Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab

doi:10.1016/j.ahj.2009.05.031

American Heart Journal

Volume 158, Issue 2, August 2009, Pages 294-301

https://doi.org/10.1016/j.ahj.2009.05.031 Get rights and content

Background

Trastuzumab prolongs survival in patients with human epidermal growth factor receptor type 2–positive breast cancer. Sequential left ventricular (LV) ejection fraction (EF) assessment has been mandated to detect myocardial dysfunction because of the risk of heart failure with this treatment. Myocardial deformation imaging is a sensitive means of detecting LV dysfunction, but this technique has not been evaluated in patients treated with trastuzumab. The aim of this study was to investigate whether changes in tissue deformation, assessed by myocardial strain and strain rate (SR), are able to identify LV dysfunction earlier than conventional echocardiographic measures in patients treated with trastuzumab.

Methods

Sequential echocardiograms (n = 152) were performed in 35 female patients (51 ± 8 years) undergoing trastuzumab therapy for human epidermal growth factor receptor type 2–positive breast cancer. Left ventricular EF was measured by 2- and 3-dimensional (2D and 3D) echocardiography, and myocardial deformation was assessed using tissue Doppler imaging and 2D-based (speckle-tracking) strain and SR. Change over time was compared every 3 months between baseline and 12 months.

Results

There was no overall change in 3D-EF, 2D-EF, myocardial E-velocity, or strain. However, there were significant reductions seen in tissue Doppler imaging SR (P < .05), 2D-SR (P < .001), and 2D radial SR (P < .001). A drop ≥1 SD in 2D longitudinal SR was seen in 18 (51%) patients; 13 (37%) had a similar drop in radial SR. Of the 18 patients with reduced longitudinal SR, 3 had a concurrent reduction in EF ≥10%, and another 2 showed a reduction over 20 months follow-up.

Conclusions

Myocardial deformation identifies preclinical myocardial dysfunction earlier than conventional measures in women undergoing treatment with trastuzumab for breast cancer.

Section snippets

Patient selection

We studied 152 serial echocardiograms from 35 consecutive female patients receiving trastuzumab as part of their treatment for either early or advanced breast cancer. Baseline characteristics are shown in Table I. Most of the patients had early breast cancer (n = 25) and typically underwent breast-conserving surgery or mastectomy with adjuvant therapy based on one of the following regimens: (1) a 4-cycle combination of doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m², followed by concomitant

Clinical characteristics

The clinical and echocardiographic details of the patients are summarized in Table I, Table II. Most patients had prior anthracycline exposure (91%) and had undergone radiotherapy with adjuvant taxane use. The median time between anthracycline commencement and the start of trastuzumab therapy was 12.5 weeks (range, 8-282 weeks).

Conventional indices of LV function

There was no significant decrease in mean 2D or 3D LVEF over time. During follow-up, 9 (26%) patients had a drop in 2D LVEF ≥10% from their initial study and 4 (11%) had

Discussion

The primary results of this study confirm that, as a sensitive marker of myocardial function, SR can identify reductions in LV function before conventional measures such as LVEF in patients with breast cancer undergoing therapy with trastuzumab. Furthermore, the use of 3D echocardiography as a more sensitive and reproducible measure of LVEF was not reliable to detect these changes.

Conclusions

The recognition of early LV dysfunction in patients with cancer undergoing trastuzumab therapy may allow the identification of individuals at risk of future heart failure, allowing targeted monitoring and possibly institution of potential therapies such as angiotensin-converting enzyme inhibitors.³¹ Although some reports indicate that many patients with acute trastuzumab-induced heart failure experience marked improvement with cessation and heart failure medication, long-term follow-up data are

Disclosures

Dr. Hare was supported by a scholarship (PC 07B 3407) cofunded by the Heart Foundation of Australia and the National Health and Medical Research Council of Australia.

References (32)

SmithI. et al.
2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial
Lancet
(2007)
HareJ.L. et al.
Performance of conventional echocardiographic parameters and myocardial measurements in the sequential evaluation of left ventricular function
Am J Cardiol
(2008)
JenkinsC. et al.
Reproducibility and accuracy of echocardiographic measurements of left ventricular parameters using real-time three-dimensional echocardiography
J Am Coll Cardiol
(2004)
PiegariE. et al.
Myocardial strain analysis in a doxorubicin-induced cardiomyopathy model
Ultrasound Med Biol
(2008)
LangR.M. et al.
Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology
J Am Soc Echocardiogr
(2005)
KukulskiT. et al.
Identification of acutely ischemic myocardium using ultrasonic strain measurements: a clinical study in patients undergoing coronary angioplasty
J Am Coll Cardiol
(2003)
ArmstrongG. et al.
Use of peak systolic strain as an index of regional left ventricular function: comparison with tissue Doppler velocity during dobutamine stress and myocardial ischemia
J Am Soc Echocardiogr
(2000)
RaysonD. et al.
Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies
Ann Oncol
(2008)
de KorteM.A. et al.
111Indium-trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: a clue to uncover the mechanisms of trastuzumab-related cardiotoxicity
Eur J Cancer
(2007)
MarwickT.H.
Measurement of strain and strain rate by echocardiography: ready for prime time?
J Am Coll Cardiol
(2006)

GanameJ. et al.

Myocardial dysfunction late after low-dose anthracycline treatment in asymptomatic pediatric patients

J Am Soc Echocardiogr

(2007)

ReantP. et al.

Experimental validation of circumferential, longitudinal, and radial 2-dimensional strain during dobutamine stress echocardiography in ischemic conditions

J Am Coll Cardiol

(2008)

RomondE.H. et al.

Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer

N Engl J Med

(2005)

SlamonD.J. et al.

Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2

N Engl J Med

(2001)

MackeyJ.R. et al.

Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab Working Group

Curr Oncol

(2008)

MercuroG. et al.

Early epirubicin-induced myocardial dysfunction revealed by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers

Oncologist

(2007)

Cited by (190)

Role of advanced cardiovascular imaging in chemotherapy-induced cardiotoxicity
2023, Heliyon
The development of cardiotoxicity induced by cancer treatments has emerged as a significant clinical problem, both in the short run, as it may influence drug administration in chemotherapeutic protocols, and in the long run, because it may determine adverse cardiovascular outcomes in survivors of various malignant diseases. Therefore, early detection of anticancer drug-related cardiotoxicity is an important clinical target to improve prevention of adverse effects and patient care. Today, echocardiography is the first-line cardiac imaging techniques used for identifying cardiotoxicity. Cardiac dysfunction, clinical and subclinical, is generally diagnosed by the reduction of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). However, myocardial injury detected by echocardiography is preceded by other alterations, such as myocardial perfusion and mitochondrial and metabolic dysfunction, that can only be recognized by second-level imaging techniques, like cardiac magnetic resonance (CMR) and nuclear imaging, which, using targeted radiotracers, may help to provide information on the specific mechanisms of cardiotoxicity. In this review, we focus on the current and emerging role of CMR, as a critical diagnostic tool of cardiotoxicity in the very early phase, due to its availability and because it allows the contemporary detection of functional alterations, tissue alterations (mainly performed using T1, T2 mapping with the evaluation of extracellular volume-ECV) and perfusional alteration (evaluated with rest-stress perfusion) and, in the next future, even metabolic changes.
Moreover, in the subsequent future, the use of Artificial Intelligence and big data on imaging parameters (CT, CMR) and oncoming molecular imaging datasets, including differences for gender and countries, may help predict cardiovascular toxicity at its earliest stages, avoiding its progression, with precise tailoring of patients’ diagnostic and therapeutic pathways.
Global Longitudinal Strain for the Early Detection of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-analysis
2022, Clinical Oncology
Left ventricular ejection fraction is used to monitor patients undergoing cardiotoxic chemotherapy. A decrease in left ventricular ejection fraction represents a relatively late stage of systolic involvement. Global longitudinal strain has been studied to detect early changes in left ventricular myocardial contractile function. The aim of the present study was to evaluate the global longitudinal strain measurement in the early detection of cardiotoxicity induced by cardiotoxic chemotherapeutic agents.
A study search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was carried out to report systematic reviews. A search on PubMed, EMBASE, Web of Science and SCOPUS was carried out using the following keywords: ‘echocardiography’ and ‘cardiotoxicity’ and their variations, without language or date restrictions (until March 2021).
In total, 4873 articles were identified for title and abstract analysis. The systematic review included 10 studies comprising 661 patients with cancer, including mainly breast cancer and haematological malignancies, mainly treated with anthracyclines. The meta-analysis included four studies: patients with cardiotoxicity showed a reduction in strain, compared with baseline, 14.13% greater than patients without cardiotoxicity (95% confidence interval 5.07–23.19; P < 0.01). No heterogeneity was observed between studies (I2 = 0).
The meta-analysis showed that strain is a tool with proper predictive capacity for the detection of cardiotoxicity.
Detection of subclinical heart failure
2021, ASE’s Comprehensive Strain Imaging
Identification of subclinical cardiomyopathy in patients with various systemic diseases provides an opportunity for early intervention and prevention of advanced heart failure. Although left ventricular ejection fraction is commonly used to identify subclinical cardiomyopathy, it often identifies late stages of myocardial dysfunction. Myocardial strain may be an ideal measure to identify early subclinical cardiomyopathy and discriminate patients at risk of subsequent advanced heart failure. In this review, we summarize the use of strain for diagnosis and prognosis in patients receiving cancer therapy, as well as those with hypertension, and diabetes.
Can post-chemotherapy cardiotoxicity be detected in long-term survivors of breast cancer via comprehensive 3D left-ventricular contractility (strain) analysis?
2019, Magnetic Resonance Imaging
Citation Excerpt :
The administration of certain anti-neoplastic chemotherapeutic agents (CTA), such as anthracyclines and trastuzumab, in breast cancer patients may lead to the complications of developing cardiotoxicity, and counter any gains in survivorship achieved with this form of treatment [1–6].
This study applied a novel and automated contractility analysis tool to investigate possible cardiotoxicity-related left-ventricular (LV) dysfunction in breast cancer patients following treatment with anti-neoplastic chemotherapy agents (CTA). Subclinical dysfunction otherwise undetected via LV ejection fraction (LVEF) was determined.
Deformation data were acquired with the Displacement Encoding with Stimulated Echoes (DENSE) MRI sequence on 16 female patients who had CTA-based treatment. The contractility analysis tool consisting of image quantization-based boundary detection and the meshfree Radial Point Interpolation Method was used to compare chamber quantifications, 3D regional strains and torsion between patients and healthy subjects (N = 26 females with N = 14 age-matched). Quantifications of patient LVEFs from DENSE and Steady-State Free Precession (SSFP) acquisitions were compared, Bland-Altman interobserver agreements measured on their strain results and differences in contractile parameters with healthy subjects determined via Student's t-tests.
A significant difference was not found between DENSE and SSFP-based patient LVEFs at 58 ± 7% vs 57 ± 9%, p = 0.6. Bland-Altman agreements were − 0.01 ± 0.05 for longitudinal strain and 0.1 ± 1.3° for torsion. Differences in basal diameter indicating enlargement, 5.2 ± 0.5 cm vs 4.5 ± 0.5 cm, p < 0.01, and torsion, 4.7 ± 1.0° vs 8.1 ± 1.1°, p < 0.001 in the mid-ventricle and 5.9 ± 1.2° vs 10.2 ± 0.9°, p < 0.001 apically, were seen between patients and age-matched healthy subjects and similarly in longitudinal strain, but not in LVEF.
Results from the statistical analysis reveal the likelihood of LV remodeling in this patient subpopulation otherwise not indicated by LVEF measurements.
Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study
2024, Cardio-Oncology
Automated segmentation of long and short axis DENSE cardiovascular magnetic resonance for myocardial strain analysis using spatio-temporal convolutional neural networks
2023, Journal of Cardiovascular Magnetic Resonance

View all citing articles on Scopus

View full text

Clinical InvestigationImaging and Diagnostic TestingUse of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab

Background

Methods

Results

Conclusions

Section snippets

Patient selection

Clinical characteristics

Conventional indices of LV function

Discussion

Conclusions

Disclosures

Lancet

Am J Cardiol

J Am Coll Cardiol

Ultrasound Med Biol

J Am Soc Echocardiogr

J Am Coll Cardiol

J Am Soc Echocardiogr

Ann Oncol

Eur J Cancer

J Am Coll Cardiol

J Am Soc Echocardiogr

J Am Coll Cardiol

Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer

N Engl J Med

Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2

N Engl J Med

Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab Working Group

Curr Oncol

Early epirubicin-induced myocardial dysfunction revealed by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers

Oncologist

Clinical Investigation
Imaging and Diagnostic Testing
Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab