Eligibility criteria included age ≥18 years and a personal history of symptoms suggestive of ischemic heart disease in which a significant atherosclerotic vessel lesion was identified on CA and classified as a CTO (coronary lesion with thrombolysis in myocardial infarction [TIMI] anterograde flow score of 0 with chronic characteristics thought to have been present for at least three months). Patients who only underwent a diagnostic study, even if they had a CTO vessel, or had an unsuccessful procedure were excluded from the study. A previously published hybrid algorithm for CTO PCI was used for revascularization, and patients were divided into two groups according to their diabetes status (T2DM and non-T2DM).15,16 T2DM was presumed in patients with a known previous diagnosis of T2DM or with a recorded inpatient random glycated hemoglobin ≥6.5%. LVEF was estimated by the modified Simpson's biplane method. Obesity was defined as a body mass index ≥30 kg/m2, and chronic renal failure as creatinine clearance of <60 ml/m2 (Cockcroft–Gault formula). Symptoms were assessed through medical records; no scales or questionnaires were applied and no patients were contacted by telephone. The use of at least one antianginal drug, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 100 mg aspirin (or anticoagulation in atrial fibrillation), dual antiplatelet therapy or dual antithrombotic therapy for at least six months, and a lipid-lowering drug (statin and/or ezetimibe) were defined as optimal medical therapy (OMT). Periprocedural myocardial infarction (MI) was assessed and defined as type 4a in accordance with the fourth universal definition of MI.17 Atherosclerotic disease progression was defined as progression of atherosclerosis in the index vessel and/or in non-CTO vessels. Baseline patient demographic data, cardiovascular risk factors, and clinical, laboratory, echocardiographic and angiographic data were also recorded.

The study abides by the ethical requirements stated in the 1975 Helsinki Declaration and received ethical approval by the local hospital ethics committee.

The study's primary outcome was recurrence of angina and/or HF symptoms (total symptom recurrence) in a two-year follow-up. HF symptoms were defined as dyspnea and/or fatigue associated with an underlying heart condition. Secondary outcomes were defined as MI and all-cause mortality.

Categorical variables were presented as frequencies and percentages, and continuous variables as means and standard deviation, or medians and interquartile range for variables with skewed distribution or a significant Shapiro–Wilk test. Comparisons between groups were performed using the chi-square test, Student's t test or Mann–Whitney test, as appropriate. Multivariate analysis was performed using logistic and Cox regression to identify predictors associated with the outcomes. A p-value <0.05 was taken to indicate statistical significance. The statistical analysis was performed using IBM SPSS Statistics, version 21.0 (IBM SPSS, Chicago, IL, USA).

A total of 191 patients were recruited, with 14 being excluded (12 had an unsuccessful procedure and two only underwent CA). All available characteristics for the final sample of 177 patients are summarized in Table 1. The groups were composed of 70 (39.5%) patients with T2DM and 107 (60.5%) without T2DM. The overall sample had a mean age of 64.5±11.4 years and 82.5% were male. Medical history included hypertension in 74.6% of patients, dyslipidemia in 72.9%, obesity in 18.2% and HF in 15.3%. T2DM patients were older, with a mean age of 67.9±10.1 (p=0.010), and more likely to have chronic renal failure (14.3%, p=0.011). Most patients were on OMT (83.1%, p=0.382) and antianginal drugs (98.3%, p=0.824), with no difference regarding diabetes status. Insulin replacement therapy was prescribed in 25 (35.7%) diabetic patients, and mean glycated hemoglobin was 8.2%.

The right coronary artery (RCA) was the most frequently occluded artery, and an anterograde approach was most frequently employed. Multivessel disease was present in 85.9% of patients. T2DM patients presented with lower creatinine clearance levels (69.3±27.9 ml/min, p=0.006), and contrast doses were therefore lower during PCI in these patients (225±84.8 ml, p=0.009). Ischemia or myocardial viability testing was performed in 43 (24.3%, p=0.718) patients, most frequently stress echocardiography (10.7%, p=0.212). Periprocedural MI occurred in 10 (5.6%, p=0.976) patients during CTO PCI. The rate of periprocedural complications was 5.1%, mainly vessel perforation (2.26%), but no differences were found between groups. Although LVEF was mildly reduced at baseline, ventricular function improved in both groups after intervention in a mean follow-up of 18 months (p<0.001) (Table 2).

The primary outcome (total symptom recurrence) occurred in 16.6% of patients, with no difference between groups (non-T2DM 13.6% vs. T2DM 21.2%, p=0.194) in two-year follow-up (mean follow-up of 18 months). Angina recurrence was significant higher in the T2DM group (15.2%, p=0.043) (Table 3).

Of the total population, 11 (6.2%) had CTO restenosis and 22 (12.4%) had atherosclerotic disease progression, mainly in the diabetic population (p=0.030 and p<0.001, respectively). In patients with symptom recurrence (total or isolated angina), there was no difference in the restenosis rate according to diabetic status (p=0.190 and p=0.790, respectively). Nevertheless, atherosclerotic disease progression was more frequent in diabetic patients with total symptom or angina recurrence (p=0.008 and p=0.013, respectively) (Table 4).

MI and all-cause mortality showed no differences between groups (T2DM 1.5%, p=0.786 and 4.5%, p=0.352, respectively, on survival analysis) (Figures 1 and 2).

Figure 1.

Kaplan–Meier curve showing time until myocardial infarction (mean follow-up of 18 months) in chronic total occlusion patients undergoing percutaneous coronary intervention, compared by diabetes status.

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Figure 2.

Kaplan–Meier curve showing time until death (mean follow-up of 18 months) in chronic total occlusion patients undergoing percutaneous coronary intervention, compared by diabetes status.

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The presence of T2DM and LVEF was not independent predictors of the primary outcome (p=0.429, hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.62–2.98 and p=0.737, HR 0.994, 95% CI 0.95–1.03, respectively). RCA as the CTO vessel was an independent predictor for total symptom recurrence after PCI (p=0.019, HR 2.68, 95% CI 1.17–6.14) (Figure 3).

Figure 3.

Multivariate analysis (Cox regression) for the primary outcome. CTO: chronic total occlusion; HR: hazard ratio; LVEF: left ventricular ejection fraction; RCA: right coronary artery; T2DM: type 2 diabetes mellitus.

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Independent predictors of all-cause mortality were LVEF and creatine clearance (p=0.039, HR 0.92, 95% CI 0.85–0.99 and p=0.013, HR 0.96, 95% CI 0.93–0.99, respectively). The presence of T2DM was not an independent predictor of all-cause mortality (p=0.975, HR 1.03, 95% CI 0.16–6.34).