warfarin and Heart-Valve-Diseases

Direct oral anticoagulants (DOACs) are increasingly used for the treatment and prevention of thromboembolic events in patients with non-valvular atrial fibrillation (AF). Evidence regarding their role in patients with AF and concurrent valvular heart disease (VHD) continues to evolve.. Post hoc analyses of randomized clinical trials suggest that DOACs are non-inferior to warfarin for the prevention of stroke or systemic embolism in patients with AF and VHD. Emerging evidence from observational data showed a favorable benefit-risk profile for DOACs compared to warfarin in patients with AF and VHD. DOACs are an attractive option for the treatment of patients with AF and VHD who cannot tolerate or have contraindications to warfarin therapy. Future studies are needed to evaluate their effectiveness, safety, and examine variability in the direction and magnitude of treatment effects in selected VHD subgroups.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Humans; Stroke; Warfarin

Mechanical heart valves (MHVs) pose significant thrombogenic risks to pregnant women and their fetuses, yet the choice of anticoagulation in this clinical setting remains unclear. Various therapeutic strategies carry distinct risk profiles that must be considered when making the decision about optimal anticoagulation.. We sought to review existing data and offer recommendations for the anticoagulation of pregnant women with MHVs, as well as management of anticoagulation in the peripartum period.. We performed a literature review of studies examining outcomes in pregnant women receiving systemic anticoagulation for mechanical valves, and also reviewed data on the safety profiles of various anticoagulant strategies in the setting of pregnancy.. Warfarin has been shown to increase rates of embryopathy and fetal demise, although it has traditionally been the favored anticoagulant in this setting. Low-molecular-weight heparin, when dosed appropriately with close therapeutic monitoring, has been shown to be safe for both mother and fetus.. We favor the use of low-molecular-weight heparin with appropriate dosing and monitoring for the anticoagulation of pregnant women with MHVs. Data suggest that this approach minimizes the thrombotic risk associated with the valve while also providing safe and effective anticoagulation that can be easily managed in the peripartum period.

Topics: Anticoagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Care; Warfarin

New oral anticoagulants (NOACs) are approved for use in nonvalvular atrial fibrillation (AF).. This study aimed to evaluate the efficacy and safety of NOACs compared with warfarin in AF and valvular heart disease (VHD).. We identified randomized controlled trials (RCTs) and post-hoc analyses comparing NOACs and warfarin in AF and VHD, including biological and mechanical heart valves (MHV). Through systematic review and meta-analysis, with the aid of the "Rev Man" program 5.3, the primary effectiveness endpoints were stroke and systemic embolism (SE). The primary safety outcome was major bleeding, and the secondary outcome included intracranial hemorrhage. Data were analyzed using risk ratios (RRs) and 95% confidence intervals (CIs), and heterogeneity was assessed using the I. Six RCTs were included, involving 13,850 patients with AF and VHD. NOACs significantly reduced the risk of stroke/SE (RR 0.78; 95% CI 0.66-0.91; P = 0.002) and intracranial hemorrhage (RR 0.51; 95% CI 0.33-0.79; P = 0.003) and lowered the risk of major bleeding (RR 0.77; 95% CI 0.58-1.02; P = 0.07) compared with warfarin.. The efficacy and safety of NOACs as thromboprophylaxis for AF and VHD are similar to those of warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Hemorrhage; Humans; Incidence; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Warfarin is the standard of care and NOAC (Novel oral anticoagulants) are a group of newer drugs for such purposes. NOAC has a generally better profile (Clear interaction, less side effect, require less monitoring). However, its efficacy on valvular atrial fibrillation remains unclear.. We researched literature articles from Embase, Cochrane and PubMed. Then we meta-analysed these six articles to assess pooled estimate of relative risk (RR) and 95% confidence intervals (Cl) using random-effects model for stroke, systemic embolic event, major bleeding and all-cause mortality. Heterogeneity across study was tested with Cochran's Q Test and I. We collected 496 articles in total and finally we included six articles in our meta-analysis. For SSEE (Stroke, Systemic Embolic Event), the pooled relative risk showed a significantly better clinical outcome of NOAC (RR: 0.66; 95% CI: 0.46 to 0.95). However, there is no significant difference in major bleeding (RR: 0.714, 95% CI:0.46 to 1.11) and all-cause mortality (RR: 0.84, 95% CI: 0.58 to 1.21).. Compared to Warfarin, NOAC is significantly more protective against the embolic event, but no significant difference in lowering risk of major bleeding, all-cause mortality or all aspects of post-TAVI (Trans-catheter aortic valve implantation).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Stroke; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Warfarin

Current guidelines endorse the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). However, little is known about their safety and efficacy in valvular heart disease (VHD). Similarly, there is a paucity of data regarding NOACs use in patients with a bioprosthetic heart valve (BPHV). We, therefore, performed a network meta-analysis in the subgroups of VHD and meta-analysis in patients with a BPHV.. PubMed, Cochrane and Embase were searched for randomised controlled trials. Summary effects were estimated by the random-effects model. The outcomes of interest were a stroke or systemic embolisation (SSE), myocardial infarction (MI), all-cause mortality, major adverse cardiac events, major bleeding and intracranial haemorrhage (ICH).. In patients with VHD, rivaroxaban was associated with more ICH and major bleeding than other NOACs, while edoxaban 30 mg was associated with least major bleeding. Data combining all NOACs showed a significant reduction in SSE, MI and ICH (0.70, [0.57 to 0.85; p<0.001]; 0.70 [0.50 to 0.99; p<0.002]; and 0.46 [0.24 to 0.86; p<0.01], respectively). Analysis of 280 patients with AF and a BPHV showed similar outcomes with NOACs and warfarin.. NOACs performed better than warfarin for a reduction in SSE, MI and ICH in patients with VHD. Individually NOACs performed similarly to each other except for an increased risk of ICH and major bleeding with rivaroxaban and a reduced risk of major bleeding with edoxaban 30 mg. In patients with a BPHV, results with NOACs seem similar to those with warfarin and this needs to be further explored in larger studies.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Bioprosthesis; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Myocardial Infarction; Network Meta-Analysis; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

The present article provides an update on anticoagulant treatment in patients with atrial fibrillation in distinct clinical scenarios requiring particular considerations, such as ischaemic heart disease, electrical cardioversion, pulmonary vein ablation, the presence of valvular disease with or without prosthetic valves, and renal insufficiency, as well as old age and frailty. In patients with non-valvular atrial fibrillation, the presence of renal insufficiency increases both thrombotic and haemorrhagic risk. In mild and moderate stages, direct-acting anticoagulants confer a greater benefit than warfarin, although they usually require dose adjustment. In renal failure/dialysis, there is no solid evidence that warfarin is beneficial and the use of direct-acting anticoagulants is not recommended. Because of its pathophysiology, oral anticoagulation could have a beneficial effect in patients with heart disease. However, vitamin K antagonists have not shown a satisfactory risk-benefit ratio. In contrast, direct-acting anticoagulants, at reduced doses, could have a beneficial effect in this scenario in association with antiplatelet agents. The use of direct-acting anticoagulants prior to electrical cardioversion in patients with non-valvular atrial fibrillation seems to be associated with a risk of cardioembolic events that is at least comparable to that of vitamin K antagonists. Their use avoids delay in the application of electrical cardioversion in patients without adequate INR levels. In the context of their use before and after atrial fibrillation ablation, dabiga-tran and rivaroxaban have demonstrated at least non-inferiority with vitamin K antagonists in terms of safety. In patients with any type or grade of valvular disease and atrial fibrillation, the indication of antithrombo-tic treatment must be evaluated in the same way as in patients with atrial fibrillation and no valvular di-sease. Whenever anticoagulation is required, direct-acting anticoagulants are the treatment of choice in nearly all situations, except in patients with mechanical valves or who have significant rheumatic mitral disease, who should be treated with vitamin K antagonists. The choice of appropriate antithrombotic stra-tegy in frail elderly patients is complex and involves multiple factors beyond assessment of embolic and haemorrhagic risk. Comprehensive geriatric assessment is essential for an individualised final decision. Moreover, any such decision should be consensus-based

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Electric Countershock; Fibrinolytic Agents; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Renal Insufficiency; Risk Assessment; Secondary Prevention; Thromboembolism; Thrombophilia; Vitamin K; Warfarin

Patients undergoing cardiac valve replacement may receive mechanical or bioprosthetic valves. Mechanical valves require lifelong anticoagulation but are durable and the need for a second surgery is up to eightfold times less than with bioprosthetic valves. Bioprosthetic valves do not require lifelong anticoagulation and thus are associated with fewer bleeding complications but they are less durable and associated with higher morbidity and mortality rates, particularly in younger patients. Anticoagulation with mechanical valves is achieved using warfarin; use of direct-acting oral anticoagulants is not indicated. Concomitant low-dose aspirin is recommended for patients with mechanical valves and as sole thromboembolism prophylaxis for patients receiving aortic or mitral bioprosthetic valves. If a patient taking warfarin is to undergo a surgical procedure that requires interruption of anticoagulation, bridging therapy with heparin is indicated if the patient has a mechanical aortic valve and any risk of thromboembolism, an older-generation mechanical aortic valve, or a mechanical mitral valve. Warfarin is teratogenic; pregnant women should take heparin. Patients with mechanical or bioprosthetic valves should receive antibiotic prophylaxis before some dental and surgical procedures to prevent endocarditis. Thrombolytic therapy should be considered in patients who develop a thrombus on a valve that does not resolve with heparin.

Topics: Antibiotic Prophylaxis; Anticoagulants; Bioprosthesis; Endocarditis; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Cardiovascular; Prosthesis Design; Thromboembolism; Warfarin

The original non-vitamin K antagonist oral anticoagulant (NOAC) trials in nonvalvular atrial fibrillation (AF) enrolled patients with native valve pathologies. The object of this study was to quantify the benefit-risk profiles of NOACs versus warfarin in AF patients with native valvular heart disease (VHD).. Trials were identified by exhaustive literature search. Trial data were combined using inverse variance weighting to produce a meta-analytic summary hazard ratio (HR) and 95% confidence interval (CI) of efficacy and safety of NOACs versus warfarin. Our final analysis included 4 randomized controlled trials that enrolled 71 526 participants, including 13 574 with VHD. Pooling results from included trials showed that NOACs versus warfarin reduced stroke or systemic embolism (HR: 0.70; 95% CI, 0.60-0.82) and intracranial hemorrhage (HR: 0.47; 95% CI, 0.24-0.92) in AF patients with VHD. However, risk reduction of major bleeding and intracranial hemorrhage was driven by apixaban, edoxaban, and dabigatran (HR for major bleeding: 0.79 [95% CI, 0.69-0.91]; HR for intracranial hemorrhage: 0.33 [95% CI, 0.25-0.45]) but not rivaroxaban (HR for major bleeding: 1.56 [95% CI, 1.20-2.04]; HR for intracranial hemorrhage: 1.27 [95% CI, 0.77-2.10]).. Among patients with AF and native VHD, NOACs reduce stroke and systemic embolism compared with warfarin. Evidence shows that apixaban, dabigatran, and edoxaban also reduce bleeding in this patient subgroup, whereas major bleeding (but not intracranial hemorrhage or mortality rate) is significantly increased in VHD patients treated with rivaroxaban. NOACs are a reasonable alternative to warfarin in AF patients with VHD.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Female; Heart Valve Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Odds Ratio; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding.. We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79).. Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.

Topics: Anticoagulants; Aortic Valve; Aspirin; Bioprosthesis; Drug Administration Schedule; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Ischemic Attack, Transient; Odds Ratio; Platelet Aggregation Inhibitors; Prosthesis Design; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Venous Thromboembolism; Warfarin

Low molecular weight heparins (LMWHs) are not approved for patients with mechanical heart valves (MHVs). However, in several guidelines, temporary LMWH off-label use in this clinical setting is considered to be a valid treatment option. Therefore, we reviewed the efficacy and safety of LMWHs in patients with MHVs.. MEDLINE and CENTRAL databases were searched from inception to June 2013. Review articles and references were also searched. We included experimental and observational studies that compared LMWHs with unfractionated heparin (UFH) or vitamin K antagonists (VKAs). Data were analyzed and pooled to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for thromboembolic and major bleeding events. Statistical heterogeneity was evaluated with the I(2) -test.. Nine studies were included: one randomized controlled trial (RCT) and eight observational studies, with a total of 1042 patients. No differences were found between LMWHs and UFH/VKAs in the risk of thromboembolic events (OR 0.67; 95% CI 0.27-1.68; I(2) = 9%) or major bleeding events (OR 0.66; 95% CI 0.36-1.19; I(2) = 0%).. The best evidence available might support the temporary use of LMWHs as a prophylactic treatment option in patients with MHVs. However, conclusions are mostly based on observational data (with large CIs), and an adequately powered RCT is urgently needed in this clinical setting.

Topics: Anticoagulants; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valves; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Observational Studies as Topic; Odds Ratio; Randomized Controlled Trials as Topic; Reproducibility of Results; Thromboembolism; Warfarin

Long-term anticoagulation is required in all patients with mechanical prosthetic heart valves to prevent complications with valve thrombosis and valve failure or systemic thromboembolism. The prothrombotic environment of pregnancy further increases the risks of these complications. Anticoagulant choices for pregnant women include oral vitamin K antagonists such as warfarin, or heparin - either unfractionated heparin (UFH) or low molecular weight heparin (LMWH). None of the options is without risk for the mother or her baby. Warfarin crosses the placenta and is associated with warfarin embryopathy and fetopathy but is very effective at preventing thromboembolic complications. The dose of warfarin may play a role in the risk of some, but not all fetal complications. Heparin does not cross the placenta but is less effective at preventing thrombosis and LMWH may be more effective than UFH. The optimal dose and target anti-Xa levels for LMWH have not been established. Measurement of trough anti-Xa levels in addition to peak anti-Xa levels may be important.

Topics: Anticoagulants; Cohort Studies; Factor Xa; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Heparin, Low-Molecular-Weight; Humans; Maternal Exposure; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Pregnancy Outcome; Risk; Thromboembolism; Thrombosis; Vitamin K; Warfarin

New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS(2) score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.

Topics: Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Heart Valve Diseases; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Morpholines; Multicenter Studies as Topic; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Severity of Illness Index; Stroke; Thiophenes; Thrombophilia; Vitamin K; Warfarin

Vitamin K is required for the activity of various biologically active proteins in our body. Apart from clotting factors, vitamin K-dependent proteins include regulatory proteins like protein C, protein S, protein Z, osteocalcin, growth arrest-specific gene 6 protein, and matrix Gla protein. Glutamic acid residues in matrix Gla protein are γ-carboxylated by vitamin K-dependent γ-carboxylase, which enables it to inhibit calcification. Warfarin, being a vitamin K antagonist, inhibits this process, and has been associated with calcification in various animal and human studies. Though no specific guidelines are currently available to prevent or treat this less-recognized side effect, discontinuing warfarin and using an alternative anticoagulant seems to be a reasonable option. Newer anticoagulants such as dabigatran and rivaroxaban offer promise as future therapeutic options in such cases. Drugs including statins, alendronate, osteoprotegerin, and vitamin K are currently under study as therapies to prevent or treat warfarin-associated calcification. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Topics: Anticoagulants; Calcinosis; Diphosphonates; Heart Valve Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperbaric Oxygenation; Muscle, Smooth, Vascular; Osteoprotegerin; Vitamin K; Warfarin

Anticoagulant therapy is an important component of treatment of patients with prosthetic heart valves. The article contains consideration of specific problems of antithrombotic therapy in patients with various types of prostheses and its tactics in different clinical situations. In the absence of national recommendations on the use of anticoagulants in these patients the authors suggest schemes of management based on recent European and American guidelines.

Topics: Anticoagulants; Aspirin; Blood Coagulation Tests; Clopidogrel; Drug Monitoring; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Monitoring, Physiologic; Platelet Aggregation Inhibitors; Prognosis; Thromboembolism; Ticlopidine; Warfarin

The use of bioprosthetic heart valves has dramatically increased over the last decade. In 2004, the ratio was 52% for mechanical and 48% for bioprosthetic valves in a survey by the Japanese Association for Thoracic Surgery. This increase in the use of bioprosthetic valves is related to evidence demonstrating the durability of such valves over the last 20 years. The guidelines of the Japanese Circulation Society recommend selection of prosthetic heart valves by considering the patient's age. In patients who received a mechanical valve in previous cardiac surgery, selection of another mechanical valve is inevitable. The age of 65 years is when patients are separated into groups receiving either mechanical (<64 years) or bioprosthetic (> or =65 years) valves. However, the evidence that a bioprosthetic valve is better for patients in their 60s is somewhat questionable, particularly in Japanese with a long life expectancy. Anticoagulation with warfarin in patients with mechanical valves leads to a higher incidence of hemorrhagic complications compared with bioprosthetic valves, although the incidence of thromboembolism is the same. Thus patients with contraindications to warfarin or a low risk of thromboembolism who are more than 65 years old are reasonable candidates for a bioprosthetic valve. It is also recommended that women of childbearing age receive bioprosthetic valves after being informed of the possibility and risks of reoperation. In addition to the information in the guidelines and physicians' preference for valve selection, factors such as the patient's lifestyle, wishes, cardiac function, other complications, and longevity must always be considered when selecting a valve prosthesis.

Topics: Adult; Age Factors; Aged; Anticoagulants; Aortic Valve; Bioprosthesis; Contraindications; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Postoperative Complications; Prognosis; Prosthesis Failure; Reoperation; Risk; Warfarin

The majority of women with bioprosthetic valves do not require anticoagulation during pregnancy. In women with mechanical valves, a detailed discussion of the advantages and disadvantages of the three anticoagulant options (warfarin, unfractionated heparin and low molecular weight heparin) is indicated. The majority of women with arrhythmias during pregnancy have a benign increased rate of atrial or ventricular premature beats. Those women who are hemodynamically stable can be reassured and do not usually require treatment. Women with more ominous arrhythmias should be managed in collaboration with a cardiologist, usually using the same agents that would be chosen in the non-pregnant patient, including electrical cardioversion when necessary. This is the fifth and final article in a series reviewing in detail the assessment and management of specific cardiac disorders in pregnancy.

Topics: Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Bioprosthesis; Electric Countershock; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Treatment Outcome; Warfarin

Topics: Animals; Antibiotic Prophylaxis; Anticoagulants; Aortic Valve Insufficiency; Aortic Valve Stenosis; Bioprosthesis; Calcinosis; Defibrillators, Implantable; Echocardiography, Doppler; Endarterectomy; Endocarditis, Bacterial; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valves; Hemodynamics; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Stenosis; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Artery; Tricuspid Valve Insufficiency; Ventricular Function, Left; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Heart Valve Diseases; Humans; Intracranial Embolism; Male; Platelet Aggregation Inhibitors; Risk; Warfarin

Intracardiac thrombosis and cardioembolisms may have impressive effects on quality of life, prognosis and therapeutic costs in patients with valve disease or replacement devices. Distinct pathophysiological differences exist regarding intracardiac thrombus formation in low-versus high-pressure areas. Important cardiac confounders for low-pressure areas are left atrial geometry and function, including atrial fibrillation or loss of active atrial contraction. In high-pressure areas, flow velocity and shear stress are raised, and this may result in flow turbulence, for example when blood passes a stenotic area. Other major factors which correlate with intracardiac thrombus formation are implantation of polymer material and the degree of endocardial damage resulting for example, from infective or rheumatic endocarditis. Because of the interaction of platelets and the plasma clotting system, a combination of oral anticoagulation therapy and antiplatelet drugs should prevent more thromboembolic events than might anticoagulation alone. Recent studies in patients with prosthetic heart valves have indicated a positive risk-benefit profile if low-dose antiplatelet drugs are added to moderate intensive oral anticoagulation therapy. Thromboembolic events and bleeding complications due to oral anticoagulation therapy are accepted key parameters to demonstrate the superiority of one replacement device over another. However, there is no consistent system for reporting morbid events. In order to organize low and narrow target INR ranges, point-of-care patient self-testing modalities have been introduced and used effectively in large sample sizes. In the near future, some promising new drugs--including direct thrombin or factor Xa inhibitors with broader therapeutic ranges and thus fewer side effects--will become available. The test for these drugs will be their potential to prevent intracardiac thrombosis and cardioembolism in a patient population which is under significant risk.

Topics: Anticoagulants; Coronary Thrombosis; Drug Therapy, Combination; Embolism; Heart Valve Diseases; Humans; Platelet Aggregation Inhibitors; Thrombolytic Therapy; Warfarin

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.

Topics: Anticoagulants; Heart Valve Diseases; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Practice Guidelines as Topic; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Risk; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Topics: Calcinosis; Endocarditis; Fibrinolytic Agents; Heart Septal Defects, Atrial; Heart Valve Diseases; Humans; Mitral Valve Prolapse; Rheumatic Heart Disease; Thromboembolism; Warfarin

Atrial fibrillation is a common condition and carries a risk of thromboembolism. There is general acceptance that those patients with atrial fibrillation secondary to valvular (and in particular mitral) heart disease or following valve replacement require anticoagulation. Since patients with non-valvular causes of atrial fibrillation are a more heterogeneous group, the indications for anticoagulation have been less clear. A number of benchmark studies clearly indicate that the risk of stroke can be reduced by up to 70% in those treated with warfarin, but only by a variable 30% with aspirin. Problems with interpretation of the results of these studies relate to the younger age range included and a low recruitment rate, leading to a possible under-estimate of the bleeding risk. Subgroup analysis provides risk stratification for patients with non-valvular atrial fibrillation so that those with three or more of any of the five following risk factors: congestive heart failure, hypertension, previous stroke, left atrial enlargement or left ventricular hypertrophy, have an 18% chance of new thromboembolic events, whereas this falls to one third of this with only one or two risk factors, and 1% with none. Those with so-called lone atrial fibrillation aged < 60 years have a very low incidence of atrial fibrillation and can be considered for aspirin alone. The trials supporting in these statements are presented.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials as Topic; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Intracranial Embolism and Thrombosis; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Warfarin

The optimal use of anticoagulants during pregnancy will continue to be controversial until appropriate randomized controlled and prospective trials with adequate sample sizes are completed. The relative low frequency of thromboembolic events, the concerns about maternal and fetal safety of both treatment and withholding treatment, and the reservations about prospectively enrolling pregnant women in treatment trials has sadly dissuaded the appropriate study of this life-threatening condition. North American trials that enroll pregnant women to evaluate the efficacy of LMWH are of preeminent importance owing to their superior bioavailability, ease in dosing, longer half-life, and side effect profile. Similarly, trials evaluating the optimal management of women of childbearing age with valvular disease are critical to reduce the considerable maternal and fetal morbidity and mortality associated with these pregnancies. Such definitive studies will need to be multicenter in design and it is hoped that the National Institutes of Health initiative to enroll pregnant women in clinical trials will at last be realized in the near future.

Topics: Anticoagulants; England; Female; Heart Valve Diseases; Heparin; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Sweden; Thromboembolism; Thrombolytic Therapy; United States; Warfarin

Cardiac causes of stroke account for approximately 20% of strokes occurring in the United States. Transthoracic echocardiography (TTE) remains the cornerstone of non-invasive cardiac imaging, but transesophageal echocardiography (TEE) is superior for identifying potential cardiac sources of emboli, including left atrial thrombi, valvular vegetations, thoracic aortic plaque, patent foramen ovale, and spontaneous left atrial echocardiographic contrast. The diagnostic yield of TEE for potential cardiac causes of thromboembolism exceeds 50%. The impact of TEE on the clinical management of this group, however, remains undefined for most TEE-specific diagnoses. Thus, routine use of TEE in these patients has been questioned. The diagnostic yield is highest if the clinical history/physical examination suggests a cardiac source. However, the clinical scenario often dictates patient management, and TEE data are used to "validate" the clinical impression. Data from large, prospective, randomized (aspirin/warfarin) studies, in which TEE data are obtained from patients with suspected cardiac thromboembolism, are needed. If specific TEE diagnoses can be identified in which defined therapies are beneficial, "source of embolism" will continue to be the most common indication for TEE referral. In this paradigm, TEE (without initial TTE) will probably become a more direct diagnostic pathway. However, if these studies demonstrate that all patients with suspected cardiac source benefit from one (or no) therapy, independent of TEE data, referrals for TEE will decline. Results of ongoing randomized trials to evaluate the efficacy of TEE in patients with cryptogenic stroke or transient ischemic attack are awaited.

Topics: Anticoagulants; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Aspirin; Cerebrovascular Disorders; Echocardiography, Transesophageal; Heart Atria; Heart Diseases; Heart Septal Defects, Atrial; Heart Valve Diseases; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Medical History Taking; Physical Examination; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Referral and Consultation; Reproducibility of Results; Thrombosis; Treatment Outcome; Warfarin

Despite the availability of anticoagulant drugs for many years, there are still controversies regarding their use in many cardiovascular conditions. In this article, the pharmacology of warfarin and heparin are reviewed, and the clinical applications of these therapies in patients with valvular heart disease, atrial fibrillation, or both, discussed.

Topics: Atrial Fibrillation; Bioprosthesis; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Risk Factors; Thromboembolism; Warfarin

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Heart Valve Diseases; Hemorrhage; Humans; Ischemic Attack, Transient; Mitral Valve; Myocardial Infarction; Rheumatic Heart Disease; Warfarin

Warfarin is the standard anticoagulation therapy for valvular atrial fibrillation (AF); however, new oral anticoagulants have emerged as an alternative. We compared the efficacy and safety of dabigatran with conventional treatment in AF associated with left-sided valvular heart disease (VHD), including mitral stenosis (MS). Patients with AF and left-sided VHD were randomly assigned to receive dabigatran or conventional treatment. The primary end point was the occurrence of clinical stroke or a new brain lesion (silent brain infarct and microbleed) on 1-year follow-up brain magnetic resonance imaging. Patients in the dabigatran group were switched from warfarin (n = 52), antiplatelets alone (n = 5), or no therapy (n = 2) to dabigatran. In the conventional group, 53 used warfarin (including 42 MS patients), and 7 used antiplatelets. No death or clinical stroke event occurred in either group during follow-up. Silent brain infarct and microbleed occurred in 20 and 2 patients in the dabigatran group and 20 and 4 patients in the conventional treatment group. The incidence rate of the primary end point did not significantly differ between groups (34% vs 40%, relative risk 0.87, 95% confidence interval 0.59 to 1.29, p = 0.491). The primary end point rate was similar between groups in 82 patients (40 in the dabigatran group and 42 in the conventional group) with MS (32% vs 34%, relative risk 0.93, 95% confidence interval: 0.57 to 1.50, p = 0.759). In conclusion, primary end point rates after treatment with dabigatran were similar to conventional treatment in patients with significant VHD and AF. New oral anticoagulants could be a reasonable alternative to warfarin in patients with AF and VHD, which should be confirmed in future large-scale studies.

Topics: Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Dabigatran; Heart Valve Diseases; Humans; Stroke; Treatment Outcome; Warfarin

We assessed the predictive accuracy of the Warfarin Pharmacogenetics Consortium (IWPC) algorithm in a prospective cohort of 376 high-risk elderly patients (≥65 years) who required new treatment with warfarin for either medical (non valvular atrial fibrillation) or surgical conditions (heart valve replacement), had ≥1 comorbid conditions, and regularly used ≥2 other drugs. Follow-up visits were performed according to clinical practice and lasted for a maximum of 1 year. Two hundred and eighty-three (75%) patients achieved a stable maintenance dose. Warfarin maintenance doses were low on average (median 20.3 mg/week, interquartile range, 14.1-27.7 mg/week) and were substantially overestimated by the IWPC algorithm. Overall the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable dose was equal to 37.5%, (95% CI 32.0-43.3%). IWPC algorithm explained only 31% of the actual warfarin dose variability. Modifications of the IWPC algorithm are needed in high-risk elderly people.

Topics: Aged; Aged, 80 and over; Algorithms; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Valve Diseases; Humans; Internationality; Male; Pharmacogenetics; Prospective Studies; Risk Factors; Warfarin

To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.. There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.. Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.. In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.. ARISTOTLE clinical trial number NCT00412984.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Atrial Fibrillation; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve; Pyrazoles; Pyridones; Stroke; Treatment Outcome; Warfarin

The clinical utility of genotype-guided warfarin dosing remains controversial. The objective of this trial was to evaluate the efficacy and safety of genotype-guided warfarin dosing in East Asians.. A double-blind, randomized control trial was performed to compare a genotype-guided dosing algorithm (CYP2C9, VKORC1, and CYP4F2) with a clinical-guided one in the initiation treatment for patients with mechanical heart valves. The primary outcomes included the time to reach a stable dose and the percentage of time in the therapeutic range (TTR).. Two hundred one patients were randomly assigned to treatment, 101 to control and 100 to study. The major bleeding and thromboembolic event-free rate in the study group was 97.0% (95% confidence interval: 90.9% to 99.2%). Compared with the control group, the study group shortened the time to reach a stable dose (mean: 42.09 ± 23.655 days versus 33.52 ± 20.044 days, p = 0.009). The TTRs were 47.257% and 47.461% in the control and study group (p = 0.941), respectively. Patients with the CYP2C9 *1/*3 genotype had higher international normalized ratio (INR) variability than patients with the CYP2C9 *1/*1 genotype (p = 0.024). Compared with normal and sensitive responders, the highly sensitive responders were at increased risk of an INR of 4.0 or greater (p < 0.05).. The genotype-guided warfarin dosing was safe and might be more efficient for the time to reach a stable dose. Pharmacogenomic testing might be beneficial to identify the patients with the CYP2C9 *1/*3 genotype and the highly sensitive responders, who were in the high-risk subgroup of patients with mechanical heart valves. An appropriately powered study is needed to further confirm these findings.

Topics: Anticoagulants; Asian People; Double-Blind Method; Female; Genotype; Heart Valve Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Warfarin

Mechanical heart valves (MHV) are extremely durable, but they require permanent use of anticoagulation to prevent thromboembolic events. The only approved therapeutic options are vitamin K antagonists (VKAs), such as warfarin. As a drug class, clinical management is difficult, therefore new alternatives need to be evaluated.. RIWA is a phase II/III, prospective, open-label, randomized, pilot study designed to investigate oral rivaroxaban 15 mg twice daily compared with dose-adjusted warfarin for the prevention of stroke (ischemic or hemorrhagic) and systemic embolism in patients with MHV, from August 2018 to December 2019. Patients will undergo transesophageal echocardiography at the beginning and the end of the study (follow-up time 90 days). On an explanatory basis, all events will be analyzed, including stroke, peripheral systemic embolism, valve thrombosis, significant bleeding and death.. Warfarin and similar VKAs are standard therapy for patients with an MHV. Even with the appropriate use of therapy, the incidence of thromboembolic events is high at 1-4% per year. Furthermore, bleeding risk is significant, ranging from 2 to 9% per year. The new frontier to be overcome in relation to use of the new oral anticoagulants is undoubtedly in patients with MHV. A significant portion of people with MHV worldwide will benefit if noninferiority of these new agents is confirmed.. ClinicalTrials.gov identifier: NCT03566303. Recruitment Status: Recruiting. First Posted: 25 June 2018. Last Update Posted: 25 June 2018.

Topics: Adolescent; Adult; Aged; Anticoagulants; Cardiac Surgical Procedures; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Echocardiography, Transesophageal; Heart Valve Diseases; Heart Valves; Humans; Middle Aged; Pilot Projects; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Warfarin; Young Adult

The use of non-vitamin K antagonist oral anticoagulants (NOACs) instead of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and coexisting valvular heart disease (VHD) is of substantial interest.. This study explored outcomes in patients with AF with and without VHD in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial, comparing edoxaban with warfarin.. Valvular heart disease was defined as history or baseline echocardiography evidence of at least moderate aortic/mitral regurgitation, aortic stenosis, or prior valve surgery (bioprosthesis replacement, valve repair, valvuloplasty). Patients with moderate to severe mitral stenosis or mechanical heart valves were excluded from the trial. Comparisons were made of rates of stroke/systemic embolic event (SSEE), major bleeding, additional efficacy and safety outcomes, as well as net clinical outcomes, in patients with or without VHD treated with edoxaban or warfarin, using adjusted Cox proportional hazards.. After adjustment for multiple baseline characteristics, compared with no-VHD patients (n = 18,222), VHD patients (n = 2,824) had a similar rate of SSEE but higher rates of death (hazard ratio [HR]: 1.40; 95% confidence interval [CI]:1.26 to 1.56; p <0.001), major adverse cardiovascular events (HR: 1.29; 95% CI: 1.16 to 1.43; p <0.001), and major bleeding (HR: 1.21; 95% CI: 1.03 to 1.42; p = 0.02). Higher-dose edoxaban regimen had efficacy similar to warfarin in the presence of VHD (for SSEE, HR: 0.69; 95% CI: 0.44 to 1.07, in patients with VHD, and HR: 0.91; 95% CI: 0.77 to 1.07, in patients without VHD; p interaction [p. The presence of VHD increased the risk of death, major adverse cardiovascular events, and major bleeding but did not affect the relative efficacy or safety of higher-dose edoxaban versus warfarin in AF. (Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs. Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [ENGAGE AF-TIMI 48]; NCT00781391).

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Heart Valve Diseases; Hemorrhage; Humans; Male; Middle Aged; Pyridines; Stroke; Thiazoles; Warfarin

The RE-LY trial (Randomized Evaluation of Long-Term Anticoagulant Therapy) compared dabigatran 150 and 110 mg twice daily with warfarin in 18 113 patients with atrial fibrillation. Those with prosthetic heart valves, significant mitral stenosis, and valvular heart disease (VHD) requiring intervention were excluded. Others with VHD were included.. This is a post hoc analysis of the RE-LY trial.. There were 3950 patients with any VHD: 3101 had mitral regurgitation, 1179 with tricuspid regurgitation, 817 had aortic regurgitation, 471 with aortic stenosis, and 193 with mild mitral stenosis. At baseline, patients with any VHD had more heart failure, coronary disease, renal impairment, and persistent atrial fibrillation. Patients with any VHD had higher rates of major bleeds (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.16-1.5) but similar stroke or systemic embolism event rates (HR, 1.09; 95% CI, 0.88-1.33). For patients receiving dabigatran 110 mg, major bleed rates were lower than for patients taking warfarin (HR, 0.73; 95% CI, 0.56-0.95 with VHD; HR, 0.84; 95% CI, 0.71-0.99 without VHD), and major bleed rates for dabigatran 150 mg were similar to those for warfarin in patients with VHD (HR, 0.82; 95% CI, 0.64-1.06) or without VHD (HR, 0.98; 95% CI, 0.83-1.15). For dabigatran 150 mg, stroke/systemic embolic event rates were lower compared with warfarin in those with VHD (HR, 0.59; 95% CI, 0.37-0.93) and those without VHD (HR, 0.67; 95% CI, 0.52-0.86), and stroke/systemic embolic event rates were similar for warfarin and dabigatran 110 mg regardless of the presence of VHD (HR, 0.97; 95% CI, 0.65-1.45; and HR, 0.88; 95% CI, 0.70-1.10). Intracranial bleeds and death rates for dabigatran 150 and 110 mg were lower compared with warfarin independently of the presence of VHD.. The presence of any VHD did not influence the comparison of dabigatran with warfarin.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Drug Administration Schedule; Female; Heart Valve Diseases; Humans; Male; Prospective Studies; Retrospective Studies; Time Factors; Warfarin

Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves.. We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.97 and HR, 0.84; 95%, CI 0.67-1.04; interaction P=0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61-1.04 and HR, 0.65; 95% CI, 0.55-0.77; interaction P=0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84-1.22 and HR, 0.84; 95% CI, 0.73-0.96; interaction P=0.10).. More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Stroke; Thromboembolism; Warfarin

The dosage of warfarin is restricted due to its narrow therapeutic index, so, the required dose must be adapted individually to each patient. Variations in warfarin dosage are influenced by genetic factors, the changes in patient diet, anthropometric and clinical parameters. To determine whether VKORC1 G3730A and CYP4F2 G1347A genotypes contribute to warfarin dosage in patients during initiation and long-term anticoagulation treatment after heart valve surgery. From totally 307 patients, who underwent heart valve surgery, 189 patients (62 %) who had been treated with warfarin more than 3 months, were included into the study. A hierarchical stepwise multivariate linear regression model showed, that during initiation clinical factors can explain 17 % of the warfarin dose variation. The addition of CYP2C9 and VKORC1 G-1639A genotype raises the accuracy about twice-to 32 %. The CYP4F2 G1347A genotype can add again about 2-34 %. During long-term treatment clinical factors explain about 26 % of warfarin dose variation. If the CYP2C9 *2, *3, VKORC1*2 alleles are detected, model can explain about 49 % in dose variation. The *3 allele of VKORC1 raises the accuracy by 1-50 %. The carriers of CYP4F2 A1347A genotype required higher daily warfarin doses during initiation of warfarin therapy after heart valve surgery than comparing to G/G and G/A carriers, but during the longer periods of warfarin use, the dosage of warfarin depended significantly on VKORC1 *3 allele (G3730A polymorphism) and on the thyroid stimulating hormone level in the blood plasma.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Female; Heart Valve Diseases; Humans; International Normalized Ratio; Male; Middle Aged; Polymorphism, Genetic; Retrospective Studies; Vitamin K Epoxide Reductases; Warfarin

Patients on warfarin for mechanical heart valves are at increased risk for thromboembolic events and intracranial hemmorhage. In current guidelines, a low dose of vitamin K is the recommended treatment for moderate over-anticoagulation based on studies in which only minority patients participating had mechanical heart valves. We performed a randomized controlled trial to compare the efficacy and safety profile of low-dose intravenous vitamin K and fresh frozen plasma (FFP) for patients with mechanical heart valves and mild to moderate over-anticoagulation (international normalized ratio [INR] 4 to 7). In a 24-month period, we randomized 102 patients to (1) vitamin K or (2) FFP. The baseline INR at presentation between the vitamin K group and the FFP group was 4.61 +/- 0.007 vs 4.78 +/- 0.07 (p = 0.11). Six hours after treatment, patients in the FFP group had a significantly lower mean INR compared with the vitamin K group (2.75 +/- 0.06 vs 3.44 +/- 0.10, p = 0.01). No patient in both groups had over-correction (INR < 2). One week later, there was no significant difference in mean INR between both groups (2.7 +/- 0.11 vs 2.56 +/- 0.12, p = 0.41). Fifty-eight percent of patients in the FFP group and 51% in the vitamin K group had an INR within the target range. There were no adverse reactions or outcomes in both groups. In conclusion, intravenous low-dose vitamin K is a safe alternative to FFP infusion for warfarin overdose in patients with mechanical heart valves.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Component Transfusion; Coagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Vitamin K; Warfarin

Mitral valve surgery seldom suppresses atrial fibrillation (AF), present prior to surgery. Maze III surgery eliminates AF in >80% of cases, the reason why combining this procedure with mitral valve surgery in patients with AF seems worthwhile. We prospectively studied the outcome of combining the Maze III procedure with mitral valve surgery.. Thirty-five patients with AF and a mean age of 64 years undergoing mitral valve surgery were prospectively randomized according to a 2.5:1 ratio to surgery with (n=25), or without (n=10) maze III and followed for at least 1 year.. At discharge and after 12 months freedom from AF was 56% and 92%, respectively, in the maze group, and 0% and 20%, respectively, in patients without maze (group differences at discharge p=0.002, after 12 months p=0.0007). Sinus node incompetence was seen in 1 of 25 maze patients requiring pacing. No in-hospital or late death occurred; stroke was observed in 1 patient (without maze). Quality of life markedly improved after surgery, but did not differ between patients with or without maze surgery.. This first prospective randomized study shows that combining maze III with mitral valve surgery resulted in a significantly better elimination of preoperative AF than mitral valve surgery alone. As the quality of life did not differ between patients with, or without maze surgery, additional maze surgery is primarily recommended in patients in whom anticoagulation therapy can be avoided after surgery, specifically in patients with scheduled mitral valve plasty.

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiac Surgical Procedures; Echocardiography, Doppler; Electric Countershock; Electrocardiography, Ambulatory; Endpoint Determination; Exercise Test; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Prospective Studies; Quality of Life; Treatment Outcome; Warfarin

Patients with mechanical heart valves are critically dependent upon adequate anticoagulation. The present patients are young, geographically dispersed and socioeconomically deprived. Hospital attendance is erratic, and compliance with conventional anticoagulation difficult. The need exists for an alternative method of anticoagulation that requires neither regular visits nor adjustment of the warfarin dose.. A five-year prospective randomized double-blind study was undertaken to compare the efficacy and safety of a predetermined, individualized fixed-dose versus adjusted-dose warfarin. Postopoeratively, 296 patients, after an initial dose-finding phase (International Normalized Ratio (INR) 2.0 - 3.5), were randomized to either fixed-dose or adjusted-dose warfarin.. For the intention-to-treat analysis, the groups were well-matched with regard to baseline characteristics. Among patients on fixed-dose warfarin, 63% of INRs were in the range 2.0 - 4.5 compared with 64% in patients on adjusted-dose warfarin. The mean follow up period was 2.4 years in both groups; total follow up was 725 patient-years. There were seven deaths in the fixed-dose warfarin group, and five in the adjusted-dose group (p = 0.52). Thirteen major thrombotic events, occurred in the fixed-dose warfarin group, and four in the adjusted-dose group (p = 0.02). Twelve major hemorrhagic events occurred in each group.. In this predominantly young, impoverished population, despite similar overall INR control, fixed-dose warfarin was associated with an increase in thromboembolic events, but no significant increase in mortality or hemorrhagic events. Fixed-dose warfarin may be an acceptable option where conventional anticoagulation is impracticable. In particular, the study highlighted the difficulties of adequate anticoagulation in a population where compliance is erratic and often non-existent.

Topics: Adolescent; Adult; Aged; Anticoagulants; Bioprosthesis; Developing Countries; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Patient Compliance; Postoperative Care; Poverty; Probability; Prospective Studies; Reference Values; Rheumatic Heart Disease; Risk Factors; South Africa; Survival Analysis; Thromboembolism; Treatment Outcome; Warfarin

Patients who had undergone prosthetic valve replacement were treated with warfarin (anticoagulant) alone or in combination of ticlopidine (200 mg/day) or aspirin (81 mg/day) (anti-platelet agents). The study of blood coagulation factors and platelet aggregation were carried out with these cases. 1) The patients (n = 24) receiving warfarin for 21 days after prosthetic valve replacement revealed marked increases in PIVKA-II and vitamin K1-epoxide. The protein C activity was significantly lower than that before the operation. High levels of more than 5 ng/ml of TAT were found before operation and after warfarin administration for 21 days. 2) Warfarin did not affect platelet aggregation, whereas ticlopidine inhibited ADP-induced platelet aggregation and aspirin inhibited both collagen-induced and arachidonic acid-induced aggregation. In conclusion, combined use of anticoagulants and antiplatelet agents after prosthetic valve replacement will suppress not only the blood coagulation but also the platelet aggregation systems.

Topics: Adult; Aged; Anticoagulants; Aspirin; Blood Coagulation; Depression, Chemical; Drug Therapy, Combination; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Thrombosis; Ticlopidine; Warfarin

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Aortic Valve; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Germany; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Mitral Valve; Phenprocoumon; Postoperative Complications; Prospective Studies; Survival Rate; Thromboembolism; Warfarin

The effects on anticoagulation of a purified trivalent sub-unit influenza vaccine and a 14-valent pneumococcal vaccine were investigated in a single-blind controlled study involving 69 well-stabilised warfarin recipients. There were no clinically or statistically significant alterations of anticoagulant control in vaccine recipients as compared with controls at 2, 7 and 21 days after vaccination. On the basis of these data, concern about warfarin-vaccine interaction should not deter practitioners from immunising warfarin recipients against influenza or infection with Streptococcus pneumoniae.

Topics: Aged; Bacterial Vaccines; Blood Coagulation; Female; Heart Valve Diseases; Humans; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccination; Warfarin

In 228 ambulatory patients receiving treatment with warfarin, there was a progressive decline in the dose required to produce an equivalent degree of anticoagulant control with increasing age from the third decade onwards. However, the relationship between age and dose was significant only in patients receiving warfarin after episodes of venous thromboembolism or because of coronary artery disease. Patient weight was also related to warfarin requirements, although it was less important a determinant than age.

Topics: Adult; Aged; Aging; Angina Pectoris; Blood Coagulation Disorders; Body Weight; Clinical Trials as Topic; Drug Administration Schedule; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Prospective Studies; Prothrombin Time; Sex Factors; Thromboembolism; Warfarin

Topics: Chloral Hydrate; Clinical Trials as Topic; Drug Synergism; Heart Valve Diseases; Humans; Myocardial Infarction; Placebos; Prothrombin Time; Thrombophlebitis; Warfarin

The use of anticoagulation is mandatory for prevention of prosthetic valve thrombosis (PVT) worldwide, regardless of the valve type or position in the heart. In case a thrombosis causes symptomatic dysfunction, treatment usually includes the use of thrombolytic therapy or surgery. We report a case of PVT involving a patient with a mechanical aortic valve which was treated entirely with the use of anticoagulation therapy (warfarin).. A 58-year-old man had an aortic valve replacement using a Carbomedics. Only a few cases of symptomatic, thrombotic mechanical aortic valve were entirely treated with anticoagulation only. Our patient is one such case who had resolution of symptoms and improvement on NYHA functional classification (IV to I).

Topics: Anticoagulants; Aortic Valve; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Thrombosis; Warfarin

Anticoagulation response to warfarin during the initial stage of therapy varies among individuals. In this study, we aimed to combine pharmacometabolomic and pharmacogenetic data to predict interindividual variation in warfarin response, and, on this basis, suggest an initial daily dose range. The baseline metabolic profiles, genotypes, and clinical information of 160 patients with heart valve disease served as the variables of the function of the last international normalized ratio measured before a patient's discharge (INR

Topics: Anticoagulants; Dose-Response Relationship, Drug; Female; Forecasting; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Metabolomics; Pharmacogenomic Testing; Random Allocation; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Dysarthria; Echocardiography, Transesophageal; Endocarditis, Non-Infective; Facial Paralysis; Heart Valve Diseases; Humans; Interdisciplinary Communication; Ischemic Stroke; Male; Middle Aged; Treatment Outcome; Warfarin

There are limited data regarding direct oral anticoagulants (DOACs) for stroke prevention in patients with bioprosthetic heart valves (BHVs) and atrial fibrillation (AF). The objectives of this study were to evaluate the ambulatory utilization of DOACs and to compare the effectiveness and safety of DOACs versus warfarin in patients with AF and BHVs. We conducted a retrospective cohort study at a large integrated health care delivery system in California. Patients with BHVs and AF treated with warfarin, dabigatran, rivaroxaban, or apixaban between September 12, 2011 and June 18, 2020 were identified. Inverse probability of treatment-weighted comparative effectiveness and safety of DOACs compared with warfarin were determined. Use of DOACs gradually increased since 2011, with a significant upward in trend after a stay-at-home order related to COVID-19. Among 2,672 adults with BHVs and AF who met the inclusion criteria, 439 were exposed to a DOAC and 2233 were exposed to warfarin. For the primary effectiveness outcome of ischemic stroke, systemic embolism and transient ischemic attack, no significant association was observed between use of DOACs compared with warfarin (HR 1.19, 95% CI 0.96 to 1.48, p = 0.11). Use of DOACs was associated with lower risk of the primary safety outcome of intracranial hemorrhage, gastrointestinal bleeding, and other bleed (HR 0.69, 95% CI 0.56 to 0.85, p < 0.001). Results were consistent across multiple subgroups in the sensitivity analyses. These findings support the use of DOACs for AF in patients with BHVs.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Female; Heart Valve Diseases; Heart Valves; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Treatment Outcome; Warfarin; Young Adult

Valvular heart disease (VHD) is frequently associated with neurologic complications. Cerebral embolism is the most common, since thrombus formation results from the abnormalities in the valvular surfaces and the anatomic and physiologic changes associated with valve dysfunction, including atrial or ventricular enlargement, intracardiac thrombi, and cardiac dysrhythmias. Prosthetic heart valves, particularly mechanical valves, are very thrombogenic, which explains the high risk of thromboembolism and the need for long-term anticoagulation. Transcatheter aortic valve replacement (TAVR) has emerged as a nonoperative alternative to surgical aortic valve replacement for patients with intermediate or high surgical risk, and the procedure also has a risk of cerebral ischemia. In addition, anticoagulation, the mainstay of treatment to prevent cerebral embolism, has known potential for hemorrhagic complications. The emergence of new oral anticoagulants with similar effectiveness to warfarin and a better safety profile has facilitated the management of patients with atrial fibrillation. However, their application in patients with mechanical heart valves is still evolving. The prevention and management of these complications requires an understanding of their natural history to balance the risks posed by valvular heart disease, as well as the risks and benefits associated with the treatment.

Topics: Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Humans; Thromboembolism; Warfarin

Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927,

Topics: Acenocoumarol; Aged; Anticoagulants; Blood Coagulation; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Retrospective Studies; Venous Thromboembolism; Warfarin

Warfarin is a commonly prescribed anticoagulant for valvular heart disease that plays an important role in clinical management to prevent thrombotic events. In this study, we aim to perform a comprehensive study to investigate the genetic biomarkers of stable warfarin dose in the Han Chinese population. We performed an integrative study on 211 Han Chinese patients with valvular heart disease. A total of 40 single nucleotide polymorphisms (SNPs) in 10 important genes (CYP2C9, VKORC1, ABCB1, CYP4F2, APOE, PROC, GGCX, EPHX1, CALU, and SETD1A) which are involved in the warfarin metabolic pathway and equilibrium of coagulation and anticoagulation were selected. We applied MassARRAY technology to genotype the 40 SNPs identified in these Han Chinese patients. Our results showed that 13 SNPs on 6 genes (CYP2C9, VKORC1, ABCB1, PROC, EPHX1, and SETD1A) were associated with the individual stable warfarin dose. Two VKORC1 SNPs (rs9934438 and rs2359612) were the strongest genetic factors determining warfarin dose requirements (P = 8 × 10-6 and 9 × 10-6, respectively). Rs4889599 in SETD1A was first reported to be associated with warfarin dose at a significant level of 0.001 in our study (Padjust = 0.040 after Bonferroni correction). We discovered that genetic variants in CYP2C9, VKORC1, ABCB1, PROC, EPHX1, and SETD1A may affect the stable warfarin dose requirement in Han Chinese patients with valvular disease. The discovery of these potential genetic markers will facilitate the development of advanced personalized anticoagulation therapy in Han Chinese patients.

Topics: Adult; Aged; Anticoagulants; Asian People; China; Clinical Decision-Making; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Predictive Value of Tests; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

Calcific aortic valve disease is a common heart disease that contributes to increased cardiovascular morbidity and mortality. There is a lack of effective pharmaceutical therapy because its mechanisms are not yet fully known. Ginkgo biloba extract (EGB761) is reported to alleviate vascular calcification. However, whether EGB761 protects against aortic valve calcification, a disease whose pathogenesis shares many similarities with vascular calcification, and potential molecular mechanisms remain unknown. In this study, porcine aortic valve interstitial cell (pAVIC) calcification was induced by warfarin with or without the presence of EGB761. Immunostaining was performed to establish and characterize the pAVIC phenotype. Calcium deposition and calcium content were examined by Alizarin Red S staining and an intracellular calcium content assay. Alkaline phosphatase activity was detected by the p-nitrophenyl phosphate method. The expression levels of bone morphogenetic protein-2 (BMP2), Runt-related transcription factor 2 (Runx2), homeobox protein MSX-2, and phosphorylated (p)-Smad1/5 were detected by reverse transcription-quantitative polymerase chain reaction (PCR) and Western blot analysis. Consistent with these in vitro data, we also confirmed the suppression of in vivo calcification by EGB761 in the warfarin-induced C57/Bl6 mice. The results indicated that both pAVICs and aortic valves tissue of mice stimulated with warfarin showed increased calcium deposition and expression of osteogenic markers (alkaline phosphatase, BMP2, homeobox protein MSX-2, and Runx2) and promoted p-Smad1/5 translocation from the cytoplasm to the nucleus. The addition of EGB761 significantly inhibited p-Smad1/5 translocation from the cytoplasm to the nucleus, thus suppressing calcification. In conclusion, EGB761 could ameliorate warfarin-induced aortic valve calcification through the inhibition of the BMP2-medicated Smad1/5/Runx2 signaling pathway.

Topics: Active Transport, Cell Nucleus; Animals; Aortic Valve; Bone Morphogenetic Protein 2; Calcinosis; Calcium; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Disease Models, Animal; Ginkgo biloba; Heart Valve Diseases; Homeodomain Proteins; Male; Mice, Inbred C57BL; Osteogenesis; Phosphorylation; Plant Extracts; Signal Transduction; Smad1 Protein; Smad5 Protein; Sus scrofa; Warfarin

Patients requiring low-dose warfarin are more likely to suffer bleeding due to overdose. The goal of this work is to improve the feedforward neural network model's precision in predicting the low maintenance dose for Chinese in the aspect of training data construction. We built the model from a resampled dataset created by equal stratified sampling (maintaining the same sample number in three dose-groups with a total of 3639) and performed internal and external validations. Comparing to the model trained from the raw dataset of 19,060 eligible cases, we improved the low-dose group's ideal prediction percentage from 0.7 to 9.6% and maintained the overall performance (76.4% vs. 75.6%) in external validation. We further built neural network models on single-dose subsets to invest whether the subsets samples were sufficient and whether the selected factors were appropriate. The training set sizes were 1340 and 1478 for the low and high dose subsets; the corresponding ideal prediction percentages were 70.2% and 75.1%. The training set size for the intermediate dose varied and was 1553, 6214, and 12,429; the corresponding ideal prediction percentages were 95.6, 95.1%, and 95.3%. Our conclusion is that equal stratified sampling can be a considerable alternative approach in training data construction to build drug dosing models in the clinic.

Topics: Adult; Aged; Anticoagulants; Cardiac Surgical Procedures; China; Dose-Response Relationship, Drug; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valves; Humans; Machine Learning; Male; Middle Aged; Neural Networks, Computer; Warfarin

When patients with extensive mitral annular calcification undergo mitral valve replacement, excessive debridement of calcification may result in fatal complications and may protract operation time. We report a case of supra-annular MVR using "the chimney technique" on a high-risk patient for severe mitral stenosis with extensive mitral annular calcification. This technique is usually used in small infants whose mitral annulus is smaller than the smallest available prosthetic valve. We apply this technique to minimize the debridement of calcification and shorten the operation time. The operation was successfully completed, and the postoperative course has been uneventful. This technique was safely and easily performed, and eliminated the need for aggressive debridement of the calcification. We believe this technique may be a good choice for high-risk patients with mitral annular calcification.

Topics: Aged; Anticoagulants; Blood Pressure; Calcinosis; Cardiopulmonary Bypass; Echocardiography; Female; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Stenosis; Tomography, X-Ray Computed; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Aortic Valve; Aortic Valve Stenosis; Benzoates; Bicuspid Aortic Valve Disease; Bioprosthesis; Chest Pain; Craniotomy; Echocardiography; Echocardiography, Three-Dimensional; Echocardiography, Transesophageal; Enoxaparin; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hematoma, Subdural, Acute; Humans; Hydrazines; Immunologic Factors; Plasma Exchange; Purpura, Thrombocytopenic, Idiopathic; Pyrazoles; Recurrence; Rituximab; Stroke Volume; Thrombosis; Ventricular Dysfunction, Left; Warfarin

Warfarin is the most commonly prescribed oral anticoagulant in sub-Saharan Africa and requires ongoing monitoring. The burden of both infectious diseases and non-communicable diseases is high and medicines used to treat comorbidities may interact with warfarin. We describe service provision, patient characteristics, and anticoagulation control at selected anticoagulation clinics in Uganda and South Africa.. We evaluated two outpatient anticoagulation services in Kampala, Uganda and three in Cape Town, South Africa between 1 January and 31 July 2018. We collected information from key staff members about the clinics' service provision and extracted demographic and clinical data from a sample of patients' clinic records. We calculated time in therapeutic range (TTR) over the most recent 3-month period using the Rosendaal interpolation method.. We included three tertiary level, one secondary level and one primary level anticoagulation service, seeing between 30 and 800 patients per month. Care was rendered by nurses, medical officers, and specialists. All healthcare facilities had on-site pharmacies; laboratory INR testing was off-site at two. Three clinics used warfarin dose-adjustment protocols; these were not validated for local use. We reviewed 229 patient clinical records. Most common indications for warfarin were venous thrombo-embolism in 112/229 (49%), atrial fibrillation in 74/229 (32%) and valvular heart disease in 30/229 (13%). Patients were generally followed up monthly. HIV prevalence was 20% and 5% at Ugandan and South African clinics respectively. Cardiovascular comorbidity predominated. Furosemide, paracetamol, enalapril, simvastatin, and tramadol were the most common concomitant drugs. Anticoagulation control was poor at all included clinics with median TTR of 41% (interquartile range 14% to 69%).. TTR was suboptimal at all included sites, despite frequent patient follow-up. Strategies to improve INR control in sub-Saharan patients taking warfarin are needed. Locally validated warfarin dosing algorithms in Uganda and South Africa may improve INR control.

Topics: Adult; Aged; Ambulatory Care; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Drug Monitoring; Female; Heart Valve Diseases; HIV Infections; Humans; International Normalized Ratio; Male; Middle Aged; Secondary Care Centers; South Africa; Tertiary Care Centers; Uganda; Venous Thromboembolism; Warfarin

Mechanical prosthetic heart valves (MPHVs) are highly thrombogenic, and a pregnancy-induced procoagulant status increases the risk of MPHV thrombosis. Despite numerous case reports, 2 major registries and meta-analyses/systematic reviews, optimal anticoagulation therapy during pregnancy remains controversial. The goal of this study was to evaluate different anticoagulation regimens in pregnant patients with MPHVs. The outcomes of anticoagulation regimens were assessed retrospectively in pregnant women (110 women; 155 pregnancies) with MPHVs. The study population was divided into 5 groups according to anticoagulation regimens used; high-dose warfarin (>5 mg/d) throughout pregnancy (group 1), low-dose warfarin (≤5 mg/d) throughout pregnancy (group 2), low molecular weight heparin (LMWH) throughout pregnancy (group 3), first trimester LMWH, 2nd and 3rd trimester warfarin (group 4), first 2 trimester LMWH, and 3rd trimester warfarin (group 5). Of 155 pregnancies, 55 (35%) resulted in fetal loss; whereas 41 (27%) cases with abortion (miscarriage and therapeutic) and 14 (9%) stillbirths occurred. The comparison of the groups showed that the whole abortion rates including therapeutic abortion were significantly higher in Group 1, and lower in groups 3 and 5 (p <0.001). However, miscarriage rates were similar between the groups. A total of 53 pregnancies (34%) suffered from prosthetic valves thrombosis (PVT) during pregnancy or in the postpartum period. Group 2 had significantly lower rates of PVT than the other groups (p <0.001). In conclusion, the current data suggests that there is no optimal therapy, and that all managements have advantages and disadvantages. Low-dose warfarin (≤5 mg/day) regimen with therapeutic international normalized ratio levels may provide effective maternal protection throughout pregnancy with acceptable fetal outcomes.

Topics: Adult; Anticoagulants; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Registries; Retrospective Studies; Thromboembolism; Warfarin

Hypo-attenuated leaflet thickening (HALT) in bioprosthetic aortic valve has been studied, but its equivalent in bioprosthetic mitral valve (bMV) remains uncharacterized. We sought to identify the prevalence, hemodynamic characteristics, and significance of anticoagulation therapy in bMV HALT.. A single-center cross-sectional study of 53 consecutive patients who underwent mitral valve replacement (MVR) with bMV between 2007 and 2017 was conducted. Cardiac-gated contrasted CT scans were obtained. Anticoagulant and antiplatelet therapy use were ascertained at the time of hospital discharge and CT scanning. Patient characteristics, postoperative stroke, and hemodynamic profile by echocardiogram were obtained to descriptively characterize the prevalence and characteristics associated with bMV HALT.. Three patients (5.7%) were found to have a HALT on bMV. The mean time from index MVR to CT scan was 3.4 ± 0.8 years in HALT cohort and 3.4 ± 2.7 years in non-HALT cohort. Fifty patients (94.3%) were discharged on warfarin, and 37 patients (69.8%) were on warfarin at the time of CT scans. One patient with HALT was on therapeutic warfarin at the time of the CT scan that identified HALT. All three patients were asymptomatic at the time of CT scan. In patients with HALT, mean transmitral pressure gradient were 8, 5, and 2.7 mmHg, all with trivial or mild mitral regurgitation.. In this study, the prevalence of HALT was low at 5.7%, all presenting without symptoms. One patient presented with HALT while on therapeutic oral anticoagulation, which may suggest thrombotic etiology may not adequately explain HALT.

Topics: Aged; Aged, 80 and over; Anticoagulants; Bioprosthesis; Cross-Sectional Studies; Echocardiography; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Platelet Aggregation Inhibitors; Postoperative Complications; Thrombosis; Tomography, X-Ray Computed; Warfarin

Controversy persists regarding the advisability of anticoagulation for the early period after biological surgical aortic valve replacement (AVR). We aim to examine the impact of various antithrombotic regimens on outcomes in a large cohort of biological AVR patients. Records of 1,111 consecutive adult patients who underwent surgical biological AVR at our institution between 2013 and 2017 were reviewed. Outcomes included stroke, bleeding, and death at 3 and 12 months. Treatment regimens included (1) no therapy, (2) anticoagulants (warfarin or Factor Xa inhibitors), (2) antiplateles (various), and (4) anticoagulants + antiplatelets. Kaplan-Meier analysis was used to track outcomes, and Cox-proportional hazards regression models were conducted to analyze effects of different therapies on adverse events. At 3 months, thromboembolic events were low and not significantly different between the no therapy group (2.2%) and anticoagulation (2.8%) or anticoagulation + antiplatelet (3.6%) or all groups (3.7%). The antiplatelet group was just significantly lower, at 2.2%. However, this was driven by non-stroke cardiovascular events in patients with coronary artery disease. The incidence of death at 3 months was low and not significantly different between all groups. At 12 months, there were no thromboembolic benefits between groups, but bleeding events were significantly higher in the anticoagulation group (no therapy (1.4%), anticoagulation (8.4%), antiplatelet (4.5%), anticoagulation + antiplatelet (7.9%)). In conclusion, none of the antithrombotic regimens showed benefits in stroke or survival at 3 or 12 months after biological AVR. Anticoagulation increased bleeding events. Routine anticoagulation after biological AVR appears to be unnecessary and potentially harmful.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Aspirin; Atrial Fibrillation; Bicuspid Aortic Valve Disease; Bioprosthesis; Coronary Artery Disease; Factor Xa Inhibitors; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Platelet Aggregation Inhibitors; Postoperative Care; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Stroke; Thromboembolism; Warfarin; Young Adult

To evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis.. A total of 76 019 individuals with AF were identified in England in 1998-2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02-1.24), 1.20 (1.05-1.36), and 1.27 (1.19-1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study.. Prevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Cardiac Valve Annuloplasty; Cause of Death; Embolism; England; Factor Xa Inhibitors; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhagic Stroke; Humans; Ischemic Stroke; Male; Middle Aged; Mortality; Phenotype; Prevalence; Prognosis; Proportional Hazards Models; Stroke; Warfarin

Topics: Anticoagulants; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Medication Adherence; Patient Education as Topic; Postoperative Complications; Prosthesis Implantation; Self-Management; Social Class; Thrombosis; Warfarin

Topics: Adult; Aged; Anticoagulants; Disease-Free Survival; Female; Heart Valve Diseases; Heart Valves; Humans; International Normalized Ratio; Male; Middle Aged; Prognosis; Retrospective Studies; ROC Curve; Warfarin

Antiphospholipid antibody syndrome (APLS) is a rare disorder characterized by a hypercoagulable state. Manifestations include arterial or venous thrombosis, recurrent fetal wastage, coronary artery disease, valvular heart disease, dilated cardiomyopathy, pulmonary artery hypertension, and intracardiac thrombus. Most commonly mitral valve is affected followed by aortic and then tricuspid valve. In this report, a rare case of spontaneous aortic thrombosis with tricuspid stenosis uncomplicated by other valve lesions is presented with clinical and echocardiographic studies and computed tomographic images.

Topics: Adult; Antiphospholipid Syndrome; Echocardiography, Doppler; Echocardiography, Transesophageal; Female; Heart Valve Diseases; Humans; Tricuspid Valve; Tricuspid Valve Stenosis; Warfarin

Anticoagulation with warfarin affects approximately 140,000 post-cardiac surgery patients every year, yet there remains limited published data in this patient population. Dosing remains highly variable due to intrinsic risk factors that plague cardiac surgery candidates and a lack of diverse literature that can be applied to those who have undergone a cardiac surgery alternative to heart valve replacement (HVR). In the present study, our aim was to compare the warfarin requirements between HVR and non-HVR patients.. This was a single-center, retrospective study of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester, from January 1st, 2013 to October 31st, 2016. The primary outcome was the maintenance warfarin dose at the earliest of discharge or warfarin day 10 between patients with HVR and non-HVR cardiac surgeries.. A total of 683 patients were assessed during the study period: 408 in the HVR group and 275 in the non-HVR group. The mean warfarin maintenance doses in the HVR and non-HVR groups were 2.55 mg [standard deviation (SD) 1.52] and 2.43 mg (SD 1.21), respectively (adjusted p = 0.65). A multivariable analysis was performed to adjust for gender, age, body mass index and drug interactions.. This was the largest study to evaluate warfarin dose requirements in post-cardiac surgery patients and is the first to compare warfarin requirements between HVR and non-HVR patients during the immediate post-operative period. Both groups had similar warfarin requirements, which supports expanding the initial warfarin dosing recommendations of the 9th edition Chest guideline to include non-HVR patients as well as HVR patients.

Topics: Aged; Anticoagulants; Cardiac Surgical Procedures; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Male; Middle Aged; Postoperative Care; Retrospective Studies; Warfarin

The most frequently used oral anti-coagulant warfarin has been implicated in inducing calcification of aortic valve interstitial cells (AVICs), whereas the mechanism is not fully understood. The low-level activation of p53 is found to be involved in osteogenic transdifferentiation and calcification of AVICs. Whether p53 participates in warfarin-induced AVIC calcification remains unknown. In this study, we investigated the role of low-level p53 overexpression in warfarin-induced porcine AVIC (pAVIC) calcification. Immunostaining, quantitative PCR, and Western blotting revealed that p53 was expressed in human and pAVICs and that p53 expression was slightly increased in calcific human aortic valves compared with non-calcific valves. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining indicated that apoptosis slightly increased in calcific aortic valves than in non-calcific valves. Warfarin treatment led to a low-level increase of p53 mRNA and protein in both pAVICs and mouse aortic valves. Low-level overexpression of p53 in pAVICs via an adenovirus vector did not affect pAVIC apoptosis but promoted warfarin-induced calcium deposition and expression of osteogenic markers. shRNA-mediated p53 knockdown attenuated the pAVIC calcium deposition and osteogenic marker expression. Moreover, ChIP and luciferase assays showed that p53 was recruited to the

Topics: Animals; Anticoagulants; Antifibrinolytic Agents; Aortic Valve; Atrial Fibrillation; Calcinosis; Cells, Cultured; Disease Models, Animal; Epigenesis, Genetic; Gene Expression Regulation; Genes, Reporter; Heart Valve Diseases; Humans; Male; Mice, Inbred C57BL; Promoter Regions, Genetic; Recombinant Proteins; Rheumatic Heart Disease; RNA Interference; Snail Family Transcription Factors; Sus scrofa; Tumor Suppressor Protein p53; Vitamin K 1; Warfarin

We examined a large community-based sample of patients with atrial fibrillation (AF) and valvular heart disease (VHD) (excluding prosthetic valves) with a goal to compare outcomes among patients with AF, with and without VHD, taking warfarin, dabigatran, and rivaroxaban.. We identified Medicare beneficiaries enrolled in Medicare Part D benefit plan from 2011 to 2013 with newly diagnosed AF (18 137 patients with VHD [dabigatran, 1979; rivaroxaban, 2027; warfarin, 14 131] and 85 596 patients without VHD [dabigatran, 13 522; rivaroxaban, 14 257; warfarin, 57 817]). Primary outcomes of all-cause mortality, ischemic strokes, major bleeding, and myocardial infarction were compared across the 3 anticoagulants using 3-way propensity-matched samples. After propensity matching, a total of 5871 patients with VHD and 40 221 patients without VHD and AF were studied. Both dabigatran and rivaroxaban were associated with significantly lower risk of death in patients with VHD with AF (dabigatran versus warfarin: hazard ratio, 0.71; 95% confidence interval, 0.52-0.98;. In this cohort of Medicare beneficiaries with VHD (excluding patients with prosthetic valves) and new-onset AF between 2011 and 2013, novel oral non-vitamin K anticoagulants were safe and effective options for prevention of systemic thromboembolism.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Follow-Up Studies; Heart Valve Diseases; Humans; Male; Medicare; Retrospective Studies; Rivaroxaban; Thromboembolism; Treatment Outcome; United States; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Endocarditis; Heart Valve Diseases; Humans; Warfarin

Topics: Age Factors; Anticoagulants; Aortic Valve; Bioprosthesis; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Life Style; Patient Compliance; Postoperative Complications; Reoperation; Risk; Transcatheter Aortic Valve Replacement; Warfarin

Despite considerations of its therapeutic range and multiple drug-food interactions, warfarin is the mainstay of oral anticoagulation in patients with mechanical heart valves (MHVs). The quality of anticoagulation demonstrates variations, with 'time in therapeutic range' (TTR) values usually lower than expected. It has been hypothesized that warfarin adherence is among the modifiable causes of suboptimal coagulation. The aim of the study was to demonstrate the ability of the 8-Item Morisky Medication Adherence Scale (MMAS-8©) to identify patients with non-adherence to warfarin, and to define the predictors of optimal coagulation when a TTR value ≥65% is used as the surrogate.. In a cross-sectional survey of 112 patients, TTR6 months and TTR12 months were calculated using the Rosendaal method. A questionnaire was used to assess the patients' warfarin knowledge, bleeding complications, and adherence. Patients were categorized into low-adherence (LA), moderate adherence (MA) and high-adherence (HA) groups based on MMAS-8 values. The target INR was 2.5-3.5, and an effective TTR was defined as ≥65%.. TTR6 months, TTR12 months and warfarin knowledge were significantly lower in the LA group than in the MA and HA groups. In addition, the bleeding score of HA patients was significantly lower than that of LA and MA patients. The MMAS-8 was the single independent predictor of effective TTR for six and 12 months on multivariate regression analysis (B = 0.506, p <0.001 and B = 0.469, p <0.001, respectively).. Warfarin adherence accounted for poor TTR values in patients with MHV, and MMAS-8 was used effectively to identify those expected to have a low TTR, to suffer more complications, and to require robust education.

Topics: Anticoagulants; Cross-Sectional Studies; Health Care Surveys; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Medication Adherence; Time Factors; Warfarin

Mechanical valve replacement is associated with positive outcomes, but patients must undergo life-long anticoagulation therapy with warfarin, which carries a significant risk of bleeding complications. Therefore, a systematic and continuous assessment and supervision of warfarin treatment is essential in such patients, and approaches that can predict the risk of bleeding in advance are required. The study aim was to develop a classification tool to predict bleeding events in South Korean patients with mechanical valve replacement undergoing oral warfarin therapy.. The retrospective cohort study included 2,453 patients followed up for at least one year after valve replacement surgery, between January 2003 and December 2012. Discriminant analysis was used to assess potential bleeding risk factors out of 31 patient- related and disease-related descriptors. The prediction capability of the descriptors was evaluated based on accuracy, sensitivity,specificity, positive predictive value, and negative predictive value.. A total of 13 descriptors including general, clinical-related and medication-related risk factors was selected as suitable predictors for bleeding risk. A novel classification tool was developed using these risk factors, and evaluated for accuracy (91.5%), sensitivity (80.2%), and specificity (95.2%).. The classification tool developed in the present study can be reliably used in a clinical context to predict bleeding events in patients with mechanical valve replacement undergoing oral warfarin therapy.

Topics: Administration, Oral; Anticoagulants; Decision Support Techniques; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Heart Valves; Hemorrhage; Humans; Predictive Value of Tests; Prosthesis Design; Reproducibility of Results; Republic of Korea; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Echocardiography; Endocarditis; Female; Heart Valve Diseases; Humans; Ischemic Attack, Transient; Lupus Erythematosus, Systemic; Tricuspid Valve; Warfarin

Essentials Required warfarin doses for mechanical heart valves vary greatly. A two-stage extreme phenotype design was used to identify novel warfarin dose associated mutation. We identified a group of variants significantly associated with extreme warfarin dose. Four novel identified mutations account for 2.2% of warfarin dose discrepancies.. Background The variation among patients in warfarin response complicates the management of warfarin therapy, and an improper therapeutic dose usually results in serious adverse events. Objective To use a two-stage extreme phenotype strategy in order to discover novel warfarin dose-associated mutations in heart valve replacement patients. Patients/method A total of 1617 stable-dose patients were enrolled and divided randomly into two cohorts. Stage I patients were genotyped into three groups on the basis of VKORC1-1639G>A and CYP2C9*3 polymorphisms; only patients with the therapeutic dose at the upper or lower 5% of each genotype group were selected as extreme-dose patients for resequencing of the targeted regions. Evaluation of the accuracy of the sequence data and the potential value of the stage I-identified significant mutations were conducted in a validation cohort of 420 subjects. Results A group of mutations were found to be significantly associated with the extreme warfarin dose. The validation work finally identified four novel mutations, i.e. DNMT3A rs2304429 (24.74%), CYP1A1 rs3826041 (47.35%), STX1B rs72800847 (7.01%), and NQO1 rs10517 (36.11%), which independently and significantly contributed to the overall variability in the warfarin dose. After addition of these four mutations, the estimated regression equation was able to account for 56.2% (R

Topics: Adult; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2C9; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3A; Female; Genetic Predisposition to Disease; Genotype; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mutation; NAD(P)H Dehydrogenase (Quinone); Phenotype; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prospective Studies; Regression Analysis; Reproducibility of Results; Syntaxin 1; Vitamin K Epoxide Reductases; Warfarin

The management of Dengue virus infection can be challenging. Varied presentations and numerous complications intrinsic to dengue by itself increase the complexity of treatment and potential mortality. When burdened with the presence of additional comorbidities and the need to continue compulsory medications, clear stepwise definitive guidance is lacking and patients tend to have more complex complications and outcomes calling to question the clinical decisions that may have been taken. The use and continuation of warfarin in dengue virus infection is one such example.. We report a 65 year old South Asian female who presented with dengue fever. She had a history bronchial asthma, a prior abdominal surgery, and was on warfarin and maintained a therapeutically appropriate internationalized normalized ratio for a mechanical aortic valve replacement. Though preemptive decision to stop warfarin was taken with decreasing platelet counts, her clinical course was complicated with the development of bilateral rectus sheath haematoma's requiring resuscitation with blood transfusions.. Though management of dengue viral fever has seen drastic evolution with recent updated guidance, clinical scenarios seen in the course of the illness still pose challenges to the managing physician. The need to continue obligatory anticoagulation which may seem counterintuitive during a complex disease such as dengue virus infection must be considered after understanding the potential risks versus that of its benefits. Though case by case decisions maybe warranted, a clear protocol would be very helpful in making clinical decisions, as the correct preemptive decision may potentially avert catastrophic and unpredictable bleeding events.

Topics: Aged; Anticoagulants; Aortic Valve; Dengue; Dengue Virus; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hematoma; Hemorrhage; Humans; International Normalized Ratio; Muscle, Skeletal; Risk Factors; Warfarin

Topics: Anticoagulants; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Warfarin

The aim of this study was to assess the efficacy of warfarin in the treatment of bioprosthetic valve thrombosis (BPVT) of surgically implanted valves.. There are limited data about treatment outcomes for BPVT.. This was a prospective study of patients with suspected BPVT of surgically implanted valves who received warfarin therapy at the Mayo Clinic from January 2013 to January 2016. BPVT score was calculated using previously described echocardiographic criteria. One point was assigned for each criterion: a 50% increase in prosthetic gradient within 5 years of implantation, increased cusp thickness, and abnormal cusp motion.. Fifty-two patients were enrolled in the study (mean age 61 ± 18 years, 34 men [66%]). The mean follow-up duration from presumed BPVT was 86 ± 24 weeks. Prosthesis positions were aortic in 31 patients (60%), mitral in 17 (32%), pulmonary in 2 (4%), and tricuspid in 2 (4%). Positive responses (defined as a 50% reduction in prosthesis gradient) occurred in 43 patients (83%) within 11 weeks (interquartile range [IQR]: 6 to 22 weeks) of anticoagulation with warfarin. Nine patients (17%) did not respond to warfarin, and these patients underwent surgical valve replacement (n = 5), transcatheter valve replacement (n = 1), and intervention (n = 3). BPVT scores were calculated for 48 patients (92%) with good-quality echocardiographic images; 9 had BPVT scores of 2, and 39 had BPVTs score of 3. A BPVT score of 3 predicted a positive response to anticoagulation therapy with sensitivity of 88% and specificity of 93%.. A trial of anticoagulation was effective in 83% of patients with suspected BPVT, and most patients responded within 3 months. BPVT score was predictive of response to therapy and should be considered during patient selection.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Bioprosthesis; Echocardiography, Doppler, Color; Echocardiography, Transesophageal; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Minnesota; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Thrombosis; Time Factors; Treatment Outcome; Warfarin

Antiphospholipid syndrome is an antiphospholipid antibody-mediated prothrombotic state leading to arterial and venous thrombosis. This condition alters routine in-vitro coagulation tests, making results unreliable. Antiphospholipid syndrome patients requiring cardiac surgery with cardiopulmonary bypass present a unique challenge in perioperative anticoagulation management. We describe 3 patients with antiphospholipid syndrome who had successful heart valve surgery at our institution. We have devised an institutional protocol for antiphospholipid syndrome patients, and all 3 patients were managed according to this protocol. An algorithm-based approach is recommended because it improves team work, optimizes treatment, and improves patient outcome.

Topics: Adult; Algorithms; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; Cardiac Valve Annuloplasty; Cardiopulmonary Bypass; Drug Substitution; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin; Humans; Male; Middle Aged; Patient Selection; Predictive Value of Tests; Risk Factors; Severity of Illness Index; Treatment Outcome; Warfarin

To investigate the morbidity of complications and pregnancy outcomes in women with mechanical heart valve replacement who received low-dose oral anticoagulation treatment with warfarin throughout the pregnancy, compare the prognosis and complications of patients who were treated with single oral warfarin treatment or the "bridging" therapy treatment, investigate the influence of using vitamin K1 before emergency cesarean section delivery on postoperative warfarin anticoagulant effect and to explore an appropriate anticoagulant regimen during perioperative period for pregnant women with mechanical heart valve replacement.. 46 pregnant women with mechanical heart valve replacement who received low-dose oral anticoagulation treatment from October 2008 to October 2014 treated at West China Women's and Children's Hospital were retrospectively reviewed. Eight patients received emergency cesarean section (CS), while 38 patients received selective CS, in which 17 patients received single oral warfarin and 21 patients received "bridging" anticoagulation treatment during postoperative period. Morbidity of complications and the time to achieve the target INR after operation were compared.. The mechanical valves were at the mitral position in 35 (76.09 %) patients, at the aortic position in 2 (4.35 %) patient and at both the mitral and aortic position in 9 (19.57 %) patients. 46 full-term healthy babies were delivered and no maternal thromboembolic was observed during pregnancy. There was no significant difference of the amount of uterine bleeding between single oral warfarin group and "bridging" treatment group during postpartum period. In single oral warfarin group, one valve thrombosis was observed and led to sudden death. No periphery thrombosis, hematoma, general hemorrhage or other sign of over-anticoagulation was observed. The INR increased more slowly in the group who received emergency CS with preoperative application of vitamin K1 than other two groups.. The use of vitamin K1 preoperatively might result in warfarin resistance and discontinuation of warfarin therapy before selective CS might be more appropriate than application of vitamin K1. The "bridging" anticoagulation treatment which combines oral warfarin and subcutaneous LMWH might be more effective and safer than single oral warfarin therapy for patients with mechanical heart valve replacement during postoperative period, no matter selective or emergency CS. The safety of low-dose oral warfarin therapy throughout pregnancy is still under controversy.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Cesarean Section; China; Delivery, Obstetric; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morbidity; Perioperative Period; Postoperative Period; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Thrombosis; Treatment Outcome; Vitamin K 1; Warfarin; Young Adult

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Databases, Factual; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin K; Warfarin; Young Adult

Time in Therapeutic Range (TTR) is a value used to assess the efficacy of Warfarin treatment. The aim of our study is to determine the effective INR levels and the rate of TTR in patients on Warfarin regimen due to Atrial Fibrillation (AF) or Mechanical Prosthetic Valve (MPV). A total of 94 patients (58 female, and 36 male, mean age: 64.9±11years) on Warfarin treatment due to AF or MPV with at least 10 INR levels measurements in the last 6 months were included in this retrospective study. The patients were divided into 2 groups. Group 1 consisted of the patients with Valvular AF (n=47); Group 2 included the patients with Non-Valvular AF (n=47); TTR and INR levels were compared. The average of INR values were found as 2,4 (min: 1,3, max: 4,3) in all patients; 2,3 (min: 1,3, max: 4,2) in Group 1; 2,6 (min: 1,3, max: 4,3) in Group 2. The average of TTR values was found 40.3% (min: 10%, max: 80%) in all patients; 43.8% (min: 10%, max: 80%) in Group 1; 36,8% (min: 10%, max: 80%) in Group 2. INR and TTR values are needed to assess the effectiveness of the Warfarin treatment. The patients in treatment with Warfarin should be well trained and frequently monitored. On the other hand, the underlying factors of the TTR values being determined as lower in the Turkish patient population might be due to the lower socio-economic and socio-cultural status, inadequate education levels, and the insufficient information on use of the medication provided by the doctors to the patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin K; Warfarin

The study sought to examine the risk of ischemic events and bleeding episodes associated with differing antithrombotic strategies in patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant atrial fibrillation (AF).. Guidelines recommend antiplatelet therapy (APT) post-TAVR to reduce the risk of stroke. However, data on the efficacy and safety of this recommendation in the setting of a concomitant indication for oral anticoagulation (due to atrial fibrillation [AF]) with a vitamin K antagonist (VKA) are scarce.. A multicenter evaluation comprising 621 patients with AF undergoing TAVR was undertaken. Post-TAVR prescriptions were used to determine the antithrombotic regimen used according to the following 2 groups: monotherapy (MT) with VKA (n = 101) or multiple antithrombotic therapy (MAT) with VKA plus 1 or 2 antiplatelet agents (aspirin or clopidogrel; n = 520). Endpoint definitions were in accordance with Valve Academic Research Consortium-2 criteria. The rate of stroke, major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death), major or life-threatening bleeding events, and death were assessed by a Cox multivariate model regression survival analysis according to the antithrombotic regime used.. During a median follow-up of 13 months (interquartile range: 3 to 31 months) there were no differences between groups in the rate of stroke (MT: 5%, MAT: 5.2%; adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 0.45 to 3.48; p = 0.67), major adverse cardiovascular events (MT: 13.9%, MAT: 16.3%; adjusted HR: 1.33; 95% CI: 0.75 to 2.36; p = 0.33), and death (MT 22.8%, MAT: 19.2%; adjusted HR: 0.93; 95% CI: 0.58 to 1.50; p = 0.76). A higher risk of major or life-threatening bleeding was found in the MAT group (MT: 14.9%, MAT: 24.4%; adjusted HR: 1.85; 95% CI: 1.05 to 3.28; p = 0.04). These results remained similar when patients receiving VKA plus only 1 antiplatelet agent (n = 463) were evaluated.. In TAVR recipients prescribed VKA therapy for AF, concomitant antiplatelet therapy use appears not to reduce the incidence of stroke, major adverse cardiovascular events, or death, while increasing the risk of major or life-threatening bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Atrial Fibrillation; Brain Ischemia; Canada; Chi-Square Distribution; Europe; Female; Heart Valve Diseases; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Stroke; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K; Warfarin

Risk factors of stroke/thromboembolism (TE) and major bleeding, and incidence of these events in specific age categories in warfarin-treated patients with mechanical heart valves (MHV) are uncertain. Our objective was to calculate event rates in specific age categories and identify risk factors for adverse events.. We identified 4,810 treatment periods with MHV between January 2006 and December 2011 in the Auricula and Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registries. There were 3,751 treatment periods with aortic valve replacements (AVR) and 866 with mitral valve replacements (MVR). Median follow-up time was 4.5 years (IQR, 1.5-6.0). Time in therapeutic range with warfarin for patients with AVR was 74.2% for international normalized ratio of 2.0 to 3.0, with 72% of the patients having this target range. Rate of stroke/TE for AVR and MVR was 1.3 and 1.6 per 100 patient years, respectively (P=.20). The rate of first major bleeding was 2.6 and 3.9 per 100 patient years with AVR and MVR, respectively (P<.001). By multivariate analysis for AVR, age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03 per year) and previous stroke (HR, 2.4; 95% CI, 1.7-3.5) emerged as independent risk factors for stroke/TE. Heart failure (HR, 0.9; 95% CI, 0.6-1.4) and atrial fibrillation (HR, 1.0; 95% CI, 0.7-1.4) were not associated to stroke/TE. For major bleeding events, age (HR, 1.02; 95% CI, 1.01-1.03 per year) and previous major bleeding (HR, 2.5; 95% CI, 1.9-3.3) emerged as independent risk factors for AVR.. In a nationwide cohort study with MHV and high time in therapeutic range, heart failure and atrial fibrillation did not appear as risk factors of stroke/TE.

Topics: Aged; Anticoagulants; Aortic Valve; Atrial Fibrillation; Cohort Studies; Female; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Mitral Valve; Multivariate Analysis; Proportional Hazards Models; Risk Factors; Stroke; Sweden; Thromboembolism; Warfarin

The anticoagulation of biological heart valves remains a 'hot spot' of discussion in various domains due to the risk of developing valve thrombosis and arterial thromboembolism. The situation has always been controversial, especially during the early postoperative phase. The American College of Cardiology/ American Heart Association and European Society of Cardiology guidelines recommend the use of warfarin for the first three months after biological aortic valve replacement (BAVR), although the American College of Chest Physicians guidelines suggest that these recommendations are experience-based and that the risk/benefit is unclear. The aim of the present study was to compare the efficacy of aspirin and warfarin in patients after BAVR.. A total of 863 patients who underwent BAVR between 2008 and 2015 was allocated to two groups. Each group was managed with a specific anticoagulation regimen, with 430 patients receiving warfarin during the first three postoperative months, and 433 receiving aspirin. The major study end points were bleeding, cerebral ischemic events, and survival.. In total, 10 and 15 postoperative cerebral ischemic events occurred between 24 h and three months after surgery in patients treated with aspirin and warfarin, respectively. After three months the incidence of cerebral ischemic events did not differ greatly between the two groups. The rate of major bleeding events and rates of stroke-free survival and overall survival were not statistically significant between the warfarin and aspirin groups.. Plasma anticoagulation with warfarin during the early postoperative phase was shown statistically to be inferior to platelet aggregation inhibition by aspirin with regards to postoperative bleeding risk, cerebral ischemic events, and survival.

Topics: Aged; Anticoagulants; Aortic Valve; Aspirin; Bioprosthesis; Blood Coagulation; Brain Ischemia; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Prosthesis Design; Retrospective Studies; Stroke; Thrombosis; Time Factors; Treatment Outcome; Warfarin

Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia, and is associated with an increased risk of death, stroke, and other thromboembolic events. Valvular heart disease (VHD) frequently coexists with AF, mostly in elderly patients. After the introduction of novel oral anticoagulants (NOACs) approved for the prevention of stroke in non-valvular atrial fibrillation (NVAF) on the basis of recent trials, the importance of a universal definition of NVAF was raised in clinical practice. In the most recent guidelines, the term valvular AF is used to imply that AF is related to rheumatic valvular disease (predominantly mitral stenosis), or prosthetic heart valves. In all the trials comparing NOACs and warfarin, a significant percentage of patients presented any type of VHD, excluding rheumatic mitral stenosis and mechanical heart valve. The subgroups analysis performed, so far showed no significant differences in terms of efficacy in the VHD subgroup compared to the general AF population. A restrictive definition of valvular AF (i.e., rheumatic mitral stenosis and mechanical heart valve) seems to be the most appropriate to contraindicate treatment with NOACs for AF thromboprophylaxis. In the remaining AF patients with significant valvular disease who per se would not require oral anticoagulation, NOACs should be allowed.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Heart Valve Diseases; Humans; Thromboembolism; Warfarin

Caseous mitral annulus calcification involving aortomitral curtain is a rare occurrence. We report a case of a 64-year-old woman with end-stage renal failure and a candidate for renal transplant who presented with late ST-elevation myocardial infarction. Intracoronary imaging, computed tomography cardiac imaging, and histopathology confirmed coronary embolus into the left main stem artery from an extensive caseous mitral annulus calcification.

Topics: Anticoagulants; Coronary Angiography; Coronary Vessels; Embolism; Female; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Middle Aged; Mitral Valve; Multimodal Imaging; Myocardial Infarction; Predictive Value of Tests; Risk Assessment; Sensitivity and Specificity; Tomography, Spiral Computed; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Interventional; Vascular Calcification; Warfarin

Topics: Adult; Aortic Valve; Aortic Valve Insufficiency; Bicuspid Aortic Valve Disease; Bioprosthesis; Drug Resistance; Echocardiography, Doppler; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Postoperative Care; Retreatment; Rivaroxaban; Severity of Illness Index; Treatment Outcome; Vitamin K Epoxide Reductases; Warfarin

In this study, we investigated two VKORC1 gene polymorphisms, -1639G/A and 1173C/T, for effects on warfarin maintenance dosage in valvular heart disease (VHD) patients after cardiac valve replacement (CVR).. A total of 219 VHD patients receiving warfarin therapy after CVR surgery were recruited to this study between June 2010 and December 2013. Basic clinical data, prothrombin time, warfarin maintenance dose, and blood samples were collected from all patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses were used to analyze the VKORC1 -1639G/A and 1173C/T polymorphisms. SPSS version 19.0 software was used for statistical analysis of the data.. Patients with either the AG+or GG genotype (n=32) of the VKORC1 -1639G/A polymorphism required a significantly higher warfarin dose compared to patients with the AA genotype (n=187) (4.36±1.03 mg/day vs. 2.95±0.94 mg/day; p<0.001). Similarly, patients carrying the CT genotype (n=28) of the VKORC1 1173C/T polymorphism also required a significantly higher warfarin dose compared to those with the TT genotype (n=191) (4.19±0.99 mg/day vs. 3.00±0.94 mg/day; p<0.001). Linear regression analysis showed that gender, age, weight, and VKORC1 -1639G/A and 1173C/T polymorphisms were correlated with individual differences in warfarin maintenance dose (all p<0.05).. We present evidence that the two VKORC1 polymorphisms, -1639G/A and 1173C/T, are key genetic factors influencing individual differences in warfarin maintenance dose in VHD patients who underwent CVR. Gender, age, and weight also independently correlated with warfarin maintenance dose.

Topics: Anticoagulants; China; Dose-Response Relationship, Drug; Female; Gene Frequency; Genetic Association Studies; Heart Valve Diseases; Heart Valves; Humans; Hydroxybutyrates; Individuality; Indoles; Maintenance Chemotherapy; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Vitamin K Epoxide Reductases; Warfarin

The quality of treatment with warfarin is mainly assessed by the time in therapeutic range (TTR) in patients with mechanical heart valve prosthesis (MHV). Our aim was to evaluate if International Normalized Ratio (INR) variability predicted a combined endpoint of thromboembolism, major bleeding and death better than TTR.. We included 394 patients at one center with MHV during 2008-2011 with adverse events and death followed prospectively. TTR 2.0-4.0 and log-transformed INR variability was calculated for all patients. In order to make comparisons between the measures, the gradient of the risk per one standard deviation (SD) was assessed. INR variability performed equal as TTR 2.0-4.0 per one SD unit adjusted for covariates, hazard ratio (HR) 1.30 (95% CI 1.1-1.5) and 0.71 (95% CI 0.6-0.8) respectively for the combined endpoint, and performed better for mortality HR 1.47 (95% CI 1.1-1.9) and 0.70 (95% CI 0.6-0.8). INR variability was categorized into high and low group and TTR into tertiles. High variability within the low and high TTR, had a HR 2.0 (95% CI 1.7-3.6) and 2.2 (95% CI 1.1-4.1) respectively, of the combined endpoint compared to the low variability/high TTR group. INR values <2.0 greatly increased the rate of thromboembolism whereas the rate of major bleeding increased moderately between INR 3.0 and 4.0 and increased substantially after INR >4.0.. The INR variability is an equal predictor as TTR of the combined endpoint of thromboembolism, major bleeding and death, and adds important information on top of TTR in patients with MHV.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Registries; Reproducibility of Results; Risk Factors; Stroke; Sweden; Thromboembolism; Treatment Outcome; Warfarin

Topics: Anticoagulants; China; Dose-Response Relationship, Drug; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Incidence; Male; Middle Aged; Neural Networks, Computer; Postoperative Complications; Prognosis; Thromboembolism; Warfarin

A 64 years old male was submitted to the surgical substitution of a deteriorated biological aortic valve prosthesis with a new Hancock II biological prosthesis. The implantation was not followed by an anticoagulation or antiaggregation therapy. Two months later he was checked at our Institution because he complained symptoms and developed echocardiographic indexes suggestive of an aortic prosthesis obstruction by a clot. Both symptoms and the echocardiographic indexes of prosthesis obstruction faded away after giving warfarin; they arose again when the anticoagulation therapy was stopped and was replaced by aspirin. The following permanent use of warfarin normalized both clinic and echocardiographic aspects. The present case report underlines the utility of early controls after a biological prosthesis, yet aortic, implantation, when it is not followed by an anticoagulant therapy, also in subjects free from thrombosis high risk factors.

Topics: Anticoagulants; Aortic Valve; Bioprosthesis; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Care; Thrombosis; Warfarin

The model for end-stage liver disease score (MELD = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 11.2*[PT-INR] + 6.4) predicts mortality for tricuspid valve surgery. However, the MELD is problematic in patients undergoing warfarin therapy, as warfarin affects the international normalized ratio (INR). This study aimed to determine whether a simplified MELD score that does not require the INR for calculation could predict mortality for patients undergoing tricuspid valve surgery. Simplified MELD score = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 6.4.. A total of 172 patients (male: 66, female: 106; mean age, 63.8 ± 10.3 years) who underwent tricuspid replacement (n = 18) or repair (n = 154) from January 1991 to July 2011 at a single centre were included. Of them, 168 patients in whom the simplified MELD score could be calculated were retrospectively analysed. The relationship between in-hospital mortality and perioperative variables was assessed by univariate and multivariate analysis.. The rate of in-hospital mortality was 6.4%. The mean admission simplified MELD score for the patients who died was significantly higher than for those surviving beyond discharge (11.3 ± 4.1 vs 5.8 ± 4.0; P = 0.001). By multivariate analysis, independent risk factors for in-hospital mortality included higher simplified MELD score (P = 0.001) and tricuspid valve replacement (P = 0.023). In-hospital mortality and morbidity increased along with increasing simplified MELD score. Scores <0, 0-6.9, 7-13.9 and >14 were associated with mortalities of 0, 2.0, 8.3 and 66.7%, respectively. The incidence of serious complications (multiple organ failure, P = 0.005; prolonged ventilation, P = 0.01; need for haemodialysis; P = 0.002) was also significantly higher in patients with simplified MELD score ≥ 7.. The simplified MELD score predicts mortality in patients undergoing tricuspid valve surgery. This model requires only total bilirubin and creatinine and is therefore applicable in patients undergoing warfarin therapy.

Topics: Aged; Bilirubin; Biomarkers; Blood Coagulation; Comorbidity; Creatinine; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hospital Mortality; Humans; International Normalized Ratio; Japan; Liver Diseases; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Tricuspid Valve; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Female; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Thromboembolism; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Female; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Thromboembolism; Warfarin

Calumenin, a molecular chaperone, exerts a regulatory effect on the vitamin K-dependent γ-carboxylation redox cycle that inhibits transfer of the reduced vitamin K from VKORC1, the pharmacological target of warfarin, to the γ-carboxylase. Because of its polymorphic structure and central role in the warfarin metabolic pathway, a contributory role for calumenin to warfarin dose variability has been posited. The current study sought to validate modulation of therapeutic dosing requirements by a single nucleotide polymorphisms (SNP) occurring in the calumenin gene (CALU) reported in previous studies. The CALU SNP was further modeled to detect interaction with SNPs occurring in VKORC1, CYP2C9, and CYP4F2 genes and characterize any additional contribution to variability in therapeutic warfarin dose requirement.. The study was undertaken in an established, well-characterized cohort of subjects treated with warfarin in the Anticoagulation Clinic of Marshfield Clinic in Marshfield, Wisconsin.. Subjects (N=491) previously genotyped for SNPS known to contribute variability to therapeutic warfarin dose requirement were genotyped for CALU SNP rs1043550, using TaqMan assays. Contribution of CALU SNP rs1043550 was modeled relative to other genotypic and phenotypic characteristics including gender, diagnosis, age, body surface area, underlying indication for warfarin, comorbidities, and pharmacological exposures. Interaction between SNPs impacting on warfarin dose requirements and calumenin SNPs was also modeled.. Small differences in warfarin dosing requirements detected among individuals encoding the mutant G allele in the calumenin SNP were not statistically or clinically significant relative to therapeutic warfarin dose requirement and did not independently contribute significantly to the warfarin dosing model. Interaction between calumenin and VKORC1 SNPs contributed only minor additional variability to that ascribed to the wild type VKORC1 genotype.. The impact of the CALU SNP on warfarin dose variability was minor and did not contribute significantly to therapeutic warfarin dose requirement in our study cohort. While no contribution was noted for the SNP examined in the present study, further examination of interaction between genetic elements contributing major impact on therapeutic warfarin dose requirements and genes exhibiting a lesser contribution is warranted.

Topics: Alleles; Anticoagulants; Arrhythmias, Cardiac; Calcium-Binding Proteins; Cohort Studies; Dose-Response Relationship, Drug; Female; Genotype; Heart Valve Diseases; Humans; Male; Models, Genetic; Pharmacogenetics; Polymorphism, Single Nucleotide; Thromboembolism; Treatment Outcome; Warfarin

The American College of Chest Physicians provides recommendations for the use of anticoagulant medications for several indications that are important in the primary care setting. Warfarin, a vitamin K antagonist, is recommended for the treatment of venous thromboembolism and for the prevention of stroke in persons with atrial fibrillation, atrial flutter, or valvular heart disease. When warfarin therapy is initiated for venous thromboembolism, it should be given the first day, along with a heparin product or fondaparinux. The heparin product or fondaparinux should be continued for at least five days and until the patient's international normalized ratio is at least 2.0 for two consecutive days. The international normalized ratio goal and duration of treatment with warfarin vary depending on indication and risk. Warfarin therapy should be stopped five days before major surgery and restarted 12 to 24 hours postoperatively. Bridging with low-molecular-weight heparin or other agents is based on balancing the risk of thromboembolism with the risk of bleeding. Increasingly, self-testing is an option for selected patients on warfarin therapy. The ninth edition of the American College of Chest Physicians guidelines, published in 2012, includes a discussion of anticoagulants that have gained approval from the U.S. Food and Drug Administration since publication of the eighth edition in 2008. Dabigatran and apixaban are indicated for the prevention of systemic embolism and stroke in persons with nonvalvular atrial fibrillation. Rivaroxaban is indicated for the prevention of deep venous thrombosis in patients undergoing knee or hip replacement surgery, for treatment of deep venous thrombosis and pulmonary embolism, for reducing the risk of recurrent deep venous thrombosis and pulmonary embolism after initial treatment, and for prevention of systemic embolism in patients with nonvalvular atrial fibrillation.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Blood Loss, Surgical; Drug Interactions; Drug Monitoring; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Outpatients; Practice Guidelines as Topic; Stroke; Venous Thromboembolism; Warfarin

There are limited data available to inform decision making regarding warfarin thromboprophylaxis early after mitral valve repair.. We studied 13,082 patients from The Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS ACSD) who underwent primary mitral valve repair between January 1, 2008, and June 30, 2010. Excluded were those having other major concomitant operations or with an indication/contraindication to warfarin. The predictors of warfarin administration at dismissal were evaluated.. In this cohort (median age 58 years; 59% male), warfarin was prescribed at hospital dismissal for 46% (5,963) of patients. Median postoperative length of stay was 5 days overall (6 days warfarin versus 5 days, p < 0.0001). Substantial surgeon and center variation existed, and multivariable analysis identified that warfarin use was more common among patients with postoperative atrial fibrillation (odds ratio [OR] 4.04, 95% confidence interval [CI]: 3.57 to 4.58), postoperative neurologic events (stroke OR 1.72, 95% CI: 1.08 to 2.71; transient ischemic attack/reversible ischemic neurologic deficit OR 6.29, 95% CI: 2.67 to 14.84), and preoperative arrhythmia (OR 2.49, 95% CI: 1.84 to 3.38). Warfarin use was less common among patients having surgery in the more recent era (OR 0.92, 95% CI: 0.89 to 0.96, per half-year increase in date of surgery), those requiring intraoperative transfusion of red blood cells (OR 0.82, 95% CI: 0.71 to 0.96), and patients with advanced heart failure (New York Heart Association functional class IV OR 0.77, 95% CI: 0.59 to 1.00).. At present, half of patients are prescribed warfarin after isolated mitral valve repair in North American cardiac surgical practice which may impact the length of hospital stay. Although patient-level predictors of warfarin prescription exist, center- and surgeon-level variations are prominent. There is a pressing need for a randomized trial both to guide therapy and to ascertain the potential for resource conservation.

Topics: Aged; Anticoagulants; Aspirin; Cohort Studies; Confidence Intervals; Databases, Factual; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Length of Stay; Male; Middle Aged; Mitral Valve; Multivariate Analysis; Needs Assessment; Odds Ratio; Patient Discharge; Postoperative Complications; Randomized Controlled Trials as Topic; Retrospective Studies; Thromboembolism; Treatment Outcome; Warfarin

Topics: Administration, Oral; Anticoagulants; Heart Valve Diseases; Humans; International Normalized Ratio; Practice Patterns, Physicians'; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Heart Valve Diseases; Humans; International Normalized Ratio; Morpholines; Rivaroxaban; Stroke; Thiophenes; Warfarin

Effective warfarin thromboprophylaxis requires maintaining anticoagulation within the recommended international normalized ratio (INR) range. INR testing rates and associations between testing and outcomes are not well understood.. INR testing rates after hospitalization for acute decompensated heart failure are suboptimal, and testing is associated with lower risks of mortality and adverse clinical events.. We conducted a retrospective cohort study of patients who were long-term warfarin users and were hospitalized for heart failure, had a medical history of atrial fibrillation or valvular heart disease, and were enrolled in fee-for-service Medicare. INR testing was defined as ≥1 outpatient INR test within 45 days after discharge. Using Cox proportional hazards models, we examined associations between testing and all-cause mortality, all-cause readmission, and adverse clinical events at 1 year.. Among 8558 patients, 7722 (90.2%) were tested. After 1 year, tested patients had lower all-cause mortality (23.5% vs 32.6%; P < 0.001) and fewer myocardial infarctions (2.0% vs 3.3%; P = 0.02). These differences remained significant after multivariable adjustment with hazard ratios of 0.72 (95% confidence interval [CI]: 0.63-0.84; P < 0.001) and 0.58 (95% CI: 0.41-0.83; P = 0.003), respectively. Differences in all-cause readmission, thromboembolic events, ischemic stroke, and bleeding events were not statistically significant.. Postdischarge outpatient INR testing in patients with heart failure complicated by atrial fibrillation or valvular heart disease was high. INR testing was associated with improved survival and fewer myocardial infarctions at 1 year but was not independently associated with other adverse clinical events.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Drug Monitoring; Female; Heart Failure; Heart Valve Diseases; Humans; Insurance, Pharmaceutical Services; International Normalized Ratio; Kaplan-Meier Estimate; Male; Medicare; Multivariate Analysis; Patient Discharge; Patient Readmission; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; United States; Warfarin

We aimed to determine the possible factors leading to re-operation in patients undergoing mechanical valve replacement and to investigate the relationship between valvular thrombus formation and mean platelet volume.. The medical records of 43 patients with mechanical valve implantation, who were admitted to the Department of Cardiovascular Surgery of Dr Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital between 2000 and 2005 were analysed retrospectively. Data recorded included demographic characteristics, valve type, size and location, implantation position, warfarin use, INR level, additional cardiac intervention, presence of left atrial thrombus, valvular thrombus, pannus formation, perivalvular leak, left atrial aneurysm, platelet count and mean platelet volume (MPV), bleeding after the primary surgery and/or revision of surgery due to other reasons, valve protection, aortic root expansion, presence of valve calcification and infective endocarditis, pre- and postoperative rhythm pattern, brand name of prosthesis, distance of the patient's house from a cardiac surgery centre, and concomitant noncardiac systemic diseases.. Mean age was 49.3 years (range 19-78 years). Of the patients, 51% (n = 22) were males and 49% (n = 21) were females. The re-operation mortality was 11.6%. Age, gender, valve type, brand of valve prosthesis, and implantation position were not risk factors for re-operation. The MPV was higher and statistically significant in patients with valvular thrombus during re-operation (p < 0.001). MPV was determined to be an independent risk factor with 85% sensitivity and 87% specificity.. MPV and INR levels should be closely monitored when designing individualised postoperative medical treatment for patients undergoing heart valve re-operation.

Topics: Adult; Aged; Anticoagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Male; Mean Platelet Volume; Middle Aged; Postoperative Complications; Predictive Value of Tests; Prosthesis Design; Prosthesis Failure; Reoperation; Retrospective Studies; Risk Factors; Thrombosis; Treatment Outcome; Turkey; Warfarin; Young Adult

Effective anticoagulation is critical in patients with mechanical prosthetic heart valve (MPHV), but remains challenging in pregnancy because both oral anticoagulation and heparins are associated with important fetal and maternal risks. A 33-year-old high-risk pregnant woman presented with MPHV thrombosis during early pregnancy. Resolution of the thrombus and eventual resumption of normal prosthetic mitral valve function was obtained through treatment with low-molecular weight heparin (LMWH). This case of early pregnancy MPHV thrombosis emphasized the importance of adequate initial coagulation prior to pregnancy and the potential need to extend measurements to both peak and trough levels to assure an adequate level of anticoagulation in women with MPHV treated with LMWH during pregnancy.

Topics: Adult; Anticoagulants; Cesarean Section; Dose-Response Relationship, Drug; Drug Monitoring; Echocardiography; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin; Humans; Mitral Valve; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Radiography; Retroperitoneal Space; Thrombosis; Treatment Outcome; Tricuspid Valve; Warfarin

Short-term postoperative warfarin therapy has been used to decrease neurologic events following mitral valve repair or bioprosthetic replacement (MVR). The study aim was to compare the short- and long-term outcomes of patients undergoing mitral valve surgery with or without short-term postoperative warfarin.. A single academic US institution retrospective review was performed on discharged patients who underwent MVR between January 1996 and March 2010. Patients were allocated to two groups: MVR with four to six weeks of postoperative warfarin (n = 315; Warfarin group) or MVR without postoperative warfarin (n = 257; No warfarin group). Patients who required either preoperative or postoperative warfarin for any disease process (e.g., atrial fibrillation, mechanical valve, deep venous thrombosis) were excluded. Logistic and Cox proportional hazards regression models were constructed to evaluate the effects of warfarin on short- and long-term outcomes, respectively. Adjusted odds ratios (AOR) and adjusted hazard ratios (AHR), with 95% confidence intervals (CI) were constructed for each outcome. To reduce selection bias, propensity scoring methods were employed to balance the groups with respect to 54 preoperative variables.. Mean age was not significantly different between groups (No warfarin group = 56.8 +/- 14.5 years versus Warfarin group 55.9 +/- 12.9 years; p = 0.46). The average length of hospital stay was 9.8 +/- 8.4 days and 7.3 +/- 4.5 days in the No warfarin and Warfarin groups, respectively (p < 0.001). At the six-week follow up the incidences of stroke (p = 0.74), pleural effusions (p = 0.88), pericardial effusions (p = 0.75), and bleeding complications (p = 0.30) were similar between the two groups. In an unadjusted Kaplan-Meier analysis, the No warfarin group had a poorer long-term survival than the Warfarin group (p < 0.001). However, after propensity adjustment, the benefit of warfarin was not statistically significant (AHR = 0.66, 95% CI 0.40-1.08, p = 0.098).. The use of postoperative warfarin following MVR does not reduce the incidence of stroke at early follow up. However, there remains a trend for improved long-term outcomes in those patients receiving postoperative warfarin therapy.

Topics: Anticoagulants; Bioprosthesis; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Georgia; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Incidence; Male; Middle Aged; Mitral Valve; Postoperative Care; Retrospective Studies; Stroke; Survival Rate; Time Factors; Warfarin

We evaluated effect of activity of cytochrome P450 CYP2C9 on maintenance doses of warfarin in 33 patients with implanted artificial heart valves. Losartan test was used for measurement of concentration of active metabolite E-3174 in urine. Concentration of E-3174 below 2500 ng/ml in patients with genotype CYP2C981/*1 with sensitivity 87% and specificity 66% predicted requirement of low doses (< 5 mg/day) of warfarin in the late postoperative period (odds ratio 14, 95% confidence interval 1.135 to 172.75).

Topics: Adult; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Biotransformation; Cardiovascular Agents; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Monitoring; Female; Genotype; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Imidazoles; Losartan; Male; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Postoperative Period; Tetrazoles; Warfarin

A retrospective analysis of the records of all the patients of heart disease with pregnancy at AIIMS, New Delhi, India, to find out the maternal and fetal outcome.. A retrospective analysis was carried out of 100 pregnancies in women with heart disease who delivered at ≥28 weeks of gestation from July 2009 through August 2012.. Cardiac disease was found to complicate 3.8 % of pregnancies. Rheumatic heart disease (n = 64, 64 %) was the predominant cardiac disease. Congenital heart disease was found to complicate 36 pregnancies (n = 36, 36 %).Cardiac complications were seen in 32 (32 %) and fetal complications in 18 (18 %) pregnancies. Fewer cardiac and postpartum complications were present in NYHA class I/II patients compared to NYHA III/IV patients (P < 0.05). Pregnancy outcome was better in rheumatic heart disease patients who had undergone cardiac intervention prior to pregnancy (n = 29, 45.2 %) compared to those whose heart disease remained uncorrected (n = 35, 54.8 %) but the difference was not statistically significant. There was one maternal mortality in a patient with Eisenmenger syndrome. Two of the newborns of the 17 women who had received anticoagulants had features of warfarin embryopathy.. Pregnancy in women in NYHA class III/IV is associated with significantly higher maternal morbidity and cardiac interventions before pregnancy, when indicated may improve pregnancy outcome.

Topics: Adult; Anticoagulants; Aortic Valve; Birth Weight; Female; Fetal Diseases; Fetal Growth Retardation; Heart Defects, Congenital; Heart Valve Diseases; Humans; Mitral Valve; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Retrospective Studies; Rheumatic Heart Disease; Severity of Illness Index; Warfarin; Young Adult

The use of warfarin is growing for the prevention or treatment of cardiovascular or cerebrovascular diseases. The risk of haemorrhagic side effects is increased in patients taking warfarin.. To evaluate risks related with withholding and resuming anticoagulation in patients with upper gastrointestinal bleeding (UGIB) while on warfarin therapy and the role of the second-look endoscopic examination (SEE).. Records of 58 patients with native valvular heart diseases who presented with non-variceal UGIB during chronic anticoagulation with warfarin were retrospectively reviewed. Age- and gender-matched patients with non-variceal UGIB during aspirin therapy because of ischaemic heart disease were recruited as the control group.. Development of both recurrent bleeding and thromboembolic events were more frequent in warfarin group than in control group (7.0% vs. 0% with p = 0.03 and 16.7% vs. 2.4% with p < 0.01, respectively). One of four cases of recurrent bleeding in warfarin group was found by SEE performed in an asymptomatic patient. There were six thromboembolic events which occurred on the 21st, 27th, 28th, 31st, 58th and 75th day from the presentation out of 36 patients who ceased anticoagulation. In contrast, only one from 41 in whom aspirin was discontinued experienced myocardial infarction. There was no difference in the failure of endoscopic haemostasis necessitating angiographic embolisation or surgery, hospital stay, the need of transfusion and overall mortality.. Anticoagulation is recommended to be resumed before the 20th day from the cessation to prevent thromboembolic events. A routine SEE before resuming anticoagulation might be helpful to detect asymptomatic recurrent bleeding.

Topics: Anticoagulants; Case-Control Studies; Drug Substitution; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hemorrhage; Heart Valve Diseases; Humans; Male; Middle Aged; Recurrence; Refusal to Treat; Retrospective Studies; Risk Factors; Treatment Outcome; Warfarin

This pilot prospective observational study aimed to evaluate the maternal and fetal outcomes of pregnancies under low-dose oral anticoagulation therapy after aortic mechanical replacement.. Need for valve replacement is still an issue for young women with native valve disease who are planning on future pregnancy. Choice of replacement device is a challenging clinical task.. A comprehensive pre-operative counseling protocol to guide choice of replacement device was developed. The pre-operative anticoagulation trial to determine the warfarin daily dosage needed to reach target international normalized ratio (INR) represented the main stem of such protocol. Pregnancies on low-dose anticoagulation therapy (target INR: 1.5 to 2.5) were allowed in a highly selected subset of mechanical aortic valve recipients.. Twenty-two patients of 40 originally referred for native valve disease surgery requiring valve replacement, safely underwent the pre-operative anticoagulation challenge. No maternal or fetal complications were detected in 16 pregnancies under low oral anticoagulation. Patterns of warfarin daily dosage and induced INRs were characterized during pregnancy.. In this small sample observational study, a pre-operative anticoagulation therapy trial helped young women scheduled for valve replacement to acquire complete information as to the choice of prosthetic device. In selected third-generation mechanical aortic prosthesis recipients, low-dose anticoagulation therapy seems safe and feasible for both mother and fetus. Further studies are needed to validate this approach.

Topics: Administration, Oral; Adult; Algorithms; Anticoagulants; Aortic Valve; Bioprosthesis; Confounding Factors, Epidemiologic; Counseling; Drug Administration Schedule; Female; Gestational Age; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Mitral Valve; Pilot Projects; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy Trimesters; Preoperative Period; Prospective Studies; Reoperation; Thrombosis; Treatment Outcome; Warfarin

Cardiac disease in pregnancy is a common problem in under-resourced countries and a significant cause of maternal morbidity and mortality. A large proportion of patients with cardiac disease have prosthetic mechanical heart valve replacements, warranting prophylactic anticoagulation.. To evaluate obstetric outcomes in women with prosthetic heart valves in an under-resourced country.. A retrospective chart review was performed of 61 pregnant patients with prosthetic valve prostheses referred to our tertiary hospital over a five-year period.. Sixty-one (6%) of 1 021 pregnant women with A diagnosis of cardiac disease had prosthetic heart valves. Fifty-nine had mechanical valves and were on prophylactic anticoagulation therapy, three had stopped their medication prior to pregnancy and two had bioprosthetic valves. There were forty-one (67%) live births, two (3%) early neonatal deaths, 12 (20%) miscarriages and six (10%) stillbirths. Maternal complications included mitral valve thrombosis (n = 4), atrial fibrillation (n = 8), infective endocarditis (n = 6), caesarean section wound haematomas (n = 7), broad ligament haematoma (n = 1) and warfarin embryopathy (n = 4). Haemorrhagic complications occurred in five patients and all five required blood transfusions.. Prophylactic anticoagulation with warfarin in patients with mechanical heart valve prostheses was associated with high rates of maternal and neonatal complications, including significant foetal wastage in the first and early second trimesters of pregnancy. Health professionals providing care for pregnant women with prosthetic heart valves must consistently advise on family planning matters, adherence to anticoagulation regimes and consider the use of prophylactic anticoagulant regimens other than warfarin, particularly during the first trimester of pregnancy.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Clinical Audit; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Incidence; Middle Aged; Nasal Bone; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Retrospective Studies; South Africa; Tertiary Care Centers; Time Factors; Warfarin; Young Adult

Topics: Adult; Anticoagulants; Echocardiography, Stress; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Kidney Failure, Chronic; Kidney Transplantation; Lupus Nephritis; Mitral Valve; Mitral Valve Annuloplasty; Monitoring, Physiologic; Preoperative Care; Risk Adjustment; Stroke; Treatment Outcome; Warfarin

Topics: Anti-Infective Agents; Anticoagulants; Aza Compounds; Drug Interactions; Female; Fluoroquinolones; Heart Valve Diseases; Humans; International Normalized Ratio; Middle Aged; Mitral Valve; Moxifloxacin; Quinolines; Tricuspid Valve; Warfarin

The need for anticoagulation after surgical aortic valve replacement (AVR) with biological prostheses is not well examined.. To perform a nationwide study of the association of warfarin treatment with the risk of thromboembolic complications, bleeding incidents, and cardiovascular deaths after bioprosthetic AVR surgery.. Through a search in the Danish National Patient Registry, 4075 patients were identified who had bioprosthetic AVR surgery performed between January 1, 1997, and December 31, 2009. Concomitant comorbidity and medication were retrieved. Poisson regression models were used to determine risk.. Incidence rate ratios (IRRs) of strokes, thromboembolic events, cardiovascular deaths, and bleeding incidents by discontinuing warfarin as opposed to continued treatment 30 to 89 days, 90 to 179 days, 180 to 364 days, 365 to 729 days, and at least 730 days after surgery.. The median duration of follow-up was 6.57 person-years. Estimated rates of events per 100 person-years in patients not treated with warfarin compared with those treated with warfarin with comparative absolute risk were 7.00 (95% CI, 4.07-12.06) vs 2.69 (95% CI, 1.49-4.87; adjusted IRR, 2.46; 95% CI, 1.09-5.55) for strokes; 13.07 (95% CI, 8.76-19.50) vs 3.97 (95% CI, 2.43-6.48; adjusted IRR, 2.93; 95% CI, 1.54-5.55) for thromboembolic events; 11.86 (95% CI, 7.81-18.01) vs 5.37 (95% CI, 3.54-8.16; adjusted IRR, 2.32; 95% CI, 1.28-4.22) for bleeding incidents; and 31.74 (95% CI, 24.69-40.79) vs 3.83 (95% CI, 2.35-6.25; adjusted IRR, 7.61; 95% CI, 4.37-13.26) for cardiovascular deaths within 30 to 89 days after surgery; and 6.50 (95% CI, 4.67-9.06) vs 2.08 (95% CI, 0.99-4.36; adjusted IRR, 3.51; 95% CI, 1.54-8.03) for cardiovascular deaths within 90 to 179 days after surgery.. Discontinuation of warfarin treatment within 6 months after bioprosthetic AVR surgery was associated with increased cardiovascular death.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Bicuspid Aortic Valve Disease; Cardiovascular Diseases; Denmark; Drug Administration Schedule; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Incidence; Male; Middle Aged; Registries; Risk; Stroke; Thromboembolism; Warfarin

Topics: Anticoagulants; Aortic Valve; Bicuspid Aortic Valve Disease; Cardiovascular Diseases; Female; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Thromboembolism; Warfarin

Good anticoagulation control in patients during the first months after heart valve surgery is important to prevent thrombotic complications. This is difficult to achieve, partly because the sensitivity to warfarin decreases progressively during approximately three months after valve surgery. A recently developed, simple but aggressive algorithm might improve anticoagulation control in this patient group. It was the objective of this study to evaluate the level of anticoagulation control when a specialised anticoagulation clinic changed from empirical dosing to the use of this new algorithm. In a before-and-after design, a cohort of consecutive patients managed with a new, aggressive dosing algorithm ('Algorithm cohort') was compared to a 'Retrospective cohort' of similar patients dosed empirically. Primary endpoint was individual time in therapeutic range (ITTR) during the first three months of warfarin therapy. Secondary endpoints included proportion of extreme International Normalised Ratio (INR) results, thrombotic and bleeding complications. Ninety-eight patients were included in the Algorithm cohort, 94 of whom were warfarin-naïve. Two hundred patients were included in the Retrospective cohort. Mean ITTR was 60.1% in the Algorithm cohort versus 48.7% in the Retrospective cohort (p <0.001). Patients in the Algorithm cohort spent 0.5% of time at an INR >5, versus 0.2 % in the Retrospective cohort. There was no major bleeding in either cohort; one patient in each cohort had a thrombotic complication. We demonstrate an improvement of the level of anticoagulation control with the use of a condition-specific, aggressive algorithm, as compared to standard dosing, in patients after heart valve surgery.

Topics: Aged; Algorithms; Anticoagulants; Blood Coagulation; Cardiac Surgical Procedures; Chi-Square Distribution; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Female; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Male; Medication Adherence; Middle Aged; Predictive Value of Tests; Prospective Studies; Republic of Korea; Retrospective Studies; Thrombosis; Time Factors; Treatment Outcome; Warfarin

To investigate the association between the apolipoprotein E (apoE) gene polymorphism and the dose for warfarin individual maintenance.. The genotypes of 249 patients with warfarin treatment in maintenance doses were determined by PCR/DHPLC assay. The doses for warfarin maintenance were compared among patients with different genotypes.. In the total of 249 patients, the frequencies of 2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4 genotype were 1.20%, 15.66%, 1.80%, 72.29%, 9.24%, 0.80%, respectively; the allele frequencies of ε2, ε3, ε4 were 9.44%, 84.74%, 5.82%, respectively. The warfarin dose of group ε2 (ε2/ε2, ε2/ε3) was (3.24 ± 1.36) mg/d, slightly higher than that of group ε3 (ε3/ε3, 2.91 ± 1.14 mg/d) or group ε4 [ε4/ε4, ε3/ε4, (2.98 ± 1.05) mg/d], but the difference of the warfarin doses among the 3 groups did not reach statistical significance (F=1.848,P>0.05).. ApoE polymorphism may be not a major genetic factor that influences the individual dose for warfarin maintenance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Apolipoproteins E; Atrial Fibrillation; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Polymorphism, Genetic; Warfarin; Young Adult

In anticoagulation treatment with warfarin, the risk of thrombo-embolic events must be weighed against the risk of bleeding. Time in therapeutic range (TTR) is an important tool to assess the quality of anticoagulation treatment, and has been shown to correlate with less bleeding and thrombo-embolic complications. AuriculA, the Swedish national quality registry for atrial fibrillation and anticoagulation, is used for follow-up and dosage control of warfarin. This is the first report of TTR in AuriculA and, in a subgroup of two centres, bleeding and thrombo-embolic complications during 2008.. Prothrombin complex (International normalized ratio) values from 18 391 patients in 67 different centres were analysed. The mean (SD) age was 70 (12) years. The main indications for warfarin treatment were: atrial fibrillation (64%), venous thromboembolism (19%), and heart valve dysfunction (13%). Time in therapeutic range for all patients was 76.2%. The mean weekly dose of warfarin decreased with age and TTR increased with age. In 4273 patients from two centres in AuriculA, the frequency of major bleedings and venous/arterial thrombo-embolism were 2.6 and 1.7% and for atrial fibrillation, 2.6 and 1.4%, per treatment year, respectively. A correlation between age and the risk of major bleeding (P< 0.001), but not thrombo-embolic complications (P= 0.147), was seen.. Compared with prospective randomized trials of warfarin treatment, TTR in the AuriculA population was higher. Complications were low, probably due to the organization of anticoagulation treatment in Sweden. Use of the AuriculA dosing programme could have contributed to the results by keeping dosing regimens consistent over all centres.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Middle Aged; Prospective Studies; Registries; Sweden; Thromboembolism; Venous Thrombosis; Warfarin

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) suffer from a number of metabolic derangements. Ectopic deposition of calcium in the skin, soft tissues, blood vessels, and viscera is a potentially devastating consequence of disorders of calcium and phosphorus homeostasis. We report the case of a patient with ESRD and secondary hyperparathyroidism receiving HD who developed metastatic pulmonary calcification and calciphylaxis following initiation of warfarin therapy after mechanical valve replacement. Because not all patients with ESRD receiving HD develop ectopic calcification, there appears to be a complex cascade of metabolic interactions that predispose patients to this process. Warfarin is a vitamin K antagonist with inhibitory effects not only on proteins of the coagulation cascade, but also on other important protein systems. Its role in ectopic calcium deposition has been the subject of theories and has been reported in the literature, but no link with metastatic pulmonary calcification has been made. Patients receiving HD have an increased incidence of conditions that require chronic anticoagulation with warfarin, such as VTE, atrial fibrillation, and valvular heart disease requiring valve replacement surgery. Bioprosthetic valves should be considered in these patients because of the potential risk of metastatic calcification when warfarin is used in the setting of mechanical valve replacement.

Topics: Adult; Anticoagulants; Calciphylaxis; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Male; Warfarin

This study was undertaken to analyze the maternal and perinatal outcome in women with prosthetic heart valves on different anticoagulant regimens.. A retrospective chart review of pregnancies in 40 women with mechanical valve prostheses at a tertiary referral centre from 1997 to 2010. The main outcome measures were major maternal complications and perinatal outcome.. The valves replaced were mitral (67.5%), aortic (15.0%), or both (17.5%). Forty-nine pregnancies (72.1%) resulted in live births, 3(4.4%) had stillbirths, and 13(19.1%) had spontaneous abortions and 1(1.4%) underwent therapeutic abortions. The live birth rate was higher in women on heparin (78.3%) compared with those on warfarin (66.9%). There were 2 maternal deaths due to acute mitral valvular thrombosis while on acenocoumarol in the second trimester. Hemorrhagic complications occurred in 3 patients on heparin in the postpartum period, 2 of whom required transfusion. In addition one patient who was on acenocoumarol developed secondary hemorrhage.. No anticoagulant regimen can be said to be entirely safe for use during pregnancy as there is a degree of risk with each regimen. Further larger studies are needed to come up with sufficient evidence-based recommendations for the best possible management of such patients to reduce the maternal risks after mechanical heart valve replacement without compromising fetal outcome.

Topics: Abortion, Spontaneous; Academic Medical Centers; Acenocoumarol; Adult; Anticoagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Incidence; India; Medical Records; Mitral Valve; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Pregnancy Outcome; Retrospective Studies; Thrombosis; Warfarin; Young Adult

To investigate distribution of CYP2C9, CYP3A4, VKORC1 and GGCX gene polymorphisms in the Han population of Guangdong.. The subjects included were 970 Chinese Han patients who received long-term warfarin anticoagulant therapy orally after valve replacement in Guangdong General Hospital between 2000 and 2008. By selecting and analyzing the 12 single nucleotide polymorphisms (SNPs) loci, rs12572351 G>A, rs9332146 G>A, rs4917639 G>T, rs1057910 A>C (CYP2C9*3), rs1934967 G>T, rs1934968 G>A, rs2242480 T>C, rs2246709 G>A, rs9923231 C>T (VKORC1-1639 G>A), rs2359612 G>A (VKORC1*2), rs10871454 C>T, and rs699664 T>C, in 4 genes including CYP2C9, CYP3A4, VKORC1 and GGCX that were possibly correlated with warfarin pharmacodynamics and pharmacokinetics through literature retrieval, the distribution of mutation frequencies of the 12 SNPs loci in Chinese Han population were obtained systematically. SNaPshot technique was used to detect gene SNPs, Hardy-Weinberg genetic equilibrium test was used to test population representativeness.. The allelic mutation frequency at CYP2C9 gene rs12572351 G>A, rs9332146 G>A, rs4917639 C>A, rs1057910 A>C (*3), rs1934967 G>T and rs1934968 G>A loci was 32.53%, 2.16%, 8.25%, 3.61%, 19.18% and 37.37%, respectively; the allelic mutation frequency at CYP3A4 gene rs2242480 T>C and rs2246709 G>A loci was 29.07% and 40.41%, respectively; the allelic mutation frequency at VKORC1 gene rs9923231 C>T, rs2359612 G>A and rs10871454 C>T SNPs loci was 87.99%, 87.94% and 91.34%, respectively; the allelic mutation frequency at GGCX gene rs699664 T>C locus was 31.86%.. It is of important clinical significance in individualized warfarin therapy to systematically study distribution of mutation frequencies at 12 polymorphisms loci in 4 genes including CYP2C9, CYP3A4 , VKORC1 and GGCX related to warfarin pharmacodynamics and pharmacokinetics in the Chinese Han population receiving valve replacement.

Topics: Adult; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; China; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP3A; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mixed Function Oxygenases; Polymorphism, Single Nucleotide; Postoperative Period; Vitamin K Epoxide Reductases; Warfarin; Young Adult

A 27-year-old woman was admitted because of breathlessness, orthopnea, and hemoptysis. The present patient was diagnosed with congenitally corrected transposition of the great arteries (cc-TGA) and underwent systemic atrioventricular valve replacement for severe insufficiency at 23 years of age. She also had been treated with oral conjugated equine estrogen (Premarin) because of congenital pituitary dysfunction. Despite appropriate anticoagulation therapy with warfarin, echocardiography and fluoroscopy showed stuck leaflets of the prosthetic valve due to thrombosis. She underwent emergent surgical valve replacement. This rare association suggests that oral hormone replacement therapy poses a risk of thrombosis especially in patients with cc-TGA after prosthetic valve replacement.

Topics: Adult; Anticoagulants; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Pituitary Diseases; Prosthesis Design; Prosthesis Failure; Radiography; Reoperation; Severity of Illness Index; Thrombosis; Transposition of Great Vessels; Treatment Failure; Warfarin

Current American Heart Association/American College of Cardiology guidelines recommend anticoagulation and antiplatelet therapy during the first 90 postoperative days; however, there is wide variability in the administration of antithrombotic therapy after bioprosthetic aortic valve replacement. We sought to determine whether early antithrombotic therapy was necessary in patients undergoing isolated bioprosthetic aortic valve implantation and who were discharged in normal sinus rhythm.. From December 2001 to October 2008, 1131 patients underwent isolated bioprosthetic aortic valve implantation at Brigham and Women's Hospital. After exclusion of patients who underwent concomitant operations (n = 138, 12%), patients who were anticoagulated preoperatively (n = 4, 0.4%), and patients who experienced postoperative refractory atrial fibrillation requiring anticoagulation at discharge (n = 128, 11%), our study base consisted of 861 patients. Patients were followed for 90 days postoperatively for the occurrence of thromboembolism, including stroke, transient ischemic attack, or peripheral thromboembolic events and bleeding complications.. Of the 861 patients included in this study, 133 (15%) were anticoagulated with warfarin sodium (AC+) postoperatively and 728 (85%) were not (AC-). Patients who received postoperative anticoagulation were older; had a higher incidence of hypertension, cerebrovascular accident, and pulmonary vascular disease; and were more symptomatic at presentation. The 90-day risk of thromboembolism (cerebrovascular accident, transient ischemic attack, or peripheral thromboembolism) after surgery was 5% (n = 6) in those who were anticoagulated and 5% (n = 39) in those who were not (P = .67). Independent predictors of thromboembolism were found to be increasing age (odds ratio, 1.03; P = .03), female gender (odds ratio, 2.23; P = .005), short stature (odds ratio, 0.97; P = .002), smoking status (P = .05), New York Heart Association III/IV (odds ratio 1.77, P = .04), and a 19-mm bioprosthetic aortic valve prosthesis (odds ratio, 2.22; P = .03). Evaluation of each predictor with postoperative acetylsalicylic acid+ and AC+ interaction terms revealed that female patients (odds ratio, 0.75; P = .03 AC+; odds ratio, 0.66; P = .02 acetylsalicylic acid+) and patients with a 19-mm bioprosthetic aortic valve (odds ratio, 0.65; P = .02 AC+; odds ratio, 0.36; P = .01 acetylsalicylic acid+) had a reduction in the incidence of thromboembolism when administered acetylsalicylic acid or warfarin sodium. Patients who were in New York Heart Association III/IV also had a reduction of thromboembolism when given vitamin K antagonist (odds ratio, 0.73; P = .04); a similar trend was observed in patients given acetylsalicylic acid (odds ratio, 0.34; P = .06).. Early anticoagulation after isolated bioprosthetic aortic valve replacement in patients in normal sinus rhythm does not seem to reduce the risk of thromboembolism except in high-risk groups. Current recommendations should be revisited, because the only patients who may benefit from anticoagulation are female, those who are highly symptomatic, and those with a small aortic prosthesis.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aspirin; Bioprosthesis; Chi-Square Distribution; Drug Administration Schedule; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Odds Ratio; Patient Selection; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Topics: Aged; Animals; Aortic Valve; Bioprosthesis; Capsule Endoscopy; Cardiac Catheterization; Cattle; Coronary Angiography; Electrocardiography; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Thrombosis; Ultrasonography; Warfarin

During the period 1991-2007, autopsy was undertaken in 13 fetuses with warfarin embryopathy. Pregnancy data and radiographic babygrams were available in each instance. Gestational age ranged from 17 to 37 weeks. Eleven of the fetuses had the characteristic nasal hypoplasia, but only three had radiological epiphyseal stippling. Cerebral hemorrhage was a major feature of autopsy in 8 of the fetuses, and it is evident that bleeding is a significant factor in the pathogenesis of warfarin embryopathy. A wide variety of additional visceral manifestations which were observed at autopsy have been tabulated. There was no obvious correlation between maternal or gestational age and the presence and severity of any specific embryopathic feature. No information was available concerning the dose and timing of warfarin administration in this series.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Anticoagulants; Autopsy; Cerebral Hemorrhage; Chondrodysplasia Punctata; Female; Fetal Development; Heart Valve Diseases; Humans; Hyperplasia; Nose; Pregnancy; Retrospective Studies; Warfarin; Young Adult

Matrix-Gla Protein (MGP) is a vitamin K-dependent protein acting as a local inhibitor of vascular calcification. Vitamin K-antagonists (oral anticoagulant; OAC) inhibit the activation of MGP by blocking vitamin K-metabolism. The aim of this study was to investigate the effect of long-term OAC treatment on circulating MGP levels in humans and on MGP expression in mice. Additionally, we tested the association between circulating inactive MGP (ucMGP) levels and the presence and severity of AVC in patients with aortic valve disease (AVD). We analysed circulating ucMGP levels in 191 consecutive patients with echocardiographically proven calcific AVD and 35 control subjects. The extent of AVC in the patients was assessed by multislice spiral computed tomography. Circulating ucMGP levels were significantly lower in patients with AVD (348.6 +/- 123.1 nM) compared to the control group (571.6 +/- 153.9 nM, p < 0.001). Testing the effect of coumarin in mice revealed that also the mRNA expression of MGP in the aorta was downregulated. Multifactorial analysis revealed a significant effect of glomerular filtration rate and long-term OAC therapy on circulating ucMGP levels in the patient group. Subsequently, patients on long-term OAC had significantly increased AVC scores. In conclusion, patients with calcific AVD had significantly lower levels of circulating ucMGP as compared to a reference population, free of coronary and valvular calcifications. In addition, our data suggest that OAC treatment may decrease local expression of MGP, resulting in decreased circulating MGP levels and subsequently increased aortic valve calcifications as an adverse side effect.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Animals; Anticoagulants; Aorta; Aortic Valve; Biomarkers; Calcinosis; Calcium-Binding Proteins; Case-Control Studies; Cross-Sectional Studies; Disease Models, Animal; Down-Regulation; Echocardiography; Extracellular Matrix Proteins; Female; Glomerular Filtration Rate; Heart Valve Diseases; Humans; Male; Matrix Gla Protein; Mice; Mice, Inbred DBA; Middle Aged; Osteopontin; Prognosis; Risk Assessment; Risk Factors; RNA, Messenger; Severity of Illness Index; Time Factors; Tomography, Spiral Computed; Vitamin K; Warfarin

Topics: Adult; Anticoagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Thrombolytic Therapy; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

For patients on warfarin therapy, an international normalized ratio (INR) recall interval not exceeding 4 weeks has traditionally been recommended. Less frequent INR monitoring may be feasible in stable patients. We sought to identify patients with stable INRs (defined as having INR values exclusively within the INR range) and comparator patients (defined as at least one INR outside the INR range) in a retrospective, longitudinal cohort study. Occurrences of thromboembolism, bleeding, and death were compared between groups. Multivariate logistic regression models were used to identify independent predictors of stable INR control. There were 2504 stable and 3569 comparator patients. The combined rates of bleeding and thromboembolism were significantly lower in stable patients. Independent predictors of stable INR control were age older than 70 years and the absence of comorbid heart failure and diabetes. Stable patients were significantly less likely to have target INR of 3.0 or higher or chronic diseases. We hypothesize that many patients demonstrating stable INR control could be safely treated with INR recall intervals greater than the traditional 4 weeks.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cohort Studies; Colorado; Comorbidity; Diabetes Mellitus; Drug Monitoring; Female; Heart Failure; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

Off-pump implantation of an apico-aortic bioprothesis-valved conduit in a 75-year-old female symptomatic patient with severe prosthesis-patient mismatch secondary to a previous aortic valve replacement, calcified ascending aorta, tight adhesion with the sternum, was successfully conducted to relieve the left ventricle from severe aortic stenosis.

Topics: Aged; Animals; Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Balloon Occlusion; Bioprosthesis; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Prosthesis Design; Reoperation; Swine; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Topics: Anticoagulants; Drug Therapy, Combination; Echocardiography, Transesophageal; Enoxaparin; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Prosthesis Failure; Thrombosis; Treatment Outcome; Warfarin

Low international normalized ratio (INR;

Topics: Aged; Ambulatory Care Facilities; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart Valve Diseases; Humans; International Normalized Ratio; Male; Medication Adherence; Prospective Studies; Risk Factors; Sex Factors; United States; Venous Thromboembolism; Vitamin K; Warfarin

Warfarin has been widely used for the prevention and treatment of thromboembolism. Warfarin therapy depends on interaction between physiological, environmental, and genetic factors. Vitamin K epoxide reductase (VKORC1) and cytochrome P450 2C9 (CYP2C9) enzyme conjointly determine the warfarin maintenance dose. The prevalence of CYP2C9 and VKORC1 variants varies among ethnic groups. The purpose of the present study was to investigate the prevalence of CYP2C and VKORC1 in the Northern Thai population.. Patients with valvular heart disease who regularly took a steady maintenance warfarin dose for at least one month were recruited into the present study. Patients who had taken amiodarone or an anti-inflammatory drug were excluded Clinical data were obtained from medical records. Five milliliters of whole blood was drawn from each patient for gene analysis and prothrombin time with international normalized ratio (INR) measurement.. From 242 patients, CYP2C9 *1/*1 was found in 230 patients (95%) and CYP2C9 *1/*3 was found in 12 patients (5%). Neither mutant CYP2C9*2 allele nor individuals homozygous for CYP2C9*3 were observed. Regarding VKORC1, haplotype AB was found in 83 patients (34.3%) and haplotype AA was found in 154 patients (63.6%). Haplotype BB (wild type) was found in five patients (2.1%).. The prevalence of CYP2C9 *1/*1 is high while the prevalence of CYP2C9*2 and CYP2C9*3 is very low. VKORC1 haplotype AA is the most common among the Northern Thai population. Further study regarding pharmacogenetic and non-genetic factors to develop warfarin-dosing algorithm is warranted

Topics: Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Female; Heart Valve Diseases; Humans; International Normalized Ratio; Male; Middle Aged; Mixed Function Oxygenases; Mutation; Pharmacogenetics; Polymorphism, Genetic; Prevalence; Risk Factors; Thailand; Vitamin K Epoxide Reductases; Warfarin

Topics: Aged; Anticoagulants; Heart Valve Diseases; Hematoma; Humans; Male; Mitral Valve; Oral Hemorrhage; Tongue Diseases; Warfarin

We aimed to evaluate left atrial appendage (LAA) exclusion in patients undergoing mitral valve surgery with respect to thromboembolic events.. LAA is the predominant source of emboli in patients with atrial fibrillation. Prophylactic LAA exclusion at the time of heart surgery has been recommended to reduce the risk of future thromboembolism.. An observational cohort of 136 patients undergoing LAA exclusion during mitral valve surgery was identified between May 1993 and November 1998 at our institution.. During a mean follow-up of 3.6 +/- 1.3 years, there were 14 (12.3%) thromboembolic events. Compared with patients who received warfarin upon hospital discharge, there were more thromboembolic events in patients not prescribed warfarin upon hospital discharge (n = 7/67, 10% vs n = 6/40, 15%, respectively). The warfarin status was not known for one patient. The majority of thromboembolic events (n = 10/14, 71%) occurred in those who underwent mitral valve repair.. In this observational study, patients who undergo LAA exclusion during mitral valve surgery to reduce the risk of thromboembolism have a significant incidence of thromboembolic events, especially when warfarin therapy is not prescribed upon hospital discharge.

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Bioprosthesis; Cohort Studies; Comorbidity; Female; Florida; Follow-Up Studies; Heart Atria; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Incidence; Male; Middle Aged; Mitral Valve; Ohio; Postoperative Complications; Risk Factors; Thromboembolism; Warfarin

Topics: Animals; Aortic Valve; Bioprosthesis; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Warfarin

Topics: Anticoagulants; Dose-Response Relationship, Drug; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Topics: Anticoagulants; Aspirin; Clopidogrel; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

Topics: Anticoagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Warfarin

Topics: Adult; Anticoagulants; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hematologic Agents; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Warfarin

An increasing number of patients are treated with warfarin worldwide, and many are monitored in general practice, often with office instruments. Bleeding or thromboembolic episodes may be consequences of inadequate treatment. We have therefore examined some important aspects of general practitioners' (GPs') knowledge of warfarin treatment.. A questionnaire including 2 case histories with familiar indications for warfarin treatment (mechanical heart valve prosthesis and pulmonary embolism) was circulated to 3781 GPs in Norway as a postanalytical quality assessment.. A total of 1547 GPs (41%) responded. There were substantial variations among GPs concerning the frequency of international normalized ratio (INR) monitoring, stated therapeutic ranges for arterial (but not venous) indications for anticoagulation therapy, and handling of a moderately high INR result of 5.9. Most GPs estimated an unrealistically high risk of serious bleeding in the latter situation (median, 15%; 10th and 90th percentiles, 4% and 50%, respectively). The critical difference necessary to change the warfarin dose was highly dependent on perceived therapeutic intervals, and about half of the GPs suggested a critical difference of 0.8 INR, which is attainable with office instruments. Sex and age of the GPs, practice size, and availability of an INR instrument in the office laboratory did not influence the results to any substantial degree, as variations within subgroups were similar.. Gross variations in practice were found, especially for aspects of warfarin treatment that lacked uniform guidelines. Evidence-based and practicable recommendations for treatment and monitoring of these patients are still needed.

Topics: Administration, Oral; Aged; Anticoagulants; Drug Monitoring; Family Practice; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Knowledge; Middle Aged; Physicians, Family; Practice Patterns, Physicians'; Primary Health Care; Pulmonary Embolism; Quality Control; Surveys and Questionnaires; Warfarin

Mechanical valves are inherently thrombogenic and require meticulous anticoagulation. Pregnancy produces a hypercoagulable state and achieving adequate anticoagulation is difficult. We present a pregnant patient who had a nonobstructive thrombus of mechanical mitral valve causing embolic acute myocardial infarction. Issues surrounding management of anticoagulation and use of thrombolytic therapy during pregnancy are discussed. Education regarding the critical nature of adequate anticoagulation in these patients is important.

Topics: Adult; Anticoagulants; Cardiomyopathy, Hypertrophic; Echocardiography, Transesophageal; Embolism; Endocarditis; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Myocardial Infarction; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Warfarin

Hemostatic physiology involves a complex interlinking of blood and endothelial factors. Its pharmacological manipulation invariably impacts at multiple molecular sites. Herein is reported an unusual case of coexistent warfarin-induced skin necrosis and heparin-induced thrombocytopenia following mitral valve replacement for thromboembolic phenomena associated with marantic endocarditis and bronchial adenocarcinoma. Thrombophilia in the face of endocarditis should be treated with a suspicion of underlying cancer.

Topics: Adenocarcinoma; Anticoagulants; Bronchial Neoplasms; Endocarditis; Fatal Outcome; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin; Humans; Intracranial Embolism; Male; Middle Aged; Mitral Valve; Necrosis; Postoperative Complications; Skin; Thrombocytopenia; Warfarin

Topics: Disease Management; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Maternal-Fetal Exchange; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

A follow-up study was performed to assess long-term survival, valve-related complications, and pregnancy outcomes in young rheumatic women undergoing isolated mitral mechanical replacement. The influence of prosthetic type on outcomes was also investigated.. Between 1975 and 2003, 267 isolated mitral mechanical prostheses were implanted. Follow-up reached 3707.8 patient-years.. Actuarial survival at 1, 5, 10, 15, 20, and 25 years was 97% +/- 0.01%, 90.4% +/- 0.017%, 85.3% +/- 0.023%, 82.3% +/- 0.025%, 71.7% +/- 0.036%, and 70.2% +/- 0.038%, respectively. At multivariate analysis, atrial fibrillation at follow-up was identified as an independent risk factor for late mortality, whereas left ventricular ejection fraction at 12 postoperative months proved to be a protective factor. Freedom from thromboembolism at 1, 5, 10, 15, 20, and 25 years was 98.1% +/- 0.01%, 94.1% +/- 0.015%, 89.1% +/- 0.021%, 85.9% +/- 0.025%, 81.1% +/- 0.031%, and 75.3% +/- 0.063%, respectively. Atrial fibrillation and Carbomedics device were significantly associated with an increase in thromboembolic events. Freedom from reoperation at 1, 5, 10, 15, 20, and 25 years was 99.2% +/- 0.005%, 95% +/- 0.014%, 91.6% +/- 0.018%, 88.6% +/- 0.022%, and 85.7% +/- 0.041%. Type of prosthesis (tilting disc) was identified as a predictor of reoperation. At the end of the study, 208 patients were still alive: 94.7% were in New York Heart Association class I or II. When receiving warfarin therapy, no patient undertaking pregnancy (n = 35) experienced adverse cardiac or valve-related events. Fetal events were significantly less frequent with a daily warfarin dose less than 5 mg.. Mechanical devices provided excellent performance, safety, and durability. The prognostic role of left ventricular function and atrial fibrillation overwhelmed any differences that might exist between different prosthetic designs. Pregnancies entail virtually no maternal risk and predictable fetal complications.

Topics: Adolescent; Adult; Anticoagulants; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Mitral Valve; Multivariate Analysis; Pregnancy; Pregnancy Outcome; Prosthesis Design; Reoperation; Retrospective Studies; Rheumatic Heart Disease; Risk Factors; Warfarin

Topics: Anticoagulants; Heart Valve Diseases; Humans; Thrombosis; Warfarin

Vitamin K antagonists, known as oral anticoagulants, affect the synthesis and function of the matrix Gla protein, which is a potent inhibitor of tissue calcification. We performed multislice spiral computed tomography in 86 patients (53 men, mean age 71 +/- 8 years) with calcific aortic valve disease to quantitate the amount of calcification in the aortic valve and coronary arteries. Patients with long-term oral anticoagulation therapy (mean duration 88 +/- 113 months; n = 23) were compared with those without anticoagulation (n = 63). No differences were found in the demographic, clinical, or echocardiographic characteristics between the 2 study groups. Patients on oral anticoagulant therapy had increased coronary calcium (coronary Agatston score 1,561 +/- 1,141 vs 738 +/- 978, respectively; p = 0.024) and valvular calcium (valvular Agatston score 2,410 +/- 1,759 vs 1,070 +/- 1,085, respectively; p = 0.002) compared with patients without anticoagulation treatment. The results of our study have demonstrated that oral anticoagulation may be associated with increased valvular and coronary calcium in patients with aortic valve disease, presumably due to decreased activation of the matrix Gla protein.

Topics: Administration, Oral; Aged; Anticoagulants; Aortic Valve; Calcinosis; Coronary Artery Disease; Female; Heart Valve Diseases; Humans; Male; Tomography, Spiral Computed; Treatment Outcome; Warfarin

In 1998, the American College of Cardiology and The American Heart Association (ACC/AHA) published guidelines for the postoperative anticoagulation of patients who have undergone heart valve replacement. The American College of Chest Physicians made similar recommendations in 2001. The present survey was conducted to review anticoagulation practice among UK consultant cardiac surgeons, and to assess compliance with these guidelines.. An anonymous postal questionnaire was distributed to 185 adult cardiac surgeons identified from the Society of Cardiothoracic Surgeons of Great Britain and Ireland (SCTS).. The analysis was based upon 97 replies. All consultants use lifelong warfarin after mechanical valve replacement. In general, target INR ranges were lower for aortic valves compared with mitral valves. Some 53% (51/97) of consultants never use warfarin after bioprosthetic aortic valve replacement (AVR), compared with 33% (28/86) after bioprosthetic mitral valve replacement (MVR). Temporary (< or = 3 months) warfarin is used by 47% (46/97) of consultants after bioprosthetic AVR and by 63% (54/86) after bioprosthetic MVR. Some 64% (52/81) of consultants use warfarin after mitral valve repair, when an annuloplasty ring is inserted. This was always temporary (< or = 6 months). Aspirin is used long term by 54% (44/82) of consultants after mitral valve repair.. All consultant cardiac surgeons adequately anticoagulate their patients after mechanical valve replacement. Only 16% (16/97) of cardiac surgeons follow current guidelines for the postoperative anticoagulation of bioprosthetic AVR. Only 28% (24/86) of consultant cardiac surgeons comply with guidelines for bioprosthetic MVR. No guidelines exist for the anticoagulation of patients after mitral valve repair. Guidelines need to be reviewed for the anticoagulation of patients undergoing bioprosthetic valve replacement and formulated for patients undergoing mitral valve repair.

Topics: Adult; Anticoagulants; Aortic Valve; Aspirin; Bioprosthesis; Consultants; Fibrinolytic Agents; Guideline Adherence; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Ireland; Mitral Valve; Practice Guidelines as Topic; Practice Patterns, Physicians'; Surveys and Questionnaires; Thoracic Surgery; Treatment Outcome; United Kingdom; Warfarin

The aim of this study was to provide guidelines for optimal anticoagulation in Chinese patients after mechanical heart valve replacement. A Carbomedics valve was implanted in 178 patients between July 2000 and July 2003. During follow-up, 22 bleeding events and 1 thromboembolic complication occurred. The linearized rates of bleeding and thromboembolism were 5.83% and 0.26% per patient-year, respectively. The linearized mortality rate was 0.79% per patient-year. The final mean international normalized ratio (INR) was 1.68+/-0.38, however there was a significant variation between the early and late periods of follow-up. For Chinese patients with mechanical heart valves, bleeding was the major complication rather than thromboembolism. Low-dose anticoagulation (international normalized ratio 1.4-2.0) could markedly decrease bleeding and effectively prevent thromboembolism. As the INR was most unstable in the first postoperative month, re-examination of patients in this period is critical.

Topics: Adolescent; Adult; Aged; Anticoagulants; Aortic Valve; Biomarkers; Cardiopulmonary Bypass; China; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Male; Middle Aged; Mitral Valve; Postoperative Hemorrhage; Prosthesis Design; Prothrombin Time; Survival Analysis; Thromboembolism; Treatment Outcome; Warfarin

The life expectancy of patients with chronic renal failure who are dependent on dialysis is very poor. This study was undertaken to determine time-related outcomes in dialysis patients requiring cardiac valve replacement.. From 1994 to 2001, 29 end-stage renal disease (ESRD) patients on hemodialysis (HD) program underwent 30 valve replacement operations: 29 received mechanical valves (97%), and one received bioprosthetic valves. The sites of valve replacement were 11 aortic (36.7%), 18 mitral (60%), and one both aortic and mitral (3.3%). Mean age was 42.46 +/- 14.26 years (range 17-75 years). Follow-up was completed in 28 patients (96.5%).. Early postoperative mortality (in the first 30 days) was 3.4% (n = 1). The overall estimated Kaplan-Meier survival was 56.7% at 36 months, 46.7% at 60 months, and 43.3% at 96 months. HD program was discontinued for two patients after renal transplantation in the follow-up period. All patients, except the one with bioprosthesis, used warfarin sodium for anticoagulation and none of them had bleeding. One of the patients had a major cerebrovascular accident (CVA) and another one had a minor CVA at the follow-up (6.7%).. Life quality is better and life expectancy is longer after valve replacement in ESRD patients who have valvular disease. Also, longer life expectancy increases the probability for finding donors for kidney transplantation.

Topics: Adolescent; Adult; Aged; Anticoagulants; Aortic Valve; Bioprosthesis; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Kidney Failure, Chronic; Kidney Transplantation; Life Expectancy; Male; Middle Aged; Mitral Valve; Renal Dialysis; Treatment Outcome; Warfarin

Myocardial infarction (MI) due to coronary artery embolization is a rare and potentially lethal complication of prosthetic heart valve thrombosis. A 58-year-old man in whom the aortic valve was replaced with a bileaflet mechanical valve presented with an acute anterior MI. Valvular dysfunction was detected by physical examination, and confirmed by two-dimensional echocardiography and cinefluoroscopy. Coronary angiography disclosed embolization of the left anterior descending artery. Thrombotic encroachment of one of the prosthetic valve leaflets was found at reoperation. Failure to achieve adequate anticoagulation was likely due to an interaction between warfarin and herbal products. These findings have significant implications regarding the diagnosis and treatment of acute MI in patients with left-sided prosthetic heart valves, and emphasizes the importance of appropriate anticoagulation in this setting.

Topics: Anticoagulants; Aortic Valve; Heart Valve Diseases; Heart Valve Prosthesis; Herb-Drug Interactions; Humans; Male; Middle Aged; Myocardial Infarction; Plants, Medicinal; Postoperative Complications; Thrombosis; Warfarin

Topics: Anticoagulants; Aortic Valve; Aspirin; Bioprosthesis; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Intracranial Embolism; Platelet Aggregation Inhibitors; Prospective Studies; Survival Analysis; Warfarin

The treatment of patients at increased risk for arterial thromboembolism who require temporary interruption of warfarin sodium therapy is a common clinical problem. We investigated the efficacy and safety of a standardized periprocedural anticoagulation regimen with low-molecular-weight heparin.. We studied 650 consecutive patients with a mechanical heart valve, chronic atrial fibrillation, or embolic stroke who required interruption of warfarin therapy because of an invasive procedure. Warfarin was stopped 5 or 6 days before the procedure, and patients received subcutaneous dalteparin sodium, 100 IU/kg twice daily, starting 3 days before the procedure. The risk of postprocedural bleeding determined postprocedural anticoagulant management. In patients undergoing a non-high-bleeding-risk procedure who had adequate postprocedural hemostasis, warfarin was resumed on the evening of the procedure, and dalteparin sodium, 100 IU/kg twice daily, was resumed on the next day and continued until the international normalized ratio was 2.0 or more. If postprocedural hemostasis was not secured, the resumption of dalteparin was delayed. In patients undergoing a high-bleeding-risk procedure, warfarin was resumed on the evening of the procedure, but dalteparin was not given after the procedure.. Patients were followed up during the preprocedural and postprocedural period for a mean of 13.8 days (range, 10-18 days). In 542 patients who underwent a non-high-bleeding-risk procedure, there were 2 thromboembolic events (0.4%), 4 major bleeding episodes (0.7%), and 32 episodes of increased wound-related blood loss that precluded postprocedural dalteparin administration (5.9%). In 108 patients who underwent a high-bleeding-risk procedure, there were 2 deaths (1.8%) possibly due to thromboembolism and 2 major bleeding episodes (1.8%).. In patients at increased risk for arterial thromboembolism who require temporary interruption of warfarin therapy, a standardized periprocedural anticoagulant regimen with low-molecular-weight heparin is associated with a low risk of thromboembolic and major bleeding complications.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Blood Loss, Surgical; Female; Fibrinolytic Agents; Follow-Up Studies; Heart Valve Diseases; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Intracranial Embolism; Male; Middle Aged; Perioperative Care; Postoperative Complications; Prospective Studies; Risk Factors; Surgical Procedures, Operative; Thromboembolism; Treatment Outcome; Warfarin

To provide some references for defining the Chinese optimal intensity of anticoagulation after mechanical heart valve prostheses replacement.. For the 178 patients with carbomedics mechanical prosthetic heart valves, the means of INR were compared between the patients with complications and those without complications at the standard of INR1. 4 - 2.0. Also, the variations of INR were compared among different follow-ups.. During the follow-up, 22 hemorrhagic and 1 thromboembolic complication occurred. The total linearized rate of anticoagulation-related hemorrhage was 5.83% pty. The total linearized rate thromboembolism was 0.26% pty. The late mortality was 0.79% pty (3 cases ). The final mean INR was 1.68 +/- 0.38. The final mean oral warfarin dose was 2.34 +/- 0.80 mg. The differences of variations of INR in five periods were significant (F = 5.072, P < 0.05). The mean INR in the first month of follow-up was 1.75 +/- 0.27.. For Chinese patients with mechanical prosthetic heart valve, hemorrhage is the principal complication, the ratio of which is much higher than that of thromboembolism. The low-dose anticoagulation (INR1. 4-2.0) could remarkably decrease hemorrhagic events as effectively as prevent the thrombolic events. Moreover the INR is the most unstable in the first month of follow-up, so re-examination for the patients in the first month after the operation is vitally important.

Topics: Adolescent; Adult; Anticoagulants; Aortic Valve; Cardiopulmonary Bypass; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Heparin; Humans; International Normalized Ratio; Male; Middle Aged; Mitral Valve; Postoperative Complications; Postoperative Period; Warfarin

An enhanced bileaflet valve, the Edwards MIRA feminine Mechanical Valve became available in 1998. Favorable hydrodynamic features and a redesigned sewing ring encouraged us to implant this device in indicated patients. Hemodynamics and clinical performance parameters were evaluated.. Between February 1998 and October 1999, 338 patients (171 males, 167 females) underwent native valve replacement with a MIRA prosthesis. Mean age 56.6+/-13.6 years, 320 patients were in NYHA class III/IV. Sixty-seven patients had echocardiographic examinations. Standard cardiopulmonary bypass was employed utilizing institutionally accepted implantation techniques. Aortic valve replacement was performed in 163 patients, mitral valve replacement in 134 patients, 35* double valve replacements and 1 triple valve replacement.. Follow-up is 98% complete. Mean follow-up is 6.9+/-3.3 months (178.2 patient years). There were no operative deaths. Four early deaths were seen (1.18%). Late deaths reported in 12 patients. Linearized rate of late mortality was 6.7% per patient year (ppy). Overall actuarial survival at 13 months is 92.2%. Mean gradients and Effective Orifice Areas (EOA's) are comparable to other bileaflet valves. Linearized rates for valve-related complications was 4.49% ppy. Only 5 transient thromboembolic events (TE = 2.81% ppy) and 3 non-structural valve dysfunction events (NSVD = 1.68%) were seen. No reports of bleeding events, prosthetic endocarditis, valve thrombosis or structural valve deterioration. One patient required mitral valve reoperation for perivalvular leak.. Short-term hemodynamic and clinical results are comparable to other bileaflet valves. The sewing ring is non-obstructive, compliant with smoother needle penetration. Early clinical results are encouraging, follow-up should be continued.

Topics: Adolescent; Adult; Aged; Anticoagulants; Aortic Valve; Biocompatible Materials; Echocardiography; Female; Follow-Up Studies; Health Status Indicators; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Prosthesis Design; Survival Rate; Treatment Outcome; Warfarin

Topics: Anticoagulants; Aortic Valve; Drug Interactions; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Panax; Thrombosis; Treatment Failure; Warfarin

The management of patients anticoagulated with warfarin and referred for coronary angiography presents a substantial challenge to the physician who must minimize risks of periprocedural hemorrhage and thromboembolism. The aim of this study was to evaluate the feasibility and safety of performing diagnostic coronary angiography and percutaneous coronary intervention during uninterrupted warfarin therapy. Patients treated with warfarin were prospectively identified and enrolled in the study. Nineteen diagnostic cardiac catheterizations and six percutaneous coronary interventions were performed in 23 patients. The mean international normalized ratio was 2.4 +/- 0.5 (range, 1.8-3.5). Hemostasis was achieved with AngioSeal following 21 procedures and with Perclose following 4 procedures. No patient experienced a predefined endpoint. Specifically, no patient experienced procedure-related myocardial infarction, major or minor bleeding. We conclude that cardiac catheterization and percutaneous coronary intervention may be considered in the setting of uninterrupted warfarin therapy.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Cerebrovascular Disorders; Clopidogrel; Coronary Angiography; Coronary Disease; Equipment Design; Feasibility Studies; Female; Follow-Up Studies; Heart Failure; Heart Septal Defects, Atrial; Heart Valve Diseases; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Ticlopidine; Treatment Outcome; Venous Thrombosis; Warfarin

A 27-yr-old woman who had been taking warfarin for 10 yr after mitral valve replacement became pregnant. After knowing her pregnancy, she received heparinization for nine weeks instead of warfarin, and took oral anticoagulant again. At 24 weeks of gestation, fetal ultrasound and MRI showed a left subdural hematoma, and the pregnancy was terminated. Subdural hematoma was demonstrated on autopsy. Fatal bleeding of the fetus is a rare complication of maternal warfarin medication, occurring mostly in the second or third trimester. There is no alternative regimen available, so that regular monitoring by fetal ultrasound and strict control of warfarin dose with regular measurement of prothrombin time are the best way to prevent intrauterine fetal death due to bleeding.

Topics: Adult; Anticoagulants; Ductus Arteriosus, Patent; Female; Fetal Diseases; Heart Valve Diseases; Hematoma; Heparin; Humans; Intracranial Hemorrhages; Maternal Exposure; Pregnancy; Pregnancy Complications, Hematologic; Prothrombin Time; Warfarin

To compare the effectiveness of pharmacists and physicians in obtaining therapeutic anticoagulation on initiation of warfarin sodium therapy immediately following prosthetic cardiac valve insertion. Secondary objectives were the percentage of days with an international normalized ratio (INR) greater than four, the percentage of days with an INR less than two, the time to stabilize the INR within the therapeutic range, and the percentage of patients experiencing at least one major bleed.. This study was a before and after comparison using a retrospective chart review of patients who received warfarin sodium following cardiac valve surgery. Physicians dosed independently and pharmacists used a warfarin sodium nomogram to manage patients.. A total of 227 patients (physician group, n=130; pharmacist group, n=97) satisfied the inclusion criteria. No differences were found between the two groups in the percentage of days in the therapeutic range (P=0.27), the percentage of days with INR less than two (P=0.06), the percentage of patients discharged before their INR stabilized (P=0.91) or the percentage of patients with a major bleed (P=0.72). The pharmacist group had 5.9% fewer days (P<0.001) with an INR greater than four than the physician group.. Appropriately trained pharmacists appear equally safe and effective as physicians when managing warfarin sodium therapy in patients who have undergone cardiac valve replacement.

Topics: Anticoagulants; Drug Monitoring; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Hospitals, Teaching; Humans; International Normalized Ratio; Length of Stay; Male; Middle Aged; Pharmacists; Pharmacy Service, Hospital; Physicians; Retrospective Studies; Treatment Outcome; Warfarin

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Blood Proteins; Drug Administration Schedule; Drug Synergism; Erectile Dysfunction; Gingival Hemorrhage; Half-Life; Heart Valve Diseases; Humans; International Normalized Ratio; Male; Piperazines; Postoperative Complications; Protein Binding; Purines; Ranitidine; Sildenafil Citrate; Sulfones; Thrombosis; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Risk Assessment; Stroke; Thromboembolism; Venous Thrombosis; Warfarin

We sought to determine whether the Cox maze procedure provides additional benefit to patients with atrial fibrillation undergoing mitral valve operations.. Between May 1992 and August 2000, we performed 258 Cox maze procedures with mitral valve replacement (n = 147) or mitral valve repair (n = 111). We compared the outcomes of these patients with those of 61 control patients with preoperative atrial fibrillation who underwent mitral valve replacement alone during the same interval. The three cohorts were similar in age, sex, and proportion of patients in preoperative New York Heart Association functional class 3 or 4.. Although 5-year survivals were similar among the groups (94% for mitral valve replacement alone, 95% for mitral valve replacement plus maze, and 97% for mitral valve repair plus maze), freedoms from atrial fibrillation at 5 years were significantly higher in the mitral valve replacement plus maze group (78%) and the mitral valve repair plus maze group (81%) than in the mitral valve replacement group (6%, P <.0001). Freedoms from stroke at 5 years were 97% for the mitral valve replacement plus maze group, 97% for the mitral valve repair plus maze group, and only 79% for mitral valve replacement group (P <.0001). Multivariable analysis with Cox hazard model revealed that the most significant risk factor for late stroke was the omission of the Cox maze procedure (P =.003).. The addition of the Cox maze procedure to mitral valve repair and replacement was safe and effective for selected patients. Elimination of atrial fibrillation significantly decreased the incidence of late stroke.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiac Surgical Procedures; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Incidence; Japan; Male; Middle Aged; Mitral Valve; Multivariate Analysis; Postoperative Care; Postoperative Complications; Preoperative Care; Recurrence; Risk Factors; Stroke; Survival Analysis; Time Factors; Treatment Outcome; Warfarin

To examine if fetal risks associated with Warfarin anticoagulation during pregnancy may have been over-estimated at the time the drug was contraindicated during pregnancy.. Seven case series with the same therapeutic objective for Warfarin anticoagulation published after 1980 were identified. The frequencies of fetal complications were calculated and compared with those of the 1980 compilation.. The frequencies of embryopathy, stillbirths, and neonatal deaths were similar to the 1980 database, but higher with respect to spontaneous abortions (24.1 vs. 8.6%) and premature deliveries (13.9 vs. 4.6%), and lower regarding live births (73.3 vs. 83.7%).. Fetal risks associated with Warfarin anticoagulation during pregnancy have not been overestimated. Warfarin should not be given in cases where other anticoagulants do not increase the risk for the expecting mother.

Topics: Abortion, Spontaneous; Anticoagulants; Contraindications; Female; Fetal Death; Fetal Diseases; Heart Valve Diseases; Humans; Infant, Newborn; Maternal Exposure; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Cardiovascular; Retrospective Studies; Risk Assessment; Warfarin

To determine the factors that affect the initial response to warfarin therapy in Korean patients after cardiac valve surgery.. A retrospective analysis of 127 patients who had undergone cardiac valve surgery at Seoul National University Hospital was performed. On the first day, most patients received warfarin 5 mg, while some received an individualized warfarin dose according to their physician's decision. Doses to be given on the following days were determined based on daily international normalized ratio (INR) and the previous doses. To measure warfarin sensitivity, the warfarin dose index (WDI), defined as the INR divided by the mean warfarin dose administered during the preceding 3 days, was introduced. The effects of age, gender, weight, serum albumin concentration, baseline INR, cardiopulmonary bypass time, and concurrent administration of amiodarone were evaluated.. The patients' weight, initial serum albumin concentration, and baseline INR value influenced their initial response to warfarin. The initial WDI correlated negatively with the initial serum albumin concentration (p < 0.001) and body weight (p < 0.05) and positively with the baseline INR (p < 0.01). The initial WDI of the patients taking amiodarone was significantly higher (mean +/- SD 0.74 +/- 0.34) than that of patients without amiodarone (0.46 +/- 0.22) (p < 0.001). Maintenance doses correlated negatively with the initial warfarin response (p < 0.001) and positively with body weight (p = 0.053).. The factors associated with an increased initial warfarin response in patients after cardiac valve surgery were high baseline INR, low postoperative serum albumin concentration, and concurrent administration of amiodarone. Thus, patients with any of these factors should receive a smaller initial warfarin dose. Also, to predict the warfarin maintenance dose from the initial response, the effect of transient changes in the sensitivity to warfarin during the initial period should be considered.

Topics: Adult; Amiodarone; Anticoagulants; Dose-Response Relationship, Drug; Drug Interactions; Ethnicity; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; International Normalized Ratio; Korea; Male; Retrospective Studies; Warfarin

A 51-year-old female underwent redo mitral valve replacement with a pericardial bioprosthesis because of acute thrombotic obstruction of a mechanical valve, in spite of adequate anticoagulation with warfarin. Her protein C level was 24% of the normal value and protein S was reduced to 54% of normal.

Topics: Acute Disease; Anticoagulants; Bioprosthesis; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Middle Aged; Mitral Valve; Protein C; Recurrence; Reoperation; Rheumatic Heart Disease; Thromboembolism; Warfarin

Topics: Anticoagulants; Aortic Valve; Enoxaparin; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Prosthesis Failure; Radiography; Thrombosis; Tissue Plasminogen Activator; Treatment Outcome; Treatment Refusal; Warfarin

A simple HPLC method was established for the determination of warfarin in plasma to investigate the relationship between warfarin concentration and anticoagulant effect.. The mixture of dichloromethane and hexane (1:9) was used as extracting solvent for the plasma samples. The chromatographic separation was on C18 column with a mobile phase consisting of methanol and 50 mmol/L ammonium acetate buffer (pH2.5, 70:30).. The calibration curve was linear within 50-2000 ng/ml. The extraction recoveries of warfarin were 78.0%-81.6%. The recoveries of methodology were 103.1%-106.5%. Inter-day and intra-day RSD were 2.33%-5.46% and 5.29%-7.73%, respectively. This method was used for determining warfarin in 70 patients after cardiac valve replacement. The results showed that 44 cases had their INR within the safety range (1.31-2.35) recommended to Chinese, and of them 37(84.1%) cases had a warfarin level at 616.2 +/- 154.8 ng/ml.. This method is useful in monitoring warfarin concentration during anticoagulant therapy.

Topics: Anticoagulants; Chromatography, High Pressure Liquid; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Postoperative Period; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Comorbidity; Diabetes Complications; Double-Blind Method; Fibrinolytic Agents; Heart Valve Diseases; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Isoindoles; Middle Aged; Phenylbutyrates; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thromboembolism; Warfarin

Pregnant women who have valvular disease represent a major challenge for physicians involved in their care. Careful history taking and physical examination, along with a judicious use of diagnostic tools (mainly echocardiography), can lead to better management and ultimately to excellent outcomes for both mother and baby.

Topics: Antibiotic Prophylaxis; Anticoagulants; Aortic Valve Stenosis; Endocarditis, Bacterial; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemodynamics; Humans; Mitral Valve Insufficiency; Mitral Valve Stenosis; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

To review anticoagulant-related bleeding in heart valve patients on warfarin at the Kenyatta National Hospital and to determine the variables associated with anticoagulant-related bleeding.. A combined retrospective and prospective review of patients operated at the Kenyatta National Hospital. Retrospective period from June 1973 to 31st July 1997, while prospective period from August 1st 1997 to June 1st 2000.. Surgical Outpatient Department, Kenyatta National Hospital, Nairobi.. Linearised occurrence rate of anticoagulant-related bleeding and the one- five- and ten- year bleed free rates. Independent risk factors associated with anticoagulant-related bleeding determined using Cox's proportional hazards.. Thirty one bleeding episodes were recorded in 150 patients followed up for a total of 745 patient-years. The risk of occurrence of the first bleed was 16.0%; while the risk of a subsequent bleed increased thereafter with a 16.7%, 50% and 50% risk after the first, second and third bleeds respectively. The linearised rate for minor anticoagulant-related bleed was 4.16% per patient per year however, half the bleeds occurred within the first year of valve implantation or previous bleeding episode. The one-, five- and ten-year bleed free rates for all valves combined were 93%, 85% and 78% respectively. There was no statistically signicant difference between the curves comparing the bleed free rates for the first and second bleeding episodes (p=0.098). The number of valves implanted, the site of implant and the time to the occurrence of bleeding were independent risk factors associated with the occurrence of bleeding (p<.05).. The occurrence of anticoagulant-related bleeding is relatively common being slightly above the internationally reported range. Most episodes of bleeding will occur within one year of hospital discharge or the previous bleeding episode. The risk of another bleeding episode occurring increases with each episode with up to a 50% risk of re-bleed after the second bleeding episode. In this study, the number of valves implanted, their position and the time of occurrence of the bleed were risk factors to the occurrence of bleeding.

Topics: Adult; Anticoagulants; Female; Heart Valve Diseases; Hemorrhage; Humans; Kenya; Male; Postoperative Complications; Postoperative Period; Proportional Hazards Models; Prospective Studies; Retrospective Studies; Risk Factors; Warfarin

To determine the pattern of anticoagulation control for post heart-valve surgery for patients on follow up at Kenyatta National Hospital (KNH).. A combined prospective and restrospective hospital-based study. Retrospective period from January 1991 to 31st August 1997, while the prospective period was from 1st September 1997 to 31st November 1999.. Cardiothoracic surgery clinic, Kenyatta National Hospital, Nairobi.. Post heart valve surgery patients on warfarin and attending the cardiothoracic surgery clinic at Kenyatta National Hospital.. Clinic attendance intervals, average warfarin dosages, interval of dosage change, INR values and variations from accepted normal.. A total of 103 patients fulfilled the criteria for inclusion into the study consisting of 77 mitral valve replacements, 18 aortic valve replacements, seven double valve replacements and one mitral valve repair. The total follow up time for the study period is 316.9 patients years. On average, patients attended their anticoagulation clinic once every 59 days. The average dose of warfarin prescribed was 6.81 mg daily (+/-2.67 mg), with double valve replacement patients receiving a statistically significant lower dosage of 6.04 mg (+/-1.36 mg), (95% confidence limits). On average, a warfarin dose change was made 1.48 times a year per patient. For all the patients, the mean INR was 2.50 (+/-1.18). The respective values for mitral, aortic, double valve replacement and the mitral repairs were 2.53 (+/-1.21), 2.32 (+/-1.04), 2.5 (+/-1.05) and 2.02 (+/-0.53), respectively. Mitral valve repair patients maintained a significantly lower level of INR (95% confidence limits). Only during 18% of the follow up time was adequate anticoagulation maintained. During the study period only 6.9% of patients were able to maintain adequate anticoagulation for 50% or more of their follow up time.. Anticoagulation control at the KNH still needs some improvements in clinic attendance and better dosage adjustments to achieve more appropriate INR values.

Topics: Anticoagulants; Blood Coagulation Disorders; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hospitals, Public; Humans; Kenya; Postoperative Complications; Practice Patterns, Physicians'; Prospective Studies; Retrospective Studies; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Chemoprevention; Drug Monitoring; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Myocardial Infarction; Pulmonary Embolism; Risk Factors; Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

To evaluate the effect of lower intensity anticoagulation therapy in patients with mechanical prosthetic valves, laboratory-based hematological assays including prothrombin time (PT), activity of factor X, antithrombin III (AT III), D-dimer, fibrinogen (Fg) and platel et al pha-granular membrane protein (GMP-140) were performed in 65 patients who had been on warfarin treatment for over one month. The patients were assigned to 3 groups on the basis of their International Normalized Ratios (INR), ranging from 2.00 to 2.50; 2.51 to 3.00; 3.01 to 4.50, respectively. The results showed that the D-dimer, Fg, GMP-140 levels were higher after mechanical valve replacement than those before operation, indicating the activation of coagulation and fibrinolysis system and the damage of platelets. Lower intensity anticoagulation therapy (INR 2.00 to 2.50) could effectively inhibit the activity of factor X and increase the level of AT III. There were no appreciable differences among D-dimer, Fg, GMP-140 and AT III in the 3 anticoagulation intensity groups. These results suggest that in patients with new generation mechanical prosthetic valves, target anticoagulation level (INR 2.00 to 2.50) may result in good protection from thrombo-embolism.

Topics: Adolescent; Adult; Anticoagulants; Factor X; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; P-Selectin; Postoperative Complications; Rheumatic Heart Disease; Thromboembolism; Warfarin

A 76-year-old woman receiving warfarin after aortic valve replacement experienced prosthetic valve thrombosis during dicloxacillin therapy. Successful thrombolysis was achieved with tissue plasminogen activator. The international normalized ratio (INR) on admission was reduced to 1.4 and an increased warfarin dosage was required for three weeks following discontinuation of dicloxacillin treatment in order to maintain therapeutic INRs. Careful monitoring of INRs and titration of the warfarin dosage is recommended when dicloxacillin is prescribed to patients receiving warfarin.

Topics: Aged; Anticoagulants; Aortic Valve; Cineradiography; Dicloxacillin; Drug Therapy, Combination; Echocardiography, Doppler; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Penicillins; Plasminogen Activators; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Urinary Tract Infections; Warfarin

Topics: Aged; Anticoagulants; Antifungal Agents; Blood Coagulation; Drug Interactions; Female; Heart Valve Diseases; Humans; Mitral Valve; Naphthalenes; Onychomycosis; Terbinafine; Warfarin

This study assesses the long-term (mean 52+/-24 months) performance of the St. Jude Medical (SJM) valve in 200 young (mean age 31+/-13 years) rheumatic patients on low-level warfarin anticoagulation combined with dipyridamole. Follow-up was 95% complete and comprised 867 patient-years. There were 33 deaths (3.8%/patient-year). Death was valve related in 12 cases and due to left ventricular dysfunction in 10. Death due to left ventricular dysfunction occurred earlier after surgery than death due to other causes (10+/-7 vs 29+/-18 months, p <0.005); these patients had larger preoperative left ventricular dimensions than the rest of the group (end-systolic diameter 51+/-13 vs 37+/-16 mm, end-diastolic diameter 66+/-13 vs 50+/-19 mm, p = 0.006). Actuarial probability of survival was 81% at 86 months and probability of event-free survival was 71%. The median international normalized ratio was 1.88+/-0.54. Thromboembolism (13 events) occurred at a linearized rate of 1.5%/patient-year. There were 11 major bleeding episodes (1.3%/patient-year), 4 cases of prosthetic valve endocarditis (0.8%/patient-year), and 12 paraprosthetic leaks (1.4%/patient-year). No valve obstructions or reoperations occurred. Thus, the SJM valve performs well on low-level anticoagulation combined with dipyridamole. Left ventricular dysfunction was a common cause of death in the early postoperative period.

Topics: Actuarial Analysis; Adult; Anticoagulants; Cause of Death; Endocarditis; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Rheumatic Heart Disease; Survival Analysis; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

High doses of warfarin cause focal calcification of the elastic lamellae in the media of major arteries and in aortic heart valves in the rat. Aortic calcification was first seen after 2 weeks of warfarin treatment and progressively increased in density at 3, 4, and 5 weeks of treatment. By 5 weeks, the highly focal calcification of major arteries could be seen on radiographs and by visual inspection of the artery. The calcification of arteries induced by warfarin is similar to that seen in the matrix Gla protein (MGP)-deficient mouse, which suggests that warfarin induces artery calcification by inhibiting gamma-carboxylation of MGP and thereby inactivating the putative calcification-inhibitory activity of the protein. Warfarin treatment markedly increased the levels of MGP mRNA and protein in calcifying arteries and decreased the level of MGP in serum. Warfarin treatment did not affect bone growth, overall weight gain, or serum calcium and phosphorus levels, and, because of the concurrent administration of vitamin K, prothrombin times and hematocrits were normal. The results indicate that the improved warfarin plus vitamin K treatment protocol developed in this study should provide a useful model to investigate the role of MGP in preventing calcification of arteries and heart valves.

Topics: Animals; Arteries; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Heart Valve Diseases; Male; Matrix Gla Protein; Rats; Rats, Sprague-Dawley; Vascular Diseases; Vitamin K; Warfarin

Prosthetic valve obstruction is caused by thrombi or fibrous tissue overgrowth, or both; thrombolysis avoids reoperation-related risks, but is effective only on clots. Hence, the study aims were to: (i) further assess our indication criteria for thrombolysis in prosthetic valve thrombosis; and (ii) evaluate treatment and follow up in a large patient population.. Between January 1991 and January 1994, 20 cases of prosthetic thrombosis were treated with thrombolysis using recombinant tissue type plasminogen activator (rt-PA). Indication criteria for thrombolysis were: (i) recent onset of symptoms; (ii) transesophageal echocardiographic (TEE) evidence of clots on the valve or cardiac chambers; and (iii) a partially preserved disc excursion. All patients were fitted with mechanical valves (four caged balls, 10 tilting discs, six bileaflets), with 17 valves located in the mitral and three in the aortic position. Symptoms of obstruction comprised cardiac failure in 11 cases and/or embolism in 10.. After rt-PA infusion, normal prosthetic function was restored in all patients, though one underwent successful reoperation five days later. During infusion, five patients had a transient ischemic attack and one a minor transient peripheral embolism. Recurrence of thrombosis occurred in three patients during follow up; subsequent thrombolysis was successful in two, without complication.. As treatment proved satisfactory, the reliability of our indicational criteria was confirmed. Only transient complications arose during treatment with recurrent thrombosis most common in those patients who had more thrombogenic valve prostheses.

Topics: Adult; Aged; Anticoagulants; Aortic Valve; Echocardiography, Doppler, Color; Evaluation Studies as Topic; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Prognosis; Thrombolytic Therapy; Thrombosis; Warfarin

We report here a case of primary antiphospholipid syndrome with all three clinical features with acute myocardial infarction. Echocardiography showed large vegetations at both mitral valve leaflets. Laboratory evaluation showed presence of antiphospholipid antibodies. High-intensity anticoagulation was begun, and repeat echocardiographic study in 4 months showed disappearance of the mitral valve vegetations.

Topics: Anticoagulants; Antiphospholipid Syndrome; Echocardiography; Echocardiography, Transesophageal; Electrocardiography; Female; Heart Valve Diseases; Humans; Middle Aged; Mitral Valve; Myocardial Infarction; Warfarin

We reviewed anticoagulant related hemorrhage (ACRH) and thromboembolism (TE) in 84 patients after valvular surgery. There were 45 females and 39 males with a mean age of 51.8 years (range 30.5-71.2 years), who underwent valvuloplasty in 14, bioprosthetic valve replacements in 17, mechanical valve replacements in 13. A mean period from the operation to the event were 2.7 years (range 0.01-12.3 years). There were 25 ACRH events after one valvuloplasty, 4 bioprosthetic valve replacements, 20 mechanical valve replacements. About half of them, the prothrombin time were less than 25%, which was considered the effect of warfarin is high, and 8% of them had infective endocarditis (IE) previously. There were 59 TE events after 13 valvuloplasties, 13 bioprosthetic valve replacements, 33 mechanical valve replacements. In the patients with atrial fibrillation, TE occurred irrespective of operative procedures. And in the patients with mechanical valve, severely impaired left ventricular function and past history of IE, thrombi of left ventricule were caused of TE. It was suggested that past history of IE was a risk factor ACRH and TE, and severely depressed left ventricular function and atrial fibrillation were for TE.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Thromboembolism; Warfarin

Topics: Anticoagulants; Cesarean Section; Developing Countries; Drug Administration Schedule; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Preoperative Care; Thrombosis; Warfarin

Between September 1986 and January 1994, 129 St. Jude Medical prostheses were implanted in 113 patients who were 18-year-old or younger at the Cardiovascular Surgery Clinic of Turkiye Yuksek Ihtisas Hospital. Thirty-seven patients underwent aortic, 60 patients mitral and the remaining 16 patients double valve replacement. Overall hospital mortality was 7.9% (9/113). All patients received 2.5 mg/day warfarin from the first postoperative day, in addition 225 mg/day dipyridamole and 100 mg/day aspirin was given following the removal of mediastinal tubes. This regimen was continued indefinitely thereafter. Follow up period ranged between 2-94 months. Total follow up experience was 276.4 patient-years. There were five late deaths; the cause of death was prosthetic valve thrombosis in two patients, intracerebral hemorrhage in one, cardiomyopathy in one, and sudden death in one. Other late complications included one endocarditis, a further anticoagulant related bleeding and one paravalvular leak. There was no case of cerebral or peripheral embolism reported. Seven-year actuarial survival was 92.4 +/- 6.8% for the entire group, 84.6 +/- 13.8% after mitral and 100% after aortic or double valve replacement. In conclusion, low dose oral anticoagulation after heart valve replacement with St. Jude Medical prosthesis in this age group showed satisfactory clinical results.

Topics: Adolescent; Anticoagulants; Aortic Valve; Aspirin; Dipyridamole; Drug Therapy, Combination; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Postoperative Period; Retrospective Studies; Warfarin

Transcranial Doppler sonography (TCD) has been used to detect microembolic signals in a variety of clinical situations. We studied the prevalence of TCD-detected microemboli in 38 acute stroke patients.. Consecutive patients with acute anterior circulation stroke were stratified into high-risk (group 1), medium-risk (group 2), and low-risk (group 3) groups based on their risk factors for cerebral embolism.. Microemboli were detected in 11% of patients. They were present in 17% of group 1, 10% of group 2, and 0% of group 3 patients. Emboli were present in patients with mechanical prosthetic valves, carotid stenosis (> 70%), and mitral valve strands with a patent foramen ovale. Patients with microemboli more frequently had a history of cerebral ischemia compared with patients without microemboli (P < .05). They also more frequently had recent (< 3 months) symptoms compared with patients without microemboli (P < .05). In patients with a cardiac source of embolization, the number of microemboli detected was directly proportional to the acuity of previous symptoms.. These data suggest that TCD-detected microemboli are associated with an increased prevalence of prior cerebrovascular ischemia. The presence of TCD-detected microemboli could be a risk factor for cerebrovascular ischemia.

Topics: Acute Disease; Aged; Atrial Fibrillation; Brain Ischemia; Carotid Stenosis; Cerebrovascular Disorders; Female; Fibrinolytic Agents; Heart Diseases; Heart Failure; Heart Septal Defects, Atrial; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Mitral Valve; Myocardial Infarction; Risk Factors; Thrombosis; Ultrasonography, Doppler, Transcranial; Warfarin

Several studies have demonstrated an association between mitral annular calcification and stroke; however, the pathophysiological explanation remains speculative.. We describe two patients with cerebral embolism in whom mitral valve calcification was demonstrated by transthoracic echocardiography. In both patients, transesophageal echocardiography identified a mass that appeared to be thrombus on the calcified portion of the mitral apparatus. There was no evidence of a hypercoagulable state or endocarditis in either case. Repeated transesophageal echocardiography after anticoagulation demonstrated resolution of the masses in both patients.. These cases support the hypothesis that thrombus formation may be a pathophysiological link between ischemic cerebral events and mitral annular calcification in some patients.

Topics: Aged; Brain Ischemia; Calcinosis; Cerebral Infarction; Cerebrovascular Disorders; Echocardiography; Echocardiography, Transesophageal; Female; Heart Valve Diseases; Humans; Intracranial Embolism and Thrombosis; Middle Aged; Mitral Valve; Thrombosis; Warfarin

In 12 patients with sinus rhythm (including 5 children and 6 young women), mitral valve replacement was performed with a microporous-surfaced valve similar to the Björk-Shiley Monostrut. After the first 3 months, permitting endothelialization of the suture ring to continue over the groove and adjacent metal valve ring, no long-term anticoagulant treatment was given. There was no thromboembolic complication in this group during follow-up for 6-8 years, during which four women gave birth to a total of seven children. In eight other cases, one mitral case with atrial fibrillation, anti-coagulant was not discontinued, and in the remaining aortic cases it was reinstituted. One of them (with atrial fibrillation) had hematuria during inadequate anticoagulant medication, but no thromboembolism. Of five patients with only aortic valve replacement, two had thromboembolic complications, one without residual symptoms and one with slight hand weakness. Another had a transient ischemic attack while on anticoagulant and acetylsalicylic acid was added. Two patients with aortic and mitral valve replacement died, one from heart tamponade and the other from venous thrombosis with pulmonary embolism.

Topics: Adolescent; Adult; Anticoagulants; Child; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Male; Mitral Valve; Pilot Projects; Postoperative Complications; Prosthesis Design; Thromboembolism; Treatment Outcome; Warfarin

We experienced two patients with a prosthetic heart valve, who underwent hepatic resection for hepatoma while on anticoagulation therapy. Patients with a prosthetic heart valve have the following characteristics; an increased risk of thromboembolism due to diminished anticoagulation in the perioperative period, a greater risk of endocarditis due to the artificial material in the heart, and impaired cardiopulmonary function including possible arrhythmia and heart failure. Furthermore, when such patients also have liver cirrhosis with a hepatoma, there is an increased risk of perioperative bleeding while on anticoagulation due to coagulopathy and also a risk of infection due to decreased cellular immunity. Patients with a prosthetic heart valve therefore require special care and attention whenever they have to undergo hepatic resection. With respect to anticoagulation, a minimal level is required to prevent bleeding and thromboembolism. Warfarin being administered preoperatively may be switched to heparin while closely monitoring the activated clotting time (biomaterial valve: 130-150 sec, non-biomaterial valve: 150-180 sec); the heparin should then be changed back to warfarin immediately after starting oral intake following operation. For the prevention of infection, a broad spectrum antibiotic should be used prophylactically both intra-operatively and postoperatively. The cardiopulmonary function must also be carefully monitored. For the assessment of postoperative liver function, lecithin: cholesterol acyltransferase, serum bilirubin and albumin are useful because there is no relevance of coagulation parameters such as prothrombin time under anticoagulation.

Topics: Carcinoma, Hepatocellular; Clinical Protocols; Combined Modality Therapy; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Hepatectomy; Humans; Liver Neoplasms; Male; Middle Aged; Mitral Valve; Postoperative Complications; Preoperative Care; Treatment Outcome; Tricuspid Valve; Warfarin

Coumadin, a long-acting antagonist of Vitamin K-dependent clotting factors, is commonly used for prevention of thromboembolism and potentially lethal clotting of mechanical heart valves. When patients require surgery for subsequent problems, inadequate perioperative management of coagulation may result in hemorrhage or thrombosis. Reversal with Vitamin K makes subsequent anticoagulation therapy difficult, and normalization of coagulation with fresh frozen plasma exposes the patient to the risk of fatal valvular thrombosis. In addition, third party payers and governmental reimbursement policies discourage most, if not all, preoperative hospitalization. Twenty-one patients on chronic Coumadin therapy required surgery for diseases unrelated to their original need for anticoagulation. Seven patients had hemorrhagic complications, and 14 did not. In these two groups, sex, current operation, reason for anticoagulation, other drugs, admitting CBC, and platelet count were similar. Preoperative hospital days averaged 5.2 days in both groups. Statistically significant differences were noted in age, preoperative Coumadin dose, admitting prothrombin times, and postoperative stays (P = 0.05). Although the perioperative prothrombin times, partial thromboplastin times, and perioperative heparin doses were similar, more patients in the bleeding group were operated with a prothrombin time > 13.0 seconds. The current evolved protocol is to discontinue Coumadin 5 days before surgery, and begin intravenous heparin @ 1000 u/hr with adjustment to keep partial thromboplastin times at therapeutic levels. Heparin is stopped early on the morning of surgery and restarted at 200-400 units/hr at 4 to 6 hours after surgery. Coumadin is restarted as soon as the patient can tolerate it. It is considered safe to operate only when the prothrombin time is less than 13 seconds.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Female; Heart Valve Diseases; Hemorrhage; Heparin; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Partial Thromboplastin Time; Patient Admission; Postoperative Complications; Preoperative Care; Prothrombin Time; Retrospective Studies; Surgical Procedures, Operative; Thromboembolism; Thrombosis; Warfarin

This is the report of a series of eight patients with pulmonary hypertension (primary and secondary) who delivered at the McMaster University Medical Centre between 1978 and 1987. Seven of the eight patients delivered vaginally and had a successful outcome. The eighth patient was admitted as an emergency and died shortly after Caesarean section under general anaesthesia, performed to save the infant. The other seven patients were all managed by a team, including anaesthetists, cardiologists and obstetricians, from about 25 wk. The patients were hospitalized pre-partum and received oxygen therapy and anticoagulation with heparin. Analgesia in labour was managed, once anticoagulation was reversed, by low concentrations of epidural bupivacaine (0.125%-0.375%) and fentanyl. The patients were monitored during labour and delivery with oximetry and arterial and central venous pressure lines. Pulmonary arterial lines were not used because of increased risk and questionable usefulness. Vaginal delivery was managed with vacuum extraction or forceps lift-out to minimize the stress of pushing. After delivery, all patients were monitored in an intensive care unit for several days, anticoagulation was restarted, and all patients were discharged home taking oral anticoagulant therapy. The successful management of pulmonary hypertension in pregnancy should include team management started early in pregnancy and controlled vaginal delivery utilizing epidural analgesia.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Delivery, Obstetric; Ductus Arteriosus, Patent; Eisenmenger Complex; Female; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Heart Valve Diseases; Heparin; Humans; Hypertension, Pulmonary; Mitral Valve; Monitoring, Physiologic; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Warfarin

Topics: Administration, Oral; American Heart Association; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Drug Interactions; Female; Heart Valve Diseases; Humans; Male; Myocardial Infarction; Pregnancy; Thromboembolism; Warfarin

An association exists between antiphospholipid antibodies and chorea. As these antibodies are associated with thrombosis, it has been suggested that cerebral infarction might cause chorea. However, CT and MRI typically do not demonstrate focal basal ganglionic lesions in such patients and an autoimmune mechanism for chorea has also been proposed. We report a young woman with left hemichorea and dyspnea. She was found to have lupus anticoagulant, large aortic and tricuspid vegetations, and pulmonary emboli. CT and MRI showed a small lesion in the head of the right caudate. In the presence of a definite cardiac source for emboli (valvular vegetations) with embolic activity (pulmonary emboli), it is likely that this patient's hemichorea was caused by cardioembolic caudate infarction.

Topics: Adult; Antiphospholipid Syndrome; Caudate Nucleus; Cerebral Infarction; Chorea; Female; Heart Valve Diseases; Heparin; Humans; Lupus Coagulation Inhibitor; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Warfarin

Cardiac valve replacement with use of only the Björk-Shiley prosthesis was performed in 1253 patients between January 1973 and December 1982. There were 828 patients having aortic valve replacement, 280 patients having mitral valve replacement, and 145 patients having double valve replacement with aortic and mitral valve prostheses. Patient outcome was stratified according to multiple variables, including valve position and valve model (spherical versus convexo-concave discs). No valve failure due to strut fracture was identified in 26 high-risk patients (mitral valve replacement with greater than or equal to 29 mm implanted in patients less than or equal to 50 years of age) followed up for a mean of 10 years postoperatively. Fifteen patients had late thrombosis of their Björk-Shiley prosthesis (0.28 per 100 patient-years), but there was no significant difference in risk of valve thrombosis comparing the spherical and convexo-concave discs (0.27 per 100 patient-years versus 0.27 per 100 patient-years). One hundred two patients had 128 thromboembolic episodes; rates of thromboembolism after aortic valve replacement, mitral valve replacement, and double valve replacement were 2.1, 4.3, and 4.6 per 100 patient-years, respectively. Percentages of patients free from thromboemboli after aortic valve replacement, mitral valve replacement, and double valve replacement were 93% +/- 1%, 86% +/- 2%, and 89% +/- 3% at 5 years postoperatively and 87% +/- 2%, 79% +/- 5%, and 77% +/- 8% 10 years postoperatively. There was no significant difference in the rates of thromboemboli for spherical and convexo-concave discs for all patients and for each of the subgroups. Ten-year actuarial survival estimates for patients dismissed alive from the hospital after aortic valve replacement, mitral valve replacement, and double valve replacement with the Björk-Shiley valve were 65% +/- 4%, 63% +/- 5%, and 55% +/- 8%, respectively. Overall event-free survival (freedom from death, thromboembolism, anticoagulant-related bleeding, endocarditis, and reoperation) was similar for the three patient groups. Performance of the Björk-Shiley valve as judged by late patient follow-up is similar to other mechanical valves, and modifications in disc design do not appear to have reduced the threat of late valve thrombosis and thromboemboli. Evidence does not support elective explantation of this prosthesis.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Aortic Valve; Endocarditis; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Mitral Valve; Prosthesis Design; Prosthesis Failure; Reoperation; Survival Rate; Thromboembolism; Thrombosis; Warfarin

Thrombotic obstruction of aortic bioprostheses is rare. Few cases have been reported involving the use of the Carpentier-Edwards (CE) prosthesis, the Hancock bioprosthesis, or the Medtronic Intact porcine valve. Thrombolytic therapy for mechanical valve thrombosis has been used frequently even though it is known to carry a high risk of embolism and recurrence. However, the use of this therapy was reported for the first time only recently, in a case of acute aortic thrombosis which occurred 3 1/2 months after bioprosthesis insertion. We report a case of late progressive thrombotic obstruction of a CE aortic valve 3 years after insertion. The case was successfully treated with coumadin therapy, as confirmed by serial Doppler echocardiographic examinations and a 3-year follow-up.

Topics: Aortic Valve; Bioprosthesis; Constriction, Pathologic; Echocardiography, Doppler; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Prosthesis Failure; Thrombosis; Warfarin

Topics: Aortic Valve; Arrhythmias, Cardiac; Aspirin; Digitalis; Echocardiography; Electrocardiography, Ambulatory; Heart Valve Diseases; Hemodynamics; Mitral Valve; Plants, Medicinal; Plants, Toxic; Warfarin

Heparin and warfarin sodium (Coumadin, Panwarfin, Sofarin) are used most often to treat acute and recurrent venous thromboembolic disease, arterial disease, valvular heart disease, and atrial fibrillation. These agents along with dextran, pneumatic compression devices, and gradient stockings are also used to prevent deep venous thrombosis and pulmonary embolism in patients at high risk (eg, those with venous stasis, lower limb or spinal cord trauma, clotting abnormalities). Anticoagulation therapy is monitored by maintaining the activated partial thromboplastin time and the prothrombin time in the therapeutic range.

Topics: Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Heparin; Humans; Postoperative Complications; Pulmonary Embolism; Recurrence; Risk Factors; Thrombophlebitis; Warfarin

to audit anticoagulant control and endocarditis prophylaxis following heart valve surgery.. retrospective review of all 190 patients living in Canterbury who had heart valve surgery between January 1981 and December 1986 to determine the incidence of endocarditis and complications of anticoagulation.. there were 35 late deaths, of which nine were attributed to thromboembolism (3), major bleeding (2), or endocarditis (4). The rate of thromboembolic events, and major bleeding was 4.6 and 3.3/100 patient years of warfarin therapy respectively, while the incidence of late endocarditis was 0.96/100 patient years. Two episodes of endocarditis occurred after minor dental procedures performed without antibiotic prophylaxis. Many dentists indicated that they would not have recommended prophylactic therapy for these procedures. Some patients had inadequate recall of important details of anticoagulant control or endocarditis prophylaxis. Only 24% knew their latest prothrombin ratio, yet a survey of general practitioners revealed that, in their view, the majority of patients may be capable of monitoring their own anticoagulant therapy.. the incidence of potentially preventable long term complications of heart valve surgery is comparable to other series. Nevertheless, these complications could be reduced by better patient education possibly enhanced by greater involvement of the patient in their anticoagulant control. The indications for antibiotic prophylaxis for dental procedures should be broadened for this group of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dental Care; Endocarditis, Bacterial; Evaluation Studies as Topic; Female; Follow-Up Studies; Heart Valve Diseases; Hemorrhage; Humans; Male; Medical Audit; Middle Aged; New Zealand; Patient Education as Topic; Postoperative Care; Postoperative Complications; Prothrombin Time; Retrospective Studies; Thromboembolism; Warfarin

The St. Jude Medical valve is a bileaflet prosthesis with excellent hemodynamic characteristics, but the long-term surgical experience with this valve, its durability, and its biocompatibility are unknown. During a 10-year period from March 1978 to 1988, 690 prostheses (290 aortic, 252 mitral, and 74 double aortic-mitral) were inserted as the initial valve replacement substitute in 616 patients (mean age 63 years). Coronary atherosclerosis was present in 58%. Follow-up totaled 2031 patient-years (mean 3.3 years) and was 95% complete (32 lost). Early (30-day) mortality rates were 5.2%, 11.9%, and 8.1% after aortic, mitral, and double valve replacement; 5- and 9-year actuarial survival rates were 71% +/- 3% and 51% +/- 8%, 59% +/- 4% and 41% +/- 6%, and 69% +/- 6% and 47% +/- 15%, respectively. Deaths were associated with extensive coronary atherosclerosis (p less than 0.001), older age (p less than 0.001), advanced preoperative New York Heart Association functional class (p less than 0.05), and malignant ventricular arrhythmias (p less than 0.05). No structural failures have been observed. Embolism (40 events) occurred at a rate of 2.0%/pt-yr (2.3% aortic, 1.6% mitral, 2.0% double). There were six cases of valve thrombosis (0.3%/pt-yr; one fatal). Hemorrhage was the most frequent complication (2.6%/pt-yr); 13 (25%) of 52 events were fatal, accounting for 62% of all valve-related deaths. After the target prothrombin time ratio was lowered, the rate of hemorrhage decreased by 44% (2.7% to 1.5%/pt-yr), while the combined rate of embolism and valve thrombosis increased slightly (2.2% to 2.5%/pt-yr, a 14% change). In summary, the St. Jude Medical valve remains a durable valve substitute. Survival was strongly related to the presence of associated coronary atherosclerosis. The most common complication has been hemorrhage; a less intensive warfarin regimen may reduce hemorrhagic risk while maintaining thromboembolic protection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aortic Valve; Child; Child, Preschool; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Reoperation; Risk Factors; Thromboembolism; Warfarin

The purpose of this study was to determine the criteria of valve selection from the long-term results of Hancock, Carpentier-Edwards, St Jude Medical and Bjork-Shiley prostheses, taking into special account the frequency of reoperation. Reoperations on the Hancock bioprosthesis were performed on six patients for tissue leaflet disruption with an incidence of 2.2 per cent/patient-year. Reoperations on the Carpentier-Edwards bioprosthesis were performed on 24 patients for tissue leaflet disruption in 23 patients and prosthetic valve endocarditis (PVE) in one, with an incidence of 3.8 per cent/patient-year. Reoperations on the Bjork-Shiley prosthesis were performed in two patients for severe hemolysis, with an incidence of 0.32 per cent/patient-year. Reoperations on the St Jude Medical prosthesis were performed on 3 patients, for valve thrombosis in one patient, PVE in one, and hemolysis in one, with an incidence of 0.23 per cent/patient-year. The overall mortality rate was 20 per cent, or 7 patients, and the indications for reoperation affected this. Patients with primary tissue failure had a mortality rate of 10.3 per cent; those with a thrombosed valve, 0 per cent; those with hemolysis, 66.7 per cent; and those with valve infection, 100 per cent. A good chance of survival may be achieved in patients facing prosthetic valve complications by performing reoperation as soon as possible after early detection, since mortality is high following emergency reoperation and in patients with severe symptoms. Currently, we recommend mechanical prostheses for valve replacement except in patients over 70 years old and in younger patients with absolute contraindications to anticoagulative therapy.

Topics: Aged; Aortic Valve; Bioprosthesis; Coronary Thrombosis; Evaluation Studies as Topic; Heart Valve Diseases; Heart Valve Prosthesis; Hemolysis; Humans; Mitral Valve; Prosthesis Failure; Reoperation; Time Factors; Tricuspid Valve; Warfarin

This article reports the methods and results of anticoagulant management in 653 patients with China-made Björk-Shiley mode Tilting Disc Cardiac Valve Prostheses. The total incidence of thromboembolic complications and valve thrombosis is 0.98 per 100 patient-years during the anticoagulation. The incidence of anticoagulant-related hemorrhage is 1.86 per 100 patient-years. In the anticoagulant period, 61 surgical operations were performed on 58 patients. The results showed that anticoagulant can be maintained in minor, superficial operations where blood ooze can be arrested by compression, temporarily discontinued in elective operations, and reversed abruptly by injecting Vitamin K1 in urgent operations. In addition we handled the contradictions between anticoagulant therapy and menses, contraceptive, pregnancy or delivery (29 patients) for 303 female patients favorably. We conclude that our methods gave excellent results, and were reasonable and practicable.

Topics: Adolescent; Adult; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Rheumatic Heart Disease; Thrombosis; Warfarin

In a routine clinic of patients taking regular oral anticoagulant therapy (warfarin, n = 140) 14% were found to have elevated levels (greater than 4 SD above normal) of anticardiolipin antibody (ACA) assessed by a well standardised enzyme linked immunosorbent assay (ELISA). There was a higher incidence of raised ACA in patients being treated for thrombotic episodes (9/47 = 19%) than in cases with heart valve replacements (8/75 = 11%). Furthermore, the highest ACA titres were in younger patients with thromboses scheduled for short-term anticoagulant treatment. Borderline DNA binding studies, together with some positive ANA results, suggested autoimmune etiology in the minority of these cases. Lupus anticoagulant was strongly detectable in only one such patient. The ACA were predominantly IgG (14/17) and did not appear to compromise the conditions of patients while on anticoagulant therapy. Raised ACA may be a highly significant marker for an acquired prothrombotic state.

Topics: Administration, Oral; Adult; Aged; Antibodies; Blood Coagulation Factors; Cardiolipins; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Thrombosis; Warfarin

104 patients who had prosthetic valve replacements were followed up for a period from 5 months to 63 months. The incidence of minor and major thromboembolism for aortic valve replacement was 1.2%/Pt.yr respectively, while the incidence for mitral valve replacement was 3.8%/Pt.yr. respectively. The haemorrhagic complication rate due to anticoagulation was 3.7%/Pt.yr. and the fatality rate due to it was 1.4%/Pt.yr. 75% of the patients who had haemorrhagic complications had a thrombotest of less than 4%. Anticoagulation related morbidity and mortality are significant in this series. Elimination of anticoagulation related complications could have improved the long term mortality rate from 2.95%/Pt.yr. to 1.4%/Pt.yr.

Topics: Adolescent; Adult; Aged; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Prosthesis Design; Thromboembolism; Warfarin

A 65-year-old female, presenting 32 weeks after mitral valve replacement with malaise and weight loss, was found to have a massive left atrial thrombus. She was treated successfully with streptokinase 1,000,000 units followed by anticoagulation with heparin then warfarin. The Doppler ultrasound recordings of left ventricular inflow were biphasic on admission but had resumed a normal appearance 11 days afterwards when clot retraction had occurred. We suggest that thrombolysis should be considered as alternative therapy in patients thought too frail for surgery.

Topics: Aged; Bioprosthesis; Drug Therapy, Combination; Echocardiography; Female; Heart Atria; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Postoperative Complications; Streptokinase; Thrombosis; Warfarin

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Anticoagulants; Bone Diseases; Female; Heart Valve Diseases; Hemorrhage; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Warfarin

Thirty children less than 18 years of age underwent cardiac valve replacement with a prosthetic valve between 1967 and 1984 and have been followed up for a mean of 6 years (range 1 to 17 years). Their mean age at the time of operation was 13 years (range 6 to 17 years). All patients were begun on a regimen of warfarin before hospital discharge. One major and four minor bleeding episodes occurred in 211 patient-years of warfarin therapy, an incidence of 2.3 per 100 patient-years. Three of those five episodes occurred in patients who were receiving excessively anticoagulation or who were participating in physical activities inappropriate for a patient on warfarin therapy. Thus, the majority of the bleeding episodes were preventable. There were five thromboembolic events in 211 patient-years, an incidence of 2.3 per 100 patient-years. Three of those five patients had intentionally stopped their warfarin therapy. The majority of thromboembolic episodes, like the bleeding episodes, were preventable. Eight teenage patients were noncompliant with the warfarin therapy. More than one third of that group experienced a thromboembolic event, an incidence of 5.5 per 100 patient-years (55 patient-years). Twenty-two patients adhered to the warfarin regimen and only two (9%) of them had a thromboembolic event, an incidence of 1.3 per 100 patient-years (156 patient-years). Warfarin therapy presented no greater risk of serious bleeding to this pediatric age group than it does to an adult age group. The incidence of thromboembolism among these patients was less than that which is generally reported for adult patients. Discontinuation of or noncompliance with warfarin therapy substantially increased the risk of thromboembolism. Continuous warfarin therapy is recommended for every child after prosthetic valve replacement.

Topics: Adolescent; Child; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Patient Compliance; Risk; Thromboembolism; Warfarin

Between January 1980 and April 1986, 204 patients were hospital survivors after aortic, mitral, or double valve replacement with the St. Jude Medical valve. One hundred ninety patients underwent anticoagulation with modest doses of warfarin (Coumadin), with prothrombin times in the range of 1.3 to 1.5 times control. Fourteen patients received aspirin and dipyridamole only. Follow-up ranged from 0.5 to 6.6 years (mean 3.1) and was 99.5% complete. The group was analyzed for occurrence of thromboembolism, hemorrhage, valve thrombosis, endocarditis, perivalvular leak, valve failure, late cardiac death, and all morbidity and mortality combined in linear and actuarial terms over the 7 year period. With this anticoagulation regimen, the linear rate for thromboembolism and hemorrhage was 0.67% and 1.3% patient-year, respectively, and the actuarial event-free incidence at 5 years was 97.4% and 94.4%, respectively. There were no instances of structural valve failure and one instance of valve thrombosis in the mitral position. Eighty-seven percent of patients were alive at 5 years and 76.7% of patients were alive and free of all complications at 5 years. We conclude that the St. Jude Medical valve has a low incidence of thromboembolism, hemorrhagic complications, and valve thrombosis in patients receiving modest doses of warfarin.

Topics: Actuarial Analysis; Adult; Aged; Aortic Valve; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Prosthesis Design; Thromboembolism; Time Factors; Warfarin

Topics: Aspirin; Dipyridamole; Heart Valve Diseases; Humans; Patient Education as Topic; Warfarin

Topics: Anticoagulants; Aortic Valve; Aspirin; Atrial Fibrillation; Bioprosthesis; Dipyridamole; Drug Therapy, Combination; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Mitral Valve; Platelet Aggregation; Postoperative Complications; Thromboembolism; Warfarin

Clinical information on the Medtronic-Hall valve prosthesis was obtained by reviewing the records of 379 patients, 164 of whom had aortic valve replacement (AVR), 163 of whom had mitral valve replacement (MVR), and 52 of whom had double valve replacement over 90 months (1,225 patient-years) (mean follow-up, 42.01 +/- 1.3 months [+/- standard error]). Mean age was 53.8 +/- 12 years. One hundred ninety-three patients (50.9%) had some type of concomitant operation, such as tricuspid annuloplasty, coronary artery bypass grafting, or resection of ascending aortic aneurysm. Ninety-one percent were in New York Heart Association (NYHA) Functional Class III or IV preoperatively. Early mortality and late mortality were 7.7% (29 patients) and 13.5% (51 patients), respectively. The actuarial survival at 7 1/2 years was 74.1 +/- 2.7% for the total group and 69.0 +/- 4.5% for those having AVR, 81.0 +/- 3.2% for those having MVR, and 67.0 +/- 8.9% for those having double valve replacement. All patients but 2 were maintained on a regimen of chronic anticoagulation with warfarin sodium. Twenty-six thromboembolic episodes occurred (2.1/100 patient-years): 13 after MVR (2.3/100 patient-years), 11 after AVR (2.1/100 patient-years), and 2 after double valve replacement (1.4/100 patient-years). Four thromboembolic episodes were fatal; no valve thrombosis occurred. There were no structural failures. Of the 350 late survivors, 92% were in NYHA Functional Classes I and II. Total valve-related complications have been minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aortic Valve; Cardiopulmonary Bypass; Evaluation Studies as Topic; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Hypothermia, Induced; Male; Middle Aged; Mitral Valve; Postoperative Complications; Prosthesis Design; Prosthesis Failure; Thromboembolism; Tricuspid Valve; Warfarin

Topics: Adult; Anticoagulants; Blood Coagulation; Dipyridamole; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Platelet Aggregation; Postoperative Complications; Thiophenes; Thrombosis; Ticlopidine; Warfarin

To evaluate the clinical performance of the St Jude Medical bileaflet heart valve prosthesis, we followed 150 consecutive patients (95 male and 55 female patients, mean age 54 years, range 1 to 74 years) for an average of 24 months. These included 74 patients with aortic, 56 patients with mitral, and 20 patients with multiple valve replacement. During the 2 year follow-up, there were a total of four perioperative and seven late deaths, two of which were prosthesis related. Reoperation was necessary in four patients, because of paravalvular leaks in two patients with mitral and one patient with aortic prostheses and because of leaflet dislodgment in one patient with a mitral prosthesis, a postoperative complication that has not been reported previously. The thromboembolic rate per 100 patient-years was 2.6 in aortic and 2.9 in mitral valve replacement, the symptoms being reversible in all patients. All patients were receiving anticoagulant therapy. A total of four complications of anticoagulant therapy (three minor and one fatal) were observed. Significant hemolysis was observed in none of the patients. In patients with dyspnea, the New York Heart Association functional classification was 2.7 +/- 0.8 preoperatively versus 1.3 +/- 0.6 postoperatively. In patients with angina, it was 2.6 +/- 0.6 preoperatively versus 1.03 +/- 0.2 postoperatively. Noninvasive Doppler measurements revealed excellent flow characteristics, values being close to those obtained in natural valves (mean +/- standard deviation of maximal flow velocity: 1.5 +/- 0.5 versus 0.9 +/- 0.1 m/sec in the aortic position; 1.1 +/- 0.3 versus 0.8 +/- 0.3 m/sec in the mitral position).

Topics: Adolescent; Adult; Aged; Aortic Valve; Blood Flow Velocity; Child; Child, Preschool; Evaluation Studies as Topic; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemolysis; Humans; Infant; Male; Middle Aged; Mitral Valve; Reoperation; Thromboembolism; Warfarin

Antithrombotic medication is effective in the prevention of thromboembolic complications after valve replacement. Therapy with oral anticoagulant (warfarin), platelet inhibitor drugs and long-term warfarin administration an have good clinical results. However, thrombosis may occur in the early postoperative period, when the oral administration of warfarin is impossible. We have evaluated treatment with urokinase, low-dose heparin and dipyridamole, administered intravenously, instead of warfarin, during the early postoperative period. This procedure was carried out in 30 patients, among whom there was no evidence of thrombosis or of such side-effects as bleeding or a marked tendency to bleed.

Topics: Aortic Valve; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Mitral Valve; Postoperative Complications; Thromboembolism; Tricuspid Valve; Urokinase-Type Plasminogen Activator; Warfarin

A 5 year experience with the bileaflet St. Jude Medical valve is reported. Between March, 1978, and June, 1982, 198 patients received 233 such valves (90 mitral, 73 aortic, and 35 double mitral-aortic valve replacements). Total follow-up was 4,896 patient-months; survivors were followed up for 1 to 5 years (mean 35 months). Early (30 day) mortality was 6.6% overall and 11.1% after mitral, 2.7% after aortic, and 2.9% after double valve replacement. Total late mortality was 15.2%; the actuarial survival rate at 4 years was 67% after mitral, 79% after aortic, and 79% after double valve replacement. Ischemic mitral valve disease was associated with an early mortality of 26.7% and a 4 year survival rate of 34%; without this high-risk subset, early mortality was 3.3% and the 4 year survival rate was 77% after mitral valve replacement. A multivariate logistic regression model identified three preoperative patient characteristics associated with increased postoperative mortality: ischemic mitral valve disease (p less than 0.001), a depressed left ventricular ejection fraction (less than 55%; p less than 0.05), and advanced New York Heart Association class (IV; p less than 0.05). Valve-related complications occurred in 14 patients (3.4% per patient-year). There were no instances of primary structural failure or hemolysis. Thromboembolism (nine patients, 2.2% per patient-year) occurred more frequently after double (3.7% per patient-year) or mitral valve replacement (2.3% per patient-year) than after aortic valve replacement (1.3% per patient-year) and more frequently in 12 patients receiving aspirin and dipyridamole (6.5% per patient-year) than in 173 patients receiving warfarin (1.9% per patient-year). No thromboembolic event was fatal. Reoperation was necessary because of one valve thrombosis, one valve erosion, and two perivalvular leaks due to endocarditis; three of the four patients survived reoperation (one valve-related death, 0.5%). Of 154 patients alive at latest follow-up, 85% were in New York Heart Association Class I or II, and 90% had improved by at least one class. This intermediate experience with the St. Jude Medical valve indicates that, in addition to its previously demonstrated excellent hemodynamic performance, there have been no instances of primary structural failure or hemolysis. Warfarin anticoagulation is recommended in all patients.

Topics: Adolescent; Adult; Aged; Aortic Valve; Child; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Reoperation; Thromboembolism; Tricuspid Valve; Warfarin

The influence of cefamandole and vancomycin used for prophylaxis on the warfarin anticoagulation response in 60 cardiac valve replacement patients during the postoperative period is presented. Patients were divided into two groups, hyper-responders prothrombin time (PT) greater than or equal to 32 sec, 48 hr after the initial warfarin dose (GrIHR), or normal responders PT less than 32 sec (GrIINR). Fifteen patients (25%) were in GrIHR (PT 44.3 +/- 10.5) and 45 in GrIINR (21 +/- 5). Fourteen of the 15 GrIHR patients received cefamandole and 1 of the 15 GrIHR patients received vancomycin p less than 0.05, as prophylaxis. Warfarin sensitivity was assessed using a warfarin dose index (WDI) calculated in the initial postoperative period (WDIINT) and at discharge (WDIDIS). GrIHR patients had greater WDIINT and WDIDIS compared to GrIINR p less than 0.001. Baseline prothrombin time measured 8 hours prior to start of warfarin therapy (PTBL), was linearly correlated to the WDIINT with r = 0.8, p less than 0.001 in cefamandole patients only. The data suggests that cefamandole increases warfarin sensitivity early in the postoperative course of oral anticoagulation therapy, which may lead to excessively high prothrombin times with the possibility for serious bleeding.

Topics: Blood Coagulation; Cefamandole; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Hypoprothrombinemias; Male; Postoperative Complications; Postoperative Period; Premedication; Retrospective Studies; Surgical Wound Infection; Thromboembolism; Vancomycin; Warfarin

A total of 479 valve replacements were performed in 469 patients for aortic, mitral, and tricuspid disease. A total of 529 valves were implanted (311 Carpentier-Edwards, 118 Hancock, 94 Björk-Shiley, and six other mechanical valves). Of the 479 operations, 51.1% (245) were carried out in male patients and 48.9% (234) were carried out in female patients. The mean age was 57.6 years; however, 28.6% (137) of the operations were performed in patients over 65 years of age. One hundred five patients (21.9%) had had previous cardiac operations of one type or another. Follow-up was 99.6% and the average length of follow-up was 36.2 months. The overall operative mortality was 5.6%. The operative mortality in the isolated aortic valve replacement group was 2.0% and that in the mitral valve replacement group, 4.4%. There was a 5.9% valve explant rate in the Hancock series; however, no valve explants were required because of valve dysfunction in either the Carpentier-Edwards or the Björk-Shiley groups. The thromboembolic rate in the aortic valve position was 2.4, 1.1, and 2.1 emboli per 100 patient-years in the Hancock, Carpentier-Edwards, and Björk-Shiley groups, respectively. The thromboembolic rate in the mitral valve position was 2.8, 2.2, and 1.0 emboli per 100 patient-years in the Hancock, Carpentier-Edwards, and Björk-Shiley groups, respectively.

Topics: Aged; Aortic Valve; Bioprosthesis; Endocarditis, Bacterial; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Reoperation; Sex Factors; Thromboembolism; Time Factors; Tricuspid Valve; Warfarin

Twenty-four children (ages 1 to 18 years, mean 12.2 years) underwent 27 operations for aortic, mitral, or combined aortic and mitral valve replacement. There was 1 operative death. Of the 23 operative survivors (12 aortic, 8 mitral, 3 combined valve replacement), only 5 were given warfarin for long-term anticoagulation. The remaining 18 (10 aortic, 8 mitral valve replacement) were given aspirin (plus dipyridamole in 5). Twelve of the 18 had at least one mechanical valve (11 Björk-Shiley and Beall valves; 1 Björk-Shiley valve was replaced with a Beall disc valve as the child grew). These 18 patients were followed for 1 to 59 months (mean, 20.4 months). There was no thrombotic, embolic, or bleeding complications. There were 2 late deaths (one cardiac). Review of the available literature indicates that in children with prosthetic cardiac valves, aspirin (with or without dipyridamole) provides adequate protection against thromboemboli and avoids the hemorrhagic complications associated with warfarin.

Topics: Adolescent; Anticoagulants; Aortic Valve; Aspirin; Bioprosthesis; Child; Child, Preschool; Dicumarol; Dipyridamole; Drug Therapy, Combination; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Infant; Mitral Valve; Postoperative Complications; Retrospective Studies; Thromboembolism; Warfarin

Topics: Adult; Aged; Anticoagulants; Coronary Disease; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Prothrombin Time; Thromboembolism; Thrombosis; Warfarin

Topics: Adolescent; Adult; Aortic Valve; Evaluation Studies as Topic; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Thrombosis; Warfarin

Topics: Adult; Danazol; Drug Interactions; Endometriosis; Female; Heart Valve Diseases; Hematemesis; Humans; Pregnadienes; Prothrombin Time; Warfarin

A retrospective analysis of 40 patients with cardiac disease who received sodium warfarin (Coumadin) therapy during pregnancy has been performed. The fetal mortality was 12,5%, but no case of congenital epiphyseal stippling was detected. The incidence of maternal postpartum haemorrhage was high. Warfarin should whenever possible be withheld during the 1st trimester of pregnancy and replaced by heparin.

Topics: Abnormalities, Drug-Induced; Adult; Female; Fetal Death; Fetus; Heart Valve Diseases; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Retrospective Studies; Rheumatic Heart Disease; Warfarin

Topics: Adult; Aged; Anticoagulants; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Prothrombin Time; Time Factors; Warfarin

The case history is presented of a woman aged 38 who received warfarin treatment because of a mitral valve replacement. During the first trimester of pregnancy, her prothrombin time was 20% of normal and kept at 40% until the 38th week of gestation. Then the patient received heparin until a few days after delivery of a normal child.

Topics: Adult; Female; Heart Valve Diseases; Humans; Infant, Newborn; Mitral Valve; Pregnancy; Pregnancy Complications, Cardiovascular; Prothrombin Time; Warfarin

Topics: Adult; Anticoagulants; Blood Coagulation; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Indoprofen; Male; Middle Aged; Phenylpropionates; Platelet Aggregation; Postoperative Complications; Thrombosis; Warfarin

Eight patients have had thrombotic obstruction of a prosthetic valve since 1971, six mitral valves and two aortic. All eight patients had a Björk-Shiley valve. During the same period 159 Björk-Shiley valves were placed, 85 in the mitral and 74 in the aortic area. This represents a valve thrombotic occlusive incidence of 4.4 percent in our series, 5.9 percent of mitral and 2.7 percent of aortic prostheses. Among the six patients with mitral prostheses only one survived. The two patients with occluded aortic valves survived. The onset of symptoms was very abrupt in most patients and progressed very rapidly. Acute pulmonary edema was observed in five patients. Anticoagulation was considered inadequate in all patients. Aspirin or dipyridamole was being used in seven patients at the time of thrombosis. The data indicate a high frequency of thrombotic occlusion of Björk-Shiley valves in the absence of full anticoagulation with warfarin derivatives and emphasizes the urgent need for surgery once valve thrombosis is suspected.

Topics: Acute Disease; Adult; Aortic Valve; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Pulmonary Edema; Thrombosis; Warfarin

In 34 patients undergoing anticoagulant therapy with warfarin a close relationship has been observed between the logarithm of the 'Thrombotest' response to a loading dose (10 mg/day for three days) and the maintenance dose required to achieve an anticoagulant response of 8-12% (thrombo-test). This relationship appears to be close enough to enable maintenance dosages to be predicted.

Topics: Administration, Oral; Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Dose-Response Relationship, Drug; Female; Heart Valve Diseases; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mitral Valve; Thrombophlebitis; Thrombosis; Warfarin

Nineteen cardiac patients were given warfarin sodium to prevent thrombosis and embolism. Empirical dosage resulted in long hospital stays to obtain a stable therapeutic prothrombin time. Using a dosage of 0 therefore 5-0 therefore 7 mg/kg, therapeutic levels were achieved in a much shorter time. When prothrombin time was excessive, it was successfully reduced with vitamin K or plasma. A haematoma in one case and haematuria in another were easily controlled. Warfarin sodium appears to be appropriate and effective for children requiring anticoagulants within the above dosage limits and with meticulous follow-up.

Topics: Administration, Oral; Adolescent; Child; Female; Heart Valve Diseases; Humans; Male; Postoperative Complications; Prothrombin Time; Thromboembolism; Warfarin

Advanced actuarial techniques are used to analyze late results in 912 patients who had isolated mitral or aortic valve replacement with ball valve prostheses from 1965 to 1974. Experience with noncloth-covered and cloth-covered valves is compared in terms of late survival, rate of thromboembolic complications and reoperation and the influence of anticoagulation. The cloth-covered prostheses have substantially reduced the incidence of emboli after mitral valve replacement (1.9 vs. 6 emboli per 100 patient years) and have thus far eliminated emboli after aortic valve replacement in patients receiving warfarin. Patients with a cloth-covered aortic valve who did not receive warfarin had nine emboli per 100 patient years. The safety of cloth-covered valves is clearly enhanced by warfarin therapy; the efficacy of anti-platelet drugs is still uncertain. Strut cloth wear was found at reoperation in 10 patients. This should be prevented in the new model 2400 composite strut ("track") valve by a narrow metal track on the inner surface of each strut. The substantial recent reductions in operative mortality and in prosthesis-related complications pose important questions regarding timing of operations and selection of prostheses. These decisions must be individualized for each patient on the basis of a thorough analysis of late results using modern statistical methods.

Topics: Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Evaluation Studies as Topic; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemolysis; Humans; Male; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Stenosis; Polyethylene Terephthalates; Polypropylenes; Polytetrafluoroethylene; Prosthesis Design; Risk; Stress, Mechanical; Thromboembolism; Time Factors; Warfarin

Porcine aortic valve xenografts stabilized with glutaraldehyde have been implanted in 91 patients with acquired and congenital valvular heart disease. The indications for use of this valve have included age, previous sensitivity to anticoagulants, or a concomitant condition contraindicating anticoagulant therapy. There were two operative deaths and three late deaths in 44 mitral, 25 aortic, 16 aortic-mitral, 5 mitral-tricuspid, and one aortic-mitral-tricuspid replacements. There were no valve failures from cusp rupture, although one valve was replaced because of annular disproportion. There was one inhospital stroke but no late emboli in a 3 to 33 month followup period, 16.5; 72 patients are functional class 1, 10 class 2, and one patient is class 3. In appropriate patients this biologic tissue valve relieves the hemodynamic abnormalities of valvular heart disease, is associated with a low embolization rate without anticoagulant therapy and, to date, has been durable.

Topics: Adolescent; Adult; Aged; Animals; Aortic Valve; Boston; Child; Child, Preschool; Female; Glutaral; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve Stenosis; Swine; Transplantation, Heterologous; Warfarin

The activated partial thromboplastin time is compared with the corresponding prothrombin ratio in 6378 samples of platelet-poor plasma from 446 patients treated for a total of more than 4500 patient/months with oral anticoagulatnts. A relative decrease in the activated partial thromboplastin time following deep vein thrombosis is described, which tends to become less obvious during the first year of treatment and is greater in older patients. Although this relative decrease is also found in patients treated after cerebrovascular accidents, it is not found in patients treated after myocardial infarction or in patients with mitral valve disease treated prophylactically with long-term oral anticoagulants. It is though possible that these changes following deep vein thrombosis might be useful in helping to determine the duration of oral anticoagulant treatment.

Topics: Adult; Blood Coagulation; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Myocardial Infarction; Phenindione; Prothrombin Time; Thrombophlebitis; Thromboplastin; Warfarin

Twenty-one patients with prosthetic cardiac valves successfully underwent transurethral prostatic resection at the Mayo Clinic. Temperature elevation in 4 patients was the only postoperative complication; in particular, neither congestive heart failure nor thromboembolic complications developed and there were no operative deaths. Preoperative evaluation and clinical management of potential complications are based on the recognition of the complications that are peculiar to these patients. Particularly important is the proper use of antibiotics and anticoagulants and avoidance of overloading the circulation with fluid from open prostatic venous sinuses.

Topics: Aged; Aortic Valve; Endocarditis, Bacterial; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Preoperative Care; Prostatectomy; Sodium; Thromboembolism; Urethra; Vitamin K 1; Warfarin

Topics: Adenosine Diphosphate; Aortic Valve; Blood Platelets; Cell Survival; Chromium Radioisotopes; Collagen; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valves; Humans; Mitral Valve; Platelet Adhesiveness; Postoperative Complications; Prognosis; Prosthesis Design; Sulfinpyrazone; Thromboembolism; Time Factors; Transplantation, Homologous; Warfarin

Topics: Angina Pectoris; Anticoagulants; Aspirin; Dicumarol; Disseminated Intravascular Coagulation; Electric Countershock; Heart Valve Diseases; Humans; Myocardial Infarction; Pulmonary Embolism; Thrombophlebitis; Thrombosis; Warfarin

Topics: Adolescent; Adult; Aortic Valve Insufficiency; Atrial Fibrillation; Cerebral Hemorrhage; Child; Death, Sudden; Endocarditis, Bacterial; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Myocardial Infarction; Postoperative Complications; Thromboembolism; Tricuspid Valve Insufficiency; Warfarin

Topics: Anticoagulants; Aortic Valve; Aspirin; Cerebral Hemorrhage; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Mitral Valve; Prosthesis Design; Thromboembolism; Tricuspid Valve; Warfarin

Topics: Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Mitral Valve; Thromboembolism; Warfarin

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Tests; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Myocardial Infarction; Phenindione; Prothrombin Time; Pulmonary Embolism; Thrombophlebitis; Thromboplastin; Warfarin

Topics: Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; New York City; Postoperative Complications; Prothrombin Time; Thromboembolism; Warfarin

Topics: Anticoagulants; Coronary Disease; Dicumarol; Heart Defects, Congenital; Heart Valve Diseases; Intracranial Arteriosclerosis; Phlebitis; Pulmonary Emphysema; Thromboembolism; Toxicology; Vascular Diseases; Warfarin

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiac Surgical Procedures; Digoxin; Endocarditis; Endocarditis, Bacterial; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Heart, Artificial; Humans; Isoproterenol; Methicillin; Middle Aged; Postoperative Complications; Psychoses, Substance-Induced; Psychotic Disorders; Thoracic Surgery; Warfarin

Topics: Anesthesia; Anesthesia, Inhalation; Aortic Valve; Cardiac Surgical Procedures; Cyclopropanes; Heart Valve Diseases; Humans; Nitrous Oxide; Pathology; Postoperative Complications; Prostheses and Implants; Protamines; Thoracic Surgery; Thromboembolism; Thrombosis; Warfarin