Is Cardizem (diltiazem) harmful to patients with heart failure?

Diltiazem in Heart Failure: Risks and Recommendations

Diltiazem is contraindicated in patients with heart failure with reduced ejection fraction (HFrEF) due to its negative inotropic effects and risk of worsening heart failure.

Guideline Recommendations

The European Society of Cardiology (ESC) guidelines explicitly state that diltiazem and verapamil "are not recommended to reduce blood pressure in patients with HFrEF because of their negative inotropic action and risk of worsening HF" 1. This recommendation carries a Class III level C recommendation, indicating potential harm.

The ESC guidelines for management of atrial fibrillation further clarify that although diltiazem effectively controls heart rate during exercise, "it adversely suppresses myocardial contraction and increases the risk of heart failure" 1. However, the guidelines do note that for patients with heart failure and preserved ejection fraction (HFpEF), diltiazem may be considered in combination with digoxin.

Mechanism of Harm

Diltiazem's FDA label explicitly warns about its negative inotropic effects and potential risks in heart failure patients:

• "Diltiazem has a negative inotropic effect in isolated animal tissue preparations"
• "Experience with the use of diltiazem hydrochloride alone or in combination with beta-blockers in patients with impaired ventricular function is very limited"
• "Caution should be exercised when using the drug in such patients" 2

Different Types of Heart Failure

The safety profile of diltiazem differs significantly based on the type of heart failure:

1. Heart Failure with Reduced Ejection Fraction (HFrEF):

   • Diltiazem is contraindicated due to negative inotropic effects 1
   • Recent research shows increased risk of clinical deterioration when used in HFrEF patients 3
   • Higher incidence of worsening heart failure symptoms compared to metoprolol 4

2. Heart Failure with Preserved Ejection Fraction (HFpEF):

   • May be considered for rate control in atrial fibrillation 1
   • ESC guidelines state that "β-blockers, verapamil or diltiazem should be considered, to improve heart failure symptoms" in patients with HFpEF 1

Recent Evidence

Recent studies have examined the safety of diltiazem in heart failure patients:

• A 2024 study found that patients with reduced EF who received diltiazem despite clinical decision support system warnings had a higher proportion of clinical deterioration (33% vs 21%, p=0.044) compared to those who did not receive diltiazem 3

• A 2022 study comparing diltiazem and metoprolol for atrial fibrillation with rapid ventricular response in heart failure patients found a significantly higher incidence of worsening heart failure symptoms in the diltiazem group (33% vs 15%, p=0.019) 4

Alternative Medications for Rate Control in Heart Failure

For patients with heart failure requiring rate control (particularly for atrial fibrillation):

1. For HFrEF patients:

   • Beta-blockers (metoprolol, carvedilol, bisoprolol) are first-line agents 5
   • Digoxin may be considered as an adjunct therapy 1
   • Amiodarone can be considered for rhythm control 1

2. For HFpEF patients:

   • Beta-blockers, verapamil, or diltiazem may be considered 1
   • Combination of digoxin with diltiazem may be more effective than monotherapy 1

Clinical Pearls and Pitfalls

1. Common pitfall: Using diltiazem for rate control in undifferentiated heart failure patients without assessing ejection fraction first.

2. Caution: Even in HFpEF patients, monitor closely for signs of worsening heart failure when using diltiazem.

3. Risk factors for adverse outcomes with diltiazem in heart failure:

   • Ejection fraction <40%
   • Recent decompensation
   • Concomitant use with beta-blockers (may cause additive effects on cardiac conduction) 2

4. Monitoring: If diltiazem must be used in heart failure patients (only appropriate in HFpEF), monitor for:

   • Hypotension
   • Worsening heart failure symptoms
   • Increased oxygen requirements
   • Need for inotropic support

Conclusion

While diltiazem may have beneficial hemodynamic effects in some cardiovascular conditions, its negative inotropic properties make it harmful for patients with heart failure with reduced ejection fraction. Current guidelines strongly recommend against its use in HFrEF patients, though it may be considered with caution in patients with preserved ejection fraction.