Can Dasatinib (Sprycel) cause diastolic heart failure?

Dasatinib and Diastolic Heart Failure

Yes, dasatinib (Sprycel) can cause diastolic heart failure, as evidenced by FDA labeling that specifically lists "diastolic dysfunction" among its cardiac adverse effects. 1

Cardiovascular Complications of Dasatinib

Cardiac Dysfunction

• The FDA label for dasatinib explicitly mentions "diastolic dysfunction" as part of the spectrum of cardiac complications that can occur with treatment 1
• Dasatinib-related cardiac dysfunction includes cardiac failure acute, cardiac failure congestive, cardiomyopathy, diastolic dysfunction, ejection fraction decreased, and left ventricular dysfunction 1
• These cardiac complications were reported in approximately 2% of patients in clinical trials 1

Pulmonary Hypertension and Related Complications

• Dasatinib is associated with pulmonary arterial hypertension (PAH) in 5% of patients compared to <1% with imatinib in the DASISION study 2, 3
• PAH can contribute to or worsen diastolic heart failure by increasing right heart pressure and affecting left ventricular filling 4, 5
• The mechanism may involve inhibition of SRC kinase, which regulates smooth muscle proliferation and vasoconstriction 3, 6

Fluid Retention Syndrome

• Dasatinib causes fluid retention in 38-51% of patients, which can exacerbate heart failure symptoms 1
• Pleural effusion is common (28-33% of patients) and can worsen cardiac function 2, 3
• Pericardial effusion occurs in approximately 4% of patients and may contribute to cardiac dysfunction 1

Risk Factors and Monitoring

High-Risk Patients

• Patients with prior cardiac history and hypertension are at increased risk of developing cardiac complications while on dasatinib 2, 7
• The European Society of Cardiology recommends avoiding dasatinib in patients with severe (NYHA class III and IV) cardiac failure 7
• Elderly patients are at higher risk for developing pleural effusions and subsequent cardiac complications 2, 4

Recommended Monitoring

• Baseline cardiac evaluation with echocardiography before initiating dasatinib therapy 4, 3
• Regular monitoring of cardiac function with echocardiography during treatment 4, 5
• Assessment for symptoms of heart failure including dyspnea, fatigue, and fluid retention 4, 1

Management of Dasatinib-Induced Cardiac Complications

When to Discontinue Therapy

• Permanently discontinue dasatinib if pulmonary arterial hypertension is confirmed 2, 4
• Consider discontinuation if significant diastolic dysfunction or heart failure develops 4, 8
• Cardiac complications are often reversible after discontinuation of dasatinib 9, 8

Alternative Treatment Options

• Consider switching to imatinib, which has a more favorable cardiovascular profile 7, 4
• Nilotinib is another alternative, though it has its own cardiovascular risk profile (particularly QT prolongation) 7, 4
• Treatment interruption and reintroduction at a lower dose (50 mg daily instead of 100 mg) may be effective for patients with mild intolerance 2, 3

Supportive Care

• Standard heart failure therapy should be initiated for patients with reduced ejection fraction or diastolic dysfunction 4, 10
• Calcium channel blockers or beta-blockers may be particularly useful in diastolic dysfunction 10
• Diuretics may help manage fluid retention symptoms 4, 10

Clinical Course and Prognosis

• Dasatinib-induced cardiac complications, including diastolic dysfunction, are often reversible after discontinuation 4, 9
• Improvement in cardiac function typically begins within one month of discontinuation 9, 8
• Complete resolution of pulmonary hypertension may take up to 4 months 4, 8

In conclusion, dasatinib can cause diastolic heart failure as part of its cardiovascular toxicity profile. Clinicians should be vigilant about monitoring cardiac function in patients receiving this medication, particularly those with pre-existing cardiovascular risk factors.