Adenosine myocardial protection: preliminary results of a phase II clinical trial.

OBJECTIVE: To evaluate the safety, tolerance, and efficacy of adenosine in patients undergoing coronary artery bypass surgery. SUMMARY BACKGROUND DATA: Inadequate myocardial protection in patients undergoing coronary artery bypass surgery contributes to overall hospital morbidity and mortality. For this reason, new pharmacologic agents are under investigation to protect the regionally and globally ischemic heart. METHODS: In a double-blind, placebo-controlled trial, 253 patients were randomized to one of three cohorts. The treatment arms consisted of the intraoperative administration of cold blood cardioplegia, blood cardioplegia containing 500 microM adenosine, and blood cardioplegia containing 2 mM adenosine. Patients receiving adenosine cardioplegia were also given an infusion of adenosine (200 microg/kg/min) 10 minutes before and 15 minutes after removal of the aortic crossclamp. Invasive and noninvasive measurements of ventricular performance were obtained before, during, and after surgery. RESULTS: The high-dose adenosine cohort was associated with a trend toward a decrease in high-dose dopamine support and a lower incidence of myocardial infarction. A composite outcome analysis demonstrated that patients who received high-dose adenosine were less likely to experience one of five adverse events: high-dose dopamine use, epinephrine use, insertion of intraaortic balloon pump, myocardial infarction, or death. The operative mortality rate for all patients studied was 3.6% (9/253). CONCLUSIONS: Adenosine treatment is safe and well tolerated and may be associated with fewer postoperative complications.

Six-year survival after coronary thrombolysis and early revascularization for acute myocardial infarction.

Six-year follow-up was conducted in a consecutive series of 192 patients receiving thrombolytic therapy for acute myocardial infarction (AMI) with ST-segment elevation. Cardiac catheterization was performed within a day, and patients with an open infarct artery routinely had early revascularization: 99 (67%) underwent coronary bypass surgery and 18 (12%) coronary angioplasty. With this treatment strategy, 6-year cardiac mortality was 14.5%, 6% (12 patients) in hospital and 9% (16 patients) for survivors of hospitalization. Multivariate analysis showed that predictors of cardiac death among survivors of hospitalization were a closed infarct artery at catheterization (p less than 0.01), diabetes (p less than 0.01) and anterior myocardial infarction (p = 0.01). A subset of 146 patients underwent radionuclide angiography before hospital discharge; for them, predictors of mortality were a closed infarct artery at catheterization (p less than 0.01), anterior wall AMI (p = 0.02), and Killip class III to IV on admission (p less than 0.06). Left ventricular ejection fraction was not a significant predictor of mortality for this subset of patients.

Determinants of hospital charges for coronary artery bypass surgery: the economic consequences of postoperative complications.

This is a prospective study of 500 consecutive patients having coronary artery bypass surgery; mean hospital charge from time of surgery to discharge was +11,900 +/- 12,700. Multiple regression analysis was performed using preoperative variables and postoperative complications. No preoperative clinical feature was a significant predictor of higher average charge. Sternal wound infection (p = 0.0001), respiratory failure (p = 0.0001) and left ventricular failure (p = 0.017) were associated with higher average hospital charge. The absence of any complication predicted a lower average charge, and postoperative death (4.4 +/- 4.5 days after surgery) was also associated with lower average charge. A cost equation was developed: hospital charge equalled $11,217 + $41,559 of sternal wound infection, + $28,756 for respiratory failure, + $5,186 for left ventricular failure, - $1,798 for no complication and - $6,019 for death. Recognition of the influence of complications on charges suggests that low average charges can only be achieved by surgical programs with a low complication rate.

The primary care physician and thrombolytic therapy for acute myocardial infarction: comparison of intravenous streptokinase in community hospitals and the tertiary referral center.

From September 1982 through December 1987, 1012 patients were treated with intravenous streptokinase within 6 hours of acute myocardial infarction. Most of them (816/1012, 81 percent) were treated in community hospitals by primary care physicians. The remaining 196 (19 percent) were treated in the referral center, usually by a cardiologist. Cardiac catheterization within 2 days showed an open infarct artery in 87 percent of the community hospital and 83 percent of the referral center patients (P = NS). Predischarge ejection fraction was similar for community hospital and referral center patients (49 percent +/- 14 percent versus 51 percent +/- 14 percent, respectively), and there was a similar rate of bleeding complications (10 percent versus 13 percent, respectively). We conclude that primary physicians can use intravenous streptokinase effectively and safely in the treatment of patients in community hospitals.

Wound complications after median sternotomy. Relationship to internal mammary grafting.

Case histories of 2582 patients requiring median sternotomy for coronary artery bypass grafting between January 1982 and August 1986 were retrospectively reviewed. Only saphenous vein grafts were used in 230 patients, one mammary artery graft was used in 1626 patients, and both mammary arteries were used in 726 patients. The relationship of potential risk factors and wound complication was evaluated. The overall incidence of wound complications was 0.81%-0.43% in the saphenous vein graft group, 0.49% in the single mammary group, and 1.65% in the bilateral mammary group. Graft type and a number of potential risk factors were analyzed in a logistic regression analysis to determine significant predictors of wound complications. The results indicated that pneumonia, obesity, reexploration, use of the intraaortic balloon pump, and diabetes were significant risk factors contributing to the probability of wound complications. Bilateral mammary grafting was significantly associated with the increased probability of a wound complication developing. Bilateral mammary grafting increased the chance of wound complication nearly five times that of saphenous vein grafting and three times that of single mammary grafting. Mammary artery grafts have been shown to achieve greater long-term patency than saphenous vein grafts, and their continued use is encouraged. However, the potential for increased wound problems should be considered along with other significant preoperative risk factors such as insulin-dependent diabetes, chronic pulmonary disease, and obesity.

Revascularization after thrombolytic therapy for acute myocardial infarction: an analysis of 573 patients.

From October, 1981, to January, 1987, at our center, 891 patients received streptokinase within 6 hours of acute myocardial infarction. A total of 318 patients were treated medically, while 388 patients (43.5%) underwent coronary artery bypass grafting (CABG) alone and 185 (20.7%) were treated with percutaneous coronary angioplasty (PTCA). Subsequent CABG was performed in 37 of 185 PTCA patients after unsuccessful angioplasty. Group characteristics were similar. However, multiple-vessel coronary artery disease was present in 70.3% of CABG patients compared with 24.1% in the PTCA groups. Procedure mortality was 3.6% for CABG alone, 5.4% for PTCA alone, and 13.5% for the combined angioplasty and operation group (p less than 0.05 compared with CABG). All deaths in the PTCA group with subsequent CABG occurred in those patients taken emergently to CABG (5 of 20 patients). We conclude that with proper patient selection both forms of revascularization are safe and effective. However, emergency coronary bypass surgery in the event of failed angioplasty has a high risk.

Early and late results of operation after thrombolytic therapy for acute myocardial infarction.

Recent reports have established the efficacy of thrombolytic therapy in limiting myocardial infarction. Between September 1981 and September 1984, 355 patients were treated with intracoronary (87) or intravenous (268) streptokinase within 6 hours of acute myocardial infarction. Thrombolysis was successful in 63% of patients receiving intracoronary streptokinase and 81% of those receiving intravenous streptokinase. Because residual critical stenosis is usually present and predisposes the patient to reinfarction, revascularization procedures were investigated as an extension of thrombolytic therapy. One hundred ninety-one patients aged 56 +/- 10 (25 to 77) years underwent early surgical revascularization 4.1 +/- 3.6 days after intracoronary or intravenous streptokinase for acute myocardial infarction. Results of this treatment were successful in 89% (170/191) of the patients. Thirteen patients (6.8%) underwent emergency coronary artery bypass grafting for failed percutaneous angioplasty. There were 3.2 +/- 1.4 grafts per patient and 3.8 +/- 2.9 units of blood were administered in the perioperative period. Operative mortality was 4.2% (8/191) with a 15.4% mortality (2/13) in the group in which angioplasty failed. Mean hospitalization time after operation was 10.9 +/- 6.8 days. Follow-up was 27 +/- 8 (12 to 48) months and was obtained on all patients. Late cardiac mortality was 1.0% (2/183). Ninety percent of the follow-up group was without angina and only 1.7% showed no improvement after operation. Reinfarction occurred in four patients (2.2%), with graft failure documented by coronary arteriography in two of these patients. This experience indicates that early revascularization after thrombolytic therapy may be performed with low operative mortality and morbidity and is associated with excellent late results.

Thrombolytic therapy followed by early revascularization for acute myocardial infarction.

During a 24-month period, 192 patients with acute myocardial infarction were treated with intracoronary or intravenous streptokinase (SK). In 147 patients (77%) an open infarct artery was demonstrated by coronary angiography; 117 of these 147 patients were judged to have viable myocardium supplied by a critically narrowed coronary artery and underwent revascularization 3 +/- 2 days after SK therapy. In-hospital mortality was 6% (12 of 192). The mortality rate over the subsequent 20 +/- 7 months of follow-up was lower for those in whom SK therapy was successful (1 of 137, 0.7%) than in those in whom it was not (6 of 43, 14%) (p less than 0.001), and tended to be lower for those treated with intravenous (2 of 111, 2%) rather than intracoronary SK (5 of 69, 7%, p = 0.11). Reinfarction occurred in 3% of the 180 survivors of hospitalization, angina pectoris in 11% and congestive heart failure in 7%. Clinical outcome was similar for patients treated with intravenous and intracoronary SK and for patients treated in community hospitals and the referral center.

Percutaneous transluminal coronary angioplasty as palliation for patients considered poor surgical candidates.

Thirty-one patients with angina inadequately controlled by medical therapy, but who were poor surgical candidates because of advanced age and poor general condition, or because of depressed left ventricular function, had percutaneous transluminal coronary angioplasty (PTCA). These high-risk patients were identified prospectively, and coronary artery bypass surgery (CABS) was planned only in the event of arterial occlusion and chest pain. PTCA was successful in 11 of 17 (65%) high-risk geriatric patients, in 11 of 12 (92%) patients with left ventricular ejection fraction less than 40%, and in two additional patients having PTCA without surgical stand-by because of technically difficult vascular anatomy for CABS. There were no PTCA-related deaths; three of the 31 high-risk patients had emergency surgery because of arterial occlusion, and the remaining four patients with PTCA failure remain on medical therapy for angina. The clinical course of the 31 high-risk patients was similar to that of 155 patients having PTCA during the study period who were considered good candidates for either PTCA or CABS. PTCA may thus be considered an intermediate, palliative procedure for patients with inadequate control of ischemic symptoms who are poor surgical candidates.

Reliability of Q-wave formation and QRS score in predicting regional and global left ventricular performance in acute myocardial infarction with successful reperfusion.

The frequency of electrocardiographic Q-wave formation and the relation of Q wave and QRS score to regional and global left ventricular (LV) performance were determined in 131 patients with acute myocardial infarction (AMI) receiving thrombolytic therapy. Thrombolytic therapy was successful in reperfusing the occluded infarct artery in 100 patients and was unsuccessful in 31. The number of patients who had 1 or more Q waves (88 vs 87%) and 2 or more Q waves (70 vs 74%) was similar. In contrast, normal wall motion was significantly more common in the infarct area in patients in whom reperfusion was successful (42 vs 15%, p less than 0.05). Total QRS scores were similar in patients in whom reperfusion was successful and in those in whom it was not (6.0 +/- 3.2 vs 6.4 +/- 4.2). Despite similar QRS scores, successfully treated patients had significantly higher LV ejection fraction (53 +/- 13% vs 46 +/- 15%, p less than 0.05). Thus, Q-wave formation after successful thrombolytic therapy for AMI is common but does not faithfully reflect regional or global LV performance. Electrocardiographic analysis alone is not a reliable method to assess efficacy of reperfusion therapy.

Effects of coronary grafting technique upon reperfusion cardiac rhythm, ventricular function, and other variables.

The effects of different techniques of aortocoronary bypass grafting on reperfusion cardiac rhythm and ventricular function have not been systematically evaluated for possible advantages or disadvantages. The placement of proximal anastomoses before cardiopulmonary bypass and sequential coronary grafting with reperfusion via both the grafts and the native circulation were prospectively compared to traditional grafting and reperfusion via native arteries. More than 40 biochemical, thermal, temporal, hemodynamic, and other variables, including arrhythmias and myocardial failure, were measured intraoperatively and postoperatively. Spontaneous resumption of a cardiac rhythm occurred more frequently with traditional grafting technique in association with a larger cardioplegia volume and a higher serum potassium. However, the disadvantage of the traditional technique was a higher incidence of cardiac failure postoperatively and greater use of isoproterenol after discontinuation of bypass. While cardiac rhythm resumed spontaneously more often with the traditional technique, the increased incidence of cardiac failure postoperatively has serious implications. Thus, placement of proximal anastomoses before cardiopulmonary bypass seems warranted.

Low-energy defibrillation: safe and effective.

During cardiopulmonary bypass, 150 cardiac surgical patients were prospectively evaluated for the number, energy, current, and success rates of direct current (DC) shocks required to terminate reperfusion ventricular fibrillation (1 degree) or ventricular fibrillation occurring subsequent to a nonfibrillatory reperfusion rhythm (2 degrees). Thirty-one percent of 1-J shocks and 58% of 2.5-J shocks defibrillated. Above 2.5 J, the defibrillation success rate reached a plateau of 50-60%. Myocardial resistance decreased significantly after the first shock but remained stable during subsequent shocks. Lower defibrillating currents and myocardial resistances than had been previously reported were observed. The feasibility of low-energy defibrillation during cardiopulmonary bypass was therefore documented.

Comparative cost of myocardial revascularization: percutaneous transluminal angioplasty and coronary artery bypass surgery.

A consecutive series of 78 patients having percutaneous transluminal coronary angioplasty for single vessel coronary artery disease and 85 patients having single vessel coronary artery bypass graft surgery were followed up prospectively for 1 year. Days in hospital and angiographic and revascularization procedures were counted in the two groups of patients and total cost of care for 12 months was calculated using current billing levels. Angioplasty was initially successful in 74% of patients; because of initial failure in 26% and late restenosis in 18%, bypass surgery was ultimately needed in 23 of 78 patients having coronary angioplasty. Nevertheless, total cost of care per patient was 43% lower for those having angioplasty as an initial procedure for single vessel coronary artery disease.

Early operative intervention after thrombolytic therapy for acute myocardial infarction.

Thrombolytic therapy effectively interrupts acute myocardial infarction but does not correct the underlying plaque causing acute thrombosis. Early operation and treatment of the residual coronary artery disease has therefore been evaluated. Over 29 months, 184 patients with acute myocardial infarction of less than 6 hours duration were treated with intracoronary (IC) or intravenous (IV) streptokinase (SK). Angiography was performed early and thrombolysis found to be successful in 70% of the IC-SK group and 82% of the IV-SK group. One hundred six patients with successful thrombolysis had early revascularization surgery performed 3.3 +/- 2.1 days following SK treatment (range 0 to 11 days). These patients were compared with 110 consecutive patients who underwent coronary artery bypass grafting for standard indications. The SK group had an average of 3.0 +/- 1.4 grafts, 4.3 +/- 3.1 units of blood, and 10.8 +/- 5.3 days in the hospital postoperatively per patient and had an operative mortality rate of 2.7%. The control group averaged 3.6 +/- 1.3 grafts, 4.0 +/- 2.4 units of blood, and 9.6 +/- 3.5 days in the hospital postoperatively per patient with an operative mortality rate of 2.7%. This experience indicates that early operation following SK therapy can be performed with low operative risk and without prolonged hospitalization.

Unanticipated postoperative ventricular tachyarrhythmias.

Eighteen (1.4%) of 1,251 patients who underwent cardiac operations during a three-year period had new sustained ventricular tachycardia (12 patients) or ventricular fibrillation (6 patients) not caused by but resulting in hemodynamic compromise. In 13 patients, the initial arrhythmia occurred in the first 48 hours postoperatively. Lidocaine was being administered to 10 of these patients for suppression of previously noted ventricular ectopy, but it did not prevent the occurrence of the arrhythmia. The initial episode was fatal for 5 patients. Two of these deaths were directly related to the adverse effects of the antiarrhythmic agents used to suppress ventricular tachycardia or fibrillation. Five of 10 survivors underwent electrophysiological studies after initial resuscitation. In all 5, programmed ventricular stimulation reproduced the clinical arrhythmia. There have been 2 late sudden deaths in patients who either did not undergo or remained uncontrolled at electrophysiological study during serial drug trials. Our experience suggests that a cardiac operation may unmask or induce potentially lethal arrhythmias that previously had not been apparent. Pharmacological suppression of ventricular ectopy does not necessarily prevent ventricular tachycardia or ventricular fibrillation in the early postoperative period. Electrophysiological study may be helpful in determining the appropriate prophylactic therapy in such patients.

Determinants of reperfusion cardiac electrical activity after cold cardioplegic arrest during coronary bypass surgery.

In a prospective study of 99 patients with coronary artery disease, reperfusion of the heart after a period of ischemia (protected by contemporary techniques of myocardial preservation) resulted in spontaneous resumption of cardiac electrical activity in 53%, spontaneous defibrillation in 10%, reperfusion ventricular fibrillation (VF) in 32% and indeterminate rhythm in 5%. In hearts spontaneously developing rhythms excluding VF (as opposed to hearts requiring direct-current shock), factors significantly associated were a higher plasma potassium concentration (5.2 vs 4.8 mEq/liter), shorter reperfusion time (1 vs 4 minutes), higher plasma magnesium concentration (1.36 vs 1.25 mg/dl) and a lower myocardial temperature (27 vs 32 degrees C). The duration of ischemia, arterial blood gas levels, plasma catecholamine levels, plasma ionized calcium levels, volume of cardioplegia and mean arterial pressure did not relate to occurrence of spontaneous episodes. However, VF developed in 39 of 52 patients (75%) with spontaneous resumption of electrical activity. This event was associated with lower myocardial temperature. Thus, direct-current shocks were ultimately required in 77 of the 99 patients (78%). Although certain thermal, biochemical and hemodynamic variables facilitate spontaneous resumption of cardiac rhythm, the development of VF may negate the potential benefit of this event in the prevention of myocardial damage from direct-current defibrillation.

Intravenous versus intracoronary streptokinase therapy for acute myocardial infarction in community hospitals.

A consecutive series of 184 patients with acute myocardial infarction (AMI) received thrombolytic therapy. The first 63 were treated in the catheterization laboratory with intracoronary streptokinase (IC-STK), and 44 (70%) had successful thrombolysis. One hundred twenty-one patients received intravenous (IV) STK immediately after diagnosis of AMI, and 99 (82%) were found to have an open infarct artery. Only 58% of patients (14 of 24) who required transfer from out-of-town hospitals for IC-STK treatment had successful thrombolysis; in contrast, IV-STK given in the local hospital resulted in an 85% (72 of 85) rate of thrombolysis (p = 0.005). IV-STK thus appears at least as effective as IC-STK for AMI and is more effective for patients treated in hospitals without catheterization facilities.

Energy dose and other variables possibly affecting ventricular defibrillation during cardiac surgery.

Previous studies have suggested that shocks of 5-10 J are required for direct ventricular defibrillation during open heart surgery. However, the efficacy of shocks of less than 5 J, the effects of thermal, biochemical, and temporal factors, and the influence of disease process on defibrillation have not been fully investigated, particularly with modern techniques of myocardial preservation. The purpose of this prospective study in 150 adult cardiac surgical patients was to evaluate the energy, current, and myocardial resistance with low energy DC shocks of 1, 2.5, and 5 J and to relate which biochemical, temporal, thermal, or other factors influence the outcome of a DC shock. Twenty-eight percent of shocks of 1 J and 55% of shocks of 2.5 J produced defibrillation. Above 2.5 J, the success rate reached a plateau at 55%. Other factors associated with the success of DC shocks were high normal serum potassium levels, high PaO2, high ionized calcium levels, and longer reperfusion times at mean arterial and coronary perfusion pressures above 50 mm Hg. Disease process may also play a role because patients with valvular heart disease were more difficult to defibrillate. Heart weight and thickness of ventricular myocardium, measured angiographically, appeared less important in direct defibrillation, except with 1 J shocks when thinner-walled ventricles defibrillated more easily.