Abstract: Background. The impact of intravascular ultrasound (IVUS) utilization for stent optimization on the long-term outcomes in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. Methods. We examined the outcomes of CTO-PCI with and without IVUS use for stent optimization in 922 CTO-PCIs performed between 2012 and 2019 at 12 United States centers. Major adverse cardiac event (MACE) was defined as the composite of cardiac death, acute coronary syndrome, and target-vessel revascularization. Results. IVUS was used in 344 procedures (37%) for stent optimization. Mean patient age was 65 ± 10 years and 83% were men. Patients in the IVUS group were less likely to have a prior myocardial infarction (39% vs 50%; P<.01), more likely to undergo right coronary artery CTO-PCI (49% vs 55%; P=.01), and had higher mean J-CTO score (2.6 ± 1.1 vs 2.4 ± 1.2; P=.04). The final crossing strategy in patients in the IVUS group was less likely to be antegrade wire escalation (54% vs 57%) and more likely to be retrograde (29% vs 21%; P<.01). Median follow-up was 141 days (interquartile range, 30-365 days). The incidence of 12-month MACE was similar in the IVUS and no-IVUS groups (20.3% vs 18.3%; log-rank P=.67). Conclusion. IVUS was used for stent optimization in approximately one-third of CTO-PCIs. Despite higher lesion complexity in the IVUS group, the incidence of MACE was similar during follow-up.
J INVASIVE CARDIOL 2020 July 22 (Epub Ahead of Issue).
Key words: CTO, IVUS, stent optimization
Use of intravascular ultrasound (IVUS) for stent optimization in complex percutaneous coronary intervention (PCI) was shown to improve acute1 and long-term clinical outcomes.2 Two randomized controlled trials have demonstrated that use of IVUS can improve long-term outcomes after chronic total occlusion (CTO)-PCI.3,4 We examined the impact of IVUS use for stent optimization on subsequent clinical outcomes in patients who underwent successful CTO-PCI with stent implantation in a multicenter CTO-PCI registry.
Patient population. We analyzed the frequency of use and 1-year outcomes of IVUS use for stent optimization among 922 CTO-PCIs performed between 2012 and 2019 at 12 United States centers: Cleveland Clinic, Cleveland, Ohio; Columbia University, New York, New York; Emory University Hospital Midtown, Atlanta, Georgia; Henry Ford Hospital, Detroit, Michigan; Massachusetts General Hospital, Boston, Massachusetts; Medical Center of the Rockies, Loveland, Colorado; Minneapolis Heart Institute, Minneapolis, Minnesota; Oklahoma Heart Institute, Tulsa, Oklahoma; Tristar Hospital, Nashville, Tennessee; UPMC Presbyterian, Pittsburgh, Pennsylvania; VA North Texas Health Care System, Dallas, Texas; and Wellstar Health Systems, York, Pennsylvania. Data collection was performed both prospectively and retrospectively and was recorded in a dedicated online database (PROGRESS CTO: Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; Clinicaltrials.gov identifier: NCT02061436). Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at Minneapolis Heart Institute Foundation.5,6
The study was approved by the institutional review board of each site and a waiver of informed consent was obtained.
Definitions. Coronary CTOs were defined as coronary lesions with Thrombolysis in Myocardial Infarction (TIMI)grade 0 flow of at least 3-month duration. Estimation of the duration of occlusion was clinical, based on the first onset of angina, prior history of myocardial infarction (MI) in the target-vessel territory, or comparison with a prior angiogram. Calcification was assessed by angiography as mild (spots), moderate (involving ≤50% of the reference lesion diameter), or severe (involving >50% of the reference lesion diameter). Moderate proximal vessel tortuosity was defined as the presence of at least 2 bends >70° or 1 bend >90° and severe tortuosity as 2 bends >90° or 1 bend >120° in the CTO vessel. A retrograde procedure was an attempt to cross the lesion through a collateral vessel or bypass graft supplying the target vessel distal to the lesion; otherwise, the intervention was classified as an antegrade-only procedure. Antegrade dissection/re-entry was defined as antegrade PCI during which a guidewire was intentionally introduced into the subintimal space proximal to the lesion, or re-entry into the distal true lumen was attempted after intentional or inadvertent subintimal guidewire crossing. A procedure was defined as having overlapping stents if at least 2 of the implanted stents overlapped. Technical success was defined as successful CTO revascularization with achievement of <30% residual diameter stenosis within the treated segment and restoration of TIMI grade 3 antegrade flow. Procedural success was defined as the achievement of technical success without any in-hospital complications. In-hospital major adverse cardiac event (MACE) included any of the following adverse events prior to hospital discharge: death, MI, recurrent symptoms requiring urgent repeat target-vessel revascularization (TVR) with PCI or coronary artery bypass graft (CABG) surgery, tamponade requiring either pericardiocentesis or surgery, and stroke. MI was defined using the Third Universal Definition of Myocardial Infarction (type 4a MI).7 The Japanese CTO (J-CTO) score was calculated as described by Morino et al,8 the PROGRESS-CTO score as described by Christopoulos et al,9 and the PROGRESS-CTO Complications score as described by Danek et al.10 One-year MACE was defined as the composite of cardiac death, acute coronary syndrome, and TVR at 12-month follow-up. Cardiac death was defined as death that was attributed to cardiac causes. Acute coronary syndrome was defined as the presence of ST-segment elevation MI, or non-ST segment elevation MI, or the presence of unstable angina. TVR was defined as the performance of either PCI or CABG surgery in order to revascularize the target vessel.
Statistical analysis. Categorical variables were expressed as percentages and were compared using Pearson’s Chi-square test or Fisher’s exact test. Continuous variables were presented as mean ± standard deviation or median (interquartile range [IQR]) unless otherwise specified and were compared using the Student’s t-test and 1-way analysis of variance (ANOVA) for normally distributed variables and the Wilcoxon rank-sum test, or the Kruskal-Wallis test for non-parametric continuous variables, as appropriate.
Cumulative incidences of the composite endpoint at 1 year were calculated using Kaplan-Meier estimates and compared using the log-rank test. Although patients could experience more than one component of the composite endpoint, each patient was assessed until the occurrence of their first event and only once during the analysis for the composite endpoint. All statistical analyses were performed using JMP, version 13.0 (SAS Institute). A P-value of .05 was considered statistically significant.
Patient characteristics. IVUS was used in 344 procedures (37%) for stent optimization. A gradual increase in the use of IVUS was observed over time (from 33% in 2012 to 58% in 2019) (Figure 1). The baseline characteristics of the study patients are summarized in Table 1. Patients in the IVUS group were less likely to have had a prior MI.
Angiographic characteristics. The baseline angiographic characteristics of the study lesions are shown in Table 2. Patients in the IVUS group were less likely to undergo CTO-PCI of the right coronary artery (RCA) and more likely to undergo PCI of the left anterior descending artery (LAD). CTOs in the IVUS group were more likely to be moderately/severely calcified and had higher mean J-CTO score than CTOs in the no-IVUS group (2.6 ± 1.1 vs 2.4 ± 1.2, respectively; P=.04).
Technical characteristics and procedural outcomes. The technical aspects of CTO-PCI are summarized in Table 3. Retrograde crossing was used more often in the IVUS group. Furthermore, there was a higher percentage of overlapping stents and longer median stent length in the IVUS group.
Procedural outcomes are summarized in Table 4. Procedural success was similar between the two groups. Median procedure time was significantly higher in the IVUS group. Median contrast volume and air kerma radiation dose were lower in the IVUS group.
Follow-up. Median follow-up was 141 days (IQR, 30-365 days). At 12 months, there was no difference in the incidence of the composite endpoint (hazard ratio [HR], 20.3% in the IVUS group vs 18.3% in the no-IVUS group; log rank P=.67) (Figure 2A). There was also no difference in the incidence of cardiac death (1.4% vs 1%; log rank P=.27) (Figure 2B), acute coronary syndrome (4.8% vs 10.4%; log rank P=.08) (Figure 2C), or TLR (3.4% vs 2%; log rank P=.42) (Figure 2D). In patients with in-stent CTOs, IVUS use was associated with numerically lower incidence of the composite endpoint (4.8% vs 11% in the no-IVUS group; P=.18).
The main findings of our study are that: (1) IVUS was used for stent optimization in approximately one-third of CTO lesions that were successfully crossed with a guidewire and its use has been gradually increasing over time; and (2) although lesions that underwent IVUS-guided optimization were more complex, follow-up outcomes were similar to outcomes in the no-IVUS group.
Rationale for using IVUS for stent optimization. IVUS can improve both the acute and long-term outcomes of CTO (and complex in general) PCI by allowing better stent sizing and guiding the need for lesion preparation and postdilation to maximize stent expansion, which may, in turn, reduce the risk for in-stent restenosis and stent thrombosis.11,12 Two randomized clinical trials have shown benefit with IVUS-guided vs angiography-guided CTO intervention. The CTO-IVUS study randomized 402 patients to IVUS-guided or angiography-guided CTO intervention and showed lower incidence of MACE (defined as the composite of cardiac death, MI, or TVR) in the IVUS group at 12 months (2.6% vs 7.1%; P<.01).4 The AIR-CTO (Angiographic and Clinical Comparisons of Intravascular Ultrasound- Versus Angiography-Guided Drug-Eluting Stent Implantation for Patients With Chronic Total Occlusion Lesions) study randomized 230 patients to IVUS-guided or angiography-guided stent implantation and showed, during a follow-up of 1 year, that IVUS-guided stenting was associated with less late lumen loss (0.28 ± 0.48 mm vs 0.46 ± 0.68 mm; P=.02) and a lower incidence of “in true lumen” stent restenosis (3.9% vs 3.7%; P=.02) than angiography-guided stent implantation.3
However, randomized trials often included selected patients — excluding, for example, patients with in-stent CTOs, who may be more likely to benefit from IVUS optimization. Observational studies have also suggested benefit with IVUS use. In the Korean-CTO registry, IVUS-guided PCI was performed in 39% of patients who had successful implantation of drug-eluting stent after CTO-PCI and was associated with lower incidence of stent thrombosis (0% vs 3%; P=.01) during 2-year follow-up.13 Choi et al analyzed 6005 patients undergoing complex PCI and showed IVUS use in 27.9% of patients, who had lower long-term risk of cardiac death compared with angiography-guided PCI (10.2% vs 16.9%; HR, 0.573; 95% confidence interval, 0.460-0.714; P<.001)14 (Table 5).
Our study’s findings are consistent with the aforementioned studies, and suggest benefit of IVUS, as clinical outcomes would be expected to be worse during follow-up in the IVUS group given higher baseline lesion complexity.
Impact of IVUS use on contrast and radiation dose. IVUS use was associated with lower contrast volume (216 mL [IQR, 155-300 mL] vs 240 mL [IQR, 162-330 mL]; P=.01) and air kerma radiation dose (2.2 Gy [IQR, 1.2-3.7 Gy] vs 2.6 Gy [IQR, 1.4-4.2 Gy]; P<.01), likely due to less need for angiographic imaging. The MOZART (Minimizing cOntrast utilization With IVUS Guidance in CoRonary angioplasTy) trial, which randomized 83 patients to angiography-guided PCI or IVUS-guided PCI, revealed a marked reduction in iodine contrast when IVUS guidance was used.15 However, IVUS for stent optimization was associated with increased procedure time (136 minutes [IQR, 99-207 minutes] in the IVUS group vs 126 minutes [IQR, 86-182 minutes] in the no-IVUS group; P<.01), which is likely at least in part due to time needed for IVUS acquisition, interpretation, and treatment adjustments according to the IVUS results.
Frequency of IVUS use for stent optimization. Despite the results of the studies described above, the frequency of IVUS use for stent optimization was low in our study (used in approximately one-third of patients). This may reflect uncertainty regarding the clinical benefits of IVUS, challenges with interpretation of the IVUS images, cost concerns, or operator fatigue during often long cases. However, our study demonstrated that IVUS use in CTO-PCI has been gradually increasing in recent years (Figure 1).
Study limitations. First, this was an observational study with all inherent limitations. Second, there were no predefined criteria about IVUS-based management, potentially leading to differences between various operators. Third, use of IVUS for stent optimization was at the discretion of the operator. Fourth, there are no detailed data on additional therapeutic actions according to the IVUS findings. Fifth, IVUS was also used for other indications during CTO-PCI in our study (for example, to guide wiring). Sixth, adherence to medical therapy after index procedure was not assessed, and could potentially affect clinical outcomes.
IVUS for stent optimization was used in approximately one-third of CTO-PCIs in this multicenter study, with its use increasing over time. Lesions in which IVUS was used for stent optimization were more complex, yet there was a similar incidence of adverse events (composite of cardiac death, acute coronary syndrome and TVR) during 1-year follow-up.
Acknowledgments. Study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at the Minneapolis Heart Institute Foundation (MHIF), Minneapolis, Minnesota. REDCap is a secure, web-based application designed to support data capture for research studies, providing: (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for importing data from external sources.
1. Chieffo A, Latib A, Caussin C, et al. A prospective, randomized trial of intravascular-ultrasound guided compared to angiography guided stent implantation in complex coronary lesions: the AVIO trial. Am Heart J. 2013;165:65-72.
2. Hong SJ, Kim BK, Shin DH, et al. Effect of intravascular ultrasound-guided vs angiography-guided everolimus-eluting stent implantation: the IVUS-XPL randomized clinical trial. JAMA. 2015;314:2155-2163.
3. Tian NL, Gami SK, Ye F, et al. Angiographic and clinical comparisons of intravascular ultrasound- versus angiography-guided drug-eluting stent implantation for patients with chronic total occlusion lesions: two-year results from a randomised AIR-CTO study. EuroIntervention. 2015;10:1409-1417.
4. Kim BK, Shin DH, Hong MK, et al. Clinical impact of intravascular ultrasound-guided chronic total occlusion intervention with zotarolimus-eluting versus biolimus-eluting stent implantation: randomized study. Circ Cardiovasc Interv. 2015;8:e002592.
5. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap) — a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377-381.
6. Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208.
7. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581-1598.
8. Morino Y, Abe M, Morimoto T, et al. Predicting successful guidewire crossing through chronic total occlusion of native coronary lesions within 30 minutes: the J-CTO (Multicenter CTO Registry in Japan) score as a difficulty grading and time assessment tool. JACC Cardiovasc Interv. 2011;4:213-221.
9. Christopoulos G, Kandzari DE, Yeh RW, et al. Development and validation of a novel scoring system for predicting technical success of chronic total occlusion percutaneous coronary interventions: the PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) score. JACC Cardiovasc Interv. 2016;9:1-9.
10. Danek BA, Karatasakis A, Karmpaliotis D, et al. Development and validation of a scoring system for predicting periprocedural complications during percutaneous coronary interventions of chronic total occlusions: the prospective global registry for the study of chronic total occlusion intervention (PROGRESS CTO) complications score. J Am Heart Assoc. 2016;5:e004272.
11. Brilakis ES, Mashayekhi K, Tsuchikane E, et al. Guiding principles for chronic total occlusion percutaneous coronary intervention. Circulation. 2019;140:420-433.
12. Galassi AR, Sumitsuji S, Boukhris M, et al. Utility of intravascular ultrasound in percutaneous revascularization of chronic total occlusions: an overview. JACC Cardiovasc Interv. 2016;9:1979-1991.
13. Hong SJ, Kim BK, Shin DH, et al. Usefulness of intravascular ultrasound guidance in percutaneous coronary intervention with second-generation drug-eluting stents for chronic total occlusions (from the Multicenter Korean-Chronic Total Occlusion Registry). Am J Cardiol. 2014;114:534-540.
14. Choi KH, Song YB, Lee JM, et al. Impact of intravascular ultrasound-guided percutaneous coronary intervention on long-term clinical outcomes in patients undergoing complex procedures. JACC Cardiovasc Interv. 2019;12:607-620.
15. Mariani J Jr, Guedes C, Soares P, et al. Intravascular ultrasound guidance to minimize the use of iodine contrast in percutaneous coronary intervention: the MOZART (minimizing contrast utilization with IVUS guidance in coronary angioplasty) randomized controlled trial. JACC Cardiovasc Interv. 2014;7:1287-1293.
16. Jakabcin J, Spacek R, Bystron M, et al. Long-term health outcome and mortality evaluation after invasive coronary treatment using drug eluting stents with or without the IVUS guidance. Randomized control trial. HOME DES IVUS. Catheter Cardiovasc Interv. 2010;75:578-583.
17. Kim JS, Kang TS, Mintz GS, et al. Randomized comparison of clinical outcomes between intravascular ultrasound and angiography-guided drug-eluting stent implantation for long coronary artery stenoses. JACC Cardiovasc Interv. 2013;6:369-376.
18. Russo RJ, Silva PD, Teirstein PS, et al. A randomized controlled trial of angiography versus intravascular ultrasound-directed bare-metal coronary stent placement (the AVID trial). Circ Cardiovasc Interv. 2009;2:113-123.
19. Zhang J, Gao X, Kan J, et al. Intravascular ultrasound versus angiography-guided drug-eluting stent implantation: the ULTIMATE trial. J Am Coll Cardiol. 2018;72:3126-3137.
20. Yoon YH, Lee PH, Lee SW, et al. Importance of stent optimization for favourable outcomes after percutaneous coronary intervention for chronic in-stent occlusions. EuroIntervention. 2019 Dec 3 (Ahead of print).
21. Hur SH, Kang SJ, Kim YH, et al. Impact of intravascular ultrasound-guided percutaneous coronary intervention on long-term clinical outcomes in a real world population. Catheter Cardiovasc Interv. 2013;81:407-416.
22. Roy P, Steinberg DH, Sushinsky SJ, et al. The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug-eluting stents. Eur Heart J. 2008;29:1851-1857.
23. Park SJ, Kim YH, Park DW, et al. Impact of intravascular ultrasound guidance on long-term mortality in stenting for unprotected left main coronary artery stenosis. Circ Cardiovasc Interv. 2009;2:167-177.
From the 1Minneapolis Heart Institute Foundation, Minneapolis, Minneapolis; 2Cleveland Clinic, Cleveland, Ohio; 3UCHealth Medical Center of the Rockies, Loveland, Colorado; 4University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; 5Wellstar Health Systems, Marietta, Georgia; 6Henry Ford Health System, Detroit, Michigan; 7Tristar Centennial Medical Center, Nashville, Tennessee; 8Oklahoma Heart Institute, Oklahoma City, Oklahoma; 9Massachusetts General Hospital, Boston, Massachusetts; 10Emory University Hospital Midtown, Atlanta, Georgia; 11Columbia University Irving Medical Center, New York, New York; 12Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, Minnesota; and 13VA North Texas Healthcare System, Dallas, Texas.
Funding: This study was funded by an Abbott Northwestern Hospital Foundation Innovation Grant and a gift from the Joseph F. and Mary M. Fleischhacker Foundation.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Alaswad reports consulting fees from Terumo, Boston Scientific; consultant (non-financial) for Abbott Laboratories. Dr Jaffer reports consultancy for Abbott Vascular, Boston Scientific, Siemens, grant support from Canon, Siemens, and National Institutes of Health. Dr Moses reports consultant income from Boston Scientific and Abiomed. Dr Lembo reports speakers’ bureau for Medtronic; advisory boards for Abbott Vascular and Medtronic. Dr Kirtane reports grant support to his institution from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, Glaxo SmithKline, and Eli Lilly. Dr Parikh reports speakers’ bureau income from Abbott Vascular, Medtronic, CSI, Boston Scientific, Trireme; advisory boards for Medtronic, Abbott Vascular, and Philips. Dr Ali reports consultant fees/honoraria from St. Jude Medical and AstraZeneca Pharmaceuticals; ownership interest/partnership/principal in Shockwave Medical and VitaBx; research support from Medtronic and St. Jude Medical. Dr Rangan reports grant support from InfraReDx and Spectranetics. Dr Garcia reports consulting fees from Medtronic. Dr Burke reports consulting and speaker honoraria from Abbott Vascular and Boston Scientific. Dr Banerjee reports grant support from Gilead and the Medicines Company; consultant/speaker honoraria from Covidien and Medtronic; ownership in MDCare Global (spouse); intellectual property in HygeiaTel. Dr Brilakis reports consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor, Circulation), Amgen, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, GE Healthcare, InfraRedx, Medtronic, Siemens, and Teleflex; research support from Regeneron and Siemens; shareholder: MHI Ventures. Dr Karmpaliotis reports speaker honoraria from Abbott Vascular, Boston Scientific, Medtronic, and Vascular Solutions. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript accepted April 1, 2020.
Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Minneapolis Heart Institute, 920 East 28th Street #300, Minneapolis, MN 55407. Email: email@example.com