Thrombolytic Therapy For Acute Infarction Research Articles

Successful repair of myocardial free wall rupture after thrombolytic therapy for acute infarction

Background. Controversy exists regarding the timing of thrombolytic administration and rupture rate. Methods. Hospital records at St. Luke’s-Roosevelt Hospital of the 4 study patients were reviewed and compared with those of 41 patients from a group of 537 patients concurrently admitted with a diagnosis of myocardial infarction (MI). Results. Four patients experienced ventricular free wall rupture after having a MI between November 17, 1993, and July 28, 1995. All received tissue plasminogen activator. In 1 patient, pericardial effusion associated with a pseudoaneurysm was discovered in the operating room. The 3 others developed clinical pericardial tamponade before surgery. All 4 patients survived and left the hospital on postoperative days 10, 11, 11, and 82, respectively. During this same time period, 537 patients were admitted with MI, 41 of whom died; the study’s 4 patients were compared with these 41. Conclusions. These data demonstrate that rupture of the ventricular free wall can occur early after thrombolytic therapy and may have a subacute course. Prompt diagnosis and surgery offer excellent chances of surviving this fatal condition.

Gender differences and the outcome of interventions for acute coronary syndromes.

Differences in the overall mortality for acute infarction in women vs men have been appreciated for some time. Some of these differences are based on the age at the time of presentation of women compared with men. Excess mortality in women is most clear at the younger end of the age spectrum. More careful examination of the data has shown differences based on factors such as greater delays in presentation in women, real biases in the types of healthcare provider, and selection of diagnostic and therapeutic interventions for women compared with men. Recently, the mode of presentation has emerged as a major defining point. Women present more frequently with unstable angina or non-Q-wave infarction and have lesser mortality with these syndromes compared with men. Thus, the overall outcomes of acute coronary syndromes vary substantially from the differences in outcome for acute Q-wave infarction alone. New data have emerged regarding differences in treatment outcome for acute infarction. Women have derived lesser benefit from thrombolytic therapy and still respond to percutaneous transluminal coronary angioplasty more favorably than thrombolytic therapy for acute infarction. Women seem to have less benefit from stent use compared with angioplasty alone for acute infarction. Although increasing scrutiny has shed a great deal of light on some of these gender differences in outcomes from acute coronary syndromes, a real difference in mortality for younger women remains unexplained. The basis for real differences in outcome with the use of various therapies for acute infarction, such as thrombolysis and stent use, are also not well elucidated.

Long-term follow-up of patients with Kawasaki disease

Cardiac sequelae of Kawasaki syndrome may range from no detectable' abnormalities to giant aneurysms with thrombosis or stenosis. The issues often debated in long-term follow-up include interval and intensity of evaluations, type of diagnostic tests to be used, choice of drugs and indications for medical and surgical interventions directed toward coronary artery problems. Although echocardiography is a powerful tool in the early follow-up, its utility is diminished during the chronic phase. Although the value of coronary angiography is undisputed, its use should be limited to the patients with large or complex aneurysms. Repeat angiography should be guided for the most part by appearance or worsening of ischemic changes by non-invasive studies. Despite normal angiographic appearance of the coronary artery following regression, recent evidences from vasoactivity studies, intravascular ultrasound, and biochemical data suggest long-term abnormalities in vascular endothelium. Stress ECG lacks in sensitivity and specificity. Stress echocardiography with exercise or dobutamine may be an acceptable alternative, but its performance is subject to the ‘learning curve.’ Myocardial scintigraphy has been shown to be sensitive in detecting ischemia. However, its specificity in Kawasaki syndrome is still debatable. Recent ‘high-tech’ diagnostic tests have limitations in clinical applicability. Regarding therapy, our midterm experience with the combined use of low-dose warfarin and low-dose aspirin in patients with giant aneurysms suggests its efficacy in preventing coronary thrombosis. Thrombolytic therapy for acute infarction or coronary thrombosis appears safe and effective. The role of coronary balloon angioplasty in the management of Kawasaki syndrome is uncertain. Controversies surround the indications for coronary artery bypass graft surgery in Kawasaki syndrome. Decision for surgery seems justified in an asymptomatic child when evidence points to a large myocardial segment in jeopardy since a high mortality rate and lack of prior warning are characteristic of myocardial infarction due to Kawasaki disease.

Usefulness of fibrinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction

Thrombin activity is increased in the setting of acute myocardial infarction (AMI) and has been shown to increase further after the administration of thrombolytic therapy for acute infarction. This increase in thrombin activity may play an important role in the 15% to 25% rate of failure to achieve initial reperfusion and in the 5% to 15% rate of early reocclusion after initially successful thrombolysis. To investigate potential mechanisms of thrombin formation in vivo, to understand better the balance of coagulation and fibrinolysis during treatment with recombinant tissue-type plasminogen activator (rt-PA), and to investigate the role of hemostatic markers as predictors of clinical events, we measured 3 markers of procoagulant activity: fibrinopeptide A (FPA), thrombin-antithrombin III complexes (TAT), and prothrombin fragment 1.2 (F1.2), and a marker of fibrinogenolytic activity (Bβ1–42) in patients enrolled in the Thrombolysis in Myocardial Infarction (TIMI)-5 study. This trial was a randomized, dose-ranging, pilot trial of hirudin versus heparin as adjunctive antithrombotic therapy with rt-PA administered to patients with AMI. Correlation of markers at 1 hour with clinical outcomes revealed that increased FPA and TAT levels were associated with increased mortality and TIMI grades 0, 1, or 2 flow at 90 minutes; increased F1.2 levels were associated with TIMI grade 0 or 1 flow at 90 minutes; and increased levels of all 3 procoagulant markers were associated with hemorrhagic events. Late (12 to 24 hours) increases in F1.2, TAT, and Bβ1–42 may be predictive of recurrent ischemia. These results suggest that selected markers of procoagulant and fibrinogenolytic activity may be useful in predicting clinical outcomes in patients treated with thrombolytic therapy for AMI.

Prognostic Importance of Previous Myocardial Infarction in Patients Receiving Thrombolytic Therapy for Acute Infarction.

This study evaluated the prognostic significance of reinfarction location by considering the previous site or type of myocardial infarction (MI) among 1601 patients with a history of previous MI who took part in the International (non-Italian) tPA/STK trial and/or the Israeli GUSTO study population. These patients were accordingly divided and hospital mortality was compared by six location groups as follows: acute inferior with previous inferior (8.1% hospital mortality), acute inferior with previous anterior (12.8%), acute anterior with previous inferior (13.3%), acute anterior with previous anterior (11.1%), acute inferior with previous non-Q-wave MI (7.6%), and acute anterior with previous non-Q-wave MI (11.2%) (p = 0.17 for comparison between the six groups). Hospital mortality tended to increase among patients with an anterior reinfarction compared with those with an inferior one (12.1% vs. 9.5%, p = 0.12). Among patients with a reinfarction at a different ECG location from the previous event, mortality tended to be higher compared with patients with two MIs at the same location (13.1% vs. 9.7%, p = 0.07). Recurrent MI following a previous Q-wave MI did not cause a higher mortality compared with a previous non-Q-wave type of MI (11.5% vs. 9.5%, p = 0.24). Among patients sustaining reinfarction, overall mortality did not differ between STK- and tPA-treated patients (11.0% vs. 11.4%, p = NS). In conclusion, the current study identified trends for higher mortality rates in patients with anterior compared with inferior reinfarction, with remote compared with the same ECG location of the two infarctions but not following a previous non-Q-wave compared with Q-wave MI. However, no particular combination of successive MIs location was significantly associated with a higher risk for hospital mortality.

725-1 Long-term Impact of a Patent Infarct-related Artery: 1-Year Survival In the GUSTO Trial

The “open-artery” hypothesis has been validated in the acute phase of coronary occlusion. Controversy remains regarding long-term survival and the need for revascularization. To examine the long-term impact of a patent infarct-related artery in the GUSTO trial, we evaluated prospectively collected data on 41,021 patients treated with thrombolytic therapy for acute infarction. Patency data were available in 12,864 patients undergoing their first post-infarction angiogram who had no prior history of PTCA or CABG and who were not enrolled in the angiographic substudy. The infarct-related artery was open in 8,810 and closed in 4,054 patients. In the open artery cohort, 50% were treated medically, 38% with PTCA, and 12% with CABG. The corresponding percentages in the closed artery cohort were 45, 41 and 14, respectively. Baseline demographics, risk factor profiles, extent of disease and time to treatment were similar for both groups. Patients with a closed artery had a slightly higher incidence of Killip Class III and IV than the open artery cohort (2% vs 1%). As expected, patients treated medically and with PTCA in both groups had a preponderance of 1 and 2 vessel disease and patients treated with CABG had a preponderance of 2 and 3 vessel disease. 1-Year Mortality Open Artery Closed Artery P-value - Medical Therapy (%) 3.3 8.5 <0.001 - PTCA(%) 2.5 88 <0.001 - CABG(%) 4.2 9.6 <0.001 Infarct-related artery patency confers a survival advantage at 1-year across all thrombolytic treatment strategies in patients with acute myocardial infarction.

Presenting pulse pressure predicts thrombolytic therapy-related intracranial hemorrhage. Thrombolytic Predictive Instrument (TPI) Project results.

In selecting patients with acute myocardial infarction for thrombolytic therapy, it is important to identify patients who are at high risk for intracranial hemorrhage, for whom thrombolytic therapy is ill advised. We hypothesized that presenting pulse blood pressure, representing the "hammer" effect on cerebral vessels and the effects of age on arterial compliance, might predict thrombolysis-related intracranial hemorrhage better than systolic, diastolic, or mean arterial blood pressures. Of 3483 Thrombolytic Predictive Instrument (TPI) Project subjects receiving thrombolytic therapy for acute infarction, we identified and obtained detailed clinical data on the 19 with treatment-related intracranial hemorrhages confirmed by computed tomography and on 175 matched controls. Systolic, diastolic, mean arterial, and pulse blood pressures were each significantly related to the occurrence of intracranial hemorrhage, with pulse pressure most highly related. The mean pulse pressure in patients who developed intracranial hemorrhage was 63 mm Hg, 34% higher than the 47 mm Hg mean value for those not developing hemorrhage (P = .0001). Excess pulse pressure, defined as the extent to which a patient's pulse pressure exceeded 40 mm Hg for systolic blood pressures of at least 120 mm Hg, was even more strongly related: its mean value of 23 mm Hg for patients was 130% higher than its mean value of 10 mm Hg for controls (P < .0001). With logistic regression models to estimate the relative risks (odds ratios) for intracranial hemorrhage conferred by each form of blood pressure, the relative risk for hemorrhage was greatest for excess pulse pressure: for each 10-point pulse pressure excess, the relative risk for intracranial hemorrhage was increased by 1.85 (P = .0002; 95% confidence interval [CI], 1.34 to 2.55) by itself and 1.76 (P = .001; 95% CI, 1.26 to 2.46) when adjusted for age. In this sample, excess pulse pressure by itself predicted hemorrhage as well as systolic pressure and age together. When excess pulse pressure was combined with age to make a logistic regression model predicting intracranial hemorrhage, age contributed less to the prediction than when combined with the other blood pressure forms, even though this model predicted better than any other combination of age and pressure (receiver-operating characteristic curve area, 0.82 versus 0.77 with systolic pressure and age, 0.75 with mean arterial pressure, 0.71 with diastolic pressure, and 0.81 with both systolic and diastolic pressures). We found that excess pulse blood pressure predicted thrombolysis-related intracranial hemorrhage better than other forms of pretreatment blood pressure, perhaps better describing the pathophysiology of intracranial hemorrhage, including the effect of age. These findings will need confirmation in larger studies with comparable clinical detail.

Cumulative meta-analysis of therapeutic trials for myocardial infarction.

The large volume of published randomized, controlled trials has led to a need for meta-analyses to track therapeutic advances. Performing a new meta-analysis whenever the results of a new trial of a particular therapy are published permits the study of trends in efficacy and makes it possible to determine when a new treatment appears to be significantly effective or deleterious. We describe the use of such a procedure, cumulative meta-analysis, to assess therapeutic trials among patients with myocardial infarction. We performed cumulative meta-analyses of clinical trials that evaluated 15 treatments and preventive measures for acute myocardial infarction. An example of this method is its application to the use of intravenous streptokinase as thrombolytic therapy for acute infarction. Thirty-three trials evaluating this therapy were performed between 1959 and 1988. We found that a consistent, statistically significant reduction in total mortality (odds ratios, 0.74; 95 percent confidence interval, 0.59 to 0.92) was achieved in 1973, after only eight trials involving 2432 patients had been completed. The results of the 25 subsequent trials, which enrolled an additional 34,542 patients through 1988, had little or no effect on the odds ratio establishing efficacy, but simply narrowed the 95 percent confidence interval. In particular, two very large trials, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial in 1986 (11,712 patients) and the Second International Study of Infarct Survival trial in 1988 (17,187 patients) did not modify the already established evidence of efficacy. We used a similar approach to study the accumulating evidence of efficacy (or lack of efficacy) of 14 other therapies and preventive measures for myocardial infarction. Cumulative meta-analysis of therapeutic trials facilitates the determination of clinical efficacy and harm and may be helpful in tracking trials, planning future trials, and making clinical recommendations for therapy.