Management of Heart Failure Secondary to Dasatinib Therapy
The most effective management of dasatinib-induced heart failure is immediate discontinuation of dasatinib and switching to an alternative tyrosine kinase inhibitor (TKI). 1
Pathophysiology and Presentation
- Dasatinib-induced cardiotoxicity can manifest as left ventricular dysfunction, heart failure, pericardial effusion, and pulmonary hypertension 1
- The mechanism involves inhibition of c-Src kinase in cardiomyocytes, which compromises cardiomyocyte viability and attenuates the activity of extracellular signal-regulated kinase (ERK) 2
- Inhibition of SRC kinase by dasatinib can also lead to increased pulmonary vascular resistance, contributing to pulmonary hypertension 1
Diagnostic Approach
- Transthoracic echocardiography is the primary diagnostic tool for evaluating cardiac function, pulmonary artery pressure, and presence of pericardial effusion 1
- Right heart catheterization is necessary to establish the definitive diagnosis of pulmonary hypertension if suspected 1
- Monitor for symptoms including dyspnea, cough, chest pain, tachycardia, and hypotension, which may indicate worsening heart failure or cardiac tamponade 1
Management Algorithm
Step 1: Immediate Management
- Discontinue dasatinib therapy 1
- Initiate standard heart failure therapy:
Step 2: Switch to Alternative TKI
- Imatinib is preferred as it has a lower incidence of cardiotoxicity compared to dasatinib 1
- Bosutinib may be considered as an alternative if imatinib is not suitable 1
- Avoid nilotinib and ponatinib in patients with cardiovascular disease due to their association with cardiovascular events 1
- Consider asciminib for patients with severe cardiac comorbidities, as it targets a different site of the BCR::ABL1 protein and has shown better cardiac safety profile 4
Step 3: Management of Specific Complications
For Pulmonary Hypertension:
- Follow monthly with echocardiogram for serial assessment of pulmonary artery pressure 1
- Consider treatment with sildenafil, endothelin antagonists, or calcium channel blockers if pulmonary hypertension persists 1
For Pleural Effusion:
- For mild to moderate effusions: treatment suspension or dose reduction of the new TKI, with or without steroids and diuretics 1
- For severe effusions (grade 3-4): thoracocentesis may be necessary 1
- If pleural effusions recur after switching TKIs, consider stepwise lowering of the dose 1
For Pericardial Effusion:
- Small to moderate asymptomatic effusions may be monitored with serial echocardiography 1
- Symptomatic effusions may require pericardiocentesis, especially if cardiac tamponade is present 1
- Consider NSAIDs and colchicine for inflammatory pericardial effusions 5
Monitoring and Follow-up
- Perform baseline and follow-up ECG and echocardiography after switching to alternative TKI 1
- Monitor for QT prolongation, especially if switching to nilotinib (QTc >440 ms requires weekly monitoring) 1
- Evaluate cardiac function periodically with echocardiography, particularly in patients with pre-existing cardiovascular risk factors 1
- Aggressive management of cardiovascular risk factors is recommended for all patients on TKI therapy 1
Prognosis
- Dasatinib-induced heart failure and pulmonary hypertension are often reversible after discontinuation of the drug 1, 6
- Partial or complete reversal of pulmonary hypertension is typically seen within 4 months after cessation of dasatinib 1, 6
- Long-term cardiac monitoring is still recommended as some patients may have residual cardiac dysfunction 7, 8
Special Considerations
- Elderly patients and those with pre-existing cardiovascular disease are at higher risk for developing dasatinib-induced cardiotoxicity 1, 5
- Patients with previous cardiac history should be monitored more carefully when on any TKI therapy 1
- Dasatinib may increase doxorubicin accumulation in myocytes if used concurrently, potentially exacerbating cardiotoxicity 8