Procedural success and outcomes with increasing use of enabling strategies for chronic total occlusion intervention: an analysis of 28,050 cases from the British Cardiovascular Intervention Society

database

Tim Kinnaird1, Sean Gallagher1, James Cockburn2, Alex Sirker3, Peter Ludman4, Mark de Belder5, Elliot Smith6, Richard Anderson1, Julian Strange7, Mamas Mamas8, and David Hildick-Smith2, on behalf of the

British Cardiovascular Intervention Society and the National Institute for Cardiovascular Outcomes Research.

1Department of Cardiology, University Hospital of Wales, Cardiff, UK; 2Department of Cardiology, Sussex Cardiac Centre, Brighton and Sussex University Hospitals, Brighton, UK; 3Department of

Cardiology, University College Hospital, London, UK; 4Department of Cardiology, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK; 5Department of Cardiology, The James Cook University Hospital, Middlesbrough, UK; 6Department of Cardiology, St Bartholomew’s Hospital, London, UK; 7Department of Cardiology, Bristol Royal Infirmary, Bristol, UK; 8Keele Cardiovascular Research Group, Institute of

Applied Clinical Sciences, University of Keele, Stoke-on-Trent and Royal Stoke Hospital, UHNM, Stoke-on-Trent, UK;

Corresponding Author:Dr. Tim KinnairdConsultant Interventional CardiologistDepartment of Cardiology, University Hospital of Wales, Cardiff, UK

Email: tim.Kinnaird2@wales.nhs.uk

Phone: +44 2920 743938Fax: +44 2920 744473

Brief title: Enabling strategies and CTO procedural success

Word Count: 4342

Conflicts of interest: No conflicts of interest for any authors, no relevant relationship with industry

Abstract

Background: Enabling strategies (ES) are increasingly used during percutaneous coronary

intervention for chronic occlusive disease (CTO-PCI) enhancing procedural success. Using the British

Cardiovascular Society dataset, we examined changes in the use of ES and procedural/clinical

outcomes for CTO-PCI. Methods and Results: ES were defined as IVUS, rotational/laser atherectomy,

dual arterial access, use of micro-catheters, penetration catheters or CrossBoss, and procedures

categorised by number of ESs used. Data were analysed on all elective CTO-PCI procedures performed

in England and Wales between 2006 and 2014. Multivariable logistic regression was used to identify

predictors of procedural success. During 28,050 CTO-PCIs there were significant temporal increases in

ES use. There was a stepwise increase in CTO success with increased ES use with 83.8% of cases

successful where ≥3 ES were used. Overall CTO-PCI success rate for the whole cohort increased from

55.4% in 2006 to 66.9% in 2014 (p<0.001) but the greatest increase in procedural success was

associated with ≥3 ES use. In multivariable analysis, any ES use and the number of ES used were

predictive of procedural success. Coronary perforation increased from 1.2% with zero ES use to 4.0%

with three or more (p<0.001). After adjustment, although an arterial complication, in-hospital

bleeding, in-hospital mortality and MACCE remained more likely with ES use, 30-day mortality was not

significantly different between groups. Conclusions: ES use during CTO-PCI was associated with

significant improvements in CTO-PCI success. ES use was associated with increased procedural

complications and in-hospital MACE, but not with 30-day mortality.

Keywords: Chronic total occlusion, enabling strategy, percutaneous coronary intervention, complications, national database, procedural success

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What is Known? Previous CTO registries have shown higher procedural success rates when adopting

specialised CTO tools and techniques.

Specialised CTO centres and operators can achieve high procedural success rates.

What the Study Adds? For the first time, national trends in CTO-PCI success are presented.

Success rates are examined on a national basis, rather than CTO specialist centres and reveal that familiarity with CTO techniques, procedural volumes and experience all improve success rates.

Use of multiple CTO techniques however is associated with more procedural complications and in-hospital bleeding/MACE, and therefore operators should be practised and familiar with managing these when they occur.

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Introduction

Percutaneous coronary intervention for chronic total occlusive disease (CTO-PCI) has evolved rapidly

in recent years. As well as steps forward in the technologies available to facilitate these procedures,

operator understanding, skills and techniques have also progressed with many international registries

now reporting success rates for CTO-PCI of over 80%.1-3 These CTO registries demonstrate superiority

of a hybrid approach, utilising enabling strategies (ES) including antegrade or retrograde wire

escalation, and dissection re-entry techniques.4-7 However, a recent study of 1,301 procedures

performed at 11 US CTO centers between 2012 and 2015 demonstrated a higher rate of major

adverse cardiovascular events associated with a retrograde approach compared to an antegrade

approach (4.3% versus 1.1%, p<0.001).8 Therefore, these and other data suggests that the high

procedural success rates now achievable with complex CTO-PCI strategies might come at a clinical

cost. Additionally, there are also limited published data on a national level on CTO-PCI procedures with

respect to success rates and outcomes, where data are not restricted to CTO specialist centres. In a

previous NCDR study, it was demonstrated that CTO-PCI was infrequently undertaken and was

associated with lower procedural success and higher complication rates compared with non-CTO PCI.9

Therefore, there is uncertainty as to whether the safety and efficacy of advanced CTO strategies

demonstrated from CTO specialists working in CTO centres can be reproduced on a wider national

basis.

In a recent study of coronary perforation using data derived from the British Cardiovascular

Intervention Society (BCIS) dataset, we identified a relationship between the number of CTO enabling

strategies utilised and coronary perforation.10,11 The current analysis examines CTO-PCI practice on a

national basis and reports the association between the number of enabling strategies used and

procedural success, the acute procedural complications associated with enabling strategy use, and

the clinical outcomes of patients categorised by the number of enabling strategies used.

Methods

The data, analytic methods, and study materials will be/have been made available to other

researchers for purposes of reproducing the results or replicating the procedure.

Study participants

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We analysed data on all percutaneous coronary intervention procedures for a chronic total occlusion

(CTO-PCI) that were undertaken for patients with stable angina in England and Wales between January

1st, 2006 and December 31st, 2014.

Setting, data source, and study size

Data on CTO-PCI practice in the United Kingdom were obtained from the British Cardiovascular

Intervention Society (BCIS) dataset that records data prospectively and publishes this information in

the public domain as part of the national transparency agenda. The quality of these data has

previously been validated.12 The data collection process is overseen by The National Institute of

Cardiovascular Outcomes Research (NICOR) (http://www.ucl.ac.uk/nicor/) with high levels of case

ascertainment. In 2013, 98.6% of all PCI procedures performed in the National Health Service (NHS)

hospitals in England and Wales (www.bcis.org.uk/) were recorded on the database. The BCIS-NICOR

database contains 113 clinical, procedural and outcomes variables with approximately 80,000 new

records added each year (https://www.bcis.org.uk/resources/bcis-ccad-database-resources/datasets-

history/). The participants of the database are tracked by the Medical Research Information Services

using data from the Office of National Statistics for subsequent mortality using the patients' NHS

number (a unique identifier for any person registered within the NHS in England and Wales). Patients

were excluded if the CTO-PCI was undertaken in the setting of an acute coronary syndrome, if

information was missing on CTO enabling strategy usage or if post-procedural CTO outcome was

incomplete. Approval for the analysis was granted by both NICOR and Health and Quality

Improvement Partnership who hold the data,.

Study definitions

A CTO was defined as a complete occlusion with TIMI flow grade 0 antegrade through the affected

segment of >3 months’ duration in the opinion of the operator based on clinical features, angiographic

features, and/or previous imaging. The definition of procedural success was as used in a previous

BCIS-derived CTO-PCI study i.e. less than a <50% residual stenosis with antegrade TIMI flow grade 3

at the end of the procedure.13 The BCIS database does not further differentiate patients with a stenosis

of <50%, and therefore other previously used definitions of CTO success such as a <30% cutoff could

not be used in this study. Enabling strategies (ES) to facilitate CTO-PCI were defined as one of the

following: dual arterial access, intra-vascular ultrasound (IVUS), atherectomy (rotational or laser),

penetration catheters (recorded in the BCIS database as Tornus,Asahi Intecc, Santa Ana, California or

Gopher Gold, Vascular Solutions, Minneapolis, Minnesota), micro-catheters or CrossBoss/Stingray

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balloon. Operator volume was defined as the total individual operator CTO-PCI volume performed in

the latter three study years. Year of procedure was also included in the data collected.

The clinical outcomes examined were access site complication, transfusion, in-hospital major bleeding,

peri-procedural myocardial infarction (MI), cerebrovascular accident (CVA), in-hospital mortality, and

30-day mortality. In-hospital major adverse cardiovascular or cerebrovascular events (MACCE) were

defined as a combination of in-hospital death, stroke, or myocardial infarction. An access site

complication was defined as either a false aneurysm, hemorrhage (without hematoma), hemorrhage

with delayed discharge, retroperitoneal hematoma, arterial dissection, or any access site complication

requiring surgical repair. In-hospital major bleeding was defined as a composite of clinical tamponade

following coronary perforation, gastrointestinal bleed, intra-cerebral bleed, retroperitoneal hematoma,

blood or platelet transfusion, or an arterial access site hemorrhage.

Data analyses

Procedures were categorised into use of no, one, two or three or more ESs and patient baseline

demographics, procedural details and complications, and outcomes are presented by ES category.

Procedural success was analysed by procedure year, by number of ES used, and by procedure year for

each number of ESs used. We tested for associations between categorical variable using a Chi-

squared test, and for continuous variables we used one-way analysis of variance. Annualised changes

in ES usage and success rates were analysed using linear regression. We performed a multivariable

analysis of the predictors of procedural success using multivariable logistic regression to investigate

the influence of variables that have the potential for being included in the model. Final model

selection was done as follows: we first imputed missing data on baseline covariate using multiple

imputations with chained equation. We then ran a stepwise forward selection with a logistic regression

with p < 0.1 as entry criteria. Factors included in the model were creatinine, age, hypertension,

peripheral vascular disease, cerebrovascular disease, previous MI, previous CABG, previous PCI,

diabetes, target vessel, number of enabling strategies, year of PCI and operator CTO-PCI volume.

The clinical outcomes were initially calculated as crude rates by ES use. To correct for potential

baseline imbalances regarding the number of enabling strategies used and their association with

clinical outcomes, we used a propensity score estimation for multiple treatments using generalized

boosting. The model as set up to generate the estimates of the average treatment effect on the

population. The stopping rule for the algorithm used the absolute standardized mean difference.

Evaluation of the performance of the algorithm and weights properties were graphically assessed

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using the twang R package. Weights were then included in the logistic regression using proc survey

logistic in SAS. Factors included in the model were age, female gender, previous MI, previous CABG,

previous PCI, diabetes, ejection fraction <30%, smoking history, hypertension, peripheral vascular

disease, cerebrovascular disease, and renal failure. To check for the balance, comparisons of the

absolute standardized mean differences between the ES categories on the covariates, before and after

weighting were undertaken (Supplementary File 1). The p-values expressed for comparison between

ES use are from tests for trends. All statistical analyses were done using SAS 9.4 and R version 3.4.1.

RESULTS

Temporal changes in CTO-PCI and enabling strategy use

Of 210,432 stable angina PCI procedures performed in England and Wales between 2006-2014,

29,507 were for chronic occlusive disease. Of these, 1,457 had missing data for ES use and were

excluded leaving 28,050 CTO-PCI procedures in the final analysis (Supplementary Figure 1). The

overall numbers of CTO-PCI peaked in 2008 (n=3,402) with a decline in overall numbers and

percentage of total PCI in later study years (Figure 1, left panel). Additionally, CTO-PCI as a total of all

stable angina declined slightly during the study period (Figure 1, right panel). There were significant

increases in annualised use of IVUS, atherectomy, penetration catheters, micro-catheters,

CrossBoss/Stingray and dual access during the study period (p<0.001 for all trends, Figure 2). The

individual components of the ES categories are presented in Figure 3. There was a steady and

significant decline in CTO-PCI cases performed using no ESs with significant increases in one, two or

three or greater ESs being used (Figure 4). However, even in 2014, 32.3% of CTO-PCI cases did not

use any ESs and only 8.5% of cases used three or more.

Baseline patient demographics and procedural detail by enabling strategy use

Increasing ES use was closely associated with patient comorbidity. A history of hypertension, diabetes,

myocardial infarction, smoking, peripheral or cerebro-vascular disease, and renal disease all increased

in a step-wise manner (p<0.001 for all trends) as the number of ESs used increased (Table 1).

Additionally, previous revascularisation with either PCI or CABG (p<0.001 for both) was also

significantly more likely with increasing ES use. During PCI, the likelihood of femoral arterial access

increased progressively with ES use (p<0.001), whilst a trainee first operator decreased significantly

with ES use (Table 2). Left main and right coronary artery PCI was associated with greater ES use

(p<0.001) whilst circumflex, left anterior descending artery and graft PCI were associated with a lower

7

ES use (p<0.001). The number of stents used, stent size and length of stent increased progressively

with ES use.

Immediate procedural outcomes for CTO-PCI, operator volume and enabling strategy use

There was a negatively skewed distribution of operator volume of CTO-PCI cases with a significant

number of low volume operators, a median total operator volume over the three study years (2012-

14) of 10 cases and a mean total operator volume of 18.9 cases. Total operator volume varied from 1

to 222 cases. Higher operator CTO-PCI volumes were associated with improved procedural success

(p<0.001 for trend, Figure 5 left panel). There was a significant increase in overall CTO-PCI success

rates from 55.4% in 2006 to 66.9% in 2014 (p<0.001 for trend, Figure 5 right panel). The greater the

number of ES used, the higher the likelihood of procedural success, rising from 56.8% with zero to

83.8% with 3 or more (p<0.001 for trend, Table 3). Within each ES category, although there were

small temporal increases in CTO-PCI success for zero and one ES between 2006 and 2014 (Figure 6),

there was a very marked increase in procedural success in association with three or more ESs (60.0%

in 2009 to 88.5% in 2014, p<0.001). Procedural complications were associated with ES use, (Table 3)

with coronary perforation occurring in 1.2% of cases with zero ES use and 4.0% of cases with three or

more, and similar increases in clinical tamponade observed (p<0.001 for both). Emergency cardiac

surgery was not associated with ES use although procedural resuscitation was required more

frequently with increased ES use (0.3% for no ESs vs. 0.8% for 2 ESs, p=0.01 for trend).

The factors associated with procedural success are presented in Supplementary Table 1. In

multivariable analysis, the factors independently associated with increased CTO-PCI success were

operator CTO volume (odds ratio per case 1.004 [95% confidence intervals 1.003-1.005], p<0.001),

year of procedure (OR per year 1.092 [1.027-1.161], p=0.005), 2 vs. no ES use (OR 1.43 [1.24-1.66],

p<0.001), 3 vs. no ES use (OR 1.95, [1.55-2.45], p<0.001), 4 or more vs. no ES use (OR 4.52, [2.22-

9.20], p<0.001), left main CTO (OR 1.48, [1.13-1.94], p=0.005) and LAD CTO (OR 1.24, [1.11-1.39],

p<0.001). Increasing patient age, previous PCI, previous MI and previous CABG were all associated

with a lower likelihood of CTO-PCI success (Table 4). Figure 7 illustrates the relationship between ES

use and procedural success.

In-hospital and 30-day outcomes and enabling strategy use for CTO-PCI

Increasing crude unadjusted in-hospital adverse outcomes were associated with ES use (Table 5).

Access site complications were observed to increase in a stepwise fashion from 1.1% with zero ES use

to 2.0% with 3 or more (p<0.001 for trend) as did in-hospital major bleeding (0.6% to 1.8%

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respectively, p<0.001). There was also a stepwise increase in unadjusted in-hospital mortality

(p=0.002 for trend), in-hospital MACCE (p=0.001 for trend) and 30-day mortality (p<0.001 for trend).

There was no difference in the acute kidney injury rates between the different ES groups (p=0.439 for

trend). After adjustment to correct for significant baseline differences between the four groups,

arterial complications (p<0.001 for trend), in-hospital bleeding (p<0.001 for trend), in hospital

mortality (p=0.040 for trend), and in-hospital MACE (p=0.018 for trend) were associated with

increased ES use. At 30-days mortality was not significantly different between the four ES groups

(Table 6).

DISCUSSION

The current study is the first national PCI database analysis of CTO-PCI to study enabling strategies in

contemporary practice, and the salient findings can be summarised as follows: 1) Enabling strategies

have evolved rapidly but even in the most contemporary study year, almost a third of CTO-PCI cases

did not utilise any; 2) Use of enabling strategies was independently associated with procedural

success; 3) Operator volume was independently associated with procedural success; 4) Enabling

strategies were associated with increased acute procedural complications such as perforation and

were also associated with increased rates of in-hospital adverse events such as mortality, bleeding

and access site complications; 5) However at 30 days, use of enabling strategies was not associated

with any increase in mortality.

The evolution of enabling strategies demonstrated in this study has most likely been driven by

emerging data demonstrating superiority of a hybrid approach - utilising enabling strategies including

antegrade escalation, and dissection re-entry techniques over the established antegrade single wire

approach.1-6 Indeed from almost no use in early study years, use rose exponentially with particularly

marked increases in dual access (to facilitate distal vessel imaging and retrograde approaches) and

micro-catheter use. Concurrent with these temporal changes in strategy, the crude overall success

rates for CTO-PCI on a national basis increased significantly from 55% to 67% between 2006 and

2014. In sub-group analysis of enabling strategy use, it is interesting to note that procedural success

rates increased when no strategies were used implying that improved guidewire technology has

contributed to procedural success even in the absence of any other strategies being used.14 This may

also be driven by better case selection as knowledge and experience accumulates. However, the

greatest increases in procedural success were associated with three or more ESs supporting the

hybrid strategy as the way forward in CTO-PCI. These data are particularly impressive given the

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increasing patient complexity associated with enabling strategy use. In multivariable analysis, the

greatest odds ratios of procedural success were associated with two and three or more enabling

strategies with almost 9 in 10 procedures successful in 2014 when three of more were use. These data

support the utility of enabling strategies in facilitating procedural success, but it is also likely that

increased ES use is a marker of operator expertise and operator volume.15 Indeed, independent of

enabling strategy use, operator CTO-PCI volume was associated with procedural success. Additionally,

later procedure years were also independently associated with improved success rates for CTO-PCI.

Taken together, these data support the concept of CTO specialists within PCI centres who can accrue

greater procedural volumes and experience, and familiarize themselves with all the available enabling

strategies to optimize CTO procedural success.

The rapid increase in success rates for three or more strategies illustrates a significant learning curve,

and reiterates the importance of being familiar with the technologies and techniques available in what

is undoubtedly complex PCI. The importance of proctoring should also not be underestimated and

many United Kingdom CTO centres run a proctorship program both in their own centre and on a

visiting basis. Indeed, a UK based study demonstrated that proctoring resulted in an increase in

overall procedural success for CTO PCI, a greater increase in the more complex CTO PCI being

undertaken and an increase in total CTO PCI activity.16 One interesting finding of the current study is

lack of growth in crude PCI numbers. The lack of growth in CTO-PCI we believe represents a

maturation of CTO-PCI practice in the United Kingdom. The data in the current study demonstrates

that the “poke and hope” approach i.e. with no ES use, has declined significantly in frequency. This

suggest that operators are now more cognizant of the skills and tools needed to achieve satisfactory

CTO-PCI outcomes and are less inclined to take on a CTO without the appropriate skillset. Most large

volume UK centres now have a proper CTO MDT and a least one dedicated CTO operator. Therefore,

we believe that the lack of growth in CTO numbers represents evidence based practice, proper patient

selection and likely full informed patient consent as to the likely benefits and risk of the procedure.

The finding of small increases in-hospital mortality associated with complex CTO-PCI is important and

most likely relates to increases in coronary perforation, transfusion, access site complications and

major bleeding. An understanding of the potential risks of these complex procedures is particularly

relevant to case selection and a fully informed consenting process. Consistent with previous data,

coronary perforation was associated with enabling strategy use.10,17-21 It is perhaps not surprising in

view of techniques such as sub-intimal tracking and retrograde techniques that such a complication is

more frequent and highlights the important of CTO operators being well trained in treating predictable

10

complications during a complex procedure. The avoidance of surgical repair is clearly highly desirable,

and the utilisation of covered stents, as well as a wider appreciation of techniques such as ping-pong

guides, and embolisation coils, distal fat or thrombus embolisation to treat wire tip perforations, have

facilitated such low rates of mortality following perforation.22-24

Another contributory factor to the excess in-hospital MACE observed with increasing ES use may be

the high rates of femoral artery use and especially dual arterial access. In a previous study of access

site choice using data derived from the BCIS database, we demonstrated that although femoral artery

utilisation fell from 84.6% in 2006 to 57.9% in 2013, major bleeding (0.8 vs. 0.2%, p<0.001),

transfusion (0.4 vs. 0%, p<0.001) and 30-day death (0.6 vs. 0.1%, p=0.002) were all more frequent in

patients undergoing CTO-PCI using femoral access compared to radial access.25 Recent data from the

RECHARGE registry demonstrate the feasibility of avoiding the femoral artery for CTO-PCI with 25% of

cases undertaken radially or bi-radially with technical success being comparable between the two

access sites.26 Other data suggests lower success rates associated with radial access for complex CTO-

PCI and therefore there remains a lack of consensus as to the role of routine radial access in this

setting.27 Despite this, as experience and techniques further evolve, and ES equipment becomes

increasingly slender, increased radial artery use may in part ameliorate the adverse in-hospital

outcomes of patients treated using several enabling strategies. At 30-days, however it is reassuring to

observe that the trend for increased in-hospital mortality associated with the use of enabling

strategies was no longer evident with equivalent survival across all four groups. Additionally, it is also

relevant to consider a previous analysis of CTO-PCI derived from the BCIS database, which showed

that at 12-months, procedural success was associated with improved survival.13

A strength of this analysis is that it is the first national scale examination of enabling strategy use and

outcomes for CTO-PCI. As such, there are sufficient numbers of cases to allow not only temporal trend

analysis of overall outcomes, but also a trend analysis for the various sub-groups of ES use.

Additionally, the large numbers of procedures allow analysis of relatively infrequent events such as

coronary perforation and in-hospital death after stable angina PCI. In considering the limitations, firstly

as with any database, the robustness of the conclusions is directly related to the quality of data

entered. Although there are high levels of case ascertainment and field completion within the

database, the accuracy of field completion for individual centres cannot be validated. Secondly, we

can only provide on fields continue within the BCIS dataset. As procedure time, fluoroscopy time and

radiation dose are not recorded, we cannot provide any data on these procedural outcomes. Although

these data have previously been derived from CTO databases such as RECHARGE,28 the lack of

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information on these relevant end-points is a limitation of the present study. Additionally, the BCIS

does not record contrast volume although it is reassured to observe a similar frequencies of acute

kidney injury between the different ES groups. Thirdly, the BCIS database does not gather data on

specific CTO techniques such knuckling, retrograde or antegrade dissection re-entry, wire escalation

or use of septal or epicardial collaterals. Therefore, although we have used the ES as defined in the

current study as surrogates for these cornerstone CTO strategies, temporal changes in their use will

undoubtedly have influenced procedural success and we are unable to add their use to the modelling

of procedural success. However, this limitation does not affect the primary finding of the study i.e.

that for the first time on a national basis, we have shown temporal changes in CTO success rates,

correlating these improvement with general changes in enabling strategy use. The BCIS database not

capture detailed CTO anatomy such as proximal cap shape or ambiguity, presence of side-branches,

length of the occlusion, or the degree of vessel calcification or tortuosity. Whilst without the

anatomical data we cannot rule out the possibility that greater ES use was associated with less

complex CTOs, this seems unlikely given that the patients and procedures were more complex as ES

use increased. Conversely, it seems more plausible that if granular anatomical data were available

and adjusted for in the procedural success modelling, that even greater odds ratios of procedural

success might be observed with greater ES use. Finally, the frequencies of certain clinical outcomes

was low in part due to the exclusion of acute coronary syndrome patients. Therefore the study is

unable to robustly study some clinical events such as peri-procedural stroke and their occurrence with

variable ES use.

CONCLUSIONS

The use of enabling strategies during CTO-PCI has increased rapidly in recent years and their use is

associated with significant improvement in CTO success. Although increases in complications such as

coronary perforation, access site bleeding, and in-hospital mortality were associated with enabling

strategy use, there were no differences in adjusted mortality at 30-days.

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CONFLICTS OF INTEREST

There are no conflicts of interest for any author.

FUNDING

No funding was provided for this work.

13

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FIGURE LEGENDS

Figure 1: Annual numbers of PCI, annual numbers of CTO-PCI, and percentage of total PCI

represented by CTO-PCI in England and Wales

Figure 2: Percentage use per case of enabling strategies during CTO-PCI between 2006 and 2014.

The p-value for the testing the slope of the linear regression line is significant for all variables

(p<0.001).

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Figure 3: Plots of the individual components of the ES score. The p-value for the testing the slope of

the linear regression line is significant for all factors (p<0.001).

Figure 4: Temporal change in annual percentages of CTO enabling strategy use (zero to 3or more per

case) during CTO-PCI between 2006 and 2014 (p<0.001 for all trends).

Figure 5: Left Panel - procedural success by operator volume, p <0.0001 for trend); Right panel -

temporal change in procedural success for all CTO-PCI procedures performed between 2006 and 2014

(p<0.001 trend).

Figure 6: Temporal change in procedural success by the number of CTO enabling strategies used for

CTO-PCI procedures performed between 2006 and 2014.

Figure 7: Association between enabling strategy use and likelihood of procedural success during

CTO-PCI performed between 2006 and 2014. Odds ratios are compared to no enabling strategy use.

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