advertisement
Browse Health

Credentials

Education ?

Medical School
University Of Cape Town (1970)
Foreign school

Awards & Distinctions ?

Awards  
One of America's Leading Experts on:
Arteriosclerosis
Heart Diseases
Stroke
Honorary M.A. Yale University of Medicine, 1990
Honorary Degree, Royal College of Physicians
Associations
American Board of Internal Medicine
Heart Rhythm Society

Affiliations ?

Dr. Ezekowitz is affiliated with 19 hospitals.

Hospital Affiliations

Score

Rankings

  • Bryn Mawr Rehabilitation Hospital
    414 Paoli Pike, Malvern, PA 19355
    •  
    Top 25%
  • Main Line Hospital - Bryn Mawr
    Cardiology
    130 S Bryn Mawr Ave, Bryn Mawr, PA 19010
    •  
    Top 50%
  • Riddle Memorial Hospital
    Cardiology
    1068 W Baltimore Pike, Media, PA 19063
    •  
    Top 50%
  • Main Line Hospital Paoli
    Cardiology
    255 W Lancaster Ave, Paoli, PA 19301
    •  
    Top 50%
  • Main Line Hospital Lankenau
    Cardiology
    100 E Lancaster Ave, Wynnewood, PA 19096
    •  
  • Hahnemann University Hospital
    Cardiology
    230 N Broad St, Philadelphia, PA 19102
    •  
  • M L Health-Paoli Memorial Hospital
  • Lankenau Medical Center
  • Womans Medical Hospital
  • Tenet HealthSystem Hahnemann LLC
  • Bryn Mawr Hospital
  • Lankenau Medical Center - On staff since
  • Yale-New Haven Hospital, Inc., New Haven CT
  • -Paoli Hospital - On staff since 2006
  • M L Hospital Lankenau
  • Medical College/Pennsylvania H
  • -Bryn Mawr Hospital - On staff since 2006
  • -Lankenau Hospital - On staff since 2006
  • M L Hospital Bryn Mawr Hospital
  • Publications & Research

    Dr. Ezekowitz has contributed to 125 publications.
    Title Forecasting the Future of Cardiovascular Disease in the United States: a Policy Statement from the American Heart Association.
    Date April 2011
    Journal Circulation
    Excerpt

    Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially.

    Title 2011 Accf/aha/hrs Focused Update on the Management of Patients with Atrial Fibrillation (updating the 2006 Guideline): a Report of the American College of Cardiology Foundation/american Heart Association Task Force on Practice Guidelines.
    Date January 2011
    Journal Circulation
    Title Gender in Atrial Fibrillation: Ten Years Later.
    Date January 2011
    Journal Gender Medicine
    Excerpt

    Atrial fibrillation (AF) is the most common arrhythmia encountered in both male and female patients.

    Title Incidence of Newly Detected Atrial Arrhythmias Via Implantable Devices in Patients with a History of Thromboembolic Events.
    Date February 2010
    Journal Stroke; a Journal of Cerebral Circulation
    Excerpt

    Evidence of atrial tachycardia/atrial fibrillation (AT/AF) is often sought in patients with ischemic stroke or transient ischemic attack. We studied patients with previous thromboembolic events (TE) who were implanted with devices capable of continuous arrhythmia monitoring to comprehensively quantify the incidence and duration of newly detected AT/AF.

    Title The Relationship Between Daily Atrial Tachyarrhythmia Burden from Implantable Device Diagnostics and Stroke Risk: the Trends Study.
    Date December 2009
    Journal Circulation. Arrhythmia and Electrophysiology
    Excerpt

    It is unknown if brief episodes of device-detected atrial fibrillation (AF) increase thromboembolic event (TE) risk.

    Title Secondary Prevention in Concurrent Coronary Artery, Cerebrovascular, and Chronic Kidney Disease: Focus on Pharmacological Therapy.
    Date October 2009
    Journal Cardiovascular Therapeutics
    Excerpt

    Patients with coronary artery disease (CAD) commonly have varying degrees of coexisting cerebrovascular disease (CVD) and chronic kidney disease (CKD), and proper management is complicated partly because of a lack of unifying guidelines. The aim of this article is to review the current literature and propose the optimal treatment regimen in patients with all three disease states. Angiotensin-converting enzyme inhibitors (ACE-I) should be universally administered. High-dose statin therapy to reach a target low-density lipoprotein (LDL) of 70-100 mg/dL is advocated, although patients with a history of cerebral bleeding must be carefully monitored for possible recurrence. Beta-blockers are appropriate after a recent coronary event, and amlodipine or thiazide diuretics should be used after a recent stroke (within 6 months). Patients with a history of stroke (with or without coexisting CAD and CKD) should receive aspirin (75-150 mg/day) indefinitely. Clopidogrel or aspirin plus extended-release dipyridamole (ER-DP) may be prescribed in patients allergic or resistant to aspirin. If stroke is attributable to cardiogenic embolism, anticoagulation is indicated. In patients with acute coronary syndromes (ACS) (excluding ST-elevated myocardial infarct) who undergo percutaneous coronary intervention (PCI), aspirin plus clopidogrel is indicated for secondary prevention for up to 12 months. There are no data supporting the use of aspirin plus clopidogrel in patients with CKD who develop ACS. Aspirin plus clopidogrel is contraindicated for stroke prevention.

    Title Reducing Stroke Rates in Patients with Atrial Fibrillation: How Low Can We Go?
    Date October 2009
    Journal Circulation
    Title The First Evaluation of a Novel Vitamin K Antagonist, Tecarfarin (ati-5923), in Patients with Atrial Fibrillation.
    Date October 2009
    Journal Circulation
    Excerpt

    Tecarfarin (ATI-5923) is a novel oral vitamin K antagonist. Unlike warfarin, it is metabolized by esterases, escaping metabolism by the cytochrome P450 system and thereby avoiding cytochrome P450-mediated drug-drug or drug-food interactions as well as genetic variations found in the cytochrome P450 system. Both tecarfarin and warfarin can be monitored with the international normalized ratio. We hypothesized that the time in therapeutic range for tecarfarin will exceed values usually experienced with warfarin.

    Title Dabigatran Versus Warfarin in Patients with Atrial Fibrillation.
    Date September 2009
    Journal The New England Journal of Medicine
    Excerpt

    Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.

    Title Combination Antiplatelet Therapy for Secondary Stroke Prevention: Enhanced Efficacy or Double Trouble?
    Date April 2009
    Journal The American Journal of Cardiology
    Excerpt

    The evaluation of antithrombotic agents for secondary stroke prevention has focused on stroke reduction. The aim of this analysis was to focus specifically on the increase in bleeding risk. The annualized rates of total and major bleeding events in secondary stroke prevention trials of antithrombotics were assessed and cross compared. A Medline search for major randomized clinical studies with a follow-up duration of > or =1 year identified 13 studies. Pooled data sets were used to compare mean bleeding rates for aspirin (< or =325 mg/day), clopidogrel, anticoagulants (warfarin and other vitamin K antagonists), aspirin plus clopidogrel, and aspirin plus extended-release dipyridamole (ER-DP). Total bleeding occurred at mean rates of 4.8% with aspirin (< or =325 mg/day) alone, 2.9% with clopidogrel alone, 3.6% with aspirin plus ER-DP, 10.1% with aspirin plus clopidogrel, and 16.8% with anticoagulation. Major bleeding occurred at mean rates of 1% with aspirin (< or =325 mg/day) alone, 0.85% with clopidogrel, 0.93% with aspirin plus ER-DP, 1.7% with aspirin plus clopidogrel, and 2.5% with anticoagulation. In conclusion, the combination of aspirin and clopidogrel is associated with significantly greater bleeding than either aspirin (< or =325 mg/day) or clopidogrel alone. Aspirin plus ER-DP has a greater bleeding rate than clopidogrel but a lower rate than aspirin (< or =325 mg/day) alone.

    Title Effect of Age on Stroke Prevention Therapy in Patients with Atrial Fibrillation: the Atrial Fibrillation Investigators.
    Date April 2009
    Journal Stroke; a Journal of Cerebral Circulation
    Excerpt

    Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation.

    Title Acc/aha/physician Consortium 2008 Clinical Performance Measures for Adults with Nonvalvular Atrial Fibrillation or Atrial Flutter: a Report of the American College of Cardiology/american Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (writing Committee to Develop Clinical Performance Measures for Atrial Fibrillation): Developed in Collaboration with the Heart Rhythm Society.
    Date March 2008
    Journal Circulation
    Title Acc/aha/physician Consortium 2008 Clinical Performance Measures for Adults with Nonvalvular Atrial Fibrillation or Atrial Flutter: a Report of the American College of Cardiology/american Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (writing Committee to Develop Clinical Performance Measures for Atrial Fibrillation) Developed in Collaboration with the Heart Rhythm Society.
    Date March 2008
    Journal Journal of the American College of Cardiology
    Title Letter Regarding Article by Connolly Et Al, "challenges of Establishing New Antithrombotic Therapies in Atrial Fibrillation".
    Date March 2008
    Journal Circulation
    Title Dabigatran with or Without Concomitant Aspirin Compared with Warfarin Alone in Patients with Nonvalvular Atrial Fibrillation (petro Study).
    Date December 2007
    Journal The American Journal of Cardiology
    Excerpt

    This is the first evaluation of dabigatran, an oral direct thrombin inhibitor, in patients with atrial fibrillation (AF). Patients (n = 502) were randomized to receive blinded doses of 50-, 150-, or 300-mg dabigatran twice daily alone or combined with 81- or 325-mg aspirin or open-label warfarin administered to achieve an international normalized ratio of 2 to 3 for 12 weeks. Dabigatran plasma concentrations, activated partial thromboplastin time, D-dimer, urinary 11-dehydrothromboxane B(2) (DTB2), and liver function were measured at baseline and at 1, 2, 4, 8, and 12 weeks. Clinical end points were assessed according to the treatment received at the time of the event. Overall, 92% of patients completed the study. Major hemorrhages were limited to the group treated with 300-mg dabigatran plus aspirin (4 of 64), and the incidence was significant versus 300-mg dabigatran alone (0 of 105, p <0.02). Total bleeding events were more frequent in the 300-mg (39 of 169, 23%) and 150-mg (30 of 169, 18%) dabigatran groups compared with the 50-mg groups (7 of 107, 7%; p = 0.0002 and p = 0.01, respectively). Thromboembolic events were limited to the 50-mg dabigatran dose groups (2 of 107, 2%). The mean trough d-dimer measurements were suppressed for the 2 highest doses of dabigatran and warfarin (international normalized ratio of 2 to 3). Aminotransferase levels >3 times the upper limit of normal were observed in 0.9% of the dabigatran recipients and in none of the warfarin recipients. Two dabigatran recipients had aminotransferase levels >5 times the upper limit of normal as a result of gallstones, which resolved. Trough activated partial thromboplastin time values were 1.2, 1.5, and 1.8 times the baseline level for the 50-, 150-, and 300-mg dabigatran groups, respectively. DTB2 concentrations after 12 weeks of 50-, 150-, and 300-mg dabigatran treatment were increased by 31%, 17%, and 23%, respectively, versus baseline (p = 0.02, p = 0.03, and p = 0.0004). In conclusion, major bleeding events were limited to patients treated with dabigatran 300 mg plus aspirin and thromboembolic episodes were limited to the 50-mg dabigatran groups. The 2 highest doses of dabigatran suppress D-dimer concentrations. Serious liver toxicity was not seen. The significance of the increase of DTB2 concentrations in dabigatran-treated patients needs resolution.

    Title Maintaining Sinus Rhythm--making Treatment Better Than the Disease.
    Date September 2007
    Journal The New England Journal of Medicine
    Title Images in Cardiovascular Medicine. The Case of a Disappearing Left Atrial Appendage Thrombus: Direct Visualization of Left Atrial Thrombus Migration, Captured by Echocardiography, in a Patient with Atrial Fibrillation, Resulting in a Stroke.
    Date October 2006
    Journal Circulation
    Title Quality of Life and Exercise Performance in Patients in Sinus Rhythm Versus Persistent Atrial Fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.
    Date September 2006
    Journal Journal of the American College of Cardiology
    Excerpt

    OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.

    Title Warfarin Therapy and Systolic Hypertension in Men with Atrial Fibrillation.
    Date September 2006
    Journal American Journal of Hypertension : Journal of the American Society of Hypertension
    Excerpt

    BACKGROUND: Warfarin decreases the activity of matrix Gla-protein and causes extensive arterial calcification leading to increased systolic blood pressure (SBP) and pulse pressure (PP) in rats. We performed post hoc analyses of the Stroke Prevention in Non-Rheumatic Atrial Fibrillation (SPINAF) trial, aiming to analyze the effects of warfarin on SBP and PP. METHODS: The SPINAF trial was a randomized, double-blind, placebo-controlled trial comparing warfarin and placebo in 525 subjects with nonrheumatic atrial fibrillation. After exclusions for inadequate follow-up, 284 subjects with average treatment lasting 23.7 months were available for analysis (144 given placebo and 140 warfarin). RESULTS: Baseline SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), and PP were 132 +/- 18, 81 +/- 9, 98 +/- 11, and 50 +/- 16 mm Hg in the warfarin group, and 133 +/- 21, 80 +/- 13, 97 +/- 14, and 54 +/- 15 mm Hg in the placebo groups (all P values, NS). There was no statistically significant difference between the placebo and warfarin groups in any of the BP parameters at any time point. However, stratified analyses showed a significant increase in PP in warfarin-treated subjects with a history of hypertension (4.9 +/- 13.1 mm Hg v 0.2 +/- 11.9 mm Hg in the placebo group, P = 0.022), and those with baseline SBP > or =140 mm Hg (4.8 +/- 18.9 mm Hg v -3.4 +/- 11.2 mm Hg in the placebo group, P = .038). A similar trend was noted in diabetic subjects but it was not statistically significant. CONCLUSIONS: Based on the study results, treatment with warfarin does not result in increased BP in men with atrial fibrillation. However, it is possible that subjects at higher baseline cardiovascular risk may be more susceptible to the chronic effects of warfarin on arterial hemodynamics.

    Title Mortality After the Hospitalization of a Spouse.
    Date May 2006
    Journal The New England Journal of Medicine
    Title Review of Antiplatelet Therapy in Secondary Prevention of Cerebrovascular Events: a Need for Direct Comparisons Between Antiplatelet Agents.
    Date January 2006
    Journal Journal of Cardiovascular Pharmacology and Therapeutics
    Excerpt

    Patients experiencing stroke or transient ischemic attack (TIA) are at high risk for recurrent (secondary) strokes, which comprise 29% of all strokes in the United States. Current recommendations for prevention of secondary stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (antiplatelet) agents for patients with a history of noncardioembolic stroke or TIA. Five agents--aspirin, ticlopidine, clopidogrel, extended-release dipyridamole (ER-DP), and triflusal--have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or stroke in patients with a history of stroke. The results of the following studies are reviewed and compared: the Swedish Aspirin Low-Dose Trial (SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial, Dutch Transient Ischemic Attack (Dutch TIA) study (aspirin), the Canadian American Ticlopidine Study (CATS), the Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet Stroke Prevention Study (AAASPS) (ticlopidine), the Clopidogrel versus Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of Atherothrombosis With Clopidogrel in High-Risk Patients study (MATCH) (clopidogrel), the second European Stroke Prevention Study (ESPS2) (aspirin plus ER-DP), and the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous stroke, ticlopidine demonstrates statistically significant improved efficacy over aspirin, and clopidogrel demonstrates nonsignificant slight improvement over aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of ticlopidine (including rash, diarrhea, and neutropenia) will probably limit its long-term use. Among combination approaches, only aspirin plus ER-DP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent. Clopidogrel plus aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study, with results expected in 2008, will directly compare aspirin plus ER-DP with clopidogrel monotherapy for the prevention of recurrent stroke and should provide statistically robust estimates of comparative efficacy for the development of improved recommendations.

    Title The Combination of Warfarin and Aspirin Reduced the Rate of Ihd Events More Effectively Than Either Agent Alone.
    Date January 2006
    Journal Evidence-based Cardiovascular Medicine
    Title The Impact of Patient Self-testing of Prothrombin Time for Managing Anticoagulation: Rationale and Design of Va Cooperative Study #481--the Home Inr Study (thinrs).
    Date November 2005
    Journal Journal of Thrombosis and Thrombolysis
    Excerpt

    BACKGROUND: Anticoagulation (AC) with warfarin reduces the risk of thromboembolism (TE) in a variety of applications, yet despite compelling evidence of the value and importance of high quality AC, warfarin remains underused, and dosing is often suboptimal. Approaches to improve AC quality include (1) an AC service (ACS), which allows the physician to delegate day-to-day details of AC management to another provider dedicated to AC care, and (2) incorporating into the treatment plan patient self-testing (PST) under which, after completing a training program, patients perform their own blood testing (typically, using a finger-stick blood analyzer), have dosage adjustments guided by a standard protocol, and forward test results, dosing and other information to the provider. Studies have suggested that PST can improve the quality of AC and perhaps lower TE and bleed rates.The purpose of Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) #481, "The Home INR Study" (THINRS) is to compare AC management with frequent PST using a home monitoring device to high quality AC management (HQACM) implemented by an ACS with conventional monitoring of prothrombin time by international normalized ratio (INR) on major health outcomes. PST in THINRS involves use of an INR monitoring device that is FDA approved for home use. STUDY DESIGN: Sites are VA Medical Centers where the ACS has an active roster of more than 400 patients. THINRS includes patients with atrial fibrillation (AF) and/or mechanical heart valve (MHV) expected to be anticoagulated indefinitely.THINRS has two parts. In Part 1, candidates for PST are evaluated for 2 to 4 weeks for their ability to use home monitoring devices. In Part 2, individuals capable of performing PST are randomized to (1) HQACM with testing every 4 weeks and as indicated for out of range values, medication/clinical changes, or (2) PST with testing every week and as indicated for out of range values, medication/clinical changes.The primary outcome measure is event rates, defined as the percent of patients who have a stroke, major bleed, or die. Secondary outcomes include total time in range (TTR), other events (myocardial infarction (MI), non-stroke TE, minor bleeds), competence and compliance with PST, satisfaction with AC, AC associated quality of life (QOL), and cost-effectiveness.To assess the effect of PST frequency on TTR and other outcomes, at selected sites patients randomized to perform PST are assigned one of three test frequencies (weekly, twice weekly, or once every four weeks).

    Title High-density Lipoprotein, but Not Low-density Lipoprotein Cholesterol Levels Influence Short-term Prognosis After Acute Coronary Syndrome: Results from the Miracl Trial.
    Date August 2005
    Journal European Heart Journal
    Excerpt

    AIMS: Patients with acute coronary syndrome (ACS) in the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study had diminished cardiovascular events after 16 weeks of treatment of atorvastatin 80 mg daily. We determined whether plasma lipoproteins at baseline and then at 6 weeks after randomization predicted clinical outcome. METHODS AND RESULTS: Cox proportional hazards models were constructed to determine relations between lipoproteins and clinical endpoint events. Baseline LDL cholesterol (LDL-C) did not predict outcome. In contrast, baseline HDL-C predicted outcome with a hazard ratio of 0.986 per mg/dL increment in HDL-C, P<0.001, indicating 1.4% reduction in risk for each 1 mg/dL increase in HDL-C. Atorvastatin treatment profoundly lowered LDL-C, but had minimal effect on HDL-C. Neither Week 6 LDL-C nor absolute change of LDL-C from baseline by Week 6 had any significant impact on clinical endpoints occurring between Week 6 and Week 16 after randomization. CONCLUSION: Plasma HDL-C, but not LDL-C, measured in the initial stage of ACS predicts the risk of recurrent cardiovascular events over the ensuing 16 weeks. LDL-C reduction does not account for the clinical risk reduction with atorvastatin treatment after ACS. This finding may suggest that the clinical benefit of atorvastatin after ACS is mediated by qualitative changes in the LDL particle and/or by non-lipid (pleiotropic) effects of the drug.

    Title Anticoagulation Interruptus: Not Without Risk.
    Date June 2005
    Journal Circulation
    Title Amiodarone Versus Sotalol for Atrial Fibrillation.
    Date May 2005
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND: The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring. RESULTS: Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups. CONCLUSIONS: Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.

    Title Stroke Prevention in Atrial Fibrillation: Anticoagulants and Antithrombotics.
    Date December 2004
    Journal The American Heart Hospital Journal
    Excerpt

    Atrial fibrillation and heart failure are growing epidemics in the developed world and often coexist. From clinical trials, warfarin is highly effective in reducing stroke in patients with atrial fibrillation. Equally important is the fact that in spite of well-designed trials, translation of the results of the data from the trials into clinical practice has been less than optimal. One of the reasons is that warfarin is a difficult drug to use. Thus there has been a concerted effort to develop an alternative to warfarin. Ximelagatran and Dabigatran, both direct thrombin inhibitors, are the furthest along in clinical development. Ximelagatran, while highly effective as an anticoagulant and safe with regard to bleeding, has been associated with liver function abnormalities; the importance of which needs resolution. Dabigatran is much earlier in development and is currently of unproven value. It is highly likely that alternatives to warfarin for stroke prevention will be available in the future and will likely result in a higher utilization rate of anticoagulants in patients with atrial fibrillation.

    Title Combination Antithrombotic Therapy with Antiplatelet Agents and Anticoagulants for Patients with Atherosclerotic Heart Disease.
    Date August 2004
    Journal The Journal of Invasive Cardiology
    Excerpt

    We reviewed the efficacy and safety of combination antithrombotic therapy with aspirin plus warfarin versus aspirin alone in patients with atherosclerotic heart disease. We performed a comprehensive MEDLINE search of English-language reports published between 1966 and 2002 and search of references and relevant papers. Only clinical research studies on primary or secondary prevention of cardiovascular events in patients at high risk for coronary artery disease or patients experiencing unstable angina or myocardial infarction were included. Despite daily aspirin treatment, many patients break through aspirin treatment and experience cardiovascular events. Individuals at high risk for coronary disease or with established disease benefit from combination therapy with aspirin plus warfarin, if compliance with warfarin is greater than 70% and the target international normalized ratio (INR) of 2.0-2.5 is achieved. Combination therapy within these parameters leads to a 29-45% reduction in the risk of death, reinfarction and/or ischemic stroke. There is a significant increase in the rate of minor and a slight increase in the rate of major bleeding with combination therapy. Other potential indications for combination therapy include myocardial infarction associated with acute left ventricular aneurysm or significant left ventricular systolic dysfunction. In spite of reluctance to use oral anticoagulants, several large, randomized clinical trials support combination therapy with aspirin plus warfarin (INR, 2.0-2.5) in high-risk patients with atherosclerotic heart disease. Combination therapy increases the risk of minor and major bleeding, but not intracranial bleeding.

    Title The Increasing Need for Anticoagulant Therapy to Prevent Stroke in Patients with Atrial Fibrillation.
    Date July 2004
    Journal Mayo Clinic Proceedings. Mayo Clinic
    Excerpt

    Ischemic stroke, a major complication of atrial fibrillation (AF), is believed to result from atrial thrombus formation caused by ineffective atrial contraction. Oral anticoagulant therapy effectively reduces the risk of ischemic stroke in patients with AF; this therapy is recommended for patients with any frequency or duration of AF and other risk factors for stroke, such as increased age (>75 years), hypertension, prior stroke, left ventricular dysfunction, diabetes, or heart failure. Recently published data comparing rate-control and rhythm-control strategies in AF emphasized the importance of maintaining an international normalized ratio higher than 2.0 during warfarin therapy and the need for continuing anticoagulant therapy to prevent stroke in high-risk patients, even if the strategy is rhythm control. Hemorrhagic complications can be minimized by stringent control of the international normalized ratio (particularly in elderly patients) and appropriate therapy for comorbidities such as hypertension, gastric ulcer, and early-stage cancers. Undertreatment of patients with AF is a continuing problem, particularly in the elderly population. Patients perceived as likely to be noncompliant, such as the functionally impaired, are less likely to receive warfarin therapy. However, stroke prevention with anticoagulants is cost-effective and improves quality of life, despite the challenges of maintaining appropriate anticoagulation with monitoring and warfarin dose titration. New medications in development with more predictable dosing and fewer drug-drug interactions may reduce the complexities of achieving optimal anticoagulation and increase the practicality of long-term anticoagulant therapy for patients with AF at risk of stroke.

    Title Epidemiology and Management of New-onset Atrial Fibrillation.
    Date June 2004
    Journal The American Journal of Managed Care
    Excerpt

    Atrial fibrillation (AF) is a common acute or chronic cardiac disorder that can result in significant morbidity and mortality. Its incidence in the United States is increasing. Projections suggest that more than 5.6 million Americans (50% of whom will be > or =80 years of age) will have AF by 2050. The American College of Cardiology, American Heart Association, and the European Society of Cardiology define AF as a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. On an electrocardiogram, AF is characterized by the replacement of P waves by rapid oscillations or fibrillatory waves that vary in size, shape, and timing. Evidence suggests that histological changes exist in the atria of patients with AF, however, it is not known if these changes are a cause or a consequence of AF. Although the fundamental mechanism underlying the disorder is not known, clinical identifying factors are associated with the condition. These may be divided into noncardiac (thyrotoxicosis, alcohol use, electrolyte imbalance, certain pharmacologic and recreational drugs) and cardiac causes (any cause of enlarged left atrium, poor ventricular function, heart surgery). The principles of treatment for this condition are to stabilize the patient hemodynamically, simultaneously determine whether a reversible cause of the AF exists, control the patient's heart rate, determine whether the patient should be cardioverted or maintained in AF, and then develop strategies to prevent the most important complications of stroke. This article will describe in detail the acute management of AF as well as its epidemiology.

    Title Tissue Factor Pathway Inhibitors As a Novel Approach to Antithrombotic Therapy.
    Date January 2004
    Journal Drug News & Perspectives
    Excerpt

    Tissue factor is the initiator of the extrinsic pathway of the coagulation cascade. It is expressed by endothelial cells when stimulated by cytokines and other mediators. The effect of tissue factor is physiologically balanced by tissue factor pathway inhibitor. Atherosclerotic plaques are rich in tissue factor. It stimulates thrombus formation when plaques rupture. The emerging role of tissue factor in cellular signaling and in the pathogenesis of atherosclerosis has directed attention to inhibitors of tissue factor as a new antithrombotic approach. In comparison to currently used anticoagulants, tissue factor pathway inhibitors have the potential advantage of inhibiting the coagulation cascade at its earliest stage. These agents also act locally at the site of endothelial injury with minimal disturbance of systemic hemostasis. In addition, their inhibitory effect on neointimal formation and restenosis after vascular intervention are appealing features in the management of the complications of atherosclerosis.

    Title Anticoagulation in the Elderly.
    Date November 2003
    Journal The American Journal of Geriatric Cardiology
    Excerpt

    This review will address the general approach to the management of the typical elderly patient requiring anticoagulation. Most of the data has been derived from studies of patients with nonvalvular atrial fibrillation. Data from postmyocardial infarction trials have also been included. A practical clinical approach to anticoagulation in the elderly is described. Emphasis has been placed on maximizing the benefit and reducing the risk of anticoagulation in the rapidly expanding group of elderly patients aged >/=75 who are at the greatest risk of stroke and are likely to benefit the most from antithrombotic therapy.

    Title Dietary Lipid Lowering Modifies Plaque Phenotype in Rabbit Atheroma After Angioplasty: a Potential Role of Tissue Factor.
    Date November 2003
    Journal Circulation
    Excerpt

    BACKGROUND: Tissue factor (TF), the main initiator of blood coagulation, is involved in cellular migration and angiogenesis processes. TF is expressed strongly in lipid-rich plaques and probably plays an important role in the thrombotic complications of plaque rupture. This study analyzes the effect of dietary lipid lowering on TF expression and cellular modifications in angioplasty-induced rabbit plaque rupture. METHODS AND RESULTS: After experimental plaque rupture by balloon angioplasty in atheromatous rabbits, animals were assigned a 0.2% or a 2% cholesterol diet, and the TF content of arterial wall and the associated histological modifications were analyzed after 4 weeks. Early effects of lipid lowering were observed: The increase of TF expression in the vascular wall was stronger in the 2% than in the 0.2% cholesterol diet group (iliac arteries: 1226+/-308 versus 72+/-29 mU TF/g artery, P<0.005). Immunohistochemistry indicated that TF expression was associated with sprout of neovessels, which was more pronounced in the 2% than in the 0.2% cholesterol group. CONCLUSIONS: This study shows that dietary lipid lowering decreases the thrombotic potential of ruptured atherosclerotic plaques through TF decrease. Moreover, high TF expression is associated with marked angiogenesis in the vascular wall, which is reduced by lipid lowering. These results provide further arguments for strong dietary lipid lowering to reduce plaque instability and thrombogenicity.

    Title Comparison of Sotalol Versus Amiodarone in Maintaining Stability of Sinus Rhythm in Patients with Atrial Fibrillation (sotalol-amiodarone Fibrillation Efficacy Trial [safe-t]).
    Date August 2003
    Journal The American Journal of Cardiology
    Excerpt

    The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

    Title Anticoagulation in Management of Atrial Fibrillation.
    Date May 2003
    Journal Current Opinion in Cardiology
    Excerpt

    Atrial fibrillation is the most common cardiac arrhythmia in adults. The prevalence of atrial fibrillation rises with age, reaching as high as 9% in those 70 years and older. Currently there are 2.2 million affected people in the United States, with twice the mortality rate of age-matched controls in sinus rhythm. Epidemiologic studies show atrial fibrillation to be responsible for as many as 15% of the total number of strokes, a higher incidence of dementia, cardiac function compromise, and decreased quality of life. Recent studies indicate that rate control and rhythm restoration are equally effective strategies in the treatment of atrial fibrillation, with a trend toward better survival in patients treated for rate control and anticoagulation. Data from several randomized controlled studies on stroke prophylaxis provided consistent evidence of the superiority of adjusted-dose warfarin over aspirin. Guidelines developed by the American College of Cardiology, the American Heart Association, the European Society of Cardiology, and ACCP provide a convenient decision-making framework for the practicing physician. The safety and effectiveness of anticoagulation in clinical practice were found to be equal to those in major trials with rigorous controls. Despite the proven effectiveness and safety of oral anticoagulation for thromboembolism prophylaxis in atrial fibrillation, warfarin remains underused, especially among the elderly (75 years and older), who are at the greatest risk of stroke and would likely benefit the most from prophylactic anticoagulation.

    Title Neuroprotective Effects of Statins May Not Be Related to Total and Low-density Lipoprotein Cholesterol Lowering.
    Date January 2003
    Journal The American Journal of Cardiology
    Title Cholesterol-induced Thrombogenicity of the Vessel Wall: Inhibitory Effect of Fluvastatin.
    Date January 2003
    Journal Thrombosis and Haemostasis
    Excerpt

    High cholesterol levels are a known risk factor for coronary events. The molecular links between high serum cholesterol and the increased thrombogenicity of the arterial wall are still matter of investigation. In the present study we investigate the relationship between plasma cholesterol, thrombus formation and TF expression in a atherosclerotic rabbit model. Hypercholesterolemic rabbits showed a pronounced TF staining as well as NF-kappaB activation in the aortic arch. A consistent vessel wall platelet deposition was also observed. Treatment with fluvastatin reduced lipid accumulation, TF overexpression (-60%), NF-kappaB activation, and platelet deposition (-56%). In vitro studies showed that the drug upregulated IkappaB alpha in unstimulated as well as in TNFalpha-stimulated cells and also impaired the TNFalpha-induced Cdc42 prenylation, indicating that fluvastatin interferes with the transcriptional activation of TF gene. These results indicate that the prothrombotic phenotype of arterial wall, associated with elevated serum cholesterol levels, is mediated by TF overexpression. Fluvastatin treatment reduces the prothrombotic tendency by inhibiting TF synthesis.

    Title Anticoagulation Management of Valve Replacement Patients.
    Date July 2002
    Journal The Journal of Heart Valve Disease
    Excerpt

    Anticoagulation regimens vary according to surgeon, nature of the valve (mechanical or biological), its position and other risk factors for stroke. The American College of Chest Physicians (2001) have made the following recommendations to protect patients with prosthetic heart valves from developing a stroke: (i) For mechanical heart valves: Anticoagulation with Warfarin at an INR range 2-3 for patients with a bileaflet mechanical valve in the aortic position; (ii) in the mitral position, an INR of 2.5-3.5 is recommended; an alternative recommendation is an INR of 2-3 in combination with aspirin (80 mg/day); and (iii) in patients with a mechanical valve and a history of systemic embolization, an INR of 2.5-3.5 combined with low-dose aspirin (80-100 mg) is recommended; when Warfarin therapy is initiated, the doses for patients aged <70 years is 4 mg, and for patients aged >70 years it is 3 mg. While it is important to recognize that the therapeutic range for Warfarin is narrow, recommendations have also been established to manage patients with high INRs and for the temporary discontinuation of anticoagulant therapy when they undergo surgical procedures. Rapid anticoagulation can be achieved either with unfractionated heparin or with low-molecular weight heparin (LMWH). Heparin is initiated with an intravenous bolus of 80 U/kg bodyweight, and an infusion of 18 U/kg/h. The activated thromboplastin time should be 60-80 s. An alternative to intravenous heparin is subcutaneous LMWH, which is prescribed in a mg/kg dose. In the event of valve thrombosis in patients who are hemodynamically unstable, surgical exploration with thrombectomy is indicated, with or without valve replacement. In patients who are hemodynamically stable, thrombolytic therapy is recommended initially.

    Title Fluvastatin Reduces Tissue Factor Expression and Macrophage Accumulation in Carotid Lesions of Cholesterol-fed Rabbits in the Absence of Lipid Lowering.
    Date May 2002
    Journal Arteriosclerosis, Thrombosis, and Vascular Biology
    Excerpt

    The expression of tissue factor (TF), mainly by infiltrated inflammatory cells, has been shown to be responsible for the thrombogenicity associated with atheroma. The contribution of the nonlipid-related effects of statins to the clinical benefits of statin therapy is currently under intense investigation. In this study, we evaluated the ability of fluvastatin to modulate TF expression and macrophage accumulation in rabbit carotid intimal lesions independently of cholesterol lowering. Male rabbits were fed for 30 days a 1% cholesterol-rich diet with or without fluvastatin at 5 mg/kg per day. Two weeks from the start of treatment, a silastic collar was placed around the carotid artery. Fifteen days later, the animals were killed, and carotid segments were excised and processed. The atherogenic diet caused a consistent increase in plasma cholesterol levels (610+/-231 mg/dL versus 50+/-9 mg/dL at baseline), which were not affected by fluvastatin (603+/-248 mg/dL). In the rabbits fed a high cholesterol diet without fluvastatin, an intimal lesion with macrophage accumulation and TF expression was detected. Fluvastatin significantly reduced TF and macrophage content of the lesion (-50% for both). Results indicate that fluvastatin may attenuate the inflammatory and thrombogenic potential of atherosclerotic lesions through a mechanism(s) other than cholesterol reduction, providing new insight regarding the complex mode of action of statins.

    Title Department of Veterans Affairs Cooperative Studies Program Clinical Trial Comparing Combined Warfarin and Aspirin with Aspirin Alone in Survivors of Acute Myocardial Infarction: Primary Results of the Champ Study.
    Date February 2002
    Journal Circulation
    Excerpt

    BACKGROUND: Both aspirin and warfarin when used alone are effective in the secondary prevention of vascular events and death after acute myocardial infarction. We tested the hypothesis that aspirin and warfarin therapy, when combined, would be more effective than aspirin monotherapy. Methods and Results- We conducted a randomized open-label study to compare the efficacy of warfarin (target international normalized ratio 1.5 to 2.5 IU) plus aspirin (81 mg daily) with the efficacy of aspirin monotherapy (162 mg daily) in reducing the total mortality in 5059 patients enrolled within 14 days of infarction and followed for a median of 2.7 years. Secondary end points included recurrent myocardial infarction, stroke, and major hemorrhage. Four hundred thirty-eight (17.3%) of 2537 patients assigned to the aspirin group and 444 (17.6%) of 2522 patients assigned to the combination group died (log-rank P=0.76). Recurrent myocardial infarction occurred in 333 patients (13.1%) taking aspirin and in 336 patients (13.3%) taking combination therapy (log-rank P=0.78). Stroke occurred in 89 patients (3.5%) taking aspirin and in 79 patients (3.1%) taking combination therapy (log-rank P=0.52). Major bleeding occurred more frequently in the combination therapy group than in the aspirin group (1.28 versus 0.72 events per 100 person years of follow-up, respectively; P<0.001). There were 14 individuals with intracranial bleeds in both the aspirin and combination therapy groups. CONCLUSIONS: In post-myocardial infarction patients, warfarin therapy (at a mean international normalized ratio of 1.8) combined with low-dose aspirin did not provide a clinical benefit beyond that achievable with aspirin monotherapy.

    Title Report of the Naspe/nhlbi Round Table on Future Research Directions in Atrial Fibrillation.
    Date February 2002
    Journal Pacing and Clinical Electrophysiology : Pace
    Title Report of the Naspe/nhlbi Round Table on Future Research Directions in Atrial Fibrillation. North American Society of Pacing and Electrophysiology.
    Date October 2001
    Journal Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing
    Title Central Clinical Research Issues in Electrophysiology: Report of the Naspe Committee.
    Date September 2001
    Journal Pacing and Clinical Electrophysiology : Pace
    Excerpt

    This article contains the results of an attempt by appointed members of the North American Society of Pacing and Electrophysiology to define the research frontier in electrophysiology and suggest areas of study as an aid in setting the research agenda.

    Title Exercise Tolerance and Quality of Life in Elderly Patients with Chronic Atrial Fibrillation.
    Date August 2001
    Journal Journal of Cardiovascular Pharmacology and Therapeutics
    Excerpt

    BACKGROUND: Atrial fibrillation is the most common arrhythmia affecting the elderly. Although the risk of cardioembolic stroke is well defined, the effects of chronic atrial fibrillation on exercise tolerance and quality of life have been less well quantified. Methods: We compared a group of 52 elderly patients with chronic atrial fibrillation to a group of 48 control patients in sinus rhythm. Each patient underwent an interview that incorporated the Short Form-36 Health Survey (SF-36) to quantify individual perceptions on quality of life. In addition each person underwent physiologic testing that included a Modified Bruce Protocol exercise tolerance test, 24-hour ambulatory monitor test, and an echocardiogram. RESULTS: Both groups were elderly, 77 vs 76 years of age (P=0.35). The two groups had similar ejection fractions, 55.4% vs 58.4% (P=0.10). The atrial fibrillation patients demonstrated a higher level of comorbidity based on the Charlson Comorbidity Index, 2.46 vs 1.57 (P=0.03). On formal exercise testing there was no statistical difference in exercise duration between the two groups 9.0 vs 10.1 minutes (P=0.24). Similarly the Physical Summary Score (PCS) and the Mental Summary Score (MCS) of the SF-36 quality of life survey did not demonstrate a statistical difference between the two groups. PCS: 43.0 vs 45.9 (P=0.24); MCS: 52.5 vs 55.7 (P=0.07). CONCLUSIONS: Despite a higher level of comorbidity, elderly, ambulatory patients with chronic atrial fibrillation demonstrate similar exercise tolerance and report similar quality of life to a group of age-matched control patients in sinus rhythm. There is a cohort of patients in chronic atrial fibrillation in whom a strategy of rate control and anticoagulation may be appropriate.

    Title Atorvastatin for Acute Coronary Syndromes.
    Date August 2001
    Journal Jama : the Journal of the American Medical Association
    Title Beneficial Effect of Glycoprotein Iib/iiia Inhibitor (az-1) on Endothelium in Escherichia Coli Endotoxin-induced Shock.
    Date July 2001
    Journal Critical Care Medicine
    Excerpt

    OBJECTIVE: To investigate the effects of AZ-1, a murine monoclonal antiglycoprotein-IIb/IIIa antibody, on endothelium and on hemostasis in a rabbit endotoxic shock model. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Thirty-five male New-Zealand rabbits. INTERVENTIONS: In vitro vascular reactivity, endothelium CD31-PECAM1 immunohistochemistry, plasma coagulation factors, and monocyte tissue factor determination were performed 1 day and/or 5 days after onset of endotoxic shock (0.5 mg/kg, intravenous bolus,Escherichia coli lipopolysaccharide) with or without treatment by AZ-1 (0.5 mg/kg intravenously) given 1 hr after lipopolysaccharide injection. MEASUREMENTS AND MAIN RESULTS: Metabolic acidosis and coagulation activation confirmed the presence of shock. AZ-1 treatment improved endothelial-dependent relaxation at 1 day (maximal effect = 87.2 +/- 4.0% vs. 60.9 +/- 5.2% in the nontreated group, p <.05) and at 5 days (maximal effect = 84.5 +/- 3.5% vs. 56.6 +/- 8.2% in the nontreated group, p <.05). Endotoxin-induced endothelial injury was decreased significantly by AZ-1 at 1 day (6.4 +/- 1.9% vs. 10.3 +/- 0.8% in the nontreated group, p <.05) and at 5 days (6.3 +/- 2.0% vs. 20.2 +/- 1.2% in the nontreated group, p <.05). Monocyte tissue factor expression was significantly reduced at 5 days. CONCLUSIONS: These data indicate that potent inhibition of platelet function via antiglycoprotein-IIb/IIIa receptor blockade can inhibit coagulation activation and protect against endothelial dysfunction and histologic injury in endotoxin-induced shock.

    Title Atrial Fibrillation: Are There Gender Differences?
    Date June 2001
    Journal The Journal of Gender-specific Medicine : Jgsm : the Official Journal of the Partnership for Women's Health at Columbia
    Excerpt

    The incidence of atrial fibrillation is greater in men than in women, but this gap closes with advancing age. More women with atrial fibrillation have underlying valvular disease, and more men with this condition have underlying coronary artery disease. Atrial fibrillation increases mortality and the incidence of stroke in both sexes. However, women in particular (especially those over 75 years old) may be at increased risk for embolism and long-term mortality. Gender is also an important feature affecting the selection of antiarrhythmic drugs for atrial fibrillation, because women are more likely to develop drug-induced arrhythmias. Stroke prevention with anticoagulation in chronic atrial fibrillation is a priority in both men and women; however, women derive the most benefit from it.

    Title Effects of Atorvastatin on Early Recurrent Ischemic Events in Acute Coronary Syndromes: the Miracl Study: a Randomized Controlled Trial.
    Date April 2001
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. OBJECTIVE: To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. DESIGN AND SETTING: A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. PATIENTS: A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. INTERVENTIONS: Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. MAIN OUTCOME MEASURES: Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. RESULTS: A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 events; P =.045). In the atorvastatin group, mean low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P<.001). CONCLUSION: For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.

    Title Approach to Management of the Patient over Age 75 with Atrial Fibrillation.
    Date April 2001
    Journal Cardiology in Review
    Excerpt

    This article will address the general approach to management of the typical patient >75 years of age with atrial fibrillation. Emphasis will be placed on optimizing the benefit and reducing the risk of anticoagulation in this important and expanding group of patients.

    Title Local Treatment with Recombinant Tissue Factor Pathway Inhibitor Reduces the Development of Intimal Hyperplasia in Experimental Vein Grafts.
    Date March 2001
    Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
    Excerpt

    BACKGROUND: Tissue factor (TF)-initiated thrombin generation has been implicated in the development of intimal hyperplasia after arterial injury. An increase in intimal TF expression has been shown to precede the development of intimal hyperplasia in vein grafts. This study examines the effects of local treatment with recombinant human tissue factor pathway inhibitor (rTFPI) in experimental vein grafts. METHODS: Thirty-six male New Zealand white rabbits underwent bypass grafting of the carotid artery by use of the reversed ipsilateral jugular vein and were divided into four groups. Twenty animals had ex vivo incubation with rTFPI treatment (50 microg x mL(-1); n = 10) or placebo vehicle (control; n = 10). Sixteen animals received both ex vivo incubation and in vivo gel treatment with rTFPI (50 microg. mL(-1); n = 8) or without rTFPI (gel-control; n = 8). After operation, vein grafts were harvested at 3 days for immunohistochemical and Western analyses and at 28 days for histomorphologic study. RESULTS: Western analysis demonstrated a 6.2-fold reduction in the expression of TF protein with rTFPI treatment in comparison to without rTFPI treatment. CD-18 leukocyte staining was diminished, whereas Tie-2 endothelial staining was increased in all rTFPI-treated vein grafts, compared with control and gel-control vein grafts. Intimal thickness was reduced by 21% with ex vivo rTFPI treatment compared with placebo (69 +/- 4 versus 87 +/- 5 microm; P <.05) and by 30% with the addition of rTFPI in vivo compared with gel-control (60 +/- 4 versus 86 +/- 5 microm; P <.01). CONCLUSION: Local administration of rTFPI exerts early beneficial effects and limits the development of intimal hyperplasia in vein grafts. Therefore blocking TF-mediated pathway may offer new therapeutic options to reduce vein graft failure.

    Title Detection of Deep Venous Thrombosis by Dmp 444, a Platelet Iib/iiia Antagonist: a Preliminary Report.
    Date December 2000
    Journal Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology
    Excerpt

    BACKGROUND: We report a method for detection of deep venous thrombosis with a technetium 99m-labeled peptide (DMP 444). The N-methyl-arginine-glycine-aspartic acid sequence on DMP 444 binds the glycoprotein IIb/IIIa receptor on activated platelets (inhibition constant [IC50] for fibrinogen binding = 6 nmol/L). METHODS: DMP 444 (23 to 27 mCi) was injected into 11 patients with clinical suspicion of deep venous thrombosis, diagnostic confirmation by ultrasound, and a positive D-dimer test result. Planar images in the anterior and posterior projections were obtained at 10 to 40 minutes, 50 to 80 minutes, and 120 to 150 minutes after injection. RESULTS: No clinically significant adverse effects were noted after DMP 444 administration. One patient (excluded from the analysis) withdrew consent, so image acquisition was not complete. By 10 to 40 minutes after injection, 8 of 10 patients demonstrated an area of increased activity that was clearly related to the abnormality noted on ultrasound. Most patients were taking warfarin (Coumadin) and heparin (n = 8) or heparin (n = 1) and warfarin (n = 1) alone at the time of the imaging. The average time from onset of symptoms to injection of DMP 444 was 5 days (range 1 to 18 days). CONCLUSION: These preliminary human studies indicate that DMP 444 is safe and may be of value in the diagnosis of deep venous thrombosis.

    Title Anticoagulation Therapy for Atrial Fibrillation and Coronary Disease.
    Date September 2000
    Journal Journal of Thrombosis and Thrombolysis
    Title Management of Arrythmias.
    Date September 2000
    Journal Clinics in Geriatric Medicine
    Excerpt

    The management of arrhythmias in elderly patients with congestive heart failure, including atrial fibrillation, ventricular tachyarrhythmias, and bradyarrhythmias, is described. Patients with atrial fibrillation can be treated with rate control anticoagulation for stroke prevention or by attempt at cardioversion and maintenance of sinus rhythm. Elderly patients remaining in atrial fibrillation benefit from anticoagulation provided that no contraindication exists. In patients surviving malignant ventricular arrhythmias, defibrillator implantation is beneficial in elderly patients with heart failure. Prognosis and treatment of nonsustained arrhythmias depends on the presence of underlying cardiac abnormalities. In the healthy elderly population, treatment is not indicated. In patients with coronary artery disease, decreased ejection fraction, and nonsustained ventricular tachycardia, electrophysiology can further stratify risk, and defibrillator implantation can improve survival if arrhythmias are induced. This benefit is as great in elderly patients as in younger patients. Symptomatic bradycardias are increasingly common with advancing age. Symptoms are improved with pacing, with maximum benefit from physiologic rather than ventricular pacing. Although the elderly population poses a unique challenge when faced with arrhythmias, an active approach not only saves lives but also reduces morbidity.

    Title Basic Fibroblast Growth Factor Increases Tissue Factor Expression in Circulating Monocytes and in Vascular Wall.
    Date May 2000
    Journal Circulation
    Excerpt

    BACKGROUND: Basic fibroblast growth factor (bFGF) promotes vascular repair and angiogenesis and can induce in vitro tissue factor (TF), a potent agent initiating thrombogenesis, which probably plays a role in angiogenesis. We investigated whether bFGF administration induced TF expression by monocytes and vascular cells. METHODS AND RESULTS: We studied TF expression in normally fed (n=16) and cholesterol-fed (2% for 6 weeks, n=16) rabbits. Animals were then randomized to receive intravenous bFGF (2.5 microg twice weekly for 3 weeks) or saline injections. TF expression was evaluated in mononuclear cells from arterial blood and in aortic sections by an immunohistochemical assay using a monoclonal anti-rabbit TF antibody (activator protein 1). Monocyte TF expression was increased by bFGF administration in both normal and hypercholesterolemic rabbits (129+/-45 versus 19+/-3 mU TF/1000 monocytes, P<0.05, and 31+/-12 versus 7+/-1 mU TF/1000 monocytes, P<0.005, respectively) and was further increased by stimulation of monocytes by endotoxin in vitro. TF expression was lower in hypercholesterolemic rabbits than in normal rabbits. In the media of the vascular wall, bFGF induced strong TF expression in normal rabbits and only weak TF expression in hypercholesterolemic ones. CONCLUSIONS: This study demonstrates that systemic administration of bFGF induces an impressive increase of TF expression in circulating monocytes and in the vascular wall in normal and to a lower extent in hypercholesterolemic rabbits. The significance of this observation in terms of inducing thrombosis in vivo needs clarification.

    Title Clinical Implication of Antiembolic Trials in Atrial Fibrillation and Role of Transesophageal Echocardiography in Atrial Fibrillation.
    Date February 2000
    Journal Current Opinion in Cardiology
    Excerpt

    Risk for stroke in patients with atrial fibrillation (AF) is highly heterogeneous. Increasing age, history of diabetes, hypertension, previous transient ischemic attack or stroke, and poor ventricular function are independent risk factors for stroke in patients with AF. Accordingly, some groups of patients with AF have low risk and some have high risk. In general, patients at high risk benefit most from anticoagulation therapy with warfarin. In general, if a patient is younger than 65 years of age and has none of the defined risk factors, the stroke rate without prophylaxis (aspirin or warfarin) is low. In patients 65 to 75 years of age with no risk factors, the risk for stroke is low with either aspirin or warfarin therapy; the choice is left to the caretaking physician. All patients older than 75 years and all patients of any age who have risk factors obtain striking benefit from the use of anticoagulation with warfarin. This benefit far outweighs any risk for major hemorrhage.

    Title Atrial Fibrillation: the Epidemic of the New Millennium.
    Date September 1999
    Journal Annals of Internal Medicine
    Title Alternate-day Dosing of Aspirin in Atrial Fibrillation: A Critical Evaluation.
    Date July 1999
    Journal American Heart Journal
    Title Pharmacological Control of Rate and Maintenance of Sinus Rhythm.
    Date June 1999
    Journal Journal of Thrombosis and Thrombolysis
    Title Preventing Stroke in Patients with Atrial Fibrillation.
    Date May 1999
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Atrial fibrillation, a common disorder that affects nearly one sixth of the population aged 75 years and older, is a major risk factor for stroke. OBJECTIVES: To review and evaluate the evidence supporting the use of warfarin and/or aspirin for stroke prevention in patients with atrial fibrillation. DATA SOURCES: Prospective, randomized trials of patients with atrial fibrillation evaluating either warfarin or aspirin or both, from MEDLINE from January 1, 1966, to February 23, 1999. STUDY SELECTION: Five primary prevention placebo-controlled studies, which had been formally pooled, 1 study evaluating secondary prevention of stroke, 1 study comparing warfarin with aspirin, and 3 studies of warfarin in combination with aspirin were identified. DATA SYNTHESIS: The risk of developing stroke is heterogeneous and increases with each decade above 65 years; history of high blood pressure, diabetes mellitus, previous transient ischemic attack, or stroke; poor ventricular function; and in women older than 75 years. For patients younger than 65 years, without risk factors, and not receiving antithrombotic therapy, the risk of stroke is 1%/y; those without risk factors between the ages of 65 and 75 years have a risk of 1.1%/y if taking warfarin and 1.4%/y if taking aspirin. For all other patients, stroke risk is reduced from an untreated rate of between 4.3%/y and more than 12%/y to a rate of 1.2%/y to 4%/y with warfarin use. CONCLUSION: The protection afforded by warfarin is most pronounced in patients at the highest risk for stroke, while aspirin treatment seems adequate in low-risk populations.

    Title Local Delivery of a Tissue Factor Antibody Reduces Early Leukocyte Infiltration but Fails to Limit Intimal Hyperplasia in Experimental Vein Grafts.
    Date January 1999
    Journal The Journal of Surgical Research
    Excerpt

    BACKGROUND. Tissue Factor-mediated thrombin generation involves the generation of VIIa and Xa and has been implicated in the pathogenesis of intimal hyperplasia. In experimental vein grafts, Tissue Factor protein is increased over the first 3 days and colocalized with CD18-positive leukocytes; this increase in Tissue Factor precedes the development of intimal hyperplasia. This study further evaluates the potential role of Tissue Factor in vein graft intimal hyperplasia by directly inhibiting Tissue Factor protein. METHODS. New Zealand white rabbits underwent interpositional bypass grafting of the common carotid artery using the external jugular vein. Perioperatively, murine anti-rabbit Tissue Factor antibody (109 microg/ml gel, 12,500x IC50 of Tissue Factor activity) was applied to the adventitial surface of the graft, using a pluronic gel (30% soln.). Tissue Factor antibody treated vein grafts were compared to control and empty gel-treated vein grafts. Vein grafts were examined at 3 days to assess CD18-positive leukocyte infiltration and the presence of residual antibody by Western blotting. At 28 days, intimal and medial dimensions were quantified using videomorphometry. RESULTS. At day 3, there was marked reduction in CD18-positive leukocytes in the Tissue Factor antibody versus control vein grafts (6.3 +/- 4.7 vs 20.8 +/- 7.4 per 200x field, P < 0.05). At 28 days, intimal hyperplasia was similar for the control (70 +/- 4 microm, mean +/- SEM), gel (73 +/- 4 microm), and Tissue Factor antibody (75 +/- 4 microm) vein grafts. However, medial thickness (76 +/- 4 microm;, P < 0.05) was significantly increased compared to the gel treated vein graft (61 +/- 5 microm). CONCLUSION. Local delivery of pharmacologic doses of an anti-rabbit Tissue Factor antibody decreased CD18-positive leukocyte infiltration but failed to limit intimal hyperplasia in experimental vein grafts. The results suggest that inhibition of Tissue Factor protein modulates polymorphonuclear leukocyte-endothelial interactions but not in the subsequent development of intimal hyperplasia. It implies that the relationship between the extrinsic coagulation cascade and intimal hyperplasia in vein grafts is complex.

    Title Enhanced Monocyte Tissue Factor Response After Experimental Balloon Angioplasty in Hypercholesterolemic Rabbit: Inhibition with Dietary L-arginine.
    Date November 1998
    Journal Circulation
    Excerpt

    BACKGROUND: There is evidence that tissue factor (TF) is a major contributor to the thrombogenicity of a ruptured atherosclerotic plaque. Nitric oxide (NO) has antiatherogenic and antithrombotic properties. We investigated whether L-arginine (L-arg), the endogenous precursor of NO, might affect the ability of monocytes to produce TF. METHODS AND RESULTS: We studied TF expression in 18 rabbits with atherosclerosis induced by bilateral iliac damage and 10 weeks of a 2% cholesterol diet. Six weeks after the initiation of the diet, an angioplasty was performed. After angioplasty, the surviving rabbits (n=15) were randomized to receive L-arg (2.25%) supplementation in drinking water (L-arg group, n=8) or no treatment (untreated group, n=7). TF expression was evaluated in mononuclear cells from arterial blood in the presence and absence of endotoxin stimulation. Monocyte TF expression, as assessed with an amidolytic assay, did not differ significantly before or after the induction of atherosclerotic lesions (87+/-15 versus 70+/-12 mU of TF/1000 monocytes, P=NS). Endotoxin-stimulated TF activity increased significantly 4 weeks after angioplasty (138+/-22 versus 70+/-12 mU of TF/1000 monocytes, P=0.02). This increase was blunted by L-arg (43+/-16 mU of TF/1000 monocytes, P=0.01). CONCLUSIONS: This study demonstrates that angioplasty-induced plaque rupture is associated with a marked increase in monocyte TF response that is blunted by the oral administration of L-arg. This suggests that the documented antithrombotic properties of NO may be related in part to an inhibitory effect on monocyte TF response.

    Title Rationale and Design of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (miracl) Study That Evaluates Atorvastatin in Unstable Angina Pectoris and in Non-q-wave Acute Myocardial Infarction.
    Date April 1998
    Journal The American Journal of Cardiology
    Excerpt

    The goal of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study is to determine whether early, rapid, and profound cholesterol lowering therapy with atorvastatin can reduce early recurrent ischemic events in patients with unstable angina or non-Q-wave acute myocardial infarction. Within 1 to 4 days of hospitalization for one of these conditions, 2,100 patients will be randomly assigned to receive atorvastatin, 80 mg/day, or placebo in a double-blind design. Both groups receive dietary counseling. Over a 16-week follow-up period, the primary outcome measure is the time to occurrence of an ischemic event, defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. Secondary outcome measures are the time to occurrence and incidence of each of the primary outcome components, as well as nonfatal stroke, worsening angina, congestive heart failure requiring hospitalization, and need for coronary revascularization not anticipated before randomization. The sample size of 1,050 patients in each group is expected to provide 95% power to detect a 30% reduction in the primary outcome measure with a 5% level of significance. The results of the MIRACL study will determine the utility of profound cholesterol lowering as an early intervention in acute coronary syndromes.

    Title Modulation of Tissue Factor Protein Expression in Experimental Venous Bypass Grafts.
    Date September 1997
    Journal Arteriosclerosis, Thrombosis, and Vascular Biology
    Excerpt

    Vein graft failure is a major limitation of coronary artery and peripheral vascular surgery. Tissue factor (TF), a transmembrane glycoprotein, generates thrombin by initiating the extrinsic coagulation cascade and plays a major role in the response to arterial injury. This study was designed to examine changes in TF protein expression in response to venous bypass grafting. New Zealand White rabbits underwent interposition bypass grafting of the common carotid artery via the ipsilateral external jugular vein. The contralateral control jugular veins (n = 6), early vein grafts (1 or 3 days after grafting, n = 18), and late vein grafts (14 or 28 days after grafting, n = 8) were examined by immunohistochemistry. The presence or absence of TF immunostaining in the intima was assessed in each vessel quadrant. In control veins, intimal TF staining was present in 5 of 24 vessel quadrants. In early vein grafts, TF staining was markedly increased in the intima (72 of 72 quadrants, P < .001 vs control veins), and TF immunostaining colocalized with CD18-positive leukocytes but not with endothelial cells, vascular smooth muscle cells, or RAM11-positive macrophages. In late vein grafts with intimal hyperplasia, TF expression was low or absent in the intima (6 of 32 quadrants, P < .001 vs early vein grafts; P = NS vs control veins), although medial smooth muscle cells expressed TF. Marked changes in TF expression occur in vein grafts. In early vein grafts, TF protein was greatly increased in the intima for at least 3 days and was associated with CD18-positive leukocytes. In late vein grafts with intimal hyperplasia, however, TF protein was not seen in the intima. These findings may have important implications for the development of therapeutic strategies to limit vein graft failure.

    Title Prevention of Thromboembolism in Patients with Atrial Fibrillation.
    Date March 1997
    Journal Cardiology Clinics
    Excerpt

    New insights into atrial physiology based on observations using transesophageal echocardiography are presented. The approach to anticoagulation of patients with both acute and chronic atrial fibrillation is reviewed within the context of the results of the major multicenter trials. These have provided some useful risk stratification guidelines for therapy. Presently available data suggest that the role of transesophageal echocardiography as a precardioversion screen is promising but requires further definition through clinical trials.

    Title Antithrombotic Potential of Polymer-coated Stents Eluting Platelet Glycoprotein Iib/iiia Receptor Antibody.
    Date February 1997
    Journal Circulation
    Excerpt

    BACKGROUND: Monoclonal anti-rabbit platelet glycoprotein (GP) IIb/IIIa antibody (AZ1) was adsorbed onto cellulose polymer-coated intracoronary stents to enhance their thromboresistance. We evaluated the antithrombotic efficacy of AZ1 antibody-eluting stents. METHODS AND RESULTS: Twenty-three polymer-coated stents with AZ1 antibody bound by passive adsorption (AZ1-eluting) were compared with 23 control polymer-coated stents adsorbed with either no antibody (base-polymer, n = 12) or isotype-matched irrelevant antibody (anti-CMV-eluting, n = 11) by implantation into balloon-damaged, flow-reduced iliac arteries of New Zealand White rabbits. In 13 animals (acute group), flow measurements were made with transit-time flow probes and platelet adhesion was ascertained by use of 111In-labeled autologous platelets. In the other 10 animals (chronic group), stent occlusion was assessed macroscopically after they were killed 28 days after stenting. Arteries with AZ1-eluting stents had significantly less platelet deposition (15.8 +/- 4.5 x 10(7)) than either base-polymer (32.1 +/- 4.3 x 10(7)) or anti-CMV-eluting (35.2 +/- 8.8 x 10(7)) controls (ANOVA, P < .0001). Compared with base-polymer or anti-CMV-eluting controls, arteries with AZ1-eluting stents showed a marked reduction in cyclic blood flow variation (P < .0001) and a significantly greater mean blood flow 2 hours after stent deployment (P < .0001). There was a significant improvement in the patency rate of AZ1-eluting stents compared with controls at both 2 hours (92% versus 46%, P = .034) and 28 days (100% versus 40%, P = .015). CONCLUSIONS: Platelet GP IIb/IIIa antibody eluting from polymer-coated stents reduces platelet deposition, improves blood flow, virtually abolishes cyclic flow variation, and improves patency rates after stent implantation in a rabbit iliac artery model. Its potential for reducing stent-related thrombosis in humans warrants further evaluation.

    Title Monoclonal Antibody Against Tissue Factor Shortens Tissue Plasminogen Activator Lysis Time and Prevents Reocclusion in a Rabbit Model of Carotid Artery Thrombosis.
    Date July 1996
    Journal Circulation
    Excerpt

    BACKGROUND: Tissue factor (TF)-dependent activation of the coagulation is important in the pathophysiology of intravascular thrombus formation. We tested the effects of a monoclonal antibody against TF (AP-1) on lysis time induced by tissue-type plasminogen activator (TPA) and on reocclusion rate in a rabbit model of carotid artery thrombosis. METHODS AND RESULTS: Intravascular thrombosis was obtained by placing an external constrictor around carotid arteries with endothelial injury. Carotid blood flow velocity ws measured continuously with a Doppler flow probe. Thirty minutes after thrombus formation, the rabbits received either AP-1 (0.15 mg/kg IV, n=8) or placebo (n=8). All rabbits also received TPA (80 microg/kg bolus plus 8 microg x kg(-1) x min(-1) infusion for up to 90 minutes or until reperfusion was achieved) and heparin (200 U/kg IV as a bolus). At reperfusion, TPA was discontinued, and the rabbits were followed for an additional 90 minutes. AP-1 shortened lysis time from 44+/-8 minutes (mean+/-SEM) in control rabbits to 26+/-7 minutes in AP-1 rabbits (P<.01). Reocclusion occurred in all control rabbits in 10+/-3 minutes, whereas it occurred in only two of eight AP-1 treated rabbits in 72 and 55 minutes (P<.01). No changes in prothrombin time and ex vivo platelet aggregation in response to various agonists were observed after AP-1 administration, indicating the absence of systemic effects by this antibody. CONCLUSIONS: TF exposure and activation of the extrinsic coagulation pathway play an important role in prolonging lysis time and mediating reocclusion after thrombolysis in this model. AP-1, a monoclonal antibody against TF, might be suitable as adjunctive therapy to TPA.

    Title Aurintricarboxylic Acid Reduces Platelet Deposition in Stenosed and Endothelially Injured Rabbit Carotid Arteries More Effectively Than Other Antiplatelet Interventions.
    Date February 1996
    Journal Thrombosis and Haemostasis
    Excerpt

    In the present study we tested the effects of different antithrombotic interventions on platelet deposition in experimentally-stenotic rabbit carotid arteries with endothelial injury. Platelet deposition, quantitated by labeling autologous platelets with 111In-oxine, was significantly reduced compared to control animals by all interventions tested, i.e., R 68070, a drug with thromboxane A2 synthase and receptor blocking properties, BN 52021, a PAF receptor antagonist, aurintricarboxylic acid (ATA), an inhibitor of platelet glycoprotein (Gp) Ib/von Willebrand factor (vWf) interaction, AZ-1, a monoclonal antibody against rabbit GP IIb/IIIa, the platelet receptor for fibrinogen, and AP-1, a monoclonal antibody against rabbit tissue factor. ATA was significantly more effective than all the other interventions in reducing platelet deposition in the stenotic vessels. We conclude that inhibition of Gp Ib/vWf interaction may be a more suitable target for antithrombotic therapy under conditions of high shear stress, like those produced in this model.

    Title Silent Cerebral Infarction in Patients with Nonrheumatic Atrial Fibrillation. The Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.
    Date November 1995
    Journal Circulation
    Excerpt

    BACKGROUND: Cerebral infarction in patients with atrial fibrillation may vary from being clinically silent to catastrophic. The prevalence of silent cerebral infarction and its effect as a risk factor for symptomatic stroke are important considerations for the evaluation of patients with atrial fibrillation. METHODS AND RESULTS: This Veterans Affairs cooperative study was a double-blind controlled trial designed primarily to determine the efficacy of warfarin for the prevention of stroke in neurologically normal patients with nonrheumatic atrial fibrillation. It also was designed to evaluate patients with silent cerebral infarction. Computed tomography scans of the head were performed at entry, at the time of any subsequent stroke, and at termination of follow-up on all patients who completed the study without a neurological event. Of 516 evaluable scans performed at entry, 76 (14.7%) had evidence of one or more silent cerebral infarcts. Age (P = .011), a history of hypertension (P = .003), active angina (P = .012), and elevated mean systolic blood pressure (P < .001) were associated with the presence of this finding. Silent cerebral infarction occurred during the study at rates of 1.01% and 1.57% per year for the placebo and warfarin treatment groups, respectively (NS). Silent cerebral infarction at entry was not an independent predictor of later symptomatic stroke, but active angina was a significant predictor; 15% of the placebo-assigned patients with angina developed a stroke compared with 5% of the placebo-assigned patients without angina. CONCLUSIONS: Silent cerebral infarction is frequently seen in asymptomatic patients with atrial fibrillation. Age, history of hypertension, active angina, and elevated mean systolic blood pressure were associated with silent infarction at entry. The sample size was too small to determine whether warfarin had an effect on the incidence of silent infarction during the trial. Active angina at baseline was the only significant independent predictor for the later development of symptomatic stroke.

    Title Contemporary Management of Atrial Fibrillation.
    Date October 1995
    Journal The Medical Clinics of North America
    Excerpt

    The incidence of atrial fibrillation approximately doubled for every 10-year increment in age in the Framingham Heart Study cohort; thus physicians will be faced with an increasing patient population with atrial fibrillation. Hypertension is observed to be the most common associated risk factor in both sexes. The management of patients with atrial fibrillation is evolving as a result of a number of published studies. Calcium channel blockers and beta-blockers are emerging as the preferred choices for rate control rather than digoxin. Low-dose anticoagulation therapy has shown beneficial effects not only in primary prevention, but also for secondary prevention of thromboembolism. Thus, patients who cannot be successfully cardioverted should be anticoagulated if there are no contraindications (Table 3) and if they do not fall into the low-risk group--defined as patients under the age of 65 without risk factors (hypertension, diabetes, previous stroke). Patients not eligible for anticoagulation should be on aspirin therapy. Patients with lone atrial fibrillation are not at higher risk for thromboembolism than the general population; therefore, they can be managed without anticoagulation or antiplatelet therapy. Antiarrhythmic treatment should be approached cautiously; amiodarone in low doses is the most effective and safe treatment, but this remains controversial.

    Title Role of Transesophageal Echocardiography in the Detection of Left Atrial Thrombus in Patients with Chronic Nonrheumatic Atrial Fibrillation.
    Date September 1995
    Journal American Heart Journal
    Excerpt

    Transesophageal echocardiography was used to assess cardiac abnormalities associated with embolization in patients who had completed the Department of Veterans Affairs Cooperative Study of Stroke Prevention in Nonrheumatic Atrial Fibrillation at the Minneapolis and West Haven Department of Veterans Affairs Medical Centers without an embolic event. Patients were men, 71 +/- 7 years old, with atrial fibrillation of 6.2 +/- 4.3 years' duration who had received warfarin (n = 32) or placebo (n = 23) for 2 years. Thrombi were found in 5 of 55 patients (warfarin 4 and placebo 1; p = 0.39); spontaneous echo contrast was seen in 4 of 5 patients. Other abnormalities identified included spontaneous echo contrast (47%), patent foramen ovale (54%), atrial septal aneurysm (7.3%), and left ventricular thrombus (3.6%). During 34 months of posttreatment follow-up, 5 patients had a stroke (1 fatal), and 10 died. Potential sources of emboli did not predict subsequent outcome. Thus warfarin therapy did not preclude the presence of thrombi. Stroke reduction likely involves the prevention of emboli from sources in addition to the atrial appendage.

    Title Amlodipine in Chronic Stable Angina: Results of a Multicenter Double-blind Crossover Trial.
    Date March 1995
    Journal American Heart Journal
    Excerpt

    The efficacy and safety of amlodipine, 10 mg, a new long-acting calcium antagonist, was compared with placebo in 103 patients with stable angina pectoris in a multicenter double-blind crossover study. The trial consisted of an initial 2-week single-blind placebo period followed by a first period of 4 weeks of double-blind therapy, which was followed by a 1 week washout period and then a second 4-week double-blind period after treatments were crossed over. Twenty-four-hour Holter electrocardiographic monitoring was carried out in 12 patients at three centers. In the first double-blind period amlodipine produced a significantly greater increase in symptom-limited exercise duration (amlodipine 478.5 to 520.6 vs placebo 484.6 to 485.2 seconds; change +8.8% vs +0.1%, respectively; p = 0.0004) and total work (amldipine 2426 to 2984 vs placebo 2505 to 2548 kilopondmeters; change +24% vs +1.7%, respectively; p = 0.0006) and a decrease in angina attack frequency (from 3 to 1 per week; p = 0.016) and nitroglycerin consumption (from 2 to 0.5 tablets/wk; p = 0.01) compared with placebo. Holter monitoring revealed significant reductions in numbers (amlodipine 4.65 to 2.22 vs placebo 1.84 to 1.54; change -52% vs +84%, respectively; p = 0.06), absolute total area (amlodipine 87.66 to 11.43 vs placebo 5.76 to 35.24; change -87% vs +513%, respectively; p = 0.02), and duration (amlodipine 12.29 to 2.95 vs 1.66 to 7.74 seconds; change -76% vs +367%, respectively; p = 0.008) of ST-segment depressions after treatment with amlodipine compared with placebo. After the treatments were crossed over changes continued to favor amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Preparation, Characterization, and Evaluation of a Monoclonal Antibody Against the Rabbit Platelet Glycoprotein Iib/iiia in an Experimental Angioplasty Model.
    Date August 1994
    Journal Circulation Research
    Excerpt

    The deposition of platelets at the site of balloon angioplasty is thought to play a major role in the pathogenesis of restenosis. The antibody AZ-1, which binds to the rabbit platelet glycoprotein IIb/IIIa receptor and inhibits platelet function both in vitro and in vivo, was produced and tested in an experimental model of angioplasty. Atherosclerosis was induced by desiccation injury of the femoral artery, followed by a 28-day diet with 2% cholesterol and 6% peanut oil. Rabbits were randomized to receive an infusion of saline, a single infusion of 0.5 mg/kg of AZ-1, or an infusion of 0.6 mg/kg AZ-1 before angioplasty. The latter group received a second infusion of 0.6 mg/kg 72 hours later. Functional platelet inhibition was demonstrated by prolongation of the bleeding time in all treated animals. Angiography was performed at baseline, immediately after a standardized angioplasty, and again 28 days after angioplasty on a total of 42 vessels. There were no significant differences between the antibody-treated group and the control group in the mean angiographic minimum luminal diameter at any of the time points. There was also no difference in the initial improvement after angioplasty (acute gain), in the decrease in luminal diameter from immediately after angioplasty to 28 days after angioplasty (late loss), or in the overall improvement from before angioplasty to 28 days after angioplasty. Quantitative histological analysis confirmed the lack of a beneficial effect of AZ-1. There were no significant differences in the area of the intima, the media, or the combined intima and media between the antibody-treated groups and the control group. Thus, potent platelet inhibition for up to 6 days after balloon angioplasty using a monoclonal antibody that inhibits platelet aggregation did not reduce the response to vascular injury after balloon angioplasty in this rabbit model of experimental atherosclerosis.

    Title Stroke Prevention in Atrial Fibrillation Ii Study.
    Date July 1994
    Journal Lancet
    Title Imaging Techniques for Identifying Left Ventricular Thrombi.
    Date April 1994
    Journal American Journal of Cardiac Imaging
    Title Potentiation of the Vasospastic Response to Angioplasty by Pretreatment with Fluoxetine. A Study in the Atherosclerotic Rabbit.
    Date June 1993
    Journal Arteriosclerosis and Thrombosis : a Journal of Vascular Biology / American Heart Association
    Excerpt

    There is evidence that angioplasty-induced vasospasm is mediated by serotonin (5-hydroxytryptamine [5-HT]) release from platelets. We tested the hypothesis that pretreatment of the atherosclerotic rabbit with fluoxetine, a platelet-uptake inhibitor of 5-HT, would reduce vasospasm after balloon angioplasty. Short-term administration of fluoxetine reduced platelet 5-HT uptake to 4% of baseline. Daily administration of fluoxetine for 7 days reduced whole-blood 5-HT levels to 28% of baseline. Thus, fluoxetine inhibited platelet 5-HT uptake in this model as predicted. Contrary to our expectations and despite the substantial reduction in whole-blood 5-HT levels, pretreatment with fluoxetine for 1 week resulted in augmentation of angioplasty-induced vasospasm in atherosclerotic rabbits. Intraperitoneal administration of fluoxetine produced vasoconstriction in normal rabbits that was augmented by 5-HT and not reversed with LY53857, a specific serotonin receptor antagonist. We postulate that this new observation is probably a result of the inhibition of the clearance mechanism for serotonin, with resultant enhancement of the effect of serotonin released by the activated platelets that are deposited on the vessel wall surface at the time of angioplasty. A direct effect of fluoxetine on serotonergic receptors is a second possible mechanism for the observed effect.

    Title Warfarin in the Prevention of Stroke Associated with Nonrheumatic Atrial Fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.
    Date November 1992
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND. Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk. METHODS. We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death. RESULTS. Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history. CONCLUSIONS. Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

    Title Mird Dose Estimate No. 15: Radiation Absorbed Dose Estimates for Radioindium-labeled Autologous Platelets.
    Date May 1992
    Journal Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
    Title South Africa Revisited--lessons to Be Learned from Mistakes in American Health Care Policy.
    Date October 1991
    Journal South African Medical Journal = Suid-afrikaanse Tydskrif Vir Geneeskunde
    Title Technical Variables Influencing the Detection of Acute Deep Vein Thrombosis by Magnetic Resonance Imaging.
    Date October 1991
    Journal Magnetic Resonance Imaging
    Excerpt

    To establish which technical variables influence the detection of deep vein thrombosis by magnetic resonance imaging, 2 dogs, 5 normal volunteers and 17 patients were studied using a 1.5 T whole-body system. A sequential slice gradient echo acquisition (TR 25, TE 13, 0 = 30 degrees, 2 NEX, flow compensation rephasing gradients) in the axial plane was found to be optimal for detecting venous thrombosis. Thus, when using appropriate technique, MRI may identify deep venous thrombosis accurately. It may also allow the diagnosis of conditions which may simulate venous thrombosis clinically since the most common of these, ruptured Baker's cyst, cellulitis, muscle tear, hematoma and external venous compression are all readily identified by MRI.

    Title Effects of Serotonin-receptor Blockade on Angioplasty-induced Vasospasm in an Atherosclerotic Rabbit Model.
    Date June 1991
    Journal Arteriosclerosis and Thrombosis : a Journal of Vascular Biology / American Heart Association
    Excerpt

    Vasospasm occurs both in patients and animal models after angioplasty and may be associated with early closure of the dilated vessel. To investigate the mechanism of angioplasty-induced vasospasm, the effect of serotonin-receptor blockade with two serotonin2 (S2) antagonists, LY53857 and sergolexole, was examined in rabbits with focal femoral artery atherosclerosis. In preliminary studies, local infusion of 1-100 micrograms serotonin caused significant femoral artery vasoconstriction (p less than 0.05) in both normal and atherosclerotic rabbits. There was no significant difference in the degree of vasoconstriction induced by equal doses of serotonin in normal and atherosclerotic animals. Infusion of 10 micrograms serotonin produced a 23 +/- 5% decrease in luminal diameter in atherosclerotic femoral arteries. This was blocked by pretreatment with both S2 inhibitors given separately in different animals before serotonin infusion (p less than 0.002). In contrast, LY53857 (sergolexole was not tested) had no significant effect on phenylephrine-induced vasoconstriction, confirming its specificity as an S2-receptor antagonist. Balloon angioplasty of atherosclerotic vessels caused a significant increase in vessel diameter at the angioplasty site (45% increase from baseline diameter, p less than 0.05). This was associated with significant luminal narrowing both proximal (21% reduction from baseline, p less than 0.05) and distal (17% reduction from baseline, p less than 0.03) to the angioplasty site. These proximal and distal changes are most likely due to vasospasm, as there was no histological evidence of thrombus or dissection at these sites to explain the luminal narrowing. Pretreatment of animals with 10 mg LY53857 or 20 mg sergolexole blocked the proximal vasospasm (2.6 +/- 0.4 before versus 2.2 +/- 0.1mm after angioplasty for LY53857, 2.1 +/- 0.4 before versus 2.1 +/- 0.4 mm after angioplasty for sergolexole; p = NS). Treatment with 20 mg LY53857 inhibited both proximal (2.3 +/- 0.1 before versus 2.2 +/- 0.2 mm after angioplasty, p = NS) and distal (1.7 +/- 0.1 before versus 1.6 +/- 0.2 mm after angioplasty, p = NS) vasospasm after angioplasty. Proximal (2.3 +/- 0.5 before versus 2.5 +/- 0.3 mm after) and distal (1.7 +/- 0.2 before versus 1.7 +/- 0.4 mm after) vasospasm was also prevented by pretreatment with 40 mg sergolexole.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Comparison of Platelet Scintigraphy, Impedance Plethysmography Gray Scale and Color Flow Duplex Ultrasound and Venography for the Diagnosis of Venous Thrombosis.
    Date March 1991
    Journal Progress in Clinical and Biological Research
    Excerpt

    The several techniques available for the diagnosis of venous thrombosis have not been directly compared in the same patient population. Thus color and gray scale duplex ultrasound (U), impedance plethysmography (IPG), 3-4 hr platelet imaging (PS) were compared to venography (V), in 104 consecutive patients (in hospital and out). PS and V were read by two, and IPG and U by one, blinded reader. Comparisons were made for the calf (CA), popliteal (Pop) and femoral (Fem) vessels. Reproducibility of V and PS was 84 and 87%. (table; see text) We conclude that PS, while having a very high specificity, has an unacceptably low sensitivity. However, while both impedance plethysmography and color flow ultrasound have excellent and similar diagnostic accuracy in the femoral, these techniques have either a low sensitivity or low technical success rate in the calf or popliteal veins.

    Title Effect of Lovastatin on Intimal Hyperplasia After Balloon Angioplasty: a Study in an Atherosclerotic Hypercholesterolemic Rabbit.
    Date February 1991
    Journal Journal of the American College of Cardiology
    Excerpt

    Restenosis, the major limitation of balloon angioplasty, is the result of intimal hyperplasia after the procedure. Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitor, may influence intimal hyperplasia by lowering serum cholesterol and by blocking deoxyribonucleic acid (DNA) synthesis. To determine whether lovastatin reduces intimal hyperplasia, a prospective, randomized blinded study was performed in 60 atherosclerotic New Zealand White male rabbits. Atherosclerosis was produced by air desiccation injury followed by a 28 day diet of 2% cholesterol and 6% peanut oil that was terminated before balloon angioplasty was performed. Angioplasty could not be performed in 14 rabbits with bilateral femoral artery occlusion, and in one rabbit the procedure was a technical failure. Forty-five rabbits underwent balloon angioplasty performed with use of a 2.5-mm balloon inflated to 10 atm for three 1 min dilations at 1 min intervals. Seven rabbits died during the procedure. Thirty-eight rabbits were randomized to either a lovastatin group (6 mg/kg body weight per day) or a control group. Angioplasty was performed on all patent vessels (n = 54); the procedure was bilateral in 16 rabbits and unilateral in 22. Fifteen lovastatin-treated and 15 control rabbits survived 39 days after angioplasty and were then killed. Angiograms, obtained before and 10 min and 39 days after balloon angioplasty, were read with use of electronic calipers by two observers who had no knowledge of treatment data. After the rabbits were killed, vessels were pressure perfused using a standardized protocol to maintain in vivo dimensions for blinded quantitative histologic analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Vascular Reactivity After Balloon Angioplasty in an Atherosclerotic Rabbit.
    Date December 1990
    Journal Circulation
    Excerpt

    Alterations in vessel wall reactivity (VR) at or adjacent to the dilation site after balloon angioplasty (BA) may vary according to the inflation protocol and the time after angioplasty and may influence outcome. In 64 atherosclerotic rabbit femoral arteries, we evaluated VR after BA with intravenous ergonovine (ERGO) (40 micrograms/min for 5 minutes) and intra-arterial nitroglycerin (NTG) (2,500 micrograms single bolus) 24-72 hours and 28 days after BA. Comparisons were made with atherosclerotic, nonangioplastied, age-matched controls. BA was standardized to three 1-minute inflations, each 1 minute apart. For each balloon size, 2.5- (appropriate size) or 3.0-mm (oversized) vessels were allocated to either 5 or 10 atm inflation pressure. For the analysis, four groups were compared: Group 1, 3.0/5; group 2, 3.0/10; group 3, 2.5/5, and group 4, 2.5 mm/10 atm. Angiographic diameters were measured at, proximal, and distal to the lesion at baseline, 10 minutes after ERGO, and 5 minutes after NTG. Angiograms were measured with electronic calipers by two blinded observers. All segments of control vessels vasoconstricted to ERGO and vasodilated to NTG (p less than 0.05 versus baseline), indicating a normal response. At 24-72 hours after dilatation, the angioplasty sites for all inflation pressure/balloon size combinations were not responsive to either ERGO or NTG. All segments distal to the dilatation sites vasoconstricted to ERGO and dilated to NTG (p less than 0.05 versus baseline), indicating a normal response. Proximal segments of vessels dilated with a 2.5-mm balloon (appropriate size) responded positively to both stimuli (p less than 0.05). Those vessels dilated with a large balloon (3.0 mm) were nonreactive in the segment proximal to the angioplasty site. Twenty-eight days later angioplasty sites dilated with a 2.5-mm balloon (appropriately sized) regained reactivity; however, segments dilated with a large balloon (3.0 mm) remained unresponsive. All proximal segments, including those from vessels dilated with a large balloon, reacted positively. All distal segments reacted appropriately. Restenosis rates were not different between the over- and appropriately sized balloon groups. These data demonstrate that immediately after angioplasty, vessels lose reactivity at the dilatation site. Those vessels dilated with the smaller-size balloon (2.5 mm) regained reactivity. For large balloons, reactivity is not regained at 28 days. For segments proximal to the site of dilatation, transient loss of reactivity is seen only when a large balloon is used. Thus, acute closure originating at the site of dilatation is not a result of spasm.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Onset of Altered Interventricular Septal Motion During Cardiac Surgery. Assessment by Continuous Intraoperative Transesophageal Echocardiography.
    Date October 1990
    Journal Circulation
    Excerpt

    Abnormal motion of the interventricular septum is frequently observed after uncomplicated cardiac surgery. We sought to elucidate the mechanism underlying this phenomenon by using continuous echocardiographic imaging of the heart from a constant transesophageal location in 21 patients undergoing their first cardiac operation. Quantitative global and regional functional analyses were performed in each patient at baseline (stage 1), after median sternotomy (stage 2), after sternal retraction (stage 3), after pericardiotomy (stage 4), after completion of cardiopulmonary bypass (stage 5), and after chest closure (stage 6). During the first four surgical stages, mean left ventricular fractional shortening varied little among regions with a fixed reference system (maximum range, 31.6-39.2%; p = NS) but changed dramatically after the discontinuation of cardiopulmonary bypass (stage 5). The apparent medial hypokinesis that was observed (4.9 +/- 4.7% [SD]) was accompanied by lateral hyperkinesis (65.2 +/- 4.1%, p less than 0.0001). These regional differences were completely eliminated with a floating reference system (33.6 +/- 2.7% for medial, and 34.8 +/- 1.7% for lateral; p = NS), suggesting cardiac translation. Quantitative curvature analysis supported this conclusion, with preservation of baseline regional curvature seen throughout the procedure. The mean length of individual translational vectors (reflecting systolic movement of the endocardial centroid) remained minimal (less than or equal to 1.0 mm) through stage 4 but increased more than fourfold at stage 5, continuing in a medial direction after chest closure (5.2 +/- 3.0 mm and 271 +/- 6 degrees from anterior). Thus, abnormal postoperative septal motion is not caused by removal of restraining forces of the pericardium or anterior mediastinum but rather appears to be directly related to events occurring during cardiopulmonary bypass.

    Title Should Patients with Large Anterior Wall Myocardial Infarction Have Echocardiography to Identify Left Ventricular Thrombus and Should They Be Anticoagulated?
    Date September 1990
    Journal Cardiovascular Clinics
    Title Identifying Left Ventricular Thrombi.
    Date July 1990
    Journal Clinical Cardiology
    Excerpt

    A number of imaging techniques are available for the identification of left ventricular thrombi. Echocardiography is the technique of choice because of its wide availability, noninvasiveness, and relative low cost. The accuracy of information from echocardiography depends on the skill of the technician and quality of equipment. Platelet scintigraphy, which reflects activity on the thrombus surface, plays a complementary role to echocardiography in detecting thrombi. Magnetic resonance imaging and computed tomography are potentially useful. Contrast ventriculography lacks sensitivity and specificity, and radio nuclide angiography lacks sensitivity in the diagnosis of left ventricular thrombi.

    Title Influence of Inflation Pressure and Balloon Size on the Development of Intimal Hyperplasia After Balloon Angioplasty. A Study in the Atherosclerotic Rabbit.
    Date November 1989
    Journal Circulation
    Excerpt

    To evaluate the effect of balloon size and inflation pressure on acute and subsequent outcome following balloon angioplasty (BA), 70 New Zealand White rabbits with bilateral femoral atherosclerosis were assigned to four groups: group 1, oversized balloon, low inflation pressure (n = 35 vessels; balloon size, 3.0 mm/inflation pressure, 5 atm); group 2, oversized balloon, high inflation pressure (n = 36; 3.0 mm/10 atm); group 3, appropriate size, low inflation pressure (n = 17; 2.5 mm/5 atm); and group 4, appropriate size balloon, high inflation pressure (n = 19; 2.5 mm/10 atm). Angiograms were obtained before, 10 minutes after, and 28 days after BA and read by two blinded observers using electronic calipers. The in vivo balloon-to-vessel ratio was measured for each group. There were eight non-BA controls. Rabbits were sacrificed either immediately (n = 34) or at 28 days after BA (n = 36), with the femoral vessels pressure perfused for histologic and morphometric analysis. The latter was performed at 28 days only. Absolute angiographic diameters increased in all groups immediately after BA (p less than 0.01). Acute angiographic success, defined as greater than 20% increase in luminal diameter, was higher using high inflation pressure (group 2, 32/36 [89%] and group 4, 16/19 [84%] vs. group 1, 23/35 [66%] and group 3, 9/17 [53%]; p less than 0.05). A 3.0-mm balloon resulted in significant oversizing irrespective of inflation pressure (balloon-to-vessel ratio, 1.5 +/- 0.1 vs. 1.1 +/- 0.1 to 1, for the 2.5-mm balloon). Vessels exposed to high inflation pressure had a significantly higher incidence of mural thrombus, dissection (p less than 0.01), and medial necrosis versus low pressure (p less than 0.05). At 28 days, the rates of restenosis (defined as greater than 50% loss of initial gain) were 14/20 (70%), 11/16 (69%), 5/10 (50%), and 5/10 (50%) for groups 1 through 4 (p = NS; a trend in favor of the groups using an oversized balloon). There was an increase in the degree of intimal hyperplasia by morphometric analysis in all groups, being most marked in group 2 (oversized balloon and high inflation pressure, 1.7 +/- 0.9 vs. 0.5 +/- 0.2 mm for controls, p less than 0.001). We reached two conclusions. First, all protocols resulted in a significant increase in luminal diameter immediately after angioplasty with the highest success rate in vessels subjected to high pressure dilatation.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Early Image Acquisition After Administration of Indium-111 Platelets in Clinically Suspected Deep Venous Thrombosis.
    Date August 1989
    Journal The American Journal of Cardiology
    Excerpt

    Indium-111 platelet scintigraphy accurately detects acute deep venous thrombosis in asymptomatic high-risk patients and may be used as a surveillance test. However, its value in symptomatic patients and its accuracy early after platelet injection are not satisfactorily established. The latter is important for timely institution of therapy. Accordingly, 65 patients (67 limbs) with suspected deep venous thrombosis (symptom duration 8 +/- 10 days, mean +/- standard deviation) were prospectively studied with platelet scintigraphy and contrast venography. Platelets were labeled with 405 +/- 101 mCi indium-111 oxine. The labeling efficiency was 80 +/- 10%. All images were acquired within 120 minutes after intravenous administration of the platelet suspension. Both platelet scintigraphy and venography were interpreted independently by 2 blinded observers (for each technique). Five separate analyses were performed. Each scintigraphic reader was compared to each venographic reader. A fifth analysis--consisting of readings with blinded agreement of both readings of the platelet scans and both readings of the venograms--was performed. Interobserver agreement was 92% for venography and 79% for scintigraphy. Excluding anticoagulated patients, the sensitivity of platelet scintigraphy was between 38 and 46% and the specificity was between 92 and 100%. Thus, early imaging of labeled platelets for the diagnosis of symptomatic deep venous thrombosis carries a high specificity but a much lower sensitivity. It is speculated that the low sensitivity is related to the inactivity of the thrombus. This may suggest that early imaging will only be useful in patients whose symptoms are of recent onset.

    Title Does Nitrous Oxide Cause Regional Wall Motion Abnormalities in Patients with Coronary Artery Disease? An Evaluation by Two-dimensional Transesophageal Echocardiography.
    Date July 1988
    Journal Anesthesia and Analgesia
    Title Detection of Acute Allograft Rejection by Indium-111 Labeled Platelet Scintigraphy in Renal Transplant Patients.
    Date March 1987
    Journal Transplantation Proceedings
    Title In Vitro Characteristics and in Vivo Viability of Platelets Contained in Granulocyte-platelet Apheresis Concentrate.
    Date February 1987
    Journal Transfusion
    Excerpt

    A paired prospective study was performed to compare the in vitro storage characteristics and in vivo kinetics of platelets stored in granulocyte-platelet concentrates prepared by apheresis with platelets prepared from whole blood. Platelet and granulocyte-platelet concentrates were collected from five healthy volunteer autologous donors and stored for 16 to 18 hours at 20 to 24 degrees C with and without agitation, respectively. After storage, pH, platelet count, percent release of beta-thromboglobulin, morphologic score, and percent osmotic recovery were measured. In addition, the granulocyte-platelet concentrates were assayed for total leukocyte count, release of lysozyme, and by several in vitro tests of granulocyte function. The platelets in both products were labeled with 111In oxine and infused into the donors. The pH of both products was above 6.0 at the end of storage. The units stored as platelet concentrates compared with those stored as granulocyte-platelet concentrates showed a higher percent release of beta-thromboglobulin, 18.4 +/- 4.0 percent versus 5.9 +/- 3.2 percent (mean +/- SD), but significantly better morphologic scores, 676 +/- 21 versus 525 +/- 56, and better osmotic recovery scores, 72 +/- 10 percent versus 40 +/- 7 percent, respectively (all p less than 0.05). The platelet concentrates (compared with the granulocyte-platelet product) had significantly better in vivo recovery, 49.5 +/- 15.8 percent versus 38.9 +/- 11.5 percent, and survival, 6.1 +/- 1.3 days versus 2.4 +/- 0.4 days, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Potential Application of Labeled Antibodies for Thrombus Detection.
    Date February 1987
    Journal International Journal of Radiation Applications and Instrumentation. Part B, Nuclear Medicine and Biology
    Excerpt

    Labeling platelets with monoclonal antibodies in whole blood for imaging thrombi is less cumbersome than the established 111In-oxine method.. 7E3, a murine monoclonal antibody directed against glycoprotein IIb and/or IIIa on both human and dog platelets was used to label canine platelets. Thrombi were induced by transcatheter placement of a copper coil followed by electrocoagulation. 7E3 was iodinated with 131I and labelled with 111In using 7E3-DTPA conjugate. Whole blood was incubated with 0.5-1.0 micrograms labeled 7E3/mL blood. In 4/4 dogs, experimental deep vein thrombi were identified using both 131I- and In 1/3 dogs, experimental coronary thrombus could be identified ex vivo at 4 h. Clot to blood ratios ranged between 7 to 13:1. Using the 111In-oxine method, 0/3 coronary thrombi were seen. Thus, 131I- and 111In-labeled 7E3 may be used to readily identify peripheral venous thrombi. For reliable and prompt identification of coronary thrombi, more rapid clearance of the labeled platelets is required.

    Title Demonstration of Superior Sagittal Sinus Thrombosis by Indium-111 Platelet Scintigraphy.
    Date October 1986
    Journal Archives of Neurology
    Excerpt

    Superior sagittal sinus thrombosis, documented by cerebral angiography, was demonstrated by indium-111 platelet scintigraphy in a 40-year-old man presenting with seizures and intracerebral hematoma. Early scintigraphy demonstrated focal increased indium-111 activity at the two ends of the thrombus, while later scintigraphy showed diffuse increased activity in the area of the sinus. This initial experience suggests that platelet scintigraphy may provide unique information regarding the natural history of intracranial venous thrombosis.

    Title Indium-111 Platelet Scintigraphy for the Diagnosis of Acute Venous Thrombosis.
    Date April 1986
    Journal Circulation
    Excerpt

    Platelets labeled with indium-111 have been used successfully as a marker of active thrombosis in man. To establish the diagnostic accuracy of platelet scintigraphy in comparison to contrast venography in the diagnosis of acute lower limb venous thrombosis, we evaluated 103 consecutive patients divided into two groups. Platelets were labeled by the indium-111 oxine method. Patients from group I (n = 73, 56 had venograms) were asymptomatic and underwent platelet scintigraphy 1.1 +/- 0.6 days (mean +/- 1 SD) after a major orthopedic procedure. Patients from group II (n = 30, all had venograms) were symptomatic and underwent platelet scintigraphy 1.2 +/- 1.7 days after venography. In group II, 15 patients with positive findings on contrast venography were treated with intravenous heparin; five others with positive venograms did not receive heparin until platelet scintigraphy was completed. Both platelet scintigraphy and contrast venography were evaluated by two blinded observers. Only studies with blinded agreement of both platelet scintigraphy and contrast venography were included in the analysis. Sensitivity and specificity of platelet scintigraphy for the whole limb were 93% and 97% in group I and 42% and 67% in group II. The lower sensitivity in group II was most likely attributable to therapy with heparin. These results demonstrate that platelet scintigraphy, a test that permits imaging for up to five days after a single injection, correlates favorably with contrast venography in patients who have not received heparin and may be used as a surveillance test in high-risk patients. The role of platelet scintigraphy in acutely symptomatic patients requires further evaluation.

    Title The Effect of Mode of Agitation and Type of Plastic Bag on Storage Characteristics and in Vivo Kinetics of Platelet Concentrates.
    Date April 1986
    Journal Transfusion
    Excerpt

    We studied the characteristics of platelet concentrates stored for 5 days at 22 degrees C. Platelets were prepared in three plastic bags (PL 732, PL 1240, and CLX) and stored on one of four platelet agitators, 1- or 6-rpm elliptical and 2- or 6-rpm circular rotators. A total of 76 studies were divided among 12 groups, each group being composed of a different storage bag-rotator combination. In vivo recovery and survival were calculated using Indium-111 oxine-labeled platelets injected into autologous volunteers. Platelet recovery was assessed at 2 hours postinjection or as the y-intercept of the multiple-hit model survival curve. Survival was calculated using linear, exponential, and multiple-hit computer models. Linear T 1/2 also was calculated as an index of platelet survival. At 5 days, the pH of all concentrates was above pH 7.0 and platelet counts were above 5.5 X 10(10) per bag except for the PL 732 with the 6-rpm elliptical rotator, which was 4.6 X 10(10) per bag. This combination also showed a significantly higher poststorage lactic dehydrogenase (LDH) discharge compared to the mean of the other 11 groups (23.6 +/- 5.4% vs. 10.4 +/- 3.0%, p less than 0.05); however, the beta-thromboglobulin (beta-TG) release was not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Indium-111 Labeling of Stored Platelet Concentrates.
    Date March 1986
    Journal Transfusion
    Title Effect of Short-duration Constant Exercise on Permeability of Cockerel Aorta to 125i-albumin.
    Date December 1985
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    To determine quantitatively the effect of short duration constant exercise on the rate of uptake (U) of intravenously injected 125I-labeled cockerel albumin (A) by the aorta of the adult cockerel, 24 birds divided into age-matched pairs, each pair consisting of an exercised and nonexercised control bird, were studied. The time period of heparinization, anesthesia, and time from injection of A (each member of each pair received about 50 microCi from the same batch) to the death of the animal (T) was identical for each member of each pair. The exercised animal was exercised at a constant speed of 3.2 kph at 0 degrees elevation for between 2 and 5 min on a treadmill. U was defined as accumulated wall radioactivity (dpm)/plasma radioactivity (dpm/ml) X endothelial surface area (cm2) X T (s). Free 125I in the injectate amounted to 1.29 +/- 0.31% (mean +/- SD). Free 125I in the plasma and the wall in the exercise and control animals was not significantly different: plasma 0.84 +/- 0.34% (mean +/- SD) and 0.55 +/- 0.18 (P less than 0.20); wall 3.38 +/- 5.64% and 6.42 +/- 4.72 (P less than 0.04). Injected A remaining in the blood at between 8 and 16 min after intravenous injection was 83 +/- 8.7% (n = 10) in the exercised and 82 +/- 10% (n = 7) in the control (P less than 0.2). U was greater in the exercise group in 9 out of 12 matched pairs (P less than 0.05). We conclude that U increases for short periods of constant exercise.

    Title Acute Infarction, Left Ventricular Thrombus and Systemic Embolization: an Approach to Management.
    Date July 1985
    Journal Journal of the American College of Cardiology
    Title Vasoactive Intestinal Polypeptide in Cardiac Myxoma.
    Date June 1985
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    A case of left atrial myxoma is reported in which tumor tissue was found to contain high levels of vasoactive intestinal polypeptide. This finding further supports the concept that myxomas are true neoplasms and may explain some of the poorly understood clinical manifestations of this tumor.

    Title Detection of Platelet Deposition at the Site of Peripheral Balloon Angioplasty Using Indium-111 Platelet Scintigraphy.
    Date March 1985
    Journal The American Journal of Cardiology
    Excerpt

    Restenosis after balloon angioplasty may be mediated through platelet deposition at the site of arterial dilatation. The purpose of this study was to determine whether platelet deposition at the site of dilatation could be detected using indium-111 platelet scintigraphy. Fifteen patients, aged 60 +/- 9 years, with iliac or femoral (n = 12), renal artery (n = 2) or distal aortic (n = 1) stenoses were studied. All patients received intravenous heparin at the time of dilatation. Labeled platelets containing 471 +/- 65 muCi indium-111 were injected 0.25 to 4 hours after dilatation and 1 to 24 hours after imaging. In 11 of 12 patients with iliac and femoral dilatations, focal uptake was demonstrated at the angioplasty site. In 4 patients (2 patients with renal, 1 patient with iliofemoral, and 1 with distal aortic stenoses), uptake at the dilatation sites was not detected. This preliminary study indicates that despite intravenous heparin, platelets accumulate at sites of balloon dilatation. Platelet scintigraphy may be useful in predicting sites of future narrowing after angioplasty and may be used to test the efficacy of antiplatelet therapy in retarding restenosis.

    Title Use of an Electromechanical Infusion Pump for Transfusion of Platelet Concentrates.
    Date January 1985
    Journal Transfusion
    Excerpt

    To determine whether platelet concentrates can be administered safely through electromechanical infusion devices, we studied stored platelet concentrates passed through one pump system (Abbott). We measured in vitro changes in platelet count and lactic dehydrogenase (LDH) and beta-thromboglobulin (beta-TG) release which occurred after passing the concentrates through the pump system. To compare in vivo survival, five normal volunteers were given an injection of autologous Indium-111-labeled platelet concentrates at two different times, once using platelets which had been passed through the pump system (test group) and once using platelet concentrates which had not (control group). In vitro studies showed no significant changes (p greater than 0.05) in platelet count, or in LDH or beta-TG release after passage through the pump system. In vivo platelet recovery at 2 hours was 39.8 +/- 4.7 percent (mean +/- 1 SD) for the control platelets and 40.7 +/- 9.3 percent for the platelets passed through the pump system (p greater than 0.05; n = 5). There was no significant difference in platelet survival measured in days between the control group and the test group using a linear (8.0 +/- 0.9 vs. 7.2 +/- 0.3), exponential (3.7 +/- 0.7 vs. 3.1 +/- 0.5), or multiple hit (5.4 +/- 2.3 vs. 4.8 +/- 1.0) (p greater than 0.05; n = 5) model. We conclude that this pump system is acceptable for use in clinical practice when control over volume and rate of platelet transfusion is important.

    Title Double-blind, Placebo-controlled Trial of Propranolol Given Once, Twice and Four Times Daily in Stable Angina Pectoris: a Multicenter Study Using Serial Exercise Testing.
    Date August 1984
    Journal The American Journal of Cardiology
    Excerpt

    To determine if propranolol given twice daily (b.i.d.) or once daily (q.d.) was as effective as 4 times daily (q.i.d.) for treatment of stable angina pectoris, 78 patients with exercise-induced ST depression of 1.5 mm were randomized to q.i.d., b.i.d., q.d. and placebo groups. All patients received 5 tablets per day, and propranolol groups received 80, 160 and 320 mg/day on successive weeks. At weekly visits, patients underwent treadmill exercise testing before the 8:00 AM dose and at 2 and 9 hours afterward. Exercise duration (seconds) was significantly improved at the final visit compared with baseline by b.i.d. (120 +/- 36 [mean +/-] standard error of the mean p less than 0.001 n = 18) and q.i.d. (100 +/- 37, p less than 0.01; n = 17) regimens, but not by the q.d. (30 +/- 33; n = 18) and placebo regimens (27 +/- 37; n = 17). There was a significant decrease from baseline in the magnitude of ST depression at the final visit, measured at maximal common exercise duration in b.i.d. (-0.96 +/- 0.20 mm, p less than 0.001), q.i.d. (-0.84 +/- 0.20 mm, p less than 0.01) and q.d. (-0.58 +/- 0.18 mm, p less than 0.05) groups, but not in the placebo group (0.03 +/- 0.2 mm). Hourly heart rate by Holter was reduced in all 3 propranolol groups; however, the mean serum propranolol level was significantly lower just before the first dose with q.d. group (56 +/- 20 ng/ml) compared with b.i.d. and q.i.d. groups (146 +/- 22 and 119 +/- 28 ng/ml) with 320 mg/day (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Detection of Active Left Ventricular Thrombosis During Acute Myocardial Infarction Using Indium-111 Platelet Scintigraphy.
    Date August 1984
    Journal Chest
    Excerpt

    Platelet scintigraphy with radioactive indium-111 may be used both to identify and to reflect the activity of thrombin in vivo in man. Forty-one patients with acute myocardial infarction were studied for active left ventricular thrombosis by platelet scintigraphy and followed until in-hospital death, discharge, or same-admission cardiac surgery for evidence of systemic embolization. A total of 4.7 +/- 2.4 X 10(9) platelets (mean +/- 1 SD) labelled with 381 mu Ci +/- 51 mu Ci of indium-111 was injected intravenously at 91 +/- 88 hours following the onset of chest pain. Patients were imaged in multiple views on the day of and three to four days after injection of the platelet suspension. Group 1 (n = 29) had transmural myocardial infarctions, of which 21 were anterior (peak total level of creatine phosphokinase [CPK], 2,272 +/- 2,026 IU; mean +/- 1 SD) and eight were inferior (CPK level, 1,673 +/- 589 IU). Group 2 (n = 12) had subendocardial myocardial infarctions (CPK level 799 +/- 751 IU). Those with subendocardial and transmural inferior myocardial infarctions had neither left ventricular thrombosis nor emboli. Ten (48 percent) of 21 with anterior transmural myocardial infarctions had left ventricular thrombosis by platelet scintigraphy. Three with and one without such thrombosis by scintigraphy had acute neurologic episodes. In the group with anterior myocardial infarctions, seven of ten patients with and four of 11 without left ventricular thrombosis received heparin subcutaneously (chi 2 = 1.22 [Yates correction]; p greater than 0.30). We conclude that platelet scintigraphy may be used to monitor antiplatelet and anticoagulant therapy in patients with anterior transmural myocardial infarctions who are at risk for left ventricular thrombosis and systemic embolization.

    Title Unsuspected Left Ventricular Pseudoaneurysm.
    Date April 1984
    Journal Ajr. American Journal of Roentgenology
    Title Indium-111 Platelet Scintigraphy, a Technique Whose Time Has Come.
    Date March 1984
    Journal International Journal of Cardiology
    Title Diagnostic Accuracy of Indium-111 Platelet Scintigraphy in Identifying Left Ventricular Thrombi.
    Date July 1983
    Journal The American Journal of Cardiology
    Excerpt

    This study defines the optimum imaging time window after injection of labeled platelet suspension for detection on left ventricular (LV) thrombi, identifies the most useful imaging views, and determines the reproducibility of this technique. A total of 662 images obtained from 64 patients were analyzed retrospectively on 2 separate occasions by 3 observers blinded as to patient identity, view (right anterior oblique, anterior, left anterior oblique, and left lateral), and time after injection of the platelet suspension that the images were obtained (0 to 2, 3 to 4, and 5 to 6 days). Images were categorized as either positive or negative. In every case surgical or autopsy verification of the presence or absence of LV thrombus was possible. The best combination of sensitivity, specificity, and diagnostic accuracy was found in the 3- to 4-day period in the left anterior oblique view and was 54 +/- 5% (mean +/- standard deviation), 98 +/- 1%, and 85 +/- 2%, respectively. Sensitivity, specificity, and diagnostic accuracy were not enhanced by adding additional views (right anterior oblique, left lateral, and anterior) to the left anterior oblique view in the 3- to 4-day time period. However, using multiple views, localization of thrombi to the left ventricle was facilitated. In a second retrospective analysis, a comparison of day 0 with day 3 to 4 images enhanced sensitivity and accuracy to 65 (p less than 0.001) and 90% (not significant), respectively. Specificity was unchanged at 99%. Mean intra- and interobserver agreement was 91 and 88%, respectively. Thus, (1) indium-111 platelet scintigraphy is a reproducible and specific technique for identifying LV thrombus, and (2) we advise imaging on day 0 and again 3 to 4 days after injection of the platelet suspension in right anterior oblique, left anterior oblique, left lateral, and anterior views to maximize accuracy and to facilitate localization of LV thrombus.

    Title Left Atrial Mass: Diagnostic Value of Transesophageal 2-dimensional Echocardiography and Indium-111 Platelet Scintigraphy.
    Date June 1983
    Journal The American Journal of Cardiology
    Title Comparison of Indium-111 Platelet Scintigraphy and Two-dimensional Echocardiography in the Diagnosis of Left Ventricular Thrombi.
    Date July 1982
    Journal The New England Journal of Medicine
    Excerpt

    In a study comparing indium-111 platelet scintigraphy and two-dimensional echocardiography as methods of identifying left ventricular thrombi, the results obtained with both techniques were verified at surgery or autopsy in 53 patients--34 with left ventricular aneurysms, and 19 with mitral-valve disease. Left ventricular thrombi were found at surgery or autopsy in 14 of the patients with aneurysms and in none of those with mitral-valve disease. Thirteen of 53 echocardiograms (25 per cent) were technically inadequate and excluded from the analysis. In the group with aneurysms, the sensitivity of scintigraphy in detecting thrombi was 71 per cent, and that of echocardiography was 77 per cent. The specificity of scintigraphy was 100 per cent, and that of echocardiography was 93 per cent. We conclude that indium-111 platelet scintigraphy and two-dimensional echocardiography have useful and complementary roles in the detection of left ventricular thrombi. Both these noninvasive techniques can be used to monitor therapy.

    Title Diagnosis of a Persistent Pulmonary Embolus by Indium- 111 Platelet Scintigraphy with Angiographic and Tissue Confirmation.
    Date July 1982
    Journal The American Journal of Medicine
    Title The Uncontrolled Proliferation of Technology.
    Date April 1982
    Journal Chest
    Title Human Platelets Labeled with In-111 8-hydroxyquinoline: Kinetics, Distribution, and Estimates of Radiation Dose.
    Date April 1982
    Journal Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
    Excerpt

    Platelets from nine normal male subjects were labeled with In-111 8-hydroxyquinoline (In-111 oxine) in the presence of plasma in either "closed" blood transfer packs or in "open" test tubes. The mean labeling efficiencies in these two systems were 27 and 53%, respectively. Mean survival time of In-111-labeled autologous platelets was 8.76 days, with a standard deviation of 1.05 according to the maximum-likelihood estimate of the gamma-function model. The initial recovery of In-111 platelets in the circulation was 57% with a standard deviation of 11%. The distribution of In-111 platelets in liver and spleen was quantitated by anterior, posterior, and transmission gamma-camera imaging. During the first 30 min, 38% of the injected dose accumulated in the spleen, 13% in the liver. No significant increase in In-111 radioactivity was observed in either of the two organs over a 3-9-day period. The bone marrow was an additional site of In-111 accumulation. The spleen was the critical organ with respect to radiation dose. The splenic dose was estimated to be 34 rad/mCi In-111 platelets, that of the liver 2.1 rad/mCi. With the injection of 100-150 microCi of In-111-labeled platelets in normal subjects, giving a splenic radiation of 5 rad, a complete 10-day survival study can be performed and uptake of In-111 in different organs can be measured quantitatively for at least 3-4 days.

    Title Failure of Aspirin to Prevent Incorporation of Indium-111 Labelled Platelets into Cardiac Thrombi in Man.
    Date October 1981
    Journal Lancet
    Excerpt

    The in vitro and in vivo behaviour of platelets was studied in eleven patients with left ventricular aneurysms and mural thrombi. Five patients were on aspirin 300-2400 mg/day; the remaining six patients were controls. In vitro function was tested by the aggregation response of platelets to adenosine diphosphate (ADP) and collagen. In vivo function was assessed by the incorporation of indium-111-labelled platelets into cardiac thrombi as measured by scintigraphy. Platelets from patients on aspirin, whether tested before or after labelling, aggregated less with collagen than did those of controls (18 vs 52%; p less than 0.01 before labelling, 13 vs 49%; p less than 0.02 after labelling). Second wave aggregation, induced by ADP, was impaired in patients on aspirin. In all patients scintigraphy showed that the autologous labelled platelets were incorporated into ventricular thrombi. Thus, although in vitro the platelets from patients on aspirin aggregated subnormally, in vivo they took part in thrombosis.

    Title Identification of Left Ventricular Thrombi in Man Using Indium-111-labeled Autologous Platelets. A Preliminary Report.
    Date May 1981
    Journal Circulation
    Title Effect of Aging on Permeability of Cockerel Aorta to 125i-albumin.
    Date January 1981
    Journal The American Journal of Physiology
    Excerpt

    The in vivo uptake of 125I-albumin (A), containing < 1% free iodide, by the cockerel aorta 10-243 min after intravenous injection was quantitatively studied in 22 normotensive normolipemic anesthetized cockerels, Uptake initially was rapid and linear with time (T) (10-37 min), thereafter slowing and approaching an equilibrium with the blood. The permeability of the wall (Pm) to A was defined as accumulated wall activity/mean blood activity X endothelium surface area X T from intravenous injection to death of animal for T in the range 10-37 min. Pm was determined in the young group, age 197 +/- 51 days (means +/- SD; n = 6), which represented cockerels close to puberty, and compared to a middle-aged group, age 591 +/- 15 days (n = 5). Pm in the older group, 1.5 X 10(-6) +/- 0.218 ml . cm-2 . s-1 (means +/- 1 SE) was twofold greater than the younger group, 0.813 X 10(-6) +/- 0.046 (P < 0.0001). Total cholesterol content, within the wall in 12 different animals, was unchanged over the period 130-320 days. It is concluded that Pm to A increases with age as part of a physiological process. This finding should be considered in any model of atherosclerosis.

    Title Isolated Drainage of the Superior Vena Cava into the Left Atrium in a 52-year-old Man: a Rare Congenital Malformation in the Adult Presenting with Cyanosis, Polycythemia, and an Unsuccessful Lung Scan.
    Date November 1978
    Journal Circulation
    Excerpt

    This report describes a 52-year-old black male with the isolated finding of an anomalous superior vena cava draining into the left atrium. The patient presented with dizziness, mild cyanosis, polycythemia and normal cardiac and pulmonary findings. The first major diagnostic clue in this confusing clinical presentation was an unsuccessful lung perfusion scan in which intravenous tracer consistently bypassed the lungs. This appears to be the first adult presenting with this rare anomaly. This condition should be suspected if cyanosis, clubbing, and a "normal" cardiac examination coexist and if the more common pulmonary and hematological causes of this triad have been excluded.

    Title Auto-immune Haemolytic Anaemia and Paroxysmal Nocturnal Haemoglobinuria Red Cell Abnormality in the Same Patient.
    Date January 1975
    Journal South African Medical Journal = Suid-afrikaanse Tydskrif Vir Geneeskunde
    Title Initiating and Maintaining Patients on Warfarin Anticoagulation: The Importance of Monitoring.
    Date
    Journal Journal of Cardiovascular Pharmacology and Therapeutics
    Excerpt

    BACKGROUND: The VA Stroke Prevention in Nonrheumatic Atrial Fibrillation study was a prospective, randomized, double-blind study comparing low-dose warfarin with placebo in patients with nonrheumatic atrial fibrillation. The trial showed a 79% reduction in stroke rate in warfarin randomized patients without an increase in bleeding complications. We examined the need for frequent prothrombin time monitoring (international normalized ratios [INR] were not measured directly) in patients receiving warfarin.</P METHODS AND RESULTS: Patients were initiated on 4.0 mg/d warfarin with a goal of maintaining the prothrombin time ratio (PTR) within the range of 1.2-1.5 (estimated INR: 1.4-2.8). PTR monitoring was performed weekly during a 12-week induction period and monthly thereafter for a total follow-up of 3 years. Two hundred sixty patients were randomized to receive warfarin. During the induction period, the proportion of patients whose PTRs were in the desired range increased from 28% at 1 week postrandomization to 65% at 12 weeks postrandomization; the proportion of patients requiring a dose adjustment decreased from 52% to 16% during the same period. During the maintenance period, the mean proportion of patients whose PTRs were within 1.2-1.5 was 60.5% +/- 6.2%. CONCLUSIONS: Low-dose anticoagulation with warfarin in outpatients should be initiated at the anticipated maintainance dose. This approach reduces the chance of being out of range on the high side. Weekly INR estimation during this phase seems optimal. Considerable dose adjusting was required during the maintenance phase to keep patients within range; monthly INRs are required. Because of the need for dose adjustments, fixed-dose warfarin regimens are unlikely to keep patients in the desired narrow therapeutic range.

    Title Atrial Fibrillation in the Elderly.
    Date
    Journal The American Journal of Geriatric Cardiology
    Title Prevention of Stroke.
    Date
    Journal The American Journal of Geriatric Cardiology
    Excerpt

    Patients with atrial fibrillation are at variable risks for developing a stroke. The risk is significantly increased among the elderly. Other risks factors include hypertension, diabetes, poor ventricular function, and a prior history of TIA or stroke. Among the elderly, it is generally recommended that those patients who are eligible for anticoagulation would benefit substantially from its use provided the INR is maintained between 2.0-3.5 and blood pressure is well controlled. In those patients that cannot be safely anticoagulated, aspirin at a dose of 325 mg is a viable alternative but is likely to offer substantially less protection than warfarin.

    Title Executive Summary: Pivotal Research in Cardiovascular Syndromes in the Elderly.
    Date
    Journal The American Journal of Geriatric Cardiology
    Excerpt

    The PRICE-1 conference was designed to identify near term priorities for funding cardiovascular research in the elderly. Twenty topics were identified with either break throughs in fundamental mechanisms of aging with cardiovascular systems or with critical importaance to cardiovascular carve of the elderly. (c) 2000 by CVRR, Inc.

    Title Identification of Tissue Factor in Experimental Aortic Valve Sclerosis.
    Date
    Journal Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
    Excerpt

    BACKGROUND: Aortic valve sclerosis (AVS) shares epidemiological and histological similarities with atherosclerosis. Tissue factor (TF), the main initiator of blood coagulation, is present in atherosclerotic plaques and contributes to their thrombogenicity. We aimed to analyze valvular TF expression in addition to other components of atherosclerosis in two models of AVS. METHODS: Forty-five rabbits were randomly assigned to receive either normal chow (Ctrl, n=15), or 1% cholesterol-enriched chow alone (Hyperchol, n=15) or associated with vitamin D(2) (VitD, n=15), for 12 weeks. Aortic valve (AV) performance, leaflet structure, cellular and lipid infiltration, and TF expression were assessed using Doppler, histology, and immunohistochemistry, respectively, and TF activity was evaluated in AV leaflets. RESULTS: Hyperchol and VitD animals developed abnormal leaflet thickening, with a significant alteration of AV performance in VitD animals. Leaflet thickening was related to the development of fatty plaque neolesions on the aortic side of the leaflets, displaying extracellular matrix disorganization, lipid and cellular infiltration, and calcification in VitD animals. TF was found on the leaflet aortic side in Ctrl animals and was identified in AVS lesions in both Hyperchol and VitD animals. TF immunostaining area and valvular activity increased significantly across the three groups. CONCLUSIONS: Experimental AVS lesions that are present on the aortic side of leaflets display numerous characteristics of vascular atherosclerosis, including TF expression. Identification of TF associated with other components of the atherosclerotic process in AVS lesions strengthens the link between atherosclerosis and AVS.

    Title Beneficial Effects of Fenofibrate on Plaque Thrombogenicity and Plaque Stability in Atherosclerotic Rabbits.
    Date
    Journal Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
    Excerpt

    BACKGROUND: Fibrates are peroxisome proliferator-activated receptor alpha (PPARalpha) agonists which modulate many aspects of lipoprotein metabolism and inflammation. They have been recently demonstrated to inhibit in vitro expression of tissue factor (TF), the main initiator of blood coagulation, which probably plays a pivotal role in thrombotic complications after plaque rupture. We investigated whether a 4-week fenofibrate treatment might affect the TF expression and cellular modifications in angioplasty-induced rabbit plaque rupture. METHODS: After plaque rupture by balloon angioplasty in atheromatous rabbits, animals were randomized in an untreated group or a group receiving fenofibrate. The TF content of arterial wall and the histological modifications were analyzed after 4 weeks. RESULTS: Fenofibrate decreased in vivo TF expression (-42%, P<.05) and plaque cholesterol content (P<.01) in iliac arteries. Fenofibrate significantly improved the reendothelialization process by 51% (P<.05) and modified cellular distribution in the plaque toward increased stabilization. CONCLUSIONS: These data indicate that the PPARalpha-activator fenofibrate reduces plaque thrombogenicity and accelerates endothelial regrowth which, altogether, might improve plaque stability. These effects may underlie the preventive effects of fibrate therapy in atherosclerosis complications.

    Title New Developments in Anticoagulation for Atrial Fibrillation.
    Date
    Journal Current Treatment Options in Cardiovascular Medicine
    Excerpt

    The incidence of stroke in patients with atrial fibrillation (AF) is five times greater than that in age-matched controls. Warfarin reduces this incidence by two thirds and is the most effective agent for this indication. However, despite its efficacy, warfarin management is tedious and is useful only in a subsegment of the population who needs anticoagulation and has no contraindications. Many agents are poised to replace warfarin as an effective anticoagulant for stroke prevention in AF. The direct thrombin inhibitor dabigatran is furthest along in clinical development, followed by the factor Xa inhibitors rivaroxaban and apixaban. All these agents seem effective, and none appears mechanistically superior over another. Dabigatran's advantage is that it was tested in two dosages in a phase 3 evaluation based on earlier phase 2 studies in patients with AF, whereas dosage data for the other agents were extrapolated from phase 2 programs for venous thromboembolism prevention. The vitamin K antagonist ATI-5923 offers clinical benefits similar to warfarin's, but with no or fewer drug-drug interactions, potentially greater time in therapeutic range, and probably less need for dose adjustment and laboratory monitoring. It challenges the newer mechanistic agents in efficacy and raises the bar for comparison in future head-to-head trials. Further analysis and clinical trial testing are still needed to determine whether one or all of these agents are effective anticoagulants for stroke prevention in patients with AF.

    Title 2011 Accf/aha/hrs Focused Update on the Management of Patients with Atrial Fibrillation (updating the 2006 Guideline): a Report of the American College of Cardiology Foundation/american Heart Association Task Force on Practice Guidelines.
    Date
    Journal Journal of the American College of Cardiology
    Title 2011 Accf/aha/hrs Focused Update on the Management of Patients with Atrial Fibrillation (updating the 2006 Guideline): a Report of the American College of Cardiology Foundation/american Heart Association Task Force on Practice Guidelines.
    Date
    Journal Heart Rhythm : the Official Journal of the Heart Rhythm Society

    Similar doctors nearby

    Dr. Mark Edelstein

    Cardiovascular Disease
    22 years experience
    Broomall, PA

    Dr. Matthew Hillis

    Internal Medicine
    11 years experience
    Broomall, PA

    Dr. Julian Gladstone

    Internal Medicine
    43 years experience
    Broomall, PA

    Dr. Antonis Pratsos

    Internal Medicine
    19 years experience
    Broomall, PA

    Dr. Richard Lichtenberg

    Internal Medicine
    37 years experience
    Broomall, PA

    Dr. Bruce Kornberg

    Cardiovascular Disease
    34 years experience
    Broomall, PA
    Search All Similar Doctors