Abstract Body (Do not enter title and authors here): Introduction: Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy has been associated with cardiotoxicity, particularly hypertension. Cardiomyopathy and ventricular arrhythmias (VA) have rarely been reported.

Case Report: A 51-year-old male with metastatic sarcoma on pazopanib, a VEGFR-TKI, for the past 4 years presented with 1 month of increasing palpitations and lightheadedness leading to a fall. On arrival, telemetry showed paroxysmal AF with RVR rates to 120 bpm followed by incessant runs of NSVT with rates 200-240 bpm. Initial labs included BNP 191 pg/mL and HS troponin-I 6 ng/L (<5 ng/L). Lidocaine infusion, amiodarone infusion, and metoprolol were required to reduce NSVT burden. Initial TTE revealed LVEF of 30-35% from baseline 55-60%. Coronary angiography showed no significant CAD. Cardiac MRI was negative for LGE or metastatic involvement. Cardiac PET-CT revealed moderate diffuse FDG uptake with focal enhancement suggestive of an inflammatory process. Pazopanib was stopped and the patient started on GDMT and prednisone taper for treatment of myocarditis.

At 2 months follow up, TTE revealed LVEF improved to 45-50% and ambulatory rhythm monitoring showed rare PVCs and few NSVT episodes. Repeat cardiac PET-CT revealed resolution of myocardial inflammation.

Due to sarcoma progression, the patient started on regorafenib, another VEGFR-TKI, 3 months after initial hospitalization. About 3 weeks later, he presented with frequent NSVT which required lidocaine and amiodarone infusions for arrhythmia control. Repeat cardiac PET demonstrated myocarditis recurrence. He received intravenous pulse dose steroids followed by prednisone taper and was transitioned to oral mexiletine and amiodarone with resolution of VA. Review of ambulatory rhythm monitoring 1 week following regorafenib initiation already showed 20.6% burden of ventricular ectopy and >8000 NSVT episodes.

Discussion: This patient had an unusual, delayed presentation of VEGFR-TKI induced myocarditis presenting with significant VA. Although TKI induced myocarditis is rare and the mechanism is not well understood, recurrence of myocarditis in this case with an alternative agent indicates a possible medication-class effect.