We assessed the 5-year cardiovascular survival of successful CTO-PCI patients with or without DM in a large-scale, prospective and real-world cohort population. Notably, we confirmed the following: (1) Diabetic patients with successful recanalization for CTO lesions are highly prone to lower LVEF, compared with non-diabetic patients. (2) Non-diabetic patients were related to better long-term survival benefit in terms of MACCE for the treatment of successful CTO-PCI.
With substantial and significant improvement in interventional devices and techniques, CTO-PCI has emerged as an effective revascularization strategy with high success rates for diabetic patients. Moreover, it is well-established that DM represents an important risk equivalent of CTO and an independent factor for increased MACE after CTO-PCI[22, 23]. Sanguineti et al. reported that DM was a significant predictor of cardiac mortality in CTO patients. Additionally, Yan et al. found that both successful CTO-PCI and CTO-CABG of right coronary artery in diabetic patients showed significant reduction of all-cause death (HR 0.445, 95% CI 0.278–0.714) during long-term follow-up. Recently, Guo et.al also reported that in DM group, successful CTO-PCI reduced MACE risk (HR 0.61, 95% CI 0.42–0.87, P = 0.005) compared to optimal medical therapy alone. Likewise, Tsai et al. also found that DM was associated with poor prognosis in patients with CTO lesions compared with non-DM. Moreover, this study also showed that successful CTO-PCI was independently associated with reduced risks of all-cause death and adverse cardiovascular events only in DM population, but not in non-DM patients, which was consistent with the finding of Guo and co-workers. These evidences highlighted the unfavorable role of DM in CTO patients and the importance of complete recanalization of CTO patients with DM. Contrary to the results of previous findings, subgroup analysis of the randomized COURAGE trial demonstrated that there was no obvious difference in the incidence of adverse events between the medical therapy group and the PCI group in DM patients with stable coronary disease. This difference may be explained by the high rate (approximately 30%) of crossover from medication to revascularization during the follow-up period, which may underestimate the actual effect of successful CTO-PCI.
Considerable evidence has demonstrated that the existence of DM has a detrimental effect on glucose and lipid metabolism, endothelial function and angiogenesis, leading to premature development and progression of coronary artery atherosclerosis, inadequate collateral development and harmful clinical outcomes[28–30]. Previous studies have showed that well-established collateral circulation after CTO is crucial to supply the downstream perfusion area, alleviate myocardial damage, reduce infarct size and eventually improve LVEF[31, 32]. Our study found that DM patients with successful CTO-PCI were more likely to have lower LVEF, which may be related to poor coronary collateral circulation. However, recently, Yang et al. reported that after successful recanalization of CTO, there was no significant distinction between diabetic and non-diabetic effects of coronary collaterals on MACCE and repeat revascularization during a median follow-up of 13.5 months. Yang and co-workers speculated that well-developed coronary collaterals may not adequately substitute normal blood supply and thus good collateral circulation is insufficient.
Recently, with regard to the long-term clinical outcomes of successful CTO-PCI in patients with versus without DM, a meta-analysis by Zhu et al. which included 9847 patients after successful CTO-PCI (4238 diabetic patients and 5069 non-diabetic patients) revealed that the prevalence of MACEs (RR 1.26, 95% CI 1.02–1.56, P = 0.03) was significantly higher, compared with patients without DM. Likewise, consistent with Guo and co-workers, our study also reported that the rates of MACCE after successful CTO-PCI were higher in diabetic patients than in non-diabetic patients. In contrast, Ruiz Garcia et al. reported that in patients who underwent successful revascularization of CTO comparable rate of MACE was observed between the diabetic and non-diabetic patients in the drug-eluting stent era. Although this was a prospective randomized clinical study, the atypical definition of CTO (occlusion longer than 2 weeks), the small sample size of its enrolled patients (75 diabetic and 132 non-diabetic patients) and the modest follow-up period of 1 year restricted the accuracy of the results. In our study, we also found that the prevalence of 2-year (shorter term) clinical outcomes was comparable between the diabetic patients and non-diabetic patients, which was consistent with the findings of Ruiz Garcia and co-workers. Thus, it is necessary to evaluate longer term prognosis for diabetic patients undergoing successful CTO-PCI.
To date, there is a paucity of data on the benefit of successful PCI for CTOs in diabetic and non-diabetic patients on long-term survival. Our findings can be explained by the following mechanisms. First, patients in DM group were more likely to have complex clinical characteristics, like lower LVEF, which had a detrimental effect on cardiac function[10, 14]. Second, DM, as a greater risk factor for adverse cardiovascular outcomes, alters glucose and lipid metabolism and influences vascular endothelial function and angiogenesis[28, 29, 33]. Third, poor collateral circulation and microcirculation in diabetic patients may also partially account for the worse long-term prognosis, compared with non-diabetic patients[31, 33, 36].
Our study had some inevitable limitations. First, it was a single-center, prospective and observational study. Although we performed propensity score matching to reduce potential selection bias and minimize the confounding factors, unadjusted confounders still existed. Second, our real-world cohort comprised of CAD patients, who had been consecutively enrolled in our study and underwent PCI. This was not a specialized CTO cohort, so we are short in sample size of CTO-PCI patients. Third, there was a lack of specific information in our database, such as coronary collateral scoring. Fourth, our center was a tertiary medical hospital which performed high volume of CTO-PCI and had many experienced cardiologists. Generalizability might be limited in less experienced center with lower number of CTO-PCI cases.