Cardiotoxicity of Novel Targeted Hematological Therapies

Figures

• 

  Figure 1. Cardiotoxicity of Bruton’s tyrosine kinase (BTK) inhibitors. BTK inhibitors can interfere with phosphoinositide 3-kinase (PI3K) pathways in cardiomyocytes, influence normal ion current, and cause action potential prolongation and abnormal automaticity leading to arrhythmias, such as atrial fibrillation (AF), premature ventricular contractions (PVC), ventricular tachycardia or fibrillation (VT/VF), and QT interval prolongation (QT/QTc). In platelets, BTK is activated by Von-Willebrand factor (VWF), collagen, and fibrinogen binding to cognate glycoproteins (e.g., Gp1b), leading to platelet activation. BTK inhibition in platelets is associated to central nervous system (CNS) bleeding or ischemia.

• 

  Figure 2. Cardiotoxicity of Janus kinase (JAK) inhibitors. JAK inhibitors can interfere with growth hormone and leptin pathways in adipocytes, causing dysregulation of lipolysis, metabolism, and blood pressure homeostasis. In adipocytes, JAK/signal transducer and activator of transcription (STAT) pathway, mainly through STAT5, is involved in regulation of lipolysis, glucose and lipid metabolism, response to insulin stimulation, and regulation of blood pressure. Inhibition of JAK/STAT in adipocytes can contribute to metabolic changes leading to weight gain and arterial hypertension development.

• 

  Figure 3. Cardiotoxicity of B cell receptor (BCR)/ABL tyrosine kinase inhibitors (TKIs). Cardiotoxicity of (A) nilotinib and (B) ponatinib. Inhibitors of BCR/ABL activity cause various forms of cardiotoxicity, such as congestive heart failure (CHF), myocardial infarction (MI), acute coronary syndrome (ACS), coronary artery disease (CAD), peripheral artery disease (PAD), peripheral arterial occlusive disease (PAOD), venous thromboembolisms (VTEs), and arrhythmias. SCD, sudden cardiac death; SVT, supraventricular tachycardia; CAVB, complete atrioventricular block; SB, sinus bradycardia. * Uncommon and rare cardiotoxicity (frequency <1% or case reports).