Cardiac magnetic resonance assessment of long-term cardiac function after early recombinant staphylokinase thrombolysis before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction patients

Introduction

Acute ST-segment elevation myocardial infarction (STEMI) is a prevalent and life-threatening cardiovascular event that leads to severe cardiac dysfunction if not treated promptly and effectively (1,2). The 2023 European Society of Cardiology guidelines recommend that, when possible, percutaneous coronary intervention (PCI) should be performed within 120 minutes of the first medical contact, and if this timeframe cannot be met, thrombolytic therapy should be initiated promptly (3). However, the guidelines do not provide a clear consensus on the use of thrombolytic therapy within the 120-minute window from first medical contact to PCI. Several earlier investigations showed that thrombolytic therapy before PCI may increase the risk of bleeding; however, among the various thrombolytic agents, recombinant staphylokinase (r-SAK) has shown promising efficacy in the treatment of STEMI in several clinical trials. For example, Chen et al. demonstrated that r-SAK thrombolysis improves the patency of the infarct-related artery and reduces the infarct size without increasing the risk of bleeding, leading to favorable short-term outcomes (4). However, the long-term effects of r-SAK thrombolysis administered before primary PCI on left ventricular (LV) and left atrial (LA) function in STEMI patients remain inadequately explored.

Cardiac magnetic resonance (CMR) imaging is the gold standard for the non-invasive assessment of cardiac function and tissue viability (5,6). It provides an accurate measurement of both ventricular volume, function, and myocardial tissue characteristics (7). CMR feature tracking enables the quantification of global and regional myocardial deformation, offering valuable insights into myocardial damage and recovery for STEMI patients (8-10). Additionally, LA function, particularly LA strain parameters derived from CMR feature tracking, such as reservoir strain and conduit strain, may serve as sensitive indicators of long-term cardiac function (11-14). These capabilities make CMR imaging an ideal tool for assessing the long-term effects of thrombolytic therapy on cardiac recovery in STEMI patients.

This study aimed to evaluate the long-term effects of early r-SAK thrombolysis before primary PCI on LV and LA function in STEMI patients using CMR. By comparing CMR-derived LV and LA parameters between the r-SAK and the normal saline (NS) groups, we sought to determine whether early r-SAK thrombolysis enhances long-term cardiac function recovery. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-816/rc).

Methods

Study population

This retrospective study collected the data of STEMI patients enrolled in the OPTIMA-5 trial (titled “Single-bolus r-SAK Before Primary PCI for ST-elevation Myocardial Infarction: Optimal Management of Antithrombotic and Thrombolytic Agent-5 Trial”). The OPTIMA-5 trial is an investigator-initiated, prospective, multi-center, randomized, controlled trial. It compares a single bolus of r-SAK with NS in STEMI patients presenting within 12 hours of symptom onset and scheduled to undergo PCI within 120 minutes. Informed consent was obtained from all the participants. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of The First Affiliated Hospital with Nanjing Medical University (No. 2021-SR-309). All the other participating centers were informed of and agreed to participate in this study.

We analyzed the data of 200 STEMI patients who were enrolled in the OPTIMA-5 study between November 2021 and August 2022. Patients were included in the study if they: (I) had a diagnosis of STEMI confirmed by clinical presentation and electrocardiogram (ECG) findings; (II) were aged 18 to 75 years and had a body weight of ≥45 kg; (III) consented to undergo the one-year CMR imaging examination and had no contraindications to magnetic resonance imaging (MRI). The exclusion criteria included prior myocardial infarction (n=2), coronary artery bypass grafting (n=1), PCI (n=1), a history of myocarditis (n=1), and/or poor-quality images (n=6). Ultimately, 66 patients were included in the study. The patients were divided into the r-SAK group (n=32) and the NS group (n=34) based on whether a single half-dose of 5 mg r-SAK or NS was administered within 120 minutes after the first medical contact and before PCI. Figure 1 shows a detailed flow chart of the study.

Figure 1 Flowchart of the study. CABG, coronary artery bypass grafting; CMR, cardiac magnetic resonance; NS, normal saline; PCI, percutaneous coronary intervention; SAK, staphylokinase; STEMI, ST-segment elevation myocardial infarction.

Demographic and clinical data

The demographic and clinical information of the patients was collected, including age, gender, body mass index, systolic blood pressure, and diastolic blood pressure. Additionally, their medical history, including hypertension, diabetes mellitus, hypercholesterolemia, smoking status, and alcohol consumption was also recorded. The following time intervals were documented: (I) the duration from symptom onset to randomization (r-SAK or NS); (II) the time from randomization to the start of reperfusion treatment; (III) the time from symptom onset to the start of reperfusion treatment; and (IV) the time of CMR scanning after primary PCI. Additionally, the peak levels of high-sensitive cardiac troponin T (hscTnT, ng/L) and peak N-terminal pro-brain natriuretic peptide (NT-proBNP, ng/L) during the course of the disease were recorded, as were the hemoglobin (Hb, g/L) values at the time of the CMR imaging examination.

We recorded bleeding events from primary PCI to CMR imaging examination using the Bleeding Academic Research Consortium (BARC) definition (15), harmonized with the parent trial, to assess differences in bleeding risk between the two groups. Definition and grading procedures are detailed in Appendix 1. Data on the use of beta-blockers, diuretics, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) at/near CMR imaging examination were collected from the patient medical records to assess any potential medication-related effects on cardiac function.

CMR imaging protocol

All the participants underwent CMR imaging on a 3-T MRI system (Philips, Ingenia, the Netherlands, or GE Healthcare, Milwaukee, WI, USA). The imaging was performed with an 18-channel phased-array coil combined with a spinal coil using ECG gating.

Cine MRI scans were acquired using balanced steady-state free precession sequences with a single excitation and retrospective ECG-triggering, including three long-axis slice images of the left ventricle (2-, 3-, and 4-chamber views), and a stack of parallel short-axis slice images covering the entire left ventricle without interval. The Philips scan parameters were as follows: time to repetition/time to echo (TR/TE) 3.5/1.4 ms; reverse angle: 45°; thickness: 8 mm, inter-slice gap: 2 mm; cardiac cycle: 25 frames; and spatial resolution: 2.0×1.6×8 mm³. The GE Healthcare scan parameters were as follows: TR/TE: 3.47/1.51 ms; reverse angle: 60°; thickness: 10 mm; cardiac cycle: 25 frames; and spatial resolution: 2.0×1.6×8 mm³.

Late gadolinium enhancement (LGE) images were acquired 10 to 15 minutes after the intravenous administration of 0.2 mmol/kg of gadoterate magnevist (Bayer Schering Pharma AG, Berlin, Germany). LGE was performed using a two-dimensional phase-sensitive inversion recovery sequence. The entire left ventricle was scanned continuously without gaps on the short-axis view, supplemented by 2-, 3-, and 4-chamber views. The Philips scan parameters were as follows: TR/TE: 6.1/3 ms; reverse angle: 25°; thickness: 8 mm; field of view: 300 mm × 300 mm; matrix: 160 × 139 mm; and spatial resolution: 1.9×1.6×8 mm³. The GE Healthcare scan parameters were as follows: TR/TE: 6.62/3.10 ms; reverse angle: 25°; thickness: 10 mm; field of view: 260 mm × 260 mm; matrix: 256 mm × 130 mm; and spatial resolution: 1.9×1.6×8 mm³.

CMR analysis

All the CMR images of the participants were analyzed using CVI42 (version 5.0, Circle Cardiovascular Imaging Inc., Calgary, Canada) software. End-diastole and end-systole were identified by an automated full-cycle volumetric search for the maximal and minimal LV cavity volumes across 25 frames, with manual verification as needed (16). Basal slices were included only when a contiguous myocardial ring ≥180° with a clear blood-pool border was present. The LV-LA boundary was set at the mitral annular plane (16). Papillary muscles and moderator bands were excluded from the volumes, and the automatically generated contours were manually adjusted as necessary. Cardiac volumetric and functional parameters were automatically generated by the CVI42 software; all the volume and mass parameters were normalized to the body surface area (BSA), including the end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI), left ventricular mass index in end-diastole (LVMI_ED), and cardiac index (CI). Left ventricular ejection fraction (LVEF), LV wall thickness at diastole and systole, LV wall motion, and LV wall thickening were also measured. LV and right ventricular (RV) stroke volumes should be similar when valvular regurgitation is not moderate or severe (17). To address the potential confounding by regurgitation and to validate the LV volumetric segmentation, we measured RVSVI and assessed the concordance between the LVSVI and RVSVI.

A global and segmental strain analysis was performed using the acquired balanced steady-state free precession cine images. A set of cine images, including short-axis and three long-axis views (2-, 3-, and 4-chamber views), were loaded into the CVI42 software’s feature-tracking module. Endocardial and epicardial contours were manually delineated at the end-diastole phase, and then automatically tracked throughout the cardiac cycle. The global strain parameters measured included the global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS). According to the myocardial segmentation method of the American Heart Association, the LV myocardium was divided into 16 segments, and the segmental strain parameters, including the segmental radial strain (SRS), segmental circumferential strain (SCS), and segmental longitudinal strain (SLS), were also assessed.

The phases of maximum volume, pre-atrial contraction, and minimum LA volume were identified on the CMR cine images. LA endocardial contours were manually delineated in the 2- and 4-chamber views at the specific phases. Subsequently, the CVI42 software automatically calculated the following LA volumes: maximal left atrial volume (LAVmax, at the LV end-systole), pre-atrial contractile volume (LAVpre-ac, at the LV diastole before LA contraction), and minimal LA volume (LAVmin, at the late LV end-diastole after LA contraction). The changes in the LA volume across three phases were recorded as follows: △LAV reservoir=LAVmax − LAVmin; △LAV conduit = LAVmax − LAVpre-ac; and △LAV booster=LAVpre-ac − LAVmin. All the LA volumetric parameters, and △LAV were normalized to the BSA. Measurements of the LA area and the lengths on the 2- and 4-chamber views of a participant are shown in Figure S1. The total, passive, and booster emptying fraction (EF) of the left atrium were calculated based on the corresponding LA volumes using the following equations (14):

LAtotalEF=LAVmax−LAVminLAVmax×100%[1]

LApassiveEF=LAVmax−LAVpre-acLAVmax×100%[2]

LAboosterEF=LAVpre-ac−LAVminLAVpre-ac×100%[3]

At the phase of maximal LA volume before mitral valve opening, LA endocardial contours were manually delineated in the 2- and 4-chamber views. The endocardial border excluded the pulmonary veins and the LA appendage, and the following LA parameters were recorded: (I) LA reservoir function: total strain (εs) and the peak positive strain rate (SRs); (II) LA conduit function: passive strain (εe) and the peak early negative strain rate (SRe), and (III) LA booster pump function: active strain (εa) and the late peak negative strain rate (SRa); these are shown in Figure 2.

Figure 2 Representative cases of the LA strain and strain rate parameters of STEMI patients in the r-SAK group (A-C) and the NS group (D-F), respectively. LA tracking contours at LV end-systole were shown in 2-chamber (A1,D1) and 4-chamber views (A2,D2), respectively. The εe (36.4%) and SRe (−3.3 1/s) measurements for a 33-year-old male patient in the r-SAK group are shown in B and C. The (E) εe (21.9%) and (F) SRe (−2.0 1/s) measurements for a 59-year-old male patient in the NS group. LA, left atrial; LV, left ventricular; NS, normal saline; r-SAK, recombinant staphylokinase; SRe, peak early negative strain rate; STEMI, ST-segment elevation myocardial infarction; εe, passive strain.

Infarcted myocardium appeared as a high-signal area on LGE images, defined as a mean signal intensity at least five standard deviations (SDs) higher than that of a reference region of interest (ROI) in the remote myocardium. The LV infarcted myocardial mass (LGE mass) and its percentage relative to the total LV myocardial mass (the LGE mass ratio) were calculated from the LGE images using dedicated CVI42 software. According to the American Heart Association myocardial segmentation model, a myocardial segment was classified as an infarcted segment if it exhibited a high signal on the LGE images. Conversely, a segment with no high signal throughout its entire area was considered a non-infarcted segment. The myocardial segment scheme is illustrated in Figure S2.

Valve regurgitation

To address potential confounding from valvular regurgitation, we reviewed the transthoracic echocardiography performed between primary PCI and the one-year CMR imaging. We graded mitral and aortic valve regurgitation according to guideline criteria. When multiple studies were available, the examination closest to the CMR imaging data was used.

Reproducibility

To evaluate intra- and inter-observer variability for the LV and LA volume and strain parameters, 20 randomly selected STEMI patients were assessed by two experienced and double-blinded observers (Y.W. with 5 years of CMR imaging experience, and H.G. with 2 years of CMR imaging experience). One measurement of related parameters in 20 STEMI patients by two investigators (Y.W. and H.G.) was recorded to evaluate the inter-observer variability. After four weeks, H.G. repeated the measurements in the same case to assess intra-observer variability. The primary analyses used the measurements of Reader 1 (H.G.).

Statistical analysis

The data were analyzed using SPSS version 25.0 (IBM, Armonk, NY, USA). The normality of the continuous data was tested using the Shapiro-Wilk method. Continuous variables were presented as the mean ± SD for normally distributed data, and the least significant difference t-test was used for comparisons between two groups. Non-normally distributed data were presented as the median (interquartile range), and the Mann-Whitney U test was used for comparisons between two groups. Categorical data were expressed as the frequency and percentage, and the chi-square test or Fisher’s exact test (as appropriate) was used for comparisons of the categorical variables. The Pearson correlation coefficient was used to describe the correlation of the normally distributed data, while the Spearman correlation coefficient was used to describe the correlation of the skewed data. The correlation coefficient r was used to indicate the strength of the correlation, with r ranging from 0 to 1 (where r<0.2 indicates a weak correlation; 0.2<r<0.5, a moderate correlation; 0.5<r<0.8, a strong correlation; and r>0.8, an extremely strong correlation). Inter- and intra-observer variabilities were assessed using the intraclass correlation coefficient (ICC). A Bland-Altman analysis was performed to evaluate the concordance between the LVSVI and RVSVI. All the statistical tests were two sided, and a P<0.05 was considered statistically significant.

Results

Baseline clinical characteristics

The baseline and coronary intervention-related characteristics of the patients who completed one-year CMR imaging versus those who did not complete one-year CMR imaging are shown in Table S1. The proportion of patients treated with r-SAK thrombolysis did not differ significantly between the two groups. Apart from a slightly higher prevalence of diabetes and minor differences in infarct-related artery distribution in the non-CMR group, no other baseline differences were observed. After excluding patients according to the study criteria, 66 patients were ultimately enrolled in this study (32 in the r-SAK group and 34 in the NS group). The baseline clinical characteristics of the patients are summarized in Table 1. The diastolic blood pressure at admission was slightly higher in the r-SAK group than the NS group (81.94±15.71 vs. 72.21±18.70 mmHg, P=0.026). There were no significant differences between the two groups in terms of the surgical procedural characteristics, including the time from symptom onset to randomization, from randomization to the start of reperfusion treatment, and from symptom onset to the start of reperfusion treatment (all P>0.05). Other parameters, including baseline characteristics and laboratory tests, also showed no significant differences between the two groups (all P>0.05). The median time of follow-up CMR imaging examination after primary PCI was 372 days in the r-SAK group and 373.5 days in the NS group.

Bleeding events from primary PCI to CMR imaging are shown in Table S2. Major bleeding events occurred in one patient in the NS group (BARC3) and in none in the r-SAK group. BARC-1 minor bleeding occurred in eight r-SAK patients and six non-SAK patients, while BARC-2 occurred in one NS patient. No statistically significant differences were observed between the two groups in terms of major or minor bleeding (all P>0.05), indicating that in this cohort, r-SAK was not associated with a higher risk of bleeding. Due to factors such as multi-center study settings, loss to follow-up, and patient refusals, the medication information was incomplete. In an available-case analysis (n=41), medication use did not differ between the groups (all P>0.05) (Table S3).

LV conventional function comparison

All the LV functional and LGE parameters for all the patients are presented in Table 2. At the one-year follow-up, the patients in the r-SAK group demonstrated significant improvements in the CI compared to those in the NS group (2.77 vs. 2.41 L/min/m², P=0.018). Additionally, the LVEDVI and LVSVI were higher in the r-SAK group than the NS group (both P<0.05). LV wall thickening (49.86% vs. 44.36%, P<0.001) and LV wall motion (6.02 vs. 5.57 mm, P=0.015) were also significantly higher in the r-SAK group than the NS group. Comparisons of the CI, LV wall motion, and LV wall thickening are shown in Figure 3A-3C. No significant differences were observed between the two groups in terms of LVEF, LVESVI, LVMI_ED, LV wall thickness, or heart rate (all P>0.05). Similarly, no significant differences were observed between the two groups in terms of the LGE parameters (all P>0.05). The correlation and consistency between LVSVI and RVSVI are shown in Figure S3. The results revealed a strong correlation and high consistency (r=0.997) with minimal bias (0.05 mL/m²) and narrow limits of agreement (−1.26 to 1.37 mL/m²).

Figure 3 Comparison of LV (A-C) and LA (D-F) functional parameters between the r-SAK and NS groups. Compared with the NS group, the r-SAK group shows superior (A) CI, (B) LV wall motion, (C) LV wall thickening, (D) LA passive EF, (E) εe, and (F) SRe. CI, cardiac index; EF, ejection fraction; LA, left atrial; LV, left ventricular; NS, normal saline; r-SAK, recombinant staphylokinase; SRe, peak early negative strain rate; εe, passive strain.

LV strain parameter comparison

The results of the comparison of the LV strain parameters between the r-SAK and NS groups are shown in Table 3. In terms of the LV global strain parameters, no significant differences were observed between the two groups for GCS, GRS, or GLS (all P>0.05). Based on the previously defined criteria for infarcted segments, there were 220 infarcted segments and 292 non-infarcted segments in the r-SAK group (n=32), and 220 infarcted segments and 324 non-infarcted segments in the NS group (n=34). In relation to the segmental strain parameters, the SCS in the non-infarcted segments was significantly better preserved in the r-SAK group than the NS group (−19.36% vs. −17.90%, P<0.001). The SRS and SLS of the non-infarcted segments in the r-SAK group were not superior to those in the NS group (both P>0.05). Additionally, no significant differences were observed between the two groups in terms of the SRS, SCS, and SLS in the infarcted segments (all P>0.05).

LA parameter comparison

Among the LA volumetric parameters, no statistically significant differences were observed between the two groups in terms of the LAVmax index, LAVpre-ac index, and LAVmin index (all P>0.05). Compared to the NS group, the r-SAK group showed better LA conduit function, with a significantly greater change in left atrial volume index (△LAVI) (8.27 vs. 5.69 mL/m², P=0.004). Additionally, the r-SAK group had significantly higher LV passive EF (27.34% vs. 20.68%, P=0.007), εe (21.80% vs. 17.05%, P=0.045), and SRe (−1.80 vs. −1.50 1/s, P=0.043) (Figure 3D-3F). The parameters reflecting LA reservoir function and booster pump function did not differ significantly between the two groups (all P>0.05). The above results are shown in Table 4.

Correlation analysis of the LV parameters, and between the LA and LV parameters

The correlations among the LV parameters are illustrated in Figure 4A-4C. The LVEDVI exhibited a strongly positive correlation with the LVSVI (r=0.698, P<0.001). The CI showed an extremely strong correlation with the LVSVI (r=0.811, P<0.001) and a moderate correlation with SCS in the non-infarcted segments (r=0.379, P=0.003). In relation to the correlation between the LA and LV parameters, the CI was moderately correlated with the LA volume change (△LAVI) (r=0.357, P= 0.005), LA passive EF (r=0.388, P=0.002), εe (r=0.371, P=0.003), and SRe (r=0.316, P=0.003). These findings are presented in Figure 4D-4G.

Figure 4 Correlation analyses of LV parameters (A-C) and between LA and LV parameters (D-G). (A) Correlation between LVEDVI and LVSVI. (B) Correlation between LVSVI and CI. (C) Correlation between SCS of non-infarcted segments and CI. (D-G) Correlations between CI and △LAVI conduit, LA passive EF, εe, and SRe, respectively. CI, cardiac index; LA, left atrial; LAVI, left atrial volume index; LVEDVI, left ventricular end-diastolic volume index; LVSVI, left ventricular stroke volume index; SCS, segmental circumferential strain; SRe, peak early negative strain rate; △LAVI, change in left atrial volume index; εe, passive strain.

Valve regurgitation

The mitral and aortic regurgitation distributions are shown in Table S4. Echocardiography between primary PCI and CMR imaging was available in 31 r-SAK and 32 NS patients (missing: 1 r-SAK, 2 NS). Mitral valve regurgitation occurred in 29 of 31 vs. 31 of 32 patients (mild: 28 vs. 29; moderate: 1 vs. 2). Aortic regurgitation occurred in 13 of 31 vs. 12 of 32 patients (all mild). There was no significant difference in mitral and aortic regurgitation between the two groups (all P>0.05).

Reproducibility

The ICC values for LA/LV volume and strain parameters are shown in Table S5. LV and LA volume showed excellent reproducibility, with both intra- and inter-observer ICC values >0.950. In relation to strain, the intra-observer reproducibility for the LV global strain (0.949–0.973), segmental strain parameters (0.859–0.962), and LA strain parameters (0.743–0.975) was excellent. Similarly, the inter-observer reproducibility for the LV global strain (0.965–0.996), segmental strain parameters (0.715–0.929), and LA strain parameters (0.715–0.968) was good.

Discussion

The main findings of this study were as follows: (I) at one-year follow-up, the patients in the r-SAK group showed a higher LVSVI and better preservation of segmental circumferential strain, indicating superior maintenance of myocardial contractility; and (II) compared to the NS group, the patients who received early r-SAK before primary PCI exhibited enhanced εe, SRe, and LA passive EF, reflecting better LA compliance and function. These findings suggest that early r-SAK thrombolysis before primary PCI significantly improves long-term cardiac function in STEMI patients.

According to the 2023 European Society of Cardiology guidelines, thrombolytic therapy should be initiated within 10 minutes of STEMI diagnosis if PCI cannot be performed within 120 minutes of first medical contact, while PCI alone is recommended for patients who can undergo it within this timeframe (3). However, evidence supporting the necessity of thrombolytic therapy in such cases is limited. Some studies have shown that thrombolysis before PCI can lead to favorable short-term outcomes (4,18-20). For example, thrombolytic therapy has been shown to improve thrombolysis in myocardial infarction (TIMI) flow grades (4), and combining half-dose alteplase with prompt PCI results in better reperfusion outcomes than PCI alone. Our study extended these findings by confirming the long-term benefits of pre-PCI thrombolysis. The CMR analysis revealed a significantly higher CI, LVSVI, LV wall thickening, and wall motion in the r-SAK group, suggesting superior preservation of myocardial function. We hypothesize that these outcomes are attributable to the shorter thrombolysis-to-PCI interval and the use of a more targeted thrombolytic agent (r-SAK) (21-25). These factors likely accelerated reperfusion, thereby minimizing damage to both infarcted and non-infarcted regions.

Surprisingly, we found that the LVEDVI was greater in the r-SAK group than the NS group. However, the CI and LVSVI were also significantly higher in the r-SAK group. These findings align with the Frank-Starling mechanism (26,27), which states that an increase in LV end-diastolic volume within a certain range enlarges the chamber and stretches myocardial fibers. This stretching enhances contraction and stroke volume as a compensatory effect. The strong correlations between LVEDVI, LVSVI, and CI further support this theory. No significant difference in mitral or aortic regurgitation was detected between the two groups, and the very high LVSVI and RVSVI concordance supports the validity of our volumetric measure. Therefore, it is unlikely that the superior LV stroke volume in the r-SAK group was due to regurgitation.

We found that the SCS of the non-infarcted myocardium was superior in the r-SAK group. Given that epicardial circumferential myofibers drive ventricular shortening, circumferential strain serves as a clinically relevant marker in patients following myocardial infarction (28-30). The improved SCS in the r-SAK group suggests that early perfusion limits ischemic injury, preserves surrounding myocardium, and enhances the adaptive function of non-infarcted segments, which in turn improves long-term myocardial compensation. These findings support the conclusion of Lange et al. that the circumferential strain of non-infarcted myocardial segments plays a compensatory role in the overall cardiac function of patients following STEMI (31). Given that all the enrolled patients had STEMI, at one-year CMR imaging, after the resolution of myocardial edema, microvascular obstruction, and intramyocardial hemorrhage, LGE predominantly reflects the final infarct core, which is established early. Even with half-dose thrombolysis, recovery of this core is limited; the principal benefit is the preservation of the peri-infarct/remote myocardium. This mechanism likely explains the lack of a significant between-group difference in the one-year LGE scar and aligns with our segmental analysis, which showed better function in the non-infarcted segments in the r-SAK group than the NS group (4,29-31).

Increasing evidence links LA function to various cardiovascular diseases, establishing LA strain as an independent prognostic indicator beyond LVEF (11,13,14). Our study found that patients who received early thrombolytic therapy before primary PCI retained better conduit function, suggesting enhanced LA compliance and function. Consistent with some previous studies (32-34), since LA and LV function are interconnected, improved LA conduit function supports more LV filling, thereby enhancing overall cardiac performance. We found that △LAVI conduit, LA passive EF, εe, and SRe were moderately correlated with CI. This suggests that LA conduit function compensates for LV ejection function in post-STEMI patients, which is consistent with several studies that have shown the contribution of LA conduit function to LV output (33,35). Additionally, LV ischemia duration is linked to myocardial relaxation and stiffness, which further influence the LA-LV interaction (33,35,36). In the r-SAK group, improved LV filling and relaxation resulted in greater suction force on the left atrium during early diastole. The better preservation of LA conduit function in the r-SAK group further implies improved LV diastolic function (37-39).

In this study, we highlighted the value of CMR-based cardiac function analysis in evaluating long-term cardiac function recovery following thrombolysis. Given that LV and LA strain parameters are more sensitive indicators of myocardial function than conventional volumetric measures, integrating CMR strain analysis into routine follow-up protocols could facilitate a more comprehensive and early assessment of STEMI patients.

Limitations

This study had several limitations. First, although it was a multi-center study, the sample size of patients who completed CMR imaging at one-year follow-up was relatively small, necessitating further validation with a larger cohort. Second, although the enrollment of STEMI patients was approximately random, the possibility of selection bias remains. Third, future studies should extend follow-up to 2–5 years to assess the sustained effects of early r-SAK thrombolysis. Fourth, as the medication data were incomplete and no multivariable adjustment was performed, residual confounding cannot be fully excluded. Finally, although overall reproducibility fell within an acceptable range, some parameters exhibited ICC values below 0.90, which might slightly dilute the observed differences between the two groups; hence, the estimates are conservative.

Conclusions

This CMR-based analysis demonstrated that r-SAK thrombolytic therapy preserves long-term LA and LV function in STEMI patients undergoing primary PCI within 120 minutes of symptom onset. For STEMI patients without contraindications, early thrombolysis before primary PCI may serve as a viable strategy to optimize cardiac recovery and improve long-term cardiac function.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-816/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-816/dss

Funding: This work was supported by grants from Kanion Pharmaceutical Group, Lianyungang, China, the Special Fund for Key R&D Plans (Social Development) of Jiangsu Province (No. BE2019754), and the National Natural Science Funding of China (No. 82170351).

Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-816/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of The First Affiliated Hospital with Nanjing Medical University (No. 2021-SR-309), and informed consent was taken from all individual participants. All the other participating centers were informed of and agreed to participate in this study

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Bahit MC, Kochar A, Granger CB. Post-Myocardial Infarction Heart Failure. JACC Heart Fail 2018;6:179-86. [Crossref] [PubMed]
2. García-García C, Oliveras T, Serra J, Vila J, Rueda F, Cediel G, Labata C, Ferrer M, Carrillo X, Dégano IR, De Diego O, El Ouaddi N, Montero S, Mauri J, Elosua R, Lupón J, Bayes-Genis A. Trends in Short- and Long-Term ST-Segment-Elevation Myocardial Infarction Prognosis Over 3 Decades: A Mediterranean Population-Based ST-Segment-Elevation Myocardial Infarction Registry. J Am Heart Assoc 2020;9:e017159. [Crossref] [PubMed]
3. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo AESC Scientific Document Group, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44:3720-826. [Crossref] [PubMed]
4. Chen P, Eikelboom JW, Tan C, Zhang W, Xu Y, Bai J, et al. Single Bolus r-SAK Before Primary PCI for ST-Segment-Elevation Myocardial Infarction. Circ Cardiovasc Interv 2024;17:e013455. [Crossref] [PubMed]
5. Buffa V, Di Renzi P. CMR in the diagnosis of ischemic heart disease. Radiol Med 2020;125:1114-23. [Crossref] [PubMed]
6. Muscogiuri G, Ricci F, Scafuri S, Guglielmo M, Baggiano A, De Stasio V, Di Donna C, Spiritigliozzi L, Chiocchi M, Lee SJ, De Cecco CN, van Assen M, Rabbat MG, Pontone G. Cardiac Magnetic Resonance Tissue Characterization in Ischemic Cardiomyopathy. J Thorac Imaging 2022;37:2-16. [Crossref] [PubMed]
7. Silva TQAC, Pezel T, Jerosch-Herold M, Coelho-Filho OR. The Role and Advantages of Cardiac Magnetic Resonance in the Diagnosis of Myocardial Ischemia. J Thorac Imaging 2023;38:235-46. [Crossref] [PubMed]
8. Gavara J, Rodriguez-Palomares JF, Valente F, Monmeneu JV, Lopez-Lereu MP, Bonanad C, et al. Prognostic Value of Strain by Tissue Tracking Cardiac Magnetic Resonance After ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Imaging 2018;11:1448-57. [Crossref] [PubMed]
9. Dobrovie M, Barreiro-Pérez M, Curione D, Symons R, Claus P, Voigt JU, Bogaert J. Inter-vendor reproducibility and accuracy of segmental left ventricular strain measurements using CMR feature tracking. Eur Radiol 2019;29:6846-57. [Crossref] [PubMed]
10. Lange T, Gertz RJ, Schulz A, Backhaus SJ, Evertz R, Kowallick JT, Hasenfuß G, Desch S, Thiele H, Stiermaier T, Eitel I, Schuster A. Impact of myocardial deformation on risk prediction in patients following acute myocardial infarction. Front Cardiovasc Med 2023;10:1199936. [Crossref] [PubMed]
11. Schuster A, Backhaus SJ, Stiermaier T, Navarra JL, Uhlig J, Rommel KP, Koschalka A, Kowallick JT, Lotz J, Gutberlet M, Bigalke B, Kutty S, Hasenfuss G, Thiele H, Eitel I. Left Atrial Function with MRI Enables Prediction of Cardiovascular Events after Myocardial Infarction: Insights from the AIDA STEMI and TATORT NSTEMI Trials. Radiology 2019;293:292-302. [Crossref] [PubMed]
12. Lange T, Schuster A. Quantification of Myocardial Deformation Applying CMR-Feature-Tracking-All About the Left Ventricle? Curr Heart Fail Rep 2021;18:225-39. [Crossref] [PubMed]
13. Zhang M, Li Z, Wang Y, Chen L, Ren Y, Wu Y, Wang J, Lu Y. Left atrial and ventricular longitudinal strain by cardiac magnetic resonance feature tracking improves prognostic stratification of patients with ST-segment elevation myocardial infarction. Int J Cardiovasc Imaging 2024;40:1881-90. [Crossref] [PubMed]
14. Leng S, Ge H, He J, Kong L, Yang Y, Yan F, Xiu J, Shan P, Zhao S, Tan RS, Zhao X, Koh AS, Allen JC, Hausenloy DJ, Mintz GS, Zhong L, Pu J. Long-term Prognostic Value of Cardiac MRI Left Atrial Strain in ST-Segment Elevation Myocardial Infarction. Radiology 2020;296:299-309. [Crossref] [PubMed]
15. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011;123:2736-47. [Crossref] [PubMed]
16. Zhuang B, Li S, Xu J, Zhou D, Yin G, Zhao S, Lu M. Age- and Sex-Specific Reference Values for Atrial and Ventricular Structures in the Validated Normal Chinese Population: A Comprehensive Measurement by Cardiac MRI. J Magn Reson Imaging 2020;52:1031-43. [Crossref] [PubMed]
17. Uretsky S, Argulian E, Narula J, Wolff SD. Use of Cardiac Magnetic Resonance Imaging in Assessing Mitral Regurgitation: Current Evidence. J Am Coll Cardiol 2018;71:547-63. [Crossref] [PubMed]
18. Pu J, Ding S, Ge H, Han Y, Guo J, Lin R, Su X, Zhang H, Chen L, He B. Efficacy and Safety of a Pharmaco-Invasive Strategy With Half-Dose Alteplase Versus Primary Angioplasty in ST-Segment-Elevation Myocardial Infarction: EARLY-MYO Trial (Early Routine Catheterization After Alteplase Fibrinolysis Versus Primary PCI in Acute ST-Segment-Elevation Myocardial Infarction). Circulation 2017;136:1462-73. [Crossref] [PubMed]
19. Bainey KR, Welsh RC, Zheng Y, Arias-Mendoza A, Ristic AD, Averkov OV, Lambert Y, Kerr Saraiva JF, Sepulveda P, Rosell-Ortiz F, French JK, Musić LB, Temple T, Ly E, Bogaerts K, Sinnaeve PR, Danays T, Westerhout CM, Van de Werf F, Armstrong PW. STREAM-2 Investigators. Pharmaco-Invasive Strategy With Half-Dose Tenecteplase in Patients With STEMI: Prespecified Pooled Analysis of Patients Aged ≥75 Years in STREAM-1 and 2. Circ Cardiovasc Interv 2024;17:e014251. [Crossref] [PubMed]
20. Van de Werf F, Ristić AD, Averkov OV, Arias-Mendoza A, Lambert Y, Kerr Saraiva JF, et al. STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial. Circulation 2023;148:753-64. [Crossref] [PubMed]
21. Nedaeinia R, Faraji H, Javanmard SH, Ferns GA, Ghayour-Mobarhan M, Goli M, Mashkani B, Nedaeinia M, Haghighi MHH, Ranjbar M. Bacterial staphylokinase as a promising third-generation drug in the treatment for vascular occlusion. Mol Biol Rep 2020;47:819-41. [Crossref] [PubMed]
22. De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation 2004;109:1223-5. [Crossref] [PubMed]
23. Li CJ, Huang J, Yang ZJ, Cao KJ. Thrombolytic efficacy of native recombinant staphylokinase on femoral artery thrombus of rabbits. Acta Pharmacol Sin 2007;28:58-65. [Crossref] [PubMed]
24. Ren K, Gong H, Huang J, Liu Y, Dong Q, He K, Tian L, Zhang F, Yu A, Wu C. Thrombolytic and anticoagulant effects of a recombinant staphylokinase-hirudin fusion protein. Thromb Res 2021;208:26-34. [Crossref] [PubMed]
25. Vakili B, Nezafat N, Negahdaripour M, Yari M, Zare B, Ghasemi Y. Staphylokinase Enzyme: An Overview of Structure, Function and Engineered Forms. Curr Pharm Biotechnol 2017;18:1026-37. [Crossref] [PubMed]
26. Li Y, Xu Y, Tang S, Jiang X, Li W, Guo J, Yang F, Xu Z, Sun J, Han Y, Zhu Y, Chen Y. Left Atrial Function Predicts Outcome in Dilated Cardiomyopathy: Fast Long-Axis Strain Analysis Derived from MRI. Radiology 2022;302:72-81. [Crossref] [PubMed]
27. Zlibut A, Cojocaru C, Onciul S, Agoston-Coldea L. Cardiac Magnetic Resonance Imaging in Appraising Myocardial Strain and Biomechanics: A Current Overview. Diagnostics (Basel) 2023;13:553. [Crossref] [PubMed]
28. Sengupta PP, Tajik AJ, Chandrasekaran K, Khandheria BK. Twist mechanics of the left ventricle: principles and application. JACC Cardiovasc Imaging 2008;1:366-76. [Crossref] [PubMed]
29. Erley J, Starekova J, Sinn M, Muellerleile K, Chen H, Harms P, Naimi L, Meyer M, Cavus E, Schneider J, Blankenberg S, Lund GK, Adam G, Tahir E. Cardiac magnetic resonance feature tracking global and segmental strain in acute and chronic ST-elevation myocardial infarction. Sci Rep 2022;12:22644. [Crossref] [PubMed]
30. Holmes AA, Romero J, Levsky JM, Haramati LB, Phuong N, Rezai-Gharai L, Cohen S, Restrepo L, Ruiz-Guerrero L, Fisher JD, Taub CC, Di Biase L, Garcia MJ. Circumferential strain acquired by CMR early after acute myocardial infarction adds incremental predictive value to late gadolinium enhancement imaging to predict late myocardial remodeling and subsequent risk of sudden cardiac death. J Interv Card Electrophysiol 2017;50:211-8. [Crossref] [PubMed]
31. Lange T, Stiermaier T, Backhaus SJ, Boom PC, Kowallick JT, de Waha-Thiele S, Lotz J, Kutty S, Bigalke B, Gutberlet M, Feistritzer HJ, Desch S, Hasenfuß G, Thiele H, Eitel I, Schuster A. Functional and prognostic implications of cardiac magnetic resonance feature tracking-derived remote myocardial strain analyses in patients following acute myocardial infarction. Clin Res Cardiol 2021;110:270-80. [Crossref] [PubMed]
32. Singh A, Addetia K, Maffessanti F, Mor-Avi V, Lang RM. LA Strain for Categorization of LV Diastolic Dysfunction. JACC Cardiovasc Imaging 2017;10:735-43. [Crossref] [PubMed]
33. Maffeis C, Morris DA, Belyavskiy E, Kropf M, Radhakrishnan AK, Zach V, Rozados da Conceicao C, Trippel TD, Pieske-Kraigher E, Rossi A, Pieske B, Edelmann F. Left atrial function and maximal exercise capacity in heart failure with preserved and mid-range ejection fraction. ESC Heart Fail 2021;8:116-28. [Crossref] [PubMed]
34. Freed BH, Daruwalla V, Cheng JY, Aguilar FG, Beussink L, Choi A, Klein DA, Dixon D, Baldridge A, Rasmussen-Torvik LJ, Maganti K, Shah SJ. Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Left Atrial Strain. Circ Cardiovasc Imaging 2016;9:e003754. [Crossref] [PubMed]
35. von Roeder M, Rommel KP, Kowallick JT, Blazek S, Besler C, Fengler K, Lotz J, Hasenfuß G, Lücke C, Gutberlet M, Schuler G, Schuster A, Lurz P. Influence of Left Atrial Function on Exercise Capacity and Left Ventricular Function in Patients With Heart Failure and Preserved Ejection Fraction. Circ Cardiovasc Imaging 2017;10:e005467. [Crossref] [PubMed]
36. Sundqvist MG, Verouhis D, Sörensson P, Henareh L, Persson J, Saleh N, Settergren M, Witt N, Böhm F, Pernow J, Tornvall P, Ugander M. The size of myocardial infarction and peri-infarction edema are not major determinants of diastolic impairment after acute myocardial infarction. Int J Cardiovasc Imaging 2025;41:103-12. [Crossref] [PubMed]
37. Marino PN, Degiovanni A, Zanaboni J. Complex interaction between the atrium and the ventricular filling process: the role of conduit. Open Heart 2019;6:e001042. [Crossref] [PubMed]
38. Silva MR, Sampaio F, Braga J, Ribeiro J, Fontes-Carvalho R. Left atrial strain evaluation to assess left ventricle diastolic dysfunction and heart failure with preserved ejection fraction: a guide to clinical practice: Left atrial strain and diastolic function. Int J Cardiovasc Imaging 2023;39:1083-96. [Crossref] [PubMed]
39. Marino PN. Left atrial conduit function: A short review. Physiol Rep 2021;9:e15053. [Crossref] [PubMed]