The midterm results of coronary endarterectomy in patients with diffuse coronary artery disease

Revascularization of diffuse coronary artery disease is still challenging for both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). These techniques often prove to be inadequate when dealing with severe diffuse coronary atherosclerosis. An alternative to achieve complete revascularization is coronary endarterectomy (CE) which was introduced in the 1950s with the first procedures performed without cardiopulmonary bypass [1]. Initially, CE followed by CABG lost popularity due to higher associated rates of perioperative morbidity and mortality as compared to CABG alone [2]. Moreover, the complications are even more fatal when CE is performed on arteries that are crucial to achieve optimal effect, such as the left anterior descending (LAD) artery, where failure to obtain optimal blood flow results in catastrophic clinical outcomes. It is debatable, however, that the difference in favorable outcomes between CE + CABG and CABG alone is due to lesion complexity. Fukui T et al., postulate that the higher risks associated with CE are due to the profile of patients with diffuse coronary vessel lesions which makes grafting challenging due to the unavailability of a soft region [3]. Data from the last 15 years report better survival rates after CE [4‐6]. Many surgeons are still reluctant to perform CE due to the absence of guidelines and varying outcomes from across centers [7, 8]. The aim of this retrospective study is to evaluate the mid-term results of coronary endarterectomy followed by coronary artery bypass grafting (CE + CABG).

A total of 238 patients underwent CE + CABG during the study period. The mean age of the patients was 65 ± 8 years in the on-pump group and 63 ± 9 years in the off-pump group; the male to female ratio was 201:37. 59.8% of patients undergoing off-pump surgery had a high lipid profile (vs 43.8% on-pump), 14.1% had suffered from previous cerebrovascular accident (vs 2.1% on-pump), 23.9% suffered from concomitant COPD (vs 4.1% on-pump), 48.9% had a calcified ascending aorta (vs 2.7% on-pump), 96.7% had RCA critical stenosis > 90% (vs 55.5% on-pump). We preferred off-pump CE + CABG in patients with known hyperlipidemia, previous cerebrovascular accidents, COPD, calcified ascending aorta, and RCA critical stenosis> 90. The complete pre-operative patient characteristics are summarized in Table 1. Our patient cohort represented 269 target coronary lesions, of which 108 (40.1%) were located on the left anterior descending (LAD) artery and sub-branches, 140 (52%) were located on the right coronary artery (RCA) and sub-branches, and 21 (8.8%) were located on the left circumflex artery and/or obtuse marginal artery (LCX/OM). The mean number of bypasses performed was 4.0 ± 0.9 (on-pump) vs 3.8 ± 0.7 (off-pump), 8.9% of on-pump patients required intra-aortic balloon pump (vs 1.1% in the off-pump group). The left internal mammary artery was used in all of the patients, saphenous vein grafts were used in more than 90% of the patients, and the radial artery was used in one-fifth of the patients (see Table 2: operative characteristics). The mean graft flow rates measured intra-operatively after endarterectomy and bypass grafting was 36 ± 8 ml/min with a mean PI value of 3.1 ± 0.8.

The mean intensive care unit stay was 2.5 ± 0.5 days for the patients who underwent on-pump surgery and 2.6 ± 0.7 days for the patients who underwent off-pump surgery. There was no significant difference in preoperative death and MACCE rates between the two groups. The occurrence of ventricular arrhythmia was significantly greater in the off-pump group (14.1% vs 4.8% in the on-pump group) (Table 3: perioperative mortality and morbidity). The average follow up time was 41.8 ± 21.4 months. Follow-up on the patients postoperatively showed a significant reduction in angina and dyspnea across the entire cohort as compared to the pre-operative period (P < 0.001). Six patients died during the 3-year follow-up period, two of whom died of neoplasms, three of cerebrovascular events and one died of unknown reasons and was considered MACCE-related for statistical purposes.

At the one-year follow-up, data of 208 (232 endarterectomized target vessels; 88.5% of the original cohort) patients were obtained. The overall graft patency was 78.4% at 1 year and 69.8% at 3 years. The left coronary graft patency rate was significantly higher than the right coronary graft patency rate (87.4% vs 73.1% at one-year, p = 0.011 and 78.2% vs 64.8% at 3 years, p = 0.032) (Table 4: follow up graft patency analysis of coronary endarterectomy). There was no significant difference in graft patency rates between the on-pump CE + CABG vs off-pump CE + CABG groups at 1 year (80.0% vs 76.9%; p = 0.599) and at 3 years (92.3% vs 91.7%; p = 0.884). At the one-year follow up, 92.3% of grafts showed grade A patency in the on-pump group versus 91.7% in the off-pump group (p = 0.884); 7.7% of grafts showed grade B patency in the on-pump group versus 8.3% in the off-pump group (p = 0.988). At the three-year follow up, 80.6% of grafts showed grade A patency in the on-pump group versus 77.4% in the off-pump group (p = 0.636); 19.4% of grafts showed grade B patency in the on-pump group versus 22.6% in the off -pump group (p = 0.636); (see: Table 5. Follow-up graft patency analysis between group on-pump and off-pump CE).

Moreover, the predictors of better graft patency are use of LIMA graft (P = 0.021), CE on LAD (P = 0.013), and intra-operative graft flow meter and PI (P = 0.002)(Table 6). Kaplan-Meier survival estimates in the on-pump CE + CABG group at one, 3 and 5 years were 0.96, 0.89 and 0.73 respectively and 0.95, 0.88 and 0.71 respectively in the off-pump CE + CABG group (Fig. 1: Mid-long term survival with group on-pump versus group off-pump after coronary endarterectomy).

Before the widespread use of CABG to treat coronary artery disease, CE was the mainstay treatment for improving blood flow to severely stenosed coronary arteries. Although the technique was introduced more than five decades ago, it rapidly fell out of usage [1]. Acute post-operative MI, a key complication following CE, might be associated to endothelial damage during the procedure and subsequent thrombosis. Intact coronary endothelium produces vasoactive factors to neutralize leukocyte adhesion and platelet aggregation, consequently reducing inflammation and thrombosis in blood vessels [9]. Furthermore, MI caused by residual lesion-induced occlusion also contribute to the postoperative morbidity and mortality of CE [10, 11].

The aim of endarterectomy is to extract the calcified intima distal to the incision and ensure adequate revascularization. Distal intimal extraction is considered adequate if obvious bleeding of the distal vascular segment and a patent vessel with normal distal intima (with thin and soft tissues) on the top is observed after endarterectomy. There are two methods of performing endarterectomy, namely the ‘open’ and ‘closed’ techniques [12, 13]. The decision to use either ‘open’ or ‘closed’ CE was by the operating surgeon using the following criteria: 1) type of occlusion (complete total occlusion, or > 50% occlusion, or > 75% occlusion), 2) length of stenosed segment, 3) location of the lesion (medial or distal), and 4)number of bypasses to be performed. In hospital-mortality, defined as death due to any cause within 30 days of the operation, was 1.3% for both groups. 3.8% of the patients developed myocardial infarction during the peri-operative period, and 8.4% developed ventricular arrhythmias. During the three-year follow-up period, six deaths occurred, of which four were considered to be MACCE-related (1.7%). A 2015 meta-analysis performed by Kirill LK et al. show a 2.07% mortality at 30 days, 6.0% at 1 year, and 12.10% at 3 years post CABG surgery. Although the authors predominantly investigate outcomes in an elderly patient cohort (> 50% of patients were > 70 years old), we consider 1.3% mortality rate at 30-days, and a 3-year MACCE rate of 1.7% to be acceptable for concomitant CE and CABG. At the very least, it indicates that CE doesn’t significantly increase the risk margin of the procedure [14].

As mentioned above, the patient cohort undergoing CE have a higher risk profile and the surgery itself is technically more challenging. For on-pump CE + CABG, this invariably translates to longer aortic cross-clamp, CPB times; and a greater incidence of intra-operative intra-aortic balloon pump implantation as compared to off-pump CABG (8.9% vs 1.1% respectively). We also performed off-pump CE + CABG on 38.7% of our cohort. In our study, we found that patients with a certain profile are more likely to be referred for off-pump surgery instead of on-pump surgery. Some patient characteristics include younger age, previous cerebrovascular accident, COPD, and calcified ascending aorta. One drawback of off-pump surgery is that it significantly increases the rate of peri-operative ventricular arrhythmias. There was no significant difference in early and late patency rates between the on-pump and off-pump CE + CABG groups. Off-pump CABG has beneficial effects on the recovery of the patient in the early post-operative period, as it decreases the operative time, and lowers the rate of MI, reduces the duration of inotropic support and ICU stay, and decreases the rate of peri-operative bleeding [15]. Our analysis on the on-pump and off-pump groups, show no significant difference in one-year and three-year graft patency rates; The results are similar to the study performed by Li S et al., where they also found no significant difference in survival at one-year between on-pump CABG and off-pump CABG [16]. Kaplan-Meier survival estimates at one-, three-, and five-years do not show a significant difference between the on-pump and off-pump CABG groups. It appears that the choice of either off-pump or on-pump in the setting of CE + CABG does not have deleterious effects on the early and mid-term outcomes of the procedure. In our study cohort, the mean discharge time after transfer to the ICU was (11 ± 3) days vs the 9.01 days and 7.7 days, reported by LaPar et al. for patients undergoing CE + CABG and CABG respectively; Nevertheless, we report lower mortality rates (1.42% vs 4.0%) despite our longer follow-up time (41.8 ± 21.4 months vs 27.7 ± 17.7 months) [17].

Complete revascularization is accompanied by added benefits such as ischemia reduction, improvement of LV function, reduction of arrhythmias, and preserved ejection fraction [17]. Moreover, the composite endpoint of death/MI/stroke is significantly more likely with higher degrees of incomplete revascularization [18]. The 2011 ACC/AHA guideline for coronary artery bypass graft surgery and the 2014 ESC/EACTS guideline on myocardial revascularization have no reference to the clinical recommendation of CE due to the absence of randomized controlled trials [19‐21]. Despite a lack of guidelines for the feasibility of complete or incomplete revascularization in the case of concomitant CE + CABG, we decided that a strategy of complete revascularization would better fit the high risk profile of our patient cohort. We obtained satisfactory results while keeping a high number of distal anastomoses (4.0 ± 0.9 vs 3.8 ± 0.7 for on-pump vs off-pump group respectively), thus ensuring a graft vessel to each perfusion territory of myocardium.

Another significant result from our study, is the higher patency of the left coronary graft at both one and 3 years, as compared to the right coronary graft (87.4% vs 73.1%, p = 0.011 at one year; 78.2% vs 64.8%, p = 0.032 at 3 years respectively). Since all endarterectomies and bypasses were performed by the same surgeon (CX) to assure consistency of technique, this suggests that the use of LIMA graft is an independent factor accounting for the superior patency rates [22]. The endothelium of internal mammary arteries produce vasodilators, are better protected from atherosclerosis, and due to postsurgical blood flow remodeling of the graft vessel, are better conduits for bypass as compared to the saphenous vein. The LIMA graft is also a predictor for better graft patency during follow-up (P = 0.021) [23, 24]. Other predictors of graft patency at follow up are presence of using LIMA graft, performing coronary endarterectomy on the LAD, and good intra-operative flow and PI values. The presence of the above mentioned factors, are highly indicative of successful CE which translates into good graft patency, and hence, can be used to score a CE procedure.

In patients with diffuse coronary disease, CE is a safe and feasible technique for a select group of patients with excellent mid-term survival rates and graft patency rates. CE produces better overall results when performed on the LAD, and grafted over with the LIMA. Similar outcomes are obtained with both on-pump and off-pump surgery. For a select group of patients, coronary endarterectomy (CE) offers an alternative choice of coronary artery reconstruction and complete coronary revascularization.