Percutaneous treatment of the left main coronary artery in older adults. Impact of frailty on mid-term results

INTRODUCTION

Calcified coronary nodules (CN) represent the most complex type of calcified lesion for percutaneous coronary intervention (PCI), as they are associated with worse angiographic and clinical outcomes after drug-eluting stent (DES) implantation.1-8

Intravascular lithotripsy (IVL) has shown favorable results in this context.9 However, stent implantation after IVL may not always be the best treatment option due to suboptimal stent expansion and severe malapposition in a non-negligible percentage of patients which, along with possible nodule protrusion through the stent struts, may be associated with an increased need for new target lesion revascularization (TLR), and a higher rate of major adverse cardiovascular events (MACE).10-12

Drug-eluting balloons (DEB) have demonstrated to be a safe and effective alternative to DES in various settings, especially in those in which stenting is associated with worse outcomes, such as small vessel disease and in-stent restenosis.13 Therefore, their use has increased exponentially in recent years and has expanded to other lesion types.14

In the specific setting of calcified lesions, there are some data on the safety and efficacy profile of DEB after an adequate plaque modification.15-19 Moreover, in this setting, DEB have shown similar clinical outcomes with favorable late lumen loss rate compared with DES.20-23

Despite the increasing use of DEB in calcified lesions, evidence on the safety and efficacy profile of CN treatment is lacking. In this setting, where the risj of suboptimal stent expansion and apposition—and the consequent likelihood of MACE— is higher,24 a leave-nothing-behind strategy using DEB following optimal plaque modification technique may be a more appealing approach.Therefore, our aim is to compare the safety and efficacy profile of the use of DEB or DES after IVL in CN within the context of a randomized controlled trial.

METHODS

Patients and study design

The DEBSCAN-IVL trial is an investigator-initiated, multicenter, open-label, prospective, randomized, controlled clinical trial including 10 high-volume centers.

Patients will be randomized to receive a DEB or a DES after optimal treatment with IVL if they meet all the inclusion criteria and have no exclusion criteria. Inclusion criteria are age ≥ 18 years with a clinical indication for PCI (presenting with chronic or acute coronary syndromes) in a CN-induced de novo severe coronary lesion (confirmed via intracoronary imaging) in vessels with a reference diameter between 2.5 mm and 4.0 mm. Patients who meet at least 1 of the following conditions will be excluded: inability to provide oral and written informed consent or unwillingness to return for systematic angiographic follow-up; pregnant or breastfeeding patients; cardiogenic shock or cardiac arrest at the time of the index procedure; inability to maintain dual antiplatelet therapy for at least 1 month; life expectancy < 1 year; index lesion located at the left main coronary artery or in an aorto-ostial location; target lesion previously treated with stents or DEB or with high thrombus burden at the time of PCI (Thrombolysis In Myocardial Infarction [TIMI] thrombus grade ≥ 3).

Patients who meet all the inclusion criteria and none of the exclusion criteria will be treated with IVL and randomized to receive final therapy with DEB or DES. Randomization will occur via a web-based system. The complete inclusion and exclusion criteria are shown in table 1, and the study flowchart in figure 1.

Table 1. Inclusion and exclusion criteria

Figure 1. Central illustration. Study design flowchart. CN, calcified coronary nodule; DEB, drug-eluting balloons; DES, drug-eluting stents; IVL, intravascular lithotripsy; OCT, optical coherence tomography; PCI, percutaneous coronary intervention.

Primary and secondary endpoints

The endpoint of this study is to evaluate and compare the safety and efficacy profile of DEB or DES as final treatment strategies for CN previously modified by IVL.

Co-primary endpoints will be the late lumen loss (LLL) and net luminal gain at 9 ± 1 months of angiographic follow-up, as assessed by an independent core laboratory, with a non-inferiority hypothesis between the 2 groups. LLL is defined as the difference between postoperative and follow-up minimal lumen diameter, whereas net gain is defined as the difference between follow-up and preoperative minimal lumen diameter, according to the latest Drug Coated Balloon Academic Research Consortium Consensus Document.25

Secondary endpoints of the study will include procedural, angiographic and clinical outcomes. Procedural endpoints will include the rate of crossover between treatment groups, angiographic success (defined as final TIMI grade-3 flow and a residual final percent diameter stenosis < 30% in the DEB group or < 20% in the DES group), device success (defined as angiographic success without crossover between treatment group), procedural success (defined as angiographic success without the occurrence of severe procedural complications, including cardiac death, target vessel perioperative myocardial infarction [MI], need for new clinically driven TLR, stent thrombosis [ST], stroke, flow-limiting dissection or vessel perforation). Angiographic endpoints will include the minimal lumen diameter measured immediately after the intervention and at the time of angiographic follow-up, the residual percent diameter stenosis at both timeframes, and the rate of binary restenosis, defined as a luminal diameter reduction o≥ 50% during follow-up.25 Secondary endpoints will include procedural adverse events (such as dissection, perforation, acute vessel occlusion, slow flow or no-reflow, and intraoperative thrombosis), major hemorrhagic events (classified as Bleeding Academic Research Consortium [BARC] type ≥ 3),26 and hemodynamic instability (requiring unplanned administration of vasopressors, inotropes, or ventricular support devices), cardiac death, target lesion-related MI (TL-MI), need for TLR, and ST, and MACE (defined as a composite of cardiac death, TL-MI, and TLR). TLR and ST are defined according to the Academic Research Consortium criteria.27 MACE and its components will be assessed during the index hospitalization and at 6-month, 1-year, and 2-year follow-up visits. Detailed endpoints definitions are shown in appendix S1.

Primary outcome assessment will be conducted by a central independent core laboratory. All medical data will be anonymized and stored, and confidentiality will be protected at any time in full compliance with the current legislation. The clinical events committee (CEC) and the independent core laboratory will be blinded to the treatment group. Secondary outcomes will be assessed via centralized angiographic analysis and structured clinical follow-up, either in person or via telephone, at scheduled time points.

Devices

• – IVL: Shockwave Balloon (Shockwave Medical, United States).
• – Optical coherence tomography (OCT) or intracoronary ultrasound (IVUS) system, based on availability at each participating center.
• – DEB: paclitaxel-eluting balloon (Pantera Lux, Biotronik, Switzerland)
• – DES: new-generation zotarolimus eluting stent (Onyx Frontier, Medtronic, United States).

Procedure

When a CN is suspected on coronary angiography, intracoronary imaging—preferably OCT, with IVUS as an alternative—will be performed to confirm the diagnosis. After confirmation of a CN in the target lesion, patients will be randomized on a 1:1 ratio to receive a DEB or a DES. Randomization will be stratified to ensure a balanced distribution of eruptive and non-eruptive nodules across both treatment groups. A CN (figure 2) will be defined as a calcified segment with an accumulation of protruding nodular calcification (small calcium deposits) with disruption of the fibrous cap (eruptive CN) or an intact thick fibrous cap (non-eruptive CN).28-30

Figure 2. Calcified nodule appearance on angiography (A), optical coherence tomography (eruptive [B] and non-eruptive [C]) and intravascular ultrasound (D).

All patients will be treated with IVL, using a balloon sized 1:1 to the vessel reference diameter. A minimum of 80 pulses per lesion is recommended. If the IVL balloon cannot cross the lesion, predilation with smaller balloons is permitted. Additionally, the use of adjuvant techniques such as rotational atherectomy or excimer laser coronary atherectomy will be allowed only when deemed necessary to facilitate IVL balloon crossing. Postdilation with a non-compliant balloon after IVL is recommended before proceeding with the final assigned treatment modality.

Once optimal lesion preparation has been achieved, defined as > 80% balloon expansion in 2 orthogonal projections with a balloon sized 1:1 to the vessel, patients will receive a DEB or a DES, according to their initial randomization. If a patient randomized to the DEB group experiences a flow-limiting dissection or exhibits a percent diameter stenosis > 50%, conversion to DES implantation will be permitted at the operator’s discretion. Similarly, any crossover from DES to DEB will be documented, along with the reasons for these procedural decisions.

It is recommended that the DEB reach the target lesion within 2 minutes, as drug loss may occur during transit.13 Thus, operators need to anticipate difficulties in reaching the target lesion (proximal coronary disease or tortuosity) and ensure optimal support prior to using the DEB. If difficulties in reaching the target lesion are anticipated, the use of guide extension catheters is recommended. The recommended DEB inflation time is 60 seconds.

The PCI will be performed according to current European Society of Cardiology (ESC) guidelines, including perio- and postoperative antithrombotic management.31,32 Patients should ideally receive dual antiplatelet therapy at least 2 to 4 hours prior to the PCI to ensure optimal platelet inhibition. In cases where this is not feasible, administration of IV antiplatelet agents, such as acetylsalicylic acid with or without cangrelor, immediately before the procedure is recommended.

Intracoronary imaging with either OCT or IVUS (the same imaging modality that was initially used) is recommended at the end of the procedure.

Angiographic analysis

Quantitative coronary imaging and intracoronary analysis of baseline and follow-up angiographies will be conducted by an independent central laboratory (Barcicore, Spain). At least 2 well-selected orthogonal views—free of foreshortening and side-branch overlap—focused on the target lesion are required after intracoronary nitroglycerine administration. These views should be obtained before treatment, after the intervention, and during follow-up angiography to ensure consistent angulation and enable accurate, reproducible measurements.

Follow-up

Post-PCI antithrombotic therapy will abide by the latest ESC clinical practice guidelines, considering the individual ischemic and bleeding risk profile of each patient.31,32 Regardless of the assigned treatment group (DEB or DES), a 6-month regimen of dual antiplatelet therapy (aspirin and clopidogrel) is recommended in patients with stable coronary artery disease, and a 12-month regimen of dual antiplatelet therapy (preferably using prasugrel or ticagrelor as a P2Y₁₂ inhibitor) in patients with acute coronary syndrome. For patients requiring chronic oral anticoagulation, the choice and duration of antithrombotic therapy will follow current guideline recommendations, with triple therapy (oral anticoagulant + aspirin + clopidogrel) limited to 1 month, whenever feasible. Electrocardiogram and troponin assessment will be performed 24 hours after the PCI. All patients will be discharged with a scheduled angiographic follow-up at 9 ± 1 months. OCT is recommended during this follow-up, especially if angiography suggests progression of coronary artery disease in the target lesion. In cases where angiography or intracoronary imaging indicates disease progression, but the percent diameter stenosis is < 90%, revascularization should be guided by ischemia and confirmed with a pressure guidewire. Clinical follow-up visits are scheduled at 12 and 24 months. Schedule of visits and data assessment throughout the study are shown in table S1.

Statistical analysis

The primary endpoint analysis will be performed by lesion and by intention-to-treat with a 1-sided Student t test with an alfa of 0.05 between the DES and the DEB group. A per-protocol analysis, including crossover cases, will also be conducted for sensitivity purposes. If the hypothesis of non-inferiority is confirmed, a superiority 2-sided analysis will be performed. Clinical endpoints will be analyzed on a per-patient basis.

Quantitative variables will be expressed as mean ± standard deviation if normally distributed, and as median with minimum and maximum values if they do not follow a normal distribution. Normality will be assessed using the Kolmogorov-Smirnov test. Qualitative variables will be described by their absolute values and frequencies, and will be expressed as absolute counts and percentages. A P < .05 will be considered statistically significant, and 95% confidence intervals (95%CI) will be reported for all main analyses. For comparisons of continuous variables between the 2 groups, the Student t test will be used if normality is confirmed, or the Mann-Whitney U test if non-parametric. For comparisons across > 2 groups, the ANOVA test or the Kruskal-Wallis test will be applied, as appropriate. Associations across categorical variables will be analyzed using the chi-square test or Fisher’s exact test when expected frequencies are small. Correlations between continuous variables will be explored using Pearson’s or Spearman’s correlation coefficient, depending on their distribution.

A multivariate analysis will be conducted using Cox proportional hazards regression with forward stepwise selection, including variables that are significantly associated with outcomes (or show a trend) in the univariate analysis. Kaplan-Meier curves will be generated for event-free survival, and differences will be assessed using the log-rank test.

Prespecified subgroup analysis

Subgroup analysis will be performed according to the following prespecified categories: type of calcified nodule (eruptive vs non-eruptive), age (< 75 vs ≥ 75 years), sex (male vs female), presence of diabetes mellitus (yes vs no), location of the calcified nodule within a true bifurcation lesion involving a side branch ≥ 2.5 mm (yes vs no), and clinical presentation (acute coronary syndrome vs chronic coronary syndrome). In addition, a prespecified OCT subgroup analysis will be performed in patients with available OCT imaging at both the end of the procedure and follow, including assessments of minimal lumen area (or minimal stent area in stented segments) and minimal lumen diameter.

Sample size calculation

The hypothesis is that DEB-PCI for CN is not inferior to state-of-the-art DES-PCI in terms of LLL and net luminal gain at the lesion. The sample size calculation was based on an expected LLL of 0.20 mm in the DES group, with a non-inferiority margin (delta) of 0.30 mm, a significance level (alpha) of 5%, and a statistical power of 80%. The estimate of LLL in the control group was derived from previous studies evaluating the same DES platform.33-35 Assuming a 20% attrition rate for angiographic follow-up, 64 patients per group (128 patients in total) will be required to provide adequate statistical power. The study is not powered for clinical endpoints, which will be considered exploratory and hypothesis-generating.

Organization and ethical concerns

The study protocol has been approved by the local ethics committees of all participant centers. Written informed consent will be obtained from all patients prior to enrollment. The DEBSCAN-IVL trial is an investigator-initiated study conducted in full compliance with Good Clinical Practice guidelines applicable to interventional and epidemiological research. The rights, safety, and well-being of all participants will be protected full compliance with the principles set forth in the Declaration of Helsinki, applicable EU legislation, and local legal requirements. Participant data will be handled confidentially and anonymously. The trial is registered at ClinicalTrials.gov (NCT06657833). The sponsor of the study is Fundación EPIC. The study is supported by unrestricted research grants from Fundación EPIC, Shockwave Medical, Biotronik, and Medtronic.

The steering committee serves as the primary decision-making body of the trial and bears full responsibility for its scientific and clinical conduct. A clinical events committee (CEC), composed of independent interventional cardiologists not participating in the study and blinded to treatment allocation, will adjudicate all clinical events and endpoints. The CEC will operate according to pre-specified definitions outlined in the study protocol and will remain blinded to the overall trial outcomes.

DISCUSSION

CN represent the most complex type of calcified lesion for PCI, as they are associated with the worst angiographic and clinical outcomes after DES implantation.1-8 Three main factors may contribute to these unfavorable results: the nature of the nodule per se, the plaque modification technique used, and the final revascularization strategy (DES or DEB). Although our understanding of the origin and behavior of calcified nodules has grown, it remains unclear which lesions are likely to respond favorably to PCI, and which are not. Eruptive CN, for instance, may be more amenable to initial modification, yet paradoxically, they have also been associated with higher rates of adverse clinical events during follow-up.29,36

Regarding plaque modification techniques, current evidence is limited. Rotational atherectomy (RA), while commonly used, is constrained by wire bias and frequently requires large burr sizes.2 Although orbital atherectomy might overcome some of these limitations, randomized data comparing it with other advanced plaque modification techniques are lacking.37 Balloon-based techniques, in contrast, may fail to cross severely stenotic nodular lesions but have the advantage of avoiding the wire bias inherent to atherectomy.

However, conventional or scoring/cutting balloons often prove insufficient to fully modify the depth of nodular calcium, and very high-pressure special balloons carry the risk of overstretching the usually normal opposite vessel wall causing perforation. In this context, IVL has emerged as a promising alternative, offering the most robust evidence to date for nodular plaque modification.29,38

Traditionally, stent implantation has been the standard definitive treatment for CN.23 However, stenting in nodular lesions frequently leads to suboptimal expansion and incomplete apposition, particularly at the shoulders of the nodule. Moreover, In these patients, TLR is often driven not by classic in-stent restenosis, but by late protrusion of the calcified nodule through the stent struts.10,11,39 These limitations have generated interest in a “leave nothing behind” strategy after effective plaque modification.

DEB have demonstrated to be safe and effective in various settings, particularly small vessel disease and in-stent restenosis, where DES implantation may be less favorable.13 Therefore, their use has grown significantly in recent years.14 In the context of calcified lesions, there are concerns that adequate drug-uptake may be compromised, but preliminary evidence suggests DEB may offer good outcomes after adequate plaque preparation.15-17 For instance, Ito et al.18 evaluated a total of 81 patients with de novo lesions treated with DEB, including 46 with calcified lesions. While LLL and restenosis appeared slightly higher in the calcified group, these differences were not statistically significant and did not translate into worse clinical outcomes at 2 years. Notably, 82% of these lesions were pre-treated with RA. Similarly, Nagai et al. reported a TLR rate of 16.3% in 190 severely calcified lesions treated with RA followed by DEB.19 Rissanen et al. found MACE rates of 14% and 20% at 12 and 24 months, respectively, in 82 complex de novo calcified lesions treated with DEB after RA and balloon predilation, with very low rates of clinically driven TLR.20 Furthermore, favorable findings have been reported by Shiraishi et al., including a subset of calcified nodules.16

Comparative studies have further explored DEB vs DES in calcified lesions. Ueno et al.21 conducted a single-center cohort study comparing the clinical outcomes of 166 severe calcified lesions treated with either DEB or DES after RA at a median follow-up of 3 years. The TLR rates were similar across the groups (15.6% vs 16.3%; P = .99), while LLL was significantly lower in the DEB group (0.09 mm vs 0.52 mm; P =.009). Iwasaki et al.22 compared 194 patients with de novo calcified lesions in non-small vessels the RA + DEB vs RA + DES strategies. There were no significant differences at 1 year in terms of MACE, cardiac death, myocardial infarction, TLR or hemorrhage.

Despite this data on the performance of DEB in calcified lesions, evidence on the safety and efficacy profile in the CN setting is lacking. However, given the high likelihood of suboptimal stent expansion and malapposition in this setting, which may lead to increased MACE risk,24 a metal-free strategy using DEB following optimal plaque modification seems to be an attractive and feasible approach.

Intracoronary imaging-guided PCI has been consistently associated with improved procedural outcomes and a reduction in major adverse cardiovascular events, including mortality, particularly in complex lesions.40 Intracoronary imaging plays a pivotal role in this context. Compared with conventional angiography, it provides a far more accurate assessment of coronary disease severity and plaque morphology.1 This is particularly relevant in calcified and complex lesions, where procedural planning and outcomes are significantly impacted by the detailed anatomical insights obtained. OCT, in particular, offers superior spatial resolution compared to IVUS, allowing for precise quantification of the calcium burden.28,41

In the case of CN, OCT enables accurate assessment of the plaque substrate and procedural results, including stent expansion and apposition, or in DEB-treated lesions, the extent of plaque modification.

The DEBSCAN-IVL trial will be comparing the safety and efficacy profile of DEB vs DES after lesion preparation with IVL in patients with CN, assessing both angiographic and clinical outcomes. Moreover, the trial will provide valuable information on the underlying plaque morphology and the response to different PCI strategies following the systematic use of intracoronary imaging. The central hypothesis of the study is that a DEB strategy, after IVL-based plaque modification in calcified nodules, is not inferior to DES implantation in terms of LLL and net gain, while potentially reducing the risk of long-term adverse events through improved biocompatibility and vessel healing. In addition, the analysis will be stratified according to nodule morphology, specifically differentiating eruptive vs non-eruptive CN, 2 entities that are thought to have distinct biological behavior and potentially different response to plaque modification and PCI.6,7,29,36 This stratified analysis may provide novel insights into the prognostic and therapeutic implications of nodule subtype and guide future individualized interventional strategies.

CONCLUSIONS

The DEBSCAN-IVL trial is an investigator-initiated, multicenter, open-label, prospective, randomized, controlled clinical trial designed to compare the safety and efficacy profile of the use of DEB or DES after IVL in CN. The co-primary endpoints are LLL and net gain at 9 ± 1 months of angiographic follow-up. The findings are expected to inform clinical decision-making and support a more individualized approach on the management of this specific type of calcified coronary disease.

DATA AVAILABILITY

This manuscript refers to the protocol of a study, therefore there is not available data related to this manuscript.

FUNDING

The DEBSCAN-IVL study was supported by non-restricted grants from Shockwave, Biotronik and Medtronic.

ETHICAL CONSIDERATIONS

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

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

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

AUTHORS’ CONTRIBUTIONS

A. Jurado-Román, M. Basile and R. Moreno drafted the manuscript. The remaining authors performed a critical review, and all authors approved the final version for publication.

CONFLICTS OF INTEREST

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. J.M. Montero-Cabezas received a research grant from Shockwave Medical and speaker fees from Abiomed, Boston Scientific, and Penumbra Inc. A. Pérez de Prado reports receiving institutional research grants from Abbott and Shockwave Medical and speaker honoraria and consulting fees from iVascular, Boston Scientific, Terumo, B. Braun, and Abbott Vascular. I.J. Amat-Santos is proctor for Boston Scientific. A. Pérez de Prado, F. Alfonso 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. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

SUPPLEMENTARY DATA

REFERENCES

INTRODUCTION

Aortic stenosis (AS) is the most common primary valvular heart disease requiring intervention.1 Its prevalence is estimated at 3–5% in individuals older than 75 years,2,3 and it is expected to increase due to longer life expectancy, growing awareness, and improved diagnostic accuracy.4 The mortality rate of untreated severe symptomatic AS reaches 10-20% within the first year and 45% at 4 years.2,5

Transcatheter aortic valve implantation (TAVI) is a well-established, less invasive alternative to surgical aortic valve replacement for patients with severe symptomatic AS.1,6 Initially reserved for high-risk patients, TAVI indications have expanded to intermediate-risk and older lower-risk patients.1,6 Improvements in device technology, procedural techniques, and operator expertise have led to fewer complications and enhanced overall safety.3 The increasing prevalence of AS and the expansion of TAVI indications highlight the need to increase procedural capacity to meet current and future clinical demands and ensure timely access to treatment.7

Current clinical practice guidelines recommend that TAVI must be performed exclusively at centers with on-site cardiac surgery (CS) backup,1,6 as surgical backup provides a safety net in complications requiring emergency cardiac surgery (ECS).8 Nonetheless, the rate of ECS has significantly decreased to 0.5-1% of TAVI,9 and the outcomes of ECS remain poor,9 with a 54% survival rate at the index event and only 22% at 1 year,10 raising concerns about the actual benefits of mandatory surgical backup.

TAVI availability remains variable, with regional disparities due to the centralized distribution of CS centers.4,11 As a result, access is often limited in regions without tertiary CS centers, leading to prolonged waiting periods associated with a worse prognosis.3 TAVI waiting list mortality rate reaches 18%, highlighting the need for timely intervention.12 Expanding TAVI to centers without on-site CS will improve access, increase procedures, reduce health care inequalities, and alleviate surgical centers, allowing them to focus on higher-risk procedures.3,13 The limited number of eligible centers constrains the national procedural volume, preventing the health system’s ability to meet the population’s growing TAVI needs.4,14

This study aims to describe our experience with TAVI in a center without on-site CS and compare outcomes to the national benchmark of centers with surgical backup.

METHODS

Study population

We conducted a retrospective, single-center cohort study including the first 300 consecutive patients who underwent TAVI at our center, Hospital Espírito Santo de Évora (Portugal), between 2020 and 2024. This study was conducted in a hospital without an on-site CS department. Patients were identified through the institutional structural heart procedure registry. The study was approved by the center ethics committee, informed consent was obtained from all participants, and the study was conducted in full compliance with the Declaration of Helsinki.

Data collection

Clinical, echocardiographic, laboratory, and procedural data were obtained from electronic health records, including imaging modalities, procedural documentation, and discharge summaries. Baseline characteristics included demographic, clinical, and echocardiographic parameters, and procedural information such as access route and valve type.

Endpoints

The primary endpoint was the 30-day all-cause mortality rate. The secondary endpoints were need for ECS, in-hospital mortality, stroke, 1-year all-cause mortality rate, 1-year cardiac death, vascular complications, major hemorrhage, and permanent pacemaker implantation. Outcomes were defined according to the Valve Academic Research Consortium-3 (VARC-3) criteria.15 ECS was defined as any unplanned cardiac surgical conversion to open surgery required to manage a life-threatening complication occurring during or shortly after the procedure, performed before the patient leaves the procedural environment.

In addition, outcomes were compared with the most recent Portuguese national TAVI registry,16 which exclusively includes centers with on-site CS, to provide a benchmark for procedural safety and efficacy profile.

Follow-up

Follow-up was performed through clinic visits at 3 and 12 months, complemented by telephone contact and review of electronic health records when in-person visits were not possible. Symptomatic improvement was evaluated based on changes in New York Heart Association (NYHA) functional class.

Statistical analysis

Categorical variables were expressed as frequencies and percentages and compared using the chi-square test or Fisher’s exact test, as appropriate. Continuous variables were assessed for normality using the Shapiro–Wilk test. Normally distributed data were expressed as mean ± standard deviation (SD) and compared using the Student t test. Non-normally distributed variables were expressed as the median and interquartile range (IQR) and compared using the Mann–Whitney U test. Statistical significance was set at a 2-tailed P-value < .05. All statistical analyses were performed using Stata version 18.0 (StataCorp, United States).

RESULTS

Baseline characteristics

The first consecutive 300 patients undergoing TAVI between 2020 and 2024 were included. The cohort mean age was 82 ± 5 years (62–101), and 54% (n = 161) were women. The median Society of Thoracic Surgery (STS) risk score was 3.8 [IQR, 2.3–6.6], with 17% (n = 51) classified as high-risk (STS > 8). Prior hospitalization for symptomatic AS occurred in 21% (n = 64). Seven patients (2%) had undergone previous surgical aortic valve replacement and were treated with the valve-in-valve procedure. Low-flow low-gradient severe AS was observed in 10% (n = 31) and bicuspid aortic valve in 6% (n = 18). The baseline characteristics of the included patients are summarized in table 1 and table 2. The Portuguese National TAVI registry included 2346 patients. Compared with our cohort, the national registry included more patients with NYHA FC > II (68% vs 51%; P < .01) and COPD (22% vs 12%; P < .01), whereas our center had a higher prevalence of chronic kidney disease (50% vs 38%; P < .01). The baseline characteristics of the Portuguese National TAVI Registry and a comparison with our cohort are shown in table 3.

Table 1. Baseline characteristics and comorbidities

Table 2. Baseline characteristics comparison between our cohort and the Portuguese TAVI registry

Table 3. Clinical context and procedural characteristics

Procedural characteristics

Most of our procedures were elective (83%; n = 249), while 17% (n = 51) were performed urgently following unplanned hospital admission for symptomatic severe AS. Cardiogenic shock was found in 5% (n = 15), and 4% (n = 12) required ventilatory support (table 3). Transfemoral access was used in 99% of cases (n = 298); the remaining 2 were performed via transcarotid and through an aortofemoral bypass graft route, both with surgical exposure by the vascular surgery team. Self-expandable valves were used in 95% of cases (n = 286), predominantly the Evolut family (Medtronic, United States) in 91%, n = 259, followed by Navitor (Abbott, United States) in 7% (n = 20) and Acurate (Boston Scientific, United States) in 2% (n = 6). The balloon-expandable valve Myval (Meril, India) was used in 5% (n = 14) (table 4).

Table 4. Procedural and follow-up outcomes

Procedural and 1-month outcomes

The primary endpoint, 30-day mortality rate, was 3.7% (n = 11), while in-hospital mortality was 2% (n = 6). Survival at the end of the procedure was achieved in 99% of patients (n = 298). No patient required ECS. Two patients (0.7%) underwent transcathether pericardiocentesis for cardiac tamponade, one due to a self-contained left ventricular guidewire perforation that did not require ECS, and the other of undetermined cause, which persisted and ultimately required delayed exploratory cardiac surgery, resulting in postoperative death. No cases of aortic valvular annulus rupture, coronary obstruction, TAVI-in-TAVI deployment, or valve embolization occurred. Stroke occurred in 2.7% (n = 8), 1.6% of which (n = 5) were disabling, while major bleeding and vascular complications were each observed in 8%. Pacemaker implantation was required in 20% (n = 61) (table 4). A detailed description of procedural and early causes of death is shown in table S1.

Follow-up outcomes

The 1-year all-cause mortality rate was 12% (n = 36), and cardiac death, 4% (n = 12). A detailed description of the causes of death is provided in table S1. Readmission occurred in 17% (n = 51), including 32 cardiovascular and 19 non-cardiovascular events. A detailed description of the causes of readmission is provided in table S1. Among surviving patients with available data, 91% reported symptomatic improvement, assessed by the NYHA functional class (table 4).

National TAVI registry comparison

Compared with the Portuguese TAVI national registry results available16 (table 5), our center demonstrated a non-statistically significant lower 30-day mortality rate (3.7% vs 4.8%; OR, 0.8; 95%CI, 0.44–1.47; P = .5) and similar 1-year mortality rates (12% vs 11%; OR, 1.0; 95%CI, 0.76–1.47; P = .8) (figure 1). The rate of ECS was equivalent in both groups (0% vs 0.4%; P = .5), as were the rates of vascular complications (8% vs 6.8%; P = .4) and major bleeding (8.3% vs 13.3%; P = .2). Our stroke rate was numerically lower (2.7% vs 4.6%; P = .1), as was the rate of acute kidney injury (6% vs 4.2%; P = .5). Pacemaker implantation rates were similar (20% vs 19%; P = .7) (figure 2). However, 1-year hospitalization was more frequent in our cohort (17% vs 9.6%; P = .03).

Table 5. Outcomes comparison between our center and the national registry

Figure 1. Forest plot comparing the odds ratios (OR) of primary endpoints between our center without on-site cardiac surgery (CS) backup and the national Portuguese TAVI registry16 (all centers with on-site CS backup).

Figure 2. Forest plot of procedural outcomes comparing our center without on-site CS backup with the national Portuguese TAVI registry16 (centers with on-site CS backup).

DISCUSSION

This single-center study is the first national experience of TAVI in a non-on-site CS backup center. Our results suggest that this model is feasible and safe, with outcomes comparable to those reported by national and international series, including centers with surgical backup. Our outcomes were similar across key endpoints vs the National Portuguese TAVI registry,16 which includes only centers with surgical backup. Although no patients from our series required ECS, and 1 patient underwent delayed surgical intervention due to persistent pericardial effusion, the procedure was unsuccessful. This observation is consistent with other reports indicating that outcomes of emergency conversion after TAVI are generally poor, even in centers with surgical backup.8,10

TAVI safety and efficacy profile have improved significantly through careful procedural planning, the involvement of a multidisciplinary heart team (including cardiac surgery), and growing operator experience supported by technological advances. As a result, the need for immediate surgical backup has become increasingly less relevant. Although the complications that require surgical intervention remain rare, they are associated with high morbidity and mortality despite surgical management. Within this context, our results support the feasibility and suggest the non-inferiority of performing TAVI without on-site CS, reinforcing its applicability across various clinical scenarios, including younger individuals and those with multivalvular or coronary artery disease.

Our program reflects the contemporary TAVI landscape, including a heterogeneous and high-risk population with a significant proportion of emergency and unstable cases, including hospitalized patients and those in cardiogenic shock. In addition, we treated patients with complex anatomical and clinical characteristics such as valve-in-valve procedures, bicuspid aortic valves, reduced LVEF, and pulmonary hypertension. This all-comers profile mirrors the real-world spectrum that structured TAVI programs must address today, extending beyond elective transfemoral procedures for native AS.

Of note, our median waiting time for the procedure was short (59 days [IQR, 22-122]), and 20% of patients were referred from outside our direct hospital catchment area. This suggests that our center has become a regional reference for TAVI despite the lack of on-site CS, which reflects both the accessibility of our program and the trust placed in our heart team’s expertise. Importantly, many of these patients were referred because traditional TAVI centers could not meet procedural demand promptly, highlighting our role in addressing unmet clinical needs within the region.

Our findings align closely with results from countries where TAVI is performed without on-site CS, including Spain,11 Germany,17 and Austria.18 In Spain, the multicenter registry reported a conversion rate to open-heart surgery of 0.3% in centers without on-site CS backup.11 The German AQUA registry, which included more than 17 000 patients, found no significant differences in outcomes between centers with and without CS, with a 30-day mortality rate of 3.8% in hospitals with visiting CS vs 4.2% in those with CS backup, with emergency surgery rates of 0.3% and 0.7%, respectively17. Similarly, a study from Austria has shown favorable outcomes in centers without on-site surgery, with no significant differences in in-hospital mortality or surgical conversion rates.18 Our outcomes are consistent with these findings, with a 30-day mortality rate of 3.7% and no cases of ECS. Consistent with previous experiences from other countries, our results demonstrate equivalent and non-inferior results compared with centers that have on-site surgical backup.

Importantly, our study reflects a more recent era, with procedures performed in lower-risk patients, using the latest-generation devices, by more experienced operators, and following more precise preoperative planning with advanced CT imaging modalities. In addition, unlike earlier studies where visiting surgeons were present, our center performed all procedures without on-site surgical support, demonstrating the feasibility of a fully independent model. This study provides contemporary real-world evidence that TAVI can be safely and effectively performed in selected patients in centers without on-site CS backup, supporting broader access while maintaining quality standards.

Our study carries important policy implications. In the context of rising TAVI demand and resource constraints in high-volume surgical centers, decentralizing care to centers without on-site CS backup may enhance access without compromising patient outcomes. Our data supports the expansion of TAVI programs under carefully controlled conditions: standardized protocols, well-trained interventional teams, strong referral networks, and access to surgical support within a structured regional pathway. Regulatory agencies may consider revisiting existing requirements for on-site surgery, fostering a model where expertise guides the safe implementation of structural heart procedures while ensuring timely access to defined surgical centers for protocoled backup in case of delayed surgical needs.

These findings highlight the safety and viability of expanding TAVI programs to selected centers without surgical backup. With rigorous patient selection, experienced operators, and standardized procedural pathways, excellent outcomes can be achieved without immediate surgical support. Our experience supports a more inclusive structural heart care model that delivers timely and effective therapy to a broader patient population without compromising safety or efficacy.

Limitations

While these results are encouraging, several limitations must be acknowledged. First, this was a single-center, retrospective study, and although data collection was comprehensive, the potential for unmeasured confounding remains. Second, long-term follow-up beyond 1 year was unavailable, limiting conclusions on valve durability and late complications. Third, patient selection and procedural planning were guided by a highly experienced heart team, which may not be generalizable to all centers without surgical backup. Finally, although the baseline characteristics of our cohort and those of the Portuguese national registry (table 3) appear to be broadly comparable, result comparisons should be interpreted with caution, as no statistical adjustment was performed, the analysis was retrospective, and patients in the registry generally had a less favorable clinical profile.

CONCLUSIONS

Our study demonstrates that TAVI can be safely and effectively performed in centers without on-site CS backup, even in a heterogeneous, all-comers population. Outcomes appear broadly comparable and support the non-inferiority of this approach relative to centers with on-site CS. The risk of ECS was very low, and its incremental benefit may be limited, while CS centers remain few and frequently overburdened. These findings suggest that, with careful case planning and growing operator experience, expanding TAVI programs to selected non-CS centers is a safe and feasible strategy to address the growing demand and improve access for patients with severe AS. Randomized controlled trials are needed to confirm these results and guide broader implementation.

DATA AVAILABILITY

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

This study was approved by Hospital Espírito Santo de Évora ethics committee, ULSAC. All procedures were performed in full compliance with the ethical standards of the center research committee and with the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study. This study was conducted in full compliance with the SAGER guidelines. Sex and gender considerations were addressed appropriately, and any potential sex- or gender-related differences were assessed and reported where relevant.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence tools were used in the preparation of this manuscript.

AUTHORS’ CONTRIBUTIONS

A. Rocha de Almeida: conceptualization, methodology, data curation, formal analysis, investigation, original draft writing and review and editing of the final draft. R. Fernandes, Â. Bento, D. Neves, D. Brás, G. Mendes were in charge of original draft writing and review and editing of the final draft. R. Rocha, M. Paralta Figueiredo and R. Viana were in charge of data curation, reviewed and edited the final draft. R. Louro and Á. Laranjeira Santos were in charge of review and editing of the final draft. L. Patrício was in charge of conceptualization, supervision, review and editing of the final draft and validation. All authors read and approved the final draft.

CONFLICTS OF INTEREST

None declared.

SUPPLEMENTARY DATA

REFERENCES

INTRODUCTION

Technological advances in coronary intervention, particularly the development of new-generation drug-eluting stents, have transformed the treatment of ischemic heart disease by effectively reducing restenosis and improving clinical outcomes for the patients.1 Nonetheless, stent thrombosis (ST) remains a rare but devastating complication, with an associated mortality rate of up to 40%.2 Its pathophysiological mechanisms are complex and multifactorial, involving patient-related factors, implantation technique, stent type, and the natural progression of the disease.3

Traditionally, coronary angiography has been the tool of choice for assessing potential complications after stent implantation. However, its inability to adequately visualize the interaction between the stent and the vessel wall limits its diagnostic utility. In this context, optical coherence tomography (OCT), owing to its excellent spatial resolution, enables in vivo identification of underlying mechanical abnormalities that may be responsible for or contribute to ST.

The primary endpoint of this study was to evaluate the role of OCT in characterizing the mechanisms involved in ST, analyzing its feasibility, safety profile, therapeutic implications, and potential to optimize revascularization strategies in this complex clinical setting. Preliminary findings from this study were reported previously,4 and the final results are presented herein.

METHODS

Study population

We conducted a prospective, single-center registry that consecutively included patients with a diagnosis of definite ST, as defined by Academic Research Consortium criteria, from October 2013 through December 2022 at Hospital Universitario de La Princesa (Madrid, Spain). Throughout this period, stents were implanted in 6881 patients. Patients with severe hemodynamic instability or lesions inaccessible with the OCT catheter were excluded.

We applied a systematic protocol that included OCT acquisition before and after treatment. If antegrade flow was not restored after crossing the lesion with the guidewire, thrombus aspiration was recommended; furthermore, when TIMI grade 0–1 flow persisted, inflation of a balloon < 2 mm in diameter at low pressure was recommended to avoid distortion of the underlying lesion. The final treatment strategy for ST was left to the operator’s discretion.

ST was classified based on the interval since implantation as acute (< 24 h), subacute (24 h to 30 d), late (30 d to 1 y), or very late (> 1 y). Stents were categorized as bare-metal, first-generation drug-eluting, new-generation drug-eluting, or bioresorbable stents.

We performed prospective clinical follow-up to assess in-hospital mortality and, after discharge, a composite of cardiac death, recurrent myocardial infarction, recurrent ST, or repeat culprit vessel revascularization.

The study protocol was approved by Hospital Universitario de La Princesa Ethics Committee, and all patients gave their prior written informed consent before being included in the study.

OCT acquisition and analysis

OCT systems available at the time (Dragonfly, St. Jude Medical, and OPTIS AptiVue, Abbott) were used. Images were acquired with a nonocclusive technique and a contrast volume of 15 mL at a rate of 5 mL/s for the left coronary system and 12 mL at a rate of 4 mL/s for the right coronary artery. The analyzed segment included the stent and 10 mm adjacent to its edges. Poor-quality studies due to insufficient flushing or artefacts were excluded. Additionally, we performed a cross-sectional morphometric analysis, including minimum lumen area, minimum and maximum stent area, reference areas and diameters, stent expansion index (minimum stent area / mean reference area ×100), thrombus burden (length and area), and malapposition (axial distance from the strut surface to the lumen border greater than the strut thickness [significant if > 200 µm]).5 Struts directly exposed to the vessel lumen were classified as uncovered. Neoatherosclerosis was defined as neointimal changes including lipidic, fibro-lipidic, or calcified tissue. Plaque rupture was assessed too. The presence of edge dissection (separation of vascular tissue extending into the media, ≥ 2 mm in length and > 60°)6 or stent edge disease (ruptured lipid plaque adjacent to the stent edge, due to incomplete coverage or disease progression)7,8 was evaluated.

Primary endpoint: mechanical abnormalities and dominant finding

We analyzed the presence of mechanical abnormalities and identified a dominant finding for each case. When multiple abnormalities coexisted, we defined the dominant finding as the one prevailing in the area with the greatest thrombus burden.9 Potentially causative mechanical abnormalities included edge dissection, underexpansion, severe malapposition, edge disease progression, neoatherosclerosis, and uncovered struts (for late and very late ST). Furthermore, we recorded the absence of mechanical abnormalities. The dominant finding was, then, assessed as the potential main cause of ST, after excluding other possible causes, such as inadequate antiplatelet therapy or prothrombotic clinical conditions. Predictors of neoatherosclerosis and plaque rupture in very late ST were also studied.

Statistical analysis

Statistical analysis was performed using R software. Continuous variables were expressed as mean (SD) or median (interquartile range, P25–P75) and compared using the Student t test or Wilcoxon test. For comparisons across more than 2 groups, ANOVA or Kruskal–Wallis tests were used. Categorical variables were compared using the chi-square test or Fisher’s exact test. Logistic regression models were applied to identify possible predictors of in-hospital mortality, and Cox regression models were used for post discharge events. Survival analyses were performed with Kaplan–Meier curves and log-rank tests. Statistical significance was defined as P < .05.

RESULTS

Clinical and angiographic characteristics

A total of 142 patients with a diagnosis of definite ST were registered, 105 of whom were included in the final analysis (figure 1). A total of 17 cases of acute ST (16%), 23 cases of subacute ST (22%), 13 cases of late ST (12%), and 52 cases of very late ST (50%) were reported. The baseline patient characteristics based on the ST timing (acute/subacute vs late/very late) are shown in table 1. The most common presentation was ST-segment elevation myocardial infarction (81.9%), and the most frequently affected vessel was the left anterior descending coronary artery (42%). Most thrombosed devices were new-generation drug-eluting stents (53.3%), followed by bare-metal stents (28.6%), first-generation drug-eluting stents (13.3%), and bioresorbable scaffolds (4.8%). Bare-metal stents were significantly more common in late/very late ST, whereas new- generation drug-eluting stents and bioresorbable scaffolds were more common in acute/subacute ST. For ST treatment, drug-eluting stents and drug-coated balloons were used significantly more often in late and very late ST, whereas glycoprotein IIb/IIIa inhibitors and balloon optimization were more frequently employed in acute and subacute ST.

Table 1. Baseline, angiographic, and procedural characteristics of the study population

Figure 1. Flowchart of patient inclusion in the study. OCT, optical coherence tomography.

OCT analysis

No complications related to the OCT technique were observed. Morphometric and stent–vessel wall interaction data are shown in table 2. A total of 24 834 cross-sections were evaluated, of which 1453 (5.8%) could not be analyzed because of abundant residual thrombus.

Table 2. Morphometric analysis and stent–vessel wall interaction according to type of stent thrombosis

There were no differences in underexpansion rates based on the type of thrombosis, and only a minimum stent area < 4.5 mm² was observed in subacute ST. The number of uncovered struts decreased significantly over time (although 30% of stents still exhibited uncovered struts at the 1-year follow-up), as did thrombus burden and malapposition (figure 2). Additionally, we analyzed these findings by stent type (table 3), showing that uncovered or malapposed struts were more frequent in drug-eluting stents than in bare-metal stents.

Table 3. Morphometric analysis according to stent type

Figure 2. Morphometric findings over time.

Primary endpoint

Underlying mechanical abnormalities were identified in 91 of 105 patients (86.7%). Of these, 10 patients also had documented nonadherence to antiplatelet therapy in the days preceding ST; therefore, a mechanical abnormality was considered the most likely single cause in 81 patients (77.1%). The global distribution of dominant findings is shown in figure 3, and representative examples of ST cases in figure 4.

Figure 3. Central illustration. Assignment of the dominant finding and most likely cause of stent thrombosis. OCT, optical coherence tomography.

Figure 4. Representative optical coherence tomography findings. A: longitudinal and cross-sectional views of a stent with marked underexpansion (line indicates minimum diameter). B: stent-edge dissection. Arrow indicates separated tissue flap from the vessel wall. C: malapposition. Arrows indicate struts associated with thrombus that are not in contact with the vessel wall. D: neoatherosclerosis with plaque rupture. Arrows indicate intimal discontinuity, and asterisks show the evacuated plaque cavity. E: uncovered struts (arrows). F and F‘: cross-sectional and longitudinal views of a stent with distal edge disease and plaque rupture (arrows).

Representative optical coherence tomography findings. A: longitudinal and cross-sectional views of a stent with marked underexpansion (line indicates minimum diameter). B: stent-edge dissection. Arrow indicates separated tissue flap from the vessel wall. C: malapposition. Arrows indicate struts associated with thrombus that are not in contact with the vessel wall. D: neoatherosclerosis with plaque rupture. Arrows indicate intimal discontinuity, and asterisks show the evacuated plaque cavity. E: uncovered struts (arrows). F and F’: cross-sectional and longitudinal views of a stent with distal edge disease and plaque rupture (arrows).

The dominant finding varied significantly by ST timing (P < .001) (table 4). In acute ST, the most frequent result was no identifiable abnormality (41.2%), and the dominant finding was stent-edge dissection (23.5%); in subacute ST, it was underexpansion (47.8%); in late ST, malapposition; and in very late ST, neoatherosclerosis (52%). However, there were no significant differences by stent type (P = .07): in bare-metal and first-generation drug-eluting stents, the most common abnormality was neoatherosclerosis (46.7% and 35.7%, respectively), whereas in new-generation drug-eluting stents, underexpansion predominated (26.8%). In very late ST, neoatherosclerosis was the most common finding in both bare-metal and drug-eluting stents (56.7% vs 50%; P = .45), regardless of whether thrombosis occurred within 5 years or later after stent implantation. Five cases of bioresorbable scaffold thrombosis were recorded whose specific findings have already been reported previously.10

Table 4. Dominant findings according to timing of stent thrombosis and stent type

Neoatherosclerosis and plaque rupture

Neoatherosclerosis was identified in 40 patients, regardless of whether it was the dominant finding. There were no differences in baseline characteristics between patients with and without neoatherosclerosis, although those with neoatherosclerosis had larger minimum stent areas, smaller minimum lumen areas, and fewer uncovered and malapposed struts (table 1 of the supplementary data). Minimum lumen area was the only factor associated with a higher risk of neoatherosclerosis (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.16–0.75; P = .013).

Plaque rupture was reported in 16 patients with neoatherosclerosis. There were no differences in baseline characteristics or in the composition of neoatherosclerosis between patients with and without plaque rupture (table 2 of the supplementary data). Despite the limited sample size, minimum lumen area was identified as a protective factor against plaque rupture (OR, 0.22; 95%CI, 0.04–0.7; P = .035). The presence of neovessels or calcium inside the stent was not associated with plaque rupture, nor was stent type.

Clinical follow-up

The in-hospital mortality rate for the overall cohort was 9.2%, with no significant differences being reported between patients who did and did not undergo OCT (8.5% vs 11%; P = .7). The main predictors of mortality were chronic kidney disease (OR, 9.56; 95%CI, 2.28–41.14; P = .002) and Killip-Kimball class III/IV status (OR, 14.8; 95%CI, 3.38–79.6; P = .001).

A total of 28 composite endpoints were recorded at the follow-up (median, 2143 days [15–2906]). Event-free survival rates at 1 and 5 years were 83.3% and 73.1%, respectively. There were 13 deaths at the follow-up. Estimated survival rates were 96% and 86.7% at 1 and 5 years, respectively (figure 1 of the supplementary data).

DISCUSSION

ST remains a serious complication with a high mortality rate.11 Understanding its pathophysiology is essential for improving prevention, diagnosis, and eventually treatment.12 In this context, OCT provides crucial real-time information, allowing for much more precise diagnosis and individualized treatment.

This study represents the largest national series of ST cases evaluated with OCT. The main findings are 1) the use of OCT in the acute phase of ST is safe and feasible in experienced centers; 2) OCT identified mechanical abnormalities in 86.7% of ST cases; 3) the dominant finding varied according to the timing of ST (in acute ST, no mechanical abnormality was most common, while underexpansion predominated in subacute ST, malapposition in late ST, and neoatherosclerosis in very late ST); 4) OCT enabled treatment guidance based on the dominant finding and might reduce the need for additional stenting; and 5) in-hospital mortality rate was low (9.2%), with Killip-Kimball class IV and chronic kidney disease being the main predictors.

An adequate-quality OCT study was achieved in 74% of patients, which is a rate considerably higher than that reported by the main European registries.9,13 Although thrombus can limit visibility, image quality can be improved with thrombus aspiration or the use of catheter extension systems. Unlike other studies in which OCT was performed in a procedure separate from the index ST, our study conducted OCT during the acute event, representing a key methodological strength.

OCT demonstrated a remarkable ability to detect mechanical abnormalities (86.7%). In this setting, the information provided by angiography is insufficient. In the PESTO trial,13 angiography identified the cause of ST in only 12% of cases, whereas OCT did so in more than 90% of the cases. The CLI-OPCI trial14 was the first to demonstrate that OCT provides information on immediate stent outcomes not appreciable on angiography, prompting additional interventions in up to one-third of patients.

Although some findings are consistent with the PRESTIGE study,9 our analysis provides relevant nuances. In particular, in acute ST, most cases showed no evident mechanical abnormalities (unlike our preliminary results, in which malapposition predominated). This finding reinforces the role of antithrombotic treatment and prothrombotic states as key factors, supported by the greater thrombus burden observed in early vs late ST. Unlike previous studies, our results emphasize the utility of OCT not only in identifying mechanical causes but also in avoiding unnecessary interventions, thereby underscoring the importance of optimal medical therapy. In addition, in our study, uncovered struts were not considered a cause of acute or subacute ST, based on the assumption that no stent is covered by neointima within the first 30 days.

The association between acute malapposition and ST remains controversial.15-17 A possible explanation is that although malapposition is almost ubiquitous after stent implantation,18,19 its relationship with thrombosis is difficult to establish because of the low probability of a later event.

Underexpansion, however, is established as one of the most important predictors of ST. In the CLI-OPCI study,20 a minimum lumen area > 4.5 mm² was identified as a threshold for discriminating events during follow-up. This cutoff value is not achievable in small vessels and does not apply to left main lesions. Relative expansion6,21 may thus be a more appropriate measure, although its superiority over absolute expansion in predicting events has not yet been established.

In late ST, malapposition was the most common finding. Most cases of nonsevere acute malapposition resolve during follow-up, although up to 30% may persist.18 One study22 reported substantially lower rates of malapposition (8%) than those observed in previous large registries,9,13 likely because the index implantation was image-guided; this also supported that 75% of cases represented acquired malapposition.

Neoatherosclerosis was detected in most late and very late ST, irrespective of stent type, unlike other studies in which it predominated in drug-eluting stents. This may be explained by the longer interval between implantation and thrombosis in bare-metal stents, which is consistent with the observation that follow-up duration is the most important predictor of neoatherosclerosis.23 The use of OCT avoided unnecessary new stenting in 48% of patients, a higher rate compared with other ST series without image guidance24 and even higher than in the PRESTIGE registry.9

Limitations

The present study has several limitations: 1) the absence of a control group precludes predictive evaluation of certain findings such as malapposition, and superiority of OCT over non–intracoronary image-guided interventions cannot be definitively established; 2) no core laboratory was used for OCT analysis, which may limit external reproducibility; 3) selection bias exists due to exclusion of the most severe patients and those with complex anatomy, which may account for favorable outcomes and could influence the prevalence of some mechanisms; 4) ST is a multifactorial process, and the dominant finding cannot be considered the definitive cause; 5) the presence of thrombus hampers evaluation of underlying structures; 6) the index stent implantation was not image-guided, preventing differentiation between acute and acquired malapposition; and 7) serial OCT studies were not performed in many patients, which means that correction of the detected abnormality could not be assessed.

CONCLUSIONS

OCT is a safe, feasible, and highly useful tool for the treatment of ST. It allows identification of the most likely cause of the event in most cases—which varies according to the timing of thrombosis—and enables individualized treatment by addressing the underlying abnormality.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

This study was approved by Hospital Universitario de La Princesa Ethics Committee. All procedures conformed to the ethical principles of the Declaration of Helsinki. This study followed the SAGER guidelines. Written informed consent for publication was obtained and archived.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence tools were used in the preparation of this manuscript.

AUTHORS’ CONTRIBUTIONS

All authors contributed equally to the conception, design, and analysis of the study, as well as to drafting and revising the manuscript. Furthermore, all authors approved the final version and are responsible for its content.

CONFLICTS OF INTEREST

F. Alfonso is Associate Editor of REC: Interventional Cardiology; the journal’s editorial procedure to ensure impartial handling of the manuscript has been followed. The remaining authors declared no conflicts of interest whatsoever.

SUPPLEMENTARY DATA

REFERENCES

INTRODUCTION

Aortic stenosis (AS) is the most common valvular heart disease, with a prevalence of 3% in individuals older than 65 years and 7.4% in those older than 85 years. AS is more common in men.1,2 It is the leading cause of valve surgery in the adult population,3 and is associated with risk factors such as advanced age.4,5 Although aortic stenosis typically develops after age 60, symptoms usually present between ages 70 and 80; once symptoms occur, the mortality rate may reach 50% within the next few years.4,6

Transcatheter aortic valve implantation (TAVI), initially reserved for patients deemed ineligible for surgical aortic valve replacement,7-11 was subsequently expanded to include those at intermediate risk and, more recently, patients at low risk.5,12-14

In Spain, the use of TAVI has increased,5 reflecting its growing acceptance within the Spanish National Health System (SNS), largely attributable to improved clinical and economic outcomes.5,15 Multiple studies have demonstrated the benefits of TAVI, including significant improvements in quality of life,16,17 lower rates of major complications,18 and reduced mortality.5,19,20

Nationwide, improvements in TAVI outcomes, shorter lengths of stay, and lower mortality rates have been reported. Furthermore, autonomous communities (AC) with higher implant volumes have a better safety and efficacy profile, lower risks of infection, reduced need for permanent pacemaker implantation, and shorter lengths of stay.5 However, the distribution of TAVI reveals notable interregional disparities, with procedural rates varying considerably according to hospital resources and volumes.21

Despite these advances, in Spain, TAVI use remains significantly lower compared with other European countries.22 Furthermore, Spain exhibits one of the highest variations in access and utilization rates among its AC (42%), which cannot be explained solely by economic differences, hospital utilization, or observed mortality.21 An analysis by de la Torre Hernández et al.21 described the need for strategies to promote equity in TAVI access across Spain.

This study analyzed heterogeneity in the use of TAVI across AC (2016–2023) and identified the factors associated with this inequality.

METHODS

TAVI data in Spain from 2016 through 2023

Data on TAVI performed from 2016 to 2023 were obtained from the Specialized Care Activity Minimum Basic Data Set23-25 using the International Classification of Diseases, 10^th revision for Spain (ICD-10-ES) (supplementary data 1). This mandatory registry, which includes all specialized care centers, is managed by the Spanish Ministry of Health and ensures strict compliance with privacy and data protection standards. The analysis included all TAVI performed in public and private hospitals across AC.

Survey

Simultaneously, we designed a survey to gather information on therapeutic decision-making in patients with AS to identify possible factors influencing TAVI implementation and interregional variability previously observed. This survey was distributed to department heads of the 123 medical centers affiliated with the Interventional Cardiology Association of the Spanish Society of Cardiology. Respondents were asked to extend the invitation to other department members to ensure representative and diverse responses.

The survey (supplementary data 2) covered clinical, structural, organizational, and patient-related aspects relevant to clinical practice during the study period, and was structured into 3 thematic blocks:

• – Center and participant characteristics (questions A1–C3): evaluation of institutional context and department composition, including variables such as the respondent’s specialty and annual budget allocation.
• – Patient selection and decision-making (questions C4–E2): identification of key clinical and demographic factors influencing therapeutic choice, as well as barriers and determinants shaping clinical team decisions.
• – Center evaluation and TAVI use (questions E3–F9): assessment of clinician perception and satisfaction regarding TAVI, and exploration of adoption, implementation, and geographic distribution of this strategy.

Responses were analyzed descriptive and qualitatively, allowing a comprehensive interpretation of factors influencing TAVI implementation and interregional heterogeneity.

RESULTS

TAVI in 2016–2023

The results of TAVI interventions, expressed as the number of cases and intervention rates per 10 000 inhabitants, are shown in figure 1. All AC experienced an increase in procedures during the study period (figure 1A), with the greatest growth observed in the Canary Islands (33 cases in 2016 and 368 in 2023) and La Rioja (2 cases in 2016 and 28 in 2023), corresponding to increases of 1.115% and 1.400%, respectively. The AC with the highest number of TAVI performed in 2023 were Andalusia (n = 1392), Catalonia (n = 1245), and the Community of Madrid (n = 1257). La Rioja had the fewest (2 cases in 2016, 28 in 2023).

Figure 1. A: total number of transcatheter aortic valve implantation (TAVI) cases by autonomous community and year (2016–2023). B: population-adjusted procedural rates adjusted (per 10 000 inhabitants) by autonomous community and year (2016–2023). C: mean and dispersion of mortality based on the number of TAVI.

Procedure rates (figure 1B) indicated that, in 2023, the AC with the highest per capita TAVI volumes were Galicia (2.82 per 10 000 inhabitants), Asturias (2.18 per 10 000), Cantabria (2.00 per 10 000), Castile and León (2.00 per 10 000), and Madrid (1.82 per 10 000), all above the national average (1.65 per 10 000). The lowest per capita TAVI volumes were found in Extremadura (1.24 per 10 000), the Balearic Islands (1.13 per 10 000), Aragón (1.12 per 10 000), La Rioja (0.87 per 10 000), and Castile-La Mancha (0.63 per 10 000).

The mean in-hospital mortality rate during the study period was 3.07% (figure 1C).

Survey

Center and participant characteristics

The survey was completed by 26 specialists with different TAVI-related profiles: 18 in interventional cardiology, 7 in clinical cardiology, and 1 in cardiac imaging, including 4 heads of cardiac surgery departments and 18 cath lab directors. The respondents’ mean professional experience was 26.5 years (range, 9–41 years) and worked in hospitals with a mean TAVI experience of 10.6 years (range, 1–16 years). Responses were obtained from hospitals in 11 of the 17 AC (64.7% of the national territory). Team composition by professional profile is provided in supplementary data 3.

Teams performed a mean of 76 TAVI (range, 0–148) in 2021 and 95 (range, 0–254) in 2022, with marked variation across hospitals. Annual budgets allocated to units ranged from €474 765 to €25 111 709, reflecting wide disparities in resource availability. Despite these differences, most respondents reported being satisfied with the extent to which purchasing committees allocated budgets to meet their teams’ clinical needs (19.2%, very satisfied; 42.3%, quite satisfied; 34.6%, moderately satisfied; 3.9%, unsatisfied).

Most participants rated continuity of care across different settings as good or improvable (54.9% and 38.5%, respectively) and gave examples of best practices as well as areas for improvement. Best practices included teleconsultation, specialized programs such as TAVI Nurse,26 periodic cross-level meetings, and shared protocols between primary and hospital care. Suggested improvements included insufficient coordination between primary and specialized care, overloaded schedules, and the need to improve clinical information systems such as integrating joint activities.

Patient selection and decision-making

The clinical indication for TAVI was determined primarily by heart team judgment (40.0%) and patient stratification (36.5%), followed by patient preference (12.5%) and resource availability (10.4%). Barriers to expanding TAVI included rigid patient stratification (25.6%), insufficient early detection (17.8%), intra-team discrepancies (14.2%), insufficient budget (13.3%) and technology (11.8%), and obstacles to multidisciplinary team integration (7.4%).

Most centers had decision-support tools for TAVI (76.9%) and specific training programs (65.4%). Tools included decision algorithms, clinical practice guidelines, consensus protocols, and software for anatomical, feasibility, and comorbidity assessment. Specific training and periodic multidisciplinary meetings were also in place.

Most centers (76.9%) conducted periodic evaluations of outcomes—described as continuous process evaluation—to optimize procedures, including registries, internal audits, analysis of complications, in-hospital mortality, and readmissions. Annual and monthly clinical meetings allowed protocol adjustments and improved care processes, with high adherence to international clinical practice guidelines.

On the other hand, respondents indicated limited satisfaction with information exchange among departments and specialists involved in TAVI decision-making (figure 2A).

Figure 2. A: respondents’ evaluation of information exchange across departments, committees, and professionals involved in decision-making for aortic valve replacement. B: respondents’ evaluation of information exchange and best practices across centers performing transcatheter aortic valve implantation in Spain.

The survey on patient profiles treated with TAVI, which is performed primarily in intermediate- and high-risk patients, showed that 96.2% of centers treat high-risk patients; 76.9%, intermediate-risk patients; and only 30.8%, low-risk patients. In general, although no major barriers to treatment based on risk profile were reported (69.3% responded negatively), some resistance from cardiac surgery (n = 5), disagreement with institutional protocols (n = 4), and infrastructure limitations expressed as restricted availability of cath labs (n = 3) were noted.

Similarly, respondents perceived that the professional background of team members influences clinical decision-making for TAVI (63.6% strongly agreed and 27.3% moderately agreed; n = 11), highlighting the importance of training, experience, and individual performance. Multidisciplinary, consensus-based decisions among specialists in clinical cardiology, imaging, interventional cardiology, and cardiac surgery allow for the consideration of specific anatomic and clinical factors. Although such multidisciplinary teams promote more objective decision-making, participation from cardiac surgery may affect the indication in low-risk patients.

Therefore, participants considered the heart team’s judgment on additional factors in the indication for TAVI to be relevant, rating it as fairly (50%) or very relevant (50%). Similarly, respondents reported overall satisfaction with the process by which clinical decisions were made within the team: 53.8% found it fairly satisfactory; 38.5%, very satisfactory; 7.7%, moderately satisfactory.

There was near-unanimous agreement (96%) on the importance of incorporating the patient’s opinion into the decision-making process for TAVI indication. When ranking the key factors guiding clinical decision-making, comorbidity and age stratification were rated as the most relevant (figure 3).

Figure 3. Weighted average of responses ranking factors by relevance in the clinical decision to indicate transcatheter aortic valve implantation.

The leading criteria for inclusion on the TAVI waiting list were the presence of comorbidities (n = 22), clinical status or overall risk (n = 20), followed by the minimum (n = 17) and maximum age threshold (n = 2).

The mean waiting time for the procedure was approximately 2 months (mean, 1.92 months; range, 0–4 months). Compared with surgical aortic valve replacement, the waiting list was generally perceived as shorter (50.0%) or equivalent (26.9%).

The primary factors influencing waiting time for TAVI were the need for computed tomography (n = 7) and cath lab availability (n = 5). Other factors included computed tomography availability (n = 3), anesthesia availability (n = 3), and waiting list length (n = 2). In line with this, respondents indicated that most patients (88.5%) undergo TAVI as scheduled procedures

Center evaluation and TAVI use

Most respondents considered the number of centers performing TAVI in Spain sufficient (n = 18, 24 respondents) and highlighted the importance of ensuring adequate procedural volume per center to optimize outcomes and minimize complications. Strengthening infrastructure, human resources, and networking was considered essential, prioritizing quality and safety over opening new centers.

Likewise, participants were generally satisfied with the exchange of information and best practices among TAVI centers in Spain (figure 2B).

There was consensus that improving the early detection of AS would, in turn, improve outcomes and patient experience (91.7%; n = 24). Conversely, most considered that regulatory thresholds for accrediting centers would not substantially affect total TAVI volume (62.5%; n = 24).

Finally, participants shared additional considerations. They emphasized prioritizing safety and clinical outcomes in TAVI programs beyond simply increasing the number of available centers. Although concentration of procedures in high-volume centers was suggested to improve health outcomes, it could also reduce the total number of procedures. The need for audits and dissemination of risk-adjusted results was highlighted to ensure transparency and care quality. Lastly, concern was expressed about the impact of health system fragmentation on equity of access.

DISCUSSION

The present study confirms the upward trend in TAVI implantation in Spain, which is consistent with previous research.5,22 From 2016 through 2023, the number of procedures increased in all AC, reflecting broader acceptance of this technique within the SNS. This trend is attributed to the consolidation of TAVI as a reference therapeutic alternative for the treatment of severe symptomatic AS, progressively expanding from high-risk to intermediate- and low-risk patients.12-14

Despite this generalized increase, results show notable interregional variability in TAVI rates. In 2023, some AC reported procedural rates well above the national average, while others were considerably lower. This inequality has been documented previously and suggests a key role for organizational factors in determining access to the procedure.21 Of note, in regions such as La Rioja, the absence of local cardiac surgery centers may partly explain the low number of TAVI. However, this does not mean that patients are not treated; rather procedures are performed in neighboring AC.

From a clinical perspective, multiple studies have shown that TAVI reduces in-hospital mortality, improves quality of life, and decreases the rate of major complications.16-20 Although these outcomes were not directly assessed in the present study, former studies have identified a relationship between higher procedural volume and improved outcomes, including reduced infection risk, decreased pacemaker need, and a shorter length of stay.5 Our analysis does not allow a direct correlation to be established between procedural volume and quality of care in Spain. This suggests that, although cumulative experience is a determinant of improved outcomes, other organizational and resource-management factors may also contribute to the observed discrepancies. Nonetheless, our findings indicate that as TAVI volume increases, the variability in mortality outcomes tends to diminish, suggesting greater standardization of practice and reduced variability across more experienced centers.

The survey analysis revealed that TAVI indication in Spain continues to depend primarily on physician judgment and patient risk stratification, with less influence from patient preference or resource availability. These findings are consistent with former studies underscoring the importance of multidisciplinary clinical judgment in decision-making, which results in patient selection aligned with clinical practice guidelines and safety criteria.27 However, organizational barriers hindering the expansion of TAVI were identified, including rigid patient stratification, insufficient identification of candidates, and difficulties integrating heart teams. Such limitations have previously been recognized as determinants of inequality in TAVI access in Spain,21 reinforcing the need for strategies to optimize care.

From a financial perspective, TAVI has been shown to be cost-effective compared with conventional surgical aortic valve replacement across various clinical scenarios.15,28 In our study, however, participants did not identify financing as a major barrier to expansion. This finding is consistent with prior Spanish investigations, which found no clear correlation between regional health spending and TAVI rates,5,21 suggesting that variability is more strongly influenced by organizational rather than economic factors.

The perception of infrastructure is relevant too, as most respondents considered the number of centers performing TAVI in Spain sufficient, while emphasizing the importance of guaranteeing a minimum procedural volume per center to optimize outcomes and minimize complications. Former studies have highlighted that cumulative team experience can improve clinical outcomes.27 However, no consensus was reached in this study on whether concentrating procedures in a smaller number of centers would favor equity of access or, conversely, limit availability in regions with restricted supply.

With respect to continuity of care, both advances and opportunities for improvement were identified. While > 90% of specialists positively evaluated the implementation of teleconsultation, specialized nursing programs (TAVI Nurse26), and shared protocols across levels of care, participants also emphasized the need to strengthen coordination between primary and specialized care, improve clinical information systems, and optimize scheduling management. These aspects have previously been highlighted as important for improving the efficiency of TAVI care processes5 and identified as cross-cutting priorities in the 2022 report of the SNS, Estrategia en Salud Cardiovascular.29

Limitations

This study has certain limitations. First, although the analysis of the Specialized Care Activity Minimum Basic Data provides information on overall TAVI trends, the Spanish Ministry of Health’s statistical portal does not include detailed patient-level clinical data, thus preventing assessment of outcomes such as complications.

Second, although the survey was designed to achieve representation from all AC, responses were obtained from only 11 of them (26 of 123 [21%] affiliated centers of the Interventional Cardiology Association), meaning that the perceptions and experiences reflected are drawn from a subset of regions, which may influence interpretation of certain findings. Nevertheless, this limitation is inherent to survey-based research, as participation greatly depends on availability and willingness of respondents. Despite this, the sample offers a representative perspective on organizational and clinical factors influencing variability in TAVI access within the SNS.

Finally, sex and gender variables were not considered in accordance with the SAGER guidelines, as the focus was on regional differences across AC. Future studies should explore sex- and gender-related influences on TAVI implementation.

CONCLUSIONS

Our findings reflect sustained growth in TAVI implementation in Spain, alongside marked interregional variability in procedural rates. Patient selection is driven primarily by physician judgment and clinical risk, while barriers to expansion are more organizational than financial. Key strategies are suggested to reduce regional variability and ensure equitable TAVI access within the SNS, including improved coordination across different levels of care, standardization of selection criteria, and strengthened resource management.

FUNDING

This work was funded by Edwards Lifesciences.

ETHICAL CONSIDERATIONS

Approval from the study ethics committee was deemed unnecessary, as it used administrative data from the Spanish Ministry of Health without accessing patient-level data. Similarly, informed consent was deemed unnecessary. Sex and gender variables were not analyzed in accordance with the SAGER guidelines, as the study focused on regional differences across AC.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

Artificial intelligence was not used in this study.

AUTHORS’ CONTRIBUTIONS

All authors were involved in the study design. A. Morán-Aja, O. Martínez-Pérez, M. Cerezales, and J. Cuervo requested the data and implemented the web-based survey. O. Martínez-Pérez conducted data analysis. All authors reviewed and validated the results. A. Morán-Aja, O. Martínez-Pérez, M. Cerezales, and J. Cuervo drafted the manuscript. All authors reviewed and approved the final version.

CONFLICTS OF INTEREST

J.M. de la Torre-Hernández is editor-in-chief of REC: Interventional Cardiology; the journal’s editorial procedure to ensure impartial handling of the manuscript. A. Morán-Aja, O. Martínez-Pérez, M. Cerezales, and J. Cuervo work for Axentiva Solutions S.L., a consultancy providing services to various pharmaceutical and medical device companies.

ACKNOWLEDGMENTS

The authors thank the Research Agency and Scientific Department of the Spanish Society of Cardiology for their support in project management and securing funding. Their collaboration was essential to the planning and execution of this study, enabling data analysis and evaluation of regional variability in TAVI implementation in Spain.

SUPPLEMENTARY DATA

REFERENCES