Impact of size-dependent differences in excimer laser coronary angioplasty in ST-elevation acute myocardial infarction: nuclear scintigraphy findings

Study population

A total of 571 consecutive patients with the first STEMI undergoing primary PCI at the Ogaki Municipal Hospital between September 2016 and December 2020 were retrospectively enrolled. STEMI was diagnosed in accordance with the 2018 Japanese Circulation Society guidelines [13]. Patients who experienced in-hospital death, who underwent PCI without ELCA, and those without scintigraphy data were excluded. In addition, patients who underwent PCI with both small- and large-diameter ELCA catheters were excluded. Finally, 123 patients with STEMI who underwent primary PCI with nuclear scintigraphy data were included. Excimer laser catheters come in 0.9, 1.4, 1.7, and 2.0-mm diameters. The 1.7-mm and 2.0-mm catheters are offered in both concentric and eccentric configurations. In the present study, no patients underwent PCI with the 2.0-mm size. Subsequently, the study patients were divided into two groups: patients who underwent PCI with a 0.9-mm ELCA catheter (0.9 mm group) and those who underwent PCI with a 1.4- or 1.7-mm ELCA catheter (1.4/1.7 mm group). The clinical events and clinical and demographic data of all patients were retrieved from their hospital medical records. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and its amendments. This was reflected in the a priori approval of the study by the Ethics Committee of Ogaki Municipal Hospital. Written informed consent was obtained from all patients or their relatives before or after the PCI procedure.

Catheter insertion procedure

As a standard of care, patients with STEMI received 200 mg of aspirin and 20 mg of prasugrel before the PCI procedure. Patients also received heparin (5000 U) as an initial bolus and additional doses to maintain an activated clotting time of > 250 s during the procedure. The decision to perform ELCA and selection of the catheter size were undertaken by the individual operator, based on angiographic data, intravascular ultrasound data when available, and a comprehensive assessment of other relevant factors. These factors included not only the vessel diameter and degree of stenosis obtained from angiographic data after wire crossing but also the overall vessel structure, such as tortuosity, the characteristics of the thrombus and plaque, and whether an eccentric lesion was present. The Spectranetics CVX-300 platform (Spectranetics, Colorado, CO, USA), consisting of an excimer laser generator (CVX-300) and a pulsed-wave xenon chloride excimer laser (X-80 Vitesse RX, Phillips Japan, Tokyo, Japan) with a wavelength of 308 nm, pulse duration of 135 ns, and pulse output of 165 mJ/pulse, was used. The available setting of the fluence was in the range 40–80 mJ/mm² at a pulse repetition rate in the range 25–80 Hz with the 0.9-mm catheter. By contrast, the fluence range was 40–60 mJ/mm² at a pulse repetition rate range of 25–40 Hz with the 1.4- or 1.7-mm catheter. The antegrade delivery of the laser catheter with nominal fluence and repetition was performed following the established safety protocols, and saline was injected before and during the laser procedure at a catheter advancement rate of 0.5 mm/s [14]. After crossing the culprit lesion, the laser catheter was gradually pulled back while performing additional ablation. During this slow pull-back, the frequency and repetition rates were increased to maximum settings as determined by the operator to achieve a larger vaporizing area. Angiographic and intravascular ultrasound (IVUS) images from representative patients with STEMI who underwent ELCA are shown in Figure 1. After ELCA ablation, the patients underwent balloon dilation via standard techniques, and drug-eluting stents were deployed if necessary. The use of other devices such as thrombus aspiration devices was at the discretion of each physician. Antegrade flow before and after PCI was assessed using the Thrombolysis in Myocardial Infarction (TIMI) flow grading scale [15]. Coronary angiograms were obtained for angiographic analysis and reviewed by two experienced observers. Quantitative coronary angiography (QCA) was performed using QAngio XA (Version 7.3, Medis Medical Imaging System BV, Leiden, the Netherlands). After PCI, the serum creatine kinase (CK) and creatine kinase–myocardial band (CKMB) values were monitored every 4 h until the peak concentrations were identified and the 12-lead electrocardiogram was verified when entering the coronary care unit.

Figure 1

Angiographic and intravascular ultrasound images from representative patients who underwent excimer laser catheter angioplasty (ELCA)

Imaging study

Gated myocardial perfusion imaging was performed to evaluate left ventricular function and myocardial viability (Figure 2). I-123 β-methyl-p-iodophenyl-pentadecanoic acid (¹²³I-BMIPP) scintigraphy was conducted 1 week after PCI to assess impaired fatty acid metabolism in at-risk myocardium, using 111 MBq of ¹²³I-BMIPP with a dual-head detector camera (Symbia Evo Excel, Siemens) [16]. Image acquisition was completed over 180° with a 20% energy window centered at 159 keV, reconstructed using filtered back projection. At 3 months after PCI, ^99mTc-tetrofosmin (^99mTc-TF) scintigraphy was performed using 740 MBq of ^99mTc-tetrofosmin, and images were similarly acquired in a gated mode for left ventricular evaluation. Short-axis images were processed using quantitative myocardial perfusion SPECT software (QPS) [17, 18]. The indices were automatically derived from MP-SPECT using a Quantitative Perfusion SPECT (QPS) program [18]. In addition, a 17-segment model with a five-point scoring system was used 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) [19]. Parameters evaluated included summed rest score (SRS) and thickening extent (Thk Ext) to measure myocardial viability, motion extent (Mot Ext) for systolic function, and peak filling rate (PFR) and mean filling rate (MFR/3) for diastolic function [20]. For each metric, the difference (dif) between baseline (¹²³I-BMIPP) and 3 months (^99mTc-TF) was calculated. All SPECT analyses were performed using the QPS program (Auto-QUANT 7.2) by trained radiological technologists blinded to patient data. Echocardiographic measurements of left ventricular ejection fraction (LVEF) were performed immediately after PCI and at the 3-month follow-up to assess left ventricular systolic function over time.

Figure 2

Schematic diagram showing the flowchart of nuclear scintigraphy methodology used in this study ^9mTc-TF – technetium-99m-tetrofosmin, ¹²³I-BMIPP – I-123 β-methyl-p-iodophenyl-pentadecanoic acid, CAG – coronary angiography, EDV – end-diastolic volume, EF – ejection fraction, ESV – end-systolic volume, LV – left ventricle, MFR/3 – mean filling rate/3, Mot Ext – motion abnormality area as a percentage of the midmyocardial surface area, PCI – percutaneous coronary intervention, PFR peak filling rate, QGS – quantitative gated single-photon emission computed tomography, SRS – summed rest score, Thk Ext – thickening abnormality area as percentage of the mid-myocardial surface area.

Study endpoint

The study efficacy endpoint included procedural success rate, final TIMI 3 flow, peak CK/CKMB values, and in-hospital major procedural adverse events, including spontaneous MI, target lesion revascularization (TLR), and stent thrombosis (ST). Additionally, left ventricular myocardial salvage, systolic function, and diastolic function were evaluated to assess potential differences in myocardial effects. Procedural success was defined as a reduction in the lumen diameter stenosis to < 30%, as calculated using QCA images, without major device-related complications. TLR was defined as revascularization performed to treat in-stent restenosis or ST in the target lesion. ST and spontaneous MI were defined according to the Academic Research Consortium definitions [21, 22]. The safety endpoints were procedural complications, including slow-flow/no-reflow, perforation, oozing rupture, coronary dissection, and distal embolism.

Slow-flow or no-reflow was defined as inadequate myocardial perfusion through a given segment of coronary circulation without angiographic evidence of mechanical vessel obstruction [23]. Perforation was defined as the persistent extravascular collection of the contrast medium beyond the vessel wall [24]. An oozing rupture was defined based on the findings of Lopez-Sendon et al. [25]. Coronary dissection was defined according to the National Heart, Lung, and Blood Institute classifications [26].

Statistical analysis

Continuous variables are expressed as mean ± standard deviation when normally distributed or as median (interquartile range) when non-normally distributed. The characteristics of each group were compared using Student’s t-test and the Mann-Whitney U test. Categorical variables are expressed as numbers (percentages) and were compared using the χ² test or Fisher’s exact test. A p-value of < 0.05 was considered statistically significant. All statistical analyses were conducted using IBM SPSS Statistics, version 21.0.

Clinical impact of ELCA catheter size on outcomes in patients with STEMI

The efficacy and safety of ELCA in STEMI treatment are well established, with thrombi vaporization and plaque debulking enhancing microcirculation, and careful techniques with saline injection and slow catheter advancement helping to prevent complications [27, 28]. The present study also showed that ELCA demonstrated not only favorable procedural outcomes but also no in-hospital major procedural adverse events and low occurrence of complications. Although catheter selection should be decided based on the vessel size and nature of the lesion [29], currently, no gold standard criteria are available for selecting the appropriate size of excimer laser catheters. It is generally understood that smaller vessel sizes warrant the use of smaller catheters. However, the choice of ELCA catheter size cannot be solely dictated by the vessel diameter. Factors such as the severity of vessel tortuosity and the presence of eccentric lesions often necessitate the use of smaller catheters, such as the 0.9-mm catheter, even in larger vessels, to enhance safety. For instance, in cases where the lesion is eccentric or the vessel exhibits significant tortuosity, a smaller 0.9-mm catheter might be preferred to minimize the risk of complications. Furthermore, when ELCA is performed, the distal flow can often be temporarily halted, particularly when larger catheters are used, leading to prolonged ischemia. The 0.9-mm catheter allows for longer irradiation times in a single pass, enabling more efficient ablation, especially in diffuse or long lesions. This preference is reflected in our data, where the stent length tended to be longer in the group using 0.9-mm catheters. This suggests that, beyond mere vessel size, considerations related to the specific characteristics of the lesion and procedural safety play a critical role in determining the optimal catheter size for ELCA, underscoring the complexity of decision-making in this context. Previous studies have investigated the relationship between catheter size and clinical outcomes. Nagamine et al. reported a difference in the outcomes with the use of a 0.9-mm versus a 1.4-mm catheter in patients with ACS [12]. They suggested that the 0.9-mm catheter is sufficient for patients with acute MI, which is consistent with the results of the present study. Furthermore, they compared the angiography findings with the short-term outcomes. In the present study, no significant differences were found in in-hospital outcomes, including the final TIMI flow and peak CK/CKMB ratio, between the two groups. In addition, regarding mid-term outcomes evaluated using nuclear scintigraphy findings, the 0.9 mm group showed better outcomes for systolic function and left ventricular viability.

There are several explanations for why the use of a smaller-diameter ELCA catheter could have resulted in better outcomes in patients with STEMI. Larger-diameter catheters, due to their size and reduced flexibility, may shave off the target lesion directly rather than exhibiting a vaporizing effect, increasing the risk of slow flow or distal embolism. By contrast, the target artery pathway can be more easily negotiated with the use of a 0.9-mm catheter owing to better tracking and maneuverability. Therefore, dedicated maneuvers can be performed, resulting in a lower risk of slow flow secondary to mechanical contact and periprocedural complications. Although not statistically significant, the number of patients who demonstrated slow flow/no-reflow and distal embolism was higher in the 1.4/1.7 mm group, suggesting a possible association with the poor results of the final TIMI flow.

Another reason may be related to the availability of high-power ELCA techniques, which can potentially enhance the efficiency of target reduction. Nagamatsu et al. compared low- and high-power ELCA for ablation in the external iliac arteries of rabbits and observed that high-power ablation resulted in more remarkable pathological changes than low-power ablation [30]. Although the 0.9-mm catheter has the advantage of better crossability, its smaller diameter could limit its impact area. However, with high-power settings, the 0.9-mm catheter may deliver sufficient power to achieve comparable results to larger sizes, as supported by our QCA findings showing no significant difference in post-ELCA percentage area of stenosis between the 0.9-mm group and the larger catheter group. This suggests that high-power settings can enable the 0.9-mm catheter to achieve a comparable debulking effect while maintaining its crossability advantage. In addition, the irradiation and rest times are 10 s and 5 s, respectively, with the use of the 0.9-mm catheter, and 5 s and 10 s, respectively, with the use of other catheter sizes. As mentioned above, the risk of antegrade coronary flow obstruction can be avoided owing to the longer ablation time with a shorter rest time with the use of the 0.9 mm catheter. Therefore, owing to the advantages described above as well as its ability to cross the target lesion, the 0.9-mm catheter may demonstrate a significantly greater debulking effect than other catheter sizes [31, 32].

This study has several limitations. First, this was a single-center retrospective analysis with a primary intervention. The study’s reliance on available nuclear scintigraphy data for inclusion criteria introduces selection bias, as patients without follow-up scintigraphy – due to various reasons including financial constraints, relocation, or referral to primary care physicians – were excluded. This selection process potentially limits the generalizability of our results to all STEMI patients undergoing ELCA. Second, the decision on the catheter size for ELCA was based on the physician’s discretion. To obtain the maximum volume reduction, it is natural to select a catheter with a larger diameter. Although no vessel evaluation data were obtained from angiography and imaging scans in the present study, the final stent size was similar, implying that there was no significant difference in the vessel size. Third, the SRS values were significantly higher at baseline in the 0.9 mm group, which may have contributed to the greater myocardial salvage observed in this group. This study was not designed as a non-inferiority trial, so while our findings suggest that the 0.9 mm catheter may achieve similar efficacy to larger catheter sizes, further research is needed to confirm these results. Fourth, the association between the effectiveness of ELCA and the target vessels was not evaluated in this study because of the limited number of patients.