Validation of the HFA-ICOS Score for Carfilzomib-Induced Cardiotoxicity in Multiple Myeloma: A Real-Life Perspective Study
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Baseline Assessment
2.2. Application of the HFO-ICOS Score
2.3. Follow-Up
2.4. Statistical Analysis
3. Results
3.1. Baseline Parameters and Cardiovascular Risk Factors
3.2. Stratification by the HFA-ICOS Score
3.3. Incidence of CVAEs During K Therapy
3.4. Accuracy of HFO-ICOS Score and the Role of Other Baseline Parameters as Predictors of CVAEs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Appendix A.1. Cardiovascular Adverse Events Definitions
Appendix A.2. Hypertensive Adverse Events Definitions
References
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Parameter | N = 169 (100%) |
---|---|
General | |
Age, y | 70.0 (63.0; 74.2) |
Male sex | 77 (45.6%) |
BMI, kg/m2 | 26.7 (23.9; 30.3) |
Individual CV risk factors and comorbidities | |
Tobacco use (prior/current) | 90 (53.3) |
Obesity (BMI ≥ 30) | 49 (29) |
Known arterial hypertension | 80 (47.3) |
Diabetes mellitus | 16 (9) |
Chronic renal failure (eGFR < 60 mL/m) | 41 (26.3) |
Ischemic heart disease | 4 (2.3) |
Atrial fibrillation | 5 (2.9) |
Dyslipidemia | 25 (14.8) |
Previous stroke | 3 (1.8) |
Office BP values | |
SBP, mmHg | 128 (116; 141) |
DBP, mmHg | 76.0 (70.0; 84.0) |
ABPM 1 , mean (SD) | |
Daytime SBP, mmHg | 124 (116; 132) |
Daytime DBP, mmHg | 74.0 (69.0; 80.0) |
Daytime MBP, mmHg | 92.0 (86.0; 96.5) |
24 h SBP, mmHg | 120 (112; 129) |
24 h DBP, mmHg | 71.0 (65.0; 76.5) |
24 h MBP, mmHg | 88.0 (82.0; 93.0) |
Nighttime SBP, mmHg | 109 (102; 120) |
Nighttime DBP, mmHg | 62.0 (57.0; 69.0) |
Night MBP, mmHg | 78.0 (73.0; 86.0) |
Blood pressure variability | 9.00 (7.0; 10.0) |
Echocardiographic parameters 2 | |
LAVi, ml/m2 | 49.0 (38.4; 61.2) |
LVMi, g/m2 | 86.4 (74.4; 102.0) |
LVH | 30 (18.8) |
Diastolic dysfunction | 9 (6.4) |
LVEF, % | 62.2 (58.3; 65.2) |
Stroke volume, mL/m2 | 47.4 (39.1; 57.9) |
GLS value, % | −21.50 (−23.40; −20.10) |
GLS value ≥ −20 % | 33 (23.1) |
Arterial stiffness evaluation 3 | |
cfPWV value, m/s | 8.00 (7.0; 9.0) |
cfPWV value ≥ 9 m/s | 49 (32.2) |
Oncological history | |
Median MM disease duration, months | 11.2 (5.23; 23.8) |
Line of K therapy | 2.85 (1; 9) |
Patients (n) | Score | |
---|---|---|
Previouscardiovascular diseases | ||
Heart failure or cardiomyopathy | 2 (1.2) | Very High |
Prior proteasome inhibitor cardiotoxicity | 0 (0) | Very High |
Venous thrombosis (DVT or PE) | 0 (0) | Very High |
Cardiac amyloidosis | na | Very High |
Arterial vascular disease (IHD, PCI, CABG, stable angina, TIA, stroke, PVD) | 7 (4.1) | Very High |
Prior immunomodulatory CV toxicity | 0 (0) | High |
Baseline LVEF < 50% | 5 (3) | High |
Borderline LVEF 50–54% | 5 (3) | Medium 1 |
Arrhythmia | 5 (3) | Medium 2 |
Left ventricular hypertrophy 1 | 30 (17.8) | Medium 1 |
Cardiac biomarkers 2 | ||
Elevated baseline troponin | 0 (0) | Medium 2 |
Elevated baseline BNP or NT-proBNP | 2 (1.2) | High |
Demographic and cardiovascular risk factors | ||
Age ≥ 75 years | 40 (23.7) | High |
Age 65–74 years | 79 (46.7) | Medium 1 |
Arterial hypertension | 80 (47.3) | Medium 1 |
Diabetes mellitus | 16 (9.5) | Medium 1 |
Hyperlipidemia | 25 (14.8) | Medium 1 |
Chronic kidney disease | 40 (23.7) | Medium 1 |
Family history of thrombophilia | na | Medium 1 |
Previous cardiotoxic cancer treatment | ||
Prior anthracycline exposure | 34 (20.1) | High |
Prior thoracic spine radiotherapy | 7 (4.1) | Medium 1 |
Current myeloma treatment | ||
High-dose of dexamethasone > 160 mg/month | 0 (0) | Medium 1 |
Lifestyle risk factors | ||
Current smoker or significant smoking history | 90 (53.3) | Medium 1 |
Obesity (BMI > 30 kg/m2) | 49 (29) | Medium 1 |
Parameter | Levels of Risk | |||||
---|---|---|---|---|---|---|
1. Low N = 20 | 2. Medium N = 65 | 3. High N = 77 | 4. Very High N = 7 | p | Comparison | |
General | ||||||
Age, y | 60.0 (54.0; 65.0) | 69.0 (63.0; 72.0) | 75.0 (68.0; 77.0) | 68.0 (66.5; 68.5) | <0.001 | 1 vs. 2/3/4; 2 vs. 3 |
Male sex | 8 (40.0) | 27 (41.5) | 38 (49.4) | 4 (57.1) | 0.677 | |
BMI, kg/m2 | 24.8 (21.8; 27.0) | 28.1 (25.2; 31.6) | 26.4 (23.7; 30.1) | 27.6 (27.3; 31.4) | 0.012 | 1 vs. 2 |
Individual CV risk factors | ||||||
Tobacco use (prior/current) | 7 (35.0) | 37 (56.9) | 41 (53.2) | 5 (71.4) | 0.275 | |
Obesity (BMI ≥ 30) | 0 (0.0) | 22 (33.8) | 24 (31.2) | 3 (42.9) | 0.005 | 1 vs. 2/3/4 |
Known arterial hypertension | 2 (10.0) | 30 (46.2) | 42 (54.5) | 6 (85.7) | <0.001 | 1 vs. 2/3/4 |
Diabetes mellitus | 0 (0) | 5 (7.7) | 10 (13.0) | 1 (14.3) | 0.253 | |
Chronic renal failure (eGFR < 60 mL/m) | 92.9 (77.3; 106) | 80.7 (64.7; 99.0) | 67.8 (54.8; 93.5) | 81.5 (68.3; 89.0) | 0.033 | 1 vs. 3 |
Ischemic heart disease | 0 (0) | 0 (0) | 0 (0) | 4 (57.1) | <0.001 | 4 vs. 1/2/3 |
Atrial fibrillation | 0 (0) | 1 (1.5) | 3 (3.9) | 1 (14.3) | 0.277 | |
Dyslipidaemia | 0 (0) | 13 (20) | 12 (15.6) | 0 (0) | 0.099 | |
Previous stroke | 0 (0) | 0 (0) | 0 (0) | 3 (42.9) | <0.001 | 4 vs. 1/2/3 |
Office BP values, mmHg | ||||||
SBP | 120 (114; 128) | 128 (119; 141) | 130 (119; 142) | 122 (104; 131) | 0.081 | |
DBP | 74.5 (70.0; 80.0) | 77.5 (70.8; 87.2) | 75.0 (69.0; 82.0) | 79.0 (65.5; 81.5) | 0.501 | |
ABPM, mmHg | ||||||
Daytime SBP | 120 (114; 130) | 126 (118; 133) | 124 (116; 132) | 114 (107; 116) | 0.095 | |
Daytime DBP | 74.0 (70.0; 80.5) | 76.5 (69.0; 82.0) | 73.0 (68.0; 78.0) | 66.5 (60.5; 72.5) | 0.066 | |
Daytime MBP | 88.5 (84.8; 96.8) | 93.0 (88.8; 99.0) | 91.0 (86.0; 95.5) | 84.5 (77.0; 92.0) | 0.104 | |
24 h SBP | 114 (107; 124) | 122 (114; 129) | 120 (112; 129) | 108 (104; 115) | 0.101 | |
24 h DBP | 70.0 (65.2; 76.8) | 73.0 (67.0; 77.5) | 70.5 (64.8; 75.0) | 64.5 (58.0; 71.0) | 0.250 | |
24 h MBP | 85.0 (79.5; 92.2) | 89.0 (84.0; 93.0) | 89.0 (82.0; 93.0) | 81.0 (72.8; 90.0) | 0.334 | |
Nighttime SBP | 104 (96.8; 112) | 110 (102; 121) | 112 (103; 121) | 99.5 (95.5; 109) | 0.093 | |
Nighttime DBP | 59.5 (56.2; 66.0) | 63.5 (59.0; 69.0) | 63.0 (58.0; 70.0) | 60.0 (53.5; 70.2) | 0.484 | |
Night MBP, | 73.5 (71.2; 80.8) | 79.0 (74.0; 86.0) | 79.0 (74.0; 88.8) | 74.5 (69.2; 82.8) | 0.147 | |
Blood pressure variability | 8.00 (7.00; 9.00) | 9.00 (7.50; 11.0) | 8.50 (7.00; 10.0) | 8.50 (6.50; 11.2) | 0.597 | |
Echocardiographic parameters | ||||||
LAVi, mL/m2 | 39.0 (33.3; 65.0) | 49.4 (41.2; 63.0) | 48.8 (38.3; 58.1) | 57.7 (49.2; 65.5) | 0.341 | |
LVMi, g/m2 | 74.5 (66.7; 84.8) | 82.7 (70.2; 95.7) | 90.4 (76.9; 104) | 115 (86.1; 119) | 0.002 | 1 vs. 3/4 |
LVH, | 1 (5.26%) | 7 (11.5%) | 18 (24.7%) | 4 (57.1%) | 0.007 | 1/2 vs. 4 |
Diastolic dysfunction | 0 (0.00%) | 4 (7.69%) | 4 (5.97%) | 1 (16.7%) | 0.451 | |
LVEF, % | 60.2 (57.6; 64.3) | 62.7 (58.9; 65.6) | 62.2 (58.6; 64.7) | 60.8 (55.0; 62.2) | 0.491 | |
Stroke volume, mL/m2 | 53.0 (39.7; 60.8) | 50.2 (40.7; 61.5) | 43.5 (36.1; 53.1) | 54.9 (53.5; 68.8) | 0.023 | |
GLS value, % | −21.90 (−23.40; −20.30) | −21.60 (−22.70; −19.60) | −21.60 (−23.90; −20.25) | −21.00 (−21.50; −21.00) | 0.707 | |
GLS value ≥ −20% | 2 (11.8%) | 15 (28.3%) | 15 (22.1%) | 1 (20.0%) | 0.580 | |
Arterial stiffness evaluation | ||||||
cfPWV value, m/s | 7.00 (6.00; 7.50) | 8.00 (7.00; 9.00) | 9.00 (7.00; 10.0) | 8.00 (7.00; 9.00) | 0.001 | 1/2 vs. 3 |
cfPWV value ≥ 9 m/s | 2 (10.5%) | 18 (30.5%) | 36 (52.2%) | 2 (40.0%) | 0.002 | 1 vs. 3 |
Events | N = 169 (100%) | CTCAE | |
---|---|---|---|
Grade 1–2 | Grade ≥ 3 | ||
Cardiovascular adverse events 1 | 36 (21.3) | ||
ACS (STEMI) | 2 (1.2) | 0 | 2 |
ACS (NSTEMI) | 4 (2.4) | 0 | 4 |
Angina | 9 (5.3) | 9 | 0 |
Heart failure | 10 (5.9) | 8 | 2 |
Arrhythmias | 12 (7.1) | 11 | 1 |
Sudden death | 1 (0.6) | na | 0 |
LVEF impairment | 5 (3) | 0 | 3 |
GLS impairment | 6 (3.6) | na | na |
Hypertensive events 1 | 77 (45.6) | ||
New onset/worsened hypertension | 67 (39.6) | 67 | 0 |
Masked hypertension | 5 (3) | 5 | 0 |
K pre-infusion hypertension permissive K infusion | 34 (20.1) | 27 | 7 |
K pre-infusion hypertension not permissive K infusion | 18 (10.7) | 11 | 7 |
K post-infusion hypertension | 20 (11.8) | 13 | 7 |
Hypertensive urgency | 5 (3) | 0 | 5 |
Hypertensive emergency | 0 (0) | 0 | 0 |
Any CVAEs | 89 (52.7) |
Baseline Parameter | Beta | OR (SD) | Wald Test | Valore di p |
---|---|---|---|---|
General | ||||
Age | 0.02 | 1.02 (0.98–1.06) | 1.12 | 0.264 |
Male sex | 0.44 | 1.55 (0.84–2.86) | 1.40 | 0.160 |
BMI | 0.03 | 1.03 (0.96–1.10) | 0.81 | 0.419 |
Office BP | ||||
SBP | 0.04 | 1.04 (1.02–1.07) | 3.94 | <0.001 |
DBP | 0.03 | 1.03 (1.00–1.06) | 2.03 | 0.042 |
ABPM | ||||
24 h SBP | 0.03 | 1.03 (1.00–1.06) | 1.97 | 0.048 |
24 h DBP | 0.02 | 1.02 (0.98–1.06) | 0.92 | 0.358 |
24 h MBP | 0.02 | 1.02 (0.99–1.06) | 1.15 | 0.249 |
Daytime SBP | 0.03 | 1.03 (1.01–1.06) | 2.41 | 0.016 |
Daytime DBP | 0.02 | 1.02 (0.99–1.06) | 1.21 | 0.225 |
Daytime MBP | 0.03 | 1.03 (1.00–1.07) | 1.85 | 0.065 |
Nighttime SBP | 0.01 | 1.01 (0.98–1.03) | 0.42 | 0.674 |
Nighttime DBP | −0.00 | 1.00 (0.96–1.04) | −0.16 | 0.872 |
Night MBP | 0.00 | 1.00 (0.97–1.04) | 0.08 | 0.936 |
Blood pressure Variability | 0.18 | 1.19 (1.07–1.35) | 3.06 | 0.002 |
Echocardiographic parameters | ||||
LAVi | 0.00 | 1.00 (0.98–1.02) | 0.17 | 0.865 |
LVEF | 0.02 | 1.02 (0.97–1.07) | 0.77 | 0.441 |
LVMi | 0.02 | 1.02 (1.01–1.04) | 2.69 | 0.007 |
LVH | 1.19 | 3.29 (1.38–8.77) | 2.55 | 0.011 |
Diastolic dysfunction | −0.94 | 0.39 (0.08–1.55) | −1.29 | 0.199 |
GLS value | 0.10 | 1.10 (0.97–1.26) | 1.47 | 0.142 |
GLS value ≥ −20 | 0.55 | 1.73 (0.78–4.02) | 1.32 | 0.188 |
Arterial stiffness evaluation | ||||
cfPWV | 0.40 | 1.49 (1.23–1.84) | 3.87 | <0.001 |
cfPWV ≥ 9 m/s | 1.58 | 4.84 (2.38–10.32) | 4.23 | <0.001 |
HFA-ICOS score | ||||
Level of risk | 0.24 | 1.27 (0.85–1.92) | 1.15 | 0.251 |
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Astarita, A.; Mingrone, G.; Airale, L.; Colomba, A.; Catarinella, C.; Cesareo, M.; Vallelonga, F.; Paladino, A.; Bruno, G.; Leone, D.; et al. Validation of the HFA-ICOS Score for Carfilzomib-Induced Cardiotoxicity in Multiple Myeloma: A Real-Life Perspective Study. Cancers 2025, 17, 2353. https://doi.org/10.3390/cancers17142353
Astarita A, Mingrone G, Airale L, Colomba A, Catarinella C, Cesareo M, Vallelonga F, Paladino A, Bruno G, Leone D, et al. Validation of the HFA-ICOS Score for Carfilzomib-Induced Cardiotoxicity in Multiple Myeloma: A Real-Life Perspective Study. Cancers. 2025; 17(14):2353. https://doi.org/10.3390/cancers17142353
Chicago/Turabian StyleAstarita, Anna, Giulia Mingrone, Lorenzo Airale, Anna Colomba, Cinzia Catarinella, Marco Cesareo, Fabrizio Vallelonga, Arianna Paladino, Giulia Bruno, Dario Leone, and et al. 2025. "Validation of the HFA-ICOS Score for Carfilzomib-Induced Cardiotoxicity in Multiple Myeloma: A Real-Life Perspective Study" Cancers 17, no. 14: 2353. https://doi.org/10.3390/cancers17142353
APA StyleAstarita, A., Mingrone, G., Airale, L., Colomba, A., Catarinella, C., Cesareo, M., Vallelonga, F., Paladino, A., Bruno, G., Leone, D., Gay, F., Bringhen, S., Veglio, F., & Milan, A. (2025). Validation of the HFA-ICOS Score for Carfilzomib-Induced Cardiotoxicity in Multiple Myeloma: A Real-Life Perspective Study. Cancers, 17(14), 2353. https://doi.org/10.3390/cancers17142353