What is the recommended dose of diltiazem (calcium channel blocker) for patients with diastolic dysfunction?

Diltiazem Dosing for Diastolic Dysfunction

For patients with diastolic dysfunction, diltiazem should be initiated at 120 mg daily (divided doses or long-acting formulation) and titrated up to a maximum of 360 mg daily based on symptom response, with careful monitoring for hypotension and bradycardia. 1, 2

Clinical Context and Mechanism

Diltiazem improves diastolic dysfunction through multiple mechanisms 1:

• Negative inotropic effects that reduce myocardial oxygen demand
• Heart rate reduction that prolongs the diastolic filling period, allowing more efficient inactivation of myocardial contractile proteins
• Direct improvement in diastolic performance measures as demonstrated in clinical studies 1

The ACCF/AHA guidelines specifically note that diltiazem has been shown to improve measures of diastolic performance and prevent myocardial ischemia, making it a reasonable second-line option when beta-blockers are not tolerated or ineffective 1.

Dosing Algorithm

Initial Dosing

• Start with 120 mg daily (either divided doses or single dose with long-acting formulations) 2
• For extended-release formulations (Cardizem CD), initiate at 120-180 mg once daily 2

Titration Strategy

• Titrate cautiously and progressively over several weeks to achieve symptom control 2
• Maximum maintenance dose is 360 mg daily (divided or single dose with long-acting formulations) 1, 2
• Monitor blood pressure and heart rate at each dose adjustment 2
• Reassess patients 1 month after initiation or dose change 2

Critical Contraindications and Precautions

Absolute Contraindications 1, 2

• Severe outflow tract obstruction (particularly in hypertrophic cardiomyopathy)
• Elevated pulmonary artery wedge pressure
• Low systemic blood pressure (hypotension)
• Second or third-degree AV block without a functioning pacemaker
• Decompensated systolic heart failure or severe LV dysfunction
• Wolff-Parkinson-White syndrome with atrial fibrillation/flutter

Use with Extreme Caution 1, 2

• Combination with beta-blockers: Risk of high-grade AV block and significant bradyarrhythmias 1, 2
• Hepatic dysfunction: Diltiazem is metabolized by the liver 2
• Renal dysfunction: May require dose adjustment 2
• PR interval >0.24 seconds: Increased risk of conduction abnormalities 2

Critical Clinical Pearls

The ACCF/AHA guidelines emphasize that diltiazem should be used cautiously in patients with severe outflow tract obstruction, elevated pulmonary artery wedge pressure, and low systemic blood pressure, because a decrease in blood pressure with treatment may trigger an increase in outflow obstruction and precipitate pulmonary edema. 1

Common Pitfalls to Avoid

• Do not use dihydropyridine calcium channel blockers (e.g., nifedipine) in patients with obstructive physiology, as their vasodilatory effects may aggravate outflow obstruction 1
• Avoid routine combination with beta-blockers unless carefully monitored, due to additive effects on AV conduction 1, 2
• Do not split or crush extended-release formulations 3

Monitoring Requirements 2

• Blood pressure and heart rate at each visit during titration
• Signs and symptoms of heart failure in at-risk patients
• ECG monitoring in patients with conduction system disease
• Liver function tests if clinically indicated
• Watch for peripheral edema (dose-related, more common in women; consider adding diuretics) 2

Special Populations

Patients with Heart Failure

Research demonstrates that diltiazem can improve left ventricular performance in severe congestive heart failure by reducing heart rate and afterload without significantly depressing contractile function 4. However, caution is warranted, and transient junctional arrhythmias may occur 4.

Uremic Patients on Hemodialysis

In uremic patients with isolated diastolic dysfunction, diltiazem 60 mg twice daily (120 mg total daily) significantly improved diastolic filling patterns and reduced intradialytic hypotension episodes 5.

Drug Interactions 2

Diltiazem is both a CYP3A4 substrate (major) and moderate CYP3A4 inhibitor. Use caution with:

• Apixaban, itraconazole, bosutinib, ceritinib, cilostazol
• Cyclosporine, everolimus, ibrutinib, idelalisib
• Ivabradine, lomitapide, olaparib, ranolazine, rifampin, simeprevir

Adverse Effects to Monitor 2

• Hypotension (most common)
• Bradycardia (may be dose-limiting)
• Worsening heart failure in patients with pre-existing ventricular dysfunction
• Peripheral edema (dose-related)
• Abnormal liver function tests and acute hepatic injury (rare)