In those patients who remain above the BP goal despite a suitably titrated regimen including a -blocker and, if appro- priate, an ACE inhibitor, then a calcium channel blocker or a diuretic can be considered as a next therapy choice.A long-act- ing dihydropyridine calcium channel blocker can effectively reduce BP and prevent graft spasm (radial artery conduit) and may offer an antianginal effect. Nondihydropyridine calcium channel blockers such as verapamil and diltiazem are effec- tive antihypertensive agents, but they are generally reserved for rate control in patients with coexisting chronic obstructive pulmonary disease and normal LV function. Diuretic therapy can be used in the CABG patient with hypertension either for volume removal if the patient is edematous or for further BP reduction when given together with an ACE inhibitor or a Selection of a diuretic class depends on the level of renal function, with thiazide-type drugs generally reserved for patients with a glomerular filtration rate >30 mL/min and loop diuretics used for patients with lower glomerular filtra- tion rates and the need for a diuretic of greater potency.234 Resistant hypertension is no more common in the post- CABG patient than in the general hypertensive population, and the approach to treatment is fairly similar. In patients already treated with an ACE inhibitor, -blocker, diuretic, and calcium channel blocker who remain above goal BP, other treatment options include compounds that reduce adrenergic activity such as clonidine or doxazosin. In addition, a min- eralocorticoid receptor antagonist such as spironolactone or eplerenone can be effective in lowering BP in the patient with resistant hypertension, particularly in the setting of LV dys- function, while affording cardiovascular benefits, including reduced myocardial fibrosis, prevention or reversal of cardiac remodeling, or a reduction in arrhythmogenesis.235 Hypertension Management Recommendations 1.


In addition, a min- eralocorticoid receptor antagonist such as spironolactone or eplerenone can be effective in lowering BP in the patient with resistant hypertension, particularly in the setting of LV dys- function, while affording cardiovascular benefits, including reduced myocardial fibrosis, prevention or reversal of cardiac remodeling, or a reduction in arrhythmogenesis.235 Hypertension Management Recommendations 1. -Blockers should be administered as soon as possi- ble after CABG, in the absence of contraindications, to reduce the risk of postoperative AF and to facili- tate BP control early after surgery (Class I; Level of Evidence A). 2. ACE inhibitor therapy should be administered after CABG for patients with recent MI, LV dysfunction, diabetes mellitus, and chronic kidney disease, with careful consideration of renal function in determin- ing the timing of initiation and dose selection after surgery (Class I; Level of Evidence B). 3. With the use of antihypertensive medications, it is reasonable to target a BP goal of <140/85 mmHg after CABG; however the ideal BP target has not been formally evaluated in the CABG population (Class IIa; Level of Evidence B). 4. It is reasonable to add a calcium channel blocker or a diuretic agent as an additional therapeutic choice if the BP goal has not yet been achieved in the peri- operative period after CABG despite -blocker ther- apy and ACE inhibitor therapy as appropriate (Class IIa; Level of Evidence B). 5. In the absence of prior MI or LV dysfunction, anti- hypertensive therapies other than -blockers should be considered for chronic hypertension manage- ment long term after CABG (Class IIb; Level of Evidence B). 6.


In the absence of prior MI or LV dysfunction, anti- hypertensive therapies other than -blockers should be considered for chronic hypertension manage- ment long term after CABG (Class IIb; Level of Evidence B). 6. Routine ACE inhibitor therapy is not recommended early after CABG among patients who do not have a history of recent MI, LV dysfunction, diabetes mellitus, or chronic kidney disease because it may lead to more harm than benefit and an unpredictable BP response (Class III; Level of Evidence B). Previous MI and LV Dysfunction Surgical revascularization is commonly performed for patients with reduced ejection fraction (EF) <40%.236 The most com- mon cause of reduced EF is previous MI, although other abnormalities such as valvular heart disease and hypertension are also recognized causes. Some patients have post-MI stun- ning or myocardial hibernation attributable to chronic isch- emia from severe CAD. Although many have improvement or recovery in their cardiac function after surgical revasculariza- tion, others have persistent heart failure and LV dysfunction The current discussion focuses on the appli- cation of secondary prevention therapies, including medical and device therapy after CABG, for patients with persistently reduced EF despite revascularization. -Blocker Therapy Elevated plasma catecholamine levels and direct sympathetic activity have deleterious effects on the heart by causing tachy- cardia, vasoconstriction, increased contractility, and ventricu- -Blockers blunt these effects and impede the maladaptive ventricular remodeling from chronic sympa- thetic activation. As described above, in addition to preventing heart failure, -blockers prevent recurrent ischemia and AF, a common postoperative condition. Most patients with persistently reduced EF after CABG are likely to have had a prior MI, and in this patient popula- tion, evidence supports the use of -blockers on top of back- ground therapy with ACE inhibitors, even in the absence of heart failure.


Most patients with persistently reduced EF after CABG are likely to have had a prior MI, and in this patient popula- tion, evidence supports the use of -blockers on top of back- ground therapy with ACE inhibitors, even in the absence of heart failure. Three specific -blockers (carvedilol, bisoprolol, and sustained-release metoprolol succinate) have documented benefits for morbidity and mortality and are highly recom- mended for patients with active or past symptoms of heart In addition, these medications reduce heart fail- ure symptoms, enhance patients overall sense of well-being, and reduce hospitalization, even among patients already tak- ing ACE inhibitors.197,208,238,239 Contraindications to -blocker use include bradycardia, hypotension, severe bronchospastic airway disease, low-output state, or severe, actively decom- pensated heart failure. ACE Inhibitor and ARB Therapy ACE inhibitors exert their effects by suppressing the effects of angiotensin II, a potent vasoconstrictor that reduces renal perfusion, stimulates LV hypertrophy and cardiac remodel- ing, and enhances the release of arginine, vasopressin, proin- flammatory cytokines, and aldosterone.237 Inhibition of ACE results in decreased levels of angiotensin II and inhibits the breakdown of bradykinin, a peptide with favorable properties, including antihypertensive, antiremodeling, and natriuretic effects.


ACE Inhibitor and ARB Therapy ACE inhibitors exert their effects by suppressing the effects of angiotensin II, a potent vasoconstrictor that reduces renal perfusion, stimulates LV hypertrophy and cardiac remodel- ing, and enhances the release of arginine, vasopressin, proin- flammatory cytokines, and aldosterone.237 Inhibition of ACE results in decreased levels of angiotensin II and inhibits the breakdown of bradykinin, a peptide with favorable properties, including antihypertensive, antiremodeling, and natriuretic effects. ARBs directly inhibit the action of angiotensin II by blocking the type 1 receptor, but their effects on bradykinin Oral ACE inhibitors have been shown to reduce symptom- atic heart failure and mortality among patients with previous MI and reduced EF.241 243 Among patients with reduced EF and active or prior heart failure symptoms, ACE inhibitors reduce mortality and heart failure hospitalization, improve New York Heart Association (NYHA) classification, reduce heart size, and prevent the need for escalating medical therapy.244 246 The routine initiation of an ACE inhibitor early after CABG is not recommended for patients with an EF >40%.233 However, it is unlikely that surgical revascularization mitigates the benefits of an ACE inhibitor in the post-CABG patient with a persis- tently reduced EF.


ARBs directly inhibit the action of angiotensin II by blocking the type 1 receptor, but their effects on bradykinin Oral ACE inhibitors have been shown to reduce symptom- atic heart failure and mortality among patients with previous MI and reduced EF.241 243 Among patients with reduced EF and active or prior heart failure symptoms, ACE inhibitors reduce mortality and heart failure hospitalization, improve New York Heart Association (NYHA) classification, reduce heart size, and prevent the need for escalating medical therapy.244 246 The routine initiation of an ACE inhibitor early after CABG is not recommended for patients with an EF >40%.233 However, it is unlikely that surgical revascularization mitigates the benefits of an ACE inhibitor in the post-CABG patient with a persis- tently reduced EF. Among patients with reduced EF who are intolerant of ACE inhibitors, an ARB can be used as an alternative therapy for those with a prior MI or symptoms of heart failure unless con- Angiotensin II can be generated by alterna- tive pathways, and its production is only partially inhibited by Therefore, concomitant treatment with both an ARB and ACE inhibitor (on a background of -blocker therapy) among patients with reduced EF may be selectively considered in patients with persistent heart failure symptoms and has been shown in clinical trials to reduce cardiovascu- lar death and heart failure hospitalization.252 Nevertheless, the combination of an ACE inhibitor and an ARB should not be used routinely, and this regimen is contraindicated if an aldosterone antagonist is also being used because of increased side effects. These side effects include excessive hypotension, hyperkalemia, and worsening renal function necessitating dis- continuation of therapy.248,249,252 Aldosterone Antagonists Spironolactone is a nonselective aldosterone antagonist that has demonstrated benefits for patients with severe heart fail- ure.


These side effects include excessive hypotension, hyperkalemia, and worsening renal function necessitating dis- continuation of therapy.248,249,252 Aldosterone Antagonists Spironolactone is a nonselective aldosterone antagonist that has demonstrated benefits for patients with severe heart fail- ure. In the RandomizedAldactone Evaluation Study (RALES), spironolactone was associated with a 30% RR reduction in overall mortality and a reduction in heart failure hospitaliza- tion and symptoms among patients with NYHA class III to IV symptoms and an EF <35%.253 Subsequently, the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) extended the benefits of aldoste- rone antagonists to patients with mild heart failure (includ- ing NYHA class II symptoms) and an EF <35% with the use It is important to note that an aldosterone receptor antagonist is indicated as an add-on therapy for patients who have persistent heart failure symptoms despite treatment with both classes of neurohormonal inhibitors ( -blockers and ACE inhibitor/ARBs). In accordance with both aforementioned studies253,254 and previous guidelines,236 aldosterone antagonists appear most applicable to post-CABG patients with persistent LV dysfunction (EF <35%) and mild or more severe heart failure symptoms. Careful monitoring of potassium, renal function, and diuretic dosing should be per- formed at initiation and serially thereafter in these patients. Aldosterone antagonists should be avoided in patients with estimated glomerular filtration rate <30 mL min 1 or potassium levels >5.0 mEq/L. Devices A substantial body of evidence supports the use of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac Kulik et al Secondary Prevention After CABG 941 death among patients with reduced EF.255 257 However, ICD therapy at the time of surgical revascularization has failed to improve patient outcomes.


Devices A substantial body of evidence supports the use of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac Kulik et al Secondary Prevention After CABG 941 death among patients with reduced EF.255 257 However, ICD therapy at the time of surgical revascularization has failed to improve patient outcomes. In the CABG Patch Trial,258 routine ICD insertion did not improve survival among patients with an EF <35% if an ICD was implanted prophylactically at the time of elective CABG. Notably, 71% of deaths in this trial were not arrhythmogenic, hence the lack of mortality benefit,258 and empirical ICD therapy was even associated with diminished quality of life 6 months after CABG.259 As per previous AHA/ ACCF guidelines, patients with reduced EF should be treated with optimal neurohormonal therapies after surgical revascu- If the EF remains severely reduced (<35%) in a noninvasive assessment of LV function 3 months after surgery, then consideration should be given to implantation of an ICD for primary prevention at that time.260 In patients with reduced LV function who undergo CABG after resuscitation from cardiac arrest, the decision for ICD therapy early after CABG should be individualized.260 Among these patients, CABG can suppress malignant arrhythmias and reduce subsequent episodes of cardiac arrest,261,262 espe- cially if the arrhythmias are related to ischemia.263 On the other hand, CABG may not mitigate all the conditions pre- disposing to ventricular arrhythmias, as in the case of patients with sustained monomorphic ventricular tachycardia and prior MI, and concomitant ICD insertion after CABG may be war- ranted in such patients. Progression of LV dysfunction to clinical heart failure is frequently accompanied by impaired electromechanical coupling, which may further diminish effective ventricular contractility.


Progression of LV dysfunction to clinical heart failure is frequently accompanied by impaired electromechanical coupling, which may further diminish effective ventricular contractility. Modification of ventricular electromechanical delay with cardiac resynchronization therapy (biventricular pacing) can improve ventricular systolic function, amelio- rate functional mitral regurgitation, and in some patients, reduce cardiac chamber dimensions.260 Cardiac resynchroni- zation therapy is generally indicated among patients with an EF <35% in the presence of left bundle-branch block, QRS interval >150 milliseconds, and NYHA class II to IIII heart failure symptoms, and it may be a reasonable therapeutic strategy if the QRS interval is in the 120- to 149-millisecond After 3 months of goal-directed postoperative medical therapy, patients recovering from CABG with these indications should receive an ICD in addition to cardiac resyn- chronization therapy, as detailed elsewhere.260 Previous MI and LV Dysfunction Recommendations 1. In the absence of contraindications, -blockers (biso- prolol, carvedilol, and sustained-release metopro- lol succinate) are recommended after CABG to all patients with reduced EF (<40%), especially among patients with heart failure or those with prior MI (Class I; Level of Evidence A). 2. In the absence of contraindications, ACE inhibitor or ARB therapy (if the patient is ACE inhibitor intoler- ant) is recommended after CABG to all patients with LV dysfunction (EF <40%) or previous MI (Class I; Level of Evidence B). 3. In the absence of contraindications, it is reasonable to add an aldosterone antagonist (on top of -blocker and ACE inhibitor therapy) after CABG for patients with LV dysfunction (EF <35%) who have class NYHA class II to IV heart failure symptoms (Class IIa; Level of Evidence B). 4.


In the absence of contraindications, it is reasonable to add an aldosterone antagonist (on top of -blocker and ACE inhibitor therapy) after CABG for patients with LV dysfunction (EF <35%) who have class NYHA class II to IV heart failure symptoms (Class IIa; Level of Evidence B). 4. Among patients with LV dysfunction (EF <35%), ICD therapy is not recommended for the prevention of sudden cardiac death after CABG until 3 months of postoperative goal-directed medical therapy has been provided and persistent LV dysfunction has been confirmed (Class III; Level of Evidence A). Diabetes Mellitus The effects of diabetes mellitus and the metabolic syndrome on the development and progression of cardiovascular disease are well established. Indeed, diabetes mellitus is associated with increased mortality and morbidity after cardiac surgery in general and CABG specifically.268 Diabetes mellitus is classified as type 1 if it results from -cell destruction or as type 2 if it results from a progressive insulin secretory defect and insulin resistance, but other causes of diabetes mellitus exist, including genetic defects in insulin secretion, drug- induced diabetes mellitus, and gestational diabetes mellitus.269 Traditionally, the diagnosis of diabetes mellitus has been based on a fasting plasma glucose >126 mg/dL, a 2-hour plasma glu- cose >200 mg/dL after oral administration of 75 g glucose, or a random plasma glucose of >200 mg/dL in a patient with the classic symptoms of diabetes mellitus.270 In 2009, however, an International Expert Committee recommended the use of the ) test be added, with a threshold >6.5% as a diagnostic criterion for diabetes mellitus.271 Because it is not always known whether a patient has dia- betes mellitus or glucose intolerance before surgery, it is reasonable for all patients undergoing CABG to have pre- operative fasting plasma glucose and HbA1c measurements.


Indeed, diabetes mellitus is associated with increased mortality and morbidity after cardiac surgery in general and CABG specifically.268 Diabetes mellitus is classified as type 1 if it results from -cell destruction or as type 2 if it results from a progressive insulin secretory defect and insulin resistance, but other causes of diabetes mellitus exist, including genetic defects in insulin secretion, drug- induced diabetes mellitus, and gestational diabetes mellitus.269 Traditionally, the diagnosis of diabetes mellitus has been based on a fasting plasma glucose >126 mg/dL, a 2-hour plasma glu- cose >200 mg/dL after oral administration of 75 g glucose, or a random plasma glucose of >200 mg/dL in a patient with the classic symptoms of diabetes mellitus.270 In 2009, however, an International Expert Committee recommended the use of the ) test be added, with a threshold >6.5% as a diagnostic criterion for diabetes mellitus.271 Because it is not always known whether a patient has dia- betes mellitus or glucose intolerance before surgery, it is reasonable for all patients undergoing CABG to have pre- operative fasting plasma glucose and HbA1c measurements. This may facilitate optimal diabetes mellitus management in the perioperative and postoperative periods. As detailed else- the perioperative control of serum glucose (glucose goal, 125 200 mg/dL) has been shown to improve both short- outcomes after CABG in most stud- ies.


As detailed else- the perioperative control of serum glucose (glucose goal, 125 200 mg/dL) has been shown to improve both short- outcomes after CABG in most stud- ies. However, an overly aggressive lowering of serum glucose during and after CABG surgery (glucose goal, 90 120 mg/ dL) may fail to improve clinical outcomes, mainly because of the adverse effects of hypoglycemic episodes, compared with more moderate glycemic control (glucose goal, 120 180 In a large observational study involving >4500 CABG patients, Bhamidipati et al277 noted that mortality and complication rates were lowest among diabetic patients who received moderate glycemic control with glucose levels of 127 to 179 mg/dL compared with those who were treated with tight ( 126 mg/dL) or liberal ( 180 mg/dL) insulin protocols. Patients with diabetes mellitus have less favorable long-term outcomes after CABG compared with nondiabetic patients.278 However, it is not well understood whether the diminished long-term survival and freedom from adverse cardiovascular events are attributable to a general progression of cardiovascu- lar disease seen in diabetic patients or if CABG patients with poorly controlled diabetes mellitus have specific characteris- tics that make them prone to diminished long-term survival. These factors may include decreased early graft patency, a more rapid progression of native vessel atherosclerosis, and a reduction in myocardial function. Vein graft patency has been reported in some studies to be diminished in patients with diabetes mellitus and the metabolic syndrome.279 This may relate to the association between type 2 diabetes mellitus and impaired endothelial function and intimal degeneration of saphenous vein grafts, changes that inversely correlate with the metabolic control of the diabetes mellitus.280 Interestingly, diabetes mellitus has much less effect on the properties of the internal mammary artery.


Vein graft patency has been reported in some studies to be diminished in patients with diabetes mellitus and the metabolic syndrome.279 This may relate to the association between type 2 diabetes mellitus and impaired endothelial function and intimal degeneration of saphenous vein grafts, changes that inversely correlate with the metabolic control of the diabetes mellitus.280 Interestingly, diabetes mellitus has much less effect on the properties of the internal mammary artery. In a long-term patency evaluation of 501 CABG patients, Lytle et al281 noted that insulin-dependent diabetes mel- litus was associated with late vein graft failure (P<0.004). Nevertheless, the adverse effects of diabetes mellitus on graft patency have not been seen in all studies. For example, in a 10-year follow-up of the VA Cooperative Study involving 1074 CABG patients, Goldman et al282 did not find diabetes mellitus to be an independent predictor of vein graft failure. Most recently, in a long-term observational study evaluating risk factors for adverse outcomes after CABG, Sabik et al164 reported that diabetes mellitus was a strong risk factor for cor- onary reintervention (either percutaneous coronary interven- tion or redo CABG) in the years after CABG. Patients treated with insulin or oral medications had a similarly elevated risk of undergoing reintervention (P<0.0001), whereas patients with diet-controlled diabetes mellitus also had an increased risk of reintervention, but lower than the risk in those treated pharma- cologically (P=0.005). Whether the degree of glucose control independently predicts vein graft patency remains unclear.283 This uncertainty likely relates to the difficulty in separating the effects of glucose control from the progression of cardio- vascular disease in general but may also be complicated by the challenges and inaccuracy of graft patency assessment, small study sample sizes, and separation of the effects of associated conditions such as hyperlipidemia and hypertension.


Whether the degree of glucose control independently predicts vein graft patency remains unclear.283 This uncertainty likely relates to the difficulty in separating the effects of glucose control from the progression of cardio- vascular disease in general but may also be complicated by the challenges and inaccuracy of graft patency assessment, small study sample sizes, and separation of the effects of associated conditions such as hyperlipidemia and hypertension. Patients having undergone surgical revascularization are at increased risk for further progression of CAD. Because there is no reason to surmise that CABG patients have any inher- ent protection from the effects of poorly controlled diabetes mellitus and because well-controlled blood sugar markedly improves survival in patients with cardiovascular disease,269 long-term glucose control should ideally be optimized for all CABG patients. Tight control of blood glucose is in a patient s best interest because cardiovascular disease is the most prevalent cause of morbidity and mortality in the dia- betic population. In terms of glucose management, CABG patients with dia- betes mellitus should receive coordinated medical care from a diabetes mellitus monitoring team. Such teams may include internists and endocrinologists, dieticians, pharmacists, and in certain cases, mental health professionals. Plasma glucose and levels should be followed up regularly, with appropri- ate adjustments made in insulin and oral hypoglycemic thera- pies.


Plasma glucose and levels should be followed up regularly, with appropri- ate adjustments made in insulin and oral hypoglycemic thera- pies. Lowering the HbA1c to 7% is a reasonable goal for most patients because this has been shown to reduce microvascular diabetic complications and, if initiated early, may also be asso- ciated with a reduction in macrovascular disease.269 A strin- goal such as 6.5% may be beneficial if treatment is not associated with hypoglycemic episodes, but it may be more reasonable to consider a less stringent goal of 8% for elderly patients and others who are prone to hypoglycemia.269 Unlike microvascular disease such as retinopathy, the progression of macrovascular disease such as CAD does not always correlate with the intensity of glucose control. However, in the Diabetes Control and Complications Trial, intensive glucose control (target HbA1c , 6%) in type 1 diabetic patients was associated with a lower risk of cardiovascular disease. Patients who were randomized to intensive glucose control after 9 years of follow-up had a 57% reduction in the risk of nonfatal MI, stroke, or cardiovascular death compared with patients in the standard arm.284 For patients with type 2 diabetes mellitus, evidence also exists that a more intensive control of plasma glucose may reduce macrovascular cardio- vascular disease.


Patients who were randomized to intensive glucose control after 9 years of follow-up had a 57% reduction in the risk of nonfatal MI, stroke, or cardiovascular death compared with patients in the standard arm.284 For patients with type 2 diabetes mellitus, evidence also exists that a more intensive control of plasma glucose may reduce macrovascular cardio- vascular disease. In the UK Prospective Diabetes Study, a 16% reduction in fatal and nonfatal MI and sudden death was noted with intensive glucose control (target fasting plasma glucose <6 mmol/L), although this failed to reach statistical signifi- Nevertheless, consistent benefits have not always been observed for patients with type 2 diabetes mellitus, with several other trials finding no added benefit of intensive glucose control over standard control on the risk of adverse cardiovascular events, even among patients with base- line cardiovascular disease at the time of trial recruitment.287 It must be recognized that none of the aforementioned stud- ies specifically enrolled diabetic patients who had undergone CABG. Regardless, although these study findings are extrap- olated from non-CABG patients to the CABG population, a moderate control of plasma glucose with a goal HbA1c of 7% would seem appropriate for most diabetic patients after CABG. In addition to optimal plasma glucose management, it cannot be overstated that all patients recovering from CABG, and especially those with diabetes mellitus, should be coun- seled to optimize their weight and diet, to quit smoking, and to institute behaviors associated with improved cardiovascular health. Diabetes Mellitus Recommendations 1. Striving to achieve an HbA1c of 7% is a reasonable goal for most patients after CABG to reduce microvascular diabetic complications and macrovascular cardiovas- cular disease (Class IIa; Level of Evidence B).


Striving to achieve an HbA1c of 7% is a reasonable goal for most patients after CABG to reduce microvascular diabetic complications and macrovascular cardiovas- cular disease (Class IIa; Level of Evidence B). Smoking Cessation According to the World Health Organization, 100 million deaths resulted from tobacco use in the 20th century, and it has been estimated that 1 billion more deaths may occur in the Compared with those who have never smoked tobacco, smokers lose on average 1 decade of life expec- This mortality risk can be lowered through smoking cessation, and if smoking cessation occurs before the age of 40, the reduction in risk associated with smoking is 90%.289 The risk of cardiovascular disease associated with cigarette smoke exposure increases in a dose-response fashion, with the greatest increase in risk occurring in individuals who have no cigarette exposure compared with those who have low levels of exposure, including secondhand smoke.1 At the time of the Kulik et al Secondary Prevention After CABG 943 first report of the Surgeon General s Advisory Committee in 1964, smoking rates in the United States approached 45%. Although significant progress has been made since then, tobacco use remains a leading modifiable cause of death in the United States, with 21.3% of adult men and 16.7% of adult women still engaging in cigarette smoking.1 In patients who have had CABG, smoking can adversely affect both short- and long-term clinical outcomes.


Although significant progress has been made since then, tobacco use remains a leading modifiable cause of death in the United States, with 21.3% of adult men and 16.7% of adult women still engaging in cigarette smoking.1 In patients who have had CABG, smoking can adversely affect both short- and long-term clinical outcomes. Early after surgery, smokers have an increased rate of atelectasis and pneumonia and an increased requirement for mechanical ventilation and intensive care support.290,291 In addition to an increased risk of pulmonary complications, smoking is associ- ated with an increased risk of deep sternal wound infections in adults who undergo cardiac surgery.292 Smokers have a higher prevalence of myocardial ischemia293 and require repeat coronary revascularization procedures more frequently.294,295 Specifically, smoking is associated with a higher rate of saphenous vein graft disease.165,296 Interestingly, despite the higher rates of morbidity in smok- ers, early mortality rates are not significantly different in smokers compared with nonsmokers. On the other hand, sig- nificant differences have been observed in long-term mortality On the basis of 30-year follow-up data, self- reported smoking cessation after CABG was associated with a life expectancy gain of 3 years, and smoking cessation had a greater effect on reducing the risk of mortality than any other intervention or treatment.295 Although smoking cessation should be addressed in all the postoperative period after CABG may be a particularly effective time to use smoking cessation strategies. Smokers undergoing CABG are hospitalized and therefore subject to the smoke-free policies of medical institu- tions, and they are also free of the usual cues to smoke.


Smokers undergoing CABG are hospitalized and therefore subject to the smoke-free policies of medical institu- tions, and they are also free of the usual cues to smoke. The conditions precipitating the need for CABG and the surgery itself may also reinforce the smoker s perceived vulnerability to the harms of tobacco use, motivating the patient to engage in an attempt at smoking cessation.299 In a Scandinavian cohort of patients undergoing cardiac surgery, approximately one half of current smokers gave up smoking after surgery. These changes in smoking behavior were most likely to occur during the first 6 postoperative months.300 As a result, CABG can serve as a teachable moment during which smoking ces- sation strategies may be highly effective. Smoking cessation strategies should begin with a full assessment of tobacco use and exposure. For instance, a cli- nician should determine the duration of smoking, the num- ber of cigarettes smoked daily, and the amount of time that passes between the patient waking up and having his or her first morning cigarette. Every smoker should be asked if he or she is interested in quitting smoking. If motivated to quit, smokers should have access to appropriate resources to assist in smoking cessation. For smokers who are not ready to quit, the clinician should assess the patient s perspective of the impact of smoking on his or her health. Education should then be provided to ensure that the patient has a full understand- ing of the adverse effects of continued smoking (including the effects of secondhand smoke on others) and the expected benefits associated with quitting. In addition, the clinician can use interviewing techniques to facilitate and engage intrinsic motivation within the patient to facilitate smoking cessation.


In addition, the clinician can use interviewing techniques to facilitate and engage intrinsic motivation within the patient to facilitate smoking cessation. Patients who are interested in quitting smoking should be offered behavioral approaches to tobacco cessation.301 Behavioral approaches to smoking cessation can be provided in a variety of formats, including direct patient-clinician encounters, telephone calls, computer programs, text messag- ing, or group-based sessions. A meta-analysis of 25 random- ized trials found that intensive counseling, which consisted of at least 1 contact during the hospital stay with continued sup- port for at least 1 month after discharge, increased the likeli- hood of smoking cessation.302 A point of emphasis in behavioral approaches to smoking cessation is having the patient set a quit day. A follow-up encounter, either in person or on the telephone scheduled soon after the patient s quit day, can strengthen the significance of the quit day and provide greater motivation for the patient to quit. In a systematic review of 10 randomized trials, no dif- ference was observed in abstinence rates between those who reduced smoking before the quit date and those who quit Thus, patients should be given the choice to reduce smoking before a quit date or to stop smoking abruptly on the quit date. In combination with counseling, nicotine replacement ther- apy can be an important adjunctive strategy to help achieve smoking cessation.


In combination with counseling, nicotine replacement ther- apy can be an important adjunctive strategy to help achieve smoking cessation. In a randomized trial of 5887 smokers, long-term rates of smoking and mortality were reduced with the application of a 10-week smoking cessation program that included a strong physician message, nicotine gum, and 12 group sessions using behavior modification.304 On the basis of a systematic review of the literature in 2008, the US Public Health Service advocated the use of 5 nicotine replacement medications (gum, patch, nasal spray, inhaler, and lozenge) and reported that the combination of a long-term nicotine patch and ad lib nicotine spray or gum produced significantly higher long-term abstinence rates than did the nicotine patch Compared with nicotine replacement medications, electronic cigarettes (e-cigarettes) have not been demonstrated to improve smoking cessation rates, and important concern has been raised about their potential for adverse health effects.306 Nicotine replacement therapy has been shown to be safe for patients with stable CAD. In a randomized, double-blind, pla- cebo-controlled trial, a 10-week outpatient course of transder- mal nicotine did not increase the rate of cardiovascular events among patients with at least 1 diagnosis of cardiovascular dis- In hospitalized patients, nicotine replacement therapy is commonly used as an effective strategy to manage nicotine but less is known about the routine use of nicotine replacement therapy during an acute cardio- vascular event.


In a randomized, double-blind, pla- cebo-controlled trial, a 10-week outpatient course of transder- mal nicotine did not increase the rate of cardiovascular events among patients with at least 1 diagnosis of cardiovascular dis- In hospitalized patients, nicotine replacement therapy is commonly used as an effective strategy to manage nicotine but less is known about the routine use of nicotine replacement therapy during an acute cardio- vascular event. In a retrospective analysis of smokers admitted with acute coronary syndromes, transdermal nicotine therapy was not associated with an increased risk of mortality.308 On the other hand, in a retrospective analysis of smokers hospital- ized during CABG, nicotine replacement therapy was asso- ciated with an increased mortality rate after adjustment for Both of these studies were limited by their observational design and specifically by the biases associated with the use of nicotine replacement therapy such as the degree of prior smoking. As a result, prospective studies are needed to determine the safety of using nicotine replace- ment therapy in patients with acute cardiovascular disease. At this time, judicious use and dosing of nicotine replacement therapy are recommended for patients admitted to hospital with an acute cardiovascular event.


At this time, judicious use and dosing of nicotine replacement therapy are recommended for patients admitted to hospital with an acute cardiovascular event. In addition to nicotine replacement medications, bupropion and varenicline can be effective adjuncts to smoking cessa- tion strategies, and their use has been supported by the US Public Health Service.305 Bupropion is generally well toler- ated and has been shown to be safe to use in the immediate period after MI.310,311 Among 629 patients with cardiovas- cular disease, a 7-week treatment with bupropion resulted in twice as many smokers quitting at 1 year compared with Varenicline has also been shown to be effective in reducing rates of smoking.313,314 In a randomized, placebo- controlled trial of 714 smokers with stable cardiovascular disease, varenicline was effective at reducing rates of smok- Based on data from this trial, however, the US Food and Drug Administration issued an advisory that varenicline may increase the risk of adverse cardiovascular events on the basis of statistically nonsignificant increases in the rates of nonfatal MI, coronary revascularization, and new peripheral vascular disease in this trial population.315 Although the car- diovascular risk profile of varenicline remains unsettled, the long-term benefits of smoking cessation far outweigh any potential adverse effects with varenicline. Therefore, it should still be carefully considered as a possible medication to assist in smoking cessation for patients with cardiovascular disease. During the process of smoking cessation, patients may face many potential obstacles to achieving their goal. They may struggle with high dependence on nicotine, severe withdrawal problems, low self-confidence, poor social support, weight gain, comorbid psychiatric illnesses, and suboptimal use of Addressing each of these issues as they arise is critical to achieving smoking cessation.


They may struggle with high dependence on nicotine, severe withdrawal problems, low self-confidence, poor social support, weight gain, comorbid psychiatric illnesses, and suboptimal use of Addressing each of these issues as they arise is critical to achieving smoking cessation. In addition, criti- cal evaluation of the helpful and unhelpful aspects of prior attempts at smoking cessation can guide the development of revised and more effective treatment plans. Even among those smokers who have initial success, it is important to remain focused on these issues because most smokers try quitting several times before they finally achieve durable success.316 Ultimately, successful smoking cessation strategies require a long-term disease management approach to achieve perma- nent abstinence. Smoking Cessation Recommendations 1. Smoking cessation is critical, and counseling should be offered to all patients who smoke, during and after hospitalization for CABG, to help improve both short- and long-term clinical outcomes after surgery (Class I; Level of Evidence A). 2. It is reasonable to offer nicotine replacement therapy, bupropion, and varenicline as adjuncts to smoking cessation counseling for stable CABG patients after hospital discharge (Class IIa; Level of Evidence B). 3. Nicotine replacement therapy, bupropion, and var- enicline may be considered as adjuncts to smoking cessation counseling during CABG hospitalization, but their use should be carefully considered on an individualized basis (Class IIb; Level of Evidence B).


Nicotine replacement therapy, bupropion, and var- enicline may be considered as adjuncts to smoking cessation counseling during CABG hospitalization, but their use should be carefully considered on an individualized basis (Class IIb; Level of Evidence B). Cardiac Rehabilitation Outpatient CR is a medically supervised, exercise-based pro- gram that is designed for patients with recent cardiovascular events to optimize overall health status and to minimize the risks for future adverse outcomes.317 325 In a meta-analysis of 48 trials involving CAD patients, CR was associated with a 26% risk reduction in the rate of cardiovascular mortality and a 20% risk reduction in overall mortality.321 Moreover, a strong, inverse dose-response relationship has been observed between the number of CR sessions attended and long-terms rates of MI and death.326 On the basis of this compelling evi- dence, CR has been strongly recommended for patients with several different cardiovascular diseases,327 including those recovering from recent CABG.3,317 The benefits of CR such as improved survival have been reported for all types of CAD patients, including younger and older patients, as well as men and women, independently of the nature of CAD diagnosis, the form of CR, and the dose of exercise intervention.317 325 The very first CR programs were launched in the 1960s, at a time when patients with cardiovascular disease were warned These initial CR programs, imple- mented for post-MI patients recovering in hospital, consisted of graded exercise programs. After a demonstration of their safety and success, these programs were later expanded into the outpatient setting.328 Over the years, CR programs have continued to adapt and to address the broad range of factors affecting cardiovascular outcomes, which has allowed them to evolve from purely supervised exercise programs to compre- hensive secondary prevention programs.


After a demonstration of their safety and success, these programs were later expanded into the outpatient setting.328 Over the years, CR programs have continued to adapt and to address the broad range of factors affecting cardiovascular outcomes, which has allowed them to evolve from purely supervised exercise programs to compre- hensive secondary prevention programs. The core components of contemporary CR programs include baseline patient assessments, nutritional counseling, risk factor management (lipids, BP, weight, diabetes mellitus, and smoking), psychosocial interventions, and physical activ- ity with counseling and exercise training.329 As a result of the broad effects of exercise training and the multiple components of these programs, CR has been shown to improve a wide range of health factors. Significant improvements have been demonstrated in CAD risk factors, functional capacity, vas- cular conditioning, and psychosocial well-being, all of which likely contribute to the robust effects of CR on overall clinical Among Medicare beneficiaries who have undergone CABG, patients are covered for up to 36 sessions of CR over the course of 1 year after the incident surgical hospitalization; other medical payers offer similar coverage plans.


Significant improvements have been demonstrated in CAD risk factors, functional capacity, vas- cular conditioning, and psychosocial well-being, all of which likely contribute to the robust effects of CR on overall clinical Among Medicare beneficiaries who have undergone CABG, patients are covered for up to 36 sessions of CR over the course of 1 year after the incident surgical hospitalization; other medical payers offer similar coverage plans. Despite the wealth of evidence and the presence of insurance coverage, CR use patterns remain poor nationwide.329 333 In an analysis of Medicare claims data, only 31% of CABG patients received at least 1 session of CR, and there was considerable geo- graphic heterogeneity in CR use patterns.333 One of the key barriers to CR use is the process of refer- ral to CR.327 Even among hospitals using the AHA Get With The Guidelines program, only 56% of eligible patients were referred to CR.332 Clearly, improving referral patterns to CR programs is a key area in need of greater focus.331 Recognizing Kulik et al Secondary Prevention After CABG 945 the importance of CR and the poor referral patterns to CR, the AHA and ACC, in collaboration with the American Association of Cardiac and Pulmonary Rehabilitation, have released performance measures for CR referral.327 Although CR referral rates are currently low, newly devel- oped referral strategies hold great promise to overcome this In a randomized trial of 2635 patients with CAD admitted to 11 different hospitals, a referral process that con- sisted of a combination of CR liaisons and an automated refer- ral system resulted in 85.8% of patients being referred to CR and 73.5% being enrolled in CR compared with 32.2% and 29.0%, respectively, in the control group.337 In addition, strat- egies such as educational interventions335 and early appoint- ments and start dates338 340 have been shown to improve CR referral and use patterns.


Despite the wealth of evidence and the presence of insurance coverage, CR use patterns remain poor nationwide.329 333 In an analysis of Medicare claims data, only 31% of CABG patients received at least 1 session of CR, and there was considerable geo- graphic heterogeneity in CR use patterns.333 One of the key barriers to CR use is the process of refer- ral to CR.327 Even among hospitals using the AHA Get With The Guidelines program, only 56% of eligible patients were referred to CR.332 Clearly, improving referral patterns to CR programs is a key area in need of greater focus.331 Recognizing Kulik et al Secondary Prevention After CABG 945 the importance of CR and the poor referral patterns to CR, the AHA and ACC, in collaboration with the American Association of Cardiac and Pulmonary Rehabilitation, have released performance measures for CR referral.327 Although CR referral rates are currently low, newly devel- oped referral strategies hold great promise to overcome this In a randomized trial of 2635 patients with CAD admitted to 11 different hospitals, a referral process that con- sisted of a combination of CR liaisons and an automated refer- ral system resulted in 85.8% of patients being referred to CR and 73.5% being enrolled in CR compared with 32.2% and 29.0%, respectively, in the control group.337 In addition, strat- egies such as educational interventions335 and early appoint- ments and start dates338 340 have been shown to improve CR referral and use patterns. However, as new referral strategies become adopted into clinical practice, it will be important for clinicians to remain active in the referral process because physician advocacy remains a strong factor in determining whether patients will enroll in CR programs.341 Beyond the challenges in the referral process, many patient and health system factors negatively affect CR use patterns.


However, as new referral strategies become adopted into clinical practice, it will be important for clinicians to remain active in the referral process because physician advocacy remains a strong factor in determining whether patients will enroll in CR programs.341 Beyond the challenges in the referral process, many patient and health system factors negatively affect CR use patterns. Referral to CR is particularly low among specific populations such as patients of low socioeconomic status, women, older adults, and ethnic minorities.323 In addition, CR program loca- tions and hours of operation prohibit the use of this service by some patients, and CR programs may not even be available in some rural or medically underserved areas. Finally, the finan- cial costs, related to copays, transportation, and time off from work, over the course of an entire CR program dissuade some patients from using this service. To address all these barriers to CR use, multiple strategies will need to be undertaken. First, greater attention will need to be paid in the referral process to identify and address an indi- vidual s unique barriers to CR use. This will require greater communication with patients and better coordination between the referring center (hospitals or office-based practices) and CR programs. Second, healthcare reform efforts will need to provide further incentives to patients and healthcare sys- tems to use CR programs. Third, new paradigms for deliv- ering comprehensive CR programs such as home-based CR programs will need to be further developed. Although these challenges are daunting, they are of central importance to improving clinical outcomes after CABG. CR Recommendations 1. CR is recommended for all patients after CABG, with the referral ideally performed early postopera- tively during the surgical hospital stay (Class I; Level of Evidence A).


CR is recommended for all patients after CABG, with the referral ideally performed early postopera- tively during the surgical hospital stay (Class I; Level of Evidence A). Self-Management of Cardiovascular Disease After CABG, CR programs help patients develop self-man- agement skills to facilitate lifestyle and behavior modifi- cation. Self-management is the process by which patients assume control of their health-related behaviors.342 Ultimately, patients decide what they will eat, if they will exercise, and what medication they will take. As healthcare experiences a paradigm shift from physician-centered to patient-centered care, CR programs play an integral role in education and transitioning patients to adopt health-related behaviors.342 CR personnel can act as health coaches, providing self-manage- ment support, collaborating with patients to establish goals, and developing problem-solving skills to foster risk factor modification. Successful CR programs stimulate patients to acquire the knowledge, skills, and confidence necessary to alter health-related behavior.342 346 The Reduction of Atherothrombosis for Continued Health (REACH) international registry reported that among patients who have undergone CABG, when secondary prevention goals are not met at 1 year, the incidence of adverse cardio- vascular events increases, regardless of the number of risk factors present at baseline. This highlights the importance of CR programs to help patients achieve their goals and to improve long-term outcomes.212 Multiple barriers exist to the adoption of preventive therapies, including knowledge defi- cit, ambivalence, comorbidities, preconceived beliefs, lack of support, employment, and readiness for change.347 349 For example, older patients with comorbidities who live alone are more likely after 1 year to remain sedentary and to have poor medication and diet compliance.350 Interventions for self-management of risk factors should be individualized to meet specific sex concerns.


This highlights the importance of CR programs to help patients achieve their goals and to improve long-term outcomes.212 Multiple barriers exist to the adoption of preventive therapies, including knowledge defi- cit, ambivalence, comorbidities, preconceived beliefs, lack of support, employment, and readiness for change.347 349 For example, older patients with comorbidities who live alone are more likely after 1 year to remain sedentary and to have poor medication and diet compliance.350 Interventions for self-management of risk factors should be individualized to meet specific sex concerns. Women in par- ticular have difficulty with self-management of heart disease because of fatigue, anxiety, and depression, as well as feel- ings of guilt that home and family responsibilities are being Adherence to physical activity remains a challenging issue; 35% of women are no longer exercising 3 months after discharge from CR.353 In contrast, men experi- ence different barriers to secondary prevention compared with women. Some of the obstacles to compliance among men include comprehension of disease, dietary barriers (depen- dence on others for meals), and activity barriers (such as employment superseding CR).354 Participation in a hospital-based outpatient CR program compared with a home-based program helps improve exer- cise adherence for both men and women, increases knowledge about the condition for men, and improves stress control for Continuation of the secondary prevention education after discharge from CR can improve adherence to long-term self-management. Secondary prevention programs should be individualized, considering the patient s knowledge deficit.


Secondary prevention programs should be individualized, considering the patient s knowledge deficit. Self-efficacy and self-management skills can be developed by incorporating education and counseling techniques in either individualized or group sessions and focusing on motivational Applying technology through the use of the Internet and mobile phones can help provide education and trained peer support for CABG patients after surgery, even for those who are unable to access CR programs because of Finally, individual diaries have been shown to increase patient accountability for self-management of exercise activity after CR.360 Self-efficacy, along with an individualized plan for behavior change, is imperative to help optimize adherence to secondary prevention after CABG. Mental Health and Cognitive Impairment The negative impact of mental illness and cognitive impair- ment after CABG is well recognized, leading to greater risk of morbidity and mortality in the perioperative period and poor adherence to secondary preventative therapies in the long term. Screening for and preventing these neuropsychological conditions from developing may therefore improve outcomes after CABG.


Screening for and preventing these neuropsychological conditions from developing may therefore improve outcomes after CABG. Depression is the most carefully studied mood disorder, having been reported in up to 33% of patients 1 year Depression is an important risk factor for the progression of CAD, and it is a more important predictor of CR success than many other variables.362 Both the presence of depressive symptoms before CABG and the worsening of these symptoms after surgery correlate with poorer physi- cal and psychosocial functioning and poorer quality of life Moreover, depression before or after surgery increases the risk of postoperative mortality and other adverse events such as heart failure hospitalization, MI, cardiac arrest, and the need for repeat revascularization.364,365 Finally, depres- sion after CABG is an important predictor for the recurrence of angina in the postoperative period.365 Interventions to help treat depression after CABG have been shown to be beneficial by improving depressive symptoms through cognitive behavioral therapy, telephone-delivered collaborative care, and supportive stress management.366,367 Participating in a CR program is another method that can help reduce postoperative depressive symptoms.368 In a random- ized, controlled trial, phone calls by nurses to patients after CABG improved depressive mood symptoms in the months Although interventions are frequently initiated postoperatively, cognitive behavioral therapy for preopera- tive depression and anxiety has also been shown to improve depressive symptoms and to reduce the length of stay in hospi- tal, justifying screening for depression even before the opera- Recently, a trial examining the efficacy of treating depression before surgery randomized 361 patients to escita- lopram 10 mg daily or placebo starting 2 to 3 weeks before elective CABG.


Depression is the most carefully studied mood disorder, having been reported in up to 33% of patients 1 year Depression is an important risk factor for the progression of CAD, and it is a more important predictor of CR success than many other variables.362 Both the presence of depressive symptoms before CABG and the worsening of these symptoms after surgery correlate with poorer physi- cal and psychosocial functioning and poorer quality of life Moreover, depression before or after surgery increases the risk of postoperative mortality and other adverse events such as heart failure hospitalization, MI, cardiac arrest, and the need for repeat revascularization.364,365 Finally, depres- sion after CABG is an important predictor for the recurrence of angina in the postoperative period.365 Interventions to help treat depression after CABG have been shown to be beneficial by improving depressive symptoms through cognitive behavioral therapy, telephone-delivered collaborative care, and supportive stress management.366,367 Participating in a CR program is another method that can help reduce postoperative depressive symptoms.368 In a random- ized, controlled trial, phone calls by nurses to patients after CABG improved depressive mood symptoms in the months Although interventions are frequently initiated postoperatively, cognitive behavioral therapy for preopera- tive depression and anxiety has also been shown to improve depressive symptoms and to reduce the length of stay in hospi- tal, justifying screening for depression even before the opera- Recently, a trial examining the efficacy of treating depression before surgery randomized 361 patients to escita- lopram 10 mg daily or placebo starting 2 to 3 weeks before elective CABG. Although the therapy had no effect on mor- bidity and mortality after CABG, depressed patients treated with escitalopram had a better quality of life and less pain Therefore, treating depression before CABG can lead to improved psychological outcomes after surgery.


Although the therapy had no effect on mor- bidity and mortality after CABG, depressed patients treated with escitalopram had a better quality of life and less pain Therefore, treating depression before CABG can lead to improved psychological outcomes after surgery. Alteration of cognitive function has been reported in up to 30% of patients after CABG.371 374 The exact frequency depends on the timing of the postoperative assessment and the criteria used to measure cognitive decline.375,376 Studies with appropriate comparison groups (including nonsurgical and healthy control subjects) have demonstrated that most patients do not suffer cognitive decline as a result of CABG.377,378 For those who do, the postoperative cognitive changes are usually mild and generally resolve within 3 months of surgery.379 Long- term cognitive decline after CABG has been reported,380,381 but studies have shown that similar late cognitive decline occurs even among patients with CAD who do not undergo surgery, supporting that the decline is not related to the operation or the use of cardiopulmonary bypass.382 Cognitive changes have also been reported after general anesthesia for noncardiac Several risk factors for short-term postoperative cognitive decline have been identified, including preoperative factors for cerebrovascular disease, central nervous system disease, and preexisting cognitive impairment.371,386,387 It had previously been suggested that cognitive decline might be less frequent after off-pump CABG compared with on-pump surgery.388 As summarized in a meta-analysis, however, taken collectively, most studies failed to show a benefit of off-pump CABG In particular, large, robust, randomized, clinical trials comparing late cognitive outcomes after on-pump and off-pump CABG surgery reported no difference.390,391 Current findings therefore do not support a recommendation for off- pump surgery as an approach to prevent cognitive decline. Mental Health and Cognitive Decline Recommendations 1.


Alteration of cognitive function has been reported in up to 30% of patients after CABG.371 374 The exact frequency depends on the timing of the postoperative assessment and the criteria used to measure cognitive decline.375,376 Studies with appropriate comparison groups (including nonsurgical and healthy control subjects) have demonstrated that most patients do not suffer cognitive decline as a result of CABG.377,378 For those who do, the postoperative cognitive changes are usually mild and generally resolve within 3 months of surgery.379 Long- term cognitive decline after CABG has been reported,380,381 but studies have shown that similar late cognitive decline occurs even among patients with CAD who do not undergo surgery, supporting that the decline is not related to the operation or the use of cardiopulmonary bypass.382 Cognitive changes have also been reported after general anesthesia for noncardiac Several risk factors for short-term postoperative cognitive decline have been identified, including preoperative factors for cerebrovascular disease, central nervous system disease, and preexisting cognitive impairment.371,386,387 It had previously been suggested that cognitive decline might be less frequent after off-pump CABG compared with on-pump surgery.388 As summarized in a meta-analysis, however, taken collectively, most studies failed to show a benefit of off-pump CABG In particular, large, robust, randomized, clinical trials comparing late cognitive outcomes after on-pump and off-pump CABG surgery reported no difference.390,391 Current findings therefore do not support a recommendation for off- pump surgery as an approach to prevent cognitive decline. Mental Health and Cognitive Decline Recommendations 1. For patients after CABG, it is reasonable to screen for depression in collaboration with a primary care physician and a mental health specialist (Class IIa; Level of Evidence B). 2. Cognitive behavior therapy or collaborative care for patients with clinical depression after CABG can be beneficial to reduce depression (Class IIa; Level of Evidence B).


Cognitive behavior therapy or collaborative care for patients with clinical depression after CABG can be beneficial to reduce depression (Class IIa; Level of Evidence B). Obesity and Metabolic Syndrome Obesity is a major risk factor for cardiovascular disease. Many epidemiological studies have shown a clear associa- tion between obesity and CAD.392 The association is mediated mostly through the effect of obesity-related cardiovascular risk factors such as hypertension, dyslipidemia, or diabetes melli- tus but also through a direct atherogenic effect by increased circulation of free fatty acids, by adrenergic stimulation, and through the effect of adipose tissue related hormones. Biologically, obesity is defined as increased body fat, but for simplicity purposes, the World Health Organization defines obesity on the basis of body weight in relation to height. The most widely accepted method to diagnose obesity is the body mass index (BMI), calculated by dividing the weight in kilo- grams by the height in meters squared. Recent studies have challenged the accuracy of BMI in detecting body adipos- ity, particularly in patients with established CAD.393,394 This new evidence suggests that the assessment of adiposity needs to go beyond total body adiposity and the measurement of With a focus on the distribution of adipose tissue, central obesity and greater amounts of visceral fat convey the highest mortality risk in patients with CAD.395 The assessment of body fat distribution can be performed in a simple manner by measuring the waist and hip circumference to calculate the waist-to-hip ratio. The metabolic syndrome is defined as the coexistence of several interrelated conditions, including central obesity, hyperglycemia, elevated systemic BP, hypertriglyceridemia, and decreased HDL.


The metabolic syndrome is defined as the coexistence of several interrelated conditions, including central obesity, hyperglycemia, elevated systemic BP, hypertriglyceridemia, and decreased HDL. The presence of 3 of these abnormali- ties establishes the diagnosis of metabolic syndrome based on the Adult Treatment Panel III consensus.397 The metabolic syn- drome has been associated with numerous pathophysiological mechanisms that can lead to cardiovascular disease, includ- ing insulin resistance, increased oxidative stress, endothelial dysfunction, and atherogenic lipid patterns. The presence of metabolic syndrome increases the risk for cardiovascular events Kulik et al Secondary Prevention After CABG 947 from 2- to 4-fold independently of the presence of diabetes mel- litus. As a well-established cardiovascular risk factor, the meta- bolic syndrome is common among patients undergoing CABG, with some studies reporting the prevalence as high as 50%.398 The metabolic syndrome has been associated with increased in-hospital mortality in subjects undergoing CABG. In a study of 5304 consecutive CABG patients, those with metabolic syn- drome had a 2.7-times higher in-hospital mortality than those without metabolic syndrome, a risk that was independent of the presence of diabetes mellitus.399 Moreover, patients with metabolic syndrome also have an increased risk for long-term mortality. Angeloni et al398 noted that all-cause mortality was 50% higher in those patients with metabolic syndrome com- pared with those without in a long-term follow-up study of 1726 CABG patients.


Angeloni et al398 noted that all-cause mortality was 50% higher in those patients with metabolic syndrome com- pared with those without in a long-term follow-up study of 1726 CABG patients. The metabolic syndrome also increased the long-term risk for cardiac arrhythmias, renal failure, and the composite outcome of major adverse cardiovascular events Patients with the meta- bolic syndrome are 2.3-times more likely to develop AF after This increased risk may be mediated by an elevated C-reactive protein level.401 Patients with metabolic syndrome are also at risk for decreased patency of saphenous vein grafts Given the multiple pathophysiological mechanisms link- ing obesity and cardiovascular disease, it is logical to expect favorable clinical outcomes after weight loss in patients with CAD. Unfortunately, there is minimal evidence proving any benefit associated with weight loss after CABG. Retrospective, observational studies assessing the association between weight loss and clinical outcomes after CABG have shown para- doxical results, with worse outcomes among patients losing weight after CABG.403 However, these studies could not dif- ferentiate between purposeful and unintentional weight loss. Unintentional weight loss could reflect comorbidities such as heart failure, cancer, and lung diseases or may reflect the sever- ity of other conditions associated with decreased survival. One of the few studies that showed improved outcomes after weight loss in patients with CAD was based in a CR setting, suggest- ing that purposeful weight loss in CAD patients may be benefi- Weight loss has an indisputable benefit for BP, diabetes mellitus, and lipid control and improves quality of life and functional capacity. Therefore, despite the limited scientific evidence, it is generally accepted that weight loss should be recommended for overweight or obese patients after CABG. Long-term, successful weight loss continues to represent a major clinical challenge.


Long-term, successful weight loss continues to represent a major clinical challenge. Most studies have noted that much of the weight lost in the first 6 months is regained at 1 year. The therapeutic options to achieve successful weight loss are limited because some of the medications that can promote weight loss are contraindicated in patients with CAD. To date, the only weight-loss strategy with effective long-term results is bariatric surgery. Observational studies have shown signifi- cant improvements in cardiometabolic parameters, quality of life, and cardiac mechanics following major weight loss after Many patients after CABG with a BMI of would qualify for bariatric surgery, and this thera- peutic modality may be considered for long-lasting weight Bariatric surgery has been shown to be safe in stable patients with CAD who have not had a recent MI.407 The cornerstone of the management of metabolic syndrome is lifestyle modification with increased exercise, improved diet, and weight loss. Lifestyle changes can improve all of the metabolic syndrome components. Diets low in carbohydrates can effectively improve hypertriglyceridemia. High protein intake, along with a high consumption of fruits, vegetables, and nonfat dairy products, can improve BP.408 Commonly, pharmacological treatment is needed for hypertension, diabe- tes mellitus, and dyslipidemia despite lifestyle changes. For patients with advanced degrees of obesity, bariatric surgery has been shown to significantly reduce the prevalence of meta- Obesity and Metabolic Syndrome Recommendations 1. The assessment of central distribution of fat is rea- sonable in CABG patients by measuring waist and hip circumference and calculating waist-to-hip ratio, even if the BMI is within normal limits (Class IIa; Level of Evidence C). 2. Bariatric surgery may be considered for CABG patients with a BMI >35 kg/m2 if lifestyle interven- tions have already been attempted without meaning- ful weight loss (Class IIb; Level of Evidence C).


Bariatric surgery may be considered for CABG patients with a BMI >35 kg/m2 if lifestyle interven- tions have already been attempted without meaning- ful weight loss (Class IIb; Level of Evidence C). Nutrition The nutritional status of patients plays an important role in the results after CABG. Approximately 20% of patients have been identified as having poor preoperative nutritional sta- tus before undergoing cardiac surgery.410 Several nutritional screening tools exist, including the Malnutrition Universal Screening Tool. When the Malnutrition Universal Screening Tool score is added to the EuroSCORE in a multivariable model evaluating perioperative risk, the prediction of the model for both postoperative complications and mortal- ity is significantly improved compared with the use of the Preoperative malnutrition, whether defined on the basis of a nutritional screening tool or serum albumin level, has been shown to predict adverse postopera- tive events such as reoperation for bleeding, postoperative renal failure, prolonged ventilatory support, vasopressor treatment for >11 days, antibiotic treatment for >21 days, intensive care unit stay, total length of stay, increased inflam- matory response, infection, positive blood cultures, and It is well established that BMI decreases after major surgery such as CABG. DiMaria-Ghalili413 assessed 91 patients under- going CABG and observed a 5% change between the preop- erative BMI level and the level measured 4 to 6 weeks after surgery. This finding corresponded to a 13.8% decrease in self-reported physical health during the same time period. At a mean follow-up of 19 months, this same investigator observed that older patients undergoing elective CABG usually did not regain the weight they lost between the preoperative period and after hospital discharge.


At a mean follow-up of 19 months, this same investigator observed that older patients undergoing elective CABG usually did not regain the weight they lost between the preoperative period and after hospital discharge. Furthermore, patients who lost more weight in the postoperative period were more likely to require subsequent hospital readmission.414 In an observational study of 100 consecutive patients under- going cardiac surgery, van Venrooij et al415 noted that low pre- operative protein intake ( 0.98 g kg 1 ) did not result in more complications or a longer hospital stay compared with a high preoperative protein intake (>0.98 g kg 1 ). On the other hand, a high-energy preoperative diet (>22 kcal kg 1 ) resulted in more postoperative complications. Racca and evaluated nutrition biomarkers in 50 nondiabetic patients on admission to a rehabilitation facility after cardiac surgery and 16 days later. Patients received a standard car- diac diet with controlled caloric support (30 kcal kg 1 ) providing 15% to 20% dietary protein, 30% fat, and 50% to 55% carbohydrates rich in fruits and vegetables. After 16 days on this standard dietary regimen, low plasma albumin levels increased, anemia improved, and markers of inflammation declined. From the above data, it would appear that controlled, com- prehensive dietary intake is effective in restoring the nutri- tional insults brought about by major surgery such as CABG but that oversupplementation may be detrimental. Although it seems justified to modulate nutritional intake to promote a quicker recovery from CABG, to date, there are no prospec- tive, randomized trials documenting a benefit associated with perioperative nutritional modification. Vitamins and Supplements The use of vitamin supplementation is a widespread prac- tice in the general population that amounts to tremendous expenditure.


Vitamins and Supplements The use of vitamin supplementation is a widespread prac- tice in the general population that amounts to tremendous expenditure. Many benefits have been attributed to the use of vitamin supplements, particularly those touted to have protective effects against cardiovascular disease and stroke. Observational studies have suggested that some vitamin supplements can reduce adverse cardiovascular events. For example, in the prospective Nurses Health Study of >80000 participants, women who voluntarily reported taking vitamin C and vitamin E supplements were noted to have a lower risk of developing CAD over more than a decade of follow-up.417,418 However, large, randomized, controlled studies of vitamins have not demonstrated such benefits in a variety of general and high-risk populations. The Physicians Health Study II was a randomized, double-blind, placebo-controlled trial of vitamin C and vitamin E supplementation that enrolled 14641 US male physicians 50 years of age. In this study, neither vitamin C nor vitamin E supplements reduced the risk of major cardiovascular events, even after more than a decade of treatment and follow-up.419,420 Among 12064 MI survivors, a placebo-controlled trial demonstrated that supplementation with folic acid and vitamin B12 also did not have beneficial effects on cardiovascular outcomes.421 This was confirmed in a meta-analysis of >37000 participants that demonstrated that high-dose B vitamins and folic acid are not effective as a secondary prevention measure for cardiovascular disease.422 Finally, a meta-analysis of 50 randomized, controlled trials with nearly 300000 participants showed no benefit of vitamin and antioxidant supplementation in reducing the risk of major cardiovascular events, including subgroup meta-analyses examining the effects of individual vitamins.423 Undergoing cardiac surgery leads to considerable stress on the body, which plays a key factor in determining outcome.


In this study, neither vitamin C nor vitamin E supplements reduced the risk of major cardiovascular events, even after more than a decade of treatment and follow-up.419,420 Among 12064 MI survivors, a placebo-controlled trial demonstrated that supplementation with folic acid and vitamin B12 also did not have beneficial effects on cardiovascular outcomes.421 This was confirmed in a meta-analysis of >37000 participants that demonstrated that high-dose B vitamins and folic acid are not effective as a secondary prevention measure for cardiovascular disease.422 Finally, a meta-analysis of 50 randomized, controlled trials with nearly 300000 participants showed no benefit of vitamin and antioxidant supplementation in reducing the risk of major cardiovascular events, including subgroup meta-analyses examining the effects of individual vitamins.423 Undergoing cardiac surgery leads to considerable stress on the body, which plays a key factor in determining outcome. Along with weight loss and protein catabolism, cardiac sur- gery is often associated with numerous derangements in stored vitamin and other metabolite levels. CABG is accompanied by a significant acute phase and inflammatory response, lead- ing to oxidative stress, free radical production, and antioxi- Louw and coworkers427 observed that this early acute-phase reaction was associated with decreases in the levels of both vitamin A and vitamin C, which are impor- tant antioxidants that aid in wound healing. Interestingly, both vitamin levels returned to normal after surgery without specific therapeutic intervention. Schindler and colleagues428 studied serial plasma samples before, during, and up to 48 hours after surgery, demonstrating significant decreases in levels of both vitamin A and vitamin E, with persistently low vitamin E levels 48 hours postoperatively.


Schindler and colleagues428 studied serial plasma samples before, during, and up to 48 hours after surgery, demonstrating significant decreases in levels of both vitamin A and vitamin E, with persistently low vitamin E levels 48 hours postoperatively. Similarly, in the early perioperative period after CABG, reductions have been noted in levels of homocysteine and folic acid, which are part of the body s antioxidant first line of defense.429 Other studies of CABG patients have documented decreases in B complex vitamins such as B6 , and thiamine, which are essential for mitochondrial function.416,427,430 Vitamin D levels have been shown to be important predictors of outcome after cardiac surgery. In a study of 4418 patients recovering from cardiac surgery, Zittermann et al431 noted that 38.0% had deficient 25(OH)D values (<30 nmol/L). In multivariable- adjusted models, a low 25(OH)D value was independently associated with a greater risk of major adverse cardiac events, longer duration of mechanical ventilatory support and inten- sive care unit stay, and higher 6- and 12-month mortality. Intuitively, from these data, vitamin supplementation should promote a faster recovery from CABG. However, very little is currently known about the value of vitamin supplementation after cardiac surgery, and studies examining the use of vita- min supplementation in CABG patients either with or with- out specific deficiencies are lacking. Only in the perioperative period as a means of preventing postoperative AF has the role of vitamin supplementation received some attention. Given the suggestion that oxidative stress may potentiate AF, several investigators have evaluated the prophylactic administration of omega-3 fatty acids and antioxidant vitamins to reduce its incidence after CABG.


Given the suggestion that oxidative stress may potentiate AF, several investigators have evaluated the prophylactic administration of omega-3 fatty acids and antioxidant vitamins to reduce its incidence after CABG. Meta-analyses on this subject have presented conflicting data, suggesting a potential for vitamins and omega-3 fatty acids to reduce the risk of perioperative AF, but the results are inconsistent, with a lack of high-quality data in the literature.432 434 Therefore, the available evidence to date remains insufficient, and additional large-scale, adequately powered clinical studies are warranted before routine admin- istration of antioxidant vitamins can be recommended for the reduction of AF after CABG. Vitamins and Supplements Recommendations 1. Vitamin supplementation in patients with specific vitamin deficiencies may be considered for patients undergoing CABG, but the effectiveness is not well established (Class IIb; Level of Evidence C). 2. Supplementation with omega-3 fatty acids and anti- oxidant vitamins may be considered to prevent post- operative AF after CABG, but additional clinical Kulik et al Secondary Prevention After CABG 949 studies are warranted before routine use of antioxi- dant vitamins can be recommended (Class IIb; Level of Evidence A).


Supplementation with omega-3 fatty acids and anti- oxidant vitamins may be considered to prevent post- operative AF after CABG, but additional clinical Kulik et al Secondary Prevention After CABG 949 studies are warranted before routine use of antioxi- dant vitamins can be recommended (Class IIb; Level of Evidence A). Vaccination Influenza is one of the most common, contagious, and mor- bid respiratory infections, with a seasonal pattern of affliction during winter climate.435 Among nontraditional risk factors, a growing interest has developed in the evaluation of influenza infection as a potential cause for subsequent cardiovascular Previous studies have suggested that seasonal influenza-like illnesses may explain the timing of acute throm- botic events in patients with CAD,438 and several epidemio- logical studies have identified an inverse relationship between influenza vaccination and the risk of fatal and nonfatal cardio- Although the mechanism underlying that risk of influenza is not clear, it may relate to triggering the rupture of a vulnerable atherosclerotic plaque, fluid overload, and heart failure or to the susceptibility of a frail and vulner- Randomized, controlled trials have since been performed to explicitly test whether influenza vaccination can reduce the risk of cardiovascular events. In one of the first trials on the subject, Gurfinkel et al443,444 randomized 200 patients with MI and 101 patients undergoing elective percutaneous coronary intervention to either multivalent influenza vaccine or pla- cebo. At 1 year of follow-up, the risk of MI and cardiovascu- lar death was significantly lower among patients who received the vaccine.


At 1 year of follow-up, the risk of MI and cardiovascu- lar death was significantly lower among patients who received the vaccine. These results were subsequently confirmed in other inpatient and outpatient CAD populations.445,446 In a ran- domized trial of 439 patients admitted with acute coronary syndrome, influenza vaccine significantly lowered the com- posite end point of death or hospitalization for CAD, heart failure, or stroke (vaccine versus placebo, 9.5% versus 19.3%; Most recently, a meta-analysis of 6 randomized trials involving 6735 patients at high risk for cardiovascu- lar disease demonstrated that influenza vaccine significantly lowered the risk of cardiovascular events (RR, 0.64; 95% CI, 0.48 0.86; P=0.003), with the greatest treatment benefit seen among the highest-risk patients with more active CAD.435 These findings provide support for the current recommenda- tions for influenza vaccination of all patients admitted with acute coronary syndrome.2,447 Within the general population, the Centers for Disease Control and Prevention currently recommends routine annual influenza vaccination for all people >6 months of age unless specific contraindications are For patients undergoing CABG, there is justification based on the evidence in the cardiology literature to provide influ- enza vaccination for those in whom no contraindication exists. Hospitalization for cardiac surgery provides an opportunity to vaccinate those people who are not immunized and to potentially lower the risk of subsequent adverse cardiovascu- lar events. However, no studies exist regarding the safety or effectiveness of influenza vaccination in reducing periopera- tive morbidity or mortality after CABG. Furthermore, peri- operative immunological alterations may reduce a patient s ability to respond to and to develop immunity after a vaccina- Thus, the optimal timing of perioperative influenza vaccination in patients undergoing cardiac surgery remains unclear.


Furthermore, peri- operative immunological alterations may reduce a patient s ability to respond to and to develop immunity after a vaccina- Thus, the optimal timing of perioperative influenza vaccination in patients undergoing cardiac surgery remains unclear. Whether patients should receive the influenza vaccine preoperatively or in the days or weeks after CABG should be the subject of future research. Vaccination Recommendations 1. Annual influenza vaccination should be offered to all CABG patients, unless contraindications exist (Class I; Level of Evidence B).


Annual influenza vaccination should be offered to all CABG patients, unless contraindications exist (Class I; Level of Evidence B). Disclosures Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/Advisory Board Other Alexander Kulik Boca Raton Regional Hospital AHA None None None None None AstraZeneca ticagrelor research study* Marc Ruel University of Ottawa Heart Institute None None None None None None None T. Bruce Ferguson East Carolina Heart Institute at ECU None None None None None None None Loren F. Hiratzka TriHealth Heart Institute at Bethesda North and Good Samaritan Hospitals None None None None None None None John S. Ikonomidis Medical University of South Carolina None None None None None None None Hani Jneid Baylor College of Medicine None None None None None None None Francisco Lopez-Jimenez Mayo Clinic None None None None None None None Sheila M. McNallan Mayo Clinic None None None None None None None Mahesh Patel Duke University None None None None None None None V ronique L. Roger Mayo Clinic None None None None None None None Frank W. Sellke Rhode Island Hospital/Brown Medical School None None None None None Boehringer Ingelheim, DSMB for clinical trial*; CSL Behring, adjudication committee for trial*; Stryker, advisory committee (pending)* None Domenic A. Sica Virginia Commonwealth University Health System None None None None None None None Lani Zimmerman University of Nebraska Medical Center None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit.


Disclosures Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/Advisory Board Other Alexander Kulik Boca Raton Regional Hospital AHA None None None None None AstraZeneca ticagrelor research study* Marc Ruel University of Ottawa Heart Institute None None None None None None None T. Bruce Ferguson East Carolina Heart Institute at ECU None None None None None None None Loren F. Hiratzka TriHealth Heart Institute at Bethesda North and Good Samaritan Hospitals None None None None None None None John S. Ikonomidis Medical University of South Carolina None None None None None None None Hani Jneid Baylor College of Medicine None None None None None None None Francisco Lopez-Jimenez Mayo Clinic None None None None None None None Sheila M. McNallan Mayo Clinic None None None None None None None Mahesh Patel Duke University None None None None None None None V ronique L. Roger Mayo Clinic None None None None None None None Frank W. Sellke Rhode Island Hospital/Brown Medical School None None None None None Boehringer Ingelheim, DSMB for clinical trial*; CSL Behring, adjudication committee for trial*; Stryker, advisory committee (pending)* None Domenic A. Sica Virginia Commonwealth University Health System None None None None None None None Lani Zimmerman University of Nebraska Medical Center None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be significant if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity.


A relationship is considered to be significant if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Reviewer Disclosures Reviewer Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Stephen E. Fremes Sunnybrook and Women s College Health Sciences Centre None None None None None None None Amit Khera UT Southwestern Medical Center None None None None None None None Peter Mason University of Wisconsin None None None None Medtronic* None None Todd Rosengart Baylor College of Medicine None None None None None None None This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be significant if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Kulik et al Secondary Prevention After CABG 951 References 1.


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