Clinical, Angiographic, and Procedural Predictors of Periprocedural Complications During Chronic Total Occlusion Percutaneous Coronary Intervention

Abstract: Objectives. To identify clinical, angiographic, and procedural factors associated with increased risk of periprocedural complications during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Background. Successful CTO PCI can provide significant clinical benefit; however, procedural risks have received limited study. We sought to identify factors associated with increased CTO PCI periprocedural risk that could be utilized to guide patient and lesion selection. Methods. The clinical, angiographic, and procedural records of 336 consecutive CTO PCI procedures performed at a single center from May 2005 through 2012 were reviewed, and data on periprocedural complications were recorded. Logistic regression was performed to identify independent predictors of periprocedural complications during CTO PCI. Results. The incidence of major and minor complications was 3.9% and 10.4%, respectively. Minor bleeding and vascular events were the most common complications (4.8%), followed by perforation (2.4%), contrast-induced nephropathy (1.8%), and transient hypotension (0.6%). Major complications were uncommon: death (0.3%); emergency coronary artery bypass grafting (0.6%); stroke (0.3%); tamponade (0.3%); clinical myocardial infarction (0.9%); donor vessel injury (0.6%); and major bleeding or vascular events (0.9%). Patients who experienced any complication had higher preprocedure troponin levels and were more likely to undergo treatment using the retrograde approach. In multivariable analysis, use of the retrograde approach was independently associated with increased risk of periprocedural complications (odds ratio, 2.057; 95% confidence interval, 1.045-4.051; P=.04). Conclusions. Major complications of CTO PCI are infrequent, but are more common with use of the retrograde approach. 

J INVASIVE CARDIOL 2014;26(3):100-105

Key words: chronic total occlusion, percutaneous coronary intervention, complications

_________________________

Chronic total occlusion (CTO) is encountered in 15%-30% of patients undergoing diagnostic coronary angiography, and successful CTO percutaneous coronary intervention (PCI) has been associated with improvement in angina, left ventricular function, and survival.^1-3 Despite these benefits, CTO PCI is performed infrequently,² likely due to historically low procedural success rates, technical complexity, high equipment utilization, and potential for major periprocedural complications.⁴ We recently performed a systematic review and meta-analysis of CTO PCI that demonstrated increasing procedural success rates, with concurrent low and declining periprocedural complication rates over the last decade.⁵ However, there is still a measurable risk associated with CTO PCI, and the ability to identify patients at increased risk for complications may provide guidance on optimal patient and lesion selection. The aim of our study was to identify clinical, angiographic, and procedural factors associated with increased risk of periprocedural complications during CTO PCI. 

Methods

Study design. The study included 336 consecutive patients who underwent CTO PCI at our institution from May 2005 through 2012. Demographic and procedural complications were extracted from medical records and entered into a dedicated database. Angiographic and procedural variables were obtained by review of each angiogram and procedural record with the consensus of three of four physicians (VP, OM, EF, and EB). The study was approved by the institutional review board.

Definitions. Coronary CTOs were defined as angiographic evidence of a total occlusion with Thrombolysis In Myocardial Infarction (TIMI) grade 0 or 1 flow, and estimated duration of at least 3 months. Estimation of occlusion duration was based upon first onset of angina, prior history of myocardial infarction in the target vessel territory, or comparison with a prior angiogram. Technical success was defined as successful CTO recanalization with achievement of <30% residual diameter stenosis within the treated segment and restoration of TIMI grade 3 antegrade flow.

Proximal cap or stump of the CTO was defined as tapered (progressive narrowing of the proximal cap with or without a clear microchannel), blunt (abrupt occlusion with no microchannel), or stumpless (proximal cap could not be angiographically defined). Proximal tortuosity of the CTO vessel was defined as straight (<70°, 1 bend), slight (≥70°, 1 bend), moderate (2 bends ≥70° or 1 bend ≥90°), or severe (2 bends ≥90° or 1 bend ≥120°). Vessel calcification was graded as none (no calcification present), mild (isolated spots of calcium visible), moderate (≤50% reference lesion diameter), or severe (>50% reference lesion diameter). A side branch was considered “present” if it was within 2 mm of the proximal CTO cap, and the distal landing zone was considered “adequate” if the size of the vessel was ≥2 mm without diffuse disease. Distal opacification was graded as good (opacified as well as the proximal vessel), faint (visible but opacified less than the proximal vessel), or none (not visible).

Procedural complications were divided into major and minor complications. Major complications were defined as death, emergency coronary artery bypass grafting (CABG), clinical myocardial infarction (MI) defined as ischemic symptoms with typical rise and fall of cardiac biomarkers, tamponade, donor vessel injury, and major bleeding or vascular events (bleeding requiring transfusion of hemoglobin drop ≥3 g/dL or need for vascular surgery). Minor complications were defined as perforation not resulting in tamponade, contrast-induced nephropathy, bleeding or vascular events not meeting the criteria of a major complication, transient hemodynamic instability, device loss not requiring surgery, or infection.

Interventional technique and guidewire crossing strategies. The operators performed CTO PCI procedures according to standard practice, typically via the femoral approach using 8 Fr systems and bilateral injections. Patients were considered to have retrograde CTO PCI if a guidewire was introduced into a collateral channel that supplied the target CTO vessel distal to the lesion. All patients were treated with heparin to achieve an activated clotting time of >250 seconds for antegrade crossing attempts, and of >350 seconds for retrograde crossing attempts.

Statistical analysis. Continuous data were presented as mean ± standard deviation and nominal variables expressed as number (%). Pearson’s chi-square tests were computed for categorical variables, and independent samples t-tests (normally distributed) or Mann-Whitney U-tests (not normally distributed) for continuous variables. Multiple logistic regression analysis was performed using a previously published SAS macro⁶ to identify predictors of any periprocedural complications of CTO PCI. Analyses were performed using JMP version 8 or SAS 9.2 for Linux (SAS Institute).

Results

Incidence of periprocedural complications. Between 2005 and 2012, a total of 336 patients underwent CTO PCI at our institution. A total of 45 patients (13.4%) experienced 48 complications (3 patients had both a major and minor complication) (Table 1). The majority of these complications were minor (35 events, 10.4%). There were 13 major complications (3.9%) as follows: death (0.3%); emergent CABG (0.6%); stroke/transient ischemic attack (0.3%); clinical myocardial infarction (0.9%); tamponade (0.3%, occurred in a patient with distal wire perforation that developed tamponade 1 hour after the end of a successful procedure); donor vessel injury (0.6%); and major bleeding/vascular events (0.9%). 

The 1 death in our series occurred after right coronary artery (RCA) CTO PCI that was complicated by acute marginal occlusion that could not be recanalized. Although stable during the procedure, the patient arrested from pulseless electrical activity arrest hours later and was unable to be resuscitated. Emergency CABG was required in 2 patients in our series. One patient undergoing PCI of a left anterior descending coronary artery using the retrograde approach developed RCA dissection. Although the patient remained hemodynamically stable, the RCA could not be recanalized and emergency CABG was performed. Another patient underwent emergency CABG because of entrapment of a Tornus catheter (Asahi Intecc) during attempts to cross an RCA CTO. 

The most common minor complications were minor bleeding/vascular events (4.8%), followed by perforation (2.4%) and contrast-induced nephropathy (1.8%). The remaining minor complications were infrequent, occurring in ≤0.6% of cases.

Baseline clinical characteristics. Compared to patients who did not experience a major or minor periprocedural complication, those who did were similar in age, coronary risk factors, ejection fraction, and history of prior CABG (Table 2). The clinical presentation was also similar in the two groups. However, precatheterization creatine kinase (CK)-MB and troponin levels were higher in those who experienced a complication.

Angiographic characteristics. Patients who experienced no complications had similar target CTO vessel occlusion duration and anatomic characteristics compared to those who had a major or minor complication (Table 3). The most common CTO target vessel was the RCA, and most CTOs were >12 months old. Tapered proximal cap with mild lesion calcification, slight proximal tortuosity, and good distal opacification were the most common anatomic features. A side branch at the proximal cap and an adequate distal landing zone were present in approximately half of the cases.

Procedural characteristics. Patients who experienced a minor complication had similar procedural characteristics compared to those who experienced no complications; however, patients with major complications were more likely to have bifemoral access, and to have undergone crossing attempts using the retrograde approach compared to those without periprocedural complications (Table 4). Patients with major complications had longer procedure time (212.1 minutes vs 135.8 minutes; P<.001) and fluoroscopy time (65.2 minutes vs 38.2 minutes; P<.001), higher contrast utilization (501.7 mL vs 351.7 mL; P<.001), and higher radiation dose area product (504323 Gray cm² vs 327483 Gray cm²; P<.001) compared to those with no complications. There was no difference in the rates of technical success or the number of stents implanted in patients with no complications compared to those with major or minor complications.

Predictors of procedural complications. Candidate parameters associated with any (major or minor) periprocedural complication during CTO PCI included precatheterization troponin level, hyperlipidemia, and use of the retrograde approach. In multiple logistic regression analysis, use of the retrograde approach was associated with an increased risk of any periprocedural complication during CTO PCI (odds ratio, 2.057; P=.04; Figure 1). No other significant predictors or confounders were identified. There was a higher rate of all major complications with the retrograde approach compared to the non-retrograde approach (Table 5). 

Discussion

To our knowledge, this is the first study to systematically evaluate the association of angiographic, clinical, and procedural parameters with periprocedural complications during CTO PCI. The main findings are that: (1) CTO PCI carries a low overall risk of major periprocedural complications; (2) clinical and angiographic/anatomic characteristics have a weak association with periprocedural risk; and (3) use of the retrograde approach is associated with an increased risk of periprocedural complications.

Periprocedural complications during CTO PCI. Major complications after routine elective PCI such as death, MI, emergent CABG, stroke, and abrupt vessel closure have declined with modern PCI techniques and the advent of stents.⁷ Similarly, there has been a decline in the rate of major complications during CTO PCI with a concomitant rise in the rate of angiographic success.⁵ The incidence of major complications such as death, emergent CABG, stroke, clinical MI, and tamponade in our study was comparable to previously published large series.^8-11

Donor vessel dissection is an uncommon but potentially life-threatening complication, as it can lead to rapid hemodynamic compromise. Sianos et al reported 2 cases (1.1%) of donor vessel dissection among 175 patients treated with the retrograde technique in the EuroCTO club.¹² Wu et al reported 3 cases (3.5%) of donor vessel dissection among 85 patients treated with the retrograde approach.¹³ Donor vessel dissection occurred in 2 patients in our series: 1 was treated with stenting and the other required emergency CABG. Prevention of donor vessel injury is of paramount importance during retrograde CTO PCI; keeping the activated clotting time above 350 seconds can prevent donor guide and vessel thrombus formation.¹⁴ Guide catheters with side holes should never be used in the donor vessel as they can mask deep guide intubation. Moreover, it is important to carefully visualize the guide catheters during wire externalization and to externalize the guidewire by pushing rather than pulling to prevent deep seating of the guide catheters, which can cause injury, especially in tortuous donor vessels. 

Similarly, device loss and entrapment can complicate CTO PCI.¹⁵ Risk of stent loss during CTO PCI is especially acute when attempting to deliver stents through tortuous and calcified coronary segments.¹⁶ Careful pretreatment of the target coronary artery can reduce the risk of device loss. If a stent becomes dislodged from the delivery balloon, it may best be deployed rather than retrieved in most cases, unless the stent is lost in a critical coronary location, such as the left main coronary artery. Unlike stent (or other device) loss, which can often be managed percutaneously, device entrapment generally requires emergency cardiac surgery.¹⁵

We found that coronary perforation was relatively rare in our study, occurring in 8 cases (2.4%). This was similar to the findings of Mehran et al, who reported a 3.5% rate of perforation among 1791 patients undergoing CTO PCI.¹⁷ An important finding of our study is that when coronary perforation did occur, it only rarely caused tamponade (1 case; 0.3%). This suggests that although perforation is one of the most feared complications of CTO PCI, when only the guidewire enters the pericardial space without advancement of a balloon or microcatheter, it is unlikely to cause tamponade.¹⁸ This also underscores the importance of dual coronary injections for determining the guidewire position during crossing attempts.¹⁹ Large-vessel coronary perforations are immediately recognizable due to rapid blood extravasation and development of tamponade. In contrast, distal wire perforations are more subtle due to the slow rate of bleeding, but can still cause tamponade even hours after the end of the procedure,¹⁹ as occurred in the single patient with tamponade in our series.

Minor complications accounted for the majority of complications in our study, occurring at a rate of 10.4%, with the most common being minor bleeding or vascular events. The majority of these events were access-site hematomas detected by clinical exam or minor decreases in hemoglobin the following day. Blood loss through the touhy can be significant during long CTO PCI procedures, and could be reduced by use of touhys with automated hemostatic valves, such as the Co-Pilot bleedback control valve (Abbott Vascular). The use of large-bore (8 Fr) bilateral femoral sheaths in most cases may have contributed to the development of vascular access complications. Use of biradial access can virtually eliminate the risk of vascular access complications while maintaining high procedural success rates;²⁰ however, it only permits use of smaller guiding catheters, which provide less support and may increase the duration of the procedure and radiation exposure for both the patient and the operator. 

Contrast-induced nephropathy was detected in 6 patients in our series, none of whom required dialysis. While this is in line with previous publications,⁵ this is likely an underestimation of the true contrast nephropathy event rate because patients were not required to have systematic creatinine evaluations at 48 hours after contrast agent exposure. Pre- and postprocedural hydration and minimization of the administered contrast volume can help reduce the risk of this complication.²¹

Predictors of procedural complications. Previous research has primarily focused on predictors of technical success when approaching CTO PCI lesions.^10,22 Rathore et al found that moderate to severe calcification and tortuosity were predictors of an unsuccessful CTO PCI procedure in logistic regression analysis.¹⁰ Data from the Multicenter CTO Registry of Japan were analyzed to develop and validate the J-CTO score, which was able to predict successful guidewire crossing within 30 minutes reasonably well.²³ Variables in the J-CTO score were previously failed lesion, blunt stump type, bending, calcification, and occlusion length ≥20 mm. To the best of our knowledge, our study is the first to systematically examine clinical, angiographic, and procedural factors that are associated with increased risk of periprocedural complications. We found that the retrograde approach was independently associated with a 2.1-fold increase in the odds of any periprocedural complication. Whether this association is causal remains controversial. Use of the retrograde approach can expose the patient to unique procedural risks (such as donor vessel dissection as described above). However, use of the retrograde approach may also be a marker for more complex CTO, as it is most often used after failure of antegrade crossing attempts.²⁴

Study limitations. There are several important limitations of our study. First, this is a retrospective study and it is thus subject to bias and confounding. Second, the number of patients is limited, although comparable to many previously published CTO registry papers. Third, there were few overall events, particularly major complications. Long-term complications (such as restenosis or stent thrombosis) were not assessed in our study. Finally, some endpoints were not systematically assessed, such as contrast-induced nephropathy.

Conclusion

In summary, chronic total occlusion percutaneous coronary intervention is associated with a low risk of major or minor periprocedural complications, which occurred more commonly among patients in whom the retrograde approach was used. CTO PCI is an attractive treatment option in patients with complex coronary artery disease. 

References

1. Fefer P, Knudtson ML, Cheema AN et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol. 2012;59(11):991-997.
2. Grantham JA, Marso SP, Spertus J, House J, Holmes DR Jr, Rutherford BD. Chronic total occlusion angioplasty in the United States. JACC Cardiovasc Interv. 2009;2(6):479-486.
3. Joyal D, Afilalo J, Rinfret S. Effectiveness of recanalization of chronic total occlusions: a systematic review and meta-analysis. Am Heart J. 2010;160(1):179-187.
4. Shah PB. Management of coronary chronic total occlusion. Circulation. 2011;123(16):1780-1784.
5. 5. Patel VG, Brayton KM, Tamayo A, et al. Angiographic success and procedural complications in patients undergoing percutaneous coronary chronic total occlusion interventions: a weighted meta-analysis of 18,061 patients from 65 studies. JACC Cardiovasc Interv. 2013;6(2):128-136. Epub 2013 Jan 23.
6. Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code Biol Med. 2008;3:17.
7. Hilliard AA, From AM, Lennon RJ, et al. Percutaneous revascularization for stable coronary artery disease temporal trends and impact of drug-eluting stents. JACC Cardiovasc Interv. 2010;3(2):172-179.
8. Galassi AR, Tomasello SD, Reifart N, et al. In-hospital outcomes of percutaneous coronary intervention in patients with chronic total occlusion: insights from the ERCTO (European Registry of Chronic Total Occlusion) registry. EuroIntervention. 2011;7(4):472-479.
9. Olivari Z, Rubartelli P, Piscione F, et al. Immediate results and one-year clinical outcome after percutaneous coronary interventions in chronic total occlusions: data from a multicenter, prospective, observational study (TOAST-GISE). J Am Coll Cardiol. 2003;41(10):1672-1678.
10. Rathore S, Matsuo H, Terashima M, et al. Procedural and in-hospital outcomes after percutaneous coronary intervention for chronic total occlusions of coronary arteries 2002 to 2008: impact of novel guidewire techniques. JACC Cardiovasc Interv. 2009;2(6):489-497.
11. Suero JA, Marso SP, Jones PG, et al. Procedural outcomes and long-term survival among patients undergoing percutaneous coronary intervention of a chronic total occlusion in native coronary arteries: a 20-year experience. J Am Coll Cardiol. 2001;38(2):409-414.
12. Sianos G, Barlis P, Di Mario C, et al. European experience with the retrograde approach for the recanalisation of coronary artery chronic total occlusions. A report on behalf of the euroCTO club. EuroIntervention. 2008;4(1):84-92.
13. Wu CJ, Fang HY, Cheng CI, et al. The safety and feasibility of bilateral radial approach in chronic total occlusion percutaneous coronary intervention. Int Heart J. 2011;52(3):131-138.
14. 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):3-19.
15. Iturbe JM, Abdel-Karim AR, Papayannis A, et al. Frequency, treatment, and consequences of device loss and entrapment in contemporary percutaneous coronary interventions. J Invasive Cardiol. 2012;24(5):215-221.
16. Brilakis ES, Best PJ, Elesber AA, et al. Incidence, retrieval methods, and outcomes of stent loss during percutaneous coronary intervention: a large single-center experience. Catheter Cardiovasc Interv. 2005;66(3):333-340.
17. Mehran R, Claessen BE, Godino C, et al. Long-term outcome of percutaneous coronary intervention for chronic total occlusions. JACC Cardiovasc Interv. 2011;4(9):952-961.
18. Brilakis E, Karmpaliotis D, Patel V, Banerjee S. Complications of chronic total occlusions angioplasty. Interv Cardiol Clin. 2012;1(3):373-389.
19. Brilakis ES, Grantham JA, Rinfret S, et al. A percutaneous treatment algorithm for crossing coronary chronic total occlusions. JACC Cardiovasc Interv. 2012;5(4):367-379.
20. Rinfret S, Joyal D, Nguyen CM, et al. Retrograde recanalization of chronic total occlusions from the transradial approach; early Canadian experience. Catheter Cardiovasc Interv. 2011;78(3):366-374.
21. Klima T, Christ A, Marana I, et al. Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial. Eur Heart J. 2012;33(16):2071-2079.
22. Morino Y, Kimura T, Hayashi Y, et al. In-hospital outcomes of contemporary percutaneous coronary intervention in patients with chronic total occlusion insights from the J-CTO Registry (Multicenter CTO Registry in Japan). JACC Cardiovasc Interv. 2010;3(2):143-151.
23. Morino Y, Abe M, Morimoto T, et al. Predicting successful guidewire crossing through chronic total occlusion of native coronary lesions within 30 minutes: the J-CTO (Multicenter CTO Registry in Japan) score as a difficulty grading and time assessment tool. JACC Cardiovasc Interv. 2011;4(2):213-221.
24. Karmpaliotis D, Michael TT, Brilakis ES, et al. Retrograde coronary chronic total occlusion revascularization: procedural and in-hospital outcomes from a multicenter registry in the United States. JACC Cardiovasc Interv. 2012;5(12):1273-1279.