Recurrent heart failure with preserved ejection fraction associated with carfilzomib administration for multiple myeloma

Yang, Eric H.; Courtney, Cynthia L.; Garg, Vinisha; Fradley, Michael G.; Schiller, Gary J.

doi:10.1186/s40959-018-0028-z

Cited by 3 publications

(2 citation statements)

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“…Patients with MM have a greater probability of developing cardiovascular events than general population independent of the established cancer treatment [ 5 ]. Among the known risks factors there are those related to the patient (age and other classic cardiovascular risk factors), those specifically related to the disease (chronic anemia, kidney failure, hyperviscosity, amyloidosis, proteinuria), and those related to oncological treatment itself such as the receptors of ASCT or specific chemotherapeutic cardiotoxicity [ 6 – 8 ].…”

Section: Discussionmentioning

confidence: 99%

Carfilzomib induced cardiotoxicity in a multiple myeloma patient

2020

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Proteasome inhibitors such as carfilzomib are indicated in multiple myeloma patients showing relapse and/or refractoriness of clonal activity. However, this therapy has been associated with a significant 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 severe congestive heart failure with positive myocardial injury biomarkers together with impaired LVEF and GLS, 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. 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.

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Section: Discussionmentioning

confidence: 99%

Carfilzomib induced cardiotoxicity in a multiple myeloma patient

2020

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“…The investigators did not find troponin to be having predictive capacity [35••]. Following BNP levels is common in other reports, including a patient on carfilzomib as a phase Ib clinical trial [96], a case series of 12 patients [90], the PROTECT study [35••], and a retrospective analysis from University of Arkansas [97], to name a few. However, it is difficult to discern whether or not elevations in BNP levels correlate with increased clinical symptoms or hospitalizations [34,74], and RCTs will be needed to answer this question definitively.…”

Section: Monitoring For Cardiotoxicity During Proteasome Inhibitor Thmentioning

confidence: 99%

Proteasome Inhibitor-Related Cardiotoxicity: Mechanisms, Diagnosis, and Management

Oren

Gertz

et al. 2020

Curr Oncol Rep

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Purpose of Review Multiple myeloma is the second most common hematologic malignancy in the USA, with over 32,000 new cases and nearly 13,000 deaths expected in 2019. The past few decades in myeloma research have yielded significant advances, leading to the expansion of novel anti-myeloma agents. This review describes the incidence and mechanisms of cardiotoxicity for the FDA-approved proteasome inhibitors in myeloma and proposes strategies to assess and manage resultant cardiovascular adverse events. Recent Findings Proteasome inhibition precipitates protein aggregation and alters transcriptional activation of NF-κB targets which contributes to a pro-apoptotic signaling cascade in myeloma cells. Similar effects in cardiomyocytes and vascular smooth muscle endothelium, along with off-target downregulation of autophagy and signaling alterations of nitric oxide homeostasis, may be linked to observed cardiotoxic effects. There is preliminary evidence for cardioprotective potential for rutin, dexrazoxane, and apremilast that could have clinical applicability in the future. Summary Of the proteasome inhibitors used in clinical practice, carfilzomib is the most strongly associated with cardiotoxicity. Patients with anticipated carfilzomib treatment should undergo assessment and optimization of baseline cardiovascular risk, with close monitoring during treatment. Previous clinical trials were not specifically designed to assess proteasome inhibitor-related cardiotoxicity, creating a need for future studies to identify and risk stratify vulnerable individuals and to develop potential cardioprotective strategies in attenuating cardiac injury.

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