Patient recruitment
We enrolled 571 patients with STEMI who underwent primary PCI between September 2016 and December 2020 in our institute from an ongoing, retrospective, single-centered, hospital-based registry. We excluded 39 patients with in-hospital death, 91 patients who underwent PCI without ELCA or manual aspiration thrombectomy, and 224 patients without scintigraphic data. Then, 74 patients who underwent both ELCA and manual aspiration thrombectomy were excluded. Finally, 63 patients who underwent ELCA (ELCA group) and 80 patients who underwent manual aspiration thrombectomy (aspiration group) were enrolled in the present study (Fig. 1).
STEMI was diagnosed based on the 2018 Japanese Circulation Society guideline [1]. Written informed consent was obtained from each patient or a relative before or after undergoing PCI. This study was approved by the Medical Ethics Committee of Ogaki Municipal Hospital and was conducted in accordance with the Declaration of Helsinki.
Catheter procedure
Patients with STEMI were administered 200 mg aspirin, 20 mg prasugrel, and 10 mg atorvastatin before undergoing PCI. Patients were also administered heparin 5,000 U in an initial bolus and in additional doses to maintain an activated clotting time > 250 s during the procedure. After ELCA became available in September 2016 at our institute, ELCA or manual aspiration thrombectomy was performed at the discretion of the attending physician based on angiographic, intravascular ultrasound, or optical coherence tomography imaging.
A pulsed-wave xenon chloride excimer laser (X-80 Vitesse RX, Phillips Japan, Tokyo, Japan) at a wavelength of 308 nm, pulse duration of 135 ns, and output of 165 mJ/pulse was used; the fluence was 30–80 mJ/mm2 at pulse repetition rates of 25–80 Hz. The laser catheters were available in sizes of 0.9, 1.4, and 1.7 mm. For the antegrade delivery of the laser catheter, we used safe laser techniques and injected saline before and during the laser procedure at a catheter advancement rate of 0.5 mm/s [13]. The retrograde laser method (frequency and repetition rate raised to 60 mJ/mm2 and 40 Hz at the maximum, catheter was pulled back, and saline was then injected) was performed at the discretion of each physician. After ELCA ablation or manual thrombus aspiration, patients underwent balloon dilatation, if necessary, and drug-eluting stents were deployed. Antegrade flow and microvascular circulation after PCI were assessed using the TIMI flow grading scale [14].
Data collection
After PCI, the clinical and demographic data of all patients were retrieved from our hospital’s medical records. We measured serum creatine kinase (CK) and creatine kinase-myocardial band (CK-MB) values every 4 h until we identified the peak concentrations and verified the 12-lead electrocardiogram when entering the high care unit. We defined complete ST resolution as a return to a normal ST-segment on a 12-lead electrocardiogram after reperfusion therapy, and ST-segment elevation exacerbation as an increased ST-segment elevation at the time of high care unit entry compared to that on admission. Almost all patients were administered 100 mg aspirin and 3.75 mg prasugrel once daily for at least 1 month after the procedure.
Scintigraphic data
The methodology of the nuclear scintigraphic study is shown in Fig. 2. I-123 β-methyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) has been used to investigate impaired fatty acid metabolism, which expresses at-risk myocardium regions. 123I-BMIPP scintigraphy was performed 1 week (3–10 d) after the initial PCI procedure. In terms of the scanning procedure, 111 MBq of 123I-BMIPP was injected while the patient was at rest in a fasting state for at least 3 h. Image acquisition was demonstrated 15 min after injection. A wide field-of-view dual-head detector camera (Symbia Evo Excel, Siemens Co., Tokyo, Japan) was equipped with a low-energy, high-resolution collimator without X-ray-based attenuation correction. Each time, 32 views were collected over 180° from the right anterior oblique to the left posterior oblique positions at 60–70 s/view through a step-and-shoot method. The energy discrimination was centered at 159 keV with a 20% window. A series of transaxial images were reconstructed using filtered back projection, after which cardiac short-axis and long-axis slices perpendicular to the cardiac axes were recognized by a nuclear medicine computer system using a filtered back-projection algorithm without attenuation correction. The short-axis, vertical long-axis, and horizontal long-axis slices, each 6 mm thick, were reconstructed.
99mTc-tetrofosmin (TF) scintigraphy was performed 3 months after the PCI procedure. In terms of the scanning procedure, 740 MBq of 99mTc-TF was injected while the patient was at rest. Image acquisition was demonstrated using a 180° non-circular orbit with 32 steps and step-and-shoot mode through a dual-head gamma camera (ADAC VertexPlus, Phillips, Amsterdam, Netherlands) equipped with a low-energy general-purpose collimator. The pixel size in a 128 × 128 matrix was 3.24 mm. A photopeak window of 99mTc-TF was set at a 20% energy window centered at 140 keV. The division of the electrocardiographic R–R interval was 16 frames per cardiac cycle (50 s per step) in gated acquisition from the left inferior oblique 45° to the right anterior oblique 45°. Using a Butterworth filter with an order of 10 and a cut-off frequency of 0.49 cycle/cm, ungated reconstruction was demonstrated with filtered back-projection. No attenuation or scatter correction was applied. Horizontal and vertical long and short axes were created for single-photon emission computed tomography (SPECT) image reconstruction. The short-axis images were anonymously exported from the Digital Imaging and Communications in Medicine (DICOM) format to the quantitative myocardial perfusion (MP)-SPECT software. LV ejection fraction (LVEF) values were automatically calculated using the QGS software program (Auto QUANT 7.2, Cedars-Sinai Medical Center, Los Angeles, CA, USA) The indices were automatically derived from MP-SPECT by applying QPS. In addition, we used a 17-segment model with a five-point scoring system on polar map images according to the recommendations of the American Heart Association using commercially available software (Heart Score View, Nihon Medi-Physics Co. Ltd., Tokyo, Japan) [15]. For cases in which the fully automated LV segmentation failed or returned unsatisfactory results, we adapted the manual mode to supply constraints to the LV segmentation algorithm by well-trained radiological technologists.
Furthermore, we evaluated LVEF, the number of patients with LVEF recovery, summed rest score (SRS), motion extent (Mot Ext, motion abnormality area as a percentage of the mid-myocardial surface area), thickening extent (Thk Ext, thickening abnormality area as a percentage of the mid-myocardial surface area), defect extent (Defect Ext, perfusion defect area as a percentage of the mid-myocardial surface area), peak emptying rate (PER), peak filling rate (PFR), and mean FR (MFR/3) [16]. LVEF, Mot Ext, and PER represent the systolic performance of the LV, whereas SRS, Thk Ext, and Defect Ext represent the viability of the residual myocardium. PFR and MFR/3 represent the diastolic performance of the LV. We defined EF recovering as patients with improved LVEF according to 99mTc-TF scintigraphy at 3 months compared to that of baseline 123I-BMIPP scintigraphy. We also defined dif as the difference between 99mTc-TF scintigraphic values at 3 months and 123I-BMIPP scintigraphic values at baseline for each parameter. All SPECT analyses were performed with the latest QGS/QPS version (Auto QUANT 7.2) by an expert radiological technologist who was blinded to the patients’ baseline characteristics and clinical courses.
Study endpoints
The study efficacy endpoint was defined as the improvement in systolic/diastolic function and viability of the LV according to the scintigraphic parameters. We also evaluated the peak serum CK/CK-MB concentrations, final TIMI flow, complete ST-segment resolution, and ST-segment elevation exacerbation. In-hospital major adverse cardio-cerebral events (MACCEs) including cardiovascular death, MI (which included stent thrombosis), and stroke were also investigated. Death was considered of cardiac origin unless an obvious non-cardiac cause was identified. Spontaneous MI and stent thrombosis were defined according to the Academic Research Consortium definitions [17]. Procedural complications included perforation, oozing rupture, slow flow/no reflow, and distal embolism.
Statistical analysis
Continuous variables are expressed as means ± standard deviations, and categorical variables are expressed as numbers and relative frequencies. Continuous variables were compared using the Student’s t-test and Wilcoxon rank-sum test, and categorical variables were compared using the chi-square test or Fisher’s exact test. Statistical significance was set at a p-value of < 0.05. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) [18].