Coronary chronic total occlusions (CTO) are associated with adverse clinical outcomes. With the development of interventional therapy equipment and technologies, percutaneous coronary intervention (PCI) of CTO is increasingly pursued, and the success rate is getting higher. However, its beneficial effect remains debatable. Some observational studies comparing successful versus failed PCI for CTO have demonstrated that successful PCI was associated with better outcomes, while a few randomized controlled trials (RCTs)’s conclusions did not consistently support the benefit of CTO PCI. Moreover, this benefit is only the improvement of clinical symptoms [1, 2]. Overall, it remains unclear whether CTO revascularization brings long-term clinical benefit. Therefore, we assessed whether successful revascularization offers a clinical benefit in the CTO patients. This study focused on the major adverse cardiac and cerebrovascular events (MACCE), the MACCE includes all-cause death, cardiac death, recurrent myocardial infarction, heart failure, target lesion revascularization, re-hospitalization, and stroke.

A total of 563 CTO patients were consecutively enrolled in the present study (Fig. 1). Of these patients, 300 (50.7%) were managed by successful PCI revascularization (CTO-R group) and 263 (44.4%) were not revascularized (CTO-NR group). The CTO-NR group included patients who initial CTO-no PCI (n = 172) and failed CTO-PCI (n = 91). The PCI success was around 77% (300 success/391 attempts). In regard to periprocedural complications, coronary artery perforation occurred in 2 patients, coronary artery dissection occurred in 1 patient, coronary thrombotic event occurred in 1 patient, and myocardial infarction occurred in 1 patient during perioperative period.

The present study showed patients with CTO not revascularised by PCI had worse outcomes compared with those with CTO revascularised, with higher incidence of cardiac death and MACCE. The presence of low-LVEF, LM-disease was associated with an incidence of cardiac death. CTO revascularised was a protected predictor of cardiac death.

In our study population, the proportion of older (age > 65 years), diabetes, LM disease and three-vessel disease was higher in the no-revascularised CTO patients. This suggests that CTO with the above characteristics is more difficult to open. More importantly, previous studies have shown that age is an independent risk factor for cardiovascular mortality [6]. Elderly patients with decreased body function are more likely to have hypertension and diabetes, which promote atherosclerosis. In addition, the treatment strategy of CTO will also take into account the age factor; older patients tend to choose conservative treatment rather than PCI intervention. Meanwhile, there were more patients with in-stent restenosis (ISR) CTO in the revascularised group, which is also consistent with clinical practice; the ISR-CTO is easier to open because of the contour of the stent.

Besides, assessing the CTO patient’s heart function is critical to judging the prognosis. Serum NT-proBNP is an important biomarker in our clinical practice. Abnormal elevation of NT-proBNP can accurately reflect the degree of heart failure [7], and its combination with LVEF can comprehensively reflect the state of cardiac function. In our study, the peak of NT-proBNP was higher and the LVEF was lower in the no-revascularised CTO patients. Moreover, low-LVEF was a harmful predictor of cardiac death. We found that the presence of low-LVEF (< 0.5) was associated with an incidence of cardiac death at least 4 times higher than those with LVEF ≥ 0.5. Overall, cardiac dysfunction is more unfavorable to the clinical prognosis of CTO patients, which can significantly increase the incidence of major adverse cardiovascular events.

CTO are a common clinical finding among patients undergoing coronary angiography, approximately 1 in 4 patients with obstructive coronary artery disease on coronary angiography had CTOs [8]. CTO have been referred to as the “final frontier” in interventional cardiology, which are complex and difficult to open [9]. With improvement in equipment and techniques, high success rates can be achieved at experienced centers; PCI for CTOs has been rapidly evolving during recent years. The PCI success was around 77% in our study, which is lower than the classical 90% of the majority of high volume CTO centers. This may be explained by the fact that the patients were too old and have a high proportion of renal insufficiency, and they cannot tolerate long-term surgical operations. Moreover, we compared the success rates of different CTO lesion locations. In regard to success rates, LCX showed lower procedural success rates (40.6%) followed by LAD (68.2%), RCA (53.9%) and ≥ 2 vessel (42.1%). There were significant differences in the success rate of different CTO vessels.

The success rate of LAD-CTO is the highest, the LAD coronary artery supplies a major portion of the left ventricle, its diagonal branches perfuse the entire anterior wall, and its septal branches supply the anterior 2/3 of the septum, especially a proximal LAD-CTO will affect the entire anterior and anteroseptal wall from base to apex. Typically such a lesion, if not revascularized, will compromise overall LV systolic function and reduces the overall LVEF to at least 35–40%, which will lead to hypotension and heart failure [10]. Therefore, clinicians are more willing to try to open LAD-CTO. This may be one of the reasons for the high success rate of LAD-CTO. Nevertheless, the success rate of CTO with more than 2 vessels was low, and the probability of choosing CABG treatment was higher (p = 0.03). This result was also consistent with the clinical practice; clinical guidelines recommend CABG as the first choice for multi-vessel disease revascularization. Many studies have suggested a long-term survival advantage for CABG compared with PCI in patients with multi-vessel disease [11]. Moreover, the success rate of LCX-CTO was the lowest; many studies have confirmed that the successful opening of LCX-CTO has not seen obvious clinical benefits [12], and LCX-CTO was more difficult to open, one of the diagnostic criteria of the PROGRESS-CTO score was LCX-CTO [13].

Although successful revascularization of CTO was significantly associated with the decrease of MACCE, in the CTO-R group, different target vessel lesions (LAD, LCX and RCA) revascularization did not affect MACCE. It can be seen from Fig. 5 that successfully opened the LCX-CTO has the least effect on prognosis and the lowest cumulative survival rate. This confirmed the limited clinical significance of opening the LCX-CTO.

Our result showed that successful CTO PCI is associated with a statistically significant improvement in cardiac death and MACCE, successful revascularization of CTO was a protected predictor of cardiac death (HR: 0.239, 95% CI 0.076–0.751) and MACCE (HR: 0.541, 95% CI 0.353–0.83). It may be that the successful opening of CTO can improve cardiac function and ultimately improve the clinical outcome. A previous meta-analysis of 34 studies with 2735 patients on the impact of CTO PCI on LV function was performed in 2018 by Michael Megaly et al. and showed a statistically significant increase in LVEF (3.8%, 95% CI 3.0–4.7, P < 0.0001) as compared with baseline [14]. Additionally, in our study, low-LVEF (< 0.5) and LM disease predicted a worse probability for cardiac death. In summary, the predictive risk factors of cardiac death in CTO patients include vascular not revascularised, LM lesions and low-LVEF.

The following limitations were present in this study. (1) This study was a retrospective cohort study. The evidence grade is lower than that of a randomized controlled trial. (2) The signs of a viable myocardium were not all evaluated in our study. (3) Although we used multivariate Cox regression analysis to adjust for differences in baseline characteristics, there may still be unknown confounding factors. Therefore, the research results should be reasonably interpreted. (4) The symptom improvement is one of the benefits of CTO recanalization; the symptom was not assessed in our study.

In summary, compared with CTO not revascularised, successful revascularization offered patients more clinical benefits, manifested by the lower incidence of cardiac death and MACCE during follow-up. Moreover, the presence of LVEF < 0.5 and LM-disease was associated with an incidence of cardiac death; CTO revascularization was a protected predictor of cardiac death. Further RCTs are needed to investigate the role of PCI for management of patients with CTO.