Showing papers by "Eric J. Topol published in 1990"

Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Multivessel Angioplasty Prognosis Study Group.

Abstract: To assess the likelihood of procedural success in patients with multivessel coronary disease undergoing percutaneous coronary angioplasty, 350 consecutive patients (1,100 stenoses) from four clinical sites were evaluated. Eighteen variables characterizing the severity and morphology of each stenosis and 18 patient-related variables were assessed at a core angiographic laboratory and at the clinical sites. Most patients had Canadian Cardiovascular Society class III or IV angina (72%) and two-vessel coronary disease (78%). Left ventricular function was generally well preserved (mean ejection fraction, 58 +/- 12%; range, 18-85%) and 1.9 +/- 1.0 stenoses per patient had attempted percutaneous coronary angioplasty. Procedural success (less than or equal to 50% final diameter stenosis in one or more stenoses and no major ischemic complications) was achieved in 290 patients (82.8%), and an additional nine patients (2.6%) had a reduction in diameter stenosis by 20% or more with a final diameter stenosis 51-60% and were without major complications. Major ischemic complications (death, myocardial infarction, or emergency bypass surgery) occurred in 30 patients (8.6%). In-hospital mortality was 1.1%. Stepwise regression analysis determined that a modified American College of Cardiology/American Heart Association Task Force (ACC/AHA) classification of the primary target stenosis (with type B prospectively divided into type B1 [one type B characteristic] and type B2 [greater than or equal to two type B characteristics]) and the presence of diabetes mellitus were the only variables independently predictive of procedural outcome (target stenosis modified ACC/AHA score; p less than 0.001 for both success and complications; diabetes mellitus: p = 0.003 for success and p = 0.016 for complications). Analysis of success and complications on a per stenosis dilated basis showed, for type A stenoses, a 92% success and a 2% complication rate; for type B1 stenoses, an 84% success and a 4% complication rate; for type B2 stenoses, a 76% success and a 10% complication rate; and for type C stenoses, a 61% success and a 21% complication rate. The subdivision into types B1 and B2 provided significantly more information in this clinically important intermediate risk group than did the standard ACC/AHA scheme. The stenosis characteristics of chronic total occlusion, high grade (80-99% diameter) stenosis, stenosis bend of more than 60 degrees, and excessive tortuosity were particularly predictive of adverse procedural outcome. This improved scheme may improve clinical decision making and provide a framework on which to base meaningful subgroup analysis in randomized trials assessing the efficacy of percutaneous coronary angioplasty.

Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. TAMI Study Group.

Abstract: To determine the clinical consequences of reocclusion of an infarct-related artery after reperfusion therapy, we evaluated 810 patients with acute myocardial infarction. Patients were admitted into four sequential studies with similar entry criteria in which patency of the infarct-related artery was assessed by coronary arteriography 90 minutes after onset of thrombolytic therapy. Successful reperfusion was established acutely in 733 patients. Thrombolytic therapy included tissue-type plasminogen activator (t-PA) in 517, urokinase in 87, and a combination of t-PA and urokinase in 129 patients. All patients received aspirin, intravenous heparin and nitroglycerin, and diltiazem during the recovery phase. A repeat coronary arteriogram was performed in 88% of patients at a median of 7 days after the onset of symptoms. Reocclusion of the infarct-related artery occurred in 91 patients (12.4%), and 58% of these were symptomatic. Angiographic characteristics at 90 minutes after thrombolytic therapy that were associated with reocclusion compared with sustained coronary artery patency were right coronary infarct-related artery (65% versus 44%, respectively) and Thrombolysis in Myocardial Infarction (TIMI) flow 0 or 1 (21% versus 10%, respectively) before further intervention. Median (interquartile value) degree of stenosis in the infarct-related artery at 90 minutes was similar between groups: 99% for reoccluded (value, 90/100%) compared with 95% for patent (value, 80/99%). Patients with reocclusion had similar left ventricular ejection fractions compared with patients with sustained patency at follow-up. However, patients with reocclusion at follow-up had worse infarct-zone function at -2.7 (value, -3.2/-1.8) versus -2.4 (SD/chord) (value, -3.1/-1.3) (p = 0.016). The recovery of both global and infarct-zone function was impaired by reocclusion of the infarct-related artery compared with maintained patency; median delta ejection fraction was -2 compared with 1 (p = 0.006) and median delta infarct-zone wall motion was -0.10 compared with 0.34 SD/chord (p = 0.011), respectively. In addition, patients with reocclusion had more complicated hospital courses and higher in-hospital mortality rates (11.0% versus 4.5%, respectively; p = 0.01). We conclude that reocclusion of the infarct-related artery after successful reperfusion is associated with substantial morbidity and mortality rates. Reocclusion is also detrimental to the functional recovery of both global and infarct-zone regional left ventricular function. Thus, new strategies in the postinfarction period need to be developed to prevent reocclusion of the infarct-related artery.

Selection of Patients with Acute Myocardial Infarction for Thrombolytic Therapy

Abstract: Purpose: To critically review the current recommendations regarding the eligibility of patients with myocardial infarction for thrombolytic therapy. Data Identification: Relevant studies published ...

Left ventricular ejection fraction may not be useful as an end point of thrombolytic therapy comparative trials

Abstract: In the era of comparative and adjunctive trials in reperfusion therapy, the need to develop alternative end points for mortality reduction is clear. Left ventricular ejection fraction, which has been commonly used as a surrogate, is problematic due to missing values, technically inadequate studies, and lack of correlation with mortality results in controlled reperfusion trials performed to date. In this paper, we present a composite clinical end point that includes, in order, severity of adverse outcome death, hemorrhagic stroke, nonhemorrhagic stroke, poor ejection fraction (less than 30%), reinfarction, heart failure, and pulmonary edema. Such a composite index may be useful to detect true therapeutic benefit in reperfusion trials without necessitating greater than 20-30,000 patient enrollment.

Intravenous recombinant tissue-type plasminogen activator in patients with unstable angina pectoris. Results of a placebo-controlled, randomized trial.

Abstract: Because thrombus formation may contribute to coronary obstruction in patients with unstable angina pectoris, we performed a pilot investigation to determine whether thrombolytic therapy can relieve coronary narrowing in this acute ischemic syndrome. Sixty-seven patients with rest angina and angiographic evidence of coronary stenosis were randomly assigned to receive either low-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 1 hour), high-dose intravenous rt-PA (0.75 mg/kg over 1 hour; total dose, 100 mg over 6 hours), or intravenous placebo followed by repeat coronary angiography at 24-48 hours to assess change in the severity of coronary narrowing. Each patient also received oral aspirin and intravenous heparin. Mean values of coronary stenosis severity (percent of diameter reduction) declined to a similar extent in each group: placebo, 75 +/- 14% to 72 +/- 14% (p = 0.07); low-dose rt-PA, 75 +/- 16% to 71 +/- 18% (p = 0.03), and high-dose rt-PA, 82 +/- 11% to 77 +/- 17% (p = 0.18), with only the low-dose rt-PA group achieving statistical significance. Resolution of intracoronary filling defects, increase in antegrade flow grade, or both also occurred equally among the three groups. There was considerable variation in individual patient response. Between 29% and 50% of patients within each group demonstrated a decrease in stenosis severity, whereas 50% to 57% noted either improvement in antegrade flow or resolution of intracoronary thrombus. There was no difference in incidence of major bleeding events among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of a pericardial friction rub after thrombolytic therapy during acute myocardial infarction in predicting amount of myocardial damage

Abstract: To evaluate the clinical incidence and outcomes of patients with pericarditis after thrombolytic therapy, 810 patients were prospectively studied during acute myocardial infarction (AMI). Pericarditis was defined as the presence of a pericardial friction rub during the hospital course. Only 5% of patients developed a rub during AMI, a low percent compared with that in the prethrombolytic era. A pericardial friction rub more often occurred in the setting of an anterior wall AMI. Patients wlth, compared to those without, a pericardial friction rub had lower ejection fractions (45 vs 51%, p = 0.002); worse regional left ventricular function (-3.2 vs 2.7, standard deviatlon per chord); higher in-hospital mortality (15 vs 6%, p = 0.056); a higher frequency of power failure (83 vs 57%); a higher frequency of anterior wall location of the AMI (53% of cases, p = 0.002); and a higher frequency of 3-vessel disease. Therefore, although the frequency of a pericardial friction rub was low (5%) compared with that in the prethrombolytic era, its occurrence denotes more extensive myocardial damage with a worse clinical outcome. Perhaps with successful reperfusion of the infarct-related vessel, transmural myocardial necrosis is prevented and with it the development of pericarditis. Cardiac tamponade did not occur clinically in any patient who developed ‘a pericardial friction rub. (Am J Cardiol 1990;66:1418-1421)

Quantitative angiographic comparison of the immediate success of coronary angioplasty, coronary atherectomy and endoluminal stenting

Abstract: Coronary atherectomy and coronary stenting effectively reduce the severity of coronary artery stenoses, but direct comparisons of these interventions with conventional balloon angioplasty have not been performed. To compare the immediate efficacy of these 3 interventions, the angiographic morphology and the severity of the residual coronary stenosis were quantitatively evaluated in 18 patients undergoing coronary atherectomy and in 21 patients treated by endoluminal coronary stenting. Each of these groups of patients was compared with a matched group of coronary angioplasty patients selected from a large, computerized database. The variables matched included patient age and sex, lesions site and severity, and lesion complexity. Both coronary atherectomy and coronary stenting more effectively reduced the severity of the coronary stenosis when compared with balloon angioplasty. The luminal diameter stenosis was reduced from 69 ± 10 to 22 ± 20% in the atherectomy group compared with a reduction from 74 ± 11 to 44 ± 14% in the matched coronary angioplasty population (p = 0.008). Similarly, the luminal diameter stenosis was reduced from 77 ± 11 to 26 ± 12% in the stented group compared with a reduction from 81 ± 10 to 42 ± 14% in the matched coronary angioplasty group (p = 0.014). In addition, moderate or severe coronary dissections were noted more frequently in the coronary angioplasty groups than in their respective atherectomy and stent groups (0 vs 33%, p = 0.008, and 5 vs 19%, p = 0.15, respectively). These data suggest that, in selected patients, both coronary atherectomy and coronary stenting more effectively reduce the severity of coronary stenoses when compared with conventional balloon angioplasty and that this may be achieved with a lower risk of medial dissection.

Results of percutaneous transluminal coronary angioplasty of high-risk angulated stenoses☆

Abstract: Percutaneous transluminal coronary angioplasty (PTCA) of angulated stenoses has been found in studies using older PTCA equipment to be associated with a heightened risk of procedure-related major ischemic events. To better understand the factors associated with procedural risk and to identify means of lessening that risk, 100 patients, treated sequentially from 1986 to 1989, who underwent PTCA of stenoses located at ≥45 ° bends, were characterized for 27 clinical, anatomic and procedural variables. Clinical outcome of angioplasty was related to these variables. In addition, results from 344 consecutive contemporary patients undergoing PTCA of nonangulated lesions were compared to those of the study group. Procedural success was achieved in only 70% of patients with angulated stenoses, compared with 306 of 344 (89%) nonangulated stenoses, and major ischemic complications (death, bypass surgery or myocardial infarction) occurred in 13% of patients with angulated stenoses compared with 12 of 344 (3.5%) with nonangulated stenoses (both p 10 mm or age ≥65 years led to an even higher risk of major complications (9 of 44 = 20.5%), whereas highly experienced angioplasty operators and the use of polyethylene terephthalate balloons appeared to decrease risk and increase the likelihood of success. PTCA of such stenoses should be undertaken only cautiously and in carefully selected patients.

A randomized pilot trial of brief versus prolonged heparin after successful reperfusion in acute myocardial infarction.

Abstract: Controversy exists as to whether and how long heparin treatment is necessary after infarct vessel recanalization. To determine the role of heparin, patients with suitable angiographic features after reperfusion therapy were randomly allocated to receive a brief infusion of intravenous heparin for less than or equal to 24 hours (group 1), adjusted to a partial thromboplastin time of 2 times control or a prolonged infusion for greater than or equal to 72 hours (group 2), using the same titration mechanism. Patients were excluded for complex intimal dissections, large residual filling defects, less than Thrombolysis in Myocardial Infarction grade 3 flow pattern or greater than 50% residual stenosis. Heparin was sustained except for discontinuation 2 to 4 hours before periaccess sheath removal, or if significant bleeding (greater than or equal to 2 units blood transfusion) occurred. The primary endpoints were 1-week patency determined by repeat catheterization or recurrent ischemia, or both, and the incidence of bleeding complications. Fifty patients were randomized, 25 in both groups. Baseline variables were similar; 14 group 1 and 15 group 2 patients received thrombolytic treatment; 20 patients in each group had coronary angioplasty. Two documented reocclusions occurred in both groups. Significant bleeding complications occurred in 0 of 25 (0%) group 1 versus 6 of 25 (24%) group 2 patients (p less than 0.05). Thus, in low-risk patients after successful reperfusion, prolonged heparin therapy does not protect against rethrombosis and is associated with a significantly higher rate of bleeding complications. Therefore, prolonged heparin therapy for greater than 24 hours does not appear to be justified in low-risk patients with successful reperfusion.

Acute intervention during myocardial infarction in patients with prior coronary bypass surgery.

Abstract: T hrombolytic intervention with or without coronary angioplasty is becoming widely accepted as standard therapy for patients who present early with acute myocardial infarction, Thrombolytic therapy has been shown to improve left ventricular function* and reduce mortality.2 Nearly all clinical trials of myocardial reperfusion have excluded patients with a history of coronary artery bypass grafting. Furthermore, the only available data for the use of thrombolytic agents in this patient group consist of case reports of intracoronary thrombolytic agents3 and a small series of intravenous thrombolytic agents4 There are no published data for the use of angioplasty or combined thrombolysis and angioplasty in patients with acute infarction after bypass surgery. Considering the increasing number of patients undergoing coronary artery bypass grafting and their propensity for future cardiac events,5 important questions regarding the optimal treatment strategy for prior coronary artery bypass patients come to bear. Accordingly, we reviewed our experience in the treatment of patients after coronary artery bypass surgery in the setting of evolving myocardial infarction. Records from the University of Michigan Cardiac Catheterization Laboratory were reviewedfrom January I, 1984, to December 30, 1987, and a database of patients with a history of coronary artery bypass grafting and acute myocardial infarction was tabulated. Acute myocardial infarction was diagnosed when an episode of characteristic chest pain lasting 130 minutes was associated with a transient, temporally appropriate increase of the total serum creatine phosphokinase above the upper limit of normal with myocardial isoenzyme fraction greater than twice normal. Data were compiled regarding the presence and type of standard electrocardiogram tracings at the time of infarction. Details of acute interventions, when performed, were accumulated, including those concerning the infarct-related vessel and whether or not the patient was treated with thrombolytic agents, direct angioplasty or a combination of the 2. Status of the infarct-related vessel after intervention was also noted. Follow-up data regarding hospital discharge, repeat catheterization, exercise stress testing and the needforfurther intervention, including repeat bypass surgery, were also obtained. Data are expressed as mean f 1 standard deviation. A comparison of the efficacy of acute intervention as defined by infarct-related vessel patency after intervention was estimated by examining a cohort of patients who presented with acute myocardial infarction and had

Possible survival benefit from concomitant beta-but not calcium-antagonist therapy during reperfusion for acute myocardial infarction.

Abstract: To test the hypothesis that long-term β- or calciumantagonist therapy begun before the time of myocardial infarction and coronary reperfusion might improve patient in-hospital survival compared with reperfusion alone, 424 consecutive patients successfully reperfused with coronary angioplasty within 12 hours of infarct symptom onset were carefully and retrospectively characterized. Forty-seven patients (11%) were taking β antagonists and 74 patients (17%) were taking calcium antagonists at the time of infarction. Patients receiving β antagonists had a more frequent history of hypertension (p ≤ 0.001) and prior infarction (p ≤0.01) than those not so treated and patients receiving calcium antagonists had a more frequent history of prior infarction, prior angina, hypertension and diabetes (all p ≤ 0.001) than their nontreated counterparts. Stepwise logistic regression analysis found significant independent correlations between inhospital death and the following variables: recurrent ischemia (p ≤ 0.001); proximal left anterior descending coronary infarct (p ≤ 0.001); 3-vessel disease (p = 0.002); patient age (p = 0.004); and initial total occlusion of the infarct artery (p = 0.022). After adjustment for these factors, β antagonist use (mortality = 0 vs 8% without treatment) was still significantly correlated with improved survival (p = 0.048), whereas calcium-antagonist therapy made no difference in survival. Heart rate and left ventricular end-diastolic pressure upon presentation were significantly lower in patients treated with β antagonists. Thus, β-antagonist therapy, but probably not calcium-antagonist therapy, taken before reperfusion for acute myocardial infarction, may improve early survival compared to reperfusion alone. Larger studies will be required to confirm or refute these observations.

Two-year outcome after angiographically documented myocardial reperfusion for acute coronary occlusion

Abstract: Reperfusion therapy has been clearly shown to decrease the early mortality after acute myocardial infarction, but the impact of this therapy on long-term survival has been less extensively evaluated. This study reports the extended follow-up of a large cohort of 810 patients treated with intravenous thrombolytic therapy combined, when considered necessary to maintain or augment infarct vessel patency, with mechanical reperfusion therapies. Each patient underwent coronary angiography within 2 hours of the initiation of the thrombolytic infusion. Coronary angioplasty was performed in 62% of the patients before hospital discharge and 21% underwent coronary artery bypass graft surgery. Follow-up was obtained in 96% to a mean of 18.8 months (range, 1.5 to 48 months). All-cause mortality over this period was 3.3%; 2.1% died from cardiac causes. Nonfatal reinfarction occurred in 5.1%. Although the low event rate limits the validity of statistical comparisons, the patients who survived the follow-up period tended to be younger (56 ± 10 vs 65 ± 7 years), to have better predischarge left ventricular function (left ventricular ejection fraction, 52 ± 11 vs 46 ± 13%) and to have a lower prevalence of multivessel coronary artery disease (45 vs 67%). This excellent long-term survival may, in part, reflect the exclusion of high-risk patients from enrollment in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) studies. It may also be attributable, however, to the frequent use of combined thrombolysis and mechanical revascularization in this population.

The United States thrombolysis and angioplasty trials for acute myocardial infarction

Abstract: There has been intense interest and clinical trial work in the United States to determine the optimal integrated strategy of intravenous thrombolysis and coronary angioplasty for acute myocardial infarction (AMI). Randomized, controlled trials have been performed by the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) study group, the Thrombolysis in Myocardial Infarction (TIMI) study group, and the Johns Hopkins University investigators. A series of trials have been performed which prospectively evaluate therapy with intravenous tissue plasminogen activator (t-PA) in combination with coronary angioplasty or as a sole intervention. Further, the precise timing of angioplasty has been considered, ranging from the immediate phase of infarction, to 18–48 hr, 72 hr, and 7 days. In this review the United States trials will be presented in detail. Using this as a foundation, the results will be compared with other similar studies and a consensus of findings will be developed.