Why is Cardizem (diltiazem) contraindicated in heart failure?

Why Diltiazem (Cardizem) is Contraindicated in Heart Failure

Diltiazem (Cardizem) is not recommended in patients with heart failure with reduced ejection fraction (HFrEF) because it increases the risk of heart failure worsening and hospitalization due to its negative inotropic effects. 1

Mechanism of Action and Negative Effects in Heart Failure

• Diltiazem is a non-dihydropyridine calcium channel blocker that exerts significant negative inotropic effects (decreases cardiac contractility) at vasodilatory dosages 2
• In patients with normal or mildly impaired left ventricular function, diltiazem's vasodilator and negative inotropic effects may be counterbalanced, but in severe left ventricular dysfunction, treatment with diltiazem can result in abrupt decompensation 2
• The negative inotropic effects can lead to development of overt pulmonary edema and hypotension in patients with compromised cardiac function 2

Guidelines and Recommendations

• The 2016 European Society of Cardiology (ESC) guidelines explicitly state that diltiazem is not recommended in patients with HFrEF (Class III recommendation, Level C evidence) 1
• Diltiazem and verapamil-type calcium antagonists are specifically contraindicated in heart failure due to systolic dysfunction 1
• The ESC guidelines classify diltiazem among "treatments that may cause harm in patients with symptomatic heart failure with reduced ejection fraction" 1

Clinical Evidence of Harm

• A 2024 study found that patients with HFrEF 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
• This clinical deterioration included increased utilization of inotropes and vasopressors, and higher rates of transfer to ICU 3

Alternative Treatments for Rate Control in Heart Failure

• Beta-blockers are preferred over calcium channel blockers for rate control in heart failure patients 1
• For patients with atrial fibrillation and heart failure, the recommended rate control agents include:
  • Beta-blockers (first-line) 1
  • Digoxin (can be used alone or in combination with beta-blockers) 1
  • Amiodarone (for rhythm control in severe heart failure) 1

Exceptions and Controversies

• Some smaller studies have suggested that diltiazem may be used cautiously in specific situations:
  • A small study (n=8) showed that carefully monitored intravenous diltiazem improved left ventricular performance in severe heart failure through heart rate and afterload reduction, but caution was advised due to potential electrophysiologic adverse effects 4
  • A 2019 retrospective study found that for acute management of atrial fibrillation with rapid ventricular response in HFrEF patients, diltiazem achieved similar rate control with no increase in adverse events compared to metoprolol, but this was a small sample (n=48) 5
  • A 2022 study also found similar safety and effectiveness between diltiazem and metoprolol for atrial fibrillation with rapid ventricular response in heart failure patients 6

Clinical Decision Making

• Despite some conflicting evidence from small studies, the major guidelines and larger studies consistently recommend against using diltiazem in heart failure patients 1, 3
• The potential risks of worsening heart failure, clinical deterioration, and increased hospitalization outweigh any potential benefits of using diltiazem in these patients 1, 3
• For rate control in heart failure patients with atrial fibrillation, beta-blockers should be used as first-line therapy, with digoxin as an alternative or adjunctive agent 1

Important Caveat

• While diltiazem is contraindicated in heart failure with reduced ejection fraction, it may still be considered in patients with heart failure with preserved ejection fraction (HFpEF) when rate control is needed, though caution is still warranted 6