Author + information
- Received January 6, 2014
- Revision received March 12, 2014
- Accepted April 7, 2014
- Published online July 22, 2014.
- Sudhakar George, MD∗∗ (, )
- James Cockburn, MD∗,
- Tim C. Clayton, MSc†,
- Peter Ludman, MD‡,
- James Cotton, MD§,
- James Spratt, MA‖,
- Simon Redwood, MD#,
- Mark de Belder, MD¶,
- Adam de Belder, MD∗,
- Jonathan Hill, MA∗∗,
- Angela Hoye, MBChB, PhD††,
- Nick Palmer, MD‡‡,
- Sudhir Rathore, MD§§,
- Anthony Gershlick, MB BS‖‖,
- Carlo Di Mario, MD, PhD##,
- David Hildick-Smith, MD∗,
- British Cardiovascular Intervention Society and the National Institute for Cardiovascular Outcomes Research
- ∗Sussex Cardiac Centre, Brighton and Sussex University Hospitals, Brighton, United Kingdom
- †London School of Hygiene & Tropical Medicine, London, United Kingdom
- ‡University Hospital Birmingham, Birmingham, United Kingdom
- §Heart and Lung Centre, Wolverhampton, United Kingdom
- ‖Edinburgh Royal Infirmary, Edinburgh, United Kingdom
- #King’s College London BHF Centre of Excellence, NIHR Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust, Cardiovascular Division, Rayne Institute, London, United Kingdom
- ¶James Cook University Hospital, Middlesbrough, United Kingdom
- ∗∗King’s College Hospital, London, United Kingdom
- ††Hull and East Yorkshire Hospitals, Yorkshire, United Kingdom
- ‡‡Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
- §§Frimley Park Hospital and St. George’s Hospital, Surrey, United Kingdom
- ‖‖NIHR Cardiovascular Biomedical Unit, University Hospitals of Leicester, Leicester, United Kingdom
- ##NIHR Cardiovascular Biomedical Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Sudhakar George, 26 High Brow, Harborne, Birmingham B17 9EN, United Kingdom.
Background Chronic total occlusion (CTO) is common, being reported in 18% to 30% of patients undergoing coronary angiography. Percutaneous coronary intervention (PCI) is usually performed to relieve anginal symptoms, but data are emerging to suggest that there may also be a mortality benefit.
Objectives This study aimed to compare outcomes of patients with successful versus unsuccessful PCI to a CTO.
Methods We analyzed the U.K. Central Cardiac Audit Database for all CTO PCI cases carried out in England and Wales between January 1, 2005, and December 31, 2009. Vital status in September 2010 was obtained from the Medical Research Information Service.
Results A total of 13,443 patients (78.8% male) had a mean age of 63.5 years and underwent 14,439 CTO procedures. CTO PCI was successful in 10,199 cases (70.6%). During follow-up of 2.65 years (interquartile range: 1.59 to 3.83 years), successful PCI of at least 1 CTO was associated with improved survival (hazard ratio [HR]: 0.72; 95% CI: 0.62 to 0.83; p < 0.001). Complete revascularization was associated with improved survival compared with partial revascularization (HR: 0.70; 95% CI: 0.56 to 0.87; p = 0.002) or failed revascularization (HR: 0.61; 95% CI: 0.50 to 0.74; p < 0.001).
Conclusions Successful CTO PCI was associated with improved long-term survival. The improvement was greatest in patients when complete revascularization was achieved. The identity of the successfully treated occluded vessel was not associated with differences in outcome.
A chronic total occlusion (CTO) is defined as a complete coronary arterial obstruction with Thrombolysis In Myocardial Infarction (TIMI) flow grade of 0 for longer than 3 months (1). CTOs have been identified in up to 20% of all patients referred for diagnostic angiography (2). CTO procedural success rates are low at 60% to 70%, compared with non-CTO percutaneous coronary intervention (PCI) success rates of 98% (2,3). Patients with a CTO are often managed conservatively or surgically rather than with PCI (4). Successful CTO intervention is associated with symptomatic relief of angina, lower rates of subsequent myocardial infarction (MI) and coronary artery bypass graft (CABG), and survival improvement (5,6).
There is some evidence that complete revascularization by PCI is associated with a survival advantage when compared with incomplete revascularization (7). Successful CTO PCI of the left anterior descending artery (LAD) was also associated with improvement, whereas successful intervention on the left circumflex artery (LCx) or right coronary artery (RCA) was not. To address these issues, we analyzed the incidence and outcomes of CTO PCI in contemporary coronary angioplasty practice in the United Kingdom. We assessed mortality related to completeness of revascularization and to the location of the occluded vessel.
The British Cardiovascular Intervention Society (BCIS) Central Cardiac Audit Database captures details of all interventional cardiology procedures carried out in England and Wales, using a data set managed by the National Institute for Cardiovascular Outcomes Research. We carried out an analysis of all CTO interventions carried out in England and Wales between January 1, 2005, and December 31, 2009. Data on patient mortality were obtained by linking with the Office for National Statistics by the Medical Research Information Service (MRIS).
• 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.
• Procedural success was defined as <50% residual stenosis with TIMI flow grade 3 antegrade. Although procedural success is often quoted using a <30% cutoff, the BCIS database does not further differentiate patients with a <50% stenosis.
• Complete revascularization was defined as successful PCI to the target CTO and post-procedural obstruction of <50% in all major epicardial coronary arteries.
• Partial revascularization was defined as successful PCI to the target CTO but with residual obstruction of >50% in ≥1 other vessels.
• Failure was defined as failure to cross the occlusion or reduce obstruction to less than 50% in the target CTO.
The primary analysis compared outcomes according to successful versus unsuccessful intervention on the target CTO(s). Additional analysis considered differences in mortality related to completeness of revascularization. Univariate and multivariate models were developed to assess the association between success of the PCI and subsequent mortality. Candidate variables included baseline demographics and other cardiovascular risk factors. A Cox proportional hazards model was used to identify those variables that were independent predictors of mortality. For assessment of the impact of revascularization success on subsequent mortality and allowing for patients undergoing several procedures, success of revascularization was entered as a time-updated covariate. For these patients, follow-up time was split into periods ending either in a further procedure, censoring, or death. Variables were included if they were independent predictors (with p < 0.01) or confounded the relationship between success of revascularization and mortality. For the other variables included in the models, unknown values were considered as absent or in the lowest-risk category as appropriate, although a sensitivity analysis including missing values as a separate category had no impact on the results of the association between success of revascularization and mortality. For descriptive purposes, Kaplan-Meier curves were used to demonstrate survival after each separate procedure, according to success of revascularization. For these curves, follow-up was censored at the time of the subsequent PCI or, for the last procedure, the end of follow-up (or death). Other analyses also considered the associations between baseline risk factors and success of revascularization using logistic regression with generalized estimating equations to allow for repeated procedures in some patients. A further sensitivity analysis using propensity score matching was calculated using logistic regression with generalized estimating equations with success of the revascularization as the outcome (8).
During the 5-year period, 15,492 CTO procedures were performed in stable elective patients. Data on success of revascularization was unavailable for 806 procedures (5.2%); mortality data from the MRIS was unavailable for 247 patients (1.6%). There were 14,439 procedures (on 13,443 patients) with complete information on both the success of the CTO attempt and patient vital status. Of those, 12,542 patients (93.3%) had a single CTO procedure, 816 patients (6.07%) had 2 CTO procedures, 75 patients (0.56%) had 3 CTO procedures, and 10 patients (0.07%) had 4 CTO procedures.
The demographics of the 13,443 patients in the study cohort are detailed in Table 1. The average age of the patients was 63.5 years, and 78.8% were male.
Procedural success was achieved in 70.6% of procedures (n = 10,199). In these cases, 8,385 (82.2%) received a drug-eluting stent, 1,394 (13.7%) received a bare-metal stent, 398 (3.9%) had no stents, and data were missing for 22 patients (0.2%). Table 1 shows the univariate associations with CTO procedural success. After multivariate analysis, increasing age, angina, smoking status, increasing body mass index, previous CABG, peripheral vascular disease, and previous MI all were associated with failure of CTO intervention (Table 2). There were 751 deaths (5.6%) among the 13,443 patients (20.4 per 1,000 person-years of follow-up). Figure 1 shows mortality according to success or failure of the CTO procedure during a median follow-up of 2.65 years (interquartile range: 1.59 to 3.83 years).
Successful revascularization of at least 1 CTO was associated with decreased mortality (unadjusted hazard ratio [HR]: 0.67; 95% CI: 0.58 to 0.78; adjusted HR: 0.72; 95% CI, 0.62 to 0.83; p < 0.001). The results and interpretation from the propensity score matching confirmed the above results (HR: 0.66; 95% CI: 0.54 to 0.80). According to the multivariate analysis, failed revascularization, increasing age, heart failure, insulin-dependent diabetes, smoking, and renal disease were associated with increased mortality (Table 3, Fig. 2).
In 20.1% of successful procedures, there were incomplete data for the percentage stenosis of each epicardial vessel. Data were available on 11,543 procedures for completeness of revascularization, with 595 deaths. Reduced mortality was observed with increasing completeness of revascularization (trend test, p < 0.001). Mortality was lower in patients with complete revascularization of all epicardial vessels compared with those with partial revascularization (adjusted HR: 0.70; 95% CI: 0.56 to 0.87; p = 0.002) and with those with failed CTO revascularization (adjusted HR: 0.61; 95% CI: 0.50 to 0.74; p < 0.001) (Central Illustration).
Of the 14,439 procedures, single CTO PCIs were attempted in 10,957 (75.9%). Of these, 3,213 procedures (29.3%) were to the LAD (successful in 72.6%); 1,947 (17.8%) to the LCx (successful in 73.3%); and 5,446 (49.7%) to the RCA (successful in 64.0%). Compared with the RCA, revascularization was more likely to be successful in the LCx (adjusted odds ratio for failure: 0.61; 95% CI: 0.52 to 0.72; p < 0.001) or LAD (adjusted odds ratio: 0.73; 95% CI: 0.64 to 0.84; p < 0.001). There was no difference in survival between patients with occluded LAD and occluded RCA (adjusted HR: 0.99; 95% CI: 0.80 to 1.21; p = 0.91) (Fig. 3). There was a suggestion that occlusion of the LCx was associated with an increase in mortality compared with the RCA (adjusted HR: 1.25; 95% CI: 1.00 to 1.58; p = 0.052). Successfully opening a major target vessel was associated with reduced mortality after multivariable analysis (LAD: HR: 0.69; 95% CI: 0.49 to 0.97; p = 0.033; LCx: HR: 0.56; 95% CI: 0.38 to 0.82; p = 0.003; RCA: HR: 0.73; 95% CI: 0.57 to 0.95; p = 0.017). The association of success with revascularization on mortality did not differ according to the epicardial vessel treated (interaction p = 0.52) (Fig. 4).
Complications included in-hospital death (0.25%), Q-wave MI (0.42%), cerebrovascular accident (0.06%), cardiac tamponade (0.15%), coronary artery dissection (4.69%), coronary artery perforation (1.26%), ventricular fibrillation (0.31%), and emergency CABG (0.10%).
The main finding from this large prospective, observational, multicenter registry of consecutive CTO recanalizations across all U.K. PCI centers between 2005 and 2009 is the strong association between successful CTO revascularization and improved survival over a median follow-up of 2.65 years (interquartile range: 1.59 to 3.83 years). This is important because a recent large observational study found an association between successful CTO intervention and fewer cardiovascular deaths but did not demonstrate an increase in absolute survival (9). The improvement in survival remained after multivariate analysis, suggesting that it is independent of measurable confounding factors. The survival outcome of successful revascularization did not vary between the different epicardial vessels.
Increasing age, diabetes, heart failure, smoking, and renal disease were confirmed as factors associated with increased all-cause mortality, whereas increasing age, smoking history, increasing body mass index, previous CABG, peripheral vascular disease, and previous MI were found on multivariate analysis to be associated with failure of CTO revascularization. Although complication rates were low, a failed procedure is different than medical therapy, and there are currently no large randomized controlled studies that have looked at differences in clinical outcome between CTO PCI versus optimal medical management. The EuroCTO study, which will address this question, started recruiting in Europe during late 2012. Results from previous cohort studies comparing successful versus failed CTO PCIs have been inconsistent with regard to potential survival benefit (5,6,10,11).
With regard to CTO PCI procedural success, the rate in our U.K. series was 70.6%, which is consistent with data from other series (2). When reasons for failure of CTO revascularization were analyzed, factors such as severity of calcification (more frequent in older patients) and tortuosity (often extreme after the distortion of the native vessel post-CABG) may be important. Unfortunately, the BCIS data set does not contain a direct record of these factors or of other anatomic predictors, such as occlusion length and absence of a stump, and so these cannot be included as potential predictors.
Serious complications, including death, MI, cerebrovascular accident, and cardiac tamponade, were noted at low rates, consistent with previously published series.
Registries suffer from a number of limitations. This is an observational study; therefore, analyses were retrospectively performed on data entered prospectively, which could introduce potential bias. Also, the accuracy and completeness of patient characteristics, procedural techniques, and outcomes were reviewed by the PCI unit’s local audit and governance processes but were not independently assessed by external observers. Our data also do not include information on the exact medical treatment that different patients were administered following their CTO procedures. Our database does not include information on specialist CTO techniques, such as retrograde approaches. Finally and most importantly, because the groups were not randomized into treatment strategies, no formal conclusions about cause and effect can be drawn.
Although causation cannot be implied, successful intervention on a CTO was associated with improved long-term survival. This improvement was greatest in patients with complete revascularization. There is no evidence that the location of the occluded vessel was associated with differences in mortality outcomes. Patients may have much to gain from CTO PCI.
COMPETENCY IN MEDICAL KNOWLEDGE: CTO lesions are present in the coronary arteries of a substantial minority of patients undergoing cardiac catheterization. Treatment of CTO lesions is associated with lower rates of morbidity and mortality compared with interventions in nonocclusive lesions.
COMPETENCY IN INTERPERSONAL AND COMMUNICATION SKILLS: In managing patients with CTO lesions, it is important to consider and discuss all treatment options, including medical therapy, percutaneous intervention, and coronary bypass surgery.
TRANSLATIONAL OUTLOOK: The mortality benefit associated with percutaneous revascularization of CTO lesions in this registry study requires confirmation in randomized trials comparing catheter-based intervention plus medical therapy versus medical therapy alone to define the optimum strategy and identify patients who will gain the most from revascularization.
Dr. de Belder has served as a clinical proctor for Boston Scientific; and has received research grants from Abbott Vascular and Medtronic. Dr. Gershlick has received lecture fees from Medtronic, Eli Lilly/Daiichi Sankyo, and Abbott Vascular; and has served on advisory boards for Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- British Cardiovascular Intervention Society
- coronary artery bypass graft
- chronic total occlusion
- left anterior descending artery
- left circumflex artery
- myocardial infarction
- percutaneous coronary intervention
- right coronary artery
- Thrombolysis In Myocardial Infarction
- Received January 6, 2014.
- Revision received March 12, 2014.
- Accepted April 7, 2014.
- American College of Cardiology Foundation
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