Abstract Body (Do not enter title and authors here): Carfilizomib is a proteasome inhibitor used in the treatment of multiple myeloma. The incidence of arrhythmias according to one pooled analysis was 13.3%, mostly linked to mild supraventricular arrhythmias. We present a case of carfilzomib-induced complete heart block (CHB).

A 66-year-old male with a history of restrictive lung disease on 2 liters (L) oxygen, moderate aortic stenosis and multiple myeloma presented with shortness of breath and mild chest discomfort that started earlier that day. His most recent chemotherapy with carfilzomib, cyclophosphamide, and dexamethasone was 3 days prior to arrival. Oxygen requirements increased to 15L. Laboratory findings showed elevated high sensitivity troponins (600s), elevated brain natriuretic peptide (800), creatinine of 1.86 above baseline of 0.9. Chest x-ray revealed pulmonary edema. Initial electrocardiogram (EKG 1) showed 2nd degree, type 1 atrioventricular block, which was new compared to a prior EKG. Subsequent EKGs showed alternating bundle branch blocks with LBBB and RBBB (EKG 2) that progressed to eventual complete heart block (EKG 3). Echocardiogram revealed an ejection fraction of 55-59% without wall motion abnormalities and unchanged valve pathologies.

The patient was treated for acute heart failure with diuretics and fluid restriction. Cardiac catheterization was deferred as he did not have classic anginal symptoms. Oncology recommended discontinuation of carfilzomib. Electrophysiology recommended implantation of a permanent pacemaker (PPM) due to persistent complete heart block, which he successfully underwent, improving his symptoms.

The general arrhythmogenic effects of carfilzomib are established, however there is limited data on the specific types of arrhythmias. This case suggests that carfilzomib can result in CHB. Additional monitoring or early discontinuation of carfilzomib should be considered to prevent severe conduction abnormalities resulting in morbidity and potential mortality. Further research is necessary to elucidate underlying mechanisms and risk factors associated with carfilzomib-induced conduction abnormalities and whether they resolve with discontinuation of the medication.