Optical coherence tomography for the diagnosis and management of stent thrombosis

INTRODUCTION

Coronary artery disease (CAD) is a significant national and global public health concern. In 2021, more than 254 million cases of CAD were diagnosed worldwide, with an incidence rate of 403.89 new cases per 100,000 people and a mortality rate of 113.94 deaths per 100,000. In Egypt, CAD is the most prevalent cardiovascular disease among men and women, with an overall prevalence of 4.27%.1 Key risk factors for CAD include smoking, gender, diabetes, hypertension, and dyslipidemia, with men experiencing a 2-fold higher rate than women.2 Computed tomography is the standard diagnostic imaging modality for stable CAD, while high sensitivity C-reactive protein is recommended for predicting stable CAD. Although regional wall motion abnormality (RWMA) is the gold standard echocardiographic marker for stable CAD, it is not effective in detecting subclinical myocardial damage.3

Two-dimensional (2D) speckle tracking echocardiography (STE) strain analysis measures myocardial deformation providing a more reliable evaluation of myocardial mechanics and addressing the limitation of RWMA in identifying subtle myocardial damage.4 Real-world evidence suggests that global (GLS) and regional longitudinal strain (RLS) offer better diagnostic accuracy and reproducibility in detecting stable CAD.5-7 GLS assesses ventricular shortening from base to apex to estimate overall strain in the left ventricle (LV), whereas RLS focuses on strain in specific LV segments. Other strain analysis methods include global radial strain (GRS), global circumferential strain (GCS), territorial longitudinal strain (TLS), regional radial strain (RRS), and regional circumferential strain (RCS), each measuring different aspects of myocardial strain.8 Our study aimed to evaluate the predictive role of TLS in stable CAD for identifying significant coronary artery lesions with ≥ 70% diameter stenosis.

METHODS

Study design

We conducted a 24-month cross-sectional, open-label, single-cohort, single-center study was at the cath lab of a tertiary care teaching hospital. Investigators were not blinded to the study group. Prior to conducting the study, its design and protocol were reviewed, approved, and registered with Ain Shams University Hospital Human Ethics Committee on 1 July 2021 under trial registration No. Md 110/2021.

Written informed consents was obtained from all human research subjects and study participants. Participant privacy rights were strictly protected, data were anonymized, and study procedures were conducted in accordance with the Egyptian National Commission for Bioethics statement on ethical conduct in human research. Furthermore, the study adhered to the SAGER guidelines to address potential sex- and gender-related bias.

Study participants

Patients with typical or atypical anginal chest pain evaluated at the outpatient clinic and cath lab of a single tertiary care center between August 2021 and August 2023 were included in the study. Patients with acute coronary syndrome, myocardial infarction, non-sinus rhythm, normal coronary angiography (CAG), prior percutaneous coronary intervention or coronary artery bypass grafting, inadequate echocardiographic window, or valvular or myocardial disease were excluded.

Study procedures

A total of 738 patients were enrolled and undewent history taking and data collection for gender, age, diabetes mellitus, hypertension, smoking, dyslipidemia, chronic kidney disease, peripheral arterial disease, stroke, sedentary lifestyle, myocardial infarction, and family history of CAD. Furthermore, patients undewent blood pressure measurements and comprehensive cardiac examination, including assessment for abnormal auscultatory findings, prior cardiac surgery, cardiomegaly, and heart failure. Moreover, all patients underwent 12-lead electrocardiogram, 2D echocardiography and 2D STE using an IE 33 ultrasound system (Philips, The Netherlands) with an X5-1 phased-array transducer; CAG with digital image acquisition and storage, complete blood count; lipid profile; liver and kidney function tests; coagulation studies (prothrombin time, activated partial thromboplastin time, and international normalized ratio); and serial cardiac enzyme measurements. The 2D echocardiography was conducted before the CAG and the 2D STE after the CAG. The cardiologists performing 2D echocardiography and 2D STE were specialized in echocardiography, held level III competency according to the European Society of Cardiology Core Curriculum, and were blinded to the coronary angiographic data.9 Furthermore, the interventional cardiologists, who analyzed the CAGs were blinded to the results of the echocardiographic evaluation. Data documented with CAG included the severity of coronary artery stenosis according to the Coronary Artery Disease-Reporting and Data System and the regional distribution of the area supplied with the epicardial coronary artery according to the 17 LV segment model. A coronary lesion of ≥ 70% diameter stenosis was considered significant, and such patients were classified as having severe stable CAD.10 A consecutive sample of 199 eligible participants with severe stable CAD was selected, assigned, and allocated to a single group (figure 1). Operators performing 2D echocardiography and 2D STE were blinded to the coronary angiographic data. Data documented with 2D echocardiography and 2D STE included RWMA, wall motion score index (WMSI), and strain analysis. RWMA was categorized into normal with an assigned score of 1, hypokinetic with an assigned score of 2, akinetic with an assigned score of 3, and dyskinetic with an assigned score of 4. The WMSI represents the average RWMA of the 17 analyzed segments in a 17 LV segment model.11 Myocardial function by strain imaging was evaluated on a frame-by-frame basis by automatic tracking of acoustic markers (speckles) throughout the cardiac cycle in a 17 LV segment model, and GLS was obtained by averaging the myocardial function of all 17 segments. The endocardial borders were traced in the end-systolic frame of the 2D images from the 3 apical views for analyses of longitudinal strains. RCS analysis was obtained from the 3 parasternal short-axis views. RRS analysis from the 3 apical views was conducted manually by tracking the average peak systolic radial excursion for each segment between 2 points (endocardial and epicardial) of 3 levels for each of the 17 segments. Peak systolic strains were obtained for 17 longitudinal, 17 radial, and 16 circumferential LV segments. All segmental values were averaged to GLS and GCS for each study participant and automatically displayed in a bull’s-eye plot. TLS measured the number of impaired territories based on the cutoff results of the RLS analysis from the segments supplied with the corresponding coronary arteries in a 17 segment LV model as follows: 7 segments for the left anterior descending coronary artery (LAD), 5 for the right coronary artery (RCA), and 5 for the left circumflex artery (LCx).12

Figure 1. Flow chart of stable coronary artery disease cohort selection. CAG, coronary angiography; STE, speckle tracking echocardiography.

Endpoints

The endpoint of the study was the predictive role of TLS in stable CAD for identifying the location and severity of significant coronary artery lesion with ≥ 70% diameter stenosis.

Statistical analysis

Our study was a cross-sectional, open-label, single cohort, single center study. The echocardiographic assessment outcomes were coded, and data were analyzed with the SPSS v29 software package (IBM, United States). Shapiro-Wilks test was used to assess normality of data. Qualitative data was expressed as frequencies (number of cases) and relative frequencies (percentages), and quantitative data as means, standard deviations, medians, and interquartile ranges. Comparisons of parametrically distributed quantitative variables were performed using the Student t test or analysis of variance (ANOVA), whereas nonparametrically distributed quantitative variables were compared using the Mann-Whitney test, and between qualitative variables using the chi-square test or Fishers exact test, as appropriate.13,14 Inter- and intra-observer variability was assessed by reanalyzing the data of 18 randomly selected study participants and reported as intraclass correlation coefficient (ICC), whose scale ranges from 0 to 1 where 1 represents perfect reliability with no measurement error and 0, no reliability. An ICC value < 0.5 indicates poor reliability; 0.5-0.75, moderate reliability; 0.75-0.9, good reliability; and > 0.90, excellent reliability.15 The area under the curve (AUC) was constructed to detect the cutoff for optimal sensitivity and specificity of regional strains. Receiver operating characteristic (ROC) curve comparison was performed using MedCalc version 10.3.1.0 (MedCalc Software, United States). Confidence interval was set to 95% and the accepted margin of error at 5%. 01. A P value <05 was considered statistically significant, and a P value < .01 was considered highly significant. Final analyses were conducted according to the per-protocol approach.

RESULTS

Baseline characteristics and sociodemographic features

The baseline characteristics and sociodemographic features of the study cohort are shown in table 1. Male predominance was the pivotal sociodemographic characteristic of the enrolled participants (56.5%), and the mean age was 60.4 ± 9.9years. Baseline risk factors and comorbidities of the study cohort included hypertension in 68.5%, diabetes mellitus in 70%, dyslipidemia in 66%, and smoking in 47%, respectively. There were no withdrawals, and all participants completed the study.

Table 1. Baseline characteristics and sociodemographic features of stable coronary artery disease cohort

Coronary angiographic characteristics of stable coronary artery disease cohort

The location and severity of significant coronary lesions with ≥ 70% diameter stenosis is shown in table 2. Most study participants had single-vessel disease (68%). Among significant lesions, 63 (22%) were located in the LCx, 121 (43%) in the LAD, and 98 (35%) in the RCA.

Table 2. Coronary angiographic characteristics of stable coronary artery disease cohort

Strain analysis of stable coronary artery disease cohort

The global strain analysis showed a GLS range of -26% to -8%, with a mean value of -16.4 ± 3.6%, and a GCS range of -35% to -10%, with a mean value of -18.4 ± 4.9%. The regional strain analysis (RSA) of 3383 segments showed RWMA in 3378 segments (99.8%), a mean WMSI of 1.3 ± 0.2 with sensitivity and specificity rates of 88% and 61%, respectively, GLS in 3365 segments (99.5%), GCS in 3184 segments (100%), global radial strain in 3352 segments (99%), significant hypoperfusion (coronary lesions with ≥ 70% diameter stenosis) in 1472 segments (43%), and normal perfusion to mild-to-moderate hypoperfusion (coronary lesions with < 70% diameter stenosis) in 1911 segments (57%). The medians and the interquartile ranges of the regional strain parameters for coronary lesions with ≥ 70% diameter stenosis demonstrated significant differences vs the corresponding pa­rameters for coronary lesions with < 70% diameter stenosis. The median RLS was -20% (IQR, -23% to -17%) for lesions < 70% diameter stenosis vs -12% (IQR, -14% to -9%) for lesions ≥ 70% diameter stenosis (P < .001). The median RRS was 40% (IQR, 38%-43%) for lesions < 70% diameter stenosis vs 33% (IQR, 21%-39%) for lesions ≥ 70% diameter stenosis (P < .001) (figure 2). The median RCS was -19% (IQR, -24% to -14%) for lesions < 70% diameter stenosis vs -17% (IQR, -22% to -12%) for lesions ≥ 70% diameter stenosis (P < .001). RWMA were detected in 38% of the segments supplied by significant coronary lesions with ≥ 70% diameter stenosis compared with 6% of the segments supplied by non-significant coronary lesions with < 70% diameter stenosis (P < .001).

Figure 2. Regional radial strain analysis of a study participant with stable coronary artery disease showing 42% strain of the mid inferoseptal segment.

Feasibility and reproducibility of stable coronary artery disease cohort

The ICC for inter- and intra-observer variability of segmental strains were measured in 21 of the 199 patients study cohort (11%). The results of the ICC for inter- and intra-observer variability of segmental strains were 0.91 and 0.96 for GLS, 0.94 and 0.97 for GCS, and 0.86 and 0.92 for GRS.

ROC curve and area under the curve analysis in patients with stable coronary artery disease

AUC was constructed to detect the cutoff for optimal sensitivity and specificity of regional strains (table 3). The AUC for RLS was 0.947 (P < .001) which detected a cutoff of ≥ -16% for optimal sensitivity and specificity of RLS. ROC curve comparison showed that RLS exhibited the highest predictive value for identifying significantly hypoperfused segments (with ≥ 70% diameter stenosis) at a cutoff of ≥ -16% vs the RRS (AUC difference, 0.149; 95%CI, 0.132-0.167; P ≤ .0001), RWMA (AUC difference, 0.277; 95%CI, 0.262-0.293; P ≤ .0001), and RCS (AUC differ- ence, 0.348; 95%CI, 0.327-0.368; P ≤ .0001), respectively (figure 3).

Table 3. Area under curve for detection of cutoff for optimal sensitivity and specificity of the regional strains

Figure 3. Receiving operating characteristic curve comparison of stable coronary artery disease cohort comparing regional longitudinal strain, regional radial strain, regional circumferential strain, and regional wall motion abnormalities in predicting significant ≥ 70% diameter stenosis. RCS, regional circumferential strain; RLS, regional longitudinal strain; RRS, regional radial strain; RWMA, regional wall motion abnormality.

ROC curve analysis of regional longitudinal strain in patients with stable coronary artery disease

Guided by the detected cutoff of ≥ -16% for the optimal sensitivity and specificity of RLS, the predictive role of TLS in stable CAD for identifying the location and severity of significant coronary artery lesions with ≥ 70% diameter stenosis was explored (table 4). The ROC curve analysis of the RLS at a cutoff of ≥ -16% demonstrated that the optimal number of impaired segments that could predict the location and severity of significant coronary lesions with ≥ 70% diameter stenosis was ≥ 3 impaired segments out of the 7 territorial segments of LAD to predict proximal or significant lesion in the mid-LAD and ≥ 3 impaired segments among the 5 territorial segments of either the LCx or RCA to predict proximal significant lesion in the LCx or RCA (figure 4).

Table 4. Receiving operating characteristic curve analysis of regional longitudinal strain

Figure 4. Territorial longitudinal strain of study participants with stable coronary artery disease. Top row: representative study participant with significant proximal left anterior descending coronary artery lesion (≥ 70% diameter stenosis; red arrow). Global longitudinal (L) strain was -18.7%. Seven segments within the left anterior descending coronary artery territory (anteroseptal, anterior regions, and apex) demonstrated impaired strain (≥ -16%), consistent with a true-positive finding, whereas left circumflex and right coronary artery territories showed preserved strain (< -16%), consistent with true-negative findings. Bottom row: representative of a study participant with a significant proximal right coronary artery lesion (≥ 70% diameter stenosis; blue arrow). Global longitudinal strain was -23.3%. Four segments within the right coronary artery territory (mid, basal inferior, and inferoseptal) demonstrated impaired strain (≥ -16%), consistent with a true-positive finding, whereas left anterior descending artery and left circumflex artery territories showed preserved strain (< -16%), consistent with true-negative findings.

DISCUSSION

Despite being the gold standard echocardiographic marker for stable CAD, RWMA is ineffective at detecting subclinical myocardial damage.3 Our study aimed to evaluate the predictive capability of TLS in identifying the location and severity of significant coronary lesions with ≥ 70% diameter stenosis.

Participants in our study had a mean age of 60.4 ± 9.9 years (range, 38-81 years), with 112 men (56.5%). Most participants had single-vessel disease (68%); 45 (23%), 2-vessel disease; and 19 (10%), 3-vessel disease. Significant coronary lesions with ≥ 70% diameter stenosis were located in the LCx, LAD, and RCA in 63 (22%), 121 (43%), and 98 cases (35%), respectively. Similarly, Koulaouzidis et al. found that 57% of their participants had single-vessel disease with ≥ 50% diameter stenosis.16 Observational studies suggest that most single-vessel coronary occlusions occur in the proximal LAD.17,18

In our cross-sectional study, GLS ranged from -26% to -8%, averaging -16.4 ± 3.6%, while RLS for lesions < 70% diameter stenosis was -20% (IQR, -23% to -17%) vs -12% (IQR, -14% to -9%) for lesions ≥ 70% diameter stenosis (P < .001). Norum et al. concluded that a GLS cutoff of -17.4% to -20.3% could predict CAD in patients with chest pain, with sensitivity rates between 51% and 81% and specificity rates between 58% and 81%.19 There is limited real-world data on RSA in stable CAD. Montgomery et al. found that summed LAD segmental strain demonstrated a sensitivity and specificity of 66% at a cutoff of -20.3% for predicting LAD lesions ≥ 50% diameter stenosis.20 Shimoni et al. demonstrated that segmental analysis using the least 10-percentile peak systolic strain (PSS) outperformed global PSS and GLS.21 Biering-Sørensen et al. observed that significant left main stenosis (≥ 70%) affected apical longitudinal strain (ALS) more than significant lesions did in the LAD or LCx, despite similar GLS results.22 Carstensen et al. studied asymptomatic CAD in patients with aortic stenosis using an 18-segment LV model, finding that only ALS and mid-longitudinal strain were significant independent predictors of asymptomatic CAD, which is consistent with other studies indicating that proximal lesions impact all defined regions.23-25 Liu et al. showed that a cutoff of ≥ -23.5% for endocardial RLS and GLS of the LAD was higher in identifying significant LAD stenosis (≥ 50%) vs strain values from other layers.26

Our findings indicate that at a cutoff of ≥ -16%, TLS can predict the location and severity of significant coronary lesions with ≥ 70% diameter stenosis. Specifically, impairment of ≥ 3 of 7 in the LAD predicted significant proximal or mid lesions, whereas impairment of ≥ 3 of 5 segments in either the LCx or RCA predicted significant proximal lesions. TLS has not been extensively studied in stable CAD. Eek et al. found that at a cutoff of ≥ -14%, impaired blood supply in ≥ 4 segments predicted acute coronary occlusion with improved sensitivity (85%) and specificity (70%) vs the left ventricular ejection fraction.12 Sarvari et al. noted that although TLS, GLS, and GCS were affected in patients with non-ST-segment elevation myocardial infarction, the differences between GLS and TLS were not statistically significant.24 Caspar et al. demonstrated that TLS has high predictive value for significant lesions with ≥ 50% diameter stenosis across the 3 major coronary territories.25

The takeaway from our study is that TLS enhances the diagnostic capacity of RLS, accurately predicting both the location and severity of significant coronary lesions with ≥ 70% diameter stenosis. While several non-invasive methods show acceptable sensitivity and specificity,27 they usually face limitations regarding availability and cost. Echocardiography is widely accessible, and strain analysis can be performed offline, making it beneficial for patients with chest pain, allowing for assessment prior to invasive procedures or costly imaging modalities. Further studies are needed to clarify the diagnostic and prognostic significance of TLS in patients with chest pain.

Strengths and limitations

Our study was conducted on a well-balanced cohort with regards to the risk factors and baseline characteristics and did not have missing data allowing robust per protocol analysis, the interventional cardiologists who analyzed the CAGs were blinded to the results of the echocardiographic evaluation, whereas the investigators who performed the 2D echocardiography and the 2D STE were blinded to the coronary angiographic data, hence observer bias was minimized. Despite its strengths, the limitations of the study require consideration. It was a single centre cross-sectional study which didn’t allow us to investigate the chronological relationship between the echocardiographic and the coronary angiographic data in stable patients with CAD. There was no invasive functional assessment of the coronary blood flow with fractional flow reserve, RRS was assessed manually, and 36 study participants (18%) with impaired myocardial function (left ventricular ejection fraction ≤ 50%) were selected for the study. Patients with stable CAD patients and coronary microvascular disease (microvascular angina) and normal CAG and patients with stable CAD and abnormal CAG with coronary lesions with < 70% diameter stenosis were excluded from the study cohort overestimating the RLS of the study cohort. Inclusion of patints with stable CAD and abnormal CAG with coronary lesions with ≥ 70% diameter stenosis could only limit the generalizability of the study results to the population with stable CAD. Ultimately, ROC curve analysis of RLS in stable CAD, used to explore the role of TLS in predicting the location and severity of significant ≥ 70% diameter stenosis relied on clinically limited metrics, namely sensitivity and specificity. As a result, the high RLS performance estimate (0.947) may be biased, and the cutoff of ≥ -16% potentially misleading. Consequently, WMSI was not included in the analyss, and no incremental diagnostic value for RLS over WMSI could be established.

CONCLUSIONS

RLS indicated potential clinical relevance in the diagnosis of stable CAD and TLS demonstrated a significant ability to predict the site and level of significant coronary lesion with ≥ 70% diameter stenosis in patients with stable CAD.

DATA AVAILABILITY

Data are available from the corresponding author upon request.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

The study design and protocol were approved by the human ethics committee of the Ain Shams University Hospital before study initiation on 1 July, 2021. The study was registered and assigned trial registration No. Md 110 / 2021. Written informed consent was obtained from all human research subjects and study participants, including consent for publication. Participant privacy was strictly protected, and all data were anonymized, informed consents were signed by study participants for publication, and the study procedures were conducted in full compliance with the Egyptian National Commission for Bioethics statement on ethical conduct in human research, and SAGER guidelines have been followed with respect to possible sex/gender bias.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

The authors declare that they have not used any type of generative artificial intelligence for the drafting of this manuscript, nor for the creation of images, graphics, tables, or their corresponding captions.

AUTHORS’ CONTRIBUTIONS

The study was designed by A. Rezq and H. Shaalan, the data was collected, analyzed, and interpreted by M.A. Hashem and A.E. Nayel, the manuscript was drafted by M.A. Hashem and critically reviewed by A. Rezq, A.K. Araquib, A.E. Nayel, and H. Shaalan, and A. Rezq, A.E. Nayel, A.K. Araquib, and H. Shaalan approved the final manuscript. The authors take full responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

CONFLICTS OF INTEREST

None declared.

REFERENCES

INTRODUCTION

Transcatheter aortic valve implantation (TAVI) is one of the treatments that has been shown to improve prognosis and reduce mortality in patients with symptomatic severe aortic stenosis.1 Currently, according to the clinical practice guidelines outlined by the European Society of Cardiology (ESC),2 TAVI is the treatment of choice in patients aged ≥ 70 years, while the American Heart Association and the American College of Cardiology (AHA/ACC) clinical practice guidelines indicate that it may be considered from the age of 65 years.3,4.

Although TAVI is considered a safe procedure, complications may occur;5 however, their incidence has declined over the years owing, among other factors, to advances in preoperative cardiac imaging, the development of improved models of transcatheter heart valves and delivery sheaths, and the increasing experience of the teams performing the procedure.6 However, not all complications are directly associated with valve implantation, and some are due to auxiliary devices used perioperatively. One example is the temporary transvenous pacemaker traditionally used for rapid right ventricular (RV) pacing, which requires an additional puncture (generally in the femoral, jugular, subclavian, or brachial vein) and the insertion of a catheter into the RV.

A meta-analysis published in 2019 reported that, even today, despite the availability of imaging modalities that facilitate implantation, transvenous temporary pacing remains associated with complications in 22.9% of patients.7 Many of these complications could be avoided by performing left ventricular (LV) pacing using the pre-shaped guidewire during TAVI, which eliminates the need for any additional vascular accesses or specific devices.8 In 2019, the randomized clinical trial EASY TAVI compared both techniques showing a similar safety and efficacy profile, resulting in lower costs and shorter procedural and fluoroscopy times with LV pacing.9 Although the utility of the SAFARI 2 (Boston Scientific, United States), Confida (Medtronic, United States), Lunderquist (Cook Medical Inc., United States), Amplatz Extra-Stiff (Cook Medical Inc.), Amplatz Super Stiff (Boston Scientific), and SavvyWire (OpSens Inc., Canada) guidewires has already been demonstrated10,11, there are no studies on the Circulo guidewire (Abbott, United States).12

The aim of this study was to evaluate the performance of the pre-shaped Circulo guidewire for LV pacing during TAVI (figure 1A).

Figure 1. A: pre-shaped Circulo guidewire. B: grounding for left ventricular pacing through the skin. C: grounding for left ventricular pacing through a guidewire.

METHODS

We conducted an observational, prospective, multicenter study. The primary endpoint was to demonstrate the efficacy of rapid LV pacing, defined as a decrease in systemic systolic pressure < 60 mmHg. Secondary endpoints included pacing threshold, the need for conversion to RV pacing, and safety.

The Circulo guidewire

Circulo is a 275-cm–long polytetrafluoroethylene–coated guidewire. It features a double curve at its distal end, with a circular configuration slightly different from that of other guidewires, which reduces ventricular compression. This characteristic is particularly notable in the smaller curve.

Study population

The study protocol was approved by Hospital Clínic de Barcelona Ethics Committee (Barcelona, Spain) in full compliance with the ethical principles outlined in the Declaration of Helsinki. A total of 50 consecutive patients with severe aortic stenosis or regurgitation undergoing TAVI in 8 Spanish centers with the pre-shaped Circulo guidewire for LV pacing were prospectively included. Patients were excluded if, in the investigators’ judgment, they required RV pacing, lacked femoral access, or underwent TAVI without the need for rapid pacing.

Baseline characteristics were collected, including sex, age, weight, height, surgical risk, history of pacemaker implantation, atrial fibrillation, ischemic heart disease, or bundle branch block. Echocardiographic characteristics included LV size, LV ejection fraction, and the presence of severe valvular heart disease.

TAVI with left ventricular pacing

TAVI was performed according to the clinical practice of each center. The grounding configuration for LV pacing and the type of TAVI were decided by each center based on patient characteristics (figure 1B-C). During LV pacing, systemic blood pressure and pacing threshold were measured. To determine the LV pacing threshold, pacemaker output was initially increased to the maximum and then gradually reduced until loss of capture was observed. The lowest voltage capable of capturing the ventricle on all beats was selected. Systemic blood pressure was measured using an arterial catheter.

Procedural characteristics were recorded, including venous access, grounding configuration for LV pacing, LV pacing threshold, systemic blood pressure during rapid LV pacing, conversion to pacing using a different LV guidewire or RV pacing, type and size of the transcatheter heart valve, need for balloon pre- or postdilatation, and complications according to the Valve Academic Research Consortium-3 (VARC-3) criteria, including vascular and access-related complications, hemorrhages, neurological events, new conduction disturbances and arrhythmias, acute kidney injury, structural heart complications, length of stay, and mortality.5

Follow-up

Follow-up was conducted 30 days after TAVI, either by telephone or in person. Complications were adjudicated according to VARC-3 criteria.5

Statistical analysis

Quantitative variables are expressed as mean and standard deviation or median and interquartile range (IQR), depending on whether distribution was normal, as previously assessed using the Kolmogorov–Smirnov test. The qualitative ones are expressed as total number and percentage. Statistical analyses were performed using IBM SPSS Statistics (version 27) and RStudio (version 4.5.1). Depending on the variable, Fisher’s exact test, the Kruskal–Wallis test, or ANOVA was applied.

RESULTS

Baseline characteristics

Baseline characteristics are shown in table 1. A total of 50 patients were included in the study, 31 (62%) women and 19 (38%) men. The mean age of the cohort was 80.56 ± 6.26 years. In terms of past medical history, the mean body mass index was 27.38 ± 4.6 kg/m²; 17 patients (34%) had ischemic heart disease; 12 (24%), atrial fibrillation; 3 (6%), a previously implanted pacemaker; 4 (11.8%), first-degree atrioventricular block (AVB); and 6 (12%), bundle branch block (4 patients had left bundle branch block and 2, right bundle branch block). The PR interval ranged from 140 ms to 240 ms, with a median of 170 ms (IQR, 158-190), and QRS duration ranged from 72 ms to 170 ms, with a median of 90 ms (IQR, 80-110). Median surgical risk, assessed using the EuroSCORE II, was 2.06% (IQR, 1.62-3.36).

Table 1. Baseline characteristics of the patients

Baseline echocardiographic evaluation demonstrated a mean LV end-diastolic diameter of 45.28 ± 7.83 mm, a mean LV ejection fraction of 58.48 ± 8.63%, and a mean transaortic gradient of 47.24 ± 19.25 mmHg. Severe aortic regurgitation was present in 6 patients (12%) and was the primary valvular heart disease in 2 cases (4%). There were no patients with severe tricuspid regurgitation.

Procedural characteristics and performance of the pre-shaped guidewire

LV pacing avoided venous access in nearly half of the patients (n = 24; 48%). Among those requiring venous access, the femoral vein was the most widely used site (n = 20; 77%), followed by the brachial (n = 4; 15%) and jugular veins (n = 2; 8%). Grounding methods for LV pacing varied, with skin grounding being the one most frequently used (n = 22; 44%), followed by grounding to a guidewire via venous access (n = 19; 38%), and needle-based grounding methods (n = 9; 18%) (table 2).

Table 2. Procedural characteristics and perioperative complications and 30-day follow-up

The Navitor valve (Abbott, United States) was the most frequently used transcatheter heart valve (n = 28; 56%), followed by the SAPIEN (Edwards Lifesciences, United States) and the Myval (Meril Life Sciences, India) valves (n = 6; 12%). The least frequently used ones were the Evolut (Medtronic, United States) and the ACURATE (Boston Scientific, United States) (n = 5; 10%). Self-expanding valves accounted for 76% of all implanted transcatheter heart valves. Valve sizes ranged from 23 mm to 34 mm, with a median of 25 mm (IQR, 23-27). Predilatation was performed in most patients (n = 41; 82%), whereas postdilatation was required in only 20% (n = 10) (table 2). The mean LV pacing threshold was 7 ± 3.48 mV, and in 100% of patients (n = 50), a decrease in systolic blood pressure < 60 mmHg was achieved without loss of capture during rapid LV pacing. Comparative data across the different guidewires are presented in table 3. No patient required conversion to an alternative LV pacing guidewire, and only 3 (6%) required RV pacing, all due to AVB following balloon predilatation or during advancement of the valve into the LV. No guidewire exchange was required to advance the TAVI delivery system (table 2).

Table 3. Performance of the preformed left ventricular pacing guidewire

Complications

The overall rate of complications was 14% (n = 7), with conduction disturbances being the most frequent. Perioperative AVB requiring temporary pacemaker implantation occurred in 6 patients (12%), 4 of whom (8%) exhibited postoperative persistent complete AVB and eventually required permanent pacemaker implantation. One patient experienced a minor vascular complication in the form of vascular occlusion, which was successfully treated by transcatheter procedure and resolved without sequelae. There were no strokes or other major adverse events. The median length of stay from TAVI to discharge was 3 days (IQR, 2-5). The in-hospital survival rate was 100%, and no readmissions or deaths were recorded at the 1-month follow-up. Perioperative complications and those occurring within 1 month after the procedure are shown in table 2.

DISCUSSION

The main findings of the study were these: a) LV pacing using the pre-shaped Circulo guidewire was effective, achieving a reduction in systolic blood pressure < 60 mmHg in 100% of patients; b) no patient required switching to an alternative LV pacing guidewire; c) only 3 patients required conversion to RV pacing, all due to AVB following predilatation; d) the procedural success rate of TAVI was 100%; and e) there were no complications related to the Circulo guidewire. These results demonstrate the safety and efficacy profile of LV pacing using the Circulo guidewire and support its usefulness during transfemoral TAVI.

In this study, the success rate of LV pacing with the Circulo guidewire was comparable to that reported in former studies using other guidewires.8-11,13,14 Only 4% of patients presented right bundle branch block on baseline electrocardiography, indicating a cohort with a low risk of developing conduction disturbances. No patient required switching to an alternative LV pacing guidewire, and only 3 (6%) required conversion to RV pacing due to the onset of AVB after balloon predilatation or during valve advancement into the LV. In 2 of these 3 cases, LV pacing had been effective, with adequate pacing thresholds of 2.5 mV and 3.0 mV; however, although the procedure could have been continued using LV pacing, the operators decided to implant a transvenous temporary pacemaker before valve implantation, anticipating the need for pacing support after the procedure. In the third case, LV pacing was attempted, but due to the absence of adequate capture, conversion to RV pacing with implantation of a transvenous temporary pacemaker was performed. These patients did not present notable clinical differences, and aside from predilatation, no additional predictive factors were identified. The pacing thresholds recorded were slightly higher than those observed in former studies (7 mV vs 3.36 mV-7.5 mV);10 however, these discrepancies were not clinically relevant and are plausibly explained by inter-operator variability inherent to the technique.

Because transvenous temporary pacemaker implantation was only required in patients who developed AVB during or after the procedure, LV pacing with the Circulo guidewire avoided the implantation of 44 temporary pacemakers among 50 cases (88%). In former studies, this approach has been shown to reduce both procedural and fluoroscopy times.9,15,16 Therefore, although LV pacing can be performed in all patients, it is most beneficial in those at low risk of AVB and subsequent pacing requirements. In such cases, transvenous temporary pacemaker implantation can be avoided, a procedure associated with potential complications, such as inadvertent arterial puncture (0.3%), major hemorrhage (2.7%), deep vein thrombosis (0.3%), pulmonary thromboembolism (0.1%), pneumothorax (0.1%), cardiac perforation (0.7%), lead dislodgement (3.4%), pacing failure (7.7%), and the need for multiple placement attempts (0.9%).7

Although it is evident that LV pacing reduces most complications associated with transvenous RV temporary pacemaker implantation, the main concerns regarding LV pacing have focused on the risk of aortic bioprosthesis embolization due to loss of capture and the risk of perforation related to advancing the guidewire inside the LV during pacing. However, multiple studies have shown no significant differences in valve embolization rates between the 2 techniques, with some reporting a trend toward a lower risk of cardiac tamponade with LV pacing, likely attributable to the greater myocardial thickness of the LV vs the RV.9,14,15 In our study, there were no cases of device embolization or cardiac tamponade or LV pacing-related complications.

Study limitations

One limitation of the present study is that guidewire selection was left to the operator’s discretion, which may have introduced selection bias. In the cohort presented, only 4% of patients exhibited right bundle branch block on baseline electrocardiography, which is representative of a population at a low risk of developing arrhythmic complications. However, the operator-dependent choice of guidewire enhances the external validity of the results, as it more accurately reflects real-world clinical decision-making. Another limitation is the absence of a comparison group undergoing RV or LV pacing with other guidewires, which limits the ability to directly compare outcomes between techniques. Instead, results were compared with those of previously published studies.

CONCLUSIONS

The use of the Circulo guidewire for LV pacing during TAVI proved to be safe and effective, with a low overall rate of TAVI-related complications and no guidewire-related complications. This approach avoids the need for transvenous temporary pacemaker implantation in most patients at low risk of arrhythmic complications, thus potentially reducing procedural risks and simplifying perioperative management.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

The study protocol was approved by Hospital Clínic de Barcelona Clinical Research Ethics Committee in full compliance with the ethical principles outlined in the Declaration of Helsinki. All participants signed informed consent prior to inclusion in the study. No sex-based subgroup analysis was performed, as this could compromise the statistical power of the study and both sexes were adequately represented in the cohort; furthermore, there is no prior evidence suggesting sex-related differences in response to LV pacing using a pre-shaped guidewire.

DECLARATION ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence was used in the development of this article.

AUTHORS’ CONTRIBUTIONS

A. Regueiro designed the protocol, database, and study framework, and coordinated statistical analysis, data interpretation, and manuscript drafting. I. Anduaga contributed to protocol design, database development, and study framework, performed statistical analysis and data interpretation, and drafted the manuscript. A. Ruberti, V. Vilalta, I.J. Amat-Santos, F. Díez-Delhoyo, L.L. Gheorghe, J.A. Baz, J.F. Díaz Fernández, L. Gutiérrez-Alonso, and X. Carrillo participated in data collection and critically reviewed the manuscript. All authors approved the final published version.

CONFLICTS OF INTEREST

A. Regueiro is a consultant for Abbott, Edwards, Haemonetics, Medtronic, and Meril. J.F. Díaz Fernández is a consultant for Abbott, Boston Scientific, and Medtronic. I.J. Amat-Santos is a proctor for Boston Scientific, Medtronic, Meril, and MicroPort. The remaining authors declared no conflicts of interest whatsoever.

REFERENCES

INTRODUCTION

Multivessel coronary artery disease is defined as the presence of ≥ 70% luminal stenosis in at least 2 major epicardial coronary arteries due to atherosclerotic plaque. Approximately 40% of patients with ST-segment elevation myocardial infarction (STEMI) exhibit multivessel coronary disease, which is associated with an increased risk of recurrent myocardial infarction and mortality.1-3 Evidence from randomized controlled trials has underscored the advantages of comprehensive revascularization with multivessel percutaneous coronary intervention (PCI) over culprit-lesion-only PCI, notably reducing the risks of cardiac death, myocardial infarction, and ischemia-driven revascularization at 1 year.4-6 There are 2 strategies to approach non-culprit lesions: immediate PCI which involves the revascularization of both culprit and non-culprit lesions during the index procedure, and staged PCI, where the treatment of non-culprit lesions is deferred to a later stage.

The 2021 clinical practice guidelines outlined by the American College of Cardiology/American Heart Association (ACC/AHA) acknowledge non-culprit vessel revascularization as a class IIb recommendation for patients with STEMI.7 However, determining the optimal timing for revascularization of non-culprit lesions remains a clinical challenge7,8 While PCI for non-culprit lesions has demonstrated superiority over a strategy of treating the culprit lesion alone,4-6 the timing of intervention, whether immediate or staged, lacks conclusive evidence.8,9

The objective of this meta-analysis was to compare staged vs immediate PCI for non-culprit lesions in hemodynamically stable patients with STEMI and multivessel disease. We hypothesize that both the staged and immediate PCI targeting non-culprit vessels will demonstrate comparable levels of safety, efficacy, and rate of complications.

METHODS

We conducted the present study following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.10 All steps were conducted in full compliance with the Cochrane Handbook of Systematic Reviews and Meta-analysis of Interventions (version 6.3).11 This meta-analysis protocol was registered on PROSPERO on 4 December, 2023, under protocol ID: CRD42023485163.l. During the peer-review process, the literature search was updated using the same search strategy, databases, and eligibility criteria described in supplementary data S1 to identify newly published randomized evidence.

Criteria of the included studies

We evaluated randomized controlled trials comparing immediate vs staged PCI for non-culprit lesions in adults with STEMI and multivessel coronary artery disease. Eligible studies were required to report extractable numerical data for at least 1 prespecified outcome of interest, as defined below. Trials reporting outcomes exclusively as Kaplan-Meier curves without corresponding event counts or effect estimates or reporting outcomes only as composite endpoints without separate data, were excluded from quantitative synthesis. No publication time limit was applied; however, the search was restricted to studies published in Spanish, English, or German. Case-control and cross-sectional studies, systematic reviews, meta-analyses, case reports, basic science research, conference abstracts, and letters to the editor were excluded.

Literature search strategy

We conducted a comprehensive and systematic search across 3 databases (PubMed, EMBASE, and COCHRANE) from their inception until 28 September, 2025. Keywords used for the search included “coronary artery disease”, “immediate multivessel percutaneous coronary intervention”, “staged multivessel percutaneous coronary intervention”, “acute coronary syndrome”, “multivessel disease”, “myocardial infarction”, “major adverse cardiovascular events”, “ST-segment elevation myocardial infarction”. These keywords were combined using Boolean operators AND and OR. The search details for each database are available in the supplementary data S1.

Screening of literature search results

All duplicates were removed using Zotero reference manager software. Records were initially screened by title and abstract by one author (E. Andrade-Arbaiza), followed by full-text assessment when potentially eligible. Two independent authors (D. Paulino-González, and L.H. García-Mena) reviewed full-text articles for inclusion and methodological quality, with disagreements being resolved by consensus or third-party adjudication (D. A. Navarro-Martínez). Studies were excluded at the full-text stage if they lacked extractable numerical data for prespecified outcomes or did not report outcomes separately, precluding quantitative synthesis. A detailed list of excluded studies with reasons for exclusion is provided in table S1. References cited in included studies were also manually screened for eligibility.

Data extraction

Data extraction was performed using standardized Excel spreadsheets to collect baseline population characteristics, key study features, outcome measures expressed as risk ratios, and domains for quality assessment. Outcome data were included only when numerical information was directly available or could be reliably derived without reconstruction from survival curves.

Assessing the risk of bias

The risk of bias of included randomized controlled trials was assessed usingvVersion 2 of the Cochrane risk-of-bias tool for randomized trials (ROB 2), in accordance with the Cochrane Handbook of Systematic Reviews of Interventions.11

Endpoints

The prespecified endpoints of this meta-analysis were cardiac death, all-cause mortality, stroke, reinfarction, and acute kidney injury (AKI). Given minor variations in endpoint definitions across trials, detailed outcome definitions as reported by each study are summarized in table S2. Outcomes were analyzed as dichotomous variables using event counts and percentages, and risk ratios with 95% confidence intervals (95%CI) were calculated.

Data analysis

Dichotomous outcomes were analyzed using pooled event data from the included studies and are reported as risk ratios with 95%CI. P values < .05 were considered statistically significant. Associations between outcomes and immediate vs staged PCI were evaluated using a random-effects model (DerSimonian–Laird method) to account for between-study heterogeneity.12 Statistical analyses and forest plots were generated using RevMan version 5.4.1 (Cochrane Collaboration) for MacOs.

Statistical analysis

Pooled risk ratios (RR) and incidence rate ratios (IRR) were estimated using random-effects models with appropriate adjustments, and heterogeneity was assessed using the I² statistic. Sensitivity analyses, trial sequential analysis, and meta-regression were performed to evaluate the robustness of findings and explore potential effect modifiers. Detailed methodological procedures are shown in the supplementary data S2.

Assessment of heterogeneity

Heterogeneity was assessed using Cochran’s Q test (P < .10) and quantified with the I² statistic, with values > 50% indicating substantial heterogeneity.

RESULTS

A total of 6 studies13-18 met the predefined inclusion criteria and were included in the analysis. The study selection process is summarized in the PRISMA flow diagram shown in figure 1. All included studies evaluated staged or immediate PCI in non-culprit arteries of patients with STEMI and multivessel disease.

Figure 1. PRISMA flow diagram. The diagram reflects the initial search and the updated search performed during peer review using the same strategy and eligibility criteria (supplementary data S1). NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction.

In the staged strategy, PCI of nonculprit lesions was performed a mean of 18.6 days (IQR, 7-34) after the index procedure. The total patient population included in our meta-analysis was 4267 patients, of whom 2479 underwent immediate PCI and 1788, staged PCI. Summary and baseline characteristics are shown in table 1. The characteristics of the included studies are summarized in table 2.

Table 1. Baseline characteristics and treatment of the included studies’ populations

Table 2. Summary of included studies.

Cardiac death

There were no significant difference between staged and immediate PCI regarding the risk of cardiac death (RR, 1.26; 95%CI, 0.89-1.79; P = .19). No heterogeneity was observed among the included studies (I² = 0%). These findings are shown in figure 2A.

Figure 2. Risk Ratios of cardiac death and all-cause mortality. A: cardiac death: risk ratio (RR) across the included trials are represented by solid squares, with horizontal lines indicating 95% confidence intervals (95%CI). B: all-cause mortality: RR across trials are shown by solid squares, with 95%CI indicated by horizontal lines. The bibliographical references cited in this figure correspond to the following studies: Politi et al.14 (2010), Maamoun et al.16 (2011), Wood et al.17 (2019), Park et al.15 (2023), Stähli et al.13 (2023), and Kim et al.18 (2025).

All-cause mortality

There were no significant differences in the risk of all-cause mortality between patients undergoing staged PCI and those treated with immediate PCI (RR, 1.18; 95%CI, 0.93-1.50; P = .17), with no heterogeneity detected among studies (I² = 0%) (figure 2B).

Reinfarction

The analysis demonstrated a statistically significant lower risk of reinfarction with immediate vs staged PCI (RR, 0.63; 95%CI, 0.40-0.98; P = .04), which amounts to an approximately 37% relative risk reduction with the former. There was no heterogeneity across trials (I² = 0%). These findings are shown in figure 3A.

Figure 3. Risk ratios for reinfarction and acute kidney injury. A: reinfarction: risk ratio (RR) across the included trials are represented by solid squares, with horizontal lines indicating 95% confidence intervals (95%CI). B: acute kidney injury: RR across trials are shown by solid squares, with 95%CI indicated by horizontal lines. The bibliographical references cited in this figure correspond to the following studies: Politi et al.14 (2010), Maamoun et al.16 (2011), Wood et al.17 (2019), Park et al.15 (2023), Stähli et al.13 (2023), and Kim et al.18 (2025).

Acute kidney injury

There were no significant differences between the 2 strategies (RR, 0.91; 95%CI, 0.64-1.31; P = .62), indicating no clear association between the revascularization strategy and the risk of AKI. There was no heterogeneity among the included studies (I² = 0%). These results are shown in figure 3B.

Stroke

Stroke was reported in only 3 of the studies included, and our analysis showed no significant differences between staged and immediate PCI for this outcome (RR, 1.17; 95%CI, 0.66-2.05; P = .59). There was no heterogeneity among the included studies (I² = 0%). These results are shown in figure S1.

Publication bias was assessed using funnel plots, Egger’s regression, and trim-and-fill analyses for reinfarction, cardiac death, and all-cause mortality. There was no visual evidence of funnel-plot asymmetry (figure S2). For reinfarction, trim-and-fill imputed 1 potentially missing study, with the pooled effect remained statistically significant (IRR, 0.59; 95%CI, 0.38-0.90). For cardiac death and all-cause mortality, 2 studies were imputed in each analysis; however, pooled effects remained non-significant, with no heterogeneity detected (I² = 0%). Overall, these results suggest no substantial publication bias, although the limited number of included trials reduces the power of formal tests for funnel plot asymmetry.

Sensitivity analyses

Leave-one-out sensitivity analyses confirmed the robustness of the pooled estimates across all primary endpoints (figure S3). For all-cause mortality and cardiac death, exclusion of individual studies did not materially alter the results, with pooled RRs remaining within the confidence intervals of the main models and I² = 0% in all scenarios. For reinfarction, estimates consistently favored immediate PCI (RR range, 0.46-0.75), with I² = 0% supporting the internal consistency of the findings.

Incidence rate ratios

At the 1-year follow-up, IRR analysis showed that immediate PCI was associated with a lower rate of reinfarction vs staged PCI. Under the random-effects model, the pooled IRR was 0.60 (95%CI, 0.39-0.94; I² = 0%), which is consistent with the common-effect model (IRR, 0.59; 95%CI, 0.38-0.92), supporting the robustness of this finding (figure S4). In contrast, there were no significant differences between the strategies regarding cardiac death (IRR, 1.26; 95%CI, 0.90-1.77; I² = 0%) or all-cause mortality (IRR, 1.17; 95%CI, 0.84-1.64; I² = 0%), indicating stable estimates with negligible heterogeneity across studies (figures S5, S6).

Trial sequential analyses

Trial sequential analysis were conducted for cardiac death, all-cause mortality, and reinfarction (figure 4A-C). For cardiac death and all-cause mortality, the accrued sample represented 33% and 58% of the required information size, respectively; in both analysis, the cumulative Z-curves remained within nonsignificant boundaries, indicating insufficient evidence to confirm or exclude a 30% relative risk reduction. For reinfarction, only 3.4% of the required information size was reached, and the Z-curve remained well within the futility zone, showing a non-significant trend favoring immediate PCI. Collectively, these results demonstrate that current data remain underpowered to establish definitive conclusions across outcomes, despite a consistent numerical pattern supporting immediate revascularization.

Figure 4. Trial sequential analysis. Trial sequential analysis for (A) cardiac death, (B) all-cause mortality, and (C) reinfarction. In all panels, the cumulative Z-curve is shown in blue, trial sequential monitoring boundaries in red, and conventional significance thresholds as horizontal magenta lines. PCI, percutaneous coronary intervention. The bibliographical references cited in this figure correspond to the following studies: Politi et al.14 (2010), Maamoun et al.16 (2011), Wood et al.17 (2019), Park et al.15 (2023), Stähli et al.13 (2023), and Kim et al.18 (2025).

Meta-regression

Exploratory meta-regression analyses were conducted to assess whether procedural timing or baseline comorbidities influenced reinfarction outcomes. The association between time to staged PCI and reinfarction risk showed a negative but non-significant slope (β = –0.016 per day; 95%CI, –0.042-0.010; P = .22), with no residual heterogeneity (I² = 0%), indicating consistent effects across studies (figure S7). Similarly, diabetes prevalence (β = 0.021 per 1% increase; 95%CI, –0.017 to 0.058; P = .22) and hypertension prevalence (β = –0.064 per 1% increase; 95%CI, –0.214 to 0.085; P = .40) were not significantly associated with reinfarction risk, with no evidence of residual heterogeneity (I² = 0% for both) (figures S8-S9). Collectively, these findings suggest that neither procedural timing nor comorbidity burden materially modified the comparative risk of reinfarction between immediate and staged PCI; however, given the study-level and exploratory design of these analyses, results should be interpreted with caution.

Risk of bias assessment

Risk of bias assessment was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials (ROB 2), as outlined in the Cochrane Handbook of Systematic Reviews of Interventions.11 Four clinical trials were judged to have a low overall risk of bias, whereas the study by Maamoun et al.16 was rated as the only clinical trial having some concerns (table 3).

Table 3. Risk of bias summary for randomized studies (RoB 2)

DISCUSSION

The present meta-analysis provides a focused comparison of immediate vs staged PCI in patients with STEMI and multivessel disease. By integrating randomized evidence using complementary analytical approaches, our findings offer an updated and clinically relevant synthesis of the safety and efficacy profile of these 2 revascularization strategies in a well-defined population.

Although cardiac death and all-cause mortality are clinically relevant, they are relatively rare outcomes in contemporary STEMI populations undergoing multivessel revascularization. In the present analysis, there were no statistically significant differences between immediate and staged PCI for either endpoint. These neutral findings should be interpreted in the context of limited statistical power, as reflected by the low cumulative incidence of events and trial sequential analysis indicating that the required information size has not yet been reached.19,20 Additional IRR analyses yielded consistent results, further supporting the absence of a clinically meaningful survival difference between strategies. Accordingly, mortality outcomes do not appear to discriminate between immediate and staged PCI, and treatment selection should instead be guided by patient-specific clinical stability and procedural considerations rather than isolated mortality endpoints alone.

Regarding reinfarction risk, immediate PCI was consistently associated with a significantly lower rate of reinfarction vs staged PCI. Exploratory meta-regression analyses did not identify procedural timing, diabetes, or hypertension prevalence as significant modifiers of this association. Trial sequential and sensitivity analyses showed consistent results across the models, with no evidence of heterogeneity. Although the required information size was not fully reached, the consistency of findings across multiple analytical approaches supports a robust association between immediate PCI and reduced recurrent ischemic events.

Regarding AKI, there were no significant differences between immediate and staged PCI, with low event rates and no heterogeneity across trials. The limited number of events precluded meaningful trial sequential analysis, highlighting insufficient power to detect small differences. Although post-PCI AKI is influenced by multiple factors, including contrast exposure and procedural complexity,21 current evidence does not support the assumption that staged PCI reduces renal risk by distributing contrast load.22 None of the included trials were specifically powered for renal outcomes, and AKI definitions varied across studies. Therefore, until adequately powered trials with standardized definitions become available, PCI timing decisions should remain individualized, taking into account baseline renal function and overall procedural risk.23

There were no significant differences in the rates of stroke between staged and immediate PCI, with few events being reported across trials, limiting statistical power. Available evidence suggests that stroke risk after PCI in STEMI is more closely related to procedural factors than to the timing of non-culprit revascularization.15 Accordingly, stroke does not appear to represent a clinically discriminative endpoint when comparing immediate and staged revascularization strategies in this population.

Historically, international clinical practice guidelines favored a staged approach to complete revascularization in STEMI with multivessel disease, largely due to concerns regarding procedural complexity, contrast exposure, and hemodynamic instability during the index intervention. However, cumulative randomized evidence has challenged this paradigm, showing that immediate complete PCI can be performed safely in hemodynamically stable patients, with outcomes comparable or superior to staged strategies.13,17,24,25 Notably, most prior trials primarily enrolled clinically stable patients following successful reperfusion, which may limit the generalizability of their findings to higher-risk STEMI populations. In this context, the OPTION-STEMI trial extends the available evidence by including patients with transient or mild hemodynamic instability, thereby providing contemporary data that better reflect real-world clinical complexity.18

Consistent with our primary findings, immediate and staged PCI did not differ in cardiac death or all-cause mortality at 1 year, while immediate PCI was associated with a lower risk of reinfarction. Beyond clinical outcomes, immediate complete revascularization may offer economic advantages by reducing the length of stay, avoiding repeat cardiac catheterizations, and optimizing resource utilization. In contrast, staged PCI often requires a second procedure and hospitalization, increasing cumulative costs by up to 50% in some analyses,26,27 and mirroring the additional expenses associated with unplanned readmissions for recurrent ischemia. In this context, a single-session revascularization strategy may provide both clinical and economic value, particularly in health care systems with constrained resources, where contemporary PCI costs remain substantial.28

From a safety and efficacy perspective, both staged and immediate PCI represent acceptable revascularization strategies in appropriately selected patients with STEMI and multivessel disease. In the present analysis, immediate PCI was primarily associated with a reduction in recurrent ischemic events, while major adverse cardiovascular events, including cardiac death and all-cause mortality did not differ significantly across strategies. Accordingly, the choice between immediate and staged PCI may increasingly be guided by patient-specific clinical characteristics and logistical considerations rather than concerns regarding procedural safety.

Although not directly assessed in this meta-analysis, emerging evidence suggests that systemic biological factors—such as inflammation, hypercoagulability, and sympathetic activation—may influence recurrent ischemic risk beyond angiographic severity alone.29,30 In addition, features of plaque vulnerability have been associated with future ischemic events in non-culprit lesions, even when angiographically mild.31 Integrating biological risk markers and clinical stability into revascularization decision-making, therefore, represents a relevant direction for future research aimed at refining individualized strategies in patients with STEMI and multivessel disease.

Limitations

Several limitations should be acknowledged. First, only 6 randomized controlled trials were included, resulting in limited statistical power, particularly for rare outcomes. Second, this analysis was restricted to patients with STEMI and multivessel disease; therefore, the findings should not be extrapolated to other acute coronary syndrome populations, and the limited number of trials reporting all prespecified outcomes may reduce the robustness of certain estimates. Third, the use of aggregate study-level data precluded adjustment for individual patient characteristics and limited the assessment of patient-level effect modification; accordingly, meta-regression analyses were exploratory and should be interpreted with caution given the small number of included studies and the potential for ecological bias. Finally, variability in the timing of staged PCI across trials may have introduced residual clinical heterogeneity, and formal assessments of publication bias were underpowered due to the limited number of studies.

CONCLUSIONS

This meta-analysis, integrating additional analytical approaches, provides a focused comparison of immediate vs staged PCI in patients with STEMI and multivessel disease. Immediate PCI was consistently associated with a lower risk of reinfarction, without significant differences being reported in cardiac death or all-cause mortality, stroke, or renal injury. Although the cumulative evidence remains below the required information size for certain hard endpoints, the consistency of findings across multiple analyses supports the robustness of the observed reduction in reinfarction events. From a clinical perspective, these results suggest that immediate complete revascularization can be performed safely in appropriately selected patients and may reduce the burden of reinfarction. Accordingly, the choice between immediate and staged strategies should increasingly be guided by patient-specific clinical stability and practical considerations rather than by concerns regarding procedural safety alone. Future research incorporating biological risk markers may further refine individualized revascularization strategies in this population.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

This meta-analysis was based exclusively on data from previously published studies and involved secondary analyses of publicly available information. Therefore, approval by an Ethics Committee or institutional review board was deemed unnecessary. As no individual patient data or case reports were included, informed consent was not applicable. All the studies included were conducted in full compliance with the ethical standards of the respective institutions at the time of their original publication.

In line with the SAGER guidelines, we assessed sex and gender reporting in the included randomized trials. While sex was generally reported at baseline, sex-disaggregated outcome data and gender-related variables were rarely available, precluding analyses by sex or gender. This limitation should be considered when interpreting the results.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

During the preparation of this work the authors used ChatGPT 5.2 to review the syntaxis and grammar of this document. After using this tool/service, the authors reviewed and edited the content as needed and took full responsibility for the content of the published article.

AUTHORS’ CONTRIBUTIONS

D. Paulino-González: conceptualization, formal analysis, drafting – review and editing. L.H. García-Mena: formal analysis, investigation, drafting – review and editing. E. Andrade-Arbaiza: methodology, investigation, drafting – review and editing. D.A. Navarro-Martínez: methodology, formal analysis; J.L. Maldonado-García: formal analysis, drafting – review and editing; S.A. Xiloj-López: investigation. C.J. Palomino-Ojeda: investigation, drafting – review and editing, R.M. Arellano-Sánchez: data curating, formal analysis. N.E. Antonio-Villa: data curating, formal analysis, drafting – review and editing. A. Ricalde-Alcocer: drafting – review and editing, supervision. D. Araiza-Garaygordobil: drafting – review and editing, supervision.

CONFLICTS OF INTEREST

None declared.

ACKNOWLEDGEMENTS

The authors respectfully honor, in memory, a beloved family member of one of the coauthors, and gratefully acknowledge the support of Dr. Pavel Pichardo-Rojas.

SUPPLEMENTARY DATA

REFERENCES

INTRODUCTION

Excimer laser coronary atherectomy (ELCA) has been applied since the 1980s in multiple anatomical and clinical settings, with several studies supporting its safety and efficacy profile.1,2 Common indications include in-stent restenoses, stent underexpansion, calcified coronary lesions, saphenous vein graft stenoses, thrombotic lesions, bifurcations, and chronic total coronary occlusions.3-14 In practice, however, ELCA is predominantly used in the setting of balloon failure–specifically uncrossable and undilatable coronary artery lesions. However, historical studies have typically applied a uniform definition of device success across both lesion types, potentially overlooking important nuances that could influence outcomes and therapeutic decision-making.

Furthermore, despite growing recognition of the value of intracoronary imaging in optimizing complex percutaneous coronary intervention (PCI),15 prior ELCA studies have largely underutilized this tool, limiting insight into the mechanisms of success or failure in balloon-resistant lesions.

The safety and efficacy profile of coronary laser in undilatable and uncrossable lesions (LUDICO) study is a real-world, observational study designed to evaluate the use of ELCA specifically in cases of balloon failure. The study has 2 primary objectives: a) to refine the definition of ELCA procedural success based on the type of balloon failure encountered—distinguishing between uncrossable and undilatable lesions—, and b) to emphasize the critical role of intracoronary imaging in guiding ELCA and interpreting procedural outcomes. By addressing these critical gaps, the study aims to provide a more precise and and clinically meaningful framework for the contemporary use of ELCA in complex coronary interventions.

METHODS

Study design and population

This is a prospective, multicentre, observational study including consecutive patients undergoing ELCA in undilatable (expansion < 80% of the distal vessel diameter after inflation of a 1:1 non-compliant balloon at 18 atm) and uncrossable coronary artery lesions (uncrossable after using a small-profile balloon with adequate support left to the operator’s discretion). At least 15 national centers will be contacted to participate in the study. Participant centers will be required to have experience with ELCA and complex PCI, with a minimum of > 5 prior ELCA cases performed. Inclusion and exclusion criteria are described in table 1. This study was conducted in full compliance with the STROBE guidelines for observational studies.16 The study protocol was registered in ClinicalTrials.gov (NCT07206082).

Table 1. Inclusion and exclusion criteria

Procedure

PCI will be performed in accordance with current clinical practice guidelines on coronary revascularization.15,17

In uncrossable lesions, following successful guidewire passage and failed balloon crossing, ELCA will be performed (as described in the following section). PCI will be completed with optional predilatation at the operator’s discretion, followed by stenting or drugcoated balloon implantation. Intravascular imaging [preferably with optical coherence tomography (OCT)] will be recommended after laser application to characterize the lesion substrate and evaluate the effect of the laser and at the end of the procedure.

In undilatable lesions, if balloon dilation is inadequate, an initial intracoronary imaging assessment will be conducted. Afterwards, laser atherectomy will be performed, followed by a second intracoronary imaging assessment to evaluate the effects of ELCA on the lesion. PCI will, then, be completed with balloon dilation and stenting or drug-coated balloon implantation, at the operator’s discretion. A third intracoronary imaging pullback will be performed to assess the final procedural outcome (figure 1).

Figure 1. Central illustration. LUDICO study flowchart. ELCA, excimer laser coronary atherectomy; NC, non-compliant; PCI, percutaneous coronary intervention.

Laser atherectomy technique

ELCA procedure will be performed using the Spectranetics CVX300 (Spectranetics, United States) and the latest generation Philips Laser System Excimer (Philips, United States) System, which is based on pulsed xenon‐chlorine laser catheters capable of delivering excimer energy (wavelength, 308 nm; pulse length, 185 ns) from 30 mJ/mm² to 80 mJ/mm² (fluencies) at pulse repetition rates of 25 Hz to 80 Hz.

The ELCA technique will be performed according to current recommendations.18 The choice of laser catheter size will be left to the operator’s discretion, selecting among the available rapid-exchange concentric probes (0.9 mm, 1.4 mm, 1.7 mm, or 2.0 mm). The selection of fluence, and repetition rate will be left to the operator’s discretion. A saline infusion technique will be recommended, although application of laser with blood or contrast will be recommended in resistant lesions. In the event of unsuccessful initial therapy, additional plaque modification techniques may be employed at the operator’s discretion and will be thoroughly recorded and described.

Clinical definitions and follow-up

Laser success will be defined differently for uncrossable and for undilatable lesions. For the former, laser success will be defined as the ability of the laser catheter to cross the lesion. Laser success will also be considered in cases where the laser catheter cannot cross the lesion but proximal laser application permits subsequent balloon crossing. For the latter, laser success will be defined as successful balloon dilation (sized 1:1 to the vessel diameter), with adequate expansion (> 80% in 2 orthogonal projections) following laser therapy without the need for other plaque modification technique.

Angiographic success will be defined as Thrombolysis in Myocardial Infarction (TIMI) grade-3 final flow and a percent diameter stenosis < 20%. Procedural success will be defined as angiographic success without severe procedural complications (death, coronary perforation, abrupt vessel closure, flow-limiting dissection). Intracoronary imaging-based success will be defined as a stent expansion ≥ 80% (OCT or intravascular ultrasound [IVUS]) or a minimal stent area (MSA) ≥ 4.5 mm² in OCT or ≥ 5.5 mm² in IVUS.

Intracoronary imaging

Intracoronary imaging will aim to describe the lesion characteristics and identify potential predictors of adequate stent expansion and procedural result. Therefore, intracoronary imaging will be highly recommended and the advised imaging modality will be OCT as its better spatial resolution vs IVUS allows better tissue characterization, plaque modification assessment and visualization of stent failure etiologies.19 A baseline intracoronary imaging evaluation is recommended, when possible, to describe the lesion characteristics and identify potential predictors of ELCA success or failure. Additionally, a second intracoronary imaging run is strongly advised immediately after laser therapy. This second run aims to describe the effect of ELCA in the coronary plaque. Evaluating and characterizing changes in the coronary plaque might help guide the optimal ELCA result and allow appropriate adjustment of therapy settings (fluence, repetition rate and infusion characteristics). Finally, a postoperative intravascular imaging run is strongly recommended once the final angiographic result is achieved. All intracoronary imaging data will be analyzed by a core laboratory. In the baseline intracoronary imaging run, lesion characteristics will be described as follows: minimum lumen area (MLA), minimum and maximum lumen diameter, lesion length, calcification angle, calcification thickness. In the post-ELCA imaging run the following parameters will be evaluated: MLA, number of calcium fractures and characteristics, presence of dissection, including its angle and length. In the final imaging run, MSA, stent apposition and dissections will be described. In both OCT and IVUS assessments, a dual-reference approach will be used: the proximal and distal reference lumen diameters will be identified, and MSA will be divided by each of these diameters separately. The final stent expansion index will be calculated as the mean of the 2 resulting values. Second, the tapered mode is only available in OCT: reference lumen profile is estimated based on the distal and proximal reference frame mean diameter and side branch mean diameter in between. With stent lengths > 50 mm, the dual method is preferred. With stent lengths < 50 mm the tapered method is often used. If the dual method is used, the stent expansion percentage of both segments will be recorded with the lower value of the two measurements used for analysis. The main variables to be evaluated by intravascular imaging are summarized and graphically shown in figure 2.

Figure 2. Example of the advised intracoronary imaging assessment in LUDICO study. A: baseline optical coherence tomography (OCT) image of a severely calcified lesion. The asterisk points to a calcium arc of 360° with a maximum thickness of 0.9 mm. B: OCT image after ELCA with contrast media. White arrow points to a dissection. The white arrowhead points to a deep calcium fracture. C: results after stenting. The yellow arrow points to a small area of malapposition. ELCA, excimer laser coronary atherectomy; MLA, minimal lumen area; MSA, minimal stent area; PCI, percutaneous coronary intervention.

Follow-up

Follow-up will be conducted at 3 different timeframes:a) after PCI; procedural success and complications will be thoroughly documented, and all patients will be evaluated for any postoperative events, such as chest pain, heart failure, bleeding, or ischemic events; b) at hospital discharge, documenting clinical status, complications and antiplatelet therapy; and c) 1 year after the index PCI; clinical events and antiplatelet therapy will be recorded.

The primary endpoint at the follow-up will be the composite endpoint of major adverse cardiovascular events, defined as the occurrence of cardiac death, target vessel-related acute myocardial infarction, target vessel revascularization, or definite/probable stent thrombosis. Secondary efficacy endpoints will include all-cause mortality, cardiac death, non-fatal myocardial infarction, target lesion revascularization, and target vessel revascularization. Secondary safety endpoints will include stroke and bleeding events (classified according to the Bleeding Academic Research Consortium [BARC] criteria). Endpoint definitions are shown in table 2.

Table 2. Procedural and clinical definitions

Sample size estimation

The planned sample size of 230 patients was determined based on expected device success rates reported in prior studies of ELCA for undilatable and uncrossable lesions. Assuming a conservative laser success rate of 80%, a cohort of 230 patients would yield a 95% confidence interval with a precision of approximately ± 5% (estimated range, 74.8%–85.2%), which is considered adequate for reliably estimating procedural efficacy in the routine clinical practice. Moreover, this sample size ensures sufficient statistical power to support multivariable analyses of predictors of both intraoperative and follow-up outcomes. With an anticipated 40–50 events, the study would allow the inclusion of approximately 4 to 5 covariates in multivariable regression models while maintaining acceptable model stability. Based on the expected procedural volume at each participant center and the required sample size, the recruitment period is 2 to 3 years.

Statistical analysis

Quantitative variables following a normal distribution will be expressed as mean ± standard deviation. Those not following a normal distribution will be reported using the median and minimum and maximum values. Qualitative variables will be expressed as absolute numbers and frequencies.

A significance level of 0.5 will be considered, and 95% confidence intervals will be calculated for the primary outcome variables. Normality of the data will be assessed using the Kolmogorov-Smirnov test. Based on the distribution, appropriate statistical tests will be applied to compare relevant variables. For comparisons of means, the Student t test for independent samples will be used, or the non-parametric Mann-Whitney U test in case of dichotomous qualitative variables. For comparisons involving non-dichotomous qualitative variables, ANOVA or the non-parametric Kruskal-Wallis test will be employed. For bivariate analysis of qualitative variables, the chi-square test or Fisher’s exact test will be used.

Multivariate analysis will be conducted using forward stepwise Cox regression analysis. Event-free survival curves will be constructed using the Kaplan-Meier method. Variables will be considered potential risk predictors in the multivariate model if they demonstrate a statistically significant association in the univariate analysis or show a trend toward significance. All statistical analyses will be conducted using Stata 16.1 (StataCorp, United States).

Ethical considerations

This study was conducted in full compliance with the principles outlined in the Declaration of Helsinki and with the International Council for Harmonization (ICH) Good Clinical Practice guidelines, including the most recent ICH E6 (R3) update. Before enrollment, patients or their legal representatives must be fully informed about the nature of the study and must provide written informed consent. The study protocol was approved by the Institutional Review Board at each participant center.

DISCUSSION

The LUDICO study will be a multicenter study to assess the safety, efficacy, and clinical outcomes of ELCA specifically in undilatable or uncrossable coronary artery lesions with lesion-specific endpoints and preferential use of intravascular imaging. We believe that this real-life approach will provide valuable insights into the 2 main clinical scenarios in which ELCA is currently used.

Three recent large registries confirmed ELCA to be a safe technique with an assumable rate of complications.20-22 However, these studies analyzed the overall procedural performance but failed to describe the lesion specific characteristics or intravascular imaging data. The findings of studies reporting balloon failure scenarios5,10-12,23,24 are summarized in figure 3. The LAVA multicenter registry set the main contemporary clinical indications for ELCA.12 This registry analysed ELCA use in 130 lesions and stratified them in 3 scenarios: uncrossable, undilatable and thrombotic. The LAVA and other studies analyzing ELCA has shown good performance of ELCA in balloon-failure, with lower rates of ELCA success in uncrossable vs undilatable lesions. However, one significant limitation is present in these studies: situations of balloonfailure include undilatable, uncrossable, or lesions with both components. In the routine clinical practice, these 2 situations are distinct; however, ELCA success has often been defined uniformly, potentially confounding the real efficacy of the device. Consequently, the LUDICO study aims to address this issue by specifically defining 2 endpoints based on the type of balloon failure, uncrossable or undilatable.

Figure 3. Timeline of key studies evaluating ELCA in uncrossable and undilatable lesions. CTO, chronic total coronary occlusion; ELCA, excimer laser coronary atherectomy; NA, not available; ISR, in-stent restenosis. a Uncrossable lesions. b Undilatable lesions.

Nonetheless, the definition of ELCA success in uncrossable lesions might be ambiguous in some cases. For instance, cases in which neither the ELCA catheter nor subsequent balloons are able to cross the lesion should not be considered procedurals failures if a microcatheter can subsequently cross and enable successful completion of the procedure using the RASER technique—a combination of ELCA and rotational atherectomy (RA). However, to simplify the endpoint, we have considered this situation a crossover to RA. In contrast, for undilatable lesions, the definition of ELCA success is less prone to interpretation; however, clearly defining what constitutes an undilatable lesion remains essential. This highlights the importance of a compliance test —that is, performing an initial balloon dilatation to objectively demonstrate that the lesion cannot be adequately expanded. Such a test is critical to identify lesions that are likely to benefit from plaque modification techniques, including ELCA. Arguably, the results of some randomized controlled trials in plaque modification devices (such as ECLIPSE25 using orbital atherectomy and ROLLERCOASTR7 using ELCA, intravascular lithotripsy and RA) may have been influenced by the absence of “compliance test”, potentially including coronary lesions in which plaque modification would not have been necessary after balloon testing, thereby reducing the differences across groups. Additionally, the recent CRATER trial showed that a total of 20.9% of patients in bailout RA group required crossover to RA because of balloon failure,26 which highlights the high frequency of this situation and underscores the importance of its prompt identification to select the most appropriate plaque modification technique such as ELCA.

RA is the most extensively studied strategy for managing uncrossable coronary lesions, supported by wide clinical experience and robust evidence.7,26,27 However, RA presents important limitations in specific scenarios where ELCA may offer clear advantages —such as in-stent restenosis or bifurcation lesions requiring side branch protection—given the risk of scaffold damage or distal embolization of debris.28 Orbital atherectomy, although less studied in uncrossable lesions,29,30 shares similar drawbacks due to its ablative mechanism. By contrast, ELCA is compatible with 6-Fr catheters, can be used over any standard guidewire, and has a less demanding learning curve.18 Of note, while RA demonstrates limited efficacy against deep calcium, ELCA can affect both superficial and deep calcification.4 Collectively, these features position ELCA as a uniquely valuable tool among plaque-modification techniques. Its capacity to safely treat in-stent restenosis, thrombotic lesions, uncrossable lesions, and bifurcations requiring side branch protection underscores advantages not readily attainable with RA or orbital atherectomy, thereby reinforcing ELCA as a superior alternative in selected complex PCI scenarios.

In conclusion, the use of intravascular imaging has been limited in most of the studies that have evaluated ELCA in balloon-failure, particularly those focused on uncrossable lesions. Additionally, none of these studies have described the findings of intravascular imaging before and after ELCA and identified potential predictors of success. In fact, the effect of ELCA in intravascular imaging remains an open question as there is a paucity of studies that have evaluated it and have been limited to in-stent restenosis.4 Therefore, one of the aims of the LUDICO study is to evaluate the effects of ELCA by intravascular imaging (preferably by OCT, due to its better spatial resolution) and identify potential predictors of ELCA success or failure and its effect on the coronary plaque. We hypothesize that recognizing potential predictors in intravascular imaging could help operators guide the procedures and identify the anatomical characteristics that best predict a favourable outcome with ELCA, thereby optimizing patient selection and procedural planning.

Limitations

First, this multicentre prospective study will be conducted in a single country, which may limit the generalizability of its findings to other settings. However, these high-volume centres, with wide experience in complex PCI comply with the international recommendations and their practice is comparable to other similar centres. Second, because of to the nonblinded study design, selection bias may have occurred, whereby certain lesions, such as extremely calcified or highly complex, were preferentially treated with alternative techniques or revascularization strategies. Additionally, there will not be a control group to assess the efficacy of the ELCA therapy vs other therapies. Finally, although intracoronary imaging will be highly recommended, we foresee that the baseline evaluation will be limited to just a few cases. In fact, by definition, uncrossable lesions will rarely have a baseline evaluation. Besides, in the event of the patient having kidney disease, OCT runs could be avoided, conducting to less OCT runs, or even to the absence of intravascular imaging.

CONCLUSIONS

The LUDICO study will be a multicenter, prospective study of ELCA therapy in uncrossable or undilatable coronary artery lesions with specific success definitions for each indication. The study aims to evaluate the safety and efficacy profile of ELCA and the clinical outcomes during the follow-up. The OCT evaluation will provide insights into the effect of ELCA in this subset of coronary lesions.

FUNDING

The LUDICO study was supported by a non-restricted grant from Biomenco.

ETHICAL CONSIDERATIONS

The study was conducted in full compliance with the principles outlined in the Declaration of Helsinki. Institutional Ethics Committee approval was obtained (institutional approval number: 5502), and all participants gave their written informed consent prior to enrolment. The confidentiality and anonymity of participants were strictly preserved throughout the study. Sex and gender considerations were addressed following the recommendations of the SAGER guidelines to ensure accurate and equitable reporting.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

Artificial intelligence assisted technologies were used exclusively to support language editing and improvement of style. No artificial intelligence tools were employed to generate, analyse, or interpret the data. The authors take full responsibility for the integrity, accuracy, and originality of the manuscript content.

AUTHORS’ CONTRIBUTIONS

A. Jurado-Román and J. Zubiaur contributed to the study equally and share first authorship. A. Jurado-Román is responsible of the study conception and design. J. Zubiaur, A. Jurado-Román, and M. Basile were involved in the draft manuscript preparation. All authors reviewed the results and approved the final version of the manuscript.

CONFLICTS OF INTEREST

R. Moreno is associate editor of REC: Interventional Cardiology; the journal’s editorial procedure to ensure impartial handling of the manuscript has been followed; moreover, he has received consulting fees and honoraria/speaker fees from Abbott vascular, Boston Scientific, Medtronic, Terumo, and Biotronik. A. Jurado-Román reported receiving consulting fees from Boston Scientific and Philips; honoraria/speaker fees from Abbott, Boston Scientific, Shockwave Medical, World Medica, and Philips; and serves as a proctor for Abbott, Boston Scientific, World Medica, and Philips. G. Galeote has received honoraria/speaker fees from Meril, Boston Scientific, Abbott SMT, and Biomenco. A. Gonzálvez-García has received honoraria from Abbott. J. Suárez de Lezo has received honoraria/ speaker fees from Abbott and Philips. F. Hidalgo has received honoraria/speaker fees from Philips. M. Basile reported receiving consulting fees and speaking fees from Iberhospitex. B. Garcia del Blanco disclosed his role as a proctor for Edwards Lifescienses and his participation on the Advisory Board of Iberhospitex. All other authors declared no conflicts of interest whatsoever.

REFERENCES