Role of Tei Index in Early Detection of Anthracycline-induced Cardiotoxicity

Abstract

Background:

Although anthracycline chemotherapy is widely used in different types of cancer, they are commonly known to induce cardiotoxicity. Early diagnosis of cardiotoxicity induced by cancer therapy is of great interest. Due to the insensitivity of left ventricular ejection fraction (LVEF) in the early identification of cardiotoxicity, global longitudinal strain (GLS) has become the best approach for early cardiotoxicity identification. The goal of our research was to assess the function of the Tei Index, a relatively new tool for evaluating both diastolic and systolic function, in the prediction of cardiac dysfunction.

Materials and Methods:

One hundred patients were enrolled in our prospective observational study. Demographic and clinical data were collected at the first visit. Assessments of LVEF, GLS, and the Tei Index were taken before initiation of therapy and subsequently at 3- and 6-month intervals (2^nd and 3^rd visit, respectively) following anthracycline.

Results:

The patients’ mean age was 44.79 ± 14.26 years, predominantly females (76%). The mean LVEF fell from 63.44 ± 3.61 to 59.90 ± 6.00 6 months following chemotherapy. At the 6-month visit, 16% patients developed evident impairment in left ventricular systolic function with LVEF below 55%. The mean GLS at the first visit was 19.94 ± 2.68 and showed a significant decrease in its values to 17.27 ± 2.1 6 months postchemotherapy, with 20% of patients having a percentage change in GLS ≥15% (subclinical cardiotoxicity). Mean Tei Index has been significantly increased from 0.42 ± 0.09 at the first visit to 0.52 ± 0.08 at the third visit. After 6 months postchemotherapy, there was a significant inverse relationship between ejection fraction (EF) and Tei Index (P < 0.001, r = −0.309); on the other hand, there was a notable direct relationship between EF and GLS (P < 0.001, r = −0.438) after 3 months and (P < 0.001, r = −0.583) after 6 months postchemotherapy. Tei Index with cutoff of 0.46 was found to have 100% sensitivity, 57% specificity, and 27.3% positive predictive value (PPV) for the prediction of cardiac dysfunction in comparison to GLS, which had 100% sensitivity, 95 specificity, and 80% PPV.

Conclusion:

Tei Index is a good negative test for ruling out the cardiac dysfunction, but not for confirming the condition. Keep in mind, follow up should be lasted longer for further assessment of the cardiac dysfunction that may become evident at longer periods. However, our primary purpose was to look for early signs of cardiotoxicity.

INTRODUCTION

Chemotherapy is considered the most effective and extensively utilized modality in treating cancer, whether administered alone or in conjunction with radiation.

Anthracyclines are the most common therapeutic agents used for various types of cancer. The most widely acknowledged mechanism for anthracyclines’ effect is topoisomerase-II inhibition (Top2). Top2α and Top2 β are the two isoenzymes that express Top2. When linked to Top2α, the resulting complex suppresses the replication of deoxyribonucleic acid, stops the cycle of cells, and causes apoptosis[1] in proliferating malignant cells. Binding to Top2 β causes mitochondrial dysfunction by suppressing the peroxisome proliferator-activated receptor, which controls oxidative metabolism. In adult mammalian cardiomyocytes, this causes mitochondrial malfunction and cell death. This is how anthracyclines cause cardiotoxicity.[2,3]

As a result, their therapeutic use may be severely restricted by cardiotoxicity, varying from silent echocardiographic abnormalities to severe cardiomyopathy and heart failure.

Echocardiography is the most available imaging modality for tracking the anthracycline cardiotoxic effects. Left ventricular ejection fraction (LVEF) is the main used parameter for monitoring the cardiac function, but unfortunately, it is not sensitive in the detection of minor pathological changes occurring in cardiac myocytes that eventually result in obvious and even permanent cardiomyopathy.

Nowadays, speckle tracking using the global longitudinal strain (GLS) has become the rising modality in follow-up cancer patients receiving chemotherapy owing to its superior sensitivity and specificity among other echocardiographic modalities in predicting those at risk for experiencing cardiotoxicity. According to the recommendations of the European Society of Cardiology, a decrease in GLS of >15% indicates subclinical cardiotoxicity.[3]

However, due to limited local expertise and availability of speckle tracking, it is not routinely used in all our cancer patients, so we were aiming to identify a more simple, available, and easy to be obtained parameter for identifying patients at risk for developing cardiotoxicity.

Tissue Doppler Tei Index is considered an easy and reliable tool to predict changes in both diastolic and systolic function. It was used by Tei and his coworkers in 1995.[4]

It can be estimated by a two-dimensional 2D transthoracic echocardiography (TTE), putting a Doppler sample at the septal mitral annulus and calculating this formula: the total of isovolumetric relaxation and contraction time divided by the ejection time.[5] It is easy to be calculated and appears not to be affected by heart rate and blood pressure. Several studies of cancer patients have reported that the Tei Index can predict early abnormalities in cardiac function. There is still controversy regarding the use of the Tei Index in the early diagnosis of subclinical cardiotoxicity; some studies support its use[6,7] and others do not.[8,9,10] We conducted this prospective study to better understand the Tei Index’s role in the early detection of subclinical cardiotoxicity in those planning to receive anthracycline chemotherapy.

MATERIALS AND METHODS

A prospective evaluation was conducted involving outpatients diagnosed with various malignancies who were receiving anthracyclines and referred to our Tanta Cardio-oncology Unit. Every patient has assigned an informed consent. Our study included patients older than 18 years old, any type of cancer requiring anthracycline chemotherapy, first use of anthracycline, baseline echocardiography with no significant abnormal findings, and LVEF ≥55%.

We excluded cancer patients who were being treated with chemotherapeutic agents other than anthracyclines, had previous chemotherapy or radiation to the chest, previous history of heart failure, LVEF <55% as assessed by echocardiography, had significant severe valvular disease, and patients with ischemic heart disease, an unstable cardiac condition such as pericardial effusion or congestive heart failure, and very poor image quality.

Each patient had a documented record, which included their age, sex, and risk factors such as hypertension, diabetes mellitus, thyroid, chest diseases, and any previous cardiac history. During the medical examination, arterial pressure was measured, while heart rhythm and rate were analyzed using 12-lead electrocardiography.

Echocardiographic evaluation and Tei Index measurement

A 2D TTE was performed for every patient at three-time visits: (1) before the start of chemotherapy, (2) after 3 months of chemotherapy, and (3) after 6 months of chemotherapy.

Echocardiographic measurements were obtained using the Vivid E9 ultrasound (General Electric [GE] Vingmed Ultrasound) using an M5S phased array transducer (2.5–5.0 MHz) and a specialized software package for the study, following the guidelines of the American and European Society of Echocardiography.

Left ventricular ejection fraction by the Simpson method

In the apical four- and two-chamber view, LVEF was estimated using the modified biplane Simpson formula: (end diastolic volume [EDV]–end systolic volume)/EDV. This approach has been agreed by the American Society of Echocardiography and the European Association of Cardiovascular Imaging as the current most accurate method for assessing left ventricular (LV) systolic function.[7]

Diastolic function assessment

For assessment of ventricular filling using the mitral inflow velocities, pulsed-wave (PW) Doppler was used in the apical four-chamber view. The following parameters were subsequently measured: peak E wave velocity (E), late mitral inflow velocity (A) and the E/A ratio, early diastolic mitral annular velocity (E′), E/E′, and deceleration time (DT).

Tei Index assessment

Tissue Doppler Tei Index was calculated from the apical four-chamber view, with the sample volume placed at the septal mitral annulus. The end of the a′-wave (the atrial contractility) to the beginning of the s-wave (myocardial systolic wave) represented the isovolumetric contraction time by tissue Doppler (tIVCT) and the end of the S-wave to the beginning of the e′-wave (early diastolic wave) represented the isovolumetric relaxation time (tIVRT); finally, tissue Doppler imaging (TDI) ejection time (tET) was the time from the start to the end of the s-wave. The TDI Tei Index was then computed by this formula: (tIVCT + tIVRT)/tET as shown in Figure 1.[7]

Figure 1.

Tei Index measurement by tissue Doppler imaging[11]

Global longitudinal strain measurement

Three apical views were archived for speckle tracking and assessment of GLS. The measuring protocol of GLS for GE machines is based on automated function imaging software. We started with the apical 3-chamber view and followed the machine’s instructions. The three-chamber view illustrates the anterior septum and inferolateral wall, the inferoseptal wall and anterolateral wall are visualized in the four-chamber view, while the two-chamber view displays the inferior and anterior walls. Hence, when the apical chamber echo window is clear, all 17 segments can be examined. We did not proceed if there were two or more segments in any imaging plane that were not accepted by the machine software for analysis, as shown by the machine’s red display. Upon completion of the study, the system utilized several forms of color coding, one for the segments studied and another for the strain characteristics of interest. GLS was obtained by averaging the three regional myocardial strain values, which was subsequently displayed using a bull’s eye map to illustrate the global and segmental strain patterns.[11] GLS was considered normal if its value was ≥−18%.[11]

Percentage change in GLS (ΔGLS) was calculated between first and follow-up visits to detect changes in GLS values from baseline measurement; a decrease in GLS values of ≥15% between pre- and postchemotherapy was considered clinically significant.[12]

Once cardiotoxicity was detected by clinical and echocardiographic data, cardioprotective drugs were prescribed for the patients according to chamber dimensions, hemodynamic state (B. blocker and/or ACEI).

Statistical analysis

Data analysis was done using the SPSS software (version 25, IBMcorp., Armonk, NY, USA. Categorical variables were summarized as frequencies and percentages. The normality of continuous variables was assessed using the K–S test. Quantitative data were expressed as range (minimum to maximum), mean with standard deviation, or median with interquartile range.

The collected data were considered significant at the 5% level, and the significance between the various phases was analyzed using the marginal homogeneity test. To compare between two studied groups for normally distributed quantitative variables, Student’s t-test was used, but to compare between more than two periods or stages for normally distributed quantitative variables, ANOVA with repeated measures was conducted. Post hoc test (adjusted Bonferroni) was used for pairwise comparisons we used.

The Pearson’s correlation coefficient was used to assess the relationship between two normally distributed quantitative variables, whereas the Spearman’s rank correlation coefficient was applied for abnormally distributed quantitative variables. The diagnostic accuracy of the studied parameters was assessed using receiver operating characteristic (ROC) curve analysis.

RESULTS

The study included 100 patients who fulfilled the inclusion criteria (mentioned before). No patients were omitted from the study due to mortality, bad imaging quality, significant cardiac symptoms, or missing follow-ups during treatment.

Among the 100 adult patients, 24% were males and 76% were females. Age ranged from 18 to 66 years (mean = 44.79 years ± 14.26). Breast cancer was the predominant malignancy included in our study, comprising 68% of the study sample. Table 1 demonstrates the baseline clinical and demographical characteristics.

Table 1.

Echocardiographic variables during baseline and follow-up visits

		Baseline (n=100)		Second visit (n=100)		Third (n=100)		P1		P2
Peak e velocity		0.66±0.14		0.59±0.13		0.55±0.11		<0.001*		<0.001*
Peak a velocity		0.62±0.14		0.65±0.14		0.69±0.13		0.008*		<0.001*
DT		171.8±52.18		171.6±51.26		180.2±44.76		1.000		0.015*
E/A ratio		1.08±0.30		0.90±0.23		0.82±0.20		<0.001*		<0.001*
E’		0.09±0.03		0.08±0.01		0.07±0.02		0.001*		<0.001*
E/e’		7.14±2.0		7.85±2.46		7.7±2.3		0.0022*		0.0112*
IVRT		57.88±11.47		64.88±10.94		68.08±10.30		<0.001*		<0.001*
Tei Index		0.42±0.09		0.47±0.08		0.52±0.08		<0.001*		<0.001*
EF		63.44±3.61		63.08±2.84		59.90±6.00		0.434		<0.026*
GLS		19.94±2.68		18.41±2.30		17.27±2.1		<0.001*		<0.001*

*Mean significant. DT=Deceleration time, IVRT=Isovolumetric relaxation time, EF=Ejection fraction, GLS=Global longitudinal strain

Diastolic function

The diastolic function parameters are listed in Table 1. The mean peak e velocity, E/A ratio, and e` have been significantly decreased throughout the study after the second visit and the third visit. The mean peak velocity and E/E` were significantly increased after 3 months of chemotherapy. The DT was significantly increased after 6 months of chemotherapy. The number of patients with diastolic dysfunction Grade I has increased from 32% to 40% and with diastolic function Grade II has increased from zero % to 24%.

Tei Index

IVRT was significantly increased after 3 months. Mean Tei Index at baseline was 0.42 ± 0.09 that was significantly increased to 0.47 ± 0.08 at the second visit and to 0.52 ± 0.08 at the 3^rd visit [Table 1].

Changes in systolic function (ejection fraction) and global longitudinal strain

Prechemotherapy LVEF by TTE was normal in all patients, with a mean of 63.64% ± 3.33%. While the mean LVEF was still in the normal range at follow-up visits in 84% of patients, we still found a marked decrease in LV systolic function 6 months postchemotherapy compared to baseline [Table 1].

Sixteen patients (16%) experienced an evident cardiotoxicity characterized by a drop in LVEF more than 10% from baseline and reached a value under 55%.

The mean GLS at baseline was −19.94 ± 2.68. At the second visit, mean GLS significantly reduced to −18.41 ± 2.30, with 20 (20%) patients having a percentage decrease in GLS by ≥15%. Six months postchemotherapy, mean GLS showed a notable decline measured at −17.27 ± 2.1 [Table 1].

Relation between Tei Index, global longitudinal strain, and ejection fraction

Pearson’s correlation analysis was done for testing the reliability of possible predictors, and we found that ejection fraction (EF) had a significant inverse relationship with Tei Index after 6 months [Table 3], and there was a significant direct relationship between EF and GLS that started after 3 months of chemotherapy [Table 2].

Table 3.

Comparison between changes in Tei Index, global longitudinal strain, and ejection fraction between Group 1 and Group 2

		Cardio toxicity				t		P
		No (n=84), mean±SD		Yes (n=16), mean±SD
EF		63.90±2.94		61.0±5.56		2.033		0.058
		63.52±2.50		60.0±3.79		3.570		0.002*
		62.05±3.36		47.5±6.0		9.423		<0.001*
Tei Index		0.42±0.08		0.43±0.11		0.347		0.732
		0.46±0.08		0.53±0.05		4.591		<0.001*
		0.51±0.07		0.60±0.07		4.714		<0.001*
GLS		20.17±2.75		18.75±1.98		2.453		0.02*
		18.88±2.05		15.7±1.69		6.652		<0.001*
		17.80±1.87		14.5±0.516		13.67		<0.001*

*Mean significant. EF=Ejection fraction, GLS=Global longitudinal strain, SD=Standard deviation

Table 2.

Relation between Tei Index, global longitudinal strain, and ejection fraction

		Baseline				Second				Third
		R		P		R		P		R		P
EF versus Tei Index		−0.068		0.497		−0.162		0.107		−0.309		0.001*
EF versus GLS		0.009		0.926		0.438		<0.001*		0.583		<0.001*
Tie Index versus GLS		−0.234		0.019*		−0.641		<0.001*		−0.616		<0.001*

*Mean significant. EF=Ejection fraction, GLS=Global longitudinal strain

Association between changes in Tei Index, changes in global longitudinal strain, and systolic dysfunction

To find out the association between impaired systolic function and Tei Index, individuals were separated into two groups: Group 1 comprised patients who did not develop cardiotoxicity and Group 2 who did. By analysis of data, we found that baseline mean Tei Index and EF did not differ significantly between the two groups; however, mean GLS showed a statistically notable variation.

During serial follow-up, the mean Tei Index in Group 2 (who developed cardiotoxicity) was significantly elevated in comparison with Group 1, as shown in Figure 2.

Figure 2.

Comparison between Group 1 and 2 regrading changes in mean Tei Index

Regarding the GLS parameter, a significant decrease in mean GLS between both groups was noticed after 3 months of chemotherapy and throughout the study, as shown in Figure 3.

Figure 3.

Comparison between Group 1 and 2 regrading changes in mean global longitudinal strain. GLS: Global longitudinal strain

These data conclude that in Group 2 patients, there was a significant rise in Tei Index and a significant decrease in GLS 3 months earlier, before the occurrence of evident clinical cardiotoxicity (after 6 months).

ROC analyses showed that Tei Index values >0.46 were able to identify patients with systolic dysfunction (sensitivity 100%, specificity 57%, area under the curve (AUC) = 0.750, a high negative predictive value (NPV) (92.9%), but low positive predictive value (PPV) of 27.3%). This low PPV reflects that the test has a high rate of false positives when used with the >0.46 cutoff as shown in Figure 4.

Figure 4.

Receiver operating characteristic curve for Δ Tie Index to diagnose abnormal ejection fraction (EF) (n = 16) versus normal EF (n = 84). AUC: Area under the curve

However, regarding the GLS, ROC analysis showed that the sensitivity and specificity of ∆GLS (≥15) to predict abnormal reduction in abnormal reduction in EF were 100% and 95%, respectively, AUC = 0.958, PPV = 80%, and NPV = 100% in Figures 5 and 6.

Figure 5.

Receiver operating characteristic curve for Δ global longitudinal strain to diagnose abnormal ejection fraction (EF) (n = 16) versus normal EF (n = 84). GLS: Global longitudinal strain

Figure 6.

Comparison of receiver operating characteristic curves of the Tei Index and global longitudinal strain in early identifying subjects with systolic dysfunction. GLS: Global longitudinal strain

DISCUSSION

The discovery of anthracyclines in the 1960s was a breakthrough in oncology. They remain the fundamental component of contemporary chemotherapeutic protocols for a wide range of malignancies, but they are often accompanied by adverse drug reactions that limit the use of them in the clinics. The most clinically concerning toxicity associated with anthracycline chemotherapy is cardiotoxicity.[13]

Therefore, careful measurement of myocardial function is important, particularly in patients predisposed to serious cardiac complications. 2D speckle tracking echocardiography has been approved to be an effective tool for predicting early abnormalities in ventricular function.[14] However, the 2D speckle tracking software is not available in all TTE machines.

Hence, our goals were to validate an accessible and accurate diagnostic approach for early detection of anthracycline-related subclinical cardiac dysfunction before the occurrence of obvious abnormalities in LVEF. In this present prospective evaluation, we assessed and then compared the diagnostic performance of two echocardiographic parameters, including the Tei Index and GLS for early cardiotoxicity detection.

The current study analyzed the diastolic function parameters of the left ventricle, including the Tei Index, and their association to systolic dysfunction in cancer patients receiving chemotherapy.

Regarding the diastolic function assessment using the PW Doppler and TDI Doppler, which included the following parameters “Peak E velocity, peak A velocity, E/A ratio, E/e` ratio, DT, IVCT, IVRT, and finally the Tei Index,” we found the following results:

Peak e velocity and E/A ratio have declined significantly after 3 months. These results are similar to that from Upshaw et al.,[15] Boyd et al.,[16] and Cochera et al.,[17] all reported that E/A ratio has been decreased with time. These findings differ from those of Anqi et al.[18] where there were no apparent changes in E, A, and E/A ratio.

Our study found that DT increased from 173 to 180 ms at the 6-month follow-up visit, which was consistent with Serrano et al.’s findings[19] (DT increased from 186 to 201 ms) and Rashid et al.[5] These findings contradict Upshaw et al.[15] and Anqi et al.,[18] who found no consistent increases in DT over time.

The (E)/E’ ratio increased, but E’ at the septal mitral annuli decreased significantly. This came in agreement with Serrano et al.[19] and Tassan-Mangina et al.[20] This came in contrast to the findings with Stoodley et al., who reported no notable variation in E′ velocity or in the E/E′ ratio postchemotherapy.[21]

However, regarding IVRT, findings varied among studies; Serrano et al.[19] and Rashid et al.[5] reported a significant increase in IVRT that is consistent with our study. Whereas, Boyd et al.[16] and Upshaw et al.[15] found no consistent changes in IVRT over time.

A statistically significant elevation in the Tei Index was noticed, with values rising from 0.42 ± 0.09 to 0.52 ± 0.08 by the end of the study time.

This is consistent with Sulaiman et al.’s finding[22] at which the mean Tei Index was significantly higher than baseline levels, and Naderi et al. also reported that the Tei Index increased significantly in children receiving anthracyclines.[23] Similarly, Contaldi et al. showed a rise in the Tei Index in patients undergoing anthracycline treatment.[24]

Our results regarding the Tei Index are not consistent with Agha et al. who found that LV Tei Index showed no significant changes postchemotherapy.[25]

Regarding the EF, in our study, there were significant changes in EF throughout the study compared to the baseline. EF significantly decreased (P < 0.001) throughout the entire study, with 16% of patients have developed cancer therapy-related cardiotoxicity after 6 months of chemotherapy. These results are in line with Bennett et al.[31] who demonstrated a significant decrease in EF, with 23% of patients diagnosed having an asymptomatic decline more than 10% and also come in agreement with Zhang et al.[26] where after 2–4 cycles of anthracycline, there was a discernible decline in LVEF, with 24 (29.3%) patients having a decrease of radionuclide LVEF by 10% from baseline and an apparent functional decline was observed in five (6.1%) patients with their LVEF dropping from normal levels to values under 50%. It is also consistent with Anqi et al.[18] where there was a significant decrease in mean LVEF throughout the study.

Other studies reported no significant decrease in EF after anthracycline treatment, as reported by Puzzovivo et al.[7] at which during the course of chemotherapy administration and follow-up, none of the patients investigated experienced a substantial reduction in LVEF.

Regarding the GLS in our study, it decreased significantly after anthracycline therapy. A decline in GLS by ≥15% which is indicative of subclinical cardiac dysfunction was observed in 20% of the studied patients. These results come in agreement with many studies that reported a significant decrease in GLS after anthracyclines, for example, Boyd et al.[16] demonstrated a significant decrease in GLS, with 29 patients (22%) developing subclinical cardiotoxicity. Anqi et al.[18] and Abo El Magd Rasheed et al.[14] also found a significant decline in GLS, similar to our results.

Isovolumic contraction time and ET are powerful systolic parameters, and they are included in the Tei Index measurement, so the Tei Index is considered a trustworthy tool for early detection of abnormalities in LV systolic function.

In our study, the Tei Index exhibited a strong negative association with both EF and GLS; higher index values are accompanied by lower EF, lower GLS values, and vice versa.

The results were comparable to other studies as LaCorte et al.[27] who reported that the Tei Index had an inverse relationship with EF as detected by echocardiogram at baseline. Similarly, a negative correlation was noted between the percent change in Tei Index and the corresponding change in EF.

Our results demonstrated that the significant rise in Tei Index started before the significant alterations in EF. This is similar with Eidem et al.[28] who reported that the marked changes in the LV Tei Index started before the changes in LV systolic function.

We compared the Tei Index in patients who developed cardiotoxicity (Group 2) and the patients who do not (Group 1) and found that at baseline, neither of these groups showed a marked difference in Tei Index. However, during follow-up, the Tei Index in Group 2 was considerably higher than in Group 1. This comes in consistency with Shaikh et al.[29] and Erdoğan et al.[30]

Hamamoto et al.[6] also reported the Tei Index was significantly elevated in patients who developed subclinical cardiac dysfunction compared to those who did not develop.

Finally, we compared between the Tei Index and GLS for the prediction of cardiac dysfunction, and we found that there is a substantial link between the Tei Index, EF as well as GLS. Higher Tei Index values are accompanied by lower EF values, but lower GLS values are associated with lower EF values.

However, regarding the sensitivity and specificity of both values, we found that GLS is more sensitive and specific (sensitivity 100% and specificity 95%) than the Tei Index (sensitivity 100% and specificity 52%) in early detection of cardiotoxicity. In other words, Tei Index values <0.45 are excellent in ruling out the future occurrence of cardiotoxicity, but values more than 0.45 can early detect patients who are predisposed to develop cardiotoxicity, and they still need to be further investigated and followed up.

These results are similar to the results of Puzzovivo et al.[7] who reported that the Tei Index evaluation can be used to detect patients at elevated risk of cardiotoxicity, as this study demonstrated a correlation between Tei-derived systolic/diastolic function and EDV during anthracycline therapy and with stroke volume at follow-up.

Similarly, Zhang et al.[26] found that the Tei Index is effective in detecting early mild impairment in LV systolic function, so it can be used as a useful parameter for the prediction of anthracycline-induced cardiotoxicity.

In addition, our findings are further supported by Bennett et al.[31] who reviewed multiple studies. Six of these studies found that a significant elevated Tei Index during follow-up was a reliable predictor for subtle cardiac dysfunction. Furthermore, comparing LVEF with the Tei Index, five studies reported that the Tei Index was superior in predicting the early cardiotoxicity before changes in LVEF. Only three studies reported that the LVEF is still superior than the Tei Index for the prediction of cardiotoxicity.

Unlike our results, a study done by Rohde et al.[32] reported different observations, at which patients were classified into two groups according to LVEF assessment by radionuclide ventriculography: group 1 included patients with normal final EF ≥50% and Group 2 who had impaired final EF <50%. These two groups had similar Tei Index values.

ROC curve for their study showed that Tei Index has a limited role for detecting the early ventricular dysfunction.

Furthermore, using 10% decrease in LVEF as parameter for diagnosing anthracycline-induced cardiotoxicity rather than using final LVEF <50% did not improve the predictive value of the Tei Index.

Follow up visits after six months of chemotherapy should be lasted longer for further assessment of the cardiac dysfunction that may become evident at longer periods. However, our primary purpose was to look for early signs of cardiotoxicity.

Limitations of the study

Follow up visits after six months of chemotherapy may be considered a short period for monitoring the cardiac function in cancer patients and it can be lasted longer for further assessment of the cardiac dysfunction that may become evident at longer periods. However, our primary purpose was to look for early signs of cardiotoxicity.

Lack of information about the cumulative dose of anthracycline due to many patients were transferred from centers outside the university hospital with no documentation of actual dose, as it may influence observed variability in cardiotoxicity rates.

Combining simultaneous different approaches incorporating both systolic and diastolic measures to compare them with histological data should be put in mind in further large prospective studies to determine the best tool for detecting early anthracycline cardiotoxicity.

CONCLUSION

Tei index is a valuable screening and rule-out tool (high sensitivity and NPV), GLS still remains the more specific and accurate method for early detection of cardiotoxicity where available.

Ethical approval

The study received prior approval from the Local Research Ethical Committee, Quality Assurance Unit, Tanta university adhering to the Helsinki Declaration (approval number: 35897/10/22).

Conflicts of interest

There are no conflicts of interest.

Funding Statement

This work was funded from Ph.D. Thesis entitled “Role of Tie Index in Early Detection of Anthracycline Induced Cardiotoxicity” by the co-author, SAshraf.