Fulminant Vascular and Cardiac Toxicity Associated with Tyrosine Kinase Inhibitor Sorafenib

Cardiovasc Toxicol. 2019 Aug;19(4):382-387. doi: 10.1007/s12012-018-9499-2.

Abstract

The use of vascular endothelial growth factor inhibitors such as sorafenib is limited by a risk of severe cardiovascular toxicity. A 28-year-old man with acute myeloid leukemia treated with prednisone, tacrolimus, and sorafenib following stem cell transplantation presented with severe bilateral lower extremity claudication. The patient was discharged against medical advice prior to finalizing a cardiovascular evaluation, but returned 1 week later with signs suggestive of septic shock. Laboratory tests revealed troponin I of 12.63 ng/mL, BNP of 1690 pg/mL, and negative infectious workup. Electrocardiogram showed sinus tachycardia and new pathologic Q waves in the anterior leads. Coronary angiography revealed severe multivessel coronary artery disease. Peripheral angiography revealed severely diseased left anterior and posterior tibial arteries, tibioperoneal trunk, and peroneal artery, and subtotal occlusion of the right posterior tibial artery. Multiple coronary and peripheral drug-eluting stents were implanted. An intra-aortic balloon pump was placed. Cardiac magnetic resonance imaging revealed chronic left ventricular infarction with some viability, 17% ejection fraction, and left ventricular mural thrombi. The patient opted for medical management. Persistent symptoms 9 months later led to repeat angiography, showing total occlusion of the second obtuse marginal artery due to in-stent restenosis with proximal stent fracture, and chronic total occlusion of the right internal iliac artery extending to the pudendal branch. Cardiac positron emission tomography/computed tomography viability study demonstrated viable myocardium, deeming revascularization appropriate. Symptom resolution was obtained with no recurrences. Sorafenib-associated vasculopathy may follow a fulminant course. Multimodality cardiovascular imaging is essential for optimal management.

Keywords: Cardio-Oncology; Cardiotoxicity; Coronary artery disease; Sorafenib; Tyrosine kinase inhibitors; Vasculopathy.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antineoplastic Agents / toxicity*
  • Cardiotoxicity
  • Cardiovascular Agents / therapeutic use
  • Coronary Artery Disease / chemically induced*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / therapy
  • Coronary Restenosis / etiology
  • Coronary Restenosis / therapy
  • Defibrillators
  • Defibrillators, Implantable
  • Drug-Eluting Stents
  • Electric Countershock / instrumentation
  • Endovascular Procedures / instrumentation
  • Humans
  • Intra-Aortic Balloon Pumping
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Myocardial Infarction / etiology
  • Myocardial Infarction / therapy
  • Peripheral Arterial Disease / chemically induced*
  • Peripheral Arterial Disease / diagnostic imaging
  • Peripheral Arterial Disease / therapy
  • Protein Kinase Inhibitors / adverse effects*
  • Sorafenib / adverse effects*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Cardiovascular Agents
  • Protein Kinase Inhibitors
  • Sorafenib