Intrinsic Wave Velocity Propagation: A Novel Parameter for Assessing the Effect of Anthracycline Chemotherapy Agents on Cardiac Diastolic Function in Breast Cancer Patients

Abstract

Objective

Anthracycline chemotherapeutic agents have significant cardiotoxicity. The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular (LV) myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation (IVP), and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment.

Methods

A total of 68 newly diagnosed breast cancer patients, who were treated with anthracycline-based chemotherapy, were analyzed. Transthoracic echocardiography was performed at baseline (T0), and after 1, 2, 3, 4 and 8 chemotherapeutic cycles (T1, T2, T3, T4 and T5, respectively). Then, the IVP, LV strain parameters [global longitudinal strain (GLS), longitudinal peak strain rate at systole (LSRs), longitudinal peak strain rate at early diastole (LSRe), longitudinal peak strain rate at late diastole (LSRa), and the E/LSRe ratio], and conventional echocardiographic parameters were obtained and further analyzed. A relative reduction of >15% in GLS was considered a marker of early LV subclinical dysfunction.

Results

Compared to the T0 stage, IVP significantly increased at the T1 stage. However, there were no significant changes in GLS, LSRs, or LSRe between the T0 and T1 stages. These parameters significantly decreased from the T2 stage. LSRa started to significantly decrease at the T5 stage, and the E/LSRe ratio started to significantly increase at the T3 stage (all P<0.05). At the T0 stage, IVP (AUC=0.752, P<0.001) had a good predictive value for LV subclinical dysfunction after chemotherapy.

Conclusions

IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.

Keywords

breast cancer / anthracycline chemotherapy drugs / intrinsic wave velocity propagation / myocardial stiffness / cardiac diastolic function

References

[1] WilkinsonL, GathaniT. Understanding breast cancer as a global health concern. Br J Radiol, 2022, 95(1130): 20211033

[2] BerryGJ, JordenM. Pathology of radiation and anthracycline cardiotoxicity. Pediatr Blood Cancer, 2005, 44(7): 630-637

[3] PiegariE, De AngelisA, CappettaD, et al.. Doxorubicin induces senescence and impairs function of human cardiac progenitor cells. Basic Res Cardiol, 2013, 108(2): 334

[4] MolinaroM, AmeriP, MaroneG, et al.. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs. Biomed Res Int, 2015, 2015: 138148

[5] McGowanJV, ChungR, MaulikA, et al.. Anthracycline Chemotherapy and Cardiotoxicity. Cardiovasc Drugs Ther, 2017, 31(1): 63-75

[6] GulatiM, MulvaghSL. The connection between the breast and heart in a woman: Breast cancer and cardiovascular disease. Clin Cardiol, 2018, 41(2): 253-257

[7] UpshawJN, FinkelmanB, HubbardRA, et al.. Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy. JACC Cardiovasc Imaging, 2020, 13(1): 198-210 Pt 2

[8] LipshultzSE, AdamsMJ, ColanSD, et al.. Longterm cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation, 2013, 128(17): 1927-1995

[9] PfefferMA, ShahAM, BorlaugBA. Heart Failure With Preserved Ejection Fraction In Perspective. Circ Res, 2019, 124(11): 1598-1617

[10] PislaruC, PellikkaPA, PislaruSV. Wave propagation of myocardial stretch: correlation with myocardial stiffness. Basic Res Cardiol, 2014, 109(6): 438

[11] PislaruC, AlashryMM, ThadenJJ, et al.. Intrinsic Wave Propagation of Myocardial Stretch, A New Tool to Evaluate Myocardial Stiffness: A Pilot Study in Patients with Aortic Stenosis and Mitral Regurgitation. J Am Soc Echocardiogr, 2017, 30(11): 1070-1080

[12] ZhangJ, DengY, TangQ, et al.. Evaluation of Myocardial Stiffness in Hypertensive Patients by Intrinsic Wave Propagation of the Myocardial Stretch. Ultrasound Med Biol, 2020, 46(10): 2683-2691

[13] NaguehSF, SmisethOA, AppletonCP, et al.. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr, 2016, 29(4): 277-314

[14] CelutkieneJ, PudilR, Lopez-FernandezT, et al.. Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC). Eur J Heart Fail, 2020, 22(9): 1504-1524

[15] LyonAR, Lopez-FernandezT, CouchLS, 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

[16] ZamoranoJL, LancellottiP, Rodriguez MunozD, et al.. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J, 2016, 37(36): 2768-2801

[17] CardinaleD, ColomboA, BacchianiG, et al.. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation, 2015, 131(22): 1981-1988

[18] GulatiG, ZhangKW, Scherrer-CrosbieM, et al.. Cancer and cardiovascular disease: the use of novel echocardiography measures to predict subsequent cardiotoxicity in breast cancer treated with anthracyclines and trastuzumab. Curr Heart Fail Rep, 2014, 11(4): 366-373

[19] ChanJ, ShiinoK, ObonyoNG, et al.. Left Ventricular Global Strain Analysis by Two-Dimensional Speckle-Tracking Echocardiography: The Learning Curve. J Am Soc Echocardiogr, 2017, 30(11): 1081-1090

[20] CharbonnelC, Convers-DomartR, RigaudeauS, et al.. Assessment of global longitudinal strain at low-dose anthracycline-based chemotherapy, for the prediction of subsequent cardiotoxicity. Eur Heart J Cardiovasc Imaging, 2017, 18(4): 392-401

[21] TimóteoAT, Moura BrancoL, FilipeF, et al.. Cardiotoxicity in breast cancer treatment: What about left ventricular diastolic function and left atrial function?. Echocardiography, 2019, 36(10): 1806-1813

[22] SritharanHP, DelaneyGP, LoQ, et al.. Evaluation of traditional and novel echocardiographic methods of cardiac diastolic dysfunction post radiotherapy in breast cancer. Int J Cardiol, 2017, 243: 204-208

[23] LiVW, CheukDK, ChengFW, et al.. Myocardial stiffness as assessed by diastolic wall strain in adult survivors of childhood leukaemias with preserved left ventricular ejection fraction. Eur Heart J Cardiovasc Imaging, 2017, 18(4): 451-458

[24] VillemainO, CorreiaM, MousseauxE, et al.. Myocardial Stiffness Evaluation Using Noninvasive Shear Wave Imaging in Healthy and Hypertrophic Cardiomyopathic Adults. JACC Cardiovasc Imaging, 2019, 12(7): 1135-1145 Pt 1

[25] EllimsAH, ShawJA, StubD, et al.. Diffuse myocardial fibrosis evaluated by post-contrast t1 mapping correlates with left ventricular stiffness. J Am Coll Cardiol, 2014, 63(11): 1112-1118

[26] PislaruC, IonescuF, AlashryM, et al.. Myocardial Stiffness by Intrinsic Cardiac Elastography in Patients with Amyloidosis: Comparison with Chamber Stiffness and Global Longitudinal Strain. J Am Soc Echocardiogr, 2019, 32(8): 958-968.e4

[27] De JesusT, AlashryMM, PadangR, et al.. Intrinsic cardiac elastography in patients with primary mitral regurgitation: predictive role after mitral valve repair. Eur Heart J Cardiovasc Imaging, 2021, 22(8): 912-921

[28] SerranoJM, GonzálezI, Del CastilloS, et al.. Diastolic Dysfunction Following Anthracycline-Based Chemotherapy in Breast Cancer Patients: Incidence and Predictors. Oncologist, 2015, 20(8): 864-872