Risk Factors for Mortality of Patients Waiting for Elective Coronary Artery Bypass Graft Surgery ()
1. Introduction
Coronary Artery Disease (CAD) is the leading cause of death in the world today. The World Health Organization (WHO) states that CAD has become a global cause of death in the past 15 years because its prevalence continues to increase rapidly in developing and developed countries [1]. Coronary Artery Bypass Graft (CABG) surgery is one of the therapeutic modalities that has been shown to be effective in prolonging the life span of patients with stable CAD [2]. CABG can improve angina complaints in the majority of patients undergoing this procedure. The more severe the CAD, the stronger the indication for CABG [3].
As the increasing progress in health facilities and patient care for their health, causing CAD detection rates to increase and the need for surgical procedures such as CABG also increases, however, the contrast occurs where the economic constraints on the health system are developing less rapidly which means lack of resources and facilities to accommodate patients requiring CABG [4]. Patients on the waiting list are at high risk for acute coronary events. The natural history of CAD will imply a critical event that can occur at any time during the waiting time from the patient’s first complaint until surgery [5]. Patients waiting for CABG have been reported to be at high risk of death and their risk of death increases when surgery is postponed because of the long waiting list [6].
Various risk factors have been known to influence mortality while waiting for surgery, including involvement of stenosis in the left main coronary artery, creatinine levels, history of myocardial infarction [7], CAD risk factors [8] [9], age [10], and impaired left ventricular function [10] [11]. No previous study was done in Indonesia to determine risk factors for mortality in patients waiting for CABG surgery, therefore it needs to be investigated further.
2. Materials and Methods
2.1. Study Design and Population
This study was a retrospective cohort study conducted using medical record data of patients waiting for CABG at Dr. Kariadi Hospital Semarang for the period January 2018 to December 2020. The inclusion criteria in this study were as follows: 1) Patients aged > 18 years to 80 years. 2) CAD patients who are candidates for CABG surgery are listed on the waiting list. Waiting time for surgery > 3 months. The exclusion criteria in this study were as follows: 1) Known to suffer from heart valve disease, congenital heart defects, malignancies, and autoimmune diseases which are thought to be the main causes of death. 2) Percutaneous Coronary Intervention (PCI) has been performed 3) Incomplete medical record data. Information about the variables was obtained from previous studies that have been shown as a risk factor for mortality in patients awaiting CABG surgery. There were 7 independent variables analyzed as independent predictors of risk factors for mortality in patients waiting for elective CABG surgery at Dr. Kariadi Hospital Semarang: 1) Age > 65 years old. 2) Number of CAD risk factors ≥ 3. 3) History of Myocardial Infarction. 4) Serum creatinine level > 1.5 mg/dl. 5) Ischemic ECG. 6) Left ventricular ejection fraction ≤ 45%. 7) Stenosis of the left main coronary artery.
2.2. Endpoints and Definitions
The endpoint parameter was death, which death from all causes that occur any time before surgery after the patient was listed on the waiting list for CABG surgery and the patient will be removed from the waiting list. Deaths were obtained from telephone interviews with families or medical records. Waiting time was defined by the time a patient starts after being accepted for the CABG procedure and was listed on the waiting list until the CABG surgery was performed, the surgery was canceled, or the patient died [8] [9].
2.3. Statistical Analysis
Data analysis includes descriptive analysis. In a descriptive analysis of continuous scale, variable data were expressed as the mean and standard deviation if the distribution were normal or median and the minimum-maximum value if the distribution were not normal. Categorical scale variable data was expressed in number (n) and percentage (%). To test the hypothesis, the relationship between each independent variable and the dependent variable was analyzed using the unpaired t-test & Mann Whitney test. Multivariate analysis was performed by using linear regression predictive value with 95% confidence interval. The p-value was considered significant if it is <0.05. The magnitude of the risk was expressed as the odds ratio obtained from the multivariate logistic regression analysis.
3. Results
3.1. Baseline Characteristics
In the period January 2018 - December 2020, 191 patients were found, of which 162 patients met the inclusion criteria. There were 29 patients excluded from the study with details of 13 patients because the waiting time for surgery was less than 3 months, 6 patients because of involvement of heart valve disease, 6 patients because of a history of percutaneous coronary intervention, 2 patients due to ventricular septal rupture, 1 patient due to medical records incomplete, 1 patient died of rectosigmoid cancer (Figure 1).
Baseline characteristics of patients waiting for CABG Surgery were shown in Table 1. The study consisted of 135 men (83.3%) and 27 women (16.7%). The mean age ranged from 59.1 ± 6.66 years with a mean body mass index of 24.83 ± 3.78. 3 patients (1.9%) with BMI Underweight, 37 patients (22.8%) normal, 51 patients (31.5%), overweight, 71 patients (43.8%) obese. From laboratory examination data for kidney function, it was found that the mean serum creatinine level was 1.3 ± 0.32 with the lowest level of 0.75 and the highest at 3. Echocardiographic findings showed that the mean left ventricular ejection fraction (LVEF) was 48.12 ± 14.63 with the lowest ejection fraction at 14% and the highest at 78%. The angiographic data found that most of the patients had lesions on their three coronary arteries, namely 156 patients (96.3%) with CAD 3VD, and there were 6 patients (3.7%) with CAD 2VD. From the coronary angiography results, it was also found that 77 patients (47.5%) had lesions involving the left main coronary artery, and 83 patients (51%) had lesions with chronic total occlusion of their coronary arteries. The mean SYNTAX Score was 30.24 + 3.66. All 162 patients (100%) received antiplatelets. Beta-blockers, ACEi or ARB, nitrates and statins each had reported use of more than 80% by the study cohort. Based on the length of waiting time for CABG surgery, the average waiting time was 9.8 ± 6.02 months.
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Figure 1. Process for selecting respondent.
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Table 1. Baseline characteristics of patients waiting for CABG surgery.
ACEi: Angiotensin-Converting Enzym inhibitor; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; CAD: Coronary Artery Disease; CCB: Calcium Channel Blocker; CTO: Chronic Total Occlusion; DM: Diabetes Mellitus; ECG: Electrocardiograhy; EF: Ejection Fraction; LAD: Left Anterior Descending; LCx: Left Circumflex; LM: Left Main; MRA: Mineralocorticoid Receptor Antagonist; RCA: Right Coronary Artery; VD: Vessel Disease.
3.2. Mortality
While waiting for CABG surgery, 32 patients died with a mean age of 60.53 ± 4.84; 59 (54 - 70) and the mean duration from the time of registering for CABG surgery until the patient died was 147 + 144; 113 (0 - 606) days. The cause of death was shown in Table 2. The most causes of death were due to cardiac arrest in 21 patients (65.6%) and 2 patients (6.3%) died from a stroke.
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Table 2. Data on causes of death in patients waiting for CABG surgery.
3.3. Bivariate Analysis
Furthermore, bivariate analysis of the variables associated with the incidence of mortality in patients waiting for CABG surgery was carried out (Table 3). For variables on an ordinal scale, the bivariate analysis of the Chi-Square test was carried out using a cut-off based on the theoretical basis of previous studies. In the bivariate analysis, a significant statistical correlation was observed in most variables: left ventricular ejection fraction ≤ 45% (RR 5.237; p = 0.000), serum creatinine ≥ 1.5 mg/dl (RR 4.276; p = 0.000), left main disease (RR 3.312; p = 0.001), number of coronary artery disease risk factors ≥ 3 (RR 3.039; p = 0.001), and ischemic ECG (RR 3.035; p = 0.017). No significant differences were observed in the history of myocardial infarction (RR 1.315; p = 0.432), and age ≥ 65 years (RR 1.210; p = 0.634).
3.4. Multivariate Analysis
The risk factor variables in the bivariate analysis which have p value < 0.25 then analyzed in the multivariate logistic regression test. These variables were serum creatinine levels ≥ 1.5 mg/dl, LM Disease, left ventricular ejection fraction ≤ 45%, number of CAD risk factors ≥ 3, and ischemic ECG. In the multivariate analysis, there were 4 risk factor variables: serum creatinine levels ≥ 1.5 mg/dl, LM Disease, left ventricular ejection fraction ≤ 45%, number of CAD risk factors ≥ 3 which reached statistical significance, and no association between ischemic ECG and mortality on the incidence of mortality in patients waiting for CABG surgery (Table 4).
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Table 3. Bivariate analysis of risk factors for mortality in patients waiting for CABG surgery.
‡ Chi-square test. § Fisher’s exact test. CAD: Coronary Artery Disease; ECG: Electrocardiography; LM: Left Main.
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Table 4. Multivariate analysis of risk factors for mortality in patients waiting for elective coronary artery bypass surgery.
CAD: Coronary Artery Disease; LM: Left Main.
4. Discussion
This study demonstrated a high rate of mortality (19.7%) in CAD patients who died while waiting for CABG surgery. In comparison, previous studies reported lower mortality rates of 11.3% in Brazil [9], 0.02% in the Netherlands [8], 0.48% in Canada [10], and 1.3% in Sweden [7]. The sharp difference in the rate of mortality could be attributable to the availability of human resources and surgical facilities, a system for prioritizing patients where patients with high risk will be operated on earlier, and also clinical characteristics backgrounds. In this study, patients showed a higher proportion of risk factors and lower left ventricular ejection fraction. Furthermore, urgent cases were included in this study, meanwhile, in another study, the respondents included were only elective cases [12].
Left ventricular ejection fraction (LVEF) less than 45% was the strongest independent predictor of mortality in patients waiting for CABG. Fonseca et al. in their study found that ejection fraction ≤ 45% was an independent predictor of mortality in patients waiting for CABG surgery (HR 2.33; 95% IK; p = 0.039). There was also significant evidence that delaying surgery for patients with severe left ventricular dysfunction likely results in an increased number of deaths while waiting for CABG (OR 2.47; 95% CI; p < 0.001) [10]. Rexius et al. revealed that patients with a decreased ejection fraction of 10% were associated with a 28% increase in the risk of death while waiting for CABG (RR 1.27; 95% CI; p = 0.007) [7].
This study found that 82% of the population had a number of CAD risk factors ≥ 2, and even 45.6% of them had a number of CAD risk factors ≥ 3. Sub-analysis was performed and 2 variables were contributed significantly, dyslipidemia and smoking (data not shown). Suttorp et al. found that smoking history increased the risk of death 9-fold in CAD patients waiting for elective CABG surgery (OR 8.7; 95% CI) [13].
Among respondents, 77 patients (47.5%) had LM disease which contributed to a higher rate of mortality. A previous study found that LM disease or multivessel CAD was also associated with a 4-fold higher incidence of early death while waiting for CABG surgery (OR 4.1; 95% CI) [13].
Serum blood creatinine ≥ 1.5 mg/dl was an independent risk factor after the multivariate logistic regression test with OR 3.71 (95% CI, p = 0.008). A previous study also found the same result, Rexius et al. found that the mean creatinine level of 104 + 53 (1.18 mg/dL) was associated with the risk of death while waiting for CABG surgery (p ≤ 0.001). It was also significantly associated with the incidence of CAD even though it was at normal values and in the absence of the metabolic syndrome.
There were 3 variables that were not proven to be independent risk factors for mortality in patients waiting for elective CABG surgery, including age; history of myocardial infarction; and ischemic ECG. In this study, patients were younger than in previous studies. A study by Cox et al. determined similar results in which there was no significant difference in age between study groups while waiting for CABG (p = 0.218) [14]. Seddon et al. in New Zealand also found that there was no significant difference in age between the priority groups while waiting for CABG (p = 0.9) [15].
This study found that the group of patients who died had a history of myocardial infarction higher than the CABG group. However, the difference between the two groups was not significant (p = 0.432). Cesena et al. reported that a history of extensive anterior myocardial infarction had no statistical effect in patients waiting for CABG (p = 0.19) [12]. Cox et al. in their study reported a high trend toward a history of myocardial infarction in patients who received priority of CABG, but statistically the results were not significant (p = 0.081) [14].
Ischemic ECG has a strong prognostic value for cardiovascular events [16], but in this study, it was not an independent predictor of patients waiting for CABG. Some of died patients had a normal ECG (9.4%) so it may affect the significance value of the ischemic ECG. The ECG examination in this study was carried out by tracing only a single ECG examination when the patient was admitted to clinic after the patient had received medical therapy. Some studies showed that a single ECG examination will be in changing conditions so that it will reduce the strength of its relative risk [17]. Several studies have reported that ST-segment abnormalities and T waves are unstable images due to the influence of drugs and other conditions such as electrolyte imbalance disorders. Study by Reykjavik et al. found that more than 36% of men with ST-T abnormalities did not show these abnormalities at subsequent follow-up [18].
The cause of death of most patients was related to the heart. Plomp et al. in their study divided 2 causes of death during waiting time: cardiac, and non-cardiac. All patients who died would be considered cardiac until the non-cardiac cause of death could be identified properly [19]. Rexius et al. reported that in about 95% of patients who died while waiting for CABG, the cause of death was cardiovascular-related as evidenced by their death certificates [7]. Ray et al. even described clearly about the cause of death in 2102 patients on the CABG waiting list. Among these patients, there were 14 (0.7%) patients who died with the cause of death mostly related to the heart [20].
Several limitations were found in this study. First, this study used retrospective secondary data that was dependent on the accuracy and completeness of medical health records. Second, the absence of surgical priority on the patient waiting list and the surgical decisions that have been taken may be subjective depending on the patient and clinician so it can affect the clinical course of the patient. Third, some data on the causes of death were obtained from interviews with the patient’s family that may not describe the exact cause of death.
5. Conclusion
Long waiting time for CABG is associated with a high mortality rate which is influenced by left ventricular ejection fraction ≤ 45%, left main disease, serum creatinine ≥ 1.5 mg/dl, and a number of coronary arteries disease risk factors ≥ 3.
Funding
This research study was funded by Direktorat Riset dan Pengabdian Masyarakat (DRPM) in PDUDT Scheme for Diponegoro University Grant Number 225-83/UN7.6.1/PP/2020.