Contrast Utilization During Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry

Abstract: Background. Administration of a large amount of contrast volume during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) may lead to contrast-induced nephropathy. Methods. We examined the association of clinical, angiographic and procedural variables with contrast volume administered during 1330 CTO-PCI procedures performed at 12 experienced United States centers. Results. Technical and procedural success was 90% and 88%, respectively, and mean contrast volume was 289 ± 138 mL. Approximately 33% of patients received >320 mL of contrast (high contrast utilization group). On univariable analysis, male gender (P=.01), smoking (P=.01), prior coronary artery bypass graft surgery (P=.04), moderate or severe calcification (P=.01), moderate or severe tortuosity (P=.04), proximal cap ambiguity (P=.01), distal cap at a bifurcation (P<.001), side branch at the proximal cap (P<.001), blunt/no stump (P=.01), occlusion length (P<.001), higher J-CTO score (P=.02), use of antegrade dissection and reentry or retrograde approach (P<.001), ad hoc CTO-PCI (P=.04), dual arterial access (P<.001), and 8 Fr guide catheters (P<.001) were associated with higher contrast volume; conversely, diabetes mellitus (P=.01) and in-stent restenosis (P=.01) were associated with lower contrast volume. On multivariable analysis, moderate/severe calcification (P=.04), distal cap at a bifurcation (P<.001), ad hoc CTO-PCI (P<.001), dual arterial access (P=.01), 8 Fr guide catheters (P=.02), and use of antegrade dissection/reentry or the retrograde approach (P<.001) were independently associated with higher contrast use, whereas diabetes (P=.02), larger target vessel diameter (P=.03), and presence of “interventional” collaterals (P<.001) were associated with lower contrast utilization. Conclusions. Several baseline clinical, angiographic, and procedural characteristics are associated with higher contrast volume administration during CTO-PCI. 

J INVASIVE CARDIOL 2016;28(7):288-294

Key words: percutaneous coronary intervention, chronic total occlusion, contrast volume, radiation, complications, air kerma, fluoroscopy

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can be challenging,¹ often leading to large radiation dose^2,3 and contrast volume administration,⁴ placing the patients at risk for radiation-related injury and contrast-induced nephropathy (CIN).^5-9 An analysis from the National Cardiovascular Data Registry (NCDR) showed that CTO-PCI was associated with significantly more contrast volume as compared with non-CTO PCI.¹⁰

Better understanding of parameters associated with higher contrast volume during CTO-PCI could facilitate procedural planning and possibly assist with selection of the mode of revascularization. We examined a large contemporary multicenter CTO-PCI registry to identify parameters associated with high contrast utilization.

Methods

Patient population. We examined demographic, clinical, and procedural data, including contrast volume among 1330 consecutive patients who underwent CTO-PCI between May 2012 and January 2016 at 12 high-volume United States centers: Appleton Cardiology, Appleton, Wisconsin; Columbia University Hospital, New York, New York; Henry Ford Hospital, Detroit, Michigan; Loveland Medical Center of the Rockies, Rockville, Colorado; Massachusetts General Hospital, Boston, Massachusetts; Minneapolis VA Medical Center, Minneapolis, Minnesota; St. Luke’s Health System’s Mid-America Heart Institute, Kansas City, Missouri; PeaceHealth St. Joseph Medical Center, Bellingham, Washington; Piedmont Heart Institute, Atlanta, Georgia; Torrance Memorial Medical Center, Torrance, California; VA San Diego Healthcare System and University of California San Diego, San Diego, California; and VA North Texas Healthcare System, Dallas, Texas. All procedures were performed by operators with expertise in CTO-PCI using a hybrid approach.¹¹ Data collection was performed both prospectively and retrospectively and recorded in a dedicated CTO database (PROGRESS CTO, Clinicaltrials.gov identifier: NCT02061436).^12-21 The study was approved by the institutional review board of each site.

Definitions. Coronary CTOs 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 myocardial infarction in the target vessel territory, or comparison with a prior angiogram. 

Calcification was assessed by angiography as mild (spots), moderate (involving ≤50% of the reference lesion diameter), or severe (involving >50% of the reference lesion diameter). Moderate proximal vessel tortuosity was defined as the presence of at least 2 bends >70° or 1 bend >90° and severe tortuosity as 2 bends >90° or 1 bend >120° in the CTO vessel. The Japanese Chronic Total Occlusion (J-CTO) score and Progress CTO score were calculated as described by Morino et al¹ and Christopoulos et al,¹⁹ respectively. 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 major adverse cardiac event (MACE). In-hospital MACE included any of the following adverse events prior to hospital discharge: death, acute myocardial infarction, urgent repeat target-vessel revascularization with PCI or coronary artery bypass graft surgery (CABG), tamponade requiring either pericardiocentesis or surgery, and stroke. 

Statistical analysis. Clinical characteristics, angiographic measures, and in-hospital outcomes were reported using descriptive statistics. Continuous variables were presented as mean ± standard deviation and compared using analysis of variance or Kruskal Wallis test, as appropriate. Categorical data are reported as frequencies or percentages and compared using Chi². The primary endpoint of this study was contrast volume utilization. Patients were divided into three tertiles based on the volume of contrast they received. 

 We used linear regression (univariable and multivariable analysis) to examine the association of several clinical and angiographic variables with contrast volume administered during CTO-PCI (the association was quantified using beta coefficients). Only variables with P<.10 on univariable analysis were included in the multivariable model. All statistical analyses were performed using JMP 11.0 (SAS Institute). Two-sided P-values <.05 were considered statistically significant.

Results

Patient and procedural characteristics. During the study period, a total of 1330 consecutive patients underwent CTO-PCI at 12 United States institutions. The baseline demographic, clinical, and angiographic characteristics of the study population are shown in Table 1. 

Overall, 85% of the patients were men with mean age of 65 ±10 years. Forty-five percent had diabetes mellitus, 34% had prior CABG, 43% had prior myocardial infarction, and 64% had prior PCI. The most common CTO target vessel was the right coronary artery (57%), followed by the left anterior descending artery (23%), and the left circumflex (20%). Overall technical and procedural success rates were 90% and 88%, respectively. The final successful crossing approach was antegrade wire escalation in 43%, antegrade dissection/reentry in 23%, and the retrograde approach in 25% of cases. 

Contrast volume utilization. Contrast volume administration during CTO-PCI ranged from 25 mL (minimum) to 1430 mL (maximum). The mean and median contrast volumes were 289 ± 138 mL and 260 mL (interquartile range [IQR], 200-360 mL), respectively. The mean and median fluoroscopy times were 55 ± 36 minutes and 46 minutes (IQR, 27-75 minutes) and the mean and median air-kerma radiation doses were 3.99 ± 2.51 Gray and 3.44 Gray (IQR, 2.05-5.40 Gray), respectively. Patients were divided in tertiles, based on the contrast volume they received: those who received >320 mL were categorized as high contrast volume group (above 67th percentile), whereas those who received ≤220 mL were categorized as low contrast volume group (33rd percentile).

As shown in Table 2, as compared with CTO-PCIs with low contrast volume, procedures with high contrast volume were longer, required more fluoroscopy time, and had higher patient radiation dose. Baseline variables associated with high contrast volume on univariable and multivariable analyses are summarized in Table 3. On univariable analysis, male gender (P=.01), smoking (P=.01), prior CABG (P=.04), moderate or severe calcification (P=.01), moderate or severe tortuosity (P=.04), proximal cap ambiguity (P=.01), distal cap at bifurcation (P<.001), side branch at proximal cap (P<.001), blunt/no stump (P=.01), occlusion length (P<.001), higher J-CTO score (P=.02), use of the antegrade dissection and reentry or retrograde approach (P<.001), ad hoc CTO-PCI (P=.04), dual arterial access (P<.001), and 8 Fr guide catheter (P<.001) were associated with higher contrast administration. In contrast, a history of diabetes mellitus (P=.01) and in-stent restenosis (P=.01) were associated with lower contrast use. 

On multivariable analysis, the presence of moderate/severe calcification (P=.04), distal cap at bifurcation (P<.001), ad hoc CTO-PCI (P<.001), dual arterial access (P=.01), 8 Fr guide catheter (P=.02), as well as use of antegrade dissection and reentry or the retrograde approach (P<.001) were independently associated with higher contrast use, whereas diabetes (P=.02), larger target vessel diameter (P=.03), and presence of “interventional collaterals” (P<.001) were associated with lower contrast utilization (Figure 1).

Discussion

The main findings of our study are that among patients undergoing CTO-PCI at experienced centers using contemporary techniques: (1) approximately one-third received high contrast volume; and (2) contrast utilization is associated with several clinical, angiographic, and procedural variables, such as proximal cap ambiguity, distal cap at bifurcation, moderate/severe calcification, blunt stump, high J-CTO score, use of antegrade dissection and reentry or the retrograde approach, large-bore guide catheters, dual arterial access, and ad hoc PCI. 

Contrast-induced nephropathy is a common complication after PCI: it is the third most common cause of acute renal failure in patients admitted to a hospital, and has been associated with increased morbidity, mortality, and medical costs.^5-9 In a recent meta-analysis of 18,061 CTO-PCIs from 65 studies, the incidence of CIN varied from 2.4%-18.1%, with a pooled estimate rate of 3.4%.²²

The first step in CIN prevention during CTO-PCI is the identification of high-risk patients, through assessment of risk factors (especially such as preexisting renal disease and diabetes mellitus, as also shown by our study) and calculation of a risk score, such as the Mehran score.²³ In high-risk patients, intravenous periprocedural hydration may reduce the risk for CIN, whereas the effectiveness of pharmaceutical agents, such as furosemide, sodium bicarbonate, mannitol, sodium chloride, atrial natriuretic peptide, dopamine, endothelin-receptor antagonists, fenoldopam, ascorbic acid, or N-acetylcysteine remains controversial.^24,25

The second step for preventing CIN is to reduce contrast volume; hence, strategies to minimize contrast utilization are important.^23,26 Our study provides useful suggestions about potentially modifiable factors that could reduce contrast volume. First and foremost, avoidance of ad hoc CTO-PCI is key.²⁷ Staging CTO-PCI reduces the amount of contrast needed for the procedure. Moreover, it allows detailed explanation of the risks and benefits of the procedure to the patient and also better preparation of the operator, which can result in more efficient and more successful procedures.²⁸ Second, angiographic parameters can help estimate the likelihood of utilizing a large amount of contrast volume; distal cap at bifurcation and proximal cap ambiguity are key indicators of complexity, as they are associated with higher contrast volume, as well as a lower likelihood of procedural success.¹⁷ In contrast, interventional collaterals likely facilitate visualization of the distal CTO arterial segment and provide additional options for crossing using the retrograde approach. Similarly, treatment of in-stent restenosis CTOs was associated with lower contrast volume on univariate analysis, likely because the previously implanted stent(s) act as a marker of the vessel course, limiting the need for contrast injections.^13,28 Moderate or severe calcification is also associated with higher lesion complexity, often requiring longer procedure time and use of multiple crossing strategies to successfully recanalize the lesion, leading to high contrast utilization.¹

Third, technical parameters can affect contrast use, specifically the use of large-bore guide catheters and dual injection. However, the use of large guide catheters and dual injection are important for achieving high success rates and keeping the procedure safe. Large-bore guide catheters (usually 8 Fr) provide better support and allow simultaneous use of multiple equipment and the trapping technique for exchanges. However, at experienced sites, high procedural success can also be achieved with the use of smaller guide catheters and the radial approach.¹² Dual injection (ideally using orthogonal projections) allows determination of distal guidewire position (within the distal true lumen, the subintimal space, or outside the vessel), preventing advancement of balloons and microcatheters in case of wire exit, hence preventing large perforations and reducing the risk for tamponade.²⁹ Although use of antegrade dissection/reentry or the retrograde approach was more common in the high contrast volume group, this was likely related to CTO lesion complexity, requiring application of multiple crossing techniques during the same procedure to achieve success.^15,30 As anticipated, failed procedures required more contrast than successful ones, highlighting the intrinsic tension between the desire to successfully complete the procedure and the desire to use the smallest possible volume of contrast.

Study limitations. Our study has some limitations. The incidence of CIN was not collected in the database; hence, our analysis was focused on contrast volume; however, contrast volume is a key parameter associated with CIN risk.²⁶ Most of the patients were men, limiting extrapolation of the results to women, but the population undergoing CTO-PCI is predominantly male. All procedures were performed by experienced operators and high-volume institutions that have invested significant resources to develop expertise in CTO-PCI, and may not apply to less experienced operators and centers. Michael et al recently reported significant decrease of contrast volume (and fluoroscopy time) with growing experience in CTO-PCI.³¹ However, experienced operators are more likely to attempt more complex lesions, which could paradoxically lead to no decrease (or even increase) in contrast volume.³²

Conclusion

In summary, CTO-PCI performed at experienced United States centers can result with administration of large volume of contrast. Several clinical, angiographic, and procedural variables can facilitate the identification of patients at increased risk for CIN and allow early application of preventive measures.

Acknowledgment. The authors would like to thank all study coordinators and support staff involved in the Progress CTO registry.

Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Texas Southwestern Medical Center.³³ REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies, providing: (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for importing data from external sources.

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From the ¹VA North Texas Healthcare System and UT Southwestern Medical Center, Dallas, Texas; ²Columbia University, New York, New York; ³Henry Ford Hospital, Detroit, Michigan; ⁴Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; ⁵Torrance Memorial Medical Center, Torrance, California;  ⁶University of Washington, Seattle, Washington; ⁷Mid America Heart Institute, Kansas City, Missouri; ⁸Piedmont Heart Institute, Atlanta, Georgia; ⁹Minneapolis VA Healthcare System and University of Minnesota, Minneapolis, Minnesota; ¹⁰Medical Center of the Rockies, Loveland, Colorado; ¹¹VA San Diego Healthcare System and University of California San Diego, San Diego, California; and ¹²Boston Scientific, Natick, Massachusetts.

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 Karmpaliotis is on the speaker’s bureau for Abbott Vascular, Medtronic, and Boston Scientific. Dr Wyman discloses honoraria/consulting/speaking fees from Boston Scientific, Abbott Vascular, and Asahi Intecc. Dr Alaswad reports consulting fees from Terumo and Boston Scientific; non-financial consultancy for Abbott Laboratories. Dr Yeh has received a Career Development Award (1K23HL118138) from the National Heart, Lung, and Blood Institute; he reports personal fees from Abbott Vascular and Boston Scientific; grant from Boston Scientific. Dr Jaffer is a consultant for Boston Scientific, Siemens, and Merck; he reports receipt of non-financial research support from Abbott Vascular and a research grant from National Institutes of Health (HL-R01-108229). Dr Lombardi reports equity with Bridgepoint Medical. Dr Grantham reports speaker fees, consulting, and honoraria from Boston Scientific and Asahi Intecc; research grants from Boston Scientific, Asahi Intecc, Abbott Vascular, and Medtronic. Dr Kandzari reports research/grant support and consulting honoraria from Boston Scientific and Medtronic Cardiovascular, and research/grant support from Abbott. Dr Lembo reports speaker’s bureau participation with Medtronic; advisory board consultancy for Abbott Vascular and Medtronic. Dr Parikh reports speaker’s bureau for Medtronic, Abbott Vascular, Boston Scientific, and St. Jude Medical; advisory board for Medtronic, Abbott Vascular, and Philips. Dr Green is supported by a career development award from the National Heart Lung and Blood Institute (K23 HL121142). Dr Garcia reports consulting fees from Medtronic. Dr Thompson is an employee of Boston Scientific. Dr Banerjee reports research grants from Gilead and the Medicines Company; consultant/speaker honoraria from Covidien and Medtronic; ownership in MDCare Global (spouse); intellectual property in HygeiaTel. Dr Brilakis reports personal fees/consulting/speaker honoraria from Abbott Vascular, Asahi Intecc, Elsevier, Somahlution, GE Healthcare, Cardinal Health, and St. Jude Medical; research support from Boston Scientific and InfraRedx; spouse is employee of Medtronic. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted February 24, 2016, provisional acceptance given February 24, 2016, final version accepted March 14, 2016.

Address for correspondence: Emmanouil S. Brilakis, MD, PhD; Dallas VA Medical Center (111A); 4500 South Lancaster Road, Dallas, TX 75216. Email: esbrilakis@gmail.com