**2. Coronary Artery Bypass Grafting and medical/demographic predictors**

#### **2.1 Coronary Artery Bypass Grafting and obesity**

The accepted medical model for outcomes following Coronary Artery Bypass Grafting Surgery can be found in Figure 1. Falling second to Coronary Artery Disease, obesity is the second leading cause of death in the United States (Mokdad et al., 2000). It is well-known that patients categorized as obese are at unique risk for developing various cardiovascular diseases, including Coronary Artery Disease. Due to the general increased morbidity and reduced life expectancy of obese patients (Fontaine et al., 2003), many researchers have hypothesized that obesity should be linked to poorer outcomes post-Coronary Artery Bypass Grafting surgery. Yet, current research investigating the association between obesity (e.g., body mass index, BMI) and cardiac surgery outcomes has been contradictory. Some studies report no difference in short-term outcomes post-Coronary Artery Bypass Grafting between obese and non-obese patients (Engel et al., 2009; Engelman et al., 1999; Potapov et al., 2003; Rahmanian et al., 2007; Reeves et al., 2003; Schwann et al., 2003; Syrakas et al.,

Typically Coronary Artery Bypass Grafting surgery is performed via Cardiopulmonary Bypass; however, there are several drawbacks associated with Cardiopulmonary Bypass which may lead to complications following or during surgery (Edmunds et al., 2003). As a result of these complications, a technique utilizing an Off-Pump Coronary Artery Bypass procedure was developed. The Off-Pump Coronary Artery Bypass technique has recently gained popularity and can also be performed without involving Cardiopulmonary Bypass (Benetti et al., 1995; Buffolo et al., 1996; Calafiore et al., 1996; Dewey et al., 2001; Guler et al., 2001; Guru et al., 2007;Magee et al., 2001; Puskas et al., 1998; Trehan et al., 2001). While Off-Pump Coronary Artery Bypass has gained notoriety, some surgeons have opted out of using the technique due to suspicions that Off-Pump Coronary Artery Bypass may compromise patient outcomes. To help clarify these suspicions, researchers have turned their focus to investigating the effectiveness of Off-Pump Coronary Artery Bypass for treating patients with Coronary Artery Disease. The results of such studies have often been counter indicative. Some studies suggest that Off-Pump Coronary Artery Bypass has similar outcomes to conventional Coronary Artery Bypass Grafting surgery with respect to length of hospital stay, morbidity, and neurological deficiencies (Halkos et al., 2008; Puskas et al., 1998; Puskas et al., 2001) as well as comparable graft patency and hospitalization costs (Puskas et al., 2004). Conversely, other studies have reported less favorable Off-Pump Coronary Artery Bypass patient outcomes (e.g., lower graft patency rates and less complete revascularization) when compared to Coronary Artery Bypass Grafting patient outcomes (Khan et al., 2004). Still several other studies report no difference in early mortality, morbidity and hospitalization costs between the two procedures (Bull et al., 2001; Cheng et al., 2005; Cheng et al., 2002; Marasco et al., 2008; Takagi et al., 2007). Clearly, the studies to date comparing the Off-Pump Coronary Artery Bypass and Coronary Artery Bypass Grafting procedures present an unclear picture of potential differential outcomes for patients. In order to further investigate the difference between these two methods, Chu and colleagues (2009a) conducted a study using a nationwide database of over 63,000 Coronary Artery Bypass Grafting and Off-Pump Coronary Artery Bypass patients. The results revealed that the Off-Pump Coronary Artery Bypass and Coronary Artery Bypass Grafting procedures had similar in-hospital mortality, post-operative stroke incidences, and routine discharge rates. However, Off-Pump Coronary Artery Bypass patients had comparatively longer hospital stays and higher hospital costs than Coronary Artery Bypass

**2. Coronary Artery Bypass Grafting and medical/demographic predictors** 

The accepted medical model for outcomes following Coronary Artery Bypass Grafting Surgery can be found in Figure 1. Falling second to Coronary Artery Disease, obesity is the second leading cause of death in the United States (Mokdad et al., 2000). It is well-known that patients categorized as obese are at unique risk for developing various cardiovascular diseases, including Coronary Artery Disease. Due to the general increased morbidity and reduced life expectancy of obese patients (Fontaine et al., 2003), many researchers have hypothesized that obesity should be linked to poorer outcomes post-Coronary Artery Bypass Grafting surgery. Yet, current research investigating the association between obesity (e.g., body mass index, BMI) and cardiac surgery outcomes has been contradictory. Some studies report no difference in short-term outcomes post-Coronary Artery Bypass Grafting between obese and non-obese patients (Engel et al., 2009; Engelman et al., 1999; Potapov et al., 2003; Rahmanian et al., 2007; Reeves et al., 2003; Schwann et al., 2003; Syrakas et al.,

**2.1 Coronary Artery Bypass Grafting and obesity** 

**1.3 Variations of Coronary Artery Bypass Grafting Surgery** 

Grafting patients.

2007). Others have found that morbid obesity independently predicts perioperative complications as well as operative mortality (Prabhakar et al., 2002). One study by Syrakas and colleagues (2007) even found that normal weight patients had a higher 30-day mortality rate than their obese peers post-surgery. In fact, overall, research seems to suggest that morbid obesity does not increase short-term mortality risk for Coronary Artery Bypass Grafting patients (Baslaim et al., 2008; Shirad et al., 2009; Syrakas et al., 2007). Since research regarding the association between obesity and cardiac surgery has included mostly shortterm outcomes, Del Prete and associates (2010) investigated the independent effect of obesity on long-term survival in patients (472 obese and 691 non-obese) who had Coronary Artery Bypass Grafting surgery. Results revealed obese and non-obese patients had similar intraoperative characteristics (e.g., cardiopulmonary bypass time, aortic cross-clamp time, and number of vein and IMA grafts) and post-operative outcomes. Of particular interest was that the rates of mortality and major adverse cardiac events after 30 days were not significantly different between the two groups. Most interestingly, the researchers determined that obese Coronary Artery Bypass Grafting patients demonstrated long-term survival (9 years follow-up) similar to non-obese Coronary Artery Bypass Grafting patients. While these findings are counterintuitive, these results combined with results of studies examining short-term outcomes seem to indicate that obesity is not a significant risk for patients undergoing Coronary Artery Bypass Grafting surgery.

#### **2.2 Coronary Artery Bypass Grafting and age**

Due to improvements in medical care, the average life expectancy has increased significantly in recent years. Subsequently, there has been an increase in the number of geriatric patients with cardiac disease that need surgical intervention such as Coronary Artery Bypass Grafting surgery. In addition, this population also tends to have multiple comorbidities which may cause complications; however, Coronary Artery Bypass Grafting procedures in octogenarian patients (those over the age of 80), have demonstrated improved morbidity and mortality outcomes (Alexander et al., 2000; Kolh et al., 2001; Shigemitsu et al., 2001). However, while most of these Coronary Artery Bypass Grafting surgeries are technically successful, they may cause significant physiological adverse events, potentially deconditioning them substantially. Unfortunately, there has not been a wealth of literature investigating these physiological outcomes which may affect the health and well-being of these patients. As a result, Gopaldas et al. (2010) conducted a study investigating the disposition of octogerians following Coronary Artery Bypass Grafting surgery.

Gopaldas identified 5,731 patients over age 80 who underwent Coronary Artery Bypass Grafting surgery. It was discovered that the surgical mortality rate was 7%, and 21% of patients had a routine hospital discharge. Those that did not have a routine discharge had home health care (27%) or were transferred to another care facility (45%). In addition, several predictors of surgical mortality and nonroutine discharge were found: older age, females, a higher comorbidity index, and referral from the emergency room were all found to be independent predictors of these unfavorable outcomes. Thus, it is clear that while mortality rate in octogenarians is low, there are several circumstances that need to be considered to ensure more favorable outcomes following discharge.

#### **2.3 Coronary Artery Bypass Grafting and gender**

Women are particularly affected by heart disease, and coronary heart disease has consistently been reported as the leading cause of morbidity and mortality of women in most developed countries (Center for Disease Control and Prevention, 2010; Lloyd-Jones et

Psychiatric Factors Which Impact Coronary Heart Disease and

routine discharge.

**2.5 Diabetes** 

Influence Outcomes Post-Coronary Artery Bypass Grafting Surgery 65

Rate Variability, and plasma norepinephrine levels with depression and Autonomic Nervous System activity in addition to their relationship to Coronary Artery Bypass Grafting outcomes. In addition, a second analysis was conducted investigating the 3 aforementioned variables in cardiac patients (Coronary Artery Disease and Depression versus Coronary Artery Disease alone) and surgery outcomes (length of hospital stay, routine versus non-routine discharge status) while controlling for other factors (medical factors such as diabetes and demographic factors such as age). It was hypothesized that patients with Coronary Artery Disease and Depression would have the greatest amount of Autonomic Nervous System dysregulation while the group without Coronary Artery Disease or depression would have the least Autonomic Nervous System dysregulation. In addition, it was hypothesized that the aforementioned variables would predict outcomes following Coronary Artery Bypass Grafting surgery. Analyses revealed that patients with Coronary Artery Disease and Depression had greater Autonomic Nervous System dysregulation when compared to those that had either Coronary Artery Disease or depression alone. Also, it was determined that depression, as well as elevated heart rate and depressed Heart Rate Variability, predicted increased length of hospital stay and non-

It has been found that systematic disease may increase the risks associated with Coronary Artery Bypass Grafting surgery. Several studies have reported that diabetes is a critical factor and mortality rates are two to three times higher than in non-diabetics (Johnson et al., 1982; Lawrie et al., 1986; Salomon et al., 1983). In addition, patients with diabetes tend to

A proposed psychological model for outcomes following Coronary Artery Bypass Grafting Surgery is proposed in Figure 1. Research has demonstrated that medical and demographic factors such as age, gender, diabetes, etc. cannot fully explain the outcomes following Coronary Artery Bypass Grafting surgery (Blumenthal et al., 2003; Saur et al., 2001). Several studies have been published investigating the association between Coronary Artery Disease and psychological functioning, primarily depression (Bankier et al., 2004; Oxland et al., 2006). It has been reported that up to 60% of patients with Coronary Artery Disease have comorbid depression which has a significant impact on the outcomes of Coronary Artery Disease (Blumenthal et al., 2003; Connerney et al., 2001; Krannich et al., 2007; Tully et al., 2008). Those with depression have higher rates of mortality as well as an overall risk of major cardiac events (Blumenthal et al., 2003; Carney et al., 1988; Connerney et al., 2001). Specifically, depressive symptoms also signicantly predict mortality 2 to 5 years after Coronary Artery Bypass Grafting surgery, independent of medical and operative factors (Blumenthal et al., 2003; Burg et al., 2003a; Burg et al., 2003b. Unlike depression, the impact of other psychological conditions, such as Post-traumatic Stress Disorder on outcomes after

have more post-CABG surgery complications which reduce long-term survival.

**3. Coronary Artery Bypass Grafting and psychological predictors** 

Coronary Artery Bypass Grafting surgery has received less attention in research.

The gap in the literature investigating the relationship between Post-traumatic Stress Disorder on outcomes after Coronary Artery Bypass Grafting surgery needs to be examined independently from depression for several reasons. Specifically, studies have demonstrated

**3.1 Depression and Post-Traumatic Stress Disorder** 

al., 2010; Stoney et al., 2003). In 2006, 1 in 6 reported female deaths were due to Coronary Artery Disease (Januzzi et al., 2000), and research suggests that being female is related to poorer Coronary Artery Bypass Grafting outcomes (Blankstein et al., 2005; Culler et al., 2008; Kim et al., 2007; Sawatzky et al., 2009). Women have higher mortality rates, remain in the hospital longer (Dao, 2010b), experience a more difficult recovery (Sawatzky et al., 2009), and self-report being less satisfied with health status after Coronary Artery Bypass Grafting surgery (Sawatzky et al., 2009).

Dao and colleagues (2011c) conducted a study investigating gender differences and outcomes following Coronary Artery Bypass Grafting surgery. It was reported that being female and having an anxiety disorder diagnosis independently and collectively contributed to in-hospital length of stay and non-routine discharge following a Coronary Artery Bypass Grafting surgery. In addition, significant differences were found between groups in age, gender, race, median household income, medical comorbidities, and having an anxiety disorder diagnosis. Specifically, patients with non-routine discharges were more likely to be older, female, non-Caucasian, have more medical comorbidities, and have an anxiety disorder diagnosis.

#### **2.4 Autonomic Nervous System dysregulation**

As mentioned previously, the association between depression and cardiac events, particularly Coronary Artery Disease, has been validated consistently in research; yet, the mechanism behind this relationship is unclear. One proposed underlying factor in this relationship is altered autonomic nervous system (Autonomic Nervous System) activity. Altered Autonomic Nervous System activity has been suggested to contribute to elevated mortality risk (and poorer general outcomes) in patients with Coronary Artery Disease, and individuals with Major Depressive Disorder often have Autonomic Nervous System dysregulation (Barnes et al., 1983; Esler et al., 1982; Lake et al., 1982). In addition, research suggests that depressed individuals have higher baseline heart rates (Lake et al., 1982; Siever et al., 1985; Veith et al., 1994), increased heart rate response to stressors (Carney et al., 1988a; Guinjoan et al., 1995), and decreased heart rate variability (HRV) (Appelhans et al., 2006; Carney et al., 1988b; Dallack et al., 1990; Rechlin et al., 1994) when compared to similar peers. In particular, increased Heart Rate Variability has been associated with greater abilities to regulate stress, arousal, and attention, while decreased Heart Rate Variability has been associated with inadequate parasympathetic modulation and increased cardiac sympathetic modulation (Task Force of the European Society of Cardiology and the North American Society for Pacing and Electrophysiology, 1995). Most relevant to this chapter, studies suggest that Heart Rate Variability is lower in Coronary Artery Disease patients with comorbid depression than those with Coronary Artery Disease alone (Krittayaphong et al., 1997; Stein et al., 2000). Taken together, this literature suggests that depressed individuals may not only have an elevated initial heart rate and higher heart rate in reaction to stressors, but they may also have lower Heart Rate Variability that makes it more difficult to manage these other elevated heart rate situations.

Another factor not previously understood was whether patients with Autonomic Nervous System dysregulation also have increased mortality with these concurrent disorders. Dao and colleagues (2010a) proposed a study investigating three variables (heart rate, Heart Rate Variability, and plasma norepinephrine levels) in the following groups: 1) Patients with Coronary Artery Disease and depression, 2) Patients with Depression alone, 3) Patients with Coronary Artery Disease alone, and 4) Patients without neither Coronary Artery Disease nor depression. The focus of the study was to compare the association of heart rate, Heart Rate Variability, and plasma norepinephrine levels with depression and Autonomic Nervous System activity in addition to their relationship to Coronary Artery Bypass Grafting outcomes. In addition, a second analysis was conducted investigating the 3 aforementioned variables in cardiac patients (Coronary Artery Disease and Depression versus Coronary Artery Disease alone) and surgery outcomes (length of hospital stay, routine versus non-routine discharge status) while controlling for other factors (medical factors such as diabetes and demographic factors such as age). It was hypothesized that patients with Coronary Artery Disease and Depression would have the greatest amount of Autonomic Nervous System dysregulation while the group without Coronary Artery Disease or depression would have the least Autonomic Nervous System dysregulation. In addition, it was hypothesized that the aforementioned variables would predict outcomes following Coronary Artery Bypass Grafting surgery. Analyses revealed that patients with Coronary Artery Disease and Depression had greater Autonomic Nervous System dysregulation when compared to those that had either Coronary Artery Disease or depression alone. Also, it was determined that depression, as well as elevated heart rate and depressed Heart Rate Variability, predicted increased length of hospital stay and nonroutine discharge.

#### **2.5 Diabetes**

64 Front Lines of Thoracic Surgery

al., 2010; Stoney et al., 2003). In 2006, 1 in 6 reported female deaths were due to Coronary Artery Disease (Januzzi et al., 2000), and research suggests that being female is related to poorer Coronary Artery Bypass Grafting outcomes (Blankstein et al., 2005; Culler et al., 2008; Kim et al., 2007; Sawatzky et al., 2009). Women have higher mortality rates, remain in the hospital longer (Dao, 2010b), experience a more difficult recovery (Sawatzky et al., 2009), and self-report being less satisfied with health status after Coronary Artery Bypass Grafting

Dao and colleagues (2011c) conducted a study investigating gender differences and outcomes following Coronary Artery Bypass Grafting surgery. It was reported that being female and having an anxiety disorder diagnosis independently and collectively contributed to in-hospital length of stay and non-routine discharge following a Coronary Artery Bypass Grafting surgery. In addition, significant differences were found between groups in age, gender, race, median household income, medical comorbidities, and having an anxiety disorder diagnosis. Specifically, patients with non-routine discharges were more likely to be older, female, non-

As mentioned previously, the association between depression and cardiac events, particularly Coronary Artery Disease, has been validated consistently in research; yet, the mechanism behind this relationship is unclear. One proposed underlying factor in this relationship is altered autonomic nervous system (Autonomic Nervous System) activity. Altered Autonomic Nervous System activity has been suggested to contribute to elevated mortality risk (and poorer general outcomes) in patients with Coronary Artery Disease, and individuals with Major Depressive Disorder often have Autonomic Nervous System dysregulation (Barnes et al., 1983; Esler et al., 1982; Lake et al., 1982). In addition, research suggests that depressed individuals have higher baseline heart rates (Lake et al., 1982; Siever et al., 1985; Veith et al., 1994), increased heart rate response to stressors (Carney et al., 1988a; Guinjoan et al., 1995), and decreased heart rate variability (HRV) (Appelhans et al., 2006; Carney et al., 1988b; Dallack et al., 1990; Rechlin et al., 1994) when compared to similar peers. In particular, increased Heart Rate Variability has been associated with greater abilities to regulate stress, arousal, and attention, while decreased Heart Rate Variability has been associated with inadequate parasympathetic modulation and increased cardiac sympathetic modulation (Task Force of the European Society of Cardiology and the North American Society for Pacing and Electrophysiology, 1995). Most relevant to this chapter, studies suggest that Heart Rate Variability is lower in Coronary Artery Disease patients with comorbid depression than those with Coronary Artery Disease alone (Krittayaphong et al., 1997; Stein et al., 2000). Taken together, this literature suggests that depressed individuals may not only have an elevated initial heart rate and higher heart rate in reaction to stressors, but they may also have lower Heart Rate Variability that makes it more difficult

Another factor not previously understood was whether patients with Autonomic Nervous System dysregulation also have increased mortality with these concurrent disorders. Dao and colleagues (2010a) proposed a study investigating three variables (heart rate, Heart Rate Variability, and plasma norepinephrine levels) in the following groups: 1) Patients with Coronary Artery Disease and depression, 2) Patients with Depression alone, 3) Patients with Coronary Artery Disease alone, and 4) Patients without neither Coronary Artery Disease nor depression. The focus of the study was to compare the association of heart rate, Heart

Caucasian, have more medical comorbidities, and have an anxiety disorder diagnosis.

surgery (Sawatzky et al., 2009).

**2.4 Autonomic Nervous System dysregulation** 

to manage these other elevated heart rate situations.

It has been found that systematic disease may increase the risks associated with Coronary Artery Bypass Grafting surgery. Several studies have reported that diabetes is a critical factor and mortality rates are two to three times higher than in non-diabetics (Johnson et al., 1982; Lawrie et al., 1986; Salomon et al., 1983). In addition, patients with diabetes tend to have more post-CABG surgery complications which reduce long-term survival.
