A head-to-head comparison of myocardial strain by fast-strain encoding and feature tracking imaging in acute myocardial infarction

Background Myocardial infarction (MI) is a major cause of heart failure. Left ventricular adverse remodeling is common post-MI. Several studies have demonstrated a correlation between reduced myocardial strain and the development of adverse remodeling. Cardiac magnetic resonance (CMR) with fast-strain encoding (fast-SENC) or feature tracking (FT) enables rapid assessment of myocardial deformation. The aim of this study was to establish a head-to-head comparison of fast-SENC and FT in post-ST-elevated myocardial infarction (STEMI) patients, with clinical 2D speckle tracking echocardiography (2DEcho) as a reference. Methods Thirty patients treated with primary percutaneous coronary intervention for STEMI were investigated. All participants underwent CMR examination with late gadolinium enhancement, cine-loop steady-state free precession, and fast-SENC imaging using a 1.5T scanner as well as a 2DEcho. Global longitudinal strain (GLS), segmental longitudinal strain (SLS), global circumferential strain (GCS), and segmental circumferential strain (SCS) were assessed along with the MI scar extent. Results The GCS measurements from fast-SENC and FT were nearly identical: the mean difference was 0.01 (2.5)% (95% CI – 0.92 to 0.95). For GLS, fast-SENC values were higher than FT, with a mean difference of 1.8 (1.4)% (95% CI 1.31–2.35). Tests of significance for GLS did not show any differences between the MR methods and 2DEcho. Average strain in the infarct-related artery (IRA) segments compared to the remote myocardium was significantly lower for the left anterior descending artery and right coronary artery culprits but not for the left circumflex artery culprits. Fast-SENC displayed a higher area under the curve for detecting infarcted segments than FT for both SCS and SLS. Conclusion GLS and GCS did not significantly differ between fast-SENC and FT. Both showed acceptable agreement with 2DEcho for longitudinal strain. Segments perfused by the IRA showed significantly reduced strain values compared to the remote myocardium. Fast-SENC presented a higher sensitivity and specificity for detecting infarcted segments than FT.


Introduction
Coronary artery disease is a major cause of heart failure worldwide, as more patients now survive myocardial infarction (MI) due to improvements in prevention as well as in the availability of primary percutaneous coronary intervention (pPCI) in the case of ST-elevation MI (STEMI) (1)(2)(3)(4). Left ventricular (LV) adverse remodeling, which may develop post-MI, is a complex process, initiated by scarring, which results in myocardial functional and anatomical deterioration (1,2,4). A myocardial scar is characterized by wall thinning and abnormal wall motion. On a global level, increased LV volumes, .
/fcvm. . partial bulging of the LV wall, and reduced left ventricular ejection fraction (LVEF) are typical characteristics of remodeling (4, 5). Beyond LV volumes and LVEF, measurements of myocardial deformation, frequently denominated "strain, " can add information on the reduction in myocardial performance not yet visible in the gold standard LVEF (6). Two-dimensional echocardiography (2DEcho) studies have demonstrated that strain may predict adverse remodeling (4, 7). 2DEcho is a time and cost-effective standard procedure in post-MI care but is limited by the skills of the operator and problems evaluating segments due to artifacts and pulmonary shadowing (8). Cardiac magnetic resonance (CMR) is considered the reference method for the assessment of LV anatomy and function but has some drawbacks, such as being time-consuming, unsuitable for claustrophobic patients, and often requiring the use of gadolinium contrast, which is contraindicated in renal failure (9)(10)(11)(12). Late gadolinium enhancement (LGE) is the method of choice for detecting myocardial necrosis and scarring (2,9,13,14).
LGE imaging is commonly performed about 10-20 min after contrast injection to detect injured myocytes, infarct scar area, and its transmural extent, features that are not available with other imaging methods (2,9,13). Strain assessment by feature tracking (FT) or fast-strain encoding (fast-SENC) CMR may add to the evaluation of patients with acute MI by identifying individuals who could be at risk of developing adverse remodeling (10,15,16). Both techniques can assess strain in the longitudinal and circumferential directions, which has been shown to predict adverse remodeling of the LV (16)(17)(18)(19). The techniques used in FT and fast-SENC are discussed in Amzulescu et al. (6). FT is computed on cineloops which are part of the standard balanced steady-state free precession (bSSFP) CMR examination (8,16). These segmented 2D cine-loops are acquired over the entire heart cycle, usually "averaged" from 5 to 10 heartbeats, which makes deformation measurement possible for each time step (6,16,20). Feature tracking (FT) uses either optical flow technology or non-rigid elastic registration (21). Fast-SENC utilizes parallel tags and needs only a single heartbeat for image acquisition, and postprocessing can be completed in <2 min. This may eliminate the need for breath-holding, which is especially valuable in patients with respiratory diseases. In patients with cardiac arrhythmia, a single heartbeat image acquisition will also result in fewer artifacts (22). The aim of this study was to establish a head-tohead comparison of myocardial strain assessment, in both longitudinal and circumferential directions between fast-SENC and FT in STEMI patients immediately post-pPCI using echocardiographic speckle-tracking strain as the reference.

Study population
Patients with STEMI, treated with pPCI were offered CMR and 2DEcho within 2 days, while still in the hospital, between 4 November 2019 and 16 November 2020. In this time span, a total  of 250 patients were treated with pPCI for STEMI at our hospital. Forty-two patients were asked to participate, 12 declined, and 30 were finally enrolled in the study after giving written and oral consent, see Figure 1. The study complied with the Declaration of Helsinki and with agreements on Good Clinical Practice. The study protocol was approved by the Swedish Ethical Review Authority in Uppsala, registration number 2019-00480.
CMR acquisition and post-processing CMR including cine bSSFP, LGE, and fast-SENC was acquired on a 1.5T scanner (Achieva d-Stream, Philips Healthcare, Best, the Netherlands). The fast-SENC acquisition had a voxel size of 4.0 × 4.0 × 10 mm 3 , which was reconstructed to 1.0 × 1.0 × 10 mm 3 . The acquisition length was one  The typical breath-hold duration was 9 s for each view, at a heart rate of 60 beats per minute. Three different LA (two-, three-, and four-chamber) and SA (at basal, midventricular, and apical levels) images were obtained, excluding the SA apical segment. CS was derived from the SA segments and LS from the LA image segments according to the AHA model (23). The images were segmented for volume, left ventricular mass (LVM), and MI scar in the Segment software (v 2.2 R7056, Medviso AB, Lund, Sweden), which also included a module that was used for FT strain analysis (non-rigid elastic registration).
LGE was acquired in the same views as the cine images, using the PSIR-technique with a resolution of 1.5 × 1.5 × 10 mm 3 with a typical breath-hold duration of 12 s for each image. All strain values were evaluated at end-systole, which was determined from aortic valve closure. One observer performed segmentation for FT strain, LV volume, and MI scar analysis. A "scar" segment was defined if the LGE-positive area was >1%. The processing time for FT and fast-SENC was recorded for 10 randomly selected patients. For analysis of intraobserver and interobserver reproducibility, patients were re-analyzed twice by one CMR operator and once by another CMR operator, both experienced in the field. Operators were certified for the acquisition and analysis of fast-SENC by the vendor.

Echocardiography
Standard transthoracic 2DEcho was recorded for clinical routine evaluation by clinically experienced technicians with the patient in the left lateral decubitus position. Speckle tracking 2DEcho allows for the evaluation of myocardial deformation by assessing the movements of small natural acoustic markers during a heart cycle. A Vivid E-95 Ultrasound System (GE Vingmed Ultrasound; Horten, Norway) equipped with a 4Vcprobe was used for assessment of myocardial function and structure via the parasternal long axis, the apical two-, three-, and four-chamber views and when necessary also the subcostal views. End-systolic global longitudinal strain (GLS) was analyzed offline using the 2DS tool in EchoPAC PC Integrated version 203.74 (GE Ultrasound, Horten, Norway), by an echocardiographic specialist experienced in speckle tracking.

Comparison methodology
Global circumferential strain (GCS) and global longitudinal strain (GLS) derived from FT and fast-SENC were compared head-to-head. Speckle tracking end-systolic GLS from the 2DEcho gray scale was calculated for reference. All strains were correlated to LVEF CMR , MI scar, and its segmental extent ("transmurality"). The diagnostic performance of segmental circumferential strain (SCS) and segmental longitudinal strain (SLS) was based on individual segments and the regional strain was calculated by assigning myocardial segments to the three major coronary artery perfusion territories according to Cerqueira et al. (23). Strain in segments belonging to the infarct-related artery (IRA) was compared to remote myocardial segments. The detection of scar segments based on strain results was presented as the area under the curve (AUC) from receiver operating characteristics curve (ROC) analysis. Sensitivity was calculated at a specificity of 80% for the detection of any infarcted segment as well as for segments with transmurality >50%.

Statistical analysis
Analysis was performed using SPSS 27 (IBM Inc, Armonk, New York, USA). Continuous variables were presented as mean with SD (in parenthesis). Differences in continuous variables were tested with the analysis of variance non-parametric Friedman's Chi square test, where the level of significance was set to p < 0.01. Pearson correlation coefficients (ρ, df) where df = N−2, were calculated to express the degree of linear association between the variables. The correlation hypothesis tested was that ρ = 0 vs. ρ = 0 with a significance level set to p < 0.01. The intraclass correlation coefficient (ICC) was calculated, scatterplot graphs were drawn to depict the linear relationship between the variables and boxplots were created to illustrate the distribution of myocardial strain. Bland-Altman difference plots were presented to evaluate the agreement between the CMR methods.

Scar and ejection fraction
The subjects were enrolled and treated with pPCI after identification of the culprit artery in each case. The cohort displayed a median door-to-balloon time of 67 min. Average scar size was 15 (9) % of LVM with a median Troponin-T of 1,640 ng/l, equivalent to 164 × upper level of normal.

Myocardial strain
Strain comparisons are given in terms of "higher" when more negative, and "lower" when less negative, according to Voigt et al. (24). The GCS measurements from fast-SENC and FT were nearly identical, with a mean difference of 0.01   Table 3 and partly in Figures 4, 5.
Average strain in the IRA segments compared to the remote myocardium was significantly (p < 0.001) lower for left anterior descending artery (LAD) and right coronary artery culprits but not for left circumflex artery culprits, Table 4 and Figure 6. The average SCS from fast-SENC showed a higher correlation to MI scar than the average SCS for FT for each IRA segment distribution (p < 0.001). The highest correlation factor was computed for the average SCS and scar in the LAD region (ρ = 0.65, p < 0.001). In general, correlations were higher for fast-SENC in both strain directions compared to FT and 2DEcho, except for SLS vs. scar in LAD segments, Table 5. Figure 7 shows a two-chamber view example of an extensive anterior      infarction with LGE, fast-SENC CMR , and speckle tracking strain from 2DEcho.

Receiver operating characteristics analysis
Fast-SENC had a higher AUC for detecting infarcted segments than FT for both SCS and SLS. SCS derived from fast-SENC detected segments with scar transmurality >50%, with the highest sensitivity (73%) at a specificity of 80% and AUC (0.88). SLS derived from 2DEcho detected scar transmurality >50%, with the sensitivity of 73% at specificity of 80%, and AUC of 0.83, Figure 8.

Discussion
We performed a head-to-head comparison of myocardial strain assessment between fast-SENC and FT in post-STEMI patients. We were able to demonstrate good interobserver reproducibility and high correlations between the MR techniques with minor differences comparing GLS CMR to GLS of 2DEcho. This is in line with Bucius et al. who found high global strain correlations between fast-SENC, FT and myocardial tagging but who also presented a considerably greater bias between the methods than shown in our study. Furthermore, Obokata et al. also demonstrated high correlation and fairly wide limits of agreement between FT and speckle tracking echocardiography (25,26).
The assessment of LV contractile dysfunction after a STEMI has important prognostic relevance (11). Although LVEF is an important parameter post-MI, it may not be sufficiently sensitive for detecting subtle changes (6). The myocardial strain has been found to decline earlier than LVEF, which makes it an important complementing method for the evaluation of the LV (25). Many of the segments in our study had a scar transmurality <25%, so only subtle wall motion abnormalities should be expected. Still, we were able to detect significant differences in strain between IRA segments compared to the remote myocardium. This illustrates that strain measurement after myocardial infarction (MI) could possibly be useful for risk stratification of patients.
We were also able to demonstrate high correlations, with slightly higher absolute values for fast-SENC compared to FT and 2DEcho, in the detection of scar segments in the three perfusion territories. Few gadolinium-free alternatives exist for the detection of infarcted myocardial regions, but GCS has been proposed for this task (14). In our study, we could confirm this correlation between GCS and infarcted segments at a level similar to that in previous studies (14).
Both MR deformation methods provide a rapid and objective assessment of myocardial function, which makes them viable alternatives to other time-consuming MR procedures. Additional larger studies with patient follow-up could further .

FIGURE
-chamber view of an extensive anterior infarction with the transmural extent of late gadolinium enhancement and zones of no-reflow in the superior viewport, distinctly positive circumferential strain by fast-SENC in the scar area (yellow, middle viewport) and the corresponding speckle tracking longitudinal strain from DEcho (pale pink, lower viewport).

Conclusion
Fast-strain encoding showed higher sensitivity and specificity for detecting infarcted segments than FT. Segmental strain calculated for the perfusion territory of the infarct-related artery showed significantly lower strain values compared to the remote myocardium and this correlated with infarct transmurality. This study was not designed to explore the reproducibility of segmental strain values, but for global strain measurement, excellent reproducibility was detected. The GLS and GCS did not differ significantly between the two methods. Both MR methods showed acceptable clinical agreement with speckle tracking GLS obtained from echocardiography. The acquisition time of fast-SENC was very short, facilitating the investigation of patients with respiratory compromise.

Limitations
This was a study of STEMI patients early after the pPCI and the results may not be applicable in all situations of reduced systolic LV function. Most infarcted segments had MI transmurality <25% which may result in a very subtle lowering of strain. The relatively low number of participants also limits the conclusions. The participating patients were somewhat younger and the male proportion was larger than average for STEMI patients in our catchment area. The presence of risk factors was typical, but the reporting of a family history of cardiac disease in first-degree relatives was probably underrepresented or forgotten by the patients. Adding tagging or displacement encoding with stimulated echoes would have complemented the assessment of deformation measurements using CMR. The present study was limited to the acute phase of STEMI treatment and did not include patient follow-up. We have used the standard AHA definition of perfusion territories, but variation between left-and right-dominated coronary vessel anatomies may especially affect the partition of segments between the LCX and RCA territories, which could have weakened the associations in our evaluation.

Data availability statement
The datasets presented in this article are not readily available because of privacy concerns of the patients. However, data can be made available through the corresponding author, upon reasonable request. Requests to access the datasets should be directed to walid.el-saadi@liu.se.

Ethics statement
The studies involving human participants were reviewed and approved by the Swedish Ethical Review Authority in Uppsala, registration number 2019-00480. The patients/participants provided their written informed consent to participate in this study.
Author contributions JE, JK, TE, MM, and SF participated in the design method and CMR acquisition, to ensure high-quality images. JE included patients, reviewed the manuscript, coordinated, and supported the study with research funding. WE-S, J-EK, and JK analyzed and interpreted the data, performed the statistical analysis, and wrote the manuscript with the assistance of all the other coauthors. JA and SS revised the manuscript for important related content and helped with the interpretation of the data and results. All authors made relevant contributions to the study. Before publication, the manuscript was reviewed and approved by all authors.

Funding
Financial support for WE-S was obtained from Futurumthe unit for research and education, the academy for health and care in County Hospital Jönköping, and the Research Council of Southeastern Sweden. The study was supported by the Faculty of Medicine and Health Sciences, Linköping University, Sweden. This study was not supported by any specific funding that could have influenced the results.