Search

Background: Cardiac operation has been associated with increased risk of postoperative cognitive decline, as well as dementia risk in the general population. Few studies, however, have examined the impact of coronary revascularization or valve replacement or repair operation on longitudinal cerebral perfusion changes or their association with cognitive function., Methods: We examined longitudinal changes in cerebral perfusion among 54 individuals with cardiac disease; 27 undergoing cardiac operation and 27 matched control patients. Arterial spin labeling magnetic resonance perfusion imaging was used to quantify cerebral blood flow within the anterior communicating artery, middle cerebral artery (MCA), and posterior communicating artery vascular territories before operation and postoperatively at 6 weeks and 1 year. Cognitive performance was examined during the same intervals by using a battery of tests that tapped memory, executive, information processing and upper extremity motor functions. Repeated measures, mixed models were used to examine for perfusion changes and the association between perfusion changes and cognition., Results: Significant postoperative increases in perfusion were observed at 6 weeks within the MCA vascular territory after cardiac operation (p = 0.035 for interaction). Perfusion changes were most notable in distal territories of the MCA and posterior communicating artery at 6 weeks, with no additional changes at 1 year. Postoperative increases in MCA perfusion at 6 weeks were associated with improved psychomotor speed (β = 0.35, p = 0.016), whereas no important differences were found between the groups in vascular territory perfusion and cognition at 1 year., Conclusions: Cardiac operation is associated with important short-term increases in MCA perfusion with associated improvements in psychomotor speed., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is a common, serious complication of cardiac surgery. Since prior studies have supported a genetic basis for postoperative AKI, we conducted a genome-wide association study (GWAS) for AKI following coronary bypass graft (CABG) surgery. The discovery data set consisted of 873 nonemergent CABG surgery patients with cardiopulmonary bypass (PEGASUS), while a replication data set had 380 cardiac surgical patients (CATHGEN). Single-nucleotide polymorphism (SNP) data were based on Illumina Human610-Quad (PEGASUS) and OMNI1-Quad (CATHGEN) BeadChips. We used linear regression with adjustment for a clinical AKI risk score to test SNP associations with the postoperative peak rise relative to preoperative serum creatinine concentration as a quantitative AKI trait. Nine SNPs meeting significance in the discovery set were detected. The rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3) were replicated with significance in the CATHGEN data set and exhibited significantly strong overall association following meta-analysis. Additional fine mapping using imputed SNPs across these two regions and meta-analysis found genome-wide significance at the GRM7|LMCD1-AS1 locus and a significantly strong association at BBS9. Thus, through an unbiased GWAS approach, we found two new loci associated with post-CABG AKI providing new insights into the pathogenesis of perioperative AKI.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major postoperative complication. Although some early recovery is common, its effect on long-term outcomes is unclear. We tested the hypothesis that early renal recovery after CSA-AKI is independently associated with improved long-term survival., Methods: Data were examined for 10,275 consecutive patients undergoing isolated coronary artery bypass grafting from 1996 to 2005. Patients with CSA-AKI were identified, defined as a peak postoperative creatinine level exceeding 50% above baseline. Renal recovery was characterized using postoperative creatinine values. The recovery variable with the strongest association with 1-year survival was selected and validated internally. The independent association of early renal recovery with long-term survival during a 10-year follow-up was assessed with Cox proportional hazards modeling., Results: CSA-AKI occurred in 1113 patients (10.8%). The renal recovery variable with the strongest association with 1-year survival was the percentage decrease in creatinine 24 hours after its peak value (PD24; C index, 0.72; p=0.002). Cox proportional hazards analysis showed a significant negative association between PD24 and long-term mortality (0.82 hazard ratio for each 10% change)., Conclusions: Early recovery of renal function is associated with improved long-term survival after CSA-AKI. This variable is clinically useful because it occurs immediately after the peak creatinine level and simultaneously helps define the severity of AKI and the magnitude of recovery. Given the high risk of death associated with postoperative AKI, early renal recovery seems to offer a distinct survival benefit and may represent an important therapeutic focus., (Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Neurocognitive dysfunction (NCD) continues to occur in a significant number of patients after cardiac procedures. The factors influencing its incidence and severity are not completely known. We hypothesized that hyperglycemia, which is known to exacerbate other forms of cerebral injury, may exacerbate NCD after cardiac operations., Methods: A total of 525 patients having on-pump coronary artery bypass graft (CABG) procedures underwent cognitive testing at baseline and 6 weeks postoperatively. Multivariable linear regression was used to determine the relationship between NCD and intraoperative hyperglycemia (glucose > or = 200 mg/dL). Diabetic and nondiabetic patients were analyzed separately to eliminate a possible confounding effects between diabetes and hyperglycemia., Results: In the nondiabetic patients, even after controlling for age, years of education, and baseline cognitive function, hyperglycemia was associated with a decrease in cognitive function at 6 weeks (p = 0.0351). Hyperglycemia had no effect on cognitive function in diabetic patients, however., Conclusions: These findings suggest that in nondiabetic patients undergoing CABG operations, intraoperative hyperglycemia is associated with an increased risk of NCD.

Millions of individuals with coronary artery or valvular heart disease have been given a new chance at life by heart surgery, but the potential for neurological injury is an Achilles heel. Technological advancements and innovations in surgical and anaesthetic technique have allowed us to offer surgical treatment to patients at the extremes of age and infirmity-the group at greatest risk for neurological injury. Neurocognitive dysfunction is a complication of cardiac surgery that can restrict the improved quality of life that patients usually experience after heart surgery. With a broader understanding of the frequency and effects of neurological injury from cardiac surgery and its implications for patients in both the short term and the long term, we should be able to give personalised treatments and thus preserve both their quantity and quality of life. We describe these issues and the controversies that merit continued investigation.

Background: Morbidity and mortality after coronary artery bypass graft surgery are directly related to specific preoperative risk factors. We assessed the influence of preoperative risk factors on the effect of pexelizumab, a C5 complement inhibitor, to reduce postoperative morbidity and mortality in this post hoc analysis of the Pexelizumab for Reduction in Myocardial Infarction and MOrtality in Coronary Artery Bypass Graft surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass., Methods: The composite endpoint of death or myocardial infarction or both through postoperative day 30 was examined in subpopulations of patients with pre-specified risk factors, which included diabetes mellitus, prior coronary artery bypass graft, urgent intervention, female sex, history of neurologic event, history of congestive heart failure, and two or more previous myocardial infarctions or a recent myocardial infarction. Stratified post hoc analyses were also performed on patients presenting with two or more and three or more of those risk factors., Results: Pexelizumab significantly reduced the incidence of the composite endpoint of death or myocardial infarction through postoperative day 30 by 28% in patients with two or more risk factors (p = 0.004) and 44% in patients with three or more risk factors (p < 0.001)., Conclusions: The C5 complement inhibitor, pexelizumab, reduced morbidity and mortality among high-risk patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

Background: Neurocognitive decline after cardiac surgery requiring cardiopulmonary bypass (CPB) may be caused in part by highly prothrombotic atheroemboli to the brain; the source of these emboli is likely the ascending aorta and aortic arch. We examined transcerebral platelet activation gradients using simultaneous measurements in arterial and jugular venous blood and then compared gradients with post-CPB-associated neurocognitive injury., Methods: Eighty-one patients undergoing elective coronary artery bypass graft surgery requiring CPB were studied. Neurocognitive function was measured preoperatively and again at 6 weeks postoperatively. Paired arterial and jugular venous blood samples were drawn before surgery, immediately before and after aortic cross-clamp removal (an event previously linked to embolic showers), and at the end of the operation. Transcerebral platelet activation gradients (venous minus arterial values) were compared in patients with and without cognitive deficit., Results: Immediately after aortic cross-clamp removal, there was a significant increase in the transcerebral platelet activation gradient (increased % P-selectin-positive platelets during transcerebral passage) in the subset of patients who subsequently developed post-CPB cognitive deficit; this platelet activation gradient did not occur in patients without cognitive injury. In contrast, there was no transcerebral gradient of platelet activation in CPB patients as an entirety, nor was there a gradient at all other time points in the patient subset who went on to have cognitive deficit develop. This fleeting gradient of transcerebral platelet activation after cross-clamp removal was also significantly correlated with the overall change in cognitive injury score., Conclusions: Transient intracerebral platelet activation after removal of the aortic cross-clamp is associated with post-CPB neurocognitive injury.

Errors in clinical research can be costly, in terms of patient safety, data integrity, and data collection. Data inaccuracy in early subjects of a clinical study may be associated with problems in the design of the protocol, procedures, and data collection tools. High-fidelity patient simulation centers provide an ideal environment to apply human-centered design to clinical trial development. A draft of a complex clinical protocol was designed, evaluated and modified using a high-fidelity human patient simulator in the Duke University Human Simulation and Patient Safety Center. The process included walk-throughs, detailed modifications of the protocol and development of procedural aids. Training of monitors and coordinators provided an opportunity for observation of performance that was used to identify further improvements to the protocol. Evaluative steps were used to design the research protocol and procedures. Iterative modifications were made to the protocol and data collection tools. The success in use of human simulation in the preparation of a complex clinical drug trial suggests the benefits of human patient simulation extend beyond training and medical equipment evaluation. Human patient simulation can provide a context for informal expert evaluation of clinical protocol design and for formal "rehearsal" to evaluate the efficacy of procedures and support tools.

Background: Perfluorooctyl bromide is a biologically inert compound with short biologic retention and high oxygen solubility. The purpose of this study was to assess the effect of the perfluorocarbon emulsion, AF0144 (Perflubron, Alliance Pharmaceutical Corp, San Diego, CA), used in conjunction with acute normovolemic hemodilution on cerebral blood flow and cerebral emboli measurements during coronary artery bypass grafting with cardiopulmonary bypass., Methods: Thirty-six adult cardiac surgical patients were enrolled in a single-institution, randomized, controlled, single-blind dose escalation trial. Autologous whole blood was harvested from each patient to target an on-bypass hematocrit of 20% to 22%. Placebo, low dose (1.8 g/kg) or high dose (2.7 g/kg) AF0144 was administered. Transcranial Doppler ultrasonography was used to quantitate cerebral emboli and xenon-133 clearance was used to measure cerebral blood flow., Results: Cerebral blood flow was increased in both AF0144-treated groups compared with placebo (p = 0.006, low dose vs control; p = 0.036, high dose vs control). Numbers of cerebral emboli were greater in the high-dose AF0144-treated group versus control during the time periods from aortic cannulation through aortic cross-clamp placement (p = 0.026) and from aortic cross-clamp placement through cross-clamp removal (p = 0.008)., Conclusions: The perfluorocarbon emulsion, AF0144, increased cerebral blood flow during cardiopulmonary bypass. In addition, total cerebral emboli load during bypass was greater in patients receiving high-dose AF0144.

Background: Renal dysfunction is a serious complication of cardiac surgery that is highly associated with short- and long-term adverse outcome. While the apolipoprotein E (APOE) epsilon4 allele has been linked to the occurrence of both postcardiac surgery acute renal injury (epsilon4 favorable) and ascending aortic arteriosclerosis (epsilon4 unfavorable), the role of epsilon4 in the relationship between these two conditions is unknown. We hypothesized that patients with and without the epsilon4 allele (E4/non-E4) would have different associations between atheroma burden and postoperative renal dysfunction., Methods: Ascending, arch, and descending aorta atheromatous burden and APOE status were evaluated for 130 coronary bypass patients. Multivariable analyses were performed for aortic regions to assess the relationship of atheroma burden and APOE epsilon4 status with peak in-hospital postoperative serum creatinine. All p < 0.05 were considered significant., Results: We found an interaction between E4 status (E4/non-E4; 24/106) and atheroma burden, with a much greater predicted peak in-hospital postoperative serum creatinine for increases in ascending aorta atheroma load for non-E4 patients versus E4 patients (beta coefficient -0.13; p = 0.002). We also confirmed the association between ascending aorta atheroma and peak creatinine (beta coefficient 0.11; p = 0.0008), after controlling for E4 status, preoperative creatinine, and the E4-atheroma interaction., Conclusions: Equivalent ascending aortic atheroma burden is associated with a greater susceptibility to postoperative renal injury among patients undergoing cardiac operation who lack the APOE epsilon4 allele. Findings may be attributable to APOE-related differences in inflammation, susceptibility to atheroma detachment (eg, during operative aortic manipulation), or renal vulnerability to embolic injury.

Background: Acute renal injury is a common serious complication of cardiac surgery. Moderate hemodilution is thought to reduce the risk of kidney injury but the current practice of extreme hemodilution (target hematocrit 22% to 24%) during cardiopulmonary bypass (CPB) has been linked to adverse outcomes after cardiac surgery. Therefore we tested the hypothesis that lowest hematocrit during CPB is independently associated with acute renal injury after cardiac surgery., Methods: Demographic, perioperative, and laboratory data were gathered for 1,404 primary elective coronary bypass surgery patients. Preoperative and daily postoperative creatinine values were measured until hospital discharge per institutional protocol. Stepwise multivariable linear regression analysis was performed to determine whether lowest hematocrit during CPB was independently associated with peak fractional change in creatinine (defined as the difference between the preoperative and peak postoperative creatinine represented as a percentage of the preoperative value). A p value of less than 0.05 was considered significant., Results: Multivariable analyses including preoperative hematocrit and other perioperative variables revealed that lowest hematocrit during CPB demonstrated a significant interaction with body weight and was highly associated with peak fractional change in serum creatinine (parameter estimate [PE] = 4.5; p = 0.008) and also with highest postoperative creatinine value (PE = 0.06; p = 0.004). Although other renal risk factors were significant covariates in both models, TM50 (an index of hypotension during CPB) was notably absent., Conclusions: These results add to concerns that current CPB management guidelines accepting extreme hemodilution may contribute to postoperative acute renal and other organ injury after cardiac surgery.

Background: Studies that have shown clinical depression to be a risk factor for cardiac events after coronary artery bypass graft (CABG) surgery have had small sample sizes, short follow-up, and have not had adequate power to assess mortality. We sought to assess whether depression is associated with an increased risk of mortality., Methods: We assessed 817 patients undergoing CABG at Duke University Medical Center between May, 1989, and May, 2001. Patients completed the Center for Epidemiological Studies-Depression (CES-D) scale before surgery, 6 months after CABG, and were followed-up for up to 12 years., Findings: In 817 patients there were 122 deaths (15%) in a mean follow-up of 5.2 years. 310 patients (38%) met the criterion for depression (CES-D > or =16): 213 (26%) for mild depression (CES-D 16-26) and 97 (12%) for moderate to severe depression (CES-D > or =27). Survival analyses, controlling for age, sex, number of grafts, diabetes, smoking, left ventricular ejection fraction, and previous myocardial infarction, showed that patients with moderate to severe depression at baseline (adjusted hazard ratio [HR] 2.4, [95% CI 1.4-4.0]; p=0.001) and mild or moderate to severe depression that persisted from baseline to 6 months (adjusted HR 2.2, [1.2-4.2]; p=0.015) had higher rates of death than did those with no depression., Interpretation: Despite advances in surgical and medical management of patients after CABG, depression is an important independent predictor of death after CABG and should be carefully monitored and treated if necessary.

Background: Maintaining normothermia during off-pump coronary artery bypass (OPCAB) surgery is a challenge not met by currently available medical devices and strategies. The purpose of this study was to determine the efficacy of a new thermoregulatory device, the Arctic Sun temperature-controlling circulating fluid adhesive pad system, in preventing hypothermia during OPCAB surgery., Methods: Thirteen consenting patients undergoing OPCAB had their temperature managed using the Arctic Sun system. They were matched with 23 consenting control OPCAB patients whose temperature was maintained with standardized, conventional therapy (elevated ambient operating room temperature, warmed intravenous fluids, and a convective forced air warming system placed under the surgical drapes). Nasopharyngeal temperature (recorded at 1-minute intervals) was compared between the two groups by analysis of both the time and area under the curve for a temperature less than 36 degrees C., Results: Multivariate linear regression analysis revealed that the average amount of hypothermia in the Arctic Sun group was significantly less than in the control group, both for time spent less than 36 degrees C (20.7 vs 121.3 minutes, p = 0.0004) and for area under the curve less than 36 degrees C (11.8 degrees C vs 78.1 degrees C x minutes, p = 0.0001)., Conclusions: The Arctic Sun temperature-controlling system is more effective than conventional warming methods in preventing hypothermia during OPCAB surgery.