Author + information
- Received December 21, 2011
- Accepted January 21, 2012
- Published online April 1, 2012.
- Patrick L. Whitlow, MD⁎,⁎ (, )
- M. Nicholas Burke, MD†,
- William L. Lombardi, MD‡,
- R. Michael Wyman, MD§,
- Jeffrey W. Moses, MD∥,
- Emmanouil S. Brilakis, MD, PhD¶,
- Richard R. Heuser, MD#,
- Charanjit S. Rihal, MD⁎⁎,
- Alexandra J. Lansky, MD††,
- Craig A. Thompson, MD††,
- FAST-CTOs Trial Investigators
- ↵⁎Reprint requests and correspondence:
Dr. Patrick L. Whitlow, Cleveland Clinic, Cardiovascular Medicine, Desk J2-3, 9500 Euclid Avenue, Cleveland, Ohio 44195
Objectives This study sought to examine the efficacy and safety of 3 novel devices to recanalize coronary chronic total occlusions (CTOs).
Background Successful percutaneous coronary intervention (PCI) of CTOs improves clinical outcome in appropriately selected patients. CTO PCI success, however, remains suboptimal.
Methods A new crossing catheter and re-entry system was evaluated in a prospective, multicenter, single-arm trial of CTO lesions refractory to standard PCI techniques. The primary efficacy endpoint was the frequency of true lumen guidewire placement distal to the CTO (technical success).
Results Enrollment included 147 patients with 150 CTOs. The mean lesion length was 41 ± 17 mm. A crossing catheter crossed 56 lesions into the distal true lumen, and a re-entry catheter facilitated tapered-wire cannulation of the distal lumen in 59 CTOs initially crossed subintimally (77% technical success). Success in the first 75 CTOs was 67%, rising to 87% in the last 75 CTOs. Mean fluoroscopy and procedure times were 45 ± 16 min and 90 ± 12 min, respectively, each significantly shorter than in historical controls (p < 0.0001 for both). Coronary perforation occurred in 14 cases (9.3%), requiring treatment in 3 cases (prolonged balloon inflation, with additional coil embolization in 1 case). No tamponade or hemodynamic instability occurred. Six patients had periprocedural non–ST-segment elevation myocardial infarction. No emergency surgery, ST-segment elevation myocardial infarction, or cardiac reintervention occurred. Two deaths occurred within 30 days, neither as a direct result of the procedure. The 30-day major adverse cardiac event rate was 4.8%.
Conclusions In CTOs failing standard techniques, use of a new crossing and re-entry system results in a high success rate without increasing complications.
- chronic stable angina
- chronic total occlusion
- coronary artery disease
- percutaneous coronary intervention
Coronary chronic total occlusions (CTOs) remain the most challenging lesion subset in percutaneous coronary intervention (PCI). Although there are isolated reports of success rates approaching 90% (1,2), most multicenter studies still report success in the 70% range (3–5) even with utilization of modern tools and retrograde collateral approaches. Failure to cross with a wire remains the most common mode of CTO PCI failure (6).
Because of slow adoption of retrograde collateral techniques and the conservative approach to CTO PCI in the United States (7) in addition to the suboptimal crossing rate, the CrossBoss catheter and Stingray re-entry system (BridgePoint Medical System, BridgePoint Medical, Plymouth, Minnesota) were developed to simplify and potentially improve antegrade recanalization success (8–10). We performed the FAST-CTOs (Facilitated Antegrade Steering Technique in Chronic Total Occlusions) trial to evaluate the BridgePoint Medical System in refractory coronary CTOs.
The FAST-CTOs trial (Clinical Trials ID: NCT00886899) was a prospective, multicenter, single-arm clinical trial designed to test the hypothesis that use of BridgePoint devices in coronary CTO lesions refractory to PCI using standard techniques is associated with superior efficacy and similar complications compared with historical controls.
The study was performed at 16 clinical sites (Online Appendix). The Food and Drug Administration approved the study protocol, and institutional review boards at all sites approved the consent form. Patients were followed for 30 days post-procedure for assessment of adverse events. An independent data and safety monitoring committee reviewed and adjudicated all adverse events.
Patients with total occlusion (Thrombolysis In Myocardial Infarction flow grade 0) of a major epicardial coronary vessel clinically determined to be >3 months old were considered for this study. Patients had to report angina or have ischemia documented on a stress test and have an angiographic landing zone ≥10 mm proximal to any major bifurcation without severe calcification. Lesion length was not considered in study eligibility.
One of 3 methods of failure to cross the CTO with standard techniques was needed to demonstrate refractoriness: a failed attempt to cross the CTO within the previous year; a failed concurrent attempt with 10 to 15 min of fluoroscopy time; or subintimal wire position during the concurrent attempt.
Exclusions included left ventricular ejection fraction <20%, vein graft or in-stent CTO target lesion, allergy to aspirin or all thienopyridines, aorto-ostial lesion location, creatinine >2.3 mg/dl, or PCI within the previous 2 weeks.
If the patient met all inclusion and no exclusion criteria before entering the catheterization laboratory, the patient could consent to enter the study. If there had been no prior failed attempt, the patient understood he/she would not be included in the trial unless standard techniques failed to cross the lesion.
The BridgePoint Medical System
Once 1 of the 3 refractory criteria was met, the BridgePoint System could be used. The system consists of 3 parts. The first is an over-the-wire catheter (Fig. 1) with a 1-mm blunt tip rotated rapidly by the operator to dissipate friction to facilitate CTO crossing. Any standard 0.014-inch guidewire can be used to deliver this catheter to the CTO. The wire is then retracted and the catheter advanced. If the crossing catheter traverses the CTO into the distal true lumen, a long PCI guidewire can be placed, and the catheter can be removed. Standard balloon angioplasty and stenting techniques are then used.
If the crossing catheter enters the subintimal space, it is advanced next to the angiographically visible true lumen distal to the CTO (re-entry site). An exchange wire is left in place, and the second component of the BridgePoint System, the re-entry balloon catheter (Fig. 2), is advanced over the guidewire to the re-entry site. This 2.5 × 10-mm flat balloon is designed to be inflated in the subintimal space to 3 to 4 atm. The inflated balloon provides leverage for a dedicated re-entry guidewire to engage 1 of 2 exit ports offset by 180°, 1 of which will always point toward the true lumen by design. The exchange guidewire is then removed. Coronary angiography is performed in multiple views to delineate the position of the re-entry balloon relative to the true lumen.
The third part of the System consists of a 12-gram tapered-tip, angulated guidewire designed for re-entry through 1 of the exit ports (Fig. 2). The re-entry wire is advanced through the exit oriented toward the true lumen. If the incorrect exit port is engaged, this is seen fluoroscopically, and the guidewire is rotated 180° to engage the correct port. The wire is directed to puncture and re-enter the distal true lumen. If the re-entry guidewire cannot be advanced in the distal vessel, it is exchanged for a softer wire that is used through the same exit port utilizing the puncture tract created by the re-entry guidewire to track the distal vessel. If intraluminal position is not achieved, the balloon is deflated and moved to attempt re-entry from another arterial segment. After re-entry, the catheter is deflated and removed. An over-the-wire balloon catheter is then inserted and the re-entry wire can be exchanged for a workhorse wire. Balloon angioplasty and stenting are used to recanalize the CTO.
CTO procedure and clinical follow-up
The CTO PCI procedures were performed at each cardiac catheterization laboratory per the institution's standard protocol. Heparin was used as the anticoagulant. Drug-eluting stents were used preferentially for stenting the occlusion. Use of aspirin and a thienopyridine was at the discretion of the operators. Three serial blood draws were taken to measure creatinine kinase (CK) and CK-myocardial band (CK-MB) every 6 to 8 h post-procedure for 24 h or through discharge. To be consistent with historical control studies, a non–ST-segment elevation myocardial infarction (NSTEMI) was diagnosed if any total CK measurement was >2 times normal and the CK-MB level was elevated. Patients returned for an office visit 30 days post-procedure to be assessed for adverse events.
The primary efficacy endpoint of the trial was technical success defined as the ability of the BridgePoint System to successfully facilitate placement of a guidewire beyond the CTO into the distal true lumen. The primary safety endpoint was major adverse coronary events (MACE) (cardiac death, myocardial infarction, target lesion revascularization, or emergency bypass surgery) through 30 days post-procedure. Secondary endpoints included total procedure time, total fluoroscopy time, and procedural success (opening of the CTO with <50% residual stenosis and final Thrombolysis In Myocardial Infarction antegrade flow grade 2 to 3 in the absence of Q-wave myocardial infarction, emergency repeat revascularization, or in-hospital death).
Quantitative coronary angiography
Two angiographic core laboratories were used for this study. The Cardiovascular Research Foundation (Columbia University, Ecaterina Cristea, MD, Director) reviewed cases to verify subintimal guidewire position in cases where this was the criterion used as the failure mode for study entry. The Yale Cardiovascular Research Group (Yale University, Alexandra Lansky, MD, Director) performed qualitative analysis and quantitative coronary angiography.
Continuous variables were summarized as mean ± 1 SD or as median (range), and discrete variables were presented as frequencies. Descriptive statistics are reported. Comparison of the event rates observed in the FAST-CTOs trial with historical data from prior published studies was performed using the most appropriate 1-sample exact test for categorical values and the Wilcoxon rank sum or Student t test for continuous variables. A p value of <0.05 was considered significant.
Power calculation and comparisons with historical controls
Using literature with similar methods and definitions of MACE to FAST-CTOs, the MACE rate of historical controls was estimated to be 7% (11–17). To demonstrate the BridgePoint System had a 30-day MACE rate that was not significantly higher than this (14%), a sample size of 141 patients was required (α = 0.05, β = 0.20 testing for noninferiority). To account for potential dropout during follow-up, a sample size of 149 was chosen.
Published literature of CTO crossing using various guidewires and devices (comparable to the primary efficacy endpoint “technical success” in the present study) showed a mean crossing rate of 59% (12,13,15–24). Procedure and fluoroscopy times in historical controls were 146 and 53 min, respectively (22–26).
Between March 2009 and July 2010, 147 patients with 150 coronary CTOs (3 patients had 2 CTOs) were enrolled. The crossing catheter was the only investigational device used for 73 CTOs (n = 70). A case example is shown in Figure 3. Seven CTOs (n = 7) were treated with the re-entry catheter and guidewire as the only investigational devices, and 70 CTOs (n = 70) were treated with all 3 new devices. A representative crossing and re-entry case is shown in Figure 4.
We defined failed attempts to cross the CTO as an attempt within the past year (61 CTOs, 41%), concurrent failure within 10 to 15 min of fluoroscopy time (51 CTOs, 34%), or guidewire entry into the subintimal space (38 CTOs, 25%). Subintimal position of the guidewire was confirmed by the angiographic core laboratory in all 38 cases.
The clinical characteristics of the patients enrolled in the trial are listed in Table 1. Of the 150 CTOs treated, 145 had images available for quantitative coronary angiography analysis by the core laboratory, shown in Table 2.
Technical success was achieved in 115 of 150 CTOs attempted (77%). The observed technical success rate was significantly better than the historical control rate of 59%, p = 0.001. Technical success was seen in 72% of cases with a previously failed prior procedure, 73% of cases with a failed concurrent attempt, and 89% of cases with subintimal guidewire position. Factors associated with higher risk for failure included smaller vessel size, severe calcification, severe tortuosity, and side-branch involvement (Table 3). Stents were implanted in 112 of 115 successfully crossed CTOs. The mean stented length was 61 ± 24 mm. Stents could not be successfully positioned in 3 cases with technical success.
The mean procedure time was 105 ± 54 min, and the fluoroscopy time was 44 ± 25 min, both significantly less than the historical control times of 146 and 53 min, respectively (p < 0.0001 for both). Procedure and fluoroscopy times by refractory status of patients were not different. Procedure time for crossing catheter–only cases (93 ± 50 min) was significantly shorter than for cases involving the re-entry system (115 ± 57 min, p = 0.01), but fluoroscopy time was not different (41 ± 25 min vs. 47 ± 25 min, respectively, p = 0.09). Procedural success was documented in 113 of 150 (75%) of the CTOs attempted, including 1 technical failure with subsequent retrograde success and 1 technical success case that could not be successfully stented and was a procedural failure.
30-day adverse events
The 30-day MACE rate was 4.8%. Two patients died. The first death occurred in a patient admitted 22 days after a successful procedure with leg pain due to an embolic occlusion of the superficial femoral artery, secondary to atrial fibrillation. The patient expired of respiratory arrest in the hospital 3 days later. The second patient died 16 days after an unsuccessful attempt to recanalize his CTO, during which he experienced an NSTEMI. He was discharged and presented to the emergency department of his local hospital with asystole and could not be resuscitated.
Four patients had asymptomatic NSTEMI following successful recanalization of their CTO. One patient without technical success had successful recanalization with a retrograde approach but also had an asymptomatic NSTEMI. The sixth patient with an NSTEMI was discussed in the previous text. No patient had an ST-segment elevation myocardial infarction, emergency bypass surgery, or target vessel revascularization. One patient experienced a left thalamic infarct with symptom resolution before 30-day follow-up.
The observed MACE rate of 4.8% was sufficiently low enough to reject the null hypothesis that the BridgePoint system has a MACE rate higher than historical controls with a p value of 0.0003. The observed 30-day MACE was not significantly different from the expected historical control MACE rate of 6.9% (p = 0.40).
Fourteen perforations (9.3%) were noted during the study. Four occurred when the crossing catheter entered a small branch, causing dye extravasation (3 Ellis grade I and 1 grade III). Two of these patients were treated with protamine administration and prolonged balloon inflation and had technical failure. Two were technically successful, and the perforations were not treated. A fifth patient had a re-entry catheter balloon burst in the artery, causing a type II perforation requiring no treatment. Nine patients had perforation noted after use of a nonstudy device (8 guidewires, 1 balloon catheter). Eight of these cases (grade I) required no treatment, and 1 (grade II) was treated with prolonged balloon inflation followed by coil embolization. There was no occurrence of tamponade, pericardiocentesis, or emergency surgery.
The FAST-CTOs trial demonstrates that use of the BridgePoint Medical System in coronary CTOs refractory to crossing with standard techniques was associated with higher technical success (77% vs. 59%, p < 0.001), shorter fluoroscopy and procedural times (p < 0.0001 for both), and similar 30-day MACE (4.8% vs. 6.9%, p = 0.40) compared with historical controls.
The BridgePoint System was designed to either primarily cross into the distal true lumen or to re-enter the true lumen from the subintimal space distal to the CTO. These new devices offer a systematic approach to CTO PCI. The over-the-wire crossing catheter can be successful in crossing into the distal true lumen and was the only step needed for technical success in 56 of 150 CTOs (37%). Advancement into the subintima, a common mode of failure in CTO PCI, can be addressed with a second step involving the use of a dedicated coronary re-entry balloon designed to provide support for guidewire penetration into the adjacent true lumen. A stiff guidewire with a short curve and distal probe was highly successful in obtaining distal true lumen positioning with technical success in 59 of 77 attempted cases (77%). Previous smaller series have been reported utilizing this coronary re-entry system (8–10), but this is the largest study detailing clinical results with coronary re-entry.
The technical success rate of 77% is higher than that of previous device studies (13,17,26). Increased familiarity with the device was associated with higher success rates (67% for the first 75 CTOs, improving to 87% in the last 75 CTOs), suggesting that familiarity with the different components of the BridgePoint System improves the likelihood of successful CTO crossing.
Over 40% of the patients entered into the current trial had previously failed procedures. In the present study, the success rate for this specific subgroup of patients was 72%. This compares favorably to the recently reported Japanese CTO registry where these previously failed cases were primarily treated with a retrograde approach by expert CTO operators, and procedural success was also 72% (4).
PCI of CTOs with the present system is quite different from the subintimal tracking and re-entry (STAR) technique described by Colombo et al. (27). With STAR, the operator tries to gain subintimal wire position as soon as possible, and extends a dissection to the distal artery where all significant-sized individual side branches are sequentially attempted to be reconnected to the true lumen, With the BridgePoint devices, over one-third of cases can be traversed via the true lumen with the crossing catheter without dissection. If the crossing catheter becomes subintimal, then this catheter is advanced only to the angiographic true lumen re-entry point where the re-entry device is employed to regain the true lumen without extending the dissection any further than necessary. Re-entry is attempted in a major epicardial vessel rather than into individual branch vessels. STAR is generally considered a method of last resort to open a CTO, where the BridgePoint system in the present study was used as a frontline device after conventional wire failure.
Stented length was quite long in both the present study (61 ± 23 mm) and in the initial report of the STAR technique (42 ± 24 mm), but possibly for different reasons. STAR cases involved a long segment of dissection by design, whereas in the present study, lesion length with ≥50% stenosis measured by the core laboratory before intervention was 41 ± 17 mm. To stent from normal segment to normal segment required a dramatic stent length in both these studies. Long-term follow-up will clearly be necessary to determine safety and durability with these techniques that require >40 mm of stent length. However, 30-day data from the present study are encouraging that acute and subacute thrombosis are at least not overwhelming issues, but the potential for delayed thrombosis has not yet been addressed.
Performing CTO PCI with low complication rates is essential because patients with symptomatic CTO generally have chronic stable angina with a good prognosis when treated medically (28). The MACE rate in the current study was acceptably low, and comparable to the rates previously found in CTO device studies. The absence of tamponade in this trial was particularly notable since most cases involved extraluminal tracking of devices.
Perforations remain a concern with CTO PCI. In the current study, perforations were documented in 14 cases, but most (11 of 14). required no treatment or only discontinuation of anticoagulation. No hemodynamic instability was encountered, and most of the perforations were caused by noninvestigational devices. Though perforation rates remain approximately 10% in this and recent CTO PCI series (4,5), most perforations are grade I (7 of 14) or II (6 of 14 in this series) and are rarely associated with MACE (0 in this study). In the global experience with the crossing catheter used in this and previous studies (8,9), perforations in a major epicardial vessel have not been seen, but infrequent perforations have been reported when this catheter is tracked into a small side branch. Therefore, operators should closely monitor the angiographic course of the crossing catheter to avoid side branch tracking and possible perforation.
Because of clinical benefit gained by patients with successful CTO PCI (angina relief, quality of life improvement , left ventricular function improvement [30,31], decreased need for coronary arterial bypass grafting , and perhaps an improvement in survival [5,33,34]), interest in CTO PCI has increased globally. However, for many reasons, CTO PCI remains relatively infrequent in the United States (7,35). Previous CTO crossing devices that do not include a re-entry platform (12–17,19) have not had a major impact on CTO PCI. However, a simplified stepwise antegrade approach with both crossing and re-entry capabilities leading to improved success with shorter procedure times may enable operators to take on more complex but clinically indicated cases, particularly in the United States, where success rates and procedure times are carefully scrutinized.
It was a single-arm study that did not include a concurrent comparator. The sequence and mode of use of each device was left to the discretion of each operator, but this more closely reflects how the device is likely to be used in everyday clinical practice. Most of the CTO lesions were located in the right coronary artery; however, technical success rates were similar for all 3 coronary artery CTOs.
The results of this study suggest that the BridgePoint System provides antegrade success higher than previous devices in refractory CTOs, with procedure and fluoroscopy times significantly shorter than previous CTO studies without increasing MACE.
The authors would like to acknowledge the efforts of the FAST-CTOs Data and Safety Monitoring Committee: David A. Cox, MD, Chair, Joseph Babb, MD, Franz Reisdorf, MD, and Jeng Mah, PhD. Thanks also to Ping-Yu Liu, PhD, for statistical support, and Loren Makke, RCIS, from Dallas VA Medical Center for additional quantitative coronary angiography support.
For a list of the clinical sites and principal investigators, please see the online version of this article.
Funding for the study was provided by BridgePoint Medical, Plymouth, Minnesota. All the authors' institutions received support for the clinical trial from BridgePoint Medical. In addition, Drs. Burke, Wyman, Lombardi, and Thompson all received consulting fees and have an equity interest in BridgePoint Medical. Dr. Whitlow received institutional grant support for patients enrolled in this study. Dr. Wyman also received honoraria/consulting fees from Boston Scientific, Terumo, and Abbott Vascular. Dr. Moses is a consultant for Abbott and Boston Scientific Corporation (minor). Dr. Brilakis received speaker honoraria from St. Jude Medical and Terumo and research support from Abbott Vascular. His spouse is also an employee of Medtronic. Dr. Thompson is also a consultant for Abbott Vascular, Terumo, and Volcano. Dr. Lombardi is also a speaker consultant advisory board member for Abbott Vascular and Boston Scientific. All other authors have stated that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- chronic total occlusion
- major adverse cardiac event(s)
- non–ST-segment elevation myocardial infarction
- percutaneous coronary intervention
- subintimal tracking and re-entry
- Received December 21, 2011.
- Accepted January 21, 2012.
- American College of Cardiology Foundation
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