vision).
  • Diarrhoea, nausea, vomiting.
  • Rare: gynaecomastia, depression.
  • Acute toxicity causes nausea and vomiting, abdo pain, confusion, altered HR and BP, and ↑K+ (due to extracellular shift). May occur in the context of intercurrent illness and/or renal impairment.

  ECG changes

  • Downsloping ST variously described as scooped, sagging, hockey stick, or reverse tick.
  • Biphasic T with negative then positive deflection, especially in V4-6.
  • These changes are simply a sign of digoxin use, and not necessarily toxicity. In toxicity, you may also see atrial tachyarrhythmias, VT, or conduction delay including AV block.

  Management

  Serum monitoring:
  • Despite narrow therapeutic index, levels only need to be checked in renal impairment or if problem suspected.
  • Take sample 6 hours post dose.
  Acute toxicity:
  • Check digoxin levels, electrolytes, renal function, glucose, and ECG.
  • Digoxin immune fab (Digibind) is the antidote. Indications: haemodynamic instability, symptomatic arrhythmias, K+ >5, or large ingestion.
  • Bradyarrhythmias can be treated with atropine while awaiting Digibind.
  • Ventricular arrhythmias require cardioversion with a type 1b anti-arrhythmic: phenytoin or lidocaine.
  • Give insulin and glucose for ↑K+, but not Ca2+ as it may cause cardiac arrest.
  • Digoxin toxicity is worsened by ↓K+ (exacerbates mechanism) and ↓Mg2+, so replace if low.