H. Vernon Anderson

Combined Accelerated Tissue-Plasminogen Activator and Platelet Glycoprotein IIb/IIIa Integrin Receptor Blockade With Integrilin in Acute Myocardial Infarction Results of a Randomized, Placebo-Controlled, Dose-Ranging Trial

BACKGROUND Platelet activation and aggregation may be key components of thrombolytic failure to restore and maintain perfusion in acute myocardial infarction. We performed a placebo-controlled, dose-ranging trial of Integrilin, a potent inhibitor of platelet aggregation, with heparin, aspirin, and accelerated alteplase. METHODS AND RESULTS We assigned 132 patients in a 2:1 ratio to receive a bolus and continuous infusion of one of six Integrilin doses or placebo. Another 48 patients were randomized in a 3:1, double-blind fashion to receive the highest Integrilin dose from the first phase or placebo. All patients received accelerated alteplase, aspirin, and intravenous heparin infusion; all but two groups also received an intravenous heparin bolus. The highest Integrilin dose group from the nonrandomized phase and the randomized patients were pooled for analysis and compared with placebo-treated patients. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 90-minute angiography. Secondary end points were time to ST-segment recovery, an in-hospital composite (death, reinfarction, stroke, revascularization procedures, new heart failure, or pulmonary edema), and bleeding variables. The highest Integrilin dose groups had more complete reperfusion (TIMI grade 3 flow, 66% versus 39% for placebo-treated patients; P = .006) and a shorter median time to ST-segment recovery (65 versus 116 minutes for placebo; P = .05). The groups had similar rates of the composite end point (43% versus 42% for placebo-treated patients) and severe bleeding (4% versus 5%, respectively). CONCLUSIONS The incidence and speed of reperfusion can be enhanced when a potent inhibitor of the glycoprotein IIb/IIIa integrin receptor, such as Integrilin, is combined with accelerated alteplase, aspirin, and intravenous heparin.

The American College of Cardiology-National Cardiovascular Data Registry™ (ACC-NCDR™): Building a National Clinical Data Repository

Diagnostic cardiac catheterization and percutaneous coronary interventions (PCIs) are critical components of the diagnosis and treatment of patients with coronary artery disease. As the prevalence of heart disease increases in our aging population and increasingly aggressive invasive approaches are

A contemporary overview of percutaneous coronary interventions: The American College of Cardiology–National Cardiovascular Data Registry (ACC–NCDR)

The American College of Cardiology (ACC) established the National Cardiovascular Data Registry (ACC-NCDR) to provide a uniform and comprehensive database for analysis of cardiovascular procedures across the country. The initial focus has been the high-volume, high-profile procedures of diagnostic cardiac catheterization and percutaneous coronary intervention (PCI). Several large-scale multicenter efforts have evaluated diagnostic catheterization and PCI, but these have been limited by lack of standard definitions and relatively nonuniform data collection and reporting methods. Both clinical and procedural data, and adverse events occurring up to hospital discharge, were collected and reported according to uniform guidelines using a standard set of 143 data elements. Datasets were transmitted quarterly to a central facility for quality-control screening, storage and analysis. This report is based on PCI data collected from January 1, 1998, through September 30, 2000.A total of 139 hospitals submitted data on 146,907 PCI procedures. Of these, 32% (46,615 procedures) were excluded because data did not pass quality-control screening. The remaining 100,292 procedures (68%) were included in the analysis set. Average age was 64 +/- 12 years; 34% were women, 26% had diabetes mellitus, 29% had histories of prior myocardial infarction (MI), 32% had prior PCI and 19% had prior coronary bypass surgery. In 10% the indication for PCI was acute MI < or =6 h from onset, while in 52% it was class II to IV or unstable angina. Only 5% of procedures did not have a class I indication by ACC criteria, but this varied by hospital from a low of 0 to a high of 38%. A coronary stent was placed in 77% of procedures, but this varied by hospital from a low of 0 to a high of 97%. The frequencies of in-hospital Q-wave MI, coronary artery bypass graft surgery and death were 0.4%, 1.9% and 1.4%, respectively. Mortality varied by hospital from a low of 0 to a high of 4.2%. This report presents the first data collected and analyzed by the ACC-NCDR. It portrays a contemporary overview of coronary interventional practices and outcomes, using uniform data collection and reporting standards. These data reconfirm overall acceptable results that are consistent with other reported data, but also confirm large variations between individual institutions.

C-Reactive Protein Linking Inflammation to Cardiovascular Complications

In the present issue, Chew and colleagues 1 show that elevated baseline C-reactive protein (CRP) levels before percutaneous coronary intervention (PCI) are associated with a progressive increase in the risk of death or myocardial infarction at 30 days. The independent association of risk attributable to the marker CRP remained, even after adjusting for a number of baseline variables that are known to influence early events after PCI. This finding is not a surprise to those who have followed the trail of CRP in the last few years. However, to those who have not followed the CRP story, some explanation is in order. See p 992 Our understanding of atherosclerosis has evolved immensely over the years. When William Osler wrote his textbook of medicine more than a century ago, atherosclerosis was viewed as being caused by the hardening of blood vessels as a consequence of the aging process. More recently, the perils of hypercholesterolemia and its causative association with atherosclerosis at all ages were uncovered through many large epidemiological studies. 2 However, cholesterol deposits in the arterial wall do not fully explain all the features of the proliferation of smooth muscle cells that attempt to form scars to wall off these lipid deposits. With the discovery of growth factors and their role in tissue repair, the “response to injury” hypothesis has become a dominant paradigm. In the last decade, however, a new perspective on atherosclerosis has been developed based on accumulating evidence that the entry of inflammatory cells such as monocytes into the arterial wall plays a pivotal role in this disease. 3,4 This new paradigm might be collectively called the inflammation hypothesis. Any inflammatory stimulus, such as oxidized LDL or infection, alters the endothelial lining of the artery to make it “sticky” through the expression of adhesion molecules (such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1) and the secretion of chemokines (such as monocyte chemoattractant protein-1) on the luminal surface. The sticky endothelium attracts or captures circulating monocytes or other inflammatory cells onto the arterial surface. Once monocytes are arrested on the surface of the endothelium, they travel across the junction between 2 endothelial cells and become tissue macrophages, which can ingest lipid deposits to form foam cells. With the continuous entry of monocytes into the arterial wall, the lesion develops from the initial fatty streak to the more advanced fibrous plaque. If one can prevent the entry of monocytes into the arterial wall, then one can ameliorate the development of atherosclerosis. This prediction has been tested and proved in many animal models.5 As inflammation began to be recognized as a major contributor to the pathogenesis of atherosclerosis, cardiologists started to ask whether markers of inflammation could be used to predict the

Local Effect of Serotonin Released during Coronary Angioplasty

BACKGROUND Serotonin is released after the aggregation of platelets, a phenomenon that may occur after coronary angioplasty. We sought to determine whether serotonin is released into the coronary circulation during coronary angioplasty and to assess whether serotonin can affect coronary-artery tone during angioplasty. METHODS Blood samples were drawn from the ascending aorta and the coronary sinus of eight patients scheduled to undergo angioplasty of the left anterior descending or circumflex coronary artery. Samples were obtained before angioplasty and after each balloon dilation. The dimensions of arterial segments distal to the site of dilation were measured angiographically before angioplasty and 5 and 15 minutes after the last dilation in these eight patients and in seven similar patients; the latter group was treated with ketanserin, a serotonin2-receptor antagonist, before angioplasty. RESULTS Before the eight patients underwent angioplasty, their mean (+/- SE) plasma serotonin level in the aorta was 2.5 +/- 0.7 ng per milliliter and that in the coronary sinus was 2.3 +/- 0.6 ng per milliliter (P = 0.34). The serotonin level in plasma from the coronary sinus rose significantly, to 31.5 +/- 13.5, 17.6 +/- 5.3, and 29.1 +/- 8.1 ng per milliliter after the first, second, and third dilations, respectively (P = 0.014 for the comparison with preoperative levels). In contrast, the serotonin level in plasma from the ascending aorta did not change. The cross-sectional area of the coronary artery was significantly reduced 5 and 15 minutes after the last dilation (from a preoperative value of 3.7 +/- 0.5 mm2 to 2.7 +/- 0.4 mm2 15 minutes after the last dilation; P = 0.011). This vasoconstriction was significantly blunted in the seven patients who received ketanserin (from 3.7 +/- 0.5 mm2 before angioplasty to 3.9 +/- 0.4 mm2 after 15 minutes) (P = 0.017 for comparison with the eight patients who did not receive ketanserin). CONCLUSIONS Serotonin is released into the coronary circulation during angioplasty, and this vasoactive substance may contribute to the occurrence of vasoconstriction distal to the dilated site. The vasoconstriction is attenuated by ketanserin, a serotonin2-receptor antagonist.

Effects of Integrelin, a Platelet Glycoprotein IIb/IIIa Receptor Antagonist, in Unstable Angina A Randomized Multicenter Trial

BACKGROUND Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.

Intracoronary adenosine administered during percutaneous intervention in acute myocardial infarction and reduction in the incidence of 'no reflow' phenomenon

Percutaneous intervention in acute myocardial infarction has been associated with a high incidence of “no reflow,” ranging from 11% to 30%, with an increased risk of complications. The role of intracoronary adenosine for the prevention of this phenomenon has not been evaluated fully. We studied the procedural outcomes of 79 patients who underwent percutaneous intervention in the context of acute myocardial infarction. Twenty‐eight patients received no intracoronary adenosine, and 51 received intracoronary adenosine boluses (24–48 μg before and after each balloon inflation). Eight patients who were not given adenosine experienced no reflow (28.6%) and higher rates of in‐hospital death, while only three of 51 patients (5.9%; P =0.014) in the adenosine group experienced no reflow. No untoward complications were noted during adenosine infusion. Intracoronary adenosine bolus administration during percutaneous intervention in the context of acute myocardial infarction is easy and safe and may significantly lessen the incidence of no reflow, which may improve the outcome of this procedure. Cathet. Cardiovasc. Intervent. 51:27–31, 2000.

Percutaneous Coronary Interventions in Facilities Without Cardiac Surgery On Site: A Report From the National Cardiovascular Data Registry (NCDR)

Since the introduction of percutaneous coronary intervention (PCI) in 1977 by Andreas Gruntzig ([1][1]), the presence of cardiac surgery backup on site has been a recommended practice to treat the potential of life-threatening complications. As a result of major improvements in technology and

Evaluation of the American College of Cardiology/American Heart Association and the Society for Coronary Angiography and Interventions lesion classification system in the current “stent era” of coronary interventions (from the ACC-National Cardiovascular Data Registry)

In 1988 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for Coronary Angioplasty proposed a lesion classification system to stratify lesions by difficulty and risk to better understand the outcomes of coronary interventions. It was a 3-level (A, B, and C) classification based on 11 lesion characteristics. A modification, dividing the intermediate B category into B1 and B2, is also in common use. Recently, a simplification of this classification was evaluated using the large Society for Cardiac Angiography and Interventions (SCAI) Registry (SCAI I = non-C/patent; SCAI II = C/patent; SCAI III = non-C/occluded; SCAI IV = C/occluded). The lesion classification systems were evaluated in 61,926 patients from the ACC National Cardiovascular Data Registry who underwent single-vessel percutaneous coronary intervention between January 1998 and September 2000. Stents were placed in 74.5% of patients. Logistic models for lesion success and complications were constructed and compared. The c statistic for success using the ACC/AHA original classification system was 0.69, 0.71 for the modified ACC/AHA system, and 0.75 for the SCAI classification. The range of complication and success rates was greater using the SCAI models, and the logistic models for success and complication were more robust for the SCAI system. Thus, in the large ACC-National Cardiovascular Data Registry, with a high percentage of stent usage, the simpler SCAI lesion classification provided better discrimination for success and complications than the more complex ACC/AHA lesion classification system-original or modified.

Total ischemic time: the correct focus of attention for optimal ST-segment elevation myocardial infarction care.

Currently accepted standards for gauging quality of care in the treatment of ST-segment elevation myocardial infarction (STEMI) mainly focus on shortening the time to treatment after the patient arrives at the hospital. But this narrow focus fails to consider the substantial duration of myocardial ischemia that exists prior to hospital arrival, and the large number of deaths that occur during the pre-hospital period. The time from symptom onset until reperfusion occurs is one estimate of total ischemic time. Several experimental studies and now human clinical studies have confirmed that infarct size and mortality are strongly correlated with the total ischemic time, and much less so with its subintervals like door-to-balloon time. This review will discuss the importance of total ischemic time in STEMI.