Abstract Proteasome inhibitors such as carfilzomib are indicated in multiple myeloma patients showing relapse and/or refractoriness of clonal activity after initial treatment. However, this therapy has been associated with a significative incidence of cardiotoxicity, especially in patients with known cardiovascular risk factors. Here we report a case of a 60-year-old woman with multiple myeloma, who developed congestive severe heart failure with positive myocardial lesion biomarkers and LVEF and strain reduction, after treatment with carfilzomib. Therefore chemotherapeutic drug was discontinued and neurohormonal blocking and diuretic therapy was started resulting in amelioration of symptoms, without changes in LVEF but with significant GLS improvement. This case illustrates the behavior of carfilzomib induced cardiotoxicity and the expected response to the appropriate pharmacological management. Although high-grade cardiotoxicity is relatively rare in patients with non previous cardiac risk factors, it was a predictable side effect of carfilzomib use. Recognition of this syndrome is critical to instauration of appropriate therapy and prevention of morbimortality.