Thomas A. Schwann

Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: Implications on operative outcome*

Objective:Acute renal injury and failure (ARF) after cardiopulmonary bypass (CPB) has been linked to low on-pump hematocrit (hematocrit). We aimed to 1) elucidate if and how this relation is modulated by the duration of CPB (TCPB) and on-pump packed red blood cell transfusions and 2) to quantify the impact of post-CPB renal injury on operational outcome and resource utilization. Design:Retrospective review. Setting:A Northwest Ohio community hospital. Patients:Adult coronary artery bypass surgery patients with CPB but no preoperative renal failure. Interventions:None. Measurements and Main Results:We quantified post-CPB renal injury via 1) the peak postoperative change in serum creatinine (Cr) level relative to pre-CPB values (%&Dgr;Cr) and 2) ARF, defined as the coincidence of post-CPB Cr ≥2.1 mg/dL and >2 times pre-CPB Cr. The separate effects of lowest hematocrit, intraoperative packed RBC transfusions, and TCPB on %&Dgr;Cr and ARF were derived via multivariate regression, overlapping quintile subgroup analyses, and propensity matching. Lowest hematocrit (22.0% ± 4.6% sd), TCPB (94 ± 35 mins), and pre-CPB Cr (1.01 ± 0.23 mg/dL) varied widely. %&Dgr;Cr varied substantially (24 ± 57%), and ARF was documented in 89 patients (5.1%). Both %&Dgr;Cr (p < .001) and ARF (p < .001) exhibited sigmoidal dose-dependent associations to lowest hematocrit that were 1) modulated by TCPB such that the renal injury was exacerbated as TCPB increased, 2) worse in patients with relatively elevated pre-CPB Cr (≥1.2 mg/dL), and 3) worse with intraoperative packed red blood cell transfusions (n = 385; 21.9%), in comparison with patients at similar lowest hematocrit. Operative mortality (p < .01) and hospital stays (p < .001) were increased systematically and significantly as a function of increased post-CPB renal injury. Conclusions:CPB hemodilution to hematocrit <24% is associated with a systematically increased likelihood of renal injury (including ARF) and consequently worse operative outcomes. This effect is exacerbated when CPB is prolonged with intraoperative packed red blood cell transfusions and in patients with borderline renal function. Our data add to the concerns regarding the safety of currently accepted CPB practice guidelines.

Improved Survival With Radial Artery Versus Vein Conduits in Coronary Bypass Surgery With Left Internal Thoracic Artery to Left Anterior Descending Artery Grafting

Background—Given its proven survival benefit, left internal thoracic artery to left anterior descending (LITA-LAD) grafting has become a fundamental part of CABG. This grafting also led to increased use of other arterial conduits, of which the radial artery is most popular. Whether radial grafting improves survival beyond that achieved by LITA-LAD alone is not known. Methods and Results—We compared 6-year outcomes in propensity-matched CABG-LITA-LAD patients (925 each) divided into those with ≥1 radial grafts and those with vein-only grafting. Matched patients had essentially identical demographics, comorbidities, coronary disease, and operative data. Perioperative outcomes, including death (radial, 11 [1.2%]; vein, 10 [1.1%]), were similar for the 2 groups. Cumulative 0- to 6-year survival was better for radial patients (risk ratio, 0.675), particularly after 3 years (P <0.03). Six-year survival in vein (86.8%) and radial (92.1%) patients indicated 67% greater overall vein mortality. Incidence rates of radial and vein repeated catheterization (190 of 925 [20.5%] versus 199 of 925 [21.5%]) and revascularization (8.8% versus 8.5%) were similar. Angiography data in restudied symptomatic patients showed a trend for greater radial patency. Vein failure (66 of 161 [41%]) was significantly worse than radial failure (46 of 157 [29.3%]) in patients receiving both types of grafts (P =0.039). Conclusions—Using radial as a second arterial conduit in CABG-LITA-LAD as opposed to vein grafting improves long-term outcomes as a result of decreased late deaths, especially after the third postoperative year.

Obesity and risk of new-onset atrial fibrillation after cardiac surgery.

Background— New-onset postoperative atrial fibrillation (AF) is a common complication of cardiac surgery that has substantial effects on outcomes. In the general (nonsurgical) adult population, AF has been linked to increasing obesity, which correlates with left atrial enlargement. It is not known whether postoperative AF is similarly linked to obesity. Methods and Results— This was a retrospective analysis of the incidence of AF in terms of body mass index (BMI). A total of 8051 consecutive cardiac surgery patients (1994 to 2004; mean age 64 [SD 11] years; 5372 men [67%]) who were free of any history of preoperative AF or flutter were included in the analysis. This series included 3164 obese patients (39%; median age 62 years) and 4887 nonobese patients (61%; median age 66 years), who were further divided on the basis of BMI (kg/m2) into 6 groups: BMI <22 kg/m2, 22≤BMI≤25 kg/m2 (normal), 2540 kg/m2 (obese III). Unadjusted AF incidence was similar in obese and nonobese patients (n=742 [23.5%] versus n=1068 [21.9%], respectively; P=0.099). Covariate-adjusted ORs for AF were systematically greater for larger patients than for patients in the normal group (adjusted OR [95% CI]=1.18 [1.00 to 1.40], 1.36 [1.14 to 1.63], 1.69 [1.35 to 2.11], and 2.39 [1.81 to 3.17] for overweight, obese I, obese II, and obese III, respectively). Other AF predictors included age (adjusted OR=1.52 [95% CI 1.46 to 1.58] per 10 years), mitral valve surgery (adjusted OR=2.42 [95% CI 1.92 to 3.06]), aortic valve surgery (adjusted OR=1.79 [95% CI 1.45 to 2.22]), chronic obstructive pulmonary disease (adjusted OR=1.28 [95% CI 1.12 to 1.46]), male gender (adjusted OR=1.24 [95% CI 1.10 to 1.40]), preoperative &bgr;-blocker use (adjusted OR=1.17 [95% CI 1.05 to 1.32]), vascular disease (adjusted OR=1.18 [95% CI 1.05 to 1.32]), white race (adjusted OR=1.33 [95% CI 1.07 to 1.66]), history of arrhythmia other than AF/flutter (adjusted OR=0.80 [95% CI 0.68 to 0.96]), ejection fraction <40% (adjusted OR=1.16 [95% CI 1.03 to 1.31]), left main disease (adjusted OR=1.15 [95% CI 1.00 to 1.32]), and off-pump surgery (adjusted OR=0.61 [95% CI 0.44 to 0.83]). The obesity-AF association was confirmed in 4 1-to-1 propensity-matched obese versus nonobese comparisons and in 2 separate derivation/validation subcohort analyses. Conclusions— Obesity is an important determinant of new-onset AF after cardiac surgery. Future postoperative AF risk models should incorporate BMI or obesity levels. Studies examining the efficacy of AF-minimizing prophylactic interventions in high-BMI patients, particularly in the elderly, may be warranted.

Late Results of Conventional Versus All-Arterial Revascularization Based on Internal Thoracic and Radial Artery Grafting

BACKGROUND Use of one or more arterial grafts to revascularize two-vessel and three-vessel coronary artery disease has been shown to improve coronary artery bypass graft surgery (CABG) survival. Yet, the presumed long-term survival benefits of all-arterial CABG have not been quantified. METHODS We compared propensity-adjusted 12-year survival in two contemporaneous multivessel primary CABG cohorts with all patients receiving 2 or more grafts: (1) all-arterial cohort (n = 612; 297 three-vessel disease [49%]); and (2) single internal thoracic artery (ITA) plus saphenous vein (SV) cohort (n = 4,131; 3,187 three-vessel disease [77%]). RESULTS Early (30-day) deaths were similar for the all-arterial and ITA/SV cohorts (8 [1.30%] versus 69 [1.67%]) whereas late mortality was substantially greater for the ITA/SV cohort (85 [13.9%] versus 1,216 [29.4%]; p < 0.0001). The risk-adjusted 12-year survival was significantly better for all-arterial (with a risk ratio [RR] = 0.60; 95% confidence interval [CI]: 0.48 to 0.75; p < 0.001), but this benefit was true only for three-vessel disease (RR = 0.58; 95% CI: 0.43 to 0.78; p < 0.001) and not for two-vessel disease (RR = 0.97; 95% CI: 0.66 to 1.43; p = 0.89). The all-arterial survival benefit was also true for varying risk subcohorts: no diabetes mellitus (RR = 0.50; 95% CI: 0.37 to 0.69), diabetes mellitus (RR = 0.77; 95% CI: 0.56 to 1.07), ejection fraction 40% or greater (RR = 0.60; 95% CI: 0.45 to 0.78), and ejection fraction less than 40% (RR = 0.62; 95% CI: 0.40 to 0.98). Lastly, the multivariate analysis indicated a strong long-term effect of completeness of revascularization, particularly for all-arterial patients, so that compared with patients with two grafts, survival was significantly better when three grafts (RR = 0.54; 95% CI: 0.33 to 0.87) or four grafts (RR = 0.40; 95% CI: 0.21 to 0.76) were completed. CONCLUSIONS All-arterial revascularization is associated with significantly better 12-year survival compared with the standard single ITA with saphenous vein CABG operation, in particular for triple-vessel disease patients. The completeness of revascularization of the underlying coronary disease is critical for maximizing the long-term benefits of arterial-only grafting.

The Effect on Long-Term Survival of Erythrocyte Transfusion Given for Cardiac Valve Operations

BACKGROUND Studies in patients undergoing coronary artery bypass grafting (CABG) have shown an increased long-term mortality rates associated with perioperative blood transfusions. However, some studies in other patient populations have shown no effect on death or even a lowered mortality rate in patients receiving blood transfusions, which suggests that the effects of blood transfusion may be disease-dependent. METHODS Data of all patients who underwent valve operations with or without associated CABG between October 2, 1991, and November 14, 2007, were obtained from the departments database and analyzed using logistic regression for 30-day and Cox models for long-term mortality to determine the effects of transfusion on death. To control for the potential interaction between transfusion and complications and sicker patients being more likely to receive blood, we separately analyzed the data for the different valve populations and used propensity analysis to control for sicker patients being more likely to receive blood. RESULTS Of 1823 patients who underwent valve operations, the operation was isolated in 993 and combined with CABG in 830. By 30 days, 125 patients (6.9%) had died, and 717 (39%) were dead at follow-up. After controlling for type of operation and factors that influenced the transfusion decision, transfusion was associated with increased death only in patients who had combined valve and CABG, and not in isolated valve operations. CONCLUSIONS Transfusion had no effect on the mortality rate after isolated valve operations but was associated with increased mortality when valve operations were combined with CABG.

The independent effects of anemia and transfusion on mortality after coronary artery bypass

BACKGROUND Both anemia and transfusions (Tx) are associated with mortality after cardiac operations. However, the relative contributions of anemia and Tx and their interaction on late mortality have not been determined. METHODS 922 patients who underwent isolated coronary artery bypass grafting (CABG) were retrospectively studied. Anemia (A+) was defined as hemoglobin<12 g/dL for men and <11 g/dL for women. Patients who received (Tx+) and did not receive (Tx-) transfusions were compared; patient characteristics were controlled for by the use of Cox analysis and then by matching Tx+ to Tx- patients based on identical hemoglobin levels at admission and by propensity matching. RESULTS 5.3% of Tx- patients died, compared with 11% of Tx+ patients (p=0.001). The interaction of anemia and Tx was associated with a greater hazard of dying. In particular, A+Tx+ (anemic, received transfusion) patients had a threefold hazard of death (2.918, 95% confidence interval=1.512-5.633, p=0.001) compared with A-Tx- (nonanemic, no transfusion) patients. A+Tx+ patients had twice the hazard of dying as did A+Tx- (anemic, no transfusion) (hazard ratio=2.087, 95% confidence interval=1.004-4.336, p=0.049). In populations matched by preoperative hemoglobin levels or by propensity scores, similar results were seen: a significant interaction between anemia and transfusion of red blood cells. A+Tx+ patients fared significantly worse than did the other three groups. Although there was no difference in mortality between A- patients who did or did not receive transfusions, A+T+ patients had triple the risk as A+T- patients, whereas A+Tx- patients had a similar risk of late mortality as A-Tx- patients. CONCLUSIONS The anemia-transfusion interaction was associated with an increased hazard of late mortality.

Late effects of radial artery vs saphenous vein grafting for multivessel coronary bypass surgery in diabetics: a propensity-matched analysis †

OBJECTIVES To determine whether the use of the radial artery (RA) vs the saphenous vein (SV) as the second grafting conduit with the internal thoracic artery (ITA) confers a late-survival advantage in diabetes mellitus (DM). METHODS We reviewed our 1996-2007 DM coronary artery bypass grafting (CABG) experience. Study patients (N = 2281) included all primary, non-salvage multigraft CABG discharged alive and receiving ≥1 ITA graft. Bilateral ITA, ITA-only grafts or concomitant valve/aortic surgery patients were excluded. A non-parsimonious, RA use propensity model (42 variables) was derived excluding five factors [gender, vessel disease, insulin, renal failure and left ventricular (LV) dysfunction] that were always strictly matched for all pairs. Greedy matching resulted in well-matched ITA/RA and ITA/SV cohorts (N = 578 each). The late follow-up was truncated at 16 years, and survival comparisons were done by Kaplan-Meier analysis. RESULTS RA grafting was used in 933 (41%) DM patients and was more frequent for non-insulin (513/1348; 49.1%) compared with insulin (271/784; 34.6%) dependent patients. Relatively fewer insulin ITA/RA (169; 62%) could be matched vs non-insulin (469; 71%). Late survival was significantly better for ITA/RA overall [hazard ratio, HR (95% confidence interval) = 0.78 (0.65-0.95); P = 0.012], but this was primarily due to the non-insulin sub-cohort [HR = 0.72 (0.56-0.91); P = 0.007] as opposed to no effect for insulin [HR = 0.92 (0.68-1.26); P = 0.61]. Sub-cohort analysis revealed a significant ITA/RA survival advantage in males, preserved LV function and three-vessel disease. No sub-cohorts were associated with superior ITA/SV survival. CONCLUSION Our analysis indicated that RA grafting confers a significant late-survival advantage and, thus, supports its liberal use in DM patients undergoing multivessel CABG.

Comparison of Late Coronary Artery Bypass Graft Survival Effects of Radial Artery Versus Saphenous Vein Grafting in Male and Female Patients

BACKGROUND This study aimed to compare the survival benefit derived from using radial artery (RA) as a second arterial conduit in combination with internal thoracic artery (ITA), as opposed to ITA plus saphenous vein (SV) in men and women. METHODS We reviewed the 1996 to 2007 primary, nonsalvage coronary artery bypass graft surgery (CABG) experience at Mercy Saint Vincent Medical Center (n = 6,384; 69% men, 31% women). Study subjects had two or more completed grafts including one ITA graft. Patients with bilateral ITA, ITA-only grafts, or concomitant valve/aortic surgery were excluded. Separate sex nonparsimonious propensity models for RA grafting based on 47 preoperative and intraoperative factors were used to identify matched ITA/RA and ITA/SV cohorts. Kaplan-Meier and Cox regression analyses were then applied to assess sex-specific 12-year survival risk ratios of RA versus SV grafting. RESULTS Patient variables for the RA and SV cohorts were well-matched in both men (n = 1,416 each; median age 62 years) and women (n = 567 each; median age 66 years). Thirty-day mortality was similar for ITA/RA versus ITA/SV in men (1.3% versus 1.2%; p = 1.0) and women (1.4% versus 1.9%; p = 0.664). Late mortality (1 to 144 months) was significantly better for ITA/RA in men (risk ratio 0.65, 95% confidence interval: 0.54 to 0.79; p < 0.001) and women (risk ratio 0.75, 95% confidence interval: 0.57 to 0.99; p = 0.045). CONCLUSIONS Late survival results suggest that male and female CABG patients benefit appreciably from use of RA as a second arterial conduit in combination with ITA. Yet, the late survival advantage derived from RA use was relatively less for women. This sex variance in benefit likely reflects differences in risk profiles of male and female CABG patients.

Late effects of radial artery versus saphenous vein grafting in patients aged 70 years or older

BACKGROUND We aimed to determine whether the reported late survival benefit of radial artery (RA) versus saphenous vein (SV) grafting in the general coronary artery bypass graft surgery (CABG) population is maintained in elderly patients aged 70 years or older. METHODS We reviewed our 1996 to 2007 experience in 2,120 elderly patients (RA, n = 607; SV, n = 1,513) who underwent primary, nonsalvage CABG with multiple completed grafts including at least one internal thoracic artery (ITA) graft. Patients were excluded in case of single-vessel disease, bilateral ITA, ITA-only grafts, or concomitant valve/aortic surgery. Kaplan-Meier 12-year survival estimates were compared for 1-to-1 matched ITA/RA and ITA/SV cohorts based on a nonparsimonious RA use propensity model (48 variables). RESULTS The ITA/RA and ITA/SV cohorts (both, aged 75 ± 4yrs and 3.5 ± 0.8 grafts) were well matched and had identical operative mortality (2.3%; 11 of 480 each). Late survival was superior ITA/RA versus ITA/SV (p < 0.001), estimated at 85.1% versus 70.6% and 70.9% versus 50.5% for 5 and 10 years, respectively. Late survival risk ratios (95% confidence interval) for RA versus SV grafting was 0.47 (0.36 to 0.61), and the relative SV to RA death hazard was greater than 1 between 1 and 144 months. CONCLUSIONS The late survival results suggest that elderly (≥70 years) primary multivessel CABG patients benefit substantially when RA is used as the second conduit in combination with ITA. Indeed, compared with previously published comparisons including all age groups, the derived risk ratio indicates that the benefit for the elderly may exceed that for younger patients in the initial decade after CABG. Use of RA should not be avoided in the elderly.

Does radial use as a second arterial conduit for coronary artery bypass grafting improve long-term outcomes in diabetics? §,§§

OBJECTIVES The evidence supporting the survival benefit of multiple arterial grafts in the general coronary bypass surgery (CABG) population is compelling. Alternatively, results of studies comparing 2 versus 1 internal thoracic artery (ITA) grafts in diabetics have reported conflicting survival data. The use of radial versus ITA as the second arterial conduit has not been studied. METHODS We obtained complete death follow-up in 1516 consecutive diabetic [64+/-10 years (mean+/-SD). Insulin/no insulin: There were 540 (36%)/976 (64%)] primary isolated CABG patients all with >or=1 ITA grafts. The series included 626 ITA/radial (41%) and 890 ITA/vein (59%) patients. Using separate radial-use propensity models, we matched one-to-one 475 (76%) ITA/radial to 475 (53%) unique ITA/vein patients; each including 166 insulin and 309 no insulin patients. RESULTS Unadjusted survival was markedly better for (1) ITA/radial (94.3%, 86.7% and 70.4% at 1, 5 and 10 years, respectively) versus ITA/vein (91.8%, 74.5% and 53.8%; p<0.0001) and (2) for no insulin (94.2%, 82.8% and 65.5%) versus insulin (90.4%, 73.1% and 49.2%; p<0.0001). In matched patients, 11-year Kaplan-Meier analysis showed essentially identical ITA/radial and ITA/vein survival for all diabetics combined (p=0.53; log rank) and for the no insulin (p=0.76) cohort. Lastly, a trend for better ITA/radial survival in insulin dependent diabetics after the second postoperative year did not reach significance (p=0.13). CONCLUSIONS Using radial as a second arterial conduit as opposed to vein grafting did not confer a survival benefit in diabetics. This unexpected result is perhaps related to relatively diminished radial graft patency and/or the augmented radial vasoreactivity characteristic of diabetics. These findings indicate that the radial survival advantage demonstrated in the general CABG population lies primarily in non-diabetics in whom this advantage may be underestimated.