Antiarrhythmic drugs — viva

Stem

Practice viva. The examiner asks how the main antiarrhythmic drugs act, how they cause arrhythmias, how drug choice changes with heart disease, what to monitor, and what to do in pre-excited AF.

Branch A — Class actions

Examiner: Classify sotalol, amiodarone, dronedarone and flecainide.^{[10][8][11][9]}

Strong answer:

• The sotalol label gives it beta-blocking (Vaughan Williams Class II) and action potential-prolonging (Class III) properties; significant Class III effects appear only at 160 mg a day and above.^[10]
• The amiodarone label calls it a class III drug with electrophysiological characteristics of all four Vaughan Williams classes.^[8]
• The dronedarone label says its mechanism of action is unknown, though it has properties of all four Vaughan-Williams classes.^[11]
• The flecainide label places it in the membrane-stabilising Class 1 group, with effects characteristic of class IC; ACC/AHA 2023 Table 23 lists it as inhibiting INa.^[9][2]

Follow-up: What ECG changes do you expect on flecainide?^[9]

• The label describes dose-related increases in PR, QRS and QT in most patients; the QT widens about 8%, mostly (about 60% to 90%) through QRS widening.^[9]
• ESC 2024 AF Table 13 says a flecainide infusion should be stopped if the QRS widens by more than 25% or bundle branch block appears; separately, in its algorithm for starting and following sodium channel blockers, ESC 2022 VA notes that a QRS increase over 25% is not an absolute cut-off but depends on the QRS width before the drug and individual risk–benefit considerations.^[1][3]

Branch B — Proarrhythmia

Examiner: Who is most at risk of torsades de pointes on sotalol?^[10]

• The label names factors such as reduced creatinine clearance, female sex, higher doses, reduced heart rate, and a history of sustained VT/VF or heart failure.^[10]
• It adds that bradycardia itself increases the risk, and that proarrhythmic events must be anticipated at initiation and with every upward dose change.^[10]
• ESC 2022 VA says hypomagnesaemia and/or hypokalaemia may be associated with TdP.^[3]

Follow-up: And why give an AV-nodal blocker with flecainide?^[1]

• The flecainide label reports 1:1 atrioventricular conduction in atrial flutter, as with other Class 1 agents, because the atrial rate slows.^[9]
• ESC 2024 AF says a beta-blocker, diltiazem or verapamil should be considered with flecainide or propafenone to prevent 1:1 conduction if the rhythm becomes flutter (Class IIa, Level C).^[1]

Branch C — Drug choice by heart substrate

Examiner: A patient with AF needs long-term rhythm control. How does the substrate change your choice?^[1]

• ESC 2024 AF: flecainide or propafenone is recommended for patients requiring long-term rhythm control, to prevent recurrence and progression of AF, excluding impaired LV systolic function, severe LV hypertrophy or coronary artery disease (Class I, Level A).^[1]
• ESC 2024 AF: dronedarone is recommended for patients requiring long-term rhythm control, including HFmrEF, HFpEF, ischaemic heart disease or valvular disease, to prevent recurrence and progression of AF (Class I, Level A).^[1]
• ESC 2024 AF: amiodarone is recommended in AF with HFrEF requiring long-term antiarrhythmic drug therapy, to prevent recurrence and progression of AF, with careful consideration and monitoring for extracardiac toxicity (Class I, Level A).^[1]
• ACC/AHA 2023: flecainide and propafenone should not be given with previous MI and/or significant structural heart disease, including HFrEF, because of the risk of worsening heart failure, potential proarrhythmia and increased mortality (COR 3: Harm, LOE B-R); dronedarone should not be given for sinus rhythm maintenance in NYHA class III–IV heart failure or after decompensated heart failure in the past 4 weeks, because of the risk of increased early mortality with worsening heart failure (COR 3: Harm, LOE B-R).^[2]

Follow-up: What trial evidence lies behind the dronedarone harm row?^[11][2]

• ANDROMEDA, as described in the label and ACC/AHA 2023, randomised patients recently hospitalised with symptomatic heart failure and severe LV systolic dysfunction to dronedarone 400 mg twice daily or placebo in a double-blind design.^[11][2]
• It was stopped after 627 patients and a median follow-up of 63 days because of excess deaths with dronedarone (25 versus 12; hazard ratio 2.13; 95% CI 1.07 to 4.25), principally from worsening heart failure.^[11][2]

Branch D — Monitoring amiodarone

Examiner: Your patient is starting oral amiodarone. What do you monitor?^[2][8]

• ACC/AHA 2023 Table 24: TSH and AST/ALT at baseline, at 3–6 months and every 6 months; ECG at baseline and annually; chest X-ray at baseline and for unexplained cough, dyspnoea or other signs or symptoms suspicious for interstitial lung disease; no baseline eye test, with testing if visual abnormalities develop; annual examination for skin and neurological effects.^[2]
• The FDA label adds baseline pulmonary function tests including diffusion capacity, repeat history, examination and chest X-ray every 3 to 6 months, and regular ophthalmic examination including funduscopy and slit-lamp examination.^[8]
• The label says to discontinue or reduce the dose if transaminases exceed three times normal, or double in a patient with an elevated baseline.^[8]

Follow-up: Which interactions do you check?^[2]

• ACC/AHA 2023 Table 23: amiodarone increases plasma warfarin, lovastatin, simvastatin, cyclosporine and digoxin; lovastatin should not exceed 40 mg daily and simvastatin should not exceed 20 mg daily.^[2]
• The label reports symptomatic bradycardia, some needing a pacemaker and at least one fatal, when ledipasvir/sofosbuvir or sofosbuvir with simeprevir was started in patients on amiodarone.^[8]

Branch E — Pre-excited AF

Examiner: A young man with pre-excitation has a fast, broad, irregular tachycardia and is haemodynamically stable. What do you give?^[3][4]

• ESC 2019 SVT, haemodynamically stable patients: intravenous ibutilide or procainamide should be considered (Class IIa, Level B); intravenous flecainide or propafenone may be considered (Class IIb, Level B).^[4]
• ACC/AHA 2023: intravenous ibutilide or procainamide is recommended as an alternative to elective cardioversion when haemodynamically stable (COR 1, LOE C-LD).^[2]
• If he becomes unstable, both guidelines recommend synchronised or electrical cardioversion (ESC 2019 SVT Class I, Level B; ACC/AHA 2023 COR 1, LOE B-NR).^[4][2]

Follow-up: Why not amiodarone?^[4]

• ESC 2019 SVT does not recommend intravenous amiodarone in haemodynamically stable pre-excited AF (Class III, Level B), and says it may not be as safe as previously thought, because enhanced pathway conduction and ventricular fibrillation have been reported.^[4]
• ACC/AHA 2023 lists amiodarone among AV-nodal blocking drugs contraindicated in pre-excited AF, because of the risk of precipitating VF or haemodynamic deterioration (COR 3: Harm, LOE B-NR); ESC 2024 AF, without a class, says to avoid it because of its delayed action.^[2][1]