Timothy R. Graham

Relation between mild renal dysfunction and outcomes after coronary artery bypass grafting

Background—Risk stratification algorithms for coronary artery bypass grafting (CABG) do not include a weighting for preoperative mild renal impairment defined as a serum creatinine 130 to 199 &mgr;mol/L (1.47 to 2.25 mg/dL), which may impact mortality and morbidity after CABG. Methods and Results—We reviewed prospectively collected data between 1997 and 2004 on 4403 consecutive patients undergoing first-time isolated CABG with a preoperative serum creatinine <200 &mgr;mol/L (2.26 mg/dL)] in a single institution. The in-hospital mortality was 2.5% (112 of 4403), the need for new dialysis/hemofiltration was 1.3% (57 of 4403), and the stroke rate was 2.5% (108 of 4403). There were 458 patients with a serum creatinine 130 to 199 &mgr;mol/L or 1.47 to 2.25 mg/dL (mild renal dysfunction group) and 3945 patients with a serum creatinine <130 &mgr;mol/L (<1.47 mg/dL). Operative mortality was higher in the mild renal dysfunction group (2.1% versus 6.1%; P<0.001) and increased with increasing preoperative serum creatinine level. New dialysis/hemofiltration (0.8%versus 5.2%; P<0.001) and postoperative stroke (2.2% versus 5.0%; P<0.01) were also more common in the patients with mild renal impairment. Multivariate analysis adjusting for known risk factors confirmed preoperative mild renal impairment (creatinine 130 to 199 &mgr;mol/L or 1.47 to 2.25 mg/dL; odd ratio, 1.91; 95% CI, 1.18 to 3.03; P=0.007) or glomerular filtration rate estimates <60 mL/min per 1.73 m2, derived using the Cockroft-Gault formula, (odds ratio, 1.98; 95% CI, 1.16 to 3.48; P=0.015) as independent predictors of in-hospital mortality. Preoperative mild renal dysfunction adversely affected the 3-year survival probability after CABG (93% versus 81%; P<0.001). Conclusions—Mild renal dysfunction is an important predictor of outcome in terms of in-hospital mortality, morbidity, and midterm survival in patients undergoing CABG.

Glucose-insulin-potassium and tri-iodothyronine individually improve hemodynamic performance and are associated with reduced troponin I release after on-pump coronary artery bypass grafting.

Background— Both glucose-insulin-potassium (GIK) and tri-iodothyronine (T3) may improve cardiovascular performance after coronary artery surgery (CABG) but their effects have not been directly compared and the effects of combined treatment are unknown. Methods and Results— In 2 consecutive randomized double-blind placebo-controlled trials, in patients undergoing first time isolated on-pump CABG between January 2000 and September 2004, 440 patients were recruited and randomized to either placebo (5% dextrose) (n=160), GIK (40% dextrose, K+ 100 mmol · L−1, insulin 70 u · L−1) (0.75 mL · kg−1 h−1) (n=157), T3 (0.8 &mgr;g · kg−1 followed by 0.113 &mgr;g · kg−1 h−1) (n=63) or GIK+T3 (n=60). GIK/placebo therapy was administered from start of operation until 6 hours after removal of aortic cross-clamp (AXC) and T3/placebo was administered for a 6-hour period from removal of AXC. Serial hemodynamic measurements were taken up to 12 hours after removal of AXC and troponin I (cTnI) levels were assayed to 72 hours. Cardiac index (CI) was significantly increased in both the GIK and GIK/T3 group in the first 6 hours compared with placebo (P<0.001 for both) and T3 therapy (P=0.009 and 0.029, respectively). T3 therapy increased CI versus placebo between 6 and 12 hours after AXC removal (P=0.01) but combination therapy did not. Release of cTnI was lower in all treatment groups at 6 and 12 hours after removal of AXC. Conclusions— Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery. Combination therapy does not provide added hemodynamic effect.

Neo-intimal development on textured biomaterial surfaces during clinical use of an implantable left ventricular assist device.

Implantable left ventricular assist systems are being developed for long term clinical use. Prototype devices are currently used as extended mechanical bridges to cardiac transplantation. The Thermo Cardiosystems Inc. (TCI) pneumatic pusher plate left ventricular assist device (LVAD) features textured blood contacting surfaces to encourage the formation of an adherent fibrin-cellular coagulum. This serves as the foundation for the development of a neo-intimal lining. The TCI LVAD was implanted in 6 male patients (age range 22-53 years) between 1986 and 1988. The duration of implantation ranged from 1-41 days. No clinical thromboembolic events or pump-related thromboembolism occurred and none was evident at necropsy. The six device linings have been fully evaluated. Explanted devices were free of thrombus and calcification. Lining samples for light and electron microscopy were collected from areas of the diaphragm identical for flex and blood shear conditions and from high and low shear areas on the static housing. Islands of collagenous tissue were deposited on the static housing amongst compact fibrin. By day 13, cells populated the surface of the developing neo-intima overlying the diaphragm. By 41 days, the surface cell density increased and the cells became spindle shaped and relatively orientated in the high shear/flex area. Immunohistochemical techniques suggest that these cells are of mesenchymal origin. Textured blood contacting surfaces appear satisfactory in the preliminary clinical use of this device.

Glucose-Insulin-Potassium Reduces the Incidence of Low Cardiac Output Episodes After Aortic Valve Replacement for Aortic Stenosis in Patients With Left Ventricular Hypertrophy Results From the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) Trial

Background— Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. Methods and Results— Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5′ adenosine monophosphate–activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked &bgr;-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. Conclusions— Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis. Clinical Trial Registration— URL: http://www.controlled-trials.com. Reference number: ISRCTN 05758301.

Patient-Prosthesis Mismatch in Patients With Aortic Stenosis Undergoing Isolated Aortic Valve Replacement Does Not Affect Survival

BACKGROUND Data suggest that patient-prosthesis mismatch (PPM) adversely effects late survival after aortic valve replacement (AVR). This study examined the incidence and implications of PPM in patients undergoing isolated AVR. METHODS Prospectively collected data on patients undergoing isolated AVR for aortic stenosis between January 1, 1997 and December 31, 2007 were analyzed. The projected effective valve orifice area from in vivo data was indexed to body surface area (EOAi). PPM was defined as moderate for EOAi of < or = 0.85 cm(2)/m(2) and severe if < or = 0.6 cm(2)/m(2). The reference group comprised patients with EOAi > 0.85 cm(2)/m(2). The effect of PPM on postoperative survival was assessed by multivariate analysis. RESULTS Of 801 patients, PPM was severe in 48 (6.0%), moderate in 462 (57.8%), and nonexistent in 291 (36.4%). Mismatch was associated with increasing age and female gender, thus resulting in an increase in the EuroSCORE (reference group, 4.9 +/- 2.6; moderate PPM, 5.8 +/- 2.4; and severe PPM, 6.1+/-2.1; p < 0.001). PPM did not significantly increase hospital mortality. Four deaths occurred in the reference group (1.4%), 12 in the moderate PPM (2.6%), and none in the severe PPM group (p = 0.311). The 5-year survival estimates were 83% in reference, 86% in moderate PPM, and 89% in severe PPM (p = 0.25). By multivariate analysis, PPM was not an independent risk factor for reduced in-hospital or late survival. CONCLUSIONS Moderate PPM is common in patients undergoing AVR for aortic stenosis, but severe mismatch is rare. Patients with PPM have similar early and late postoperative survival rate.

Mild renal dysfunction predicts in-hospital mortality and post-discharge survival following cardiac surgery

OBJECTIVES To assess the impact of preoperative renal dysfunction on in-hospital mortality and late survival outcome following adult cardiac surgery. METHODS Prospectively collected data were analysed on 7621 consecutive patients not requiring preoperative renal-replacement therapy, who underwent CABG, valve surgery or combined procedures from 1/1/98 to 1/12/06. Preoperative estimated glomerular filtration rate was calculated using Cockcroft-Gault formula. Patients were classified in the four chronic kidney disease (CKD) stage classes defined by the National Kidney Foundation Disease Outcome Quality Initiative Advisory Board. Late survival data were obtained from the UK Central Cardiac Audit Database. RESULTS There were 243 in-hospital deaths (3.2%). There was a stepwise increase in operative mortality with each CKD class independent of the type of surgery. Multivariate analysis confirmed CKD class to be an independent predictor of in-hospital mortality (class 2 OR 1.45, 95% CI 1.1-2.35, p=0.001; class 3 OR 2.8, 95% CI 1.68-4.46, p=0.0001; class 4 OR 7.5, 95% CI 3.76-15.2, p=0.0001). The median follow-up after surgery was 42 months (IQR 18-74) and there were 728 late deaths. Survival analysis using a Cox regression model confirmed CKD class to be an independent predictor of late survival (class 2 HR 1.2, 95% CI 1.1-1.6, p=0.0001; class 3 HR 1.95, 95% CI 1.6-2.4, p=0.0001; and class 4 HR 3.2, 95% CI 2.2-4.6, p=0.0001). Ninety-eight percent (7517/7621) of patients had a preoperative creatinine <200 micromol/l, which is not included as a risk factor in most risk stratification systems. CONCLUSIONS Mild renal dysfunction is an important independent predictor of in-hospital and late mortality in adult patients undergoing cardiac surgery.

Glucose-Insulin-Potassium Reduces the Incidence of Low Cardiac Output Episodes After Aortic Valve Replacement for Aortic Stenosis in Patients With Left Ventricular Hypertrophy

Background— Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. Methods and Results— Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5′ adenosine monophosphate–activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked &bgr;-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. Conclusions— Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis. Clinical Trial Registration— URL: http://www.controlled-trials.com. Reference number: ISRCTN 05758301.

Bleeding in cardiac surgery: The use of aprotinin does not affect survival

OBJECTIVE The antifibrinolytic drug aprotinin has been the most widely used agent to reduce bleeding and its complications in cardiac surgery. Several randomized trials and meta-analyses have demonstrated it to be effective and safe. However, 2 recent reports from a single database have implicated the use of aprotinin as a risk for postoperative complications and reduced long-term survival. METHODS In this single-institution observational study involving 7836 consecutive patients (1998-2006), we assessed the safety of using aprotinin in risk reduction strategy for postoperative bleeding. RESULTS Aprotinin was used in 44% of patients. Multivariate analysis identified aprotinin use in risk reduction for reoperation for bleeding (odds ratio, 0.51; 95% confidence interval, 0.36-0.72; P = .001) and need for blood transfusion postoperatively (odds ratio, 0.67; 95% confidence interval, 0.57-0.79; P = .0002). The use of aprotinin did not affect in-hospital mortality (odds ratio, 1.03; 95% confidence interval, 0.71-1.49; P = 0.73), intermediate-term survival (median follow-up, 3.4 years; range, 0-8.9 years; hazard ratio, 1.09; 95% confidence interval, 0.93-1.28; P = .30), incidence of postoperative hemodialysis (odds ratio, 1.16; 95% confidence interval, 0.73-1.85; P = .49), and incidence of postoperative renal dysfunction (odds ratio, 0.78; 95% confidence interval, 0.59-1.03; P = .07). CONCLUSION This study demonstrates that aprotinin is effective in reducing bleeding after cardiac surgery, is safe, and does not affect short- or medium-term survival.

Platelets and cardiopulmonary bypass

Exposure of blood to an extracorporeal circulation, such as CPB, causes a variety of physiological responses. Haematological derangements are just one of many potential dangers to the patient who undergoes CPB. The paradox of CPB-related problems with the haematological system is that there are some factors tipping the balance towards a bleeding tendency, and others that favour a prothrombotic state. Both of these issues must be dealt with independently to create the safest environment for surgery. It has been demonstrated that platelets play a key role in both haemostatic dysfunction and thrombotic complications of CPB. Much has been achieved, both clinically and in the laboratory, in the understanding of the precise role platelets play in these events, but the exact mechanisms involved have yet to be completely identified. As research progresses, our understanding will increase, but until then clinical practice must be dictated by the current evidence available.

Deep sternal wound infection requiring revision surgery: impact on mid-term survival following cardiac surgery.

OBJECTIVE To assess the impact of deep sternal wound infection on in-hospital mortality and mid-term survival following adult cardiac surgery. METHODS Prospectively collected data on 4586 consecutive patients who underwent a cardiac surgical procedure via a median sternotomy from 1st January 2001 to 31st December 2005 were analysed. Patients with a deep sternal wound infection (DSWI) were identified in accordance with the Centres for Disease Control and Prevention guidelines. Nineteen variables (patient-related, operative and postoperative) were analysed. Logistic regression analysis was used to calculate a propensity score for each patient. Late survival data were obtained from the UK Central Cardiac Audit Database. Mean follow-up of DSWI patients was 2.28 years. RESULTS DSWI requiring revision surgery developed in 1.65% (76/4586) patients. Stepwise multivariable logistic regression analysis identified age, diabetes, a smoking history and ventilation time as independent predictors of a DSWI. DSWI patients were more likely to develop renal failure, require reventilation and a tracheostomy postoperatively. Treatment included vacuum assisted closure therapy in 81.5% (62/76) patients and sternectomy with musculocutaneous flap reconstruction in 35.5% (27/76) patients. In-hospital mortality was 9.2% (7/76) in DSWI patients and 3.7% (167/4510) in non-DSWI patients (OR 1.300 (0.434-3.894) p=0.639). Survival with Cox regression analysis with mean propensity score (co-variate) showed freedom from all-cause mortality in DSWI at 1, 2, 3 and 4 years was 91%, 89%, 84% and 79%, respectively compared with 95%, 93%, 90% and 86%, respectively for patients without DSWI ((p=0.082) HR 1.59 95% CI (0.94-2.68)). CONCLUSION DSWI is not an independent predictor of a higher in-hospital mortality or reduced mid-term survival following cardiac surgery in this population.