Introduction
Multiple myeloma (MM) is a malignant plasma cell disease characterized by abnormal proliferation of bone marrow plasma cells with excessive production of monoclonal immunoglobulin or light chain M protein, which seriously affect the quality of life of patients. 1 In the current study, the application of proteasome inhibitors (PIs) and immunomodulators can effectively improve the survival outcome of MM patients. 2 , 3 Carfilzomib, a new type of PI, is composed of a tetrapeptide epoxy ketone structure. 4 In 2012, it was approved by the U.S. Food and Drug Administration for patients with relapsed or refractory MM, and then a variety of carfilzomib combination regimens were successively approved. 5 , 6 In 2021, carfilzomib was approved for sale in China, providing a new treatment for MM patients in China. 7 Common causes of dose adjustment or treatment interruption of carfilzomib include neutropenia, hypertension, coronary heart disease, and renal insufficiency. 8 – 10 We reported the clinical diagnosis and treatment process of a case of bradycardia caused by carfilzomib in a patient with MM, and summarized the relevant literature, aiming to attract the attention of clinicians to strengthen the monitoring of relevant indicators.
Case presentation
This was a case of a 55-year-old female with MM (158 cm, 59.5 kg, body surface area: 1.63 m 2 ). In August 2024, the patient presented with intermittent pain in the right upper arm, which had aggravated for more than half a month, and resulted in a limitation of mobility. The examination conducted at the local hospital showed a lesion in the right humerus. To obtain further diagnosis and treatment, the patient came to our hospital on September 13. The patient self-reported no history of hypertension, heart disease, or familial genetic disorders. Given the limited efficacy of conservative treatment, surgical intervention was considered (high-sensitivity troponin: 0.003 μg/L; B-type natriuretic peptide precursor (proBNP): 48.2 ng/L). On September 18, a partial osteotomy of the right humerus was performed. Intraoperative frozen section diagnosis showed malignant round cell tumors Postoperative pathological and blood bone marrow cell morphological examination results were consistent with plasma cell myeloma (IgA type; Durie-Salmon, stage ⅢA; International Staging System, stage Ⅱ). The patient was subsequently admitted for chemotherapy. The timeline of this case was summarized in Figure 1 .
The patient was treated with VLD regimen (bortezomib (2 mg i.h. d1, d4), doxorubicin liposome (20 mg i.v. d2, d3) and dexamethasone (20 mg i.v. d1)) since September 20. After the end of the second cycle, the patient developed significant enlargement of the local mass along with tenderness (normal electrocardiogram (ECG); proBNP: 67 ng/L). Subsequently, the chemotherapy regimen was changed to KT-DECP (carfilzomib 30 mg i.v. d1, d2, 43 mg i.v. d8, d9, d15, d16; thalidomide 100 mg p.o. qn; dexamethasone, 20 mg i.v. d1, d2, d3, d4; etoposide, 60 mg i.v. d3, d4, d5, d6; cyclophosphamide, 600 mg i.v. d3, d4, d5, d6; cisplatin, 16 mg i.v. d3, d4, d5, d6). Subsequently, the patient was discharged after the symptoms of the right upper arm swelling and tenderness were relieved. On January 10, 2025, the patient was admitted to further treatment, and the admission examination showed a slow heart rate. As no additional adverse reactions were observed, KT-DECP treatment was continued. On January 14, the patient developed palpitation, breathlessness and chest tightness after chemotherapy (heart rate: 38–45 bpm; high-sensitivity troponin: 0.003 μg/L; proBNP: 762 ng/L, RR interval: 1.91 s). The RR interval refers to the time interval between two consecutive R waves on ECG, which reflects the duration of one cardiac cycle corresponding to ventricular electrical depolarization and repolarization. Both the ECG report and the long RR interval suggested that the patient suffered sinus bradycardia with arrhythmia ( Figure 2 ). The 24H dynamic ECG results revealed that the lowest heart rate was 33 bpm, while the highest was 112 bpm, both of which were consistent with sinus rhythm. Occasional atrial premature beats and ventricular premature beats were observed. Additionally, a downward displacement of the ST segment was noted, but no conduction abnormalities were detected. Fortunately, the results of echocardiography were normal, and the biplane ejection fraction was more than 50%, indicating that the cardiac structure was unaffected.
After evaluation by clinical pharmacists and doctors, sinus bradycardia caused by carfilzomib was considered. Other causes such as hypothyroidism, electrolyte imbalance, and conduction system disease were considered but ruled out based on the results of the examination. Consequently, carfilzomib was discontinued, and trimetazidine hydrochloride tablets (20 mg p.o. tid) and salbutamol sulfate sustained-release capsules (8 mg p.o. bid) were given for symptomatic treatment. And then the indicators returned to normal levels (normal ECG; proBNP: <20 ng/L) and the patient was discharged. On February 10, the patient was re-admitted to the hospital, and the regimen was changed to DaraV (Daratumumab, bortezomib)-DECP. There was no cardiac discomfort that occurred again. Therefore, the diagnosis of sinus bradycardia induced by carfilzomib was established. Up to October 2025, ECG results of the patient demonstrated normal findings. Follow up at 1- and 3-months post-discontinuation showed sustained normal heart rate and no recurrence of bradycardia.
Discussion and review of literature
In this article, we introduce a case of sinus bradycardia that occurred in a patient during carfilzomib therapy for MM. Cardiac toxicity is a common adverse reaction in the treatment of carfilzomib, and among the PIs used in clinical practice, carfilzomib has the strongest correlation with cardiac toxicity. In a 55-year-old female patient, several potential causes of sinus bradycardia were considered. First, the patient had no history of cardiovascular disease, and echocardiography revealed no abnormalities, suggesting that the bradycardia was not secondary to cardiac insufficiency. Second, thyroid function was assessed after the patient presented with symptoms such as chest tightness. The measured thyroid-stimulating hormone level was 0.64 mIU/L, which excluded hypothyroidism as a cause of the sinus bradycardia. Third, hyperkalemia was also considered as a potential etiology. Repeated serum potassium measurements during treatment consistently showed values below 5.5 mmol/L, ruling out hyperkalemia as a contributing factor.
Additionally, the potential relationship between the carfilzomib and adverse reactions was evaluated using multiple assessment methods. According to the evaluation method for the association of adverse drug reactions by the National Adverse Drug Reaction Monitoring Center: (1) The patient in this case had no history of bradycardia or other related symptoms but developed sinus bradycardia with arrhythmia following the application of carfilzomib. Therefore, there is a reasonable time relationship between the use of carfilzomib and the occurrence of cardiac toxicity (+); (2) According to the clinical application guidelines for the treatment of MM with carfilzomib, 11 cardiac toxicity meets the known adverse reaction types of carfilzomib (+); (3) After discontinuing the carfilzomib, the results of ECG returned to normal (+); (4) After the first use of carfilzomib, ECG monitoring prompts heart rate to slow down. The patient experienced palpitations and chest tightness when administered again. The ECG report showed sinus bradycardia with arrhythmia, meeting the same adverse reaction event occurred (+); (5) Thalidomide, discontinued at the same time, may also cause cardiac toxicity. Although there are few reports on this, it cannot be entirely ruled out (±). However, the temporal relationship with carfilzomib administration and resolution upon its discontinuation strongly supports carfilzomib as the primary cause. The clinical pharmacist evaluated the association between carfilzomib and sinus bradycardia as “highly probable.” In addition, we also evaluated the relationship between carfilzomib and sinus bradycardia by the Naranjo adverse drug reaction probability scale. The results showed that the relationship between carfilzomib and bradycardia was “most likely” (score of 7). 12 The details were shown in Table 1 .
Table 1.
The Naranjo score results for carfilzomib-induced bradycardia.
| Relativity problem | Yes | No | Not known or not done | Score |
| 1. Are there previous conclusive reports on this reaction? | √ | 1 | ||
| 2. Did an adverse event appear after the suspected drug was given? | √ | 2 | ||
| 3. Did the adverse reaction improve when the drug was discontinued or a specific antagonist was given? | √ | 1 | ||
| 4. Did the adverse reaction appear when the drug was readministered? | √ | 2 | ||
| 5. Are there alternative causes that could have caused the reaction? | √ | 0 | ||
| 6. Did the reaction reappear when a placebo was given? | √ | 0 | ||
| 7. Was the drug detected in any body fluid in toxic concentrations? | √ | 0 | ||
| 8. Was the reaction more severe when the dose was increased, or less severe when the dose was decreased | √ | 0 | ||
| 9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure? | √ | 0 | ||
| 10. Was the adverse event confirmed by any objective evidence? | √ | 1 |
After reviewing literatures and guidelines, clinical pharmacists further confirmed that the adverse reaction is closely related to carfilzomib. The reasons are as follows: the 2022 ESC (European Society of Cardiology) Oncology Cardiology Guidelines 13 states that when patients apply PIs, the risk of serious cardiovascular adverse events increases. Therefore, strict cardiovascular risk assessment, early prevention, and proper monitoring and management are necessary before using carfilzomib treatment. We recommend continuous ECG monitoring during the first few cycles of carfilzomib therapy, especially in patients with pre-existing cardiac risk factors. In addition, the global phase III clinical trial ENDEAVOUR study also reported efficacy and safety data of carfilzomib. 14 The results showed that compared with the bortezomib + dexamethasone regimen, the incidence of heart failure was significantly increased with the carfilzomib + dexamethasone regimen (4.8% vs 1.1%).
PIs, including bortezomib, carfilzomib, and ixazomib, are the main therapeutic drugs for MM. In recent years, a variety of cardiac adverse reactions during treatment induced by PIs have been of concern. We investigated previously reported cases of cardiotoxicity associated with PIs, with a total of 23 publications compassing 26 cases ( Table 2 ). 15 – 37 The patients we studied are predominantly over 50 years old, with a significant proportion having a history of cardiovascular diseases such as hypertension. We hypothesize that elderly individuals with underlying diseases have weakened cardiac function, thereby increasing the likelihood of experiencing adverse cardiac reactions following the administration of PIs. And in 26 patients, there were 15 cases of heart failure, 4 cases of ventricular dysfunction, and one case each of myocarditis, pericardial effusion, angina, myocardial scar, hypertension, myocardial infarction, and Brugada syndrome. The majority of patients developed symptoms after four to five cycles of treatment. The time to symptom onset ranged from as early as 1 day to as long as nine cycles among the enrolled patients. At present, there is no case of sinus bradycardia with arrhythmia caused by carfilzomib similar to that reported in this paper. Studies have shown that carfilzomib cardiotoxicity may involve direct myocardial injury, autonomic dysfunction, or ischemic effects. The mechanism of bradycardia remains unclear but may relate to impaired conduction or autonomic modulation. 38 In addition, only four patients chose to continue the original PIs treatment after symptom relief. It is also worth noting that three patients died because of the rapid progression of the cancer after drug withdrawal. In the early detection of abnormal heart rate, electrocardiography, echocardiography, cardiac magnetic resonance imaging, and monitoring of certain biochemical markers (such as troponin, myocardial enzymes, and proBNP) remain the primary tools utilized by most researchers. These methods hold significant value for guiding the management of subsequent clinicians. Long-term follow-up and monitoring are necessary, since abnormal ECG caused by chemotherapy drugs can increase the risk of cardiovascular disease in patients. 39 These cases remind us to strengthen the monitoring of PIs administration, which is critical for ensuring patient medication safety and should be highly prioritized by clinical physicians.
Table 2.
Summary of previous studies reporting cardiotoxicity caused by PIs.
PIs: proteasome inhibitor; ECG: electrocardiogram; ST: plateau phase of the ventricular myocyte action potential; aVR: augmented Vector Right; aVF: augmented Vector Foot; QTc: corrected QT interval.
| Study | Gender/age | PIs | Latent period | Type of cardiotoxicity | Past history of cardiovascular disease | Sympotoms | Treatment and prognosis | The effect on PIs |
| Bockorny et al. 15 | Female/56 | Bortezomib | 4 times, 12 weeks | Pericardial effusion and mitral regurgitation | Hypertension | Exertional dyspnea, paroxysmal nocturnal dyspnea, orthopnea | Angiotensin II receptor antagonist and β-blockers; symptomatic improvement | Discontinued |
| Médrrez-Toro and colleagues 16 | Female/60 | Carfilzomib | 30 times, 140 days | Congestive severe heart failure | Chronic anemia | Paroxysmal nocturnal dyspnea and orthopnea | Enalapril 5 mg twice a day, carvedilol 25 mg twice a day, spironolactone 25 mg daily, and intravenous furosemide 10 mg four times a day; symptomatic improvement | Discontinued |
| Takamatsu et al. 17 | Female/79 | Bortezomib | 5 days | Acute myocardial infarction | None | Left chest pain and an ECG showed an ST elevation in aVR and ST depression in I, II, aVF and V3–V6 | Nitroglycerin, heparin, oxygen, metal stents, aspirin (100 mg/day) and clopidogrel (75 mg/day); symptomatic improvement | Discontinued |
| Gupta and colleagues 18 | Female/70 | Bortezomib | 22 times, 157 days | Congestive cardiac failure | Myocardial infarction, hypertensive, inferior wall myocardial ischemia, left ventricular dysfunction | Severe backache | Diuretics, nitroglycerine drip, low molecular weight heparin; symptomatic improvement | Discontinued |
| Subedi and colleagues 19 | Male/86 | Bortezomib | 22 days | Acute congestive heart failure | Myocardial infarction | Acute shortness of breath | Oxygen, diuretics, β-blocker, and angiotensin-converting enzyme inhibitor; symptomatic improvement | Discontinued |
| Serra et al. 20 | Male/65 | Carfilzomib | 4 times, 50 days | Heart failure | Hypertension, dyslipidemia | Worsening dyspneaatrial, fibrillation with a high ventricular rate, left ventricular systolic dysfunction, right ventricular hypokinesia | Diuretic, β-blocker, angiotensin converting enzyme inhibitor, mineralocorticoid-receptor antagonist therapy; symptomatic improvement | Discontinued |
| Meseeha and colleagues 21 | Female/66 | Bortezomib | 3 times | Acute left ventricular dysfunction | Hypertensive, left bundle branch block | Acute shortness of breath, palpitations | Symptomatic improvement | Discontinued |
| Feng et al. 22 | Female/52 | Bortezomib | 14 days | Heart failure | None | Palpitation, dyspnea | Oxygen therapy, strong heart, diuresis, anti-infection, anti acid, hemostasis; symptomatic improvement | Discontinued |
| Feng et al. 22 | Male/58 | Bortezomib | 6 days | Acute left heart failure, arrhythmia | None | Palpitation, dyspnea | Correct hypoxia, sedation, asthma, cardiac, diuretic; symptomatic improvement | Discontinued |
| Honton et al. 23 | Male/58 | Bortezomib | 4 months | Asymptomatic heart failure | None | \ | Symptomatic improvement | Reused |
| Takakuwa et al. 24 | Female/74 | Carfilzomib | 2 days | Acute heart failure | None | Peripheral oxygen saturation reduced to 88%, ejection fraction reduced from 59% to 28%, radiography revealed pulmonary congestion with pleural effusions | Norepinephrine, dobutamine, furosemide, and human atrial natriuretic peptide; death | Discontinued |
| Diwadkar and colleagues 25 | Male/66 | Bortezomib | 8 cycles | Complete heart block and evidence of myocardial scar | Hyperlipidemia | Myocardial thinning, small subendocardial perfusion defect in the midinferolateral segment with focal late gadolinium enhancement | Implanted a permanent dualchamber pacemaker. | Discontinued |
| Jakubowiak and colleagues 26 | Female/68 | Carfilzomib | 30 days | Acute congestive cardiac failure with fluid overload | Hypertension | Orthopnea, demonstrated hypoxemia | Lasix, enalapril, carvedilol; symptomatic improvement | Discontinued |
| Jakubowiak and colleagues 26 | Male/70 | Carfilzomib | 12 days | Hypertension | Hypertension | Nausea, vomiting, dizziness | Injection of normal saline and furosemide; symptomatic improvement | Reused |
| Chakraborty and colleagues 27 | Female/58 | Bortezomib | 112 days | Left ventricular dysfunction | Hypertension | Generalized weakness, nausea and vomiting | Lisinopril, carvedilol, isosorbide dinitrate; symptomatic improvement | Discontinued |
| McGregor and colleagues 28 | Male/71 | Carfilzomib | 2 months | Right ventricular dysfunction | Hypertension | Acute dyspnea | Symptomatic improvement | Discontinued |
| Pandey et al. 29 | Male/49 | Bortezomib | 5 times, 137 days | Heart failure with reduced ejection fraction | None | ECG showed severely decreased left ventricular systolic function | Symptomatic improvement | Discontinued |
| Azad et al. 30 | Female/63 | Carfilzomib | 4 days | Biventricular heart failure | None | Tachypneic | Bilevel-positive air pressure, furosemide 20 mg intravenous injections; symptomatic improvement | Discontinued |
| Alali and Baljevic 31 | Female/40 | Bortezomib | 5 times, 22 days | Perimyocarditis | None | Ventricular tachycardia, syncope | Spironolactone, captopril, intravenous furosemide, sotalol; symptomatic improvement | Discontinued |
| Ghisoni et al. 32 | Female/65 | Carfilzomib | 20 days | Brugada syndrome | Hypertension | ST-segment elevation in V1–V2 and a QTc interval of 498 ms | symptomatic improvement | Reused |
| Voortman and Giaccone 33 | Male/53 | Bortezomib | 84 days | Heart failure | None | Fatigue, orthopnea, dyspnea | symptomatic improvement | Discontinued |
| Ikoma et al. 34 | Male/76 | Carfilzomib | 3 months | Congestive heart failure | Hypertension | Dyspnea, orthopnea | Diuretics; symptomatic improvement | Discontinued |
| Ikoma et al. 34 | Female/75 | Carfilzomib | 5 months | Heart failure | None | Dyspnea on exertion, exacerbated lower limb edema, coarse crackles in the bilateral chest | Diuretics; the cardiac function was not restored | Discontinued |
| Toro and colleagues 35 | Female/60 | Carfilzomib | 105 days | Congestive heart failure | Chronic anemia | Paroxysmal nocturnal dyspnea, orthopnea | Enalapril 5 mg bid, carvedilol 25 mg bid, spironolactone 25 mg, intravenous furosemide 10 mg qid; symptomatic improvement | Discontinued |
| Uruno et al. 36 | Female/59 | Carfilzomib | 1 month | Cardiac dysfunction | None | Palpitations, fatigue, exertional dyspnea, facial edema | Phosphodiesterase-5 inhibitor, endothelin receptor antagonist, prostaglandin derivatives; symptomatic improvement | Discontinued |
| Yasui et al. 37 | Male/70 | Bortezomib | 90 days | Coronary spastic angina | None | Chest pain | Benidipine (4 mg, bid); symptomatic improvement | Reused |
Conclusion
This article focuses on the pharmacovigilance of cardiac toxicity in patients with MM who are treated with carfilzomib. Clinical pharmacists play an essential role in evaluating heart rate and ECG findings, enabling timely discontinuation of carfilzomib to prevent severe consequences such as heart failure. Pharmacists are deeply involved in both treatment and monitoring, summarizing effective strategies for patient care, including: (1) Comprehensive assessments of the cardiac health status of the patient, particularly left ventricular function and electrophysiological parameters, should be conducted prior to initiating treatment to facilitate personalized treatment planning. (2) Closely monitoring cardiac function indicators (ECG, echocardiography, blood pressure, heart rate, troponin I, high-sensitivity troponin I, B-type natriuretic peptide, proBNP) during treatment to detect early changes in cardiac function, adjust medication regimens promptly, and minimize harm caused by cardiotoxic reactions. (3) Managing severe respiratory distress, hypertension, or heart failure appropriately, reducing or discontinuing medication as required, and continuing cardiovascular risk assessment for 12 months post-treatment with carfilzomib.
The authors thank the staff of the Hematology Department of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine for their collaboration.
ORCID iD: Xincai Zhao https://orcid.org/0000-0001-7713-4339
Consent for publication: Written informed consent was obtained from the patient for their anonymized information to be published in this article.
Author contributions: XCZ conceived and designed this study. XCZ and DMS did the literature review and drafted the manuscript. RX, SDZ, and YQ assisted in data collection and patient follow-up. GC and CKC made substantial contributions to general supervision of the research group. JPZ and CKC reviewed and revised the manuscript critically for important intellectual content, and approved the final version. All authors read and approved the manuscript.
Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Shanghai Sixth People’s Hospital Institutional-Level Research Project on Hospital Management (No. Lygl202407) and Shanghai Municipal Health Commission (No. 2020YJZX0205).
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data availability statement: Data sharing is not applicable to this article as no data sets were generated or analyzed during this study.
References
1 Cowan AJ Green DJ Kwok M , et al . Diagnosis and management of multiple myeloma . JAMA 2022 ; 327 ( 5 ): 464 . 35103762 10.1001/jama.2022.0003
2 Moreau P Richardson PG Cavo M , et al . Proteasome inhibitors in multiple myeloma: 10 years later . Blood 2012 ; 120 ( 5 ): 947 – 959 . 22645181 10.1182/blood-2012-04-403733 PMC4123429
3 Gandolfi S Laubach JP Hideshima T , et al . The proteasome and proteasome inhibitors in multiple myeloma . Cancer Metast Rev 2017 ; 36 ( 4 ): 561 – 584 . 10.1007/s10555-017-9707-8 29196868
4 Jayaweera SPE Wanigasinghe KSP Rajalingam D , et al . Carfilzomib: a promising proteasome inhibitor for the treatment of relapsed and refractory multiple myeloma . Front Oncol 2021 ; 11 : 740796 . 34858819 10.3389/fonc.2021.740796 PMC8631731
5 Stewart AK Rajkumar SV Dimopoulos MA , et al . Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma . N Engl J Med 2015 ; 372 ( 2 ): 142 – 152 . 25482145 10.1056/NEJMoa1411321
6 Herndon TM Deisseroth A Kaminskas E , et al . U.S. Food and Drug Administration Approval: carfilzomib for the treatment of multiple myeloma . Clin Cancer Res 2013 ; 19 ( 17 ): 4559 – 4563 . 23775332 10.1158/1078-0432.CCR-13-0755
7 Zhao W Liu J Chen LY , et al . Efficacy and safety of carfilzomib-based regiments for the treatment of relapsed or refractory multiple myeloma: single-center real-word data . Blood 2024 ; 144 : 7024 .
8 Buck B Kellett E Addison D , et al . Carfilzomib-induced cardiotoxicity: an analysis of the FDA Adverse Event Reporting System (FAERS) . J Saudi Heart Assoc 2022 ; 34 ( 3 ): 134 – 141 . 36127934 10.37616/2212-5043.1311 PMC9458320
9 Harvey D. Incidence and management of adverse events in patients with relapsed and/or refractory multiple myeloma receiving single-agent carfilzomib . Clin Pharmacol 2014 ; 6 : 87 – 96 . 24855395 10.2147/CPAA.S62512 PMC4020895
10 Chavda SJ Pocock R Cheesman S , et al . Association of hypertension and cardiac events in patients with multiple myeloma receiving carfilzomib: practical management recommendations . Br J Haematol 2020 ; 190 ( 5 ): 16889 . 10.1111/bjh.16889 32535901
11 Multiple Myeloma Expert Committee of Chinese Society of Clinical Oncology (CSCO) . Chinese guideline principles for clinical application of carfilzomib in multiple myeloma (2024 version) . J Leukemia Lymphoma 2024 ; 33 : 577 – 586 .
12 Naranjo CA Busto U Sellers EM , et al . A method for estimating the probability of adverse drug reactions . Clin Pharmacol Ther 1981 ; 30 : 239 – 245 . 7249508 10.1038/clpt.1981.154
13 Lyon AR López-Fernández T Couch LS , et al . 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS) . Eur Heart J 2022 ; 43 ( 41 ): 4229 – 4361 . 36017568 10.1093/eurheartj/ehac244
14 Dimopoulos MA Goldschmidt H Niesvizky R , et al . Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial . Lancet Oncol 2017 ; 18 ( 10 ): 1327 – 1337 . 28843768 10.1016/S1470-2045(17)30578-8
15 Bockorny M Chakravarty S Schulman P , et al . Severe heart failure after bortezomib treatment in a patient with multiple myeloma: a case report and review of the literature . Acta Haematol 2012 ; 128 ( 4 ): 244 – 247 . 22964848 10.1159/000340050
16 Méndez-Toro A Díaz-Brochero C Acosta-Gutiérrez E. Carfilzomib induced cardiotoxicity in a multiple myeloma patient . Cardiooncology 2020 ; 6 ( 1 ): 17 . 32944287 10.1186/s40959-020-00074-8 PMC7487899
17 Takamatsu H Yamashita T Kotani T , et al . Ischemic heart disease associated with bortezomib treatment combined with dexamethasone in a patient with multiple myeloma . Int J Hematol 2010 ; 91 ( 5 ): 903 – 906 . 20458563 10.1007/s12185-010-0586-9
18 Gupta A Pandey A Sethi S. Bortezomib-induced congestive cardiac failure in a patient with multiple myeloma . Cardiovasc Toxicol 2011 ; 12 ( 2 ): 184 – 187 . 10.1007/s12012-011-9146-7 21952908
19 Subedi A Sharma LR Shah BK. Bortezomib-induced acute congestive heart failure: a case report and review of literature . Ann Hematol 2014 ; 93 ( 10 ): 1797 – 1799 . 24599584 10.1007/s00277-014-2026-z
20 Serra W Fantin A Longo C , et al . Carfilzomib: a tale of a heartbreaking moment: case report and concise review of the literature . Cardiovasc Hematol Disord Drug Targets 2019 ; 19 ( 3 ): 253 – 258 . 30516116 10.2174/1871529X19666181205100705
21 Meseeha MG Kolade VO Attia MN , et al . Partially reversible bortezomib-induced cardiotoxicity: an unusual cause of acute cardiomyopathy . J Community Hosp Int Med Perspect 2015 ; 5 ( 6 ): 28982 . 10.3402/jchimp.v5.28982 PMC4677580 26653686
22 Feng Y Yang S Gao L , et al . Bortezomib-induced multiple organ failure: report of two cases and review of literature . Int J Clin Exp Med 2016 ; 9 ( 6 ): 12263 – 12268 .
23 Honton B Despas F Dumonteil N , et al . Bortezomib and heart failure: case-report and review of the French Pharmacovigilance database . Fund Clin Pharmacol 2013 ; 28 ( 3 ): 349 – 352 . 10.1111/fcp.12039 23781941
24 Takakuwa T Otomaru I Araki T , et al . The first autopsy case of fatal acute cardiac failure after administration of carfilzomib in a patient with multiple myeloma . Case Rep Hematol 2019 ; 2019 : 1 – 5 . 10.1155/2019/1816287 PMC6512067 31183224
25 Diwadkar S Patel AA Fradley MG. Bortezomib-induced complete heart block and myocardial scar: the potential role of cardiac biomarkers in monitoring cardiotoxicity . Case Rep Cardiol 2016 ; 2016 : 1 – 5 . 10.1155/2016/3456287 PMC4749759 26942019
26 Jakubowiak AJ DeCara JM Mezzi K. Cardiovascular events during carfilzomib therapy for relapsed myeloma: practical management aspects from two case studies . Hematology 2017 ; 22 ( 10 ): 585 – 591 . 28545322 10.1080/10245332.2017.1328165
27 Chakraborty R Mukkamalla SKR Calderon N. Bortezomib induced reversible left ventricular systolic dysfunction: a case report and review of literature . Br J Med Pract 2013 ; 6 ( 4 ): a631.
28 McGregor PC Boosalis V Aragam J. Carfilzomib-induced pulmonary hypertension with associated right ventricular dysfunction: a case report . SAGE Open Med Case Rep 2021 ; 9 : 1 – 4 . 10.1177/2050313X21994031 PMC7890743 33643656
29 Pandey S Tan EFS Bellamkonda A , et al . Cyclophosphamide, bortezomib, and dexamethasone and severe systolic heart failure: a case report . Cureus 2024 ; 16 ( 3 ): e56966. 10.7759/cureus.56966 PMC11044976 38665754
30 Azad F Moyer R Miranda CJ , et al . Carfilzomib-induced tumor lysis syndrome and biventricular heart failure in a patient with multiple myeloma . Cureus 2023 ; 15 ( 1 ): e33538. 10.7759/cureus.33538 PMC9907735 36779143
31 Alali Y Baljevic M. Bortezomib-induced perimyocarditis in a multiple myeloma patient: a case report . Case Rep Oncol 2021 ; 14 ( 3 ): 1853 – 1859 . 35111020 10.1159/000520382 PMC8787553
32 Ghisoni E Marandino L Lombardi P , et al . Safe use of carfilzomib in a patient with multiple myeloma and intermittent type 1 Brugada ECG pattern: a case report . Acta Haematol 2020 ; 143 ( 5 ): 481 – 485 . 31553985 10.1159/000502538
33 Voortman J Giaccone G. Severe reversible cardiac failure after bortezomib treatment combined with chemotherapy in a non-small cell lung cancer patient: a case report . BMC Cancer 2006 ; 6 ( 1 ): 129 . 16689991 10.1186/1471-2407-6-129 PMC1475607
34 Ikoma T Saotome M Sano M , et al . Cardiotoxicity of carfilzomib in two Japanese Patients with relapsed multiple myeloma . Intern Med 2019 ; 58 ( 11 ): 1577 – 1581 . 30713316 10.2169/internalmedicine.2194-18 PMC6599935
35 Toro AM Diaz-Brochero C Acosta-Gutierrez E. Carfilzomib induced cardiotoxicity in a multiple myeloma patient . Cardiooncology 2020 ; 7 : 1 – 8 . 10.1186/s40959-020-00074-8 PMC7487899 32944287
36 Uruno K Iwano H Hayashi T , et al . Carfilzomib-induced pulmonary hypertension in a patient with multiple myeloma . J Cardiol Cases 2024 ; 30 ( 5 ): 172 – 175 . 39534307 10.1016/j.jccase.2024.07.006 PMC11551454
37 Yasui T Shioyama W Oboshi M , et al . Coronary spastic angina in a multiple myeloma patient treated with bortezomib, lenalidomide, and dexamethasone . J Cardiol Cases 2020 ; 21 ( 5 ): 197 – 199 . 32373247 10.1016/j.jccase.2020.02.002 PMC7195564
38 Forghani P Rashid A Sun F , et al . Carfilzomib treatment causes molecular and functional alterations of human induced pluripotent stem cell-derived cardiomyocytes . J Am Heart Assoc 2021 ; 10 ( 24 ): e022247. 10.1161/JAHA.121.022247 PMC9075231 34873922
39 Sara SS Malihehsadat A Eisa N , et al . Predictive value of ECG ischemic pattern changes for the10-year occurrence of ischemic heart disease . Ann Noninvas Electro 2025 ; 30 ( 5 ): e70111. 10.1111/anec.70111 PMC12457696 40988348