Transcatheter mitral edge-to-edge repair vs optimal medical therapy in secondary mitral regurgitation: a meta-analysis

INTRODUCTION

Acute coronary syndrome, particularly ST-segment elevation myocardial infarction (STEMI), is the leading cause of out-of-hospital cardiac arrest.1 The main underlying mechanism is reversible ischemia, provided that reperfusion is achieved within the first few hours after STEMI.2 Approximately 1 in 20 patients with STEMI presents with cardiac arrest as the initial or early sign of myocardial infarction.3-5 Resuscitated cardiac arrest before primary angioplasty (RCABPA) is an important prognostic marker, and has been associated with 30-day mortality rates of 40% to 60%.3,6 Published studies differ regarding the long-term prognosis of patients who survive the in-hospital phase after RCABPA. Some registries have reported no long-term differences in outcomes,7,8 whereas others have found higher mortality, even after adjustment for the poorer baseline clinical profile of patients with RCABPA.9,10 However, all available studies consistently show that most events occur during the in-hospital phase or within the first 30 days after RCABPA.

“STEMI network” programs are designed to ensure rapid identification of STEMI and timely delivery of the most appropriate reperfusion strategy, preferably primary angioplasty.5 Studies evaluating the characteristics and prognosis of RCABPA have generally paid little attention to the specific point in the STEMI care pathway at which cardiac arrest occurs. Their inclusion criteria have typically included patients with RCABPA occurring outside the hospital setting, without specifying whether the cardiac arrest occurred before or after first medical contact or how close the patient was to resources for advanced cardiopulmonary resuscitation (CPR). In addition, the prognosis of RCABPA occurring in hospitals with CPR capability but without primary angioplasty capability has not been specifically analyzed. The poor short-term prognosis associated with RCABPA may be related to the clinical characteristics and consequences of the STEMI per se or to delays and limitations in CPR when cardiac arrest occurs outside the hospital setting.

Therefore, analyzing the characteristics and consequences of RCABPA based on the place of occurrence may help identify opportunities to improve the care and prognosis of patients with STEMI.

The aim of this study was to analyze short-term mortality in patients with RCABPA, with particular attention to the place where cardiac arrest occurred within the care pathway initiated by activation of the STEMI code after diagnosis.

METHODS

Design

This observational study used a historical cohort of consecutive patients admitted for primary angioplasty with a diagnosis of STEMI and an indication for reperfusion.

Study population

We included all patients who arrived at the cath lab of Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Murcia, Spain) between 1 January, 2021, and 31 December, 2024 through the regional STEMI code program and with an indication for primary angioplasty. In patients with > 1 episode during the inclusion period, only the index episode was included. In 2023, the reference population covered by the regional STEMI code program for the study center was 1,132,310 inhabitants. Six non–PCI-capable hospitals referred patients to the study hospital, which served as the reference center. According to the STEMI code protocol, activation must occur at first medical contact, and patients should be transferred directly from the place of activation to the cath lab, without intermediate stops at other hospitals or emergency departments.

Variables

Data were obtained from the prospective patient registry of the cath lab at the reference hospital for primary angioplasty, where demographic characteristics, clinical presentation, procedural data, and follow-up information are systematically recorded. Missing data were completed by reviewing the regional electronic health record or by contacting patients or their relatives by telephone.

RCABPA was defined as cardiac arrest with return of spontaneous circulation after cardiopulmonary resuscitation maneuvers. Cardiac arrests occurring after arrival at the cath lab were excluded. Patients who died before or during transfer to the reference hospital were not included.

Patients were classified into 5 groups according to the location where RCABPA occurred: a) in-hospital RCABPA, occurring in referral hospitals before transfer or at the reference hospital prior to the arrival at the cath lab; b) RCABPA in a medicalized ambulance occurring in an ambulance with defibrillation capability; c) RCABPA in primary care, occurring in a health center or out-of-hospital emergency department with defibrillation capability; d) RCABPA outside the health care setting, occurring at home or in a public place without medical or paramedical personnel present; and e) no RCABPA, used as the control group.

All primary care centers and medicalized ambulances have the capacity to provide advanced CPR. We could not determine the exact number of patients with out-of-hospital RCABPA who may have exceptionally benefited from the proximity of a defibrillation team.

For comparisons by grouped location, groups a, b, and c were classified as RCABPA occurring in a health care setting, whereas groups b and c were classified as RCABPA occurring in an out-of-hospital health care setting.

Vital status at 30 days was obtained from the patients’ electronic health records or, when unavailable, by telephone contact.

The study was conducted in full compliance with the principles outlined in the Declaration of Helsinki. Episodes were collected retrospectively. The study was approved by the local ethics committee.

Statistical analysis

Quantitative variables are expressed as mean and standard deviation or as median and 25^th-75^th percentiles when they did not meet normality criteria, as assessed with the Shapiro-Wilk test. Quantitative variables that did not meet the normality criteria were compared using the nonparametric Mann-Whitney U test; normally distributed variables were compared using the Student t test for independent samples. Qualitative variables are expressed as absolute frequencies and percentages and were compared using the Pearson chi-square test. As specified in the tables and Results section, patients without RCABPA and those with in-hospital RCABPA were used as reference groups, as appropriate. Thirty-day mortality was assessed using Kaplan-Meier survival analysis. Survival curves were plotted for patients without RCABPA and for those with RCABPA at each individual and grouped location. Survival curves were compared using the log-rank test, with patients without RCABPA and those with in-hospital RCABPA used as reference groups. In all cases, P values < .05 were considered statistically significant.

To determine the contribution of RCABPA to 30-day mortality compared with the absence of RCABPA, as well as the contribution of RCABPA according to its location, logistic regression models were constructed. Models were adjusted for variables that were asymmetrically distributed across the study subgroups in the univariate analysis (P > .1) or that have been associated in the literature with higher mortality: age, diabetes, cardiogenic shock, performance of percutaneous coronary intervention (PCI), anterior infarct location, and delay from symptom onset to first medical contact. The absence of significant multicollinearity among the included variables was confirmed. The predictive performance of each model was assessed using the receiver operating characteristic curve, based on 30-day mortality predicted by the models and observed mortality.

Statistical analyses were performed using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., United States), and SigmaPlot for Windows, version 11.0 (Systat Software, Inc., United States).

RESULTS

Population description

During the 4-year study period, there were 2463 activations of the STEMI code program with an indication for primary angioplasty. A total of 119 cases (4.9%) were excluded because they had previously been referred for primary angioplasty, leaving a final sample of 2344 patients, 170 of whom (7.3%) experienced RCABPA: 40 (1.7%) in a hospital setting, 13 (0.6%) in primary care, 33 (1.4%) in an advanced life support ambulance, and 84 (3.6%) outside the health care setting. Eight aborted STEMI code activation due to patient death before arrival at the cath lab were recorded, including 3 deaths in an advanced life support ambulance. The final cause of death could not be determined. All these patients had cardiogenic shock at the time of activation and were not included in the study.

The initial rhythm of RCABPA was shockable in 158 cases (92.9%). Baseline characteristics and infarct presentation based on the presence of RCABPA are shown in table 1. Patients with RCABPA underwent PCI less frequently than those without RCABPA (76.5% vs 85.6%; P = .001). PCI was not performed in 2 cases of RCABPA because the patients died before the procedure could be initiated, or in 28 cases because no culprit coronary lesion was identified.

Table 1. Baseline, acute myocardial infarction presentation, and procedural characteristics according to the occurrence or absence of resuscitated cardiac arrest before primary angioplasty

Baseline characteristics and infarct presentation based the presence and location of RCABPA are shown in table 2.

Table 2. Baseline, acute myocardial infarction presentation, and procedural characteristics based on the location of resuscitated cardiac arrest before primary angioplasty

A total of 32 patients received mechanical circulatory support, representing 1.4% of the overall population and 17.6% of patients with cardiogenic shock. In this group, the 30-day mortality rate was 47%. Mechanical circulatory support was used in 10 patients with cardiogenic shock and RCABPA (21.2%; 30-day mortality, 70%) and in 22 patients with cardiogenic shock without RCABPA (16.3%; 30-day mortality, 36.4%).

Mortality based on the location of RCABPA

The 30-day all-cause and cardiovascular mortality rates are shown in table 3, and mortality grouped by RCABPA location is shown in figure 1. The 30-day all-cause mortality rate was significantly higher in patients with RCABPA than in those without RCABPA (31.2% vs 6.3%; P < .0005). Mortality increased progressively from in-hospital RCABPA to RCABPA occurring outside the health care setting, where it approached 50% (48.8%). Compared with in-hospital RCABPA, RCABPA occurring outside the hospital was associated with a significantly higher 30-day mortality rate or showed a clear trend toward a higher mortality rate (table 3 and figure 2).

Figure 1. Thirty-day mortality according to the location of resuscitated cardiac arrest before primary angioplasty (RCABPA).
^a Comparison with patients without RCABPA.
^b Comparison with patients with in-hospital RCABPA.

Table 3. Interventional procedure outcome and 30-day mortality based on the location of resuscitated cardiac arrest before primary angioplasty

Figure 2. Kaplan-Meier curves for 30-day survival and significance of the log-rank test, using patients without resuscitated cardiac arrest before primary angioplasty (RCABPA) as the reference group.

Patients with RCABPA in a nonhospital health care setting and those with out-of-hospital RCABPA had a significantly higher 30-day mortality rate compared with patients without RCABPA (19.6% vs 6.3%; P < .0005, and 38.5% vs 6.3%; P < .0005, respectively). The 30-day mortality rate among patients with RCABPA in a nonhospital health care setting was numerically much higher than that among patients with in-hospital RCABPA, although the difference did not reach statistical significance (19.6% vs 7.5%; P = .123). When out-of-hospital RCABPA was analyzed as a grouped category, the mortality rate was significantly higher than that observed for in-hospital RCABPA (38.5% vs 7.5%; P < .0005) (figure 2).

After adjustment in logistic regression models, RCABPA was independently associated with a higher 30-day mortality rate, regardless of the presence of cardiogenic shock and other variables associated with poorer prognosis (OR, 5.99; 95%CI, 3.78-9.51; P < .0005). This association was not observed for in-hospital cardiac arrest. Furthermore, the independent predictive value for mortality was observed for out-of-hospital RCABPA (OR, 9.15; 95%CI, 5.59-14.95; P < .0005) and for RCABPA occurring outside the health care setting (OR, 20.9; 95%CI, 11.40-38.30; P < .0005). When in-hospital RCABPA was used as the reference category, the independent predictive value was maintained for virtually all nonhospital RCABPA locations. There was no significant interaction between cardiogenic shock and RCABPA in any of the models. The areas under the receiver operating characteristic curves exceeded 85% for all models (table 4).

Table 4. Adjusted contribution of recovered cardiac arrest before primary angioplasty, based on location, to 30-day mortality. Logistic regression analysis with predictors of 30-day mortality

DISCUSSION

To our knowledge, this study analyzes the largest series of patients with RCABPA in the setting of STEMI based on the location where cardiac arrest occurred. The main findings were as follows: a) approximately half of RCABPA episodes in patients with STEMI treated within a STEMI code program occurred in a health care setting; b) although STEMI complicated by RCABPA before arrival at the cath lab was associated with a significantly higher 30-day mortality rate, prognosis varied based on RCABPA location; c) patients with in-hospital RCABPA did not have a higher crude or adjusted mortality rate compared with patients without RCABPA; and d) the prognostic differences observed based on RCABPA location may reflect differences in CPR availability and effectiveness, rather than differences in RCABPA per se. These findings suggest that improvements in the STEMI code care pathway could reduce mortality (figure 3).

Figure 3. Central illustration. Study design and main results. PCI, percutaneous coronary intervention; RCABPA, resuscitated cardiac arrest before primary angioplasty; STEMI, ST-segment elevation myocardial infarction.

Incidence of cardiac arrest before reperfusion in patients with STEMI

Although it has been estimated that approximately half of sudden deaths are of coronary origin, these cannot be definitely classified because they represent the first sign of ischemic heart disease and patients are not resuscitated.11,12 STEMI code programs have reported an incidence of RCABPA ranging from 2% to 10%,3,6,13-15 with variability depending on inclusion criteria and delays to reperfusion. In our series, the incidence of RCABPA was 7.3%, which is close to the highest reported rates. This may be explained by the comprehensive nature of the registry, its regional coverage, and the median interval from symptom onset to reperfusion, which exceeded 200 minutes. A Danish nationwide case-control study16 including 1901 patients with STEMI reported an 11.6% incidence of ventricular fibrillation before primary angioplasty; although 83% of these episodes occurred outside the hospital, the precise location was not specified.

We found no previous studies that analyzed prognosis based on the location of RCABPA within the STEMI care pathway. This limits comparisons with our series, except for episodes occurring during transfer in an advanced life support ambulance. The first trials showing the superiority of primary angioplasty over thrombolysis in patients requiring transfer for angioplasty reported ventricular fibrillation during ambulance transport in 1.4% of the patients from the DANAMI-2 trial17 and 0.7% of the patients from the PRAGUE-2 trial.18 These figures are similar to the 1.4% observed in our cohort. In an observational study of 7393 patients with myocardial infarction transferred to a tertiary referral center, 5.6% experienced cardiac arrest before hospital arrival.19 In our series, > 35% of RCABPA episodes occurred in the out-of-hospital health care setting, underscoring the importance of appropriate training and the availability of material and human resources to provide high-quality cardiac resuscitation in these settings.

Differences in the prognosis of cardiac arrest in patients with STEMI based on location

Despite its high mortality rate, out-of-hospital cardiac arrest of coronary origin has a better prognosis than cardiac arrest of noncoronary origin.20 Currently, most studies21 assessing the characteristics or prognosis of out-of-hospital RCABPA in patients with or without ST-segment elevation myocardial infarction, have defined it simply as cardiac arrest occurring outside the hospital, without considering the specific setting or whether cardiopulmonary resuscitation was immediately available. In the present study, prognosis differed significantly based on the location of out-of-hospital RCABPA. Mortality increased progressively from RCABPA occurring at the hospital or health care setting to RCABPA occurring in a nonhospital or outside the health care setting (7.5%, 19.6%, and 48.8%, respectively). These differences do not appear to be fully explained by the patients’ baseline clinical characteristics or infarct presentation, because the independent predictive value of RCABPA location for 30-day mortality persisted after adjustment in the different multivariate models. Notably, mortality among patients with in-hospital RCABPA was not significantly different from that observed in patients without RCABPA (7.5% vs 6.3%; P = .748; figure 2). By contrast, mortality was 3 times higher among those with RCABPA occurring in a nonhospital health care setting (19.6% vs 6.3%; P < .0005). In the adjusted model (table 4), RCABPA occurring in a nonhospital health care setting was significantly associated with a higher 30-day mortality rate compared with patients without RCABPA and those with in-hospital RCABPA (OR, 13; P = .044). A previous study analyzing the prognosis of in-hospital cardiac arrest in 40 670 patients with STEMI22 reported an in-hospital mortality rate of 53%, which is substantially higher than that observed in our cohort and significantly higher than that among patients without cardiac arrest. However, unlike in our study, cardiac arrests in that series occurred throughout hospitalization and therefore probably reflected, in many cases, more severe clinical deterioration, including potentially irreversible situations.

Despite the adjustments made, we cannot rule out that patients with RCABPA had location-related characteristics that influenced prognosis. However, our findings suggest that, although health care settings have defibrillation capability and advanced CPR, and although almost all cardiac arrests are caused by shockable rhythms, in-hospital RCABPA is treated more effectively than out-of-hospital RCABPA.

Although in the present study, most RCABPA episodes involved shockable rhythms, RCABPA was associated with poor prognosis regardless of cardiogenic shock. This suggests that most RCABPA episodes were not primarily related to an irreversible hemodynamic condition, but rather that prognosis may have been determined by the consequences of delayed rhythm reversal. This interpretation is supported by the absence of significantly worse prognosis when cardiac arrest occurred in the hospital setting.

The diversity observed in mortality between in-hospital RCABPA and RCABPA occurring in other locations suggests that prognosis may be more closely related to the quality and immediacy of CPR than to cardiac arrest per se. We consider this one of the most important findings of our study, because it identifies potential opportunities to improve survival among patients with RCABPA occurring in out-of-hospital health care setting. Future studies should further explore differences in the clinical presentation and treatment of patients within the health care system outside and inside the hospital to identify actionable areas for improvement.

Prognosis of RCABPA outside the health care setting

Although most studies report in-hospital mortality rates of 55% to 70% among survivors of out-of-hospital cardiac arrest,12 the precise location of arrest is usually not specified. Cause of cardiac arrest, initial rhythm, comorbidity, and socioeconomic status have all been associated with prognosis.23 Rapid initiation of resuscitation, even by the first witness,24,25 is a key determinant of survival.23,26 In our study, mortality among patients with RCABPA occurring outside the health care setting was 6 times higher than that among patients with in-hospital RCABPA and more than twice that among patients with RCABPA occurring in out-of-hospital health care settings. This difference persisted after adjustment for the main variables associated with prognosis. These findings support the importance of population-based campaigns aimed at improving recognition of cardiac arrest and promoting early defibrillation. Current CPR guidelines27 recommend facilitating access to defibrillators in public places and training the general population in CPR maneuvers.

Two studies have analyzed differences in all-cause mortality after out-of-hospital cardiac arrest based on the precise place of occurrence.28,29 In both studies, mortality was highest when cardiac arrest occurred at home, probably because of poorer access to defibrillation and CPR. In our series, the precise location of out-of-hospital RCABPA episodes could not be determined; therefore, differences within this group based on whether they occurred in a public or private place cannot be ruled out.

Limitations

The study design does not allow to determine precisely how many patients with cardiac arrest in the context of STEMI died before STEMI code activation. An undetermined number of patients may have died before the arrival of emergency teams, during first contact, or after unsuccessful resuscitation attempts. Although nonresuscitated cardiac arrest after activation but before arrival at the cath lab is exceptional, this may not be the case for patients who experience sudden death before contact with health care services, without successful circulatory restoration allowing transfer to the cath lab. This may introduce biases that are difficult to control. We believe this limitation is common to most registries of out-of-hospital cardiac arrest and reflects the real-world clinical practice setting of the study. The similarity between our RCABPA rates and those reported in previous studies on primary angioplasty or STEMI suggests that our findings are representative of the routine clinical practice.

Some differences in mortality according to RCABPA location may be explained by clinical characteristics that were not controlled for in the multivariate analyses. Information on the presence of witnesses, availability of a semiautomatic external defibrillator, and qualifications of the first rescuer was not available in our series; therefore, their influence on the observed results could not be assessed. Despite these unmeasured variables, we believe that the observed differences, particularly within the health care setting, suggest important opportunities for improvement in STEMI code programs. The high area under the receiver operating characteristic curve observed in the different models reduces the relevance of these potential uncontrolled variables.

CONCLUSIONS

Cardiac arrest in patients with STEMI before reperfusion occurs in 7.3% of cases referred for primary angioplasty, and approximately half of these events occurred outside the health care setting. Although RCABPA was associated with significantly higher mortality rates, prognosis varied based on the location of the cardiac arrest. In-hospital RCABPA may not adversely affect prognosis, whereas out-of-hospital RCABPA, particularly when occurring outside the health care setting, was associated with significantly higher mortality rates. Improvements in regional STEMI code programs focused on early medical care and out-of-hospital CPR could reduce mortality.

FUNDING

This study received no funding.

ETHICAL CONSIDERATIONS

This study was approved by the local ethics committee, with a waiver of informed consent because it was an anonymized retrospective study. The SAGER guidelines were followed with respect to possible sex/gender bias.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

Artificial intelligence was not used in the preparation of this work.

AUTHORS’ CONTRIBUTIONS

R. López-Palop contributed to the conception and design of the study, data acquisition, analysis, and interpretation, drafting of the original project and final manuscript, and final approval. P. Carrillo Sáez collaborated in data acquisition, analysis, and interpretation, and in drafting, reviewing, and approving the manuscript. R. López-Palop López collaborated in data acquisition, analysis, and interpretation, drafting of the initial project, and review and final approval of the manuscript. M.D. Vallés García collaborated in data acquisition, analysis, and interpretation. N. Fernández Villa collaborated in drafting, reviewing, and final approval of the manuscript. J.R. Gimeno Blanes, J.M. Durán Hernández, F.J. Lacunza Ruiz, J. García de Lara, J.A. Hurtado Martínez, A. Riquelme Pérez, and E. Pinar Bermúdez collaborated in data acquisition and in review and final approval of the manuscript. D. Pascual-Figal participated in reviewing, drafting, editing, and final approval of the manuscript.

CONFLICTS OF INTEREST

None declared.

REFERENCES

INTRODUCTION

Coronary artery calcification (CAC) is a consequence of the progression of atherosclerotic disease, as well as an independent predictor of major adverse cardiovascular events (MACE).1,2 The etiology of CAC is multifactorial, and, among other clinical conditions, is associated with conventional cardiovascular risk factors, ethnicity, and chronic kidney disease.3-6

Patients with CAC have worse short- and long-term follow-up outcomes after percutaneous coronary intervention (PCI), including lower rates of complete revascularization and higher risks of stent underexpansion, coronary dissection, coronary perforation, and stent deformation or loss.7-10 Furthermore, CAC has been associated with a higher risk of in-stent restenosis and a greater long-term need for target lesion revascularization (TLR). In addition, approximately 50% of stents implanted in calcified lesions show asymmetric expansion, which increases the risk of stent thrombosis or in-stent restenosis.11-14 Adequate lesion preparation before stent implantation is therefore essential to reduce procedural difficulty and prevent complications. Dedicated techniques for calcified lesion modification, including calcium ablation or fracture, can improve vascular compliance. Among these techniques, orbital atherectomy (OA) has shown favorable results in the treatment of CAC and is the focus of the present study.15

METHODS

We conducted a retrospective observational study including all patients with significant calcified coronary lesions treated with OA. The aim of the study was to assess the safety and efficacy profile of OA for the treatment of patients with CAC in a hospital without on-site cardiac surgery in Spain.

The primary endpoint was procedural success, defined as treatment of the target vessel with residual percent diameter stenosis < 20% and final TIMI grade-3 flow. A composite endpoint, defined as target vessel failure (TVF) at 12 months, included cardiac death, target vessel myocardial infarction, and target vessel revascularization (TVR).

Procedure-related secondary safety endpoints included acute or subacute stent thrombosis, slow-flow or no-reflow phenomena, type C-F coronary dissections, and coronary perforations.

Clinical follow-up of the patients was performed by telephone consultation at 6 months and an in-person visit at 12 months.

The OA clinical database was approved by the Ethics Committee of the Servicio Gallego de Salud, with waiver of informed consent because of the characteristics of the study. Sex and gender variables were considered in full compliance with the SAGER guidelines.

Orbital atherectomy technique

OA is an ablative coronary technique performed using a 1.25-mm diamond-coated crown (Diamondback 360, Abbott, United States), a dedicated guidewire (ViperWire Advance, Abbott, United States), and a lubricant infused during ablation (ViperSlide, Abbott, United States). Driven by centrifugal force, the crown orbits at 2 rotational speeds (80 000 rpm or 120 000 rpm), sanding the calcium within the arterial wall and causing deep calcium fractures.16,17

Statistical analysis

Qualitative variables are expressed as number and percentage, and the quantitative ones as mean and SD. Survival curves were generated using the Kaplan-Meier method, and statistical differences in events between patients undergoing scheduled procedures and those admitted for acute coronary syndrome (ACS) were assessed using the log-rank test. A multivariate Cox regression analysis was performed to identify factors independently associated with TVF at 1 year. Variables associated with TVF in the univariable analysis at P < .1 were entered into the regression. Afterwards, the least associated variables were removed one by one using backward stepwise regression until a parsimonious model was obtained in which all variables were associated with TVF. Statistically significant difference was set at P < .05. Analyses were performed using SPSS statistical software version 17 (IBM, United States).

RESULTS

From April 2021 through April 2025, a total of 116 patients with CAC were treated with OA. Regarding the patients’ clinical charac- teristics, their mean age was 73.24 years, most were men (82.8%), and exhibited multiple classic cardiovascular risk factors. The mean left ventricular ejection fraction (LVEF) was 50.3 ± 11.9%, and up to 37.1% of patients had LVEF < 50%. Chronic kidney disease, defined as glomerular filtration rate < 60 mL/min, was present in 38.8% of patients; in 10 patients (8.6%) glomerular filtration rate was < 20 mL/min. Approximately one third of patients (30.2%) had chronic ischemic heart disease; of these, 25 (21.6%) had previously undergone revascularization by PCI and 16 (13.8%) by coronary artery bypass grafting (table 1).

Table 1. Baseline characteristics of patients treated with orbital atherectomy

Regarding clinical presentation, 77 patients (66.4%) were admitted with ACS, 61 (52.1%) with non-ST-segment elevation acute coronary syndrome (NSTEACS) and 16 (13.8%) with ST-segment elevation acute coronary syndrome (STEACS). Among the latter, the artery treated with OA was the infarct-related artery in 5 cases (4.3%) (table 2). Regarding the extent of coronary artery disease, 32 patients (27.6%) had 3-vessel disease and 27 (23.3%) had left main coronary artery disease (figure 1).

Table 2. Distribution of cases based on clinical presentation

Figure 1. Distribution of cases treated with orbital atherectomy based on the number of coronary arteries with severe disease (n = 116). LMCA, left main coronary artery.

Regarding procedural characteristics, radial access was the most widely used vascular approach (77.2%). The vessel most frequently treated with OA was the left anterior descending coronary artery, in 57 cases (49.1%), followed by the right coronary artery in 34 cases (29.3%) and the left main coronary artery in 18 cases (15.5%). Intravascular imaging was used before the PCI in 42 cases (37.2%), mainly intravascular ultrasound, and after the PCI in 18 cases (15.4%). As an adjunctive plaque-modification technique to OA, a cutting balloon was used in 61 cases (52.6%), excimer laser atherectomy in 2 cases (1.7%), and intravascular lithotripsy in 1 case (0.9%). Rotational atherectomy was not used in any patient. In most patients, 1 or 2 stents were implanted (35.3% and 28.4%, respectively), with a mean stent length of 23.3 ± 6.4 mm and a mean stent diameter of 3.3 ± 0.6 mm. The mean procedure duration was 85 ± 29.5 minutes; mean fluoroscopy time, 28.7 ± 17 minutes; and mean contrast volume, 179.3 ± 65.2 mL. Procedural success rate, with an adequate angiographic result and final TIMI grade-3 flow was achieved in 98.3% of cases. Immediate complications included 1 intraprocedural death (0.9%), and in 1 case the device failed to cross the lesion (0.9%). Regarding the secondary safety endpoint, 1 patient had acute or subacute stent thrombosis (0.9%), 2 had type C-F coronary dissections (1.7%), 3 had coronary perforations (2.6%), and 2 had slow-flow or no-reflow phenomena (1.7%). Of note, all complications occurred in the subgroup of patients with ACS (table 3).

Table 3. Characteristics and materials of percutaneous coronary intervention with orbital atherectomy

Mean follow-up was 1.63 ± 1.2 years, with a median of 1.48 years, Q1 of 0.53 years, and Q3 of 2.58 years. Out-of-hospital follow-up was lost in 2 cases (1.7%).

During follow-up, 11 patients had acute myocardial infarction, with a 4-year cumulative incidence rate of 19.3% (95%CI, 11.7-26.9) (figure 2A); 8 required TVR, with a 4-year cumulative incidence rate of 16.3% (95%CI, 3.7-28.9) (figure 2B); 2 had stent thrombosis, with a 4-year cumulative incidence rate of 1.8% (95%CI, 0-4.3) (figure 2C); and 4 required symptom-guided TLR, with a 4-year cumulative incidence rate of 8.7% (95%CI, 0.1-16.3) (figure 2D). There were no admissions for STEACS.

Figure 2. Cumulative incidence curves for events during follow-up: myocardial infarction (A), target vessel revascularization (B), stent thrombosis (C), and symptom-guided target lesion revascularization (D).

During follow-up, 13 patients died, with a 4-year cumulative incidence rate of 16.7% (95%CI, 7.2-26.2) (figure 3A). Cardiovascular mortality occurred in 7 cases, with a 4-year cumulative incidence rate of 5.4% (95%CI, 1.3-9.5) (figure 3B). When noncardiovascular mortality was analyzed, 3 patients died of severe infection or septic shock, 2 of cancer, and 1 of an accidental cause.

Figure 3. Kaplan-Meier mortality curves during follow-up: all-cause (A) and cardiovascular mortality (B).

The composite endpoint occurred in 10 patients, with a 12-month cumulative incidence rate of 10% (95%CI, 3.8-16.2).

Multivariable analysis showed that age < 70 years (HR, 0.35; 95%CI, 0.14-0.92), LVEF as a continuous variable (HR, 0.92; 95%CI, 0.88-0.96), and presentation as ACS (HR, 3.95; 95%CI, 1.12-13.97) were independent predictors of TVF during follow-up.

DISCUSSION

CAC is associated with an increase in adverse clinical events related to percutaneous revascularization procedures.18 OA has emerged as a safe and effective technology for the percutaneous treatment of CAC across its entire clinical spectrum. Although robust scientific evidence exists for uncrossable lesions remains limited, favorable clinical experiences with its use have been reported.19

In the registry by Lee et al.,18 stent implantation was successful in 99.1% of patients, with low rates of angiographic complications. The 30-day MACE rate, defined as a composite of cardiac death, myocardial infarction, target vessel revascularization, and stroke, was 1.7%, and the 30-day all-cause mortality rate was low, at 1.3%. Although our registry included a smaller sample, the proportions of patients with acute myocardial infarction, a past medical history of chronic ischemic heart disease, and chronic kidney disease were higher, reflecting a greater burden of high-risk clinical features. Despite this, our procedural success and immediate complication rates were comparable.

The ORBIT I study evaluated OA for the treatment of de novo calcified coronary lesions and showed sustained favorable outcomes at 5 years. Procedural success was achieved in 94% of cases. The cumulative MACE rate, defined as a composite of cardiac death, myocardial infarction, and target vessel revascularization, was 4% during hospitalization, 6% at 30 days, 8% at 6 months, 18.2% at 3 years, and 21.2% at 5 years. The rate of cardiovascular mortality was 6.1% at 2 years, 9.1% at 3 years, and 12.1% at 5 years.20-22 Of note, compared with the ORBIT I study, our registry included more than twice as many patients and a population at higher cardiovascular risk. Even so, procedural success was higher in our series (98%), and cardiovascular mortality at a mean follow-up of 1.6 years was lower than that reported in the ORBIT I beyond 2 years (5.4% vs 6.1%).

The ORBIT II study evaluated OA for de novo calcified lesions, with successful stent implantation in 97.7% and residual percent diameter stenosis < 50% in 98.6% of patients. Regarding complications, immediate and 30-day cardiovascular mortality rate was 0.2%, with low rates of severe coronary dissection, coronary perforation, slow-flow phenomenon, and acute coronary occlusion.23 These rates were similar to or lower than those reported in previous studies of rotational atherectomy, such as the ROTAXUS.24,25 The MACE rate in the ORBIT II, defined as a composite of cardiac death, myocardial infarction, and target vessel revascularization, was 16.4% at the 1-year follow-up, 19.4% at 2 years, and 23.5% at 3 years. The cardiovascular mortality at 1, 2, and 3 years was 3%, 4.3%, and 6.7%, respectively.26-28 In our registry, with a mean follow-up of 1.6 years, the rate of cardiovascular mortality was slightly higher than that reported in the ORBIT II study at 2 years (5.4% vs 4.3%). A factor that could have possibly influenced our results is that > 60% of patients in our series presented with ACS, whereas this population was excluded from the ORBIT II. In addition, the ORBIT II study excluded patients with chronic kidney disease, except those receiving dialysis, patients with serum creatinine levels > 2.5 mg/dL, and those with LVEF ≤ 25%, whereas our study included a higher-risk cardiovascular population. The ROLLER COASTR-EPIC2229 study compared rotational atherectomy, intravascular lithotripsy, and excimer laser atherectomy for the treatment of patients with CAC. The study showed that intravascular lithotripsy is noninferior to rotational atherectomy in terms of stent expansion, whereas excimer laser atherectomy did not meet the criterion for noninferiority compared with rotational atherectomy. In this context, we believe that a clinical trial including OA would be necessary and of substantial practical value to compare the optimal strategy for the treatment of CAC.

The ECLIPSE study compared OA with balloon angioplasty in severely calcified lesions and concluded that the ideal scenario for OA use would be lesions with severe superficial or nodular calcification that are nondilatable or cannot be crossed with a balloon.30 In the ECLIPSE study, 12-month TVF in the OA group was 11.5%, compared with 10% in our series, and procedural success was 86%, compared with 98% in our series. Compared with our registry, the ECLIPSE population had lower cardiovascular risk characteristics: 44% of patients had diabetes compared with 50% in our study, 24% had chronic kidney disease compared with 38.8% in our study, and the mean age was 70 years compared with 73 years in our study. In addition, the ECLIPSE study only included 13.7% of patients with ACS, including 1.3% with STEACS, compared with 66.4% with ACS (13.8% with STEACS) in our study. Thus, despite including a higher-risk population, our registry showed a higher stent implantation success rate and a slightly lower 12-month TVF rate.

Limitations

This study has several limitations. First, it is a retrospective observational registry from a single hospital; therefore, the findings may not be generalizable of other centers. Second, the OA technique is associated with a learning curve, and the results cannot be extrapolated to hospitals without experience in this technique. Third, the use of intravascular imaging was relatively low, at approximately 40% of cases, which may have led to underestimation of the severity of coronary lesion calcification. However, the use of intravascular imaging in this registry was slightly higher than that reported in previous real-world registries.

CONCLUSIONS

This large real-world registry of patients with CAC treated with OA showed a high procedural success rate and a low complication rate during long-term follow-up.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

The orbital atherectomy care database was approved by the Ethics Committee of the SERGAS of Hospital Universitario Lucus Augusti, and the requirement for informed consent was waived because of the characteristics of the study. Sex and gender variables were considered in full compliance with the SAGER guidelines.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

Artificial intelligence was not used in the preparation of the article.

AUTHORS’ CONTRIBUTIONS

J. Bayón drafted the manuscript and prepared the images. R.A. Mori-Junco reviewed the manuscript. A. Negrete-Marcolongo and A. López-Pena participated in the literature search. C. González- Juanatey performed the final review of the manuscript. All authors approved the final version.

CONFLICTS OF INTEREST

J. Bayón is a proctor for Abbott Diamondback 360 orbital atherectomy. The remaining authors declared no conflicts of interest whatsoever.

REFERENCES

INTRODUCTION

Coronary artery calcification constitutes a major challenge during percutaneous coronary intervention (PCI), as it reduces procedural success and increases the risk of complications. It limits optimal stent expansion, which predicts restenosis, stent thrombosis, and the need of target lesion revascularization.1-3 Several plaque modification techniques (PMT) have been developed to improve clinical outcomes in this setting. Rotational atherectomy has long been considered the standard approach for managing resistant calcified lesions. However, the development of newer technologies such as intravascular lithotripsy (IVL), together with increasing interest in excimer laser coronary atherectomy (ELCA), has expanded the range of available therapeutic options.4-7

The ROLLER COASTR-EPIC22 trial was the first randomized trial comparing rotational atherectomy, IVL, and ELCA in patients with moderate-to-severe calcified coronary lesions. Procedural success, safety and 1-year clinical outcomes were similar across all techniques.8

Elderly patients (≥ 75 years), who often present with increased comorbidity and complex coronary anatomy, remain underrepresented in clinical trials and may experience higher procedural risk and higher long-term mortality.9 In this post-hoc analysis of the ROLLER COASTR-EPIC22 trial, we assessed the impact of age on outcomes of PCI for moderately to severely calcified coronary stenosis treated with contemporary plaque-modification techniques. Specifically, we compared stent expansion, procedural success, in-hospital complications and 1-year clinical outcomes between patients < 75 and ≥ 75 years of age. Exploratory analyses of individual PMT within age strata were performed but were not powered for formal between-technique comparisons.

METHODS

Study design and population

ROLLER COASTR-EPIC22 trial was a multicenter randomized trial (NCT04181268) conducted at 8 high-volume centers in Spain.10 Complete inclusion and exclusion criteria, as well as the randomization process and procedural details, have been previously described.11 Briefly, eligible patients had moderate-to-severe calcification estimated by coronary angiography, and culprit lesions of ST-segment elevation acute coronary syndromes were excluded. All patients gave therir prior written informed consent before participation. Included patients were randomized 1:1:1 to rotational atherectomy, IVL, or ELCA from July 2019 through December 2023.10,11

Stratification and endpoints

This study is a post-hoc age-stratified analysis. Patients were stratified by age in 2 groups: < 75 years (n = 118) and ≥ 75 years (n = 53). Comparisons within age subgroups are exploratory and should be viewed as descriptive rather than confirmatory.

The primary endpoint was stent expansion assessed by optical coherence tomography (OCT), calculated as minimal stent area divided by the mean reference lumen area, analyzed according to the intention-to-treat principle.11

The secondary endpoints included angiographic success (final Thrombolysis in Myocardial Infarction grade-3 flow, assessed at both < 20% and < 30% residual stenosis), procedural success (angiographic success without major perioperative complications), clinical success (procedural success without in-hospital major adverse cardiovascular events [MACE]), device success (defined as achievement of adequate plaque modification with the initial device without the need for a second advanced PMT), minimal stent area by OCT, and in-hospital complications.11

Major perioperative complications were defined as death, perforation, flow-limiting dissection, abrupt vessel closure, or stent thrombosis. MACE was defined as the composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, and definite/probable stent thrombosis.11

Procedures and imaging

Procedures have been previously described and followed latest European guideline recommendations.10 Pre- and post-PMT OCT imaging were recommended to characterize the lesion. Predilation with low-profile balloons was permitted to allow OCT catheter crossing prior to PMT. After plaque modification, drug-eluting stent implantation and optimization were performed, followed by the final mandatory OCT. OCT image acquisition and stent optimization protocols have been previously described.11

Rotational atherectomy, IVL and ELCA were performed according to current recommendations and device instructions, as previously described.6,12,13

Statistical analysis

The principal analyses were conducted in the intention-to-treat population. An additional analysis was performed in an as-treated fashion, based on the last PMT used. Continuous variables are expressed as mean ± standard deviation if normally distributed or median [IQR] otherwise, and categorical variables as counts and percentages. Between-group comparisons used the chi-square test or Fisher’s exact test for categorical variables and Student t test or Mann–Whitney U test for continuous variables. Noninferiority of IVL and ELCA vs rotational atherectomy for stent expansion was tested with a 1-sided t test against a prespecified noninferiority margin of −7%. This margin was adopted from the pivotal ROLLER COASTR-EPIC22 trial and was defined a priori by the steering committee as the smallest absolute difference in stent expansion considered clinically relevant, based on previous studies.11,14,15 Statistical significance was set at P < .05.10,11

Because this was an exploratory, post-hoc age-stratified analysis with a relatively small sample size in the elderly subgroup, no formal adjustment for multiple comparisons was applied. Given the large number of comparisons (2 age groups, 3 PMT and several procedural and clinical endpoints), conservative corrections such as Bonferroni would have markedly reduced statistical power and increased the risk of type II error. Instead, all effect estimates, 95% confidence intervals and exact P values are reported to allow readers to interpret the results with appropriate caution, and all subgroup findings are considered hypothesis-generating rather than confirmatory.

Given the low number of events, survival was assessed with Kaplan–Meier curves and log-rank tests. All statistical analyses were conducted using R version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria).

RESULTS

Patient allocation and baseline characteristics

A total of 171 patients were enrolled, of whom 118 (69%) were younger than 75 years (mean age, 66.8 ± 6.4 years; 79.5% male) and 53 (31%) were aged ≥ 75 years (mean age, 79.7 ± 3.7 years; 73.6% male). In patients < 75 years (n = 118), age was 66.8 ± 6.4 years (median, 68; IQR 64–71; range, 44–74), whereas in those ≥ 75 years (n = 53) age was 79.7 ± 3.7 years (median, 79; IQR 77–82; range, 75–89) (table S1 and figure S1).

Baseline clinical characteristics were broadly comparable between age groups, including rates of diabetes, hypertension, and prior revascularization. However, older patients had a lower prevalence of active smoking (15.1% vs 33.6%; P = .02), lower body mass index (27.0 ± 3.8 vs 28.5 ± 4.3 kg/m²; P = .04), and lower haemoglobin (12.8 ± 1.8 vs 13.5 ± 2.0 g/L; P = .04). No significant differences were observed in left ventricular ejection fraction, basal creatinine or clinical presentation, although elderly patients showed a trend towards a more frequent presentation as acute coronary syndrome (table 1).

Table 1. Baseline clinical characteristics

Angiographic and procedural data

Target vessels and lesion characteristics, including severity and length of calcification, were comparable across age strata and treatment arms. Most procedures were performed via radial access (> 80%), and treatment allocation was well balanced across age strata. Procedural duration, sheath size, and use of ad hoc PCI did not differ by age. Angiographic and procedural details are summarized in table S2.

OCT findings

The optional pre-plaque modification OCT was performed in 39 of 118 patients < 75 years (33.1%) and in 20 of 53 patients ≥ 75 years (37.7%), with no significant difference between age groups (P = .67).

Final OCT runs were obtained in more than 75% of patients. OCT parameters of calcification, assessed by an independent central core laboratory, consistently demonstrated a heavy calcium burden across all cases, with no significant differences between age groups or treatment modalities. OCT findings are presented in table S3.

Primary and secondary endpoints

No significant differences in terms of final stent expansion, minimal stent area, or final residual stenosis were observed between groups (table 2, figure S2). Angiographic, procedural, and clinical success rates exceeded 90% (considering < 30% residual percent diameter stenosis) in both age groups and did not differ by technique (table 2, figure 1).

Table 2. Procedural outcomes and complications

Figure 1. Angiographic, procedural, and clinical success of each technique. Angiographic success defined as final Thrombolysis in Myocardial Infarction grade-3 flow with < 30% residual percent diameter stenosis. Procedural success was considered angiographic success without major perioperative complications. Clinical success was defined as procedural success without in-hospital major adverse cardiovascular events.

Among patients ≥ 75 years, mean stent expansion values were broadly similar across the 3 PMT, and no statistically significant between-technique differences were detected; however, 95%CI, were wide because of the small sample size in each subgroup (table S3). Exploratory analyses of mean differences in stent expansion between techniques yielded results that were directionally consistent with the overall ROLLER COASTR-EPIC22 trial but were clearly underpowered in this age-stratified cohort and should be interpreted as hypothesis-generating only (figure 2 and table S4).

Figure 2. One-year MACE-free survival. Kaplan-Meier curves showing 1-year freedom from MACE in the intention to-treat population. MACE was defined as the composide endpoing of cardiac death, target vessel myocardial infarction, target lesion revascularization, stent thrombosis. MACE, major adverse cardiovascular events.

Overall, device success rate was 88.3% overall and was similar by age: < 75 (89.7%) vs ≥ 75 years (85.7%); P = .76. The causes of crossover differed by device: as in the pivotal trial, in the rotational atherectomy arm most crossovers were prompted by inadequate lesion dilation after atherectomy, whereas in the IVL and ELCA arms the primary driver was inability to cross the lesion with the dedicated balloon or laser catheter (figure S3 and table S5). In-hospital complication rates (perforations, bleeding, death) were low and balanced by age (table 2).

In 1-year follow-up (table 3, figure 2), patients aged ≥ 75 years had a markedly higher rate of MACE than those < 75 years (11.3% vs 1.7%; P = .01). All-cause mortality was also greater in the older cohort (9.4% vs 0.9%; P = .01).

Table 3. One-year event rates

Although less frequent, each individual component of the composite endpoint was numerically higher in patients ≥ 75 years without reaching statistical significance: cardiac death (11.3% vs 0%; P = .1), target vessel myocardial infarction (3.8% vs 0%; P = .1), target lesion revascularization (3.8% vs 0.8%; P = .23), target vessel revascularization (7.5% vs 1.7%; P = .08) and stent thrombosis (3.8% vs 0%; P = .10).

In a multivariable logistic regression including age ≥ 75 years, anemia, acute coronary syndrome presentation and renal dysfunction, age ≥ 75 years remained the strongest predictor of 1-year endpoints. For MACE, age ≥ 75 years was associated with an adjusted OR, 7.4 (95%CI, 1.5–53.9; P = .02), whereas none of the other covariates showed a clear independent association with the composite endpoint. For all-cause mortality, the adjusted OR for age ≥ 75 years was 10.7 (95%CI, 1.5–218.7; P = .04) and none of the other covariates demonstrated a clear independent effect. These findings are presented in table S6 and figure S4.

DISCUSSION

In this post-hoc age-stratified analysis of the ROLLER COASTR-EPIC22 trial and its 1-year follow-up, we observed that the overall safety and efficacy of PMT appeared consistent across age groups. However, at 1 year older patients experienced significantly higher rates of MACE (11.3% vs 1.7%; P = .01) and all-cause mortality (9.4% vs 0.9%; P = .01) despite comparable in-hospital complication rates.

After adjustment for anemia, acute coronary syndrome presentation, and renal dysfunction, age ≥ 75 years remained associated with higher adjusted odds of both 1-year MACE and all-cause mortality. None of the adjustment covariates demonstrated a clear independent effect, suggesting that unmeasured factors closely related to aging, such as frailty, are likely to account for much of the excess risk observed in older patients.

Randomized evidence directly comparing contemporary PMT in calcified coronary disease remains scarce. The ROLLER COASTR-EPIC22 trial was the first trial to randomize patients among rotational atherectomy, IVL, and ELCA.10 Previous device-specific studies and registries have demonstrated the feasibility of each technique, but none had evaluated all 3 within a single randomized framework.16-18

Coronary calcium is independently associated with long-term mortality risk, and age is not only a key predictor of coronary calcification but also an independent predictor of MACE, regardless of calcium burden.19 Nevertheless, elderly patients are underrepresented in PMT studies, leaving limited evidence to guide the choice of the optimal PMT strategy. Regarding rotational atherectomy, there is little evidence in elderly patients, but retrospective data suggests similar success and in-hospital complication rates compared with younger individuals.20 Similarly, the BENELUX-IVL prospective registry demonstrated the safety profile and technical success of IVL in patients aged ≥ 80 years.21 ELCA, however, has not been specifically studied in the elderly population.

Selecting elderly patients for revascularization requires balancing benefits and risks. Comorbidities (anemia, chronic kidney disease, acute coronary syndrome) and limitations in physiological reserve increase complexity and may reduce revascularization uptake in this population.22,23 Our findings support that chronological age alone should not preclude revascularization, as PMT appeared effective and safe when performed by experienced operators, regardless of age. These results, however, should be interpreted cautiously given the limited sample size and exploratory, post-hoc nature of the age-stratified analysis. The importance of operator experience in PMT for complex scenarios has been highlighted by the CRATER trial program, which evaluated rotational atherectomy in patients with chronic kidney disease and severely calcified lesions and reported high procedural success but also substantial perioperative and long-term event rates, largely reflecting the extreme baseline risk of this population.24,25

Notably, our analysis suggests no excess perioperative complications in older adults, although the study was not powered for subgroup comparisons and 95%CI, were wide, particularly in the elderly ELCA subgroup. We advocate for meticulous patient selection, based on preoperative risks and comorbidities; however, PMT should be used when necessary for adequate lesion preparation to maximize stent expansion and avoid suboptimal implantation, a known driver of adverse clinical events.

In our cohort, elderly patients achieved similar procedural success, stent expansion and in-hospital safety outcomes vs younger patients yet experienced a markedly higher rate of 1-year MACE and all- cause mortality. This pattern is consistent with the e-ULTIMASTER and MOSCA FRAIL trials, in which frailty, rather than age per se, emerged as the main determinant of adverse outcomes in older adults undergoing PCI.26,27 Taken together, these data support that revascularization decisions in elderly patients should not rely exclusively on chronological age, but should incorporate assessment of frailty, functional capacity and comorbidity to individualize the benefit–risk balance of an invasive strategy. The lack of formal frailty indices in our study therefore represents an important limitation. Future trials in elderly patients undergoing complex PCI should prospectively integrate standardized frailty tools to better guide patient selection and tailor treatment.

In the subset of patients with available baseline OCT, we did not observe relevant differences in calcium burden or morphology nor in angiographic severity or extent of disease, between patients < 75 and ≥ 75 years. This suggests that the underlying calcific process is biologically similar across age groups, even if it becomes clinically manifest at different ages, and is consistent with the comparable postoperative stent expansion and minimal stent area observed in both strata. Nevertheless, despite similar stent optimization, the ≥ 75-year group showed a numerically higher rate of definite/probable stent thrombosis and cardiovascular death at 1 year (3.8%), which is clinically meaningful in this context. As underexpansion alone is unlikely to fully explain these events, age-related factors such as greater comorbidity and frailty, a prothrombotic milieu and a reduced myocardial reserve, may have contributed to the excess risk observed in older patients, even after apparently adequate angiographic and OCT-guided results.

Contemporary randomized PMT trials (such as ROTAXUS, PREPARE-CALC, ISAR-CALC 2 or ECLIPSE ) enrolled patients with a mean age around 70 years, but none of them reported age-specific outcomes for those ≥ 75 years, limiting its applicability to older populations.28-32 Our analysis contributes to fill this knowledge gap suggesting procedural success and safety of PMT in the elderly. However, due to the nonprespecified nature of our analysis, these results should be considered hypothesis-generating. Future randomized studies should integrate objective frailty and functional measures and include sufficient follow-up to assess both procedural and long-term outcomes in this growing population.

Study limitations

This study has several limitations to consider. First, it was a post-hoc analysis and the findings should be regarded as hypothesis- generating rather than definitive. Second, because age stratification was not prespecified in the trial design, the study was not statistically powered for subgroup comparisons based on age, and the relatively small number of patients aged ≥ 75 years may limit the generalizability of the results.

Third, frailty status and functional capacity –both known to strongly influence outcomes in elderly patients– were not assessed, which limits the clinical granularity of the findings.

Fourth, the study was not powered to detect differences in clinical events and results should be interpreted cautiously due to the limited number of events.

Fifth, posttreatment OCT images were not available in slightly more than 20% of patients, with a higher proportion of missing studies in the ≥ 75-year group. This pattern of missing data may introduce selection bias, as patients without analyzable postoperative OCT could differ systematically from those with complete imaging, potentially limiting the internal validity and generalizability of the stent expansion findings, particularly in the elderly subgroup.

Sixth, randomization was based on angiographic calcification alone, without prior evaluation of lesion crossability or balloon dilatability, which could have impacted the need for secondary PMT. Indeed, some patients required a second PMT, complicating the interpretation of the intention-to-treat analysis, although complementary as-treated and per-protocol analyses were performed to mitigate this limitation. Additionally, not all patients underwent complete pre- and post-PCI OCT, which may have influenced both device selection and the assessment of stent expansion metrics.

Seventh, the 1-year follow-up provides only mid-term outcome data and does not address long-term endpoints such as stent durability or the need for target lesion revascularization. Lastly, the trial was conducted in high-volume centres by experienced operators, which may limit the applicability of these results to lower-volume settings or institutions with less experience in complex PCI and PMT.

CONCLUSIONS

In this age-stratified analysis of the ROLLER COASTR-EPIC22 trial, elderly patients undergoing PCI for calcified coronary lesions achieved similar procedural success, stent expansion, and in-hospital safety outcomes as younger patients. However, patients aged ≥ 75 years experienced significantly higher rates of MACE and all-cause mortality at 1 year (figure 3).

Figure 3. Central illustration. Senior-ROLLER: age-related outcomes of plaque modification in coronary stenosis. Procedural success, stent expansion, and major procedural complications were similar in patients < 75 and those ≥ 75 years; however, the 1-year MACE and all-cause mortality rates were higher in the elderly, which highlights the need for careful patient selection and individualized treatment strategies. BARC, Bleeding Academic Research Consortium; ELCA, excimer laser coronary atherectomy; IVL, intravascular lithotripsy; MACE, major adverse cardiovascular events; RA, rotational atherectomy.

DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

FUNDING

The ROLLER COASTR-EPIC22 trial was supported by an unrestricted grant from Fundación EPIC.

ETHICAL CONSIDERATIONS

This is a subanalysis of the ROLLER COASTR-EPIC22 trial (NCT04181268), which was approved by the institutional ethics committee at each participant center and conducted in full compliance with the principles outlined in the Declaration of Helsinki. The authors confirm that written informed consent was obtained from all participants before enrolment.

Sex and gender aspects were considered according to the Sex and Gender Equity in Research (SAGER) guidelines.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

Artificial intelligence was not used in this manuscript.

AUTHORS’ CONTRIBUTIONS

J. Vila-García and M. Basile contributed equally to the manuscript and share first authorship. J. Vila-García and M. Basile contributed equally to several phases of the study, including conception and design, and acquisition, analysis and interpretation of the data. In addition, J. Vila-García contributed to the drafting of the original manuscript and to the writing and revision of the final version, while M. Basile was primarily responsible for the critical review of the article. A. Gómez-Menchero, J. Caballero-Borrego, B. Rivero- Santana, G. Galeote, I.J. Amat-Santos, S. Jiménez-Valero, G. Miñana, S. Ojeda, A. Gonzálvez-García, D. Tébar-Márquez, S. Camacho- Freire, J. Zubiaur, R. Ocaranza-Sánchez and A. Domínguez participated in the acquisition of the data and in the review and editing of the final text. A. Jurado-Román and R. Moreno participated in the conception and design of the study, in the acquisition, analysis and interpretation of the data, in the drafting, review, editing and approval of the final manuscript, and in the overall supervision of the project. A. Jurado-Román was responsible for funding and administration. All authors approved the final version of the manuscript.

CONFLICTS OF INTEREST

S. Ojeda and R. Moreno are associate editors of REC: Interventional Cardiology; the journal’s editorial procedure to ensure impartial handling of the manuscript has been followed. A. Jurado-Román is a proctor for Abbott, Boston Scientific, World Medica, and Philips; has received consulting fees from Boston Scientific and Philips; and has received speaker fees from Abbott, Boston Scientific, Shockwave Medical, Philips, and World Medica. S. Ojeda has received consulting fees from Medtronic and Edwards Lifesciences; and has received speaker fees from Abbott, Boston Scientific, Philips, and World Medical. All other authors report no relationships relevant to the contents of this article to disclose.

ACKNOWLEDGMENTS

We thank the ROLLER COASTR-EPIC22 trial investigators, coordinators, and participating patients for their dedication.

SUPPLEMENTARY DATA

REFERENCES

INTRODUCTION

Chronic total occlusions (CTO) are common among patients undergoing coronary angiography and represent one of the most technically demanding scenarios for percutaneous coronary intervention (PCI). Although contemporary CTO PCI programs achieve high success rates,1 these procedures frequently require prolonged fluoroscopy time, dual arterial access,2,3 and sustained patient immobility. In addition, ischemia-related chest discomfort may occur during complex procedural strategies.4,5

Anxiety is common in patients undergoing coronary procedures in the cath lab and may contribute to procedural discomfort and the need for pharmacologic sedation or analgesia.6-8 In routine practice, premedication and intraoperative administration of benzodiazepines or opioids are often used to mitigate anxiety and pain; however, their benefits are modest, and pharmacologic strategies and their use varies across centers.9 CTO PCI may be particularly associate with anxiety due to its typical duration, access strategy, and potential for procedural chest pain.

Virtual reality (VR) is an immersive audiovisual distraction strategy that can reduce procedural pain and anxiety across clinical settings. A systematic review demonstrated that VR-based distraction is effective for pain reduction in multiple procedural contexts.10

In interventional cardiology, early evidence suggests feasibility and potential benefit of VR during procedures performed under conscious sedation, including transcatheter aortic valve implantation and atrial fibrillation ablation.11,12 However, there are no randomized data evaluating VR during CTO PCI, a setting in which nonpharmacologic anxiolysis could be particularly valuable.

The ReViCTO trial was designed to test whether VR use during elective CTO PCI reduces the maximum level of patient-reported procedural anxiety vs usual care. Secondary endpoints included procedural pain, the use and dose of intraoperative anxiolytic or analgesic drugs, and patient satisfaction with the VR intervention. Figure 1 summarizes the main findings.

Figure 1. Central illustration. ReViCTO trial overview and main findings. Elective CTO PCI is a prolonged, technically complex procedure frequently associated with patient anxiety and discomfort. In the ReViCTO randomized trial (N = 59), patients were assigned to immersive audiovisual distraction using VR goggles (n = 31) or usual care (n = 28). VR use was feasible and well tolerated but did not significantly reduce peak procedural anxiety (VAS 0–10) or pain or intraoperative sedative or analgesic requirements vs usual care; 80.6% of VR patients reported willingness to use VR again in a future intervention. CTO, chronic total occlusion; PCI, percutaneous coronary intervention; VAS, visual analogue scale; VR, virtual reality.

METHODS

Trial design and oversight

The ReViCTO trial is an investigator-initiated, single-center, randomized, controlled, open-label, superiority trial with 2 parallel groups comparing immersive VR goggles vs usual care during elective CTO PCI. The study received no external funding. The rationale and full trial design have been published previously.13

The trial was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines. The protocol was approved by the Clinical Research Ethics Committee of Hospital Clínico Universitario de València on 28 February, 2022, and all patients gave their prior written informed consent. The trial was registered at ClinicalTrials.gov (NCT05458999).

Participants

Adults (age > 18 years) scheduled for elective CTO PCI at Hospital Clínico Universitario de València were screened for eligibility. Key exclusion criteria were any condition precluding VR use, such as significant visual impairment, dementia, language barrier (inability to communicate fluently in Spanish or English), or other circumstances preventing safe use of the headset. Eligibility criteria were prespecified in the protocol publication.13

Randomization and trial procedures

Patients were randomized in a 1:1 ratio to the VR group or the control group using computer-generated permuted blocks to reduce the risk of imbalance in group sizes in a small trial.14 Allocation concealment was implemented via a web-based application that generated a unique trial identification number and assigned treatment arm after enrollment, preventing post-randomization modification or deletion. Due to the nature of the intervention, no blinding was applied to participants, operators, or outcome assessors.

CTO PCI was performed according to contemporary clinical practice by an experienced CTO team. Pharmacologic management of anxiety and pain was not protocolized and was left to the discretion of the primary operator in both groups. Specifically, morphine chloride and/or midazolam could be administered on demand during the procedure according to observed or reported anxiety or pain, in accordance with the trial protocol.

Interventions

Virtual reality group

A commercially available head-mounted display (Oculus Quest 2, Meta Platforms, United States) was used. Participants viewed the documentary series Our Planet via a video-streaming application (Netflix) in a virtual “theater” environment, starting with episode 1 with sequential autoplay thereafter, as specified in the protocol. The headset was applied before arterial puncture and was maintained throughout the intervention unless the patient requested removal or a serious complication occurred. Patient status was monitored at regular intervals during the procedure.

Control group

Participants assigned to control underwent CTO PCI under usual care without VR goggles.

Outcomes

The prespecified primary endpoint was the maximum level of anxiety perceived by the patient during the procedure, assessed immediately after the procedure and before leaving the cath lab using a visual analogue scale for anxiety (VASa). Secondary endpoints included maximum patient-perceived pain during the procedure (VASp), the use and total dose of intraoperative anxiolytic or analgesic drugs (midazolam and morphine chloride), procedure-related nausea or dizziness, and patient satisfaction with the VR intervention, including willingness to use VR again. Endpoint definitions and timing of assessment followed the protocol publication.

For analysis, VAS scores were treated as numeric ratings ranging from 0 (none) to 10 (worst), consistent with the trial questionnaires and the observed data range. Baseline angina-related health status was measured using the Seattle Angina Questionnaire (SAQ) to contextualize symptom burden.15

Data collection and management

Demographic characteristics, medical history, comorbidities, baseline symptom status (including SAQ), and procedural characteristics (arterial access strategy, procedure duration, fluoroscopy time, and radiation dose metrics) were collected from institutional electronic health records and procedure reports, supplemented by direct patient interview when necessary. Immediately after completion of CTO PCI, a trained study nurse administered the postoperative questionnaire and recorded VAS anxiety and pain, as well as nausea, dizziness, and satisfaction items. Intraoperative administration of morphine and midazolam and their total doses were recorded contemporaneously by the study nurse.

Data were entered into a dedicated electronic database incorporating range checks for numeric variables and duplicate checks for hospital identifiers and stored on a restricted-access workstation as described in the protocol.

Sample size estimation

The target sample size (58 patients, 29 per group) was calculated based on the primary endpoint, assuming a common standard deviation of 2.7 points for VAS anxiety and aiming to detect an absolute between-group difference of at least 2 points with a 2-sided alpha of 0.05 and 80% power. The standard deviation assumption was informed by prior cath lab anxiety studies.9,16

Statistical analysis

Continuous variables are expressed as mean (standard deviation, SD) or median (interquartile range, IQR) as appropriate (for the primary endpoint and Japan Chronic Total Occlusion (J-CTO) score, both measures are reported to allow comparison with sample size assumptions and to account for non-normal distribution). Categorical variables as counts and percentages. Between-group comparisons were performed using the Student t test for normally distributed continuous variables and the Mann–Whitney U test otherwise; categorical variables were compared using Fisher’s exact test or the chi-square test, as appropriate. Post hoc, we performed an analysis of covariance (ANCOVA) model with VASa as the dependent variable and treatment group as the main effect, adjusting for baseline anxiety. As a sensitivity analysis, we additionally adjusted for intraoperative opioid and benzodiazepine administration. Finally, to address the randomization imbalance in angiographic complexity, a multivariable linear regression analysis was conducted with maximum procedural anxiety as the dependent variable, adjusting for baseline anxiety and the J-CTO score. All tests were 2-sided, with a significance threshold of P < .05. Analyses were performed using R (V. 4.3.2, R Foundation for Statistical Computing, Austria). Reporting followed CONSORT guidelines for trial conduct and prespecified analyses (checklist in the supplementary data).17

RESULTS

Patients

Between 1 March 2022 and 23 October 2025, a total of 119 scheduled CTO PCI were performed. Fifteen patients declined the use of the headset, and in 44 cases the VR device was not available. One patient was excluded due to visual impairment (blindness). Overall, 59 patients were randomized to VR goggles (n = 31) or usual care (n = 28), as shown in figure 2.

Figure 2. Study flow diagram. CTO PCI, percutaneous coronary intervention for chronic total occlusion; VR, virtual reality.

Enrolment was prospective; however, randomization was contingent on operational availability of the VR system. Early in the study, a single trained investigator was responsible for device preparation and operation, so randomization could only occur when this investigator was present in the cath lab (eg, during vacations or other clinical/research commitments). From June 2023 onward, a second investigator was trained, increasing coverage. In addition, the VR system was out of service for approximately 2 months due to changes in the required internet infrastructure. Importantly, nonrandomization during these periods was driven by logistical constraints rather than patient characteristics.

Baseline characteristics

Baseline clinical characteristics were broadly similar between groups. Median age was 67 [60;70] years in the VR group and 60 [58;66] years in the control group, and most participants were men (29 [93.5%] vs 26 [92.9%]). The prevalence of hypertension (51.6% vs 60.7%) and diabetes (41.9% vs 46.4%) was comparable; dyslipidemia was numerically less frequent in the VR group (58.1% vs 82.1%). Baseline anxiety assessed before entering the cath lab was moderate and did not differ significantly between groups (VAS anxiety: mean ± SD, 3.35 ± 3.10 vs 4.21 ± 3.05; P = .289; median [IQR], 2 [0; 6] vs 5 [2; 6]). Baseline pain was minimal in both groups (VAS pain baseline: 0.06 ± 0.36 vs 0.00 ± 0.00; P = .346; median [IQR], 0 [0 to 0] in both). Baseline angina-related health status was similar. The SAQ score was 52.4 [36.3; 64.3] in the VR group and 50.0 [44.0; 64.3] in the control group (P = .475), as shown in table 1.

Angiographic complexity differed between groups. The J-CTO score was higher in the VR group (mean ± SD, 3.10 ± 1.11; median [IQR], 3 [2; 4]) than in the control group (2.32 ± 1.36; median [IQR], 2 [1; 3]) (Student t test P = .019; Mann-Whitney U test P = .040).

Procedural characteristics and clinical outcomes

The distribution of procedural approach (antegrade, retrograde, or hybrid) was similar between groups (P = .826). Procedural duration, fluoroscopy time, radiation dose-area product, and contrast volume were not significantly different between groups, although radiation exposure tended to be higher in the VR group.

Technical success was achieved in 25 of 31 patients (80.6%) in the VR and 25 of 28 patients (89.3%) in the usual care group (P = .477). Procedural complications occurred in 4 of 31 patients (12.9%) in the VR group and 4 of 28 patients (14.3%) in the control group (P = 1.00) (table 1).

Table 1. Baseline characteristics, lesion and procedural characteristics

Primary endpoint

The primary endpoint (maximum procedural anxiety; [VASa]) and key secondary endpoints (maximum procedural pain [VASp] and intraoperative drug administration) were available for all randomized participants.

Maximum procedural anxiety did not differ significantly between groups. Mean VASa was 3.23 ± 2.78 with VR and 3.75 ± 2.77 with usual care (mean difference, −0.52 points; 95% confidence interval (95%CI), −1.97 to 0.92; Student t test P = .472). Median [IQR] values were 4 [0; 5] and 4 [2; 6], respectively. Because the VASa distribution was skewed, results were consistent using the Mann–Whitney U test (P = .379) (figure 3, table 2 and table S1).

Figure 3. Patient-reported procedural anxiety and pain, and intraoperative drug use. A: maximum procedural anxiety assessed immediately after the procedure using a visual analogue scale for anxiety (VASa; 0–10). B: maximum procedural pain assessed using a visual analogue scale for pain (VASp; 0–10). C: total intraoperative dose (mg) of midazolam and morphine by treatment group; zero values indicate no drug administration. In panels A and B, dots represent individual patients; the right-side estimation plot shows the mean between-group difference (VR minus usual care) with its 95% confidence interval. P values correspond to prespecified between-group comparisons. VAS, visual analogue scale; VR, virtual reality.

Table 2. Endpoints and safety

In a post hoc ANCOVA adjusting for baseline anxiety, VR was not associated with lower peak procedural anxiety (adjusted mean difference, −0.21; 95%CI, −1.62-1.20; P = .773). Results remained consistent after additional adjustment for intraoperative morphine and midazolam dose (table S1 and table S2).

Given the significantly higher angiographic complexity in the VR group, a sensitivity analysis was conducted using multivariable linear regression. After adjusting for J-CTO score and baseline anxiety, the effect of VR on procedural anxiety remained non-significant (adjusted coefficient -0.40; 95%CI, -1.81 to 1.02; P = .576). In this model, procedural complexity was not independently associated with patient-reported anxiety (P = .370); see table S1.

Secondary endpoints

VASp was similar in the 2 groups: 3.68 ± 3.39 with VR and 3.64 ± 2.33 with usual care (mean difference, 0.03; 95%CI, −1.50-1.57; P = .964). Median [IQR] values were 4 [1; 6] and 4 [2; 5], respectively (P = .777).

Intraoperative pharmacologic treatment did not differ between groups. Morphine was administered to 14 of 31 patients (45.2%) in the VR group and 13 of 28 (46.4%) in the control group (P = 1.00). Total morphine dose (including zero valus for nonuse) was 2.74 ± 3.61 mg and 2.00 ± 2.71 mg, respectively (P = .379). Midazolam was administered to 2 of 31 patients (6.5%) in the VR group and 3 of 28 (10.7%) in the control group (P = .661), with total midazolam doses of 0.29 ± 1.19 mg and 0.50 ± 1.95 mg, respectively (P = .617) (figure 3 and table 2).

Safety and acceptability

Symptoms potentially attributable to VR were uncommon. Nausea occurred in 1 patient (3.2%) in the VR group and in no patients in the control group (P = 1.00). Dizziness occurred in 1 patient (3.2%) in the VR group and in no patients in the control group (P = 1.00).

Among patients assigned to VR, 25 of 31 (80.6%) reported that they would be willing to use a relaxation video again during a future intervention; 5 (16.1%) would not, and 1 (3.2%) was uncertain.

DISCUSSION

We conducted a randomized trial to evaluate whether VR-based audiovisual distraction during elective CTO PCI can improve the patient experience. Several key findings emerge. First, VR did not meaningfully reduce patient-reported peak procedural anxiety, and pain outcomes were similarly neutral, arguing against a clinically relevant anxiolytic or analgesic effect with the intervention as delivered. Second, VR did not reduce the use of intraoperative opioid or benzodiazepine requirements, suggesting limited incremental benefit beyond contemporary usual care in the cath lab. Third, VR implementation appeared feasible and was not associated with signals of procedural harm, with overall procedural outcomes remaining comparable despite an imbalance toward greater angiographic complexity in the VR group. Finally, acceptability was generally high among patients assigned to VR, supporting its role as a patient-centered option for selected individuals even when average effects on anxiety are modest.

Interpreting the neutral result in the context of prior interventional cardiology VR trials

Several factors may explain the absence of a measurable anxiolytic effect in ReViCTO. First, peak procedural anxiety levels were relatively low, leaving limiting the potential for improvement and increasing the likelihood of a floor effect. A similar pattern has been observed in contemporary minimally sedated structural interventions, in which overall anxiety burden is modest and VR has not consistently produced detectable differences on global assessments.18

Second, anxiety and pain were assessed immediately after the procedure as a single recalled measure of peak intensity. Although pragmatic and consistent with the study protocol, this approach relies on retrospective recall and may underestimate brief, procedure-specific peaks of discomfort that are particularly relevant in CTO PCI, such as arterial puncture, prolonged immobility, complex device manipulation, or episodes of ischemic chest pain.19 Consequently, any benefit limited to these discrete high-stress intervals may have been diluted when summarized as a single postprocedural peak value.

Third, the VR content in the ReViCTO consisted of passive content (documentary viewing). Across procedural settings, the magnitude of VR’s effect appears to depend on how strongly the experience captures attention and induces relaxation. Interventions incorporating guided relaxation, hypnosis-based modules, or interactive elements have more consistently demonstrated larger and more reproducible effects than passive viewing alone.20-22

In the context of the broader interventional cardiology literature, the neutral effect of VR on peak intraoperative anxiety in ReViCTO is therefore less surprising. Existing cath lab and structural heart studies suggest that observable benefit depends on when VR is delivered, which patients are targeted, particularly those with higher baseline anxiety, and how outcomes are measured. In transcatheter aortic valve implantation (TAVI), early randomized studies reported lower VAS-based procedural anxiety, supporting feasibility and a potential anxiolytic effect.11 In contrast, a larger minimalistic TAVI randomized study found improvements in state anxiety (State-Trait Anxiety Inventory, state scale [STAI-S]) and perceived procedure duration, yet less consistent effects on VAS-based anxiety or pain, underscoring the influence of measurement instruments on signal detection.23 Evidence from coronary procedures is similarly nuanced. In the VR InCard program, which targeted patients with elevated preoperative anxiety and incorporated structured preprocedural sessions, the primary analysis was neutral but adjusted analyses suggested modest reductions, with heterogeneity by clinical context.24,25 Similarly, a randomized trial conducted before coronary angiography reported anxiety reduction using questionnaire-based assessments rather than a single recalled postoperative peak rating.26 Collectively, these data support the interpretation that VR may be most effective when targeted to patients with higher baseline anxiety, delivered during anticipatory or discrete high-stress phases, and evaluated using instruments sensitive to global state anxiety, rather than relying solely on a single recalled peak score.22,27

Pharmacologic co-intervention and post hoc adjustment

A key pragmatic feature of ReViCTO was that background anxiolysis and analgesia were not protocolized, reflecting real-world practice in the cath lab where conscious sedation and intraoperative comfort measures are typically individualized. This approach is consistent with contemporary cath lab randomized studies evaluating patient comfort under usual care conditions.28,29 In the final dataset, intraoperative morphine and midazolam use were similar, and dose distributions did not differ materially. To align with current analytic recommendations, we performed a post hoc ANCOVA adjusting peak anxiety for baseline anxiety, an approach that can improve precision when baseline values are prognostic.30 Baseline anxiety was strongly associated with peak anxiety, while VR assignment was not (adjusted VR effect approximately -0.32 VAS points; P = .64). Adding opioid and benzodiazepine doses did not materially change the VR estimate, supporting that the neutral primary result is unlikely to be explained by baseline imbalance or differential pharmacologic rescue. Baseline anxiety was higher in the usual care group; adjusted analyses yielded consistent findings.

Feasibility, tolerability, and patient-center implementation

From a feasibility standpoint, VR use in CTO PCI appeared safe and compatible with the cath lab environment, with nausea and dizziness reported rarely and no signal suggesting increased procedural instability. The practical challenge was tolerability during long procedures: early discontinuation of the headset occurred in 9 VR patients, which is consistent with broader evidence that fully immersive head-mounted displays can trigger discomfort or cybersickness in a minority of users, particularly with extended exposure.31 Implementation studies further indicate that device-related factors—such as physical interference, usability barriers, and the need for individual tailoring—can influence both uptake and sustained use, supporting a selective rather than universal deployment strategy.32 These observations support a patient-center approach: VR may be most useful when offered to patients with higher baseline anxiety, a clear preference for audiovisual distraction, or anticipated prolonged immobility, and when focused around discrete high-stress phases. Preoperative counseling remains essential with VR serving as a complementary, rather than substitutive, strategy.

Limitations

This trial has limitations that should be considered. First, it was a single-center, open-label study and subjective outcomes may be susceptible to reporting buas; however, randomization, standardized outcome collection, and consistently neutral findings across patient-reported outcomes and medication use make a major bias-driven effect unlikely. Second, recruitment was not consecutive and 12.6% of eligible patients declined participation, which may limit generalizability; nonetheless, this also reflects real-world acceptability of a wearable intervention, and the decliner rate is transparently reported. Third, anxiety and pain were assessed as a single postoperative peak rating rather than repeated measures during predefined high-stress phases; this approach was identical in both groups, and recalled peak experience remains clinically relevant for satisfaction and willingness to undergo future procedures. Fourth, anxiolysis and analgesia were not protocolized and were operator-directed, potentially attenuating any incremental benefit of VR. Nevertheless, this pragmatic design improves applicability and bailout medication was systematically recorded. Fifth, VR content was passive and exposure time likely varied due to early discontinuation; the intention-to-treat analysis therefore estimates the real-world effect of offering VR. Finally, although angiographic complexity (J-CTO score) was higher in the VR group, multivariable analyses indicated this imbalance did not explain the neutral anxiety results and complexity was not a significant predictor of distress in this cohort. Benzodiazepine amnesia may attenuate recall; midazolam use was low and balanced.

CONCLUSIONS

In this randomized trial of patients undergoing elective CTO PCI, although immersive VR was feasible and well tolerated, it did not reduce patient-reported peak intraoperative anxiety or pain, or the need for intraoperative morphine or midazolam vs usual care.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

The protocol was approved by the Clinical Research Ethics Committee of Hospital Clínico Universitario de València (28 February, 2022), and all participants gave their prior written informed consent. Sex distribution is reported, and reporting adhered to SAGER guidelines to mitigate potential sex- and gender-related bias.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

Generative artificial intelligence was used to support language editing and formatting of the revised manuscript. No artificial intelligence tools were used to analyze study data. All content was reviewed and approved by the authors, who take full responsibility for the manuscript.

AUTHORS’ CONTRIBUTIONS

A. Fernández-Cisnal and B. Silla conceived the study and designed the trial. A. Fernández-Cisnal, B. Silla, C.E. Vergara-Uzcategui, J.M. Ramón, E. Valero, and C. Romero Menor contributed to patient inclusion and data acquisition. A. Fernández-Cisnal performed the statistical analyses and drafted the manuscript. B. Silla, C.E. Vergara- Uzcategui, J.M. Ramón, E. Valero, C. Romero Menor, J. Núñez, V. Bodí, and G. Miñana critically revised the manuscript for important intellectual content. All authors approved the final version and agreed to be accountable for all aspects of the work.

CONFLICTS OF INTEREST

None declared.

SUPPLEMENTARY DATA

REFERENCES