warfarin and Heart-Defects--Congenital

Patients with a Fontan circulation for single-ventricle physiology are at increased risk of developing thromboembolic events. Thromboembolic events can lead to failure of the Fontan circulation, chronic sequelae in case of stroke, and early mortality. Controversies exist regarding the substrates, risk factors, and optimal detection methods for thromboembolic events. Despite the major clinical implications, there is currently no consensus regarding the optimal antithrombotic therapy to prevent or treat thromboembolic events after the Fontan procedure. In this review we aimed to untangle the available literature regarding antithrombotic prophylaxis and treatment for pediatric and adult Fontan patients. A decision-tree algorithm for thromboprophylaxis in Fontan patients is proposed. Additionally, the current state of knowledge is reviewed with respect to the epidemiology, pathophysiology, and detection of thromboembolic events in Fontan patients, and important evidence gaps are highlighted.

Topics: Adult; Anticoagulants; Child; Fontan Procedure; Heart Defects, Congenital; Humans; Stroke; Venous Thromboembolism; Warfarin

The Fontan procedure has transformed the lives of children born with single-ventricle physiology, previously deemed inoperable. Worldwide, there are an increasing number of children with Fontan circulation, with the potential for survival into adulthood. Due to the abnormal circulation, Fontan patients have an increased risk of thromboembolic (TE) events, with up to 25% of events leading to death. Despite the importance of preventing TE events in this patient population, there is currently no clinical consensus on the optimal monitoring, thromboprophylaxis therapies, and treatment of these events. This paper reviews the available literature regarding anticoagulation in the pediatric and adult Fontan population, including the mechanisms for thrombosis and current antithrombotic therapies.

Topics: Anticoagulants; Aspirin; Fibrinolytic Agents; Fontan Procedure; Heart Defects, Congenital; Humans; Thromboembolism; Thrombolytic Therapy; Thrombosis; Warfarin

This report reviews the current status of antithrombotic therapy, including anti-platelet therapy, in pediatric patients with congenital heart disease. The current medications utilized and dose recommendations are emphasized, and indications for their use are reviewed.

Topics: Anticoagulants; Child; Dipyridamole; Fontan Procedure; Heart Defects, Congenital; Heart Valve Prosthesis; Heparin; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Thrombosis; Warfarin

Warfarin dosing is challenging due to a multitude of factors affecting its pharmacokinetics (PK) and pharmacodynamics (PD). A novel personalised dosing algorithm predicated on a warfarin PK/PD model and incorporating CYP2C9 and VKORC1 genotype information has been developed for children. The present prospective, observational study aimed to compare the model with conventional weight-based dosing. The study involved two groups of children post-cardiac surgery: Group 1 were warfarin naïve, in whom loading and maintenance doses were estimated using the model over a 6-month duration and compared to historical case-matched controls. Group 2 were already established on maintenance therapy and randomised into a crossover study comparing the model with conventional maintenance dosing, over a 12-month period. Five patients enrolled in Group 1. Compared to the control group, the median time to achieve the first therapeutic INR was longer (5 vs. 2 days), to stable anticoagulation was shorter (29.0 vs. 96.5 days), to over-anticoagulation was longer (15.0 vs. 4.0 days). In addition, median percentage of INRs within the target range (%ITR) and percentage of time in therapeutic range (%TTR) was higher; 70% versus 47.4% and 83.4% versus 62.3%, respectively. Group 2 included 26 patients. No significant differences in INR control were found between model and conventional dosing phases; mean %ITR was 68.82% versus 67.9% (p = 0.84) and mean %TTR was 85.47% versus 80.2% (p = 0.09), respectively. The results suggest model-based dosing can improve anticoagulation control, particularly when initiating and stabilising warfarin dosing. Larger studies are needed to confirm these findings.

Topics: Adolescent; Anticoagulants; Blood Coagulation; Cardiac Surgical Procedures; Child; Child, Preschool; Cross-Over Studies; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; International Normalized Ratio; Male; Postoperative Period; Prospective Studies; Vitamin K Epoxide Reductases; Warfarin

Providing education to patients requiring anticoagulant therapy may be associated with improved outcomes. This study investigated the knowledge outcomes of a validated educational intervention.. Parents of children with congenital heart disease requiring warfarin therapy took part in an educational intervention. Warfarin knowledge was assessed prior to commencing the program, immediately following its completion and 6 months following completion.. Parents demonstrated a statistically significant improvement in their warfarin knowledge immediately following completion of the program (p < 0.0001), with this improvement being sustained over time.. Current approaches to educating parents of children requiring warfarin therapy are likely suboptimal. Using a validated model of education may be associated with improved knowledge outcomes for patients.. Consideration to the processes used in delivering patient education may result in improved patient knowledge outcomes.

Topics: Adolescent; Adult; Anticoagulants; Child; Female; Health Education; Health Knowledge, Attitudes, Practice; Heart Defects, Congenital; Humans; Male; Models, Educational; Parents; Victoria; Warfarin

The lack of oral anticoagulant guidelines specific to paediatric practice has led to the adoption of adult regimens, often without scientific evidence of efficacy or safety. A two year prospective study of anticoagulant control was carried out in 45 children aged 9 months to 18 years, the majority of whom were receiving primary prophylactic anticoagulation. The main indication was congenital heart disease, either with (n = 8) or without (n = 34) mechanical valve prosthesis. During a follow up period of 602 patient months the average interval between visits was three weeks. Target international normalised ratios (INRs) were achieved on 62% and 39% of visits for children with low target INR (2.0-3.0) and high target INR (3.0-4.0) respectively. However warfarin dose was altered on only 22% of visits. Warfarin doses required to achieve a stable INR of 2.0-3.0 in 33 children were strongly correlated with weight [dose (mg/d) = 0.07 x weight (kg) + 0.54] but independently influenced by age. No thrombotic complications were recorded, and haemorrhagic events were infrequent (2.1% of visits) and, with one exception, minor. Safe outpatient oral anticoagulation is feasible in children, whose warfarin requirements appear moderately predictable and whose control is no more erratic than that of adults.

Topics: Adolescent; Aged; Aged, 80 and over; Anticoagulants; Body Weight; Child; Child, Preschool; Drug Administration Schedule; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Valve Prosthesis; Humans; Infant; Male; Middle Aged; Prospective Studies; Thromboembolism; Warfarin

Topics: Adolescent; Adult; Angiocardiography; Blood Circulation; Child; Child, Preschool; Clinical Trials as Topic; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infant; Male; Pulmonary Artery; Pulmonary Valve Stenosis; Radiography, Thoracic; Tolazoline; Warfarin

COVID-19 and Fontan physiology have each been associated with an elevated risk of venous thromboembolism (VTE), however little is known about the risks and potential consequences of having both.. A 51 year old male with tricuspid atresia status post Fontan and extracardiac Glenn shunt, atrial flutter, and sinus sick syndrome presented with phlegmasia cerulea dolens (PCD) of the left lower extremity in spite of supratherapeutic INR in the context of symptomatic COVID-10 pneumonia. He was treated with single session, catheter directed mechanical thrombectomy that was well-tolerated.. This report of acute PCD despite therapeutic anticoagulation with a Vitamin K antagonist, managed with emergent mechanical thrombectomy, calls to attention the importance of altered flow dynamics in COVID positive patients with Fontan circulation that may compound these independent risk factors for developing deep venous thrombosis with the potential for even higher morbidity.

Topics: Amputation, Surgical; Atrial Flutter; COVID-19; Fontan Procedure; Gangrene; Heart Defects, Congenital; Humans; Image Processing, Computer-Assisted; Lower Extremity; Male; Mechanical Thrombolysis; Middle Aged; Phlebography; Postoperative Complications; Sick Sinus Syndrome; Thrombophlebitis; Tomography, X-Ray Computed; Treatment Outcome; Tricuspid Atresia; Warfarin

Because of the nature of the Fontan physiology, patients are at an increased risk of thromboembolic complications. As such, warfarin or aspirin is generally prescribed lifelong for thromboprophylaxis. This study aimed to compare long-term rates of cerebrovascular injury, thrombosis, bleeding, bone mineral density, and quality of life in people living with Fontan circulation receiving warfarin compared with aspirin.. This was a multicenter study of a selected cohort from the Australia and New Zealand Fontan population. Participants underwent cerebral magnetic resonance imaging to detect the presence of cerebrovascular injury (n = 84) and dual-energy X-ray absorptiometry to assess bone mineral density (n = 120). Bleeding (n = 100) and quality of life (n = 90) were assessed using validated questionnaires: Warfarin and Aspirin Bleeding assessment tool and Pediatric Quality of Life Inventory, respectively.. Stroke was detected in 33 participants (39%), with only 7 (6%) being clinically symptomatic. There was no association between stroke and Fontan type or thromboprophylaxis type. Microhemorrhage and white matter injury were detected in most participants (96% and 86%, respectively), regardless of thromboprophylaxis type. Bleeding rates were high in both groups; however, bleeding was more frequent in the warfarin group. Bone mineral density was reduced in our cohort compared with the general population; however, this was further attenuated in the warfarin group. Quality of life was similar between the warfarin and aspirin groups. Home international normalized ratio monitoring was associated with better quality of life scores in the warfarin group.. Cerebrovascular injury is a frequent occurrence in the Australia and New Zealand Fontan population regardless of thromboprophylaxis type. No benefit of long-term warfarin prophylaxis could be demonstrated over aspirin; however, consideration must be given to important clinical features such as cardiac function and lung function. Furthermore, the association of reduced bone health in children receiving warfarin warrants further mechanistic studies.

Topics: Anticoagulants; Aspirin; Australia; Bone Density; Chemoprevention; Child; Cohort Studies; Female; Fontan Procedure; Heart Defects, Congenital; Hemorrhage; Humans; Long Term Adverse Effects; Male; New Zealand; Outcome Assessment, Health Care; Postoperative Complications; Quality of Life; Thromboembolism; Warfarin

Spontaneous spinal epidural hematoma (SSEH) is considered to be a relatively rare disease that can result in serious neurological sequelae. The pathogenesis and risk factors of SSEH are still unknown, and its differential diagnosis varies widely. Misdiagnosis with more common conditions such as stroke or aortic syndromes can occur. We report the case of a 27-year-old man who developed sudden upper back pain with no specific precipitant. Five days later, he visited our emergency department complaining of weakness in both lower limbs and dysuria. He had a history of intracardiac repair and a Blalock-Park procedure for an interrupted aortic arch and ventricular septal defect in infancy. Additionally, he had undergone an aortic root dilatation and aortic valve replacement at the age of 10 because of progression of aortic and supra-aortic stenosis and had received chronic anticoagulation and antiplatelet therapy with warfarin and aspirin, respectively. An emergency spine magnetic resonance imaging scan indicated a mass at the Th3-Th5 level with severe compression of the dural sac and the spinal cord. Emergency excision showed a spinal epidural hematoma. Mild postoperative gait disturbance and dysuria persisted, requiring rehabilitation and intermittent self-urethral catheterization. As patients with adult congenital heart disease have an increased risk of bleeding, they may be at risk of developing SSEH. However, this is the first report to describe such an association.

Topics: Adult; Anticoagulants; Aortic Valve Stenosis; Aspirin; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Heart Valve Prosthesis Implantation; Hematoma, Epidural, Spinal; Humans; Magnetic Resonance Imaging; Male; Platelet Aggregation Inhibitors; Postoperative Complications; 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

Thromboembolic complications occur frequently in Fontan patients with atrial arrhythmias and are a cause of significant morbidity and all-cause mortality. We report the case of an adult woman with direct atriopulmonary connection and atrial arrhythmia who developed a right atrial thrombus. She was switched to apixaban therapy because of echocardiographic evidence of thrombus progression despite combined therapy with warfarin and aspirin. After 1 year of treatment, there was evidence of complete thrombus resolution, in the absence of bleeding events. Our case shows that direct oral anticoagulants can be effective and safe for the treatment of thrombosis in adult patients with complex CHD.

Topics: Administration, Oral; Adult; Anticoagulants; Dose-Response Relationship, Drug; Echocardiography; Female; Fontan Procedure; Heart Defects, Congenital; Heart Diseases; Humans; Postoperative Complications; Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Cardiac Catheterization; Coronary Angiography; Echocardiography, Doppler, Color; Heart Defects, Congenital; Heart Valve Prosthesis Implantation; Humans; Male; Pulmonary Valve; Pulmonary Valve Insufficiency; Thrombosis; Treatment Outcome; Warfarin

The most effective method of long-term thromboprophylaxis after the Fontan procedure is not clear. We compared the rates of thromboembolic events between patients receiving aspirin and warfarin after an extracardiac conduit Fontan procedure in a bi-national registry.. All patients who underwent an extracardiac conduit Fontan procedure from 1997 to 2010 in Australia and New Zealand were identified. Medication status and routine follow-up and echocardiographic data were obtained from all patients. Survival analysis with propensity score matching and adjustment was performed to determine the treatment effect of warfarin compared with that of aspirin beyond the first year of follow-up, after which time patients had settled on their long-term thromboprophylaxis strategy.. Of 570 eligible patients, the data of 475 patients who were regularly followed up without mechanical valve replacement were available for analysis. Long-term thromboprophylaxis consisted of warfarin in 301 patients (63%), aspirin in 157 (33%) and none in 17 (4%). The 10-year rate of freedom from all thromboembolic events was 91% [95% confidence interval (CI) 88-94%]. Thromboembolic events beyond the first year of follow-up occurred in 18 patients (6 on aspirin and 12 on warfarin). After (i) propensity score adjustment and (ii) matching yielding 164 pairs, the hazard rates of thromboembolic events beyond the first year were not statistically different between the warfarin and aspirin groups [(i) hazard ratio (HR) 2.3, 95% CI 0.7-7.4, P = 0.2 and (ii) HR 1.5, 95% CI 0.5-4.7, P = 0.5, respectively].. No difference in the hazard rates of late thromboembolic events was observed between aspirin and warfarin beyond the first year after the extracardiac conduit Fontan procedure.

Topics: Anticoagulants; Aspirin; Australia; Female; Fontan Procedure; Heart Defects, Congenital; Hemorrhage; Humans; Long-Term Care; Male; New Zealand; Postoperative Care; Propensity Score; Registries; Thromboembolism; Treatment Outcome; Warfarin

Children with chronic diseases are at risk for low bone mineral density (BMD). There are no studies of BMD in children with congenital heart disease and particularly single ventricle (SV). Children with this defect are often treated with warfarin, suspected to negatively impact BMD in adults. We assessed BMD in patients with SV physiology and compared the BMD of subjects taking warfarin to those who were not. Subjects 5-12 years with SV were included. BMD z scores by dual-energy X-ray absorptiometry of the spine and total body less head (TBLH) were obtained. Calcium intake, activity level, height, and Tanner stage were assessed. Linear regression models and t tests were used to investigate differences between participants and normative data as well as between subjects' subgroups. Twenty-six subjects were included and 16 took warfarin. Mean BMD z score at the spine was significantly lower than expected at -1.0 ± 0.2 (p < 0.0001), as was the BMD z score for TBLH at -0.8 ± 0.2 (p < 0.0001). Those results remained significant after adjusting for height. Subjects who were on warfarin tended to have lower BMD at both the spine and TBLH than those who were not, with a z score difference of 0.6 ± 0.46 at the spine (p = 0.106) and a difference of 0.4 ± 0.34 at TBLH (p = 0.132). BMD is significantly reduced in children with SV. Warfarin appears to lower BMD but the effect is less conclusive. Continued evaluation is recommended for these patients at risk for reduced bone density. Evaluation of other cardiac patients on warfarin therapy should also be considered.

Topics: Absorptiometry, Photon; Anticoagulants; Body Height; Bone Density; Calcium; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Ventricles; Humans; Male; Motor Activity; Nutrition Assessment; Warfarin

Congenital heart disease is the leading cause of stroke in children. Warfarin therapy can be difficult to manage safely in this population because of its narrow therapeutic index, multiple drug and dietary interactions, small patient size, high-risk cardiac indications, and lack of data to support anticoagulation recommendations. We sought to describe our institution's effort to develop a dedicated cardiac anticoagulation service to address the special needs of this population and to review the literature. In 2009, in response to Joint Commission National Patient Safety Goals for Anticoagulation, Boston Children's Hospital created a dedicated pediatric Cardiac Anticoagulation Monitoring Program (CAMP). The primary purpose was to provide centralized management of outpatient anticoagulation to cardiac patients, to serve as a disease-specific resource to families and providers, and to devise strategies to evolve clinical care with rapidly emerging trends in anticoagulation care. Over 5 years the CAMP Service, staffed by a primary pediatric cardiology attending, a full-time nurse practitioner, and administrative assistant with dedicated support from pharmacy and nutrition, has enrolled over 240 patients ranging in age from 5 months to 55 years. The most common indications include a prosthetic valve (34 %), Fontan prophylaxis (20 %), atrial arrhythmias (11 %), cardiomyopathy (10 %), Kawasaki disease (7 %), and a ventricular assist device (2 %). A patient-centered multi-disciplinary cardiac anticoagulation clinic was created in 2012. Overall program international normalized ratio (INR) time in therapeutic range (TTR) is favorable at 67 % (81 % with a 0.2 margin) and has improved steadily over 5 years. Pediatric-specific guidelines for VKOR1 and CYP2C9 pharmacogenomics testing, procedural bridging with enoxaparin, novel anticoagulant use, and quality metrics have been developed. Program satisfaction is rated highly among families and providers. A dedicated pediatric cardiac anticoagulation program offers a safe and effective strategy to standardize anticoagulation care for pediatric cardiology patients, is associated with high patient and provider satisfaction, and is capable of evolving care strategies with emerging trends in anticoagulation.

Topics: Adolescent; Adult; Anticoagulants; Blood Coagulation; Boston; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Infant; International Normalized Ratio; Male; Middle Aged; Primary Health Care; Warfarin; Young Adult

This study identified tracheobronchial cartilage calcification in children with congenital heart disease. Calcification of the tracheobronchial airways has been found previously in adults receiving warfarin and in children receiving warfarin after mitral valve replacement. A 9-year-old girl who had received a Fontan repair 6 years previously underwent a cardiac computed tomography (CT) scan to evaluate pulmonary artery size. The result was an incidental finding of extensive tracheobronchial cartilage calcification. A retrospective review of all pediatric Fontan patients who had undergone cardiac CT was conducted to search for calcification of the tracheobronchial cartilage. The study investigated ten pediatric Fontan patients who had undergone cardiac CT scanning. Two patients with extensive calcification of the tracheobronchial airways were identified. The index case had hypoplastic left heart syndrome, and the patient had undergone a staged repair with the Fontan at the age of 3 years. A 16-year-old boy with tricuspid atresia had undergone staged repair and Fontan at the age of 3.5 years. These two patients had received continuous warfarin therapy for 6 and 13 years, respectively. Other common causes of airway calcification were excluded from the study. This report describes warfarin-induced tracheobronchial calcification in patients after the Fontan procedure. This finding has possible implications for airway growth and vascular calcification.

Topics: Adolescent; Anticoagulants; Bronchi; Calcinosis; Child; Child, Preschool; Female; Fontan Procedure; Heart Defects, Congenital; Humans; Male; Postoperative Period; Time; Tomography, X-Ray Computed; Trachea; Warfarin

Topics: Anticoagulants; Blindness; Echocardiography, Doppler, Color; Heart Defects, Congenital; Humans; Male; Middle Aged; Retinal Artery Occlusion; Visual Acuity; Visual Fields; 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

Topics: Adult; Anticoagulants; Citric Acid; Fibrinolytic Agents; Fontan Procedure; Heart Defects, Congenital; Heparin; Humans; International Normalized Ratio; Male; Recurrence; Thrombosis; Warfarin

Patients with univentricular hearts and Fontan palliation are at risk for thromboembolic complications. While aspirin and warfarin therapies are currently the mainstay of prophylaxis, controversy exists as to the optimal prevention strategy.. A cohort study was conducted on the New England registry of patients born in 1985 or earlier with Fontan surgery at Boston Children's Hospital, in order to assess and compare the effect of prophylactic aspirin and warfarin on incident thromboembolic events.. A total of 210 qualifying patients (49% male) underwent Fontan surgery at a median age of 8.5 years: 48.6% had a right atrium to pulmonary artery anastomosis, 11% a right atrium to right ventricle conduit, 38.6% a lateral tunnel, and 1.9% an extracardiac conduit. No thromboembolic prophylaxis was prescribed to 50.0%, whereas 24.3% received aspirin, and 25.7% warfarin. In multivariate analyses, lack of aspirin or warfarin was associated with a significantly higher thromboembolic event rate when compared to therapy with either [hazard ratio 8.5, 95% confidence interval (3.6-19.9), P < 0.001], with no difference between the two treatment strategies (P = 0.768). Twenty-year freedom from thromboemboli was 86% versus 52% in patients with and without thromboprophylaxis, respectively. Other factors independently associated with thromboemboli were a low post-operative cardiac index [hazard ratio 2.6, 95% confidence interval (1.2, 5.9)] and atrial fibrillation or flutter [hazard ratio 3.1, 95% confidence interval (1.2, 8.0)].. Prophylaxis with either aspirin or warfarin was associated with a significantly lower rate of incident thromboembolic events following Fontan palliation, with no difference between the two therapies.

Topics: Adolescent; Aspirin; Child; Child, Preschool; Cohort Studies; Female; Follow-Up Studies; Fontan Procedure; Heart Defects, Congenital; Heart Ventricles; Humans; Male; Registries; Thromboembolism; Treatment Outcome; Warfarin

Topics: Aspirin; Child, Preschool; Drug Substitution; Drug Therapy, Combination; Fibrinolytic Agents; Fontan Procedure; Graft Occlusion, Vascular; Heart Defects, Congenital; Heart Ventricles; Hemodynamics; Humans; Male; Pleural Effusion; Thrombosis; Time Factors; Treatment Outcome; Vascular Patency; Warfarin

Warfarin is a common anticoagulant with narrow therapeutic window and variable anticoagulation effects. Single gene polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) have been shown to impact warfarin dosing in adults. Insufficient data exists on genetic and clinical factors which influence warfarin dosing in children. Pediatric patients with heart disease who received long-term warfarin therapy were tested for VKORC1 and CYP2C9 polymorphisms. Clinical and demographic data were reviewed in those children who achieved stable therapeutic international normalized ratio (INR). Multiple linear regression modeling was used to assess relationships between stable warfarin doses and genetic or clinical variables. Fifty children were tested for VKORC1 and CYP2C9 polymorphisms; 37 patients (M 26: F 11) had complete data, achieved stable therapeutic INR, and were included in dose variability analysis. There were predominance of white race 73% and male sex 70.3%. The mean age was 9.6 years (1.8-18.6 years). The mean weight was 37.8 kg (7.7-95 kg). Fontan physiology and mechanical cardiac valves were two most common indications for chronic warfarin therapy (25/37 or 67.6%). Twelve patients (32.4%) had ≥ 2 indications for warfarin therapy. Three patients had documented venous or arterial clots, and 5 patients had strokes. Congenital heart disease was present in 29 patients (78.4%), including Fontan physiology (20), complex biventricular physiology (4), and congenital mitral valve disease (5). Acquired heart disease was present in 8 patients (21.6%), including Kawasaki disease with coronary aneurysms (3), acquired mitral valve disease (3), and Marfan syndrome (2). Stable warfarin dose (mg/kg/day) was strongly associated with VKORC1 polymorphism (p < 0.0001) and goal therapeutic INR (p = 0.009). Negative correlations were observed between stable warfarin dose and age, weight, height, and BSA (p = 0.04, 0.02, 0.02, and 0.02 respectively). Factors which did not influence warfarin dose included CYP2C9 polymorphism (p = 0.17), concurrent medications (p = 0.85), sex (p = 0.4), race (p = 0.14), congenital heart disease (p = 0.09), and Fontan physiology (p = 0.76). The gene-dose effect was observed in children with homozygous wild type VKORC1 CC, who required higher warfarin dose compared to those carrying heterozygous TC or homozygous TT (p = 0.028 and 0.0004 respectively). The full multiple linear regression model revealed that VKORC1 genot

Topics: Adolescent; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Child; Child, Preschool; Cytochrome P-450 CYP2C9; Female; Genotype; Heart Defects, Congenital; Humans; Infant; International Normalized Ratio; Linear Models; Male; Mixed Function Oxygenases; Polymorphism, Single Nucleotide; Prospective Studies; Vitamin K Epoxide Reductases; Warfarin

Hypertrophic cardiomyopathy is a complex and relatively common genetic disorder characterized by left ventricular (LV) hypertrophy, usually associated with a nondilated and hyperdynamic chamber with heterogeneous phenotypic expression and clinical course. On the other hand, LV noncompaction is an uncommon cardiomyopathy characterized by the persistence of fetal myocardium with a pattern of prominent trabecular meshwork and deep intertrabecular recesses, systolic dysfunction, and LV dilatation. We report a 29-year-old man with these two different inherent conditions. Our case raises the possibility of a genetic mutation common to these two clinical entities or different gene mutations existing in the same individual.

Topics: Adrenergic beta-Antagonists; Adult; Anticoagulants; Carbazoles; Cardiomyopathy, Hypertrophic; Carvedilol; Diagnosis, Differential; Heart Defects, Congenital; Humans; Male; Propanolamines; Treatment Outcome; 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

Topics: Adult; Female; Heart Defects, Congenital; Hemorrhage; Humans; Warfarin

To describe the incidence of thrombotic complications across all 3 stages of single ventricle palliation and the association between thromboprophylaxis use and thrombotic risk.. Two separate cross-sectional studies were performed that included 195 patients born between 2003-2008 and 162 patients who underwent Fontan after 2000.. The incidence of thrombotic complications was 40% and 28% after initial palliation and superior cavopulmonary connection (SCPC), respectively; 5-year freedom from thrombotic complications after Fontan was 79%. Thromboprophylaxis was initiated for 70%, 46%, and 94% of patients after initial palliation, SCPC, and Fontan, respectively. Thromboprophylaxis with enoxaparin (vs no thromboprophylaxis) was associated with a reduction in risk of thrombotic complications after initial palliation (hazard ratio [HR] 0.5, P = .05) and SCPC (HR 0.2, P = .04). Thromboprophylaxis with warfarin was associated with a reduction in thrombotic complications after Fontan (HR 0.27, P = .05 vs acetylsalicylic acid; HR 0.18, P = .02 vs no thromboprophylaxis). Thrombotic complications were associated with increased mortality after initial palliation (HR 5.5, P < .001) and SCPC (HR 12.5, P < .001). Three patients experienced major bleeding complications without permanent sequelae (2 enoxaparin, 1 warfarin).. Given the negative impact of thrombotic complications on survival, the low risk of serious bleeding complications, and the association between thromboprophylaxis and lowered thrombotic complication risk across all 3 palliative stages, routine use of thromboprophylaxis from the initial palliation to the early post-Fontan period in this population may be indicated.

Topics: Anticoagulants; Cross-Sectional Studies; Enoxaparin; Female; Fontan Procedure; Heart Defects, Congenital; Heart Ventricles; Humans; Infant; Infant, Newborn; Male; Palliative Care; Postoperative Complications; Thrombosis; Warfarin

Management of warfarin in pediatric patients remains a clinical challenge. Warfarin may be administered after congenital heart surgery, and the risks of morbidity can be high. Currently, no data exist to describe the initiation of warfarin and the risk factors for morbidity in post-congenital heart surgery patients. This study aimed to characterize the time required to reach anticoagulation for patients administered warfarin therapy after cardiac surgery and to identify and characterize the risk factors for supratherapeutic anticoagulation and adverse events after warfarin initiation. This retrospective study reviewed all patients between 2006 and 2011 who received warfarin anticoagulation after cardiac surgery at our institution. Factors associated with a prolonged time required to reach an international normalized ratio (INR) of 2 and factors related to supratherapeutic anticoagulation (INR ≥ 4) were identified. The inclusion criteria were met by 59 patients. The median time required to reach an INR of at least 2 after initiation of warfarin was 2 days (interquartile range (IQR), 2-4). The only groups that required a significantly longer time to reach an INR of 2 were those with a postoperative delay in initiation of warfarin and those receiving heparin anticoagulation before and during warfarin initiation. Nine patients experienced an INR of 4 or more. However, no thrombotic events occurred, and significant bleeding was uncommon. In the largest reported group of patients undergoing anticoagulation after cardiac surgery, warfarin was well tolerated across all age groups. The median time required to reach an INR of 2 after loading with warfarin was 2 days, and adverse events were uncommon.

Topics: Adolescent; Adult; Analysis of Variance; Anticoagulants; Child; Child, Preschool; Female; Heart Defects, Congenital; Hospitals, Pediatric; Humans; Infant; International Normalized Ratio; Linear Models; Male; Retrospective Studies; Risk Factors; Statistics, Nonparametric; Treatment Outcome; Warfarin

The objective of this study was to evaluate the underlying diseases, thrombus localization, and other risk factors in pediatric patients with recurrent thrombosis in order to obtain a sense of early awareness of the possible recurrences. We retrospectively evaluated both inherited and acquired thrombophilic risk factors in children with recurrent thrombosis that were diagnosed and treated at Hacettepe University, School of Medicine, Department of Pediatric Hematology, Ankara, Turkey. Both congenital and acquired risk factors associated with recurrent thrombosis, and treatment modalities were analyzed in detail. Among 569 children with thrombosis, 32 (5.6%) presented with recurrent thrombosis. Median age at first presentation in these 32 patients [11 women (34.4%) and 21 men (65.6%)] was 132 months. In all, 29 (90.6%) of the 32 patients had an underlying chronic disorder: the most common of which was congenital heart disease [n = 11 (34.4%)]. At presentation intracardiac localization, including the entrance of the inferior and superior vena cava, was observed in 10 of the patients (31.2%). Thrombosis recurred at the same location in 15 (47%) patients and at a different location in 17 (53%). Median time interval between the first and second episode of thrombosis was 6.5 months (range: 1-180 months). Considering both acquired and congenital thrombophilic factors, three (9.3%) patients, four (12.5%) patients, and 14 (43.8%) patients had five, four, and three risk factors, respectively. More than half of the patients had elevated plasma FVIII (>150 IU/dl) and D-dimer (>0.5 mg/ml) levels. Thrombectomy was performed in three patients with organized, chronic intracardiac thrombus. Tissue plasminogen activator (t-PA) was used more frequently to treat recurrence than the first event (15.6 vs. 28.1%) and consequently the complete resolution rate was higher (40 vs. 77.7%) at the second event. Thrombi partially resolved in 11 of the patients during the initial episode and in 10 patients during recurrence (34 vs. 32%). In all, 29 (87.5%) patients were using prophylaxis at the time of recurrence. [coumadin (n = 16), low molecular weight heparin (n = 12) and aspirin (n = 1)]. In total, four patients (12.5%) died because of their underlying disorders and six (18.7%) developed postthrombotic syndrome during the follow-up. Recurrent thrombosis should be expected, especially in cases with congenital heart disease, incomplete thrombus resolution, and elevated plasma FVIII/D-d

Topics: Adolescent; Adult; Anticoagulants; Aspirin; Child; Child, Preschool; Chronic Disease; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Heart Defects, Congenital; Heparin, Low-Molecular-Weight; Humans; Infant; Male; Postthrombotic Syndrome; Recurrence; Retrospective Studies; Risk Factors; Thrombectomy; Thrombophilia; Thrombosis; Tissue Plasminogen Activator; 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

The primary aim of the present study was to evaluate the effect of the genotype of vitamin K epoxide reductase complex 1 (VKORC1) on warfarin dose requirements in Japanese pediatric patients. Forty-eight pediatric patients (0.42-19.25 years old) in whom stable anticoagulation was achieved by warfarin were enrolled in this study, and the polymorphic alleles of VKORC1 and CYP2C9 were determined for each subject. The relative impact of covariates on the anticoagulant effect of warfarin was evaluated by multiple regression analysis. It was found that VKORC1 genotype and age were major factors affecting the relationship between the weight-normalized warfarin dose and the therapeutic prothrombin time-international normalized ratio (PT-INR). Because only one patient had the CYP2C9*3 allele, we could not evaluate the effect of CYP2C9 polymorphisms on the anticoagulant effect of warfarin. In contrast, the anticoagulant effect of warfarin in patients with the VKORC1 1173CT or 1173CC genotype was 52.3% of that in patients with the 1173TT genotype. In addition, the anticoagulant effect of warfarin was shown to increase by 10.5% per year in Japanese pediatric patients. In conclusion, genotyping of VKORC1 will be useful in establishing individual anticoagulant therapy with warfarin, and it should be noted that a higher weight-normalized dose of warfarin is required in younger pediatric patients.

Topics: Adolescent; Age Factors; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Asian People; Body Weight; Child; Child, Preschool; Cytochrome P-450 CYP2C9; Drug Interactions; Female; Genotype; Heart Defects, Congenital; Humans; Infant; Likelihood Functions; Male; Mixed Function Oxygenases; Models, Biological; Polymorphism, Single Nucleotide; Prothrombin Time; Regression Analysis; Vitamin K Epoxide Reductases; Warfarin; Young Adult

Topics: Adult; Anticoagulants; Diagnosis, Differential; Disease Progression; Echocardiography; Follow-Up Studies; Fontan Procedure; Heart Defects, Congenital; Heart Diseases; Humans; Male; Severity of Illness Index; Thrombosis; Time Factors; Warfarin

Warfarin is an important therapy for children with heart disease. We assessed the impact of a computerized warfarin-dosing software program on measured INR values using a historical case-control design. Children (infant to 20 years of age) with cardiac disease managed with warfarin between September 1, 2006, and August 31, 2009 were included in the analysis. Warfarin therapy was tailored to specific underlying conditions based on consensus guidelines. Before the use of dosing software, medication adjustments were made by physicians using published guidelines. After software implementation, dosing adjustments were based on the software algorithm. There were 86 subjects in this analysis, and the most common indication for warfarin was prosthetic valve. Overall, the incidence of adverse bleeding events was 1.3% per patient-year. An analysis of patient-related factors associated with a low percentage of time within goal range demonstrated that both female sex (P = 0.048) and nonwhite race (P = 0.037) were significantly associated with less time in the target range. Use of the software program was associated with an increase in the percentage of time during which the INR was within the target range from 41.4 to 53.1% (P < 0.001). Incorporation of a computerized software program to assist dosing can improve the percentage of time that children with cardiac disease requiring warfarin remain within the target therapeutic range. Strategies to improve management and decrease sex and racial disparities in this population are needed.

Topics: Adolescent; Anticoagulants; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Diseases; Heart Valve Prosthesis; Humans; Infant; International Normalized Ratio; Male; Risk Factors; Software; Warfarin; Young Adult

Home international normalized ratio (INR) monitors are being increasingly used for monitoring the adequacy of anticoagulation in children on long-term warfarin. Their safety and effectiveness in the home setting has not been fully established. The purpose of this study was to explore the safety and effectiveness of home INR monitoring service in managing anticoagulation in children with congenital heart disease. At the Pediatric Cardiology Regional Referral Center, we studied records of 41 children on warfarin and assessed the control of anticoagulation and frequency of adverse reactions over a 1-year period. User satisfaction was assessed by means of telephone interviews. The study found that the therapeutic INR range was maintained for over 57% of the total study period. There were no reported instances of major or minor hemorrhages. On six occasions, subtherapeutic INR levels necessitated hospitalization for heparinization. Mitral valve replacement was significantly associated with poor control (p < 0.05). User satisfaction was high for all aspects of the service evaluated. The hospital-assisted home INR monitoring service is a safe and effective means of managing anticoagulation in children. In addition, it ensures good compliance and a high level of user satisfaction.

Topics: Adolescent; Anticoagulants; Child; Child, Preschool; Consumer Behavior; Drug Monitoring; Female; Heart Defects, Congenital; Hemorrhage; Home Care Services, Hospital-Based; Humans; International Normalized Ratio; Male; Safety; Telemedicine; United Kingdom; Warfarin

The outcomes of 33 consecutive extracardiac Fontan operations performed between 1999 and 2008 in patients who mostly had initial Glenn shunts beyond infancy were reviewed. Preoperatively, the median oxygen saturation was 76.2% and mean pulmonary artery pressure was 10.5 mm Hg. The median age was 4.1 years at Glenn shunt procedure and 10 years at Fontan operation. The duration of chest tube drainage was longer in these patients than in series where Glenn shunts were created at a younger age. All patients received warfarin for 1 year, then warfarin and/or aspirin. At follow-up (median, 14 months), there was no significant ventricular dysfunction. Median oxygen saturation at the last follow-up was 92%. All patients in sinus rhythm preoperatively continued in this status. There was no Fontan failure or mortality. All patients were in New York Heart Association class I or II, although objective cardiopulmonary exercise evaluation in 8 patients showed impaired exercise tolerance. Despite a trend towards prolonged pleural effusion, there was no adverse outcome in the short or intermediate term. Long-term follow-up is required to see whether delayed creation of a Glenn shunt is associated with late disadvantages.

Topics: Adolescent; Anticoagulants; Aspirin; Blood Pressure; Chest Tubes; Child; Child, Preschool; Drainage; Drug Therapy, Combination; Exercise Tolerance; Female; Fontan Procedure; Heart Bypass, Right; Heart Defects, Congenital; Humans; India; Male; Oxygen; Platelet Aggregation Inhibitors; Pleural Effusion; Pulmonary Artery; Retrospective Studies; Time Factors; Treatment Outcome; Warfarin; Young Adult

Topics: Anticoagulants; Antihypertensive Agents; Bosentan; Diagnostic Imaging; Drug Therapy, Combination; Electrocardiography; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Middle Aged; Pulmonary Artery; Sulfonamides; Warfarin

Topics: Abnormalities, Multiple; Anticoagulants; Bioprosthesis; Cardiac Surgical Procedures; Drug Administration Schedule; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Infant; Postoperative Care; Thromboembolism; Time Factors; Treatment Outcome; Tricuspid Valve Insufficiency; Warfarin

The necessity for chronic anticoagulation of Fontan patients remains controversial. We determined the prevalence of thromboembolic complications after the Fontan procedure in relation to different long-term anticoagulation strategies.. The clinical outcomes, postoperative anticoagulation strategies and occurrence of thromboembolic complications in 102 ethnic Chinese patients who had undergone Fontan procedure between 1980 and 2002 were reviewed.. The early and late surgical mortalities, all unrelated to thromboembolism, were 10.8% (11/102) and 5.8% (6/104), respectively. Of the 85 survivors, 46 (54%) were maintained on long-term warfarin therapy, 8 (9%) on aspirin prophylaxis while 31 (37%) were not on chronic anticoagulation. Four (4.5%) patients, two with and two without warfarin prophylaxis, developed thromboembolic complications at 0.14 to 7.7 years after the Fontan procedure (0.74%/patient-year). Three had a grossly dilated right atrium after atriopulmonary connection, two of whom had atrial fenestrations. The other had atrial tachycardia. Freedom from development of thromboembolic complications (mean+/-S.E.) at 1, 5 and 10 years after surgery was 97+/-19%, 96+/-2.5% and 92+/-4.2%, respectively. When compared with those on long-term warfarin therapy, patients without chronic anticoagulation were followed-up longer (p=0.001), more likely to have undergone atriopulmonary connection (p<0.001), less likely to have fenestrations (p=0.02) and cardiac arrhythmias (p=0.02) but not predisposed to increased risk of thromboembolism (p=1.00).. The study supports the contention that chronic anticoagulation may not be required for majority of ethnic Chinese Fontan patients. Nonetheless, it may perhaps be considered in those with grossly dilated right atrium, cardiac arrhythmias and residual right-to-left shunts.

Topics: Anticoagulants; Child; Child, Preschool; Female; Follow-Up Studies; Fontan Procedure; Heart Defects, Congenital; Humans; Male; Retrospective Studies; Risk Assessment; Risk Factors; Thromboembolism; Time Factors; Warfarin

A woman with double outlet left ventricle (DOLV) had undergone a Rastelli operation using a prosthetic Björk Shiley valve and who was receiving anticoagulant drug delivered a healthy male infant. Oral warfarin was replaced by heparin from the 5th to the 13th week of gestation and for the last 5 weeks of gestation. Successful pregnancy in patients with DOLV after a Rastelli operation using a prosthetic valve is possible with careful maintenance.

Topics: Adult; Anticoagulants; Cesarean Section; Drug Administration Schedule; Female; Heart Defects, Congenital; Heart Valve Prosthesis; Heart Ventricles; Heparin; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Prosthesis Failure; Pulmonary Valve; Thrombosis; Warfarin

Inflammatory processes seem to be involved in pulmonary arterial hypertension (PAH). CD40 ligand (L) may promote inflammation and thrombus formation, and we hypothesized that CD40L could be involved in the pathogenesis of PAH.. Several significant findings were revealed when examining the possible role of CD40L in PAH. (1) Patients with primary (n=13) and secondary (n=11) PAH but not those with chronic thromboembolic pulmonary hypertension (n=8) had increased plasma levels of soluble (s) CD40L compared with control subjects (n=8). (2) PAH patients using warfarin had markedly lower sCD40L levels than those without such therapy. (3) sCD40L levels were higher in arterial (femoral artery) compared with mixed venous blood (pulmonary artery), suggesting enhanced release or reduced clearance in the pulmonary vasculature. (4) Platelets from PAH patients showed enhanced spontaneous and SFLLRN-stimulated release of sCD40L compared with control subjects. (5) In vitro, recombinant sCD40L induced monocyte chemoattractant protein (MCP)-1 and interleukin-8 gene expression in endothelial cells, and plasma levels of these chemokines were raised in all PAH groups, significantly correlated to sCD40L and hemodynamic parameters. (6) Although prostacyclin therapy (3 months) showed clinical benefit, this therapy had no effect on sCD40L and increased MCP-1 levels in PAH patients, and prostacyclin enhanced MCP-1 in CD40L-stimulated endothelial cells.. Our findings suggest a role for CD40L in the pathogenesis of PAH, possibly operating through an interaction between platelets and endothelial cells involving chemokine-related mechanisms.

Topics: Aged; Anticoagulants; Blood Platelets; CD40 Ligand; Cells, Cultured; Chemokine CCL2; Collagen Diseases; Endothelial Cells; Endothelium, Vascular; Epoprostenol; Female; Femoral Artery; Gene Expression Regulation; Heart Defects, Congenital; HIV Infections; Humans; Hypertension, Pulmonary; Interleukin-8; Liver Cirrhosis; Male; Middle Aged; Peptide Fragments; Pulmonary Artery; Recombinant Proteins; Solubility; Thromboembolism; Umbilical Veins; Warfarin

Fetal warfarin syndrome (FWS) or warfarin (coumadin) embryopathy is a rare condition as a result of fetal exposure to maternal ingestion of warfarin during pregnancy. A male infant, whose mother was treated with the anticoagulant (warfarin) because of a mechanical heart valve replacement after rheumatic heart disease, presented with signs of warfarin embryopathy. The facial dysmorphism included hypoplasia of nasal bridge, laryngomalacia, pectus carinatum, congenital heart defects (atrial septal defect and patent ductus arteriosus), ventriculomegaly, stippled epiphyses, telebrachydactyly, and growth retardation. The pathogenesis and management of FWS are discussed.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Anticoagulants; Female; Growth and Development; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Maternal Exposure; Nose; Pregnancy; Prenatal Exposure Delayed Effects; Warfarin

Uhl's anomaly, or parchment right ventricle is a myocardial disorder of unknown cause that mainly involves the right ventricle. Uhl's anomaly may represent a cause of right heart dilatation, failure, and premature sudden death due to ventricular arrhythmias. Although most of the cases of Uhl's anomaly end fatally in infancy or childhood, a limited number of cases have been reported in advanced ages. Also, in pregnant women, this situation increases the risk to both mother and baby and requires special management. This is the first report of six successful consecutive gestations and vaginal deliveries without special managements in a patient with Uhl's anomaly.

Topics: Angiotensin-Converting Enzyme Inhibitors; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Furosemide; Gestational Age; Heart Defects, Congenital; Heart Failure; Heart Ventricles; Humans; Parity; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Ventricular Dysfunction, Right; Warfarin

Between 1979 and 1985, 5 patients underwent pulmonary valve replacement with a St. Jude Medical valve. During follow-up ranging from 30 months to 18 years, there were 6 episodes of valve thrombosis in 4 patients. Three episodes were treated by thrombolysis. Reoperation was necessary in 3 patients. Although the St. Jude Medical valve in the pulmonary position can occasionally function long-term without anticoagulation, these cases show the high risk of thrombosis and need for anticoagulation.

Topics: Adolescent; Adult; Anticoagulants; Child; Follow-Up Studies; Heart Defects, Congenital; Heart Valve Prosthesis; Humans; Infant; Pulmonary Valve; Reoperation; Thromboembolism; Warfarin

The choice of the most appropriate substitute in children with irreparable aortic valve lesions remains controversial. The aim of this study was to assess early and late outcomes following aortic valve replacement (AVR) with mechanical prostheses in children.. Fifty-six patients (42 male, 14 female, mean age 11.2, range 1-16 years) undergoing AVR with mechanical prostheses between October 1972 and January 1999 were evaluated. Thirty-six patients (64.2%) underwent previous cardiac surgery. Disease aetiology was congenital in 47 patients (congenital aortic stenosis in 33, and other congenital abnormalities in 14) (83.9%), infective in four (7. 1%), rheumatic in two (3.4%), and three (5.3%) had connective tissue disorders. Haemodynamic indication for AVR was aortic regurgitation (AR) in 24 (42.8%), aortic stenosis (AS) in 22 (39.2%) and mixed disease in ten (17.8%). Twenty-eight patients (50.0%) were in New York Heart Association (NYHA) class III-IV before surgery. Concomitant procedures were performed in 31 patients (55.3%), including aortic root enlargement in 28 (50%). The mean size of implanted valves was 22.4 mm (range 17-27 mm). All patients received long-term anticoagulation treatment with sodium warfarin, aiming to maintain an international normalized ratio (INR) between 2.5-3.0. The mean follow-up was 7.3 years (range 0-26, total 405 patient-years).. Operative mortality was 5.3% (three patients). Three patients developed complete heart block requiring pacing, two of them permanently. Late events included valve thrombosis (one), transient stroke (one), paravalvular leak of a mitral prosthesis (one), aneurysm of sinus of Valsalva (one) and pannus ingrowth (one). There was no major haemorrhagic event. Five patients required re-operation (8.9%), but none due to outgrowth of the valve. Regarding actuarial freedom from thrombo-embolism, any valve-related event and re-operation at 20 years was 93, 86.6 and 86. 4%. There were three late deaths. Actuarial survival, including operative mortality, at 10 and 20 years was 91 and 84.9%. The actuarial survival for the group of the patients with congenital AS (n=33) at 10 and 20 years was 93.5%, whereas for the children with other congenital heart problems (n=14) this was 85.7 and 64.3% (P=0. 09). At the latest clinical evaluation, 44 children were in NYHA class I and six were in class II. The mean gradient across the aortic prosthetic valve on echocardiography was 17.9 mmHg (range 0-47 mmHg).. Mechanical AVR, with enlargement of the aortic root if necessary, remains an excellent treatment option in children. It is associated with acceptable operative mortality, low incidence of late events and re-operation, and provides good long-term survival. It clearly represents a good alternative to available biological substitutes, including the pulmonary autograft (Ross procedure).

Topics: Actuarial Analysis; Anticoagulants; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Child; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Prosthesis Design; Warfarin

This study aims to evaluate the efficacy of a low dose warfarin regimen for Chinese children requiring anticoagulation therapy and its safety when monitored on an outpatient basis. Current recommendations are based on extrapolations from the adult experience and a high target international normalised ratio (INR) is adopted amongst the Western countries.. This is a 10-year retrospective study from January 1986 to June 1996. Effectiveness of warfarin therapy was monitored by the prothrombin time, standardised and expressed as the INR. A target INR of 1.5-2.5 was adopted for children with cardiac diseases requiring anticoagulation therapy for primary and secondary prophylaxis against thromboembolism. From the clinical records, demographic data, induction warfarin dosage, changes of dosages and related events on follow-up, frequency of outpatient visits, complications and serial INR results were reviewed.. Thirty-five patients (23 boys, 12 girls) were included with a mean age at initiation of warfarin therapy of 8.4+/-5.8 years. Amongst these, 66% (n = 23) were after isolated valvar replacement, 28% (n = 10) after Fontan operation with or without valvar replacement and 6% (n = 2) after deep vein thrombosis. Regression estimate of the induction dose was 0.05-0.13 mg x kg(-1) in order to achieve the target INR range after 2 days of warfarin therapy. The daily maintenance warfarin dose was correlated with the bodyweight [dose (mg x day(-1))= 0.04 x bodyweight (kg) + 0.87, r = 0.63, P<0.0001]. Young children required significantly higher daily warfarin maintenance dose when adjusted for bodyweight [dose (mg x kg day(-1)) = antilog(10)¿-0.02 x age (years)- 0.80¿, r = -0.74, P<0.0001]. The mean maintenance warfarin dosage was significantly lower in patients after the Fontan operation, with or without valvar replacement, in the absence of apparent liver dysfunction. The total period of followup was 159 patient-years. No serious bleeding complications or embolic phenomena were documented. One patient died of thrombosis of the mitral valve prosthesis. The overall incidence of thrombosis was 0.6 per 100 patient-years.. A low dose warfarin regimen to maintain a target INR of 1.5-2.5 provides adequate protection in Chinese children against thromboembolism whilst allowing safe outpatient monitoring of the anticoagulation status.

Topics: Administration, Oral; Anticoagulants; Child; Child, Preschool; Female; Heart Defects, Congenital; Hong Kong; Humans; International Normalized Ratio; Male; Prothrombin Time; Retrospective Studies; Thromboembolism; Warfarin

We sought to determine the frequency of spontaneous cerebrovascular events in adult patients with cyanotic congenital heart disease and to evaluate any contributing factors.. Cerebrovascular events are a serious complication of cyanotic congenital heart disease in infants and children but are said to be uncommon in adults.. Between 1988 and 1995, 162 patients with cyanotic congenital heart disease (mean age 37 years, range 19 to 70) were retrospectively evaluated for any well documented cerebrovascular events that occurred at > or = 18 years of age. Events related to procedures, endocarditis or brain abscess were excluded.. Twenty-two patients (13.6%) had 29 cerebrovascular events (1/100 patient-years). There was no significant difference between those with and without a cerebrovascular event in terms of age, smoking history, degree of erythrocytosis, ejection fraction or use of aspirin or warfarin (Coumadin). Patients who had a cerebrovascular event had a significantly increased tendency to develop hypertension, atrial fibrillation, microcytosis (mean corpuscular volume < 82) and history of phlebotomy (p < 0.05). Even when patients with hypertension or atrial fibrillation were excluded, there was an increased risk of cerebrovascular events associated with microcytosis (p < 0.01).. Adults with cyanotic congenital heart disease are at risk of having cerebrovascular events. This risk is increased in the presence of hypertension, atrial fibrillation, history of phlebotomy and microcytosis, the latter condition having the strongest significance (p < 0.005). This finding leads us to endorse a more conservative approach toward phlebotomy and a more aggressive approach toward treating microcytosis in adults with cyanotic congenital heart disease.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Heart Defects, Congenital; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Smoking; Warfarin

In 14 patients aged 5-329 (mean 131) months a CarboMedics valve was implanted because of congenital heart disease. The preoperative NYHA function class was III-IV in ten cases. Seven aortic and seven atrioventricular valves were replaced without early mortality. All patients were followed up, with mean observation time 27 months (total 384 months). One of the 14 patients died of heart failure 10 months postoperatively. Thrombosis occurred in four valves, three in tricuspid and one in mitral position. In all patients who received only warfarin, anticoagulation was demonstrably inadequate. Consequently we now recommend antiplatelet medication in addition to warfarin for children with atrioventricular mechanical valve replacement. In our experience the complication rate with CarboMedics prosthesis is acceptable, provided that anticoagulant therapy is adequate.

Topics: Aortic Valve; Aspirin; Child; Dipyridamole; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Postoperative Complications; Prosthesis Design; Thrombosis; Time Factors; Tricuspid Valve; Warfarin

This study aimed at elucidating the role of anticoagulation in the genesis of late pericardial effusion and tamponade after cardiac surgery. Using serial 2-D echocardiography, 141 patients undergoing surgery for coronary artery bypass (56), valvular (69) or congenital (16) [corrected] heart disease were studied postoperatively. Group 1 (74 patients) received full anticoagulation (warfarin 73; heparin 1) and group 2 (67 patients) received either antithrombotic agents (aspirin plus dipyridamole), or no treatment. Fifty percent (70/141) of patients developed effusion. There was no significant difference between the two groups in the incidence of either effusion in general (43/74; 58% vs 27/67; 40%, respectively) or small or medium sized effusion. However, a large effusion was significantly more common in group 1 than in group 2 (32% vs 4%, P < 0.005). Twelve patients (12/141; 8.5%) developed late tamponade, 7 to 33 (15 +/- 7.3 mean +/- SD) days after surgery. All had a large effusion demonstrated by echo, drained by pericardiocentesis, and none died. All 12 patients with tamponade belonged to group 1 (P < 0.001). Excess anticoagulation was detected at least once in 41 of the 74 group 1 patients (55%). When compared to properly anticoagulated patients, excessively anticoagulated patients had a similar overall incidence of effusion and a similar incidence of small or moderate effusion, but a higher incidence of large effusion (18% vs 44%, [corrected] P < 0.05) and tamponade (3% vs 27%, P < 0.025). We conclude that, unlike small or medium-sized effusions, large pericardial effusions and tamponade are more likely to occur among anticoagulated patients, especially if they are excessively anticoagulated.

Topics: Adult; Anticoagulants; Aspirin; Cardiac Surgical Procedures; Cardiac Tamponade; Coronary Artery Bypass; Dipyridamole; Echocardiography; Female; Heart Defects, Congenital; Heart Valves; Heparin; Humans; Male; Pericardial Effusion; Postoperative Complications; Warfarin

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