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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiarrhythmic, electrophysiologic and hemodynamic effects of a new antiarrhythmic agent, ACC-9358, were evaluated. In anesthetized dogs, ACC-9358 converted ouabain-induced ventricular tachycardia to normal sinus rhythm at a cumulative dose equal to encainide or flecainide and less than disopyramide. In 24-hr coronary artery ligated dogs, ACC-9358 suppressed spontaneous ventricular arrhythmias for up to 6 hr after oral or i.v. administration. The antiarrhythmic effect and plasma concentrations of ACC-9358 correlated well for both oral (r = 0.88) and i.v. (r = 0.87) administration. ACC-9358, flecainide and disopyramide were equieffective in converting crush-stimulation-induced atrial flutter in anesthetized dogs to normal sinus rhythm. In alpha-chloralose-anesthetized, closed-chest dogs, ACC-9358 slowed impulse conduction through the atria, atrioventricular node, His-Purkinje system and ventricles and prolonged atrial functional refractory period. In conscious dogs, ACC-9358 increased heart rate, reduced stroke volume and had no effect on mean arterial pressure, systemic vascular resistance or cardiac output. In alpha-chloralose-anesthetized dogs, ACC-9358-induced sinus tachycardia was unaffected by propranolol but was blocked by hexamethonium or vagotomy. In isolated cat ventricular muscle, the IC50 for the negative inotropic effect of ACC-9358 was significantly greater than flecainide or disopyramide. These results indicate that ACC-9358 is a potent, broad-spectrum, long-acting, orally and intravenously active class Ic antiarrhythmic agent that 1) may be devoid of active metabolites, 2) exerts little or no vascular effects and 3) has less direct cardiodepressant activity than flecainide or disopyramide.
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PMID:Antiarrhythmic, electrophysiologic and hemodynamic effects of ACC-9358. 369 32

In the area of myocardial infarction one is reminded of the publication of the CADILLAC study which has reopened the debate on the systematic use of GpIIbIIIa inhibitors in the acute phase of myocardial infarction complementing primary angioplasty with the placement of an endoprosthesis. New modalities for thrombolysis are in the course of evaluation, notably Eptibaphide Alteplase combination in the INTRO-AMI study and Tenecteplase Abciximab in association with enoxaparine or non-fractionated heparin in the TIMI 23 study. Several studies comparing angioplasty to lysis have been published. STOPAMI 2 evaluated myocardial salvage in the framework of primary angioplasty with placement of an endoprosthesis combined with abciximab infusion in comparison with half dose fibrinolysis associated with abciximab. CAPTIM is a strategy evaluation comparing the results of pre-hospital fibrinolysis with primary angioplasty. With the RITA 3 study the interventional approach definitely comes top in comparison with a conservative approach for the treatment of unstable angina. One is equally reminded of the changes in the ACC/AHA recommendations for the management of unstable angina. The debate continues on the indications for thrombolysis in submassive pulmonary embolus. In the therapeutic area, one is reminded of the update on the interactions between angiotensin converting enzymes and aspirin in treatment and long term coronary syndrome. Finally, at the end of 2001, the work of French teams was published concerning the evaluation of risk of relapse for cerebral vascular accident in the presence of a foramen ovale or an aneurysm of the inter-atrial septum.
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PMID:[The best of thrombosis in 2002]. 1261 65

Atrial fibrillation (AF) is the most common clinically encountered arrhythmia affecting 0.4% of the general population. Its prevalence increases with age, affecting more than 6% of people over 80 years of age. The annual risk of ischemic stroke in patients with lone AF is approximately 1.3%. This annual risk increases up to 10% -12% in patients with a prior stroke or transient ischemic attack. Randomized clinical trials (RCT) comparing adjusted-dose oral anticoagulation and placebo showed a risk reduction of 61% (95% CI 47% to 71%). The absolute risk reduction for stroke with oral anticoagulants is about 3% per year. Aspirin has been shown in meta-analyses to have on average a 20-25% relative risk reduction, and is inferior to oral anticoagulants. In high risk patients with AF warfarin is a class I ACC/AHA indication unless there is a contraindication for anticoagulation. Unfortunately, this therapy requires frequent monitoring with blood samples and the interaction with food and several medications makes its use difficult and sometimes unreliable. It requires strict patient compliance and its use is also linked to potentially serious bleeding complications. In clinical practice, less than 60% of patients who do not have contraindications to oral anticoagulation are actually receiving them. Additionally, of those that receive oral anticoagulation, less than 50% are consistently within therapeutic targets. As such, the "real world" efficacy of a strategy towards prescribing oral anticoagulants is likely significantly lower than that demonstrated in clinical trials. As such, the need to discover other methods of anticoagulation with oral bioavailability, predictable pharmacokinetics, and minimal interactions with diet and other pharmacological agents is imperative. Low molecular weight heparin has a more predictable bioavailability and a longer half-life, but its subcutaneous mode of administration and long-term risks, in particular, osteoporosis makes the chronic use of this medication non-feasible. Antiplatelet agents such as clopidogrel have proven efficacy and superiority compared to aspirin to prevent systemic vascular events in at-risk patient populations, but currently they do not play an important role in the prevention of AF related thromboembolic events. The ACTIVE study is a randomized trial comparing the combination of clopidogrel and aspirin therapy to oral anticoagulation with warfarin in patients with AF, and was unfortunately terminated prematurely by the data safety and monitoring board because of increased events in the antiplatelet arm. Direct thrombin inhibitors, such as ximelagatran, may be as effective as warfarin for stroke-risk reduction in patients with AF. No anticoagulation monitoring is needed and it has excellent bioavailability, with a twice-daily oral dose. Elevation of liver enzymes was an initial concern regarding the use of this new drug, which is not available for general use. Ongoing pharmacological research and future clinical trials may one day leave the "warfarin days" behind. Unfortunately, the new therapies that are being tested seem to be at least several years away from being available on a widespread basis. In this review, we discuss the underlying pathophysiology of AF and stroke. We also provide a comprehensive discussion regarding various available therapies to treat AF.
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PMID:Evaluation and management of atrial fibrillation. 1737 69

Atrial fibrillation (AF) is the most common sustained tachyarrhythmia and its prevalence is increasing. It is an independent risk factor for stroke and is associated with significant morbidity and mortality. AF currently accounts for 1% of NHS expenditure. The management of AF has a broad evidence base and both the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) and the National Institute for Clinical Excellence (NICE) have recently published guidelines. Some controversy persists regarding stroke risk stratification and appropriate anticoagulation regimes although a general consensus is now emerging. Rate and rhythm control strategies have been shown to be comparable in terms of clinical outcomes. Current anti-arrhythmic drugs have limited efficacy and significant side-effect profiles. Electrophysiological and surgical interventions have a role in both strategies. This article broadly reviews the evidence for different management strategies in AF and presents a practical approach to treatment in light of the recently published national and international guidelines.
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PMID:Key issues in the management of atrial fibrillation--protecting the patient and controlling the arrhythmia. 1787 12

Since the introduction of off-pump coronary artery bypass grafting (OPCAB) for coronary multivessel disease there was growing interest to evaluate the impact of OPCAB surgery compared to conventional coronary artery bypass grafting (CCAB) with cardiopulmonary bypass and cardioplegic arrest. However, subsequent prospective randomized studies and meta-analyses comparing OPCAB and CCAB surgery were performed on low-risk patients or mixed-risk populations. They usually failed to demonstrate a significant benefit of OPCAB surgery on early mortality or perioperative major cardiac and cerebrovascular events. In recent years, efforts were made to analyze the meaning of beating-heart concepts for patients with specific cardiac and extracardiac risks like ischemic cardiomyopathy, older age, renal failure, acute coronary syndrome, left main stenosis and others. For these subsets of patients several mono- and multicenter studies are available today. Even if most of them were nonrandomized and thus failed to reach evidence level A according to the AHA/ACC (American Heart Association/American College of Cardiology) definition, they still allow analyzing interim results for each specific perioperative risk factor. Particularly multi-risk patients and patients with severely reduced left ventricular function seem to benefit in terms of perioperative mortality and major morbidity by avoiding cardiopulmonary bypass and cardioplegic arrest. Analyzing early results and long-term follow-up of 364 patients with severely reduced ejection fraction<20%, the authors found a long-term benefit for patients when using OPCAB strategies particularly due to reduced perioperative mortality. Moreover, for most subsets of patients with significant extracardiac risk factors the incidence or perioperative stroke was reduced. In patients with preoperative renal and pulmonary dysfunction a decrease of corresponding organ failure was found for OPCAB strategy. For most risk populations transfusion requirements were significantly lower in OPCAB compared to CCAB surgery. In none of the patients an unfavorable outcome of beating-heart surgery compared to CCAB was shown. For emergency patients with an acute coronary syndrome presenting stable and unstable hemodynamics the authors found a clinical benefit by using beating-heart strategies. Particularly in patients with cardiogenic shock, cardiopulmonary bypass was often required to guarantee adequate perioperative organ perfusion. However, these patients seemed to benefit from avoiding global cardiac ischemia and maintaining native coronary blood flow. Follow-up results were comparable for these patients. In conclusion, beating-heart coronary artery bypass grafting seems to be advantageous in various risk populations and should be considered for patients with more than average risks for cardiopulmonary bypass and cardioplegic arrest.
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PMID:[Coronary artery bypass grafting on the beating heart in high-risk patients]. 1788 73

For neurorehabilitation to advance from art to science, it must become evidence-based. Historically, there has been a dearth of evidence from which to construct rehabilitation interventions that are properly framed, accurately targeted, and credibly measured. In many instances, evidence of treatment response has not been sufficiently robust to demonstrate a change in function that is clinically, statistically, and economically important. Research evidence of activity-dependent central nervous system (CNS) plasticity and the requisite motor learning principles can be used to construct an efficacious motor recovery intervention. Brain plasticity after stroke refers to the regeneration of brain neuronal structures and/or reorganization of the function of neurons. Not only can CNS structure and function change in response to injury, but also, the changes may be modified by "activity". For gait training or upper limb functional training for stroke survivors, the "activity" is motor behavior, including coordination and strengthening exercise and functional training that comprise motor learning. Critical principles of motor learning required for CNS activity-dependent plasticity include: close-to-normal movements, muscle activation driving practice of movement; focused attention, repetition of desired movements, and training specificity. The ultimate goal of rehabilitation is to restore function so that a satisfying quality of life can be experienced. Accurate measurement of dysfunction and its underlying impairments are critical to the development of accurately targeted interventions that are sufficiently robust to produce gains, not only in function, but also in quality of life. The Classification of Functioning, Disability, and Health Model (ICF) model of disablement, put forth by the World Health Organization, can provide not only some guidance in measurement level selection, but also can serve as a guide to incorporate function and quality of life enhancement as the ultimate goals of rehabilitation interventions. Based on the evidence and principles of activity-dependent plasticity and motor learning, we developed gait training and upper limb functional training protocols. Guided by the ICF model, we selected and developed measures with characteristics rendering them most likely to capture change in the targeted aspects of intervention, as well as measures having membership not only in the impairment, but also in the functional or life role participation levels contained in the ICF model. We measured response to innovative gait training using a knee flexion coordination measure, coefficient of coordination consistency (ACC) of relative hip/knee (H/K) movement across multiple steps (H/K ACC), and milestones of participation in life role activities. We measured response to upper limb functional training according to measures designed to quantify functional gains in response to treatment targeted at wrist/hand or shoulder elbow training (Arm Motor Ability Test for wrist/hand (AMAT W/H) or shoulder/elbow (AMAT S/E)). We found that there was a statistically significant advantage for adding FES-IM gait training to an otherwise comparable and comprehensive gait training, according to the following measures: H/K ACC, the measure of consistently executed hip/knee coordination during walking; a specific measure of isolated joint knee flexion coordination; and a measure of multiple coordinated gait components. Further, enhanced gains in gait component coordination were robust enough to result in achievement of milestones in participation in life role activities. In the upper limb functional training study, we found that robotics + motor learning (ROB ML; shoulder/elbow robotics practice plus motor learning) produced a statistically significant gain in AMAT S/E; whereas functional electrical stimulation + motor learning (FES ML) did not. We found that FES ML (wrist/hand FES plus motor learning) produced a statistically significant gain in AMAT W/H; whereas ROB ML did not. These results together, support the phenomenon of training specificity in that the most practiced joint movements improved in comparison to joint movements that were practiced at a lesser intensity and frequency. Both ROB ML and FES ML protocols addressed an array of impairments thought to underlie dysfunction. If we are willing to adhere to the ICF model, we accept the challenge that the goal of rehabilitation is life role participation, with functional improvement as in important intermediary step. The ICF model suggests that we intervene at multiple lower levels (e.g., pathology and impairment) in order to improve the higher levels of function and life role participation. The ICF model also suggests that we measure at each level. Not only can we then understand response to treatment at each level, but also, we can begin to understand relationships between levels (e.g., impairment and function). With the ICF model proffering the challenge of restoring life role participation, it then becomes important to design and test interventions that result in impairment gains sufficiently robust to be reflected in functional activities and further, in life role participation. Fortunately, CNS plasticity and associated motor learning principles can serve well as the basis for generating such interventions. These principles were useful in generating both efficacious gait training and efficacious upper limb functional training interventions. These principles led to the use of therapeutic agents (FES and robotics) so that close-to-normal movements could be practiced. These principles supported the use of specific therapeutic agents (BWSTT, FES, and robotics) so that sufficient movement repetition could be provided. These principles also supported incorporation of functional task practice and the demand of attention to task practice within the intervention. The ICF model provided the challenge to restore function and life role participation. The means to that end was provided by principles of CNS plasticity and motor learning.
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PMID:Construction of efficacious gait and upper limb functional interventions based on brain plasticity evidence and model-based measures for stroke patients. 1816 18

Pay for performance is gaining momentum as a means to improve the quality of clinical care. Recently, the Centers for Medicare & Medicaid Services has expanded pay for performance initiatives to incorporate 9 emergency care metrics, including indicators for cardiac, pneumonia, and stroke care. The American College of Cardiology and American Heart Association (ACC/AHA) have published methodology for the selection and creation of performance measures for quantifying the quality of cardiovascular care. The purpose of this study is to grade each of the 9 Physician Quality Reporting Initiative emergency medicine process measures according to the ACC/AHA criteria related to clinical evidence (yes, no, indeterminate). Five of the 9 recently selected metrics in emergency medicine do not appear to meet all of the ACC/AHA criteria for measurement selection. Several of the metrics, including aspirin for acute myocardial infarction (mean hospital adherence 94.7%; SD 6.7%) and pulse oximetry for community-acquired pneumonia (mean 99.4%; SD 2.0%), already have high levels of performance nationally, which raises uncertainty about the overall cost-effectiveness of quality improvement interventions for these measures. Formal methodology needs to be established for future selection of performance measures for quality improvement programs in emergency care. These performance measures should focus on unique aspects of emergency and acute care, including recognition and treatment of time-sensitive life-threatening conditions, assessment of patients with undifferentiated signs and symptoms, and care of all-inclusive geographically based patient populations. In key emergency therapeutic areas, the evidence linking treatment and improved patient outcomes will require additional study before inclusion in pay for performance programs. New research initiatives are needed to assess the effect of timely administration of emergency department interventions on patient outcomes.
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PMID:Evidence-based perspectives on pay for performance and quality of patient care and outcomes in emergency medicine. 1835 66

Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.
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PMID:[Low molecular weight heparin and non valvular atrial fibrillation]. 1894 23

Management of patients with atrial fibrillation in clinical practice represents a major challenge. The 2001 ACC/AHA/ESC Atrial Fibrillation Guidelines have gained wide acceptance but recent advances have required their revision in 2006. Large strategy trials comparing rhythm control to rate control using drug therapy has shown no difference in terms of major endpoints including mortality. The reason suggested by substudy analysis was that the benefits of sinus rhythm obtained with antiarrhythmic agents were offset by their side-effects. The 2006 revised Guideline version in terms of management strategy does not differ significantly from the 2001 version as both rhythm control and rate control strategies were considered acceptable. The selection of an antiarrhythmic agent is still based on the presence and the type of underlying heart disease as the fruit of a consensus more than on evidence in a safety first approach. The only difference is that class Ia agents were deleted from the treatment algorithm. Catheter ablation techniques represent one of the major developments in recent years in the management of AF patients. The Guidelines recommend catheter ablation as a second line therapy in every branch of the therapeutic flow chart. In this respect, the 2006 version of the Guidelines although consistent with current practice is not evidence-based as randomized trials comparing ablative techniques to conventional management in AF are still lacking. Furthermore, the paroxysmal form and the persistent or chronic forms are not differentiated as for the persistent and long-standing AF the results of catheter ablation are less convincing. Catheter ablation techniques are complex and carry the risk of recurrences requiring a repeat operation in 20-40% of cases and the risk of serious complications that may be life-threatening if not appropriately detected and managed. Atrial fibrillation identifies a subset of patients at high risk of stroke. The 2006 Guidelines have stratified the stroke risk into three group levels in order to better define the group for whom oral anticoagulation with warfarin is mandatory in the absence of contra-indication. In this regard, the 2006 Guideline version represents a helpful improvement.
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PMID:Current atrial fibrillation guidelines and therapy algorithms: are they adequate? 1897 67

The rationale behind combined statin-acetylsalicylic acid therapy is based on the beneficial effects ofacetylsalicylic acid on thrombosis, the leading immediate cause of the majority of occlusive cardiovascular events, and those of statins on atherosclerosis, which is the main underlying cause. The clinical benefits of combined pravastatin-acetylsalicylic acid in the management of coronary patients have been demonstrated by a meta-analysis of five randomized clinical trials for secondary prevention; compared with pravastatin alone, the pravastatin-acetylsalicylic acid combination reduced the risk of fatal or non fatal myocardial infarction by 26%, the risk of ischemic stroke by 31%, and the risk of cardiovascular events at 5 years by 13%. Combined pravastatin-acetylsalicylic acid therefore appears to significantly reduce the cardiovascular risk in coronary patients. Following the AHA/ACC and National Cholesterol Education Program (NCEP) I and II guidelines, the proportion of patients treated by acetylsalicylic acid, beta-blockers and statins increased significantly: 94%, 57% and 91% respectively at one year versus 68%, 18% and 10% before the guidelines were applied. The impact of these treatments on clinical outcomes is statistically significant in terms of recurrent myocardial infarction, the need for re-hospitalization, sudden death or all-cause mortality. Patients treated with combined statin-acetylsalicylic acid therapy have significantly improved clinical outcome and a significantly lower rate of coronary events at 1 year of follow-up. These data therefore confirm the importance of optimizing therapeutic management of coronary patients, and in particular with combined acetylsalicylic acid-statin therapy.
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PMID:[Pravastatin and acetylsalycilic acid fixed-combination: a strategy to improve cardiovascular outcomes]. 1983 82


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