Joseph P. Mathew

Depression as a risk factor for mortality after coronary artery bypass surgery

Summary 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 ⩾16): 213 (26%) for mild depression (CES-D 16–26) and 97 (12%) for moderate to severe depression (CES-D ⩾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.

American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography

UNLABELLED ACCREDITATION STATEMENT: The American Society of Echocardiography (ASE) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASE designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.trade mark Physicians should only claim credit commensurate with the extent of their participation in the activity. The American Registry of Diagnostic Medical Sonographers and Cardiovascular Credentialing International recognize the ASEs certificates and have agreed to honor the credit hours toward their registry requirements for sonographers. The ASE is committed to resolving all conflict-of-interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated. TARGET AUDIENCE This activity is designed for all cardiovascular physicians, cardiac sonographers, and nurses with a primary interest and knowledge base in the field of echocardiography; in addition, residents, researchers, clinicians, sonographers, and other medical professionals having a specific interest in contrast echocardiography may be included. OBJECTIVES Upon completing this activity, participants will be able to: 1. Demonstrate an increased knowledge of the applications for contrast echocardiography and their impact on cardiac diagnosis. 2. Differentiate the available ultrasound contrast agents and ultrasound equipment imaging features to optimize their use. 3. Recognize the indications, benefits, and safety of ultrasound contrast agents, acknowledging the recent labeling changes by the US Food and Drug Administration (FDA) regarding contrast agent use and safety information. 4. Identify specific patient populations that represent potential candidates for the use of contrast agents, to enable cost-effective clinical diagnosis. 5. Incorporate effective teamwork strategies for the implementation of contrast agents in the echocardiography laboratory and establish guidelines for contrast use. 6. Use contrast enhancement for endocardial border delineation and left ventricular opacification in rest and stress echocardiography and unique patient care environments in which echocardiographic image acquisition is frequently challenging, including intensive care units (ICUs) and emergency departments. 7. Effectively use contrast echocardiography for the diagnosis of intracardiac and extracardiac abnormalities, including the identification of complications of acute myocardial infarction. 8. Assess the common pitfalls in contrast imaging and use stepwise, guideline-based contrast equipment setup and contrast agent administration techniques to optimize image acquisition.

ASE/SCA guidelines for performing a comprehensive intraoperative multiplane transesophageal echocardiography examination: recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography.

Since the introduction of transesophageal echocardiography (TEE) to the operating room in the early 1980s,1-4 its effectiveness as a clinical monitor to assist in the hemodynamic management of patients during general anesthesia and its reliability to make intraoperative diagnoses during cardiac operations has been well established.5-26 In recognition of the increasing clinical applications and use of intraoperative TEE, the American Society of Echocardiography (ASE) established the Council for Intraoperative Echocardiography in 1993 to address issues related to the use of echocardiography in the operating room. In June 1997, the Council board decided to create a set of guidelines for performing a comprehensive TEE examination composed of a set of anatomically directed cross-sectional views. The Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography has endorsed these guidelines and standards of nomenclature for the various anatomically directed cross-sectional views of the comprehensive TEE examination. This document, therefore, is the collective result of an effort that represents the consensus view of both anesthesiologists and cardiologists who have extensive experience in intraoperative echocardiography. The writing group has several goals in mind in creating these guidelines. The first is to facilitate training in intraoperative TEE by providing a framework in which to develop the necessary knowledge and skills. The guidelines may also enhance quality improvement by providing a means to assess the technical quality and completeness of individual studies. More consistent acquisition and description of intraoperative echocardiographic data will facilitate communication between centers and provide a basis for multicenter investigations. In recognition of the increasing availability and advantages of digital image storage, the guidelines define a set of cross-sectional views and nomenclature that constitute a comprehensive intraoperative TEE examination that could be stored in a digital format. These guidelines will encourage industry to develop echocardiography systems that allow quick and easy acquisition, labeling, and storage of images in the operating room, as well as a simple mechanism for side-by-side comparison of views made at different times. ASE/SCA Guidelines for Performing a Comprehensive Intraoperative Multiplane Transesophageal Echocardiography Examination: Recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography

Central nervous system injury associated with cardiac surgery

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.

The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac Surgery

UNLABELLED Neurocognitive dysfunction is a common complication after cardiac surgery. We evaluated in this prospective study the effect of rewarming rate on neurocognitive outcome after hypothermic cardiopulmonary bypass (CPB). After IRB approval and informed consent, 165 coronary artery bypass graft surgery patients were studied. Patients received similar surgical and anesthetic management until rewarming from hypothermic (28 degrees -32 degrees C) CPB. Group 1 (control; n = 100) was warmed in a conventional manner (4 degrees -6 degrees C gradient between nasopharyngeal and CPB perfusate temperature) whereas Group 2 (slow rewarm; n = 65) was warmed at a slower rate, maintaining no more than 2 degrees C difference between nasopharyngeal and CPB perfusate temperature. Neurocognitive function was assessed at baseline and 6 wk after coronary artery bypass graft surgery. Univariable analysis revealed no significant differences between the Control and Slow Rewarming groups in the stroke rate. Multivariable linear regression analysis, examining treatment group, diabetes, baseline cognitive function, and cross-clamp time revealed a significant association between change in cognitive function and rate of rewarming (P = 0.05). IMPLICATIONS Slower rewarming during cardiopulmonary bypass (CPB) was associated with better cognitive performance at 6 wk. These results suggest that a slower rewarming rate with lower peak temperatures during CPB may be an important factor in the prevention of neurocognitive decline after hypothermic CPB.

The effect of aprotinin on outcome after coronary-artery bypass grafting.

BACKGROUND Aprotinin has recently been associated with adverse outcomes in patients undergoing cardiac surgery. We reviewed our experience with this agent in patients undergoing cardiac surgery at Duke University Medical Center. METHODS We retrieved data on 10,275 consecutive patients undergoing surgical coronary revascularization at Duke between January 1, 1996, and December 31, 2005. We fit data to a logistic-regression model predicting each patients likelihood of receiving aprotinin on the basis of preoperative characteristics and to models predicting long-term survival (up to 10 years) and decline in renal function, as measured by increases in serum creatinine levels. RESULTS A total of 1343 patients (13.2%) received aprotinin, 6776 patients (66.8%) received aminocaproic acid, and 2029 patients (20.0%) received no antifibrinolytic therapy. All patients underwent coronary-artery bypass grafting, and 1181 patients (11.5%) underwent combined coronary-artery bypass grafting and valve surgery. In the risk-adjusted model, survival was worse among patients treated with aprotinin, with a main-effects hazard ratio for death of 1.32 (95% confidence interval [CI], 1.12 to 1.55) for the comparison with patients receiving no antifibrinolytic therapy (P=0.003) and 1.27 (95% CI, 1.10 to 1.46) for the comparison with patients receiving aminocaproic acid (P=0.004). As compared with the use of aminocaproic acid or no antifibrinolytic agent, aprotinin use was also associated with a larger risk-adjusted increase in the serum creatinine level (P<0.001) but not with a greater risk-adjusted incidence of dialysis (P=0.56). CONCLUSIONS Patients who received aprotinin had a higher mortality rate and larger increases in serum creatinine levels than those who received aminocaproic acid or no antifibrinolytic agent.

Modulation of Platelet Surface Adhesion Receptors during Cardiopulmonary Bypass

Alterations in platelet receptors critical to adhesion may play a role in the pathogenesis of the qualitative platelet defect associated with cardiopulmonary bypass. Using flow cytometry, we measured changes in the following platelet surface adhesive proteins: the von Willebrand factor receptor, glycoprotein Ib; the fibrinogen receptor, glycoprotein IIb/IIIa; the thrombospondin receptor, glycoprotein IV; the adhesive glycoprotein granule membrane protein 140, whose expression also reflects platelet activation and alpha-granule release; and, as a control, the nonreceptor protein HLA, A,B,C. Glycoprotein Ib decreased during cardiopulmonary bypass (P less than 0.05) and reached a nadir at 72% (P less than 0.05) of its baseline value at 2-4 h after bypass. This decrease correlated (r = 0.76) with the magnitude of platelet activation (alpha-granule release) in any given patient, but even platelets that were not activated demonstrated a decrease in glycoprotein Ib expression. Glycoprotein IIb/IIIa also decreased in both the activated (47% of baseline, P less than 0.01) and unactivated (63% of baseline, P less than 0.01) subsets of platelets at the end of cardiopulmonary bypass. Glycoprotein IV and HLA A,B,C did not decrease, but instead increased 2-4 h after cardiopulmonary bypass (P less than 0.05). We conclude that cardiopulmonary bypass produces selective decreases in surface glycoproteins Ib and IIb/IIIa as well as in platelet activation; that these two alterations are temporally but not necessarily mechanistically linked; and that these changes have the potential to adversely affect platelet function.

Association of neurocognitive function and quality of life 1 year after coronary artery bypass graft (CABG) surgery.

Objective: Although coronary artery bypass grafting (CABG) has been shown to improve quality of life and functional capacity for many patients, recent studies have demonstrated that a significant number of patients exhibit impairment in cognitive function immediately following surgery and beyond. We sought to determine the impact of this postoperative cognitive dysfunction on quality of life (QOL) and to characterize the dysfunction from the patient’s perspective. Methods: With Institutional Review Board (IRB) approval and written informed consent, 732 patients at Duke University Hospital undergoing CABG were enrolled. Five hundred fifty-one (75%) completed baseline, 6-week, and 1-year neurocognitive tests and psychometric measures designed to assess QOL. Neurocognitive status was assessed by a composite cognitive index score representing the mean of the scores in four cognitive domains. Change in QOL was assessed by subtracting baseline from 1-year scores for each of 10 QOL measures. The association between QOL and cognitive dysfunction was investigated using multivariable linear regression analysis. Results: Cognitive decline limited improvement in QOL, with substantial correlation between change in cognition and change in QOL. One-year QOL measures are associated with both 6-week and 1-year change in cognition (Instrumental Activities of Daily Living, p < .0001; Duke Activity Status Index, p < .02; Cognitive Difficulties, p < .0001; Symptom Limitations, p = .0001; Center for Epidemiologic Study Depression, p < .0001; General Health Perception, p = .0001). Conclusions: Postoperative cognitive decline may diminish improvements in QOL. Strategies to reduce cognitive decline may allow patients to achieve the maximum improvement in QOL afforded by CABG, as even short-term cognitive dysfunction has implications for QOL 1 year later. CABG = coronary artery bypass graft; QOL = quality of life; IADL = instrumental activities of daily living; DASI = Duke Activity Status Index; STAI = Spielberger State Anxiety Inventory; WAIS-R = Wechsler Adult Intelligence Scale-Revised; CPB = cardiopulmonary bypass; CI = Cognitive Index; SF-36 = Medical Outcomes Study 36-Item Short Form Health Survey; CES-D = Center for Epidemiological Studies Depression Scale.

Prospective Randomized Trial of Normothermic versus Hypothermic Cardiopulmonary Bypass on Cognitive Function after Coronary Artery Bypass Graft Surgery

Background Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques, and anesthetic management, central nervous system complications occur in a large percentage of patients undergoing surgery requiring CPB. Many centers are switching to normothermic CPB because of shorter CPB and operating room times and improved myocardial protection. The authors hypothesized that, compared with normothermia, hypothermic CPB would result in superior neurologic and neurocognitive function after coronary artery bypass graft surgery. Methods Three hundred patients undergoing elective coronary artery bypass graft surgery were prospectively enrolled and randomly assigned to either normothermic (35.5–36.5°C) or hypothermic (28–30°C) CPB. A battery of neurocognitive tests was performed preoperatively and at 6 weeks after surgery. Four distinct cognitive domains were identified and standardized using factor analysis and were then compared on a continuous scale. Results Two hundred twenty-seven patients participated in 6-week follow-up testing. There were no differences in neurologic or neurocognitive outcomes between normothermic and hypothermic groups in multivariable models, adjusting for covariable effects of baseline cognitive function, age, and years of education, as well as interaction of these with temperature treatment. Conclusions Hypothermic CPB does not provide additional central nervous system protection in adult cardiac surgical patients who were maintained at either 30 or 35°C during CPB.

Metabolomic Profiling Reveals Distinct Patterns of Myocardial Substrate Use in Humans With Coronary Artery Disease or Left Ventricular Dysfunction During Surgical Ischemia/Reperfusion

Background— Human myocardial metabolism has been incompletely characterized in the setting of surgical cardioplegic arrest and ischemia/reperfusion. Furthermore, the effect of preexisting ventricular state on ischemia-induced metabolic derangements has not been established. Methods and Results— We applied a mass spectrometry–based platform to profile 63 intermediary metabolites in serial paired peripheral arterial and coronary sinus blood effluents obtained from 37 patients undergoing cardiac surgery, stratified by presence of coronary artery disease and left ventricular dysfunction. The myocardium was a net user of a number of fuel substrates before ischemia, with significant differences between patients with and without coronary artery disease. After reperfusion, significantly lower extraction ratios of most substrates were found, as well as significant release of 2 specific acylcarnitine species, acetylcarnitine and 3-hydroxybutyryl-carnitine. These changes were especially evident in patients with impaired ventricular function, who exhibited profound limitations in extraction of all forms of metabolic fuels. Principal component analysis highlighted several metabolic groupings as potentially important in the postoperative clinical course. Conclusions— The preexisting ventricular state is associated with significant differences in myocardial fuel uptake at baseline and after ischemia/reperfusion. The dysfunctional ventricle is characterized by global suppression of metabolic fuel uptake and limited myocardial metabolic reserve and flexibility after global ischemia/reperfusion stress in the setting of cardiac surgery. Altered metabolic profiles after ischemia/reperfusion are associated with postoperative hemodynamic course and suggest a role for perioperative metabolic monitoring and targeted optimization in cardiac surgical patients.