What is the treatment for cardiomyopathy induced by dasatinib (Sprycel) in patients with preserved heart failure?

Treatment of Cardiomyopathy Induced by Dasatinib in Preserved Heart Failure

The primary treatment for dasatinib-induced cardiomyopathy with preserved heart failure is immediate discontinuation of dasatinib and initiation of standard heart failure therapy, including ACE inhibitors/ARBs and beta-blockers, with consideration of switching to an alternative tyrosine kinase inhibitor with a more favorable cardiovascular profile such as imatinib. 1

Initial Management

• Discontinue dasatinib therapy immediately as recommended by the American College of Cardiology 1
• Perform transthoracic echocardiography to evaluate cardiac function, pulmonary artery pressure, and presence of pericardial effusion 1
• Monitor for symptoms including dyspnea, cough, chest pain, tachycardia, and hypotension, which may indicate worsening heart failure 1

Pharmacological Management

• Initiate standard heart failure therapy for preserved ejection fraction:

  • Beta-blockers to lower heart rate and increase diastolic filling period 2, 1
  • Verapamil-type calcium antagonists may be beneficial for improving relaxation and cardiac distensibility 2
  • ACE inhibitors to improve relaxation and cardiac distensibility 2, 1
  • Diuretics for episodes of fluid overload, used cautiously to avoid excessive preload reduction 2, 1

• If ventricular tachycardia is present, consider antiarrhythmic therapy:

  • Amiodarone and bisoprolol have been used successfully in cases of dasatinib-induced cardiomyopathy with ventricular tachycardia 3

Alternative Cancer Treatment Options

• Consider switching to imatinib as an alternative TKI, which has a lower incidence of cardiotoxicity compared to dasatinib 1, 4
• If continuation of tyrosine kinase inhibitor therapy is necessary, the European Society of Cardiology recommends avoiding dasatinib in patients with severe (NYHA class III and IV) heart failure 4
• Monitor for QT prolongation if switching to nilotinib, as it has its own cardiovascular risk profile 1

Monitoring and Follow-up

• Perform baseline and follow-up ECG and echocardiography after switching to an alternative TKI 1
• Evaluate cardiac function periodically with echocardiography 1
• Monitor for reversal of pulmonary hypertension, which typically occurs within 4 months after cessation of dasatinib 1

Pathophysiological Considerations

• Dasatinib-induced cardiotoxicity is primarily mediated through inhibition of c-Src kinase in cardiomyocytes 5
• Cardiomyocytes are the most sensitive cardiac cell type to dasatinib-induced cell death 5
• Dasatinib can cause left ventricular dysfunction, heart failure, pericardial effusion, and pulmonary hypertension 1, 6

Special Considerations

• Elderly patients and those with pre-existing cardiovascular disease are at higher risk for developing dasatinib-induced cardiotoxicity 1
• Patients with prior cardiac history and hypertension require particularly careful monitoring 4
• Dasatinib-induced heart failure and pulmonary hypertension are often reversible after discontinuation of the drug 1

Treatment Algorithm

1. Immediately discontinue dasatinib 1
2. Assess cardiac function via echocardiography 1
3. Initiate heart failure therapy with beta-blockers and ACE inhibitors 2, 1
4. Add diuretics if fluid overload is present 2, 1
5. Consider calcium channel blockers (verapamil type) if no contraindications exist 2
6. Switch to imatinib as alternative cancer therapy 1, 4
7. Monitor cardiac function regularly with follow-up echocardiography 1
8. Aggressively manage cardiovascular risk factors 1