**3. Peripheral arterial disease and CABG outcomes**

of 638 patients with acute coronary syndrome undergoing emergency CABG out of which 240 were operated off pump and 398 had standard on-pump CABG. 14.5% of patients were in cardiogenic shock along with serum creatinine greater than 1.8 mg /dl. Follow-up was up to 5 years. The results showed that in the off pump CABG group, in-hospital outcomes were significantly better. With off-pump CABG, skin incision to culprit lesion revascularization time was significantly reduced. There was less requirement for prolonged mechanical venti‐ lation, less need for inotropic support, less incidence of atrial fibrillation, lower stroke rate (2.5 % vs. 6.7%), shorter intensive care unit stay and less sternal wound healing complica‐ tions (2.5% vs. 3.5%). The overall hospital mortality rate was also reduced (5.7%) as com‐

As we have discussed, numerous studies have shown that patients with CKD have worse outcomes including an increased mortality and other complications after undergoing CABG, when compared to patients without CKD. However, an increasing number of patients with ESRD continue to undergo CABG and additionally, these patients are getting more complex a higher presence of comorbidities including diabetes, hypertension and obesity [Figure 1]. However, fortunately, in-hospital mortality rates have declined remarkably from over 31% to 5.4% in patients with ESRD (versus 4.7% to 1.8% among patients without ESRD) [45]. However, the mortality in ESRD patients remains 3-fold higher which indicates the need of

**Figure 1.** Graph depicting the increasing trend in the number of patients with end-stage renal disease (ESRD) under‐ going coronary artery bypass grafting (CABG) over a 15-year period (Data from Parikh DS, Swaminathan M, Archer LE, et al. Perioperative outcomes among patients with end-stage renal disease following coronary artery bypass surgery in

pared to those on cardiopulmonary bypass (8.6%) [44].

continued work to improve outcomes in these patients [Figure 2].

the USA. Nephrol. Dial. Transpl 2010; 25(7):2275-2283).

**2.9. Conclusion**

446 Artery Bypass

The presence of peripheral arterial disease (PAD) plays a significant role in the potential morbidity and mortality of patients undergoing CABG. Coexisting CAD and PAD signifi‐ cantly influences long term survival adversely [49,50]. In the Coronary Artery Surgery Study (CASS), PAD was found to carry a higher risk of mortality even when compared to patients who had previously experienced myocardial infarction and angina [51].PAD is in‐ cluded as a major risk factor when calculating risk of mortality in patients undergoing CABG [1,2]. Non-invasive diagnostic testing for PAD includes segmental pressure measure‐ ment, treadmill stress, and Doppler ultrasound with the most significant information pro‐ vided by the ankle-brachial index (ABI). Normally it is greater than 1.0 while <0.9 is considered abnormal. In patients with critical limb ischemia, the ABI is commonly <0.4. It is suspected that in PAD patients, poor surgical outcomes after CABG could be related to rap‐ id progression of atherosclerotic coronary artery disease and more extensive small vessel CAD with poor target foci for intervention resulting in higher mortality rates. Also the high‐ ly variable rates of CAD progression in patients with and without PAD leads to poor out‐ comes as well [52].

and smoking being the major ones. Diabetes is a major predictor of outcomes of CABG in patients with PAD. It is associated with more than 50% of major amputations in patients with PAD. In a study of 261 patients by Jonason et al (47 diabetic and 224 non diabetic), at six year follow up, showed an incidence of gangrene in 31% of diabetics as compared to 5% in non-diabetics [66]. Also hypertension, strong family history of premature atherosclerotic vascular disease, and hyperlipidemia are also contributory. Progression to severe ischemia or amputation in symptomatic patients with intermittent claudication occurs at 1.4% per

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The rate of all-cause mortality in patients with large-vessel PAD compared with the normal population is three times greater, while the risk of cardiovascular mortality is six-fold more, with the most common etiology being myocardial infarction or stroke [67]. In an analysis of 900 patients with LVEF of 0.35 or less, among whom 38% were diabetics, all-cause mortality was 26% in diabetics and 24% in non-diabetics (p>0.05). However, 4 -year re-hospitalization rates were 85% in diabetics and 69% in non-diabetics (p = 0.0001). The incidence of superfi‐ cial sternal wound infection was 3.3 times higher and of renal failure was 2.2 times greater

Finally, a combination of CKD and PAD is even worse for the overall outcomes of pa‐ tients undergoing CABG. In a prospective study of 36,641 CABG patients over a ten year period, long term survival rates of patient groups stratified as non- diabetic, dia‐ betic with PAD and CKD, and diabetics without PAD and CKD were determined. The follow up was equivalent to 154,140 person-years. Annual mortality rates for non-dia‐ betic and diabetic groups were 3.1 deaths per 100 person-years and 4.4 deaths per 100 person-years, respectively. The annual mortality rate for diabetic subjects with CKD, PAD, or both was significantly higher at 9.4 deaths per 100 person-years. Thus, pa‐ tients undergoing CABG who are diabetic along with having PAD and CKD are at

Carotid artery stenosis is an important risk factor in determining post CABG outcomes such as stroke and additionally, has a direct impact on perioperative mortality [70,71]. Duplex ultrasonography or contrast-based techniques can be utilized pre-operatively in high risk patients with age greater than 65 years and multiple risk factors such as dia‐ betes mellitus, hypertension, and previous transient ischemic attacks or stroke. In case of severe carotid disease, surgical planning might need to include carotid endarterecto‐ my along with CABG simultaneously versus consideration for endovascular repair of

In a study of 582 patients undergoing CABG, preoperative carotid artery duplex scans were performed to assess the presence of asymptomatic carotid artery stenosis. >50% uni- or bilateral stenosis was present in 22% while >80% uni- or bilateral stenosis was present in 12% of patients. The post-operative hemispheric stroke rate in patients with carotid stenosis >50% was 3.8% as compared to 0.34% in patients without carotid

year with poor prognosis in patients with diabetes and smoking [66,67].

highest mortality risk over long term follow up of 10 years [69].

**3.1. Impact of cerebrovascular disease on outcomes of CABG**

carotid disease pre-operatively.

in diabetic patients as compared to non- diabetics [68].

In comparison with PCI, CABG has been shown to improve mortality significantly more in patients with PAD. Data from 1305 consecutive patients undergoing coronary revasculariza‐ tion (PCI, n = 341; CABG, n = 964) between 1994 and 1996 showed that patients with PAD undergoing CABG had better survival at 3 years when compared to PCI (hazard ratio 0.68; 95% CI 0.46-1.00; p = 0.05) [53].

In a retrospective analysis on 1,164 consecutive patients who underwent CABG (370 with PAD), it was shown that PAD did not impact 30-day mortality. However, multivariable analysis showed that patients with PAD had a significantly worse 9-year survival rate com‐ pared to patients without PAD (72.9% vs. 82.8%; adjusted hazard ratio, 1.7; p = 0.004) [54]. Trachiotis et al studied long-term survival in 11,830 CABG patients, 744 of whom had LVEF <0.35. Among all patients, regardless of ventricular function, diabetes was linked with a 59% increase in the relative risk of death [55]. It was shown by Birkmeyer et al that patients un‐ dergoing CABG with history of PAD had a 20% five-year mortality rate as compared to 8% for those without known PAD [56,57]. Kaul et al showed that after risk factor adjustment, patients with PAD had mortality rates twice as high as patients without PAD [58]. Loponen et al showed in a multicenter study on 3000 patients that patients with PAD undergoing CABG had a 71% greater in-hospital mortality rate than those without PAD [59].

In a ten year prospective study of 8000 patients with PAD undergoing CABG, it was seen that they had a higher incidence of various intra- and post-operative complications includ‐ ing arrhythmias, stroke, pulmonary complications, low cardiac output state, longer hospital stay, infections, and acute renal failure. These results have been borne out by other studies as well [60-63].

The anatomic diversity of obstructive atherosclerotic disease process is particularly interest‐ ing. Patient can have isolated cerebrovascular disease involving carotid arteries, or lower ex‐ tremity arterial disease or a combination thereof. It has been shown that as the number of involved arterial beds increases, the mortality increases. In a study on 2817 patients under‐ going CABG, it was demonstrated that when compared to patients with CAD alone, the mortality was 1.6 times, 2.5 times, and 2.8 times higher for patients with concomitant cere‐ brovascular disease, lower extremity arterial disease and both cerebrovascular and lower ex‐ tremity arterial disease, respectively [64]. Another study found that in patients younger than 40 years, the most common pattern of lower extremity arterial disease is aortoiliac disease while in patients older than 40 years, femoro-popliteal disease is predominant and causes intermittent claudication in 65% of these patients [65].

Commonly, patients with iliac disease have hemodynamically significant stenoses, while majority of patients with femoral disease have total occlusions characteristically involving long segments of the superficial femoral artery. Consequently, percutaneous revasculariza‐ tion of the femoral arterial segments is technically difficult as compared to iliac endovascu‐ lar repair. The risk factors associated with PAD are similar to those for CAD, with diabetes and smoking being the major ones. Diabetes is a major predictor of outcomes of CABG in patients with PAD. It is associated with more than 50% of major amputations in patients with PAD. In a study of 261 patients by Jonason et al (47 diabetic and 224 non diabetic), at six year follow up, showed an incidence of gangrene in 31% of diabetics as compared to 5% in non-diabetics [66]. Also hypertension, strong family history of premature atherosclerotic vascular disease, and hyperlipidemia are also contributory. Progression to severe ischemia or amputation in symptomatic patients with intermittent claudication occurs at 1.4% per year with poor prognosis in patients with diabetes and smoking [66,67].

CAD with poor target foci for intervention resulting in higher mortality rates. Also the high‐ ly variable rates of CAD progression in patients with and without PAD leads to poor out‐

In comparison with PCI, CABG has been shown to improve mortality significantly more in patients with PAD. Data from 1305 consecutive patients undergoing coronary revasculariza‐ tion (PCI, n = 341; CABG, n = 964) between 1994 and 1996 showed that patients with PAD undergoing CABG had better survival at 3 years when compared to PCI (hazard ratio 0.68;

In a retrospective analysis on 1,164 consecutive patients who underwent CABG (370 with PAD), it was shown that PAD did not impact 30-day mortality. However, multivariable analysis showed that patients with PAD had a significantly worse 9-year survival rate com‐ pared to patients without PAD (72.9% vs. 82.8%; adjusted hazard ratio, 1.7; p = 0.004) [54]. Trachiotis et al studied long-term survival in 11,830 CABG patients, 744 of whom had LVEF <0.35. Among all patients, regardless of ventricular function, diabetes was linked with a 59% increase in the relative risk of death [55]. It was shown by Birkmeyer et al that patients un‐ dergoing CABG with history of PAD had a 20% five-year mortality rate as compared to 8% for those without known PAD [56,57]. Kaul et al showed that after risk factor adjustment, patients with PAD had mortality rates twice as high as patients without PAD [58]. Loponen et al showed in a multicenter study on 3000 patients that patients with PAD undergoing

CABG had a 71% greater in-hospital mortality rate than those without PAD [59].

intermittent claudication in 65% of these patients [65].

In a ten year prospective study of 8000 patients with PAD undergoing CABG, it was seen that they had a higher incidence of various intra- and post-operative complications includ‐ ing arrhythmias, stroke, pulmonary complications, low cardiac output state, longer hospital stay, infections, and acute renal failure. These results have been borne out by other studies

The anatomic diversity of obstructive atherosclerotic disease process is particularly interest‐ ing. Patient can have isolated cerebrovascular disease involving carotid arteries, or lower ex‐ tremity arterial disease or a combination thereof. It has been shown that as the number of involved arterial beds increases, the mortality increases. In a study on 2817 patients under‐ going CABG, it was demonstrated that when compared to patients with CAD alone, the mortality was 1.6 times, 2.5 times, and 2.8 times higher for patients with concomitant cere‐ brovascular disease, lower extremity arterial disease and both cerebrovascular and lower ex‐ tremity arterial disease, respectively [64]. Another study found that in patients younger than 40 years, the most common pattern of lower extremity arterial disease is aortoiliac disease while in patients older than 40 years, femoro-popliteal disease is predominant and causes

Commonly, patients with iliac disease have hemodynamically significant stenoses, while majority of patients with femoral disease have total occlusions characteristically involving long segments of the superficial femoral artery. Consequently, percutaneous revasculariza‐ tion of the femoral arterial segments is technically difficult as compared to iliac endovascu‐ lar repair. The risk factors associated with PAD are similar to those for CAD, with diabetes

comes as well [52].

448 Artery Bypass

as well [60-63].

95% CI 0.46-1.00; p = 0.05) [53].

The rate of all-cause mortality in patients with large-vessel PAD compared with the normal population is three times greater, while the risk of cardiovascular mortality is six-fold more, with the most common etiology being myocardial infarction or stroke [67]. In an analysis of 900 patients with LVEF of 0.35 or less, among whom 38% were diabetics, all-cause mortality was 26% in diabetics and 24% in non-diabetics (p>0.05). However, 4 -year re-hospitalization rates were 85% in diabetics and 69% in non-diabetics (p = 0.0001). The incidence of superfi‐ cial sternal wound infection was 3.3 times higher and of renal failure was 2.2 times greater in diabetic patients as compared to non- diabetics [68].

Finally, a combination of CKD and PAD is even worse for the overall outcomes of pa‐ tients undergoing CABG. In a prospective study of 36,641 CABG patients over a ten year period, long term survival rates of patient groups stratified as non- diabetic, dia‐ betic with PAD and CKD, and diabetics without PAD and CKD were determined. The follow up was equivalent to 154,140 person-years. Annual mortality rates for non-dia‐ betic and diabetic groups were 3.1 deaths per 100 person-years and 4.4 deaths per 100 person-years, respectively. The annual mortality rate for diabetic subjects with CKD, PAD, or both was significantly higher at 9.4 deaths per 100 person-years. Thus, pa‐ tients undergoing CABG who are diabetic along with having PAD and CKD are at highest mortality risk over long term follow up of 10 years [69].

#### **3.1. Impact of cerebrovascular disease on outcomes of CABG**

Carotid artery stenosis is an important risk factor in determining post CABG outcomes such as stroke and additionally, has a direct impact on perioperative mortality [70,71]. Duplex ultrasonography or contrast-based techniques can be utilized pre-operatively in high risk patients with age greater than 65 years and multiple risk factors such as dia‐ betes mellitus, hypertension, and previous transient ischemic attacks or stroke. In case of severe carotid disease, surgical planning might need to include carotid endarterecto‐ my along with CABG simultaneously versus consideration for endovascular repair of carotid disease pre-operatively.

In a study of 582 patients undergoing CABG, preoperative carotid artery duplex scans were performed to assess the presence of asymptomatic carotid artery stenosis. >50% uni- or bilateral stenosis was present in 22% while >80% uni- or bilateral stenosis was present in 12% of patients. The post-operative hemispheric stroke rate in patients with carotid stenosis >50% was 3.8% as compared to 0.34% in patients without carotid stenosis (p = 0.0072). Also the risk of hemispheric stroke was 5.3% in patients with unilateral 80% to 99% stenosis, or bilateral 50% to 99% stenosis, or unilateral occlusion with contralateral 50% or greater stenosis. Patients with a unilateral 50% to 79% steno‐ sis did not suffer a stroke in this study [70].

fraction less than 40%, small body mass index, or clinical presentation in acute or emergency setting. So, there is a proven consistent trend of protective LIMA effect in

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A major cause of short-term mortality post CABG and therefore, poor surgical out‐ come is graft failure. In 1972, Lesperance et al reported that out of a total of 105 sa‐ phenous vein grafts (SVG) used during CABG, 20% had early occlusion [76]. In a review of SVG disease, Motwani and Topol showed an early SVG occlusion rate of 15% and elucidated the diverse etiology of SVG closure [77]. At one month post CABG, the major cause of graft failure is thrombosis. From a month to one year post CABG, intimal hyperplasia is the chief contributor while after one year, atherosclerotic changes have been primarily implicated. They also demonstrated that arterial runoff was the single most important determinant of short-term graft survival. Occluded ves‐

The internal diameter of the mid-LAD is approximately1.7 mm, while that of the sa‐ phenous vein is 4-5 mm. This difference leads to variable flow rates and slow flow ve‐ locity in the SVG as compared to mid-LAD. The sluggish flow causes red blood cell sledging and consequent thrombosis. The internal diameter of the IMA is almost equivalent the mid-LAD, and thus there is decreased risk of graft thrombosis. They al‐ so highlighted that LIMA graft in addition to matching favorable dimensions of native LAD, lacks valves, has less endothelial fenestrations, and has a greater resistance to trauma while it is being harvested [78]. Other advantageous physiological characteris‐ tics of the IMA include higher flow reserve and shear stress, greater nitric oxide and prostacyclin production leading to vasodilation and inhibition of platelet aggregation, appropriate relaxation response to thrombin, less vasoconstrictor sensitivity and high vasodilator sensitivity along with decreased number of fibroblast growth factor recep‐

In a patent population in whom both radial artery and SVG grafts were used for CABG, it

Off pump CABG (OPCAB) is referred to as CABG without use of cardiopulmonary bypass or cardioplegia while on pump CABG is referred to the use of cardiopulmonary bypass and cardioplegia. There have been various studies which generally show benefits of OPCAB as compared to standard CABG. Benefits include less bleeding complications, stroke and renal

In a retrospective analysis of 68,000 patients by Ractz et al, 9000 OPCAB revascularizations were performed with this group comprising many high-risk patients including those with >60 years of age, female gender, low LVEF, previous history of CABG, stroke, PAD, conges‐

was found that radial artery grafts fared worse than SVGs in patients with PAD [79].

sels distal to the SVG anastomosis resulted in thrombosis and graft failures.

high risk groups as well [75].

**3.4. Impact of PAD on graft failure in CABG**

tors thus reducing plaque formation [78].

**3.5. Off pump CABG and standard CABG**

failure after OPCAB.

In a study of 3344 patients undergoing CABG who were followed over a three year period to assess the effect of carotid artery stenosis on perioperative stroke and mortality, it was found that the clinical outcomes were directly related to the degree of carotid stenosis. Pa‐ tients with carotid stenosis <60% had a significantly less risk of suffering perioperative stroke and mortality when compared to patients with >60% stenosis, especially patients with a totally occluded carotid artery [71].

These studies signify carotid artery disease as an important subset of patients with PAD which can adversely affect post CABG outcomes in terms of incidence of stroke and mortality rates.
