If I need rhythm control, what options besides ablation and amiodarone exist?

For your situation — sick sinus syndrome, a pacemaker, and failed amiodarone — the evidence for rhythm-control options beyond ablation and amiodarone is thin and mostly from studies that excluded your exact combination.

The retrieved evidence does not contain a single trial that tested a rhythm-control drug in patients with sick sinus syndrome and a pacemaker. What exists is indirect. Dofetilide, a class III antiarrhythmic, converted about 30% of patients with chronic atrial fibrillation at 500 mcg twice daily and maintained sinus rhythm at one year in 58%, but the SAFIRE-D trial (2000) excluded patients with sick sinus syndrome and required in-hospital QT monitoring [2]. Dronedarone is less toxic than amiodarone but is contraindicated in heart failure because it increased mortality in the ANDROMEDA trial — and your scenario includes heart failure [1]. Sotalol and flecainide carry proarrhythmia risks that are amplified in the presence of structural heart disease and pacing; no trial in this retrieval tested them in your population.

The pacing strategy matters. The DANPACE trial (2011) compared single-lead atrial pacing (AAIR) to dual-chamber pacing (DDDR) in 1,415 patients with sick sinus syndrome and found no difference in mortality, but AAIR increased paroxysmal atrial fibrillation (28.4% vs 23.0%) and doubled the risk of pacemaker reoperation [3]. An older study (1992) found that ventricular pacing (VVI) produced a 19% incidence of atrial fibrillation versus 4% with DDD pacing [4]. The message: minimizing ventricular pacing and using dual-chamber mode may reduce the substrate for atrial arrhythmia.

My call: the safest next step is to review pacemaker settings — minimize ventricular pacing and confirm dual-chamber mode — then consider dofetilide with in-hospital initiation if the heart failure is compensated and renal function allows. Catheter ablation remains the intervention with the strongest mechanistic rationale, but the evidence was never built for your situation. Confidence: low for any drug option in this specific combination, moderate for pacing optimization as a first step.