Based on the results of this large sample size registry-based cohort study, distribution of risk factors and predictors of mortality and non-fatal CCVE were not the same in each EF group but had many points in common. Diabetes mellitus is the common risk factor of mortality and CCVE in all EF groups. Impaired renal function (GFR<60 ml/min) was associated with a higher risk of mortality after CABG regardless of EF level. Older age, diabetes mellitus, history of CVA, and COPD were associated with a higher risk of mortality in the EF<50% group (both mild to moderate and severely reduced groups).
Although the mortality rate was significantly higher in the severely reduced EF group, this was not statistically significant for non-fatal CCVE. Similar to our findings, Maltais et al. evaluated 1250 patients who underwent off-pump CABG and showed that major adverse cardiac events (MACEs) were not significantly different in patients with LVEF<35% and LVEF≥35% after adjustment for potential risk factors (18). However, another study conducted by El-Shafey et al evaluated 170 patients who underwent CABG and showed that non-fatal CCVE occurred more significantly in patients with LVEF <40% (19).
Another important and noticeable finding was the role of the female gender in post-CABG outcomes. Although female gender was not significantly associated with higher mortality, it was associated with higher non-fatal CCVE in patients with normal and mild to moderately reduced EF. Similar to our findings, Kurlansky et al. evaluated all patients who underwent coronary revascularization and found that outcomes (MACEs and all-cause mortality) were worse in women who underwent either CABG or PCI (20). Also, Huckaby et al. evaluated 6163 patients undergoing coronary revascularization and showed that 1-year outcomes (MACE and death) were worse among women with multivessel disease who underwent either CABG or PCI (21). Besides, a meta-analysis of 20 studies showed that women had an increased risk of short-, mid-, and long-term mortality after isolated CABG compared to men (22). Another study conducted by Ergunes et al. found that the in-hospital mortality rate was higher in female patients however, the mid-term survival was similar between males and females (23). However, according to our results, the female gender was not associated with an increased risk of mortality.
Patients with impaired LVEF and CAD have multiple hemodynamic and metabolic abnormalities at rest such as altered myocardial oxygen consumption and lactate metabolism (24). Therefore, patients with low EF who undergo CABG are a distinctive group of patients and may have different risk factors associated with postoperative outcomes compared to those with normal EF (3). Therefore, identification of risk factors associated with adverse outcomes after CABG and selection of patients is important for achieving the optimal postoperative outcome.
According to the surgical treatment for ischemic heart failure extension (STICHES) trial, CABG had clear survival benefits over medical therapy in patients with LVEF <35% at 10-year follow-up (8). Although CABG is superior to medical therapy in terms of better survival, the outcomes of patients with low LVEF were shown to be worse compared to those with normal EF (10). Besides the role of net EF value in the post-op outcome, other preoperative predictors also play an important role here. As mentioned before, the distribution and the strength of these predictors are different in each EF group.
Topkara et al. (11) analyzed 55,515 patients who underwent CABG and showed that independent predictors of in-hospital mortality in patients with EF ≤20% are older age, female gender, renal failure, previous myocardial infarction (<6 hours), and previous open-heart operation. According to our results, older age was the independent predictor of all-cause mortality in patients with EF <50, and female gender was the independent predictor of non-fatal CCVEs in patients with reduced EF (35%≤ EF< 50%). Shapira et al. (25) evaluated 115 patients with EF ≤30% who underwent isolated CABG. They found that female gender, renal failure, respiratory complications, and mitral regurgitation are independent predictors of mid-term (36 months) mortality in these patients’ groups. Kamal et al. (12) evaluated two propensity-score matched groups (EF <50% and EF ≥50%) who underwent isolated CABG. They showed that the use of an intra-aortic balloon pump was the independent predictor of early mortality in patients with EF <50%. Soliman Hamad et al. (3) assessed 413 patients with EF ≤30% who underwent isolated CABG. They found that age, hemoglobin levels, and creatinine levels are predictors of early mortality after CABG. Vickneson et al. (26) analyzed CABG results of 346 patients with EF ≤30% and found that hemodynamic instability and kidney dysfunction are independent predictors of 30-day mortality. Similarly, we showed that anemia and eGFR<60 ml/min are independent predictors of all-cause mortality in patients with reduced EF (35%≤ EF< 50%). Khaled et al. (27) evaluated 110 patients with EF <50% who underwent CABG. They showed that diabetes mellitus, diastolic dysfunction, and the use of intra-aortic balloon pumps were predictors of mortality in the study population. Similarly, we found that diabetes mellitus was the independent predictor of all-cause mortality and non-fatal CCVEs in patients with EF <50%. Higher rates of adverse outcomes in patients with diabetes mellitus may be due to adverse effects of insulin therapy, inflammatory response, and hormonal overreaction which leads to disruption of cardiovascular function (28). Gatti et al. (29) conducted a study of 300 patients with EF ≤35% and showed that poor glycemic control and GFR <50 ml/min were independent risk factors for in-hospital mortality.
According to our results, dyslipidemia and positive family history were protective factors for all-cause mortality in the reduced EF group. This observation could be partly explained by the utilization of cardiovascular medications such as aspirin, beta-blockers, and statins in patients with a family history of coronary disease (30). Moreover, they are more likely to exercise, have a healthy diet, be aware of cardiovascular risks, and manage modifiable risk factors such as hypertension (31, 32). Also, patients with dyslipidemia are more likely to use lipid-lowering medications such as statins. It has been shown that statin therapy is associated with a lower risk of all-cause mortality and MACE after CABG (33, 34).
Similarly, Abdi-Ali et al. (30) reported that in patients with proven coronary disease, positive family history was associated with a 23% relative risk reduction of all-cause mortality over 5.6 years. Two other studies conducted by Canto et al. (35) and Agarwal et al. (36) showed that in a large population of patients with acute myocardial infarction, positive family history is associated with lower in-hospital mortality.
Strength and limitation
The present study should be interpreted in the context of several possible limitations. Our findings were based on midterm follow-up (median 5.61 years), and further studies with longer follow-up are needed to achieve more accurate results. This study was conducted in a single center and the generalizability of our results should be assessed. Still, THC is a referral educational university that serves patients from all over the country.
The major strengths of this study are as follows; First, large sample size presented a considerably high prevalence of events which enhances the power of the study; Second, our data extracted from THC registry data bank which records patient’s data prospectively; Third, to overcome surgical expertise limitation, we chose expert surgeons which conducted at least 100 off-pump and 400 on-pump CABG procedures previously.