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 LVEF༜0.5, 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 [5]. 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 patient 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.
Evaluation of cardiac function in patients with CTO is of great significance for their prognosis. Serum NTproBNP is an important biomarker in our clinical practice. Abnormal elevation of NTproBNP can accurately reflect the degree of heart failure[6], and its combination with LVEF can comprehensively reflect the state of cardiac function. In our study, the peak of NTproBNP was higher and the LVEF was lower in the no-revascularised CTO patient. Moreover, low-LVEF was a harmful predictor of cardiac death, we found that the presence of 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 [7]. CTO have been referred to as the “final frontier” in interventional cardiology, which are complex and difficult to open [8]. Although overall success rates remain low, 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. Our study compared the opening rates of different CTO sites, the results showed that the opening rates of LAD, LCX, RCA, and > 2 vessels were 68.4%, 40.8%, 53.9% and 42.1%, respectively. There were significant differences in the opening rate of different CTO vessels (p = 0.000).
We can found that the opening 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[9]. Therefore, clinicians are more willing to try to open LAD-CTO. This may be one of the reasons for the high opening rate of LAD-CTO. Nevertheless, the success rate of CTO with more than 2 vessels was low, and the probability of choosing CABG treatment is higher (p = 0.03). This result is also consistent with the clinical practice; CABG is the first choice for multi-vessel coronary artery disease. Many studies have suggested a long-term survival advantage for CABG compared with PCI in patients with multi-vessel coronary artery disease [10]. 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 [11], and LCX-CTO is more difficult to open, one of the diagnostic criteria of the PROGRESS-CTO score is LCX-CTO [12].
Although the successful opening of CTO lesion vessels 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, CTO revascularised was a protected predictor of cardiac death (HR: 0.32, 95% CI 0.11–0.94) and MACCE (HR: 0.57, 95% CI 0.37–0.87). 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[13]. Additionally, in our study, lower LVEF (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.
Limitations
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 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. Moreover, the randomized clinical trials should be conducted to verify the results in the future.