Author + information
- Received April 29, 2016
- Revision received August 1, 2016
- Accepted August 2, 2016
- Published online November 1, 2016.
- Joren Maeremans, MSca,b,
- Simon Walsh, MDc,
- Paul Knaapen, MD, PhDd,
- James C. Spratt, MDe,
- Alexandre Avran, MDf,
- Colm G. Hanratty, MDc,
- Benjamin Faurie, MD, PhDg,
- Pierfrancesco Agostoni, MDh,i,
- Erwan Bressollette, MDj,
- Peter Kayaert, MDk,
- Alan J. Bagnall, MD, PhDl,m,
- Mohaned Egred, MDl,m,
- Dave Smith, MDn,
- Alexander Chase, MD, PhDn,
- Margaret B. McEntegart, MD, PhDo,
- William H.T. Smith, MB, BChir, PhDp,
- Alun Harcombe, MDp,
- Paul Kelly, MDq,
- John Irving, MDr,
- Elliot J. Smith, MDs,
- Julian W. Strange, MDt and
- Joseph Dens, MD, PhDa,b,∗ ()
- aFaculty of Medicine and Life Sciences, Universiteit Hasselt, Hasselt, Belgium
- bDepartment of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium
- cDepartment of Cardiology, Belfast City Hospital, Belfast, United Kingdom
- dDepartment of Cardiology, VU University Medical Center, Amsterdam, the Netherlands
- eDepartment of Cardiology, Forth Valley Royal Hospital, Edinburgh, United Kingdom
- fDepartment of Cardiology, Clinique de Marignane, Marignane, France
- gDepartment of Cardiology, Groupe Hospitalier Mutualiste, Grenoble, France
- hDepartment of Cardiology, Universitair Medisch Centrum Utrecht, Utrecht, the Netherlands
- iDepartment of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands
- jDepartment of Cardiology, Nouvelles Cliniques Nantaises, Nantes, France
- kDepartment of Cardiology, Universitair Ziekenhuis Brussel, Brussels, Belgium
- lDepartment of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- mInstitute of Cellular Medicine, Newcastle University, United Kingdom
- nDepartment of Cardiology, Morriston Hospital, Swansea, United Kingdom
- oDepartment of Cardiology, Golden Jubilee National Hospital, Glasgow, United Kingdom
- pDepartment of Cardiology, Nottingham University Hospital, Nottingham, United Kingdom
- qDepartment of Cardiology, Essex Cardiothoracic Centre, Basildon Hospital, Essex, United Kingdom
- rDepartment of Cardiology, Ninewells Hospital, Dundee, United Kingdom
- sDepartment of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom
- tDepartment of Cardiology, Bristol Heart Institute, Bristol, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Joseph Dens, Department of Cardiology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600 Genk, Belgium.
Background The hybrid algorithm for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) was developed to improve procedural outcomes. Large, prospective studies validating the algorithm in a broad multicenter setting with operators of different experience levels are lacking.
Objectives The RECHARGE (REgistry of Crossboss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom) registry aims to report achievable results using the hybrid algorithm.
Methods Between January 2014 and October 2015, consecutive patients undergoing hybrid CTO-PCI were prospectively enrolled in 17 centers. Procedural techniques, outcomes, and in-hospital complications were analyzed.
Results A total of 1,253 CTO-PCIs were performed in 1,177 patients, of which 86% were men. Mean age was 66 ± 11 years. The average Japanese CTO score was 2.0 ± 1.0, and was higher in the failure group (2.6 ± 0.6 vs. 1.9 ± 1.0; p < 0.001). Overall procedure success was 86% and major in-hospital complications occurred in 2.6%. Antegrade wire escalation was the preferred primary strategy in 77%, followed by retrograde (17%) and antegrade dissection re-entry strategies (7%). Primary strategies were successful in 60%. Consecutive strategies were applied in 34% and were successful in 74%. Antegrade dissection re-entry and retrograde strategies were the most common bailout strategies and were successful in 67% and 62%, respectively. Median procedure and fluoroscopy time were 90 (interquartile range [IQR]: 60 to 120) min and 35 (IQR: 21 to 55) min, contrast volume was 250 (IQR: 180 to 340) ml, and radiation doses (air kerma and dose area product) were 1.6 (IQR: 1.0 to 2.7) Gy and 98 (IQR: 57 to 168) Gy·cm2, respectively.
Conclusions High procedure and patient success rates, combined with a low event rate and improved procedural characteristics, support further use of the hybrid algorithm for a broad community of appropriately trained CTO operators.
Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has gained an increased interest over recent years. Due to development of more advanced materials and teachable methods (e.g., retrograde wiring and antegrade [ADR] and retrograde dissection and re-entry [RDR] techniques), success rates have improved and complex lesions are tackled more frequently by more interventional cardiologists (1–11).
The “hybrid algorithm” was developed (Central Illustration) (12,13) to optimize the application of the techniques and materials. By assessing key angiographic characteristics, optimal crossing strategy (antegrade wire escalation [AWE], ADR, retrograde wire escalation [RWE], RDR) and bailout or consecutive strategies are determined up front. To date, only small (single center) studies, case reports, or studies with highly experienced CTO-PCI operators have reported outcomes of the algorithm (13–22). RECHARGE (REgistry of CrossBoss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom) registry aims to provide a real-world image of current results using the hybrid algorithm and assess the contribution of different crossing techniques to successful CTO revascularization.
Between January 2014 and October 2015, consecutive patients treated electively for CTO-PCI were prospectively included in the RECHARGE registry by CTO operators in 17 European centers, including Belgium, France, the Netherlands, and the United Kingdom. Ethical approval was obtained according to local regulations. Operators had a spectrum of experience with hybrid techniques, but they had performed ≥25 hybrid procedures. All were certified ADR operators (by Boston Scientific, Marlborough, Massachusetts). The mean number of annual CTO procedures per operator was 64 ± 40; 32% performed <50 procedures/year, 36% performed 50 to 100 procedures/year, and 32% >100 procedures/year (Table 1). Operators used the hybrid algorithm as a guide in switching strategies. They performed the procedures and inclusions conforming to institutional guidelines. All patients gave written informed consent according to country regulations.
Patient selection for CTO-PCI was based on clinical symptoms or documented ischemia and left ventricular viability, rather than perceived likelihood of success. All CTO-PCIs were treated according to the hybrid algorithm, leaving the operator free in choice of strategies. Per algorithm requirements, a pre-operative angiographic study of the CTO lesion characteristics was performed to determine the primary or consecutive strategies. AWE is the suggested first strategy for CTOs characterized by a clear proximal cap, a good distal landing zone, and a short lesion length (≤20 mm). For longer lesions, ADR is preferred. In CTOs having proximal cap ambiguity or a diseased distal landing zone but good “interventional” collaterals, a retrograde approach is recommended. RWE is preferred for short lesions, and RDR (generally reverse Controlled Antegrade and Retrograde subintimal Tracking [reverseCART]) for longer lesions (Central Illustration). CTOs are “classified” according to the most suited primary crossing strategy. Data on the planned strategies were captured in all continental and 2 UK centers. Data on applied strategies were captured for all centers. Choice of materials, devices, and techniques was left to the discretion of the operator. Clinical, angiographic, procedural, and outcome data were collected using a web-based reporting system (OpenClinica Community, Waltham, Massachusetts). Additional information was obtained by reviewing the medical records locally or via telephone contact, as necessary. The Japanese CTO score (J-CTO) and PROGRESS (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) score were used to describe the CTO lesion complexity. The first report of the new PROGRESS CTO score will be provided in a broad, multicenter setting of hybrid CTO-PCI (23,24).
Study definitions and endpoints
CTOs were defined as a lesion of a native coronary artery that exhibited Thrombolysis In Myocardial Infarction (TIMI) antegrade flow grade equal to 0 for at least 3 months. Occlusion length was estimated from the angiographic image using a bilateral arterial approach or the stent and balloon length as reference. Presence of calcification in the CTO segment was determined by fluoroscopy without contrast injection. An unsuitable distal landing zone was defined as the presence of a significant bifurcation at the re-entry zone, the presence of significant coronary artery disease, or a distal lumen diameter <2 mm. Hyperlipidemia was diagnosed if already treated or having a total cholesterol ≥190 mg/dl.
AWE is defined as antegrade wiring from true-to-true lumen with increasing guidewire tip loads and penetration force if needed. Subintimal tracking and re-entry and limited antegrade subintimal tracking techniques were defined as wire-based ADR techniques. In the former, re-entry is performed by advancing a knuckled guidewire until it spontaneously re-enters the true lumen. In the latter, a stiff polymer-jacketed or stiff tapered guidewire is directed into the distal true lumen (6,25). True-to-true crossing of in-stent occlusions using the CrossBoss catheter (Boston Scientific, Boston, Massachusetts) is generally not considered an ADR technique (due to the absence of a dissection) nor an AWE technique, but was classified as part of the ADR technique, with the specification of a true-to-true lumen crossing treatment for in-stent occlusions. Non–in-stent occlusions for which the CrossBoss catheter was used with the intention of re-entry, but which resulted in CrossBoss true-to-true lumen crossing, were classified as a subtype of ADR. Any retrograde approach to the distal CTO cap is considered as a retrograde procedure (including RWE and RDR).
Success was defined as successful CTO revascularization with achievement of <30% residual diameter stenosis within the stented segment and restoration of TIMI flow grade 3 antegrade.
In-hospital major adverse cardiac and cerebrovascular events (MACCE) included death, periprocedural myocardial infarction (MI) (i.e., non–ST-segment elevation MI), target vessel failure (i.e., vessel was occluded at follow-up) followed by urgent repeat target vessel revascularization with PCI or coronary artery bypass graft surgery, and stroke, and were counted mutually exclusively. Because collection of myocardial enzymes was not mandatory, a MI was defined as ongoing chest pain, electrocardiogram changes, and positive cardiac enzymes. Patients in whom cardiac markers were available and increased, but who were without clinical symptoms and only had transient ST-segment elevation changes during the procedure were not considered to have clinically important MI, but rather procedural enzyme leaks. Other complications included life-threatening and major bleeding (Bleeding Academic Research Consortium criteria) (26), major vascular complications, acute shock, and renal failure requiring prolonged hospitalization. Life-threatening bleeding was defined as fatal bleeding, bleeding in a critical area or organ (intracranial, intraspinal, intraocular, pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome), bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery, and overt source of bleeding with a drop in hemoglobin of ≥5 g/dl or whole blood or packed cells transfusion ≥4 U. Major bleeding was defined as access-related and retroperitoneal bleeding, associated with a hemoglobin level drop of at least 3 g/dl or requiring transfusion of ≥2 U whole blood or packed cells or causing prolonged hospitalization or permanent injury, or requiring surgery, and included coronary perforation resulting in tamponade without the need of pericardiocentesis. Coronary perforations are reported separately. Major vascular complications included coronary perforation necessitating the use of unplanned endovascular (coronary graft or covered stents, coils, fat embolization) or surgical intervention as well as access site or access-related vascular injury (dissection, perforation, arteriovenous fistula, pseudoaneurysm, hematoma), associated with or leading to death, life-threatening or major bleeding, visceral ischemia, or neurological impairment. Other major vascular complications included aortic dissection, access site–related nerve injury (permanent or requiring surgery), and any new ipsilateral lower extremity ischemia, documented by patients symptoms, physical exam, or decreased or absent blood flow on lower extremity angiogram.
The primary endpoint was to validate the effectiveness of the hybrid algorithm and determine the success rate achievable in CTO lesions with regard to relevant complexity as determined by the Japanese CTO (J-CTO) score. Secondary endpoints included outcomes of the different individual techniques (AWE, ADR, RWE, RDR), procedural safety characteristics (i.e., radiation doses, contrast volume, fluoroscopy times), and determination of in-hospital MACCE events.
Baseline, angiographic, and procedural data were analyzed using descriptive statistics. Numerical values were expressed as mean ± SD or median (interquartile range [IQR]) as appropriate, whereas categorical variables were expressed as percentages. Normality was assessed using the Shapiro-Wilk statistic. Comparisons between groups were performed using Pearson chi-square test for categorical variables and the independent Student t test, 1-way analysis of variance, Mann-Whitney U test, or Kruskal-Wallis H test for continuous variables, as appropriate. Univariate logistic regression analyses were performed to assess the relationship between the patients’ baseline and angiographic characteristics and technical success. All statistical analyses were carried out using SPSS version 22 (IBM, Armonk, New York).
Demographics and angiographic characteristics
A total of 1,253 CTO-PCI procedures were performed in 1,177 patients, of which 832 and 421 procedures were performed by continental European and UK centers, respectively. Patients could be included multiple times, either for a reattempt of the same CTO lesion, a secondary CTO lesion treated at a later stage in time, or a second CTO lesion treated at the same procedure. In case of a reattempt, CTO angiographic characteristics of the first procedure were used. Inclusion start dates differed among centers, and increased throughout the study (first quarter: 23 inclusions/month; second quarter: 43 inclusions/month; third quarter: 83 inclusions/months; fourth quarter: 73 inclusions/month). The inclusion rate of the fourth quarter compared with that of the third quarter is lower, due to termination of inclusions early in October. The average inclusion duration per center was 13 ± 6 months.
Patient demographics are summarized in Table 2. Most patients were men (86%), and mean age was 66 ± 11 years. Success was achieved in 1,075 of 1,253 procedures (86%). Patients in whom CTO-PCI failed had a significantly higher frequency of prior MI (48% vs. 38%; p = 0.011), prior coronary artery bypass grafts surgery (35% vs. 15%; p < 0.001), and prior bypass graft surgery on CTO target vessel (25% vs. 11%; p < 0.001) (Table 2).
CTO target vessels were right coronary artery (61%), left anterior descending artery (23%), circumflex (16%), and left main coronary artery (0.3%). A high proportion of negative angiographic characteristics (blunt cap, lesion length ≥20 mm, tortuosity (≥45°), presence of calcification, proximal cap ambiguity, proximal cap side branch ≥2 mm, lack of interventional collaterals and diseased distal landing zone) were present. Apart from the lack of interventional collaterals, the previously mentioned angiographic characteristics with negative prognostic outcomes were significantly more frequent in the failure group. More patients in the failure group were included for a second or third attempt (27% vs. 21%; p = 0.050). The high prevalence of negative angiographic characteristics corresponded to a significantly higher J-CTO lesion complexity score in the failure group compared with the successful group (3.0 ± 1.1 vs. 2.0 ± 1.2; p < 0.001). With lesion complexity determined by J-CTO score, there were 116 easy, 249 intermediate, 385 difficult, and 503 very difficult CTO lesions included. The average PROGRESS score, 1.2 ± 1.0, was significantly higher in the failure group (1.6 ± 1.0 vs. 1.0 ± 1.0; p < 0.001). Overall, 310, 506, 324, 101, and 12 patients had 0, 1, 2, 3, and 4 PROGRESS score points, respectively (24). Both J-CTO and PROGRESS scores were significantly higher in failed procedures (Table 2).
Overall success was 86% per procedure (Tables 1 and 2). The average success of centers or operators performing >100 cases/year was significantly higher compared with lower-volume operators (91% vs. 82% vs. 83%; p < 0.001) (Table 1). Calculated success rates were 99% (n = 115 of 116) for easy, 95% (n = 237 of 249) for intermediate, 87% (n = 335 of 385) for difficult, and 77% (n = 388 of 503) for very difficult. For PROGRESS scores, success rates were 94% (n = 292 of 310), 86% (n = 434 of 506), 83% (n = 269 of 324), 74% (n = 75 of 101), and 42% (n = 5 of 12) for 0, 1, 2, 3, and 4 points, respectively. Thirty-nine patients underwent repeat PCI attempt for the same CTO resulting in increased technical success to 89% (Figure 1).
Dual catheter access and injection was applied in 77%. Reasons not to use bilateral injection were complete antegrade visualization by bridge or ipsilateral collaterals. A biradial or combined radial–femoral approach was followed in 24% (n = 306 of 1,253) and 44% (n = 550 of 1,253) of the cases, respectively. Overall procedure time was 90 (IQR: 60 to 120) min, fluoroscopy time to 35 (IQR: 21 to 55) min, air kerma to 1.6 (IQR: 1.0 to 2.7) Gy, dose area product to 98 (IQR: 57 to 168) Gy·cm2, and contrast volume to 250 (IQR: 180 to 340) ml. Radiation values for air kerma and dose area product were not captured in 34% and 16%, respectively. On average, 5.2 ± 3.8 guidewires, 3.5 ± 2.8 balloons, and 1.2 ± 0.6 microcatheters were used per procedure. If AWE was applied (n = 997), the most frequent wire used to start with was from the Fielder XT-family (Abbott Vascular, Abbott Park, Illinois): 57% (n = 571 of 997) including XT-A (n = 356), XT-R (n = 45), and XT (n = 170). If the CTO was successfully crossed (n = 623), the most frequent crossing wire was as well the Fielder wire (40% [n = 252 of 623] including XT-A [n = 176], XT-R [n = 16], and XT [n = 60]) (Figure 2). An average of 2.4 ± 1.1 stents were implanted, with an average stent length of 72 ± 34 mm. Of note, stents were used in 99% of successful procedures (n = 1,063 of 1,075), the remaining being treated with plain balloon angioplasty. Significantly more guidewires (but not balloons or stents) were used in failed procedures compared with successful procedures, and the use of balloons, stents, and guidewires all increased significantly as the difficulty of the procedure increased (Table 3).
In-hospital MACCE occurred in 33 cases (2.6%). Three patients died: 1 due to sudden death during the night post-procedure, 1 due to aortic dissection 6 h post-procedure requiring surgery and resulting in death after 3 days, and 1 due to shock after a staged non-target vessel PCI during the same hospitalization. Other MACCE outcomes included stroke (n = 3), acute MI (n = 27), and acute vessel closure requiring immediate target vessel revascularization (n = 1). In-hospital major coronary complications occurred in 23 cases—2 coronary dissections and 18 perforations. One was associated with ventricular fibrillation and 6 with MI. In 16 patients, a major coronary complication led to pericardial effusion. Eight were treated medically, resulting in 3 MIs, and 8 required pericardiocentesis due to life-threatening bleeding, resulting in 1 MI. Major peripheral vascular complications (n = 8) occurred: retroperitoneal bleeding (n = 2), stuck radial guiding requiring surgical removal (n = 1), 4 due to a subintimal access site–related hematoma leading to life-threatening or major bleeding (n = 4), and 1 major aortic dissection leading to death (as described previously). Other major bleeding occurred in 8 patients, 6 related to the access site and 2 due to retroperitoneal hemorrhage (Table 4).
Hybrid CTO crossing strategies
Four hybrid techniques were applied 1,824 times individually to tackle the 1,253 CTOs. AWE, ADR, or retrograde techniques were applied at any stage during the procedure in 80%, 23%, and 34%, respectively, corresponding to an average of 1.5 ± 0.7 applied strategies per procedure, and an average of 0.5 ± 0.7 strategy changes. AWE was the primary strategy in 77% (n = 958 of 1,253), followed by a retrograde technique in 17% (n = 207 of 1,253) and ADR in 7% (n = 88 of 1,253) (Figure 3). Primary ADR was most commonly used for in-stent occlusions (27%), long lesion lengths (92%), a blunt proximal cap (61%), a good distal landing zone (70%), and reattempts (30%); most commonly after a previously failed AWE procedure). A primary retrograde strategy was mainly applied on long lesion lengths (83%), a blunt proximal stump (73%), proximal cap ambiguity (60%), and a diseased distal landing zone (60%) (Table 5).
The primary crossing techniques AWE, ADR, and retrograde strategies (RWE and RDR) were successful in 62% (n = 594 of 958), 67% (n = 59 of 88), and 50% (n = 104 of 207) of the times, respectively (Figure 3). An average success rate of 60% (n = 757 of 1,253) was achieved with a primary strategy alone. The primary strategy was successful in 91% (n = 106 of 116) of easy, 80% (n = 199 of 249) of intermediate, 62% (n = 238 of 385) of difficult, and 43% (n = 214 of 503) of very difficult CTO lesions. The primary strategy failed in 5% of cases (n = 67 of 1,253) and no further strategies were applied. Second, third, or more bailout crossing strategies were used in 34% of cases (n = 429 of 1,253) and were successful 74% of the time (n = 318 of 429), leading to an overall technical success rate of 86% (n = 1,075 of 1,253) per attempt. The final successful crossing strategy was AWE in 58% (n = 623 of 1,075), ADR in 18% (n = 192 of 1,075), and retrograde in 24% (n = 260 of 1,075).
The dissection and re-entry and retrograde techniques were primarily used in a later phase during the procedure, most commonly when a primary antegrade wiring attempt was unsuccessful. If an AWE technique was applied first, success rates were high in easy (99%; n = 104 of 112) and intermediate (83%; n = 184 of 223) lesions, but low in difficult (62%; n = 192 of 312) and very difficult (37%; n = 114 of 311) J-CTO procedures. Consequently, in case of higher complexity (J-CTO ≥2), primary or bailout AWE was less successful (50%, n = 328 of 654) and ADR and retrograde strategies were applied more frequently, 29% (n = 256 of 888) and 42% (n = 371 of 888), respectively (Figure 2). Moreover, in those CTO procedures for which multiple different (i.e., AWE, ADR, or retrograde) strategies were planned in advance, the success rate was significantly higher. Data on pre-planned primary strategies were captured for 880 cases. In this subset, 1, 2, or 3 different strategies were planned up front in 220, 401, and 259 cases, respectively. Success rates increased with the number of planned strategies, 78% (n = 172 of 220), 85% (n = 342 of 401), and 86% (n = 223 of 259), respectively (p = 0.034).
Although the primary crossing strategy is determined by the hybrid algorithm (Central Illustration), the planned primary strategies actually differed slightly from strategies that were actually applied. Pre-planned (primary) strategies were determined up front for 880 cases. Of these cases, the planned primary strategy was applied in 97% (n = 855 of 880) and was successful in 65% (n = 553 of 855). In cases where the planned primary strategy was not followed and another crossing strategy was applied instead (3%; n = 25 of 880), the success rate of the applied primary strategy was very low (36%; n = 9 of 25).
The hybrid algorithm suggests an optimal primary strategy based on angiographic characteristics. According to these suggestions 225, 219, and 564 of all cases (n = 1,008 of 1,253) should have been tackled using AWE, ADR, or a retrograde strategy (either RWE or RDR), respectively. The primary strategy was concordant with the algorithm's predicted strategy in 95% (n = 213 of 225), 16% (n = 34 of 219), and 19% (n = 107 of 564), respectively, and in concordant cases the strategy was successful in 86% (n = 184 of 213), 76% (n = 26 of 34), and 65% (n = 70 of 107), respectively. When the primary strategy was not concordant with the algorithm (n = 654), success rates were lower: 50% (n = 6 of 12), 61% (n = 112 of 185), and 45% (n = 205 of 457), respectively.
Antegrade dissection and re-entry
In all procedures, ADR was applied at any stage during the procedure in 292 CTOs (23%), either as a first (7%; n = 88) or as a consecutive strategy (17%; n = 210). In 6 cases, the technique was applied twice, at different stages during the procedure. The technique was successful in 66% (n = 192 of 292) overall. Primary and consecutive ADR strategies were successful in 67% (n = 59 of 88) and 63% (n = 133 of 210), respectively. ADR was used more with increasing lesion complexity (Figure 2). ADR was applied in 3% (n = 3 of 116), 13% (n = 33 of 249), 22% (n = 86 of 385), and 34% (n = 170 of 503) of J-CTO 0, 1, 2, and 3 respectively. Success was obtained in 100% (n = 3 of 3), 64% (n = 21 of 33), 72% (n = 62 of 86), and 62% (n = 106 of 170) of these cases, respectively. Among successful cases (n = 192), the CrossBoss device was used in 80% (n = 153). This resulted in true lumen crossing in 24% (n = 36 of 153), of which 56% (n = 20 of 36) related to in-stent occlusions, or as part of a dissection strategy (76%; n = 117 of 153). In case of dissection, CrossBoss was used as a stand-alone device in 68% (n = 79 of 117) or combined with wire-based technology (i.e., subintimal guidewires, knuckled guidewires) in 32% (n = 38 of 117). Apart from the CrossBoss device, wire-based technology alone could also be applied for subintimal lumen dissection (20%; n = 39 of 192). Altogether, a successful dissection strategy was applied in 81% (n = 156 of 192) of successful ADR attempts. After dissection, a re-entry strategy was used to regain access to the distal true lumen. Successful re-entry techniques comprised the use of the Stingray system (Boston Scientific, Boston, Massachusetts) (78%; n = 121 of 156), subintimal tracking and re-entry (8%; n = 13 of 156), or limited antegrade subintimal tracking (14%; n = 22 of 156) (Table 6).
A retrograde approach was used in 421 cases; either RWE (56%; n = 236) or reverseCART (66%; n = 276) were applied at any stage and were successful in 28% (n = 67 of 236) and 67% (n = 186 of 276), respectively. In 91 cases, an RWE strategy failed, after which reverseCART was applied. In 79% (n = 72 of 91), reverseCART was then successful. Besides RWE and reverseCART, re-entry was also performed using wire-based technology (i.e., guidewire re-entry) or CART (1.7%) and was successful in 7 cases after failure of reverseCART. As with ADR, retrograde strategies were applied more often as lesion complexity increased: 9% (n = 10 of 116) easy, 19% (n = 47 of 249) intermediate, 35% (n = 136 of 385) difficult, and 63% (n = 319 of 503) very difficult. They were successful in 60% (n = 6 of 10), 57% (n = 27 of 47), 57% (n = 77 of 136), and 47% (n = 150 of 319), respectively (Figure 2). In general, septal collaterals, epicardial collaterals, or a combination were used in 64% (n = 268 of 421), 25% (n = 105 of 421), and 5% (n = 21 of 421), respectively. Bypass grafts were explored as a retrograde conduit in 6% (n = 24 of 421). Of 260 successful retrograde strategies, septal, epicardial, and both collaterals were used in 72% (n = 188), 20% (n = 52), and 2% (n = 5). Bypass conduits were used in 5% (n = 13). Wire externalization could be performed in 98% (n = 255 of 260) of successful retrograde cases (Table 6). The most common cause of failure for retrograde techniques was failure to cross the collateral with a guidewire (69%; n = 111 of 161).
Our study demonstrates the effectiveness and safety of the hybrid techniques for CTO-PCI, in a real-world, multicenter setting. A high level of success was obtained (86%) with a low incidence of MACCE (2.6%). Moreover, analysis showed that operators could achieve even higher success rates (89% per patient) by performing repeat attempts. Operators needed a minimum of experience with the hybrid algorithm and training in CrossBoss and Stingray use (17,27). There was no specific criterion for retrograde experience, but all operators had performed retrograde cases. On average, the mean number of annually performed CTO procedures per operator was 64, and 32% of the operators performed fewer than 50 procedures/year.
In the hybrid algorithm, the presence or absence of 4 angiographic characteristics are identified to determine the primary strategy. However, in practice, not all CTO lesions are perfectly “classifiable,” nor was the algorithm applied dogmatically. If CTO characteristics were analyzed according to these criteria, 80% (n = 1,008 of 1,253 cases) could be classified for a specific primary strategy. In classifiable lesions, a primary AWE approach should only have been applied in 22%, indicating that the algorithm was challenged.
Despite the fact that the operator started with a different strategy, when applying the hybrid characteristics strictly, several of the “required” angiographic characteristics were still in accordance with the performed strategy. Indeed, primary ADR was mainly applied for long lesion lengths, on blunt proximal caps and a good distal target zone, whereas primary retrograde strategies were most frequently applied in long CTO lengths, with proximal cap ambiguity and bluntness, as well when a diseased distal landing zone was present. In case bluntness and ambiguity can be resolved via wire puncture or knuckling, a primary ADR strategy is justified, just as the hybrid algorithm recommends. Likewise, in the presence of proximal cap ambiguity and distal disease, a retrograde first strategy is correct according to the algorithm.
Despite a high degree of several of these negative (hybrid) angiographic characteristics, AWE was the most frequently used first technique in our study population (77%). AWE was successful in 62% (n = 594 of 958), with low success rates in very difficult CTOs. A number of factors may explain this. First, several (hybrid) characteristics are open for interpretation. For example, an initial question that determines either an ante- or retrograde approach is proximal cap ambiguity. However, evaluation of proximal cap ambiguity is subjective and depends on operator experience and perception. The ambiguity can often be resolved with an antegrade attempt, either by probing with a wire, by the use of intravascular ultrasound imaging (IVUS), or by using more advanced CTO techniques of cap modification (28–30).
Second, the algorithm’s suggestion that lesion length (≥20 mm) should drive the strategy from AWE to ADR was followed less strictly than expected. In one-half of cases in which primary AWE was applied, the lesion length was ≥20 mm. This may be because “true” CTO lesion length is often not clear from the angiographic images due to incomplete retrograde artery filling. Moreover, if the proximal cap contains soft tissue, the first millimeters can be crossed quickly, reducing the length of the “difficult-to-cross” part of the CTO body. In this scenario, the operator might prefer to wire the remaining CTO length, mainly driven by the presence of an angiographically healthy and clear distal target. If this strategy fails, he or she still has the option to shift to ADR as a second strategy. Further improvements in CTO-dedicated materials (i.e., more directionable wires and new microcatheters with lower crossing profiles) have increased success rates of AWE, as well as the use of double-lumen microcatheters to redirect the wire, especially in lesions of low J-CTO complexity. Of note, parallel wiring was rarely applied in the registry. A successful AWE circumvents the need for other more complex techniques (i.e., ADR, retrograde), which require specific skills and are often associated with specialized materials, increased procedural characteristics and cost. Finally, if an antegrade wire tracks the subintimal space, switching strategy to ADR or RDR technique is still feasible. In almost all CTO procedures irrespective of final strategy, antegrade puncture of the proximal cap and lesion preparation is required at some stage during the procedure, such that many operators advocate that AWE is tried first, prior to applying ADR or retrograde strategies. However, the threshold to switch between strategies should be low (i.e., within 15 to 30 min), to reduce procedure times, contrast and radiation exposure, especially in more complex lesions; our results demonstrate the ineffectiveness of the AWE approach in these types of lesions (<40% primary AWE success for J-CTO ≥3) and thus reinforces limiting the primary use of AWE when faced with higher complexity (Figure 2).
Subsequent strategies were needed in one-third of the patients, resulting in a high final success rate. This applies to all techniques: the likelihood of successful revascularization using a primary strategy alone decreases with increasing J-CTO lesion complexity. Overall, a primary strategy resulted in success 60% of the time, whereas the availability of subsequent strategies is crucial to further increase this success to >85% (Figures 2 and 3). Patients with limited options (i.e., no suitable interventional collaterals) will have a greater risk for procedural failure, especially in case of higher J-CTO and PROGRESS lesion complexity. In the RECHARGE registry, ADR and retrograde approaches were successful in 66% and 62%, respectively. The reported outcomes of these techniques are within that range, compared to the most recently published data in the United States, Japanese, and European Registry of Chronic Total Occlusion (ERCTO) data (66% for ADR and 63% to 75.3% for retrograde techniques) (16,31,32). Despite an overall lower retrograde success rate, our success with multiple strategies (including a primary retrograde strategy) was 75%, similar to the ERCTO results.
The application of hybrid techniques resulted in a high success rate (86%) in our population of 1,253 CTOs. Although success rates are similar to the EuroCTO (82.9%) and Japanese results (88.4%), success rates from United States and Canadian hybrid operators are even higher, between 90% and 95% (14,16,19,22,33,34). These were achieved by highly experienced CTO operators or high-volume CTO-PCI centers, and thus do not directly reflect success rates obtainable in broader communities. We aimed to validate the effectiveness and safety of the hybrid algorithm in a real-world setting, and determine the level of success that can be achieved by less highly experienced operators, while at the same time trying to improve procedure duration, fluoroscopic time, radiation exposure and contrast use. In comparison to the most recent Japanese, United States, and EuroCTO reports, our results show a reduction of 15 to 69 min in procedure duration, 7 to 28 min in fluoroscopy time, and a reduction from 1.8 to 3.1 Gray in radiation air kerma, although these differences can be the result of many factors, such as different baseline characteristics (body mass index, lesion complexity), operator perseverance, and use of different (low) radiation equipment. Apart from the Japanese study by Habara et al. (31), a 10 to 143 ml reduction in contrast volumes was also noted (14,16,19,31,33,35).
Given the low rate of complications, the safety of the different techniques was shown. The complication rates were also consistent with the results of the United States and the recent weighted meta-analysis of more than 18,061 patients by Christopoulos et al. (16) and Patel et al. (36).
To apply hybrid CTO-PCI efficiently, both training and experience are crucial for optimal results. Not all centers started inclusion at the same time, and experience among some operators could have increased in the meantime, influencing outcomes. Furthermore, the hybrid algorithm was not used as a dogma but as a guideline. The choice to switch between first and subsequent strategies, as well as the choice in materials, was operator dependent, and thus could influence outcomes. Procedural outcomes as well as lesion-specific angiographic characteristics depended on operator reports, without an independent core lab, due to financial considerations. However, 35% (n = 440 of 1,253) of the cases were reviewed by 3 independent readers, with a 98% agreement of the reported success rate (limits of agreement: 97% to 99%). Because pre- and post-procedural laboratory tests were only available in a minority of the patients, especially the number of periprocedural MIs are underreported. In several cases, radiation doses were missing for air kerma or dose area product. To be reassured there is no bias in the reported results, an additional comparison of the fluoroscopic time between cases with missing and those with available radiation dose was performed, and showed no significant difference.
This study demonstrates that hybrid techniques for CTO-PCI as applied by dedicated CTO operators with a variety of experience have high success rates. The associated low level of in-hospital events, in addition to notably improved procedural characteristics supports the applicability of the hybrid algorithm for a broad community. An AWE technique was found to be highly unlikely to be successful in complex lesions. Although retrograde and ADR approaches have their limitations, both techniques enhance overall success, especially in those patients in whom all techniques can be applied.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: A hybrid algorithm based on angiographic characteristics and specifying the procedure for percutaneous revascularization of chronically occluded coronary arteries has been developed and validated. Application of the hybrid algorithm by experienced operators at several clinical centers in Europe improved procedural outcomes.
TRANSLATIONAL OUTLOOK: Additional research is needed to identify specific clinical predictors of angiographic success of the hybrid algorithm and techniques in patients with CTOs undergoing coronary intervention, as well as methods to select patients most likely to gain long-term benefit from this interventional strategy.
The authors thank Pieter-Jan Palmers, MD, Stefan Schumacher, MD, and Andrew Ladwiniec, MD, for their assistance with the independent review of the cases.
This research project is supported by a research grant from Boston Scientific (Marlborough, Massachusetts). Dr. Maeremans is researcher for the Limburg Clinical Research Program UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. Drs. Walsh has served as a consultant for Abbott Vascular, Boston Scientific, Medtronic, and Vascular Solutions; and has received research funding from Abbott Vascular, Boston Scientific, and Nitiloop. Drs. Knaapen, Spratt, and Bressollette have served as proctors for and received proctor honoraria from Boston Scientific. Dr. Avran has received grants from Abbott Vascular, Boston Scientific, and Biosensor for teaching courses and proctoring. Dr. Hanratty has served as consultant for Abbott Vascular, Boston Scientific, Medtronic, and Vascular Solutions. Dr. Faurie has served as a proctor for Boston Scientific; and as a consultant for CORDIS. Dr. Bagnall has received proctor and speaker fees from Abbott Vascular and AstraZeneca. Dr. Egred has served as a proctor for and received honoraria from Boston Scientific, Abbott Vascular, Vascular Perspectives, Volcano, and Spectranetics. Dr. Elliot Smith has served as a proctor for Boston Scientific; and received honoraria from Vascular Solutions, Abbott Vascular, Vascular Perspectives, and Cardi Red. Dr. Kelly has served on the advisory boards of Boston Scientific and Abbott Vascular. Dr. Irving has served as a proctor for Boston Scientific and Vascular Perspectives. Dr. Dens has received grants from TopMedical (distributor of Asahi Intecc Co. Materials), Boston Scientific, and Orbus Neich for teaching courses and proctoring. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- antegrade dissection and re-entry
- antegrade wire escalation
- chronic total occlusion
- Japanese chronic total occlusion
- major adverse cardiac and cerebrovascular events
- myocardial infarction
- percutaneous coronary intervention
- retrograde dissection and re-entry
- reverse controlled antegrade and retrograde subintimal tracking
- retrograde wire escalation
- Received April 29, 2016.
- Revision received August 1, 2016.
- Accepted August 2, 2016.
- American College of Cardiology Foundation
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