Showing papers by "Eric J. Topol published in 1989"

A randomized controlled trial of intravenous tissue plasminogen activator and early intravenous heparin in acute myocardial infarction.

Abstract: To evaluate the coronary thrombolytic efficacy of tissue plasminogen activator (t-PA) and early intravenous heparin, 134 patients with acute myocardial infarction were randomly assigned to combination therapy or t-PA only. At a median of 2.78 hours from symptom onset, 64 patients received both t-PA (1.5 mg/kg/4 hr) and a bolus of 10,000 units heparin, whereas 70 patients received t-PA alone at the same dose. All patients underwent coronary angiography 90 minutes after initiation of therapy to determine infarct vessel patency status, after which time the control group patients were eligible to receive heparin. Baseline demographic and angiographic characteristics were similar for the groups. Infarct vessel patency was 50 of 63 (79%) for combination t-PA and heparin and 54 of 68 (79%) for t-PA alone. Bleeding complications, as reflected by need for transfusion, were similar in the two groups: 13% in the patients treated with t-PA and heparin compared with 18% in patients treated with t-PA only (p = 0.53). The only intracranial hemorrhage in the trial occurred in a patient initially treated without heparin. Fibrinogen at 50 minutes after therapy was 32% decreased from baseline for the t-PA and heparin-treated patients compared with a 39% decrease in the control group. Predischarge left ventricular ejection fraction was similar for the two groups: 49.0 +/- 10.1% versus 50.2 +/- 11.9% for combined versus t-PA only therapy, respectively. We conclude that early intravenous heparin does not facilitate the fibrinolytic effect of t-PA at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent ischemia without warning. Analysis of risk factors for in-hospital ischemic events following successful thrombolysis with intravenous tissue plasminogen activator.

Abstract: Ischemic events after successful thrombolysis have been reported to occur in 18-32% of patients treated for acute myocardial infarction with thrombolytic therapy, and previous studies in which patients received streptokinase suggest that risk of early recurrent ischemia is closely related to the presence of a high-grade residual stenosis. If these events are predictable after intravenous recombinant tissue-plasminogen activator (rt-PA) thrombolytic therapy, then further intervention after its use could be targeted at selected patients. One-hundred ninety-two patients from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I and TAMI III trials had successful rt-PA-mediated thrombolysis without immediate coronary angioplasty (PTCA). One-hundred seventy-four of these patients (92%) had prehospital discharge angiography. The mean age was 56 +/- 11 years; 81% were men; the infarct-related artery was the left anterior descending in 76 (39.8%), the left circumflex in 24 (12.6%), and the right coronary artery in 91 (47.6%). Thrombolysis with rt-PA resulted in a residual 73 +/- 13% diameter and 0.95 +/- 0.51 mm stenosis by quantitative coronary arteriography, and Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 in 59.2% and 3 in 40.8% of stenoses as assessed on angiograms obtained 90 minutes after the initiation of rt-PA therapy. Recurrent ischemic events (ischemia requiring emergency percutaneous transluminal coronary angioplasty or urgent bypass surgery, reocclusion of the infarct-related artery, or cardiac death) occurred in 41 patients (21.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors, time course and treatment effect for restenosis after successful percutaneous transluminal coronary angioplasty of chronic total occlusion.

Abstract: Advances in technology and operator experience, and increased use of angiography early after myocardial infarction have led to greater use of percutaneous transluminal coronary angioplasty (PTCA) for chronic, total coronary artery occlusions. To better assess long-term outcome, 257 consecutive patients with successful PTCA of a total occlusion with late angiographic follow-up from 484 patients (53%) with PTCA success were reviewed. The mean ± standard deviation patient age was 54 ± 10 years, 79% were men, the duration of total occlusion was 11 ± 15 weeks and the post-PTCA diameter stenosis was 24 ± 12%. Eighty-two, 27 and 63% of patients received long-term aspirin, dipyridamole and warfarin therapy, respectively. Angiography at 8 ± 8 months demonstrated restenosis (≥50% diameter stenosis) in 41% of patients restudied within 6 months and in 66% of patients restudied within 12 months by life table analysis. In multivariate regression analysis of 19 variables, 2 were independently correlated with the occurrence of restenosis: post-PTCA diameter stenosis > 30% (p = 0.02) and coronary artery dilated (left anterior descending and right coronary arteries greater than the left circumflex coronary artery) (p = 0.05). In log rank analysis that also considered the timing of angiographic detection of restenosis, dilatation of a proximal left anterior descending stenosis was also a significant predictor of restenosis (p = 0.01), and dilatation within 4 weeks of the presumed time of occlusion was only weakly predictive (p = 0.11). Thirty-five patients (27% of those with restenosis) had reocclusion at the site of PTCA, but only 3 patients (2%) had an associated myocardial infarction. There was no relative beneficial effect of any treatment on the risk of restenosis. Thus, (1) restenosis after PTCA of chronic total occlusion is very common; (2) restenosis is predicted by the angioplasty results and angioplasty site; (3) the clinical detection of restenosis does not appear to plateau at 6 months; (4) reocclusion is not uncommon, but seldom results in myocardial infarction; and (5) there was no apparent relative treatment effect of aspirin, dipyridamole or warfarin.

Bleeding during thrombolytic therapy for acute myocardial infarction: mechanisms and management.

Abstract: Hemorrhage is the major adverse effect of thrombolytic therapy, but its incidence can be reduced by careful selection of patients and avoidance of unnecessary invasive procedures. More than 70% of bleeding episodes occur at vascular puncture sites. Hypofibrinogenemia and elevation of fibrinogen degradation products have been weakly correlated with the risk of hemorrhage. Although depletion of factors V and VIII may occur, the role of such depletion in bleeding is unknown. Several in-vitro studies have shown plasmin-induced platelet dysfunction, but clinical data are limited. Nevertheless, the role of platelet inhibition should be considered because many patients are treated with antiplatelet agents. Most patients who have bleeding can be managed by interruption of thrombolytic and anticoagulant therapy, volume replacement, and manual pressure applied to an incompetent vessel. Protamine should be considered if heparin has been administered within 4 hours of the onset of bleeding. In the few patients who fail to respond to these conservative measures, judicious use of transfusion products may be indicated. Transfusion of cryoprecipitate, fresh frozen plasma, and platelets should be considered with clinical and laboratory reassessment after each administration. A target fibrinogen level of 1 g/L is desirable with cryoprecipitate infusion. Antifibrinolytic agents are available as a last alternative. We have developed an algorithm for using these products.

Prognostic implications and predictors of enhanced regional wall motion of the noninfarct zone after thrombolysis and angioplasty therapy of acute myocardial infarction. The TAMI Study Groups.

Abstract: Although impairment of left ventricular function in acute myocardial infarction is closely related to extent of necrosis, function in the noninfarct zone also contributes to global performance and thus may be of prognostic importance. We evaluated left ventricular regional wall motion by the centerline chord method in 332 patients treated with intravenous tissue-type plasminogen activator (t-PA) in the multicenter Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial. All patients had acute contrast ventriculograms of suitable quality for analysis, and 266 patients had paired acute and day 7 ventriculograms. Enhanced function of the noninfarct zone was present during acute catheterization (+0.3 SD/chord) and was associated with preservation of the acute ejection fraction (p = 0.0001). Multiple linear regression analysis revealed the most powerful clinical factor associated with enhanced function of the noninfarct zone was the absence of multivessel disease (p = 0.0001). Clinical factors that were related weakly to noninfarct zone function included female gender (p = 0.08) and higher flow in the infarct artery (p = 0.03). Neither the degree of infarct zone dysfunction nor infarct location was associated with hyperkinesis of the noninfarct zone. In hospital, mortality was closely related to function in the noninfarct zone (p = 0.006), ejection fraction (p = 0.025), and the number of diseased vessels (p = 0.009) but was not related to infarct zone function (p = 0.128).(ABSTRACT TRUNCATED AT 250 WORDS)

Emerging strategies for failed percutaneous transluminal coronary angioplasty.

Abstract: Second only to the problem of restenosis, abrupt closure during percutaneous transluminal coronary angioplasty (PTCA) represents a significant procedural complication. Of the 200,000 PTCA procedures performed in the United States in 1987, abrupt closure occurred in approximately 10,000 patients-resulting in triage to emergency coronary artery bypass surgery in >6,000 patients and >l,OOO deaths.1-3 Current approaches to this problem have been limited. After intracoronary nitroglycerin is given, intracoronary or intravenous thrombolytic therapy has been used in some cases. However, spasm or thrombosis is very rarely the principal cause of abrupt closure. Typically, the inciting event is a complex intimal tear. Definite establishment of the etiology is confounded by the lack of adequate angiographic distinction between thrombus and dissection; our methods for decision-making under these circumstances are relatively crude. A standard approach, which has evolved empirically to “tack up” the tear, is the use of prolonged inflations (2 to 5 minutes), with a larger balloon dilatation catheter (0.5-mm size increase) at low pressure (3 to 5 atmospheres).4 The direct intracoronary administration of propranolol or fluorinated hydrocarbons has increased our capacity to prolong inflations by virtue of a decelerated induction of myocardial ischemia. v Combined with these various pharmacologic interventions, this overall “t.ack up” strategy appears to represent the best current approach to the management of abrupt closure.

Emergency percutaneous transluminal coronary angioplasty during acute myocardial infarction for patients more than 70 years of age

Abstract: Thirty-five patients >70 years of age with acute myocardial infarction (AMI) were treated with emergency percutaneous transluminal coronary angioplasty (PTCA). Seventeen (49%) patients received previous thrombolytic therapy: streptokinase (10 patients), tissue plasminogen activator (6) and combined tissue plasminogen activator and urokinase (1). Infarct-related artery patency was achieved in 26 patients (74%) after PTCA. Total in-hospital mortality was 34%. Univariate analysis showed a higher in-hospital mortality in patients with an occluded vessel after PTCA (78%) than in those patients with a patent infarct-related artery (19%) (p = 0.003). Symptomatic coronary reocclusion occurred in 3 patients (15%) during the hospital stay. Compared with emergency PTCA in 200 consecutively treated patients

Clot-selective coronary thrombolysis with pro-urokinase.

Abstract: Recognition that myocardial infarction is caused by coronary thrombosis has stimulated a search for a safe, rapidly acting, and effective thrombolytic regimen. Tissue plasminogen activator (t-PA) can provide relatively clot-selective thrombolysis, but one quarter of patients fail to achieve reperfusion, lysis speed is not optimal, and higher doses have been associated with an increased incidence of hemorrhagic stroke. We report the results of a multicenter study of pro-urokinase, a second naturally occurring plasminogen activator that has structural similarities to t-PA but has a different mechanism of action. Pro-urokinase was administered 3.9 +/- 1.1 hours after the onset of chest pain to 40 patients with acute myocardial infarction with angiographically confirmed complete coronary occlusion (TIMI grade 0). After a 90-minute intravenous infusion of pro-urokinase (4.7-9 million units, 36-69 mg) 51% (20 of 39) of the patients demonstrated reperfusion (TIMI grade 2 or 3) occurring 64.8 +/- 22.3 minutes after initiation of therapy. Fibrinogen levels fell only 10 +/- 17% from baseline, confirming the fibrin specificity of pro-urokinase. As with t-PA, however, this specificity was only relative. alpha 2-Antiplasmin decreased to 39% and plasminogen decreased to 64% of initial values. Fibrinogen degradation products increased 63% and the fibrin-specific D-dimer increased 8.7-fold. Thus, pro-urokinase produces relatively clot-selective coronary thrombolysis similar to that produced by t-PA, but the use of either pro-urokinase or t-PA alone in higher doses would be likely to produce more nonspecific effects.

Incidence and predictors of early recurrent ischemia after successful percutaneous transluminal coronary angioplasty for acute myocardial infarction

Abstract: Two hundred forty consecutive patients with acute myocardial infarction treated within 48 hours by successful percutaneous transluminal coronary angioplasty (PTCA) were analyzed to determine the incidence and predictors of recurrent ischemic events during hospitalization. Thirty-nine patients had recurrent ischemia: 20 patients had chest pain or electrocardiographic changes requiring repeat PTCA or bypass surgery, or resulting in a second creatine kinase elevation suggestive of myocardial infarction; 12 had total occlusion of the dilated artery on follow-up angiography; and 7 had exercise-induced ischemia and greater than or equal to 70% diameter stenosis that required PTCA or bypass surgery before hospital discharge. In-hospital mortality was 15% in the recurrent ischemia group, compared to 1% in the group without recurrent myocardial ischemia (p less than 0.001). Angiographic follow-up before hospital discharge was obtained in 198 patients, including 38 of the 39 patients with ischemic events. Thus, the true incidence of recurrent ischemic events was between 39 of 199 and 39 of 240, or 16 and 20%. In multivariate analyses, recurrent ischemia was predicted by translesional gradient greater than 25 mm Hg (p = 0.001), dissection (p = 0.01) and post-PTCA Thrombolysis in Myocardial Infarction 2 flow pattern (p = 0.016). However, even in the absence of these risk factors recurrent ischemic events occurred in 13% of patients. Post-PTCA percent diameter stenosis (whether assessed by objective or visual assessment), degree of the early systemic fibrinolytic state, post-PTCA residual minimal diameter and concomitant use of thrombolytic agents were not predictive.(ABSTRACT TRUNCATED AT 250 WORDS)

Atherectomy of the left main coronary artery with percutaneous cardiopulmonary bypass support.

Abstract: Left main (LM) coronary artery stenoses have conventionally been precluded from percutaneous coronary angioplasty because of the prohibitive risk of irreversible hemodynamic collapse after acute closure of the artery, and a relatively high risk of late sudden death. 1 When protected by left anterior descending and circumflex coronary artery by-pass grafts, angioplasty of the LM coronary artery can be safely performed but is limited by a rate of recurrent stenosis in excess of 50%. 2 Coronary atherectomy has recently been advocated as an alternative procedure because of preliminary data suggesting a lower incidence of acute closure and restenosis after peripheral atherectomy. 3 A percutaneous cardiopulmonary support system has also been reported to reduce the hazards of high risk conventional angioplasty including angioplasty of the LM coronary artery. 4 We report the successful combined use of percutaneous cardiopulmonary bypass and LM coronary atherectomy in a patient incompletely protected by aortocoronary bypass grafts.

Restenosis after excellent angiographic angioplasty result for chronic total coronary artery occlusion--implications for newer percutaneous revascularization devices.

Abstract: The incidence of restenosis after coronary angioplasty for treatment of chronic total coronary occlusion is unacceptably high. 1 The pathophysiology of restenosis after coronary angioplasty may be conceptually divided into an exuberant myointimal proliferation, 2 and a residual partial obstruction that serves as a platform for atheroma regrowth and may potentiate that process by augmenting blood flow turbulence and platelet deposition. The techniques of atherectomy or laser ablation 3 may lessen the likelihood of restenosis by minimizing the residual stenosis, although currently each may require supplemental balloon angioplasty to achieve this result. However, the effect of these techniques on later myointimal proliferation in human beings is largely unknown. The concept that intracoronary stenting 4 may reduce restenosis is based largely on the supposition that, by forcing and maintaining the obstructive atheroma out of the normal arterial lumen, turbulence and hence platelet deposition would be reduced 5 and a large amount of myointimal proliferation would be required to recreate an obstruction of physiologic consequence.

Early hospital discharge in the myocardial reperfusion era

Abstract: The prognosis of patients with acute myocardial infarction has improved dramatically over the past several decades. New treatment strategies, however, have incrementally increased the expense of treating these patients. Early hospital discharge is one potential way of offsetting some of this expense. Cardiac catheterization can greatly facilitate patient selection for early discharge by defining patients with low-risk anatomy who do not require additional diagnostic testing or therapy, by documenting infarct artery patency, an important predictor of a favorable prognosis, and by diagnosing patients who can expeditiously be revascularized by coronary angioplasty.