Outcome of pregnancy in women with congenital shunt lesions. (1/1606)

OBJECTIVE: To evaluate the outcome of pregnancy in women with congenital shunt lesions. SETTING: Retrospective study in a tertiary care centre. METHODS: Pregnancy history was obtained by a standardised questionnaire and medical records were reviewed. PATIENTS: 175 women were identified, at a mean (SD) age of 42 (14) years. Pregnancies occurred in 126 women: 50 with an atrial septal defect, 22 with a ventricular septal defect, 22 with an atrioventricular septal defect, 19 with tetralogy of Fallot, and 13 with other complex shunt lesions. RESULTS: 309 pregnancies were reported by 126 woman (2.5 (1.6) pregnancies per woman). The shortening fraction of the systemic ventricle was 40 (8)%, and 98% were in New York Heart Association class I-II at last follow up. Spontaneous abortions occurred in 17% of pregnancies (abortion rate, 0.4 (0.9) per woman). Gestational age of the 241 newborn infants was 8.8 (0.8) months. There were no maternal deaths related to pregnancy. Pre-eclampsia and embolic events were observed in 1.3% and 0.6%, respectively of all pregnancies. Women with complex shunt lesions more often underwent caesarean section (70% v 15-30%, p = 0.005) and gave birth to smaller babies for equivalent gestation (2577 (671) g v 3016 (572) to 3207 (610) g, p < 0.05). The recurrence risk of congenital heart disease was 2.5%. CONCLUSIONS: The outcome of pregnancy is favourable in women with congenital shunt lesions if their functional class and their systolic ventricular function are good. Such patients can be reassured.  (+info)

Prospective evaluation of the thrombotic risk in children with acute lymphoblastic leukemia carrying the MTHFR TT 677 genotype, the prothrombin G20210A variant, and further prothrombotic risk factors. (2/1606)

The reported incidence of thromboembolism in children with acute lymphoblastic leukemia (ALL) treated with L-asparaginase, vincristine, and prednisone varies from 2.4% to 11.5%. The present study was designed to prospectively evaluate the role of the TT677 methylenetetrahydrofolate reductase (MTHFR) genotype, the prothrombin G20210A mutation, the factor V G1691A mutation, deficiencies of protein C, protein S, antithrombin, and increased lipoprotein (a) concentrations in leukemic children treated according to the ALL-Berlin-Frankfurt-Muenster (BFM) 90/95 study protocols with respect to the onset of vascular events. Three hundred and one consecutive leukemic children were enrolled in this study. Fifty-five of these 301 subjects investigated had one established single prothrombotic risk factor: 20 children showed the TT677 MTHFR genotype; 5 showed the heterozygous prothrombin G20210A variant; 11 were carriers of the factor V G1691A mutation (heterozygous, n = 10; homozygous, n = 1); 4 showed familial protein C, 4 protein S, and 2 antithrombin type I deficiency; 9 patients were suffering from familially increased lipoprotein (a) [Lp(a)] concentrations (>30 mg/dL). In addition, combined prothrombotic defects were found in a further 10 patients: the FV mutation was combined with the prothrombin G20210A variant (n = 1), increased Lp(a) (n = 3), protein C deficiency (n = 1), and homozygosity for the C677T MTHFR gene mutation (n = 1). Lp(a) was combined with protein C deficiency (n = 2) and the MTHFR TT 677 genotype (n = 2). Two hundred eighty-nine of the 301 patients were available for thrombosis-free survival analysis. In 32 (11%) of these 289 patients venous thromboembolism occurred. The overall thrombosis-free survival in patients with at least one prothrombotic defect was significantly reduced compared with patients without a prothrombotic defect within the hemostatic system (P <.0001). In addition, a clear-cut positive correlation (P <.0001) was found between thrombosis and the use of central lines. However, because the prothrombotic defects diagnosed in the total childhood population studied were all found within the prevalences reported for healthy Caucasian individuals, the interaction between prothrombotic risk factors, ALL treatment, and further environmental factors is likely to cause thrombotic manifestations.  (+info)

Bileaflet mechanical prostheses for aortic valve replacement in patients younger than 65 years and 65 years of age or older: major thromboembolic and hemorrhagic complications. (3/1606)

OBJECTIVE: To determine major thromboembolic and hemorrhagic complications and predictive risk factors associated with aortic valve replacement (AVR), using bileaflet mechanical prostheses (CarboMedics and St. Jude Medical). DESIGN: A case series. SETTING: Cardiac surgical services at the teaching institutions of the University of British Columbia. PATIENTS AND METHODS: Patients 2 age groups who had undergone AVR between 1989 and 1994 were studied. Group 1 comprised 384 patients younger than 65 years. Group 2 comprised 215 patients 65 years of age and older. RESULTS: The linearized rates of major thromboembolism (TE) occurring after AVR were 1.54%/patient-year for group 1 and 3.32%/patient-year for group 2; the rates for major TE occurring more than 30 days after AVR were 1.13%/patient-year for group 1 and 1.55%/patient-year for group 2. The crude rates for major TE occurring within 30 days of AVR were 1.04% for group 1 and 3.72% for group 2. The death rate from major TE in group 1 was 0.31%/patient-year and in group 2 was 0.88%/patient-year. Of the major TE events occurring within 30 days, 100% of patients in both age groups were inadequately anticoagulated at the time of the event, and for events occurring more than 30 days after AVR, 45% in group 1 and 57% in group 2 were inadequately anticoagulated (INR less than 2.0). The overall linearized rates of major hemorrhage were 1.54%/patient-year for group 1 and 2.21%/patient-year for group 2. There were no cases of prosthesis thrombosis in either group. The mean (and standard error) overall freedom from major TE for group 1 patients at 5 years was 95.6% (1.4%) and with exclusion of early events was 96.7% (1.3%); for group 2 patients the rates were 90.0% (3.2%) and 93.7% (3.0%), respectively. The mean (and SE) overall freedom from major and fatal TE and hemorrhage for group 1 patients was 90.1% (2.3%) and with exclusion of early events was 91.2% (2.3%); for group 2 patients the rates were 87.9% (3.1%) and 92.5% (2.9%), respectively. The 5-year rate for freedom from valve-related death for group 1 patients was 96.3% (2.1%) and for group 2 patients was 97.2% (1.2%). CONCLUSION: The thromboembolic and hemorrhagic complications after AVR with bileaflet mechanical prostheses occur more frequently and result in more deaths in patients 65 years of age and older than in patients years younger than 65 years.  (+info)

Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment. (4/1606)

The inherited thrombophilias--deficiencies of protein C, protein S, and antithrombin III--and the prothrombotic polymorphisms factor V G1691A and factor II G20210A predispose patients toward venous thromboembolism (VTE). The aim of this study was to determine the prevalence of single and combined prothrombotic factors in patients with idiopathic VTE and to estimate the associated risks. The study group consisted of 162 patients referred for work-up of thrombophilia after documented VTE. The controls were 336 consecutively admitted patients. In all subjects factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were analyzed by specific polymerase chain reactions and restriction enzymes. Activities of antithrombin III and protein C, free protein S antigen, and lupus anticoagulant were determined in a subset of 109 patients who were not receiving oral anticoagulants. The prevalences of heterozygotes and homozygotes for factor V G1691A and factor II G20210A among patients and controls were 40.1% versus 3.9% and 18.5% versus 5.4%, respectively (P=0.0001). The prevalence of homozygotes for MTHFR C677T in patients was 22.8% and in controls, 14.3% (P=0.025). Heterozygous and homozygous factor V G1691A, factor II G20210A, and homozygous MTHFR C677T were found to be independent risk factors for VTE, with odds ratios of 16.3, 3.6, and 2.1, respectively. Two or more polymorphisms were detected in 27 of 162 patients (16.7%) and in 3 of 336 controls (0.9%). Logistic regression analysis disclosed odds ratios of 58.6 (confidence interval [CI], 22.1 to 155.2) for joint occurrence of factor V and factor II polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphisms, and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Among 109 patients in whom a complete thrombophilic work-up was performed, 74% had at least 1 underlying defect. These data indicate that in most patients referred for evaluation of thrombophilia due to idiopathic VTE, 1 or more underlying genetic predispositions were discernible. The presence of >1 of the prothrombotic polymorphisms was associated with a substantial risk of VTE.  (+info)

Pulmonary embolism: one-year follow-up with echocardiography doppler and five-year survival analysis. (5/1606)

BACKGROUND: The long-term prognosis for patients with pulmonary embolism (PE) is dependent on the underlying disease, degree of pulmonary hypertension (PH), and degree of right ventricular (RV) dysfunction. A precise description of the time course of pulmonary artery pressure (PAsP)/RV function is therefore of importance for the early identification of persistent PH/RV dysfunction in patients treated for acute PE. Other objectives were to identify variables associated with persistent PH/RV dysfunction and to analyze the 5-year survival rate for patients alive 1 month after inclusion. METHODS AND RESULTS: Echocardiography Doppler was performed in 78 patients with acute PE at the time of diagnosis and repeatedly during the next year. A 5-year survival analysis was made. The PAsP decreased exponentially until the beginning of a stable phase, which was 50 mm Hg at the time of diagnosis of acute PE was associated with persistent PH after 1 year. The 5-year mortality rate was associated with underlying disease. Only patients with persistent PH in the stable phase required pulmonary thromboendarterectomy within 5 years. CONCLUSIONS: An echocardiography Doppler investigation performed 6 weeks after diagnosis of acute PE can identify patients with persistent PH/RV dysfunction and may be of value in planning the follow-up and care of these patients.  (+info)

In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement. (6/1606)

OBJECTIVES: The purpose of this study was to target acoustically reflective liposomes to atherosclerotic plaques in vivo for ultrasound image enhancement. BACKGROUND: We have previously demonstrated the development of acoustically reflective liposomes that can be conjugated for site-specific acoustic enhancement. This study evaluates the ability of liposomes coupled to antibodies specific for different components of atherosclerotic plaques and thrombi to target and enhance ultrasonic images in vivo. METHODS: Liposomes were prepared with phospholipids and cholesterol using a dehydration/ rehydration method. Antibodies were thiolated for liposome conjugation with N-succinimidyl 3-(2-pyridyldithio) propionate resulting in a thioether linkage between the protein and the phospholipid. Liposomes were conjugated to antifibrinogen or anti-intercellular adhesion molecule-1 (anti-ICAM-1). In a Yucatan miniswine model, atherosclerosis was developed by crush injury of one carotid and one femoral artery and ingestion of a hypercholesterolemic diet. After full plaque development the arteries were imaged (20-MHz intravascular ultrasound catheter and 7.5-MHz transvascular linear probe) after injection of saline, unconjugated liposomes and antibody conjugated liposomes. RESULTS: Conjugated liposomes retained their acoustically reflective properties and provided ultrasonic image enhancement of their targeted structures. Liposomes conjugated to antifibrinogen attached to thrombi and fibrous portions of the atheroma, whereas liposomes conjugated to anti-ICAM-1 attached to early atheroma. CONCLUSIONS: Our data demonstrate that this novel acoustic agent can provide varying targeting with different antibodies with retention of intravascular and transvascular acoustic properties.  (+info)

A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. (7/1606)

BACKGROUND: Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. METHODS: In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. RESULTS: A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months. Of 83 patients assigned to continue to receive placebo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 percent reduction in the risk of recurrent venous thromboembolism (95 percent confidence interval, 63 to 99 percent). Three patients assigned to the warfarin group had nonfatal major bleeding (two had gastrointestinal bleeding and one genitourinary bleeding), as compared with none of those assigned to the placebo group (3.8 vs. 0 percent per patient-year, P=0.09). CONCLUSIONS: Patients with a first episode of idiopathic venous thromboembolism should be treated with anticoagulant agents for longer than three months.  (+info)

Arterial thromboembolism in patients with sick sinus syndrome: prediction from pacing mode, atrial fibrillation, and echocardiographic findings. (8/1606)

OBJECTIVE: To evaluate whether thromboembolism in sick sinus syndrome can be predicted by pacing mode, atrial fibrillation, or echocardiographic findings. METHODS: Patients were randomised to single chamber atrial (n = 110) or ventricular (n = 115) pacing. They were divided into subgroups with and without brady-tachy syndrome at time of randomisation. The occurrence of atrial fibrillation and thromboembolism during follow up were investigated and compared with echocardiographic findings. RESULTS: The annual risk of thromboembolism was 5.8% in patients with brady-tachy syndrome randomised to ventricular pacing, 3.2% in patients without brady-tachy syndrome randomised to ventricular pacing, 3% in patients with brady-tachy syndrome randomised to atrial pacing, and 1.5% in patients without brady-tachy syndrome randomised to atrial pacing. In atrial paced patients without brady-tachy syndrome at randomisation and without atrial fibrillation during follow up, the annual risk of thromboembolism was 1.4%. Left atrial size measured by M mode echocardiography was of no value in predicting thromboembolism. CONCLUSIONS: Arterial thromboembolism in patients with sick sinus syndrome is very common and is associated primarily with brady-tachy syndrome at randomisation and with ventricular pacing. The risk of thromboembolism is small in atrial paced patients in whom atrial fibrillation has never been documented.  (+info)