ORIGINAL CONTRIBUTION

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1 ORIGINAL CONTRIBUTION The Efficacy and Safety of the Hybrid Approach to Coronary Chronic Total Occlusions: Insights From a Contemporary Multicenter US Registry and Comparison With Prior Studies Georgios Christopoulos, MD 1 ; Rohan V. Menon, BS 1 ; Dimitri Karmpaliotis, MD 2 ; Khaldoon Alaswad, MD 3 ; William Lombardi, MD 4 ; Aaron Grantham, MD 5 ; Vishal G. Patel, MD 1 ; Bavana V. Rangan, BDS, MPH 1 ; Anna P. Kotsia, MD 1 ; Nicholas Lembo, MD 6 ; David Kandzari, MD 6 ; Harold Carlson, MD 6 ; Santiago Garcia, MD 7 ; Subhash Banerjee, MD 1 ; Craig A. Thompson, MD, MMSc 8 ; Emmanouil S. Brilakis, MD, PhD 1 Copyright 2014 HMP NonCommercial Use Only ABSTRACT: Background. Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is challenging and has been associated with low success rates. However, recent advancements in equipment and the flexibility to switch between multiple technical approaches during the same procedure ( hybrid percutaneous algorithm) have dramatically increased the success of CTOPCI. We sought to compare the contemporary procedural outcomes of hybrid CTOPCI with previously published CTOPCI studies. Methods. The procedural outcomes of 497 consecutive CTOPCIs performed between January 2012 and August 2013 at five highvolume centers in the United States were compared with the pooled success and complication rates reported in 39 prior CTOPCI series that included 100 patients and were published after Results. The baseline clinical and angiographic characteristics of the study patients were comparable to those of previous studies. Technical and procedural success was achieved in 455 cases (91.5%) and 451 cases (90.7%), respectively, and were significantly higher than the pooled technical and procedural success rates from prior studies (76.5%, P<.001 and 75.2%, P<.001, respectively). Major procedural complications occurred in 9/497 patients (1.8%) overall and included death (2 patients), acute myocardial infarction (5 patients), repeat target vessel PCI (1 patient), and tamponade requiring pericardiocentesis (2 patients). The incidence of major complications was similar to that of prior studies (pooled rate 2.0%; P=.72). Conclusion. Use of the hybrid approach to CTOPCI is associated with higher success and similar complication rates compared to prior studies, supporting its expanded use for treating these challenging lesions. J INVASIVE CARDIOL 2014;26(9): KEY WORDS: percutaneous coronary interventions, coronary obstructions Percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) has traditionally been limited by relatively low success rates, 1 mainly due to failure to cross the occlusion with a guidewire. 2 In the past decade, several techniques have been developed to improve CTOPCI outcomes, such as the retrograde approach 35 and antegrade dissection and reentry. 6,7 However, most CTO operators have limited themselves to a single crossing approach per procedure mainly due to contrast and radiation exposure limitations. More recently, the hybrid approach to CTO PCI (Figure 1) was described, which assesses the angiographic characteristics of the occlusion to provide a standardized and reproducible method for crossing CTOs. 812 The hybrid algorithm uses all available techniques (antegrade, retrograde, truetotrue lumen crossing, or reentry) tailored to the specific case in the most safe, effective, and efficient way. 810 As a result, it provides the operator with the flexibility to apply multiple modes of intervention during the same procedure, increasing chances of successful revascularization and sparing the need for subsequent hospitalization for a repeat procedure. The goal of the present study was to examine contemporary outcomes with the hybrid approach to CTOPCI and compare them to those reported in prior published studies. We hypothesized that the hybrid approach to CTOPCI would be associated with higher technical and procedural success rates and similar periprocedural major complications. Methods Hybrid CTOPCI patients. We collected the clinical and angiographic characteristics and procedural outcomes of patients undergoing hybrid CTOPCI between January Vol. 26, No. 9, September

2 Outcomes of Hybrid CTOPCI CHRISTOPOULOS, et al. Outcomes of Hybrid CTOPCI CHRISTOPOULOS, et al and August 2013 at five highvolume CTOPCI centers in the United States: Appleton Cardiology, Appleton Wisconsin; Piedmont Heart Institute, Atlanta Georgia; St Joseph Medical Center, Bellingham Washington; St Luke s Health System s MidAmerica Heart Institute, Kansas City, Missouri; and VA North Texas Healthcare System, Dallas, Texas. A single operator performed all CTO procedures in two centers (Appleton Cardiology, St Joseph Medical Center), whereas in the other centers CTO procedures were performed by highvolume operators or operators who worked with a highvolume operator. Data from 497 CTO procedures were collected both prospectively and retrospectively using a dedicated centralized database (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention [PROGRESS CTO], Clinicaltrials.gov Identifier: NCT ).The study was approved by each center s Institutional Review Board. All procedures were performed by operators with significant expertise in CTO PCI using the hybrid approach. The first step in the hybrid algorithm is the performance of dual injection to assess four key angiographic characteristics: (1) proximal cap ambiguity; (2) quality of the vessel distal to the occlusion; (3) lesion length; and (4) presence of adequate collateral vessels. Initial antegrade wire escalation is favored for <20 mmlong lesions, whereas antegrade dissection and reentry is favored for 20 mmlong lesions. An initial retrograde (primary retrograde) approach is favored for lesions with ambiguous proximal cap, diffuse distal disease, and bifurcation at the distal cap, when appropriate collateral vessels are present. Early change of crossing strategy is recommended if the initially selected crossing strategy is unsuccessful or if no significant progress is achieved within a short period of time. 812 Literature review. We performed a comprehensive search of the Pubmed and Cochrane Library databases for manuscripts on CTOPCI. Bibliographies of the retrieved studies were searched by hand for other relevant studies. Human studies in English published between January 2000 and August 2013 were included if they reported technical or procedural success and complication rates from 100 consecutive CTOPCI cases. Series that included nonconsecutive CTOPCI cases based on the use of a specialized technique (such as retrograde or dissection/reentry only) were excluded. Review articles, letters to the editor, case reports, and studies in which procedural complications could not be accurately assessed from the published manuscript were also excluded. A list of the included studies is shown in Supplemental Table 1 (available online at The pooled technical and procedural success and complication rates were calculated from the above studies in accordance to the Metaanalysis of Observational Studies in Epidemiology (MOOSE) guidelines. 13 Baseline clinical and angiographic characteristics as well as CTOPCI efficiency data (fluoroscopy times, radiation exposure, and contrast administration) could not be pooled due to the lack of raw data. The authors of the present manuscript developed the hybrid approach and have published all related literature to date; hence, we are fairly certain that the hybrid approach was not used in prior reports. Moreover, each published study was carefully evaluated to ascertain that the hybrid approach was not used. Definitions. Chronic total occlusions were defined as coronary obstructions with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 of at least 3month duration. Estimation of the occlusion duration was based on first onset of anginal symptoms, prior history of myocardial infarction in the target vessel territory, or comparison with a prior angiogram. Technical success was defined as angiographic evidence of <30% residual stenosis with restoration of TIMI 3 antegrade flow in the CTO target vessel. 14 Procedural success was defined as technical success with no procedural major adverse cardiac event (MACE), including death, Qwave myocardial infarction (troponin or creatine kinase leak was not classified as a major complication as it often occurs transiently post CTOPCI and resolves spontaneously), recurrent cardiac symptoms requiring repeat target vessel PCI or coronary artery bypass surgery (CABG), cardiac tamponade requiring pericardiocentesis or surgery, and stroke before hospital discharge. Major bleeding was defined as bleeding causing hemoglobin drop 3 g/dl or bleeding requiring transfusion or surgical intervention. Vascular access complications included major bleeding from the access site (see above) or other complication requiring surgical intervention. Statistical analysis. Continuous data were summarized as mean ± standard deviation for normally distributed data or median and interquartile range (IQR) for nonnormally distributed data, and compared using ttest or Wilcoxon ranksum test as appropriate. Categorical data were presented as frequencies or percentages and compared using chi square or Fisher s exact test, as appropriate. A twosided Pvalue of <.05 was considered statistically significant. Analyses were performed using JMP version 9.0 (SAS Institute). Copyright 2014 HMP NonCommercial Use Only Results Clinical and angiographic characteristics. Between January 2012 and August 2013, a total of 497 patients underwent hybrid CTOPCI at the 5 participating centers. The clinical and baseline angiographic characteristics are presented in Table 1. Mean age was 64.7 ± 9.9 years and most patients (87%) were men, with high frequency of diabetes mellitus (42%), prior myocardial infarction (37%), and prior CABG (36%). All CTO target vessels (except one in a saphenous vein graft) were in a native coronary vessel. A prior CTOPCI attempt had been performed in 18% of cases. The target CTO vessel was the right coronary artery in 61% of patients, followed by the left anterior descending (21%) and left circumflex artery (13%). The median visually estimated CTO occlusion length was 30 mm (IQR, 2255 mm) and CTO reference vessel diameter was 2.8 ± 0.5 mm. Median occlusion duration was 21 months (IQR, 3 to 72 months). Table 1. Clinical and angiographic characteristics of the study patients. Age (years) 64.7 ± 9.9 >75 years 14% Men 87% CTO duration Known by prior angiography 31% Estimated based on clinical history 69% CTO lesion age based on angiography (months) 21 (372) Diabetes mellitus 42% Dyslipidemia 95% Hypertension 91% Current or recent (within 1 year) smoking 40% Prior myocardial infarction 37% Prior PCI 61% Prior CABG 36% Prior valve surgery 3% LVEF (%) 55 (4560) <40% 19% CTO vessel LAD 21% LCX 13% RCA 61% Others 6% Severe calcification, ie, 50% reference lesion 15% diameter Severe proximal tortuosity, ie, 2 bends >90 or 1 bend >120 6% CTO occlusion length (mm) 30 (2255) CTO reference vessel diameter (mm) 2.8 ± 0.5 Prior attempt to open CTO 18% Instent CTO 12% JCTO score 2.7 ± 1.2 Data given as mean ± standard deviation or median (interquartile range). LAD = left anterior descending artery; LCX = left circumflex artery; RCA = right coronary artery. Procedural techniques and outcomes. Technical success and procedural success were 455/497 (91.5%) and 451/497 (90.7%), respectively (Table 2). The final successful CTO crossing strategy was antegrade in 41%, retrograde in 32%, and antegrade dissection/reentry in 28%. The retrograde approach was used in 218 patients (44%) with 86% technical and 85% procedural success and 3.2% incidence of MACE. Stents were implanted in 98% of successful cases, and were mainly drugeluting stents (99.8%). Median contrast volume and fluoroscopy time were 260 ml (IQR, ml) and 41 min (IQR, 2667 min), respectively. Radial access (unilateral or bilateral) was used in 18% of the CTOPCI cases. Table 2. Procedural characteristics and outcomes of the study patients. Technical success 91.5% Procedural success 90.7% Radial access (unilateral or bilateral) 18% Successful crossing strategy Antegrade wiring 41% Antegrade dissection and reentry 28% Retrograde 32% Stenting in successful cases 98% Total stents implanted (n) 1117 DES 99.8% BMS 0.2% Stents per patient (n) 2.6 ± 1.1 Fluoroscopic time (min) 41 (2667) Contrast (ml) 260 (195375) Air kerma radiation dose (Gray) 3.8 (2.25.9) Dose area product fluoroscopy dose 267 (152413) (Gy cm²) Total procedural time (min) 108 (75158) MACE 1.8% Death 0.4% Acute myocardial infarction 1.0% Urgent repeat PCI on target vessel 0.2% Cardiac tamponade requiring pericardiocentesis 0.4% Data given as percentage, mean ± standard deviation, or median (interquartile range). DES = drugeluting stent; BMS = bare metal stent; MACE = major adverse cardiac event; PCI = percutaneous coronary intervention. Table 3. Comparison of procedural complications between the present study and previously published CTOPCI cases. Variable Present Study n/n (%) Other Studies n/n (%) Death 2/497 (0.4%) 77/18,536 (0.4%).96 MACE 9/497 (1.8%) 216/10,555 (2.0%).72 Qwave MI 5/497 (1.0%) 91/14,772 (0.6%).28 Emergency CABG 0 45/17,003 (0.3%).25 Cerebrovascular accident Perforation, per lesion Cardiac tamponade 0 21/18,364 (0.1%).45 16/497 (3.2%) 382/14,097 (2.7%) P.49 2/497 (0.4%) 65/12,955 (0.5%).76 Bleeding 3/497 (0.6%) 28/3,735 (0.7%).72 MACE = major adverse cardiac events; MI = myocardial infarction; CABG = coronary artery bypass graft surgery. 428 The Journal of Invasive Cardiology Vol. 26, No. 9, September

3 Outcomes of Hybrid CTOPCI CHRISTOPOULOS, et al. Outcomes of Hybrid CTOPCI CHRISTOPOULOS, et al. FIGURE 1. Overview of the hybrid CTO crossing algorithm. The algorithm starts with dual coronary injection (box 1) to allow assessment of several angiographic parameters (box 2) and allow selection of a primary antegrade (boxes 3 to 5) or primary retrograde (box 6) strategy. Strategy changes are made (box 7) depending on the progress of the case. CTO = chronic total occlusion; LaST = limited antegrade subintimal tracking. Modified with permission from reference. 8 Major adverse cardiac events occurred in 8 patients (1.8%), as follows: death (2 patients), acute myocardial infarction (5 patients), urgent target vessel revascularization with PCI (1 patient) and cardiac tamponade requiring pericardiocentesis (2 patients). No patient experienced a stroke and no patient required emergency coronary artery bypass graft surgery. Perforation (not resulting in MACE) was the most common procedural adverse effect (3.2%), followed by dissection (2.4%) and vascular access complications (1.6%). Comparison with prior studies. Database and bibliography search retrieved 448 publications, of which 409 were excluded because they did not directly report success and complication rates or only studied a specific interventional approach (such as retrograde), thus leaving 39 studies that were included in the present analysis. Overall success ranged between 54.3% and 88.9% (Supplemental Table 1, available at The technical and procedural success rates in our study were significantly higher than the pooled success rates reported in prior studies (technical success 91.5% vs 76.5%, P<.001 and procedural success 90.7% vs 75.2%, P<.001). Technical success continued to be higher, even when analyses were limited to the most recent studies published between 2010 and 2013 (91.5% vs 76.4%; P<.001). Complication rates from previous studies were similar to our study (Table 3): MACE occurred in 2.0% of patients, 0.6% of patients had Qwave myocardial infarction, 0.3% required emergent coronary artery bypass graft surgery, and 1.2% had a stroke. Perforations occurred in 2.7% of the lesions and were the most common procedural adverse effect. Copyright 2014 HMP NonCommercial Use Only FIGURE 2. CTOPCI technical success and complication rates among studies published between 2000 and MACE = major adverse cardiac events. Discussion The main finding of our multicenter registry is that the hybrid approach to CTOPCI is associated with significantly higher success and similar complication rates compared to published CTOPCI series. The hybrid approach was developed through the combined experiences of highvolume North American CTO PCI operators aiming to open the occluded vessel, using all feasible techniques (antegrade, retrograde, truetotrue lumen crossing or reentry) in the most safe, effective, and efficient way. 8 The basic underlying principle of the hybrid approach is that no single procedural crossing strategy should be pursued to exhaustion, but an alternative strategy should be attempted if a given crossing strategy does not progress. 10 Hence, the hybrid CTOPCI strategy places emphasis not only on procedural success, but also on procedural efficiency and forms the basis of contemporary CTO program development. 15 The optimal techniques and technologies are applied during the specific time of the procedure when they are most likely to be effective. The practical ramifications of this method are that changes of strategy should occur very early, and often cycle rapidly, to maximize the likelihood of early successful crossing. To the best of our knowledge, this is the first published series of the hybrid approach to CTOPCI. A hybrid registry of 144 cases performed at CTOPCI workshops between January 2011 and October 2012 was presented at the 2013 CTO Summit (New York, New York) demonstrating 94% procedural success, although lesion complexity was high (average JCTO score was 2.3 and 46% of lesions had a JCTO score >3). Similar to that registry, our technical and procedural success rates were 91.5% and 90.7%, respectively. This is the first allcomer publication reporting >90% success rates in CTOPCI (Supplemental Table 1 and Figure 1). Such high success rates have thus far only been reported for retrograde CTOPCI series in Japan. Kimura et al reported technical and procedural success of 92.4% and 90.6%, respectively, among 224 patients treated with the retrograde approach in 43 centers. 16 Tsuchikane et al reported 98.9% success (in 92/93 cases) in a twooperator series. 17 Rathore et al reported 100% success among 31 patients treated with intravascularultrasound guided reverse controlled antegrade and retrograde tracking and dissection (CART). 18 Our results extend the high success rates to an unselected, highly complex CTOPCI population with very high frequency of prior coronary artery bypass graft surgery (36%), which has been associated with lower CTOPCI success rates. 19 The prior collective experience of many of the centers participating in the current registry was recently published, showing 85.4% technical success among 1361 patients who were treated before the routine application of the hybrid approach. 20 Hence, although overall CTOPCI success rates have been modestly increasing over time (Figure 1), use of the hybrid approach to CTOPCI has resulted in a significant and clinically meaningful increase in procedural success. Importantly, this was achieved without incurring a penalty in terms of procedural complications. Study limitations. Our study has important limitations. It was observational without independent review of the coronary angiograms by an angiographic core laboratory and without adjudication of the clinical outcomes by a clinical events committee. However, adjudication would be unlikely to affect reporting of death, urgent repeat revascularization, and the need for pericardiocentesis. Serial cardiac biomarker measurements were not performed and only Qwave myocardial infarction was recorded as part of the study. All participating centers have established CTOPCI programs 15 with expertise in all crossing techniques that are part of the hybrid algorithm; hence, the outcomes observed in the study may not be achievable by less experienced centers. Furthermore, operator experience can significantly increase success rates of CTOPCI and this relation has been previously described. 4 Finally, longterm clinical or angiographic followup was not performed. Conclusion Our findings have important implications for everyday clinical practice. First, they suggest that the efficacy of CTOPCI has significantly improved; hence, the presence of a CTO may not necessarily need to be linked with lower level recommendation for PCI in the appropriateness use criteria for coronary revascularization. 21 Second, they suggest that such results can be achieved across various hospitals and operators. Third, they demonstrate that high success can be achieved without incurring more complications, 1 which is important for an elective procedure, such as CTOPCI. References 1. Patel VG, Brayton KM, Tamayo A, et al. Angiographic success and procedural complications in patients undergoing percutaneous coronary chronic total occlusion interventions: a weighted metaanalysis of 18,061 patients from 65 studies. JACC Cardiovasc Interv. 2013;6(2): Garcia S, Abdullah S, Banerjee S, Brilakis ES. Chronic total occlusions: patient selection and overview of advanced techniques. Curr Cardiol Rep. 2013;15(2): Brilakis ES, Grantham JA, Thompson CA, et al. The retrograde approach to coronary artery chronic total occlusions: a practical approach. Catheter Cardiovasc Interv. 2012;79(1): Thompson CA, Jayne JE, Robb JF, et al. Retrograde techniques and the impact of operator volume on percutaneous intervention for coronary chronic total occlusions an early U.S. experience. JACC Cardiovasc Interv. 2009;2(9): Karmpaliotis D, Michael TT, Brilakis ES, et al. Retrograde coronary chronic total occlusion revascularization: procedural and inhospital outcomes from a multicenter registry in the United States. JACC Cardiovasc Interv. 2012;5(12): Michael TT, Papayannis AC, Banerjee S, Brilakis ES. Subintimal dissection/reentry strategies in coronary chronic total occlusion interventions. Circ Cardiovasc Interv. 2012;5(5): Whitlow PL, Burke MN, Lombardi WL, et al. Use of a novel crossing and reentry system in coronary chronic total occlusions that have failed standard crossing techniques: results of the FASTCTOs (Facilitated Antegrade Steering Technique in Chronic Total Occlusions) trial. JACC Cardiovasc Interv. 2012;5(4): Brilakis ES, Grantham JA, Rinfret S, et al. A percutaneous treatment algorithm for crossing coronary chronic total occlusions. JACC Cardiovasc Interv. 2012;5(4): Thompson CA. The hybrid approach for percutaneous revascularization of coronary chronic total occlusions. Interv Cardiol Clin. 2012;1: Sabbagh AE, Banerjee S, Brilakis ES. Illustration of the hybrid approach to chronic total occlusion crossing. Interv Cardiol. 2012;4: Michael TT, Mogabgab O, Fuh E, et al. Application of the hybrid approach to chronic total occlusion interventions: a detailed procedural analysis. J Interv Cardiol. 2014;27(1): Brilakis ES, ed. Manual of Coronary Chronic Total Occlusion Interventions. A StepByStep Approach. Waltham, MA: Elsevier; Stroup DF, Berlin JA, Morton SC, et al. Metaanalysis of observational studies in epidemiology: a proposal for reporting. Metaanalysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15): Levine GN, Bates ER, Blankenship JC, et al ACCF/AHA/SCAI guideline for percutaneous coronary intervention: executive summary. A report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24): The Journal of Invasive Cardiology Vol. 26, No. 9, September

4 Outcomes of Hybrid CTOPCI CHRISTOPOULOS, et al. 15. Karmpaliotis D, Lembo N, Kalynych A, et al. Development of a highvolume, multipleoperator program for percutaneous chronic total coronary occlusion revascularization: procedural, clinical, and costutilization outcomes. Catheter Cardiovasc Interv. 2013;82(1): Kimura M, Katoh O, Tsuchikane E, et al. The efficacy of a bilateral approach for treating lesions with chronic total occlusions the CART (controlled antegrade and retrograde subintimal tracking) registry. JACC Cardiovasc Interv. 2009;2(11): Tsuchikane E, Katoh O, Kimura M, Nasu K, Kinoshita Y, Suzuki T. The first clinical experience with a novel catheter for collateral channel tracking in retrograde approach for chronic coronary total occlusions. JACC Cardiovasc Interv. 2010;3(2): Rathore S, Katoh O, Tuschikane E, Oida A, Suzuki T, Takase S. A novel modification of the retrograde approach for the recanalization of chronic total occlusion of the coronary arteries intravascular ultrasoundguided reverse controlled antegrade and retrograde tracking. JACC Cardiovasc Interv. 2010;3(2): Michael TT, Karmpaliotis D, Brilakis ES, et al. Impact of prior coronary artery bypass graft surgery on chronic total occlusion revascularisation: insights from a multicentre US registry. Heart. 2013;99(20): Michael TT, Karmpaliotis D, Brilakis ES, et al. Procedural outcomes of revascularization of chronic total occlusion of native coronary arteries (from a Multicenter United States Registry). Am J Cardiol. 2013;112(4): Patel MR, Dehmer GJ, Hirshfeld JW, Smith PK, Spertus JA. ACCF/SCAI/ STS/AATS/AHA/ASNC/HFSA/SCCT 2012 Appropriate use criteria for coronary revascularization focused update: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, American Society of Nuclear Cardiology, and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol. 2012;59(9): Copyright 2014 HMP NonCommercial Use Only From 1 VA North Texas Healthcare System and UT Southwestern Medical Center, Dallas, Texas; 2 Columbia University, New York, New York; 3 Appleton Cardiology, Appleton, Wisconsin; 4 PeaceHealth Cardiology, Bellingham, Washington; 5 Mid America Heart Institute, Kansas City, Missouri; 6 Piedmont Hospital, Atlanta, Georgia; 7 Minneapolis VA Healthcare System and University of Minnesota, Minneapolis, Minnesota; and 8 Yale University School of Medicine, New Haven, Connecticut. Acknowledgment: Study data were collected and managed using REDCap electronic data capture tools hosted at University of Texas Southwestern Medical Center. 1 REDCap (Research Electronic Data Capture) is a secure, webbased 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 Paul A. Harris, Robert Taylor, Robert Thielke, Jonathon Payne, Nathaniel Gonzalez, Jose G. Conde, Research electronic data capture (REDCap) A metadatadriven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2): Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award NumberUL1TR The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Disclosures: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Karmpaliotis is on the speaker s bureau for Abbott Vascular, Boston Scientific, Asahi, and Medtronic. Dr Alaswad reports consulting fees from Terumo and Boston Scientific; consultant (nonfinancial capacity) for Abbott Laboratories. Dr Lombardi reports stock with Bridgepoint Medical; honoraria from Abbott Vascular, Medtronic, and Terumo; consultancy with Abbott Vascular, Bridgepoint Medical, and Medtronic. Dr Grantham reports speaking fees, consulting, and honoraria from Boston Scientific, Asahi Intecc; research grants from Boston Scientific, Asahi Intecc, Abbott Vascular, Medtronic. Dr Lembo is a member of the speaker s bureau at Medtronic; advisory board for Abbott Vascular and Medtronic. Dr Kandzari reports research/grant support and consulting honoraria from Boston Scientific and Medtronic Cardiovascular; research/grant support from Abbott Vascular. Dr Garcia reports consulting fees from Medtronic. Dr Banerjee reports research grants from Gilead and the Medicines Company; consultant/speaker honoraria from Covidien and Medtronic; ownership in MDCare Global (spouse); intellectual property in HygeiaTel. Dr Thompson is a consultant for Abbott Vascular, Bridgepoint, Terumo, Volcano; reports equity in Bridgepoint Medical. Dr Brilakis reports consulting honoraria/speaker fees from Sanofi, Janssen, St Jude Medical, Terumo, Asahi, Abbott Vascular, Elsevier, and Boston Scientific; research grant from Guerbet; spouse is an employee of Medtronic. The remaining authors report no disclosures. Manuscript submitted February 10, 2014, provisional acceptance given February 19, 2014, final version accepted March 18, Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Dallas VA Medical Center (111A), 4500 South Lancaster Road, Dallas, TX esbrilakis@gmail.com 432 The Journal of Invasive Cardiology

5 Supplemental Table 1. CTO PCI studies including >100 patients that were published between 2000 and August Year Author Center Number of Patients (Lesions) Age (years) Diabetes (%) Previous MI (%) Previous CABG (%) Lesion Length (mm) Calcification (%) Tortuosity (%) Instent Restenosis (%) Technical Success (%) Procedural Success (%) MACE (%) 2013 Christopoulos et al. VA North Texas Health Care System 497 (497) 64.7± (2255) 15 (severe) 6 (severe) /497 (91.5) 451/497 (90.7) 8/497 (1.8) 11.3± Noguchi et al. (1) National Cardiovasc Center, Japan 226 (226) 61±9 61± ± /226 (59.3) Serruys et al. (2) Multicenter, Europe 303 (303) 84.7 (laser) 72.9 (mechanical) 15.3 (laser) 13.2 (mechanical) 58.3 (laser) 54.1 (mechanical) 9.7 (laser) 5.0 (mechanical) Mid America Heart Suero et al. (3) 2007 (2074) 60.6± Institute, USA 196/303 (64.7) 1448/2007 (72.3) 1448/2007 (69.9) 1

6 5.9 (moderate Olivari et al. (4) Multicenter, Italy 376 (390) 58.3± ±9.13 to severe) Baim et al. (5) Multicenter, USA 116 (116) 62.4± ± Hadassah Medical Dong et al. (6) 253 (283) 62.7± in 43.5% (severe) Center, Israel ,7 Sheyang General Han et al. (7) 1263 (1596) 60 (2586) >15 in 57.9% (moderate to (moderate to Hospital, China severe) severe) Medical University in Drozd et al. (8) 459 (459) 57.3± Poland, Poland 58.8 (5267) >20 in 64.9% Royal Blackburn Aziz et al. (9) 543 (570) Hospital, UK 58.8 (5265.4) % 301/376 (77.2) 63/116 (54.3) 215/253 (85.0) 1445/1625 (88.9)* 298/459 (64.9) 377/543 (69.4) 286/376 4/376 (1.1) (73.3) 3/116 (2.6) 293/459 4/459 (0.9) (63.8) 2

7 63.1± Prasad et al. (10) Mayo Clinic, USA 1262 (1277) 63.7± /1262 (69.7) 65/1262 (5.2) Royal Brompton 167/ Barlis et al. (11) 202 (203) 64.4± ± (severe) 12.4 Hospital, UK (82.7) 64.7±11.1 >20 in 70% Valenti et al. (12) Careggi Hospital, Italy 486 (527) 344/ ± (71) 67% Mitsudo et al. (13) Multicenter, Japan 110 (116) 66.3± ± / Tiroch et al. (14) Multicenter, USA 125 (125) 62.8± ± (severe) 3.2 (60.8) 146/ Sianos et al. (15) Multicenter, Europe 175 (175) 61.4± ± (severe) 28.6 (83.4) 1/202 (0.5) 2/486 (0.4) 103/116 2/110 (1.8) (88.7)* 3/125 (2.4) 1/175 (0.6) 3

8 Paizis et al. (16) Onassis Cardiac Surgery, Greece 106 (106) 59± ± /106 (77.0) Rathore et al. (17) Toyohashi Heart Center, Japan 806 (904) 65.42± ± ± ±6.01 Severe in Severe in /904 (87.5)* 779/904 (86.2)* 18/806 (2.2) (nonretrograde (nonretrograde (nonretrograde (nonretrograde Thompson et al. (18) Yale, St Joseph s, USA 636 (636) operator) 65.1 operator) 30.0 operator) 23.2 operator) /636 (69.0) (retrograde (retrograde (retrograde (retrograde operator) operator) operator) operator) Park et al. (19) Catholic University of Korea 134 (136) 62.6± ± /134 (86.4) 4

9 63.92± ± Chen et al. (20) Multicenter, China 152 (152) 67.68± ± Morino et al. (21) Multicenter, Japan 498 (528) 66.9± ± Werner et al. (22) Germany 674 (714) 67 (5872) ±10.7 (radial) Chang Gung Memorial, 32 (radial) (radial) (radial) Yang et al. (23) 419 (419) 60.6±13.2 Taiwan 21 (femoral) (femoral) (femoral) (femoral) Liu et al. (24) Toho University, Japan 116 (120) 65± >20 in 47.5% Tomasello et al. (25) Ferrarotto, Italy 303 (328) 61.0± >20 in 56.5% 8.9 (severe) 10.1 (severe) /152 (86.8) 457/528 (86.6)* 405/674 (60.1) 97/120 (80.8)* 283/328 (86.3)* 11/152 (7.2) 5/498 (1.0) 292/419 10/419 (2.4) (69.7) 2/116 (1.7) 5

10 18 ( ) 63.7± Borgia et al. (26) UK 302 (302) ± ( ) Galassi et al. (27) Multicenter, Europe 1914 (1983) 64.1± >20 in 69.7% 11.8 (severe) 32.7 (severe) (51 67) 10.2 (median, 237/302 (78.5) 1607/1983 (81.0)* 3/302 (1.0) 25/1914 (1.3) Jolicoeur et al. (28) Duke, USA 346 (346) 61 (55 70) success) 12.3 (median, 213/346 (64.5) 2/346 (0.6) failure) 6

11 Univ Witten/Herdecke, Bufe et al. (29) 331 (338) (antegrade) German (retrograde) 30.1 (antegrade) 29.6 (retrograde) 12.9 (antegrade) 12.5 (retrograde) Moderate to severe in (antegrade) Severe in (antegrade) (antegrade) (retrograde) (retrograde) (retrograde) Galassi et al. (30) Ferrarotto Hospital, Italy 172 (179) 60.5± >20 in 50.2% ± ± Lee et al. (31) 2 centers, Korea 333 () ± ± /338 (81.1)* 144/179 (80.4)* 251/333 (75.4) 6/331 (1.8) 7

12 61.2± ± Mehran et al. (32) Mutlicenter, USA, Italy, Korea 1791 (1852) 62.1± ± /1852 (67.8)* Fefer et al. (33) Multicenter, Canada 162 () 63± ± /162 (75.9) Jones et al. (34) UK 836 (836) 63.7± /836 (69.6) 19/836 (2.3) 64± Niccoli et al. (35) 2 centers Italy 317 (317) 66± Valenti et al. (36) Careggi Hospital, Italy 1035 () 68± /317 (61.8) 38±21 802/1035 (77.5) 8

13 66.9± Yamamoto et al. (37) Multicenter, Japan 1524 (1584) 66.2± /1524 (78.2) 30/1524 (2.0) Isaaz et al. (38) France 156 (164) 67± ± /164 (83.5)* Michael et al. (39) Multicenter, USA 1361 (1361) 64.5± /1361 (85.4) 1146/1361 (84.2) Data presented as mean ± standard deviation or median (interquartile range). * Lesions 9

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