Does diltiazem (Calcium Channel Blocker) have negative inotropic effects?

From the Guidelines

Diltiazem does have negative inotropic effects, which can reduce the force of heart contractions and should be used with caution in patients with heart failure or significantly impaired left ventricular function. Diltiazem is a calcium channel blocker that works by blocking L-type calcium channels in cardiac and vascular smooth muscle cells, which reduces the influx of calcium during depolarization. In the heart, this calcium channel blockade decreases myocardial contractility, resulting in a negative inotropic effect. This property makes diltiazem useful in treating conditions like hypertension, angina, and certain arrhythmias. According to the 2012 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1, calcium-channel blockers like diltiazem should be discontinued unless absolutely necessary due to their negative inotropic effect. The negative inotropic effect of diltiazem is also dose-dependent and generally less pronounced than with non-dihydropyridine calcium channel blockers like verapamil, as noted in the 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation 1. Clinicians should monitor patients for signs of worsening heart failure when initiating diltiazem, particularly in those with pre-existing cardiac dysfunction.

Some key points to consider when using diltiazem include:

• Typical doses range from 120-360 mg daily for extended-release formulations, with lower doses recommended for elderly patients or those with hepatic impairment.
• Diltiazem should be used with caution in patients with heart failure or significantly impaired left ventricular function, as it can worsen these conditions.
• The medication can cause hypotension, and patients should be monitored for signs of symptomatic hypotension, such as dizziness, light headedness, or confusion.
• If symptomatic hypotension occurs, the dose of diltiazem may need to be reduced or stopped, as recommended in the 2012 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1.

Overall, while diltiazem can be a useful medication for certain conditions, its negative inotropic effects must be carefully considered and monitored, particularly in patients with pre-existing cardiac dysfunction. As stated in the 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care 1, caution is advised when using AV nodal blocking agents like diltiazem, especially in patients with heart failure or significantly impaired left ventricular function.

From the FDA Drug Label

Although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function have not shown a reduction in cardiac index nor consistent negative effects on contractility (dP/dt)

• Negative inotropic effect is present in isolated animal tissue preparations
• However, in humans with normal ventricular function, no consistent negative effects on contractility were observed
• Caution is advised when using diltiazem in patients with impaired ventricular function due to limited experience 2

From the Research

Diltiazem's Inotropic Effects

• Diltiazem has been found to have negative inotropic effects, although the degree of this effect varies depending on the study and the specific context [(3,4)].
• One study ranked the negative inotropic effects of calcium antagonists, with verapamil having the greatest effect, followed by nifedipine, diltiazem, and then isradipine 3.
• However, other studies have suggested that diltiazem's negative inotropic effects are relatively weak, particularly at therapeutic concentrations [(5,6)].

Comparison with Other Calcium Antagonists

• Diltiazem's negative inotropic effects are generally considered to be less pronounced than those of verapamil, but more significant than those of nifedipine [(3,5,4)].
• The haemodynamic effects of diltiazem are similar to those of verapamil, but with less potency in inducing arterial dilatation and a greater tendency to slow the heart rate 4.

Clinical Implications

• The negative inotropic effects of diltiazem may be a concern in patients with compromised cardiac function, particularly those with congestive heart failure [(3,5)].
• However, diltiazem's relative lack of negative inotropic effects may make it a safer choice for patients with heart failure, particularly when control of supraventricular tachyarrhythmia is required 5.
• The use of diltiazem in patients with heart failure should be approached with caution, and its effects on cardiac function should be carefully monitored 7.