The success rate of recanalization of coronary chronic total occlusion (CTO) has improved in recent years, but the clinical benefit associated with successful CTO recanalization in the drug-eluting stent (DES) era is not well known. A cohort of 317 consecutive patients (mean age 65 ± 10, 84% men) with CTOs (defined as Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 and duration >3 months) of native coronary vessels in which percutaneous coronary intervention was attempted was enrolled from June 2005 to March 2009. All successful procedures (196 patients) were performed by DES implantation. The incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and repeat revascularization) was assessed during a mean follow-up period of 3 years. MACE predictors were assessed in clinical, angiographic, and procedural data, including procedural success. Patients with successful percutaneous coronary intervention experienced a significantly lower MACE rate compared to those with failed procedures (17 [9%] vs 32 [26%], p = 0.008). Patients with multivessel disease experienced MACEs more frequently than those with single-vessel disease (45 [22%] vs 4 [4%], p = 0.002). On multiple Cox regression analysis, the presence of multivessel disease and CTO opening failure were independent predictors of MACEs (hazard ratio 2.31, 95% confidence interval 1.17 to 4.96, p = 0.01, and hazard ratio 1.81, 95% confidence interval 1.33 to 4.12, p = 0.02, respectively). The worst prognosis was confined to patients with multivessel disease and failed procedures (hazard ratio 2.73, 95% confidence interval 1.21 to 3.92, p = 0.03). In conclusion, successful recanalization of CTOs with DES translates into a reduction of the 3-year MACE rate compared to failed procedures, and the worst prognosis is observed in patients with failed procedures and multivessel disease, a notion that might be taken into account in the management of patients with coronary CTOs.
Percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) is characterized by low primary success and high restenosis rates despite remarkable advances in procedural techniques in the past 25 years. The introduction of dedicated guidewires and the development of new techniques have improved the success rate in crossing CTO lesions. Furthermore, the use of bare-metal stents has reduced the risk for abrupt closure and restenosis compared to balloon angioplasty. The introduction of drug-eluting stents (DES) has further reduced the occurrence of restenosis and the need for repeat revascularization, especially target lesion revascularization, during short-term, mid-term, and long-term follow-up. However, the clinical benefit of CTO recanalization is still a matter of debate, as previous studies have provided conflicting results, and data regarding the clinical benefit associated with successful CTO recanalization in the DES era are few. In this study, we aimed to compare the outcome of successful PCI with DES implantation versus failed procedures in consecutive patients presenting with CTO and to identify subgroups that may benefit most from successful recanalization.
Methods
From June 2005 to March 2009, 317 consecutive patients who underwent PCI for 1 CTO of a native coronary vessel at 2 high-volume centers in Rome, Italy, were included in this study. CTO was defined as a coronary obstruction with Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 and an estimated duration of >3 months. The duration of the occlusion was determined by the interval from the last episode of acute coronary syndromes or, in patients without histories of acute coronary syndromes, from the first episode of effort angina consistent with the location of the occlusion or by previous coronary angiography. In patients without histories of angina who were admitted for acute coronary syndromes or ST-segment elevation acute myocardial infarctions with definite identification of the culprit vessel, associated total occlusion of a nonculprit vessel was considered a chronic occlusion if there was angiographic evidence of filling the vessel through collaterals. The indication for the percutaneous treatment of CTO was the demonstration of viable or ischemic myocardium in the territory of the occluded vessel by echographic or scintigraphic provocative tests in patients with multivessel disease, while the indication for the percutaneous treatment of CTO in patients with single-vessel disease was angina with evidence of inducible ischemia due to CTO. Patients with stent occlusions (n = 71), CTO of a venous graft (n = 54), or >1 CTO PCI attempt were excluded (n = 37), as were patients with failed CTO PCI who underwent in-hospital coronary artery bypass grafting (CABG; n = 54). No CTO angiographic characteristic was considered an absolute contraindication to PCI attempt. Moreover, patients lost to follow-up were excluded (n = 24).
In all patients, cardiovascular risk factors were obtained, including history of acute myocardial infarction, previous CABG, diabetes (fasting blood glucose >126 mg/dl or treated diabetes), dyslipidemia (low-density lipoprotein >130 mg/dl, high-density lipoprotein <45 mg/dl, triglycerides >150 mg/dl, or total cholesterol >200 mg/dl), smoking (current regular use [any amount] or cigarette withdrawal <2 months), and hypertension (systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg or treated hypertension).
All procedures were performed using the femoral or radial approach. The radial approach was used in 178 patients (57%) and the femoral approach in 136 patients (43%). Intravenous heparin was given at the start of the procedure to maintain an activated clotting time of 220 to 300 seconds. The choice of guidewires, balloons, and DES type was left to the discretion of the operators. Successful PCI was defined as final TIMI flow grade 3 and a visual residual stenosis <10% after stent implantation. All successful procedures were performed using the standard anterograde approach and with the implantation of first-generation DES (sirolimus- or paclitaxel-eluting stents). Additionally, PCI of non-CTO lesions was performed after attempting CTO recanalization in all patients showing coronary multivessel disease during the index procedure.
All patients received aspirin and clopidogrel (600 mg) ≥2 hours before the procedure. After PCI, lifelong aspirin was prescribed, along with clopidogrel for 12 months. The mean follow-up duration was 1,122 ± 133 days. The primary end point of the study was the incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, myocardial infarction, and repeat revascularization. Cardiac death was ascertained by contacting the family or the hospital where the patients died. Myocardial infarction was defined as a more than threefold elevation of creatine kinase levels above the upper normal limit associated with typical chest pain. Repeat revascularization was defined as repeat PCI or CABG because of stent failure on a CTO or a stenosis treated during the index admission. Among repeat PCI, repeat revascularization included repeat PCI of CTO lesions or non-CTO lesions in the group of patients who underwent successful CTO PCI and repeat PCI of non-CTO lesions in the group with failed CTO PCI. Of note, PCI of non-CTO lesions performed before discharge was not considered a MACE, while repeat PCI, as previously defined, or CABG, after discharge, in the patients with failed CTO PCI or successful CTO PCI, were included in our MACE analysis.
Postdischarge follow-up was obtained by telephone contact with patients or with their physicians. All adverse events were confirmed by reviewing the medical records of the patients. All patients gave informed consent, and the study was approved by the ethics committee of the university.
Two expert angiographers (F.B. and F.D.F.), unaware of clinical follow-up, evaluated angiographic images and assessed the culprit vessel, the CTO vessel segment (proximal vs nonproximal), the number of diseased vessels (with multivessel disease defined as ≥2-vessel disease), and stent number.
Continuous variables are expressed as mean ± SD and categorical variables as proportions. Continuous variables were compared using Student’s t test or the Mann-Whitney U test as appropriate, whereas categorical variables were compared using Fisher’s exact test. Survival duration was measured from the date of discharge to the occurrence of a MACE or to the date of last known follow-up evaluation. No patient experienced repeated events at different times of follow-up. As primary analysis, we performed a simple Cox regression analysis using all variables on their original continuous scale to estimate the unadjusted hazard ratios (HRs) of all variables. We also calculated the 95% confidence interval (CI) of the coefficient of the Cox regression. Because the number of MACEs was 49 in our population and the number of variables for inclusion in a multiple Cox regression analysis should be 49/10 ≈ 5, we performed a multiple Cox regression analysis including the following variables: failure of CTO PCI, multivessel disease, PCI revascularization of non-CTO vessels, and left anterior descending coronary artery as the location of the culprit lesion, along with the presence of diabetes mellitus and a left ventricular ejection fraction <40%, which are known to affect prognosis. Cumulative survival analyses were performed using the Kaplan-Meier method, and the difference between curves according to variables of interest was assessed using the log-rank test. A landmark analysis (with the landmark set at 1 year from study entry) was also performed. Stratified HRs for MACEs and cardiac death were calculated with success or failure as the independent variable and single-vessel or multivessel disease as strata, and a p value for interaction was reported. A p value <0.05 was considered statistically significant. All analyses were conducted using SPSS version 17.0 (SPSS, Inc., Chicago, Illinois) and Stata version 10.1 (StataCorp LP, College Station, Texas).
Results
The study included 317 patients (mean age 65 ± 10 years, 84% men); 196 patients (62%) underwent successful CTO PCI, while in the remaining 121 (38%), failed CTO PCI was reported. The baseline clinical and angiographic characteristics according to successful or failed CTO PCI are listed in Table 1 , along with procedural data in successful CTO PCI patients. Of note, 53% of the overall population underwent PCI of non-CTO lesions, with similar rates between patients with successful and failed CTO PCI (p = 0.34). With regard to PCI of non-CTO lesions, DES were used in 123 patients (73%), of whom 70 (57%) were in the successful CTO PCI group and 53 (43%) were in the failed CTO PCI group (p = 0.18).
| Variable | Failure (n = 121) | Success (n = 196) | p Value |
|---|---|---|---|
| Age (years) | 66 ± 10 | 64 ± 11 | 0.79 |
| Man | 107 (88%) | 160 (82%) | 0.12 |
| Hypertension | 80 (66%) | 137 (70%) | 0.53 |
| Diabetes mellitus | 45 (37%) | 66 (34%) | 0.55 |
| Dyslipidemia | 57 (47%) | 105 (54%) | 0.29 |
| Smoker | 37 (31%) | 83 (42%) | 0.27 |
| Previous acute myocardial infarction | 31 (26%) | 63 (32%) | 0.25 |
| Previous CABG | 12 (10%) | 30 (15%) | 0.23 |
| Ejection fraction <40% | 19 (16%) | 24 (12%) | 0.40 |
| DES type | |||
| Sirolimus-eluting stent | 117 (60%) | ||
| Paclitaxel-eluting stent | 79 (40%) | ||
| Left anterior descending coronary artery | 69 (57%) | 69 (35%) | 0.001 |
| Multivessel coronary disease | 95 (78%) | 113 (58%) | 0.02 |
| Proximal vessel segment | 70 (58%) | 106 (54%) | 0.56 |
| Stent number | |||
| 1 | 66 (34%) | ||
| 2 | 78 (40%) | ||
| 3 | 35 (18%) | ||
| 4 | 14 (7%) | ||
| 5 | 3 (1%) |
Clinical outcomes at 3-year follow-up according to successful and failed CTO PCI are reported in Table 2 . In patients with failed CTO PCI, the risk for MACEs did not differ according to the presence of diabetes mellitus (p = 0.99), an ejection fraction <40% (p = 0.78), left anterior descending coronary artery as the culprit vessel (p = 0.68), or proximal vessel location (p = 0.68).
| Variable | Failure (n = 121) | Success (n = 196) | p Value |
|---|---|---|---|
| Follow-up (days) | 1,196 ± 124 | 1,165 ± 118 | 0.81 |
| MACEs | 32 (26%) | 17 (9%) | 0.008 |
| Cardiac death | 10 (8%) | 5 (3%) | 0.11 |
| Myocardial infarction | 5 (4%) | 2 (1%) | 0.24 |
| Cardiac death/myocardial infarction | 15 (12%) | 7 (4%) | 0.08 |
| Repeat revascularization | 17 (14%) | 10 (5%) | 0.07 |
| PCI | 5 (4%) | 7 (4%) | 0.77 |
| CABG | 12 (10%) | 3 (1%) | 0.07 |
Patients with failed CTO PCI more frequently experienced MACEs compared to those with successful CTO PCI (26% vs 9%, p = 0.008). Of note, 1 cardiac death was due to probable stent thrombosis of a CTO lesion that occurred 2 days after stent deployment, while 1 myocardial infarction was due to definite late stent thrombosis of a non-CTO lesion of a patient with failed CTO PCI, defined according to the Academic Research Consortium classification.
Patients with multivessel disease more frequently experienced MACEs compared to those with single-vessel disease (22% vs 4%, p = 0.002). In particular, 20 of 45 MACEs in patients with multivessel disease were due to cardiac death or myocardial infarction (14 cardiac deaths and 6 myocardial infarctions), with more than half (11 of 20) due to non-CTO lesion–driven events; furthermore, 25 of 45 MACEs were due to repeat revascularization, with 15 non-CTO lesion–driven events, causing CABG at follow-up in 9 patients (60%).
Univariate Cox regression analysis is listed in Table 3 . On multiple Cox regression analysis, the presence of multivessel coronary disease and the failure of recanalization of CTOs were independent predictors of MACEs (HR 2.31, 95% CI 1.17 to 4.96, p = 0.01, and HR 1.81, 95% CI 1.33 to 4.12, p = 0.02, respectively). Kaplan-Meier curves of MACE-free survival in patients with single-vessel or multivessel disease and failed or successful CTO PCI are reported in Figure 1 . The Kaplan-Meier curve for MACE-free survival was significantly higher in patients with successful CTO PCI compared to patients with failed CTO PCI (log-rank p = 0.002). Moreover, the Kaplan-Meier curve for MACE-free survival was significantly higher in patients with single-vessel disease compared to those with multivessel disease (log-rank p = 0.03). Table 4 lists HRs for MACEs and cardiac death according to procedural success or failure stratified for number of diseased vessels. Finally, a landmark analysis, starting 1 year after the index procedure, confirmed lower MACE-free survival in patients with failed CTO PCI and in those with multivessel disease (p = 0.001 and p = 0.02, respectively, Figure 2 ). Interestingly, among the 15 CABG procedures occurring at follow-up, 13 occurred after 1 year and were driven mainly by disease progression in non-CTO vessels causing ischemic symptoms (n = 9 patients), while 2 patients experienced acute coronary syndromes due to restenosis of the stent previously implanted for CTO treatment, and 2 patients were referred for CABG because of significant ischemia detected on stress testing in the absence of symptom recurrence (1 patient with CTO restenosis and 1 patient with disease progression in non-CTO segments).
| Variable | HR | 95% CI | p Value |
|---|---|---|---|
| Age | 1.04 | 0.96–1.04 | 0.85 |
| Male gender | 1.20 | 0.39–3.61 | 0.74 |
| Hypertension | 1.18 | 0.55–2.52 | 0.67 |
| Diabetes mellitus | 0.87 | 0.37–2.01 | 0.74 |
| Dyslipidemia | 0.95 | 0.51–1.81 | 0.89 |
| Smoking | 0.93 | 0.31–2.79 | 0.90 |
| Previous CABG | 1.17 | 0.51–2.63 | 0.71 |
| Ejection fraction <40% | 1.20 | 0.43–3.36 | 0.72 |
| Failed CTO PCI | 2.89 | 1.24–4.87 | 0.01 |
| DES type | 1.12 | 0.65–2.12 | 0.98 |
| Left anterior descending coronary artery | 0.52 | 0.31–1.03 | 0.55 |
| Proximal vessel segment | 1.56 | 0.98–1.67 | 0.28 |
| Multivessel coronary disease | 2.14 | 1.12–3.41 | 0.03 |
| Stent number | 0.99 | 0.40–2.44 | 0.99 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
