Michel Abdelnoor

Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris ☆: Clinical results from The Norwegian Randomized Trial

OBJECTIVES The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris. BACKGROUND Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published. METHODS One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2. RESULTS Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.) CONCLUSIONS Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.

Completely heparinized cardiopulmonary bypass and reduced systemic heparin: Clinical and hemostatic effects

BACKGROUND When heparinized circuits are used for cardiopulmonary bypass, the amounts of heparin and protamine administered systemically can be reduced. However, it is not entirely known what effects this reduction in systemic anticoagulation has on clinical performance and on the coagulation and fibrinolytic systems. METHODS Two hundred three patients undergoing first-time elective myocardial revascularization were prospectively randomized either to a group in which a completely heparin-coated circuit was used for perfusion (group H; n = 101 patients) and in which a reduced heparin dose was given (activated clotting time, > 250 seconds) or to a control group (group C; n = 102 patients) in which an uncoated, but otherwise identical, circuit was used and in which full systemic heparinization was induced (activated clotting time, > 480 seconds). Indicators of thrombin generation, platelet activation, and fibrinolytic activity were studied in a subset of 34 patients. RESULTS The total amount of postoperative mediastinal drainage was significantly reduced in group H (median, 575 mL) compared with that in group C (median, 635 mL; p = 0.002). Two patients in group C but none in group H received homologous red blood cell transfusions (p = not significant). The loss of hemoglobin in group H was a median of 21 g/L, and this was significantly lower than the 25 g/L noted in the control group (p = 0.006). During cardiopulmonary bypass, the plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in both groups. At the end of cardiopulmonary bypass the plasma levels of these markers of thrombin formation were significantly higher in group H, although the increase was modest compared with the major increase observed 2 hours after operation in both groups. There were no significant intergroup differences in the platelet counts, the concentration of beta-thromboglobulin, or the plasma levels of fibrinogen and D-dimer. No differences in perioperative morbidity, the postoperative kidney function, or the intubation time were observed, and there were no hospital deaths. CONCLUSIONS The combination of complete heparin-coated cardiopulmonary bypass circuits and low systemic heparinization is safe for patients undergoing elective coronary artery bypass procedures and reduces the perioperative blood loss. There was no evidence of increased thrombogenicity, fibrinolytic activity, or consumption of coagulation factors. No clinical or technical side effects were observed.

Cerebral Microembolic Signals During Cardiopulmonary Bypass Surgery Frequency, Time of Occurrence, and Association With Patient and Surgical Characteristics

BACKGROUND AND PURPOSE We sought to determine the number of cerebral microembolic signals (MES) and their time of occurrence during the two most frequent types of cardiopulmonary bypass (CPB) surgery: coronary artery bypass grafting (CABG) and cardiac valve replacement (VR). Furthermore, we sought to examine the association between MES, patient characteristics, and intraoperative parameters. METHODS Forty-two patients were studied, 15 of whom had CABG and 27 VR. Cerebral MES were detected with the use of transcranial Doppler monitoring of the right middle cerebral artery. RESULTS Cerebral MES were detected in all patients. The number was significantly higher during VR (median, 1048) than during CABG (median, 82) (P < .001). In VR patients, 85% of the MES were detected when the heart regained effective ejection. During CABG, the highest number was detected when the aorta was cross-clamped (18%) and on release of the side clamp (13%). The numbers of MES during the period when the aorta was cross-clamped and in association with surgical procedures were not significantly different in the two patient groups. The total number of MES was inversely correlated to nasopharyngeal temperature (P < .01). CONCLUSIONS A significantly higher number of cerebral MES were detected during VR than during CABG. The highest number occurred in VR patients when effective heart ejection was regained and in CABG patients when the aorta was cross-clamped and on release of the side clamp. The total number of MES increased at lower nasopharyngeal temperatures. Transcranial Doppler monitoring may alert the surgical team when emboli enter the cerebral circulation during CPB surgery, thus allowing preventive measures to be taken.

Complement and granulocyte activation in two different types of heparinized extracorporeal circuits

Complement and granulocyte activation were studied in cardiopulmonary bypass circuits completely coated with either end-attached covalent-bonded heparin, the Carmeda BioActive Surface, or with the Duraflo II bonded heparin, in combination with reduced systemic heparinization (activated clotting time > 250 seconds). The control groups were perfused with uncoated circuits and full heparin dose (activated clotting time > 480 seconds). Altogether 67 patients undergoing elective first-time myocardial revascularization were investigated, having extracorporeal perfusion with a Duraflo II coated circuit (n = 17), an identical but uncoated circuit (n = 17), a Carmeda coated circuit (n = 17), or an equivalent uncoated circuit (n = 16). During cardiopulmonary bypass, the C3 activation products C3b, iC3b, and C3c (C3bc) and the terminal SC5b-9 complemented complex increased markedly in all four groups compared with baseline, but significantly less in the two coated groups than in their control groups. Additionally, a significantly lower concentration of C3bc was observed in the Carmeda coated group, with maximal increase of median 28 AU/ml compared with 50 AU/ml in the Duraflo II coated group (p = 0.003). Similarly, in the Carmeda coated group, the maximal increase of terminal complement complex was considerably lower (0.8 AU/ml) than the levels recognized in the Duraflo II coated group (2.4 AU/ml) (p < 0.001). The release of the granulocyte activation myeloperoxidase and lactoferrin increased from the beginning of the operation, with peak levels at the end of bypass. A significant reduction of lactoferrin release was recognized when comparing the coated groups with the control groups. The difference between the two coated groups (Carmeda 228 micrograms/L; Duraflo II 332 micrograms/L; p = 0.05) was marginally significant. For myeloperoxidase, no significant differences were observed between the coated and uncoated groups. In conclusion, both types of heparin-coated circuits reduced complement activation and release of lactoferrin, but the Carmeda circuit proved to be more effective than the Duraflo II equipment.

Effects on Coagulation and Fibrinolysis With Reduced Versus Full Systemic Heparinization and Heparin-Coated Cardiopulmonary Bypass

BACKGROUND Extracorporeal circulation with circuits coated with surface-bound heparin has allowed reduced levels of systemic heparinization. Clinical benefits have included reduced postoperative bleeding and less homologous blood usage. However, the effects on the hemostatic and fibrinolytic systems have remained in part unknown. METHODS AND RESULTS Indications of thrombin generation, platelet activation, and fibrinolytic activity were investigated in patients undergoing coronary artery bypass surgery. Two groups were perfused with cardiopulmonary bypass (CPB) circuits completely coated with surface-bound heparin: one group with low systemic heparin dose (activated clotting time [ACT] > 250 seconds; n = 17) and a second group having a full heparin dose (ACT > 480 seconds; n = 18). A third control group was perfused with ordinary uncoated circuits and full heparin dose (n = 17). The plasma level of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in all groups during bypass, and somewhat more in both the heparin-coated groups toward the end of CPB, compared with the control group (P < .01). However, the increase during CPB was minimal compared with the major elevation observed 2 hours after surgery in all groups. Platelet release of beta-thromboglobulin increased in all groups (P < .01) during CPB and significantly more in the high-dose group compared with the other two groups (P = .03). Fibrinolytic activities were similar in all groups, and there were no indications of major consumption of coagulation factors. CONCLUSIONS Reduced systemic heparinization (ACT > 250 seconds) in patients having extracorporeal circulation with completely heparin-coated circuits did not lead to increased thrombogenicity. Thrombin formation remained within low ranges during CPB compared with patients receiving a full heparin dose and with the major elevations observed after surgery.

Continued symptomatic improvement three to five years after transmyocardial revascularization with co2laser: A late clinical follow-up of the norwegian randomized trial with transmyocardial revascularization

Objectives The goals of this study were to assess late clinical outcome and left ventricular ejection fraction (LVEF) after transmyocardial revascularization with CO2laser (TMR). Background During the 1990s TMR emerged as a treatment option for patients with refractory angina not eligible for conventional revascularization. Few reports exist on clinical effects and LVEF >3 years after TMR. Methods One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized 1:1 to receive continued medical treatment or medical treatment combined with TMR. The patients were evaluated at baseline and after 3, 12 and 43 (range: 32 to 60) months with end points to angina, hospitalizations due to acute myocardial infarctions or unstable angina, heart failure and LVEF. Mortality was registered and MOS 36 Short-Form Health Survey answered at baseline and after 3, 6 and 12 months. Results Forty-three months after TMR, angina symptoms were still significantly improved, and unstable angina hospitalizations reduced by 55% (p < 0.001). Heart failure treatment (p < 0.01) increased, whereas the number of acute myocardial infarctions, LVEF and mortality was not affected. Quality of life was improved 3, 6 and 12 months after TMR. Conclusions Forty-three months after TMR, angina symptoms and hospitalizations due to unstable angina were significantly reduced, heart failure treatment increased and LVEF and mortality were seemingly unaffected.

Conventional blood conservation techniques in 500 consecutive coronary artery bypass operations

With use of a nonpharmacological, simple, and inexpensive program for blood conservation, 500 consecutive patients underwent elective coronary artery bypass grafting without need of homologous red cell transfusions in 493 (98.6%). At least one internal mammary artery was grafted in all but 1 patient, with supplemental saphenous vein grafts. Intraoperatively, autologous heparinized blood was removed before bypass and retransfused at the conclusion of extracorporeal circulation. The volume remaining in the oxygenator and tubing set was returned without cell processing or hemofiltration. Using the hard-shell cardiotomy reservoir from the heart-lung machine, autotransfusion of the shed mediastinal blood was continued hourly up to 18 hours after operation. The mean postoperative mediastinal blood loss was 643 +/- 354 mL, whereas 624 +/- 296 mL was autotransfused. Thirteen patients (2.6%) needed reexploration for bleeding, of whom 7 (7/500, 1.4%) received homologous blood. No other patients required red cell transfusions. In addition, 9 patients were given a mean of 2.6 units of fresh frozen plasma because of suspected coagulopathy. No platelets were transfused, and no cryoprecipitate therapy was undertaken. Thus, in total, 484 patients (96.8%) were not exposed to any homologous blood products during the hospital stay. At discharge, the mean hemoglobin concentration was 121 +/- 14 g/L (12.1 +/- 1.4 g/dL) and the hematocrit, 0.36 +/- 0.04. Postoperative complications were few. There was one in-hospital death (0.2%).

Complement activation in injured patients occurs immediately and is dependent on the severity of the trauma

In order to study the factors related to complement activation, the complement activation products C3bc and TCC were measured in plasma at admittance and during the stay in the intensive care unit in 108 consecutive patients with multiple injuries. These patients were admitted to the surgical department during a 4-month period. Complement activation occurred immediately after the trauma and correlated strongly with the Injury Severity Score and was inversely correlated to the Base Excess. Complement activation also correlated with the number of transfusions. Sepsis caused complement activation later during the stay in hospital. All seven patients developing the adult respiratory distress syndrome (ARDS) had increased complement activation, either on admission or later during the stay in the intensive care unit. Complement activation is known to contribute to organ damage following ischemia and reperfusion. Clinical studies have demonstrated the importance of early restoration of adequate circulation and the present demonstration of a strong negative correlation between complement activation and Base Excess indicates that early restoration of aerobic metabolism may reduce complement activation and the risk for organ dysfunction.

Diabetes Mellitus and Morbidity and Mortality Risks after Coronary Artery Bypass Surgery

Of 1025 patients (912 men, 113 women) who underwent coronary artery bypass grafting and were followed up for a mean of 7.4 years, 45 (4.4%) had diabetes mellitus. Norwegian population is 1.8-2%). Early mortality was not significantly greater among diabetics than in non-diabetics (2.2 vs. 3.1%, odds ratio--OR-0.44, confidence interval--CI- 0.05-3.56). Diabetic patients had no increased risk of perioperative myocardial infarction (OR = 0.87, CI 0.36-2.10) or of low-output syndrome necessitating intraortic balloon pumping (OR = 0.42, CI 0.55-3.05), and no excess incidence of late non-fatal myocardial infarction (relative risk = 0.69, CI 0.10-1.28) or late chronic heart failure (OR = 2.50, CI 0.5-11.0). Long-term mortality was increased in the diabetic patients (relative risk 1.87, CI 1.60-2.14). Thus diabetes did not entail heightened risk of early mortality, perioperative myocardial infarction or low-output syndrome. Nor was there excess risk of recurrent angina pectoris, late non-fatal myocardial infarction or chronic heart failure among the diabetic patients, but the late mortality risk was increased.

Coronary artery bypass surgery in women and in men; early and long-term results. A study of the Norwegian population adjusted by age and sex

OBJECTIVE We wished to analyse early mortality, postoperative low-output syndrome needing intra-aortic balloon pumping support (IABP), total mortality, recurrent angina pectoris and total non-fatal myocardial infarction in women compared with men. Also, the standard mortality ratio (SMR) was estimated to compare the mortality data to the general Norwegian population of comparable sex and age. METHODS A total of 1025 patients; 113 women and 912 men, were submitted to coronary artery bypass surgery at Rikshospitalet, Oslo between August 1982 and December 1986. The patients were followed up until the 1st of January 1993, representing a mean follow-up time of 7.4 years. An exposed/non-exposed cohort study design was used. A power study was carried out. The standardized mortality ratios for women and men were calculated after adjusting for age and sex. RESULTS Crude odds ratio (ORC) of early mortality was 2.0 with a 95% confidence limit (CL95%) of 0.7-5.4. Odds ratio of low output syndrome needing intra-aortic balloon support was 1.7 (CL95% = 0.8-4.2). Statistical significance was not achieved for these end-points. Women did not run an increased hazard of total mortality (ORC = 0.9; CL95% = 0.5-1.5), recurrent angina pectoris (ORC = 1.4; CL95% = 0.8-2.4) or of total non-fatal myocardial infarction (ORC = 0.8; CL95% = 0.4-1.6) when compared with men. Adjusting for confounders did not significantly alter the results. When matched on sex and age and compared to the normal Norwegian population, we found an increased SMR in both men (2.5; CL95% = 2.2-2.9) and women (4.1; CL95% = 2.2-4.9). CONCLUSION The risk of early mortality and low-output syndrome needing intra-aortic balloon support tended to be higher in women compared with men. Women did not run an increased risk of total mortality, recurrent angina or of total non-fatal myocardial infarction. The standard mortality ratio was increased in both men and women, but in particular higher in women, suggesting a more aggressive course of coronary artery disease in operated women than in operated men. However, this difference did not show in the long term follow-up, due to the beneficial effect of coronary artery bypass surgery in both men and women.