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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 38-43

Evaluation of left ventricular function using speckle-tracking echocardiography in patients on chemotherapy and/or thoracic radiotherapy


Department of Cardiology, Dr. RMLIMS, Lucknow, Uttar Pradesh, India

Date of Submission24-May-2020
Date of Decision17-Jun-2020
Date of Acceptance20-Jun-2020
Date of Web Publication4-Aug-2020

Correspondence Address:
Dr. Ashish Jha
Department of Cardiology, Dr. RMLIMS, Vibhuti Khand, Gomti Nagar, Lucknow - 226 010, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_18_20

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  Abstract 


Background: Chemotherapy and radiotherapy in cancer patients are associated with significant cardiotoxicity. Novel technique of speckle-tracking echocardiography (STE) may help in the early detection of cardiotoxicity in these patients.
Aims and Objectives: The aim and objective of this study is to evaluate the left ventricular (LV) strain by STE in newly diagnosed cancer patients at baseline and to study the impact of chemotherapy and radiotherapy on these parameters in these patients. The present study was a prospective, observational study, done at a tertiary care center in North India.
Methods and Results: This study was carried out on 30 patients with newly diagnosed malignancy and 15 aged- and gender-matched healthy controls. These patients underwent two-dimensional (2D) echocardiography and STE at baseline and after the completion of their treatment. Baseline characteristics and echocardiographic parameters were similar between the cases and controls. No significant difference in left ventricular ejection fraction was seen before and after cancer therapy (64.27 ± 3.25 vs. 62.6 ± 3.12; P = 0.63), whereas global longitudinal strain reduced significantly from –21.16 ± 2.50 before cancer therapy to –19.86 ± 3.22 after it (P < 0.01). The global circumferential strain was also reduced significantly from –23.60 ± 7.36 before cancer therapy to –21.33 ± 6.97 after it. A significant reduction in segment-wise longitudinal strain rate was observed among the cases after cancer therapy in all segments.
Conclusions: The present study revealed that there was a significant worsening of LV systolic function as measured by the strain parameters on STE in cancer patients on chemotherapy and/or radiotherapy which was not detected by 2D echocardiography alone. STE may thus be a valuable tool in picking up early cardiotoxic changes in cancer patients.

Keywords: Cardiotoxicity, global circumferential strain, global longitudinal strain, left ventricular ejection fraction, speckle-tracking echocardiography


How to cite this article:
Singh DK, Jha A, Tiwari BC. Evaluation of left ventricular function using speckle-tracking echocardiography in patients on chemotherapy and/or thoracic radiotherapy. Heart India 2020;8:38-43

How to cite this URL:
Singh DK, Jha A, Tiwari BC. Evaluation of left ventricular function using speckle-tracking echocardiography in patients on chemotherapy and/or thoracic radiotherapy. Heart India [serial online] 2020 [cited 2020 Sep 19];8:38-43. Available from: http://www.heartindia.net/text.asp?2020/8/2/38/291354




  Introduction Top


The mortality rates among cancer patients have decreased significantly in the past few decades.[1] The cardiac toxicity (cardiotoxicity) from cancer therapy has become one of the leading cause of morbidity and mortality in survivors.[2] Therefore, it is important to screen for cardiac dysfunction, so that cardioprotective agents can be instituted before irreversible cardiac dysfunction has set in.

Conventionally, cardiac function analysis is done by the serial measurements of left ventricular ejection fraction (LVEF).[3] The use of LVEF, however, has several limitations. First, the measurement of LVEF preload dependent and heavy reliance on the echocardiographer makes it unreliable.[4] Further, the reduction in LVEF is often a late and irreversible phenomenon, with up to 58% of patients having failed normalization of LVEF despite interventions.[5]

It is therefore essential to detect myocardial dysfunction early. In recent years, there has been a growing interest in identifying the markers of early myocardial dysfunction, so that preventive medications such as dexrazoxane could be implemented on time.

Speckle-tracking echocardiography (STE) is a promising technique, to quantify regional left and right ventricular function which appears to be valuable for unmasking of cardiac pathologies. By measuring the myocardial deformation throughout the cardiac cycle, STE provides a more sensitive and comprehensive evaluation of myocardial function than the simple two-dimensional (2D) echocardiographic assessment of LVEF. In addition, the STE is an angle-independent technique which allows an accurate assessment of segmental myocardial deformation by gray-scale-based imaging analysis frame by frame.

The aim of the present study is to evaluate the left ventricular (LV) strain and deformation by STE in patients with malignancy and to evaluate the effect of chemotherapy and/or radiotherapy on LV strain and deformation in patients undergoing cancer therapy.


  Subjects and Methods Top


The present study was a prospective, observational study, done at a tertiary care center in North India. The study enrolled patients with malignancy undergoing cancer therapy in the form of chemotherapy and/or radiotherapy between March 2017 and September 2018. Written informed consent was obtained from all the study participants, and the study protocol was approved by the Institutional Ethics Committee.

Patients underwent 2D echocardiography and STE. This study was carried out on 30 patients with malignancy and 15 age- and sex-matched healthy subjects as a control group. Controls had no detectable cardiovascular risk factors and not receiving any medications, who were volunteers recruited from among the hospital staff, medical, and nursing students and members of the local community.

Patients were included in the study if they were more than 18 years old and had a newly diagnosed malignancy or already known malignancy but who have not yet been started on chemotherapy or radiotherapy, provided they consented to participate in the study.

The patients were excluded from the study, if they had any preexisting LV systolic dysfunction (LVEF < 55%), known coronary artery disease, established valvular heart disease or any other structural heart disease, diabetes mellitus, chronic obstructive pulmonary disease, pregnancy, or chronic kidney disease.

Conventional 2D echocardiography and 2D speckle-tracking imaging was performed using Philips IE 33. Images were obtained with patients in the left lateral decubitus position at end-expiration according to the recommendations of the American Society of Echocardiography and connected to single-lead electrocardiography. All standard measurements were recorded in the parasternal long- and short-axis views, apical four-chamber view. The LV dimensions were quantified using the M-mode echocardiography.

STE and 2 D strain imaging were done using Philips QLAB 10, cardiac and vascular ultrasound quantification software. After manual tracing of the endocardial border of 2D tomographic images of LV in longitudinal and short-axis plane at the mid cavity level at the end-systolic frame and selecting the appropriate region of interest, including the entire transmural wall, the software automatically determined six segments in each view. Each segmental strain curve was obtained by frame-by-frame tracking of the acoustic markers in the myocardial tissue. The tracking quality was scored as valid or poor. Segments with poor tracking despite manual readjustments of the region of interest were excluded from the analysis. Peak-systolic longitudinal strain (LS) was measured in seven segments (the apex, apical septum, mid inferior septum, basal inferior septum, basal anterolateral wall, mid anterolateral [MAL] wall, and apicolateral walls). Three cardiac cycles were analyzed and averaged value was taken as mean of regional and global longitudinal strain (GLS). Peak circumferential strain (CS) was measured in six segments (mid anterior, mid anterior septum, mid inferior septum, mid inferior, mid inferior lateral wall, and mid anterolateral wall) from a mid-LV short-axis view. Three cardiac cycles were analyzed, and the values were averaged and taken as the mean CS. The image acquisition was done using the standard protocol.

A detailed 2D echocardiography and STE were done at baseline and after 6 months of cancer therapy in both the arms.

Statistical analysis

The results are presented in frequencies, percentages, and mean ± standard deviation and percentages. The Chi-square test was used to compare the categorical variables between the groups. The unpaired t-test was used to compare the continuous variables between the groups. The paired t-test was used to compare the mean change in continuous variables from baseline to 6 months. P < 0.05 was considered statistically significant. All the analysis was carried out by using IBM SPSS 21.0 version (Chicago, IL, Inc., USA).


  Results Top


A total of 30 cases and 15 controls were included in the study. The mean ages of patients of cases and controls were 43.73 ± 13.75 and 42.76 ± 13.34 years, respectively. Females constituted nearly half of both cases and control arm. There was no significant difference in age or gender distribution between the groups [Table 1]. The baseline parameters of LVEF and STE were similar between the case and control arm. No significant changes were observed in LVEF or STE parameters at 6 months as compared to the baseline values in the control arm.
Table 1: Study population demography and baseline echocardiographic parameters

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In the case arm, there was no significant difference in LVEF (by M-mode) between the cases before (64.27 ± 3.25) and after (62.6 ± 3.12) cancer therapy, whereas GLS reduced from −21.16 ± 2.50 before cancer therapy to −19.86 ± 3.22 after it, and the difference was statistically significant [Table 2]. There was a significant reduction in segment wise LS between the cases before and after cancer therapy in all segments except in mid anterolateral, apex and mid inferoseptal segments.
Table 2: Echocardiographic parameters of cases at baseline and at 6-month follow-up

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The global circumferential strain (GCS) reduced from −23.60 ± 7.36 before cancer therapy to −21.33 ± 6.97 after it, and the difference was statistically significant (P < 0.01). There was a significant reduction in segment wise CS between the cases before and after cancer therapy in all segments except in basal anteroseptal (BAS) segment [Table 2].

A statistically significant (P < 0.05) reduction in segment wise longitudinal strain rate (LSR) was observed among the cases before and after cancer therapy in all segments. There was a statistically significant (P < 0.05) reduction in segment wise circumferential strain rate (CSR) between the cases before and after cancer therapy in all segments except in basal inferolateral segment [Table 3]. Postcancer therapy, there was a percent change of 9.06 ± 10.30% in GCS and a percent change of 6.59 ± 5.26% in GLS, and the difference was statistically significant (P < 0.05).
Table 3: Speckle-tracking echocardiography parameters of cases at baseline and at the 6-month follow-up

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The mean values of GLS in cases before and after cancer therapy were statistically not significantly different with different chemotherapeutic agent used [Table 4], except for taxanes and thoracic radiotherapy (P < 0.05). [Table 4] shows the percent changes in GLS after cancer therapy in cases based on whether or not patients received thoracic radiation added over chemotherapy. In cases only on chemotherapy without radiotherapy, it was- −5.93% ± 5.11%, whereas in those who received both, it was −6.93% ± 5.43%. The values were statistically significant (P < 0.05).
Table 4: Factors affecting global longitudinal strain pre- and post-therapy

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  Discussion Top


There has been a progressive improvement in the survival of cancer patients due to the availability of effective therapeutic options. Cardiac dysfunction related to cancer therapeutics remains an important management issue in these patients. It is thus important to assess the myocardial functions of any cancer patient before starting him on chemotherapy and/or radiotherapy and during the course of the treatment.

Traditional echo parameters such as LVEF and fractional shortening reflect only the global cardiac contractile function and do not take regional abnormalities in systolic function into consideration. These parameters are relatively insensitive to detect the early myocardial damage.

We studied GLS/GCS, regional strain, and strain rates, measured by STE, in patients with cancer (n = 30), being started on some form of cancer therapy, and in age- and sex-matched control group (n = 15). The two groups were age and gender matched.

Historically, several definitions of cardiotoxicity have been proposed. The most commonly used definition of a ≥5% reduction in symptomatic patients (or ≥10% reduction in asymptomatic patients) in the LVEF from baseline to a LVEF <53%.[6] In the present study, the mean baseline LVEF was 64.27 ± 3.25%, whereas that after 6 months was 62.6% ± 3.12%. The difference was neither statistically significant (P = 0.63), nor of the magnitude to define cardiotoxicity as per Δ LVEF (a mean decrease of 2.6% only). Hence, the study population in our study was one with preserved systolic function as per the LVEF criteria.

Despite preserved LVEF postcancer therapy, the mean GLS worsened from −21.16 ± 2.50 at baseline to −19.86 ± 3.22 at 6 months (P < 0.01), with a percent change of −6.59% ± 5.26% [Figure 1]. Our finding was similar to the finding by Negishi et al.,[7] where it changed from −20.0 ± 2.0 at baseline to −19.7 ± 2.0 at 6 months (percent change of −0.2% ± 8.6%) among patients without cardiotoxicity (LVEF criteria) and from −20.7 ± 2.6 to −18.3 ± 2.1 among those with cardiotoxicity (percent change of 11.4% ± 9.8%). Thavendiranathan et al.[4] also observed that in patients where a relative change in GLS was unavailable, absolute levels of GLS <-19% and −20.5% early during therapy had been associated with cardiotoxicity.
Figure 1: Global longitudinal strain and global circumferential strain of case arm at baseline and at 6 months

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Negishi et al.[7] found that GLS may be used as an independent and incremental early predictor of later reduction in EF in patients at risk for chemotherapy-induced cardiotoxicity. In patients with baseline strain measurements, reductions of strain of <8% appeared not to be meaningful, and those >15% were very likely to be abnormal.

As the case with GLS, cancer therapy was also found to negatively affect GCS. In our study, mean GCS reduced from −23.60 ± 7.36 to −21.33 ± 6.57 (P < 0.05) during our follow-up at 6 months, translating into a change of −9.06% ± 10.30% [Figure 1]. In a study by Negishi et al.,[7] GCS worsened from −17.0 ± 4.0 to −16.4 ± 3.0 (change of −1.0% ± 29.7%) in patients without cardiotoxicity and from −16.4 ± 3.0 to −15.7 ± 4.3 (change of −9.3 ± 27.4) in those with cardiotoxicity. An important limitation of GCS is the lower reproducibility of these measurements, which makes the identification of changes between before and after chemotherapy more challenging.

In the present study, segment-wise evaluation of CS revealed statistically significant (P < 0.05) deterioration in postcancer therapy values in all the segments except BAS, thereby underlining the widespread ongoing subclinical dysfunction in the absence of any significant reduction in LVEF. However, since none of the participants developed cardiotoxicity (i.e., >10% reduction in LVEF) during the study period, it remains to be established, how these changes in strain parameters correlate with the actual development of cardiotoxicity on further follow-up.

Strain rate assessment between precancer and postcancer therapy states revealed statistically significant (P < 0.05) reduction in both LSR and CSR in all the segments except for CSR in BIL segment. Negishi et al.[7] observed a mean GLSR of −1.05 ± 0.16 at baseline and −1.05 ± 0.18 at 6 months, with a mean change of 0.2% ± 16.8% in patients without cardiotoxicity, and a change of 12.8% ± 19.4% in patients with cardiotoxicity (from −1.17 ± 0.27 to −1.00 ± 0.15) (P < 0.05).

In the present study, the additive negative effect of radiotherapy on cardiac function, when given with chemotherapy was reemphasized. There was a statistically significant (P < 0.001) greater reduction in GLS (6.93% ± 5.43%) in patients on chemotherapy plus thoracic radiation than in those only on chemotherapy (5.93% ± 5.11%). Tsai et al.[8] showed that the patients who had received anthracycline and mediastinal radiotherapy had a significantly reduced GLS compared to those who had undergone chemotherapy alone (−16.1% ± 1.9% vs. −17.5% ± 1.7%, P < 0.05).

There are some important limitations of the present study. The sample size is small, and study duration is brief, so there is a limited power of the study. The sample size was too small to evaluate the impact of individual chemotherapeutic agents on the myocardial function. The echocardiographer was not blinded to the diagnosis of the patient. The reproducibility of the estimates of systolic strain using the speckle-tracking method was not recorded: Thus, there could have been measurement bias, especially in the small sample size study population.

Furthermore, it is not clear whether early identification of subclinical LV systolic dysfunction using 2D-STE will translate into the long-term cardiovascular benefits, and it warrants further investigation.


  Conclusions Top


The present study revealed that there was a significant worsening of LV systolic function as measured by the strain parameters on STE in cancer patients on chemotherapy and/or radiotherapy which was not detected by 2D echocardiography alone. STE may be a valuable tool in detecting the early myocardial damage in cancer patients undergoing chemotherapy or radiotherapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical Approval

All procedures followed were in accordance with the ethical standards of institutional ethics committee and with the Helsinki Declaration of 1964 and later versions. Informed consent was obtained from all patients participating in the study.



 
  References Top

1.
International Agency for Research on Cancer. World Cancer Fact Sheet. Geneva, Switzerland: World Health Organization; 2012. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer. [Last accessed on 2013 Sep 01].  Back to cited text no. 1
    
2.
Doyle JJ, Neugut AI, Jacobson JS, Grann VR, Hershman DL. Chemotherapy and cardiotoxicity in older breast cancer patients: A population-based study. J Clin Oncol 2005;23:8597-605.  Back to cited text no. 2
    
3.
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr., Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:1495-539.  Back to cited text no. 3
    
4.
Thavendiranathan P, Grant AD, Negishi T, Plana JC, Popović ZB, Marwick TH. Reproducibility of echocardiographic techniques for sequential assessment of left ventricular ejection fraction and volumes: Application to patients undergoing cancer chemotherapy. J Am Coll Cardiol 2013;61:77-84.  Back to cited text no. 4
    
5.
Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, de Giacomi G, et al. Anthracycline-induced cardiomyopathy: Clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 2010;55:213-20.  Back to cited text no. 5
    
6.
Virizuela JA, García AM, de Las Peñas R, Santaballa A, Andrés R, Beato C, et al. SEOM clinical guidelines on cardiovascular toxicity (2018). Clin Transl Oncol 2019;21:94-105.  Back to cited text no. 6
    
7.
Negishi K, Negishi T, Haluska BA, Hare JL, Plana JC, Marwick TH. Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection. Eur Heart J Cardiovasc Imaging 2014;15:324-31.  Back to cited text no. 7
    
8.
Tsai HR, Gjesdal O, Wethal T, Haugaa KH, Fossa A, Fossa SD, et al. Left ventricular function assessed by two-dimensional speckle tracking echocardiography in long-term survivors of Hodgkin's lymphoma treated by mediastinal radiotherapy with or without anthracycline therapy. Am J Cardiol 2011;107:472-7.  Back to cited text no. 8
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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