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and increased baseline CV risk.282,283 PI have been associated with a variety of CV toxicities including hypertension, HF,284 acute coronary syndromes (ACS),66 arrhythmias,285 PH,286 and VTE (Figure 16).287,288 During therapy, cardiac biomarkers and TTE are important diagnostic and prognostic tools that can inform clinical decision-making (Figure 17).66 HF—especially HF with preserved ejection fraction (HFpEF)—is a frequent manifestation of cardiac amyloidosis, but it is also an important adverse effect of PI therapy, especially under carfilzomib. In a safety analysis of patients with MM being treated with carfilzomib, 7.2% of patients were found to have new HF.284 In another study, 23% of patients with MM treated with carfilzomib developed clinical HF and/or LVD.289 The mechanism is not well understood but is possibly related to PI-induced oxidative stress within myocytes, inhibition of the proteasome, or transient endothelial dysfunction.281,283 Although no studies have yet addressed the optimal follow-up scheme in patients with MM treated with PI, a common scheme consists of 3–6-monthly visits with ECG, complete blood Clinical assessment Clinical assessment BP and ECG TTE TTE every 3 cycles under carfilzomib Baseline During therapy NP Proteasome inhibitors surveillance protocol Lowmoderate risk High and very high risk Cardiac amyloidosis Clinical assessment BP and ECG TTE TTE every 3 cycles under carfilzomib NP NP every cycle during the first 6 cycles under carfilzomib or bortezomiba Clinical assessment BP and ECG TTE and CMR TTE every 3 cycles NP and cTn NP and cTn every 3-6 months BP at every clinical visit BP home monitoring Class 1 Class 1Ia Class 1Ib BP at every clinical visit BP home monitoring Clinical assessment BP at every clinical visit BP home monitoring Clinical assessment NP every cycle during the first 6 cycles under carfilzomib or bortezomiba Figure 17 Cardiovascular monitoring in patients with multiple myeloma receiving proteasome inhibitors. BP, blood pressure; CMR, cardiac magnetic resonance; cTn, cardiac troponin; ECG, electrocardiogram; NP, natriuretic peptides; TTE, transthoracic echocardiography. aEvery 2 months for patients treated with ixazomib. Downloaded from academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 07 October 2026