Cardiovascular Outcomes in High-Risk Patients Undergoing OPCAB Surgery Compared to Traditional CABG Analisis Luaran Kardiovaskular Pasien Risiko Tinggi pada Operasi OPCAB Dibandingkan CABG Tradisional

The benefit of coronary artery bypass graft (CABG) for coronary artery disease (CAD) with Ejection Fraction (EF) 30% and ischemic burden (IB) 10% is still debatable. The objective of this study is to analyze mortality and morbidity in patients with EF 30% and ischemic burden 10% undergoing OPCAB compared to traditional CABG (TCABG). The retrospective analytic cohort study was performed using data from January 2015–November 2018 at National Cardiovascular Center Harapan Kita Jakarta, Indonesia. 109 patients were included. 35 patients undergoing OPCAB and 74 patients undergoing TCABG. The primary outcomes were mortality rate, morbidity rate, and length of stay. Arrhythmia is statistically lower in OPCAB compared to TCABG (8.6% vs 39.2%; p=0.001). Kidney injury is statistically lower in OPCAB (8.6% vs 27.0 %; p=0.027). Stroke is statistically lower in OPCAB (1.0 % vs 17.6%; p=0,032). There is no significant difference between OPCAB and TCABG in mortality, 5.7% vs 16.2%, (RR=3.20; CI 95%=0.67–15.12; p= 0.126). There was a statistically significant difference in the occurrence of postoperative morbidity in CAD patients with EF <30% and IB<10% who underwent OPCAB surgery compared with patients who underwent TCABG. Mortality that occurred after OPCAB procedure was lower in CAD patients with EF < 30% and IB<10% compared to TCABG although the statistical difference was not significant. Therefore, patients with this condition are more advisable to undergo OPCAB. Keyword: Ischemic burden, left ventricular dysnfunction, off-pump coronary artery bypass grafting


INTRODUCTION
Single photon emission computed tomography (SPECT) is regularly used to assess myocardial viability and ischemic burden before CABG (1). Ischemic burden shows the amount of ischemic-induced myocardium which can still improve at rest. The benefit of revascularization in patients with EF ≤ 30% and ischemic burden ≤ 10% remains questionable because of the high risks of postoperative mortality and morbidity. Furthermore, ischemic burden ≤ 10% reveals that only a small amount of myocardial ischemia improves at rest (2). However, myocardial ischemia that does not enhance at rest is due to either myocardial necrosis or myocardium stunning or hibernation (3).
CABG procedures can be performed using a cardiopulmonary bypass (CPB) machine, referred to as traditional coronary artery bypass grafting (TCABG), or without utilizing a CPB machine, termed as off-pump coronary artery bypass grafting (OPCAB). To date, there are no guidelines available for the selection of surgical techniques that can reduce postoperative mortality and morbidity in CAD patients with EF ≤ 30% and ischemic burden ≤ 10% with high perioperative risks. Many surgical specialists prefer TCABG to OPCAB, following that hemodynamic instability, hypotension, or sudden cardiac arrest are common problems in this group of patients (4,5). Surgery with the TCABG technique makes it easier for surgeons in performing coronary artery anastomosis due to heart immobility (4). The CPB machine and administration of cardioplegic fluid to stop the heart from beating provide a bloodless surgical field, without the movement of the heart muscle during CABG procedures. However, any contact with the CPB machine will cause a systemic inflammatory response and coagulopathy and potentially induce dysfunction of various organs, myocardial ischemia, and edema which further reduce myocardial function, thus increasing the risks of postoperative morbidity and mortality (4,6). The OPCAB procedure performed without using the CPB machine is expected to reduce such risks.
The purpose of this study was to compare the characteristics and the clinical outcomes between OPCAB and TCABG in patients with EF 30% and ischemic burden 10%. The results would help surgeons to decide which procedure is the best option for patients with this condition.

METHOD
This study used a retrospective analytic cohort study design to determine mortality and morbidity in 109 CAD subjects with EF ≤30% and ischemic burden ≤10%, by comparing OPCAB with TCABG over a period of January 2015 to November 2018 at the Harapan Kita National Cardiovascular Heart Center and by satisfying the study's inclusion and exclusion criteria. The inclusion criteria of this study were CAD subjects with EF ≤30% & ischemic burden ≤10% who underwent elective CABG procedures, while the exclusion criteria were CAD subjects with ischemic burden ≤10% who underwent emergency or urgent CABG procedures, CAD subjects with concomitant ruptured ventricular septum, CAD subjects accompanied by heart valve disease with moderate to severe degree requiring intervention that had been confirmed by echocardiography examination, and subjects with cardiac surgery other than CABG procedures. The study was conducted by taking the medical record data of the patients involved after obtaining permission from the research ethics committee of the Harapan Kita National Cardiovascular Heart Center.

Statistical Analysis
All data were analyzed using SPSS for Macintosh version 20.0 (SPSS, Inc. Chicago, Illnois). In the univariate analysis, nominal data were presented as proportions and frequencies in descriptive tables or narratives and tested using the Kolmogorov Smirnov test for normality test. Pearson's chi-square was applied for nominal variables and Student's T-test for continuous variables. For the bivariate analysis, Chi-Square test was performed with a 2x2 table and Relative Risk (RR) analysis. To assess the relationship of numerical dependent variables based on the categorical independent variables, a t-test was carried out when the data were normally distributed. However, when the data were not normally distributed, the Mann-Whitney test was conducted. Test results with p-value <0.05 were considered statistically significant.

Baseline of Operative Characteristics of Patients
The baseline characteristics of 109 patients who underwent OPCAB and TCABG are described in Table 1. The results indicated that there were no statistically significant differences in the characteristics of the research subjects and the intraoperative data of the two groups. Therefore, it could be inferred that the two groups were homogeneous. Based on the data in this study, the median (min-max) age of the patients with the OPCAB procedure compared to that of those with the TCABG procedure was not statistically significant [58 (41-67) years vs 57 (40-74) years, respectively; P=0.642].

Intraoperative Data of Patients
The intraoperative data as provided in Table 2 (2)(3)(4)(5) in the TCABG group, where these values too were statistically insignificant, with p=0.157. The intraoperative data of the two groups were also homogeneous because they were not statistically significant.

Postoperative Data of Patients
The length of stay in the hospital as given in Table 3 was statistically significantly lower after the OPCAB procedure than after the TCABG procedure, at 6 (4-27) days and 10 (1-35) days respectively, with p-value <0.001. This is generally caused by the fact that the incidence of morbidity was relatively lower in the OPCAB group than in the TCABG group.

DISCUSSION
Unlike the OPCAB technique, the TCABG technique is performed using a CPB machine that provides hemodynamic support for patients, allowing surgeons to manipulate the heart as needed without impairing their hemodynamic stability. However, the use of the CPB machine is related to the activation of the inflammatory system and has the potential to induce the failure of various organs after surgery. On the other side, the OPCAB technique has the advantage of limiting ischemia only to anastomosed coronary arteries which will reduce myocardial injury to provide better postoperative outcomes (8).
The length of stay in the hospital was statistically significantly lower after the OPCAB procedure than after the TCABG procedure. Generally, the incidence of morbidity is lower in the OPCAB group than in the TCABG group. This is supported by Elmahrouk, et al. (2018), who reported that the length of stay after the OPCAB procedure was lower than that after the TCABG procedure (9.8 + 5.6 and 12.86 + 9.86 days respectively, with p-value <0.001), showing significance in statistical difference (9).
In this research found that the morbidity during treatment in the OPCAB group lower than in the TCABG group. The morbidities were sourced from arrhythmias, renal failure, and postoperative stroke. Atrial fibrillation becomes the most common complication after cardiac surgery, affecting 10% to 40% of patients post CABG procedures. These arrhythmias occur most often in the first five days of the postoperative period, ranging from 24 to 72 hours, but they rarely come to happen after the first week (10).
Another complication in this study was postoperative acute renal failure which occurred at a lower rate after the OPCAB procedure. There is no comprehensive mechanism to explain kidney failure associated with heart surgery. It is thought to be the result of a complex interaction between a number of related factors. Clinical variables related to renal ischemia caused by arteriosclerosis and decreased cardiac Postoperative outcomes which produced statistically significantly different results were also found in the incidence of stroke. In this case, the occurrence of it after the OPCAB procedure was lower than after the TCABG procedure. Neurological dysfunction after CABG procedures can manifest as stroke, encephalopathy, delirium, and postoperative cognitive dysfunction (8).
Perioperative stroke is defined as a temporary or permanent, focal or global neurological deficit that occurs within 30 days after surgery or in hospital care. Prolonged reversible ischemic neurological deficits are defined as events lasting > 24 hours. All stroke results included in this study were examined by a neurologist and diagnosed with a computed tomography (CT-scan) of the head used for assessment of lesions, which were further confirmed by a radiology specialist (12).
In a multicenter prospective study of more than 2,000 patients, ascending aortic atherosclerosis is the strongest independent predictor of stroke associated with CABG procedures (13). Atheromatous flake embolization from the aorta may take place during aortic cannulation to connect to the CPB machine, when aortic cross clamps are installed or removed or when site aortic biting is utilized in proximal conduit anastomosis (14). Cerebral hypoperfusion can be worsened by carotid artery stenosis. In general, observational studies consistently suggest that the OPCAB procedure can reduce the risk of stroke, but this relationship has not been confirmed in a few randomized controlled trials (15 (17).
Although this research method is a retrospective analysis without random studies using medical record data, which caused some samples to be excluded due to data incompleteness, it is found that the samples of both groups remain homogeneous to reduce selection bias. This study has several limitations. One of them is the evaluation of postoperative outcomes which were only assessed during hospitalization. In fact, medium-term and long-term evaluations must be conducted to examine whether the OPCAB technique is better than the TCABG technique in terms of comparative survival, such as re-treatment in hospital, interventions reset, and quality of life. Another limitation is that these types of CABG procedures were not carried out by the same operator. The admission of patients to either of the groups was not random, but it was decided by the choice of the operator.
There were statistically significant differences in the occurrence of morbidities, including arrhythmias, kidney failure, and postoperative stroke, between CAD patients with EF ≤30% and ischemic burden ≤10% who underwent the OPCAB surgery and patients who underwent the TCABG surgery. Mortality was lower in patients with EF ≤30% and ischemic burden ≤10% after the OPCAB procedure than after the TCABG procedure, despite the fact that the difference was not statistically significant.