Can procainamide be used in heart failure with reduced ejection fraction (HFrEF)?

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Last updated: August 7, 2025View editorial policy

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Use of Procainamide in Heart Failure with Reduced Ejection Fraction

Procainamide should not be used in patients with heart failure with reduced ejection fraction (HFrEF) except in very limited circumstances for pharmacological conversion of atrial fibrillation, and even then it is considered a Class 2b (weak) recommendation.

Current Guidelines on Procainamide in HFrEF

The 2023 ACC/AHA/ACCP/HRS guidelines for atrial fibrillation management specifically address the use of antiarrhythmic medications in the context of HFrEF:

  • For patients with HFrEF (LVEF <40%) and atrial fibrillation requiring pharmacological cardioversion, IV amiodarone is the preferred first-line agent (Class 2a recommendation) 1
  • Procainamide carries only a Class 2b recommendation (may be considered) in patients with normal left ventricular function 1
  • The guidelines explicitly show that procainamide is not recommended for use in HFrEF patients in the treatment algorithm for pharmacological conversion of AF 1

Rationale for Avoiding Procainamide in HFrEF

  1. Negative Inotropic Effects: Procainamide, as a Class IA antiarrhythmic, has significant negative inotropic properties that can further depress myocardial contractility in patients with already compromised cardiac function.

  2. Proarrhythmic Risk: Patients with structural heart disease, including HFrEF, have increased susceptibility to proarrhythmic effects of Class I antiarrhythmic drugs.

  3. Preferred Alternatives: The guidelines clearly establish IV amiodarone as the preferred agent for rhythm control in HFrEF patients with atrial fibrillation 1.

Guideline-Directed Medical Therapy for HFrEF

Current guideline-directed medical therapy (GDMT) for HFrEF focuses on four main drug classes that have demonstrated mortality benefit:

  • Renin-angiotensin system inhibitors (ACE inhibitors, ARBs, or ARNIs)
  • Evidence-based beta-blockers
  • Mineralocorticoid receptor antagonists
  • SGLT2 inhibitors 2

None of these guideline recommendations include procainamide or other Class I antiarrhythmic drugs as part of standard HFrEF management.

Special Considerations

While a small study from 1996 suggested that procainamide pharmacokinetics may not be significantly altered in patients with stable CHF receiving medical therapy (particularly ACE inhibitors) 3, this does not override the safety concerns and lack of efficacy data for procainamide in HFrEF.

Conclusion

Based on current guidelines, procainamide should be avoided in patients with HFrEF. For rhythm control in HFrEF patients with atrial fibrillation, IV amiodarone is the preferred pharmacological agent. Management should focus on optimizing guideline-directed medical therapy with proven mortality benefits.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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