Kidney function after off-pump or 
on-pump coronary artery bypass 
graft surgery 
Wisit Cheungpasitporn 
October 3, 2014
Disclosure 
• None
Coronary Revascularization - Surgical 
Historical Review: 
• 1946 Vineberg IMA implant into cardiac muscle 
• 1954 Murray Experimental anastomosis (IMA/SVG) 
• 1962 Sabiston First CABG (SVG to RCA) 
• 1964 Garrett First CABG to LAD without pump 
• 1967 Kolessov Lima-LAD, thoracotomy 
• 1968 Favaloro Initial experience with SVG with pump 
• 1970 Johnson Expanded experience CABG 
• 1972 Ankeney USA 1st Single graft series w/o CPB
Classic Procedure- CABG 
1. Sternotomy 
2. IMA Harvest 
3. SVG 
4. Cannulation for CP Bypass 
5. Arrest Heart 
6. Anastomosis Heparin 
7. Wean From Bypass 
8. Reverse heparin and 
Stop Bleeding
On-pump CABG
On-pump CABG 
Geissler H J et. al. MMCTS 2006
On-Pump CABG 
Consumption of coagulation factors Bleeding 
Platelet damage 
Leukocyte damage (pyrogen) Fever 
Leukocyte & platelet-mediated 
endothelial damage Edema 
Complement-induced increased 
vascular permeability 
Bradykinin Vasoconstriction 
Platelet & fibrin microemboli Organ dysfunction 
Sellke FW et. al. Circulation. 2005
Sellke FW et. al. Circulation. 2005
Off-pump CABG- (OPCAB) tissue stabilization and heart positioning devices. 
Verma S et al. Circulation. 2004;109:1206-1211
Conventional coronary bypass surgery Beating Heart Coronary Surgery 
Heart lung machine 
Myocardial protection 
Stopping the heart 
Verma S et al. Circulation. 2004;109:1206-1211
• Click here to watch a short clip
OPCAB- “beating heart surgery” 
• Extensive ascending aortic atheromatous or calcific 
changes 
• In U.S., OPCAB ~ 25% in 2001 of isolated CABG and 
has not changed since then. 
• Disadvantage 
• Incomplete revascularization if exposure of the back 
of the heart is challenging 
• Decreased graft patency because of suboptimal 
conditions during the construction of the distal 
anastomosis. 
Lazar HL et. al. Circulation. 2013;128(4):406-13
Relative Contraindications- OPCAB 
- Intramyocardial Coronary a. 
- Very small arteries 
- Calcified arteries. 
- Hemodynamic Instability/Ischemia. 
- Cardiogenic shock. 
Lazar HL et. al. Circulation. 2013;128(4):406-13
Møller CH et. al. Cochrane Database Syst Rev. 2012
Møller CH et. al. Cochrane Database Syst Rev. 2012
Møller CH et. al. Cochrane Database Syst Rev. 2012
Seabra VF et al. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.
Seabra VF et al. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.
Seabra VF et al. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.
GOPCABE study 
• Patients 
• 75 years or older with 
elective first time CABG 
• 2539 patients randomized 
• Intervention 
• Off-pump vs On-pump 
CABG 
• Outcomes 
• Composite of death, MI, 
stroke, revascularization, 
new RRT 
OR = 0.95 (0.71-1.28) for 30 days 
OR = 0.93 (0.76-1.16) for 12 months 
Diegeler et al. NEJM. 2013
GOPCABE study 
• 1612 (67%) had available data on kidney function 
AKI: 47.3% for off-pump vs 52.7% for on-pump (p = 0.17) 
Reents et al. Ann Thorac Surg. 2014 
CKD
Lamy A et. al. NEJM. 2012.
CORONARY TRIAL 
• RCT with blinded adjudicated outcome assessment 
• Off pump vs On pump CABG 
• Randomization 
• 24-hour automated voice-activated telephone service 
• All patients and investigators - aware of study assignments 
• Primary outcomes 
• Composite of death, nonfatal stroke, nonfatal MI, new renal failure 
requiring dialysis 
• An adjudication committee whose members were unaware of study-group 
assignment
Participants 
Inclusion criteria 
• Isolated CABG with median 
sternotomy 
• One of the following: 
• PVD 
• Stroke 
• Renal insufficiency 
• Age ≥ 70 yr 
• If < 70 years 
• ≥ 1 risk factor if 60-69 yr 
• ≥ 2 risk factors if 55-59 yr 
• Risk factor – DM, urgent, smoker, 
LVEF ≤ 35% 
Exclusion criteria 
• Planned additional cardiac procedure 
• Contraindication to off-pump or on-pump 
CABG 
• Life expectancy < 2 years 
• Emergency or re-do CABG
4752 patients from 79 sites in 19 countries 
Netherlands (27) 
Sweden (56) 
United Kingdom (227) 
France (4) 
Italy (48) 
November 2006 – October 2011 
Argentina (257) 
Canada (830) 
Brazil (358) 
USA (68) 
Czech Republic (298) 
Estonia (91) 
Turkey (132) 
Ukraine (11) 
Colombia (57) 
Australia (29) 
Uruguay (34) 
China (781) 
India (1307) 
Chile (137)
Lamy A et al. N Engl J Med 2012;366:1489-1497. 
Crossover 
7.9% 
Crossover 
6.4%
Result – 30 days 
Lamy A et al. N Engl J Med 2012;366:1489-1497.
AKIN stage 1 = 50% increase from baseline or increase ≥ 0.3 mg/dL within 48 hours
Result – 1 year 
Lamy A. et. al. NEJM 2013
Lamy A. et. al. NEJM 2013
JAMA, 311: 2191-2198, 2014.
OBJECTIVES 
• To characterize the risk of acute kidney injury with an 
intervention in a randomized clinical trial. 
• To determine if there is a difference between the 2 
treatment groups in kidney function 1 year later.
Study design and setting 
• Substudy of CORONARY trial 
• 69 of 79 study sites participated 
• January 2010 – June 2011 
• Each site randomized into the protocol 
4752 patients in CORONARY trial 
1777 excluded 
-1336 from participating sites prior to substudy initiation 
-441 from nonparticipating sites 
2975 patients enrolled
Patients 
• Per the CORONARY trial 
• Additional exclusion 
• ESRD - eGFR < 15 ml/min/1.73m2 or chronic dialysis 
• No SCr before randomization
Outcomes 
• Postoperative AKI 
• > 50% increase in SCr from baseline within 30 days of CABG 
• Baseline SCr obtained within 7 days before randomization 
• Highest SCr within 30 days after surgery was assessed for AKI 
• Loss of kidney function at 1 year 
• > 20% loss in eGFR from baseline 
• SCr at 1 year was measured 
• CKD-EPI for eGFR
Statistical analysis 
• Logistic regression – Relative risk 
• Adjusted analysis for pre-specified covariates assessed prior surgery 
• Age 
• Sex 
• LV function 
• DM 
• Long-term use of ACEI or ARB 
• Statin use 
• Diuretic use 
• Urgent/elective surgery 
• CKD (eGFR ≤ 60 ml/min/1.73m2) 
• Subgroup analysis by CKD
Statistical analysis 
• With the enrollment of 2932 patients 
• > 80% power to detect 25% RR reduction in kidney function 
loss at 1 year 
• Missing data 
• SCr – carried forward the prerandomization SCr 
• eGFR at 1 year 
• ESRD patients (≥ 3 mo of dialysis) or died shortly after 
acute dialysis for severe AKI  5 ml/min/1.73 m2
Result 
2975 patients enrolled 
2932 patients included 
43 excluded 
-39 ESRD 
-4 missing SCr before surgery 
1472 off-pump CABG 1460 on-pump CABG 
102 (6.9%) in off-pump group underwent on-pump CABG 
105 (7.2%) in on-pump group underwent off-pump CABG
Result – postoperative AKI 
In survivors, most patients with AKI no longer met the definition 
169/236 (72%) in off-pump vs 180/280 (64%) in on-pump (p=0.08)
Result – kidney function loss at 1 year 
Off pump On pump P-value 
Mean eGFR at 1 year 72±19 73±19 NS 
Mean absolute change in eGFR -3±16 -2±16 0.04
Subgroup analysis 
CKD Non-CKD 
Absolute risk reduction 
for AKI 
-11% (-17.4, -4.6) -1.1% (-4.2, 2.1)
Complete Case As-Treated Analysis
Observational Cohort Analysis 
Kidney function loss at 1 year: 32.1% in AKI vs 12.5% in non-AKI patients 
Adjusted OR = 3.37 (95% CI, 2.65-4.28); p < 0.001
Discussion 
• Off-pump CABG reduces the risk of AKI 
• Benefit was higher in pts with preoperative CKD 
• An intervention that prevents AKI better preserves long-term kidney 
function – remain unproven in RCT 
• Too small magnitude of AKI reduction with off-pump CABG and affect 
too few patients to have an effect on long-term kidney function 
• Too short follow-up 
• Errors with SCr as a measure of kidney function 
• Differential care in follow-up between off- and on-pump CABG 
• Mild to moderate AKI may not cause substantial CKD
Limitations 
• Multiple measurement of kidney function over time both 
before and long after AKI 
• Use of new markers of kidney function or injury 
• Enroll a greater number of pts with baseline CKD 
• a causal relationship between AKI and long-term kidney 
function more likely to observed if exist
Strengths of this study 
• Largest AKI prevention trial conducted to date. 
• International recruitment across 19 countries will 
provide generalizable estimates of the treatment effect 
• Use of a rigorous randomized trial method 
• concealed allocation 
• blinded central adjudication of outcomes 
• No evidence of differential ascertainment of kidney 
outcomes in two surgical groups 
• Complete follow-up 
• >90% had 1-year SCr measured
Conclusion 
• The use of off-pump vs on-pump CABG surgery 
• Reduced the risk of postoperative AKI; 
• Failed to observe better kidney function with off-pump 
vs on-pump CABG surgery 1 year later.
Questions & Discussion

Renal Function After Off-Pump CABG: Journal Club

  • 1.
    Kidney function afteroff-pump or on-pump coronary artery bypass graft surgery Wisit Cheungpasitporn October 3, 2014
  • 2.
  • 3.
    Coronary Revascularization -Surgical Historical Review: • 1946 Vineberg IMA implant into cardiac muscle • 1954 Murray Experimental anastomosis (IMA/SVG) • 1962 Sabiston First CABG (SVG to RCA) • 1964 Garrett First CABG to LAD without pump • 1967 Kolessov Lima-LAD, thoracotomy • 1968 Favaloro Initial experience with SVG with pump • 1970 Johnson Expanded experience CABG • 1972 Ankeney USA 1st Single graft series w/o CPB
  • 4.
    Classic Procedure- CABG 1. Sternotomy 2. IMA Harvest 3. SVG 4. Cannulation for CP Bypass 5. Arrest Heart 6. Anastomosis Heparin 7. Wean From Bypass 8. Reverse heparin and Stop Bleeding
  • 5.
  • 6.
    On-pump CABG GeisslerH J et. al. MMCTS 2006
  • 7.
    On-Pump CABG Consumptionof coagulation factors Bleeding Platelet damage Leukocyte damage (pyrogen) Fever Leukocyte & platelet-mediated endothelial damage Edema Complement-induced increased vascular permeability Bradykinin Vasoconstriction Platelet & fibrin microemboli Organ dysfunction Sellke FW et. al. Circulation. 2005
  • 8.
    Sellke FW et.al. Circulation. 2005
  • 9.
    Off-pump CABG- (OPCAB)tissue stabilization and heart positioning devices. Verma S et al. Circulation. 2004;109:1206-1211
  • 10.
    Conventional coronary bypasssurgery Beating Heart Coronary Surgery Heart lung machine Myocardial protection Stopping the heart Verma S et al. Circulation. 2004;109:1206-1211
  • 11.
    • Click hereto watch a short clip
  • 12.
    OPCAB- “beating heartsurgery” • Extensive ascending aortic atheromatous or calcific changes • In U.S., OPCAB ~ 25% in 2001 of isolated CABG and has not changed since then. • Disadvantage • Incomplete revascularization if exposure of the back of the heart is challenging • Decreased graft patency because of suboptimal conditions during the construction of the distal anastomosis. Lazar HL et. al. Circulation. 2013;128(4):406-13
  • 13.
    Relative Contraindications- OPCAB - Intramyocardial Coronary a. - Very small arteries - Calcified arteries. - Hemodynamic Instability/Ischemia. - Cardiogenic shock. Lazar HL et. al. Circulation. 2013;128(4):406-13
  • 14.
    Møller CH et.al. Cochrane Database Syst Rev. 2012
  • 15.
    Møller CH et.al. Cochrane Database Syst Rev. 2012
  • 16.
    Møller CH et.al. Cochrane Database Syst Rev. 2012
  • 18.
    Seabra VF etal. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.
  • 19.
    Seabra VF etal. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.
  • 20.
    Seabra VF etal. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.
  • 21.
    GOPCABE study •Patients • 75 years or older with elective first time CABG • 2539 patients randomized • Intervention • Off-pump vs On-pump CABG • Outcomes • Composite of death, MI, stroke, revascularization, new RRT OR = 0.95 (0.71-1.28) for 30 days OR = 0.93 (0.76-1.16) for 12 months Diegeler et al. NEJM. 2013
  • 22.
    GOPCABE study •1612 (67%) had available data on kidney function AKI: 47.3% for off-pump vs 52.7% for on-pump (p = 0.17) Reents et al. Ann Thorac Surg. 2014 CKD
  • 23.
    Lamy A et.al. NEJM. 2012.
  • 24.
    CORONARY TRIAL •RCT with blinded adjudicated outcome assessment • Off pump vs On pump CABG • Randomization • 24-hour automated voice-activated telephone service • All patients and investigators - aware of study assignments • Primary outcomes • Composite of death, nonfatal stroke, nonfatal MI, new renal failure requiring dialysis • An adjudication committee whose members were unaware of study-group assignment
  • 25.
    Participants Inclusion criteria • Isolated CABG with median sternotomy • One of the following: • PVD • Stroke • Renal insufficiency • Age ≥ 70 yr • If < 70 years • ≥ 1 risk factor if 60-69 yr • ≥ 2 risk factors if 55-59 yr • Risk factor – DM, urgent, smoker, LVEF ≤ 35% Exclusion criteria • Planned additional cardiac procedure • Contraindication to off-pump or on-pump CABG • Life expectancy < 2 years • Emergency or re-do CABG
  • 26.
    4752 patients from79 sites in 19 countries Netherlands (27) Sweden (56) United Kingdom (227) France (4) Italy (48) November 2006 – October 2011 Argentina (257) Canada (830) Brazil (358) USA (68) Czech Republic (298) Estonia (91) Turkey (132) Ukraine (11) Colombia (57) Australia (29) Uruguay (34) China (781) India (1307) Chile (137)
  • 27.
    Lamy A etal. N Engl J Med 2012;366:1489-1497. Crossover 7.9% Crossover 6.4%
  • 28.
    Result – 30days Lamy A et al. N Engl J Med 2012;366:1489-1497.
  • 29.
    AKIN stage 1= 50% increase from baseline or increase ≥ 0.3 mg/dL within 48 hours
  • 30.
    Result – 1year Lamy A. et. al. NEJM 2013
  • 31.
    Lamy A. et.al. NEJM 2013
  • 32.
  • 33.
    OBJECTIVES • Tocharacterize the risk of acute kidney injury with an intervention in a randomized clinical trial. • To determine if there is a difference between the 2 treatment groups in kidney function 1 year later.
  • 34.
    Study design andsetting • Substudy of CORONARY trial • 69 of 79 study sites participated • January 2010 – June 2011 • Each site randomized into the protocol 4752 patients in CORONARY trial 1777 excluded -1336 from participating sites prior to substudy initiation -441 from nonparticipating sites 2975 patients enrolled
  • 35.
    Patients • Perthe CORONARY trial • Additional exclusion • ESRD - eGFR < 15 ml/min/1.73m2 or chronic dialysis • No SCr before randomization
  • 36.
    Outcomes • PostoperativeAKI • > 50% increase in SCr from baseline within 30 days of CABG • Baseline SCr obtained within 7 days before randomization • Highest SCr within 30 days after surgery was assessed for AKI • Loss of kidney function at 1 year • > 20% loss in eGFR from baseline • SCr at 1 year was measured • CKD-EPI for eGFR
  • 37.
    Statistical analysis •Logistic regression – Relative risk • Adjusted analysis for pre-specified covariates assessed prior surgery • Age • Sex • LV function • DM • Long-term use of ACEI or ARB • Statin use • Diuretic use • Urgent/elective surgery • CKD (eGFR ≤ 60 ml/min/1.73m2) • Subgroup analysis by CKD
  • 38.
    Statistical analysis •With the enrollment of 2932 patients • > 80% power to detect 25% RR reduction in kidney function loss at 1 year • Missing data • SCr – carried forward the prerandomization SCr • eGFR at 1 year • ESRD patients (≥ 3 mo of dialysis) or died shortly after acute dialysis for severe AKI  5 ml/min/1.73 m2
  • 39.
    Result 2975 patientsenrolled 2932 patients included 43 excluded -39 ESRD -4 missing SCr before surgery 1472 off-pump CABG 1460 on-pump CABG 102 (6.9%) in off-pump group underwent on-pump CABG 105 (7.2%) in on-pump group underwent off-pump CABG
  • 41.
    Result – postoperativeAKI In survivors, most patients with AKI no longer met the definition 169/236 (72%) in off-pump vs 180/280 (64%) in on-pump (p=0.08)
  • 42.
    Result – kidneyfunction loss at 1 year Off pump On pump P-value Mean eGFR at 1 year 72±19 73±19 NS Mean absolute change in eGFR -3±16 -2±16 0.04
  • 43.
    Subgroup analysis CKDNon-CKD Absolute risk reduction for AKI -11% (-17.4, -4.6) -1.1% (-4.2, 2.1)
  • 44.
  • 45.
    Observational Cohort Analysis Kidney function loss at 1 year: 32.1% in AKI vs 12.5% in non-AKI patients Adjusted OR = 3.37 (95% CI, 2.65-4.28); p < 0.001
  • 46.
    Discussion • Off-pumpCABG reduces the risk of AKI • Benefit was higher in pts with preoperative CKD • An intervention that prevents AKI better preserves long-term kidney function – remain unproven in RCT • Too small magnitude of AKI reduction with off-pump CABG and affect too few patients to have an effect on long-term kidney function • Too short follow-up • Errors with SCr as a measure of kidney function • Differential care in follow-up between off- and on-pump CABG • Mild to moderate AKI may not cause substantial CKD
  • 47.
    Limitations • Multiplemeasurement of kidney function over time both before and long after AKI • Use of new markers of kidney function or injury • Enroll a greater number of pts with baseline CKD • a causal relationship between AKI and long-term kidney function more likely to observed if exist
  • 48.
    Strengths of thisstudy • Largest AKI prevention trial conducted to date. • International recruitment across 19 countries will provide generalizable estimates of the treatment effect • Use of a rigorous randomized trial method • concealed allocation • blinded central adjudication of outcomes • No evidence of differential ascertainment of kidney outcomes in two surgical groups • Complete follow-up • >90% had 1-year SCr measured
  • 49.
    Conclusion • Theuse of off-pump vs on-pump CABG surgery • Reduced the risk of postoperative AKI; • Failed to observe better kidney function with off-pump vs on-pump CABG surgery 1 year later.
  • 50.

Editor's Notes

  • #4 Standard coronary artery bypass graft surgery (CABG) employs a midline incision through the sternum, placement of the patient on cardiopulmonary bypass, and arrest of the heart with cardioplegia. This approach allows for optimal exposure of the coronary arteries and a motionless (non-beating) heart, both of which optimize the suturing of the distal anastomoses of the bypass.
  • #9 Composition of cardioplegic solutions
  • #16 Figure 1. OPCAB tissue stabilization and heart positioning devices. Top, the Genzyme Immobilizer, which utilizes a stabilization platform and silastic vessel loops. Middle, the Medtronic Octopus4 tissue stabilizer and Starfish2 heart positioner, which utilize vacuum suction to stabilize and position the heart. Bottom, the Coro-Vasc System (CoroNeo Inc), which illustrates silastic snares that are looped around the target coronary vessel and then fixed to a small immobile plate, thus directly immobilizing the target vessel.
  • #33 Directed acyclic graph of the causal pathway between coronary artery bypass grafting (CABG) surgery type (off-pump vs on-pump), mediating variable acute kidney injury (AKI) and dependent variable renal function 1 year after surgery. The dashed arrows indicate that the causal relationship is unknown but will be investigated.