Management of Heart Failure Secondary to Dasatinib Therapy

Pathophysiology and Presentation

Dasatinib-induced cardiotoxicity can manifest as left ventricular dysfunction, heart failure, pericardial effusion, and pulmonary hypertension, according to the American College of Cardiology 1, 2, 3
Inhibition of SRC kinase by dasatinib can also lead to increased pulmonary vascular resistance, contributing to pulmonary hypertension, as noted by the American College of Cardiology 1

Transthoracic echocardiography is the primary diagnostic tool for evaluating cardiac function, pulmonary artery pressure, and presence of pericardial effusion, recommended by the American College of Cardiology 1, 2
Right heart catheterization is necessary to establish the definitive diagnosis of pulmonary hypertension if suspected, according to the American College of Cardiology 1, 4
Monitor for symptoms including dyspnea, cough, chest pain, tachycardia, and hypotension, which may indicate worsening heart failure or cardiac tamponade, as suggested by the American College of Cardiology and Leukemia 5, 2

Discontinue dasatinib therapy, as recommended by the American College of Cardiology 1, 2, 4
Initiate standard heart failure therapy, including ACE inhibitors or ARBs for patients with reduced ejection fraction, and beta-blockers, as suggested by the American Heart Association 6
Consider imatinib as an alternative TKI, which has a lower incidence of cardiotoxicity compared to dasatinib, according to the National Comprehensive Cancer Network 7, 8

Perform baseline and follow-up ECG and echocardiography after switching to alternative TKI, as recommended by Leukemia 8, 9
Monitor for QT prolongation, especially if switching to nilotinib, and evaluate cardiac function periodically with echocardiography, as suggested by Leukemia 9, 8
Aggressive management of cardiovascular risk factors is recommended for all patients on TKI therapy, according to the American Heart Association 6

Dasatinib-induced heart failure and pulmonary hypertension are often reversible after discontinuation of the drug, as noted by the American College of Cardiology 1, 4
Partial or complete reversal of pulmonary hypertension is typically seen within 4 months after cessation of dasatinib, according to the American College of Cardiology 1

Elderly patients and those with pre-existing cardiovascular disease are at higher risk for developing dasatinib-induced cardiotoxicity, as suggested by Leukemia and the National Comprehensive Cancer Network 5, 7
Patients with previous cardiac history should be monitored more carefully when on any TKI therapy, according to the National Comprehensive Cancer Network 7

Dasatinib is associated with pulmonary arterial hypertension (PAH) in 5% of patients compared to <1% with imatinib in the DASISION study, which can contribute to or worsen diastolic heart failure 10
Pleural effusion is common (28-33% of patients) and can worsen cardiac function, as reported in the Journal of the National Comprehensive Cancer Network 10

Patients with prior cardiac history and hypertension are at increased risk of developing cardiac complications while on dasatinib, according to the National Comprehensive Cancer Network 10
Elderly patients are at higher risk for developing pleural effusions and subsequent cardiac complications, as noted in the Journal of the National Comprehensive Cancer Network 10

Permanently discontinue dasatinib if pulmonary arterial hypertension is confirmed, as recommended by the National Comprehensive Cancer Network 10
Treatment interruption and reintroduction at a lower dose (50 mg daily instead of 100 mg) may be effective for patients with mild intolerance, according to the National Comprehensive Cancer Network 10