Left ventricular trabecular complexity for risk stratification of cancer therapy–related cardiac dysfunction in breast cancer

Abstract

The left ventricular trabecular fractal dimension (LVTFD) derived from cardiac magnetic resonance reflects myocardial trabecular complexity, which is associated with cardiovascular disease risk. Baseline risk stratification of cancer therapy–related cardiac dysfunction (CTRCD) in patients with breast cancer who received anthracycline is a very important clinical issue. In this study, we used the Cox model to derive and validate a new score system based on LVTFD for baseline risk stratification of CTRCD in breast cancer patients receiving anthracycline. We also compare the performance of LVTFD-based score with the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) score using C-index. This study enrolled 370 participants, of whom 73 participants developed CTRCD. The C-indices of LVTFD-based score integrating age, hypertension, previous cardiovascular disease, and maximal apical fractal dimension were higher than those of HFA-ICOS score for stratifying CTRCD (0.834 vs. 0.642 and 0.834 vs. 0.633, respectively, in derivation and validation cohort). LVTFD-based score can stratify the CTRCD risk, but HFA-ICOS score cannot. The above results reveal that the LVTFD-based score is an alternative method for baseline risk stratification of CTRCD in breast cancer who received anthracycline.

Keywords

breast cancer / cardiotoxicity / magnetic resonance imaging

References

[1] Lewinter C, Nielsen TH, Edfors LR, et al. A systematic review and meta-analysis of beta-blockers and renin-angiotensin system inhibitors for preventing left ventricular dysfunction due to anthracyclines or trastuzumab in patients with breast cancer. Eur Heart J. 2022; 43(27): 2562-2569.

[2] Lu D, Chatterjee S, Xiao K, et al. A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. Eur Heart J. 2022; 43(42): 4496-4511.

[3] Curigliano G, Lenihan D, Fradley M, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020; 31(2): 171-190.

[4] Lyon AR, Dent S, Stanway S, et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail. 2020; 22(11): 1945-1960.

[5] Mehta LS, Watson KE, Barac A, et al. Cardiovascular disease and breast cancer: where these entities intersect: a scientific statement from the American Heart Association. Circulation. 2018; 137(8): e30-e66.

[6] Gevaert SA, Halvorsen S, Sinnaeve PR, et al. Evaluation and management of cancer patients presenting with acute cardiovascular disease: a clinical consensus statement of the Acute CardioVascular Care Association (ACVC) and the ESC Council of Cardio-Oncology-Part 2: acute heart failure, acute myocardial diseases, acute venous thromboembolic diseases, and acute arrhythmias. Eur Heart J Acute Cardiovasc Care. 2022; 11(11): 865-874.

[7] Zheng H, Zhan H. Cardio-oncology guidelines and strength of the evidence. JACC Cardiooncol. 2023; 5(1): 149-152.

[8] Zhang N, Yang G, Gao Z, et al. Deep learning for diagnosis of chronic myocardial infarction on nonenhanced cardiac cine MRI. Radiology. 2019; 291(3): 606-617.

[9] Negishi T, Thavendiranathan P, Penicka M, et al. Cardioprotection using strain-guided management of potentially cardiotoxic cancer therapy: 3-year results of the SUCCOUR trial. JACC Cardiovasc Imaging. 2023; 16(3): 269-278.

[10] Liu JE, Barac A, Thavendiranathan P, Scherrer-Crosbie M, Strain imaging in cardio-oncology. JACC Cardiooncol. 2020; 2(5): 677-689.

[11] Thavendiranathan P, Negishi T, Somerset E, et al. Strain-guided management of potentially cardiotoxic cancer therapy. J Am Coll Cardiol. 2021; 77(4): 392-401.

[12] Meyer HV, Dawes TJW, Serrani M, et al. Genetic and functional insights into the fractal structure of the heart. Nature. 2020; 584(7822): 589-594.

[13] Camporeale A, Moroni F, Lazzeroni D, et al. Trabecular complexity as an early marker of cardiac involvement in Fabry disease. Eur Heart J Cardiovasc Imaging. 2022; 23(2): 200-208.

[14] Wang J, Li Y, Yang F, et al. Fractal analysis: prognostic value of left ventricular trabecular complexity cardiovascular MRI in participants with hypertrophic cardiomyopathy. Radiology. 2021; 298(1): 71-79.

[15] Lancellotti P, Suter TM, Lopez-Fernandez T, et al. Cardio-oncology services: rationale, organization, and implementation. Eur Heart J. 2019; 40(22): 1756-1763.

[16] Lyon AR, Lopez-Fernandez 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.

[17] Suntheralingam S, Fan CS, Calvillo-Arguelles O, Abdel-Qadir H, Amir E, Thavendiranathan P. Evaluation of risk prediction models to identify cancer therapeutics related cardiac dysfunction in women with HER2+ breast cancer. J Clin Med. 2022; 11(3): 847.

[18] Cronin M, Crowley A, Davey MG, et al. Heart Failure Association-International Cardio-Oncology Society risk score validation in HER2-positive breast cancer. J Clin Med. 2023; 12(4): 1278.

[19] Captur G, Karperien AL, Hughes AD, Francis DP, Moon JC. The fractal heart—embracing mathematics in the cardiology clinic. Nat Rev Cardiol. 2017; 14(1): 56-64.

[20] Kawel-Boehm N, McClelland RL, Zemrak F, et al. Hypertrabeculated left ventricular myocardium in relationship to myocardial function and fibrosis: the multi-ethnic study of atherosclerosis. Radiology. 2017; 284(3): 667-675.

[21] Dawes TJW, Cai J, Quinlan M, et al. Fractal analysis of right ventricular trabeculae in pulmonary hypertension. Radiology. 2018; 288(2): 386-395.

[22] Captur G, Zemrak F, Muthurangu V, et al. Fractal analysis of myocardial trabeculations in 2547 study participants: multi-ethnic study of atherosclerosis. Radiology. 2015; 277(3): 707-715.

[23] Zheng T, Ma X, Li S, et al. Value of cardiac magnetic resonance fractal analysis combined with myocardial strain in discriminating isolated left ventricular noncompaction and dilated cardiomyopathy. J Magn Reson Imaging. 2019; 50(1): 153-163.

[24] Li Q, Feng Q, Zhou H, et al. Mechanisms and therapeutic strategies of extracellular vesicles in cardiovascular diseases. MedComm. 2023; 4(6): e454.

[25] Paterson DI, Wiebe N, Cheung WY, et al. Incident cardiovascular disease among adults with cancer: a population-based cohort study. JACC Cardiooncol. 2022; 4(1): 85-94.

[26] Cai J, Bryant JA, Le TT, et al. Fractal analysis of left ventricular trabeculations is associated with impaired myocardial deformation in healthy Chinese. J Cardiovasc Magn Reson. 2017; 19(1): 102.

[27] Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015; 131(22): 1981-1988.

[28] Sawicki KT, Sala V, Prever L, Hirsch E, Ardehali H, Ghigo A. Preventing and treating anthracycline cardiotoxicity: new insights. Annu Rev Pharmacol Toxicol. 2021; 61: 309-332.

[29] Tahir E, Azar M, Shihada S, et al. Myocardial injury detected by T1 and T2 mapping on CMR predicts subsequent cancer therapy-related cardiac dysfunction in patients with breast cancer treated by epirubicin-based chemotherapy or left-sided RT. Eur Radiol. 2022; 32(3): 1853-1865.

[30] Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2014; 27(9): 911-939.

[31] Ezaz G, Long JB, Gross CP, Chen J. Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Heart Assoc. 2014; 3(1): e000472.

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