Author + information
- Received February 21, 2017
- Revision received June 26, 2017
- Accepted June 29, 2017
- Published online November 6, 2017.
- Alfredo R. Galassi, MDa,b,∗ (, )
- Marouane Boukhris, MDa,c,
- Aurel Toma, MDd,
- Zied Ibn Elhadj, MDc,
- Lobna Laroussi, MDc,
- Oliver Gaemperli, MDb,
- Michael Behnes, MDe,
- Ibrahim Akin, MDe,
- Thomas F. Lüscher, MDb,
- Franz J. Neumann, MDd and
- Kambis Mashayekhi, MDd
- aDepartment of Experimental and Clinical Medicine, University of Catania, Catania, Italy
- bUniversity Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
- cCardiology Department, Abderrhamen Mami Hospital, Ariana, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
- dDivision of Cardiology and Angiology II, University Heart Center Freiburg – Bad Krozingen, Bad Krozingen, Germany
- eFirst Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
- ↵∗Address for correspondence:
Dr. Alfredo R. Galassi, Via Antonello da Messina 75, Acicastello, 95021 Catania, Italy.
Objectives The study sought to assess the outcome of percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) in patients with low left ventricular ejection fraction (LVEF) (≤35%).
Background Data regarding the outcome of PCI in patients with low LVEF affected by CTO are scarcely reported.
Methods The authors performed a prospective longitudinal multicenter study including consecutive patients undergoing elective PCI of CTOs. Patients were subdivided into 3 groups: group 1 (LVEF ≥50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF ≤35%).
Results A total of 839 patients (mean 64.6 ± 10.5 years of age, 87.7% men) underwent CTO PCI attempts. Baseline LVEF ≤35% was present in 72 (8.6%) patients. The angiographic success was high (overall 93.6%) and similar among the 3 groups (93.5% vs. 94.4% vs. 91.7%, respectively; all p = NS). In group 3, no periprocedural complications of CTO PCI were observed. Mean clinical follow-up of 16.3 ± 8.2 months duration was available in 781 (93.1%) patients including those with LVEF ≤35%. At 2 years, major cardiac and cerebrovascular events (MACCE) free survival was similar in the 3 groups (86% vs. 82.8% vs. 75.2%; all p = NS). In patients with LVEF ≤35%, LVEF improved significantly in the presence of a successful CTO PCI from 29.1 ± 3.4% to 41.6 ± 7.9% (p < 0.001).
Conclusions In CTO patients with low LVEF, PCI could represent a safe and effective revascularization strategy achieving good midterm outcome and LVEF improvement.
Coronary chronic total occlusion (CTO) represents a frequent lesion subset observed in about 15% of patients undergoing coronary angiography (1–3), with a higher prevalence in those with previous coronary artery bypass grafting (CABG) (1,4). The presence of a CTO confers a negative impact on long-term outcome in different clinical situations. Indeed, in patients experiencing an acute coronary syndrome, a coexisting CTO is associated with increased early and late mortality (5,6). Similarly, in the setting of stable multivessel coronary artery disease, CTO was the strongest independent predictor of incomplete percutaneous revascularization, and associated with adverse clinical outcomes (7–9).
On the other hand, left ventricular ejection fraction (LVEF) represents one of the strongest predictors of cardiovascular events in patients with coronary artery disease (10). Very recently, it has been shown that in patients with ischemic heart failure (LVEF ≤35%), the presence of CTO was related to worse long-term outcome (11). Although PCI might often remain the last available option to manage patients with low LVEF, outcome data of percutaneous recanalization of CTO subtending viable myocardium in this subset of patients are scarcely reported.
Accordingly, we aimed to assess the impact of LVEF on success rates and in-hospital outcome of CTO PCI, and to evaluate the midterm outcome of patients with low LVEF treated by PCI for a CTO.
We performed a prospective multicenter study including consecutive patients undergoing elective PCI of CTO at 3 European centers from January 2013 to December 2015 (Online Figure 1). All procedures were scheduled (not ad hoc PCI), and performed by experienced CTO operators. Patients were selected on the basis of the presence of symptoms, viability, and inducible ischemia (>10%) in the CTO artery territory, as demonstrated by functional imaging tests. In presence of impaired LVEF, CTO revascularization was only considered for lesions subtending viable myocardial territory judged to be of hemodynamic importance. The decision of the revascularization strategy (PCI or CABG, and lesions to be revascularized) for each patient was left to the local heart team in the participating center. In case of surgical indication rejected by the patient, PCI was proposed if considered to be feasible by the local heart team.
According to the LVEF, our study population was subdivided into 3 groups: group 1 (LVEF ≥50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF ≤35%).
The study was carried out in accordance to the Helsinki declaration; all patients provided written informed consent.
Definitions and endpoints
Coronary CTOs were defined as angiographic evidence of total occlusions with Thrombolysis In Myocardial Infarction flow grade 0 within a major epicardial coronary artery of at least 2.5 mm, and estimated durations of at least 3 months (12).
The complexity of CTO lesion and the difficulty of CTO PCI attempt were assessed according to the J-CTO (Japanese multicenter registry) score and the ORA (O = ostial, R = filling < Rentrop 2, A = age ≥75 years) score, respectively (8,13). Angiographic success was defined as final residual stenosis <30% (by visual estimation) and TIMI flow grade 3 after CTO recanalization. Clinical success was defined as an angiographic success with no periprocedural complications including cardiac death, Q-wave and non–Q-wave myocardial infarction (MI), tamponade, stroke, and need for emergency CABG. Coronary perforations were defined and described as previously shown (14). In all patients, creatine kinase-myocardial band was evaluated 6 h after the procedure and until normalization if the levels were abnormal. Non–Q-wave MI was defined as creatine kinase-myocardial band enzyme elevation >3 times the upper limit of normal (9). Tamponade was defined as an epicardial effusion requiring pericardiocentesis. Major bleeding was defined according to Acuity criteria (15).
In patients with LVEF ≤35%, the baseline SYNTAX score (bSS) and the residual SYNTAX score (rSS) (after achieving the target level of revascularization) were determined. SYNTAX Revascularization Index (SRI) was then calculated using the following formula: SRI = (bSS − rSS)/bSS × 100 (16).
At follow-up, major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of cardiac death, MI, stroke and further revascularization (CTO target vessel revascularization [TVR] or non-TVR).
Arterial access was usually established via right or left femoral arteries. The size of the guiding catheters used for the occluded artery was 7-F in the majority of cases. Dual injection was considered routinely if contralateral collaterals were present.
The sequence of use of wiring techniques, the guidewire selection and the primary CTO strategy (antegrade, retrograde, or hybrid) was completely left to the operator’s discretion, as well as the use of percutaneous mechanical circulatory support (pMCS).
Patients received an initial bolus of intravenous unfractionated heparin (100 IU/kg). The activated clotting time was monitored every 30 min to determine if an additional bolus of unfractionated heparin was necessary to maintain an activated clotting time >350 s. Upstream use of glycoprotein IIb or IIIa inhibitor therapy or bivalirudin was avoided.
In patients with LVEF ≤35%, we aimed to perform functional revascularization in 1 PCI procedure or in a staged manner during the same hospitalization, to achieve the lowest possible rSS.
Only drug-eluting stents were implanted. Antiplatelet therapy and heart failure medication (if necessary) were prescribed according to recognized standard of care (17,18).
Baseline symptoms evaluation
Dyspnea and angina were assessed according to New York Heart Association functional class and Canadian Cardiovascular Society class, respectively, before the indexed CTO procedure.
Baseline LVEF and viability assessment
A 2-dimensional echocardiogram was performed in all patients 48 to 72 h before CTO PCI attempt. LVEF was assessed by Simpson’s biplane method. In presence of normal wall motion or hypokinesia in the territory subtended by the CTO artery, no further viability testing was performed, whereas in patients with akinesia or dyskinesia in CTO territory, assessment of viability was performed by myocardial scintigraphy or magnetic resonance imaging (19).
Clinical follow-up was obtained either by a clinical visit or by a telephone interview. Details regarding MACCE occurrence were additionally collected by the physicians through the revision of clinical source documentation. Symptoms (angina and dyspnea) were reassessed at 6 months.
In patients with LVEF ≤35% who underwent successful CTO PCI, LVEF was assessed at 6 months. In this latter subset of patients, repeat angiography was scheduled between 8 and 12 months, unless previously clinically indicated. Reocclusion was defined as a TIMI flow grade 0 to 1 in the target CTO vessel, whereas restenosis was defined as >50% luminal narrowing at the segment site including the stent and 5 mm proximal and distal to the stent edges.
Continuous variables were presented as mean ± SD, and were compared using the unpaired Student t test. Categorical variables were presented as counts and percentage and compared using the chi-square test when appropriate (expected frequency >5); otherwise, the Fisher exact test was used. The predictors of the angiographic success were identified using a logistic regression. All clinical and angiographic characteristics were tested. All univariate variables with a p < 0.10 were included in a statistical model to detect the independent predictors using multivariate regression analysis with the Wald method.
MACCE-free survival during follow-up was evaluated according to the Kaplan-Meier method and compared between successful and failed CTO PCI using the log-rank test. Univariate Cox regression was used to assess the impact of pMCS use and that of SRI ≥70% on MACCE occurrence in CTO patients with LVEF ≤35%. Univariate analyses were performed, and multivariate Cox proportional hazards regression modeling using purposeful selected covariates was applied to determine the independent predictors of long-term MACCE occurrence in all population. All univariate variables with p values <0.10 were included in the model. Variables judged to be of clinical importance from previous published research were included in the multivariate model-building process despite p values >0.10. A p value <0.05 was considered to indicate statistical significance. All data were processed using SPSS version 21 (IBM Corporation, Armonk, New York).
CTO PCI was attempted in a total of 839 patients (mean 64.6 ± 10.5 years of age, 87.7% men). According to baseline LVEF, the study population was subdivided as follows: group 1 (LVEF ≥50%) 552 (65.8%) patients; group 2 (LVEF 35% to 50%) 215 (25.6%) patients; and group 3 (LVEF ≤35%) 72 (8.6%) patients (Figure 1).
In comparison with patients with preserved LVEF (group 1), those with low LVEF (group 3) had more comorbidities (e.g., diabetes, peripheral artery disease, chronic kidney disease; all p < 0.05), more previous MI (59.7% vs. 37.5%; p < 0.001) and showed more frequent 3-vessel coronary artery disease (58.3% vs. 38.2%; p < 0.001). Group 3 patients were more often diabetic (45.8% vs. 31.2%; p = 0.018) and had undergone less prior PCI (23.6% vs. 39.1%; p = 0.012) in comparison with group 2. Table 1 summarized the clinical characteristics of the study population. CTO patients with LVEF ≤35 complained more often of severe dyspnea and less often of angina than did those with preserved or mildly impaired LVEF (all p < 0.05).
The rate of previously failed CTO procedures that were reattempted in our study population was lower in patients with low LVEF (≤35%) than in those patients with preserved LVEF (22.2% vs. 34.4%; p = 0.024). Although J-CTO score was similar in the 3 groups (J-CTO score ≥3: 49.5% vs. 45.1% vs. 44.4%; all p = NS), CTO PCI attempts were considered to be more difficult in group 3 in comparison with group 1, as assessed by the ORA score (ORA score ≥3: 20.8% vs. 9.6%; p = 0.006) (Table 2).
The angiographic success was high (overall 93.6%) and similar among the 3 groups (93.5% vs. 94.4% vs. 91.7%; all p = NS), as well as the clinical success (92% vs. 92.1% vs. 91.7%; all p = NS) (Figure 2A). Similar success rate was achieved among the 3 participating centers (Online Figure 1). Multivariate analysis identified female sex (odds ratio [OR]: 2.64; 95% confidence interval [CI]: 1.17 to 5.99; p = 0.02, J-CTO score ≥3 (OR: 8.26; 95% CI: 3.77 to 18.08; p < 0.001), and ORA score ≥3 (OR: 4.09; 95% CI: 1.77 to 9.47; p = 0.001) as independent predictors of angiographic failure, whereas LVEF ≤35% was not associated with failure (OR: 1.43; 95% CI: 0.55 to 3.70; p = 0.464).
The use of antegrade and retrograde approaches was similar between the 3 groups, and no difference was observed in terms of using conventional wire escalation and dissection re-entry techniques (all p = NS) (Figures 2B and 2C). Furthermore, in successfully recanalized patients, the stiffness of guidewires crossing the CTO lesions was similar between the 3 groups (Figure 2D).
Both procedural and fluoroscopy times, as well as air kerma radiation exposure were similar in the 3 groups; whereas, less contrast load was used in patients with LVEF ≤35% in comparison with group 1 and group 2 (295.6 ± 159 ml vs. 369.9 ± 213.9 ml vs. 349.1 ± 197.7 ml; p = 0.005 and p = 0.038, respectively). Procedural details are summarized in Table 3.
In patients with LVEF ≤35%, viability in the territory subtended by the CTO was assessed by myocardial scintigraphy and magnetic resonance imaging in 15 (20.8%) and 17 (23.6%) patients, respectively, whereas in the remaining 40 (55.6%) patients 2-dimensional echocardiography revealed hypokinesia in CTO territory. Figure 3 illustrates the distribution of coronary artery disease within the 3 major epicardial vessels, in patients with low LVEF. pMCS devices were used in 10 (13.8%) patients: intra-aortic balloon pump in 8 cases and extracorporeal membrane oxygenation in 2 cases. In patients with LVEF ≤35% who underwent successful CTO PCI, an rSS of 11.5 ± 4.1 (bSS 36.5 ± 18.3) was obtained (Figure 3B); and an SRI ≥70% was achieved in 48 (72.7%) patients. Except 3 cases of type I perforation (Ellis classification), no other periprocedural complications of CTO PCI attempts were observed in CTO patients with LVEF ≤35% (Table 4).
Clinical follow-up was available in 781 (93.1%) patients, including all those with LVEF ≤35% (mean follow-up period 16.3 ± 8.2 months). In patients with LVEF ≤35% successfully revascularized, only 1 cardiac death (1.5%) was observed in a 75-year-old diabetic man with 2-vessel disease who underwent successful antegrade CTO PCI of the proximal left circumflex artery, then staged PCI of the left anterior descending artery 3 days later. The patient experienced sudden cardiac death 7 days after discharge. Two noncardiac deaths were also noticed due to gastrointestinal bleeding and renal carcinoma. Among patients with failed CTO attempts, 2 (with left anterior descending artery CTO) experienced cardiac death (33.3%) due to refractory heart failure, 2 and 5 months after the failed CTO PCI. MACCE occurred less frequently in patients with successful CTO PCI (16.6% vs. 50.0%; p = 0.083) and were especially driven by non-CTO TVR (n = 6 [9.1%]) (Table 5).
At midterm follow-up, in case of successful CTO PCI, no difference in MACCE occurrence was observed in the 3 groups (10.2% vs. 13.9% vs. 16.6%; all p = NS), whereas in case of failed CTO PCI cardiac death was more frequently observed in patients with LVEF ≤35% in comparison with those with mildly impaired and preserved LVEF (33.3% vs. 8.3% mildly impaired LVEF, p = 0.001; and vs. preserved LVEF 3%, p < 0.001 (Table 5). At 2 years, MACCE-free survival was similar in the 3 groups (86% vs. 82.8% vs. 75.2%; all p = NS) (Figure 4). Of note, health care center did not affect the midterm clinical outcome (hazard ratio [HR]: 1.07; 95% CI: 0.93 to 1.23; p = 0.821).
On multivariate Cox regression, independent predictors of MACCE at midterm follow-up were as follows: age (per decade) (HR: 1.40; 95% CI: 1.07 to 1.98; p = 0.037), diabetes mellitus (HR: 2.71; 95% CI: 1.17 to 4.90; p = 0.017), and CTO PCI failure (HR: 3.45; 95% CI: 1.74 to 6.32; p < 0.001]; LVEF ≤35% did not predict MACCE occurrence (HR: 1.52; 95% CI: 0.66 to 2.92; p = 0.398) (Figure 5).
Regarding symptoms, a significant improvement of dyspnea was only observed in patients with LVEF ≤35%, whereas an improvement of angina occurred in patients with preserved LVEF (Figure 6).
In patients with LVEF ≤35%, the use of pMCS (HR: 1.10; 95% CI: 0.13 to 8.96; p = 0.929) and the achievement of SRI ≥70% (HR: 1.17; 95% CI: 0.28 to 4.94; p = 0.829) did not influence MACCE occurrence. In patients with LVEF ≤35% who underwent successful CTO PCI, LVEF improved significantly at 6 months (from 29.1 ± 3.4% to 41.6 ± 7.9%; p < 0.001) (Figure 7). Angiographic control was performed in 49 (74.2%) patients (4 driven by ischemia and 45 systematically) after a mean period of 8.7 ± 2.3 months, whereas the remaining 14 alive patients had improved symptoms and refused angiographic control. Focal nonocclusive restenosis of CTO target vessel was found in 4 cases (8.2%), requiring further revascularization, whereas neither diffuse restenosis nor reocclusion was observed.
The most important findings of our study can be summarized as follows: 1) PCI represents an efficient as well as safe strategy in patients with low LVEF (≤35%) affected by CTOs; 2) successful CTO PCI in these patients was associated with significant improvement of LVEF and symptoms, in particular dyspnea, at 6-month follow-up; 3) successful CTO PCI improved the midterm clinical outcome in patients with LVEF ≤35% as well in those with mildly impaired and preserved LVEF; and 4) low LVEF did not represent an independent predictor of MACCE at follow-up.
Severe ischemic left ventricular dysfunction is associated with higher morbidity, an increased risk of sudden death due to ventricular arrhythmias, poor quality of life, and frequent re-hospitalization for heart failure. In the COMMIT-HF (ConteMporary Modalities In Treatment of Heart Failure) registry including 675 patients with ischemic systolic heart failure (LVEF ≤35%) who underwent elective coronary angiography, a CTO was present in 278 patients, accounting for an overall prevalence of 41.2% (11). The patients with CTO had a higher frequency of previous MI, higher prevalence of diabetes, and higher percentage of multivessel coronary artery disease (11). Our data confirmed that CTO patients with low LVEF had higher risk profile with more comorbidities and more diffuse CAD in comparison with those with preserved and mildly impaired LVEF.
Tajstra et al. (11) also found that in patients with systolic heart failure, 12-month all-cause mortality (19.4% vs. 13.1%; p < 0.001) and cardiovascular death (16.2% vs. 8.3%; p = 0.001) were higher in presence of CTO than without. The presence of CTO independently increased the risk of 12-month mortality (relative risk: 1.84; 95% CI: 1.18 to 2.85; p = 0.006). Importantly, in the latter study, only a minority of patients was affected by CTOs attempted percutaneously (3.5%) (11). Current guidelines and appropriate use criteria for myocardial revascularization do not provide any recommendation regarding the most appropriate management strategy in CTO patients with low LVEF (20,21).
Thanks to the development of dedicated equipment and the growing expertise of CTO PCI operators, the success rate has dramatically increased among different interventionalists’ communities (9,22,23). In addition, despite the increasing complexity of CTO lesions, complication rates remained low (9). Interestingly, CTO lesions in patients with LVEF ≤35% included in our study population were less previously attempted than in those with preserved and mildly impaired LVEF. This fact might underline the reluctance of non-CTO expert interventionalists to attempt such more difficult procedures in this high-risk subset of patients, preferring to refer them to CTO expert operators or to open heart surgery.
In our study, the angiographic success rate of CTO PCI attempts was 93.6% in all population and 91.7% in patients with LVEF was ≤35%. Moreover, low LVEF did not predict CTO PCI failure. Although the CTO recanalization techniques used in this latter subset of patients were comparable to those used in patients with preserved and mildly impaired LVEF, some particularities should be emphasized. For instance, in patients with a dilated left ventricle (left ventricular end-diastolic diameter ≥70 mm), the retrograde approach requires longer microcatheters and in some cases brachial access with shortened guiding catheters (80 cm) to facilitate externalization. In addition, the use of pMCS, albeit not associated with improved midterm outcome, could be of benefit while attempting CTO in such high-risk patients, particularly due to the danger of hemodynamic collapse in a severe depressed LVEF (24). Special attention should also be paid to the amount of contrast used, as these patients are at high-risk of contrast-induced nephropathy. Indeed, Liu et al. (25) developed a pre-procedural risk score to predict contrast induced nephropathy after CTO PCI based on 3 variables, and including LVEF ≤40%.
Similar to other recent reports (9,26), a low rate of periprocedural complications was observed in our study. Importantly, except 3 cases of type I perforations (Ellis classification), no patients with low LVEF experienced severe periprocedural complications after CTO PCI. Hence, our data suggest that in experienced hands, CTO PCI represents a safe strategy even in high-risk patients, able to achieve a high degree of revascularization, as witnessed by the achievement of SRI ≥70% in almost three-quarters of patients. In patients with multivessel coronary artery disease, incomplete revascularization has been recognized to be associated with increased risk of death or cardiac adverse events, proportionally to the level of incompleteness of the revascularization (27). Nonetheless, a body of evidence is emerging and suggesting that complete revascularization could not be the only overriding tenet. Indeed, especially in high-risk patients, reduction of the procedural risk may be a preferred strategy, and a groundswell of published data supports the concept of reasonable incomplete revascularization as a valuable option in this subset of patients (28). In this respect, Généreux et al. (29) considered an SRI ≥70% representing a “reasonable” goal for patients with complex coronary artery disease.
Several observational studies and meta-analyses showed that successful CTO PCI was associated with improved cardiovascular prognosis in comparison with unsuccessful procedures (30–33). In the current study, a good clinical midterm outcome was achieved in the 3 groups and low LVEF was not demonstrated to be an independent predictor of MACCE at midterm follow-up. Indeed, in patients with LVEF ≤35% who underwent successful CTO recanalization: only 1 cardiac death (1.5%) occurred and the majority of MACCE were due to non-CTO TVR. Although LVEF ≤35% did not predict the occurrence of MACCE, in case of failed CTO PCI more patients experienced cardiac death in low LVEF group than in presence of mildly impaired or preserved LVEF (Table 5), underlying the need not only for expertise to treat CTOs but also for appropriate models to predict success in such a subset of patients to achieve better outcome.
Hoebers et al. (31) performed a weighted meta-analysis of 34 studies (including 2,243 patients) addressing the change of LVEF after successful CTO PCI. After a follow-up period ranging from 1 to 36 months, LVEF increased significantly with a pooled estimate of 4.44% (p < 0.01). Although it is common to consider a difference of at least 5% in LVEF as clinically significant, the impact of CTO revascularization on LVEF was relatively underestimated in the latter meta-analysis because of the heterogeneity (I2 = 44%) between studies due to the difference in cohort sizes, CTO definition, CTO location, success definition, imaging modality, and follow-up duration (33). However, in the case of reocclusion of the target CTO vessel, LVEF was similar and even relatively worse than that at baseline (–0.15%). This latter fact might be explained by the loss of the protective effect of collaterals after initial restoration of antegrade flow (32). Additionally, 8 studies reported significant decreases in left ventricle end-diastolic volume (6.14 ml/m2; 95% CI: −9.31 to −2.97; p < 0.01) (32). In our study, a significant improvement of LVEF (+42.9%; p < 0.001) was obtained 6 months after successful CTO PCI in patients with LVEF ≤35%. Similarly, in a cardiac magnetic resonance study including 29 CTO patients with LVEF ≤40%, Cardona et al. (34) showed that successful CTO PCI resulted in a significant increase in LVEF (from 31.3 ± 7.4% to 37.7 ± 8.0%; p < 0.001) and a significant decrease in left ventricular end-systolic volume (from 160 ± 54 ml to 143 ± 58 ml; p = 0.029). Hence, percutaneous revascularization of CTOs subtending viable myocardial territory of hemodynamic importance, in the setting of systolic dysfunction leads to improved LVEF and reduced adverse remodeling resulting in positive clinical consequences, particularly in absence of reocclusion.
In the recent EXPLORE (Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Elevation Myocardial Infarction) trial, 150 patients were randomly assigned to early PCI of the CTO and 154 patients were assigned to conservative treatment without PCI of the CTO (35). At 4-month follow-up, mean LVEF did not differ between the 2 groups. Nonetheless, this finding was likely due to a more substantial impact of the infarct-related artery than the CTO itself on left ventricle dysfunction. Interestingly, subgroup analysis revealed that patients with CTO located in the left anterior descending coronary artery who were randomized to the CTO PCI strategy had significantly higher LVEF compared with patients randomized to the no CTO PCI strategy (47.2 ± 12.3% vs. 40.4 ± 11.9%; p = 0.02) (35).
On the other hand, several observational studies showed that successful CTO revascularization is associated with improved quality of life (36,37). The European CTO club has reported the long-term outcome of 5-year retrograde experience showing a significant improvement in both angina and dyspnea status after a median follow-up period of 23 months (9). Symptomatic patients with CTO particularly tend to adapt to their condition, and will frequently avoid symptom-generating physical activity. In addition, many of them (not only those with low LVEF) will experience dyspnea more than from angina on exertion (19). Our results confirmed a significant improvement in symptoms after CTO PCI: less dyspnea in patients with low LVEF and less angina in those with preserved LVEF. The results of the randomized EURO-CTO (Randomized Multicenter Trial to Evaluate the Utilization of Revascularization or Optimal Medical Therapy for the Treatment of Chronic Total Occlusions) (NCT01760083) are expected to better evaluate the impact of PCI on the quality-of-life parameters in patients affected by CTO when compared with optimal medical therapy alone.
Finally, needless to say that improvement of survival and symptoms in patients with left ventricular dysfunction undergoing myocardial revascularization (of either CTO or non-CTO lesions) is only obtained when viability is demonstrated (38).
First, the number of CTO patients with LVEF ≤35% was relatively small; however, it reflects a real-world multicenter experience, and patients with low LVEF currently account for a minority of CTO patients referred for PCI. Second, all procedures were performed by CTO expert operators; hence, the present results may not be applicable to the entire population of interventionalists. Third, the definition used for non–Q-wave MI could underestimate its occurrence. Fourth, the LVEF was assessed by 2-dimensional echocardiography in the different centers involved, and no core lab analysis was performed. Fifth, bSS and rSS were only calculated in patients with LVEF ≤35%. Sixth, 53 patients were lost at follow-up; nonetheless, complete data were available in 93.1% of our initial cohort. Seventh, angiographic control was only performed in 74.2% of low LVEF CTO patients successfully revascularized, whereas no angiographic follow-up data were collected in other LVEF groups. Eighth, no adjustment was made for multiple statistical comparisons. Finally, our study did not compare the results of PCI versus CABG in patients with low LVEF.
Patients with ischemic left ventricular dysfunction (LVEF ≤35%), particularly those affected by CTOs, belong to a high-risk subset of patients, in whom the appropriate management strategy is not well established yet. Our results showed that in experienced hands, PCI could represent a safe and efficient management strategy able to improve LVEF and symptoms, and to ensure good midterm outcome.
WHAT IS KNOWN? In patients with ischemic left ventricular dysfunction, the presence of CTO is associated with reduced survival and worse cardiovascular outcome.
WHAT IS NEW? PCI represents a safe and efficient management strategy in CTO patients with low LVEF, able to improve LVEF and symptoms and ensure good midterm outcome.
WHAT IS NEXT? Further studies are required to confirm these preliminary data regarding the outcomes of CTO PCI in such a high-risk subset of patients.
Dr. Lüscher has received research and educational grants from AstraZeneca, Biotronik, Eli Lilly, Medtronic, Boston Scientific, Abbott, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- baseline SYNTAX score
- coronary artery bypass grafting
- chronic total occlusion
- hazard ratio
- left ventricular ejection fraction
- major adverse cardiac and cerebrovascular event(s)
- myocardial infarction
- odds ratio
- percutaneous coronary intervention
- residual SYNTAX score
- SYNTAX Revascularization Index
- target vessel revascularization
- Received February 21, 2017.
- Revision received June 26, 2017.
- Accepted June 29, 2017.
- 2017 American College of Cardiology Foundation
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