Utility of nuclear stress imaging in predicting long-term outcomes one-year post CABG Surgery.

BACKGROUND: Early MPI after CABG is currently considered rarely appropriate in asymptomatic patients. This study aimed to identify prognostic value of nuclear stress-imaging post-CABG. METHODS: This was a single center prospective study looking at long-term outcomes post-CABG. Per protocol participants underwent SPECT-MPI stress testing and coronary angiogram on the same day, 1-year following CABG. Defect size was semi-quantified. The primary outcomes were the composite of death and congestive heart failure. RESULTS: Eighty-four participants underwent nuclear stress-imaging and angiography, with a median follow-up of 11.1 years. Three separate stress findings predicted the primary outcome: inability to reach stage 3 of a Bruce protocol (OR 7.3, CI 2.4-22.1, P < 0.001), LVEF < 45% (OR 4.0, CI 1.1-15.3, P = 0.041) and a moderate-large stress defect size (HR 2.31, CI 1.1-1.5, P = 0.04). These findings appear to be additive and strongest among patients who underwent exercise stress testing (HR 10.6, CI 3.6-30.6, P < 0.001). Graft disease was identified in 39 (46%) patients and compared to those individuals with no graft disease, did not predict long-term adverse outcomes (P = 0.29). CONCLUSION: In clinically stable patients early after revascularization with CABG, SPECT-MPI can identify patients at higher risk of heart failure and death.

Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery.

Chronic cardiac ischemia that impairs cardiac function, but does not result in infarct, is termed hibernating myocardium (HM). A large clinical subset of coronary artery disease (CAD) patients have HM, which in addition to causing impaired function, puts them at higher risk for arrhythmia and future cardiac events. The standard treatment for this condition is revascularization, but this has been shown to be an imperfect therapy. The majority of pre-clinical cardiac research focuses on infarct models of cardiac ischemia, leaving this subset of chronic ischemia patients largely underserved. To address this gap in research, we have developed a well-characterized and highly reproducible model of hibernating myocardium in swine, as swine are ideal translational models for human heart disease. In addition to creating this unique disease model, we have optimized a clinically relevant treatment model of coronary artery bypass surgery in swine. This allows us to accurately study the effects of bypass surgery on heart disease, as well as investigate additional or alternate therapies. This model surgically induces single vessel stenosis by implanting a constrictor on the left anterior descending (LAD) artery in a young pig. As the pig grows, the constrictor creates a gradual stenosis, resulting in chronic ischemia with impaired regional function, but preserving tissue viability. Following the establishment of the hibernating myocardium phenotype, we perform off-pump coronary artery bypass graft surgery to revascularize the ischemic region, mimicking the gold-standard treatment for patients in the clinic.

Magnetic resonance imaging assessment of cardiac function in a swine model of hibernating myocardium 3 months following bypass surgery.

OBJECTIVE: Clinical studies demonstrate delayed recovery of hibernating myocardium (HM) following coronary artery bypass graft (CABG) surgery. Cardiac magnetic resonance (CMR) imaging is effective in identifying HM in clinical settings. Our animal model of HM shows partial but incomplete functional recovery 1 month following CABG using echocardiography. This study uses CMR imaging to determine completeness of recovery 3 months post-CABG. METHODS: Swine (N = 12) underwent left anterior descending artery (LAD) 1.5-cm constrictor placement creating a territory of HM over 12 weeks. CMR at 12 weeks confirmed hibernation without infarction (N = 12). Off-pump left internal thoracic artery (LITA) to the LAD was performed in 9 animals. Three animals were killed as HM controls. CMR imaging was repeated in revascularized animals before death at 1 (n = 4) or 3 months (n = 5). CMR imaging was performed at baseline and with dobutamine infusion (5 µg/kg/min). RESULTS: Twelve weeks after constrictor placement, CMR imaging confirmed viability in LAD region and LAD stenosis in all animals. In HM, wall thickening is reduced at baseline but with contractile reserve present during dobutamine infusion. Following revascularization, CMR imaging confirmed patent LITA graft (n = 9). Analysis of baseline regional function shows incomplete recovery of HM following CABG, with reduced contractile reserve at both 1 and 3 months post-CABG. CONCLUSIONS: CMR imaging provides accurate spatial resolution of regional contractile function and confirms the presence of HM at 12 weeks following instrumentation of the LAD. Three months following CABG, partial recovery of HM with contractile reserve is present in the single LAD territory.

Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of CoQ10 on Contractile Reserve Following Bypass Surgery.

There is conflicting clinical evidence whether administration of coenzyme Q10 (CoQ10) improves function following coronary artery bypass graft surgery (CABG). Using a swine model of hibernating myocardium, we tested whether daily CoQ10 would improve contractile function by MRI at 4-week post-CABG. Twelve pigs underwent a thoracotomy and had a constrictor placed on the left anterior descending (LAD). At 12 weeks, they underwent off-pump bypass and received daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo. At 4-week post-CABG, circumferential strain measurements in the hibernating LAD region from placebo and CoQ10 groups were not different and increased to a similar extent with dobutamine (-14.7 ± 0.6 versus -14.8 ± 0.1, respectively (NS)). Post-sacrifice, oxidant stress markers were obtained in the mitochondrial isolates and protein carbonyl in the placebo, and CoQ10 groups were 6.14 ± 0.36 and 5.05 ± 0.32 nmol/mg, respectively (NS). In summary, CoQ10 did not improve contractile reserve or reduce oxidant stress at 4-week post-CABG.

Long-Term Outcomes of Patients Who Had Cardiac Arrest After Cardiac Operations.

BACKGROUND: Cardiac arrest after cardiac procedures has a case fatality rate of approximately 60%. However, the long-term risk of death and outcomes among survivors of postoperative cardiac arrest is less clear. METHODS: We examined the mortality and outcomes of 6,979 consecutive patients who underwent cardiac operations from 1991 to 2014 in the Minneapolis Veterans Affairs Health Care System. RESULTS: Cardiac arrest occurred in 182 patients (2.6%) at a median of 3 days (range, 0 to 39 days) after the operation. Of these, 93 (51%) died during the same hospitalization, and an additional 24 (13%) died within 1 year. Mortality at 30 days (51% vs 1.9%; p < 0.0001), at 1 year (64% vs 6%; p < 0.0001), and after a mean follow-up of 7.5 ± 5.5 years (81% vs 34%; p < 0.0001), was higher in those with vs without cardiac arrest. After adjusting for age, sex, year, and type of operation, an in-hospital cardiac arrest was associated with a 4.7-times (95% confidence interval [CI], 3.9 to 5.6; p < 0.0001) higher risk of long-term death in the entire cohort, 2.0-times (95% CI, 1.6 to 2.7; p < 0.0001) higher risk among those who survived 30 days, and 1.3-times (95% CI, 0.9 to 1.9; p = 0.14) higher risk among those who survived 1 year after the operation. Being discharged to a facility (hazard ratio, 3.97; 95% CI, 1.52 to 10.32; p = 0.005) and renal dysfunction (hazard ratio, 3.35; 95% CI, 1.42 to 7.89; p = 0.006) were independent predictors of death amongst cardiac arrest survivors. CONCLUSIONS: Long-term mortality remains high in patients discharged alive after postoperative cardiac arrest. Discharge disposition and renal dysfunction after cardiac arrest have important prognostic implications.

Expression of uncoupling protein-2 remains increased within hibernating myocardium despite successful coronary artery bypass grafting at 4 wk post-revascularization.

BACKGROUND: We have previously shown that mitochondrial uncoupling protein-2 (UCP-2) is increased in a swine model of hibernating myocardium (HM). Although UCP-2 reduces oxidant stress, it can promote inefficiency of the electron transport chain. In this study, we tested whether UCP-2 remains increased in revascularized HM (RHM) after coronary artery bypass grafting (CABG). METHODS: Seven swine underwent thoracotomy with placement of a constrictor on the left anterior descending artery (LAD). Twelve weeks later, a left internal mammary artery graft was placed on the distal LAD. Four weeks post-CABG, computed tomography angiography documented patent grafts and function. At the terminal study, blood flow to the LAD and remote territories were assessed during high dose dobutamine and mitochondria isolated from both regions for analysis. Comparisons were made to a group of swine with HM who underwent constrictor placement without bypass grafting (n = 4). RESULTS: During dobutamine infusion, RHM demonstrated lower blood flows (2.44 ± 0.23 versus 3.43 ± 0.30 mL/min/g; P < 0.05) and reduced wall thickening (33 ± 9% versus 52 ± 13%; P < 0.05) compared with remote regions. RHM had lower respiratory control indices (3.7 ± 0.3 versus 4.3 ± 0.4; P < 0.05) with persistently increased UCP-2 content. CONCLUSIONS: Despite patent grafts, RHM demonstrates a submaximal response to dobutamine infusion and increased mitochondrial UCP-2 expression. These data support the notion that recovery of the mitochondria in RHM is delayed early post-CABG and may contribute to impaired oxygen consumption and contractile reserve during catecholamine challenges.

Perioperative outcomes after on- and off-pump coronary artery bypass grafting.

Although numerous reports describe the results of off-pump coronary artery bypass grafting (CABG) at specialized centers and in select patient populations, it remains unclear how off-pump CABG affects real-world patient outcomes. We conducted a large, multicenter observational cohort study of perioperative death and morbidity in on-pump (ON) versus off-pump (OFF) CABG. We reviewed Veterans Affairs Surgical Quality Improvement Program data for all patients (N=65,097) who underwent isolated CABG from October 1997 through April 2011 (intention-to-treat data were available from 2005 onward). The primary outcome was perioperative (30-day or in-hospital) death; the secondary outcomes were perioperative stroke, dialysis dependence, reoperation for bleeding, mechanical circulatory support, myocardial infarction, ventilator support ≥ 48 hr, and mediastinitis. Propensity scores calculated from age, 17 preoperative risk factors, and year of surgery were used to match 8,911 OFF with 26,733 ON patients. In the complete cohort, compared with the ON patients (n=53,468), the OFF patients (n=11,629) had less perioperative death (2.02% vs 2.53%, P=0.0012) and lower incidences of all morbidities except perioperative myocardial infarction. In the matched cohort, perioperative death did not differ significantly between OFF and ON patients (1.94% vs 2.28%, P=0.06), but the OFF group had lower incidences of all morbidities except for perioperative myocardial infarction and mediastinitis. A subgroup intention-to-treat analysis yielded similar but smaller outcome differences between the ON and OFF groups. Off-pump CABG might be associated with decreased operative morbidity but did not affect operative death, compared with on-pump CABG. Future studies should examine the effect of off-pump CABG on long-term outcomes.

Completeness of coronary revascularization and survival: Impact of age and off-pump surgery.

OBJECTIVES: We conducted a multicenter observational cohort study of the effect of completeness of revascularization on long-term survival after coronary artery bypass grafting. We also investigated the impact of age and off-pump surgery. METHODS: The Veterans Affairs Continuous Improvement in Cardiac Surgery Program was used to identify all patients (N=41,139) with left main and 3-vessel coronary artery disease who underwent nonemergency coronary artery bypass grafting from October 1997 to April 2011. The primary outcome measure, all-cause mortality, was compared between patients with complete revascularization and patients with incomplete revascularization. Survival functions were estimated with the Kaplan-Meier method and compared by using the log-rank test. Propensity scores calculated for each patient were used to match 5509 patients undergoing complete revascularization to 5509 patients undergoing incomplete revascularization. A subgroup analysis was performed in patients aged at least 70 years and patients who underwent off-pump coronary artery bypass grafting. RESULTS: In the unmatched groups, several risk factors were more common in the incomplete revascularization group, as was off-pump coronary artery bypass grafting. In the matched groups, risk-adjusted mortality was higher in the incomplete revascularization group than in the complete revascularization group at 1 year (6.96% vs 5.97%; risk ratio [RR], 1.17; 95% confidence interval [CI], 1.01-1.34), 5 years (18.50% vs 15.96%; RR, 1.16; 95% CI, 1.07-1.26), and 10 years (32.12% vs 27.40%; RR, 1.17; 95% CI, 1.11-1.24), with an overall hazard ratio of 1.18 (95% CI, 1.09-1.28; P<.0001). The hazard ratio for patients aged 70 years or more was 1.125 (95% CI, 1.001-1.263; P=.048). The hazard ratio was 1.47 (95% CI, 1.303-1.655) for the unmatched off-pump coronary artery bypass grafting group and 1.156 (95% CI, 1.000-1.335) for the matched off-pump coronary artery bypass grafting group. CONCLUSIONS: Incomplete revascularization is associated with decreased long-term survival, even in elderly patients. Surgeons should consider these findings when choosing a revascularization strategy, particularly if off-pump coronary artery bypass grafting is contemplated.

Trends over time in the relative use and associated mortality of on-pump and off-pump coronary artery bypass grafting in the Veterans Affairs system.

IMPORTANCE: Numerous studies have compared the results of on-pump and off-pump coronary artery bypass grafting (CABG), but little is known about how either the relative use of these procedures or their associated perioperative mortality have changed with time. OBJECTIVE: To examine trends in off- and on-pump CABG use and outcomes over time. DESIGN: Retrospective analysis of data from the Veterans Affairs Surgical Quality Improvement Program (VASQIP). SETTING: Data were collected from 42 Veterans Affairs cardiac surgery centers. PARTICIPANTS: All Veterans Affairs patients (n = 65,097) who underwent isolated primary CABG from October 1997 to April 2011. INTERVENTIONS: Patients underwent either on-pump (ON) or off-pump (OFF) CABG. MAIN OUTCOMES AND MEASURES: The percentages of ON vs OFF cases as a function of time. We also evaluated trends over time in rates of conversion from OFF to ON CABG, perioperative mortality (30-day or in-hospital), and VASQIP predicted risk of mortality. RESULTS: The relative use of OFF CABG peaked at 24% in 2003, followed by a slow and mostly consistent decline to stabilize at about 19%. The conversion rate decreased with time and has stayed less than 3.5% since 2007 (P < .001). Perioperative mortality rates decreased over time for both ON and OFF CABG (P < .001) and have stayed less than 2% for the entire cohort since 2006. The mortality associated with converted cases was high regardless of the surgery year and exceeded the VASQIP predicted risk of mortality. CONCLUSIONS AND RELEVANCE: There has been a decline in the relative use of OFF CABG in the Veterans Affairs system since 2003. This trend may affect the training of future generations in OFF surgery and influence conversion rates and outcomes.

Performing coronary artery bypass grafting off-pump may compromise long-term survival in a veteran population.

BACKGROUND: There are ample data regarding the short-term outcomes of on-pump and off-pump coronary artery bypass grafting (CABG), but little is known about the long-term survival associated with these approaches. METHODS: Using the Veterans Affairs (VA) Continuous Improvement in Cardiac Surgery Program, we identified all VA patients (n = 65,097) who underwent primary isolated CABG from October 1997 to April 2011. The primary outcome measure was all-cause mortality. Age, 17 preoperative risk factors, and year of operation were used to calculate propensity scores for each patient. A greedy-match algorithm using the propensity scores matched 8,911 off-pump with 26,733 on-pump patients. Survival functions were estimated by the Kaplan-Meier method and compared by using the log-rank test. RESULTS: In the complete cohort, off-pump was used in 11,629 of 65,097 (17.9%) operations. For the matched cohort, the median follow-up was 6.7 years (interquartile range, 3.72 to 9.35 years). Risk-adjusted mortality did not differ significantly between the off-pump and on-pump groups at 1 year (4.67% vs 4.78%; risk ratio [RR], 0.98; 95% confidence interval [CI], 0.88 to 1.09) or 3 years (9.21% vs 8.89%; RR, 1.04; 95% CI, 0.96 to 1.12). However, risk-adjusted mortality was higher in the off-pump group at 5 years (14.47% vs 13.45%; RR, 1.08; 95% CI 1.02 to 1.15) and 10 years (25.18% vs 23.57%; RR, 1.07; 95% CI, 1.03 to 1.12). Overall, the hazard ratio for off-pump vs on-pump was 1.06 (95% CI, 1.00 to 1.13; p = 0.04). CONCLUSIONS: Off-pump CABG may be associated with decreased long-term survival. Further studies are needed to identify the reasons behind this finding.

Percutaneous coronary intervention versus coronary bypass surgery in United States veterans with diabetes.

OBJECTIVES: This study sought to determine the optimal coronary revascularization strategy in patients with diabetes with severe coronary disease. BACKGROUND: Although subgroup analyses from large trials, databases, and meta-analyses have found better survival for patients with diabetes with complex coronary artery disease when treated with surgery, a randomized trial comparing interventions exclusively with drug-eluting stents and surgery in patients with diabetes with high-risk coronary artery disease has not yet been reported. METHODS: In a prospective, multicenter study, 198 eligible patients with diabetes with severe coronary artery disease were randomly assigned to either coronary artery bypass grafting (CABG) (n = 97) or percutaneous coronary intervention (PCI) with drug-eluting stents (n = 101) and followed for at least 2 years. The primary outcome measure was a composite of nonfatal myocardial infarction or death. Secondary outcome measures included all-cause mortality, cardiac mortality, nonfatal myocardial infarction, and stroke. RESULTS: The study was stopped because of slow recruitment after enrolling only 25% of the intended sample size, leaving it severely underpowered for the primary composite endpoint of death plus nonfatal myocardial infarction (hazard ratio: 0.89; 95% confidence interval: 0.47 to 1.71). However, after a mean follow-up period of 2 years, all-cause mortality was 5.0% for CABG and 21% for PCI (hazard ratio: 0.30; 95% confidence interval: 0.11 to 0.80), while the risk for nonfatal myocardial infarction was 15% for CABG and 6.2% for PCI (hazard ratio: 3.32; 95% confidence interval: 1.07 to 10.30). CONCLUSIONS: This study was severely underpowered for its primary endpoint, and therefore no firm conclusions about the comparative effectiveness of CABG and PCI are possible. There were interesting differences in the components of the primary endpoint. However, the confidence intervals are very large, and the findings must be viewed as hypothesis generating only. (Coronary Artery Revascularization in Diabetes; NCT00326196).

Utility of nuclear stress imaging for detecting coronary artery bypass graft disease.

BACKGROUND: The value of single photon emission computed tomography stress myocardial perfusion imaging (SPECT-MPI) for detecting graft disease after coronary artery bypass surgery (CABG) has not been studied prospectively in an unselected cohort. METHODS: Radial Artery Versus Saphenous Vein Graft Study is a Veterans Affairs Cooperative Study to determine graft patency rates after CABG surgery. Seventy-nine participants agreed to SPECT-MPI within 24 hours of their coronary angiogram, one-year after CABG. The choice of the stress protocol was made at the discretion of the nuclear radiologist and was either a symptom-limited exercise test (n = 68) or an adenosine infusion (n = 11). The SPECT-MPI results were interpreted independent of the angiographic results and estimates of sensitivity, specificity and accuracy were based on the prediction of a graft stenosis of ≥70% on coronary angiogram. RESULTS: A significant stenosis was present in 38 (48%) of 79 patients and 56 (22%) of 251 grafts. In those stress tests with an optimal exercise heart rate response (>80% maximum predicted heart rate) (n = 26) sensitivity, specificity and accuracy of SPECT-MPI for predicting the graft stenosis was 77%, 69% and 73% respectively. With adenosine (n = 11) it was 75%, 57% and 64%, respectively. Among participants with a suboptimal exercise heart rate response, the sensitivity of SPECT-MPI for predicting a graft stenosis was <50%. The accuracy of SPECT-MPI for detecting graft disease did not vary significantly with ischemic territory. CONCLUSIONS: Under optimal stress conditions, SPECT-MPI has a good sensitivity and accuracy for detecting graft disease in an unselected patient population 1 year post-CABG.

Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning.

Altered expression of mitochondrial electron transport proteins has been shown in early preconditioned myocardial tissue. We wished to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated during subsequent ischemia. Fourteen pigs underwent a SWOP protocol with ten 2-minute balloon inflations in the LAD artery, each separated by 2 minutes reperfusion. Twenty-four hours later, mitochondria were isolated from SWOP and SHAM pig hearts and analyzed for uncoupling protein (UCP)-2 content by western blot analysis, proteomic changes by iTRAQ(®) and respiration by an oxygen electrode. In parallel in vivo studies, high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP and SHAM pigs at baseline and during sustained low-flow ischemia. Compared with SHAM mitochondria, ex vivo SWOP heart tissue demonstrated increased expression of UCP-2, Complex IV (cytochrome c oxidase) and Complex V (ATPase) proteins. In comparison with SHAM pigs during in vivo conditions, transmural energetics in SWOP hearts, as estimated by the free energy of ATP hydrolysis (ΔG(0)), were similar at baseline but had decreased by the end of low-flow ischemia (-57.0 ± 2.1 versus -51.1 ± 1.4 kJ/mol; P < 0.05). In conclusion, within isolated mitochondria from preconditioned SWOP hearts, UCP-2 is increased and in concert with enhanced Complex IV and V proteins, imparts a favorable energetic state during low-flow ischemia. These data support the notion that mitochondrial adaptations that may reduce oxidant damage do not reduce the overall efficiency of energetics during sustained oxygen deprivation.

Radial artery grafts vs saphenous vein grafts in coronary artery bypass surgery: a randomized trial.

CONTEXT: Arterial grafts are thought to be better conduits than saphenous vein grafts for coronary artery bypass grafting (CABG) based on experience with using the left internal mammary artery to bypass the left anterior descending coronary artery. The efficacy of the radial artery graft is less clear. OBJECTIVE: To compare 1-year angiographic patency of radial artery grafts vs saphenous vein grafts in patients undergoing elective CABG. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized controlled trial conducted from February 2003 to February 2009 at 11 Veterans Affairs medical centers among 757 participants (99% men) undergoing first-time elective CABG. INTERVENTIONS: The left internal mammary artery was used to preferentially graft the left anterior descending coronary artery whenever possible; the best remaining recipient vessel was randomized to radial artery vs saphenous vein graft. MAIN OUTCOME MEASURES: The primary end point was angiographic graft patency at 1 year after CABG. Secondary end points included angiographic graft patency at 1 week after CABG, myocardial infarction, stroke, repeat revascularization, and death. RESULTS: Analysis included 733 patients (366 in the radial artery group, 367 in the saphenous vein group). There was no significant difference in study graft patency at 1 year after CABG (radial artery, 238/266; 89%; 95% confidence interval [CI], 86%-93%; saphenous vein, 239/269; 89%; 95% CI, 85%-93%; adjusted OR, 0.99; 95% CI, 0.56-1.74; P = .98). There were no significant differences in the secondary end points. CONCLUSION: Among Veterans Affairs patients undergoing first-time elective CABG, the use of a radial artery graft compared with saphenous vein graft did not result in greater 1-year patency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00054847.

Preoperative coronary artery revascularization and long-term outcomes following abdominal aortic vascular surgery in patients with abnormal myocardial perfusion scans: a subgroup analysis of the coronary artery revascularization prophylaxis trial.

BACKGROUND: Abdominal aortic operations have the highest perioperative cardiac risk. To test the impact of preoperative coronary artery revascularization (PR) in this high-risk subset, a post hoc analysis was performed in patients undergoing aortic surgery within the Coronary Artery Revascularization Prophylaxis (CARP) trial. METHODS: The study cohort was a subset of 109 CARP patients with myocardial ischemia on nuclear imaging randomized to a strategy of PR (N = 52) or no PR (N = 57) before their scheduled abdominal aortic vascular operation. The clinical indications for vascular surgery were an expanding aneurysm (N = 62) or severe claudication (N = 47). The composite end-point of death and nonfatal myocardial infarction (MI) was determined by an intention-to-treat analysis following randomization. RESULTS: The median time (Interquartiles) from randomization to vascular surgery was 56 (40, 81) days in patients assigned to PR and 19 (10, 43) days in patients assigned to no PR (P < 0.001). At 2.7 years following randomization, the probability of remaining free of death and nonfatal MI was 0.65 with PR and 0.55 with no PR [unadjusted P = 0.08, odds ratio = 1.67, 95% confidence interval (0.93, 2.99)]. Using a Cox proportional hazard model, predictors of the composite of death and nonfatal MI (odds ratio; 95% confidence interval) were no PR (1.90; 1.06-3.43; P = 0.03) and anterior ischemia on preoperative imaging (1.79; 0.99-3.23; P = 0.07). CONCLUSIONS: In patients with an abnormal cardiac imaging before abdominal aortic vascular surgery, PR was associated with a reduced risk of death and nonfatal MI while anterior ischemia was an identifier of poor outcome independent of the revascularization status.

Continued depression of maximal oxygen consumption and mitochondrial proteomic expression despite successful coronary artery bypass grafting in a swine model of hibernation.

OBJECTIVE: Clinical studies indicate incomplete functional recovery of hibernating myocardium after coronary artery bypass grafting. We hypothesized that persistent contractile abnormalities after coronary artery bypass grafting are associated with decreased mitochondrial proteins involving electron transport chain that might limit maximal oxygen consumption. METHODS: Seven pigs with hibernating myocardium underwent off-pump revascularization with left internal thoracic artery to mid left anterior descending artery. At 4 weeks, left internal thoracic artery anastomosis was patent by multidetector computed tomography. Regional function (transthoracic echocardiography) and blood flow (microspheres) were assessed at rest and during high-dose dobutamine (40 µg/[kg · min]). Expression of electron transport chain proteins was analyzed with isobaric tags for relative and absolute quantification. RESULTS: After revascularization, multidetector computed tomography confirmed severe left anterior descending stenosis and patent left internal thoracic artery graft. Regional function and blood flow normalized at rest; however, function in left anterior descending distribution remained depressed relative to remote regions, and myocardial blood flow in that region did not increase normally when challenged with high-work state. Concomitant with reduced maximal blood flow response in left anterior descending region was more than 40% reduction in electron transport chain proteins essential to adenosine triphosphate production. CONCLUSIONS: Despite successful revascularization of hibernating myocardium, regional function and blood flow remained depressed during catecholamine stress. Electron transport chain proteins known to be downregulated during adaptive process within hibernating myocardium did not normalize after revascularization. These data demonstrate a potential bioenergetic cause of persistent dysfunction and heart failure within successfully revascularized hibernating myocardium.

Culprit coronary lesions requiring percutaneous coronary intervention after vascular surgery often arise from in-stent restenosis of bare metal stents.

BACKGROUND: The natural history of coronary artery disease (CAD) after vascular surgery is poorly defined. The aim of this study was to determine the temporal change of coronary artery lesions requiring revascularization with a percutaneous coronary intervention (PCI) after elective vascular surgery and to determine the utility of preoperative biomarkers on predicting those patients at risk for new coronary lesions. METHODS: The Coronary Artery Revascularization Prophylaxis Trial tested the long-term survival benefit of coronary artery revascularization before elective vascular surgery. Among randomized patients who subsequently required PCI after surgery, the stenosis of the culprit lesion from the follow-up angiogram was compared with the preoperative vessel stenosis at the identical site on the baseline angiogram. RESULTS: A total of 30 patients underwent PCI for progressive symptoms at a median of 11.5 (interquartiles: 4.5-18.5) months postsurgery. Of 30 patients, 16 (53%) had nonobstructive CAD preoperatively (group 1) with a stenosis that increased from 17 +/- 6% to 91 +/- 2% (P < 0.01) and 14 (47%) had severe CAD at the culprit site preoperatively (group 2), with a stenosis that increased 89 +/- 2% (P = 0.15). The only biomarker that was an identifier of early coronary artery lesion formation in group 1 compared with group 2 patients was a higher baseline homocysteine level (14.6 +/- 1.4 vs. 10.6 +/- 0.7 mg/dL; P = 0.02). CONCLUSIONS: Culprit coronary artery lesions requiring PCI after an elective vascular operation often arise from in-stent restenosis. Therapies that either stabilize existing plaques or prevent restenosis, particularly among patients with elevated homocysteine levels, have the greatest promise for improving postoperative outcomes.

Preoperative pulmonary function and mortality after cardiac surgery.

BACKGROUND: The aim of the study was to examine the relationship between preoperative pulmonary function and outcomes after cardiac surgery. METHODS: We performed preoperative pulmonary function tests (PFTs) in 1,169 patients undergoing cardiac surgery at the Minneapolis Veterans Affairs Medical Center. Airway obstruction was defined as forced expiratory volume in 1 minute (FEV(1)) to forced vital capacity ratio <0.7. RESULTS: Of the 1,169 patients, 483 (41%) had a prior history of chronic obstructive pulmonary disease (COPD). However, 178 patients with a history of COPD had no airway obstruction on PFT. Conversely, 186 patients without a COPD history had airway obstruction on PFT. Thus, PFT results helped reclassify the COPD status of 364 patients (31%). Operative mortality was 2% in patients with no or mild airway obstruction versus 6.7% in those with moderate or severe obstruction (ie, FEV(1) to forced vital capacity ratio <0.7 and FEV(1) <80% predicted). Postoperative mortality was higher (odds ratio 3.2, 95% CI 1.6-6.2, P = .001) in patients with moderate or severe airway obstruction and in patients with diffusing capacity of the lung for carbon monoxide <50% of predicted (odds ratio 4.9, 95% CI 2.3-10.8, P = .0001). Notably, mortality risk was 10x higher (95% CI 3.4-27.2, P = .0001) in patients with moderate or severe airway obstruction and diffusing capacity of the lung for carbon monoxide <50% of predicted. CONCLUSIONS: These data show that PFT before cardiac surgery reclassifies the COPD status of a substantial number of patients and provides important prognostic information that the current risk estimate models do not capture.

Perioperative complications after vascular surgery are predicted by the revised cardiac risk index but are not reduced in high-risk subsets with preoperative revascularization.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is useful for risk stratifying patients before noncardiac operations. Among patients with documented coronary artery disease who undergo vascular surgery, it is unclear whether preoperative revascularization reduces postoperative cardiac complications in high-risk subsets defined by the RCRI. METHODS AND RESULTS: The Coronary Artery Revascularization Prophylaxis Trial was a randomized, controlled trial that tested the long-term benefit of a preoperative coronary artery revascularization before elective vascular surgery. Using preoperative baseline characteristics to determine the RCRI, we tested the benefit of preoperative revascularization on death and nonfatal myocardial infarction in patients with multiple risks. Among 462 patients undergoing vascular surgery, there were 72 complications (15.6%) within 30 days postsurgery, including 15 deaths (3.2%) and 57 nonfatal myocardial infarctions (12.3%). The postoperative risk of death and nonfatal myocardial infarction after surgery increased according to the RCRI (odds ratio, 1.73; 95% CI, 1.26 to 2.38; P<0.001), with a rate of 1.6% in patients with no risk that increased to 23.4% in patients with > or =3 risks. Preoperative revascularization had no influence on the incidence of complications in any risk subset (odds ratio, 0.86; 95% CI, 0.50 to 1.49; P=0.60). Among those individuals with > or =2 risks who also demonstrated ischemia on a preoperative stress-imaging test (N=146), the incidence of events was 23% in patients with and without preoperative revascularization (P=0.95). CONCLUSIONS: The risk of death and nonfatal myocardial infarction is accurately predicted by the RCRI in patients undergoing vascular surgery but is not reduced in any high-risk subset of the RCRI with preoperative coronary artery revascularization.

Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers.

BACKGROUND: Previous studies on the effects of Statins in preventing atrial fibrillation (AF) after cardiac surgery have shown conflicting results. Whether statins prevent AF in patients treated with postoperative beta blockers and whether the statin-effect is dose related are unknown. METHODS: We retrospectively studied 1936 consecutive patients who underwent coronary artery bypass graft (CABG) (n = 1493) or valve surgery (n = 443) at the Minneapolis Veterans Affairs Medical Center. All patients were in sinus rhythm before the surgery. Postoperative beta blockers were administered routinely (92% within 24 hours postoperatively). RESULTS: Mean age was 66+10 years and 68% of the patients were taking Statins. Postoperative AF occurred in 588 (30%) patients and led to longer length of stay in the intensive care unit versus those without AF (5.1+7.6 days versus 2.5+2.3 days, p < 0.0001). Patients with a past history of AF had a 5 times higher risk of postoperative AF (odds ratio 5.1; 95% confidence interval 3.4 to 7.7; p < 0.0001). AF occurred in 31% of patients taking statins versus 29% of the others (p = 0.49). In multivariable analysis, statins were not associated with AF (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.7 to 1.2; p = 0.59). However, in a subgroup analysis, the patients treated with Simvastatin >20 mg daily had a 36% reduction in the risk of postoperative AF (OR 0.64, 95% CI 0.43 to 0.6; p = 0.03) in comparison to those taking lower dosages. CONCLUSION: Among cardiac surgery patients treated with postoperative beta blockers Statin treatment reduces the incidence of postoperative AF when used at higher dosages.