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A Systematic Review and Meta-Analysis of Clinical Outcomes of Patients Undergoing Chronic Total Occlusion Percutaneous Coronary Intervention
Abstract
Objectives. Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can improve patient symptoms, but it remains controversial whether it impacts subsequent clinical outcomes. Methods. In this systematic review and meta-analysis, we queried PubMed, ScienceDirect, Cochrane Library, Web of Science, and Embase databases (last search: September 15, 2021). We investigated the impact of CTO-PCI on clinical events including all-cause mortality, cardiovascular death, myocardial infarction (MI), major adverse cardiovascular event (MACE), stroke, subsequent coronary artery bypass surgery, target-vessel revascularization, and heart failure hospitalizations. Pooled analysis was performed using a random-effects model. Results. A total of 58 publications with 54,540 patients were included in this analysis, of which 33 were observational studies of successful vs failed CTO-PCI, 19 were observational studies of CTO-PCI vs no CTO-PCI, and 6 were randomized controlled trials (RCTs). In observational studies, but not RCTs, CTO-PCI was associated with better clinical outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, MACE, and MI were 0.52 (95% CI, 0.42-0.64), 0.46 (95% CI, 0.37-0.58), 0.66 (95% CI, 0.50-0.86), respectively for successful vs failed CTO-PCI studies; 0.38 (95% CI, 0.31-0.45), 0.57 (95% CI, 0.42-0.78), 0.65 (95% CI, 0.42-0.99), respectively, for observational studies of CTO-PCI vs no CTO-PCI; 0.72 (95% CI, 0.39-1.32), 0.69 (95% CI, 0.38-1.25), and 1.04 (95% CI, 0.46-2.37), respectively for RCTs. Conclusions. CTO-PCI is associated with better subsequent clinical outcomes in observational studies but not in RCTs. Appropriately powered RCTs are needed to conclusively determine the impact of CTO-PCI on clinical outcomes.
J INVASIVE CARDIOL 2022;34(11):E763-E775. Epub 2022 October 13.
Key words: chronic total occlusion, clinical outcomes, meta-analysis, percutaneous coronary intervention, systematic review
Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can improve clinical symptoms, such as angina and dyspnea, but it remains unclear whether it can also reduce the risk for subsequent adverse clinical events.1-4 Most studies examining the impact of CTO-PCI on clinical events are observational, which is subject to bias and confounding. In addition, randomized controlled trials (RCTs) conducted to date were not powered for clinical events. Therefore, we performed a systematic review and meta-analysis of all publications on CTO-PCI that included data on subsequent clinical events by stratifying them based on study type.
Methods
The present study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (Supplemental Materials). The study was designed and registered in the International Prospective Register of Systematic Reviews (PROSPERO) before comprehensive search was commenced (PROSPERO registration number: CRD42021284789).
Search strategy. A comprehensive search on PubMed, Science Direct, Embase, Cochrane Library, and Web of Science was performed by 2 independent researchers (BS and SK) with the following terms: “chronic coronary occlusion” or “chronic total coronary occlusion” or “chronic total occlusion” or “total coronary artery occlusion” (final search date: September 15, 2021). In addition, a manual search of the references of included studies was performed based on the “snowball” method to identify any potentially relevant but missed articles.
Study selection and data extraction. All citations were downloaded and imported into EndNote x8.2, where duplicates were removed. The remaining citations were uploaded into the rayyan.ai website, where they were reviewed for inclusion/exclusion criteria (Figure 1). The PICOS (population/participants, intervention, comparison, outcomes, and study design) framework was used to define study selection criteria. Population/participants were defined as patients undergoing clinically indicated CTO-PCI and their corresponding comparison groups. Interventions were defined as CTO-PCIs. Comparisons were defined as successful vs failed CTO-PCI (cohort studies), CTO-PCI vs no CTO-PCI (cohort studies), and RCTs. Outcomes were defined as all-cause mortality, cardiovascular (CV) death, major adverse cardiovascular event (MACE), myocardial infarction (MI), stroke, subsequent coronary artery bypass graft (CABG), target-vessel revascularization (TVR), and heart failure (HF) hospitalizations.
Study design: cohort studies and RCTs. Studies were excluded if they did not include any of these clinical events or were subgroup analyses of other included studies. If several studies were published from the same center with overlapping procedure dates, only the largest study was included to avoid duplication. Absolute numbers for the outcomes and baseline characteristics were extracted from the publications. In cases where absolute numbers were not reported, we calculated the absolute numbers by multiplying patients in the group of interest with the incidence/prevalence of the baseline characteristic/outcome and rounded to the closest number. The extracted data were reviewed by 2 authors (BS and SK) and disagreements were resolved through revisiting the published articles.
The studies included in the meta-analysis were divided into 3 groups: (1) cohort studies where patients who underwent CTO-PCI were followed and clinical outcomes were compared based on technical success (successful vs failed CTO-PCI); (2) cohort studies where patients underwent CTO-PCI or did not (CTO-PCI vs no CTO-PCI); and (3) studies where patients were randomized either to CTO-PCI or control (RCTs).
Risk for bias and certainty in evidence. We used the Newcastle-Ottawa Scale (NOS) to perform quality assessment for nonrandomized studies (Supplemental Materials). Adequacy of follow-up length and rate were set at 90 days and 90%, respectively, for the outcomes of interest before data extraction in the NOS. The Cochrane Risk of Bias tool was used for RCTs (Supplemental Materials).
Statistical analysis. Meta-analysis was carried out to compare all-cause mortality, CV death, MACE, MI, stroke, subsequent CABG, TVR, and HF hospitalizations. Heterogeneity between studies was assessed by I2 index. I2 index was used to assess heterogeneity for each reported pooled analysis with >50% accepted as high heterogeneity. A pooled analysis with random-effects model was performed using Stata, version 17.0 (StataCorp LLC). After performing the pooled analysis, we performed a sensitivity analysis only incorporating studies that had >90% drug-eluting stent (DES) use and were published during or after 2015. Studies that did not comment on stent type (bare metal vs drug eluting) were excluded from this analysis. Outcomes within studies and the results of pooled analyses were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was assessed with the visual inspection of funnel plots (Begg’s method) and Egger’s test (Supplemental Materials).
Results
Of 24,685 citations identified in the literature search, 58 publications were included in the meta-analysis (Figure 1); 33 were comparisons of successful vs failed CTO-PCI (38,048 patients),5-37 19 were comparisons of CTO-PCI vs no CTO-PCI (cohort studies) (14,622 patients),38-56 and 6 were RCTs of CTO-PCI vs no CTO-PCI (1890 patients).1-4,57,58 The included 58 publications had a total of 54,560 patients, of whom 45,527 (83%) underwent CTO-PCI.
In the full cohort, median age was 64 years (interquartile range [IQR], 61-66) and 78% were men. The most common CTO vessel was the right coronary artery in all 3 study types (41%), followed by left anterior descending (38%) and circumflex (21%). Patients had a high prevalence of hypertension (58%), hyperlipidemia (56%), current smoking (27%), diabetes mellitus (32%), chronic kidney disease (6%), family history of coronary artery disease (33%), history of CABG (11%), history of HF (18%), history of stroke (5%), history of MI (37%), and prior PCI (30%). The baseline characteristics including procedural success and DES use stratified by study type are reported in Table 1.
All-cause mortality. A total of 24 successful vs failed CTO-PCI studies reported 2699 all-cause deaths (7.6%) during a median follow-up of 2.7 years (IQR, 1.3-4.1). Successful CTO-PCI was associated with 48% lower all-cause mortality (OR, 0.52; 95% CI, 0.42-0.64; I2=71%). In 9 CTO-PCI vs no-CTO PCI studies, 1416 events were reported with a 62% lower all-cause mortality in the CTO PCI group (OR, 0.38; 95% CI, 0.31-0.45; I2=29%). In RCTs, there was a total of 41 events (3 RCTs were double-zero events and 1 was a single-zero event), all-cause mortality was not statistically different between the study groups (OR, 0.72; 95% CI, 0.39-1.32; I2=0%) (Figure 2). In a sensitivity analysis of studies with >90% DES use, a total of 12 studies reported 571 all-cause deaths (6.7%). Successful CTO-PCI or CTO-PCI were associated with 50% lower all-cause mortality compared with failed CTO-PCI or no CTO-PCI (OR, 0.50; 95% CI, 0.37-0.67; I2=34%).
Cardiovascular death. A total of 17 successful vs failed CTO-PCI studies reported 546 CV death events. Successful CTO-PCI was associated with a 60% lower incidence of CV death (OR, 0.40; 95% CI, 0.32-0.49; I2=16%). In 12 CTO-PCI vs no CTO-PCI studies, 882 events were reported with 58% lower incidence of CV death with CTO-PCI (OR, 0.42; 95% CI, 0.32-0.56; I2=55%). In RCTs, there were a total of 26 events (4 RCTs were double-zero events; OR for CTO-PCI, 0.81; 95% CI, 0.30-2.18; I2=9%). In sensitivity analysis, a total of 12 studies reported 370 CV deaths (3.7%). Successful CTO-PCI or CTO-PCI were associated with 36% lower CV death compared with failed CTO-PCI or no CTO-PCI (OR, 0.64; 95% CI, 0.42-0.97; I2=46%).
Major adverse cardiovascular events. A total of 24 successful vs failed CTO-PCI studies reported 4163 incidents of MACE. Successful CTO-PCI was associated with a 54% lower MACE rate (OR, 0.46; 95% CI, 0.37-0.58; I2=80%). In 9 CTO-PCI vs no CTO-PCI studies, 1513 events were reported with a 43% lower MACE rate favoring CTO-PCI (OR, 0.57; 95% CI, 0.42-0.78; I2=78%). In RCTs, there were a total of 215 events (2 RCTs were double-zero events and 1 was a single-zero event for MACE) with no significant difference between the 2 study groups (OR, 0.69; 95% CI, 0.38-1.25; I2=35%) (Figure 4). In sensitivity analysis, a total of 13 studies reported 1659 incidents of MACE (15%). Successful CTO-PCI or CTO-PCI were associated with a 32% lower MACE rate compared with failed CTO-PCI or no CTO-PCI (OR, 0.68; 95% CI, 0.52-0.90; I2=74%).
Myocardial infarction. A total of 19 successful vs failed CTO-PCI studies reported 547 MIs. Successful CTO-PCI was associated with a 34% lower MI rate (OR, 0.66; 95% CI, 0.50-0.86; I2=34%). In 9 CTO-PCI vs no CTO-PCI studies, 581 events were reported with 35% lower MI risk among CTO-PCI patients (OR, 0.65; 95% CI, 0.42-0.99; I2=70%). In RCTs, there were a total of 24 events, 2 RCTs were double-zero events and 2 were single-zero events for MI (OR for CTO-PCI, 1.04; 95% CI, 0.46-2.37; I2=0%) (Figure 5). In sensitivity analysis, a total of 12 studies reported 253 MIs (2.7%; OR for successful CTO-PCI or CTO-PCI, 0.84; 95% CI, 0.56-1.27; I2=29%).
Stroke. A total of 6 successful vs failed CTO-PCI studies reported 107 strokes. Successful CTO-PCI was associated with a 22% lower stroke rate, which was not statistically significant (OR, 0.78; 95% CI, 0.50-1.20; I2=0%). In 4 CTO-PCI vs no CTO-PCI studies, 107 events were reported with 50% lower stroke rate favoring CTO-PCI (OR, 0.50; 95% CI, 0.20-1.22; I2=0%). In RCTs there were a total of 18 events (4 RCTs were double-zero events and 1 was a single-zero event for stroke) (OR for CTO-PCI, 0.56; 95% CI, 0.24-1.34; I2=0%) (Figure 6). In sensitivity analysis, a total of 9 studies reported 45 strokes (1%; OR for successful CTO-PCI or CTO-PCI, 0.65; 95% CI, 0.34-1.22; I2=1.7%).
Subsequent coronary artery bypass graft surgery. A total of 17 successful vs failed CTO-PCI studies reported 815 CABGs during follow-up. Successful CTO-PCI was associated with 83% lower likelihood for subsequent CABG (OR, 0.17; 95% CI, 0.11-0.26; I2=80%). In 1 CTO-PCI vs no CTO-PCI study, 74 events were reported with 70% lower CABG rate favoring CTO-PCI (OR, 0.30; 95% CI, 0.18-0.50). In RCTs there were a total of 4 events (4 RCTs were double-zero events and 1 was a single-zero event for subsequent CABG) (OR for CTO-PCI, 1.28; 95% CI, 0.31-5.29; I2=0%) (Figure 7). In sensitivity analysis, a total of 8 studies reported 44 subsequent CABGs (1.3%; OR for successful CTO-PCI or CTO-PCI, 0.37; 95% CI, 0.08-1.71; I2=65%).
Target-vessel revascularization. A total of 17 successful vs failed CTO-PCI studies reported 1521 TVRs. Successful CTO-PCI was associated with a 42% lower risk of TVR (OR, 0.58; 95% CI, 0.42-0.82; I2=81%). In 1 CTO-PCI vs no CTO-PCI study, 5 events were reported with 49% higher TVR rate favoring no CTO-PCI (OR, 1.49; 95% CI, 0.24-9.07). In RCTs, there were a total of 89 events (1 RCT was a double-zero event and 1 was a single-zero event for TVR) (OR for CTO-PCI, 0.98; 95% CI, 0.63-1.51; I2=0%). In sensitivity analysis, a total of 8 studies reported 361 TVRs (6%; OR for successful CTO-PCI or CTO-PCI, 0.68; 95% CI, 0.32-1.43; I2=80%).
Heart failure hospitalizations. A total of 3 successful vs failed CTO-PCI studies reported 41 HF hospitalizations. Successful CTO-PCI was associated with a 55% lower risk of HF hospitalizations (OR, 0.45; 95% CI, 0.23-0.88; I2=0%). A total of 5 CTO-PCI vs no CTO-PCI studies reported 186 HF hospitalizations (OR for CTO-PCI, 0.63; 95% CI, 0.33-1.22; I2=64%). In RCTs, no HF hospitalizations were reported. In sensitivity analysis, a total of 2 studies reported 114 HF hospitalizations (14%; OR for successful CTO-PCI or CTO-PCI, 0.57; 95% CI, 0.21-1.57; I2=69%).
Bias. The Egger’s test reported potential publication bias for all-cause mortality and subsequent CABG need in successful vs failed CTO-PCI studies with P=.11 and P=.09, respectively, and HF hospitalizations in CTO-PCI vs no CTO-PCI (observational studies) with P=.01 (Supplemental Materials).
Discussion
Our meta-analysis is the largest to date investigating the impact of CTO-PCI on clinical events during long-term follow-up. We performed separate analyses for 3 study designs (observational studies of successful vs failed CTO-PCI and CTO-PCI vs no CTO-PCI, and RCTs of CTO-PCI vs no CTO-PCI) and found that CTO-PCI was associated with better outcomes in observational studies but not in RCTs. In sensitivity analysis that excluded studies that were published before 2015 and/or had <90% DES use, successful CTO-PCI or CTO-PCI was associated with significantly better clinical outcomes as compared with failed CTO-PCI and no CTO-PCI.
There are 2 potential explanations for the discrepancy between observational studies and RCTs: (1) the RCT findings are true, ie, CTO-PCI does not impact subsequent clinical events; or (2) the RCT findings are false, ie, CTO-PCI reduces the risk of subsequent clinical events.
If CTO-PCI does not affect the subsequent risk of adverse cardiac events, then the observational study findings would be a “false positive,” likely due to selection bias. For example, patients with multiple comorbidities and poor prognosis may be less likely to be offered CTO-PCI. This could explain why the stroke rates were lower in the CTO-PCI arm of our analysis. Another potential reason explaining why stroke rates might be lower could be a higher rate of antiplatelet agent use in patients undergoing CTO-PCI. Moreover, patients with failed CTO-PCI have worse clinical and angiographic characteristics compared with patients in whom CTO-PCI is successful. A lack of benefit in hard endpoints from coronary revascularization in patients with chronic coronary syndromes would be supported by the findings of the COURAGE and ISCHEMIA trials.59,60
If CTO-PCI can reduce the risk of subsequent adverse cardiac events, then the RCT findings would be a “false negative.” There are several reasons why this is possible. First, the power of the RCTs published to date is low, due to the small number of patients enrolled and limited follow-up. The 2 largest trials (EuroCTO and DECISION-CTO) stopped enrollment prematurely prior to reaching the desired patient number and 3 RCTs did not report any death during follow-up.1,4,61 Second, sicker and more symptomatic patients who would be most likely to derive a benefit from CTO revascularization were less likely to enroll in RCTs (14% of the DECISION-CTO patients had mild or zero symptoms).61 Finally, extensive crossover occurred in some trials (20% of patients randomized to no CTO-PCI immediately crossed over to CTO-PCI due to operator preference in DECISION-CTO), thereby diluting a potential benefit of the procedure.61
Two ongoing RCTs could provide a more definitive answer on the clinical benefits (or lack thereof) of CTO-PCI: NOBLE-CTO (NOrdic-Baltic Randomized Registry Study for Evaluation of PCI in Chronic Total Occlusion; NCT03392415) and ISCHEMIA-CTO (International Randomized Trial on the Effect of Revascularization or Optimal Medical Therapy of Chronic Total Coronary Occlusions With Myocardial Ischemia; NCT03563417). NOBLE-CTO plans to enroll 2000 patients with reversible perfusion defect and a CTO lesion in a major coronary artery with the primary outcomes of all-cause mortality and quality-of-life assessment at 6 months. ISCHEMIA-CTO is enrolling 1560 patients with myocardial ischemia in a CTO vessel territory with the primary outcome of major adverse cardiovascular and cerebrovascular events over a 5-year follow-up period.
Study limitations. First, in CTO-PCI vs no CTO-PCI studies, long-term event rates in publications generally do not include in-hospital events, which are expectedly more common in patients who undergo CTO-PCI compared with the no CTO-PCI group. Second, certain outcomes of interest were missing in most studies (such as subsequent need for CABG surgery in CTO-PCI vs no CTO-PCI observational studies) and RCTs have limited follow-up and event accrual in most outcomes. Third, use of bare-metal stents was common in older studies, and several included studies used balloon angioplasty only, without stent implantation, which could decrease the potential benefits of CTO-PCI; yet our findings remained positive for CTO-PCI after excluding studies with <90% DES utilization. Finally, there are inherent limitations of observational studies, such as selection bias and confounding.
Conclusion
In summary, current observational studies show an association of CTO-PCI with better subsequent clinical outcomes, whereas RCTs do not (Figure 8). Additional data from RCTs are needed to determine the impact of CTO-PCI on clinical events.
Acknowledgments. Rayyan.ai was used to sort out articles from the databases used in the study. The authors are grateful for the philanthropic support of our generous anonymous donors, and the philanthropic support of: Drs Mary Ann and Donald A. Sens; Mrs Diane and Dr Cline Hickok; Mrs Wilma and Mr Dale Johnson; Mrs Charlotte and Mr Jerry Golinvaux Family Fund; the Roehl Family Foundation; and the Joseph Durda Foundation. The generous gifts of these donors to the Minneapolis Heart Institute Foundation’s Science Center for Coronary Artery Disease (CCAD) helped support this research project.
Affiliations and Disclosures
From the 1Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Minneapolis, Minnesota; 2Henry Ford Hospital, Detroit, Michigan; 3Gagnon Cardiovascular Institute, Morristown Medical Center, New Jersey; 4Emory University; 5Division of Cardiology and Angiology II, University Heart Center Freiburg, Bad Krozingen, Germany; 6Medizinische Klinik I Cardiology & Intensive Care, Klinikum Darmstadt GmbH, Darmstadt, Germany; 7Department of Cardiology, Golden Jubilee National Hospital, Glasgow, United Kingdom; 8Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 9Cleveland Clinic Foundation, Cleveland, Ohio; 10Department of Cardiology, Wellington Hospital, Wellington, New Zealand; 11Pasteur Institute, Nancy, France; 12Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; 13Cardiology Division, Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital, Taiwan; 14First Department of Cardiology, American Hellenic Educational and Progressive Association University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; 15Department of Cardiology, Sayama Hospital, Saitama, Japan; 16Acute Cardiac Care Unit Athens Naval and Veterans Hospital, Greece; 17Division of Cardiology, VCU Health Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia; 18Maria Pia Hospital, GVM Care & Research MD, Torino, Italy; 19International Medical Center, Jeddah, Saudi Arabia; 20North Oaks Health System, Louisiana; 21Department of Internal Medicine, Yale New Haven Hospital, Yale University School of Medicine, New Haven, Connecticut; 22Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; 23Prince of Wales Hospital, Hong Kong; 24Department of Cardiology, Toyohashi Heart Center, Japan; 25Division of Structural Interventional Cardiology, Careggi University Hospital, Florence, Italy; 26University of Palermo, Italy; 27Department of Invasive Cardiology, Maria Vittoria Hospital, Turin, Italy; 28Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands; 29Department of Cardiology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea; the 30Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea; and the 31Section of Cardiology, University Hospitals, Case Western Reserve University, Cleveland, Ohio.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Alaswad reports being a consultant and speaker for Boston Scientific, Abbott Cardiovascular, Teleflex, and CSI. Dr Karmpaliotis reports honoraria from Boston Scientific and Abbott Vascular; equity from Saranas, Soundbite, and Traverse Vascular. Dr Jaber reports Medtronic and proctoring fees from Abbott. Dr Nicholson reports being a proctor, speakers’ bureau, and advisory board for Abbott Vascular, Boston Scientific, and Asahi Intecc; intellectual property with Vascular Solutions. Dr Rinfret reports consulting for Abbott Vascular, Abiomed, Boston Scientific, SoundBite Medical, and Teleflex. Dr Mashayekhi reports consulting, speaking, proctoring honoraria from Abbott Vascular, Abiomed, Asahi Intecc, AstraZeneca, Biotronik, Boston Scientific, Cardinal Health, Daiichi Sankyo, Medtronic, Shockwave Medical, Teleflex, and Terumo. Dr Khatri reports being a speaker and proctor for Medtronic, Abbott, Boston Scientific, Terumo, and Asahi Intecc. Dr Harding reports institutional research grants from Asahi Intecc and consulting/speakers’ fees from Boston Scientific, Abbott Vascular, and Terumo. Dr Avran reports teaching courses and proctoring for Abbott Vascular, Boston Scientific, and Biosensor. Dr Jaffer reports sponsored research support from Kowa, Canon, Siemens, Teleflex, Shockwave, and Amarin; consulting for Boston Scientific, Abbott Vascular, Siemens, Magenta Medical, Asahi Intecc, and IMDS; equity interest in Intravascular Imaging and DurVena; Massachusetts General Hospital has a patent licensing arrangement with Terumo, Canon, and Spectrawave. Dr Doshi reports speakers’ bureau for Abbott Vascular, Boston Scientific, and Medtronic and research support from Biotronik. Dr Kao reports speakers’ bureau, honorarium, proctor, and research grant from Abbott Vascular, Asahi Intecc, Biotronik, Boston Scientific, Edwards Lifesciences, Elixir, Medtronic, Microport, and Terumo. Dr Azzalini reports honoraria from Abbott Vascular, Guerbet, Terumo, and Sahajanand Medical Technologies; research support from ACIST Medical Systems, Guerbet, and Terumo. Dr Garbo reports consulting/proctoring for Abbott, Boston Scientific, IMDS, Philips Volcano, Kardia Asahi, and Terumo. Dr Tammam reports proctorship agreement with Terumo. Dr Rangan reports research grants from InfraReDx and Spectranetics. Dr Burke is a stockholder in MHI Ventures and Egg Medical. Dr Garcia reports consulting for Medtronic, Boston Scientific, Edwards Lifesciences, and Abbott Vascular. Dr Croce reports proctoring, consulting, honoraria, and advisory board for Abbott, Boston Scientific, Philips, Abiomed, Cordis, Cardiovascular Systems, Inc, Takeda, Biotronik, Teleflex, and Dyad; grant and research support from Teleflex, Takeda, and Abbott. Dr Wu reports support from Abiomed, OrbusNeich, and Asahi Intecc; consulting honoraria from Boston Scientific and Abbott Vascular; member of the board of directors for APCTO Club; stock in Abbott Vascular. Dr Tsuchikane reports consulting for Asahi Intecc, Boston Scientific, and Kanaka. Dr Di Mario reports research grants from Abbott Vascular, Boston Scientific, Behring, Chiesi, Daiichi Sankyo, Edwards Lifesciences, Medtronic, and Philips Volcano. Dr Gagnor reports consulting for Boston Scientific and Terumo. Dr Knaapen reports honoraria from Boston Scientific for proctoring. Dr Brilakis reports consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor, Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), ControlRad, CSI, Elsevier, GE Healthcare, IMDS, InfraRedx, Medicure, Medtronic, Opsens, Siemens, and Teleflex; owner, Hippocrates LLC; shareholder in MHI Ventures and Cleerly Health. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript accepted April 27, 2022.
Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Director of the Center for Complex Coronary Interventions, Minneapolis Heart Institute, Chairman of the Center for Coronary Artery Disease at the Minneapolis Heart Institute Foundation, 920 East 28th Street #300, Minneapolis, MN 55407. Email: esbrilakis@gmail.com
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