ADVERTISEMENT
Predictors and Outcomes of Side-Branch Occlusion in Coronary Chronic Total Occlusion Interventions
Abstract: Objectives. We investigated whether side-branch loss during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) could adversely impact clinical outcomes. Background. Side-branch occlusion during PCI has been associated with periprocedural myocardial infarction and higher incidence of major adverse cardiac event (MACE), but has received limited study in CTO-PCI. Methods. We retrospectively reviewed the medical records and coronary angiograms for 109 consecutive CTO-PCI cases performed at our institution during 2012 and 2013. Post-PCI patency of ≥1 mm diameter side branches and associated clinical outcomes were assessed. Results. Mean age was 65 ± 8 years and 99.1% of the patients were men. The CTO target vessel was the right coronary artery (54%), circumflex (26%), and left anterior descending artery (20%). Side-branch loss occurred in 28 cases (25.7%) due to antegrade dissection/reentry (n = 9), retrograde dissection/reentry (n = 5), stenting over the branch (n = 12), and dissection during antegrade crossing attempts (n = 2). Recanalization of the occluded side branch was pursued in 8 cases (28.6%) and was successful in 4 patients. Patients with side-branch loss had higher post-PCI increase in CK-MB levels (8.4 ng/mL [interquartile range, 2.7-33.5 ng/mL] vs 1.8 ng/mL [interquartile range, 0.025-6.775 ng/mL]; P<.001) and higher 12-month incidence of all-cause death (17.3% vs 2.8%; P=.02) and cardiovascular death (7.4% vs 0.0%; P=.02). Conclusions. Side-branch loss occurs in approximately 1 in 4 CTO-PCIs and is associated with higher risk for periprocedural myocardial infarction and higher mortality.
J INVASIVE CARDIOL 2016;28(4):168-173. Epub 2016 January 15.
Key words: chronic total occlusion, percutaneous coronary intervention
_____________________________________________________
Side-branch (SB) occlusion occurs in 4.5%-26.0% of percutaneous coronary interventions (PCIs),1-4 and has been associated with periprocedural myocardial infarction (MI), which in turn has been linked to higher incidence of major adverse cardiac event (MACE).5 However, the frequency and impact of SB occlusion during chronic total occlusion (CTO)-PCI has received limited study.4,6,7
We retrospectively examined a contemporary CTO-PCI registry to determine the frequency and angiographic mechanism of SB loss, examine strategies implemented to restore SB flow, and correlate the impact of SB loss on periprocedural MI and clinical outcomes.
Methods
We examined the clinical and angiographic characteristics, procedural techniques, and outcomes of 109 consecutive CTO-PCIs performed between January 2012 and December 2013 at our institution.
Definitions. Coronary chronic total occlusions were defined as coronary lesions with Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow of at least 3-month duration. Estimation of the occlusion duration was based on first onset of anginal symptoms, prior history of MI in the target vessel territory, or comparison with a prior angiogram. The J-CTO score was calculated as described by Morino et al.8Side branches were defined as vessels ≥1 mm in diameter visualized angiographically at any point during the procedure. Technical success of CTO-PCI was defined as successful CTO revascularization with achievement of <30% residual diameter stenosis within the treated segment and restoration of TIMI grade 3 antegrade flow. Procedural success was defined as achievement of technical success with no in-hospital MACE.
All patients underwent creatine kinase-myocardial band (CK-MB) and troponin I measurement before PCI and at 8-12 and 18-24 hours after PCI. Periprocedural myocardial infarction was defined as CK-MB increase ≥3x the upper limit of normal (ULN), if the baseline CK-MB levels were below ULN. Periprocedural MI rates were also reported using various cutoffs (CK-MB ≥3x ULN, CK-MB ≥10x ULN per the new proposed Society for Cardiac Angiography and Interventions [SCAI] definition, and troponin ≥5x ULN or >20% above baseline per the Third Universal Definition of MI). The upper limits of normal for CK-MB and troponin at our institution were 6.3 ng/mL and 0.03 ng/mL, respectively. The cause of death during follow-up was determined through review of the medical chart and the death certificate.
Statistical analysis. Continuous data were summarized as mean ± standard deviation (normally distributed data) or median and interquartile range (non-normally distributed data) and compared using t-test or Wilcoxon rank-sum test, as appropriate. Categorical data were presented as frequencies or percentages and compared using c2 or Fisher’s exact test, as appropriate. The Kaplan-Meier method was used to estimate the incidence of MACE, death, and target-lesion revascularization during follow-up, which were compared using the log-rank test. Logistic regression analysis was performed to assess the relative contribution of various angiographic and procedural variables to SB loss. A P-value of <.05 was considered statistically significant. Statistical analyses were performed using JMP version 11.0 and SAS version 9.2 (SAS Institute).
Results
Clinical and angiographic characteristics. The baseline characteristics of the study population are shown in Table 1. Mean age was 65.1 ± 7.6 years, and 99.1% of the patients were men, with high prevalence of diabetes mellitus, hypertension, prior coronary artery bypass graft (CABG) surgery, and smoking. The CTO target vessel was the right coronary (54%), circumflex (26%), or left anterior descending (20%) artery. Median CTO occlusion length was 30 mm (IQR, 20-50 mm) and mean J-CTO score was 2.6 ± 1.0.
Location and mechanisms of side-branch loss. Among 109 consecutive patients who underwent CTO-PCI, SB loss occurred in 28 patients (25.7%). SB loss was due to antegrade dissection/reentry (n = 9), retrograde dissection/reentry (n = 5), stenting over the SB (n = 12), and dissection during antegrade crossing attempts (n = 2) (Figure 1). As compared with patients who did not have SB loss, patients with SB loss were more likely to have had retrograde CTO crossing (35.7% vs 17.1%; P=.03) and had longer procedure time (175 minutes [IQR, 113-211 minutes] vs 120 minutes [IQR, 81-174 minutes]; P=.01) and fluoroscopy time (46 minutes [IQR, 32-65 minutes] vs 34 minutes [IQR, 20-51 minutes]; P=.04). The lost SB was most often located in the right coronary artery (Figure 2). Attempts to recanalize the occluded SB were made in 8 of 28 cases (28.6%) and were successful in 4 cases.
Procedural outcomes and complications. Technical success was achieved in 96.4% of patients with SB loss and 87.8% of patients without SB loss (P=.28). The corresponding rates for procedural success were 92.9% and 85.2%, respectively (P=.51).
Overall, major procedural complications occurred in 2 of 109 patients (1.8%); 1 patient had a perforation requiring emergent pericardiocentesis and 1 patient had acute stent thrombosis within 24 hours of the initial procedure requiring urgent repeat PCI. A third patient developed a femoral pseudoaneurysm necessitating surgical repair.
Periprocedural myocardial infarction. Patients with SB loss had higher post-PCI increase in CK-MB (8.4 ng/mL [IQR, 2.7-33.5 ng/mL] vs 1.8 ng/mL [IQR, 0.025-6.775 ng/mL]; P<.001) (Figure 3). A similar trend was found for post-PCI change in troponin I (1.065 ng/mL [IQR, 0.435-3.77 ng/mL] vs 0.385 ng/mL [IQR, 0.043-1.238 ng/mL]; P=.02). Results were similar after excluding 4 cases of proximal SB loss (CK-MB: 6.2 ng/mL [IQR, 1.4-19 ng/mL] vs 2.1 ng/mL [IQR, 0.1-6.9 ng/mL] P=.01; troponin I: 1 ng/mL [IQR, 0.4-3.33 ng/mL] vs 0.43 ng/mL [IQR, 0.04-1.26 ng/mL] P=.046). The increase in post-PCI cardiac biomarkers was not related to SB location (proximal to the proximal cap, within the occluded segment, or distal to the distal cap; P=.33 for change in CK-MB and P=.20 for change in troponin by SB location).
The incidence of periprocedural MI was higher among the SB loss cases (32% vs 12% [P=.03] when MI was defined as CK-MB ≥3x ULN and 86% vs 61% [P=.02] when MI was defined as troponin ≥5x ULN or >20% above baseline level). However, when the SCAI periprocedural MI definition (CK-MB increase ≥10x ULN)9 was used, the incidence of periprocedural MI was low and similar in the two groups (11% vs 5%; P=.39).
Follow-up. During a median follow-up of 11.3 months (IQR, 6.7-19.1 months), MACE (death, acute coronary syndrome, and repeat revascularization with PCI or CABG) occurred in 40 of 109 patients (36.7%). MACE-free survival was similar among patients with and without SB loss (74.4% vs 60.7%, respectively, at 12 months and 53.5% vs 54.1%, respectively, at 24 months; P=.67). Four deaths occurred in the SB loss group; 2 were cardiac and 2 were non-cardiac (due to infection and malignancy). Two deaths occurred in the no SB loss group; both were non-cardiac (due to infection). At 12 months, the SB loss group had a higher incidence of all-cause death (17.3% vs 2.8%; P=.02) and cardiovascular death (7.4% vs 0%; P=.02) (Figure 4).
Repeat revascularization was performed in 22 of 109 patients (20.2%), with 81.8% representing target-lesion revascularization (TLR), which was performed in approximately two-thirds of patients with balloon angioplasty and in one-third of patients with stenting. TLR occurred predominantly (in 68% of patients) during elective surveillance/follow-up catheterization.
Non-target vessel revascularization was performed for 1 patient with non-ST segment elevation MI, 2 patients for staged complete revascularization, and 1 patient with angina and significant obstructive disease detected in non-CTO vessels during surveillance catheterization.
Predictors of side-branch loss. In univariate logistic regression analysis, the use of dissection/reentry strategy, procedure time, and stenting over a side branch were associated with higher incidence of SB loss, whereas J-CTO score, CTO occlusion length, SB at the proximal cap, and intravascular ultrasound to assist during crossing were not (Table 2). On multivariable analysis, the number of stents and stenting over a SB were independently associated with SB loss (Table 2).
Discussion
The main findings of our study are that SB loss occurs in approximately one-quarter of CTO-PCIs, is associated with the use of dissection/reentry techniques and stenting over the SB, and has adverse clinical consequences (higher incidence of periprocedural MI and survival). Salvage of an occluded SB was infrequently attempted and was successful in only one-half of the attempted cases.
Frequency. In a single-center prospective CTO-PCI registry study from China, 47% of patients had bifurcating lesions (n = 254; 134 proximal and 120 distal). A two-stent technique was more likely to be utilized for proximal bifurcating lesions (24.6% vs 6.7%; P<.001). However, there was no difference in MACE rate at 1 year. SB closure occurred in 5.2% of the proximal group and 18.3% of the distal group and was associated with increased rate of periprocedural MI.6 In another study from Italy, bifurcating lesions were found in 26.5% (n = 244; 11.5% proximal, 43.4% within, 45.1% distal) of CTO-PCIs and were associated with lower technical success rate, higher contrast use, longer procedure time, higher number of stents, and more frequent coronary perforation with tamponade.7 In our study, the frequency of SB loss was 25.7%, demonstrating remarkable consistency between different populations and centers.
Mechanisms. The main causes underlying SB loss during CTO-PCI were use of dissection/reentry techniques and stenting over the SB. Side-branch loss is a recognized complication of dissection/reentry techniques; stenting the subintimal space commonly results in SB occlusion. Use of extensive dissection/reentry techniques, such as the subintimal tracking and reentry (STAR) technique, have been associated with high rates of restenosis and reocclusion, likely in part due to decreased outflow from SB loss, although more favorable results have been observed using limited dissection/reentry strategies.10-13 Therefore, limiting the extent of dissection (for example by using dedicated reentry devices, such as the Stingray balloon and guidewire or using the Guideliner reverse controlled antegrade and retrograde tracking and dissection (Guideliner reverse CART) technique,14 is highly desirable.
Stenting over SBs can also lead to occlusion, especially in heavily diseased vessels. Use of two-stent bifurcation strategies may be desirable for preserving SBs, especially in the setting of CTO lesions, where dissections are common even when true to true lumen guidewire advancement is achieved.15 Wiring of the SB before stenting could help minimize the risk of occlusion and could be facilitated by use of a dual-lumen microcatheter, such as the Twin Pass (Vascular Solutions) in the United States or the Crusade (Kaneka) in Japan. Occasionally, use of the retrograde technique may be required (if technically feasible) to preserve the compromised branch of a bifurcation.16 Alternatively, subintimal crossing into the SB can be performed, followed by reentry into the true lumen.17
Careful study of the coronary angiogram before CTO-PCI is critical for identifying the presence and location of SBs, devising a plan to preserve (or restore) flow into those branches, and to serve as the reference point for comparison with the post-PCI angiogram.18
Consequences. Our study suggests that SB occlusion during CTO-PCI is not inconsequential; it was associated with higher incidence or periprocedural MI and with higher risk for adverse clinical events during follow-up.
We recently demonstrated that periprocedural MI is more common with retrograde as compared with antegrade CTO crossing techniques (13.8% vs 6.7%, respectively; P=.04) and was associated with higher risk of adverse clinical events during a median follow-up of 2.3 years.5 Therefore, the higher incidence of periprocedural MI associated with SB loss could also in part account for the higher mortality observed during follow-up, likely due to myocardial cell loss. Choi et al recently demonstrated delayed hyper-enhancement in 86% of patients with CTOs;19 hence, additional myocardial damage due to SB loss could further jeopardize the likelihood for myocardial recovery. Another potential mechanism leading to worse outcomes is decreased outflow, which could result in higher risk for restenosis and reocclusion of the recanalized vessel.
Study limitations. Our study has important limitations. First, it was a retrospective, single-center study that included a relatively small number of patients; however, it did have enough power to detect significant differences in the short-term and long-term outcomes after CTO-PCI. Second, clinical outcomes were not adjudicated by an independent clinical events committee; however, post-PCI cardiac biomarker measurement was performed in all patients, and mortality is a hard endpoint that is unlikely to be affected by adjudication. Third, our cases were performed by experienced CTO-PCI operators and may not be generalizable to PCI settings with less experience in CTO-PCI. Fourth, repeat revascularization rates may have been increased because of participation in some studies that required follow-up surveillance angiography.
Conclusion
SB loss occurred in approximately 1 in 4 CTO-PCIs, was associated with use of subintimal dissection/reentry techniques and with stenting over the SB ostium, and was associated with higher risk for periprocedural MI and lower survival. Strategies to prevent and treat SB occlusion could significantly improve the short-term and long-term outcomes of CTO-PCI.
References
1. Louvard Y, Lefèvre T, Morice MC. Percutaneous coronary intervention for bifurcation coronary disease. Heart. 2004;90:713-722.
2. Routledge HC, Morice MC, Lefèvre T, et al. 2-year outcome of patients treated for bifurcation coronary disease with provisional side branch T-stenting using drug-eluting stents. JACC Cardiovasc Interv. 2008;1:358-365.
3. Steigen TK, Maeng M, Wiseth R, et al. Randomized study on simple versus complex stenting of coronary artery bifurcation lesions: the Nordic bifurcation study. Circulation. 2006;114:1955-1961.
4. Paizis I, Manginas A, Voudris V, Pavlides G, Spargias K, Cokkinos DV. Percutaneous coronary intervention for chronic total occlusions: the role of side-branch obstruction. EuroIntervention. 2009;4:600-606.
5. Lo N, Michael TT, Moin D, et al. Periprocedural myocardial injury in chronic total occlusion percutaneous interventions: a systematic cardiac biomarker evaluation study. JACC Cardiovasc Interv. 2014;7:47-54.
6. Chen SL, Ye F, Zhang JJ, et al. Clinical outcomes after recanalization of a chronic total occluded vessel with bifurcation lesions: results from single-center, prospective, chronic total occlusion registry study. Chinese Med J. 2012;125:1035-1040.
7. Galassi AR, Boukhris M, Tomasello SD, et al. Incidence, treatment, and in-hospital outcome of bifurcation lesions in patients undergoing percutaneous coronary interventions for chronic total occlusions. Coron Artery Dis. 2015;26:142-149.
8. Morino Y, Abe M, Morimoto T, et al. Predicting successful guidewire crossing through chronic total occlusion of native coronary lesions within 30 minutes: the J-CTO (Multicenter CTO Registry in Japan) score as a difficulty grading and time assessment tool. JACC Cardiovasc Interv. 2011;4:213-221.
9. Moussa ID, Klein LW, Shah B, et al. Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI). J Am Coll Cardiol. 2013;62:1563-1570.
10. Mogabgab O, Patel VG, Michael TT, et al. Long-term outcomes with use of the CrossBoss and stingray coronary CTO crossing and re-entry devices. J Invasive Cardiol. 2013;25:579-585.
11. Rinfret S, Ribeiro HB, Nguyen CM, Nombela-Franco L, Urena M, Rodes-Cabau J. Dissection and reentry techniques and longer-term outcomes following successful percutaneous coronary intervention of chronic total occlusion. Am J Cardiol. 2014;114:1354-1360.
12. Michael TT, Papayannis AC, Banerjee S, Brilakis ES. Subintimal dissection/reentry strategies in coronary chronic total occlusion interventions. Circ Cardiovasc Interv. 2012;5:729-738.
13. Wosik J, Shorrock D, Christopoulos G, et al. Systematic review of the BridgePoint system for crossing coronary and peripheral chronic total occlusions. J Invasive Cardiol. 2015;27:269-276.
14. Vo M, Brilakis ES. Faster, easier, safer: “GuideLiner reverse CART” for retrograde chronic total occlusion interventions. Catheter Cardiovasc Interv. 2014;83:933-935.
15. Muhammad KI, Lombardi WL, Christofferson R, Whitlow PL. Subintimal guidewire tracking during successful percutaneous therapy for chronic coronary total occlusions: insights from an intravascular ultrasound analysis. Catheter Cardiovasc Interv. 2012;79:43-48.
16. Kotsia A, Christopoulos G, Brilakis ES. Use of the retrograde approach for preserving the distal bifurcation after antegrade crossing of a right coronary artery chronic total occlusion. J Invasive Cardiol. 2014;26:E48-E49.
17. Al Aloul B, Guigari P, Nicholas Burke M. “Head-to-toe” kissing balloon angioplasty during PCI of right coronary artery chronic total occlusion. Catheter Cardiovasc Interv. 2013;82:E672-E675.
18. Brilakis ES. Manual of Coronary Chronic Total Occlusion Interventions. A Step-by-Step Approach. Waltham, MA: Elsevier; 2013.
19. Choi JH, Chang SA, Choi JO, et al. Frequency of myocardial infarction and its relationship to angiographic collateral flow in territories supplied by chronically occluded coronary arteries. Circulation. 2013;127:703-709.
_____________________________________________
From the VA North Texas Health Care System, Dallas, Texas and University of Texas Southwestern Medical School, Dallas, Texas.
Funding: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kumbhani reports consultant/speaker honoraria from the American College of Cardiology. Dr Addo reports consultant/speaker honoraria from AstraZeneca, Merck, the Medicines Company and Medicure. Dr Banerjee reports research grants from Boston Scientific and Merck; consultant/speaker honoraria from Medtronic; ownership in MDCare Global (spouse); intellectual property in HygeiaTel. Dr Brilakis reports consulting/speaker honoraria from Abbott Vascular, Asahi Intecc, Boston Scientific, Elsevier, Somahlution, St. Jude Medical, and Terumo Corporation; research support from Boston Scientific and InfraRedx; spouse is employee of Medtronic. The remaining authors report no disclosures regarding the content herein.
Manuscript submitted August 5, 2015, provisional acceptance given September 14, 2015, final version accepted November 2, 2015.
Address for correspondence: Emmanouil S. Brilakis, MD, PhD, VA North Texas Health Care System, The University of Texas Southwestern Medical Center at Dallas, Division of Cardiology (111A), 4500 S. Lancaster Rd, Dallas, TX 75216. Email: esbrilakis@gmail.com
