Hyperbaric oxygen and thrombolysis in myocardial infarction: the ''HOT MI'' randomized multicenter study

Reactions mediated by the brain are part of the response to intraperitoneal administration of endotoxin, a model of gram-negative bacterial infection. To test the hypothesis that a compromised blood-brain barrier (BBB) may contribute to these reactions, the integrity of the BBB was measured following lipopolysaccharide administration. Rats received intraperitoneal injections of 50 microg/kg or 2 mg/kg of endotoxin. Brain uptake of a macromolecular vascular marker, 3H-labelled rat serum albumin, and of a poorly permeable low molecular weight substance, [14C]sucrose, was then measured with the intravenous bolus injection method. Compared to controls, neither dose of endotoxin affected the BBB permeability for these tracers. This was true when brain uptake was measured 5 min or 2 h after lipopolysaccharide injection. It is concluded that intraperitoneal endotoxin even at a high dose does not acutely disrupt the BBB.     

Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase

BACKGROUND: It has been demonstrated that therapeutic ultrasound effects ultrasound thrombolysis by selectively disrupting the fibrin matrix of the thrombus. This study was conducted to evaluate the clinical feasibility of percutaneous transluminal coronary ultrasound thrombolysis in acute myocardial infarction (AMI). METHODS AND RESULTS: Consecutive patients (n = 15) with evidence of anterior AMI and Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow in the left anterior descending artery underwent coronary ultrasound thrombolysis. Angiographic follow-up was performed after 10 minutes and 12 to 24 hours. Ultrasound induced successful reperfusion (TIMI grade 3 flow) in 87% of the patients. Adjunct percutaneous transluminal coronary angioplasty (PTCA) after ultrasound thrombolysis produced a final residual stenosis of 20 +/- 12% as determined by quantitative coronary angiographic analysis. There were no adverse angiographic signs or clinical effects during the procedure. There was no change in the degree of flow in any of the patients at the 12- to 24-hour angiograms. During hospitalization, 1 patient had recurrent ischemia on the fifth day after the procedure, and emergent catheterization revealed occlusion at the treatment site. The patient was successfully treated with PTCA. CONCLUSIONS: These results suggest that ultrasound thrombolysis has the potential to be a safe and effective catheter-based therapeutic modality in reperfusion therapy for patients with AMI and other clinical conditions associated with intracoronary thrombosis.     

Cardiac event rates after acute myocardial infarction in patients treated with verapamil and trandolapril versus trandolapril alone. Danish Verapamil Infarction Trial (DAVIT) Study Group

Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), but mortality may be as high as 10% to 15% after 1 year. Verapamil prevents cardiac events after an AMI in patients without CHF. We hypothesized that in postinfarct patients with CHF already prescribed diuretics and an ACE inhibitor, additional treatment with verapamil may reduce cardiac event rate. In this multicenter, double-blind study, patients with CHF receiving diuretic treatment were consecutively randomized to treatment with trandolapril 1 mg/day for 1 month and 2 mg/day the following 2 months (n = 49), or to trandolapril as mentioned plus verapamil 240 mg/day for 1 month and 360 mg/day for 2 months (n = 51). Trial medication started 3 to 10 days after AMI. All patients were followed for 3 months. End points in the trandolapril/trandolapril-verapamil groups were death 1/1, reinfarction 7/1, unstable angina 9/3, and readmission for CHF 6/2. The 3-month first cardiac event rate was 35% in trandolapril-treated patients and 14% in trandolapril-verapamil-treated patients (hazard ratio 0.35, 95% confidence interval 0.15 to 0.85, p = 0.015). These data suggest that verapamil reduces cardiac event rates in post-AMI patients with CHF when added to an ACE inhibitor and a diuretic.     

Cost comparison of immediate angioplasty versus thrombolysis followed by conservative therapy for acute myocardial infarction: a randomized prospective trial. Mayo Coronary Care Unit and Catheterization Laboratory Groups

OBJECTIVE: Immediate angioplasty and thrombolysis followed by conservative therapy are treatment strategies for acute myocardial infarction. The objective of this study was to compare the costs of these two strategies during a 12-month period. METHODS: Of 103 patients with acute myocardial infarction who sought medical assistance within 12 hours after onset of symptoms, 4 were excluded from analysis for various reasons, 51 received tissue plasminogen activator, and 48 underwent immediate angioplasty as the initial revascularization strategy. The main outcome determinants were direct monetary costs and indirect measures of costs, including duration of hospital stay and return to work. RESULTS: No significant difference in monetary costs between the two initial treatment strategies could be demonstrated. A trend was noted toward a briefer hospital stay and fewer late in-hospital procedures for patients treated initially with immediate angioplasty. Other measures of indirect costs were not statistically different. CONCLUSION: The hypothesis that thrombolysis followed by conservative therapy would be more cost-effective than immediate angioplasty in the treatment of patients with acute myocardial infarction could not be substantiated. The two strategies seem to have similar cost-effectiveness.     

Beneficial effects of captopril on prognosis in patients with acute myocardial infarction. Shanghai Secondary Prevention of Acute Myocardial Infarction Study Group

OBJECTIVES: To assess the effects of early and long-term angiotensin-converting enzyme inhibitor treatment with captopril on clinical outcome in patients with acute myocardial infarction (AMI). METHODS: Eight hundred and twenty-two patients with AMI who were hospitalised within 72 hours of symptoms and had no cardiogenic shock were randomly allocated to captopril (n = 478, Group I) and conventional treatment (n = 344, Group II). Cardiac events including congestive heart failure, reinfarction, severe arrhythmias and cardiac death during hospitalization and follow-up period (average 20 months) were determined. RESULTS: The overall mortality rate during hospitalization was lower in group I than in group II (P = 0.0001), this was true for patients with anterior (P = 0.0003), inferior (P = 0.0411) and anterior inferior AMI (P = 0.0232). During follow-up, despite similar occurrence rate of reinfarction and severe arrhythmias in the two groups, the mortality rate (P = 0.0324) and total cardiac event rate (P = 0.055) were lower in group I than in group II. CONCLUSIONS: After AMI, early and long-term treatment with captopril exerts a beneficial effect on the prognosis of patients.     

Comparison of double bolus urokinase versus front-loaded alteplase regimen for acute myocardial infarction. Thrombolysis in Myocardial Infarction in Korea (TIMIKO) study group

This study was performed to compare the double bolus urokinase regimen with the front-loaded alteplase regimen for acute myocardial infarction. Double bolus urokinase is an easy, safe, and effective thrombolytic regimen with comparable results to standard front-loaded alteplase in acute myocardial infarction.     

Intensive medical therapy versus coronary angioplasty for suppression of myocardial ischemia in survivors of acute myocardial infarction: a prospective, randomized pilot study

BACKGROUND: Patients who have inducible ischemia after acute myocardial infarction (AMI) generally undergo coronary angiography with the intent to revascularize. Whether this approach is superior to intensive treatment with anti-ischemic medications is unknown. METHODS AND RESULTS: We performed a prospective, randomized pilot study comparing intensive medical therapy with coronary angioplasty (PTCA) for suppression of myocardial ischemia in 44 stable survivors of AMI. Myocardial ischemia was quantified with adenosine 201Tl tomography (SPECT) performed 4.5+/-2.9 days after AMI. All patients at baseline had a large total (>/=20%) and ischemic (>/=10%) left ventricular perfusion defect size (PDS). SPECT was repeated at 43+/-26 days after therapy was optimized. The total stress-induced PDS was comparably reduced with medical therapy (from 38+/-13% to 26+/-16%; P<0.0001) and PTCA (from 35+/-12% to 20+/-16%; P<0.0001). The reduction in ischemic PDS was also similar (P=NS) in both groups. Cardiac events occurred in 7 of 44 patients over 12+/-5 months. Patients who remained clinically stable had a greater reduction in ischemic PDS (-13+/-9%) than those who had a recurrent cardiac event (-5+/-7%; P<0.02). Event-free survival was superior in the 24 patients who had a significant (>/=9%) reduction in PDS (96%) compared with those who did not (65%; P=0.009). CONCLUSIONS: In this small pilot study, intensive medical therapy and PTCA were comparable at suppressing ischemia in stable patients after AMI. Sequential imaging with adenosine SPECT can track changes in PDS after anti-ischemic therapies and thereby predict subsequent outcome. Corroboration of these preliminary findings in a larger cardiac-event trial is warranted.     

ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction

BACKGROUND: The goal of thrombolytic treatment in acute myocardial infarction is reperfusion of the infarct-related coronary artery. Duteplase is a double-chain recombinant tissue-type plasminogen activator. Its efficacy and safety were evaluated in patients with acute myocardial infarction treated within 4 h of onset of chest pain in this multicentre, open, non-controlled trial. METHODS AND RESULTS: A total of 273 patients were enrolled and treated with duteplase 0.6 MU.kg-1 over 4 h, with concomitant oral aspirin and intravenous heparin. Coronary arteriography was performed at 60 min, 90 min and approximately 24 h after the start of duteplase infusion to assess the perfusion grade (TIMI scoring) of the infarct-related coronary artery. Safety was assessed by monitoring patients closely for bleeding and for all other adverse experiences during the 72-h study period. Reinfarction during the study period was also recorded, and deaths at any time during the period in hospital were documented. TIMI grade 2 or 3 patency of the infarct-related coronary artery at 90 min was achieved in 70% of the patients and 7% of these "patent' infarct-related coronary arteries had reoccluded by 20 to 36 h. Clinical reinfarction during the 72-h study period was observed in 7%. Total in-hospital mortality was 8%. Serious or life-threatening bleeding occurred in 4% of the patients. There was one haemorrhagic stroke, and this was fatal. CONCLUSIONS: Weight-adjusted duteplase infusion, together with oral aspirin and intravenous heparin, in acute myocardial infarction resulted in patency of the infarct-related coronary artery and a safety profile comparable to those reported for the other form of tissue-type plasminogen activator, alteplase. However, there remains a problem with reocclusion and reinfarction after initially successful thrombolysis.     

Myocardial contrast echocardiography versus dobutamine echocardiography for predicting functional recovery after acute myocardial infarction treated with primary coronary angioplasty

OBJECTIVES: We sought to compare myocardial contrast echocardiography with low dose dobutamine echocardiography for predicting 1-month recovery of ventricular function in acute myocardial infarction treated with primary coronary angioplasty. BACKGROUND: The relation between myocardial perfusion and contractile reserve in patients with acute myocardial infarction, in whom anterograde flow is fully restored without significant residual stenosis, is still unclear. METHODS: Thirty patients with acute myocardial infarction treated successfully with primary coronary angioplasty underwent intracoronary contrast echocardiography before and after angioplasty and dobutamine echocardiography 3 days after the index infarction. One month later, two-dimensional echocardiography and coronary angiography were repeated in all patients and contrast echocardiography in 18 patients. RESULTS: After coronary recanalization, 26 patients showed myocardial reperfusion within the risk area, although 4 did not. At 1-month follow-up, all patients had a patient infarct-related artery without significant restenosis. Both left ventricular ejection fraction and wall motion score index within the risk area significantly improved in the patients with reperfusion ([mean +/- SD] 38 +/- 8% vs. 48 +/- 12%, p < 0.005; and 2.35 +/- 0.5 vs. 2 +/- 0.6, p < 0.001, respectively), but not in those with no reflow. Of the 72 nonperfused segments before angioplasty, 27 showed functional improvement at follow-up. Myocardial contrast echocardiography had a sensitivity and a negative predictive value similar to dobutamine echocardiography in predicting late functional recovery (96% vs. 89% and 89% vs. 93%, respectively), but a lower specificity (18% vs. 91%, p < 0.001), positive predictive value (41% vs. 86%, p < 0.001) and overall accuracy (47% vs. 90%, p < 0.001). CONCLUSIONS: Microvascular integrity is a prerequisite for myocardial viability after acute myocardial infarction. However, contrast enhancement shortly after recanalization does not necessarily imply a late functional improvement. Thus, contractile reserve elicited by low dose dobutamine is a more accurate predictor of regional functional recovery after reperfused acute myocardial infarction than microvascular integrity.     

Ultrasonic tissue characterization in predicting residual ischemia and myocardial viability for patients with acute myocardial infarction

The identification of viable myocardium and residual ischemia in patients with acute myocardial infarction has important prognostic implications. The ultrasonic tissue characterization with integrated backscatter and dobutamine-atropine stress echocardiography were performed 8.3+/-3 days after AMI in 30 patients. After coronary angioplasty for the residual stenosis of infarct-related artery, both modalities were repeated. The parameter obtained from ultrasonic tissue characterization, phase-weighted variation, could differentiate the myocardium with residual coronary stenosis or nonviable myocardium from the viable myocardium without residual coronary stenosis (p < 0.001). Using the cutoff value of 5.8 dB, the sensitivity, specificity and accuracy for detecting viable myocardium without residual coronary stenosis were 75%, 100% and 90.2%, respectively. The phase-weighted variation of the viable infarction zone restored after the coronary stenosis was relieved. In contrast, the nonviable myocardium had a small phase-weighted variation that was irrelevant to the patency of the infarct-related artery. The ultrasonic tissue characterization may be used in identifying patients with acute myocardial infarction whose infarction zones are viable without residual ischemia.     

Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy

BACKGROUND: In the Acute Infarction Ramipril Efficacy (AIRE) Study, the effect of angiotensin-converting-enzyme (ACE) inhibition on the survival of patients with clinical heart failure after acute myocardial infarction (AMI), was assessed. At an average follow-up time of 15 months after randomisation, all-cause mortality was reduced from 22.6% (placebo group) to 16.9% (ramipril group) representing an absolute mortality reduction of 5.7% and a relative risk reduction of 27% (95% CI 11-40%; p = 0.002). Our aim in this study was to assess the long-term (3 years after the AIRE Study closed) magnitude, duration, and reliability of the survival benefits observed after treatment with ramipril (target dose 5 mg twice a day) when compared with placebo. METHODS: We investigated the mortality status of all 603 patients recruited from the 30 UK centres involved in the AIRE Study. Through government records we were able to confirm the death or survival of all 603 patients exactly 3 years after the close of the AIRE Study. Follow-up was for a minimum of 42 months and a mean of 59 months. The average duration of treatment with masked trial medication was 13.4 months for placebo and 12.4 months for ramipril. FINDINGS: By 0000 h March 1, 1996, death from all causes had occurred in 117 (38.9%) of 301 patients randomly assigned placebo and 83 (27.5%) of 302 patients randomly assigned ramipril, representing a relative risk reduction of 36% (95% CI 15-52%; p = 0.002) and an absolute reduction in mortality of 11.4% (114 additional 5-year survivors per 1000 patients treated for an average of 12.4 months). INTERPRETATION: Our data provide robust evidence that administration of ramipril to patients with clinically defined heart failure after AMI results in a survival benefit that is not only large in magnitude, but also sustained over many years.     

Effect of reperfusion modality on outcome in nonsmokers and smokers with acute myocardial infarction (a Primary Angioplasty in Myocardial Infarction [PAMI] substudy). PAMI Investigators

BACKGROUND: We present our experience with laparoscopic cholecystectomy in pregnant patients, with consideration of the physiological changes of pregnancy affecting anesthetic and surgical management. METHODS: We reviewed the medical records of all pregnant patients undergoing laparoscopic surgery at Brigham and Women's Hospital between January 1, 1991 and April 30, 1995. RESULTS: Laparoscopic cholecystectomy was performed without complication in ten patients (gestational age 9-30 weeks). Details of anesthetic and surgical management are described. The anesthetic and surgical implications of pregnancy-associated physiological changes in the gastrointestinal, respiratory, cardiovascular, and central nervous system are reviewed. CONCLUSIONS: With appropriate attention to the altered physiology of pregnancy, laparoscopic cholecystectomy can be performed safely and effectively during pregnancy.     

Management and outcomes for black patients with acute myocardial infarction in the reperfusion era. National Registry of Myocardial Infarction 2 Investigators

Data from a national registry of myocardial infarction patients from June 1994 to April 1996 were analyzed to compare the presenting characteristics, acute reperfusion strategies, treatment patterns, and clinical outcomes among black and white patients. Blacks presented much later to the hospital after the onset of symptoms (median 145 vs 122 minutes, p <0.001), were more likely to have atypical cardiac symptoms (28% vs 24%, p <0.001), and nondiagnostic electrocardiograms during the initial evaluation period compared with whites (37% vs 31%, p <0.001). Also, blacks were less likely to receive intravenous thrombolytic therapy (adjusted odds ratio [OR] 0.76, 95% confidence intervals [CI] 0.71 to 0.80), coronary arteriography (adjusted OR 0.85, 95% CI 0.77 to 0.95), other elective catheter-based procedures (adjusted OR 0.87, 95% CI 0.78 to 0.96), and coronary artery bypass surgery (adjusted OR 0.66, 95% CI 0.58 to 0.75) than their white counterparts. Despite these differences in treatment, there were no significant differences in hospital mortality between blacks and whites.     

Transdermal nitroglycerin patch therapy improves left ventricular function and prevents remodeling after acute myocardial infarction: results of a multicenter prospective randomized, double-blind, placebo-controlled trial

BACKGROUND: Nitrates are widely used in the treatment of angina in patients with acute myocardial infarction (AMI). Short-term administration prevents left ventricular (LV) dilation and infarct expansion. However, little information is available regarding their long-term effects on LV remodeling in patients surviving Q-wave AMI. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled trial designed to investigate the long-term (6-month) efficacy of intermittent transdermal nitroglycerin (NTG) patches on LV remodeling in 291 survivors of AMI. Patients meeting entry criteria had baseline gated radionuclide angiography (RNA) followed by randomization to placebo or active NTG patches delivering 0.4-, 0.8-, or 1.6-mg/h. RNA was repeated at 6 months and 6.5 days after withdrawal of double-blind medication. The primary study end point was the change in end-systolic volume index (ESVI). Both ESVI and end-diastolic volume index (EDVI) were significantly reduced with 0.4-mg/h NTG patches (-11.4 and -11.6 mL/m2, respectively, P<.03). This beneficial effect was observed primarily in patients with a baseline LV ejection fraction < or =40% (deltaESVI, -31 mL/m2; deltaEDVI, -33 mL/m2; both P<.05) and only at the 0.4-mg/h dose. After NTG patch withdrawal, ESVI significantly increased but did not reach pretreatment values. CONCLUSIONS: Transdermal NTG patches prevent LV dilation in patients surviving AMI. The beneficial effects are limited to patients with depressed LV function and only at the lowest (0.4-mg/h) dose. Continued administration is necessary to maintain efficacy. Whether these remodeling effects confer a clinical or survival advantage will need to be addressed in an adequately powered cardiac event trial.     

Segmental right ventricular function after acute myocardial infarction: two-dimensional echocardiographic study in 63 patients

Right ventricular (RV) segmental contraction was studied in 63 patients with acute myocardial infarction (MI), using 2-dimensional (2-D) echocardiography. Group A included 32 patients with ischemic RV dysfunction: 19 had a disproportionate increase in right atrial pressure at the time of the examination (Group AI) and in 13 patients, right atrial pressure was normal when the echocardiogram was obtained (Group AII). Group B included 31 patients without ischemic RV dysfunction. Alkinesia or dyskinesia of the RV wall was found in 30 patients: 19 from Group AI, 8 from Group AII, and 3 from Group B. Asynergy could be identified in all segments of the RV wall including the outflow tract, RV apex, and anterior wall, but was more frequently found in the posterior wall (29 patients), best seen in the transversal subcostal short-axis view. A significant difference was found either in the frequency of wall motion abnormalities or in the number of segments with asynergy among the 3 groups (p less than 0.001). However, asynergy of the RV wall may be present in some patients with normal right heart hemodynamic function, suggesting that asynergy may be more sensitive than hemodynamic function in the diagnosis of acute RV infarction. Paradoxical septal motion was found in 8 patients, all in Group AI, and all had a right atrial pressure equal to or greater than pulmonary capillary pressure.     

TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators

BACKGROUND: Bolus thrombolytic therapy is a simplified means of administering thrombolysis that facilitates rapid time to treatment. TNK-tissue plasminogen activator (TNK-tPA) is a highly fibrin-specific single-bolus thrombolytic agent. METHODS AND RESULTS: In TIMI 10B, 886 patients with acute ST-elevation myocardial infarction presenting within 12 hours were randomized to receive either a single bolus of 30 or 50 mg TNK-tPA or front-loaded tPA and underwent immediate coronary angiography. The 50-mg dose was discontinued early because of increased intracranial hemorrhage and was replaced by a 40-mg dose, and heparin doses were decreased. TNK-tPA 40 mg and tPA produced similar rates of TIMI grade 3 flow at 90 minutes (62.8% versus 62.7%, respectively, P=NS); the rate for the 30-mg dose was significantly lower (54.3%, P=0.035) and was 65. 8% for the 50-mg dose (P=NS). A prespecified analysis of weight-based TNK-tPA dosing using median TIMI frame count demonstrated a dose response (P=0.001). Similar dose responses were observed for serious bleeding and intracranial hemorrhage, but significantly lower rates were observed for both TNK-tPA and tPA after the heparin doses were lowered and titration of the heparin was started at 6 hours. CONCLUSIONS: TNK-tPA, given as a single 40-mg bolus, achieved rates of TIMI grade 3 flow similar to those of the 90-minute bolus and infusion of tPA. Weight-adjusting TNK-tPA appears to be important in achieving optimal reperfusion; reduced heparin dosing appears to improve safety for both agents. Together with the safety results from the parallel Assessment of the Safety of a New Thrombolytic: TNK-tPA (ASSENT I) trial, an appropriate dose of this single-bolus thrombolytic agent has been identified for phase III testing.