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Supraventricular Tachyarrhythmias: Management of Atrial Fibrillation (AF) and Atrial Flutter (AFL)

• Goals of Care:

  • Mitigation of symptoms.

  • Improvement in quality of life (QoL).

  • Avoidance of morbidity associated with the arrhythmia, specifically avoiding tachycardia-induced cardiomyopathy.

• Management Strategies:

  • Rate Control: Focuses on regulating the ventricular response.

  • Rhythm Control: Focuses on restoring and maintaining sinus rhythm.

  • The approach differs between AF and AFL, and is further divided into acute management and long-term therapy.

Rate vs. Rhythm Control in Atrial Fibrillation

• Established AF (Duration $\ge 1\,year$): Randomised controlled trials, such as the AFFIRM trial, have demonstrated equivalent cardiovascular outcomes between rate and rhythm control strategies.

• New Diagnosis AF (Duration $\le 1\,year$): The EAST-AFNET 4 trial ($N \text{ Engl J Med } 2020; 383:1305-1316$) studied $2789$ patients with a median follow-up of $5\,years$.

  • Results: Demonstrated a reduction in the composite of cardiovascular mortality, stroke, and hospitalisation for heart failure or acute coronary syndrome.

  • Hazard Ratio (HR): $0.79$

  • P-value: $p = 0.005$

  • Adverse Effects: Rhythm control had a higher rate of treatment-related adverse effects compared to rate control ($4.9\%$ vs. $1.4\%$), primarily bradycardia and non-specific "toxic effects" from drugs, but no increase in cardiac arrest or ventricular arrhythmias.

  • Commonly used drugs in trial: Flecainide ($35.9\%$), Amiodarone ($19.6\%$), and Dronedarone ($16.7\%$).

  • Conclusion: There is an increased interest in initial rhythm control for patients with a new diagnosis ($\le 1\,year$).

Acute Management of Atrial Fibrillation

• Hemodynamic Instability: Defined as AF causing hypotension, acute coronary syndrome, or pulmonary edema. Requires urgent cardioversion regardless of anticoagulation status, though stability concerns may overrule thromboembolism risks.

• Anticoagulation Timing:

  • Initiate oral anticoagulation as soon as possible, ideally before cardioversion.

  • Cardioversion without $\ge 3\,weeks$ of anticoagulation (or a transesophageal echocardiogram [TEE] to rule out left atrial thrombus) carries an elevated risk of thromboembolism if AF duration is $> 12\,hours$.

  • Apply CHADS-65 criteria for initiation.

Pharmacologic Cardioversion Options for AF

• Class Ia: Procainamide (IV)

  • Time to Conversion: $\sim 60\,min$

  • Risks: Hypotension ($5\%$), bradycardia, QT prolongation/TdP, QRS widening.

  • Notes: $50-60\%$ effective in AF; $30\%$ in AFL. Contraindicated if $LVEF < 40\%$ due to negative inotropy.

• Class Ic: Flecainide and Propafenone (PO)

  • Time to Conversion: $2-6\,hours$

  • Risks: Hypotension, bradycardia, conversion pauses, AFL with $1:1$ conduction.

  • Notes: MUST combine with an AV nodal blocker. Flecainide is slightly more efficacious.

• Class III: Ibutilide (IV)

  • Time to Conversion: $30-60\,min$

  • Risks: QT prolongation/TdP (monitor closely), hypotension.

  • Notes: Effective for AF ($30-50\%$) and AFL ($50-75\%$). Contraindicated if $LVEF < 30\%$, baseline $QTc > 440\,ms$, or if on other QT-prolonging drugs. Consider pre-treatment with $1-4\,g$ of IV magnesium sulfate; avoid in hypokalemia/hypomagnesemia.

• Class III: Amiodarone (IV)     Time to Conversion: $8-12\,hours$     Risks: Bradycardia/AV block, QT prolongation/TdP, phlebitis.     Notes: Short-term efficacy for cardioversion is poor: $5\%$ at $90\,minutes$, $22\%$ at $4\,hours$ (AVRO study).

• Other: Vernakalant (IV)

  • Time to Conversion: $10-30\,min$

  • Risks: Hypotension (avoid if baseline systolic BP is low), bradycardia, QT prolongation.

  • Notes: $> 50\%$ effective within $15\,minutes$. Avoid in recent ACS ($30\,days$), NYHA class III-IV heart failure, or severe aortic stenosis.

Long-Term Rate Control in AF

• Target Heart Rate: Resting HR goal of $< 100\,bpm$. Stricter targets may be needed for heart failure, mitral stenosis, or stable angina.

• Exercise Target: For active patients, target HR $< 110\,bpm$ during moderate exercise (6-minute walk) and a maximal HR of $110\%$ of standard age-predicted maximum at peak exertion.

First-Line Agents

• Beta-blockers: Preferred for recent MI and heart failure. Beta-1 selective agents are usually preferred (Bisoprolol, Metoprolol, Atenolol, Esmolol, Acebutolol, Betaxolol).

  • Mnemonic: "Beta- (Bisoprolol) Blockers (Betaxolol) Acting (Atenolol) Exclusively (Esmolol) At (Acebutolol) Myocardium (Metoprolol)".

  • Bisoprolol is the most Beta-1 selective.

  • Carvedilol requires monitoring for hypotension (alpha-1 antagonism).

• Non-DHP Calcium Channel Blockers (Diltiazem, Verapamil): Preferred in hypertension or reactive airway disease.

  • Strong negative inotropes; avoid in reduced LVEF.

  • Inhibitors and substrates of CYP3A4.

  • Rarely used with beta-blockers due to risk of excessive AV block.

Second-Line Agent

• Digoxin:

  • Mainly used in addition to first-line agents or in sedentary patients.

  • RATE-AF Study: Compared Bisoprolol and Digoxin in patients $>60\,years$ with permanent AF and HF. No difference in rate control or QoL, but digoxin had significantly fewer adverse events ($142 \text{ vs } 29$, $p < 0.001$).

  • Controversial association with negative clinical outcomes (may reflect "sicker" patient populations).

Long-Term Rhythm Control in AF

• Pharmacologic Therapy:

  • Amiodarone: Most effective for maintaining sinus rhythm. Loading dose of $10-12\,g$ total (oral) is standard (based on volume of distribution $60\,L/kg$ and $50\%$ bioavailability). Maintenance is $\le 200\,mg$ daily. Long-term use restricted due to organ toxicities.

  • Sotalol: Risks include QT prolongation and Torsades de Pointes (TdP). Avoid if $LVEF \le 40\%$ or $CrCl < 40\,mL/min$. Monitor ECG at baseline and after the 4th dose.

  • Dronedarone: Reduces hospitalisations/mortality in paroxysmal/persistent AF (ATHENA trial). Contraindicated in permanent AF or heart failure ($LVEF \le 40\%$) due to increased mortality. Monitor liver function tests (LFTs) every $3\,months$ for year 1, then every $6\,months$.

  • Class Ic (Flecainide/Propafenone): Must combine with AV nodal blocker. Avoid in structural heart disease (reduced LVEF, LV hypertrophy, or ischemic heart disease). Monitor PR/QRS; if QRS increases $> 25\%$, reassess.

• Non-Pharmacologic Therapy:

  • Catheter Ablation: $60\%-80\%$ effective at eliminating AF; $98\%$ reduction in AF burden. Pulmonary Vein Isolation (PVI) is the primary method because cardiomyocytes in pulmonary veins initiate AF in up to $94\%$ of patients.

  • Pill-in-the-Pocket (PIP): Propafenone or Flecainide for infrequent symptomatic AF ($< \text{once monthly}$) lasting $\ge 2\,hours$ in patients without structural heart disease.

    • Protocol: Administer AV nodal blocker (e.g., Metoprolol tartrate $25\,mg$) $30\,minutes$ before Class Ic medication.

    • Dose: Flecainide $300\,mg$ (if $\ge 70\,kg$) or $200\,mg$ (if $< 70\,kg$).

Management of Atrial Flutter (AFL)

• Rate Control Challenges: AFL is harder to rate control than AF because the AV node is bombarded less randomly. Atrial rate is often $\sim 300\,bpm$. Achieving a ventricular rate of $100\,bpm$ (3:1 conduction) or $75\,bpm$ (4:1 conduction) without causing total blockade is difficult.

• Rhythm Control:

  • Pharmacologic rhythm control is less successful in AFL.

  • Radiofrequency Catheter Ablation: Considered "curative" therapy ($> 90\%$ success).

  • Post-Ablation Risk: Up to $50\%$ develop new AF within $30\,months$, rising to $> 80\%$ at $5\,years$.

• Drug Specifics in AFL:

  • Ibutilide is effective but rarely used due to TdP risk.

  • Class Ic agents MUST be combined with AV nodal blockers to prevent $1:1$ AV conduction (where ventricular rates can exceed $200\,bpm$ as the atrial rate slows).

Thromboembolic Prophylaxis

• Risk Scores:

  • CHADS-65: Used to determine clinical indication for anticoagulation.

  • CHADS2 & CHA2DS2-VASc: Quantification of annual thromboembolism risk.

    • CHADS2 score of $6 = 13.0\%$ annual rate.

    • CHA2DS2-VASc score of $9 = 12.2\%$ annual rate.

  • HAS-BLED Score: Assesses bleeding risk. Score $\ge 5$ indicates a $12.5\%+$ major bleeding risk per year.

Anticoagulation & Cardioversion

• Rule of 12/48: Embolic risk increases after $12\,hours$ of arrhythmia (previously thought to be $48\,hours$) based on the FinCV study.

• Requirements:

  • Immediate cardioversion without anticoagulation is only for patients with AF onset $< 12\,hours$ (and no stroke/TIA in prior $6\,months$) OR nonvalvular AF with CHADS2 $0-1$ and onset $12-48\,hours$.

  • Others require $\ge 3\,weeks$ of anticoagulation pre-cardioversion or a TEE rule-out.

  • ALL patients require $\ge 4\,weeks$ of antithrombotic therapy post-cardioversion.

Choice of Oral Anticoagulant (OAC)

• Direct-Acting Oral Anticoagulants (DOACs): Recommended over warfarin for most patients with nonvalvular AF.

  • Dabigatran: Direct thrombin inhibitor. Dose: $150\,mg$ po bid (or $110\,mg$ bid if $\ge 80\,years$). Avoid if $CrCl < 30\,mL/min$.

  • Rivaroxaban: Anti-Xa. Dose: $200\,mg$ daily (or $15\,mg$ if $CrCl 15-50\,mL/min$).

  • Apixaban: Anti-Xa. Dose: $5\,mg$ bid (or $2.5\,mg$ bid if $2+$ of: age $\ge 80$, weight $\le 60\,kg$, SrCr $\ge 133\,\mu mol/L$).

  • Edoxaban: Anti-Xa. Dose: $60\,mg$ daily (or $30\,mg$ if $CrCl 30-50\,mL/min$ or weight $\le 60\,kg$).

• Warfarin: Inhibition of factors II, VII, IX, X and Proteins C/S.

  • Mnemonic: "Canada (Protein C) vs. Soviets (Protein S), 1972 (Factors 10, 9, 7, 2)".

  • Only option for Valvular AF (mechanical valves or mod-severe mitral stenosis).

Case Scenario Summaries

• Case OL: $61\,year$ old female, HR $139\,bpm$, history of CAD, asthma, and GERD.

  • Rhythm: Atrial Fibrillation.

  • Acute Rate Control: Considerations must account for her asthma (limiting non-selective beta-blockers) and CAD.

• Case KF: $73\,year$ old female, weight $55\,kg$, SrCr $136\,\mu mol/L$.

  • Anticoagulation Choice: Apixaban would require dose reduction to $2.5\,mg$ bid because she meets two criteria (weight $\le 60\,kg$ and SrCr $\ge 133\,\mu mol/L$).

  • Optimization: Discontinue NSAID (ibuprofen) to lower HAS-BLED bleeding risk.