What anti-arrhythmics are appropriate for Heart Failure with preserved Ejection Fraction (HFpEF)?

Anti-Arrhythmic Management in Heart Failure with Improved Ejection Fraction (HFimpEF)

Direct Answer

For patients with HFimpEF, continue evidence-based beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) as first-line therapy for both heart failure management and arrhythmia control, particularly if atrial fibrillation is present. 1 If rhythm control is needed beyond rate control, amiodarone is the preferred anti-arrhythmic agent due to its low proarrhythmic risk and dual benefit for both rate and rhythm control. 1

Understanding HFimpEF Context

• HFimpEF represents patients whose ejection fraction has improved from previously reduced levels, typically now in the 41-49% range or higher 1
• These patients should continue guideline-directed medical therapy (GDMT) that was initiated when they had HFrEF, as discontinuation may lead to deterioration 1
• The anti-arrhythmic approach depends heavily on whether the patient has concurrent atrial fibrillation, which is present in up to 40% of heart failure patients 1

First-Line Anti-Arrhythmic Strategy: Beta-Blockers

Evidence-based beta-blockers remain the cornerstone anti-arrhythmic therapy for HFimpEF:

• Continue carvedilol (target 25-50 mg twice daily), metoprolol succinate (target 200 mg daily), or bisoprolol (target 10 mg daily) at maximally tolerated doses 1
• Beta-blockers provide mortality benefit established during the HFrEF phase and should not be discontinued even after EF improvement 1
• For rate control in atrial fibrillation with HFimpEF, beta-blockers are the preferred first-line agents 1

When Atrial Fibrillation is Present

Rate Control Strategy (Preferred Initial Approach)

Rate control is generally preferred over rhythm control unless AF is causing tachycardia-induced cardiomyopathy: 1

• Beta-blockers: First-line for rate control in HFimpEF with AF 1
• Digoxin: Effective adjunct to beta-blockers for resting heart rate control; can be combined for better exercise rate control 1
• Target heart rate: 60-100 beats/min at rest, with physiological range during exercise 1

Avoid these agents in HFimpEF:

• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) should be used with extreme caution or avoided if EF remains <50%, as they have negative inotropic effects 1
• Dronedarone is contraindicated in decompensated heart failure 1

Rhythm Control Strategy (When Indicated)

Consider rhythm control if: 1

• AF with rapid ventricular response is suspected of causing or perpetuating cardiomyopathy (tachycardia-induced)
• Patient remains symptomatic despite adequate rate control and optimized HF therapy
• New-onset AF in the setting of acute decompensation

Amiodarone is the preferred anti-arrhythmic for rhythm control in HFimpEF:

• Loading and maintenance: Initiate amiodarone 1 month before planned cardioversion and continue for <6 months 1
• Dual benefit: Amiodarone provides both effective rate control and rhythm control with low proarrhythmic risk 1
• Acute setting: Intravenous amiodarone is recommended for acute rate control when other measures fail or are contraindicated 1

Other anti-arrhythmics to avoid:

• Class IC agents (flecainide, propafenone) are contraindicated in structural heart disease 1
• Sotalol has beta-blocking properties but higher proarrhythmic risk and is generally avoided 1

Acute Management Algorithm

For HFimpEF patients presenting with AF and rapid ventricular response:

1. Hemodynamically stable with congestion: IV digoxin or IV amiodarone for rate control 1
2. Hemodynamically stable without congestion: IV beta-blocker (metoprolol 2.5-5 mg IV) with caution 1
3. Hemodynamically unstable: Emergent electrical cardioversion 1
4. Avoid: IV non-dihydropyridine calcium channel blockers in decompensated HF 1

Advanced Interventional Options

When pharmacological therapy fails or is not tolerated:

• AV node ablation with pacing: Reasonable approach for refractory rate control, but only after pharmacological trial 1
• Cardiac resynchronization therapy (CRT): Consider if AV node ablation is performed and ventricular pacing is needed 1
• Catheter ablation of AF: May improve LV function and quality of life, though less effective than in patients without structural heart disease 1

Critical Pitfalls to Avoid

• Never perform AV node ablation without first attempting pharmacological rate control 1
• Do not discontinue beta-blockers in HFimpEF even if EF has normalized, as this may lead to recurrent HF 1
• Avoid IV beta-blockers or calcium channel blockers in overtly decompensated HF with hypotension or pulmonary edema 1
• Do not use non-dihydropyridine calcium channel blockers as monotherapy in patients with EF <50% due to negative inotropic effects 1

Monitoring and Optimization

• Assess heart rate control during exercise, not just at rest, and adjust therapy to maintain physiological range 1
• Monitor for signs of decompensation when initiating or up-titrating anti-arrhythmic therapy 1
• Evaluate for reversible causes of AF including thyroid disease, alcohol use, and uncontrolled hypertension 1
• Assess thromboembolic risk and initiate anticoagulation according to CHA₂DS₂-VASc score 1

Complementary HF Therapy

Continue disease-modifying therapies for HFimpEF:

• SGLT2 inhibitors (empagliflozin or dapagliflozin) should be added if not already prescribed 1
• ACE inhibitors, ARBs, or ARNIs should be continued 1
• Mineralocorticoid receptor antagonists may be beneficial, particularly if EF is in the lower range (41-49%) 1