Table 3.
Summary of Key Symptoms, Testing, Risk Stratification, and Suggested Management for BTK Inhibitor Associated Cardiotoxicities
| Atrial fibrillation | |
| Symptoms | Palpitations, shortness of breath, chest pain |
| Testing | Obtain 12-lead ECG, transthoracic echocardiogram; consider extended Holter monitoring |
| Risk-stratification | Atrial dilation, depressed LVEF, myocardial fibrosis on CMR, CHA2DS2-VASc >1 |
| Treatment | Anticoagulation (consider if CHA2DS2-VASc >1), rate control with beta-blockers, consider switching to alternative BTK inhibitor or dose reduction |
| Hypertension | |
| Symptoms | Elevated blood pressure >130/80 mm Hg in a continued pattern |
| Testing | In-office and ambulatory blood pressure monitoring, 12-lead ECG, transthoracic echocardiogram |
| Risk-stratification | Elevated blood pressure on 2 or more readings in office or at home over 3 months, LVH on echocardiography or CMR, or LVH on ECG |
| Treatment | Target blood pressure of <130/80 mm Hg giving priority to RAAS agents, beta-blockers |
| Ventricular arrhythmias | |
| Symptoms | Palpitations, chest pain, syncope, signs of heart failure |
| Testing | Obtain 12-lead ECG, transthoracic echocardiogram; consider extended Holter monitoring. If VA noted or clinical suspicion is high, obtain CMR |
| Risk-stratification | Evidence of late-gadolinium enhancement or abnormal T1/T2 on CMR, depressed LVEF on echocardiography or CMR |
| Treatment | Consider holding BTK inhibitor (immediately if prolonged VT or cardiac arrest); resume with caution or consider alternative therapy |
| Heart failure | |
| Symptoms | Dyspnea, exertional intolerance, edema, orthopnea |
| Testing | Obtain 12-lead ECG, transthoracic echocardiogram, consider BNP and CMR |
| Risk-stratification | Reduced LVEF (<50%) on functional cardiac assessment |
| Treatment | Consider holding BTK inhibitor. Initiate RAAS agents, beta-blockers, SGLT2 inhibitors as able. Periodic functional assessment every 6-12 mo with echocardiography or CMR |
| Stroke | |
| Recommendations | Anticoagulation with DOAC for those patients with AF and elevated CHA2DS2-VASc score (eg, >1) in whom bleeding risk is not prohibitive (eg, no prior issues with bleeding) |
| Bleeding | |
| Recommendations | Majority of bleeding events are minor, and most patients can continue therapy. However, if a patient has a history of major hemorrhage, this may warrant further risk-benefit analysis if anticoagulation is to be considered for patients with AF on BTK inhibitor |
Note: Shared decision-making with patients should be considered where appropriate.
AF = atrial fibrillation; BNP = B-type natriuretic peptide; BTK = Bruton’s tyrosine kinase; CMR = cardiac magnetic resonance imaging; DOAC = direct oral anticoagulant; LVEF = left ventricular ejection fraction; LVH = left ventricular hypertrophy; RAAS = renin-angiotensin-aldosterone-system; SGLT2 = sodium-glucose cotransporter-2; VA = ventricular arrhythmia; VT = ventricular tachycardia.