Does coronary artery bypass surgery improve survival?

OBJECTIVES: According to guide-lines, coronary bypass surgery improves survival in high risk patients. The evidence for this is more than 20 years old and may be questioned. Long waiting lists for coronary bypass surgery are detrimental but offer the possibility to compare the risk of death before and after surgery. We hypothesized that the risk of death is lower after bypass surgery than before the operation in high risk patients in a more recent cohort. DESIGN AND RESULTS: Death hazard functions were calculated by the use of Poisson regression scheduled for bypass surgery between 1 Jan 1995 and 31 July 2005. The analyses were performed in two states: 1) in the period after triage until admission for surgery during which optimal medication was intended and 2) after surgery and up to 11 years (corresponding to 57,548 patient years). The probability of death was calculated by entering individual risk profile data into the two multivariable functions. There were several significant differences between the hazard functions in the two states. All variables reflecting angiographic severity of coronary lesions indicated lower risk of death after bypass surgery. The risk associated with left ventricular impairment was lower after surgery (beta coefficients - 0.0546 vs. - 0.0234, p <0.001). Only one variable, age, indicated higher risk after surgery (which is also seen in a general population over time). The reduction of risk was dependent on preoperative risk with a large reduction when preoperative risk was high and vice versa. When preoperative risk was low, however, the risk increased due to surgical mortality. CONCLUSIONS: The risk of death is lower after bypass surgery than before the operation in high risk patients. This is most likely explained by a prognostic gain from bypass surgery. The gain is largest in high-risk patients but small or absent in low risk patients.

High or low risk coronary patients - who gets the highest priority?

Coronary revascularisation is more often used in patients at small risk and with little to gain than in patients at high risk and much to gain. This is against current guide-lines and is wasteful. The problem if aggravated by socioeconomic bias. A redesigned reimbursement system, based on measured improved quality of life and survival, would encourage a more efficient use of resources.

Incomplete revascularization reduces survival benefit of coronary artery bypass grafting: role of off-pump surgery.

OBJECTIVE: We sought to analyze the influence, if any, of incomplete revascularization and on/off-pump techniques on long-term mortality after coronary artery bypass grafting. METHODS: A total of 9408 patients undergoing coronary artery bypass grafting, 8461 on pump and 947 off pump, operated on between 1995 and 2004 were included in the study. Adjusted hazard function for long-term mortality was estimated with Poisson regression analysis in a model that included variables reflecting completeness of revascularization, operative method (on/off pump), and background risk factors for death. RESULTS: Mean follow-up after surgical intervention for survivors was 5.0 +/- 2.8 years (range, 0.5-10.5 years), with a total follow-up of 45,076 patient years. Leaving 1 diseased vascular segment without a bypass graft in 2- or 3-vessel disease did not increase the hazard ratio for death in comparison with complete revascularization (hazard ratio, 1.05; 95% confidence interval, 0.87-1.27; P = .60). In contrast, leaving 2 vascular segments without a bypass graft in 3-vessel disease was associated with an increased hazard ratio for death (hazard ratio, 1.82; 95% confidence interval, 1.15-2.85; P = .01). Incomplete revascularization was more common in the off-pump group (P < .001) in our study. If adjusting for incomplete revascularization, there was no significant influence of the use of on/off-pump techniques on the hazard ratio for death (hazard ratio, 1.08; 95% confidence interval, 0.82-1.40; P = .57). CONCLUSIONS: Incomplete revascularization of patients with 3-vessel disease is an independent risk factor for increased long-term mortality after coronary artery bypass grafting. In contrast, the use of on- or off-pump techniques had no significant effect on survival after adjusting for incomplete revascularization.

Does off-pump coronary surgery endanger long term survival?

In this issue Ibrahim and co-authors report on technical hazards of off-pump (without heart lung machine) coronary surgery 1. Their findings are in line with meta-analyses of randomized trials which indicate that under-grafting and graft-failures are more common after off-pump than after standard operations. The risk that the objectives of coronary bypass surgery are endangered is discussed in relation to evidence based medicine. A moratorium is suggested until conclusive data are available.

Myocardial substrates in children with congenital heart disease: relationship to substrate supply, age, growth and desaturation.

AIM: The myocardial uptake of substrates in children has only been investigated on a small scale. The purpose of this study was to define myocardial substrate uptake in relation to the arterial supply of substrates, age, growth and oxygen saturation. METHODS: Thirty patients with congenital heart disease, aged 3 months to 16 years, were studied during cardiac catheterization. Arterial and coronary sinus blood was analyzed for the major fuel metabolites and amino acids. RESULTS: The uptake of all major substrates correlated significantly with the arterial supply: free fatty acids (r = 0.52, p = 0.004), beta-hydroxybutyrate (r = 0.74, p < 0.0001), lactate (r = 0.70, p < 0.0001) and glucose (r = 0.48, p = 0.01). Free fatty acids were the dominant substrate, irrespective of age, growth and saturation. With age, there was an increase in the uptake of lactate (r = 0.61, p = 0.0004) and a decrease in the uptake of beta-hydroxybutyrate (r =-0.41, p = 0.02). In multivariate analyses, these changes were explained by the arterial supply of the substrates, while age per se did not contribute significantly. CONCLUSION: The uptake of myocardial metabolites correlated with the arterial supply. Free fatty acids were the dominant substrate at all ages. The uptake of lactate and beta-hydroxybutyrate, although varying with age, was also determined by the arterial supply.

Myocardial metabolism is better preserved after blood cardioplegia in infants.

BACKGROUND: We have previously reported improved hemodynamic function after blood cardioplegia in comparison with crystalloid cardioplegia. Furthermore, lactate was released from the heart after crystalloid cardioplegia but not after blood cardioplegia. The purpose of this study was to determine whether the difference in substrate metabolism between the two cardioplegia methods was restricted to lactate, or whether the difference in metabolic derangement was more extensive. METHODS: Thirty consecutive infants with complete atrioventricular septal defects were included in this prospective, randomized, controlled study. Arterial and coronary sinus blood concentrations of substrates and amino acids were measured after weaning from bypass. RESULTS: After crystalloid cardioplegia, there was a myocardial uptake of glutamate (p = 0.003), leucine (p = 0.03), lysine (p = 0.003), and beta-hydroxybutyrate (p = 0.004), whereas lactate was released (p = 0.03). After blood cardioplegia, there was a myocardial uptake of free fatty acids (p = 0.01) but no uptake of amino acids and no release of lactate. CONCLUSIONS: There are differences in myocardial substrate metabolism between blood cardioplegia and crystalloid cardioplegia, which involve carbohydrates and amino acids. The differences may include lipids but our data in this respect are not conclusive.

Blood cardioplegia provides superior protection in infant cardiac surgery.

BACKGROUND: We hypothesized that blood cardioplegia preserves myocardial metabolism and function more effectively than St Thomas' crystalloid cardioplegia in infant cardiac surgery. METHODS: Thirty infants with atrioventricular septal defects were randomly allocated to either blood or crystalloid intermittent cold (4 degrees C) cardioplegia. Arterial and coronary sinus blood was analyzed for lactate and oxygen. Cardiac output (thermodilution) and left ventricular function (echocardiography) were evaluated. RESULTS: The lactate concentration in coronary sinus blood early after bypass was significantly higher after crystalloid cardioplegia than after blood cardioplegia (2.1 +/- 0.3 vs 1.3 +/- 0.1 mmol/L, p = 0.006), with a significant myocardial release of lactate after crystalloid but not after blood cardioplegia. Oxygen extraction (arterial-coronary sinus O2 content) was higher early after crystalloid cardioplegia (3.02 +/- 0.13 vs 2.35 +/- 0.22 mmol/L, p = 0.01), possibly reflecting a difference in oxygen debt. The cardiac index was higher after blood cardioplegia (4.9 +/- 0.3 vs 4.0 +/- 0.3 L/min(-1)/m(-2), p = 0.04) and echocardiographic grading of left ventricular function was better (4.1 +/- 0.17 vs 3.5 +/- 0.22 arbitrary units, p = 0.046). CONCLUSIONS: This study indicates that blood cardioplegia preserves myocardial metabolism and function more effectively than crystalloid cardioplegia in infant cardiac surgery. The clinical significance of this finding is uncertain, but the more than 20% increase in cardiac index in the critical phase during weaning from bypass may be advantageous.

A closed perfusion system with heparin coating and centrifugal pump improves cardiopulmonary bypass biocompatibility in elderly patients.

BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory and hemostatic activation, which may contribute to postoperative complications. Our aim was to compare the inflammatory response, coagulation, and fibrinolytic activation between two different perfusion systems: one theoretically more biocompatible with a closed-circuit, complete heparin coating, and a centrifugal pump, and one conventional system with uncoated circuit, roller pump, and a hard-shell venous reservoir. METHODS: Forty-one elderly patients (mean age, 73 +/- 1 years, 66% men) undergoing coronary artery bypass grafting or aortic valve replacement were included in a prospective, randomized study. Plasma concentrations of complement factors (C3a, C4d, Bb, and sC5b-9), proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-8), granulocyte degradation products (polymorphonuclear elastase), and markers of coagulation (thrombin-antithrombin) and fibrinolysis (D-dimer, tissue plasminogen activator antigen and tissue plasminogen activator-plasminogen activator inhibitor-1 complex) were measured preoperatively, at bypass during rewarming (35 degrees C), 60 minutes after bypass, and on day 1 after surgery. RESULTS: The mean concentrations of C3a (-39%; p = 0.008), Bb (-38%; p < 0.001), sC5b-9 (-70%; p < 0.001), interleukin-8 (-60%; p = 0.009), polymorphonuclear-elastase (-55%; p < 0.003), and tissue plasminogen activator antigen (-51%; p = 0.012) were all significantly lower in the biocompatible group during rewarming. Sixty minutes after bypass, the mean concentrations of sC5b-9 (-39%; p = 0.006) and polymorphonuclear-elastase (-55%; p < 0.001) were lower in the biocompatible group. CONCLUSIONS: The results suggest that a closed perfusion system with a heparin-coated circuit and a centrifugal pump may improve cardiopulmonary bypass biocompatibility in elderly cardiac surgery patients in comparison with a conventional system.

Changes in hemostasis during pediatric heart surgery: impact of a biocompatible heparin-coated perfusion system.

BACKGROUND: This study describes the response in hemostasis during open-heart surgery with cardiopulmonary bypass (CPB) in children (<== 10 kg) and tests the hypothesis that the use of a biocompatible perfusion system, in comparison with a conventional system, causes less hemostatic activation. METHODS: Prospective, randomized, controlled clinical study. Forty consecutive children <== 10 kg were included and divided into two groups: group bioc. (n = 19) treated with a fully heparin-coated system, centrifugal pump, and a closed circuit, and group conv. (n = 21) treated with an uncoated system, roller pump, and a hard shell venous reservoir. Concentrations of plasma thrombin-antithrombin (TAT), D-dimer, tissue plasminogen activator antigen (t-PA ag), and the complex consisting of tissue plasminogen activator and its inhibitor plasminogen activator inhibitor-1 (t-PA-PAI-1) were measured. RESULTS: The biochemical variables measured increased significantly in both groups during the study period. There was less activation of fibrinolysis during cardiopulmonary bypass (t-PA ag: p = 0.009) in patients treated with the biocompatible perfusion system than in patients treated with the conventional system. A trend in favor of the biocompatible system based on the D-dimer and TAT data (p = 0.07 for both measurements) was observed but no significant intergroup differences regarding these variables or t-PA-PAI-1 were found. CONCLUSIONS: Open-heart surgery with cardiopulmonary bypass in children (<== 10 kg) causes transient activation of the coagulation and fibrinolytic systems. This study demonstrates that the use of a biocompatible perfusion system results in a lower extent of activation of fibrinolysis during CPB than the use of a conventional system.

Influence of two different perfusion systems on inflammatory response in pediatric heart surgery.

BACKGROUND: This study tests the hypothesis that a cardiopulmonary bypass system that combines complete heparin-coating, a centrifugal pump, and a closed circuit in comparison with a conventional system (uncoated system, roller pump, and hard shell venous reservoir) attenuates the inflammatory response in pediatric heart surgery. METHODS: In a prospective randomized controlled clinical study 40 consecutive children weighing 10 kg or less were included and divided into two groups. Concentrations of complement proteins (C3a, sC5b-9, C4d, and Bb), granulocyte degranulation products (polymorphonuclear [PMN] elastase), and proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and IL-8) were measured. RESULTS: C3a and sC5b-9 concentrations were lower (C3a, p < 0.001; sC5b-9, p = 0.01) in the combined (heparin-coated/centrifugal pump/closed reservoir) group, the peak values being 58% and 37% of conventional group values. The Bb- and C4d-fragment values indicated activation of the complement system through the alternative pathway in both groups. PMN elastase concentrations were lower (p = 0.02) in the combined group, the peak values being 43% of conventional group values. There were no significant intergroup differences regarding TNF-alpha, IL-6, or IL-8 concentrations. CONCLUSIONS: The use of a fully heparin-coated system, a centrifugal pump, and a closed circuit during CPB in children (10 kg or less) leads to a lower degree of complement activation and PMN elastase release compared with a conventional system.

Predictors of allograft ischemic injury in clinical heart transplantation.

OBJECTIVES: 1. Identify clinical, biochemical and inflammatory predictors of allograft ischemic injury in clinical heart transplantation. 2. Evaluate the impact of high dose insulin (GIK) on allograft metabolism during blood cardioplegia and post-ischemic injury. DESIGN: A clinical, prospective, randomized open trial comprising 25 consecutive heart transplantations at a university hospital. Ischemic injury was evaluated from plasma levels of creatine kinase isoenzyme MB (CK-MB). Blood cardioplegic arterial and coronary sinus concentrations of C3a, IL-6, substrates, amino acids and blood gases were measured at the end of the implantation period, prior to reperfusion. Twelve patients received high dose insulin with glucose, potassium and amino acids. RESULTS: CK-MB increased from 1.9 +/- 0.2 to 161 +/- 13 microg/l (range 47-293 microg/l). The peak level of CK-MB correlated with donor age (r = 0.48, p = 0.02) and implantation time (r = 0.53, p = 0.02); and with recipient plasma IL-6 (r = 0.56, p = 0.02), allograft oxygen extraction (r = 0.56, p = 0.02), lactate release (r = 0.47, p = 0.02) and allograft arterial-coronary sinus (cs) pH (r = 0.47, p = 0.02) all during final cardioplegia before reperfusion. Seventy-two percent of the variance of CK-MB was explained by a model which included donor age, art-cs pH difference and arterial IL-6. In contrast, CK-MB was unrelated to total ischemic time (r = -0.17, p = 0.38). Insulin infusion had no effect on myocardial substrates during cardioplegia, or on post-ischemic CK-MB. CONCLUSION: Donor age, duration and quality of the implantation period are significant predictors of allograft ischemic injury in heart transplantation. High dose insulin had no detectable effects on allograft metabolism during cardioplegia, or on subsequent ischemic injury.