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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 1  |  Page : 7-13

Comparison between two and three-dimensional speckle-tracking echocardiography and cardiac T2* magnetic resonance imaging in ß-thalassemia


1 Department of Echocardiography, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Department of CMR, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
3 Blood Transfusion Research Center, Iran University of Medical Sciences, Tehran, Iran
4 Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
5 Cardiovascular Research Center, Kerman University of Medical Sciences, Kerman, Iran

Date of Submission13-Mar-2021
Date of Decision20-Apr-2021
Date of Acceptance20-Apr-2021
Date of Web Publication29-Jun-2021

Correspondence Address:
Dr. Batoul Naghavi
Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/rcm.rcm_15_21

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  Abstract 


Objective: We evaluated the accuracy of two-dimensional speckle-tracking echocardiography (2DSTE) and 3DSTE to identify early cardiac dysfunction in comparison with cardiac T2* magnetic resonance imaging (MRI) in patients with blood transfusion-dependent β-Thalassemia. Methods: A total of 48 consecutive patients (36 males) successfully underwent 2DSTE, 3DSTE, and MRI on the same day. We calculated left ventricular segmental global longitudinal strain (GLS) (%) and segmental global circumferential strain (GCS) (%) from strain curves. Cardiovascular MRI was performed with the relevant protocols to measure the T2*. Results: In this study, we found that the GLS and GCS derived from 3DSTE correlated with cardiac T2* (r = −0.50, r = −0.49, respectively), whereas no correlation was detected between 2DSTE parameters and cardiac T2*. We calculated the area under the receiver operating characteristic area under the curve to determine the capability of 3DSTE parameters including GLS (<−23.5%) and GCS (<−33.4%) to discriminate between patients with (cardiac magnetic resonance T2* <20 ms) and those without myocardial iron overload. Conclusion: The study will clarify GLS and GCS's superiority derived from 3DSTE over the 2DSTE parameters in the detection of myocardial iron overload in patients with blood transfusion-dependent β-Thalassemia.

Keywords: Cardiac magnetic resonance imaging, iron overload, magnetic resonance imaging T2*, speckle tracking, thalassemia, three-dimensional echocardiography


How to cite this article:
Fattahi H, Parsaee M, Rezaeian N, Azarkeivan A, Meimand SE, Mohammadi K, Naghavi B. Comparison between two and three-dimensional speckle-tracking echocardiography and cardiac T2* magnetic resonance imaging in ß-thalassemia. Res Cardiovasc Med 2021;10:7-13

How to cite this URL:
Fattahi H, Parsaee M, Rezaeian N, Azarkeivan A, Meimand SE, Mohammadi K, Naghavi B. Comparison between two and three-dimensional speckle-tracking echocardiography and cardiac T2* magnetic resonance imaging in ß-thalassemia. Res Cardiovasc Med [serial online] 2021 [cited 2021 Aug 2];10:7-13. Available from: https://www.rcvmonline.com/text.asp?2021/10/1/7/319787




  Introduction Top


β-Thalassemias are heterogeneous autosomal recessive hereditary hemoglobin disorders characterized by the declined or absent synthesis of β-globin chains. It is the most common genetic disease worldwide, and about 1.5% of the global population carries the gene for β thalassemia. There are three types of β-Thalassemia, including β-thalassemia major (TM), β-thalassemia intermedia (TI), and β-Thalassemia minor. Patients with β-thalassemia major need numerous transfusions to survive and relieve clinical manifestations, while individuals with TI have anemia with less severity and blood transfusion is required less often.[1],[2] Despite advancements in thalassemia's therapeutic management, a common clinical problem in patients with manifold blood transfusions is iron overload, which mandates chelation therapy. The sediment of iron in the myocardium causes iron-mediated cardiomyopathy and it is major cause of death and morbidity.[3],[4],[5] Cardiovascular magnetic resonance (CMR), precisely the T2* imaging technique, is the gold standard for detecting myocardial and hepatic iron load, thus being an acceptable modality for therapeutic guidance.[6],[7],[8] Due to its convenience and wide availability, echocardiography is usually the first-line imaging modality for assessing the LV ejection fraction (EF) and fractional shortening (FS). However, it is not accurate enough for the early diagnosis of cardiac iron overload. Two-dimensional speckle-tracking echocardiography (2DSTE) is a simple noninvasive technique for the quantification of left ventricular (LV) function and deformation (longitudinal, circumferential, and radial strains) in various cardiomyopathies. Because of inherent shortcomings of 2DSTE such as foreshortened views, interobserver and intraobserver variability, and geometric assumptions, 3DSTE is preferred to 2DSTE and is a more accurate and reproducible echocardiographic technique for the assessment of LV mechanics.[9],[10],[11],[12],[31],[14] This study aimed to define whether 2DSTE and 3DSTE could identify early cardiac dysfunction compared to cardiac MR T2* value in patients with blood transfusion-dependent β-Thalassemia.


  Methods Top


Subjects

We studied 48 ß-thalassemia patients (26 males and 22 females), attending a thalassemia center in an endemic area for thalassemia, known cases for receiving long-term blood transfusions, and undergoing iron chelation therapy. The patients met the following criteria: No hypertension (newly diagnosed or treated), no history of cardiac symptoms or disease, no LV dysfunction defined as EF <50%, no more than mild valvulopathy, no atrial fibrillation or flutter, no other significant pathologies such as renal disease and no current smoking. We did cardiac and liver magnetic resonance imaging (MRI) for assessing iron loading using T2* mapping and echocardiography. In all patients, mostly scheduled on the same day. Ferritin levels and other lab tests were measured in all cases at the hospital's laboratory simultaneously as MRI and echocardiography were done. One skilled fellow of echocardiography did echocardiographic examinations. All included patients had proper image quality for speckle-tracking and were in normal sinus rhythm. The ethics committee of Rajaie Cardiovascular, Medical and Research Center (Tehran, Iran) approved the study protocol, and informed consent was obtained from all the recruited study participants.

Echocardiographic imaging and analysis

Echocardiographic evaluations were performed on commercially available echocardiography devices for all patients: EPIQ 7 (Philips Healthcare). LV segmental global longitudinal strain (GLS) (%) and segmental global circumferential strain (GCS) (%) and time-to-peak strain (ms) of 17 segments cardiac model in eyeball tomogram were calculated from strain curves during the entire cardiac cycle by 2D and 3D speckle tracking echocardiography (STE) method at three views of apical 2 chambers, apical 3 chambers, and apical 4 chambers. We also measured the LV end-systolic volume, LV end-diastolic volume, EF, and other echocardiographic factors.

Cardiac magnetic resonance imaging and analysis

The iron stored in the heart and liver was measured using the T2* CMR technique. CMR scans were performed using an 18-element torso coil on a 1.5 Tesla MRI scanner (Siemens Avanto Germany). A standard black-blood T2* sequence was performed in a single breath-hold electrocardiogram-gated. All parametric mappings for myocardial T2* were acquired from the ventricular septum in the short-axis view which avoids possible artifacts. MRI T2* of the liver was measured from a single axial view with 10 mm thickness and gradient-echo sequence was scanned at 12 different echo times in a single breath-hold. All MRI studies were Interpreted by a certified radiologist with a subspecialty in cardiovascular imaging. T2* values were categorized into 4 groups including severe (T2* <10 ms), moderate (10 < T2* <14 ms), mild (14 < T2* <20 ms), and acceptable (T2* >20 ms).[15],[16]

Statistical analysis

We compared data as means ± standard deviation and group P values using two-tailed Student's t-tests. In this study, linear regression by Pearson correlation coefficient test was used to evaluate the correlation between the two methods and we considered P < 0.05 as significant. Receiver-operating characteristic curves were constructed for each strain parameter individually to find a cutoff point for GLS and GCS based on detecting cardiac iron overload. All statistical analyses were performed, using the Statistical Package for Social Sciences version 17.0 (SPSS Inc., Chicago, IL, USA).


  Results Top


MRI and speckle-tracking echocardiography were measured with reliable tracking quality in 48 patients in this study. The patients were 31 ± 8 years of age. Other clinical characteristics are displayed in detail [Table 1]. The patients were divided into two groups based on cardiac T2* value (T2*<20 and T2*≥20) and their echocardiography findings were compared together [Table 2].
Table 1: Clinical characteristics (n=48) of the study population

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Table 2: Comparison of echocardiographic findings between cardiac T2* based classified groups

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In this study, there is a significant moderate correlation between cardiac T2* with 3D GLS (r = −0.50, P < 0.001), 3D GCS (r = −0.49, P < 0.001), LVOT VTI (r = −0.49, P < 0.001), AV VTI (r = 0.47, P = 0.001) and Ferritin Level (r = −0.60, P < 0.001). Correlation between cardiac T2* value and E/e ′was weak (r = −0.36, P = 0.01). There is significant not strong correlation between liver T2* with cardiac T2* (r = 0.34, P = 0.016) and 3D GCS (r = −0.29, P = 0.04). There is a significant moderate correlation between liver T2* with Ferritin Level (r = −0.46, P = 0.001). Other correlations are briefly summarized in [Table 3] and [Table 4]. GLS and GCS values were significantly higher in 3DSTE in comparison to 2D STE. Strain parameters were significantly correlated between 2D and 3D modes. A GLS and GCS rate <23.5 and −33.4 could predict a cardiac T2* level below 20 and a GLS and GCS rate <22.3 and − 33.0 could predict a cardiac T2* level below 10 (severe myocardial iron loading), respectively. Other values are demonstrated in details [Figure 1] and [Figure 2].
Table 3: Echocardiographic findings and their correlation with cardiac magnetic resonance imaging T2* findings

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Table 4: Global strain values obtained by two-dimensional and three-dimensional speckle-tracking echocardiography

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Figure 1: Receiver operating characteristic curves to show the trade-off between sensitivity and specificity of global longitudinal strain and global circumferential strain and magnetic resonance imaging using using T2* value between T2*value and gt; 20 ms and T2* value and lt; 20 ms as an indicator of deposition of iron in the heart

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Figure 2: Receiver operating characteristic curves to show the trade-off between sensitivity and specificity of global longitudinal strain and global circumferential strain and magnetic resonance imaging using T2* value between T2*value and gt; 10 ms and T2* value and lt; 10ms as an indicator of deposition of iron in the heart

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3DSTE in all segments had significant relation with difference of T2* value between the two groups (T2*>20 and T2*<20) in comparison to 2DSTE that it had no significant relation [Table 2].


  Discussion Top


TM patients require numerous blood transfusions that put them at the risk of iron overload, cardiomyopathy, and heart failure which is the main cause of mortality (70%). With this in mind, early detection of iron overload in these patients is necessary to initiate chelation therapy as soon as possible and improve patients' survival.[3],[4],[17] Nowadays, T2-star (T2*) cardiac magnetic resonance (CMR) is a precise noninvasive modality to assess iron loading in these patients and lower limit of T2* value is defined as 20 ms (1.1 mg/g dw).[15],[18],[19],[20]

However, the availability and cost of CMR limits its use. Deposition of iron and anemia determines cardiac dysfunction progression; Cardiac dysfunction is associated with both the quantity of iron deposition in the myocytes and the extent of fiber involvement.[20],[21] In the early stages of this process, few cardiac remodeling is present and conventional echocardiography which examines factors such as EF (EF) and diastolic function indices (peak late diastolic flow velocity [A], the ratio of E and A [E/A], etc) is not accurate enough for neither the early stages of iron overload cardiomyopathy nor myocardial iron deposition.[13],[20],[22] 2DSTE has proved to be a simple technique to detect subclinical cardiac involvement sooner than an alteration in other conventional echocardiography parameters.[5],[21] 3DSTE is an advanced imaging technique that has several advantages over 2DSTE and is a promising tool to precisely quantify LV strain and may overcome the limitations of 2D-based speckle-tracking strain images such as foreshortened views and geometric modeling.[23],[24] To the best of our knowledge, limited data exist on the correlation of myocardial strain measurements by 3DSTE with T2* value in CMR of TM patients. This study is first of its kind that directly compares global LV strain between 2DEST and 3DEST and their correlation with T2* CMR in blood transfusion-dependent β-Thalassemia patients. In our study myocardial iron loading (T2*<20) was found in 16 patients (33.3%).

Ferritin level correlated moderately with myocardial T2* (r = −0.60, P < 0.001) and also there was a significant moderate correlation between liver T2* with Ferritin level (r = −0.46, P = 0.001) as we expected,[25] Although Abtahi et al.[13] have noticed no correlation between cardiac T2* MRI and ferritin level.[13] Range of serum ferritin levels in this study was widespread from 150 to 19,000 ng/mL in patients with cardiac T2*<20. Data from our study and also previous studies indicate that ferritin level does not necessarily show iron overload.

We revealed significant but poor correlation between diastolic indices such as septal early diastolic velocity (mm/sec)(P = 0.005), lateral early diastolic velocity (cm/sec) (P = 0.001), late mitral inflow velocity (A wave) (m/sec) (P = 0.035) and E/e ′(P = 0.012) with CMR T2*, concordant with Barzin et al. study[22] which showed a good correlation of diastolic echocardiographic parameters including DT, Tei index, E/Em index, and E/A with CMR T2* but no significant correlation between mitral deceleration time (msec) and cardiac T2*value. Poor correlation was demonstrated between cardiac T2* value and classic parameters for evaluation of diastolic function in other studies as well as in our study.[26],[27] These findings show that LV diastolic function still could be normal until the final stages of the disease. Patients with thalassemia in our study patients without overt heart failure but with severe iron overload (T2*<20) had mean LVEF of 54% and patients without both overt heart failure and severe iron overload (T2*>20) had mean LVEF of 55.8% respectively (P = 0.07) which shows no significant difference between these two groups. However, patients with cardiac T2*<20 ms had significant lower Septal systolic Velocity (cm/sec) (0.005) and LV stroke volume index (cc/m2) (P = 0.023) in comparison to cardiac T2*>20 ms populations. In the present study, we found a significant but moderate correlation between tricuspid annular plane systolic excursion (TAPSE) and cardiac T2* (r = 0.40, P = 0.004). It is noteworthy that in a study conducted by Abtahi et al.,[13] there was no significant difference in right ventricular (RV) systolic function regarding Sm and TAPSE thalassemia patients and a normal control group. Based on the present study, there is no significant association between cardiac T2* and GLS (P = 0.653) and GCS (P = 0.195) measured by 2DSTE. Di Odoardo et al.[5] and Parsaee et al.,[26] have shown that GLS (2DEST) did not correlate with cardiac T2* values in agreement with our findings.

The new technique based on 3DSTE was developed and is a promising tool to precisely quantify LV strain and overcome the limitations of 2D-based speckle-tracking strain images such as foreshortened views and geometric modeling.[19],[20],[23],[24] To the best of our knowledge, limited data exist on the correlation of myocardial strain measurements by 3DSTE with T2* CMR in TM patients. Our first study directly compares global LV strain between 2DEST and 3DEST and their correlation with T2* CMR in blood transfusion-dependent β-Thalassemia. In our study, myocardial iron loading (T2* <20) was found in 16 patients (33.3%). the ferritin level correlated moderately with cardiac T2* (r = −0.60, P < 0.001) also there was a significant moderate correlation between liver T2* with Ferritin level (r = −0.46, P = 0.001). These findings are similar to other studies that found a significant but weak correlation (r = −0.28) between cardiac T2* MRI and serum ferritin.[25] However, Abtahi et al.[13] have noticed no correlation between cardiac T2* MRI and ferritin level. This study's range of serum ferritin levels varied widely from 150 to 19,000 ng/mL in patients with cardiac T2*<20. The data from this study and previous studies indicate that ferritin level does not necessarily reflect iron overload. We demonstrated a significant poor correlation between diastolic indices including septal early diastolic velocity (mm/sec), lateral early diastolic velocity (cm/sec), late mitral inflow velocity (A wave) (m/sec), and E/e ′(e prime) with CMR T2* and no significant correlation of mitral deceleration time (msec) with cardiac T2*. Barzin et al.[22] also showed a good correlation of diastolic echocardiographic parameters including DT, Tei index, E/Em index, and E/A with CMR T2*. The poor correlation was also demonstrated between cardiac T2* value and classic parameters of diastolic function in other studies as well as in our study.[26],[27] This finding reveals that LV diastolic function could still be normal until the final stages of the disease. Thalassemic patients in our study did not have overt heart failure with mean LVEF, 54.0, and 55.8% in cardiac T2*<20 ms and cardiac T2*>20 ms populations, respectively (P = 0.071). However, the cardiac T2*<20 ms group had significant lower Septal systolic Velocity (cm/sec) and LV stroke volume index (cc/m2) versus cardiac T2*>20 ms population (P = 0.005 and P = 0.023 respectively). There was a significant but moderate correlation between TAPSE and cardiac T2* (r = 0.40, P = 0.004). In a study conducted by Abtahi et al.,[13] there were no significant differences in RV systolic function regarding Sm and TAPSE between the thalassemia patients a normal control group. Our study demonstrated that cardiac T2* had no association with 2DEST parameters (GLS and GLS). Di Odoardo et al.[5] and Parsaee et al.,[26] have shown that GLS (2DEST) did not correlate with cardiac T2* values in agreement with our findings. In contrast, Abtahi et al.[13] and Pizzino et al.[28] have shown that GLS (2DEST) showed a significant correlation with T2* values. It seems that 2DEST cannot replace CMR-T2* in the assessment of cardiac iron overload. We found that 3DEST including both GLS and GCS were significantly higher than 2DEST with significant moderate correlations (r = 0.54, P < 0.001 and r = 0.46, P = 0.001 respectively). 3DEST parameters were significantly correlated with cardiac T2*. Li et al.[29] have shown that T2* value correlated positively with global 3D strain (r = 0.74, P < 0.001). Iron deposition occurs predominantly on the subepicardial layer.[30] CS is indicative of deformation of the mid-or subepicardial fibers.[31] In contrast, the subendocardium plays a vital role on the longitudinal component of LV deformation,[32] expectation is that with iron deposition, CS will decrease more than LS. In agreement with this pathophysiology, we demonstrated that the 3D GCS correlated with cardiac T2* (r = –0.49, P < 0.001) but in contrast, no correlation was found between torsion and twist with cardiac T2*. Two studies found a 2D global LV longitudinal strain cutoff value of − 17 and − 19.5% or less predicted a T2* value < 20 ms with a sensitivity of 76%, 82%, and the specificity of 88%, 86% respectively.[13],[28] Given that there's different treatment of TM patients with T2*>10 and 10 < T2 *20 we evaluated both thresholds for sensitivity and specificity of detection of iron loading. Some experts initiate angiotensin-converting enzymes[33] and beta blockers[6] to improve LV FS in patients with 10 < T2*<20 (mild to moderate iron overload). In our study, 3DSTE had a statistically significant correlation with T2* <20, and when taking a threshold of − 23.5 and − 33.4%, as the cutoff value for GLS and GCS, it could detect iron deposition with a sensitivity of 68.8%, 75.0%, and specificity of 65.6%, 78.1% respectively. Also, the threshold of − 22.3 and − 33.0%, as the cutoff value for GLS and GCS, could detect severe Iron deposition (T2* <10) with a sensitivity of 87.5%, 75.0%, and specificity of 72.5%, 72.5%, respectively. Significant relation of 3DSTE and high sensitivity and specificity and these findings may suggest that assessment of 3DSTE can be used as a useful, less expensive, and available tool for screening cardiac iron overload, especially in countries with a limited MRI availability. Furthermore, many of TM patients have implanted ICD and many of them are not MRI compatible and another modality for the evaluation of iron loading is mandatory.

Limitations

We should mention several limitations. We obtained this study's results from a small group of patients. We did not include a control group in our study; This may limit the statistical power and find the specific cut off points for 3DSTE parameters to discriminate cardiac iron overload condition from its absence. Besides, the study's cross-sectional nature does not allow us to evaluate the prognostic implications of abnormal 3DSTE parameters in patients for early detection of cardiac iron overload during long-term monitoring and follow-ups. Intraobserver variability was not assessed in our study; thus, further studies are required to omit intraobserver variability that may affect the reliability of 3DSTE on assessing cardiac functions.


  Conclusion Top


Our study's novel contribution was the demonstration of the superiority of 3DSTE over the 2DSTE parameters in the detection of myocardial iron overload. Future prospective studies are warranted to determine the usefulness of 3DSTE as a screening tool for early detection of myocardial iron overload in patients with beta-thalassemia major requiring intensification of iron chelation therapy.

Ethical clearance

Ethical approval was obtained from the ethics committee of Rajaie Cardiovascular, Medical and Research Center in 8-February-2019.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

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



 

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Abstract
Introduction
Methods
Results
Discussion
Conclusion
References
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