Showing papers by "Elliott M. Antman published in 1997"

Risk of Initiating Antiarrhythmic Drug Therapy for Atrial Fibrillation in Patients Admitted to a University Hospital

Abstract: Background: The risks of antiarrhythmic therapy are increasingly recognized, but the risks associated with the initiation of antiarrhythmic therapy in patients hospitalized for atrial fibrillation ...

A Critical Pathway for Management of Patients with Acute Chest Pain Who Are at Low Risk for Myocardial Ischemia: Recommendations and Potential Impact

Abstract: Background: Use of resources for patients with acute chest pain may be improved with clinical strategies that integrate research, Bayesian analysis, and expert opinion. Objectives: To 1) develop a ...

Angioplasty Guidewire Velocity: A New Simple Method to Calculate Absolute Coronary Blood Velocity and Flow

Abstract: The Thrombolysis In Myocardial Infarction (TIMI) frame count is a relative index of coronary flow that measures time by counting the number of frames required for dye to travel from the ostium to a standardized coronary landmark in a cineangiogram filmed at a known speed (frames/s). We describe a new method to measure distance along arteries so that absolute velocity (length divided by time) and absolute flow (area x velocity) may be calculated in patients undergoing percutaneous transluminal coronary angiography (PTCA). After PTCA, the guidewire tip is placed at the coronary landmark and a Kelly clamp is placed on the guidewire where it exits the Y-adapter. The guidewire tip is then withdrawn to the catheter tip and a second Kelly clamp is placed on the wire where it exits the Y-adapter. The distance between the 2 Kelly clamps outside the body is the distance between the catheter tip and the anatomic landmark inside the body. Velocity (cm/s) may be calculated as this distance (cm) divided by TIMI frame count (frames) x film frame speed (frames/s). Flow (ml/s) may be calculated by multiplying this velocity (cm/s) and the mean cross-sectional lumen area (cm2) along the length of the artery to the TIMI landmark. In 30 patients, velocity increased from 13.9 +/- 8.5 cm/s before to 22.8 +/- 9.3 cm/s after PTCA (p <0.001). Despite TIMI grade 3 flow both before and after PTCA in 18 patients, velocity actually increased 38%, from 17.0 +/- 5.4 to 23.5 +/- 9.0 cm/s (p = 0.01). For all 30 patients, flow doubled from 0.6 +/- 0.4 ml/s before to 1.2 +/- 0.6 ml/s after PTCA (p <0.001). In the 18 patients with TIMI grade 3 flow both before and after PTCA, flow increased 86%, from 0.7 +/- 0.3 to 1.3 +/- 0.6 ml/s (p = 0.001). Distance along coronary arteries (length) can be simply measured using a PTCA guidewire. This length may be combined with the TIMI frame count to calculate measures of absolute velocity and flow that are sensitive to changes in perfusion. TIMI grade 3 flow is composed of a range of velocities and flows.

Evidence-Based Coronary Care

Abstract: Since Herrick's classic description of acute myocardial infarction was published in 1912, the management of this condition has gone through four phases. The first, which may be called the clinical observation phase of coronary care, lasted about half a century and consisted of the simple assessments that were possible at that time. Vital signs were recorded frequently, especially on the first day after infarction; clinical examinations were done and electrocardiograms were obtained daily for the first few days; and chest roentgenograms were obtained once or twice a week. The infarcted heart was considered to be a wounded organ, the repair of which required the equivalent of the immobilization of a fractured bone. Treatment therefore consisted of strict bed rest and sedation. Digitalis was administered for heart failure, and quinidine was given for frequent premature ventricular contractions. Patients were usually hospitalized for 5 to 6 weeks. The major debates during this phase revolved around whether ambulation could be started early (1 week) or late (2 to 3 weeks) after admission. There was also considerable controversy about the indications for anticoagulant agents, which were administered primarily to prevent pulmonary thromboembolism, a major complication of bed rest. The in-hospital mortality rate approached 30%; after discharge, patients usually led restricted lives, and 15% died during the remainder of the first year. The situation changed radically during the early 1960s in the so-called coronary care unit phase [1]. This phase was marked by the refinement of techniques for closed-chest cardiac resuscitation and the gathering in a single location in the hospital of equipment for continuous electrocardiographic monitoring and teams of trained physicians and nurses who could efficiently use the newly available antiarrhythmic agents (such as lidocaine) and could use direct-current defibrillators and pacemakers to treat life-threatening arrhythmias. During this period, patients enjoyed the benefit of a halving of the in-hospital mortality rate for acute myocardial infarction but remained susceptible to the late consequences of large infarctions: heart failure and malignant ventricular arrhythmias. This resulted in a continued high incidence of late deaths and serious disability. The third phase of coronary care, the high-technology phase, began in the 1970s and was characterized by the appearance of several new diagnostic and therapeutic methods driven by advances in instrumentation and pharmaceuticals. Notable among these advances was the introduction of the Swan-Ganz catheter for bedside assessment of hemodynamics, which was done to define subsequent management [2]. A battery of tests that sometimes provided overlapping information was often carried out before hospital discharge; these tests included 24-hour ambulatory (Holter) electrocardiography, which was occasionally followed by electrophysiologic testing. Exercise electrocardiography, radionuclide ventriculography, and myocardial perfusion scintigraphy were often performed, both at rest and during exercise, and they were often followed by coronary arteriography and myocardial revascularization. It was during this era that the concept of protecting the ischemic myocardium was developed [3]; this led first to the use of -blockers and then to early myocardial reperfusion-thrombolytic therapy and primary coronary angioplasty. Coronary care was based primarily on the rational application of pathophysiologic principles. The clinical outcome of patients with acute myocardial infarction improved further, and the in-hospital mortality rate was reduced to less than 10%. The patients' postdischarge prognosis also improved. Because early reperfusion often limited the infarction size, patients were left with more viable myocardium, which reduced the risk for subsequent heart failure and fatal arrhythmias [4]. Because of the perception that all or most of the aforementioned diagnostic and therapeutic measures had to be applied to a large fraction of patients with acute myocardial infarction, a veritable army of subspecialists-clinical cardiologists, interventional cardiologists, nuclear cardiologists, cardiac electrophysiologists, cardiac radiologists, and surgeons-all participated in the care (and billing) of patients with acute myocardial infarction. The costs of care skyrocketed, even though the hospital stay was shortened. As concern about costs mounted, questions were raised. Had the pendulum swung too far? Were too many expensive diagnostic procedures performed, resulting in overly aggressive, expensive, and unnecessary therapy? The stage was set for the commencement of a new phase, which might appropriately be termed the evidence-based coronary care phase. The analysis of coronary care by Peterson and colleagues in this issue [5] is an excellent starting point for an understanding of this phase. These authors argue persuasively that the performance of a specialized test in a patient with acute myocardial infarction is only justified if the test can provide incremental information that will change the clinician's practice so as to favorably affect clinical outcome. It now seems that the tests (such as Holter electrocardiography) that were developed and widely applied in the high-technology phase of coronary care fail to provide information that influences care in many patients. Other tests, such as nuclear imaging techniques, frequently offer only redundant information [6]. Coronary angiography after acute infarction leads to management decisions that improve outcome in only a minority of patients [7]. The reasons why many of the tests in the high-technology phase of coronary care had limited clinical value are complex. Chief among these reasons is a progressively lower pretest likelihood of adverse outcome (largely due to improvements in the care of patients with acute myocardial infarction), which produced low positive predictive values for many tests. The basic strategy described by Peterson and colleagues is 1) to assess risk continuously during the patients' course, especially at the initial presentation, at 24 hours, during the late hospital phase, and before discharge and 2) to drive management at each point according to the results of these assessments. Notably, the simple demographic characteristics (such as age) and clinical findings (such as pulse and blood pressure) that so preoccupied clinicians during the clinical observation phase of coronary care have now been shown to be the most important descriptors of risk [8, 9]. Quantitative assessment of left ventricular function should be obtained during hospitalization. Clinicians should select one of the following on the basis of clinical circumstances and local institutional expertise: echocardiography, radionuclide angiography, or left ventriculography. Stress electrocardiography, sometimes supplemented by two-dimensional transthoracic echocardiography, can be used to select the subset of patients in whom coronary arteriography is likely to provide the most useful information. As suggested by Table 4 of the paper by Peterson and colleagues, the routine use of exercise myocardial perfusion imaging is not indicated because of reduced specificity and lack of improvement in positive predictive value for adverse outcome compared with conventional exercise electrocardiography. Coronary revascularization done using surgical or catheter-based techniques is not ordinarily performed simply because coronary obstruction is present. Rather, its use is limited to subgroups of patients in whom it has clearly been shown to prolong life or improve quality of life. Risk factors for recurrent coronary events are assessed at the time of admission, and secondary prevention using diet; optimization of blood pressure, serum lipid levels, and glucose levels; and smoking cessation is begun early in the hospital course and continued aggressively after discharge. Two major forces have converged to bring us into the evidence-based coronary care phase. The first is the widespread agreement that it is no longer acceptable to base the use of diagnostic tests and therapeutic measures on anecdotal experience or on the results of retrospective cohort studies, especially for a condition such as acute myocardial infarction, which is so common and has been studied so intensively. The second is the advent of managed, particularly capitated, care, which places such a high priority on reducing costs by using only those diagnostic tests and therapeutic interventions that have a proven effect on clinical outcome. During this phase of evidence-based coronary care, we can look forward to maintaining and even improving on the excellent results developed during the high-technology phase, with the additional benefit of returning patients to work and to a normal lifestyle much more rapidly than before. Early attention to secondary prevention is likely to result in substantial further improvement in long-term outcome. It should be possible to accomplish this while preventing further escalation of costs; in many instances, the costs of care may even be reduced. Many challenges remain in the care of patients with acute myocardial infarction. Even though in-hospital mortality rates have been reduced by approximately two thirds since the end of the clinical observation phase 35 years ago, about 500 000 patients in the United States still die of acute myocardial infarction each year [10]. What causes these fatal outcomes? Most of the deaths are sudden and occur before the patient reaches the hospital. Most of the remainder result from massive infarctions that cause cardiogenic shock or internal or external cardiac rupture. Although reperfusion therapy (thrombolysis or primary percutaneous transluminal coronary angioplasty) has enormously improved the care of patients with acute myocardial infarction and ST-segment elevations who present to the ho

Reexamination of the Thrombin Hypothesis: What We Have Learned from TIMI 9B and GUSTO IIb.

Abstract: Several lines of evidence support a central role for thrombin in the molecular and cellular processes following plaque rupture: (1) thrombus formation at sites of vascular injury in vivo is primarily mediated by thrombin through activation of the coagulation cascade and stimulation of platelet aggregation; (2) thrombin is a key mediator of early smooth muscle cell proliferation following arterial injury; (3) thrombin potentiates the proliferative effects of multiple growth factors; and (4) thrombin regulates in_ammatory processes in neutrophils, monocytes, and their respective counterreceptors by endothelium [1]. Prior studies have demonstrated that thrombin’s effects can be neutralized by direct or indirect inactivation and by inhibition of thrombin production via the intrinsic or extrinsic limbs of the coagulation pathway [1]. Pilot studies [2–4] in humans with hirudin, a potent, direct, and highly speci~c inhibitor of free and clotbound thrombin, were promising. Favorable trends in 90 minute infarct-related artery patency rates were seen with hirudin compared to heparin [2,4], and clinical events were lower at the highest doses of hirudin [3]. However, all 3 of the initial large phase III clinical trials (HIT-III, TIMI 9A, GUSTO IIa) testing direct thrombin inhibition with hirudin vs. the indirect action of heparin had to be suspended due to higher than expected hemorrhagic complications. An unacceptable rate of bleeding, especially in an intracranial location, was observed. Following reduction in doses of both heparin and hirudin, and institution of additional hemorrhagic safety precautions, the TIMI 9B [5] and GUSTO IIb [6] trials were carried out. The TIMI 9B study evaluated hirudin vs. heparin as adjunctive therapy in 3,002 patients with acute myocardial infarction who also received aspirin and either streptokinase or accelerated dose tPA. There was no signi~cant difference in the primary endpoint of unsatisfactory clinical outcome (death, recurrent nonfatal myocardial infarction, or development of severe congestive heart failure or cardiogenic shock) by 30 days between the heparin-treated patients (11.9%) and the hirudin-treated patients (12.9%). Similarly, there was no difference in the secondary endpoint of death and nonfatal myocardial infarction (see Table 1). Subgroup analyses failed to identify a patient pro~le that bene~tted more from hirudin. Likewise, a multivariate logistic regression analysis that included previously established risk factors for poor prognosis failed to demonstrate that the antithrombin to which the patient was randomized correlated with unsatisfactory outcome or the sum of death and reinfarction by 30 days. Rates of major hemorrhage (heparin 5.3%, hirudin 4.6%) and intracranial hemorrhage (heparin 0.9%, hirudin 0.4%) were also similar for the 2 antithrombins. In GUSTO IIb, 12,142 patients with acute coronary syndromes were randomized to heparin vs. hirudin. Of the 4,131 patients with ST elevation who were treated with aspirin and tPA or streptokinase, there was no signi~cant difference in the composite endpoint of death and non-fatal reinfarction at 30 days (see Table 1). Similarly for the 8,011 patients with ST depression, there was no signi~cant difference in combined mortality and nonfatal reinfarction between the heparinand hirudin-treated patients at 30 days. For the entire cohort of 12,142 patients, however, a small bene~t of borderline statistical signi~cance was seen for the hirudintreated patients (Table 1). Intracranial hemorrhage rates were 0.4% and 0.5% in patients with ST segment elevation for heparin and hirudin patients respectively. In patients without ST segment elevation, the rates were 0.02% for heparin and 0.2% for hirudin. What are possible explanations for this lack of clinical bene~t despite the theoretical advantages of hirudin over heparin? One possibility is that although hirudin, unlike heparin, is active against both clotbound as well as _uid-phase thrombin [7], heparin has Journal of Thrombosis and Thrombolysis 1997;4:321–323 © Kluwer Academic Publishers. Boston. Printed in the Netherlands