Thrombolytic therapy before percutaneous coronary intervention improves short-term cardiac function evaluated by cardiac magnetic resonance for ST-segment elevation myocardial infarction

Abstract

Background

The necessity of thrombolytic therapy before percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients remains controversial, requiring further evaluation of potential benefits.

Purpose

To explore the efficacy of half-dose recombinant staphylokinase (r-SAK) intravenous bolus before PCI in STEMI patients.

Material and Methods

Patients with STEMI were allocated to r-SAK or normal saline groups before PCI. Cardiac magnetic resonance (CMR) at 5 days after MI evaluated cardiac function, myocardial tissue characteristics, and strain. Segments were classified by late gadolinium enhancement (LGE) extent.

Results

A total of 64 STEMI patients were divided into the r-SAK group (n = 33) and NS group (n = 31). Patients in the r-SAK group had a significantly higher left ventricular ejection fraction and cardiac output index (P = 0.045 and 0.024). There was no significant difference between the two groups in mapping parameters, infarct size, area at risk, or the incidence of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH) (all P >0.05). Regardless of the extent of LGE in the segments, patients in the r-SAK group exhibited significantly better segmental longitudinal strain (all P <0.001). In addition, patients from the r-SAK group had a better segmental circumferential strain in LGE segments (P = 0.044).

Conclusion

For STEMI patients expected to undergo PCI within 120 min of presentation, a single bolus of half-dose r-SAK administrated before PCI improved short-term cardiac function without increasing incidence of MVO or IMH.

Keywords

Cardiac magnetic resonance ST-segment elevation myocardial infarction thrombolytic therapy

Introduction

Acute myocardial infarction (AMI) presents significant health risks and imposes considerable financial burdens on healthcare systems due to its high morbidity and mortality rates (1). Primary percutaneous coronary intervention (PCI) is the preferred option for ST-segment elevation myocardial infarction (STEMI), provided it can be performed within 120 min of the patient's presentation (2).

Previous studies have demonstrated the safety and efficacy of administering a half-dose fibrinolytic agent before PCI for STEMI patients (3,4). The recent trial showed that a single bolus of half-dose recombinant staphylokinase (r-SAK) can improve patency of the infarct related artery (IRA) and reduce infarct size without increasing major bleeding in STEMI patients scheduled for PCI within 120 min of presentation (5). However, most of these studies have primarily focused on the patency rate of IRA and short clinical outcomes. Few studies have specifically analyzed short-term cardiac function in STEMI patients who received thrombolytic therapy before PCI.

Cardiac magnetic resonance (CMR) has emerged as a preferred modality for characterizing myocardial tissue and assessing cardiac function after myocardial infarction (MI). In addition to infarct size, CMR can evaluate infarct-related edema, estimated as area at risk (AAR), and detect subtle changes in myocardial function, quantified by myocardial strain (6 –11). It has also become the reference standard for identifying microvascular injuries, such as intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO), both of which are associated with worse clinical outcome (12 –14).

The aim of the present study was to further comprehensively compare the details of AAR, IMH, MVO, and infarct size in territory of IRA using CMR parameters to present the effect of a single bolus of r-SAK administrated before PCI on myocardium on STEMI patients. This comparison aims to offer insights into the potential benefits of thrombolytic therapy before PCI in STEMI patients.

Material and Methods

Study population

We analyzed the data from STEMI patients enrolled in a trial. The trial is an investigator-initiated, prospective, multi-center, randomized, controlled trial comparing a single bolus of r-SAK with normal saline (NS) in STEMI patients presenting within 12 h of symptom onset and expected to undergo PCI within 120 min (5). This study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice and was approved by the Research Ethics Board of the First Affiliated Hospital of Nanjing Medical University (reference no. 2021-SR-309) (5). Written informed consent was obtained from all participants.

In the present analysis, of the 200 patients included in the trial between October 2021 and August 2022, we excluded 64 patients who did not undergo CMR, 62 patients without T1 or T2 mapping, 7 patients who did not undergo PCI, and 3 patients with poor image quality. Finally, 64 patients were included. Among them, 33 patients were included in analysis, of whom 33 received a single bolus of half-dose r-SAK before PCI, and the remaining 31 received NS. Fig. 1 showed a detailed flow chart.

Fig. 1.

Flowchart of the trial. CMR, cardiac magnetic resonance; NS, normal saline; PCI, percutaneous coronary intervention; r-SAK, recombinant staphylokinase; STEMI, ST-segment elevation myocardial infarction.

Demographic and clinical data

The following demographic and clinical data were collected: patient age, sex, body mass index, medical history (hypertension, diabetes mellitus, hypercholesterolemia, smoke, alcohol), systolic blood pressure (SBP), and diastolic blood pressure (DBP).

The following were recorded: time of symptom onset to r-SAK or NS; time of r-SAK or NS infusion to start of reperfusion; time of symptom onset to start of reperfusion; and time of PCI to CMR scanning for patients. In addition, peak hscTnT (high-sensitive cardiac troponin T [ng/L]) during disease and peak N-terminal pro-brain natriuretic peptide (NT-proBNP [ng/L]) were also collected. In addition, blood test results were collected, including hemoglobin (Hb), alanine transaminase (ALT), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin (HbA1c).

CMR imaging

Scans were performed 5 days after reperfusion on a 3-T magnetic resonance imaging (MRI) system (Ingenia CX; Philips Healthcare, the Netherlands) with a 16-channel phased-array abdominal coil. All images were acquired under the electrocardiogram (ECG)-gated breath-hold condition.

Cardiac cine images (for function and strain) including three long-axis (LAX) slices of the left ventricle (LV; two-, three-, and four-chamber views) and 10–12 layers of the short axis (SAX), covering the entire LV without interval were obtained by balanced steady-state free precession sequences with retrospective ECG triggering. The scan parameters were as follows: TR/TE = 3.5/1.4 ms; flip angle = 45°; layer thickness = 8 mm; 25 frames/cardiac cycle; and spatial resolution = 2.0 × 1.6 × 8 mm³.

Dark-blood T2-weighted (T2W) imaging (for IMH and AAR) was acquired using an inversion recovery (STIR) sequence, capturing 10–12 layers of the SAX. The scan parameters were as follows: TR/TE = 2/75 ms; flip angle = 90°; layer thickness = 8 mm; field of view (FOV) = 300 × 300 mm; matrix = 160 × 139 mm; and spatial resolution = 1.3 × 1.65 × 8 mm³.

T1 mapping of the SAX view at the basal, mid, and apical levels of the LV was performed using the Modified Look-Locker STIR sequence before and 10–15 min after administration of 0.2 mmol/kg gadoterate magnevist (Bayer Schering Pharma AG, Germany). The scan parameters were as follows: TR/TE = 2.6 ms/1.2 ms; flip angle = 20°; layer thickness = 8 mm; interval = 12 mm; FOV = 340 × 380 mm; matrix = 192 × 172 mm; and spatial resolution = 2 × 2 × 8 mm³.

T2 mapping at the same slice positions as T1 mapping was collected using gradient spin echo. The scan parameters were as follows: TR/TE = 3.3/1.0 ms; flip angle = 90°; echo spacing = 8.9 ms; echo number = 8. The interval, FOV, matrix, and spatial resolution were the same as for T1 mapping.

Late gadolinium enhancement (LGE) (for infarct size and MVO) was performed 10–15 min after intravenous administration of gadoterate magnevist (Bayer Schering Pharma AG, Germany) using a 2D Phase-Sensitive Inversion Recovery sequence. The entire left ventricle was to be covered (with scan location was the same as dark-blood T2W imaging), and additional two-, three-, and four-chamber LAX images were obtained. The scan parameters were as follows: TR/TE = 6.1/3 ms; flip angle = 25°; slice thickness = 8 mm thick; FOV: 300 × 300 mm; matrix: 160 × 139 mm; spatial resolution: 1.9 × 1.6 × 8 mm³.

Image analysis

CMR images were analyzed using CVI⁴² software (version 5.0, Circle Cardiovascular Imaging Inc., Calgary, Canada). All CMR analysis were performed by two independent radiologists (with 6 and 3 years of experience in cardiovascular radiology, respectively). A senior radiologist with 25 years of experience provided adjudication when necessary. The reviewers were blinded to the patients’ clinical data.

Left ventricular conventional parameters, indexed to body surface area, including end-diastolic/end-systolic volume index (EDVI/ESVI), stroke volume index (SVI), LV mass index (LVMI), and cardiac output index (CI), were automatically measured by tracing LV endocardial and epicardial borders on cine images, ensuring the exclusion of endocardial trabeculations and papillary muscles. LV ejection fraction (LVEF) was measured.

The segmental strain analysis was performed on cine images. Endocardial contours were manually delineated on the end-diastolic images and then automatically tracked throughout the cardiac cycle to determine strain. LV segmental radial strain (SRS), segmental circumferential strain (SCS), and segmental longitudinal strain (SLS) were measured using the two-, three-, and four-chamber and short-axis views in segments.

Remote myocardium was identified as the region that showed no hyperintensity in LGE images and 180° away from the acutely infarcted segments. Infarcted myocardium was defined on LGE images as region with mean signal intensity that was at least 5 SDs higher than that of a reference region of interest (ROI) drawn in remote myocardium. AAR was determined on T2W imaging as the region with mean signal intensity that was at least 2 SDs greater than that of a reference ROI drawn in the remote myocardium. IMH was defined as hypointense core visualized within the increased signal intensity representing edema on T2W imaging with volume >5% of infarcted myocardium (13) (Fig. 2a and b). MVO was defined as a hypointense core inside an area of LGE (Fig. 2c and d).

Fig. 2.

IMH and MVO. (a, b) IMH (arrow) was the hypointense core visualized within the increased signal intensity representing edema on T2W imaging (a) and LGE imaging (b). (c, d) MVO (arrow) was the hypointense core inside an area of LGE (d) without decreased signal intensity on T2W imaging (c). IMH, intramyocardial hemorrhage; LGE, late gadolinium enhancement; MVO, microvascular obstruction; T2W, T2-weighted.

Global myocardial tissue characteristics included infarct size, AAR, MVO mass, and incidence of MVO and IMH. Infarct size was expressed as the percentage of LGE mass relative to the total LV mass on LGE images. AAR was calculated as the percentage of AAR mass to LV mass on T2W imaging. MVO mass was manually calculated by delineating the hypointense core on LGE images.

Segmental LGE was qualitatively assessed across the 16 myocardial segments, as reported by the American Heart Association. Myocardial segments were grouped into segments without LGE (LGE−), segments with an infarct size <50% (LGE+), and segments with an infarct size ≥50% (LGE++).

Native and post-contrast T1 value and T2 value of AAR and remote myocardium were measured (Fig. 3). ECV value of AAR and remote myocardium were evaluated using the following formula (15):

ECV (%) = \frac{R 1 myo postGd - R 1 myo preGd}{R 1 blood postGd - R 1 blood preGd} \times (100 - hematocrit),

where R1 = 1/T1, myo = myocardium, blood = blood pool, and hematocrit = cellular volume fraction of blood (%).

Fig. 3.

ROI of AAR zone in T2W imaging, Infarct zone in LGE, native, and post-contrast T1 mapping. (a) AAR was the area with increased signal intensity on T2W imaging. (b) Infarcted myocardium was the area with increased signal intensity on LGE imaging. (c, d) ROI in blue circle in native and post-contrast T1 mapping was defined as remote myocardium, which was drawn 180° away from the acutely infarcted segments with no LGE. ROI in pink circle in native and post-contrast T1 mapping was defined as AAR, which was drawn according to T2W imaging. AAR, area at risk; LGE, late gadolinium enhancement; ROI, region of interest; T2W, T2-weighted.

Reproducibility

Inter- and intra-observer variabilities for infarct size and AAR, SLS, SCS, and SCS were assessed in 15 randomly selected patients (8 patients in the r-SAK group and 7 patients in the NS group).

Statistical analysis

Normality of data was determined using the Kolmogorov–Smirnov test. Normally distributed data are presented as mean ± SD, while non-parametric data are presented as median (interquartile range [IQR]). Statistical comparisons were performed using Student's t-test or the Mann–Whitney U test, as appropriate. Inter- and intra-observer variabilities were assessed using intraclass correlation coefficient (ICC). Categorical data and frequencies were compared using the chi-square or Fisher's exact test, as appropriate. Statistical tests were two-tailed, and statistical significance was defined as P <0.05.

Results

Baseline clinical characteristics

A retrospective image analysis was conducted on a total of 64 STEMI patients with 33 patients in the r-SAK group and 31 patients in the NS group. The baseline characteristics of these patients are summarized in Table 1. No statistically significant differences were observed between the two groups in terms of baseline characteristics, procedural details, or laboratory test results.

Table 1.

Baseline, procedural characteristics and laboratory tests of patients.

	r-SAK group (n = 33)	NS group (n = 31)	P value
Baseline characteristics
Men	29 (87.9)	29 (93.5)	0.437*
Age (years)	55.6 ± 9.1	59.2 ± 10.2	0.140^†
Height (m)	1.7 ± 0.1	1.7 ± 0.1	0.740^†
Weight (kg)	74.1 ± 12.0	70.5 ± 9.2	0.176^†
BMI (kg/m²)	25.7 ± 3.5	24.3 ± 2.4	0.069^†
SBP (mmHg)	133.2 ± 22.7	128.9 ± 25.6	0.482^†
DBP (mmHg)	84.9 ± 13.6	79.1 ± 15.1	0.114^†
Hypertension	18 (54.5)	14 (45.2)	0.453*
Diabetes mellitus	12 (36.4)	7 (22.6)	0.228*
Hypercholesterolemia	4 (12.1)	4 (12.9)	0.925*
Smoking	23 (69.7)	23 (74.2)	0.689*
Alcohol	17 (51.5)	18 (58.1)	0.599*
Procedural characteristics
Symptom onset to r-SAK or NS infusion (min)	335.0 (138.5–461.0)	205.0 (126.0–360.0)	0.127^‡
r-SAK or NS infusion to start of reperfusion (min)	55.0 (48.0–72.5)	55.0 (30.0–70.0)	0.416^‡
Symptom onset to start of reperfusion (min)	384.0 (211.0–556.5)	250.0 (190.0–420.0)	0.127^‡
Infarct related artery			0.129*
LAD	12 (36.4)	19 (61.3)
LCX	6 (18.2)	2 (6.5)
RCA	15 (45.4)	10 (32.2)
Location			0.126*
Proximal	15 (45.5)	20 (64.5)
Mid to distal	18 (54.5)	11 (35.5)
Laboratory tests
Peak hscTnT (ng/L)	5565.0 (1983.0–9905.0)	4803.0 (1946.0–10,000.0)	0.773^‡
NT-proBNP (ng/L)	560.2 (250.3–1336.3)	639.3 (301.5–2002.5)	0.459^‡
Hb (g/L)	151.0 (144.0–159.5)	151.0 (141.0–155.0)	0.291^‡
ALT (U/L)	32.2 (22.8–48.6)	40.7 (31.1–61.0)	0.216^‡
LDL-C (mmol/L)	2.9 ± 1.0	3.1 ± 1.0	0.320^†
HbA1c (%)	6.6 (5.5–9.5)	6.0 (5.6–6.6)	0.247^‡

Values are given as n (%), mean ± SD, or median (range).

*P values were calculated using the chi-square or Fisher's exact test, as appropriate.

†

P values were calculated using Student’s t-test.

‡

P values were calculated using the Mann–Whitney U-test.

ALT, alanine transaminase; BMI, body mass index; DBP, diastolic blood pressure; Hb, hemoglobin; HbA1c, glycated hemoglobin; hscTnT, high-sensitive cardiac troponin T; LDL-C, low-density lipoprotein cholesterol; NS, normal saline; NT-proBNP, N-terminal pro-brain natriuretic peptide; r-SAK, recombinant staphylokinase; SBP, systolic blood pressure.

The median time from symptom onset to r-SAK or NS infusion, from r-SAK or NS infusion to reperfusion, and from symptom onset to reperfusion were 335 min, 55 min, and 384 min in the r-SAK group, and 205 min, 55 min, and 250 min in the NS group, respectively. There were no significant differences between the two groups (all P >0.05) (Table 1).

CMR scans were performed at a mean of 5.4 ± 1.5 days after reperfusion in the r-SAK group and 5.0 ± 1.3 days in the NS group, with no significant difference between the groups (P >0.05).

Global MR parameters

Compared to the NS group, patients in the r-SAK group exhibited higher mean LVEF and CI (49.6% ± 8.7% vs. 44.7% ± 10.1%; P = 0.045, and 2.8 ± 0.6 L/min/m² vs. 2.5 ± 0.7 L/min/m²; P = 0.024) (Table 2, Fig. 4a and b). In the r-SAK group, 18/33 (54.5%) patients had a LVEF ≥50%, compared to 8/31 (25.8%) in the NS group (P = 0.019). No significant difference was observed between the two groups in terms of LV EDVI, LV ESVI, LV SVI, LVMI, or HR (Table 2).

Fig. 4.

The comparison of global MR parameters between the r-SAK and NS groups. (a, b) Higher LVEF and cardiac output index were shown in the r-SAK group. (c, d) No significant difference was observed between two groups regarding infarct size or area at risk. LV, left ventricular ejection fraction; NS, normal saline; r-SAK, recombinant staphylokinase.

Table 2.

Global MR parameters comparison between r-SAK and NS group.

	r-SAK group (n = 33)	NS group (n = 31)	P value
Functional parameters
LVEF (%)	49.6 ± 8.7	44.7 ± 10.1	0.045*
CI (L/min/m²)	2.8 ± 0.6	2.5 ± 0.7	0.024*
HR (bpm)	73.2 ± 11.7	70.2 ± 12.2	0.322*
LV EDVI (mL/m²)	81.0 ± 17.8	79.3 ± 12.6	0.661*
LV ESVI (mL/m²)	41.6 ± 13.7	43.9 ± 11.0	0.447*
LV SVI (mL/m²)	39.7 ± 9.3	35.3 ± 9.1	0.065*
LV MI (g/m²)	62.6 ± 8.9	62.5 ± 9.2	0.977*
Mapping parameters
Native T1_AAR (ms)	1493.9 ± 92.9	1483.8 ± 85.9	0.665*
Native T1_remote (ms)	1258.4 ± 56.1	1257.2 ± 74.7	0.945*
T2_AAR (ms)	66.5 ± 9.8	66.9 ± 9.9	0.584*
T2_remote (ms)	45.2 ± 8.9	45.8 ± 7.3	0.797*
ECV_AAR (%)	42.8 ± 4.7	41.4 ± 8.3	0.456*
ECV_remote (%)	26.9 ± 4.6	26.2 ± 3.6	0.529*
Myocardial tissue characteristics
Infarct size (%)	23.0 ± 10.3	22.4 ± 13.8	0.852*
AAR (%)	28.7 ± 9.8	33.1 ± 16.1	0.097*
Incidence of MVO	22 (66.7)	16 (51.6)	0.220^†
MVO mass (g)	1.15 (0.00–2.00)	0.26 (0.00–2.04)	0.307^‡
Incidence of IMH	14 (42.4)	11 (35.5)	0.570^†

Values are given as n (%), mean ± SD or median (range).

*P values were calculated using Student’s t-test.

†

P values were calculated using a chi-square or Fisher's exact test, as appropriate.

‡

P values were calculated using a Mann–Whitney U-test.

AAR, area at risk; CI, cardiac output index; HR, heart rate; IMH, intramyocardial hemorrhage; LV EDVI, left ventricular end-diastolic volume index; LV ESVI, left ventricular end-systolic volume index; LV MI, left ventricular mass index; LV SVI, left ventricular stroke volume index; LVEF, left ventricular ejection fraction; MVO, microvascular obstruction; NS, normal saline; r-SAK, recombinant staphylokinase.

There were no significant differences between the two groups in mean infarct size or AAR (23.0% ± 10.3% vs. 22.4% ± 13.8%; P = 0.852, and 28.7% ± 9.8% vs. 33.1% ± 16.1%; P = 0.097) (Table 2, Fig. 4c and d). MVOs were present in 66.7% of patients in the r-SAK group, involving a median mass of 1.15 g (IQR = 0.00–2.00 g), and in 51.6% of patients in the NS group, involving a median mass of 0.26 g (IQR = 0.00–2.04 g). IMH were present in 42.4% of patients in the r-SAK group and 35.5% in the NS group (Table 2), with no significant differences between the groups.

In the AAR zone, both groups displayed similar native T1 and T2 values, as well as ECV values (Table 2). Similarly, in the remote zone, there were no significant differences in native T1, T2, or ECV values between the r-SAK and NS groups (Table 2).

Notably, no LV thrombus was detected in our cohort of 64 patients.

Segmental strain

In LGE segments, there was less impairment in SLS in the r-SAK group (median = −11.6%, IQR = −14.0% to −8.0%), compared to the NS group (median = −10.1%, IQR = −12.5% to −7.1%) (Table 3, Fig. 5a). Similar trends were seen in LGE + segments (−11.3%, IQR = −14.3% to −9.5% vs. −8.7%, IQR = −12.0% to −5.4) and LGE++ segments (−9.4%, IQR = −13.0% to −7.1% vs. −8.4%, IQR = −10.3% to −6.3%) (all P <0.001) (Table 3, Fig. 5b and c). A significantly better SCS in the r-SAK group (median = −18.5%, IQR = −21.9% to −15.0%) compared to the NS group (median = −17.8%, IQR = −21.4% to −13.9%), was found in LGE− segments (P = 0.044) (Table 3, Fig. 5a).

Fig. 5.

The comparison of segmental strain between the r-SAK and NS groups. (a) Regarding LGE− segments, STEMI patients in the r-SAK group exhibited better SCS and SLS than those in the NS group. (b) Regarding LGE+ segments, STEMI patients in the r-SAK group exhibited better SLS than those in the NS group. (c) Regarding LGE++ segments, STEMI patients in the r-SAK group exhibited better SLS than those in the NS group. LGE, late gadolinium enhancement; NS, normal saline; r-SAK, recombinant staphylokinase; SCS, segmental circumferential strain; SLS, segmental longitudinal strain; STEMI, ST-segment elevation myocardial infarction.

Table 3.

Comparison of segmental strain between the r-SAK and NS groups.

LGE	r-SAK group	NS group	P value
LGE−	n = 298	n = 262
SRS (%)	32.7 (22.9–44.9)	32.0 (23.3–47.8)	0.776
SCS (%)	−18.5 (−21.9 to −15.0)	−17.8 (−21.4 to −13.9)	0.044
SLS (%)	−11.6 (−14.0 to −8.0)	−10.1 (−12.5 to −7.1)	<0.001
LGE+	n = 134	n = 139
SRS (%)	21.0 (13.5–32.4)	22.8 (13.2–33.6)	0.398
SCS (%)	−12.9 (−16.7 to −9.2)	−13.2 (−17.4 to −10.6)	0.313
SLS (%)	−11.3 (−14.3 to −9.5)	−8.7 (−12.0 to −5.4)	<0.001
LGE++	n = 96	n = 95
SRS (%)	12.8 (6.8–24.8)	11.1 (5.4–18.5)	0.183
SCS (%)	−7.9 (−11.8 to 5.3)	−8.8 (−12.8 to −5.5)	0.235
SLS (%)	−9.4 (−13.0 to −7.1)	−8.4 (−10.3 to −6.3)	0.026

Values are given as median (range).

NS, normal saline; r-SAK, recombinant staphylokinase; SCS, segmental circumferential strain; SLS, segmental longitudinal strain; SRS, segmental radial strain.

Reproducibility

Intra-observer reproducibility of infarct size (ICC = 0.942, IQR = 0.838∼0.980) and AAR (ICC = 0.977, IQR = 0.933∼0.992) were excellent. Similarly, intra-observer reproducibility of SRS (ICC = 0.737, IQR = 0.673∼0.790), SCS (ICC = 0.809, IQR = 0.761∼0.849), and SLS (ICC = 0.787, IQR = 0.733∼0.831) were good.

Inter-observer reproducibility of infarct size (ICC = 0.925, IQR = 0.793∼0.974), AAR (ICC = 0.912, IQR = 0.758∼0.969) were excellent. Similarly, inter-observer reproducibility of SRS (ICC = 0.696, IQR = 0.625∼0.756), SCS (ICC = 0.781, IQR = 0.727∼0.826), and SLS (ICC = 0.693, IQR = 0.621∼0.753) were good.

Discussion

In this study, STEMI patients in the r-SAK group exhibited significantly better LVEF and CI compared to the NS group, without an increase in the incidence of MVO or IMH. Segmental strain analysis showed improved SLS in the r-SAK group, regardless of the extent of LGE in the segments (LGE−, LGE+, and LGE++). In addition, in LGE− segments, SCS was also superior in the r-SAK group compared to the NS group. These findings suggested that pretreatment with a single bolus of half-dose r-SAK before PCI in STEMI patients may have a positive impact on cardiac function.

Reperfusion therapy, which includes thrombolysis and PCI, is crucial treatment for STEMI patients. The recommendation is that primary PCI should be the preferred reperfusion strategy for STEMI patients who are expected to have PCI within 120 min of their presentation (2). However, in some situations, primary PCI may not be immediately available. When timely PCI cannot be performed, fibrinolytic therapy is recommended in patients without contraindications (2). In our study, the median time from r-SAK infusion to start of PCI was 55 min in the r-SAK group. This indicates that for STEMI patients expected to undergo PCI within 120 min, there was still a nearly 1-h delay between r-SAK administration and PCI. However, this delay may have allowed patients to achieve earlier reperfusion and reopening of the IRA compared to if they had received PCI alone.

Several studies have demonstrated that fibrinolysis followed by PCI results in effective reperfusion in STEMI patients (3,4,16). The trial showed that the r-SAK group exhibited a smaller infarct size, which was not observed in this study. The discrepancies may be partially explained by the short time from symptom onset to treatment in the NS group. Notably, the median time from symptom onset to r-SAK/NS infusion was longer in the r-SAK group (335 min vs. 205 min), though no statistical significance was observed (P = 0.127). This may relate to logistical variations in treatment initiation, and the lack of significance could be attributed to the small sample size. While prolonged ischemia theoretically increases myocardial injury, the r-SAK group still demonstrated improved cardiac function. These findings suggested that, beyond the importance of timely reperfusion, the combination of thrombolysis (using r-SAK) and PCI may lead to better clinical outcomes compared to PCI alone. This is in line with previous research showing that a Pharmaco-invasive strategy with half-dose alteplase and timely PCI can offer more reperfusion compared to PCI alone (4). Therefore, the importance of timely treatment cannot be overstated.

In light of the above clinical rationale for using r-SAK plus PCI, our findings explicitly demonstrated that the r-SAK group exhibited significantly higher LVEF and CI compared to the NS group — two core parameters for quantifying global cardiac function. These parameters can, in principle, also be obtained by conventional transthoracic echocardiography, which is widely available, portable, and suitable for bedside assessment in acute STEMI. However, the purpose of this study was not only to document global pump function but also to characterize the quality and completeness of myocardial reperfusion achieved by r-SAK pretreatment followed by PCI. For this reason, CMR was preferred because in a single examination it allows quantitative evaluation of infarct size/LGE extent, AAR, and microvascular injury (MVO and IMH), and thus provides imaging markers that are more closely linked to subsequent remodeling and prognosis. In this setting, CMR therefore offers incremental value over echocardiography.

The LV myocardium has a complex three-layer architecture comprising circumferential fibers in the mid-wall layer and longitudinal fibers in the endocardial and epicardial layers. In our study, patients in the r-SAK group had a better SLS than those in the NS group in LGE−, LGE+, and LGE++ segments. This finding might be attributed to the recovery of epicardial longitudinal cardiac function in the r-SAK group, as demonstrated in previous study, which showed that the combination of half-dose alteplase and timely PCI provided more comprehensive epicardial and myocardial reperfusion than PCI alone (4). This combined approach may have help prevent or minimize myocardial injury in these regions. Although PCI alone can restore flow in large vessels, microcirculation disorders may still occur in some patients. Thrombolytic agents can dissolve microthrombi, promoting blood flow in the microcirculation and helping in the recovery of cardiac function. In contrast, patients in the NS group, who did not receive thrombolytic therapy, may have experienced persistent ischemia and injury to the endocardial layer, which was the first to be affected during ischemic event, thereby affecting longitudinal cardiac function. In contrast, SRS reflects overall LV wall thickening and represents the combined contribution of all three myocardial layers. Accordingly, it is inherently less sensitive to ischemic injury that predominantly involves the subendocardial layer. Moreover, SRS is more prone to regional heterogeneity and lower reproducibility than longitudinal strain, and together with the relatively small sample size in this study, this may have limited our ability to detect between-group differences.

Emerging clinical evidence suggests that, in STEMI patients, not only the infarcted myocardium but also the non-infarcted remote myocardium may experience acute inflammation and injury (17 –19). This is likely due to the systemic inflammatory response triggered by MI, which can extend to remote myocardial tissue. Notably, when considering LGE segments, patients in the NS group exhibited worse SCS and SLS compared to those in the r-SAK group in this study. The improved function in non-infarcted areas of the r-SAK group could be attributed to the reduced ischemia and injury, resulting from the combination of thrombolytic therapy (using r-SAK) and PCI, which benefits not only the infarcted myocardium but the remote areas as well. The inflammatory response after MI may be less severe in the r-SAK group compared to the NS group. Complete reperfusion achieved through this strategy may have mitigated the inflammatory cascade, leading to reduced injury in the non-infarcted remote myocardium. The acute response of non-infarcted myocardium could serve as a predictor of long-term major adverse events (17). Therefore, the worse SCS and SLS observed in the NS group might indicate a poor outcome in the future.

The present study has some limitations. First, this study involved a relatively small cohort of patients; therefore, the generalizability of our findings is limited. The potential for type II errors in these parameters should be acknowledged. Several parameters showed only a trend toward improvement but did not reach statistical significance, highlighting the need for validation in larger, independently recruited cohorts. In addition, no formal a priori power analysis for the CMR endpoints was performed, because the sample size was mainly determined by CMR availability in this sub-study of the trial. Second, this was a cross-sectional study that analyzed only the early/short-term CMR findings in STEMI patients; the long-term myocardial effects of the different treatment strategies still need to be clarified in future follow-up studies. Third, the gold standard for the diagnosis of IMH is T2* mapping (20); in this study, IMH was diagnosed using T2W imaging, which may limit the accuracy of the results.

In conclusion, for STEMI patients expected to undergo PCI within 120 min of presentation, a single bolus of half-dose r-SAK before PCI improved short-term cardiac function without increasing the incidence of MVO or IMH.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Jiani Yin

Hao Gong

Yunfei Wang

Jun Wang

Chunjian Li

Xiaomei Zhu

Yi Xu

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