Optical coherence tomography predictors of clinical outcomes after stent implantation: the ILUMIEN IV trial

Abstract

Background and Aims

Observational registries have suggested that optical coherence tomography (OCT) imaging-derived parameters may predict adverse events after drug-eluting stent (DES) implantation. The present analysis sought to determine the OCT predictors of clinical outcomes from the large-scale ILUMIEN IV trial.

Methods

ILUMIEN IV was a prospective, single-blind trial of 2487 patients with diabetes or high-risk lesions randomized to OCT-guided versus angiography-guided DES implantation. All patients underwent final OCT imaging (blinded in the angiography-guided arm). From more than 20 candidates, the independent OCT predictors of 2-year target lesion failure (TLF; the primary endpoint), cardiac death or target-vessel myocardial infarction (TV-MI), ischaemia-driven target lesion revascularization (ID-TLR), and stent thrombosis were analysed by multivariable Cox proportional hazard regression in single treated lesions.

Results

A total of 2128 patients had a single treated lesion with core laboratory-analysed final OCT. The 2-year Kaplan–Meier rates of TLF, cardiac death or TV-MI, ID-TLR, and stent thrombosis were 6.3% (n = 130), 3.3% (n = 68), 4.3% (n = 87), and 0.9% (n = 18), respectively. The independent predictors of 2-year TLF were a smaller minimal stent area (per 1 mm² increase: hazard ratio 0.76, 95% confidence interval 0.68–0.89, P < .0001) and proximal edge dissection (hazard ratio 1.77, 95% confidence interval 1.20–2.62, P = .004). The independent predictors of cardiac death or TV-MI were smaller minimal stent area and longer stent length; of ID-TLR were smaller intra-stent flow area and proximal edge dissection; and of stent thrombosis was smaller minimal stent expansion.

Conclusions

In the ILUMIEN IV trial, the most important OCT-derived post-DES predictors of both safety and effectiveness outcomes were parameters related to stent area, expansion and flow, proximal edge dissection, and stent length.

Structured Graphical Abstract

The independent optical coherence tomography predictors of clinical outcomes in 2128 patients with a single treated lesion in the ILUMIEN IV trial are shown here. Minimal stent area is defined as the smallest stent area within the contiguous stent segment. Minimal stent expansion is defined as the minimal stent area divided by the average of proximal and distal reference lumen areas × 100. Intra-stent flow (lumen) area is defined as stent area minus intra-stent plaque protrusion or thrombus area. HR, hazard ratio; ID-TLR, ischaemia-driven target lesion revascularization; MSA, minimal stent area; MSE, minimal stent expansion; OCT, optical coherence tomography; TLF, target lesion failure; TV-MI, target-vessel myocardial infarction

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See the editorial comment for this article ‘Optical coherence tomography for optimal stent implantation: what to check?’, by E. Romagnoli et al., https://doi.org/10.1093/eurheartj/ehae626.

Introduction

The superior resolution of optical coherence tomography (OCT) compared with intravascular ultrasound (IVUS) leads to more accurate dimensional measurements and enhanced detection of suboptimal percutaneous coronary intervention (PCI) results including edge dissections, stent mal-apposition, and thrombus.¹ However, not all of these findings are necessarily clinically relevant.^1–3 Prior observational studies have identified variable OCT imaging predictors of adverse clinical outcomes after PCI^4–9; however, the validity of these parameters is uncertain given the heterogeneity in study design and analyses and lack of prospective validation.

The OCT-Guided Coronary Stent Implantation Compared with Angiography: A Multicenter Randomized Trial in PCI (ILUMIEN IV: OPTIMAL PCI) was a prospective, randomized, single-blind trial in which 2487 patients with medication-treated diabetes or complex coronary artery lesions were randomly assigned to OCT-guided PCI or angiography-guided PCI.¹⁰ A novel aspect of ILUMIEN IV was the performance of a final OCT assessment in all patients, which was blinded to the operator in the angiography-guided group. Herein, we report a pre-specified analysis from the ILUMIEN IV trial examining the relationship between post-PCI OCT-derived parameters and subsequent clinical outcomes during 2-year follow-up after drug-eluting stent (DES) implantation.

Methods

Trial design and oversight

The prospective, single-blind, randomized ILUMIEN IV trial was conducted at 80 sites in 18 countries, including in North America, Europe, the Middle East, and Asia-Pacific region. The trial was approved by the institutional review board or ethics committee at each site, and all patients provided written informed consent. The sponsor (Abbott, Santa Clara, CA, USA) funded the trial and participated in site selection and data analysis. The principal investigators and study chair had unrestricted access to the data, prepared the manuscript, and attested to the accuracy of the analyses.

Patients

Patients 18 years of age or older with evidence of myocardial ischaemia who were undergoing PCI and qualified as a high-risk patient or had one or more high-risk coronary artery lesions were enrolled. A high-risk patient was defined as having medication-treated diabetes mellitus. High-risk coronary lesions were defined as a lesion deemed responsible for a recent myocardial infarction; long or multiple lesions requiring >28 mm of stent; a bifurcation lesion with planned stenting of both the main and side branches; a severely calcified lesion; a chronic total occlusion; or diffuse or multifocal in-stent restenosis.

Interventions

Eligible patients were randomly assigned in a 1:1 ratio to undergo OCT-guided or angiography-guided PCI with XIENCE cobalt chromium everolimus-eluting stents (Abbott). In the OCT-guided group, PCI was performed with a technique modified from the ILUMIEN III trial to allow optimization of stent sizing and length determination.¹¹ A detailed description of the OCT-guidance and optimization algorithm has been published.^10,12 Briefly, the distal reference mean external elastic lamina (EEL)-based diameter was measured and rounded down to the nearest available stent size in 0.25 mm increments to determine stent diameter. If the distal reference EEL could not be adequately visualized, the stent diameter was chosen using the mean lumen diameter at the distal reference rounded up to the next 0.25 mm stent size. Stent length was determined by the distance from distal to proximal reference site using the OCT-automated lumen detection feature. After stent deployment, optimization was performed with non-compliant balloons in the proximal and distal segments of the stent based on the respective EEL or lumen diameter measurements by rounding down (if EEL diameter was available) or up (if only lumen diameter was available) to the nearest non-compliant balloon size. Following optimization, OCT imaging was repeated and, if necessary, iterative high-pressure or larger non-compliant balloon inflations were performed, based on new reference segment measurements, to achieve acceptable stent expansion [a minimal stent area (MSA) of at least 90% in both the proximal and distal segments of the stent relative to the closest reference segment] if possible. The post-stent proximal and distal reference segments, defined as 5 mm from the edges of the stent, were also examined for inflow/outflow disease. If both the proximal and distal reference segments had a minimal lumen area (MLA) ≥ 4.5 mm², no further treatment was deemed necessary. If there was untreated reference segment disease (defined as a focal MLA < 4.5 mm² in either the proximal or distal reference segment), an additional DES was to be implanted unless anatomically prohibitive (e.g. biological vessel tapering, distal diffuse disease, and absence of landing zone). An additional DES was also recommended for treatment of a major edge dissection (defined as ≥60° of the circumference of the vessel at site of dissection and ≥3 mm in length).

A final OCT imaging run was performed at the end of the PCI procedure. For patients assigned to angiography guidance alone, these results were blinded to the operator.

Optical coherence tomography analysis

Optical coherence tomography data were analysed at an independent imaging core laboratory [Cardiovascular Research Foundation (CRF), New York, NY, USA] without knowledge of randomized group. Optical coherence tomography images were considered not analysable if quantitative measurements were impaired from poor blood flush, significant non-uniform rotational distortion, or other reasons. All qualitative analyses were done using all available frames (0.2 mm frame intervals). All quantitative analyses were done every 1 mm. The key intra-stent OCT measurements were MSA, minimal stent expansion (MSE), intra-stent and total flow areas, major or minor tissue (plaque or thrombus) protrusion, major or minor stent mal-apposition, and stent deformation or fracture. The key stent edge-related OCT measurements were untreated reference segment disease that was further classified as focal or diffuse and lipidic or non-lipidic and major or minor dissection that was further categorized as intimal, medial (with or without haematoma), or adventitial. Detailed definitions of each of these parameters are provided in the Supplementary data.

Clinical endpoints

Clinical follow-up was performed at 1, 12, and 24 months after the procedure; patients, healthcare providers, and outcomes assessors were blinded to treatment assignment group as previously described.^10,12 Clinical events were adjudicated by an independent committee blinded to randomization assignment (CRF). The primary clinical endpoint for the current analysis was target lesion failure (TLF) defined as a composite of death from cardiac causes, target-vessel myocardial infarction (TV-MI) or ischaemia-driven target lesion revascularization (ID-TLR) at 2-year follow-up. Secondary endpoints were the composite of cardiac death or TV-MI, ID-TLR, and stent thrombosis (definite or probable). The definitions of these endpoints are described in detail in the Supplementary data.

Statistical analysis

To be able to accurately relate lesion-specific post-PCI OCT parameters to events likely to have arisen from that lesion, the present analysis cohort was restricted to patients with a single treated coronary lesion who had a final OCT assessment that was analysable by the core laboratory. All analyses were performed on an intention-to-treat basis. Continuous variables are shown as mean ± standard deviation and were compared with a two-sample t-test. Categorical variables are shown as frequencies and were compared with a χ² or Fisher's exact test. Time-to-first event estimates were generated with the Kaplan–Meier method and were compared using the log-rank test. Associations between OCT findings and clinical outcomes were evaluated using univariable and multivariable Cox proportional hazard regression and are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). The functional form of each of the continuous variables was checked at the univariate level via martingale residuals, and no evidence of violation of the linearity assumption was detected. Variables that were eligible for inclusion in the multivariable models (i) had a univariable P-value of ≤.2; (ii) were present in ≥85% of the subjects in the analysis; (iii) had no subgroup with <30 patients (for categorical variables); and (iv) had the stronger statistical significance if highly correlated with another variable (|correlation coefficient| > 0.5). The associations between final MSA as a continuous variable and clinical outcomes are graphically presented with penalized spline curves with optimization of the degree of freedom using the Akaike information criteria based on the maximized log-likelihood of the model. All analyses were two sided, and P-values <.05 were considered significant. Missing data were not replaced. All statistical analyses were performed with SAS software, v9.4 (SAS Institute, Cary, NC, USA).

Results

Clinical and procedural characteristics

A total of 2487 patients were randomized between 17 May 2018 and 29 December 2020, of whom 2128 (85.6%) had a single treated lesion with evaluable final OCT data that were included in the present analyses; 1056 patients were assigned to OCT-guided PCI and 1072 to angiography-guided PCI (Figure 1). Clinical and angiographic characteristics of patients included in the present analyses are shown in Table 1 and Supplementary data online, Table S1, and procedural characteristics are shown in Table 2. Medication-treated diabetes was the qualifying high-risk patient characteristic in 39.2% of patients, and the most common qualifying high-risk lesion characteristics were long lesions (66.5%) and non-ST-segment elevation MI culprit lesion (23.6%). By angiographic core laboratory assessment, the mean reference vessel diameter was 2.93 ± 0.42 mm, the mean lesion length was 31.9 ± 15.9 mm, and 30.7% of lesions were severely calcified. All baseline characteristics were well matched between groups except for lesion length, which was longer in the OCT arm. Advanced lesion preparation, implanted stent length and diameter, number of post-dilatation balloons, and stent inflation pressures were higher in the OCT-guided group compared with the angiography-guided group. Procedure times, fluoroscopy duration, radiation dose, and contrast volume were also greater with OCT guidance. Medication use during follow-up is shown in Supplementary data online, Table S2.

Optical coherence tomography findings

The final post-PCI OCT findings in all patients and per randomized group are shown in Table 3. Optical coherence tomography guidance resulted in larger stent dimensions (including greater MSA, MSE, and intra-stent and total flow areas), less major but more minor tissue protrusion, less major mal-apposition, and fewer distal dissections (of all types) and fewer proximal and distal medial dissections (including fewer medial haematomas), compared with angiography guidance.

Clinical endpoints

The 2-year Kaplan–Meier rates of TLF, cardiac death or TV-MI, ID-TLR, and stent thrombosis were 6.3% (n = 130), 3.3% (n = 68), 4.3% (n = 87), and 0.9% (n = 18), respectively. Similar to the principal results from the entire trial,¹⁰ event rates in this study cohort were not significantly different between the randomized groups, except for stent thrombosis that occurred less frequently after OCT guidance compared with angiography guidance (Table 4).

Optical coherence tomography predictors of clinical outcomes

As shown in Table 5, the univariable (unadjusted) OCT correlates of 2-year TLF were smaller stent dimensions (including MSA, MSE, intra-stent flow area, and total flow area) and proximal reference segment dissection, especially medial and minor dissections. By multivariable analysis, the independent predictors of 2-year TLF were smaller MSA (per 1 mm² increase: HR 0.76, 95% CI 0.68–0.86, P < .0001) and proximal edge dissection (HR 1.77, 95% CI 1.20–2.62, P = .004) (Table 6). The distribution and relationship between MSA and the 2-year rate of TLF in the randomized groups are shown in Figure 2. A non-linear relationship was present wherein the rate of TLF increased exponentially below an MSA of 4.0 mm².

The unadjusted correlates of cardiac death or TV-MI, ID-TLR, and stent thrombosis are shown in Supplementary data online, Tables S3–S5. As shown in Table 6, the independent predictors of cardiac death or TV-MI were smaller MSA (per 1 mm² increase: HR 0.82, 95% CI 0.70–0.95, P = .009) and longer stent length (per 5 mm increase: HR 1.08, 95% CI 1.02–1.15, P = .009); of ID-TLR were smaller intra-stent flow area (per 1 mm² increase: HR 0.72, 95% CI 0.62–0.84, P < .0001) and proximal edge dissection (HR 1.88, 95% CI 1.16–3.03, P = .01), with major tissue protrusion being of borderline significance (HR 1.95, 95% CI 0.97–3.92, P = .06); and of stent thrombosis was smaller MSE (per 10% increase: HR 0.71, 95% CI 0.55–0.93, P = .01). The number and percentage of missing values for these analysed variables are shown in Supplementary data online, Table S6.

Discussion

In the present pre-specified analysis from ILUMIEN IV, the largest, prospective, randomized trial to date of intravascular imaging guidance vs. angiography guidance for PCI, we examined the immediate post-PCI OCT imaging predictors of clinical outcomes during a 2-year follow-up period in patients with a single treated lesion. The main findings of the present analysis are as follows. First, OCT guidance led to greater mean MSA, MSE, and intra-stent and total flow areas compared with angiography guidance alone. Optical coherence tomography guidance also reduced the frequency of post-PCI major tissue protrusion, major mal-apposition, proximal and distal medial dissections (including fewer medial haematomas), and distal dissections of all types. Second, only smaller MSA and the presence of a proximal edge dissection independently predicted the occurrence of TLF during follow-up. Third, the only independent OCT predictors of the composite of cardiac death or TV-MI were smaller MSA and stent length; of ID-TLR were intra-stent flow area and proximal edge dissection; and of stent thrombosis was smaller MSE (Structured Graphical Abstract).

As summarized in Supplementary data online, Table S7, prior studies have examined the association between intravascular imaging findings and clinical outcomes. Most of these studies were retrospective, many were single centre, not all used an independent core laboratory, and all were substantially smaller than the present prospective, multi-centre trial. Nonetheless, a smaller MSA has consistently been identified as the strongest predictor of future adverse events after DES implantation.^7,8,13–16 Based on these findings, the current European consensus document on intravascular imaging guidance of PCI endorses a MSE ≥ 80% and/or MSA > 4.5 mm² by OCT as acceptable.² Notably, the median MSE was 79.1% in the present study, and patients with a treated lesion above this median had a lower TLF rate and a lower rate of cardiac death or TV-MI, supporting the European Association of Percutaneous Cardiovascular Interventions recommendations. The present findings strongly reinforce the concept that achieving larger absolute stent areas and greater relative stent expansion should remain the primary target for OCT-guided PCI optimization. We found a smaller MSA to be an independent predictor not only of TLF but also of the composite outcome of cardiac death or TV-MI. Correspondingly, we found that the intra-stent flow area, a variable co-linear with MSA, independently predicted ID-TLR, and MSE, another variable co-linear with MSA, independently predicted stent thrombosis. The present analysis does not afford a ready explanation as to why one or the other variable (MSA vs. MSE vs. intra-stent flow area) that was all entered into each multivariable analysis as covariates was the strongest independent predictor of the different safety and effectiveness outcomes after DES. Nonetheless, they all point to the consistent conclusion that optimizing stent dimensions and expansion with OCT guidance is associated with subsequent freedom from stent-related adverse events.

In this regard, in the ILUMIEN IV trial, DES implanted with OCT guidance had a larger mean MSA compared with angiography guidance alone, but paradoxically, this did not result in a significant reduction in the 2-year rate of the primary study outcomes of target vessel failure (HR 0.90).¹⁰ Specifically, while there were numerically fewer cardiac deaths and TV-MIs and significantly fewer stent thromboses with OCT guidance, the rates of ID-TLR in the OCT-guided and angiography-guided groups were almost identical.¹⁰ One potential explanation for the discordance between the different group mean MSAs and non-significant difference in target vessel failure (or TLF in the present analysis) relates to the absolute MSAs achieved. Spline analysis from the present study demonstrated a steep and exponential risk of TLF with decreasing OCT-MSA below 4 mm². However, the post-PCI mean MSAs achieved in both groups in ILUMIEN IV (OCT 5.72 ± 2.04 mm²; angiography 5.36 ± 1.87 mm²)¹¹ were greater than in previous studies that reported an optimal MSA cut-off for DES of 4.5–5.3 mm² (see Supplementary data online, Table S7). In part, this may be explained by the fact that the mean maximum device size was larger in the present trial (3.54 ± 0.52 mm) than in most prior studies, and inflation pressures were notably higher, even in the control arm. Thus, while OCT did result in fewer patients with post-PCI MSA < 4 mm² than angiography guidance (as seen in Figure 2), the absolute proportion of patients favouring OCT guidance in this critical range may not have been sufficient to drive a significant difference in outcomes (other than for stent thrombosis). In this regard, a small MSE was a stronger predictor of stent thrombosis than a small MSA. Since an adequate MSA can still be achieved with stent under-expansion, this finding highlights the potential aetiologic importance of abnormal rheology on stent thrombosis.

The high resolution of OCT identifies peri-stent dissections in up to 40% of cases,¹¹ ∼80% undetectable by angiography, and many of which may heal without consequence.^17–19 As such, identifying which dissections lead to adverse clinical outcomes is important. Some studies have identified major stent edge dissections detected by OCT as a predictor of poor outcomes (see Supplementary data online, Table S7).^6,8,9,19 In the CLI-OPCI registry, a dissection with width > 200 μm at the distal edge (but not at the proximal edge) was associated with a 2.5-fold hazard of major adverse cardiovascular events (MACE).^6,8 In a detailed analysis of OCT-identified edge dissections, van Zandvoort et al.¹⁹ reported that cavity depth at the distal edge, reference lumen area at the proximal edge, and overall dissection length were predictors of MACE. In contrast, the present larger study identified proximal edge but not distal edge dissections as an independent predictor of TLF and ID-TLR. Importantly, this finding was independent of untreated reference segment disease (at either edge), which was not retained in the multivariable model. In addition, we were unable to demonstrate that major dissections were of greater risk than minor dissections, although by univariable analysis medial dissections, especially when a haematoma was visualized by OCT, may portend greater risk. However, even ILUMIEN IV did not contain enough dissections of each type to state with certainty, which are of greatest clinical relevance, a topic warranting future studies with even larger OCT databases. Until that time, we believe that treating major proximal (and distal) dissections as identified by OCT is prudent. Finally, also of note is the finding that acute stent mal-apposition was not an independent predictor of adverse outcomes, a finding consistent with nearly all prior studies.²⁰ As such, while stent mal-apposition is often a dramatic finding on OCT (often more so than with IVUS), most cases of acute stent mal-apposition do not require treatment unless associated with a small MSA or stent under-expansion.

Limitations

To isolate the effect of post-PCI OCT parameters on outcomes, we restricted our analyses to cases with a single treated lesion, potentially excluding higher-risk patients. Moreover, the present analysis focused on lesion-specific OCT predictors of clinical outcomes and not on vessel or patient predictors. Also, the OCT treatment algorithm mandated treatment of major mal-apposition, tissue protrusion, and major dissection, resulting in ∼25%–50% fewer such findings in the OCT arm. Further detailed analysis of the impact of these untreated conditions in the two arms (which may be of different severity) is warranted and is underway. However, as shown herein, the relationship between post-PCI MSA and TLF was consistent after OCT guidance and angiography guidance. Because IVUS often overestimates quantitative measures compared with OCT,²¹ the critical values for OCT-MSA described in the present report cannot be translated to IVUS guidance. Notably, operators detected suboptimal OCT findings, such as stent expansion < 90%, untreated reference segment disease, dissection, mal-apposition, and tissue protrusion at a lower rate compared with the core lab (see Supplementary data online, Table S8), highlighting the potential importance of incorporating artificial intelligence algorithms into OCT platforms. Another potential limitation of OCT guidance is the lack of data on coronary physiology. However, OCT-based virtual fractional flow reserve systems have been developed, and the combination of OCT-derived imaging and functional data may provide synergistic benefits. Finally, the COVID-19 pandemic may have reduced elective revascularization procedures in patients with recurrent angina or ischaemia, contributing to the low and similar rates of ID-TLR in the randomized groups.¹⁰ This issue did not have a major effect on the present study in which the relationship between final OCT findings and clinical outcomes in both the OCT-guided and angiography-guided study arms was analysed together. We cannot, however, exclude the possibility that additional predictors of clinical outcomes might have been detected had the study sample size been larger.

In conclusion, the present study, the largest analysis to date of intravascular imaging-derived predictors of clinical outcomes after PCI demonstrates that both a smaller absolute MSA and lower relative stent expansion are strongly associated with adverse safety and effectiveness outcomes after coronary DES implantation. Proximal edge dissections as detected by OCT were also an independent predictor of TLF and ID-TLR. Additional studies are warranted to determine whether optimizing these parameters with OCT guidance to an even greater extent than was achieved in ILUMIEN IV may further improve DES outcomes.

Supplementary data

Supplementary data are available at European Heart Journal online.

Declarations

Disclosure of Interest

U.L. reports research grant support from Abbott, Bayer, and Novartis; consulting fees from Abbott. Z.A.A. reports research grants from Abbott, Abiomed, Acist, Amgen, Boston Scientific, CathWorks, Canon, Conavi, HeartFlow, Inari, Medtronic Inc., National Institute of Health, Nipro, OpSens Medical, Medis, Philips, Shockwave, Siemens, SpectraWAVE, and Teleflex; consulting fees Abiomed, Astra Zeneca, Boston Scientific, CathWorks, OpSens, Philips, and Shockwave; speaker honoraria from Abiomed, Astra Zeneca, Boston Scientific, CathWorks, OpSens, Philips, and Shockwave; equity in Elucid, Lifelink, SpectraWAVE, Shockwave, VitalConnect; and expert testimony and several interventional cardiology patents. A.M. reports consulting fees from Boston Scientific, Shockwave, Philips, and Abbott; lecture fees from Nipro; and advisory board fees from SpectraWAVE. M.M. reports consulting fees from Terumo and Boston Scientific. R.A.S. has no conflicts of interest to report. G.G. reports grants from Abbott; consulting fees from Abbott, Infraredx, Panorama Scientific, Gentuity, and Innova; lecture fees from GE Medical, Nipro, and Abbott; travel fees from Abbott; advisory board fees from Boston Scientific; and advisory board leadership role fees from ConneX Biomedical. M.J.P. reports consulting fees from Abbott, Medtronic, Boston Scientific, Philips, and WL Gore and lecture fees from ACIST, Medtronic, Abbott, Boston Scientific, Philips, and Shockwave. J.M.H. reports consulting fees from Abbott, Shockwave, Boston Scientific, Abiomed, and Medtronic; lecture fees from Abbott, Shockwave, Boston Scientific, Abiomed, and Medtronic; payment for expert testimony from Shockwave; travel fees from Abbott, Shockwave, and Abiomed; advisory board fees from Abbott, Medtronic, and Shockwave; and stock or stock options from Shockwave. T.A. reports research grants from Abbott, Daiichi Sankyo, Nipro, and Terumo; consulting fees from Terumo; lecture fees from Abbott, Daiichi Sankyo, Otsuka, and Boehringer Ingelheim; and unpaid leadership role in Asian Pacific Society of Cardiology, World Heart Federation, and Japanese Circulation Society. F.P. has no conflicts of interest to report. H.G.B. reports consulting fees from Abbott and Gentuity and lecture fees from Abbott. W.W. reports research grants from MicroPort; advisory board from Argonauts, Rede Optimus Research, and Corrib Core Laboratory, University of Galway; and chairmanship of PCR. D.L. reports consulting fees and lecture fees from Abbott. P.C. reports research grants from Terumo, Daiichi Sankyo, Abbott, Boston Scientific, Sanofi, Novartis, and Bristol Myers Squibb and consulting fees from Abbott, Boston Scientific, Amgen, and Amarin. F.A. has no conflicts of interest to report. F.F. has no conflicts of interest to report. G.C. has no conflicts of interest to report. R.M.O. reports lecture fees from Abbott and Philips/Volcano. S.A. reports board membership for European Society of Cardiology. C.T. reports research grants from Medtronic and Chiesi and lecture fees from Medtronic, Abbott, Boston Scientific, Terumo, and Abiomed. B.S. has no conflicts of interest to report. R.J.M., R.W.M., S.-W.Y., and J.B. are employees of Abbott Vascular. G.W.S. has received speaker honoraria from Medtronic, Pulnovo, Abiomed, Amgen, Boehringer Ingelheim; has served as a consultant to Abbott, Daiichi Sankyo, Ablative Solutions, CorFlow, Cardiomech, Robocath, Miracor, Vectorious, Apollo Therapeutics, Elucid Bio, Cardiac Success, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, HighLife, Elixir, Remote Cardiac Enablement, Aria; and has equity/options from Cardiac Success, Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWAVE, Orchestra Biomed, Aria, Valfix, and Xenter. G.W.S.'s employer, Mount Sinai Hospital, receives research grants from Shockwave, Abbott, Abiomed, BioVentrix, Cardiovascular Systems Inc., Phillips, Biosense Webster, Vascular Dynamics, Pulnovo, and V-wave.

Data Availability

The data, methods used in the analysis, and materials used to conduct the research will not be made publicly available. The authors will provide data for reproducing the results for the purposes of audit or governance under a confidentiality agreement. Any relevant inquiry should be emailed to the study chairman G.W.S. (Email: [email protected]).

Funding

This clinical trial was funded by Abbott.

Ethical Approval

The trial was approved by the institutional review board or ethics committee at each site, and all patients provided written informed consent.

Pre-registered Clinical Trial Number

The pre-registered clinical trial number is ClinicalTrials.gov NCT03507777.

References